Frontiers Media SA Acta Medica Okayama 2297-7775 11 2026 Navigating inherited “intensive surveillance” within Japan's structural norms of autonomy: maternal identity negotiation among long-term Peruvian migrant mothers (1990–2025) 1944754 EN Katia Sara Huaman Palomino Graduate School of Humanities and Social Sciences, Okayama University Yoshitsugu Hirata Faculty of Education, Okayama University Introduction: This study examines how Peruvian mothers who have settled in Japan for decades rework their identities as mothers. These women were raised with the belief that being a good mother means constantly watching over and protecting their children. But in Japan, child-rearing pushes children toward independence from a young age. This study asks: What happens when these two different approaches of mothering meet? Methods: We interviewed 21 Peruvian mothers who had lived in Japan for 17–35 years. Results: The analysis identified four identity positions to this cultural friction. The first is holding firmly to Peruvian maternal scripts (“Ideological Retention”). The second is following Japanese conventions in public while keeping Peruvian ways at home (“Compartmentalization”). The third is moving away from inherited protective scripts and adopting Japanese norms of independence (“Assimilation”). The fourth is blending elements of both into a maternal self that is “neither the one nor the other” (a “Third Space”). Discussion: This study helps us understand that migrant mothers do not simply choose between their home and new cultures. Instead, they actively work to create a way of mothering through a process we call Reflexive Continuity that makes sense for their unique situations. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-1729 16 10 2026 Purification, Structural Characterization, and Genomic Insights of an Anti-MRSA Peptide from Mangrove-Derived Brevibacillus sp. A34 1697 EN Thanyamai Thongin School of Pharmacy, Walailak University Namfa Sermkaew School of Pharmacy, Walailak University Apichart Atipairin School of Pharmacy, Walailak University Sucheewin Krobthong Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University Chanat Aonbangkhen Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University Jumpei Uchiyama Department of Infectious Diseases, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan Nuttapon Songnaka School of Pharmacy, Walailak University The widespread prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in community and healthcare settings has driven the urgent search for novel antibacterial agents. Mangrove sediments are an underexplored source of antimicrobial-producing bacteria. This study characterized an antimicrobial fraction and the genome of the mangrove-derived isolate Brevibacillus sp. A34. The active fraction was purified via ammonium sulfate precipitation, cation-exchange chromatography, and reversed-phase chromatography. De novo MS/MS analysis assigned the octapeptide LLLLLLAH (905.19 Da), designated as A34 AMP, which was further confirmed by chemical synthesis. This active peptide inhibited all four tested S. aureus strains, including three MRSA strains, with a minimum inhibitory concentration (MIC) of 62 µg/mL. At 2× and 4× MIC, A34 AMP exhibited a concentration-dependent bactericidal effect within 20 h. Increased SYTOX Green uptake and morphological alterations supported a membrane permeabilization mechanism, and antimicrobial activity was retained following thermal, pH, protease, and surfactant treatments. Genome mining identified 23 putative biosynthetic gene clusters, including an 11-module nonribosomal peptide synthetase (NRPS) cluster linked to A34 AMP through three-dimensional adenylation-domain modeling. Collectively, these findings highlight A34 AMP from Brevibacillus sp. A34 as a promising bioactive anti-staphylococcal peptide scaffold. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2227-9032 14 20 2026 Cross-Cultural Adaptation and Initial Psychometric Evaluation of the Japanese Version of the Chronic Kidney Disease Self-Efficacy Scale (CKDSE-J) 3393 EN Tingting Geng Doctor’s Program, Graduate School of Health Sciences, Okayama University Yuki Kajiwara Faculty of Health Sciences, Okayama University Michiko Morimoto Faculty of Health Sciences, Okayama University Background/Objectives: Self-efficacy is an important determinant of self-care among adults with chronic kidney disease (CKD). The Chronic Kidney Disease Self-Efficacy Scale (CKD-SE) is a disease-specific measure, but its use has not been reported in Japan. This study translated and culturally adapted the CKD-SE into Japanese and conducted an initial psychometric evaluation. Methods: A cross-sectional survey was conducted among Japanese adults with CKD stages G3a–G5 not receiving dialysis. Structural validity and internal consistency were evaluated in 227 participants, and construct validity was evaluated in 222. Structural validity was examined using confirmatory factor analysis (CFA) and exploratory structural equation modeling (ESEM). Results: The original 25-item four-factor CFA showed a poor fit, and ESEM yielded an improper solution involving Item 19. Sequential evaluation resulted in a 23-item structure. The 23-item CFA showed mixed fit, whereas Target ESEM showed improved overall fit (CFI = 0.935, TLI = 0.902, RMSEA = 0.060, SRMR = 0.033). However, several autonomy items showed weak target loadings and cross-loadings. Proposed subscale scores correlated positively with self-care behavior (r = 0.27–0.46), and McDonald’s omega ranged from 0.84 to 0.90. Conclusions: The 23-item CKDSE-J showed improved overall model fit under Target ESEM, but the structural definition of autonomy remained uncertain. Because the structure was refined and evaluated in the same sample, independent replication and further psychometric evaluation are needed. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 3 2026 Bioinformatic Prediction of Activation States in Molecular Network Pathways of Eukaryotic Initiation Factor 2 (EIF2) Signaling and Coronavirus Pathogenesis 1525 EN Shihori Tanabe Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences Sabina Quader Innovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion Ryuichi Ono Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences Hiroyoshi Y. Tanaka Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Horacio Cabral Department of Bioengineering, Graduate School of Engineering, The University of Tokyo Eukaryotic initiation factor 2 (EIF2) signaling plays a crucial role in regulating mRNA translation and initiating eukaryotic protein synthesis. Computational molecular network pathway analysis of the canonical pathways of the coronaviral infection revealed that EIF2 signaling is inactivated when the coronavirus pathogenesis pathway is activated and vice versa. Our computational analyses indicated that the coronavirus pathogenesis pathway and EIF2 signaling had inverse activation states. Computational investigation of upstream or downstream microRNA (miRNA) revealed that EIF2 signaling directly interacted with miRNAs, including let-7, miR-1292-3p (miRNAs with the seed CGCGCCC), miR-15, miR-34, miR-378, miR-493, miR-497, miR-7, miR-8, and MIRLET7. A total of 36 nodes, including 8 molecules (ATF4, BCL2, CCND1, DDIT3, EIF2A, EIF2AK3, EIF4E, and ERK1/2), 1 complex (the ribosomal 40s subunit), and 1 function (apoptosis) in the coronavirus pathogenesis pathway, overlapped with EIF2 signaling. Alterations in EIF2 signaling may play a role in the pathogenesis of coronavirus. No potential conflict of interest relevant to this article was reported.

Japanese Circulation Society Acta Medica Okayama 1346-9843 89 6 2025 Clinical Impact of Genetic Testing for Long QT Syndrome　― Evidence From a Nationwide LQTS Registry in Japan ― 835 844 EN Takeshi Aiba Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center (NCVC) Seiko Ohno Medical Genome Center, National Cerebral and Cardiovascular Center (NCVC) Misa Takegami Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center (NCVC) Yoshiaki Kato Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center (NCVC) Heima Sakaguchi Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center (NCVC) Keiko Shimamoto Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center (NCVC) Keiko Sonoda Medical Genome Center, National Cerebral and Cardiovascular Center (NCVC) Kazufumi Ida Division of Counseling for Medical Genetics, National Cerebral and Cardiovascular Center (NCVC) Naokata Sumitomo Department of Pediatric Cardiology, Saitama Medical University International Medical Center Taisuke Nabeshima Department of Pediatric Cardiology, Saitama Medical University International Medical Center Takashi Murakami Department of Child Health, Institution of Medicine, University of Tsukuba Yumiko Ninomiya Department of Pediatrics, National Hospital Organization Kagoshima Medical Center Koichi Kato Department of Cardiovascular Medicine, Shiga University of Medical Science Megumi Fukuyama Department of Cardiovascular Medicine, Shiga University of Medical Science Takeru Makiyama Department of Cardiology, Kyoto University Kenshi Hayashi Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences Kunio Ohta Department of Medical Education, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University Graduate School of Medical Sciences Hiroshi Morita Okayama University Graduate School of Medicine Tadashi Nakajima Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine Yoshiaki Kaneko Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine Nobue Yagihara Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences Sou Otsuki Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences Tomoki Kosho Department of Medical Genetics, Shinshu University School of Medicine Yoko Yoshida Osaka City General Hospital Motoki Takamuro Hokkaido Children’s Hospital Michihiko Ueno Department of Pediatrics, Teine-Keijinkai Hospital Tatsunori Takahashi Department of Pediatrics, Yamagata University Faculty of Medicine Yasuya Inden Department of Cardiology, Nagoya University Graduate School of Medicine Yasunobu Hayabuchi Department of Pediatrics, Tokushima University Shota Muraji Fukuoka Children’s Hospital Shigeo Watanabe Yokohama City University Kunihiro Nishimura Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center (NCVC) Yoshihiro Asano Department of Genomic Medicine, National Cerebral and Cardiovascular Center (NCVC) Hitoshi Horigome Department of Child Health, Institution of Medicine, University of Tsukuba Masao Yoshinaga Department of Pediatrics, National Hospital Organization Kagoshima Medical Center Minoru Horie Department of Cardiovascular Medicine, Shiga University of Medical Science Wataru Shimizu Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center (NCVC) Kengo Kusano Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center (NCVC) Background: Genetic testing for long QT syndrome (LQTS) is useful for diagnosis, risk stratification, and therapeutic strategies. This study investigated the clinical impact of genetic testing for LQTS patients. Methods and Results: Total 3,851 patients (proband: 2,316 [60%]; female: 2,283 [59%]; median age: 14 years [interquartile range 9–36 years]) diagnosed with LQTS (LQTS score ≥3.5, QTc ≥500 ms, pathogenic variants in LQTS-associated genes, or unexplored syncope with QTc 480–499 ms) were enrolled in this study. Of these patients, 1,146 (29.8%) experienced syncope and 322 (8.5%) experienced ventricular fibrillation (VF) or cardiopulmonary arrest (CPA) at ≤70 years of age. Genetic testing using a next-generation sequencing panel and/or Sanger sequencing was performed for 3,770 (98%) patients, genotype was then identified in the following LQTS-associated genes: KCNQ1 (45%), KCNH2 (34%), SCN5A (8%), KCNE1 (0.1%), KCNE2 (0.03%), KCNJ2 (2.7%), CACNA1C (1.2%), and CALM1,2 (0.3%). Forty-seven (1.2%) patients had double or compound heterozygous variants in LQTS-associated genes, whereas the genotype remained unknown in 220 (5.8%) patients. When comparing phenotype with genotype, QTc was significantly longer in CALM1,2 patients than in others except for CACNA1C, whereas QTc was almost normal in KCNJ2 patients. The incidence of the first cardiac event (syncope, VF/CPA) differed among the genotypes, and prognosis was significantly worse for CALM1,2 patients. Conclusions: Comprehensive genetic testing, including non-major LQTS genes, is important for diagnosis and risk stratification of LQTS. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-2607 14 10 2026 Single-Cell Genomics Uncovers an Unexpectedly Abundant, Phylogenetically Hyperdiverse Patescibacteria (Candidate Phyla Radiation) Community in Agricultural Paddy Soil 2213 EN Arslan Ali Institute of Plant Science and Resources, Okayama University Daisuke Saisho Institute of Plant Science and Resources, Okayama University Keiichi Mochida RIKEN Center for Sustainable Resource Science Akio Tani Institute of Plant Science and Resources, Okayama University Patescibacteria, also known as the Candidate Phyla Radiation (CPR), are among the most diverse yet functionally reduced bacterial lineages whose diversity in agricultural soils remains poorly characterized. We applied single-cell genomics to bulk soil from an unfertilized paddy field after rice harvest and drainage. From 384 randomly sorted single cells, 126 medium-to-high-quality SAGs (Single-Amplified Genomes) were recovered, spanning 24 bacterial and archaeal phyla. Unexpectedly, 108 of the 384 SAGs (28.1%) were assigned to Patescibacteria—the most frequently recovered phylum—including 42 of the 126 reliable SAGs. These genomes were notably small (mean 973 kb vs. 1.4–3.2 Mb for other phyla). Because CheckM underestimates completeness in reduced CPR genomes, CheckM2 was applied, raising mean completeness from 59.9% to 83.3% and reclassifying 15 genomes as near-complete (>90%). Phylogenomic analysis using 16 ribosomal protein markers revealed extensive diversity and low average amino acid identity to reference genomes (mean 44.6%), indicating substantial taxonomic novelty. Despite this diversity, functional annotation and OrthoFinder analysis showed a conserved, reduced gene repertoire dominated by translation and DNA repair genes and depleted in amino acid, cofactor, and nucleotide biosynthesis. These results show that modest soil sampling can recover outsized Patescibacteria diversity, underscoring the need for CPR-appropriate completeness assessment. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 3059-3700 2 1 2026 Delta morphology reveals timings of early ocean regression and hydrologic shift on ancient Mars 37 EN Ren Kito Institute for Planetary Materials, Okayama University Hitoshi Hasegawa Faculty of Science and Technology, Kochi University Trishit Ruj Institute for Planetary Materials, Okayama University Tetsuji Muto Department of Environmental Science, Nagasaki University Gian Gabriele Ori International Research School of Planetary Sciences, Università d’Annunzio Goro Komatsu International Research School of Planetary Sciences, Università d’Annunzio Mars’ ancient hydrologic history remains a subject of debate, with competing interpretations suggesting either a large ocean or scattered lacustrine environments. Here, we show that delta morphology on Mars records a shift between these hydrologic regimes. Through controlled tank experiments, we identify two distinct delta types: “lobe-extruding deltas” formed during water-level falls and “stepped fan-deltas” formed during rising water levels. The lobe-extruding deltas occur near proposed paleo-coastlines and are dated to ~3.8–3.2 Ga, consistent with the existence of a Late Noachian–Hesperian ocean and its subsequent regression in the Late Hesperian. In contrast, stepped fan-deltas are found at a wider range of elevations and exhibit significantly younger ages (~2.1–0.1 Ga), suggesting episodic, localized lake formation during the Amazonian. Our findings constrain the timing of the planetary-scale transition from a global hydrosphere to localized aqueous environments and refine the understanding of Mars’ paleoclimate evolution and potential habitability. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1718-7729 33 6 2026 Limited Immune-Mediated Efficacy of Anti-PD-L1/VEGF in EGFR-TKI-Naïve Egfr-Mutant Lung Cancer with Non-Inflamed Tumor Microenvironment 315 EN Atsuko Hirabae Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadahiro Kuribayashi Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Sachi Okawa Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takamasa Nakasuka Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuya Nishii Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Nishimura Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Go Makimoto Department of Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Hisao Higo Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kammei Rai Center for Innovative Clinical Medicine, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Masamichi Sugimoto Product Research Department, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Immune checkpoint inhibitors (ICIs) show limited efficacy in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma due to its non-inflamed tumor microenvironment (TME). While quadruple therapy combining chemotherapy, anti-programmed death-ligand 1 (PD-L1), and anti-vascular endothelial growth factor (VEGF) antibodies has shown inconsistent results in EGFR-tyrosine kinase inhibitor (TKI)-pretreated patients, whether anti-VEGF therapy can modulate the intrinsic non-inflamed TME remains unknown. We employed an EGFR-TKI-naïve syngeneic Egfr-mutant mouse model and evaluated effects of anti-VEGF, anti-PD-L1, carboplatin, and paclitaxel as monotherapies and combinations, with TME analysis via immunohistochemistry (IHC), flow cytometry, and RNA sequencing. Anti-PD-L1 showed no antitumor effect, and adding anti-VEGF failed to convert the TME to an inflamed status. Although paclitaxel—but not carboplatin—combined with low-dose anti-VEGF inhibited tumor growth, adding anti-PD-L1 provided no benefit, indicating the anti-VEGF-A antibody evaluated here has a limited role in sensitizing tumors to anti-PD-L1 regardless of chemotherapy. CD8+ T-cell depletion did not attenuate the effect of paclitaxel plus low-dose anti-VEGF, and IHC and RNA sequencing revealed increased natural killer cell infiltration, suggesting a CD8+ T-cell-independent, innate immune mechanism. These findings provide preclinical evidence that the evaluated anti-VEGF has limited immunomodulatory activity in EGFR-TKI-naïve Egfr-mutant tumors with a non-inflamed TME, and suggest immunotherapeutic strategies beyond CD8+ T-cell-mediated immunity warrant investigation. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0047-6374 234 2026 The eukaryotic host–microbe–phage–nutrition interplay determines the bacterial effectors of supplemental lysine’s health benefits: An experimental cellular senescence model of digestive conditions in older adults 112260 EN Darab Ghadimi Department of Microbiology and Biotechnology, Max Rubner-Institut Sophia Blömer Faculty of Medicine, Christian-Albrechts-University of Kiel Aysel ŞAHİN KAYA Department of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim University Sandra Krüger Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein Christoph Röcken Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein Heiner Schäfer Laboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus Kiel Geraldine de Heer University Center for Nutritional Medicine, University Medical Centre Hamburg-Eppendorf Dominik Jarczak University Center for Nutritional Medicine, University Medical Centre Hamburg-Eppendorf Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shigenobu Matsuzaki Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University Wilhelm Bockelmann Department of Microbiology and Biotechnology, Max Rubner-Institut Recently, the consumption of various forms of the nutritive amino acid lysine (e.g., nutraceuticals and dietary supplements) has increased, particularly among the elderly, as it cannot be synthesized by the human body and plays a crucial role in several cellular physiological processes, including intestinal calcium and iron absorption, proteinogenesis, and fatty acid metabolism. However, the biochemical and immunological events that occur within the eukaryotic host-microbe-phage-nutrition interaction, especially when high amounts of lysine are consumed in nutraceutical or dietary supplement form by the elderly due to age-related requirements, as well as the impact on gut bacteria-derived metabolites, have not yet been fully studied. We hypothesized that (1) within an infectious-inflamed digestive milieu, the metabolism of excess extracellular lysine differs between young and senescent digestive cells, and (2) phages within the milieu exhibit alterations in host-microbe cometabolite signal profiles. To address this, we examined how gut microbes and phages, key regulators of eukaryotic host physiology, influence the immunometabolism of excess lysine. By combining two models of young and senescent digestive cells, the pathogenic P. aeruginosa PAO1, the Pseudomonas phage KPP22, and the anti-inflammatory bacterium Intestinimonas butyriciproducens, and simulating the pathogenesis of the interactive process of excessive lysine ingestion, we developed a five-way screening approach to explore key cell readouts, including viability, integrity, and function of the epithelial barrier, as well as cellular immunometabolic responses to exogenous lysine supplementation in cultures under infectious inflammation. Our findings are consistent with the possibility that host–microbe–microbe interactions involving lysine utilization and cross-feeding may influence the effects of lysine supplementation. These effects, whether beneficial or detrimental, can depend on the bacterial community, including the presence of pathogenic or potentially beneficial bacteria, interactions with intestinal phages, and the physiological conditions and metabolic requirements of the host and individual microbial taxa. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 19 2026 Impaired Myostatin Function Alters Body Composition Without Detectable Attenuation of Imiquimod-Induced Psoriasiform Dermatitis 8518 EN Yoshihiro Matsuda Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Morizane Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuma Sakamoto Department of Immunology and Molecular Genetics, Kawasaki Medical School Nobuyasu Baba Department of Immunology and Molecular Genetics, Kawasaki Medical School Masanori Iseki Department of Immunology and Molecular Genetics, Kawasaki Medical School Daiki Takezaki Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshio Kawakami Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin-Ichiro Nishimatsu Department of Natural Sciences, Kawasaki Medical School Yutaka Ohsawa Department of Neurology, Kawasaki Medical School Yoshihide Sunada Department of Neurology, Kawasaki Medical School Tomoyuki Mukai Department of Immunology and Molecular Genetics, Kawasaki Medical School Psoriasis is a chronic inflammatory skin disease closely associated with obesity and metabolic dysfunction. While excess adiposity is considered a key risk factor, the independent contribution of body composition to psoriatic inflammation remains unclear. Myostatin negatively regulates skeletal muscle growth, and its inhibition leads to muscle hypertrophy and reduced adiposity. In this study, we investigated whether altered body composition due to impaired myostatin function affects imiquimod (IMQ)-induced psoriasiform dermatitis. Wild-type (WT) and dominant-negative myostatin transgenic mice were fed either a normal diet or a high-fat diet (HFD) for 10 weeks, followed by topical IMQ treatment to induce dermatitis. Mutant mice exhibited increased skeletal muscle mass and reduced visceral fat compared with WT controls, indicating marked changes in body composition. In WT mice, HFD feeding increased fat mass and tended to aggravate IMQ-induced ear swelling. In contrast, no significant effect of impaired myostatin function on ear thickness, epidermal hyperplasia, or the expression of psoriasis-associated genes was detected, despite reduced visceral fat. Under the present experimental conditions, these changes in body composition were not associated with a detectable attenuation of psoriasiform skin inflammation. Our results suggest that obesity-related psoriasis is influenced by metabolic and immunological factors beyond body composition. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2475-0328 2026 The Geriatric Nutritional Risk Index Predicts Short‐ and Long‐Term Outcomes in the Oldest‐Old With Colorectal Cancer: A Multi‐Institutional Analysis of 225 Nonagenarians EN Toshiaki Toshima Department of Surgery, Kagawa Rosai Hospital Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Hospital Satoe Takanaga Department of Gastroenterological Surgery, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Ryo Inada Department of Surgery, Kochi Health Sciences Center Tsuyoshi Ohtani Department of Surgery, Saiseikai Okayama Hospital Ryosuke Yoshida Department of Surgery, Okayama Rosai Hospital Naoto Hori Department of Surgery, Tottori Municipal Hospital Kaoru Shigemitsu Department of Surgery, Tsuyama Chuo Hospital Sumiharu Yamamoto Department of Surgery, Okayama City Hospital Tetsushi Kubota Department of Surgery, Kobe Red Cross Hospital Yuka Okano Department of Surgery, Onomichi City Hospital Tetsuji Nobuhisa Department of Surgery, Himeji Red Cross Hospital Fumitaka Taniguchi Department of Surgery, National Hospital Organization Iwakuni Clinical Center Wataru Ishikawa Department of Surgery, Fukuyama City Hospital Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Hospital Tatsuo Matsuda Department of Surgery, Matsuda Hospital Tatsuo Umeoka Department of Surgery, Matsuyama City Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Hospital The Setouchi Colorectal Neoplasm Registration Study Group Aim: Surgical outcomes for colorectal cancer (CRC) in nonagenarians remain uncertain due to frailty, comorbidities, and malnutrition. The Geriatric Nutritional Risk Index (GNRI) is associated with surgical outcomes in older patients with CRC, but its prognostic value in nonagenarians is unclear. This study evaluated the GNRI's predictive value for short- and long-term surgical outcomes in this population. Methods: We retrospectively analyzed 225 nonagenarians undergoing surgical resection of CRC at 15 institutions between 2011 and 2022. Patients were stratified by GNRI-high/low status using two cutoffs: 98 (Cohort 1) and 86 (Cohort 2). Outcomes included postoperative complications, length of hospital stay, and overall survival (OS). Stabilized inverse-probability-of-treatment weighting (IPTW) was used to adjust for measured confounding. Results: The median age was 92 years (female, 64.9%; colon cancer, 79.6%). GNRI-high patients had higher body mass index and albumin levels. Complication rates did not differ between the groups. After adjustment, GNRI-high patients in Cohort 1 had a shorter expected hospital stay (ratio 0.70, 95% CI 0.51–0.96; p = 0.025) but no significant OS difference. In Cohort 2, GNRI-high patients had better OS (p < 0.01), confirmed by adjusted Cox models (HR 0.54, 95% CI 0.35–0.82; p < 0.01). Conclusions: Preoperative GNRI was associated with hospital stay and OS in nonagenarians undergoing CRC surgery, although the OS association was significant only with the cohort-derived cutoff of 86, which requires external validation, and not with the literature-based cutoff of 98. The GNRI is a simple tool to stratify surgical risk and optimize perioperative nutritional status in this vulnerable population. No potential conflict of interest relevant to this article was reported.

Japanese Society of Preventive Medicine Acta Medica Okayama 2758-7916 2 3 2024 Relationship between food security and dietary habits and subjective sense of health and subjective sense of well-being among residents of large-scale housing complexes in Japan 45 56 EN Keiko Wakimoto School of Food Sciences and Nutrition, Mukogawa Women’s University Miyuki Yokoro-Hisanari Faculty of Education, Okayama University Akira Ohtsubo Community Liaison Division for Education and Research, Mukogawa Women’s University Tatsuya Fujii School of Education, Mukogawa Women’s University Jotaro Kato School of Letters, Mukogawa Women’s University Hitoshi Ogasawara School of Nursing, Mukogawa Women’s University Daisuke Kudo School of Nursing Science, Meiji University of Integrative Medicine Minae Fukui Ichikan Nursing Development center for Diversity, Kobe City College of Nursing Yuichi Fujita School of Nursing, Mukogawa Women’s University Background: This study aimed to determine the relationship between food security and dietary habits and subjective health and subjective well-being among residents of a large-scale housing complex in Japan. Methods: This study used a cross-sectional design through a self-administered questionnaire survey. The study subjects were residents of Mukogawa Danchi in Nishinomiya City, Hyogo Prefecture, Japan, and data from 515 households out of 6,857 total dwelling units were used for the analysis. Food security status (HFSSM), dietary diversity score (HDDS), diet, eating behavior, subjective sense of health, and subjective sense of well-being were examined using logistic regression analysis. Results: Food insecurity was negatively associated with household dietary diversity scores (OR [95%CI]:0.49 [0.24–0.98] p = 0.044). Similarly, food insecurity was negatively associated with having a nutritionally balanced diet and having a satisfactory amount of food. There was also a negative association with family meals. There was a negative association between food insecurity and a subjective sense of health and a negative association (0.35 [0.15–0.78] p = 0.011) with a subjective sense of well-being among those aged 65 and older. Conclusions: In a large-scale housing complex in Japan, inadequate dietary intake was observed in food-insecure households; they ate meals less frequently with their families. Additionally, residents experiencing food insecurity tended to have lower subjective health and subjective well-being, depending on their age. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2624-5175 7 1 2025 Association Between Alcohol Use Patterns and Insomnia Symptoms or Poor Sleep Quality Among Adult Women: An Internet Cross-Sectional Survey in Japan 5 EN Suguru Nakajima Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Yuichiro Otsuka Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Yoshitaka Kaneita Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Osamu Itani Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Yuki Kuwabara Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University Aya Kinjo Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University Ruriko Minobe National Hospital Organization Kurihama Medical and Addiction Center Hitoshi Maesato National Hospital Organization, Ryukyu Hospital Susumu Higuchi National Hospital Organization Kurihama Medical and Addiction Center Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Yoshimoto Department of Family Medicine, General Practice and Community Health, Faculty of Medicine, University of Tsukuba Maki Jike Department of Food Science and Nutrition, Faculty of Life and Environmental Science, Showa Women’s University Hideaki Kasuga Department of Hygiene and Preventive Medicine, Fukushima Medical University Teruna Ito Department of Food and Nutrition, Koriyama Women’s University Yoneatsu Osaki Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University It is unclear whether patterns of alcohol consumption are associated with sleep disturbance. We aimed to investigate the relationship between comprehensive alcohol-related factors and insomnia symptoms, as well as sleep quality, among adult women in Japan. Responses to an online cross-sectional survey were gathered from 12,000 women. The survey items included demographic characteristics, alcohol consumption (Alcohol Use Disorders Identification Test, nightcaps, years of drinking), sleep-related factors (sleep duration, insomnia symptoms, sleep quality), lifestyle-related factors, and mental health. Binary logistic regression was used to investigate the relationship between alcohol consumption and both insomnia symptoms and sleep quality. A total of 10,233 women were included in the final analysis. The results revealed that several alcohol-related behaviors, including the consumption of nightcaps and years of drinking, were significantly associated with insomnia symptoms and poor sleep quality. Specifically, nightcaps were significantly associated with all types of insomnia symptoms and poor sleep quality, with a higher odds ratio than other alcohol-related items. Our findings suggest that specific alcohol-related behaviors, particularly the consumption of nightcaps, are associated with insomnia symptoms and poor sleep quality among women. Intervention programs for alcohol consumption should be provided to prevent sleep problems among women. No potential conflict of interest relevant to this article was reported.

EpiSmart Science Vector Ltd Acta Medica Okayama 2476-762X 26 1 2025 Preoperative Nutritional Status Influences Enteral Nutrition Weaning 6 Months Post-Surgery in Patients with Esophageal Cancer 263 267 EN Mika Sonoi Department of Foods and Human Nutrition, Faculty of Human Life Sciences, Notre Dame Seishin University Yasuhiro Shirakawa Department of Surgery, Hiroshima City Hiroshima Citizens Hospital Norihiro Sonoi Center for Education in Medicine and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunsuke Tanabe Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoaki Maeda Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective: This study aimed to clarify whether nutritional status at admission affects enteral nutrition weaning 6 months after surgery in patients with esophageal cancer. Methods: This was a retrospective study of 81 patients who underwent subtotal esophageal cancer resection between April 2014 and February 2016. The survey items were as follows: 1) sex, 2) age, 3) presence or absence of family members living together, 4) clinical stage, 5) surgical procedure, 6) reconstructed organs, 7) nutritional status at admission, 8) presence or absence of postoperative complications (anastomotic leakage, chylothorax, and recurrent laryngeal nerve paralysis), and 9) presence or absence of treatment other than surgery (chemo- or radiotherapy). Results: The enteral nutrition withdrawal rate after 6 months was 15.5% in the malnutrition group and 84.5% in the normal nutrition group (p = 0.007). In a comparison between groups with and without enteral nutrition after 6 months, a significant association was observed with surgical procedure, nutritional status at admission, and postoperative complications (p < 0.05). Logistic regression analysis showed that the odds of discontinuing enteral nutrition 6 months later were 5.692 (hazard ratio: 1.545–20.962) for malnutrition on admission and 11.921 (hazard ratio: 3.449–41.207) for complications. Conclusion: Regardless of the presence or absence of treatment other than surgery, preoperative nutritional improvement is beneficial for increasing postoperative oral intake. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2079-6382 14 3 2025 Influence of Educational Films on Antiviral Prescription for COVID-19: Insights from Web-Based Survey in Japan 276 EN Kosaku Komiya Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine Akihiko Hagiwara Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine Yuichiro Shindo Department of Respiratory Medicine, Nagoya University Graduate School of Medicine Kazufumi Takamatsu Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University Naoki Nishimura Department of Respiratory Medicine, National Center for Global Health and Medicine Yukako Takechi Iki-iki Clinic Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Takahiro Takazono Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences Shinyu Izumi Department of Respiratory Medicine, National Center for Global Health and Medicine Shimpei Gotoh Department of Clinical Application, Center for iPS Cell, Research and Application, Kyoto University Seiichiro Sakao Department of Pulmonary Medicine, School of Medicine, International University of Health and Welfare Takehiro Izumo Department of Respiratory Medicine, Japanese Red Cross Medical Center Kazuko Yamamoto Division of Infectious, Respiratory, and Digestive Medicine, First Department of Internal Medicine, University of the Ryukyus Graduate School of Medicine Kazuhiro Yatera Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, Japan Hiroshi Kakeya Department of Infection Control Science, Osaka Metropolitan University Graduate School of Medicine Yoko Shibata Department of Pulmonary Medicine, Fukushima Medical University School of Medicine Keisuke Tomii Department of Respiratory Medicine, Kobe City Medical Center General Hospital Hironori Sagara Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine Yuka Sasaki Center for Pulmonary Disease, National Hospital Organization Tokyo Hospital Toyohiro Hirai Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University Akihito Yokoyama Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University Hiroshi Mukae Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences Takashi Ogura Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center Background: Prescribing antiviral agents for severe acute respiratory syndrome coronavirus 2 requires careful consideration based on the patient’s risk factors for severe disease progression and their vaccination status. However, effective interventions ensuring the appropriate use of antiviral agents by physicians have yet to be fully established. Thus, this study evaluated the impact of an educational film on antiviral prescription rates for coronavirus disease 2019 (COVID-19). Methods: This prospective, nationwide, web-based survey enrolled 1500 physicians. They were instructed to view a short educational film and assess the necessity of prescribing antiviral agents in 16 fictitious scenarios featuring adult patients with COVID-19 with varying risk factors for severe disease and vaccination statuses. We compared the antiviral prescription rates before and after viewing the educational film. Results: There was a significant increase in the antiviral prescription rates after viewing the educational film, particularly nirmatrelvir/ritonavir prescribed in cases involving immunocompromised patients (from 31.3% to 49.4%) and those with obesity (from 15.1% to 33.7%) who were unvaccinated and had no risk of drug interactions. However, viewing the educational film made little to no impact on the prescription rates for the patients with hypertension and hyperlipidemia or those with no underlying conditions. Conclusions: Short educational films may promote the appropriate use of antiviral agents for COVID-19. However, their impact on altering prescription behavior appears limited and varies according to the clinical context. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-2607 14 9 2026 Virotherapy for Spinal and Spinal Cord Tumors: Current Evidence and Future Perspectives 2110 EN Koji Uotani Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Takatori Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazutaka Yamashita Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenzaburo Matsumoto Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Oda Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Shinohara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tumors of the spine and spinal cord, including primary and metastatic vertebral tumors, intramedullary gliomas, and refractory intradural lesions, are challenging to treat because curative local therapy is limited by the eloquent, nonregenerating neural tissue surrounding them. Oncolytic virotherapy may offer a rational alternative by combining tumor-selective oncolysis with the induction of systemic antitumor immunity, while sparing normal neural cells. This review summarizes the current field of oncolytic viruses, including adenovirus, herpes simplex virus, reovirus, and others, in the context of spinal and spinal cord tumors. Clinical data in the spine remain scarce; however, the rationale is based on histological evidence from sarcomas and other tumors, extensive glioma experience, including diffuse intrinsic pontine glioma, and preclinical activity in nerve sheath and meningioma models. We discuss the telomerase-specific oncolytic adenovirus OBP-301 and its derivatives, whose hTERT-driven replication provides histology-agnostic tumor selectivity, while sparing the telomerase-silent spinal cord. This telomerase dependence, however, limits activity against tumors that maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, such as many osteosarcomas and some spinal cord astrocytomas. We also discuss delivery and safety within the confined spinal canal, combination strategies, and future directions, such as extracellular vesicle-mediated delivery and biomarker-guided patient selection. Although clinical translation to the spine will require dedicated preclinical and early-phase studies, virotherapy represents a promising, mechanistically grounded modality for these therapeutically challenging tumors. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2311-5521 11 9 2026 First-Order Wall-Slip-Induced Departure from Inverse-Cubic Scaling of Levitation-Pressure RMS in a Push–Pull Levitation Stage 218 EN Eisuke Umesaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroki Suzuki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Junji Sakamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Toshinori Kouchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University This study clarifies how rarefaction-induced wall slip in a thin gas film affects the established inverse-cubic scaling law for the spatial nonuniformity of levitation pressure in a push–pull levitation stage. The levitation force in this stage is generated by the combined action of blowing and suction. The continuum-based stress description is retained, and only the wall boundary condition is changed from the no-slip condition to a first-order slip condition. Three-dimensional incompressible unsteady Stokes simulations in a thin-gap unit-cell model are combined with a lubrication-theory scaling analysis. The effects of levitation height, blowing-velocity distribution, port-radius ratio, and computational-domain width are examined systematically. The results show that wall slip has only a minor influence at relatively large levitation heights. As the levitation height decreases, however, rarefaction-induced slip increases the flow-rate conductance. Consequently, the intensity of the spatial variation in levitation pressure is systematically reduced below that predicted by the no-slip inverse-cubic scaling law. This departure is well described by a correction relation derived from the lubrication approximation and remains robust against changes in the prescribed blowing-velocity distribution and geometric conditions. These findings provide an incompressible baseline for predicting levitation-pressure nonuniformity within the nominal gap-based Knudsen-number range examined here. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2073-4395 16 16 2026 Genetic Dissection and Fine-Mapping of QTL for Salinity Tolerance at the Reproductive Stage on Chromosome 2 of Rice Variety Nona Bokra 1518 EN Farjana Rauf Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tran Thi Thu Hien Graduate School of Environmental and Life Science, Okayama University Nguyen Thi Thu Thuy Graduate School of Environmental and Life Science, Okayama University Asami Tomita Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshihiko Hirai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Soil salinity is a major constraint limiting rice productivity, particularly at the reproductive stage. To elucidate the genetic basis of reproductive stage salinity tolerance, this study validated and fine-mapped quantitative trait loci (QTL) for yield-related traits using a salinity-tolerant line SL506, identified through screening of Nona Bokra–CSSLs in a Koshihikari background. In 2016, the F2 population derived from SL506/Koshihikari was evaluated under long-term salt stress; three QTLs associated with plant dry weight, panicle number, and grain weight were detected on chromosome 2. In 2023, validation analysis using F3 individuals confirmed the presence of these QTLs. Subsequent fine-mapping using F4 near-isogenic lines (NILs) delimited the QTL to a 1.7 Mb interval and high-resolution mapping using an F5 recombinant population progressively refined it to a 473 kb genomic region containing 69 annotated genes. Variant Effect Predictor analysis identified 15 deleterious nonsynonymous variants (SIFT < 0.05) in six candidate genes. Based on annotated gene functions, predicted variant effects, and their membership in stress-related gene families, OsPP2C24, OsFbox102, and OsWAK14 were suggested as the most promising candidate genes underlying qPDW2. These findings provide insights into the genetic basis of reproductive-stage salinity tolerance from valuable resources for the future improvement of salt tolerance and yield stability in rice. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2673-7655 6 2 2026 Effects of Different Heading Dates on Agronomic and Yield-Related Traits Under Salt Stress in Rice 28 EN Sadia Afrin Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sayuri Ito School of Agriculture, Okayama University M M Emam Ahmed Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shuto Ogino School of Agriculture, Okayama University Asami Tomita Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshihiko Hirai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Salinity is a major abiotic stress limiting rice production worldwide. This study aims to elucidate the effects of heading date on salt tolerance in rice. Five near-isogenic lines (NILs) developed from the SL2038/Koshihikari backcross population were grown with or without salt stress. SL2038 is a salt-tolerant line with delayed heading (~18 days) compared to the salt-sensitive background Koshihikari. The results showed that late-heading NILs produced significantly higher plant dry weight, panicle weight, percentage of filled grains, and grain weight (p < 0.05) under long-term salt stress. In Koshihikari, which exhibited delayed heading due to long-day treatment, the percentage of white heads was low, and panicle and grain weights were significantly higher under salt stress. Experiments with different sowing times indicated that late heading, such as sowing in June, resulted in higher grain weights. This is the first report to assess the impact of heading date on agronomic and yield-related traits under salt stress. In conclusion, even with a prolonged salt treatment period, heading during periods of low temperature and solar radiation results in higher grain weight under salt stress. This is proposed as one of the strategies for salt escape. These findings can be used to improve rice yield and implement crop management in salt-affected regions. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 18 2026 Salivary miR-324-5p Is Associated with Periodontal Inflamed Surface Area in People Living with HIV Receiving Antiretroviral Therapy: A Case–Control Study 8117 EN Mohammad Nurhamim Department of Preventive Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aya Yokoi Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideharu Hagiya Department of Infectious Diseases, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Periodontitis is a common inflammatory disease that affects the tooth-supporting tissues. Salivary microRNA (miRNA) expression in extracellular vesicles (EVs) can reflect periodontal status. Both the prevalence and severity of periodontitis are higher in people with human immunodeficiency virus (PWH). This study aimed to identify miRNA in salivary EVs associated with periodontitis in PWH receiving antiretroviral therapy (ART). The case group comprised PWH with periodontitis undergoing ART, while the control group included individuals with periodontitis but without HIV infection. The study was conducted in two phases. In the first phase, a specific miRNA was identified in the case group using next-generation sequencing analysis, resulting in the selection of hsa-miR-324-5p as a candidate marker of periodontitis. In the second phase, the association between miRNA expression of hsa-miR-324-5p and periodontal status in the case group was evaluated using real-time-quantitative PCR (RT-qPCR). RT-qPCR analysis demonstrated that hsa-miR-324-5p expression was significantly associated with periodontal inflamed surface area (PISA). Bioinformatic analysis identified 10 potential hub genes for hsa-miR-324-5p that are involved in protein kinase binding and are associated with the adherens junction pathway, that may be contributing to the pathogenesis of periodontitis. Salivary hsa-miR-324-5p derived from EVs may be associated with the severity of periodontitis among PWH receiving ART. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-5204 22 2025 Prevalence, characteristics, and outcomes of suicide-related out-of-hospital cardiac arrest among patients committing self-harm and suicide-attempts in Japan: A nationwide registry study 100923 EN Takashi Hongo Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Tetsuya Yumoto Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Shunta Jinno Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Yuka Yamamura Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Epidemiology Takafumi Obara Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Tsuyoshi Nojima Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Kohei Tsukahara Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Hiromichi Naito Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Takashi Yorifuji Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Epidemiology Atsunori Nakao Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Background: Suicide-related out-of-hospital cardiac arrest (OHCA) is characterized by extremely low survival rates and represents a considerable global public health concern. This study aimed to investigate the prevalence, characteristics, and outcomes of suicide-related OHCA. Methods: This multicenter, retrospective cohort study is an analysis of data collected from the JAPAN Registry of Self-harm and Suicide Attempts. Patients were divided into two groups, the OHCA group and the non-OHCA group. The primary outcome was death at 30 days. Results: Among 1,960 self-harm and suicide attempts patients, 213 patients (10.9 %) were assigned to the OHCA group and 1,747 (89.1%) were in the non-OHCA group. Patients in the OHCA group were older (44 vs. 33 years old, p < 0.001), and the OHCA group had a higher proportion of males compared to the non-OHCA group (122 [57.3%] vs. 604 [34.6%], p < 0.001). Despite missing and unknown data, lower proportions of psychiatric consultation history (54 [30.8%] vs. 1177 [70.5%], p < 0.001), psychiatric hospitalization history (9 [5.1%] vs. 386 [23.1%], p < 0.001), and previous suicide attempts (16 [9.2%] vs. 807 [48.4%], p < 0.001) were observed in the OHCA group. Risk of death at 30 days was significantly higher in the OHCA group (200 [93.9%] vs. 31 [1.8%], p < 0.001). Conclusion: Suicide-related OHCA was rare and associated with poorer prognosis compared to patients without OHCA. It was more common in middle-aged men without a history of psychiatric care or prior suicide attempts, although the study was limited by missing data. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 16 8 2026 Study protocol for a phase II clinical trial evaluating the safety and efficacy of favipiravir injection combined with oseltamivir in influenza treatment e106715 EN Sayaka Hikida Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Hidetoshi Nomoto Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Yukari Uemura Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security Tadaki Suzuki Department of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health Security Koichi Izumikawa Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences Hiroki Ohge Project Research Center for Nosocomial Infectious Diseases, Hiroshima University Masaya Yamato Infectious Diseases Center, Rinku General Medical Center Yasuyuki Kato Department of Infectious Diseases, International University of Health and Welfare Narita Hospital Ryota Hase Department of Infectious Diseases, Japanese Red Cross Narita Hospital Tetsuji Aoyagi Department of Clinical Microbiology and Infection, Tohoku University Graduate School of Medicine Hideharu Hagiya Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoko Nukui Department of Infection Control & Laboratory Medicine, Kyoto Prefectural University of Medicine Kazuko Yamamoto First Department of Internal Medicine, Division of Infectious, Respiratory, and Digestive Medicine, University of the Ryukyus Graduate School of Medicine Yoshio Takesue Chita Peninsula General Medical Organization, Rinku Hospital Kota Sawada Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security Yosuke Shimizu Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security Sho Miyamoto Department of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health Security Namiko Tamura Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Kozue Takahashi Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Sho Saito Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Kazuki Miyazaki Center for Clinical Sciences, Japan Institute for Health Security Eriko Morino Center for Clinical Sciences, Japan Institute for Health Security Daisuke Tokita Center for Clinical Sciences, Japan Institute for Health Security Norio Ohmagari Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Introduction Older adults are at an increased risk of influenza-related hospitalisation and mortality due to a combination of risk factors. Severe influenza and excess mortality in this population remain major public health concerns, underscoring the need for novel treatment strategies. Methods and analysis This multicentre, investigator-initiated, randomised, double-blind clinical trial evaluated the efficacy and safety of the investigational drug favipiravir injection (T-705IV) in combination with oseltamivir phosphate, compared with oseltamivir monotherapy in hospitalised patients with influenza aged ≥65 years. Both T-705IV and oseltamivir phosphate will be administered for 5 days. The primary endpoint is time from randomisation to recovery within 15 days. Recovery is defined as either actual hospital discharge or sustained clinical status permitting discharge for 3 consecutive days. Clinical status will be assessed using a 7-point ordinal scale based on hospitalisation status and oxygen requirement. The primary analysis employs a Bayesian Cox proportional hazards model with a non-informative prior to estimate the posterior probability that the HR exceeds 1.0. The secondary endpoints include the distribution of 7-point scale scores over a 29-day period; rates of clinical worsening at days 15 and 29; duration of fever; all-cause mortality; intensive care unit admission within 29 days; pneumonia complication rate at 15 days; and changes in viral titre and viral RNA load on days 1, 2, 3 and 7. Safety will be assessed through the collection of adverse events (AEs) up to day 29. Pharmacokinetic evaluation will include measurement of plasma favipiravir concentrations on day 3. The planned sample size is 80 patients (40 per group). Ethics and dissemination Written informed consent will be obtained from all participants. This study was approved by the Center Hospital of the National Center for Global Health and Medicine Institutional Review Board (approval number: NCGM-I-022-24a) and registered in the Japan Registry of Clinical Trials. Study findings will be disseminated through peer-reviewed publications and/or presentations at academic conferences. Trial registration number jRCT2031240586, No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-4426 16 10 2026 Efficacy and Safety of Switching from Nalfurafine to Difelikefalin in Hemodialysis Patients with Refractory Pruritus 489 EN Yoshimasa Sakurabu Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kumiko Tokunaga Sugimoto Clinic Yuko Ogiso Sugimoto Clinic Miwako Motoie Sugimoto Clinic Megumi Yoshitake Sugimoto Clinic Taro Sugimoto Sugimoto Clinic Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Hemodialysis-associated pruritus is common and can substantially impair quality of life. Given its heterogeneous pathophysiology and variable treatment response, individualized therapeutic strategies are needed. This study investigated the prevalence and severity of pruritus and clinical outcomes after switching from nalfurafine to difelikefalin. Methods: Clinical data from 108 maintenance hemodialysis patients whose pruritus severity was assessed using the Numerical Rating Scale (NRS) were retrospectively reviewed. Ten patients with persistent moderate-to-severe pruritus (NRS ≥ 3) despite treatment with nalfurafine were switched to difelikefalin in routine clinical practice, of whom eight completed the 16-week follow-up and were included in the switch group. Eight patients matched for age, sex, dialysis vintage, and baseline NRS served as controls. Changes in NRS scores at weeks 4 and 16, as well as adverse events, were evaluated. Results: Among 108 patients, 21 (20%) had no pruritus, while 20 (18.5%), 47 (43.5%), and 20 (18.5%) had mild, moderate, and severe pruritus, respectively. Of 14 patients receiving nalfurafine, 13 (92.9%) had persistent moderate-to-severe pruritus. In the switch group, mean NRS decreased from 5.9 ± 1.7 at baseline to 2.3 ± 2.3 at week 4 and 2.0 ± 0.9 at week 16 (p = 0.0156 and p = 0.0078, respectively), with no meaningful change in controls. No serious adverse events strongly related to difelikefalin were identified. Conclusions: Pruritus was highly prevalent in this cohort. Switching to difelikefalin was associated with rapid and sustained improvement in patients inadequately responsive to nalfurafine, with favorable tolerability, supporting its potential role as an individualized treatment option. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0031-3998 2026 Long-term association between the COVID-19 pandemic and language development at 3 years of age EN Rumi Matsuo Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazue Nakamura Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Few studies have examined the long-term association between the COVID-19 pandemic and language development in preschoolers or its effect modifiers. We therefore examined this association during health checkups of 3-year-olds in Japan. Methods: This repeated cross-sectional study included 40,898 3-year-olds who underwent checkups in Okayama City, Japan. We compared children examined before (2017–2019) and during the pandemic (2020–2023). The primary outcome was physician-determined risk of language difficulties. The secondary outcome was children’s infrequent questions using words such as “what,” “who,” and “where.” Modified Poisson regression estimated RRs adjusted for confounders. Subgroup analyses examined effect modification by sex, childcare setting, and family size. Results: The COVID-19 pandemic was associated with increased risk of language difficulties (RR 1.52, 95% CI 1.35–1.72). The association peaked in fiscal year 2021 and remained elevated throughout the pandemic. Secondary outcome showed elevated risk (RR 1.16, 95% CI 1.05–1.29). Girls and home-care children showed higher RRs than boys and preschool attendees. Conclusions: The COVID-19 pandemic was associated with risk of language difficulties among 3-year-old children, with associations varying by sex and childcare setting. These findings suggest the importance of maintaining social interaction opportunities for young children during public health crises. No potential conflict of interest relevant to this article was reported.

The Korean Geriatrics Society Acta Medica Okayama 2508-4798 30 2 2026 Variation in the Association between Frailty and Disability over 10 Years: A Cohort Study 143 150 EN Akikazu Hagiyama Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Soshi Takao Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Although frailty is associated with disability, its long-term persistence and changes over time remain unclear. This study aimed to investigate the long-term association between frailty and the incidence of disability over a 10-year follow-up period, evaluating how this association changed over time. Methods: This cohort study was conducted in Okayama City, Japan. Community-dwelling older adults aged ≥65 years were included. Frailty was assessed using the Kihon Checklist, and disability was defined as a new certification for long-term care insurance. The association between frailty and disability was examined across five time periods (years 1–2, 3–4, 5–6, 7–8, and 9–10) using a marginal structural model with inverse probability of treatment weighting and inverse probability of censoring weighting. Results: The final analysis included 45,291 participants, with 17.3% classified as frail. The adjusted odds ratios (ORs) for the association between frailty and the incidence of disability gradually decreased over time but remained throughout the 10-year follow-up period. The adjusted ORs and 95% confidence intervals were 2.90 (2.55–3.29) for years 1–2, 2.40 (2.09–2.75) for years 3–4, 2.03 (1.76–2.34) for years 5–6, 1.75 (1.52–2.01) for years 7–8, and 1.58 (1.38–1.82) for years 9–10. Conclusion: Frailty was consistently associated with the incidence of disability over a 10-year follow-up period, with a stronger association in the earlier years and a gradual decline over time. No potential conflict of interest relevant to this article was reported.

Public Library of Science (PLoS) Acta Medica Okayama 1932-6203 21 3 2026 Incidence of pelvic fractures after definitive radiotherapy for cervical cancer: A retrospective multicenter cohort study (The IPFAR study) e0344384 EN Shinsuke Shirakawa Department of Obstetrics and Gynecology, Okayama University Shoji Nagao Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kotaro Yoshio Department of Radiology, Okayama University Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Noriaki Imafuku Department of Obstetrics and Gynecology, Fukuyama Medical Center Dan Yamamoto Department of Obstetrics and Gynecology, Fukuyama Medical Center Masae Yorimitsu Department of Obstetrics and Gynecology, Hiroshima City Hiroshima Citizens Hospital Junichi Kodama Department of Obstetrics and Gynecology, Hiroshima City Hiroshima Citizens Hospital Hisako Nagasaka Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital Yoshie Nakanishi Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Objective This multicenter study aimed to identify the risk factors for pelvic insufficiency fractures (PIFs) in women who received definitive radiotherapy (RT) as the initial treatment for cervical cancer and to examine the differences in the incidence of PIFs across institutions. Patients and Methods The medical records of 208 women were reviewed. These women received definitive RT as an initial treatment for cervical cancer at four institutions between January 2016 and December 2018. Results The median age was 61.5 years (range: 29–93 years). Overall, 59 patients (28.4%) developed PIF, with 48 (81.4%) of them developing it within two years after completion of RT. Multivariate analysis identified postmenopausal status and treating institution as independent risk factors. The incidence of PIF varied significantly among institutions, ranging from 18.9% to 50.0%, despite no significant differences in patient demographics or RT protocols. Conclusion Substantial inter-institutional variation in PIF incidence was observed, even under standardized treatment conditions. These findings underscore the need for individualized risk assessment and institutional quality control in the long-term management of cervical cancer survivors. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2328-8957 12 3 2025 Effects of Amikacin Liposome Inhalation Suspension and Amikacin Resistance Development in Patients With Refractory Mycobacterium avium Complex Pulmonary Disease ofaf118 EN Yu Kurahara Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center Shiomi Yoshida Clinical Research Center, NHO Kinki Chuo Chest Medical Center , Osaka , Asami Osugi Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Yuya Tanaka Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center Takehiko Kobayashi Clinical Research Center, NHO Kinki Chuo Chest Medical Center Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Yohei Kawasaki Department of Biostatistics, Graduate School of Medicine, Saitama Medical University Satoshi Mitarai Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Kazunari Tsuyuguchi Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center Background. Amikacin liposome inhalation suspension (ALIS) is key for treating refractory Mycobacterium avium complex pulmonary disease (MAC-PD). However, microbiological efficacy by subtype remains unknown. The frequency and mechanism of amikacin (AMK) resistance during ALIS administration are also unclear. Methods. We retrospectively analyzed data from refractory MAC-PD patients who received ALIS for at least 6 months as an adjunct to guideline-based therapy at the NHO Kinki Chuo Chest Medical Center. We investigated the efficacy of ALIS and analyzed gene expression and the frequency of AMK resistance. Results. We enrolled 44 patients (median age, 72.0 years): 19 (43.2%) with the noncavitary nodular bronchiectatic (NC-NB) subtype and 25 (56.8%) with the cavitary subtype. Overall, sputum culture conversion was 56.8% (25/44): 84.2% (16/19) in the NC-NB subtype and 36.0% (9/25) in the cavitary subtype (P = .001). During intermittent dosing, conversion occurred in 50.0% (9/18). In patients with C-reactive protein (CRP) ≥1 mg/dL, cavitary subtype, and clarithromycin (CLM) resistance, the risk ratio for persistently positive cultures was 10.81 (95% CI, 1.66–70.40) compared with those with CRP <1 mg/dL, NC-NB subtype, and CLM susceptibility. Of all participants, 15.9% (7/44) had isolates with AMK resistance (minimum inhibitory concentration ≥128 µg/mL), and of these 71.4% (5/7) had rrs mutations. Conclusions. Regimens that included ALIS achieved higher culture conversion in NC-NB than cavitary MAC-PD cases. High CRP levels, cavitary disease, and CLM resistance predicted persistent culture positivity. AMK resistance acquired during ALIS administration may limit treatment options for refractory MAC-PD. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 6 2026 Routine Generative AI Use and Acceptance of Medical AI: A Cross-Sectional Survey of Healthcare Workers and the Public in Japan e110118 EN Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Background Acceptance of medical artificial intelligence (AI) is critical for successful implementation, yet its acceptance may vary by clinical application and stakeholder group. Whether routine use of generative AI (GAI) is associated with acceptance of medical AI remains unclear. Methods A cross-sectional web survey was conducted in Japan in November 2025 using web-panel convenience sampling from an online research panel. The small analytic sample comprised 200 participants aged 20-69 years, including 100 healthcare workers and 100 non-healthcare workers. GAI use was assessed using two five-point items (GAI use at work and in daily life) and dichotomized as at least monthly use in either daily life or work versus less than monthly use in both settings, based on prespecified criteria. Acceptance of medical AI was measured for five scenario-based applications - AI-assisted imaging interpretation, AI-based health risk prediction, AI-based treatment recommendations, AI-enabled triage guidance, and AI-assisted robotic surgery - using a four-point acceptability scale; responses were dichotomized as acceptable versus not acceptable. Calibration weights were constructed to approximate Japanese internet users by raking on sex-by-age group and household income, normalized to the analytic sample size, and truncated at prespecified bounds. Adjusted prevalence ratios (aPRs) were estimated using modified Poisson regression with robust standard errors, stratified by occupation; covariates were selected a priori using a modified disjunctive cause criterion. This study was exploratory; therefore, adjustments for multiple comparisons were not performed. Results Among healthcare workers, the lower-use group had a higher prevalence of non-acceptance of AI-based health risk prediction (aPR 6.980, 95% CI 1.412-34.506) and AI-based treatment recommendations (aPR 4.364, 95% CI 1.331-14.305), whereas estimates for imaging interpretation, triage guidance, and robotic surgery remained statistically uncertain. Among non-healthcare workers, the lower-use group had a higher prevalence of non-acceptance of AI-assisted imaging interpretation (aPR 13.906, 95% CI 1.624-119.052), AI-based health risk prediction (aPR 4.861, 95% CI 1.133-20.862), AI-based treatment recommendations (aPR 6.288, 95% CI 1.386-28.530), and AI-assisted robotic surgery (aPR 6.173, 95% CI 1.435-26.561); the adjusted estimate for AI-enabled triage guidance was not statistically supported (aPR 1.840, 95% CI 0.521-6.505). Several estimates had wide confidence intervals, indicating substantial imprecision. Conclusions In this small exploratory web-panel convenience sample, lower-frequency GAI use was associated with higher non-acceptance of several medical AI applications. Associations were observed across more applications among non-healthcare workers than among healthcare workers. Because the study was cross-sectional, used convenience sampling, and included imprecise estimates with wide confidence intervals, the findings should not be interpreted causally. Larger studies using longitudinal or interventional designs are needed to clarify temporality and mechanisms. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0016-7037 430 2026 Pervasive and rapid enrichment of nitrogen in newly erupted oceanic basalt 249 262 EN Juan Felipe Bustos-Moreno Department of Earth and Environmental Sciences, Lehigh University Tobias B. Weisenberger Geology and Sustainable Mining Institute, University Mohammed VI Polytechnic Ryoji Tanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Hiroshi Kitagawa The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Gray E. Bebout Department of Earth and Environmental Sciences, Lehigh University The alteration of oceanic crust by seawater is a critical sink in the global nitrogen (N) cycle, yet the mechanisms and timescales of N enrichment remain poorly constrained. We present N concentrations and isotope compositions from a 192-meter drill core (SE-02b) retrieved from the then 50-year-old Surtsey Island in Iceland, a pristine analog for rapid alteration of young oceanic basalt. The altered basaltic tuffs show significant N enrichment (average 11 ± 8 μg/g), relative to unaltered Icelandic basalt glasses (0.028 ± 0.026 μg/g) and MORB (∼1.1 to 1.5 μg/g), matching the global average for altered oceanic crust (11 μg/g; ranging in ages from 5 to 170 Ma). Nitrogen isotope compositions (δ15Nair = −1.7 ± 4.6‰) are primarily consistent with incorporation of seawater- and meteoric-derived ammonium (NH4+), more likely into secondary K-minerals, palagonitized glass and smectites throughout the core. To a lesser extent, N could be incorporated into Na/Ca-minerals such as analcime in the meteoric water altered zone and sulphates such as anhydrite and gypsum when present. Incorporation of NH4+ into secondary phases occurs with little isotope fractionation consistent with equilibrium fractionation between clay and aqueous NH4+. We demonstrate that seawater-rock interaction alone can produce the ubiquitous background N enrichment of the oceanic crust without the addition of remobilized N from sedimentary sources. Such magnitude of enrichment is also observed via meteoric water alteration. Localized high enrichments in N in areas of enhanced fluid flow at core SE-02b with exceptionally low δ15N values (as low as −20.1‰), are attributed to abiotic reduction of dissolved N2 under anoxic conditions and/or microbial activity. We propose that N incorporation into the oceanic crust can occur rapidly in days to decades rather than at a constant rate over geologic time. This has major implications for N transfer in subduction zones, N exchange between the oceanic crust, seawater and the atmosphere and for planetary habitability. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 3050-5976 2 1 2026 Older patients with LBCL show comparable outcomes to younger patients and product-specific profiles in CAR-T therapy 100037 EN Sho Shibata Department of Hematology, Kyoto University Hospital Yasuyuki Arai Department of Hematology, Kyoto University Hospital Junya Kanda Department of Hematology, Kyoto University Hospital Daisuke Kaji Department of Hematology, Toranomon Hospital Daisuke Minakata Division of Hematology, Department of Medicine, Jichi Medical University Toshio Kitawaki Department of Hematology, Kyoto University Hospital Kazuyuki Shimada Department of Hematology and Oncology, Nagoya University Graduate School of Medicine Tatsu Shimoyama Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Satoshi Yoshihara Department of Hematology, Hyogo Medical University Hospital Shinichi Makita Department of Hematology, National Cancer Center Hospital, Tokyo Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Go Yamamoto Department of Hematology, Toranomon Hospital Emiko Sakaida Department of Hematology, Chiba University Hospital Yasuhiro Nakashima Department of Hematology, Osaka Metropolitan University Hospital Akiyo Yoshida Division of Transfusion Medicine, Kanazawa University Hospital Yoshihiro Umezawa Department of Hematology, Institute of Science Tokyo Hospital Jun Kato Division of Hematology, Department of Medicine, Keio University School of Medicine Haryoon Kim Division of Hematology, Department of Medicine, Keio University School of Medicine Keisuke Kataoka Division of Hematology, Department of Medicine, Keio University School of Medicine Hideki Goto Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Koji Kato Department of Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a key treatment option for patients with relapsed or refractory large B-cell lymphoma (LBCL). However, data on its effectiveness and safety in older populations remain limited, particularly in real-world clinical practice. Moreover, comparative outcomes among different CAR-T products across age groups have not yet been fully characterized. We conducted a nationwide retrospective cohort study using data from the Japanese Society for Transplantation and Cellular Therapy. A total of 908 patients who received CAR-T therapy between January 2019 and September 2024 were included. Patients were categorized as younger (aged <65 years) or older (aged ≥65 years). Subgroup analyses were performed by CAR-T product (tisagenlecleucel [tisa-cel], lisocabtagene maraleucel [liso-cel], and axicabtagene ciloleucel [axi-cel]). In univariate analysis, 1-year overall survival (OS) and progression-free survival (PFS) were comparable between younger and older patients (OS, 69.4% vs 65.7% [P = .40]; PFS, 47.9% vs 54.1% [P = .17]). In multivariate analysis, age ≥65 years showed no significant association with OS (hazard ratio, 0.88; 95% confidence interval, 0.65-1.21; P = .44). The incidence of immune effector cell–associated neurotoxicity syndrome was significantly higher in older patients (12.7% vs 7.0%; P = .005). Compared with tisa-cel, axi-cel and liso-cel were associated with superior PFS, predominantly in younger patients. Among older patients, axi-cel was associated with higher nonrelapse mortality rate than tisa-cel. CAR-T therapy is feasible and effective for older patients with LBCL. These findings support age-adapted treatment strategies that consider both the efficacy and toxicity of each product. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2047-9980 15 3 2026 Long‐Term Outcomes and Risk Factors for Mortality After Single Ventricle Palliation for Asplenia Syndrome e044756 EN Yasuyuki Kobayashi Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital Shunji Sano Department of Pediatric Cardiac Surgery Showa Medical University Toyosu Hospital Yuhei Tokuda Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital Ayari Kimura Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital Steven J. Staffa Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston Harvard Medical School David Zurakowski Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston Harvard Medical School Shingo Kasahara Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital Yasuhiro Kotani Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital Background: This study evaluated the long‐term outcomes of asplenia syndrome with single ventricle palliation, hypothesizing that total anomalous pulmonary vein connection (TAPVC), pulmonary atresia (PA), and greater than or equal to moderate atrioventricular valve regurgitation increase mortality risk. Methods: This retrospective review analyzed 151 patients with asplenia syndrome who underwent single ventricle palliation between 1990 and 2024. The primary end point was mortality, with risk factors assessed by Cox regression analysis over a mean follow‐up of 9.3 years. Results: The median age at initial operation was 35 days, including 70 neonates (46%). Overall, 62 (41%) patients died, whereas 66 (44%) patients are alive post‐Fontan completion. Survival probabilities at 1 and 20 years were 75.7% (95% CI, 67.9–81.8) and 53.7% (95% CI, 44.5–62.0), respectively. TAPVC (P=0.014), PA (P=0.007), and greater than or equal to moderate atrioventricular valve regurgitation (P=0.040) emerged as independent risk factors for mortality in the overall cohort. In the TAPVC cohort, independent risk factors for mortality included PA (P=0.019), infracardiac TAPVC (P=0.045), and neonatal TAPVC repair (P=0.018). When stratified by the risk factors of TAPVC, PA, or greater than or equal to moderate atrioventricular valve regurgitation, survival probabilities did not differ between patients with none or 1 of these conditions (P=0.181) but were significantly lower in those with ≥2 risk factors (P<0.001, at 15 years: 0, 72.9%; 1, 59.1%; ≥2, 32.8%). Conclusions: Survival after single ventricle palliation for asplenia syndrome remains suboptimal, particularly when TAPVC, PA, and greater than or equal to moderate atrioventricular valve regurgitation are present in combination rather than in isolation. Improved strategies or surgical techniques are required for this complex asplenia syndrome cohort. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1660-3397 24 9 2026 A Marine Brevibacillus-Derived Membrane-Lytic Peptide: Molecular Insight and Biophysical Characterization of a Novel AMP, FNL62-AMP 309 EN Namfa Sermkaew School of Pharmacy, Walailak University Apichart Atipairin School of Pharmacy, Walailak University Sucheewin Krobthong Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University Chanat Aonbangkhen Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University Yodying Yingchutrakul National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency Jumpei Uchiyama Department of Infectious Diseases, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nuttapon Songnaka School of Pharmacy, Walailak University This study characterizes the genomic identity, functional efficacy, and computational biophysics of FNL62-AMP, a novel antimicrobial peptide isolated from a phylogenomically distinct, newly identified Brevibacillus species. Production kinetics revealed a late-exponential phase onset of antibacterial activity with sustained potency against methicillin-resistant Staphylococcus aureus (MRSA). LC-MS/MS analysis identified the peptide sequence as NH2-LLLLFR-COOH. FNL62-AMP demonstrated excellent formulation resilience, retaining full anti-MRSA activity under high thermal stress (80 °C for 6 h) and showing robust resistance to generic trypsin and proteinase K proteolysis. Formulative co-incubation assays demonstrated charge-dependent compatibility, where nonionic Triton X-100 preserved baseline efficacy while ionic surfactants induced antagonism. In vitro time-kill kinetics, scanning electron microscopy, and SYTOX Green assays confirmed rapid, concentration-dependent bactericidal action driven by immediate membrane permeabilization. Molecular dynamics simulations successfully captured the spontaneous self-assembly of 64 FNL62-AMP monomers into a stable macro-aggregate. This consolidation process was quantitatively characterized by a simultaneous contraction in the radius of gyration (Rg), a sharp drop in solvent-accessible surface area (SASA), and a transitional plateau in mean squared displacement (MSD). Ultimately, the high thermal stability, structural resilience, and predictable surfactant compatibility of FNL62-AMP propose ways to be developed for lead optimization and druggability. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 33 5 2026 Breast ultrasound screening in young adult women undergoing infertility treatment at an infertility clinic: a retrospective observational study 1093 1101 EN Kanako Nakano Department of Radiology, Okayama Couple’s Clinic Women’s Health Checkup Center Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Reina Maeda Department of Breast and Endocrine Surgery, Okayama University Hospital Marie Saji Department of Breast and Endocrine Surgery, Okayama University Hospital Rei Hirata Department of Senior Embryologist, Okayama Couple’s Clinic Motomi Yukawa Department of Radiology, Okayama Couple’s Clinic Women’s Health Checkup Center Shizuka Okuda Department of Radiology, Okayama Couple’s Clinic Women’s Health Checkup Center Miyu Hirano Department of Medical Technology, Okayama Couple’s Clinic Toshihiro Habara Department of Reproductive Medicine, Okayama Couple’s Clinic Nobuyoshi Hayashi Department of Reproductive Medicine, Okayama Couple’s Clinic Background Young adult women are increasingly undergoing infertility treatment; however, evidence regarding breast cancer screening in this population remains limited. Given that most women in this age group have dense breast tissue, for which mammography has limited sensitivity, breast ultrasound (US) is often used as a screening modality. A diagnosis of breast cancer during infertility treatment may affect both oncologic management and reproductive planning. This study aimed to examine the clinical relevance of breast US in women in their 30s undergoing infertility treatment at an infertility clinic. Methods We retrospectively analyzed 1,336 women aged 30–39 years who underwent screening breast US between November 1, 2018, and June 30, 2025. Analyses were performed on a per-woman basis, including only the first screening examination for each participant. Breast composition was categorized according to the BI-RADS 5th edition Atlas. Screening outcomes—including recall rate, positive predictive value (PPV), cancer detection rate, and US findings (mass and non-mass findings)—were assessed using medical records. The continuation of infertility treatment, defined as ongoing or resumed treatment during the diagnostic evaluation period, was descriptively evaluated as part of the clinical context. Results Of the 1,336 women, 1,277 (95.6%) were classified as having dense breasts. A total of 140 (10.5%) women were recalled for further evaluation. In these recalled cases, 147 findings were identified, comprising 113 mass lesions (76.8%) and 34 non-mass findings (23.1%). Four breast cancers were identified, corresponding to a cancer detection rate of 0.30% and a PPV of 2.86%. Histological diagnoses included one mucinous carcinoma, two invasive carcinomas of no special type (NST), and one ductal carcinoma in situ (DCIS). Following diagnostic evaluation, 124 recalled women (88.6%) continued infertility treatment. Conclusions Breast US screening in women in their 30s undergoing infertility treatment provides descriptive findings within a specific clinical setting. The observed cancer detection rate appears to be within the range reported in previous studies; however, direct comparisons are limited due to differences in study populations and clinical contexts. The clinical course following recall was described as part of the screening pathway. Further prospective and multicenter studies are required to clarify the clinical significance of breast US screening in this population. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0028-3940 2026 Angioarchitectural characterization of transdural supply in brain arteriovenous malformations: a multicenter retrospective study EN Yasuyuki Kaku Department of Neurosurgery, Kumamoto University Hospital Tetsu Satow Department of Neurosurgery/Stroke Center, Kindai University Hospital Shuichi Tanoue Department of Radiology, Kurume University School of Medicine Masafumi Hiramatsu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiko Ozaki Department of Neurosurgery, University of Osaka Graduate School of Medicine Wataro Tsuruta Department of Endovascular Neurosurgery, Toranomon Hospital Yushin Takemoto Department of Neurosurgery, Kumamoto University Hospital Timo Krings Division of Neurointerventional Radiology, Lahey Hospital & Medical Center – Beth Israel Lahey Health, UMass Chan Medical School Hiro Kiyosue Department of Radiology, Kumamoto University, Graduate School of Medical Sciences, Kumamoto University Purpose Transdural supply (TDS) is a recognized angioarchitectural feature of brain arteriovenous malformations (bAVMs). We aimed to systematically characterize the angioarchitecture of TDS in bAVMs, focusing on whether transdural feeders terminated within the nidus or connected directly to the draining vein. TDS prevalence and its associated clinical features were also investigated. Methods This retrospective study enrolled 521 patients (524 bAVMs) from 16 centers who underwent systematic six-vessel digital subtraction angiography. bAVMs were classified as nidus- or fistula-dominant. Angiography was evaluated with specific focus on the presence of TDS and the termination site of transdural feeders. TDS was classified as TDS-Nidus (fistulous point within the nidus) or TDS-DV (fistulous point at the draining vein wall). Results TDS was identified in 88 bAVMs (16.8%). The fistula-dominant type was more frequent in bAVMs with TDS (P < 0.01). Among TDS cases, 25 (28.4%) demonstrated TDS-DV. Fistula-dominant morphology was the only independent predictor of TDS-DV (P < 0.01). No significant differences in complete occlusion rates or modified Rankin Scale score after treatment were observed between the TDS-Nidus and TDS-DV groups. Older age (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.02–1.06), larger nidus size (OR: 1.95; 95% CI: 1.60–2.42), occipital location (OR: 3.12; 95% CI: 1.28–7.62), eloquent area involvement (OR: 3.23; 95% CI: 1.61–6.50), and headache (OR: 2.85; 95% CI: 1.26–6.44) were independently associated with TDS. Conclusion TDS-DV was identified in 28% of bAVMs with TDS and was strongly associated with fistula-dominant morphology. Recognition of this angioarchitectural pattern may facilitate angiographic characterization of bAVMs with TDS. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-4418 16 17 2026 Granular Swollen Epithelial Cells in Native Kidney Biopsies: Prevalence, Clinicopathological Associations and Kidney Outcomes 2822 EN Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Granular swollen epithelial cells (GSECs) have been described primarily in mitochondrial cytopathies, in which they are regarded as a characteristic pathological finding that may aid in the diagnosis of mitochondrial dysfunction; however, their prevalence and clinical significance in native kidney disease remain unclear. We aimed to evaluate the prevalence, clinicopathological associations, and prognostic significance of GSECs in native kidney biopsy specimens. Methods: Among 1165 adults who underwent native kidney biopsy between 2011 and 2024, 501 patients with evaluable medullary tissue were included in this retrospective cohort study. GSECs were defined as enlarged tubular epithelial cells with conspicuous granular cytoplasm in medullary tubules, and cases were classified as GSEC-positive when at least one unequivocal GSEC was identified. Clinical and histopathological characteristics were compared between groups, and kidney outcomes were evaluated using Cox proportional hazards models. Results: The mean baseline eGFR was 60.8 ± 26.3 mL/min/1.73 m2, and the median urinary protein excretion was 1.1 g/gCr. During a median follow-up of 2.3 years, 112 patients (22.3%) reached the composite kidney outcome. GSECs were identified in 18% of native kidney biopsy specimens containing evaluable medullary tissue, and were observed across a broad spectrum of kidney diseases. GSEC positivity was associated with older age and underlying pathological diagnoses but was not associated with baseline kidney function or proteinuria. Kaplan–Meier and multivariable Cox analyses revealed no significant association between GSECs and kidney prognosis. Conclusions: GSECs are not specific to kidney allografts and are observed in a subset of diverse native kidney diseases. Although associated with certain clinical characteristics, no independent association between GSECs and kidney outcomes was observed in this cohort. These findings suggest that GSECs may reflect disease-dependent biological responses to tubular epithelial stress, potentially related to metabolic or mitochondrial alterations, rather than a marker of progressive kidney injury. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1474-9718 25 5 2026 UNC45B Reduction With Aging: A Myofiber-Intrinsic Promoting Factor for Sarcopenia e70502 EN Taiga Mishima Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Taiga Nagamune Department of Life Science and Applied Chemistry, Nagoya Institute of Technology Saori Tada Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Daiki Watanabe Graduate School of Sport and Health Sciences, Osaka University of Health and Sport Sciences Nao Tokuda Graduate School of Health Sciences, Sapporo Medical University Takashi Yamada Graduate School of Health Sciences, Sapporo Medical University Akiko Hashimoto‐Hachiya Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Sayaka Higo‐Yamamoto Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Kohei Kido Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University Aoi Ikedo Division of Integrative Pathophysiology, Proteo‐Science Center, PIAS, Ehime University Yuuki Imai Division of Integrative Pathophysiology, Proteo‐Science Center, PIAS, Ehime University Ryo Fujita Division of Regenerative Medicine, Transborder Medical Research Center, Institute of Medicine, University of Tsukuba Seiya Mizuno Laboratory Animal Resource Center in Transborder Medical Research Center, Institute of Medicine, University of Tsukuba Satoru Takahashi Laboratory Animal Resource Center in Transborder Medical Research Center, Institute of Medicine, University of Tsukuba Katsutaka Oishi Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Satoru Ato Faculty of Medical Science, Nippon Sport Science University Riki Ogasawara Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Skeletal muscle mass and force decline with age, and the loss of muscle force precedes muscle atrophy. However, the underlying mechanisms remain unclear. Here, we investigated the role of the myosin co-chaperone, uncoordinated mutant number-45 myosin chaperone B (UNC45B), in regulating muscle mass and force. UNC45B expression decreased in mouse gastrocnemius muscle with age, particularly at 24 months old, and adeno-associated virus vector-mediated knockdown of Unc45b in 3-month-old mouse triceps surae muscle first reduced plantar flexor torque and then decreased gastrocnemius muscle mass. In addition, Unc45b knockdown in the triceps surae muscle resulted in lower bone mineral density. While maximum Ca2+-activated force in mechanically skinned fibers was not affected by Unc45b knockdown, Unc45b knockdown decreased the ratio of depolarization-induced force to the maximum Ca2+-activated force. We established tamoxifen-inducible skeletal muscle-specific Unc45b knockout (Unc45b imKO) mice to investigate whether the muscle atrophy and weakness due to the loss of Unc45b impacts metabolism and behavior. We found that Unc45b imKO reduced muscle mass and force at a whole-body level, but did not influence systemic glucose tolerance, insulin sensitivity, or the respiratory exchange ratio. However, Unc45b imKO mice reduced the amount of deeper non-rapid eye movement sleep, locomotor activity, and body temperature during the sleep phase. We conclude that UNC45B is essential for maintaining fast-twitch muscle mass and muscle force. In addition, Unc45b deficiency-mediated muscle loss is also associated with bone fragility, decreased body temperature, and impaired sleep quality. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2673-9801 6 3 2026 The Antioxidant Activity of α-Tocopherol Metabolites in Comparison with the Parent Compound in Hepatocytes 26 EN Tomoka Nishio Graduate School of Environmental and Life Science, Okayama University Kasumi Amako Graduate School of Environmental and Life Science, Okayama University Daiki Moriya Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University α-Tocopherol (αT) is the major form of vitamin E. Although it is metabolized in the liver when high levels of αT are present, the function of its metabolites has not yet been fully elucidated. This study aimed to evaluate the antioxidant activities of the αT metabolites, α-carboxyethyl hydroxychroman (αCEHC) and α-carboxymethylbutyl hydroxychroman (αCMBHC), in comparison with their parent compound. The pretreatment with αT and its metabolites showed a cytoprotective effect on the cytotoxicity induced by hydrogen peroxide in the mouse hepatoma Hepa1c1c7 cells. To elucidate the mechanism underlying the effect, in vitro assays and assessments of antioxidant-related genes and proteins were conducted. The in vitro assays showed that these compounds showed little scavenging activity against hydrogen peroxide but exhibited scavenging activity against DPPH radicals. On the other hand, assessments of antioxidant-related genes and proteins showed that αT and its metabolites significantly upregulated the expression of heme oxygenase-1 (HO-1) possibly through activation of the transcript factor Nrf2. Moreover, the cytoprotective effects of αT and its metabolites against hydrogen peroxide were counteracted by HO-1 inhibitors. These results suggest that not only αT but also its metabolites are potential cytoprotective factors against oxidative stress-induced cytotoxicity, and that their effects are exerted not through a direct action of scavenging hydrogen peroxide in the body, but rather through the regulation of gene expression. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 3 2026 Chloride-Transporting OsHKT1;1 Splice Variants and Their Expression Profiles Under Salinity Stress in Rice 1178 EN Shahin Imran Institute of Plant Science and Resources, Okayama University Shuntaro Ono Institute of Plant Science and Resources, Okayama University, Kurashiki 710-0046, Okayama, Japan Rie Horie Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University Maki Katsuhara Institute of Plant Science and Resources, Okayama University Tomoaki Horie Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University OsHKT1;1, a member of the high-affinity K+ transporter (HKT) family, plays a key role in Na+ homeostasis and salinity tolerance in rice. In our previous study, multiple potential OsHKT1;1 splicing variants were identified, as well as the full-length (FL) OsHKT1;1 transcript from the salt-tolerant rice Pokkali. However, most previous studies focused solely on the full-length protein, leaving the transport functions of splice variants largely unexamined. In this study, we focused on the splice variant OsHKT1;1-V2 and compared its function and gene expression with those of OsHKT1;1-FL. Two-electrode voltage clamp experiments using Xenopus laevis oocytes revealed that the 1st start codon of OsHKT1;1-V2 is functional to exhibit bidirectional currents in bath solutions containing NaCl. Unlike the Na+-selective feature of OsHKT1;1-FL, OsHKT1;1-V2 primarily mediated Cl− transport with weak Na+ selectivity, which was supported by the higher Cl− accumulation in OsHKT1;1-V2–expressing oocytes. Subcellular localization analyses using oocytes and Arabidopsis mesophyll cells indicated plasma membrane localization of OsHKT1;1-V2, similar to OsHKT1;1-FL. Functional assays using a yeast mutant further indicated that OsHKT1;1-FL, but not OsHKT1;1-V2, mediates Na+ uptake. The same OsHKT1;1 variants were identified in the japonica cultivar Nipponbare, and OsHKT1;1-V2 of the cultivar showed Cl− transport properties similar to the one from Pokkali. Quantitative PCR analyses revealed higher abundance of OsHKT1;1-FL transcripts in Nipponbare than in Pokkali with markedly lower OsHKT1;1-V2 levels in Pokkali under salt stress. This study provides a new insight into HKT-mediated ion homeostasis under salinity stress. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0924-8579 67 10 2026 Clinical characteristics and therapeutic dilemmas in nocardiosis: Insights from a case series 107906 EN Hidemasa Akazawa Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Tomoyuki Miyahara Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Sakura Ogawa Microbiology Division, Clinical Laboratory, Okayama University Hospital Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Objectives: Nocardiosis often requires prolonged antimicrobial therapy, and trimethoprim–sulfamethoxazole (TMP–SMX) is considered the cornerstone of treatment. However, TMP–SMX–related adverse events frequently complicate long-term therapy, and real-world data regarding treatment continuity and outcomes remain limited.<br.> Methods: We conducted a retrospective observational study of patients with Nocardia species isolated from clinical specimens at a tertiary-care academic hospital in Japan between January 2015 and April 2025. Clinical characteristics, antimicrobial therapy, adverse events, and outcomes were reviewed. Results: Eleven cases were enrolled, with a median age of 65 years. The cohort comprised seven patients with severe nocardiosis (disseminated disease, brain abscess, and pneumonia in transplant recipients) and four patients with mild nocardiosis (cutaneous infection and pneumonia). Nine patients received TMP–SMX as part of the initial regimen, of whom seven required modification of therapy within 1 day to 3 months because of adverse events. Following modification of TMP–SMX, patients were treated with alternative regimens, including fluoroquinolone—and minocycline-based therapies, as well as β-lactam–containing combinations. Importantly, no cases of treatment failure or death were observed, and no relapses were identified during the available follow-up period, even among patients with those clinically complex diseases. Conclusions: Although TMP–SMX is the first-line therapy for nocardiosis, the majority of our patients did not tolerate the drug. Nevertheless, favorable outcomes were observed with alternative regimens, even in patients with clinically complex disease, suggesting that alternative regimens may be reasonable options when TMP–SMX is not tolerated. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 17 2026 Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer’s Disease in a Mouse Model 7542 EN Momoko Nakahara Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Kataoka Department of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama University Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mohammad Nurhamim Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Yixuan Zhang Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Daiki Fukuhara Department of Preventive Dentistry, Dental School, Okayama University Yoko Uchida-Fukuhara Laboratory of Biological Anthropology, Research Center for Integrative Evolutionary Science, The Graduate University for Advanced Studies, SOKENDAI Md Monirul Islam Centre for Policy Studies, University College Cork Manabu Morita Department of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health Care Takashi Saito Department of Neuropathology, Graduate School of Medicine, The University of Tokyo Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The purpose of the present study was to investigate how periodontitis and diabetes mellitus (DM) are associated with Alzheimer’s disease (AD) through microRNA (miRNA) using AD model mice. The experimental period was 8 weeks. Twenty-four male knock-in mice (B6-AppNL-G-F/NL-G-F/J) were divided into four groups: control group fed a normal diet (C), DM group fed a high-fat/sucrose diet (DM), periodontitis (P) group, and DM + periodontitis (DM+P) group. Memory performance was compared using the Y-maze test. Next-generation sequencing was performed on brain samples, and fold changes in miRNA expression were calculated by comparing the DM+P and C groups. Integrated miRNA–mRNA analysis identified putative miRNA-targeted mRNAs, and protein expression of the top candidate gene was assessed. Memory function in the DM+P group was significantly lower than in the C group. Among the seven mRNAs identified by the integrated analysis, Neurod1 showed the greatest decrease in expression, and it was predicted to be regulated by miR-693-3p. Neurod1 protein expression in the hippocampus was significantly lower in the DM+P group than the C group. Our results suggest that the combined exposure to periodontitis and DM was associated with AD-like pathological changes and identified the miR-693-3p/Neurod1 pair as a candidate regulatory axis. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2059-1381 12 1 2026 Potential effects of intradialytic exercise therapy on physical performance in hemodialysis patients based on the intervention period: a systematic review and meta-analysis 19 EN Daisuke Uchida Department of Internal Medicine, Teikyo University Hospital Mizonokuchi Yu Honda Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine Shigeki Kojima Kojima Kidney and Dialysis Clinic Hiromasa Miyake Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Masatoshi Nishimoto Department of Nephrology, Nara Medical University Akihito Hishikawa Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine Shun Tonomura Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine Tadashi Sofue Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University Naohiko Fujii Department of Nephrology, Hyogo Prefectural Nishinomiya Hospital Masakazu Saitoh Department of Physical Therapy, Faculty of Health Science, Juntendo University Ichiei Narita Niigata Institute for Health and Sports Medicine, Niigata Sports Association Kunihiro Yamagata Department of Nephrology, Institute of Medicine, University of Tsukuba Junichi Hoshino Division of Preventive and Sports Nephrology, Graduate School of Comprehensive Human Sciences, Tokyo Women’s Medical University Hiroo Kawarazaki Department of Internal Medicine, Teikyo University Hospital Mizonokuchi Tsutomu Sakurada Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine Background Intradialytic exercise during hemodialysis (HD) improves physical function and shows high adherence. In Japan, the 2018 guideline by the Japanese Society of Renal Rehabilitation supports intradialytic exercise, but medical insurance only covers the first 90 days. As new studies have emerged since the guideline was published, we conducted a systematic review and meta-analysis to evaluate the impact and optimal duration of exercise interventions beyond 12 weeks. Methods We followed a preregistered protocol (PROSPERO CRD42025642273) and PRISMA-P guidelines. Randomized controlled trials of adult patients undergoing HD performing structured exercise were identified via MEDLINE database (PubMed, March 2017–November 2024) and ICHUSHI-Web database. Two independent reviewers screened studies, extracted data, and assessed risk of bias using Cochrane RoB 2.0. Outcomes included peak oxygen uptake (VO2peak), maximal oxygen uptake (VO2max), 6 min walk distance, timed up and go (TUG) test, handgrip strength, sit-to-stand (STS) performance, and biochemical measures (hemoglobin, standard weekly urea Kt/V [std Kt/V]). Pooled mean differences (MD) with 95% confidence intervals (CI) were calculated using a mixed-effects model (Hartung–Knapp–Sidik–Jonkman method). Results A total of 71 studies, including 43 newly identified studies, were included. Risk of bias was moderate-to-high. Interventions > 12 weeks significantly improved 6 min walking distance (MD 52.4 m [95% CI 35.4–69.3], p < 0.01), VO2peak (MD 3.5 mL/kg/min [95% CI 1.96–5.04], p < 0.01), VO2max (MD 5.29 mL/kg/min [95% CI 2.36–8.22], p < 0.01), hemoglobin (MD 0.94 g/dL [95% CI 0.09–1.78], p = 0.03), and std Kt/V (MD 0.16 [95% CI 0.12–0.20], p < 0.01). TUG (MD −1.68 s [95% CI −2.96 to −0.41], p = 0.02), handgrip strength (MD 4.08 kg [95% CI 1.95–6.22], p < 0.01), and STS performance (MD −2.75 s [95% CI −4.45 to −1.05], p < 0.01) significantly improved in the integrated results of undefined study periods, with nonsignificant trends in studies of > 12 weeks of exercise. Conclusions Our findings suggest that exercise interventions lasting more than 12 weeks can enhance physical performance. Nevertheless, the applicability of these results to older patients remains uncertain, as most evidence is derived from middle-aged cohorts. Trial registration Registered in the PROSPERO database (CRD42025642273). No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-2615 16 15 2026 The Impact of Cold Storage and Seasonality on Raw Cow Milk Microbiota, Assessed by Conventional and Viability PCR 2302 EN Phong Dinh Tran Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takeshi Tsuruta Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Naoki Nishino Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The microbiota of healthy Holstein cow’s milk was analyzed to evaluate the effects of immediate (freezing at the farm: on-site workflow) and delayed processing (freezing after cool transport: laboratory workflow) and to investigate seasonal changes in September, November, and January. Propidium monoazide (PMA) was also used to distinguish between viable and non-viable cells. Microbiota composition differed between the laboratory and the on-site workflow. After cool transport, the abundances of Lactobacillus and Turicibacter increased, while those of Streptococcus, Bradyrhizobium, and Acinetobacter decreased. Based on the β-diversity assessment, the difference between viable and non-viable cells was marginal compared with the difference between on-site and laboratory workflows. In the subsequent on-site workflow experiment, seasonal variation was clearly demonstrated. The relative abundances of Lactobacillus, Turicibacter, and Bacillus were high in September; Staphylococcus, Phenylobacterium, and Bradyrhizobium in November; and Phyllobacterium in January. The seasonal effect was greater than the PMA treatment effect. Despite the study’s limitations, such as a limited number of milk samples and data from only one farm with a single management system, our findings indicate that storage and transport at low temperatures could lead to inaccurate assessments, particularly of opportunistic environmental microbiota. Viability PCR could help improve our understanding of the factors involved but would not substantially alter the raw milk microbiota. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 18 10 2026 Racial/Ethnic Disparities in Neoplasm-Related Mortality and the Social Determinants of Health 1572 EN Yoshito Nishimura Division of Hematology, Mayo Clinic Mariko Fujii Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nanami Sako Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Quynh Thi Vu Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ko Harada Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital, Urshila Durani Division of Hematology, Mayo Clinic Stephen M. Ansell Division of Hematology, Mayo Clinic James R. Cerhan Department of Quantitative Health Sciences, Mayo Clinic Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Racial/ethnic and regional disparities in neoplasm-related mortality remain a significant public health challenge. In this study, we aimed to evaluate long-term trends in county-level neoplasm-related mortality rates by race/ethnicity in the United States and examine associations with social determinants of health. Methods: We conducted a cross-sectional ecological study using population-based data from the Global Burden of Disease Study, including individuals residing in 50 states of the United States and the District of Columbia from 2000 to 2019. We analyzed age-standardized neoplasm-related mortality rates by ethnicity/race. Joinpoint regression analysis was used to identify significant changes in mortality trends, summarized as average annual percentage change. County-level correlations between mortality and key social determinants of health were also assessed. Results: Neoplasm-related mortality rates declined across all racial/ethnic groups from 2000 to 2019; however, disparities persisted. The age-standardized neoplasm-related mortality rates per 100,000 population decreased in all racial/ethnic subgroups. The average annual percentage change ranged from −0.94% (Hispanic and non-Hispanic American Indian or Alaska Native) to −1.90% (Black). Sex-specific analyses revealed similar trends. Southeastern states experienced slower declines than Northeastern states did. County-level smoking and poverty rates were positively correlated, whereas the primary care physician-to-population ratio, excessive alcohol consumption rate, mammography screening rate, and median household income were inversely correlated with neoplasm-related mortality rate, varying by race/ethnicity. Conclusions: Targeted, community-specific interventions are required to reduce inequities in cancer outcomes. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 15 13 2026 Changing Trends in Cardiovascular Disease Burden in North Africa and the Middle East, 1990–2023: A Joinpoint Analysis of GBD 2023 Data 4866 EN Hanane Ouddoud Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Judah Israel Ong Lescano Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Keith Pardillada Belangoy Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yoshito Nishimura Division of Hematology and Oncology, Mayo Clinic Ko Harada Division of Hematology and Oncology, Mayo Clinic Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Quynh Thi Vu Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Naohiro Iwata Department of Pharmacy, Okayama University Hospital Tatsuaki Takeda Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background/Objectives: Cardiovascular disease (CVD) burden decreased in the North Africa and Middle East (NAME) region between 1990 and 2019. This study used Global Burden of Disease (GBD) 2023 data to examine whether trends in mortality, disability-adjusted life years (DALYs), incidence, and prevalence continued through 2023 across all 21 NAME countries. Methods: We analysed age-standardised CVD mortality, incidence, prevalence, and DALY rates from 1990 to 2023. Joinpoint regression identified changes in temporal trends and calculated the annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals (CIs). Results: Age-standardised CVD mortality decreased from 579.6 per 100,000 in 1990 to 358.2 in 2023 (AAPC: −1.42%; 95% CI: −1.48 to −1.35). However, no significant reduction occurred between 2019 and 2023 (APC: −0.33%; 95% CI: −1.37 to 1.75). DALY, incidence, and prevalence rates followed similar patterns, with no significant decline in the final years of this study. Egypt was the only country with a long-term increase in CVD mortality, which accelerated after 2020 (APC: +5.20%; 95% CI: 1.20 to 12.87). High systolic blood pressure, dietary risks, lead exposure, and air pollution were the leading modifiable risk factors. Conclusions: The earlier decline in CVD burden in the NAME region did not clearly continue after 2019. The region is currently off track to meet Sustainable Development Goal 3.4 by 2030. Future progress may depend on improved blood pressure control, lipid management, dietary habits, and environmental risk reduction. No potential conflict of interest relevant to this article was reported.

American Society of Clinical Oncology (ASCO) Acta Medica Okayama 0732-183X 43 11 2025 Trastuzumab-Pertuzumab Plus Eribulin or Taxane as First-Line Chemotherapy for Human Epidermal Growth Factor 2–Positive Locally Advanced/Metastatic Breast Cancer: The Randomized Noninferiority Phase III EMERALD Trial 1302 1313 EN Toshinari Yamashita Department of Breast Surgery and Oncology, Kanagawa Cancer Center Shigehira Saji Department of Medical Oncology, Fukushima Medical University Toshimi Takano Department of Breast Medical Oncology, The Cancer Institute Hospital of JFCR Yoichi Naito Department of General Internal Medicine, National Cancer Center Hospital East Michiko Tsuneizumi Department of Breast Surgery, Shizuoka General Hospital Akiyo Yoshimura Department of Breast Oncology, Aichi Cancer Center Hospital Masato Takahashi Department of Breast Surgery, Hokkaido University Hospital Junji Tsurutani Advanced Cancer Translational Research Institute, Showa University Tsuguo Iwatani Breast and Endocrine Surgery, Okayama University Hospital Masahiro Kitada Department of Breast Disease Center, Asahikawa Medical University Hospital Hiroshi Tada Department of Surgery, Division of Breast and Endocrine Surgery, Tohoku University Hospital Natsuko Mori Department of Breast Surgery, Seirei Hamamatsu General Hospital Toru Higuchi Department of Breast Unit, Japanese Red Cross Saitama Hospital Tsutomu Iwasa Department of Medical Oncology, Kindai University Hospital Kazuhiro Araki Department of Breast Medical Oncology, Gunma Prefectural Cancer Center Kei Koizumi Department of Surgery 1, Division of Breast Surgery, Hamamatsu University School of Medicine Hiroki Hasegawa Medical HQs, Eisai Co, Ltd Yohei Uchida Medical HQs, Eisai Co, Ltd Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University Norikazu Masuda Department of Breast Surgery, Graduate School of Medicine, Kyoto University Purpose Trastuzumab-pertuzumab (HP) plus taxane is a current standard first-line therapy for recurrent or metastatic human epidermal growth factor 2 (HER2)+ breast cancer (BC). We investigated noninferiority of eribulin to a taxane when combined with dual HER2 blockade as first-line systemic treatment for locally advanced/metastatic HER2+ BC. Methods In the phase III EMERALD trial (target sample size, 480; ClinicalTrials.gov identifier: NCT03264547/UMIN000027938), patients were randomly assigned (1:1) to receive eribulin 1.4 mg/m2 once daily on days 1 and 8 (eribulin group) or a taxane (docetaxel 75 mg/m2 once on day 1 or paclitaxel 80 mg/m2 once daily on days 1, 8, and 15; taxane group) intravenously in a 21-day cycle, each with HP on day 1. The primary end point was progression-free survival (PFS; intention-to-treat population). Secondary end points included objective response rate, overall survival (OS), patient-reported quality of life (QoL), and safety. Noninferiority was tested using the stratified Cox proportional hazards model to estimate hazard ratios (HRs) for PFS events, with a noninferiority HR margin of 1.33. Results Between August 2017 and June 2021, 446 patients (median age, 56.0 years) were enrolled. The median PFS was 14.0 and 12.9 months in the eribulin group (n = 224) and taxane group (n = 222 [docetaxel/paclitaxel, n = 186/36]), respectively (HR, 0.95 [95% CI, 0.76 to 1.19]), which confirmed the noninferiority of the study regimen. The median OS was 65.3 months in the taxane group but has not been reached in the eribulin group. Median time to QoL deterioration was numerically longer with eribulin than with taxane. Adverse event (AE) rates were similar, despite the longer duration of eribulin use. Infusion reaction, skin-related AEs, diarrhea, and edema were more common with taxane, whereas neutropenia was more common with eribulin. Conclusion The results suggested that eribulin + HP is an option for first-line treatment of locally advanced/metastatic HER2+ BC. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2227-9032 12 12 2024 Toloese Generates Nitric Oxide through Natural Radiation of Far Infrared Rays, Reducing Serum Glucose, Cholesterol, and Triglycerides 1227 EN Min-Ho Yeo Department of Clinical Laboratory Science, Catholic University of Pusan Young-Hyeon Lee Department of Clinical Laboratory Science, Catholic University of Pusan Mi-Jin Ryu Department of Clinical Laboratory Science, Catholic University of Pusan Yong-Hak Choi SayM Co., Ltd. Hye-Sook Kim Division of International Infectious Diseases Control, Faculty of Pharmaceutical Sciences, Okayama University Kyung-Soo Chang Department of Clinical Laboratory Science, Catholic University of Pusan Toloese, a bed composition, is formulated with a combination of minerals of various wavelengths by utilizing a specific ratio and particle size. A maturation mixing technique is used without additional compression processes, resulting in the natural formation of numerous fine pores in the bed structure. At 40 °C, far infrared radiation in the range of 5–20 μm is emitted with a 0.916 radiant ratio, and the measured emitted radiant energy is 3.69 × 102 W/m2·μm. This study aimed to investigate the influence of far infrared radiation emitted from a Toloese bed on endogenous nitric oxide production. Clinical trials were conducted with 20 healthy adults aged 20 years. Blood samples were collected before and after Toloese bed usage for 1 h daily for 3 weeks. Nitric oxide levels in the saliva and blood of men and women significant increased after they used the Toloese bed for 1 h. Additionally, sweating sharply increased in the upper and lower body regions after Toloese bed usage. No hematological changes or adverse effects were observed, but blood glucose, cholesterol, and triglycerides decreased after Toloese bed usage compared with those before Toloese bed usage. These findings demonstrated that far infrared radiation emitted by the Toloese bed induced endogenous nitric oxide production and contributed to significant reductions in blood glucose, cholesterol, and triglyceride levels. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1648-9144 62 7 2026 Diabetes Burden in the Middle East and North Africa Region, 1990–2023: An Ecological Time-Trend Analysis of GBD Estimates 1352 EN Hanane Ouddoud Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Judah Israel Ong Lescano Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Keith Pardillada Belangoy Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yoshito Nishimura Division of Hematology and Oncology, Mayo Clinic Ko Harada Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Quynh Thi Vu Faculty of Pharmacy, Haiphong University of Medicine and Pharmacy Naohiro Iwata Department of Pharmacy, Okayama University Hospital Tsukasa Higashionna Department of Pharmacy, Okayama University Hospital Tatsuaki Takeda Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background and Objectives: The Middle East and North Africa (MENA) region has one of the highest age-standardized diabetes prevalence rates globally, yet all-age, diabetes-specific evidence incorporating GBD 2023 estimates through 2023 remains limited. Materials and Methods: Using Global Burden of Disease (GBD) 2023 estimates for 21 MENA countries from 1990 to 2023, this ecological time-trend analysis quantified 33-year trends in incidence, prevalence, mortality, and disability-adjusted life-years (DALYs); compared pre-2019 and post-2019 trajectories using joinpoint regression; characterized age- and sex-specific burden patterns; and quantified contributions of modifiable risk factors. Results: Age-standardized incidence increased 92%, from 251.7 (95% uncertainty interval [UI]: 231.5 to 272.4) to 482.5 (95% UI: 451.5 to 516.4) per 100,000, and prevalence more than doubled, from 5564 (95% UI: 5088 to 6024) to 11,247 (95% UI: 10,382 to 12,132) per 100,000. In 2023, males exhibited higher DALY rates than females in most adult age groups from age 15 years onward, shifting away from the female-predominant pattern seen in 1990; female rates remained higher at several of the oldest age groups. Children aged 0 to 14 years were the only group with declining DALY rates (−52% to −57%). Post-2019 incidence was higher in 15 of 21 countries, and six countries had higher DALY trends with non-overlapping confidence intervals. Because we only have four to five years of data, these short trends are preliminary and require care when evaluating. High body-mass index was the leading modifiable risk factor. Conclusions: These data support country-specific prevention and chronic-care strategies across the MENA region. No potential conflict of interest relevant to this article was reported.

S. Karger AG Acta Medica Okayama 2296-9403 10 1 2025 Efficacy and Safety of Three Janus Kinase Inhibitors in Ulcerative Colitis Patients over and under 65 Years of Age: A Real-World Comparative Analysis 180 186 EN Shintaro Akiyama Department of Gastroenterology, Institute of Medicine, University of Tsukuba Hiromichi Shimizu Department of Gastroenterology and Hepatology, Institute of Science Tokyo Akiko Tamura Department of Gastroenterology and Hepatology, Institute of Science Tokyo Kaoru Yokoyama Department of Gastroenterology, Kitasato University School of Medicine Toshiyuki Sakurai Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine Mariko Kobayashi Department of Gastroenterology, Institute of Medicine, University of Tsukuba Makoto Eizuka Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University Shunichi Yanai Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University Kei Nomura Department of Gastroenterology, Juntendo University School of Medicine Tomoyoshi Shibuya Department of Gastroenterology, Juntendo University School of Medicine Masahiro Takahara Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Minako Sako Center for Inflammatory Bowel Disease, Tokyo Yamate Medical Center, Japan Community Healthcare Organization Atsushi Yoshida Center for Gastroenterology and Inflammatory Bowel Disease, Ofuna Chuo Hospital Kozo Tsuruta Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine Shinichiro Yoshioka Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine Miki Koroku Institute of Gastroenterology, Tokyo Women’s Medical University Teppei Omori Institute of Gastroenterology, Tokyo Women’s Medical University Masayuki Saruta Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine Takayuki Matsumoto Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University Ryuichi Okamoto Department of Gastroenterology and Hepatology, Institute of Science Tokyo Kiichiro Tsuchiya Department of Gastroenterology, Institute of Medicine, University of Tsukuba Toshimitsu Fujii Department of Gastroenterology and Hepatology, Institute of Science Tokyo Introduction: It remains unclear whether Janus kinase (JAK) inhibitors differ in efficacy and safety between elderly and non-elderly patients with ulcerative colitis. Methods: We retrospectively compared outcomes between patients who started a JAK inhibitor at ≥65 years (elderly group) and those <65 years (non-elderly group). Results: Among 228, 215, and 159 patients treated with upadacitinib, filgotinib, and tofacitinib, we identified 14, 36, and 13 elderly patients, respectively. There were no significant differences in efficacy between elderly and non-elderly patients for any of the three JAK inhibitors. The elderly group had a 3-fold higher risk of herpes zoster infection with upadacitinib or tofacitinib compared to the non-elderly group, whereas the risk with filgotinib was less than 3% in both groups. The non-elderly group had a 3-fold higher risk of acne with upadacitinib. Conclusion: Adverse event risks with JAK inhibitors should be considered by age. Given the limitations of this study, including its retrospective design and small sample size, further studies with larger sample sizes are needed to validate our findings. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1439-7595 36 1 2025 Vaccination in paediatric, adolescent, and transitional-age rheumatic diseases: a systematic review 97 112 EN Takuma Ohnishi Department of Pediatrics, Keio University School of Medicine Hiroyuki Wakiguchi Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine Shingo Ishimori Department of Pediatrics, Kobe University Graduate School of Medicine Naohiro Itoh Faculty of Medical Sciences, Department of Pediatrics, University of Fukui Masato Yashiro Department of Pediatrics, Okayama University Hospital Susumu Yamazaki Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine Ikuo Okafuji Department of Pediatrics, Kobe City Medical Center General Hospital Yoshiyuki Ohtomo Department of Pediatrics, Juntendo University Nerima Hospital Ichiro Kobayashi Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center Objectives: This systematic review evaluated the efficacy and safety of vaccination in patients with paediatric, adolescent, and transitional-age rheumatic diseases as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. Methods: An independent investigator systematically searched PubMed to identify relevant studies published by September 2022. The search results were divided into vaccines or toxoids for diphtheria, pertussis, tetanus, pneumococcus, influenza virus, hepatitis A virus, hepatitis B virus, human papillomavirus, poliovirus, measles virus, mumps virus, rubella virus, varicella zoster virus, and tuberculosis. Results: A meta-analysis was not feasible due to the lack of randomized controlled trials with standardized patient backgrounds and conditions. Non-live vaccines are generally immunogenic and safe for patients with rheumatic diseases. In contrast, live attenuated vaccines should usually be withheld in patients on immunosuppressants, corticosteroids, biologics, or Janus kinase inhibitors. However, for necessary immunizations against measles, rubella, mumps, or varicella, live attenuated vaccines may be considered for patients receiving low-dose corticosteroids, methotrexate, or tumour necrosis factor inhibitors. Conclusions This review highlights the significant gap in evidence for paediatric populations compared with adults, particularly concerning new biological therapies and Janus kinase inhibitors. Further evidence is needed regarding vaccination in paediatric patients with rheumatic diseases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 Spinous Process Plate Fixation Alone for an AO Spine Osteoporotic Fracture (OF) 5 Diffuse Idiopathic Skeletal Hyperostosis (DISH)-Associated Thoracolumbar Fracture in a Nonagenarian 259 264 EN Satoru Yabuno Department of Neurosurgery, Kagawa Rosai Hospital Masatoshi Yunoki Department of Neurosurgery, Kagawa Rosai Hospital Saori Takeuchi Department of Neurosurgery, Kagawa Rosai Hospital Koji Hirashita Department of Neurosurgery, Kagawa Rosai Hospital Case Report 10.18926/AMO/71070 Diffuse idiopathic skeletal hyperostosis (DISH) predisposes the spine to highly unstable fractures because of long lever-arm biomechanics. Unstable injuries, including AO Spine Osteoporotic Fracture (OF) type 5, are typically treated with long-segment posterior instrumentation; however, pedicle-screw fixation may be infeasible in very elderly patients with severe osteoporosis, critically narrow pedicles, and/or significant comorbidities. A 93-year-old Japanese woman presented with severe back pain without apparent trauma. Computed tomography (CT) revealed a T12 fracture with DISH, classified as OF5. The pedicles were critically narrow (3.7-4.1 mm), and dual-energy X-ray absorptiometry confirmed severe osteoporosis. Because conventional pedicle-screw fixation was considered technically unsafe and excessively invasive, limited posterior stabilization was performed using a single spinous process plate spanning T10-L1. The operative time was 48 min and the estimated blood loss was 10 ml. Immediate postoperative CT confirmed appropriate implant positioning and maintained alignment. At the 1-year follow-up, CT demonstrated solid bony union with preserved alignment and no implant failure; the patient had remained pain-free and ambulatory. This case demonstrates that spinous process-plate fixation can be a minimally invasive salvage option for carefully selected very-elderly patients with DISH when pedicle-screw instrumentation is not feasible. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 Video-Assisted Thoracoscopic Resection of an Upper Mediastinal Ectopic Parathyroid Adenoma 241 246 EN Yuta Hasegawa Department of Surgery, National Defense Medical College Hospital Hironori Tsujimoto Department of Surgery, National Defense Medical College Hospital Naoyuki Uehata Department of Surgery, National Defense Medical College Hospital Risa Kariya Department of Surgery, National Defense Medical College Hospital Asuma Ide Department of Surgery, National Defense Medical College Hospital Takafumi Suzuki Department of Surgery, National Defense Medical College Hospital Seiichiro Fujishima Department of Surgery, National Defense Medical College Hospital Keita Kouzu Department of Surgery, National Defense Medical College Hospital Yoshihisa Yaguchi Department of Surgery, National Defense Medical College Hospital Kosuke Miyai Department of Laboratory Medicine, National Defense Medical College Hospital Ayumu Kurihara Department of Laboratory Medicine, National Defense Medical College Hospital Sho Ogata Department of Laboratory Medicine, National Defense Medical College Hospital Susumu Matsukuma Department of Laboratory Medicine, National Defense Medical College Hospital Hideki Ueno Department of Surgery, National Defense Medical College Hospital Case Report 10.18926/AMO/71067 Primary hyperparathyroidism (pHPT) is typically caused by a parathyroid adenoma, although some cases arise from ectopic glands. Accurate preoperative localization is essential for guiding surgical strategy, particularly for mediastinal lesions. We report successful video-assisted thoracoscopic surgery (VATS) for an upper mediastinal parathyroid adenoma. A 68-year-old woman was referred for hypercalcemia during evaluation for recurrent ureteral stones. Laboratory tests revealed elevated serum calcium (13.2 mg/dl) and intact parathyroid hormone (iPTH) levels (266 pg/ml). Contrast-enhanced computed tomography, magnetic resonance imaging, and 99mTc-methoxyisobutylisonitrile scintigraphy identified a 20-mm mass adjacent to the right esophageal wall. VATS was performed due to the tumor’s mediastinal location. The lesion was resected with intraoperative nerve monitoring (IONM) to avoid recurrent laryngeal nerve damage. Postoperatively, iPTH and calcium levels rapidly normalized. Transient hypocalcemia and mild hoarseness occurred but resolved with calcium supplementation and conservative management. Pathological examination confirmed a parathyroid adenoma without malignancy. VATS offers a safe and minimally invasive approach for upper mediastinal parathyroid adenomas. IONM and vigilant calcium management are crucial for minimizing these complications. This case highlights the importance of comprehensive imaging, surgical planning, and postoperative care in managing upper mediastinal pHPT. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 Regional Prevalence of Carbapenemase-Producing Enterobacterales and Extended-Spectrum Beta-Lactamase-Producing Enterobacterales in Okayama and Neighboring Prefectures, Japan 233 240 EN Sakura Ogawa Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidemasa Akazawa Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sachie Namba Department of Laboratory Testing, Okayama Medical Laboratory Center Chiyoko Hirota Department of Laboratory Testing, Okayama Medical Laboratory Center Tomoyoshi Kishiue Department of Laboratory Testing, Okayama Medical Laboratory Center Shohei Ibara Department of Laboratory Testing, Okayama Medical Laboratory Center Takayuki Kondo Department of Laboratory Testing, Okayama Medical Laboratory Center Genshi Fukuda Department of Sales Promotion, Okayama Medical Laboratory Center Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/71066 Carbapenemase-producing Enterobacterales (CPE) and extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-E) are representative antimicrobial-resistant pathogens. We investigated the prevalence of CPE and ESBL-E in Okayama, Japan to clarify their current epidemiology and potential clinical burden. Active surveillance for CPE and ESBL-E was performed first, using stool samples submitted to the Okayama Medical Laboratory (Japan) in the years 2024-2025. Screening was performed using a selective agar (CHROMagar mSuper CARBA/ESBL). Phenotypic identification was conducted with the use of a modified carbapenem inactivation method and double-disk phenotypic confirmatory tests. Clinical information including patient age, sex, sampling date, and hospital address were collected, and the data were analyzed according to specimen origin (hospitals, clinics, and health checkups). A total of 2,000 stool samples were screened, of which two CPE isolates (0.1%) and 285 ESBL-E isolates (14.3%) were identified. By specimen origin, the ESBL-E positivity rate was significantly higher in hospitals (17.4%) than in clinics (11.8%). By age category, the late elderly (> 75 years) exhibited the highest ESBL-E positivity rate (22.6%) compared to other age groups. In the clinics and health checkups, infants (0 years) demonstrated high ESBL-E positivity rates (18.2% and 14.3%, respectively). Escherichia coli was the most common ESBL-E organism in the hospitals (77.2%), clinics (88.8%), and health checkups (87.5%). Our active screening demonstrated that the prevalences of CPE and ESBL-E were within the reported ranges; however, in this era of increasing internationalization, continuous surveillance of these notifiable pathogens is warranted. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 8 2026 Incidence and Time to Onset of Pseudophakic Cystoid Macular Edema (Irvine-Gass Syndrome) After 1,325 Consecutive Cataract Surgeries Performed by a Single Surgeon Over Four Years e114802 EN Toshihiko Matsuo Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems Chie Nakago-Matsuo Orthodontics, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Objectives Macular edema after cataract surgery is known as pseudophakic cystoid macular edema or Irvine-Gass syndrome. The aim of this study was to determine the incidence and time to onset of cystoid macular edema after uncomplicated cataract surgery. Methods A retrospective review was conducted of 1,325 consecutive cataract surgeries performed by a single surgeon at a single institution over four years, from January 2022 to December 2025. Results Among 1,325 eyes, one or more macular cysts were detected by optical coherence tomography in 27 eyes (2.0%) of 22 patients who complained of blurred vision or decreased visual acuity after having no symptoms immediately after surgery. The 22 patients (27 eyes: 12 right and 15 left) comprised 12 men and 10 women. Their ages at the time of surgery ranged from 57 to 82 years, with a median of 75.5 years. Of the 27 eyes that developed macular cysts, 13 eyes with no preoperative or intraoperative risk factors for inflammation received topical 0.1% bromfenac twice daily as the only postoperative anti-inflammatory treatment, together with topical antibacterial 0.5% moxifloxacin four times daily. In contrast, the remaining 14 eyes, which had risk factors for inflammation, such as exfoliation, floppy iris, poor mydriasis, extracapsular cataract extraction, or diabetes mellitus, received topical bromfenac twice daily and 0.1% betamethasone (or 0.1% fluorometholone in two eyes) four times daily, as well as topical moxifloxacin. The time from surgery to the diagnosis of macular cysts ranged from one week to eight months, with a median of two weeks, in the 13 eyes treated with topical bromfenac only. In the 14 eyes treated with the combination of topical bromfenac and betamethasone, the time to diagnosis ranged from two weeks to 13 months, with a median of two months. In 26 of the 27 eyes, the macular cysts disappeared and visual acuity returned to normal without residual symptoms within two weeks to seven months, with a median of one month, after topical betamethasone four times daily was initiated or resumed. Conclusions Pseudophakic macular cysts developed during the postoperative course in eyes with no preoperative or intraoperative risk factors that received topical bromfenac alone. They also developed later in the postoperative course after the combination of topical bromfenac and betamethasone was discontinued in eyes with risk factors for inflammation. The macular cysts disappeared following the initiation or resumption of topical betamethasone, accompanied by recovery of visual acuity and resolution of symptoms. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1433-8726 44 1 2026 Preoperative membranous urethral length predicts quality-of-life recovery and urinary incontinence after holmium enucleation of the prostate 552 EN Naoya Nagasaki Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takuya Sadahira Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ichiro Tsuboi Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomofumi Watanabe Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shin Kanemoto Department of Urology, Kochi Health Sciences Center Yusuke Tominaga Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoshi Katayama Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shingo Nishimura Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kensuke Bekku Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masami Watanabe Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toyohiko Watanabe Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Motoo Araki Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Purpose Holmium laser enucleation of the prostate (HoLEP) relieves bladder outlet obstruction, but postoperative quality-of-life (QOL) recovery and stress urinary incontinence (SUI) differ among patients. We evaluated whether preoperative membranous urethral length (MUL) on MRI predicts QOL recovery and SUI after HoLEP, independent of clinical and surgical factors. Methods This single-center retrospective study included 135 patients with preoperative MRI. MUL was measured on sagittal T2-weighted images. The primary outcome was 6-month International Prostate Symptom Score (IPSS) -QOL ≤ 1. SUI was defined as the use of ≥1 pad per day at 6 months. IPSS-QOL changes were analyzed with generalized estimating equations. For 6-month QOL recovery and SUI, logistic regression was adjusted for age, enucleated weight, prostate volume, baseline QOL, and surgeon. We evaluated thickness of posterior wall of membranous urethral sphincter (TPWMUS), membranous urethral volume (MUV), and a short-MUL/thin-TPWMUS phenotype. Results The 6-month IPSS-QOL ≤ 1 rate was 40.0%; SUI occurred in 19/135 patients (14.1%). Longer MUL was linked to better QOL recovery at every time point (p ≤ 0.015) and independently predicted both 6-month QOL recovery (adjusted odds ratio [aOR] 1.35, 95% CI 1.14–1.61) and lower SUI risk (odds ratio [OR] 0.76, 0.61–0.93), remaining significant after adjustment. Adding MUL improved prediction (AUC for SUI 0.588→0.704; for QOL 0.716→0.760). Across MUL tertiles, QOL recovery rose from 13.9% to 56.1% ,and SUI fell from 20.0% to 2.2%. Short MUL/thin-TPWMUS showed higher SUI and poorer QOL recovery. Conclusions Preoperative MUL on MRI independently predicted QOL recovery and continence after HoLEP. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0919-8172 33 8 2026 Burden of Lower Urinary Tract and Genital Symptoms in Young Transgender Men: Prevalence and Impact on Daily Life e70553 EN Tomoko Kobayashi Department of Urology, Okayama University Hospital Takatoshi Moriwake Department of Urology, Okayama University Hospital Yusuke Tominaga Department of Urology, Okayama University Hospital Nariaki Ozaki Department of Urology, Okayama University Hospital Satoshi Horii Department of Urology, Okayama University Hospital Ichiro Tsuboi Department of Urology, Okayama University Hospital Kasumi Yoshinaga Department of Urology, Okayama University Hospital Tomoaki Yamanoi Department of Urology, Okayama University Hospital Tatsushi Kawada Department of Urology, Okayama University Hospital Takuya Sadahira Center for Innovative Clinical Medicine, Okayama University Hospital Takehiro Iwata Department of Urology, Okayama University Hospital Satoshi Katayama Department of Urology, Okayama University Hospital Shingo Nishimura Department of Urology, Okayama University Hospital Kensuke Bekku Department of Urology, Okayama University Hospital Yuko Matsumoto Miyakekai Good-Life Hospital Miyabi Inoue Miyabi Urogyne Clinic Okayama Japan Masami Watanabe Center for Innovative Clinical Medicine, Okayama University Hospital Ayano Ishii Department of Urology, Okayama University Hospital Toyohiko Watanabe Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Motoo Araki Department of Urology, Okayama University Hospital Objectives: To investigate the prevalence of lower urinary tract symptoms (LUTS) and genital symptoms among transgender men in Japan, and to evaluate their impact on daily life, including limitations resulting from concerns about toilet accessibility. Methods: We conducted a cross-sectional, single-center survey of assigned-female-at-birth individuals aged 16 years or older who had been approved for gender-affirming hormone therapy at our gender center. A self-administered questionnaire included the Core Lower Urinary Tract Symptom Score (CLSS), vaginal and urethral symptom items, toilet use outside the home, preferences regarding male urinals, and activity restriction related to toilet access. Data were analyzed descriptively, and multivariable logistic regression analyses were performed. Results: Data from 322 participants (median age 33 years) were analyzed. Overall, 80% reported at least one LUTS, 46% reported at least one bothersome symptom, and 14% had a CLSS global quality-of-life (QOL) score of ≥ 4. Vaginal symptoms occurred in 13% of participants, and 2% reported post-micturition leakage. Most participants (62%) did not use male urinals but wished to use them. Activity restriction due to toilet-related concerns, defined as avoiding or limiting activities such as travel, shopping, or going to the cinema, was reported by 20%, and higher total CLSS was associated with both activity restriction and poor urinary-related QOL. Conclusions: LUTS and genital symptoms are common in young transgender men, and greater LUTS burden is linked to urinary-related QOL impairment and toilet-related activity restriction. These findings highlight the need for targeted clinical care and improved accessibility of public toilets for transgender men. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2304-6767 14 8 2026 Oral Supplementation of Bacillus subtilis Attenuated Alveolar Bone Loss in a Mouse Model of Ligature-Induced Periodontitis 494 EN Yixuan Zhang Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Naoki Toyama Dental School, Okayama University Mohammad Nurhamim Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Momoko Nakahara Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daiki Fukuhara Dental School, Okayama University Takayuki Maruyama Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Ekuni Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: This study aimed to investigate the effects of oral Bacillus subtilis (BS) on alveolar bone loss, intestinal morphology, and gut microbiota in a mouse model of ligature-induced periodontitis. Methods: A total of 24 male C57BL/6J mice (6 weeks old) were allocated to control, periodontitis (P), BS, and BS+P groups. Periodontitis was induced by bilateral ligation of maxillary second molars, and BS was orally administered for 18 consecutive days. Gut microbiota composition was analyzed by 16S rDNA sequencing, alveolar bone loss and gut morphology were evaluated using ImageJ version 1.54g, and ELISA-detectable serum vitamin D metabolite concentrations were measured using an enzyme-linked immunosorbent assay. Results: Compared with the P group, the BS+P group showed reduced bone loss. Serum vitamin D metabolite concentrations, small-intestine villus height, and villus height-to-crypt depth ratios were higher in the BS+P group. In gut microbiota, alpha diversity differed significantly among groups based on the Shannon index. Bray–Curtis-based beta diversity differed significantly among groups. Conclusions: Oral supplementation of BS attenuated the progression of ligature-induced periodontitis in a mouse model, and changes in gut microbiota may be associated with this effect. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2352-5789 66 2026 Pembrolizumab-based systemic therapy associated with opportunities for subsequent local treatment in advanced or recurrent neuroendocrine carcinoma of the cervix: a five-case series 102156 EN Naoyuki Ida Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoji Nagao Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Tanaka Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Fujikawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Momoko Tanioka Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoko Imatani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Tani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hanako Sugihara Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirofumi Matsuoka Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Okamoto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Haraga Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Neuroendocrine carcinoma (NEC) of the cervix is a rare, highly aggressive malignancy with limited evidence supporting immune checkpoint blockade. We evaluated the clinical activity of pembrolizumab-based therapy in patients with advanced or recurrent cervical NEC. Methods: We retrospectively reviewed five consecutive patients with advanced or recurrent cervical NEC treated with pembrolizumab-based therapy at Okayama University Hospital between November 2022 and April 2025. Clinical characteristics, radiologic responses, molecular profiles, adverse events, local treatments, and survival outcomes were analyzed. Results: The median age was 52 years. Three patients had newly diagnosed stage IVB disease, and two had recurrent metastatic disease after radical surgery and postoperative irinotecan plus cisplatin chemotherapy. All patients received paclitaxel plus carboplatin with pembrolizumab. An objective response was observed in all patients, including one complete response and four partial responses according to RECIST version 1.1. The median maximum tumor shrinkage was 78.5%, and median progression-free survival was 10.0 months. Comprehensive genomic profiling in four patients showed microsatellite-stable tumors with low tumor mutational burden in all evaluated cases. HPV association was supported by HPV16/18 sequences in three patients and diffuse p16 expression in one additional patient. Immune-related adverse events were grade 2 or lower. In three patients, systemic disease control allowed subsequent local treatment, including radiotherapy, conversion surgery, and stereotactic radiotherapy. Conclusion: Pembrolizumab-based therapy showed encouraging clinical activity despite microsatellite-stable status and low tumor mutational burden in evaluated cases. Sustained systemic disease control may provide an opportunity for multimodal treatment incorporating subsequent local treatment. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 18 5 2026 The New Era of Intraperitoneal Carboplatin in Ovarian Cancer: From Biological Rationale to Clinical Implementation 764 EN Shoji Nagao Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Fujikawa Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yui Tanaka Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Momoko Tanioka Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryoko Imatani Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Tani Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hanako Sugihara Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Okamoto Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirofumi Matsuoka Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoyuki Ida Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junko Haraga Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikako Ogawa Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hisashi Masuyama Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Epithelial ovarian cancer is predominantly characterized by peritoneal dissemination, providing a strong biological rationale for intraperitoneal (IP) chemotherapy. Although IP cisplatin-based regimens have demonstrated substantial survival benefits in pivotal randomized trials, toxicity and catheter-related complications limit their widespread adoption. IP carboplatin has emerged as a pragmatic alternative with improved tolerability while preserving its pharmacokinetic advantages. This review summarizes the biological and pharmacological rationale for IP carboplatin and critically examines the clinical evidence, with a particular emphasis on the Intraperitoneal Carboplatin for Ovarian Cancer (iPocc) trial and its divergence from Gynecologic Oncology Group (GOG)-252. We further discuss the potential applicability of IP carboplatin beyond the traditional setting of minimal residual disease, including patients undergoing neoadjuvant chemotherapy and interval debulking surgery, as well as its possible use in the contemporary era of maintenance therapy. Collectively, the accumulated evidence supports renewed consideration of IP carboplatin as a versatile component in modern ovarian cancer management. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 5 2025 Influence of Wearing Corsets During Radiation Therapy in Patients With Thoracic or Lumbar Spinal Bone Metastases e84093 EN Yoshite Akezaki Division of Physical Therapy, Kochi Professional University of Rehabilitation Eiji Nakata Department of Orthopedic Surgery, Okayama University Hospital Masato Kikuuchi Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Yoshimi Katayama Department of Rehabilitation Medicine, Okayama University Hospital Haruyoshi Katayama Department of Orthopedic Surgery, Okayama University Hospital Takuto Itano Department of Orthopedic Surgery, Okayama University Hospital Masanori Hamada Department of Rehabilitation Medicine, Okayama University Hospital Shinsuke Sugihara Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Background This study aimed to examine the influence of wearing a corset with radiation therapy (RT) on pain, activities of daily living (ADL), and quality of life (QoL) in patients with thoracic or lumbar spinal bone metastases one month after RT. Methodology Fifty-two patients (24 males and 28 females) with thoracic or lumbar spinal bone metastases whose measurements were recorded at our institute between July 2012 and December 2016 were included in this study. Age, sex, ADL, pain, spinal instability, and QoL were investigated in our analyses. Patients were divided into stable (0-6 points) and unstable (7-18 points) groups based on their spinal instability neoplastic score. Patients in the stable and unstable groups performed early mobilization depending on their condition. The unstable group wore corsets. The corsets were soft and were worn for three months from the start of RT. Results The unstable group showed significant improvements in ADL and QoL and a significant reduction in pain one month after RT (P < 0.05). The stable group showed a significant improvement in QoL one month after RT (P < 0.05). Conclusions Corsets were effective for enabling early movement without lowering QoL in patients with spinal instability of thoracic or lumbar bone metastases. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 16 11 2024 Accuracy of Cup Alignment in Total Hip Arthroplasty: A Comparison Between Portable Navigation and Goniometer e74176 EN Tomonori Tetsunaga Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoko Tetsunaga Department of Orthopaedic Surgery, Okayama University Hospital Kazuki Yamada Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Koura Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Inoue Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichiro Okuda Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasutaka Masada Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sho Muguruma Department of Orthopaedics, Okayama Medical Center Yuki Okazaki Department of Orthopaedics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Navigation systems, including portable navigation systems, used for total hip arthroplasty (THA) are useful for achieving higher cup alignment accuracy. NAVBIT, a newly available portable navigation system, uses a unique registration method, the table tilt registration. However, its accuracy is unclear. This retrospective study aimed to investigate whether THA with a portable navigation system in the lateral position with the flip technique is more accurate than THA with a cup goniometer in the supine or lateral positions. Methodology This study included 96 consecutive patients (77 women, 19 men) who underwent primary cementless THA using either a portable navigation system in the lateral position with the flip technique or a cup goniometer in the supine or lateral positions. The average age of the patients was 66.8 years (range = 29-91) and the average body mass index was 24.6 kg/m2 (range = 17.5-39.9). The accuracy of cup orientation was compared among the three groups. Results The absolute values of the difference in cup inclination and anteversion with the NAVBIT (2.1 ± 1.7°, 2.0 ± 1.4°) were smaller than that with the cup goniometer in the supine (3.4 ± 2.4°, 3.4 ± 2.2°) and lateral decubitus positions (3.4 ± 2.5°, 5.0 ± 3.5°). Overall, 91%, 64.5%, and 56.3% were within 5° of the target angles in the navigation, supine goniometer, and lateral goniometer groups, respectively. Conclusions The accuracy of cup alignment with the portable navigation system using the flip technique was significantly higher than that with the cup goniometer in the supine and lateral decubitus positions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1936-0568 20 1 2026 Early-Stage Oral Squamous Cell Carcinoma in Adolescents and Young Adults Compared with Older Patients Exhibits Distinct Clinicopathological Features 88 EN Sawako Ono Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsutoshi Hirose Department of Oral and Maxillofacial Pathology, Osaka University Graduate School of Dentistry Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuya Abe Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Shintaro Sukegawa Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Masanori Masui Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chihoko Ikeda Department of Oral Pathology, Osaka Dental University Madoka Isomura Department of Diagnostic Pathology, School of Medicine, Fujita Health University Yuri Tachibana Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Faculty of Medicine Junya Ono Department of Pathology, The Nippon Dental University School of Life Dentistry at Niigata Katsumitsu Shimada Department of Clinical Pathophysiology, School of Dentistry, Matsumoto Dental University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetaka Yamamoto Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose This study aimed to compare the clinicopathological features of stage I–II oral squamous cell carcinoma (OSCC) between adolescents and young adults (AYAs) and older patients, and to identify prognostic factors in AYA OSCC. Methods Forty-eight AYA patients aged 15–39 years and 69 older patients aged ≥ 65 years with surgically treated stage I–II OSCC were retrospectively analyzed. Histological evaluation, survival analysis, immunohistochemistry for p53, p16, and MTAP, high-risk HPV RNA in situ hybridization, and fluorescence in situ hybridization for CDKN2A and MTAP were performed. Results Compared with older patients, OSCCs in AYAs were more frequently located on the tongue (93.7% vs. 47.8%) and more often exhibited a superficial spreading growth pattern (60.4% vs. 31.8%). AYA tumors more frequently showed modified WPOI-1, high tumor budding, and abnormal p53 immunophenotypes (85.4% vs. 68.1%). AYA patients showed significantly better overall and disease-free survival than older patients. Within the AYA group, depth of invasion (DOI) > 5 mm was associated with distant metastasis and poorer overall and disease-free survival. Postoperative lymph node metastasis occurred in 31.2% of AYAs. Univariable analysis suggested that clinical stage II, tumor thickness > 5 mm, DOI > 5 mm, and tumor budding scores 1–2 were associated with postoperative lymph node metastasis. Molecular status, including p53, p16/CDKN2A, and MTAP, did not provide robust prognostic stratification. Conclusion Early-stage AYA OSCC exhibits distinct clinicopathological features. DOI was the strongest prognostic indicator, whereas clinical stage, tumor thickness, and tumor budding may provide additional prognostic information regarding the risk of late nodal metastasis. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0305-1846 52 4 2026 Frontotemporal Lobar Degeneration‐TDP Type C With Striatal Glial Cytoplasmic Inclusions and Motor Neuron Degeneration e70090 EN Akiko Uchino Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Kazutomi Kanemaru Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Airi Tarutani Department of Clinical Medical Sciences, Tokyo Metropolitan Institute of Medical Science Masato Hasegawa Department of Clinical Medical Sciences, Tokyo Metropolitan Institute of Medical Science Hiroya Naruse Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shigeo Murayama Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Yuko Saito Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-2607 14 7 2026 Upregulation of the Outer Membrane Protein OmpV and Its Role in Polymyxin B Stress Adaptation in Vibrio mimicus 1527 EN Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuta Onodera Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunki Annoi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Basilua Andre Muzembo Research Center for Intestinal Health Science, Okayama University Daisuke Imamura Research Institute of Nursing Care for People and Community, University of Hyogo OmpV is an outer membrane protein found in a variety of Gram-negative bacteria. In this study, we demonstrated that V. mimicus strain CS-66, isolated from a patient with diarrhea, was resistant to polymyxin B (PL-B) and colistin (CL) but susceptible to chloramphenicol and ciprofloxacin. When strain CS-66 was cultured in Luria–Bertani broth containing a sub-minimal inhibitory concentration of each antibiotic used for the susceptibility tests, ompV expression as assayed by reverse transcription-qPCR, significantly increased regardless of the antibiotic tested. In contrast, cell aggregation during the early log phase was observed only when the strain was grown in the broth supplemented with PL-B or CL. A space-filling model of V. mimicus OmpV was generated. The model showed that, although OmpV adopted a β-barrel conformation, it had closed top and bottom ends and possessed a lateral cavity. Structural analysis further indicated that the interior of this lateral cavity was negatively charged and sufficiently large to accommodate PL-B. These results suggest that V. mimicus may adapt to PL-B stress through physical sequestration within the negatively charged cavity of OmpV. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0916-9636 49 7 2026 Effect of population-approach programs promoting salt reduction and potassium intake in Japan: the Population-based Sodium/Potassium Improvement Program (PoSPIP) 1992 2003 EN Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Minako Kinuta Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayoshi Ohkubo Department of Hygiene and Public Health, Teikyo University School of Medicine Takuya Tsuchihashi Cardiovascular Center, Steel Memorial Yawata Hospital Katsushi Yoshita Department of Public Health, Nutrition, School of Human Life and Ecology, Osaka Metropolitan University Yukari Takemi Faculty of Nutrition, Kagawa Nutrition University Hitomi Hayabuchi Graduate School of Health and Environmental Sciences, Fukuoka Women’s University Yukiko Okami Gunma University Center for Food Science and Wellness Kaori Kitaoka NCD Epidemiology Research Center, Shiga University of Medical Science Keiko Sakaguchi Faculty of Nursing and Nutrition, Shukutoku University Atsushi Hozawa Division of Epidemiology, School of Public Health, Tohoku University Graduate School of Medicine Tomonori Okamura Department of Preventive Medicine and Public Health, Keio University School of Medicine Hiroshi Itoh Japanese Society of Hypertension Hiromi Rakugi Japanese Society of Hypertension Koichi Node Japanese Society of Hypertension Katsuyuki Miura NCD Epidemiology Research Center, Shiga University of Medical Science Reducing sodium intake in populations is essential, but insufficient for preventing and managing high blood pressure, while the importance of increasing potassium intake is overlooked. We investigated the effects of 1-year population-approach programs (2021–2022) promoting salt reduction and potassium intake using urinalysis feedback and food environment improvement. This retrospective observational study included 7649 participants (mean age, 54.0 years; 45.3% women) from 11 municipalities and 4 workplaces. Outcomes in intensive support programs—including urinary sodium, potassium, and sodium-to-potassium (Na/K) ratio measurements with feedback, dietary promotion, and food environment improvement—were compared with standard support programs providing usual health guidance. In linear regression adjusted for demographics, lifestyle factors, and medical history, the reduction in urinary Na/K ratio was greater in the intensive support group (n = 4064) than in the standard support group (n = 3585) (mean difference −0.14 [95% confidence interval, −0.27 to −0.01]). Although estimated potassium intake decreased in both groups, the decline was smaller in the intensive support group (mean difference 31 [12 to 51] mg/day). Estimated salt intake did not differ between the groups. The intensive support group showed greater increases in diastolic blood pressure and high-density lipoprotein cholesterol and smaller increases in blood glucose, as well as greater reductions in hemoglobin A1c and Salt Check Sheet scores. Mean differences between the groups for endpoints were not heterogeneous across intensive support program types. Our findings support the development of hypertension prevention and management strategies that promote healthier dietary behaviors and can be implemented in community and workplace settings, with broad public health applicability. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0721-832X 2026 Dissociation between globe shape-induced rectus muscle pulley displacement and abduction limitation in patients aged 40 years and older with high myopic strabismus EN Reika Kono Department of Ophthalmology, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences Ichiro Hamasaki Lino Eye Clinic Fumiko Kishimoto Division of Ophthalmology, Ibara City Hospital Kiyo Shibata Lino Eye Clinic Shin Morisawa Department of Ophthalmology, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences Purpose We hypothesized that high myopia (HM)-induced globe deformation displaces rectus muscle (RM) pulleys, contributing to mild ocular motility restriction. This study investigated the effects of globe shape on RM pulley positions in older Japanese patients with acquired strabismus (AS) and mild motility restriction—defined as the ability to abduct both eyes beyond the midline. Methods In this retrospective case series, 28 patients (mean age ± standard deviation: 61.2 ± 9.0 years) with adult-onset AS were included: 6 patients with (LAB group) and 22 patients without abduction limitation (NLAB group). In each subject, the eye with the longer axial length (AL ≥ 26 mm), measured using an AL measurement apparatus, was analyzed using magnetic resonance imaging (MRI). RM pulley positions relative to the globe center and equatorial diameter (ED) were measured; the ED-to-AL ratio (EAR) was calculated. We compared these parameters between groups and analyzed correlations of globe-shape factors (EAR, AL, and ED) with pulley positions and age. Results No significant differences in EAR, AL, ED, or pulley positions were detected between LAB and NLAB groups, possibly owing to the limited sample size and group imbalance, in the analyzed eyes. However, as EAR decreased (prolate deformation), the superior rectus (SR) pulley (r = 0.68, P < 0.01) and inferior rectus (IR) pulley (r = 0.40, P = 0.03) significantly displaced nasally. AL (r = -0.52, P < 0.01) correlated with the horizontal SR pulley position. Furthermore, age significantly correlated with AL (r = 0.45, P = 0.02) and decrease in EAR (r = -0.41, P = 0.03). Conclusions In older Japanese patients with HM and AS, prolate globe deformation was associated with age and significantly correlated with SR and IR pulley positions. While the direct relationship between these structural changes and the clinical degree of mild abduction limitation requires further investigation in larger cohorts, EAR sensitively reflected age-related morphological shifts; thus, when used in conjunction with AL, EAR may represent a readily measurable MRI-based parameter associated with restrictive motility tendencies in strabismus with high myopia. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1664-462X 17 2026 Quantitative resistance to Rhizoctonia solani AG-4 develops independently in leaves and roots of Brachypodium distachyon 1875734 EN Rozi Fernanda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Niranjan Mahadevan Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Natsuka Kohno School of Agriculture, Okayama University Reiko Nagao School of Agriculture, Okayama University Megumi Watanabe Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yusuke Kouzai Crop Stress Management Group, Division of Plant Molecular Regulation Research, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO) Keiichi Mochida RIKEN Center for Sustainable Resource Science Yoshiteru Noutoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Rhizoctonia solani is a soil-borne phytopathogen with a broad host range, classified into multiple anastomosis groups (AGs). While the rice sheath blight pathogen AG-1 IA is well-studied, defense mechanisms against AG-4, which infects diverse monocots and dicots, remain unclear. Here, we screened 153 Brachypodium distachyon accessions for resistance to AG-4 HG-I+II using both leaf and soil inoculation assays. The accessions exhibited a quantitative resistance spectrum in both assays. Some accessions were resistant to both methods, while others showed resistance in only one, indicating that leaf and root defenses operate independently. Unlike the salicylic acid (SA)-dependent resistance observed in several accessions against AG-1 IA, AG-4 leaf resistance appears to be largely SA-independent. Among 22 resistant accessions, only eight induced the SA marker BdWRKY38, whereas twelve induced the jasmonic acid (JA) marker BdAOS. Additionally, resistance in Bd3–1 was unaffected by expression of the SA hydroxylase NahG. These results are consistent with previous findings that exogenous application of SA, JA, or ethylene fails to confer AG-4 resistance. Instead, most AG-4-resistant accessions showed common upregulation of cell wall biosynthesis-related genes following leaf infection, suggesting that cell wall fortification may contribute to defense against AG-4. These findings establish B. distachyon as a valuable model for dissecting resistance mechanisms against R. solani AG-4. No potential conflict of interest relevant to this article was reported.

Japan Atherosclerosis Society Acta Medica Okayama 1340-3478 33 1 2026 Safe Continuation of Apheresis during Pregnancy using the Double-Filtration Plasmapheresis Thermo Mode in a Pregnant Female with Familial Hypercholesterolemia: A Case Report 109 115 EN Yoshimasa Sakurabu Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yuka Okuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Eriko Eto Department of Obstetrics and Gynecology, Okayama University Hospital Kanako Takasugi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Tomohiko Asakawa Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Katsuyoshi Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shugo Okamoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Natsumi Matsuoka-Uchiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Chihiro Fujihara Department of Clinical Engineering Center, Okayama University Hospital Keiko Tanaka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hidemi Takeuchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Ryoko Umebayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated LDL cholesterol levels and an increased risk of early-onset atherosclerotic cardiovascular disease. In pregnant female with FH, apheresis is the preferred treatment because standard therapeutic agents such as statins are contraindicated during pregnancy. LDL adsorption therapy is commonly used; however, after 27 weeks of gestation, it is often switched to dual filtration plasma exchange (DFPP) due to the significant drop in blood pressure caused by bradykinin production. However, DFPP has limited ability to adapt to the increase in circulating plasma volume associated with pregnancy. Here we discuss the case of a 32-year-old female with homozygous FH who underwent different apheresis strategies during her pregnancies. In her first pregnancy, she continued LDL adsorption therapy using DFPP but ultimately delivered a small-for-gestational-age infant via cesarean section. For her second pregnancy, double-filtration plasmapheresis thermo mode, DF-thermo, was introduced to mitigate the limitations of DFPP and LDL adsorption therapies, such as hypotension during apheresis and albumin loss. By minimizing these complications, DF-thermo allowed for a successful delivery without compromising fetal growth. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1877-0568 112 3 2026 Relationship between the Hounsfield Unit value of the greater trochanter and the risk of greater trochanteric fractures in anterolateral muscle-sparing minimally invasive total hip arthroplasty 104642 EN Ryuichiro Okuda Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Tomonori Tetsunaga Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Yamada Department of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama University Tomoko Tetsunaga Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Inoue Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Yasutaka Masada Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Tetsuya Yamamoto Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Shin Matsumoto Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Yuki Okazaki Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Background: No previous studies have investigated the association between the risk of greater trochanteric fractures and the Hounsfield Unit (HU) of the greater trochanter in muscle-sparing minimally invasive total hip arthroplasty (MIS-THA). This study aimed to investigate the risk factors for greater trochanteric fractures in anterolateral MIS-THA. Hypothesis: Lower HU values of the greater trochanter are associated with a higher risk of intraoperative and early postoperative greater trochanteric fractures. Patients and methods: This single-center retrospective observational study included 223 patients (257 hips) who underwent primary THA for osteoarthritis or osteonecrosis between January 2010 and August 2024 using a minimally invasive anterolateral approach in the lateral position. All surgeries were performed by four surgeons. Preoperative CT was used to reconstruct coronal sections including the femoral head center and proximal femoral axis, and cancellous HU values of the greater trochanter were measured. Postoperative CT (1 week) with metal artifact reduction was routinely performed; fractures were defined as cortical fracture lines on 3D-reconstructed CT and assessed by two independent orthopedic surgeons. Patients were divided into two groups according to the presence or absence of fractures. Results: The incidence of greater trochanteric fractures was 6.6% (17/257 hips). Twelve of these fractures (70.6%) were recognized intraoperatively or immediately postoperatively. Full hydroxyapatite (HA)-coated stems were associated with an increased fracture risk compared with other designs (relative risk [RR], 2.68; 95% CI, 1.07–6.68). Age, sex, BMI, ASA physical status, and diagnosis were not significantly associated with fractures. Multivariate analysis identified lower HU values (odds ratio [OR], 0.973; p < 0.0001) and full HA-coated stems (OR, 13.3; p = 0.04) as independent predictors. Receiver operating characteristic (ROC) analysis determined an optimal cut-off of 72.0 HU (sensitivity, 0.941; specificity, 0.742), with a value ≤72.0 HU demonstrating high predictive power (RR, 36.7; p < 0.0001). Conclusion: Preoperative measurement of HU values in the greater trochanter is a useful screening tool for identifying patients at increased risk of fractures in anterolateral MIS-THA. While an HU value of ≤ 72.0 necessitates careful intraoperative management and increased vigilance, it should be interpreted as an indicator of risk rather than a definitive predictor of fracture due to its moderate specificity. Level of evidence: IV; retrospective study. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Asthma-like bronchodilator responsiveness in patients with neuronal intranuclear inclusion disease 16760 EN Daisuke Tahara Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Nao Tahara Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Chisato Tamai Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Akio Akagi Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Yuichi Riku Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Hiroaki Miyahara Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Rei Kobayashi Department of Neurology, NHO Nagoya Medical Center Hisashi Okada Department of Neurology, NHO Nagoya Medical Center Michi Kawamoto Department of Neurology, Kobe City Medical Center General Hospital Junko Ishii Department of Neurology, Kobe City Medical Center General Hospital Hiroki Yamazaki Department of Neurology, Tokushima University Graduate School of Biomedical Science Takashi Kurashige Department of Neurology, NHO Kure Medical Center and Chugoku Cancer Center Atsuhiko Sugiyama Department of Neurology, Chiba University Akiko Nagaishi Department of Neurology, NHO Nagasaki Kawatana Medical Center Katsuya Nishida Department of Neurology, NHO Hyogo Chuo National Hospital Kazuma Sugie Department of Neurology, Nara Medical University Hospital Takayasu Fukudome Department of Neurology, NHO Nagasaki Kawatana Medical Center Kazuko Hasegawa Department of Neurology, NHO Sagamihara National Hospital Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruki Koike Department of Neurology, Saga University Takashi Kasai Department of Neurology, Kyoto Prefectural University of Medicine Toshiki Mizuno Department of Neurology, Kyoto Prefectural University of Medicine Masahiro Ando Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Yujiro Higuchi Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Fumiaki Tanaka Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine Yuishin Izumi Department of Neurology, Tokushima University Graduate School of Biomedical Science Gen Sobue Aichi Medical University Yasushi Iwasaki Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Satoru Ito Division of Respiratory Medicine and Allergology, Department of Internal Medicine, School of Medicine, Aichi Medical University Jun Sone Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative condition characterized by the presence of intranuclear inclusions in neuronal and visceral cells. Patients with NIID can present respiratory symptoms; however, data on pulmonary functions in NIID are lacking. This study investigated the respiratory conditions in NIID patients diagnosed with histopathological and genetic studies. We conducted two spirometries before and after administrating the bronchodilator in NIID patients with asthmatic histories or symptoms. We statistically compared pre- and post-measured values including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF). Before two spirometries, we also measured fractional concentration of exhaled nitric oxide (FeNO), if possible. Of the 51finally enrolled patients, 17 (33.3%, 95% CI 20.8% to 47.9%) patients had asthmatic histories or symptoms, and 14 patients received two spirometries. After administrating the bronchodilator, FEV1 and PEF significantly increased by 150 mL (6.01%, p = 0.002) and 260 mL/s (6.72%, p = 0.017), respectively. The median (interquartile range) of FeNO measured in nine patients was 15 (10–21) ppb. Patients with NIID have airflow reversibility like asthma. This condition appears to be less associated with airway inflammation and may be related to autonomic dysfunction. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6643 18 11 2026 GLP-1 Receptor Agonists in the Rehabilitation of Patients with Heart Failure: Mechanisms, Clinical Evidence, and Future Perspectives 1688 EN Luh Oliva Saraswati Suastika Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuko K. Bando Department of Molecular Physiology and Cardiovascular Biology, Mie University Graduate School of Medicine Keiji Hoshino Division of Cardiology, Gunma Prefectural Cardiovascular Center Norimichi Koitabashi Division of Cardiology, Gunma Prefectural Cardiovascular Center Yukihiro Saito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Heart failure (HF) remains associated with high morbidity and mortality, with heart failure with preserved ejection fraction (HFpEF) becoming increasingly prevalent and therapeutically challenging despite advances in pharmacological and rehabilitative care. Beyond their glucose-lowering effects, glucagon-like peptide-1 receptor agonists (GLP-1RAs) confer cardiometabolic benefits and may serve as effective adjuncts to cardiac rehabilitation (CR), particularly in obese patients with HFpEF. Obesity plays a central role in the pathophysiology of HFpEF, and GLP-1RAs promote weight loss, reduce insulin resistance and leptin signaling, and improve hemodynamic and metabolic abnormalities associated with HFpEF. Accumulating evidence suggests that the benefits of GLP-1RAs are phenotype-specific and more pronounced in patients with HFpEF than in patients with HF with reduced ejection fraction. Current clinical guidelines recommend GLP-1RAs for patients who have type 2 diabetes mellitus and established cardiovascular (CV) disease or are at high CV risk, with recent updates recognizing their potential benefits in patients with HFpEF and obesity. Cardiac rehabilitation, delivered through multidisciplinary programs, remains a cornerstone of HF management. Although caloric restriction and aerobic exercise can be beneficial in patients with HFpEF and obesity, these interventions alone are often insufficient. Sarcopenia is common in older patients with HFpEF and contributes to adverse outcomes, underscoring the importance of incorporating resistance training into CR programs. The most frequent adverse effects of GLP-1RAs are gastrointestinal events, which are generally mild to moderate but may lead to treatment discontinuation in some patients. Future studies should investigate the potential synergistic effects of GLP-1RAs and CR, clarify their long-term safety and efficacy in HF populations, and define their role beyond obese HFpEF phenotypes. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0300-9572 225 2026 Decline in rescue breathing and its impact on outcomes in pediatric out-of-hospital cardiac arrest due to drowning: a nationwide study, 2012–2023 111049 EN Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: Rescue breathing is considered essential in pediatric out-of-hospital cardiac arrest (OHCA) due to drowning, a type of asphyxial arrest where hypoxia precedes circulatory collapse. However, the increasing promotion of compression-only CPR (CO-CPR) may have contributed to changes in bystander CPR practices, including a decline in rescue-breathing CPR (RB-CPR). Whether such temporal changes have influenced outcomes in pediatric drowning OHCA remains unclear. Methods: We analyzed nationwide data from the All-Japan Utstein Registry (2012–2023), including pediatric OHCA patients (≤17 years old) whose arrests were caused by drowning and received bystander CPR from laypersons. Patients were categorized into RB-CPR and CO-CPR groups. The primary outcome was 30-day mortality; secondary outcomes included prehospital absence of return of spontaneous circulation (ROSC) and 30-day unfavorable neurological survival, defined as Cerebral Performance Category score 3–5. We used multivariable Poisson regression to estimate adjusted risk ratio (aRR) and conducted analyses by age and witnessed status. Results: Among 740 eligible patients, 41.6% received RB-CPR and 58.4% received CO-CPR. The proportion of RB-CPR declined over the study period. CO-CPR was associated with higher 30-day mortality (aRR 1.38, 95% CI 1.14–1.67), higher prehospital absence of ROSC, and worse neurological outcomes compared with RB-CPR. The adverse association of CO-CPR was most pronounced in unwitnessed arrests, where ventilation may be particularly important. Conclusions: In pediatric drowning OHCA, CO-CPR was associated with worse survival and neurological outcomes than RB-CPR. These findings underscore the necessity for rescue breathing and the importance of ventilation-focused bystander CPR training in pediatric and drowning-related scenarios. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2047-9980 15 9 2026 Insomnia and the Risk of Atrial Fibrillation: A Nationwide, Real‐World Cohort Study e045149 EN Takuro Masuda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidehiro Kaneko Department of Cardiovascular Medicine, The University of Tokyo Yuta Suzuki Department of Advanced Cardiology, The University of Tokyo Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Taya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Iwasaki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akira Okada Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo Katsuhito Fujiu Department of Cardiovascular Medicine, The University of Tokyo Norifumi Takeda Department of Cardiovascular Medicine, The University of Tokyo Hiroyuki Morita Department of Cardiovascular Medicine, The University of Tokyo Hideo Yasunaga Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo Norihiko Takeda Department of Cardiovascular Medicine, The University of Tokyo Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Insomnia is one of the most prevalent diseases observed in clinical practice, contributing to increased death and a range of chronic diseases. While numerous studies have explored the relationship between insomnia and cardiovascular disease, research on its association with atrial fibrillation (AF) remains limited. This study aimed to investigate the association between insomnia and incident AF in the general population by comprehensive, nationwide, real‐world data in Japan. Methods: A total of 1 780 764 individuals without prior cardiovascular disease including AF from the DeSC database were included between April 2014 and August 2023. Insomnia was defined by International Classification of Diseases, Tenth Revision (ICD‐10) codes (F510, G470) before the baseline health checkup. The primary outcome was incident AF (I480–I482 and I489). Cox proportional hazards models were used to estimate hazard ratios of AF according to present insomnia (versus absent). Results: Insomnia was observed in 216 919 individuals (12.2%), showing a significant association with incident AF after adjusting for potential confounding factors (adjusted hazard ratio, 1.14 [95% CI, 1.10–1.18]). Among subgroups, a similar pattern in the association between insomnia and incident AF was seen, while the association was stronger in younger individuals aged <65 years (versus ≥65 years) and women (versus men) (P for interaction=0.01 and 0.03, respectively). Conclusions: Insomnia was significantly associated with the risk of AF. It highlighted the importance of recognizing insomnia as a risk factor for AF, given its high prevalence in the general population and the substantial impact of AF on quality of life and prognosis. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1465-3621 2026 Impact of pre-existing schizophrenia spectrum disorder on the receipt of invasive and systemic therapy for gastric cancer: a multicenter nationwide cohort study in Japan hyag102 EN Myo Min Khant Department of Psychiatry, Faculty of Medicine, Shimane University Masaki Fujiwara Department of Neuropsychiatry, Medical Development Field, Okayama University Yuto Yamada Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center Taisuke Ishii Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center Tomone Watanabe Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center Takashi Fukao Department of Neuropsychiatry, Medical Development Field, Okayama University Maiko Fujimori Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center Naoki Nakaya Tohoku Medical Megabank Organization, Tohoku University Toshihiko Kawamura Department of Medical Informatics, Shimane University Hospital Koji Otsuki Department of Psychiatry, Faculty of Medicine, Shimane University Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Taichi Shimazu Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center Shiro Hinotsu Department of Biostatistics and Data Management, Sapporo Medical University Yosuke Uchitomi Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine Masatoshi Inagaki Department of Psychiatry, Faculty of Medicine, Shimane University Background: Patients with schizophrenia spectrum disorders (SSD) experience higher cancer mortality, partly because of later-stage diagnosis and lower rates of recommended treatments. While treatment disparities have been reported across several cancer types, no study has specifically examined stage-appropriate treatment for gastric cancer among patients with SSD. Methods: We conducted a retrospective cohort study using a nationwide Hospital-Based Cancer Registry linked to administrative data in Japan. Patients who received initial treatment for gastric cancer between 2018 and 2021 were included. Multivariable logistic regression models examined the association between SSD and the receipt of stage-appropriate cancer treatments, adjusting for age, sex, clinical stage, Charlson Comorbidity Index, and Barthel Index. Results: Among 189 447 patients from 709 hospitals, 1312 had SSD. Patients with SSD were more likely to be diagnosed at advanced stages. In crude analysis, SSD was associated with lower rates of surgical or endoscopic treatment; however, this association was not statistically significant after adjustment (adjusted odds ratio [aOR], 0.90; 95% confidence interval [CI], 0.75–1.08). In contrast, SSD was independently associated with lower rates of postoperative adjuvant chemotherapy for pathological stage II/III disease (aOR, 0.64; 95% CI, 0.45–0.91) and systemic therapy for stage IV disease (aOR, 0.36; 95% CI, 0.28–0.47). Conclusions: Among patients with gastric cancer, SSD was associated with reduced receipt of systemic therapy but not surgical or endoscopic treatment. Efforts to improve early detection among patients with SSD may be important for reducing treatment disparities, alongside strengthened support for systemic therapy to ensure equitable access to guideline-recommended gastric cancer care. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1478-6362 27 1 2025 Performance of the modified 2022 ACR/EULAR giant cell arteritis classification criteria without age restriction for discriminating from Takayasu arteritis 19 EN Takahiko Sugihara Department of Rheumatology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Masayoshi Harigai Division of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of Medicine Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hajime Yoshifuji Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University Yasuhiro Maejima Department of Cardiovascular Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Jun Ishizaki Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine Yoshiko Watanabe Department of General Medicine, Kawasaki Medical School Hiroaki Dobashi Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University Yoshinori Komagata Department of Nephrology and Rheumatology, Kyorin University School of Medicine Naoto Tamura Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine Yoshikazu Nakaoka Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS) Objective To evaluate the ability to discriminate giant cell arteritis (GCA) from Takayasu arteritis (TAK) according to the modified 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) GCA classification criteria. Methods Patients enrolled in the Japanese nationwide retrospective registry were evaluated using the criteria with partial modification; wall thickening of descending thoracic-abdominal aorta were mainly diagnosed by contrast-enhanced computed tomography (CT) or magnetic resonance imaging instead of evaluating with positron emission tomography (PET)-CT. The discriminability of the criteria was evaluated using C-statistic (> 0.7: good ability). Results Newly diagnosed patients with GCA (n = 139) and TAK (n = 129) were assessed, and 23.3% of TAK were aged 50 years or older at onset. The sensitivity of the modified 2022 ACR/EULAR GCA classification criteria with a score ≥ 6 was 82.0%, 68.5%, and 32.1% in all GCA, GCA with large-vessel involvement, and GCA without cranial arteritis, respectively. The specificity of the modified criteria was 96.1% for the 129 TAK as controls. Five patients with late-onset TAK met the modified criteria, and four had cranial signs and symptoms, two had bilateral axillary artery involvement, and four had descending thoracic-abdominal aorta involvement. The discriminability of the criteria was good (C-statistic: 0.986, 95% confidence interval [CI]: 0.976–0.996) and remained good after excluding age (C-statistic: 0.927, 95% CI: 0.894–0.961). The discriminability of a set of large-vessel lesions (bilateral axillary artery and descending thoracic-abdominal aorta) and inflammatory markers was markedly decreased with poor C-statistic value (C-statistic: 0.598, 95% CI: 0.530–0.667). Discriminability was improved after adding polymyalgia rheumatica (PMR) (C-statistic: 0.757, 95% CI: 0.700–0.813) or age (C-statistic: 0.913, 95%CI: 0.874–0.951) to the set of large-vessel lesions. In GCA patients with a score ≤ 5, 52% had bilateral subclavian and/or axillary artery involvement. Conclusion The modified 2022 ACR/EULAR GCA classification criteria well performed in classifying GCA and TAK without PET-CT in routine clinical practice. A set of items included in the modified GCA classification criteria had good discriminative ability for GCA and TAK, even when age was excluded. However, age restriction or PMR was required to distinguish GCA without cranial lesions from TAK. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0803-5253 114 2 2024 Outdoor playing during preschool was associated with a reduced risk of school-age obesity in Japan 303 309 EN Takahiro Tsuge Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soshi Takao Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aim: This study investigated the association between outdoor play habits during preschool and school-age obesity. Methods: We conducted a longitudinal cohort study of all children born in Japan during 2 weeks in January and July 2001. We defined outdoor play habits at age 2.5 years (third survey) as exposure, while parent-reported height and weight at age 7 years (seventh survey) were defined as overweight and obesity status using the WHO reference. Logistic regression models were used to estimate odds ratios (ORs) for associations between preschool outdoor play habits and school-age obesity, adjusting for parental and child factors. Results: Of 53 575 children born, 42 812 had data on outdoor play habits at age 2.5 years, with 91% (38 970) having such habits. At age 7 years, 31 743/42 812 (74%) children had height and weight data, with 3249/31 743 (10%) classified as overweight or obesity (BMI SD score ≥1.0). Outdoor play habits were negatively associated with obesity (adjusted OR 0.85, 95% confidence interval (CI): 0.74–0.97). Conclusion: Outdoor play habits in early preschool years are associated with a reduced risk of school-age obesity. Parents and caregivers may consider encouraging their children to outdoor play habits at an early age to help prevent obesity later in life. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 7 2026 Reappraisal of the Entity of Pediatric Uveitis: Bilateral Iridocyclitis With Retinal Capillaritis (BIRC) in Juveniles in 18 Additional Cases e112232 EN Toshihiko Matsuo Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Objectives: Bilateral iridocyclitis with retinal capillaritis (BIRC) in juveniles is a newly recognized entity of juvenile chronic uveitis with no systemic involvement. In this study, 18 additional consecutive patients with BIRC were reported to show that the entity would be useful in the differential diagnosis. Methods: Clinical features were retrospectively reviewed in 18 consecutive patients diagnosed with BIRC in juveniles at Okayama University Hospital, Okayama, Japan, between 1996 and 2025. Results: The 18 patients comprised 6 males and 12 females, with an age at onset ranging from 9 to 16 years (median, 13 years). All patients presented with aqueous cells and mutton-fat keratic precipitates in both eyes, and fluorescein angiography revealed varying degrees of optic disc leakage and retinal capillary leakage in the midperipheral to peripheral fundus of both eyes. None had systemic symptoms, including skin rashes, joint pain, or fever, and no abnormalities were detected on blood examinations, urinalysis, or plain chest x-rays. Oral prednisolone, tapered from 30 mg daily, together with topical 0.1% betamethasone four times daily, was administered to five patients: two with optic disc edema and three with macular edema in both eyes or the unilateral eye. The remaining 13 patients were treated with topical 0.1% betamethasone eye drops alone. In patients who developed elevated intraocular pressure, often due to a steroid response, the instillation of topical 0.1% betamethasone was reduced to twice daily, or intraocular pressure-lowering eye drops were used in combination. In two patients who showed relapse of unilateral macular edema after oral prednisolone was tapered or discontinued, oral colchicine (1 mg daily) was introduced, resulting in the subsidence of macular edema. Bilateral uveitis in all 18 patients subsided within 6 months to a few years until 19 years of age, and all topical medications were discontinued, with relapse occurring in only one patient. Conclusions: BIRC in juveniles should be included in the differential diagnosis for school-age children and young adolescents. BIRC follows a chronic course of a few years and subsides completely with a good prognosis. In cases of macular edema or optic disc edema that affects vision, oral corticosteroid treatment is recommended, whereas patients with no sight-threatening signs can be treated with topical corticosteroid eye drops alone. The entity of BIRC may be distinct from juvenile chronic iridocyclitis in young girls with onset at preschool age, which shares common features with juvenile idiopathic arthritis-associated uveitis. No potential conflict of interest relevant to this article was reported.

Society for Human Environmental Studies Acta Medica Okayama 1348-5253 24 1 2026 Relationships between awareness of age-related change, subjective well-being, and psychological stress 69 77 EN Natsue Shiraishi Graduate School of Social and Cultural Sciences, Okayama University Allyson Brothers Human Development and Family Studies, Colorado State University Yasuhiro Yamamoto Faculty of Education, Okayama University Takeshi Nakagawa Graduate School of Human Sciences, University of Osaka Takashi Horiuchi Faculty of Humanities and Social Sciences, Okayama University 本研究は、加齢に伴う変化の認識（Awareness of Age-Related Change: AARC）、主観的幸福感（Subjective Well-Being:SWB）、および心理的ストレスの縦断的関係の検討を行った。AARC は、ライフスパン発達理論に基づき、心理的適応に重要な役割を果たすとされる。先行研究ではAARC と幸福感の関連が報告されているが、多くは横断研究であり、時間的方向性を考慮した検討は不十分である。そこで本研究では、日本の40 歳以上の成人585 名を対象に、AARC 短縮版（AARC-10 SF）、人生満足度尺度（SWLS）、心理的ストレス尺度（K6）を用いて、2 時点（2022 年7 月、2023 年10 月）でオンライン調査を実施した。交差遅延効果モデルの分析の結果、AARC-gains とSWLS の間に双方向の関連が認められ、AARC-gains が高い人ほど後の主観的幸福感が高く、その逆も成立することが示された。一方、心理的ストレスはAARC-losses に対して一方向の関連が確認され、ストレスが高い人ほど後のAARC-losses が高いことが示された。これらの結果は、ライフスパン発達理論の枠組みと整合し、加齢に伴う適応過程の理解を深めるものである。介入においては、AARC-gains を促進し幸福感を高めることが高齢者のサクセスフル・エイジングに寄与する可能性がある。 No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-4701 15 2 2025 A Review on the Magnetovolume Effect of the Full Heusler Alloys Ni2MnZ (Z = In, Sn, Sb) 215 EN Takeshi Kanomata Research Institute for Engineering and Technology, Tohoku Gakuin University Xiao Xu Department of Materials Science, Graduate School of Engineering, Tohoku University Takuo Sakon Faculty of Advanced Science and Technology, Ryukoku University Yuki Nagata Faculty of Advanced Science and Technology, Ryukoku University Shin Imada College of Science and Engineering, Ritsumeikan University Toshihiro Omori Department of Materials Science, Graduate School of Engineering, Tohoku University Ryosuke Kainuma Department of Materials Science, Graduate School of Engineering, Tohoku University Tetsujiro Eto Kurume Institute of Technology Yoshiya Adachi Graduate School of Science and Technology, Yamagata University Takumi Kihara Research Institute for Interdisciplinary Science, Okayama University Yasushi Amako Faculty of Science, Shinshu University Masaaki Doi Research Institute for Engineering and Technology, Tohoku Gakuin University Yoshiya Uwatoko Institute for Solid State Physics, The University of Tokyo The full Heusler alloys Ni2MnZ (Z = In, Sn, Sb) exhibit ferromagnetic properties with a Curie temperature (TC) above room temperature. The magnetic properties of Ni2MnZ (Z = In, Sn, Sb) were studied through a combination of experiments and band calculations under ambient and elevated pressures. The main results of this study open up further prospects for controlling the magnetic properties of the multifunctional Heusler alloys Ni2Mn1+xZ1−x (Z = In, Sn, Sb) and their practical application. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2673-8937 5 1 2025 The Early Response After Radiation Therapy on Three-Dimensional Oral Cancer Model Using Patient-Derived Cancer-Associated Fibroblasts 12 EN Izumi Yamamoto Neutron Therapy Research Center, Okayama University Kazuyo Igawa Neutron Therapy Research Center, Okayama University Natsuko Kondo Particle Radiation Oncology Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University Yoshinori Sakurai Particle Radiation Oncology Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University Atsushi Fujimura Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Peng Huang Neutron Therapy Research Center, Okayama University Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenji Izumi Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Background/Objectives: Cancer-associated fibroblasts (CAFs), which are an important component of the tumor microenvironment, have been reported to have an adverse effect on conventional radiotherapy. This study aims to elucidate the effects of CAFs in boron neutron capture therapy (BNCT) using a three-dimensional (3D) oral cancer model. Methods: Three-dimensional cancer models were fabricated using patient-derived CAFs or patient-derived normal oral fibroblasts (NOFs) and a human oral squamous cell carcinoma cell line. Each 3D cancer model was performed with either a conventional X-ray treatment or BNCT and additionally analyzed histomorphologically. Results: The 3D oral cancer-CAFs model demonstrated a greater depth of cancer cell invasion than the 3D oral cancer-NOFs model. Radiation therapy for the 3D oral cancer models indicated a trend for decreasing cancer cell invasion and cell number with dose dependence in both X-ray and BNCT. In comparison with X-rays, BNCT showed a consistent increase in the number of NOFs and a significant reduction in the number of CAFs. Conclusions: BNCT for the 3D oral cancer model was shown to be effective against cancer cells and CAFs but not against NOFs, indicating its usefulness as a minimally invasive treatment for advanced cancer. Furthermore, it is indicated that the 3D oral cancer-CAFs model is a valuable tool to evaluate cancer treatment and research, particularly in high-grade malignant tumors with invasion. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1718-7729 32 6 2025 Global Incidence Trend of Early-Onset Obesity-Related and Non-Obesity-Related Cancers 324 EN Miyu Terashima Okayama University Medical School Kota Nakayama Okayama University Medical School Satoko Ugai Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA Hwa-Young Lee Graduate School of Public Health and Healthcare Management, The Catholic University of Korea Yuta Tsukumo Department of Epidemiology, Harvard T.H. Chan School of Public Health Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroki Mizuno Department of Epidemiology, Harvard T.H. Chan School of Public Health Minkyo Song Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health Naoko Sasamoto Public Health Sciences Division, Fred Hutchinson Cancer Center Ichiro Kawachi Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health Tomotaka Ugai Department of Epidemiology, Harvard T.H. Chan School of Public Health The global rise in obesity prevalence and the incidence of early-onset cancer (diagnosed between 20 and 49 years of age) is a serious public health concern. We, therefore, evaluated the recent global trends in the incidence of early-onset obesity-related cancers and compared them to those of non-obesity-related cancers. We obtained age-standardized incidence rates of early-onset cancers diagnosed between 2000 and 2012 in 44 countries from the Cancer Incidence in Five Continents database. Using joinpoint regression models, we calculated the average annual percentage changes (AAPCs) and their corresponding 95% confidence intervals (95% CIs) for combined and individual categories of obesity-related cancers (11 and 9 cancer types in females and males, respectively) and non-obesity-related cancers (12 cancer types in both females and males). Differences in the AAPC were assessed by comparing 95% CIs, where nonoverlapping 95% CIs were considered statistically significantly different. We observed statistically significant positive AAPCs for early-onset obesity-related cancers in all available countries combined among females (global AAPC, 4.3%; 95% CI, 4.1–4.6%) and males (global AAPC, 1.4%; 95% CI, 1.2–1.7%). When analyzed by countries, we observed statistically significant positive AAPCs in 26 countries among females and 11 countries among males. AAPCs for early-onset obesity-related cancers were statistically significantly higher than those of non-obesity-related cancers in several regions, especially North America and Oceania. In conclusion, this study indicates that the incidence of early-onset obesity-related cancers exhibited a more pronounced increasing trend than non-obesity-related cancers among both sexes in many countries and regions. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 3042-6081 2 2 2026 Interfacial Bond Strength of Resin Cement to Polyetheretherketone (PEEK) Using Experimental Primers Doping Multifunctional Methacrylate and Acrylate Monomers 12 EN Yukinori Maruo Department of Prosthodontics, Okayama University Kumiko Yoshihara Health Research Institute, National Institute of Advanced Industrial Science and Technology Masao Irie Okayama University Dental School Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Naoki Kodama Department of Prosthodontics, Okayama University Yuki Tanaka Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miho Kuwahara Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Akiyama Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Polyetheretherketone (PEEK) is a high-performance thermoplastic polymer with low surface energy, chemical inertness, and a highly crystalline structure, which limit durable adhesion to resin-based materials and require improved bonding strategies. This in vitro study evaluated the effect of incorporating multifunctional methacrylate (TMPTMA) and acrylate monomers (A-TMPT and A-DPH) into an experimental primer on the 24 h shear bond strength (SBS) of resin cement to PEEK (n = 6 per group). Experimental primers were prepared by adding varying amounts (100–500 µL) of each multifunctional monomer to a UDMA/MMA-based primer, and SBS was measured after cementation with a dual-cure resin cement. TMPTMA-containing primers produced median SBS values of approximately 10–12 MPa, while acrylate-based primers showed slightly higher values, particularly at higher concentrations, reaching up to ~15.8 MPa; however, no statistically significant improvement over the control group was observed (p > 0.05). Failure modes were predominantly mixed across all conditions. These findings indicate that multifunctional monomers, despite their potential to enhance cross-link density and wetting, do not substantially overcome the intrinsic adhesion-resistant nature of polished PEEK. The results underscore that monomer modification alone is insufficient and that effective adhesion to PEEK likely requires integrated strategies combining chemical activation with mechanical surface conditioning. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-1729 16 6 2026 Disease-Suppressive Activity of Lecithin Against Foliar Infection by Rhizoctonia solani Isolates in Cabbage, Rice, and Brachypodium distachyon 998 EN Tran Xuan Cuong Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Misaki Asano School of Agriculture, Okayama University Daiki Honma School of Agriculture, Okayama University Moeko Soeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Megumi Watanabe Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University, Okayama 700-8530, Japan Yuki Ichinose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kentaro Ikeda Faculty of Bioscience and Applied Chemistry, Hosei University Yoshiteru Noutoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Rhizoctonia solani is a necrotrophic phytopathogenic fungus that causes disease in various crops. In agriculture, many crops suffer from root or seedling rot caused by this soil-borne pathogen, whereas cabbage and rice develop lesion-like symptoms on aboveground tissues. Diseases caused by R. solani are generally controlled using chemical fungicides; however, environmentally friendly alternatives are needed for sustainable agriculture. In this study, we evaluated the efficacy of lecithin, a mixture of phospholipids previously registered in Japan as an agrochemical for controlling cucumber powdery mildew, against Rhizoctonia diseases. In cabbage, foliar spraying of 0.2–1.0% soybean lecithin effectively suppressed leaf symptoms caused by R. solani isolate RhiCa-2, which was identified as AG-1 IB. In rice and Brachypodium distachyon, 0.2–1.0% lecithin significantly suppressed leaf symptoms induced by R. solani AG-1 IA. Hyphal staining of inoculated leaves revealed reduced hyphal density on lecithin-treated leaves. Consistently, hyphal growth of R. solani on cellophane placed on water agar was retarded by lecithin treatment. However, 5.0% lecithin induced phytotoxicity in B. distachyon. Egg yolk-derived lecithin also exhibited disease-suppressive activity in cabbage and B. distachyon, with efficacy comparable to that of soybean lecithin under the conditions tested. These results suggest that lecithin suppresses foliar infection by R. solani, at least in part, through direct inhibitory effects on fungal hyphae, and may serve as a potential alternative material for disease control in sustainable crop production. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-1729 16 6 2026 UGT76B1 and 41 Additional Arabidopsis UDP-Glycosyltransferases Show No Detectable In Vitro Glycosylation Activity Toward N-Hydroxypipecolic Acid 992 EN Jiyuan Bao Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taiga Uchiyama Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuki Kusunoki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuka Shinohara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yurika Tanigawa School of Agriculture, Okayama University Megumi Watanabe Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiteru Noutoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University N-hydroxypipecolic acid (NHP) is a key mobile signal in systemic acquired resistance in plants, and its glycosylation has been proposed to regulate immune signaling. Previous studies have demonstrated that the UDP-glycosyltransferase UGT76B1, known as an SA glycosyltransferase in Arabidopsis thaliana, also catalyzes NHP glycosylation. In this study, we re-evaluated NHP glycosylation activity of UGT76B1 using an in vitro enzyme-coupled fluorescence assay that quantitatively detects UDP released during UDP-sugar-dependent glycosylation. Unexpectedly, our biochemical analyses demonstrated that UGT76B1 lacks genuine glycosylation activity toward NHP under the in vitro assay conditions tested, although this system clearly detected UGT76B1 activity toward salicylic acid (SA), as well as the activities of UGT74F1 and UGT72B1 toward SA and hydroquinone, respectively. To explore potential UGTs responsible for NHP glycosylation, we evaluated the enzymatic activities of 41 UGT candidates successfully expressed in Escherichia coli, which are selected based on transcriptomic responses to tenoxicam treatment, molecular docking simulations using AlphaFold3/AutoDock Vina, phylogenetic criteria, and previous reports. Within this selected and successfully expressed UGT panel, none exhibited authentic NHP glycosylation activity, although this does not preclude the possibility that other members of the Arabidopsis UGT family possess NHP glycosyltransferase activity. Our findings challenge the prevailing view that UGT76B1 is the primary glycosyltransferase for NHP in A. thaliana and indicate that NHP metabolism may rely on undiscovered non-canonical enzymes or distinct metabolic pathways that warrant further investigation. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1999-5903 18 6 2026 A Batch-Based VNF Deployment Mechanism for Privacy-Preserving Multi-Domain SFC Deployment Using Deep Reinforcement Learning 312 EN Arif Indra Irawan Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yukinobu Fukushima Faculty of Environmental, Life, Natural Science and Technology, Okayama University Future 6G networks require higher performance and wider service coverage. Multi-domain Service Function Chain (SFC) deployment enables service provisioning across multiple network domains to meet these demands. However, when collaboration occurs among different network operators, privacy-preserving mechanisms are required to protect sensitive information such as internal topology and resource availability. Existing SIRM-based mechanisms, such as the Privacy-Preserving Deployment Mechanism (PPDM), address this challenge but suffer from structural limitations: PPDM performs whole-chain feasibility evaluation with extensive virtual occupation. This paper proposes a ℬ-Batch Sequential Deployment mechanism for privacy-preserving multi-domain SFC deployment. Instead of evaluating whole-chain feasibility at once, the proposed ℬ-Batch mechanism partitions each incoming SFC into fixed-size VNF batches and constructs a batch-level SIRM. This design confines virtual occupation to the current batch and reduces both its magnitude and duration while remaining fully compatible with the SIRM privacy model and the hierarchical multi-domain control architecture. A Deep Q-Network (DQN) is employed to learn substrate node selection policies based solely on SIRM-based state information, without exposing domain-internal topology or resource details. Simulation results on a three-domain AARNET substrate topology demonstrate that the proposed mechanism consistently improves deployment robustness under varying traffic intensities and SFC lengths, including short (3–6 VNFs), medium (6–9 VNFs), and long (9–12 VNFs) service chains. Compared with PPDM, the proposed ℬ-Batch mechanism achieves higher acceptance ratios under moderate-to-heavy traffic while reducing end-to-end delay and improving average substrate resource utilization. Node selection analysis further shows that smaller batch sizes preserve feasibility through compact node reuse, whereas larger batch sizes encourage broader substrate exploration. Overall, the proposed ℬ-Batch mechanism enhances feasibility preservation and deployment robustness in privacy-preserving multi-domain SFC orchestration. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Determination of the Side Responsible for Bilateral Pneumothorax due to Pleural Communication 225 228 EN Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruchika Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kumi Nakajima Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidejiro Torigoe Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/70859 Simultaneous bilateral spontaneous pneumothorax associated with pleuro-pleural communication is a rare but potentially life-threatening condition, most commonly occurring after major thoracic surgery. We report the case of an 81-year-old man with severe emphysema and a history of esophagectomy who presented with sudden-onset dyspnea. Chest computed tomography revealed bilateral pneumothorax with pleuro-pleural communication. Although bilateral chest tube drainage was performed, the primary side of air leakage could not be identified preoperatively. After induction of general anesthesia, a double-lumen endotracheal tube clamping test identified the right pleural cavity as the source of air leakage, thereby enabling appropriate thoracoscopic surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Peripheral Blood T-Cell Receptor Repertoire and Host Immune Background in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy 169 178 EN Yuki Nakamura Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Takayuki Iwamoto Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Yukiko Kajiwara Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital Akira Hida Department of Pathology, Matsuyama Shimin Hospital Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Yuichiro Miyoshi Department of Breast Endocrine Surgery, Kagawa Prefectural Center Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Masahiko Ikeda Department of Breast and Thyroid Surgery, Fukuyama City Hospital Hiroyoshi Doihara Department of General Surgery, Kawasaki Medical School General Medical Center Ryohei Ogata Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Yoshikazu Koike Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Tsunehisa Nomura Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Katsuhiro Tanaka Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Kazutaka Nakashima Department of General Surgery, Kawasaki Medical School General Medical Center Tomoki Yamatsuji Department of General Surgery, Kawasaki Medical School General Medical Center Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Original Article 10.18926/AMO/70852 The association between peripheral blood T-cell receptor (TCR) repertoire and chemotherapy response remains unclear. We evaluated peripheral blood TCR repertoire and gut microbiota in 21 breast cancer patients receiving neoadjuvant chemotherapy (NAC) who were enrolled in the SBP-14 prospective cohort study between October 2019 and March 2022. We analyzed stool samples obtained pre-NAC and peripheral blood samples obtained pre- and post-NAC. The primary endpoint was the association between baseline peripheral blood TCR repertoire and treatment response. Eleven patients (52%) had hormone receptor-positive breast cancer. All patients received anthracyclines and taxanes, with anti-HER2 therapy for HER2-positive disease. TCR diversity (TCR alpha chain [TRA], p=0.095; TCR beta chain [TRB], p=0.051) and clonality (TRA, p=0.271; TRB, p=0.500) were not significantly associated with treatment response. Gut microbiota diversity was not correlated with TCR diversity (TRA: ρ=0.046, p=0.845; TRB: ρ=0.021, p=0.929); however, three bacterial orders (Erysipelotrichales, Bacillales, and Pasteurellales) were significantly associated with TCR repertoire. Baseline TCR repertoire was not associated with treatment response in this cohort of breast cancer patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Self-Reported Adolescent Menstrual Symptoms and Delayed Gynecologic Consultation among Japanese Women with Endometriosis 159 168 EN Tomoko Ikeda Faculty of Health Sciences, Okayama University Mikiya Nakatsuka Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/70851 Endometriosis symptoms often first appear during adolescence, yet delays in seeking gynecologic consultation remain a persistent challenge worldwide. Despite growing international evidence, the specific patterns of symptom recognition and consultation delay among Japanese women — particularly in relation to self-monitoring behaviors and cultural barriers — remain poorly understood. This study aimed to provide foundational data to guide menstrual education and preconception care strategies by conducting a cross-sectional online survey with retrospective recall among women with endometriosis to assess menstrual characteristics and symptom patterns from adolescence to initial care seeking. The survey was conducted in Japan in January 2024 and enrolled 166 women with endometriosis and 200 controls. Participants reported current and adolescent menstrual characteristics, symptom recognition, analgesic and low-dose estrogen–progestin use, school/work impact, and age at first gynecologic consultation for menstrual problems. Women with endometriosis reported heavier bleeding, stronger pain, and greater school/work absence than controls, both currently and retrospectively. The median age at first recognition of heavy bleeding or school/work absence was 16 years, whereas consultation occurred at approximately 21-23 years, indicating a consultation delay of 5-6 years. Notably, while self-monitoring of symptoms was more frequent among women with endometriosis, it only modestly shortened consultation delays. This study provides evidence from Japan that consultation delay persists despite active self-monitoring of symptoms, highlighting the influence of educational and cultural barriers on health-seeking behavior. These findings underscore the importance of integrating menstrual education with clinical guidance to promote timely gynecologic consultation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0721-832X 2026 Age-related changes in the orbital pulley array of older Japanese adults with acquired exotropia EN Reika Kono Department of Ophthalmology,, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ichiro Hamasaki Lino Eye Clinic Fumiko Kishimoto Division of Ophthalmology, Ibara City Hospital Kiyo Shibata Lino Eye Clinic Shin Morisawa Department of Ophthalmology,, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology,, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Purpose: To evaluate age-related changes in the orbital pulley array using magnetic resonance imaging (MRI) in older Japanese adults with acquired exotropia (XT) compared with young healthy participants (YHP). Methods: In this retrospective cross-sectional case series, MRI images of 30 eyes from fifteen patients (age ≥ 60 years) with distance XT and no high myopia were compared with those of 14 eyes from seven YHP. Rectus muscle (RM) pulley positions relative to the globe center were assessed. The lateral rectus muscle–superior rectus (LR–SR) band was evaluated for rupture. Results: Mean age of patients with XT was 73.7 ± 5.5 years. Compared with YHP, patients with XT showed significant inferior displacement of the lateral rectus (LR) pulley (–3.6 ± 1.2 mm vs. − 2.0 ± 1.1 mm, p < 0.01) and temporal displacement of the superior rectus (SR) pulley (–0.4 ± 1.2 mm vs. − 1.6 ± 0.8 mm, p < 0.01). No significant differences were observed in medial rectus or inferior rectus pulley positions. Inferior LR pulley displacement correlated with inferior SR pulley displacement (r = 0.41, p = 0.03), whereas no significant relationship was observed between LR pulley position and MR or IR pulley position. Rupture of the LR–SR band was observed in 24 orbits (80.0%). Conclusion: Older Japanese adults with XT exhibit localized pulley displacement and LR–SR band rupture. These structural changes differ from the global sagging observed in sagging eye syndrome and may contribute to the pathogenesis of acquired exotropia in older adults. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2197-1153 13 1 2026 Association between discoid lateral meniscus and medial meniscus posterior root tear: A retrospective cohort study e70666 EN Ryosuke Yamashita Department of Orthopaedic Surgery, Okayama University Hospital Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Hospital Keisuke Kintaka Department of Orthopaedic Surgery, Kochi Health Sciences Center Koki Kawada Department of Orthopaedic Surgery, Okayama University Hospital Toshiki Kohara Department of Orthopaedic Surgery, Okayama University Hospital Takayuki Furumatsu Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Purpose: Medial meniscus (MM) posterior root tear (PRT) has gained increasing attention because of its biomechanical impact and rapid progression to osteoarthritis. Identifying the risk factors for MMPRT is essential for early diagnosis. Although the discoid lateral meniscus (DLM) is a common congenital variant, no studies have reported on the relationship between MMPRT and DLM. This study aimed to examine the relationship between MMPRT and DLM. Methods: This retrospective cohort study included 94 matched knees that underwent arthroscopic surgery between 2015 and 2021 (58 with MMPRT and 36 with other MM injuries). The matching was performed according to age and sex. Morphological analysis of the lateral meniscus (LM) was performed using coronal magnetic resonance imaging (MRI). DLM was defined as an LM ratio (LM width/tibial width) > 0.20. LM width, LM ratio and DLM prevalence were compared between the two groups. In the MMPRT group, subgroup analysis compared the preoperative and 1-year postoperative clinical outcomes between patients with and without DLM. Results: The PRT group showed significantly greater LM width (12.6 ± 3.1 mm vs. 11.1 ± 2.2 mm; p = 0.03) and LM ratio (0.18 ± 0.04 vs. 0.16 ± 0.03; p = 0.01) compared with the other group. The incidence of DLM was also significantly higher in the PRT group (29.3% vs. 8.3%; p = 0.02). No significant differences in clinical scores were observed between the two subgroups either preoperatively or 1 year postoperatively. However, both groups demonstrated significant improvement in all clinical outcomes 1 year postoperatively (p < 0.01). Conclusions: DLM was significantly more prevalent in patients with MMPRT than in those with other MM injuries. Favourable clinical outcomes were achieved following pullout repair in MMPRT knees regardless of the presence of DLM. Level of Evidence: Level III, retrospective cohort study. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 11 2026 Rice Genotype-Dependent Phyllosphere Microbiome Assembly and Isolation of Antagonistic Burkholderia for Sheath Blight Biocontrol 4879 EN Andrews Danso Ofori State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University Zohreh Nasimi State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University Muhammad Irfan Ahmed State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University Yaoting Yan State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University Wang Li State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University Abdul Ghani Kandro State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University Kazunori Okada Agro-Biotechnology Research Center, The University of Tokyo Keiichi Mochida Bioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource Science Yoshiteru Noutoshi Graduate School of Environmental and Life Science, Okayama University Aiping Zheng State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University Rice sheath blight (RSB), caused by Rhizoctonia solani, causes 10–50% yield losses globally. Using 16S rRNA sequencing of 100 rice cultivars, we found that resistant varieties harbor significantly more diverse bacterial communities (3230 OTUs; 2064 unique) than susceptible cultivars (599 OTUs; 36 unique). Resistant varieties were enriched in beneficial Burkholderiaceae, Bacillaceae, and Pseudomonadaceae, while Sphingobacteriaceae and Enterobacteriaceae were predominant in the susceptible rice varieties. From the 260 bacterial isolates, Burkholderia vietnamiensis J14EPLEAF2 presented potent antifungal activity (77% inhibition), suppressed lesion development, and abolished sclerotia formation. This strain displayed multiple plant growth-promoting traits, enhanced seed germination, and primed defense responses by upregulating PR5 and PR10. Hypersensitive response assays confirmed B. vietnamiensis as non-pathogenic, unlike B. gladioli and B. cepacia. This study identifies B. vietnamiensis J14EPLEAF2 as a promising, safe biocontrol agent for sustainable rice disease management. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 11 2026 Genomic Basis of Lifestyle Divergence in Rice-Associated Burkholderia: From Pathogenesis to Plant Growth Promotion 4730 EN Andrews Danso Ofori State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University Zohreh Nasimi State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University Frank Kwekucher Ackah Department of Crop Science, School of Agriculture and Natural Sciences, University of Cape Coast Muhammad Irfan Ahmed State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University Yaoting Yan State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University Wang Li State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University Abdul Ghani Kandro State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University Kazunori Okada Agro-Biotechnology Research Center, The University of Tokyo Keiichi Mochida Bioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource Science Yoshiteru Noutoshi Graduate School of Environmental and Life Science, Okayama University Aiping Zheng State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University The genus Burkholderia encompasses both plant pathogenic and beneficial species, yet the genomic determinants underlying this lifestyle divergence remain poorly understood. Using 16S rRNA sequencing of 100 rice cultivars, our companion study demonstrated that resistant varieties are enriched in beneficial Burkholderiaceae, leading to the isolation of three phenotypically contrasting strains. Here, we present comparative genomic analyses of non-pathogenic biocontrol strain Burkholderia vietnamiensis J14EpLeaf2 and pathogenic strains Burkholderia gladioli A1EpSeed5 and Burkholderia cepacia J14Eple. Pathogenic strains possess significantly larger genomes (8.36–8.46 Mb) enriched in mobile genetic elements compared to the streamlined 6.95 Mb genome of B. vietnamiensis. CAZyme analysis revealed broader repertoires of glycoside hydrolases and polysaccharide lyases in pathogens, consistent with enhanced plant cell wall degradation. B. gladioli possesses a complete T3SS and expanded T6SS with 301 predicted effectors, while B. cepacia lacks structural T3SS genes but harbors 271 candidate effectors predicted to be secreted via alternative secretion pathways, compared to 180 in B. vietnamiensis. Notably, B. cepacia harbors cystic fibrosis-associated markers (cable pili, ZmpA/ZmpB), raising significant biosafety concerns that preclude its agricultural application. LC-MS validated IAA, ornibactin, and AHL production in B. vietnamiensis, supporting its plant growth-promoting and biocontrol functions. Computational PPI networks predicted distinct interaction landscapes requiring experimental validation. This study provides a genomic framework for distinguishing pathogenic from beneficial Burkholderia and supports B. vietnamiensis as a safe biocontrol agent while cautioning against B. cepacia J14Eple. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1877-959X 17 3 2026 Epidemiological and molecular characteristics of human-biting ticks in areas endemic to Japanese spotted fever: a prospective study 102635 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Sunami Sumiyoshi Fujii Hospital Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenta Nakamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidemasa Akazawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshimi Hidani Numakuma Hospital Kouji Kida Okayama Prefectural Institute for Environmental Science and Public Health Go Tsurumi Okayama Prefectural Institute for Environmental Science and Public Health Hideharu Hagiya Tick-borne diseases (TBDs) have become a great health concern worldwide. This study aimed to clarify the pathogenic and potentially pathogenic microorganisms carried by ticks that bite humans and to assess the risk of acquiring tick-borne infections in regions endemic for Japanese spotted fever. Tick specimens were prospectively collected from patients who presented with tick bites at 10 medical institutions in the Hiroshima, Okayama, and Kagawa prefectures, Japan between May 2023 and December 2024. The evaluated parameters included the estimated bite location, date of bite, patient age, tick species identification, and presence of TBD-associated pathogens in the collected ticks. Overall, 191 ticks were collected from 181 patients. Among patients with known sex, females were slightly more prevalent than males, and 45.9% of the patients were aged ≥ 70 years. Seasonal distribution demonstrated a peak incidence from April to July, with the highest number of cases observed in June (29.3%). Amblyomma testudinarium was the predominant species, accounting for 152 (79.6%) ticks, followed by Haemaphysalis hystricis (7.3%) and Haemaphysalis longicornis (6.8%). Nymphs represented the majority (83.8%), whereas adults and larvae accounted for 14.6% and 1.0%, respectively. A total of 27 ticks (14.1%) carried Rickettsia species, including two identified species (Rickettsia tamurae and Rickettsia monacensis) and one unclassified Rickettsia species. However, molecular analysis did not detect any known human pathogenic organisms, including Ehrlichia and Anaplasma species, Francisella tularensis, or Rickettsia japonica. Further epidemiological data regarding the abundance of tick-borne pathogens will provide valuable surveillance information with significant clinical utility for disease diagnosis and management. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-1262 41 1 2026 Navigating long-term patient-reported outcomes after colorectal cancer surgery in older adults: ostomy, nutritional status, and living conditions as determinants in a prospective cohort study 97 EN Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Hospital Shiori Itagaki Perioperative Management Center, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Rie Tamura Perioperative Management Center, Okayama University Hospital Yoshikazu Matsuoka Perioperative Management Center, Okayama University Hospital Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Hospital Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Hospital Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Hospital Yoshitaka Kondo Department of Gastroenterological Surgery, Okayama University Hospital Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Hospital Purpose To elucidate determinants of long-term patient-reported outcomes (PROs) following colorectal cancer (CRC) surgery in older adults, focusing on the impact of ostomy creation, nutritional status, and living conditions on functional independence and quality of life (QoL). Methods This single-center, prospective observational study included patients aged ≥ 75 years who underwent elective CRC resection between July 2020 and December 2023. Comprehensive geriatric assessments were performed preoperatively, and PROs—including Instrumental Activities of Daily Living (IADL), EQ-5D, and EQ-VAS—were reassessed more than one year postoperatively. The primary outcomes were postoperative changes in IADL and QoL. Modified Poisson regression identified independent determinants of long-term decline in each PRO domain. Results Sixty patients (median age 79 years; 60% female) completed one-year follow-up. IADL declined in 35.6% of patients, EQ-5D in 26.6%, and EQ-VAS in 43.3%. Multivariate analysis revealed that stoma formation was independently associated with IADL decline (adjusted RR = 3.37, 95% CI 1.50–7.54, p = 0.003), whereas living alone postoperatively correlated with preserved IADL (adjusted RR = 0.14, 95% CI 0.02–0.87, p = 0.035). Low preoperative BMI (< 20 kg/m2) was significantly associated with EQ-5D deterioration (adjusted RR = 5.25, 95% CI 1.20–22.94, p = 0.027). No significant predictors were identified for EQ-VAS decline. Conclusion Among older CRC patients, stoma creation predicts long-term functional decline, while low BMI predicts QoL deterioration. Conversely, independent living appears protective for functional maintenance. Integrating PROs into perioperative assessment and tailoring surgical, nutritional, and social interventions may enhance survivorship outcomes in this aging population. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 18 7 2026 Predictive Nomogram for Recurrence After Upfront Surgery for Resectable Pancreatic Ductal Adenocarcinoma: A Multicenter Study (OS-HBP-2) 1181 EN Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masayoshi Hioki Department of Surgery, Fukuyama City Hospital Takehiro Okabayashi Department of Surgery, Kochi Health Sciences Center Toru Kojima Department of Surgery, Okayama Saiseikai General Hospital Yoshikatsu Endo Department of Surgery, Himeji Red Cross Hospital Daisuke Nobuoka Department of Surgery, Fukuyama City Hospital Kenta Sui Department of Surgery, Kagawa Prefectural Hospital Masaru Inagaki Department of Surgery, National Hospital Organization Fukuyama Medical Center Susumu Shinoura Department of Surgery, Tsuyama Chuo Hospital Masashi Kimura Department of Surgery, Matsuyama Shimin Hospital Tatsuo Matsuda Department of Surgery, Tenwakai Matsuda Hospital Hideki Aoki Department of Surgery, National Hospital Organization Iwakuni Clinical Center Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background/Objectives: Postoperative recurrence is a critical issue in the treatment of resectable pancreatic ductal adenocarcinoma (rPDAC). Moreover, the prognosis after early recurrence is extremely poor. This study aimed to develop a recurrence prediction model and to define early recurrence after upfront surgery (UFS) for rPDAC. Methods: This multicenter retrospective study included patients who underwent UFS for anatomically rPDAC between January 2013 and December 2017. Multivariate analyses were conducted to identify the risk factors for recurrence-free survival and to construct a recurrence prediction model. Subsequently, a minimum p value approach was used to determine the optimal cutoff values for early and late recurrence. Results: The cohort included 603 patients (325 men and 278 women). During the median follow-up period of 25 months (interquartile range, 15–38 months), 381 patients (63.2%) experienced a recurrence. Multivariate analyses revealed carbohydrate antigen 19-9 ≥37 U/mL (hazard ratio [HR], 1.58; p < 0.001), tumor size ≥ 2.2 cm (HR, 1.59; p < 0.001), lymph node metastasis (HR, 1.86; p < 0.001), R1 resection (HR, 1.56; p = 0.002), and no adjuvant chemotherapy (HR, 1.54; p < 0.001) as independent predictors. The recurrence prediction model demonstrated an area under the curve of 0.72–0.75. The optimal threshold for early and late recurrences was a recurrence-free interval of five months. Carbohydrate antigen 19-9 ≥ 156 U/mL was a significant predictor of early recurrence (OR, 3.28; p < 0.001). Conclusions: This study identified the prognostic risk factors for recurrence and developed a recurrence prediction model for patients undergoing UFS for rPDAC. Moreover, a recurrence-free interval of five months was identified as the optimal threshold for distinguishing between early and late recurrences. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 18 4 2026 Outcomes After Robot-Assisted Versus Open Pancreatoduodenectomy: A Propensity Score-Matching Analysis in a High-Volume Center (TAKUMI-7) 602 EN Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuzo Umeda Department of Hepatobiliary Pancreatic Surgery, Ehime University Graduate School of Medicine Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atene Ito Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naohiro Okada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shohei Yokoyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background/Objectives: Although the safety and feasibility of robot-assisted pancreatoduodenectomy (RPD) compared to open pancreatoduodenectomy (OPD) have been reported, studies investigating the advantages of RPD remain limited. Moreover, only a few studies have investigated the effects of robotic surgery on textbook outcomes (TO). Methods: This single-center retrospective study included 400 patients who underwent RPD and OPD at our institution between January 2017 and December 2025. Outcomes were compared between the RPD (n = 162) and OPD (n = 238) groups using propensity score-matching (PSM) analysis. The factors associated with TO were examined. Results: Before PSM, significant differences were observed between the groups. PSM yielded RPD (n = 117) and OPD (n = 117) with equal preoperative factors. The RPD group demonstrated a significantly shorter operative time (402 vs. 444 min, p < 0.001), lesser blood loss (75 vs. 270 mL, p < 0.001), shorter postoperative hospital stays (13 vs. 22 days, p < 0.001), and fewer major complications (17.1 vs. 44.4%, p < 0.001), resulting in a higher TO achievement rate (76.9 vs. 52.1%, p = 0.001). Adjusted multivariate analyses identified robotic surgery (odds ratio 3.04, p < 0.001) as an independent predictor of TO. Conclusions: This study demonstrated that RPD was potentially superior to OPD in terms of short-term outcomes. Robotic surgery was significantly associated with TO after pancreatoduodenectomy at the expert’s hand. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 22 2025 Prognosis Prediction Model After Upfront Surgery for Resectable Pancreatic Ductal Adenocarcinoma: A Multicenter Study (OS-HBP-2) 3694 EN Kosei Takagi Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ryuichi Yoshida Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuya Yasui Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masayoshi Hioki Department of Surgery, Fukuyama City Hospital Takehiro Okabayashi Department of Surgery, Kochi Health Sciences Center Toru Kojima Department of Surgery, Okayama Saiseikai General Hospital Yoshikatsu Endo Department of Surgery, Himeji Red Cross Hospital Daisuke Nobuoka Department of Surgery, Fukuyama City Hospital Kenta Sui Department of Surgery, Kagawa Prefectural Hospital Masaru Inagaki Department of Surgery, National Hospital Organization Fukuyama Medical Center Susumu Shinoura Department of Surgery, Tsuyama Chuo Hospital Masashi Kimura Department of Surgery, Matsuyama Shimin Hospital Tatsuo Matsuda Department of Surgery, Tenwakai Matsuda Hospital Hideki Aoki Department of Surgery, National Hospital Organization Iwakuni Clinical Center Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background/Objectives: Upfront surgery (UFS) remains the standard treatment for patients with resectable pancreatic ductal adenocarcinoma (PDAC). We aimed to investigate the prognostic factors for survival after UFS in patients with resectable PDAC and to develop a prognostic prediction model. Methods: This multicenter, retrospective study included 603 patients who underwent UFS for resectable PDAC between January 2013 and December 2017. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival (OS). We constructed a prognostic prediction model for OS after UFS. An internal validation was performed to evaluate the discriminative performance of the model. Results: The 1-, 3-, and 5-year OS rates were 83.7%, 48.2%, and 37.5%, respectively. The Cox proportional hazards model showed that tumor size > 2 cm (hazard ratio [HR] 1.50, p = 0.001); tumor contact with the portal and superior mesenteric veins of ≤180° (HR 1.47, p = 0.003); carbohydrate antigen 19-9 levels of 40 to 500 U/mL (HR 1.59, p = 0.002) and ≥500 U/mL (HR 2.16, p < 0.001); and a modified Glasgow Prognostic Score of two (HR 1.56, p = 0.038) were predictors associated with OS. The prognostic prediction model for 5-year OS demonstrated an area under the curve of 0.68. The calibration plots indicate a concordance index of 0.63. Conclusions: We identified the preoperative prognostic factors for OS and developed a prognostic prediction model to estimate OS in patients undergoing UFS for resectable PDAC. Our model may be useful and internally validated for predicting OS. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 18 2025 Outcomes of Robotic Pancreatectomy in the Octogenarian: A Multicenter Retrospective Cohort Study 3038 EN Kosei Takagi Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuichiro Uchida Department of Surgery, Fujita Health University Tomokazu Fuji Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takeshi Takahara Department of Surgery, Fujita Health University Kazuya Yasui Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takeyoshi Nishiyama Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ichiro Uyama Department of Advanced Laparoscopic and Robotic Surgery, Fujita Health University Koichi Suda Department of Surgery, Fujita Health University Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background/Objectives: Due to the increasing incidence of pancreatic and periampullary cancers with advancing age, coupled with the growing evidence supporting minimally invasive pancreatectomy, the demand for such procedures is rising. However, data on the feasibility of robotic pancreatectomy in octogenarian patients remain scant. This study aimed to investigate overall outcomes of robotic pancreatectomy and evaluate its safety and feasibility in octogenarian patients. Methods: A multicenter, retrospective study was conducted, including 380 patients who underwent robotic pancreatectomy at two high-volume centers in Japan from April 2020 to December 2024. Using prospectively collected data, we compared outcomes between younger patients (<80 years) and octogenarian patients (≥80 years). Multivariable logistic regression analyses were performed to assess the impact of age on postoperative outcomes. Results: Among the 380 patients, with a median age of 72 (interquartile range: 61–77) years, 213 underwent robotic pancreatoduodenectomy (RPD), and 167 underwent robotic distal pancreatectomy (RDP). Octogenarian patients were found to have more comorbidities and a higher incidence of malignant diseases. Octogenarians experienced significantly longer hospital stays post-RPD (22 [octogenarian; n = 36] vs. 14 [younger; n = 177] days, p < 0.001) and post-RDP (14 [n = 23] vs. 10.5 [n = 144] days, p = 0.02), yet their perioperative outcomes were comparable. Multivariable analyses indicated that age (≥80 years) was not a significant risk factor for major complications following robotic pancreatectomy (odds ratio, 1.33; 95% confidence interval, 0.59–2.84; p = 0.479). Conclusions: This multicenter study conducted at high-volume centers suggests that robotic pancreatectomy can be safely performed in carefully selected octogenarian patients. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2026 Atezolizumab + Chemotherapy in Older Patients With Lung Cancer in Japan 1 13 EN Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Hospital Makoto Nishio Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Atsushi Osoegawa Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine Eiki Kikuchi Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University Hideharu Kimura Department of Respiratory Medicine, Kanazawa University Hospital Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Ichiro Yoshino International University of Health and Welfare Narita Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Kozo Yoshimori Department of Clinical Oncology, Japan Anti‐Tuberculosis Association, Fukujuji Hospital Kazuhiko Shibata Department of Medical Oncology, Kouseiren Takaoka Hospital Takeshi Tsuda Division of Respiratory Medicine, Toyama Prefectural Central Hospital Masahiro Seike Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Takahiro Ota Department of Respiratory Medicine, Kyoto City Hospital Koichi Samata Chugai Pharmaceutical Co., Ltd. Yuki Kobayashi Chugai Pharmaceutical Co., Ltd. Misa Tanaka Chugai Pharmaceutical Co., Ltd. Akihiko Gemma Nippon Medical School Pivotal phase 3 trials leading to the approvals of atezolizumab─chemotherapy combinations for non-small cell and extensive-stage small cell lung cancer (NSCLC and ES-SCLC) had strict eligibility criteria. J-TAIL-2 was a prospective, observational study in Japan that evaluated atezolizumab regimens for advanced NSCLC/ES-SCLC, including patients ineligible for global trials. The primary endpoint was 12-month overall survival (OS); safety and efficacy in subgroups defined by age, ECOG PS and/or G8 score, and creatinine clearance were key secondary endpoints. As of February 3, 2023, 1217 patients were treated in clinical practice based on Japanese labeling/treatment guidelines. Patients received atezolizumab with either carboplatin and nab-paclitaxel (atezo + CnP), carboplatin/cisplatin and pemetrexed (atezo + PP), or bevacizumab and carboplatin and paclitaxel (atezo + bev + CP) in the NSCLC cohort (n = 814) or with carboplatin and etoposide (atezo + CE) in the ES-SCLC cohort (n = 403). Overall, 53.5% were ≥ 70 years old, and 11.8% had ECOG PS ≥ 2; median G8 scores were 13 (NSCLC cohort) and 12 (ES-SCLC). Patients < 70 and ≥ 70 years had similar median (m)OS and progression-free survival (mPFS) across treatment regimens. Patients with ECOG PS < 2 and G8 score ≥ median had the highest mOS/PFS vs. patients with ECOG PS ≥ 2 and G8 score<median. Patients ≥ 70 years had higher incidence of Grade ≥ 3 adverse events with atezo + CnP and atezo + PP than patients < 70 years; incidences were similar between groups for other regimens. Older vs. younger patients also had higher incidence of interstitial lung disease. Overall, these results suggest that atezolizumab-containing regimens remain effective in older patients, with no new safety signals. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 15 10 2026 Exploratory Analysis of Serum IGF-I Levels and Symptom Trajectories in Long COVID During the Omicron Period 3702 EN Atsuhito Suyama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Matsuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Takase Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Omura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Oguni Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Ueda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Although several risk factors have been reported for long COVID (LC), reliable biomarkers for this illness remain lacking. Insulin-like growth factor (IGF)-I, a major mediator of growth hormones, plays an important role in metabolism, neuroprotection, and systemic homeostasis, and therefore may be useful in predicting the severity and prognosis of LC. Methods: This study included patients who visited a specialized clinic for long COVID between 2022 and 2025 during the Omicron period and had serum IGF-I measurements taken. IGF-I levels were expressed as age- and sex-adjusted standard deviation scores (IGF-I SD), and patients were classified into low (SD < −1.0), normal (−1.0 ≤ SD < 1.0), and high (SD ≥ 1.0) groups. Clinical characteristics, patient-reported outcomes, laboratory data, and follow-up duration were analyzed. Results: A total of 811 patients were included (median 42 years; 52.5% female). Compared with the normal group, the low-IGF-I group exhibited higher fatigue (FAS: 37.0 vs. 34.0; p < 0.05) and depressive (SDS: 50.0 vs. 49.0; p < 0.05) status. Multivariable linear regression analyses identified lower IGF-I SD as independently associated with higher scores of both FAS and SDS. IGF-I SD values showed negative correlations with ferritin (ρ = −0.125, p < 0.05) and TSH (ρ = −0.202, p < 0.01) and positive correlations with albumin (ρ = 0.227, p < 0.01) and FT4 (ρ = 0.165, p < 0.01). Among the 237 patients who completed follow-up, the median duration from the initial visit to recovery tended to be longer in the low-IGF-I group (221 days) compared with the normal (191 days) and high (109 days) groups, although these differences were not statistically significant overall. In patients aged < 50 years, the low-IGF-I group showed a relatively longer follow-up duration (p < 0.05). Furthermore, the low-IGF-I group had a longer time to recovery compared to the high-IGF-I group (p < 0.05), and this difference was more pronounced in patients under 50 years of age, with significant differences observed among the three IGF-I groups. Conclusions: Lower IGF-I levels in LC may be associated with greater fatigue and depressive symptoms and longer recovery time, particularly in younger patients. Further studies are needed to clarify the clinical significance of these findings. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0039-6060 195 2026 Biliverdin supplementation in perfusate and preservation solution attenuates ischemia-reperfusion injury in a rat donation-after-circulatory-death heart transplantation model 110231 EN Kohei Tokioka Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Hirayama Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Ageta Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuro Igawa Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Aokage Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Heart transplantation faces a persistent donor shortage; therefore, hearts from donation after circulatory death have become a feasible option despite unavoidable warm ischemia and subsequent ischemia-reperfusion injury. Biliverdin, an endogenous bile pigment with strong antioxidant and anti-inflammatory properties, has shown protective effects against ischemia-reperfusion injury in several organ transplantation models. Whether biliverdin attenuates warm ischemic injury in donation after circulatory death heart transplantation remains unclear. This study evaluated biliverdin supplementation in the perfusate and preservation solution in a rat donation after circulatory death model. Methods: Circulatory death was induced under deep anesthesia, and warm ischemia was maintained for 18 minutes, including the mandatory 5-minute stand-off period. Donor hearts were then flushed and subsequently cold-stored in the same biliverdin-supplemented extracellular-type trehalose–containing Kyoto solution, whereas control grafts received extracellular-type trehalose–containing Kyoto without biliverdin at both stages before heterotopic transplantation. Grafts were assessed at 3 and 24 hours after reperfusion (n = 6 per group). Evaluations included early graft recovery, myocardial injury markers, histological and ultrastructural changes, and inflammatory and stress-response gene expression. Results: Biliverdin significantly improved early graft recovery, shortening reanimation time and increasing left ventricular fractional shortening at 24 hours. Serum troponin I levels were lower in biliverdin-treated grafts. Biliverdin also reduced histological injury and inflammatory cell infiltration. Ultrastructural analysis showed preserved mitochondrial architecture and ultrastructural integrity. Early proinflammatory gene expression was suppressed. Conclusion: Biliverdin supplementation in the perfusate and preservation solution attenuates ischemia-reperfusion injury in the experimental rat donation after circulatory death heart transplantation model. These findings provide proof of concept for further mechanistic and translational evaluation of biliverdin for myocardial protection in donation after circulatory death. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0007-1048 208 6 2026 Decreased renal function predicts severe cytokine release syndrome after CAR-T-cell therapy for large B-cell lymphoma 2124 2133 EN Yasuyuki Arai Department of Hematology, Graduate School of Medicine, Kyoto University Tomoyasu Jo Department of Hematology, Graduate School of Medicine, Kyoto University Takayuki Sato Department of Hematology and Oncology, Kurashiki Central Hospital Masatoshi Sakurai Division of Hematology, Department of Medicine, Keio University School of Medicine Daisuke Kaji Department of Hematology, Toranomon Hospital Toshio Kitawaki Department of Hematology, Graduate School of Medicine, Kyoto University Kazuyuki Shimada Department of Hematology and Oncology, Nagoya University Graduate School of Medicine Tatsu Shimoyama Division of Clinical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Satoshi Yoshihara Department of Hematology, Hyogo Medical University Hospital Shinichi Makita Department of Hematology, National Cancer Center Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Go Yamamoto Department of Hematology, Toranomon Hospital Keisuke Kataoka Division of Hematology, Department of Medicine, Keio University School of Medicine Emiko Sakaida Department of Hematology, Chiba University Hospital Hideki Goto Department of Hematology, Hokkaido University Hospital Yasuhiro Nakashima Department of Hematology, Osaka Metropolitan University Hospital Akiyo Yoshida Department of Hematology, Kanazawa University Hospital Yoshihiro Umezawa Department of Hematology, Institute of Science Tokyo Hospital Haryoon Kim Division of Hematology, Department of Medicine, Keio University School of Medicine Motohiro Kato Department of Pediatrics, The University of Tokyo Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Koji Kato Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital Cytokine release syndrome (CRS) remains a major toxicity of chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL), and robust pre-infusion predictors are needed for risk-adapted management. We retrospectively analysed LBCL patients in the Japanese nationwide registry who underwent CD19 CAR-T-cell therapy between 2019 and 2024. Among 900 patients (median age 62 years), cumulative incidences of CRS within 30 days after infusion were 75.0% for any grade, 20.8% for grade ≥ 2 and 14.0% for grade ≥ 3. In multivariable analysis, lower estimated glomerular filtration rate (eGFR) (adjusted hazard ratio [aHR] 1.108 per 10 mL/min per 1.73 m2 decrease; 95% confidence interval [CI] 1.015–1.209; p = 0.022), higher ferritin (aHR 1.006 per 100 ng/mL; 95% CI 1.001–1.010; p = 0.016), C-reactive protein (CRP) (aHR 1.142 per mg/dL; 95% CI 1.091–1.195; p < 0.001) and lactate dehydrogenase (LDH) (aHR 1.073 per 100 U/L; 95% CI 1.008–1.142; p = 0.028) independently predicted grade ≥ 2 CRS. We then built a four-factor CRS pre-infusion risk evaluation model, cytokine release syndrome-pre-infusion risk evaluation (CRS-PRE), that stratified grade ≥ 2 CRS risk into low, intermediate and high groups with incidences of 2.8%, 26.0% and 50.0% respectively. Decreased eGFR, a surrogate of host renal reserve, with elevated ferritin, CRP and LDH emerged as predictors of high-grade CRS. The CRS-PRE may facilitate risk-adapted monitoring and intervention in clinical practice. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Post-weaning maternal presence exerts a protective effect against social isolation-induced behavioural alterations in mice 44248 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Eriko Kitano Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Parental “watchful presence” is considered an important factor influencing behavioural and emotional development in offspring across mammalian species, including humans. However, the effects of such parental presence remain insufficiently understood, even in human studies. In laboratory mice, offspring are typically weaned at approximately three weeks of age, leaving the impact of post-weaning maternal presence on behavioural development largely unexplored. This study aimed to investigate whether maternal presence in an adjacent cage after weaning can attenuate behavioural effects of social isolation stress in mice. Furthermore, we sought to assess whether this experimental paradigm could serve as a novel animal model for studying the effects of parental watchful presence, with potential relevance to human parent–child relationship research. Mouse pups were weaned at postnatal day 21 and housed either adjacent to their mother (maternal presence group) or without maternal presence (control group). The pups were subsequently housed either in groups with littermates or individually until eight weeks of age. After maturation, behavioural tests were conducted to assess locomotor activity, anxiety-like behaviour, social behaviour, and depression-like behaviour. In group-housed mice, maternal presence did not influence behavioural outcomes. However, in individually housed mice, maternal presence partially attenuated social isolation-induced behavioural alterations, suggesting a subtle protective effect, including hyperlocomotion, reduced anxiety-like behaviour, and abnormal social interactions. Our findings demonstrate that maternal presence during the post-weaning period can offer a protective effect against certain behavioural abnormalities induced by social isolation stress in mice.　This simple adjacent-cage paradigm provides a novel and practical model for elucidating the impact of parental watchful presence on behavioural and emotional development, offering insights relevant to the understanding of parent–child relationships in humans. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 31 6 2026 Barriers and facilitators for online genetic care for hereditary cancer in Japan: findings from surveys of both clients and medical professionals 1063 1074 EN Sayaka Ueno Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusaku Urakawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumino Kato Arisa Ueki Division of Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research Keika Kaneko Division of Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research Koji Matsumoto Division of Clinical Genetics, Hyogo Cancer Center Hiromi Sugawara Division of Clinical Genetics, Hyogo Cancer Center Sayoko Takeuchi Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Reiko Yoshida Department of Medical Genetics and Genomics, Saitama Cancer Center Miho Kakuta Center for Genomic Diagnosis, International University of Health and Welfare (IUHW) Narita Hospital Kiwamu Akagi Center for Genomic Diagnosis, International University of Health and Welfare (IUHW) Narita Hospital Kazuo Tamura Center for Genomic Diagnosis, International University of Health and Welfare (IUHW) Narita Hospital Akira Hirasawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Online genetic care can offer a promising solution to the shortage of qualified medical professionals in genetic medicine, which leads to regional disparities in access. However, despite global adoption, its use in Japan remains limited. Methods Two questionnaire surveys were conducted to investigate potential needs and barriers regarding online genetic care: one involving 858 medical professionals (738 physicians and 120 genetic counselors or nurses), and the other involving 443 clients who received in-person genetic counseling. Results Only 14.0% of the medical professionals had experience with online genetic care, although 85.9% of the professionals engaged in cancer genetics were willing to consider providing it in the future. Notably, a discrepancy was found regarding hospital selection: clients prioritized access to specialized medical care, whereas professionals assumed clients valued accessibility for family members. Professionals expressed greater concerns about adequacy of online communication, client environments and internet security. Among clients, 89.1% estimated they would sufficiently understand and accept total content of counseling session if were conducted online. Older age and infrequent internet use were associated with lower acceptance and higher anxiety regarding online methods. Concerns about ability to use the necessary technology affected clients’ willingness to encourage online care for their relatives. Conclusion Online genetic care shows high potential for client acceptance and can effectively address regional disparities in Japan. To bridge the gap between client needs and professional perceptions and to overcome the digital divide, it is necessary to develop secure, accessible systems and provide education for both patients and healthcare providers. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 6 2026 Minimal Association Between Immunoglobulin A Coating and Gut Microbiota Alterations Induced by High-Fat Diets with Distinct Fatty Acid Compositions 2645 EN Mao Teraoka Faculty of Environmental, Life, Natural Science and Technology, Okayama University Naoki Nishino Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tianyang Wang Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kuiyi Chen Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takeshi Tsuruta Faculty of Environmental, Life, Natural Science and Technology, Okayama University High-fat diets (HFDs) containing dietary fats with different fatty acid (FA) compositions alter gut microbiota composition in a fat-source-dependent manner. Immunoglobulin A (IgA) and unabsorbed lipids in the distal gut are potential regulators of the gut microbiota. However, their roles in mediating gut microbiota alterations induced by dietary fats with different FA compositions remain unclear. This study aims to examine the associations of these two factors with fat-source-dependent gut microbiota alterations. BALB/c mice were fed a normal diet, a high-lard diet, a high-olive oil diet, or a high-soybean oil diet for 27 weeks. Fecal samples were collected to assess microbiota composition, the IgA coating index (ICI)—which quantifies the extent of IgA coating on gut microbiota—and fecal fatty acid concentrations. At the phylum level, the concentration of fecal total long-chain fatty acids (LCFAs) was positively correlated with the relative abundance (RA) of Bacillota and negatively correlated with that of Bacteroidota. In addition, a trend toward a positive association between the RA and the ICI was observed for Bacillota but not for Bacteroidota. At the genus level, the RAs of 12 taxa were positively correlated with fecal LCFA concentrations, whereas those of 6 taxa were negatively correlated. Although the RAs of most taxa appeared to be influenced by unabsorbed lipids and additional factors, only four Bacillota genera exhibited a positive correlation between the RA and the ICI. Our observations suggest that IgA coating of the gut microbiota may have a minimal association with fat-source-specific alterations in gut microbiota composition during HFD intake. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 18 10 2026 Activation of TAS2R Signaling by Diphenidol Suppresses Tumor Growth and Remodels the Tumor Immune Microenvironment in Oral Squamous Cell Carcinoma 1527 EN Nisrina Ekayani Nasrun Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido Akihiko Tanimura Division of Pharmacology, Department of Oral Biology, School of Dentistry, Health Sciences University of Hokkaido Koki Yoshida Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido Osamu Uehara Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido Yuki Kunisada Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyofumi Takabatake Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Hosoya Division of Craniofacial Development and Tissue Biology, Tohoku University Graduate School of Dentistry Hiroaki Takebe Division of Histology, Department of Oral Biology, School of Dentistry, Health Sciences University of Hokkaido Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Abiko Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido Muhammad Ruslin Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hasanuddin University Tsuyoshi Shimo Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido Background: Oral squamous cell carcinoma (OSCC) remains a clinically challenging malignancy characterized by aggressive behavior and limited therapeutic options. Bitter taste receptors (TAS2Rs), expressed across multiple tissues and cancer types, have recently emerged as regulators of tumor biology and immune responses; however, their functional significance in OSCC remains poorly understood. Methods: Immunohistochemical analysis was performed using surgically resected human tongue OSCC specimens and a tissue microarray (TMA) cohort. In parallel, four TAS2R agonists were evaluated in SCC7 cells to assess intracellular calcium responses. RNA sequencing was conducted to analyze transcriptional changes following diphenidol treatment, and functional assays, including proliferation, migration, and apoptosis analyses, were performed in vitro. Antitumor effects were further evaluated in a syngeneic SCC7 mouse model, followed by TUNEL staining and flow cytometry to assess apoptosis and immune cell infiltration. Results: TAS2R38 expression was markedly upregulated in dysplastic and invasive OSCC lesions with predominant nuclear localization and was associated with histological grade and clinical stage, indicating an early and sustained alteration during tumor progression. Among the agonists tested, diphenidol most strongly induced IP3-dependent intracellular Ca2+ elevation. RNA sequencing revealed upregulation of Il1rl1 and Lzts2. Functionally, diphenidol significantly suppressed SCC7 cell proliferation and migration and induced apoptosis in vitro. In vivo, diphenidol reduced tumor volume and weight and increased apoptotic activity. Flow cytometry demonstrated a marked reduction in tumor-infiltrating CD4+CD25+Foxp3+ regulatory T cells, indicating modulation of the tumor immune microenvironment. Conclusions: TAS2R activation by diphenidol suppresses tumor growth through both tumor-intrinsic mechanisms and modulation of the tumor immune microenvironment in OSCC. These findings define TAS2R-mediated calcium signaling as a novel axis linking tumor progression and immunoregulation. Given that diphenidol is a clinically approved drug with an established safety profile, our results provide a strong rationale for TAS2R-targeted drug repurposing strategies in cancer therapy. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 0090-3493 54 6 2026 Institutional Variability in Brain-Dead Organ Donation Processes and Practices: A Multicenter Cohort Study 1319 1328 EN Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mineji Hayakawa Department of Emergency Medicine, Hokkaido University Hospital Shoji Yokobori Department of Emergency and Critical Care Medicine, Nippon Medical School Kei Nishiyama Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science Takahiro Atsumi Department of Emergency and Disaster Medicine, Hamamatsu University School of Medicine Osamu Tasaki Acute and Critical Care Center, Nagasaki University Hospital Junya Tsurukiri Emergency and Critical Care Medicine, Tokyo Medical University Hachioji Medical Center Mariko Hayamizu Department of Emergency Medicine, Hokkaido University Hospital Shimon Murahashi Acute and Critical Care Center, Nagasaki University Hospital Munehiro Hayashi Department of Emergency and Critical Care Medicine, Japanese Red Cross Medical Center Takeshi Nishimura Department of Emergency and Critical Care Medicine, Hyogo Emergency Medical Center Yukari Goto Department of Emergency Medicine, Nagoya Ekisaikai Hospital Hiromichi Narumiya Department of Emergency and Critical Care Medicine, Japanese Red Cross Kyoto Daini Hospital Atsushi Mizutani Department of Emergency Medicine, Hamamatsu Medical Center Mamoru Miyajima Emergency and Critical Care Center, Nagaoka Red Cross Hospital Junya Shimazaki Department of Emergency and Critical Care Medicine, Kansai Medical University Medical Center Takeshi Miura Department of Emergency and Critical Care Medicine, Institute of Medicine, University of Tsukuba Hospital Nozomu Shima Department of Emergency and Critical Care Medicine, Wakayama Medical University Kazuki Deuchi Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science Hitomi Nakayasu Emergency and Critical Care Medicine, Seirei Hamamatsu General Hospital Hitoshi Kano Department of Emergency and Critical Care Medicine, Nippon Medical School Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Japan Comprehensive Process for End-of-Life Care and Organ Donation after Brain Death (J-RESPECT) study group OBJECTIVES: To determine whether key institutional and clinical differences exist between highly and moderately active hospitals in Japan with respect to brain-dead organ donation practices. DESIGN: Retrospective multicenter cohort study. SETTING: Sixteen tertiary emergency and critical care centers across Japan. PATIENTS: All brain-dead organ donors from participating institutions who had at least one organ procured and transplanted between July 17, 2010, and December 31, 2023. Hospitals were categorized as highly active (≥ 14 donations) or moderately active (≤ 13 donations) during the study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Institutional donation practices were compared, including donor management strategies, use of vasopressors and corticosteroids, time intervals in the donation process, and frequency of multidisciplinary team meetings. A total of 204 donors were included; the median age was 47 years (interquartile range, 37–56), and 92 (45.1%) were female. Donor characteristics were similar between groups. Vasopressin was used in nearly all donors, though dosing protocols varied. Corticosteroid use was significantly higher in highly active hospitals compared with moderately active ones (58.3% vs. 38.0%; p = 0.004). Time from admission to coordinator notification was similar; however, time to family consent (median, 8 vs. 5 d; p < 0.001) and time to organ procurement (median, 12 vs. 9 d; p = 0.006) were longer in highly active hospitals. These hospitals also conducted more multidisciplinary meetings during donor management (median, 2 vs. 0; p < 0.001). CONCLUSIONS: Highly active hospitals demonstrated more intensive donor management practices, longer timeframes for key donation steps, and greater multidisciplinary engagement. Standardization of donation practices may enhance efficiency and support broader dissemination of effective institutional strategies to improve brain-dead organ donation rates in Japan. No potential conflict of interest relevant to this article was reported.

Japan Medical Association Acta Medica Okayama 2433-3298 9 3 2026 Post Hoc Analysis of Frailty and Tracheostomy Risk in Older Patients Intubated and in an Intensive Care Unit in Japan: An Inverse Association in Older Patients with Advanced Age 643 650 EN Takehide Umeda Takashi Hongo Mototaka Inaba Hiromichi Naito Yoshinori Ariyasu Takashi Yorifuji Introduction: This post hoc analysis of a prospectively collected intensive care unit (ICU) cohort examined the association between frailty and the likelihood of tracheostomy in older Japanese patients (aged ≥65 years). Frailty, a condition of increased vulnerability to stressors, is common among older patients in the ICU and may influence clinical decision-making and outcomes. We aimed to explore whether baseline frailty is associated with the likelihood of receiving tracheostomy in older patients in the ICUs. Methods: We analyzed data from a multicenter prospective study conducted from November 2019 to April 2020 at 17 hospitals in Japan. Patients aged ≥65 years, admitted directly from the emergency department, and requiring mechanical ventilation, were included. After excluding early deaths (≤5 days) or treatment-limit cases, 363 patients with intubation remained. Frailty was assessed using the Clinical Frailty Scale (CFS), with primary cutoff CFS ≥4. The primary outcome was the occurrence of tracheostomy during ICU stay. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using generalized linear models with a Poisson distribution, adjusted for age, sex, Charlson Comorbidity Index, and Acute Physiology and Chronic Health Evaluation II score. Results: Among 363 patients, patients with frailty (CFS ≥4) had a significantly lower adjusted risk of having tracheostomy than did those with less frailty (CFS <4) (adjusted RR: 0.40; 95% CI: 0.27-0.61). In patients aged ≥75 years, the adjusted RR for CFS ≥4 was 0.32 (95% CI: 0.20-0.50), indicating a pronounced reduction in tracheostomy use among patients with frailty. Conclusions: Frailty (CFS ≥4) was independently associated with a lower likelihood of tracheostomy, particularly in patients aged ≥75 years. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1341-8076 52 5 2026 Survey to Document the Adverse Reactions After Human Papillomavirus Vaccination Among Japanese Female Youth at a University e70314 EN Chigusa Higuchi Educational and Research Management Field, Health Management Department, Okayama University Chikako Ogawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Yoshiaki Iwasaki 1Educational and Research Management Field, Health Management Department, Okayama University Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Aim: Concerns about possible adverse events remain a critical barrier in implementing human papillomavirus (HPV) vaccination among Japanese youth. This study aimed to understand the time course of adverse events experienced by HPV vaccine recipients. Methods: An online questionnaire survey was given to students, faculty, and staff aged 18–26 years, at Okayama University Hospital, who received the HPV vaccine. The survey gathered information on the number of HPV vaccine doses received, prevaccination health conditions, adverse reactions within 2 h and between 2 h and 7 days postvaccination, menstrual irregularities after vaccination, reasons for getting vaccinated, feelings before and after vaccination, and factors providing reassurance during vaccination. Prevalence of symptoms was expressed as numbers and percentages, and analyses were performed using Chi-squared or Fisher's exact tests. Results: Responses were obtained from 299 participants, yielding a 75% response rate. Approximately 60% participants reported local pain, 30% swelling, and 4% fever. Most symptoms resolved on the vaccination day itself or the following day, although some persisted for 3–7 days. Over 80% participants rated their pain between 0 and 3 on numerical rating scale of 0–10. While 60% experienced anxiety before vaccination, 90% reported no anxiety afterward. Conclusions: Our study presents one of the first comprehensive accounts of post-HPV vaccination adverse events and their time course, and underpins the importance of disseminating detailed information about vaccine-associated adverse reactions to encourage greater vaccine uptake. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0915-5635 38 3 2026 Effectiveness and Safety of Enteroscopy-Assisted ERP-Guided Versus EUS-Guided Pancreatic Duct Drainage for Pancreaticojejunostomy Strictures: A Multicenter Observational Study e70128 EN Shogo Ota Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University Hideyuki Shiomi Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Masataka Kano Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center Masaaki Shimatani Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center Naoki Fujita Department of Gastroenterology and Neurology, Kagawa University Hideki Kamada Department of Gastroenterology and Neurology, Kagawa University Saori Ueno Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University Takeshi Ogura Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University Mamoru Takenaka Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University Kae Nagao Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine Arata Sakai Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine Shuhei Shintani Department of Gastroenterology, Shiga University of Medical Science Osamu Inatomi Department of Gastroenterology, Shiga University of Medical Science Koh Kitagawa Department of Gastroenterology, Nara Medical University Ryota Nakano Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University Mitsuhito Koizumi Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine Yoshiki Imamura Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine Akihisa Ohno Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University Nao Fujimori Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University Takaaki Tamura Second Department of Internal Medicine, Wakayama Medical University Tsukasa Miyagahara Department of Gastroenterology, National Hospital Organization Beppu Medical Center Mikio Nakajima Emergency and Critical Care Center, Tokyo Metropolitan Hiroo Hospital Masayuki Kitano Second Department of Internal Medicine, Wakayama Medical University Objectives: Enteroscopy-assisted endoscopic retrograde pancreatography-guided pancreatic duct drainage (eERP-PDD) and endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD) are minimally invasive alternatives to surgery for pancreaticojejunostomy stricture (PJS); however, comparative data remain limited. We compared the effectiveness and safety of these approaches and identified factors associated with technical failure. Methods: This multicenter retrospective study included 88 patients (111 procedures) who underwent endoscopic intervention for PJS at 13 Japanese tertiary centers. We compared clinical outcomes between eERP-PDD and EUS-PDD. The primary outcome was technical success; secondary outcomes included clinical success, procedure time, and adverse events (AEs). Propensity-score overlap weighting was used to adjust for baseline differences. Results: As initial treatment, 77 patients underwent eERP-PDD and 11 underwent EUS-PDD. After adjustment, EUS-PDD achieved higher technical success (eERP-PDD, 28% vs. EUS-PDD, 71%; p = 0.012) and clinical success (22% vs. 71%; p = 0.003), with shorter procedure time (76 min vs. 41 min; p = 0.001). AE incidence was higher with EUS-PDD before adjustment (5% vs. 27%; p = 0.039) but comparable after adjustment (7% vs. 29%; p = 0.15); all AEs resolved with conservative management. Age < 75 years, male sex, and main pancreatic duct (MPD) diameter ≥ 5 mm were independently associated with eERP-PDD failure. Conclusions: EUS-PDD demonstrated higher technical and clinical success than eERP-PDD for PJS, with comparable safety after adjustment. An MPD diameter ≥ 5 mm was associated with eERP-PDD failure. An MPD-based algorithm is proposed: eERP-PDD for MPD < 5 mm with EUS-PDD as salvage, and EUS-PDD for MPD ≥ 5 mm. This algorithm is hypothesis-generating and requires prospective validation. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-3643 7 3 2026 Potential Immune Microenvironment Biomarkers in SCLC: J-TAIL-2 Observational Study 100926 EN Masayuki Shirasawa Department of Thoracic Oncology, National Cancer Center Hospital Makoto Nishio Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Atsushi Osoegawa Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine Eiki Kikuchi Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University Hideharu Kimura Department of Respiratory Medicine, Kanazawa University Hospital Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Hospital Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Ichiro Yoshino International University of Health and Welfare Narita Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Yasushi Yatabe Department of Diagnostic Pathology, National Cancer Center Hospital Tatsuya Yoshida Department of Thoracic Oncology, National Cancer Center Hospital Jumpei Kashima Department of Diagnostic Pathology, National Cancer Center Hospital Masahide Oki Department of Respiratory Medicine, NHO Nagoya Medical Center Hisao Ashimura Chugai Pharmaceutical Co., Ltd. Yuki Kobayashi Chugai Pharmaceutical Co., Ltd. Misa Tanaka Chugai Pharmaceutical Co., Ltd. Akihiko Gemma Nippon Medical School Introduction: Effective predictors of response to atezolizumab plus carboplatin/etoposide (CE) therapy in extensive-stage SCLC (ES-SCLC) remain limited. This exploratory analysis from J-TAIL-2 aimed to identify markers of survival benefit with atezolizumab plus CE therapy in ES-SCLC. Methods: J-TAIL-2 (ClinicalTrials.gov ID, NCT04501497) was a multicenter observational study that enrolled patients receiving atezolizumab plus CE (ES-SCLC cohort) in clinical practice in Japan per local label and treatment guidelines. In this exploratory analysis, the association of CD8+ tumor-infiltrating lymphocyte (TIL) density and SCLC subtypes (SCLC-A [ASCL1 dominant], SCLC-N [NEUROD1 dominant], SCLC-P [ASCL1/NEUROD1 double-negative with POU2F3 expression], and SCLC-O [ASCL1/NEUROD1 double-negative not otherwise specified]) with overall survival (OS) and progression-free survival (PFS) was evaluated. SCLC subtyping was performed by immunohistochemistry. Results: SCLC samples (n = 100; data cutoff, February 3, 2023) were categorized as SCLC-A (73%), SCLC-N (16%), SCLC-P (8%), and SCLC-O (3%). Among 96 patients who received first-line atezolizumab plus CE, median age was 72 (range, 39–87) years and 81% were male. Furthermore, 56 patients were classified into the CD8+ TIL-high subgroup and 40 into the TIL-low subgroup. Median (m)PFS with atezolizumab plus CE was 6.1 months (95% confidence interval [CI]: 4.5–7.5) in the TIL-high versus 4.4 months (95% CI: 4.0–5.1) in the TIL-low subgroup (p = 0.01); mOS was 18.4 (95% CI: 11.8–not estimable) versus 10.8 months (95% CI: 7.7–16.2; p = 0.04). mOS and mPFS were not significantly different between SCLC subtypes but were numerically shorter in the SCLC-N group. Conclusions: CD8+ TIL density is a potential biomarker of clinical benefit in ES-SCLC and may facilitate patient selection for atezolizumab combination therapy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2407 26 1 2026 High-risk soft-tissue sarcomas in elderly patients: does perioperative radiotherapy improve local control and prognosis? 329 EN Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiharu Mitsuhashi Centre for Innovative Clinical Medicine, Medical Development Field, Okayama University Yutaka Nezu Department of Orthopaedic Surgery, Yokohama City University Takashi Tajima Department of Orthopaedic Surgery, Kyorin University Faculty of Medicine Shinji Miwa Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Toshio Kojima Department of Orthopaedic Surgery, Nihon University School of Medicine Shuichi Fujiwara Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Akira Kawai Department of Musculoskeletal Oncology, National Cancer Centre Hospital Kazuhiro Tanaka Department of Advanced Medical Sciences, Oita University Faculty of Medicine Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Aims Accumulating evidence suggests that advanced age is associated with poor local control and prognosis in patients with soft-tissue sarcomas (STSs), highlighting the need to optimise treatment for this age group. However, real-world data on treatment details and outcomes in elderly patients are limited. This study aimed to clarify the role of perioperative radiotherapy (RT) for treating high-risk STSs in elderly patients. Methods Patients aged ≥ 70 years who underwent surgery for localised, high-grade, deep-seated non-small round cell STSs measuring ≥ 5 cm were included in the Bone and Soft Tissue Tumour Registry in Japan. Patients with small-round cell STSs or myxoid liposarcomas, or those who received perioperative chemotherapy or intraoperative RT, were excluded. Results Among the 1,214 patients who met the criteria, 47 (4%), 219 (18%), and 2 (0.2%) received neoadjuvant, adjuvant, and both neoadjuvant and adjuvant RT, respectively. The 5- and 10-year disease-specific survival (DSS) rates were 72.7% and 64.7%, respectively. Tumour size ≥ 10 cm, intralesional margin, and local recurrence were associated with poorer DSS; however, perioperative RT did not affect DSS. The 5- and 10-year cumulative probabilities of local recurrence (LR) were 14.6% and 19.5%, respectively. Trunk wall tumours, dedifferentiated liposarcomas, marginal margins, and intralesional margins were associated with a higher probability of LR. Adjuvant RT was associated with a reduced LR probability in patients with intralesional (p = 0.005) or marginal margins (p = 0.044); however, no such benefit was observed in patients with wide margins, who constituted the majority of the cohort, resulting in no significant association between perioperative RT and LR in overall analyses. In the propensity score-matched cohort, no significant differences in DSS or cumulative probability of LR were observed between patients with and without perioperative RT. Conclusion Adjuvant RT was associated with reduced LR rates in elderly patients with high-risk STSs who had intralesional or marginal margins. However, because most patients achieved wide margins and no benefit of perioperative RT was observed in this group, RT was not associated with reduced LR or improved survival in the overall or propensity score–matched analyses. Prospective trials are warranted to define the role of perioperative RT in elderly patients with high-risk STSs. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2227-7390 14 12 2026 Toward Convergence in Multi-Agent Reinforcement Learning: Best-Response Space Shrinking as a Sufficient Condition 2134 EN Natchanon Manatphaiboon Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akito Monden Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Zeynep Yücel Department of Environmental Sciences, Informatics and Statistics, Ca’Foscari University of Venice We study convergence in multi-agent reinforcement learning (MARL) through the lens of sufficient conditions, using a single-point-of-failure analysis applied to multi-agent policy iteration integrated with linear programming (MAPI-LP), where results are proven for pure coordination games, and extension to broader settings is conjectured. We identify two sufficient conditions for convergence to Markov Perfect Equilibrium (MPE). The first is stability in best-response space that emerges from value monotonicity. The second, monotonic best-response space shrinking (MBRSS), is a novel condition requiring that each agent’s best-response space contracts monotonically across iterations until it collapses to a stable space. Furthermore, we show that MBRSS does not necessarily imply monotonic improvement in this setting. However, value monotonicity and stability in best-response space imply each other when a complementary condition is applied. Building on this hierarchical relationship, we propose conjectures on sufficient condition relationships in both serial and parallel MARL. In addition, we propose conjectures on generalized MBRSS to arbitrary finite repeated games and validation of stability in best-response space. We further discuss connections between MBRSS and existing related frameworks, and outline directions toward a taxonomy of sufficient conditions for MARL convergence. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 2 2026 Possible Involvement of Hypothalamic Dysfunction in Long COVID Patients Characterized by Delayed Response to Gonadotropin-Releasing Hormone 832 EN Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuhito Suyama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Takase Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Oguni Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yohei Masuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Omura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Matsuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Ueda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic–pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. Between February 2021 and November 2025, 1251 patients with long COVID were evaluated, of whom 207 (19%) had relatively low random ACTH or cortisol levels. Ultimately, 16 underwent anterior pituitary stimulation tests and were included. All tests were performed in an inpatient setting without exogenous steroids. Fifteen patients (six women, mean age 35.6 years) underwent corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH) tests. All patients had mild acute COVID-19, eight had ≥2 vaccinations, and the mean interval from infection was 343 days. Frequent symptoms included fatigue (100%), insomnia (66.7%), headache (60.0%), anorexia/nausea (40.0%), and brain fog (40.0%). Mean early-morning cortisol and 24 h urinary free cortisol were 7.5 μg/dL and 41.0 μg/day, respectively. MRI showed an empty sella in one case. Peak hormonal responses were preserved (ΔACTH 247%, ΔTSH 918%, ΔPRL 820%, ΔFSH 187%, ΔLH 1150%); however, peaks were delayed beyond 60 min in ACTH (13%), LH (33%), and FSH (87%). Notably, significantly delayed elevations remained at 120 min in the responses of TSH (4.1-fold), PRL (1.8-fold), LH (9.3-fold), and FSH (2.8-fold), suggesting possible hypothalamic involvement, particularly in the gonadotropin responses. Additionally, serum IGF-I was lowered (−0.70 SD), while GH response (mean peak 35.5 ng/mL) was preserved by growth hormone-releasing peptide (GHRP)-2 stimulation. Low-dose hydrocortisone and testosterone were initiated for three patients. Although direct viral effects and secondary suppression have been proposed, our findings may suggest that, at least in part, the observed response characteristics are consistent with functional secondary hypothalamic dysfunction rather than irreversible primary injury. These findings highlight the need for objective endocrine evaluation before initiating hormone replacements. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-1569 30 1 2026 Three-dimensional virtual planning reduces operative time in orthognathic surgery: a procedure-specific retrospective study incorporating additive manufacturing 94 EN Yuki Kunisada Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Norie Yoshioka Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akiyoshi Nishiyama Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masanori Masui Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koichi Kadoya Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroaki Takakura Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kyoichi Obata Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kisho Ono Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koki Umemori Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose Three-dimensional virtual surgical planning (3D-VSP) is increasingly used in orthognathic surgery; however, procedure-specific evidence regarding its real-world impact on operative efficiency and intraoperative blood loss remains limited. This study evaluated the association between 3D-VSP implementation and operative time, and intraoperative blood loss across different orthognathic procedures. Methods This retrospective cohort study included consecutive patients who underwent orthognathic surgery at a single academic institution before (2019–2020) and after (2023–2024) the full implementation of 3D-VSP integrated with in-house additive manufacturing (n = 344). Procedure-specific multivariable linear regression analyses were performed, adjusting for age, sex, and surgeon experience. Results After 3D-VSP implementation, operative time was reduced by approximately 36 min in sagittal split ramus osteotomy (SSRO), 50 min in Le Fort I (LF1) combined with SSRO, and 42 min in segmental LF1 combined with SSRO, representing a 15–20% reduction in total operative time. No meaningful reduction was observed in intraoral vertical ramus osteotomy (IVRO)-based procedures. A statistically significant, but modest, reduction in intraoperative blood loss was observed only in SSRO. The time-saving effect was independent of surgeon experience. Conclusion The clinical benefit of 3D-VSP in orthognathic surgery is procedure-dependent and most evident in geometrically complex SSRO-based operations. These findings support the targeted implementation of digital planning and additive manufacturing workflows to improve operative efficiency in routine practice. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1999-4907 17 5 2026 Photosynthetic Response of Larix gmelinii var. japonica Saplings After Exogenous Glutathione Foliar Application 530 EN Resa Sri Rahayu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Wataru Ishizuka Forestry Research Institute, Hokkaido Research Organization Ayu Narita Forestry Research Institute, Hokkaido Research Organization Rie Miyata Forestry Research Institute, Hokkaido Research Organization Naoko H. Miki Faculty of Environmental, Life, Natural Science and Technology, Okayama University Hirokazu Kon Forestry Research Institute, Hokkaido Research Organization Yuko Miyazaki Faculty of Environmental, Life, Natural Science and Technology, Okayama University Sapling survival and growth depend on photosynthetic assimilates. Therefore, improving physiological performance during early stages may enhance subsequent performance and nursery production. This study evaluated whether exogenous oxidized glutathione (GSSG), reported to enhance photosynthesis, improves the photosynthetic, physiological, and growth-related traits of Larix gmelinii var. japonica saplings. Sixteen saplings were assigned to four treatments: GSSG, 5-aminolevulinic acid, Hyponex, and a water control. Photosynthetic, nitrogen-related, and growth traits were measured before treatment and at 3, 6, 13, and 31 days after treatment, and biomass was assessed after three months. The GSSG treatment showed no difference in the net CO2 assimilation rate (Amax) compared with the control, but exhibited a significantly earlier peak at 6 days than the other treatments. This response was supported by the stability of GSSG-treated saplings against photoinhibition (Fv/Fm) and a tendency toward greater resilience to midday light stress (ΦPSII). Enhanced photosynthetic performance was associated with reduced carbon and nitrogen fluctuations and was accompanied by numerically greater root and stem biomass in the 2024 terminal shoots. Although fertilization effects were generally weak and transient, GSSG elicited notable responses, suggesting that the immediate enhancement of photosynthesis underlies its impact. However, its antioxidant properties under stressful conditions warrant further investigation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2431 26 1 2026 Hypernatremia during the first week of life in very preterm infants and neurodevelopmental outcomes at 3 to 4 years of age: a cohort study 181 EN Michiko Murakami Division of Neonatology, NHO Okayama Medical Center Kei Tamai Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihito Takeuchi Division of Neonatology, NHO Okayama Medical Center Makoto Nakamura Division of Neonatology, NHO Okayama Medical Center Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Misao Kageyama Division of Neonatology, NHO Okayama Medical Center Background Hypernatremia is a common electrolyte disorder in both term and preterm infants. Previous studies have suggested a correlation between hypernatremia and short-term complications in preterm infants, such as intraventricular hemorrhage and chronic lung disease. However, the relationship between hypernatremia and neurodevelopmental outcomes is less well understood. This study aimed to assess the association between hypernatremia during the first week of life and neurodevelopmental outcomes at 3–4 years of age in very preterm infants. Methods This single-center, retrospective cohort study analyzed data from preterm infants born at less than 32 weeks of gestation between 2010 and 2020. Infants with peak whole blood sodium levels > 145 mEq/L during the first week of life were included in the hypernatremia group and those with ≤ 145 mEq/L in the non-hypernatremia group. The primary outcome was neurodevelopmental impairment (NDI) at 3–4 years of age, defined as developmental impairment (developmental quotient < 70), cerebral palsy, hearing impairment, or visual impairment. Secondary outcomes were the components of the primary outcome. We conducted Poisson regression analyses with robust variance, adjusting for perinatal confounders. Results Of 272 infants with neurodevelopmental data, 82 and 190 infants were in the hypernatremia and non-hypernatremia groups, respectively. The median (interquartile range) gestational age and birth weight were 26.4 (25.1–28.0) and 28.7 (26.6–30.3) weeks and 860 (670–1062) and 997 (778–1264) g for infants in the hypernatremia and non-hypernatremia groups, respectively. Infants in the hypernatremia group had a greater incidence of NDI (29.3% vs. 14.7%, adjusted risk ratio [RR] 1.75, 95% CI 1.08–2.84) and cerebral palsy (8.5% vs. 1.6%, adjusted RR 5.5, 95% CI 1.72–17.63) than those in the non-hypernatremia group. Conclusions Hypernatremia during the first week of life was associated with an increased risk of NDI at 3–4 years of age in very preterm infants. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0902-0063 40 6 2026 Risk Factors for Waiting List Mortality in Lung Transplant Candidates With Post‐Hematopoietic Stem Cell Transplantation Non‐Infectious Pulmonary Complications e70582 EN Hisao Higo Department of Respiratory Medicine, Okayama University Hospital Satoru Senoo Department of Respiratory Medicine, Okayama University Hospital Satoko Makimoto Department of Radiology, Okayama University Hospital Tomohiro Nagano Department of Hematology, Okayama University Hospital Takumi Kondo Department of Hematology, Okayama University Hospital Haruchika Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Maeda Department of Respiratory Medicine, Okayama University Hospital Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Nobuaki Miyahara Department of Respiratory Medicine, Okayama University Hospital Background: Late-onset non-infectious pulmonary complications (LONIPCs) following hematopoietic stem cell transplantation (HSCT) are a known indication for need of lung transplantation. This study aimed to clarify the clinical characteristics of patients with LONIPCs after HSCT who were registered for lung transplantation and reveal the risk factors for waiting list mortality. Methods: We retrospectively reviewed the clinical data of patients with LONIPCs after allogeneic HSCT who were referred to Okayama University Hospital and registered in the Japan Organ Transplant Network for deceased-donor lung transplantation between 2005 and 2023. Pediatric patients aged <18 years at the time of registration were excluded. Results: Thirty-four patients were included in this study. Notably, two distinct phenotypic groups were identified: One with a bronchiolitis obliterans pattern on high-resolution computed tomography and a mixed ventilatory defect, and the other with a pleuroparenchymal fibroelastosis pattern and a restrictive ventilatory defect. The median waiting duration for a deceased-donor lung transplant was 662 days, and 16 patients died during the waiting period. The cumulative incidence of waiting list mortality was 20.6% (95% confidence interval [CI], 8.9%–35.6%) at 1 year and 46.1% (95% CI, 27.8%–62.7%) at 3 years. A history of pneumothorax, greater dyspnea on exertion, and higher serum Krebs von den Lungen-6 levels were associated with an increased risk of waiting list mortality. Conclusion: In patients with LONIPCs after HSCT, a history of pneumothorax may be a marker of a poor prognosis and could serve as a criterion for referral of lung transplantation. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1664-042X 17 2026 Bee larvae ameliorate andropause-like symptoms via a hormone-independent, antioxidant mechanism 1850114 EN Takashi Ito Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Nobuaki Okumura Institute for Bee Products & Health Science, Yamada Bee Company, Inc. Takumi Oti Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Hirotaka Sakamoto Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Late-onset hypogonadism (LOH), also known as the male menopause, is characterized by a decline in sexual function as well as various physical and psychological symptoms, including anxiety. Although bee larvae have historically been utilized as a traditional food and medicine, their efficacy and physiological mechanisms of action against male menopausal symptoms remain unclear. In this study, we investigated the effects of bee larvae (BL) on sexual and anxiety-like behaviors using two rodent models of the male menopause: aged rats and castrated mice. In the aged rat model (64 weeks old), dietary BL supplementation for 4 weeks significantly attenuated the age-associated decline in ejaculation frequency compared to controls, while no significant effects were observed on mount or intromission frequencies. Notably, plasma analysis revealed no significant differences in testosterone or dihydrotestosterone levels between the BL and control groups. To elucidate the underlying mechanism, we evaluated sexual function using a castrated mouse model. While BL supplementation did not affect sexual behavior in intact mice, post-castration BL treatment significantly shortened intromission latency without altering mount frequency. In the elevated plus maze test, BL significantly alleviated castration-induced anxiety-like behaviors and improved exploratory activity. Furthermore, in vitro assays demonstrated that the BL extract exerts potent protective effects against oxidative stress, a pathological factor contributing to both erectile dysfunction and anxiety. These results suggest that BL improves erectile function and anxiety via hormone-independent mechanisms, potentially by mitigating oxidative stress in vascular and neural tissues. Thus, bee larvae represent a promising functional food for ameliorating the multi-faceted physical and psychological symptoms associated with male menopause. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0892-0362 115 2026 Long-term neurological and neurocognitive deficits in adults prenatally exposed to methylmercury: Minamata disease 107590 EN Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuka Yamamura Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Itsuka Nagano Non-Profit Organization Hamachidori Mariko Yasuda Clinical Psychology Center, Kawasaki Medical School Hospital Teruko Morooka Division of Medical Support, Okayama University Hospital Yoko Kado Department of Psychology, Faculty of Letters, Kansai University Minamata disease, officially recognized in 1956, is a well-known food poisoning event that was caused by the consumption of fish and seafood contaminated with methylmercury. Although patients with congenital Minamata disease (CMD) with severe neurological impairments after birth are widely recognized, few studies have examined the effects of prenatal methylmercury exposure among residents, which is likely at lower levels than in CMD patients. We aimed to investigate the relationship between prenatal methylmercury exposure and subsequent neurological and neurocognitive outcomes. We conducted a cross-sectional study during 2024–2025 among 51 individuals aged approximately 70 years, 27 residents from an existing cohort established in 1970 in Minamata and 24 age-matched individuals who had lived in less-exposed regions. We performed a battery of neurological and neurocognitive tests in both groups and compared the results using multiple linear regression analyses. We also examined the association between intelligence scores obtained in 1970, and intelligence scores obtained in the present investigation, only among exposed participants. We found that exposed individuals had unfavorable neurological and neurocognitive test scores, in comparison with less-exposed controls. Scores on the Montreal Cognitive Assessment, Japanese Edition were 5.91 points lower (95% confidence interval: 3.09 to 8.73) for exposed residents than for the less-exposed group. Moreover, intelligence scores evaluated during exposed participants' adolescence were correlated with their neurocognitive scores in adulthood. Our findings showed that prenatal methylmercury exposure affected subsequent neurological and neurocognitive functions, including among individuals with lower exposure than in CMD patients, and even approximately 70 years after the initial exposure. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2673-3943 7 2 2026 Relationship Between Numbers of Patients Registered and Procedures Performed at Lung Transplantation Centers in Japan 9 EN Takashi Inoue Department of General Thoracic Surgery, School of Medicine, Dokkyo Medical University Masayuki Chida Department of General Thoracic Surgery, School of Medicine, Dokkyo Medical University Yoshinori Okada Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University Masaaki Sato Department of Thoracic Surgery, University of Tokyo Hidemi Suzuki Department of General Thoracic Surgery, Chiba University Graduate School of Medicine Yasushi Hoshikawa Department of Thoracic Surgery, Fujita Health University School of Medicine Toyofumi Chen-Yoshikawa Department of Thoracic Surgery, Nagoya University Graduate School of Medicine Daisuke Nakajima Department of Thoracic Surgery, Kyoto University Graduate School of Medicine Yasushi Sintani Department of General Thoracic Surgery, The Osaka University Graduate School of Medicine Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama Toshihiko Sato Department of General Thoracic, Breast and Pediatric Surgery, Fukuoka University School of Medicine Takeshi Shiraishi Department of General Thoracic, Breast and Pediatric Surgery, Fukuoka University School of Medicine Keitaro Matsumoto Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences Takahiro Nakajima Department of General Thoracic Surgery, School of Medicine, Dokkyo Medical University Sumiko Maeda Department of General Thoracic Surgery, School of Medicine, Dokkyo Medical University Background: Recently, there has been a dramatic increase in deceased lung transplantation (DLT) procedures performed in Japan. However, there is concern that the number of transplantations may reach the limit of capacity in some centers. The present study was conducted to analyze the relationship between the numbers of individuals registered for DLT by the Japan Organ Transplantation Network (JOT) and procedures subsequently performed at lung transplantation centers. Methods: Using a database and registry reports provided by the Japanese Society of Lung and Heart-lung Transplantation, the numbers of individuals registered in the JOT and DLT procedures performed from January 2014 to December 2023 were analyzed. Results: The number of registrations was found to be correlated with the number of DLTs, with the coefficient of determination (R2) 0.962 and slope of the regression line (X coefficient) 0.407. The facility with the greatest number of registrations, with a registration-to-transplantation ratio of 0.353, was identified as an outlier (p < 0.05) and excluded from analysis. This exclusion increased both the correlation coefficient value to 0.986 and X coefficient value to 0.461. Conclusions: The present analysis showed that the number of DLTs was well correlated with number of registrations at each of the transplantation facilities. Both registration and transplantation numbers have increased in the recent decade. The facility with the highest number of registrations showed a lower registration-to-transplantation ratio, because the increase in registrations outpaced the number of transplantations. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 15 10 2026 Long-Term Outcomes of Endoscopic Ultrasound-Guided Gallbladder Drainage for Acute Cholecystitis in Non-Surgical Candidates: A Multicenter Retrospective Study 3621 EN Kei Harada Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Endoscopy, Okayama University Hospital Kosaku Morimoto Department of Internal Medicine, Tsuyama Chuo Hospital Eijiro Ueta Department of Gastroenterology, National Organization Iwakuni Clinical Center Yutaka Akimoto Department of Gastroenterology, Japanese Red Cross Okayama Hospital Nao Hattori Department of Gastroenterology and Hepatology, Okayama University Hospital Taisuke Obata Department of Gastroenterology and Hepatology, Okayama University Hospital Ryosuke Sato Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Endoscopy, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama 700-8558, Japan Hiroyuki Terasawa Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Endoscopy, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama 700-8558, Japan Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Background/Objectives: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is a minimally invasive alternative for managing acute cholecystitis in patients who are unsuitable for surgery. Although its short-term efficacy is well-established, its long-term outcomes, especially in patients with malignancy-associated cholecystitis, remain unclear. Methods: This multicenter, retrospective study included 139 patients who underwent EUS-GBD with a plastic stent for inoperable acute cholecystitis between January 2010 and October 2023. Patients were divided into two groups: a malignant group (n = 60) with cystic duct obstruction caused by cancer invasion or self-expandable metal stents, and a benign group (n = 79) with calculous or acalculous cholecystitis. The outcomes assessed included cholecystitis recurrence, time to recurrence, adverse events, and risk factors for recurrence. Results: Technical success was achieved in all patients, with an overall clinical success rate of 94.6%. Cholecystitis recurred significantly more frequently in the malignant group than in the benign group (13.3% vs. 2.5%; p = 0.015). Univariate analysis identified malignancy as a significant risk factor of recurrence (odds ratio, 5.92; p = 0.028). Conclusions: EUS-GBD is a safe and effective long-term treatment for cholecystitis in non-surgical candidates. However, malignancy-associated cholecystitis carries a high risk of recurrence, warranting careful follow-up and individualized management. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 1525-2027 27 5 2026 Chemical Geodynamics of Granitoid Magmatism During a Pacific‐Philippine Sea Plate Transition in Southwest Japan e2026GC012945 EN Nghiem V. Dao The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University at Misasa Tsegereda A. Yemer The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University at Misasa Tulibako T. Mwaisuba The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University at Misasa Chie Sakaguchi The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University at Misasa Hiroshi Kitagawa The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University at Misasa Katsura Kobayashi The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University at Misasa Teruyoshi Imaoka Division of Earth Science, Graduate School of Sciences and Technology for Innovation, Yamaguchi University Eizo Nakamura The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University at Misasa Granitoid magmatism along the western Pacific margin records interactions between subduction dynamics and crust–mantle processes; however, the links between plate reorganization and magma-source evolution remain debated. Here we integrate U–Pb zircon geochronology with Pb–Sr–Nd–Hf isotope systematics to investigate Cretaceous–Paleogene granitoids in Southwest Japan. Zircon U–Pb ages define two discrete magmatic episodes at 110–60 Ma and 45–30 Ma, separated by a magmatic hiatus of ∼10–15 Myr. These granitoid groups exhibit distinct isotopic signatures, indicating derivation from isotopically distinct magma sources linked to the paleo-Pacific (Izanagi) plate and the Philippine Sea plate, respectively. Isotope-based mass-balance modeling indicates higher sediment contributions to the older granitoids, with decreasing sediment input both landward and through time. The magmatic lull at ca. 52–40 Ma coincides with an abrupt isotopic shift and is interpreted to reflect plate reorganization, during which subduction of the paleo-Pacific plate was replaced by a transform or highly oblique plate boundary associated with the northward migration of the proto–Philippine Sea plate. Independent constraints from convergence rates, sediment flux, and accretionary complex development support this interpretation. These results demonstrate that granitoid magmatism in Southwest Japan was fundamentally controlled by temporal changes in subducted lithosphere and sediment flux driven by plate reorganization, highlighting the sensitivity of arc magmatism to transient tectonic regimes. No potential conflict of interest relevant to this article was reported.

John Wiley & Sons Ltd Acta Medica Okayama 1362-1017 31 3 2026 Early sedation intensity and psychological outcomes in critically ill adults e70500 EN Mikiko Iwatani Okayama University Hospital; Graduate School of Health Sciences, Doctoral Program, Okayama University Michiko Morimoto Faculty of Health Sciences, Okayama University Background: Long-term psychological impairment is a major concern for intensive care unit (ICU) survivors. Early deep sedation during mechanical ventilation has been associated with poor short-term outcomes and mortality after ICU discharge; however, its relationship with psychological outcomes remains unclear. Aim: To investigate sedation intensity during the first 24 h of mechanical ventilation and its association with psychological impairment 3 months after ICU discharge. Study Design: This retrospective ancillary analysis of a single-centre cohort study was conducted in two general ICUs at a university hospital in Japan. Eligible patients stayed in the ICU for more than 48 h and received mechanical ventilation for more than 8 h. Sedation intensity was quantified using the Sedation Index (SI) and Agitation Index (AI) derived from Richmond Agitation-Sedation Scale scores during the first 24 h. Psychological impairment 3 months post-ICU discharge was assessed based on symptoms of post-traumatic stress, anxiety and depression. Associations were examined using hierarchical logistic regression. Results: Among 130 participants, the median age was 64 years, and the median ventilation duration was 14 h. The median SI was 3.0; 47% had SI > 3, and 8.5% had AI > 0. Sedation intensity showed no significant association with psychological impairment (SI: adjusted odds ratio [OR] 0.87, 90% confidence interval [CI] 0.57–1.33, p = 0.59; AI: adjusted OR 0.21, 90% CI 0.01–3.08, p = 0.34). However, any agitation during the ICU stay was associated with psychological outcomes (adjusted OR 2.61, 90% CI 1.16–5.88, p = 0.05). Conclusions: This study did not identify a statistically significant association between early sedation intensity and psychological impairment 3 months after ICU discharge. Relevance to Clinical Practice: Critical care nurses should carefully titrate sedation from the initiation of mechanical ventilation to avoid unnecessary deep sedation, considering sedation intensity over time, while actively assessing agitation and its underlying causes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 2026 Sex-related differences in blood concentrations and emergence profiles following total intravenous anesthesia with remimazolam and remifentanil 13650 EN Riko Sato Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Higuchi Department of Dental Anesthesiology, Okayama University Hospital Yukiko Nishioka Department of Dental Anesthesiology, Okayama University Hospital Saki Miyake Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Miyawaki Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Remimazolam is a novel, short-acting benzodiazepine, which is characterized by rapid onset and quick recovery. The clinical efficacy and metabolism of many intravenous anesthetics are known to be influenced by sex; however, the effects of sex on the anesthetic efficacy and metabolism of remimazolam remain unclear. This prospective observational study examined sex-related differences in pharmacokinetics and emergence profiles after total intravenous anesthesia was induced with remimazolam and remifentanil in patients undergoing oral and maxillofacial surgery. Thirty-five American Society of Anesthesiologists Physical Status 1 adults (19 females, 16 males), aged 18–49 years, received standardized dosing based on their actual body weights. Serum remimazolam concentrations were measured at the end of administration and immediately before extubation using high-performance liquid chromatography. Although the emergence time did not differ significantly between the sexes, the mean emergence time of the females was approximately 80 s shorter. Serum remimazolam concentrations were significantly lower in females at both measurement time points (p < 0.001). This may suggest that remimazolam is metabolized more rapidly in women. Although these sex-related pharmacokinetic differences did not affect the time to awakening under combined remimazolam and remifentanil anesthesia, clinicians should be aware of potential sex differences in the pharmacokinetics of remimazolam. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2334 25 1 2025 Phenotypic and potential virulence features of Salmonella enterica serotypes from cancer patients in Kolkata, India 1263 EN Goutam Chowdhury Collaborative Research Centre of Okayama University for Infectious Diseases at ICMR- NICED Sanjay Bhattacharya Tata Medical Center Gaurav Goel Tata Medical Center Soumyadip Chatterji Tata Medical Center Kei Kitahara Collaborative Research Centre of Okayama University for Infectious Diseases at ICMR- NICED Ayumu Ohno Collaborative Research Centre of Okayama University for Infectious Diseases at ICMR- NICED Melissa Glenda Lewis Division of Biostatistics, ICMR - National Institute for Research in Bacterial Infections Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Thandavarayan Ramamurthy Division of Bacteriology, ICMR - National Institute for Research in Bacterial Infections Asish K. Mukhopadhyay Division of Bacteriology, ICMR - National Institute for Research in Bacterial Infections Background Salmonella enterica is a leading cause of gastroenteritis and enteric fever. In this study, we sought to investigate the phenotypic and genotypic characteristics of S. enterica isolated from the cancer patients admitted at the Tata Medical Center, Kolkata over a period of eight years (2016–2023). Methods Salmonella enterica isolates were identified by standard biochemical and serotyping. Antimicrobial susceptibility was tested by disk diffusion method and virulence genes were identified by PCR. The genetic relatedness of strains was determined by pulsed-field gel electrophoresis (PFGE) methods. Results A total of 122 S. enterica isolates were identified and classified into 18 different serovars. S. Typhimurium (28.7%), S. Kentucky (22.1%), S. Enteritidis (13.9%), S. Typhi (5.7%) and S. Agona (5.7%) were identified as the common serovars. S. enterica infection was more often detected in adults (77.9%) than in children of 6–18 years old (11.4%) and < 5 years of age (10.6%). The maximum number of S. enterica was isolated from blood (52.4%) followed by those isolated from stool (36.9%) and urine (5.7%). S. enterica infections were detected among patients with chronic myelogenous leukemia (CML)/acute lymphoblastic leukemia (ALL) (24.6%) than Hodgkin lymphoma/non-Hodgkin lymphoma (16.4%), multiple myeloma (9.8%), lung adenocarcinoma (9%), prostate adenocarcinoma (6.6%), and endometrium carcinoma (5.7%). S. Kentucky showed a statistically significant association with hematologic malignancies (p < 0.001), whereas S. Enteritidis was significantly present in Hodgkin lymphoma and acute lymphoblastic leukemia/Chronic myelogenous leukemia cancer types (p = 0.004). Most of the S. enterica isolates displayed resistance to erythromycin (62.9%), nalidixic acid (62.9%) and tetracycline (33.9%). Salmonella pathogenicity island (SPI)-associated genes (orgA, ssaQ, misL, invE/A, spi4D, pipA and ttrc) were uniformly present in majority of the isolates. The hyper invasive locus (hilA), Salmonella enterotoxin (stn), Salmonella outer protein (sopB), virulence plasmid (spvC), and plasmid encoded fimbriae (pefA) genes were present in 76%, 69%, 51%, 32% and 17% of the isolates, respectively. Clonal analysis of the representative homologous serovars using pulsed-field gel electrophoresis revealed specific clusters with 40 to 90% similarity within each serotype. Conclusions Cancer patients are at increased risk of morbidity due to secondary infections, like S. enterica. Continuous monitoring of antimicrobial resistance patterns and virulence gene profiles in S. enterica isolates from this vulnerable group is critical to guide clinical management and treatment strategies. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 2 2026 Impact of Proteinuria on Postoperative Complications Following Colorectal Cancer Surgery 131 139 EN Shunsuke Nakata Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Fumiaki Takatsu Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Yoshihiro Mikuriya Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Tomokazu Kakishita Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Shinji Hato Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Koji Ohta Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Takaya Kobatake Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Original Article 10.18926/AMO/70455 Colorectal surgery is associated with a high incidence of postoperative complications regardless of the advances in surgical techniques and multidisciplinary treatment. Proteinuria is common in patients with malignancies, but few studies have investigated the association between preoperative proteinuria and patient prognoses, especially postoperative complications. We investigated the impact of proteinuria on patients undergoing colorectal surgery in a single-center, retrospective cohort study of 767 patients who underwent surgical resection for colorectal cancer between January 2016 and December 2022 at the National Hospital Organization Shikoku Cancer Center. Among them, 81 patients with preoperative proteinuria were compared with the control group of 686 patients without proteinuria. Our analyses revealed that the patients with proteinuria had malnutrition with a significantly lower prognostic nutritional index compared to the no-proteinuria control group (p<0.001). The proteinuria group had a significantly advanced tumor stage (p=0.005), experienced more bleeding during the surgery (p=0.002), and required more transfusions (p<0.001). Postoperative complications were significantly more frequent in the proteinuria group (p=0.03), thus demonstrating that proteinuria was independently associated with postoperative complications (p=0.045). Proteinuria in patients undergoing colorectal cancer surgery can therefore be considered a risk factor for postoperative complications. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 2 2026 Mini-open Corpectomy and Posterior Spinal Fixation with Single-Position Surgery in Lateral Decubitus Position for Osteoporotic Thoracolumbar Vertebral Collapse in Elderly Patients 119 129 EN Hisanori Ikuma Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital Tomohiko Hirose Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital Keisuke Kawasaki Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital Kazutoshi Otsuka Otsuka Orthopedic Clinic Original Article 10.18926/AMO/70454 We evaluated the clinical outcomes and limitations of anterior and posterior combined surgery with a mini-open corpectomy applying an expandable cage (Xcore®) and percutaneous pedicle screw (PPS) fixation using single-position surgery in the lateral decubitus position in patients aged > 75 years with thoracolumbar vertebral collapse. The cases of 30 consecutive patients who underwent this procedure and had ≥ 1-year follow-up were retrospectively analyzed. The mean operative time was 78.8 min and the estimated blood loss was 115.7 ml per level. The complications included adjacent junctional failure (n=9, 30%), deep venous thrombosis (n=3, 10%), delirium (n=3, 10%), pleural injury (n=2, 6%), screw backout (n=1, 3%) kidney injury (n=1, 3%), chylothorax (n=1, 3%), and wound dehiscence (n=1, 3%). Seven cases (23.3%) required reoperation. Local kyphosis showed significant improvement (p<0.05) that was maintained at the final follow-up. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire and a visual analogue scale indicated significant improvement in all categories at the final follow-up (p<0.05). The use of mini-open corpectomy and posterior fixation with SPAPS can thus provide reliable radiological correction and good postoperative clinical outcomes even in patients aged > 75 years. However, a limitation of this procedure is the rate of reoperation (23.3%) for osteoporosis-related adjacent segment fracture and screw backout. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 2 2026 A Mixed-Methods Study on Changes in Interprofessional Education Attitudes and Fundamental Competencies: A Pre–Post Analysis of Clinical Training in Dietetic Students 109 117 EN Mika Sonoi Department of Foods and Human Nutrition, Faculty of Human Life Sciences, Notre Dame Seishin University Norihiro Sonoi Center for Education in Medicine and Health Sciences, Okayama University Yoko Koyama Department of Foods and Human Nutrition, Faculty of Human Life Sciences, Notre Dame Seishin University Original Article 10.18926/AMO/70453 This study examined the effects of interprofessional education (IPE) on dietetics students during clinical training, focusing on changes in their attitudes toward IPE and their fundamental competencies. Eighty third-year female students (mean age, 21.0 years) at a Japanese women’s university participated. Self-administered surveys were conducted before and after clinical training to assess attitudes toward IPE using the Readiness for Interprofessional Learning Scale (RIPLS) and the Shakaijin Kisoryoku (SKL; Fundamental Competencies for Working Persons) scale. Quantitative data were analyzed using paired t-tests, chi-squared tests, and cluster analyses. Qualitative data from open-ended responses were analyzed thematically. RIPLS and SKL scores increased significantly, from 65.3 to 68.9, and from 28. 4 to 33. 2, respectively (p<0.001). All 12 SKL items showed significant improvement. In free responses, “initiative” (66 mentions), “communication” (10), and “execution” (8) were the most frequently cited as improved competencies. Cluster analysis identified three groups: increasing scores (n=25), high baseline (n=30), and minimal change (n=25). No significant correlation was found between changes in RIPLS and SKL scores (r=−0.108, p=0.355). IPE integrated into clinical training may enhance dietetics students’ attitudes toward interprofessional collaboration and contribute to the development of professional identity. Individualized, phased IPE implementation is recommended to accommodate differences in learner readiness. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 2 2026 Effects of Nonsurgical Periodontal Treatment on Bacterial and Clinical Parameters in Down Syndrome Patients Based on 16S rRNA Gene Amplicon Sequencing 85 97 EN Takahiko Shiba Department of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Mitsuhito Takamori Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sayaka Katagiri Department of Oral Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Ryota Kobayashi Department of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Aki Kawauchi Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Yujin Ohsugi Department of Oral Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Peiya Lin Department of Oral Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiko Egusa The center for Special Needs Dentistry, Medical Development Field, Okayama University Takanori Iwata Department of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Shigeru Maeda Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Original Article 10.18926/AMO/70451 Individuals with Down syndrome (DS) are more susceptible to periodontal disease; however, microbial changes following treatment remain insufficiently understood. This study evaluated the effects of nonsurgical periodontal therapy on clinical outcomes and oral microbiome dynamics in 6 patients with DS using 16S rRNA gene amplicon sequencing. Bacterial diversity, composition, network structure, and predicted functional pathways were analyzed using dental plaque samples. Bleeding on probing decreased significantly (p=0.047) after treatment, with a trend toward reduction in periodontal inflamed surface area (p=0.05). The abundance of Fusobacteria at the class level decreased significantly after treatment. The abundance of Mogibacterium timidum was higher in the pretreatment group than in the posttreatment group. M. timidum was positively correlated with Treponema denticola and associated with multiple bacterial taxa in the network during pretreatment. Predicted functional pathways related to aromatic compound degradation were more abundant in posttreatment samples than in pretreatment samples. An increase in the abundance of Fusobacterium and the positive correlation between T. denticola and M. timidum, together with their associations with other periodontal pathogens before treatment, may contribute to the development of periodontitis in individuals with DS. Nonsurgical periodontal therapy produces measurable clinical improvement and promotes microbial shifts in patients with DS. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2079-6447 5 2 2026 Solution-Processable Near-Infrared-Absorbing Dye: Thiophene-Substituted N-Phenylphenothiazine Radical Cations for Stable Thin Films 14 EN Masafumi Yano Faculty of Chemistry, Material and Bioengineering, Kansai University Kengo Sakai Faculty of Chemistry, Material and Bioengineering, Kansai University Minami Ueda Faculty of Chemistry, Material and Bioengineering, Kansai University Koichi Mitsudo Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yukiyasu Kashiwagi Osaka Research Institute of Industrial Science and Technology We report a π-extended N-phenylphenothiazine dye bearing thiophene substituents, designed to address the practical compromise between long-wavelength near-infrared (NIR) absorption and the isolability of a stable radical cation state. The target compound was synthesized via Suzuki–Miyaura cross-coupling and exhibited good solubility in common organic solvents. Cyclic voltammetry in dichloromethane showed a reversible one-electron oxidation at E0 = 0.19 V vs. Fc/Fc+. Chemical oxidation afforded the corresponding radical cation, which showed an intense NIR absorption maximum at 910 nm. DFT calculations support thiophene-induced narrowing of the HOMO–SOMO gap and predict a pronounced bathochromic shift of the main absorption band. The radical cation was isolated as a stable PF6− salt and readily processed into spin-coated films, which retained strong NIR absorption and remained stable for months under ambient conditions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0770-3198 45 5 2026 Global trends in systemic sclerosis-related mortality, 2001–2023: an epidemiological analysis using World Health Organization mortality data 2741 2748 EN Keith Pardillada Belangoy Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yoshito Nishimura Division of Haematology and Oncology, Mayo Clinic, Rochester Ko Harada Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Quynh Thi Vu Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hanane Ouddoud Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Judah Israel Ong Lescano Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Michio Yamamoto Graduate School of Human Sciences, The University of Osaka Tatsuaki Takeda Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Objectives This study aimed to evaluate the global trends in systemic sclerosis (SSc)-related mortality by age, sex, and geographic region. SSc is a multisystem autoimmune disease characterized by tissue fibrosis, vascular dysfunction, and multi-organ involvement, which is associated with a high mortality risk. Methods Using the World Health Organization Mortality Database, we examined trends in SSc-related crude mortality rates (SSc-CRs) and age-standardized mortality rates (SSc-ASMR) per 1,000,000 population from 2001 to 2023. Locally weighted regression was applied to visualize long-term patterns, and Joinpoint regression was used to assess the national trends from 2010 to 2023. Results Across 74 countries, 85,291 SSc-related deaths were reported, with 79.41% occurring in females. The SSc-CR steadily increased from 1.97 (95% confidence interval [CI]: 1.71–2.23) in 2001 to 2.34 (95% CI: 2.01–2.68) in 2023, while the SSc-ASMR decreased from 1.58 (95% CI: 1.42–1.74) to 1.29 (95% CI: 1.08–1.50), respectively. Regionally, mortality was the highest in the Western Pacific region and declined in the Americas and Europe, with temporal fluctuations. The SSc-ASMR was highest in countries with a middle sociodemographic index (SDI). Conclusions While overall age-standardized mortality from SSc has declined in many regions, disparities persist. These results underscore the importance of sustaining research and enhancing disease awareness, as well as developing strategies to reduce mortality in high-risk populations and regions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Pseudohypoxia induced by iron chelators preserves working memory performance in aged mice 11550 EN Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Iwasaki Health Service Section, Environment Health & Safety Intelligence Department, Okayama University Tomonari Kasai Department of Applied Energy, Graduate School of Engineering, Nagoya University Toru Yamashita Department of Neurology, Graduate School of Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shiho Komaki Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Hamada Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Pseudohypoxia refers to a physiological condition wherein hypoxia-inducible factor (HIF) is pharmacologically upregulated under normoxia, thereby modulating immune responses. We hypothesized that pseudohypoxia, induced by iron chelators, may similarly potentiate systemic immune responses in aged mice, concurrently triggering neuro-regenerative signaling pathways and enhancing cognitive performance. In this study, aged mice (43–48 weeks old) were orally administered two iron chelators, Super Polyphenol 10 (SP10) or Roxadustat, to induce a pseudohypoxia. An 8-week oral regimen of SP10 and Roxadustat significantly preserved working memory, as assessed by the Y-maze test (YMT). White blood cell counts and hippocampal volume, as assessed by magnetic resonance imaging (MRI), were elevated in the treatment groups relative to controls. Pseudohypoxia induced by SP10 tended to enhance neuro-regenerative signaling, specifically involving the Tau and JNK pathways, and potentially modulated Doublecortin (DCX) expression, although statistical significance was limited by sample size. Importantly, inflammatory markers, such as ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), were not elevated by treatment. Collectively, these findings suggest that pseudohypoxia induced by iron chelators preserves working memory performance accompanied by leukocytosis, without concomitant neuroinflammation. No potential conflict of interest relevant to this article was reported.

Japan Medical Association Acta Medica Okayama 2433-3298 9 1 2026 Relationship between Maternal Body Composition during Pregnancy and Newborn Birth Weight in Japan 189 197 EN Eriko Eto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masakazu Kato Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoe Kirino Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Chiaki Kuriyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shujiro Sakata Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hikari Nakato Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sakurako Mishima Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akiko Ohira Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Introduction: This study aimed to investigate the changes in maternal body composition during pregnancy in Japanese women and the relationship between maternal body composition and newborn birth weight using pre-pregnancy body mass index (BMI) in all trimesters. Methods: A total of 1,851 pregnant Japanese women were enrolled in this study. Body composition was measured using TANITA MC-190EM. The associations between newborn birth weight and maternal BMI, fat mass (FM), fat-free mass (FFM), total body water (TBW), muscle mass (MM), FM gain, FFM gain, and weight gain were evaluated. Results: The participants’ age and pre-pregnancy BMI were 34.1 years and 21.4 kg/m2, respectively. Among the patients, 13.4%, 73.0%, 10.3%, and 3.3% were underweight, average weight, overweight, and obese, respectively. The FM showed no significant change from the second to third trimesters in the underweight, overweight, and obese groups. Moreover, the FM in the overweight and obese groups did not change during any period. The FFM, TBW, and MM significantly increased from the first to second and second to third trimesters. In BMI-stratified multivariate regression analyses, FFM in the normal and overweight groups was positively associated with birth weight, whereas FM gain was negatively associated in the underweight and normal groups. No significant associations were observed in the obese group. Conclusions: Changes in maternal body composition during pregnancy in Japanese women varied by pre-pregnancy BMI. Associations with birth weight also differed by BMI group. Further prospective studies are needed to confirm these relationships and investigate the mechanisms. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 5 2026 Aerobic Exercise Attenuates Epidermal Hyperplasia in an Obesity-Associated Psoriasiform Dermatitis Model 2308 EN Yoshihiro Matsuda Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daiki Takezaki Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuma Sakamoto Department of Immunology and Molecular Genetics, Kawasaki Medical School Nobuyasu Baba Department of Immunology and Molecular Genetics, Kawasaki Medical School Masanori Iseki Department of Immunology and Molecular Genetics, Kawasaki Medical School Yoshio Kawakami Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsushi Shiomi Department of Pathology, Kawasaki Medical School Tomoyuki Mukai Department of Immunology and Molecular Genetics, Kawasaki Medical School Obesity is an important risk factor for psoriasis, and clinical studies indicate that exercise interventions can improve disease severity. However, the mechanisms by which exercise influences psoriatic pathogenesis remain insufficiently understood. To investigate the effects of aerobic exercise on obesity-associated psoriasis, wild-type mice were fed a high-fat diet (HFD) for 7 weeks to induce obesity and subsequently underwent moderate-intensity treadmill running for 3 weeks. Psoriasiform dermatitis was induced by daily topical application of imiquimod (IMQ) to the skin for five consecutive days. HFD increased body weight, epididymal fat mass, and serum cholesterol. HFD-fed mice developed more severe IMQ-induced psoriatic skin changes compared with normal diet-fed mice. Treadmill exercise modestly reduced body weight gain and attenuated epidermal hyperplasia in HFD-fed mice. In contrast, inflammatory cytokine expression, including Tnfa, Il17a, and Il23a, showed modest increases in the skin of HFD-fed exercised mice, which did not parallel the improvement in epidermal hyperplasia. Overall, these findings indicate that while obesity exacerbates psoriasiform dermatitis, aerobic exercise ameliorates epidermal hyperplasia in obese mice without corresponding changes in inflammatory cytokine expression in the skin, suggesting that exercise may influence psoriatic skin changes through multiple metabolic and immunological pathways. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2073-4360 18 7 2026 Effect of Universal Adhesives on Resin Cement–Fiber Post–Core Materials 810 EN Masao Irie Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Okada Department of Dental Biomaterials, Graduate School of Dentistry, Tohoku University Yukinori Maruo Department of Prosthodontics, Okayama University Kenraro Akiyama Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kumiko Yoshihara Health Research Institute, National Institute of Advanced Industrial Science and Technology Akimasa Tsujimoto Department of Operative Dentistry, School of Dentistry, Aichi Gakuin University Takuya Matsumoto Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study evaluated eleven resin cements used as core build-up materials by examining the following properties: (a) push-out force between root dentin and the fiber post; (b) pull-out force between the fiber post and the core build-up material; (c) shear bond strength of the resin cement to root dentin; (d) flexural strength of the resin cement; and (e) flexural modulus of elasticity of the resin cement. The purpose of this investigation was to clarify the relationships between recently available universal adhesives, core build-up materials, resin cements, and fiber posts. All experiments were performed at two evaluation periods: after 1 day of water storage (Base) and after 20,000 thermocycles (TC 20k). For the push-out test, simulated post spaces were prepared in single-rooted human premolars. The specimens were sectioned perpendicular to the long axis into 2 mm-thick slices and then subjected to push-out testing to assess the bond strength of the dentin–resin cement–fiber post complex. No significant differences in bonding performance were found between Base and TC 20k. These findings suggest that universal adhesives used for pretreatment of multiple substrates in fiber post cementation can provide not only strong but also durable adhesion over time. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 2 2026 Porphyromonas gingivalis Vesicles Control Osteoclast–Macrophage Lineage Fate 831 EN Elizabeth Leon Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Shin Nakamura Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Satoru Shindo Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Maria Rita Pastore Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Tomoki Kumagai Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Alireza Heidari Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Elaheh Dalir Abdolahinia Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Tomoya Ueda Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Takumi Memida Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Ana Duran-Pinedo Department of Oral Biology, College of Dentistry, University of Florida Jorge Frias-Lopez Department of Oral Biology, College of Dentistry, University of Florida Xiaozhe Han Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Xin Chen Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Shengyuan Huang Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Guoqin Cao Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Sunniva Ruiz Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Jan Potempa Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville Toshihisa Kawai Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA Porphyromonas gingivalis (Pg), a keystone pathogen of chronic periodontitis, releases outer membrane vesicles (OMVs) that act as nanoscale vehicles to disseminate virulence factors within periodontal tissues and systemically beyond the oral cavity. Although Pg-OMVs are increasingly recognized as critical mediators of host–pathogen interactions, their effects on the differentiation and function of monocyte–macrophage/osteoclast lineage cells remain unclear. Here, we examined the impact of Pg-OMVs on the differentiation of RAW264.7 monocyte/macrophage-like cells into osteoclasts (OC) and/or macrophages (MΦ) in the presence of receptor activator of nuclear factor-κB ligand (RANKL). OMVs were isolated from Pg W83 and applied to RANKL-primed RAW264.7 cells using three distinct stimulation schedules: (1) simultaneous treatment with Pg-OMVs and RANKL at Day 0; (2) RANKL priming at Day 0 followed by Pg-OMV stimulation at Day 1; and (3) RANKL priming at Day 0 followed by Pg-OMV stimulation at Day 3. In all schedules, cells were cultured for 7 days from the initial RANKL exposure. Remarkably, simultaneous exposure to Pg-OMVs and RANKL (Schedule 1) markedly suppressed osteoclastogenesis (OC-genesis) while promoting M1 macrophage polarization. In contrast, delayed Pg-OMV stimulation of RANKL-primed cells (Schedules 2 and 3) significantly enhanced OC-genesis while reducing M1 polarization. These schedule-dependent effects were consistent with altered expression of osteoclastogenic markers, including dc-stamp, oc-stamp, nfatc1, and acp5. Importantly, a monoclonal antibody against OC-STAMP counteracted the Pg-OMV-induced upregulation of OC-genesis in Schedules 2 and 3. Furthermore, levels of Pg-OMV phagocytosis were inversely correlated with osteoclast formation. Finally, co-stimulation with RANKL and Pg-OMVs (Schedule 1) enhanced macrophage migratory capacity, whereas delayed stimulation with Pg-OMVs (Schedules 2 and 3) did not. Collectively, these findings indicate that Pg-OMVs exert stage-specific effects on the OC/MΦ lineage: stimulation at early stages of RANKL priming suppresses OC-genesis and promotes M1 polarization, whereas stimulation at later stages enhances OC-genesis without inducing M1 differentiation. Thus, Pg-OMVs may critically influence the fate of the OC/MΦ unit in periodontal lesions, contributing to disease progression and tissue destruction. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 7 2026 CXCR2-Dependent Infiltration of Tumor-Associated Neutrophils Is Linked to Enhanced CD8+ T Cell Effector Function and Reduced Lung Metastasis in 4T1 Breast Cancer 3143 EN Tiantian Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miao Tian Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Gakushi Nishida Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Triple-negative breast cancer (TNBC) is characterized by prominent neutrophil infiltration; however, its significance remains controversial. Here, we investigated the role of neutrophil chemoattractant receptors in TNBC progression and metastasis. In contrast to wild-type (WT), Fpr1−/−, and Fpr2−/− mice, neutrophils were almost completely absent in 4T1 tumors from Cxcr2−/− mice, indicating a dominant role for CXCR2 in the recruitment of tumor-associated neutrophils, leading us to use Cxcr2−/− mice for further studies. Primary tumor growth was comparable between WT and Cxcr2−/− mice, whereas lung metastasis was significantly increased in Cxcr2−/− mice, with reduced expression of inflammatory cytokines, chemokines and cytotoxic molecules, including granzyme B and perforin, in primary tumors and metastatic lungs of Cxcr2−/− mice. In vitro, WT, but not Cxcr2−/−, neutrophils enhanced CD8+ T cell activation, partly via ICAM-1, and directly induced tumor cell death, supporting their anti-tumor function. To assess clinical relevance, transcriptomic data were analyzed. High neutrophil infiltration combined with elevated CXCR2 expression, and to a lesser extent CXCR1 expression, was associated with improved prognosis in patients with basal-like BC that largely overlaps with TNBC. Collectively, these findings suggest that CXCR2-mediated neutrophil recruitment exerts protective, anti-tumor effects and may represent a new prognostic marker for TNBC patients. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-2607 14 4 2026 The Role of Nitrate-Reducing Bacteria Isolated from Helicobacter pylori-Infected Individuals in Gastric Cancer Development 760 EN Serika Kuwagi Department of Bacteriology, Academic Field of Health Sciences, Okayama University Kazuyoshi Gotoh Department of Bacteriology, Academic Field of Health Sciences, Okayama University Marina Komatsubara Department of Bacteriology, Academic Field of Health Sciences, Okayama University Shuma Tsuji Department of Bacteriology, Academic Field of Health Sciences, Okayama University Shyoutarou Okanoue Department of Gastroenterology and Hepatology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Okada Himeji Red Cross Hospital Jumpei Uchiyama Department of Bacteriology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Akari Watanabe Department of Oral Health Care and Rehabilitation, Institute of Biomedical Sciences, Graduate School, Tokushima University Kenji Yokota Department of Bacteriology, Academic Field of Health Sciences, Okayama University Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric mucosa, with a global prevalence in humans of approximately 40%. It is likely the cause of 90% of gastric cancer (GC) cases and thus considered the most prominent driver of GC development. However, during gastric mucosal atrophy, other bacteria such as nitrate-reducing bacteria (NRB) also proliferate. In this study, we isolated NRB from patients with gastritis and GC to examine their effects on the epithelial cell cycle and production of various cytokines in monocytic cell lines. Bacterial counts (excluding H. pylori and NRB) increased with the progression of gastric mucosal atrophy and were significantly higher in patients with GC. Gastric epithelial cell lines were stimulated with isolated NRB, and the proportion of cells in each cell cycle was measured. Strains from patients with open-type gastritis progressed more rapidly through cell cycles than those from patients with GC. NRB isolated from gastric cancer had high nitrate-reducing activity. Thus, NRB may contribute to GC progression during H. pylori-induced carcinogenesis. Therefore, evaluating gastric atrophy and microbiota may be important for managing the risk of GC. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2410-387X 9 4 2025 Role-Based Efficient Proactive Secret Sharing with User Revocation 80 EN Yixuan He Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuta Kodera Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Samsul Huda Interdisciplinary Education and Research Field, Okayama University Proactive secret sharing (PSS), an extension of secret-sharing schemes, safeguards sensitive data in dynamic distributed networks by periodically refreshing shares to counter adversarial attacks. In our previous work, we constructed a non-interactive proactive secret scheme by integrating threshold homomorphic encryption (ThHE) while reducing the communication complexity to 𝑂(𝑛). Not only is refreshing shares important but revoking the shares of users who have left the system is also essential in practical dynamic membership scenarios. However, the previous work was insufficient for supporting explicit user revocation. This study strengthens the description of roles for authorized users and proposes a scheme to achieve non-interactive share refresh and dynamic user management. In each epoch, authorized users are classified into three roles: retain, newly join, and rejoin, and they receive a broadcast of the compact ciphertext encoding both the refresh information and the revocation instructions from the trusted center (dealer). Authorized users independently derive new shares through homomorphic computations, whereas revoked users are unable to generate new shares. Hash functions are used to bind revocation parameters to the cryptographic hashes of valid users in order to guarantee integrity during revocation, allowing for effective verification without compromising non-interactivity. Our new scheme not only extends the revocation structure but also preserves the 𝑂(𝑛) communication complexity. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1424-8220 25 21 2025 Integrated Authentication Server Design for Efficient Kerberos–Blockchain VANET Authentication 6651 EN Maya Rahayu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Md. Biplob Hossain Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Samsul Huda Interdisciplinary Education and Research Field, Okayama University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Vehicular Ad Hoc Network (VANET) is a fundamental component of the intelligent transportation systems (ITS), providing critical road information to users. However, the volatility of VANETs creates significant vulnerabilities from malicious actors. Thus, verifying joining entities is crucial to maintaining the VANET’s communication security. Authentication delays must stay below 100 ms to meet VANET requirements, posing a major challenge for security. Our previous research introduced a Kerberos–Blockchain (KBC) authentication system that contains two main components separately: Authentication Server (AS) and Ticket Granting Server (TGS). However, this KBC architecture required an additional server to accommodate increasing vehicle volumes in urban environments, leading to higher infrastructure costs. This paper presents an integrated authentication server that merges AS and TGS into a Combined Server (CBS) while retaining blockchain security. We evaluate it using OMNeT++ with SUMO for traffic simulation and Ganache for blockchain implementation. Results show that CBS removes the need for an extra server while keeping authentication delays under 100 ms. It also improves throughput by 104% and reduces signaling overhead by 45% compared to KBC. By optimizing authentication without compromising security, the integrated server greatly enhances the cost-effectiveness and efficiency of VANET systems. No potential conflict of interest relevant to this article was reported.

岡山大学大学院ヘルスシステム統合科学研究科 Acta Medica Okayama 2436-3227 6 2026 介護技術論試論―高齢者介護を事例として― 7 16 EN Yasuyuki YOSHIBA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University 10.18926/interdisciplinary/70326 In the first part of this paper, it was confirmed that the term “kaigo” (nursing care) was coined and its meaning defined during discussions on enacting social welfare legislation accompanying societal aging, as the care aspect was being “differentiated” from the “family’s health and welfare functions.” The paper also examined how the term “kaigo gijutsu”(nursing care technique) has been defined and used. In the latter part, based on the author’s own definition of “kaigo gijutsu”(nursing care technology), an attempt was made to analyze examples of technology utilization in nursing care settings, focusing on papers published in specialized welfare and nursing care technology journals. Through this preliminary study, it was shown that the author’s definition of “nursing care technology” clearly distinguishes between the means for care activities—such as welfare equipment—and the care recipients and caregivers who make use of them, and that this definition is useful for grasping the essence of challenges in nursing care settings. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-4418 16 6 2026 Seasonal Variations in the Risk of Outpatient Acute Kidney Injury in Patients with Chronic Kidney Disease 845 EN Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Haraguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Acute kidney injury (AKI) frequently occurs in the outpatient setting and is associated with adverse renal and survival outcomes. However, there is no established definition of outpatient AKI, and the risk factors, especially seasonal variation, remain limited. This study aimed to investigate seasonal variation in the risk of outpatient AKI. Methods: This retrospective observational study used routinely collected clinical laboratory data from a single hospital in Japan between 2007 and 2022. Outpatient AKI was defined as ≥35% relative decline in estimated glomerular filtration rate (eGFR) compared with a preceding outpatient measurement obtained within 14–90 days. Monthly and seasonal variations in outpatient AKI risk in patients with chronic kidney disease (CKD) were evaluated using logistic regression models. Subgroup analyses were performed according to AKI stage, age group, and CKD stage. Results: A total of 203,853 outpatient records were analyzed. The incidence of outpatient AKI was highest in August and lowest in November. Analyses demonstrated significantly increased odds ratios of outpatient AKI in January, February, July, and August. Seasonally, the risk was significantly higher during the summer. Stage-specific analyses showed that AKI stage 1 was more frequent in the summer, whereas AKI stage 2 tended to increase during the winter. Conclusions: Outpatient AKI exhibits distinct seasonal patterns, with increased risk during both summer and winter and differential associations according to AKI severity and baseline kidney function. Recognition of these patterns may help identify vulnerable populations and inform targeted preventive strategies for outpatient AKI. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1424-8220 26 5 2026 A Proposal of Secure and Automated Over-the-Air Firmware Update Mechanism for IoT Devices Using Continuous Integration and Continuous Delivery 1535 EN Noprianto Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Htoo Htoo Sandi Kyaw Department of Information and Communication Systems, Okayama University Komang Candra Brata Department of Information and Communication Systems, Okayama University I Nyoman Darma Kotama Department of Information and Communication Systems, Okayama University The Internet of Things (IoT) technology has grown rapidly over the past decade, resulting in deployments of thousands of IoT devices around the world. Then, managing firmware updates for these numerous devices poses significant challenges. Firmware updates face issues such as version rollback, modified firmware files, and potential man-in-the-middle (MITM) attacks, highlighting the need for a secure over-the-air (OTA) firmware update mechanism. In this paper, we propose an automated OTA firmware update mechanism, integrated with continuous integration (CI) and continuous delivery (CD) to ensure trusted sources for firmware origins. It offers security, error handling during firmware updates, and monitoring of the update process. For evaluations, we implemented the proposal with the SEMAR IoT application server that has been implemented in our previous studies. Then, we verified the integrity and authentication, measured the performance and resource utilization, and performed benchmarking tests to assess the efficiency. The results demonstrate that the proposal is sufficiently reliable and efficient. No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 57 3 2026 AI 共生時代における消費者行動の再理論化―AIBCBM フレームワーク― 41 91 EN Sawut Shazadigul Faculty of Humanities and Social Sciences, Okayama University 10.18926/OER/70263 　本研究は，AIが意思決定の前段階から介入する環境において，企業・消費者・AIの三者相互作用を体系的に説明する理論枠組みとして，Artificial Intelligence-Based Consumer Behavior Model（AIBCBM）を構築し，提示することを目的とする。まず，既存の消費者行動モデルが，アルゴリズム露出，再帰的学習ループ，AI媒介型社会的影響（Algorithmic Social Influence）といった現代的現象を十分に扱えないという決定的な理論的限界を明らかにする。そのうえで，AI共生時代における消費者行動を，「企業－AI－消費者」の三者循環構造として捉えるAIBCBMを提示する。 　モデル構築に際しては，複雑な現実を過度に単純化するのではなく，三者共進化構造モデル（図２），行動生成の動態を示す行動プロセスモデル（表３），概念構造モデル（図３），行動類型モデル（図４）に分離することで，理論的明瞭性と分析可能性を確保した。本研究の理論的貢献は，①System １を行動生成メカニズムとして再定義した点，②意思決定主体と権力構造を再定義した点，③消費者行動における非線形・高速フィードバックループを理論化した点，④非消費やJOMOを，幸福と主体性に根ざした戦略的行動として理論的に再定義した点，⑤消費者行動を「意思決定モデル」から「行動生成モデル」へ理論的に転換した点に集約される。さらに，本研究が提示する，アルゴリズムによる効用の向上と自律性の毀損が併存しうるという二面性は，AI時代におけるマーケティング戦略および政策設計に対して，規範的かつ理論的な新たな評価軸を提供する。AIBCBMは，これらの視座を統合する理論的プラットフォームとして，今後の実証研究に向けた基盤として機能する。とりわけ， AIBCBMは，JOMOや非消費行動を，アルゴリズム環境からの受動的撤退ではなく，AIによって構築された選択環境との距離を意図的に調整し，人間らしさ（人間としての主体性やウェルビーイング）を保持するための戦略的行動として位置づける点に独自性を有する。さらに本モデルは，AI設計（企業側）・アルゴリズム動態（AI側）・主体性とウェルビーイング（Well-being）（消費者側）を同一枠組みで接続することで，AI共生時代の実証研究と規範設計を架橋する理論的座標軸を確立する。 No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1547-5271 22 9 2025 Aging of the tricuspid valve annulus detected by photon-counting detector computed tomography: Importance of aortic root compression on occurrence of arrhythmias e772 e780 EN Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Satoshi Nagase Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center Yoshihisa Morimoto Department of Cardiovascular Medicine, Fukuyama City Hospital Takuro Masuda Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Akira Ueoka Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Saori Asada Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Masakazu Miyamoto Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Norihisa Toh Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Toru Miyoshi Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Background The aortic root compresses the heart in elderly patients, potentially influencing the conduction system and causing atrial tachyarrhythmias. However, actual anatomic alterations in the right side of the heart because of aortic root compression have not yet been fully evaluated. Objective This study aimed to elucidate the alterations in the tricuspid valve annulus (TVA) caused by aortic root compression using a 3-dimensional endoscopic view of the heart constructed by photon-counting detector computed tomography, an emerging medical technology. Methods We analyzed 147 consecutive patients who underwent photon-counting detector computed tomography at our institute after excluding those with diseases that directly influenced the right side of the heart. Results Aortic root compression caused significant TVA deformation. We defined severe TVA compression as the length of the TVA compressed by the aortic root ≥80% of the major axis of the TVA. Severe compression was more prevalent in elderly patients (age ≥75 years [44%]; P < .01). The distance between the membranous septum and ostium of the coronary sinus was shortened, whereas the cavotricuspid isthmus was elongated in older patients. The regression analysis identified aging as a significant contributor to TVA compression. The short minor and long major axes of the TVA, incidence of atrial tachyarrhythmias (74% vs 45%; P < .01), and atrioventricular conduction disturbances (35% vs 15%; P < .01) were more frequently observed in patients with severe compression. Conclusion Aortic root compression deforms the TVA and alters the anatomic relationship between the atrioventricular conduction system and the cavotricuspid isthmus. Therefore, aortic root compression may contribute to the occurrence of atrial tachyarrhythmias and conduction disturbances in older patients. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1478-6362 28 1 2026 Real-world comparative effectiveness of sarilumab versus Janus kinase inhibitors as monotherapy in rheumatoid arthritis 32 EN Yuji Nozaki Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Kazuya Kishimoto Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Tetsu Itami Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Daisuke Tomita Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Yumiko Wada Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University Takuya Kotani Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University Tohru Takeuchi Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University Toshihiko Hidaka Rheumatology Center, Miyazaki Zenjinkai Hospital Shoichi Hino Department of Rheumatology and Clinical Immunology, Izumi City General Medical Center Toshiaki Miyamoto Miyamoto Internal Medicine and Rheumatology Clinic Hirofumi Miyake Department of General Internal Medicine, Tenri Hospital Kazunari Hatta Department of General Internal Medicine, Tenri Hospital Kenji Mamoto Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka Metropolitan University Yutaro Yamada Center for Senile Degenerative Disorders (CSDD), Osaka Metropolitan University Graduate School of Medicine Tadashi Okano Center for Senile Degenerative Disorders (CSDD), Osaka Metropolitan University Graduate School of Medicine Takaichi Okano Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine Jun Saegusa Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine Masahiro Horita Department of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama University Keiichiro Nishida Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Koji Kinoshita Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Shinya Rai Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Background: Sarilumab (SAR), an interleukin-6 receptor inhibitor (IL-6Ri), and Janus kinase inhibitors (JAKi) are approved options for rheumatoid arthritis (RA) when methotrexate (MTX) cannot be used. Real-world evidence for MTX-free monotherapy remains limited. Methods: We conducted a multicenter retrospective cohort study of RA patients receiving SAR or JAKi as MTX-free monotherapy. To reduce confounding, 1:1 propensity score matching was performed in the overall cohort (n = 252, 126 per group) and separately within treatment-line strata: Phase 2 first-line biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs: 45 per group), Phase 3 second-line b/tsDMARDs (53 per group), and Phase 3 ≥ third-line b/tsDMARDs (47 per group). Outcomes over 12 months included drug retention, change in Clinical Disease Activity Index (CDAI), glucocorticoid (GC) tapering and discontinuation, low disease activity (LDA, CDAI ≤ 10), and safety profiles. Predictors of LDA were evaluated with logistic regression. This multicenter real-world. Results: Across matched strata by prior b/tsDMARDs, retention and CDAI change did not differ significantly between SAR and JAKi through 12 months. When classified by cause, adverse events (AEs)-related discontinuation was higher with JAKi, yielding lower AE-specific retention. Both groups demonstrated GC sparing overtime, with a greater increase in GC discontinuation for SAR than for JAKi in Phase 2. Baseline predictors of achieving LDA at 12 months included higher C-reactive protein (CRP) and platelet count (Plt) in both groups, with additional associations of younger age and lower hemoglobin (Hb) in the SAR. In safety analyses, overall AEs were less frequent with SAR than with JAKi, driven by lower risks of infection including herpes zoster, while other categories were similarly infrequent. Conclusion: SAR and JAKi showed no statistically significant differences in 12-month retention or disease control in MTX-free monotherapy settings. Higher CRP and Plt with lower Hb, particularly in younger patients, identified better response to SAR and support biomarker guided selection between IL-6Ri and JAKi. In Phase 2, GC discontinuation with SAR suggests a practical strategy to reduce AEs while maintaining efficacy. Prospective studies should validate these findings and define actionable thresholds. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-3417 16 5 2026 Concentration-Dependent Synergistic Interfacial Interactions Between Multifunctional Acrylate and Silane Coupling Agents in an Organic–Inorganic Nanohybrid Material 2339 EN Yukinori Maruo Department of Prosthodontics, Okayama University Kumiko Yoshihara Health Research Institute, National Institute of Advanced Industrial Science and Technology Masao Irie Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University Naoki Kodama Department of Prosthodontics, Okayama University Mai Yoshizane Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaro Akiyama Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Synergistic effects of a multifunctional acrylate and a long-chain silane coupling agent were investigated in an organic–inorganic nanohybrid material. We tested the bond strength of nanohybrid composites treated with experimental primers containing silane coupling agents—3-methacryloxypropyl trimethoxysilane (γ-MPTS) or 8-methacryloxyoctyl trimethoxysilane (8-MOTS)—with or without multifunctional acrylates—trimethylolpropane triacrylate (A-TMPT) or dipentaerythritol hexaacrylate (A-DPH). Shear bond strength was evaluated after 24 h of water storage at 37 °C. Untreated control and silane-only groups exhibited low shear bond strengths (e.g., control: 2.4 ± 2.0 MPa) and failed exclusively at the adhesive interface. While addition of A-TMPT did not significantly improve bond strength, addition of A-DPH produced significantly higher shear bond strengths. Highest strength was achieved with 30% 8-MOTS and A-DPH (22.4 ± 6.1 MPa), followed by 20% γ-MPTS and A-DPH (19.0 ± 7.0 MPa), and A-DPH groups produced cohesive failures. Regardless of the silane used (γ-MPTS or 8-MOTS), incorporating A-DPH in the primer consistently yielded superior bond strengths, indicating a promising strategy for improved adhesion for such nanohybrid systems. These findings provide new insights into optimizing resin–filler interfacial interactions and may contribute to the development of restorative materials with improved long-term clinical durability. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2056-5933 12 1 2026 Dental infection is associated with early relapse in patients with ANCA-associated vasculitis e006392 EN Shoichi Nawachi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshia Miyawaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Moe Sakamoto-Tokunaga Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Natsuki Kubota Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuya Terajima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Hirose Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takato Nakadoi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manami Hirata-Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Hayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruki Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eri Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Takano-Narazaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shigetomo Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-Ei Sada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic autoimmune disease where infections can trigger relapses. Dental infections, being common and associated with systemic inflammation, may play a role in AAV relapse, though their impact remains unclear. We aimed to evaluate the association between severe dental infections and early relapse in patients with AAV. Methods This retrospective cohort study included patients newly diagnosed with AAV between January 2011 and July 2022. Patients with severe dental infections requiring tooth extraction were placed in the dental infection group, while the remaining patients were assigned to the control group. The primary outcome was defined as either vasculitis relapse or all-cause mortality within 1 year of treatment initiation. Adjusted HRs (aHRs) and 95% CIs were estimated using Cox proportional hazards models. Results A total of 93 patients were enrolled with a median age of 74 years. 41 patients (44.1%) had severe dental infections in this cohort. Over the 1-year follow-up period, 13 patients experienced a relapse and two died, resulting in a composite event rate of 20.9 per 100 person-years. Dental infection was independently associated with the composite outcome (aHR, 3.78 (95% CI 1.13 to 12.66); p=0.031). Exploratory analysis indicated that composite outcome rates were similar regardless of tooth extraction among patients with dental infections. Conclusions Severe dental infections were associated with increased risk of early relapse or mortality in AAV. These findings highlight the importance of early dental evaluation in AAV management. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2218-273X 16 2 2026 Targeting the Gut in Sepsis: Therapeutic Potential of Medical Gases 199 EN Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, often resulting in multiorgan dysfunction. Among affected systems, the gastrointestinal tract plays a central role in sepsis progression by promoting systemic inflammation through impaired barrier function, immune imbalance, and microbiome alterations. Recent research has identified selected medical gases and gasotransmitters as promising therapeutic candidates for preserving gut integrity in sepsis. In particular, hydrogen, carbon monoxide, and hydrogen sulfide exhibit antioxidative, anti-inflammatory, and cytoprotective properties. These gases act through defined molecular pathways, including activation of Nrf2, inhibition of NF-κB, and preservation of tight junction integrity, thereby supporting intestinal barrier function. In addition, they influence immune cell phenotypes and autophagy, with indirect effects on the gut microbiome. Although most supporting evidence derives from preclinical models, translational findings and emerging safety data highlight the potential of gut-targeted gas-based strategies. This review summarizes current mechanistic and translational evidence for gut-protective medical gases in sepsis and discusses their integration into future organ-specific and mechanism-based therapeutic approaches. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0021-5155 2026 Real-world six-month outcomes after switching from aflibercept 2 mg to aflibercept 8 mg for neovascular age-related macular degeneration EN Hiroya Kindo Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mio Morizane Hosokawa Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chihiro Ouchi Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Matoba Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tetsuro Morita Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junko Hayashi Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Morizane Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose To investigate 6-month outcomes in eyes with neovascular age-related macular degeneration (nAMD) switched from intravitreal aflibercept 2 mg to intravitreal aflibercept 8 mg. Study design Retrospective observational study. Methods We reviewed records of consecutive nAMD eyes switched from aflibercept 2 mg to 8 mg. In eyes continuing aflibercept 8 mg, best-corrected visual acuity (BCVA), treatment intervals, and anatomical/exudative parameters were evaluated at 6 months. In eyes that could not continue, reasons for discontinuation were examined. Results Forty-four eyes from 44 patients were included. At 6 months, 35 eyes (79.5%) continued and 9 (20.5%) discontinued aflibercept 8 mg. Discontinuing eyes had significantly shorter pre-switch treatment intervals and more frequent prior therapies than continuing eyes. In the continuation group, BCVA remained stable (median 0.05 to 0.00 logMAR, P = 0.351), while the treatment interval was significantly extended (median 7.0 to 9.0 weeks, P < 0.001). Central retinal thickness and pigment epithelial detachment height decreased significantly (P = 0.035 and P = 0.021, respectively). The proportion of eyes with subretinal fluid significantly decreased from 74.3 to 37.1% (P = 0.003). Of the discontinuations, 4 were due to worsening exudation and 5 to inability to extend to ≥8 weeks as required by labeling. No intraocular inflammation or serious adverse events occurred. Conclusions Switching to aflibercept 8 mg achieved anatomical improvements and longer treatment intervals in ~80% of nAMD cases, suggesting it may be a useful alternative to aflibercept 2 mg. However, continuation may be difficult in refractory cases requiring frequent injections before switching. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1462-8910 27 10 2025 D3 lymph node dissection in colon cancer patients aged 90 years and over: Is it justified? A multi‐institutional retrospective study e70269 EN Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Hospital Satoe Takanaga Department of Gastroenterological Surgery, Okayama University Hospital Ryo Inada Department of Surgery, Kochi Health Sciences Center Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Toshiaki Toshima Department of Surgery, Kagawa Rosai Hospital Tsuyoshi Ohtani Department of Surgery, Saiseikai Okayama Hospital Ryosuke Yoshida Department of Surgery, Okayama Rosai Hospital Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Hospital Setouchi Colorectal Neoplasm Registration study group collaborators Aim: The oncological benefit of D3 lymph node dissection (D3 LND) for colon cancer in patients aged ≥90 years remains unclear. This study aimed to evaluate the impact of D3 LND on outcomes in this specific, vulnerable population. Method: This retrospective cohort study evaluated 166 patients aged ≥90 years with pathological Stages II–III colon cancer undergoing non-D3 or D3 LND from a multicentre database (2011–2022). Postoperative complications, overall survival and cancer-specific survival were compared between LND groups using propensity score-weighted analyses. Results: D3 LND group had significantly more females and laparoscopic procedures. Operation time was longer, and blood loss was lower in the D3 LND group. Postoperative complications and severe complications were significantly fewer, and postoperative hospital stay was shorter in the D3 LND group. The number of harvested lymph nodes and distal margin was significantly higher in the D3 group. While unadjusted analysis showed better overall survival with D3 LND (p < 0.001), adjusted cancer-specific survival showed no significant difference (p = 0.10). Adjusted mortality risk was significantly higher in the non-D3 group (p = 0.001). Conclusion: In nonagenarian colon cancer patients, D3 LND is safe and feasible without increasing complications, but lacks survival benefit. Careful consideration is warranted, and high-quality D2 LND must be consistently ensured when limited surgery is chosen. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1435-2451 411 1 2025 Surgical outcomes and patient selection in nonagenarians with colon cancer: a comparative multi-institutional study of laparoscopic and open approaches 21 EN Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoe Takanaga Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Ryo Inada Department of Surgery, Kochi Health Sciences Center Toshiaki Toshima Department of Surgery, Kagawa Rosai Hospital Tsuyoshi Ohtani Department of Surgery, Saiseikai Okayama Hospital Ryosuke Yoshida Department of Surgery, Okayama Rosai Hospital Naoto Hori Department of Surgery, Tottori Municipal Hospital Kaoru Shigemitsu Department of Surgery, Tsuyama Chuo Hospital Sumiharu Yamamoto Department of Surgery, Okayama City Hospital Tetsushi Kubota Department of Surgery, Kobe Red Cross Hospital Yuka Okano Department of Surgery, Onomichi City Hospital Tetsuji Nobuhisa Department of Surgery, Himeji Red Cross Hospital Fumitaka Taniguchi Department of Surgery, National Hospital Organization Iwakuni Clinical Center Wataru Ishikawa Department of Surgery, Fukuyama City Hospital Tatsuo Matsuda Department of Surgery, Matsuda Hospital Tatsuo Umeoka Department of Surgery, Matsuyama City Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Setouchi Colorectal Neoplasm Registration study group collaborators Purpose The appropriate surgical approach for colon cancer (CC) in nonagenarian patients remains a subject of clinical debate. This study aimed to compare the short-term outcomes of laparoscopic (Lap) versus open (Open) surgery in patients aged ≥ 90 years with resectable colon cancer. Methods This multi-institutional retrospective cohort study included oldest-old patientswith pathological Stage II/III CC who underwent elective surgery at 15 hospitals between 2011 and 2022. Patients with rectal cancer, Stage 0/I/IV disease, or emergency surgery were excluded. To address selection bias, inverse-probability-weighted regression adjustment and stabilized inverse probability of treatment weighting (sIPTW) were applied. The primary outcome was postoperative complications; secondary outcomes included overall survival (OS). Results Median age was 92 years in both groups. Before adjustment, the Lap group had a higher proportion of female patients (p = 0.038) and lower ASA scores (p = 0.01). Laparoscopic surgery was associated with a significantly longer operative time (220 vs. 171 min, p = 0.046) but less intraoperative blood loss (10 vs. 78 mL, p < 0.01). Postoperative complication rates were comparable (Lap: 31.8%, Open: 33.8%), while the Lap group had a significantly shorter hospital stay (13 vs. 17 days, p < 0.01). D3 lymph node dissection was more frequently performed in the Lap group (p < 0.01). After sIPTW, overall survival did not differ significantly between groups (p = 0.61). Conclusion Both laparoscopic and open surgery are feasible options for selected nonagenarians with colon cancer. Laparoscopic surgery may offer benefits in terms of reduced blood loss and shorter hospitalization, despite longer operative times. Careful patient selection considering frailty and comorbidities is essential in determining the most appropriate surgical approach. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2038-131X 2025 Early C-reactive protein as a predictive biomarker for postoperative complications following robot-assisted surgery for rectal cancer EN Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryusei Takahashi Department of Surgery, NHO Fukuyama Medical Center Hiroki Okabayashi Department of Surgery, NHO Fukuyama Medical Center Masashi Utsumi Department of Surgery, NHO Fukuyama Medical Center Hideaki Miyaso Department of Surgery, NHO Fukuyama Medical Center Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Masaru Inagaki Department of Surgery, NHO Fukuyama Medical Center This retrospective cohort study aimed to assess the predictive value of early postoperative C-reactive protein (CRP) levels for complications following robot-assisted rectal surgery (RARS) for rectal cancer. We analyzed data from 117 consecutive patients who underwent elective RARS at Okayama University Hospital between September 2020 and January 2025. Serum CRP levels were routinely measured preoperatively and on postoperative days (POD) 1 and 4. The primary outcome was the occurrence of any postoperative complication within 30 days, classified according to the Clavien–Dindo grading system. Postoperative complications were observed in 26 patients, representing 22.2% of the cohort. Univariate analysis revealed that several factors were significantly associated with complications, including older age, higher ASA score, neoadjuvant therapy, stoma creation, prolonged operative time, and elevated CRP levels on POD1 and POD4. Notably, multivariate logistic regression analysis identified POD1 CRP as a robust independent predictor of overall postoperative complications (adjusted odds ratio 0.77, 95% confidence interval (CI) [0.63–0.93], p < 0.01). In the ROC analysis, the AUC was 0.735 (bootstrap bias-corrected 95% CI 0.544–0.848). The optimal cutoff value of POD1 CRP was 5.63 mg/dl, at which Youden’s index, yielding a sensitivity of 0.615 and specificity of 0.868. In conclusion, early postoperative measurement of CRP on POD1 serves as a valuable and independent biomarker for predicting complications following RARS for rectal cancer. Incorporating POD1 CRP into postoperative surveillance may facilitate the early identification of high-risk patients, thereby facilitating timely interventions and ultimately improving surgical outcomes in this patient population. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0964-2633 70 3 2025 Prevalence and Modifiable Risk Factors of Dementia in People With Down Syndrome: Cross‐Sectional Study of Japan in Collaboration With the Intellectual Diversity for Goodness Research Consortium (INDIGO‐2019) 329 336 EN Shintaro Takenoshita Department of Neuropsychiatry, Okayama University Hospital Seishi Terada Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomokazu Inoue Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Taku Kurozumi Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Manabu Takaki Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryozo Kuwano Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Shigeru Suemitsu Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Background: People with Down syndrome (DS) have a strong genetic predisposition to Alzheimer's disease (AD). However, the clinical burden and associated risk factors in diverse, non-Western populations remain less understood. This study aimed to investigate the prevalence of dementia in Japanese adults with DS and to identify modifiable clinical factors associated with dementia. Methods: This cross-sectional multicentre study surveyed 133 adults with DS (mean age 50.1 years) residing in 45 welfare facilities across Japan in 2019. Dementia was diagnosed by a consensus panel of physicians using established criteria (DSM-5, ICD-10, DC-LD) after comprehensive assessments, including the Japanese version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID-J). Logistic regression analysis was performed to identify factors independently associated with dementia. Results: Forty-six participants (34.6%) were diagnosed with dementia. The prevalence rose sharply with age: 0% in their 30s, 30.8% in their 40s, 31.6% in their 50s and 65.5% in their 60s. After adjusting for covariates, older age, female sex, dyslipidaemia and visual impairment were independently associated with dementia. Conclusions: This study, the largest of its kind in Asia, confirms a high prevalence of dementia in institutionalized Japanese adults with DS. Crucially, this study is the first to identify dyslipidaemia and visual impairment as independent and potentially modifiable risk factors in this population. These findings highlight tangible targets for clinical interventions aimed at mitigating dementia risk in people with DS. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2261 25 1 2025 Prognostic value of right atrial strain in patients with chronic heart failure 908 EN Rie Nakayama Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Yoichi Takaya Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Mitsutaka Nakashima Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Takahiro Nishihara Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Norihisa Toh Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Miyoshi Toru Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Kazufumi Nakamura Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Shinsuke Yuasa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Aims Right ventricular dysfunction is a well-established prognostic marker in patients with heart failure (HF). However, the prognostic significance of right atrial (RA) function remains unclear. Given its sensitivity to systemic congestion, RA function may provide additional insights into HF disease progression and management. This study aimed to investigate whether RA reservoir function serves as an independent prognostic indicator in patients with chronic HF. Methods A total of 613 patients with chronic HF and a left ventricular (LV) ejection fraction of less than 50% who underwent echocardiographic assessment at Okayama University Hospital between January 2018 and March 2023 were included (median age: 68 (58–76) years; 69% male). RA reservoir function was quantified using two-dimensional speckle-tracking echocardiography. The primary endpoint was cardiovascular death or HF-related hospitalization. Kaplan–Meier survival analysis was performed to examine the association between RA reservoir function and clinical outcomes. Results During a median follow-up period of 41 months (range: 12–91 months), 119 patients experienced cardiac events. Compared with event-free patients, those with cardiac events exhibited a significantly larger RA maximum volume index (38 mL/m2 vs. 31 mL/m2, P < 0.001) and a significantly lower RA reservoir longitudinal strain (RASr) (17% vs. 22%, P < 0.001). Kaplan–Meier analysis demonstrated that patients with RASr ≤ 20% had significantly poorer event-free survival than those with RASr > 20%, even without RA volume enlargement (log-rank test, P < 0.001). Multivariate Cox regression analysis identified RASr as an independent predictor of cardiac events (hazard ratio: 0.95, 95% confidence interval: 0.93 to 0.97, P < 0.001). Conclusions In patients who experienced adverse cardiac events, a reduced RASr and an increased RA maximum volume were observed. Furthermore, a reduced RASr was independently associated with an increased risk of cardiovascular death and HF-related hospitalization in patients with chronic HF and LV dysfunction. These findings indicate that RASr may serve as a valuable prognostic marker for the risk stratification and management of chronic HF. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1546-0096 23 1 2025 Comparison of clinical practices during the transitional and young adult phases between patients with oligoarticular/polyarticular juvenile idiopathic arthritis and those with rheumatoid arthritis in Japan 120 EN Sho Mori Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine Kosuke Shabana Department of Pediatrics, Osaka Medical and Pharmaceutical University Toshihiro Matsui Department of Rheumatology Research, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital Tomo Nozawa Department of Pediatrics, Graduate School of Medicine, Yokohama City University Yuko Sugita Department of Pediatrics, Osaka Medical and Pharmaceutical University Minako Tomiita Department of Allergy and Rheumatology, Chiba Children’s Hospital Yasuo Nakagishi Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children’s Hospital Yuichi Yamasaki Department of Pediatrics, Kagoshima University Hospital Hiroaki Umebayashi Department of General Pediatrics, Miyagi Children’s Hospital Masato Yashiro Department of Pediatrics, Okayama University Hospital Naomi Iwata Department of Infection and Immunology, Allergy and Immunology Center, Aichi Children’s Health and Medical Center Junko Yasumura Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences Hiroyuki Wakiguchi Department of Pediatrics, Yamaguchi University Graduate School of Medicine Takeshi Yamamoto Department of Pediatrics, Chiba University Graduate School of Medicine Shunichiro Takezaki Department of Pediatrics, Faculty of Medicinea and Graduate School of Medicine, Hokkaido University Yuka Okura Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center Tadafumi Yokoyama Department of Pediatrics, Kanazawa University Masaki Shimizu Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Masahiro Hirayama Department of Pediatrics, Mie University Graduate School of Medicine Shigeto Tohma Department of Rheumatology, National Hospital Organization Tokyo National Hospital Nami Okamoto Department of Pediatrics, Osaka Medical and Pharmaceutical University Masaaki Mori Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine Background Juvenile idiopathic arthritis (JIA) is a chronic inflammatory condition that frequently persists into adulthood, posing long-term challenges in disease control and quality of life. However, clinical management during the transitional and young adult phases remains insufficiently characterized, especially in comparison with adult-onset rheumatoid arthritis (RA). This study aimed to compare disease activity, medication use, and treatment practices between patients with oligoarticular/polyarticular JIA and those with RA, focusing on individuals aged 16–30 years. Methods Data were derived from two nationwide multicenter databases in Japan—NinJa (National Database of Rheumatic Diseases in Japan) for RA and CoNinJa (a pediatric counterpart of NinJa) for JIA. A total of 176 JIA and 152 RA patients, all aged 16–30 years, were analyzed. Clinical parameters, disease activity indices, and medication profiles were compared using the Mann–Whitney U test and Fisher’s exact test. Results Compared to RA patients, JIA patients demonstrated significantly lower disease activity (median SDAI 0.6 vs. 2.4) and higher remission rates, particularly Boolean remission (70% vs. 44%) (p < 0.001). MTX usage was less frequent in JIA (49% vs. 68%, p < 0.001), whereas biologic use was notably more common (69% vs. 38%, p < 0.001), with 31% involving off-label prescriptions. Among patients in CDAI remission, biologic monotherapy was observed more frequently in JIA (29% vs. 7%, p < 0.001). Discontinuation of MTX was most commonly attributed to disease improvement (58%) or gastrointestinal intolerance (nausea, 29%). Subcutaneous tocilizumab, though unapproved for JIA in Japan, had the lowest discontinuation rate (4%), suggesting favorable tolerability. Conclusions Despite an overlap in age, patients with JIA and RA exhibit distinct disease characteristics and therapeutic patterns. These differences underscore the need to expand approved treatment options for JIA, promote equitable access to biologics, and strengthen transitional care frameworks. Further research is warranted to explore long-term outcomes, reproductive health considerations, and socioeconomic barriers that influence treatment continuity in young adults with childhood-onset arthritis. No potential conflict of interest relevant to this article was reported.

American Medical Association (AMA) Acta Medica Okayama 2574-3805 8 11 2025 Trastuzumab Deruxtecan for ERBB2-Mutant Metastatic Non–Small Cell Lung Cancer With or Without Brain Metastases: A Secondary Analysis of Randomized Clinical Trials e2543107 EN Pasi A. Jänne Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute David Planchard Department of Medical Oncology, Thoracic Cancer Group, Gustave Roussy, Medical Oncology Koichi Goto Department of Thoracic Oncology, Nation Cancer Center Hospital East Egbert F. Smit Department of Pulmonary Diseases, Leiden University Medical Center Adrianus Johannes de Langen Department of Thoracic Oncology, Netherlands Cancer Institute Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Toshio Kubo Center for Clinical Oncology, Okayama University Hospital Maurice Pérol Department of Medical Oncology, Centre Léon Bérard Enriqueta Felip Department of Medical Oncology, Vall d’Hebron University and Vall d’Hebron Institute of Oncology Hidetoshi Hayashi Department of Medical Oncology, Kindai University Faculty of Medicine Kazuhiko Nakagawa Department of Medical Oncology, Kindai University Faculty of Medicine Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Misako Nagasaka Division of Hematology-Oncology, Department of Medicine, University of California Irvine Kaline Pereira Daiichi Sankyo Inc Ayumi Taguchi Daiichi Sankyo Co Ltd Ahmed Ali Daiichi Sankyo Europe GmbH Maha Karnoub Daiichi Sankyo Inc Rie Yonemochi Daiichi Sankyo Inc David Leung Daiichi Sankyo Inc Bob T. Li Thoracic Oncology and Early Drug Development Service, Global Research Program, Memorial Sloan Kettering Cancer Center Importance Brain metastases reduce overall survival rates of patients with non–small cell lung cancer (NSCLC); patients with epidermal growth factor receptor 2 (ERBB2 [formerly HER2])–mutant NSCLC are more likely to have baseline brain metastases. Trastuzumab deruxtecan (T-DXd) is an approved ERBB2-directed treatment for previously treated unresectable or metastatic ERBB2-mutant NSCLC. Objective To assess the clinical effectiveness and safety of T-DXd 5.4 mg/kg and 6.4 mg/kg doses in patients with previously treated ERBB2-mutant metastatic NSCLC with or without untreated or previously treated stable brain metastases. Design, Setting, and Participants This post hoc secondary analysis pooled patients from the DESTINY-Lung01 (data cutoff date: December 3, 2021) and DESTINY-Lung02 (data cutoff date: December 23, 2022) clinical trials by T-DXd dose (5.4 mg/kg and 6.4 mg/kg). DESTINY-Lung01 was a multicenter, open-label, 2-cohort, nonrandomized phase 2 study, while DESTINY-Lung02 was a dose-blinded, multicenter, 2-cohort, randomized phase 2 study. Participants had a previously treated ERBB2-mutant metastatic NSCLC with or without untreated or previously treated stable brain metastases at baseline. All statistical analyses were performed from April 2023 to October 2024. Intervention Patients received a T-DXd dose of either 5.4 mg/kg or 6.4 mg/kg intravenously every 3 weeks. Main Outcome and Measure Systemic and intracranial effectiveness by blinded independent central review using RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1, sites of progression, and safety. Results This analysis included 102 patients in the T-DXd 5.4-mg/kg dose group (65 females [64%]; median [range] age, 57.5 [37.0-83.0] years and 59.5 [30.0-79.0] years in patients with and without brain metastases, respectively) and 141 patients in the T-DXd 6.4-mg/kg dose group (94 females [67%]; median [range] age, 62.5 [29.0-88.0] years and 59.0 [27.0-83.0] years in patients with and without brain metastases, respectively). In each group, 31% (32 of 102) and 38% (54 of 141) of patients, respectively, had baseline brain metastases and 53% (17 of 32) and 44% (24 of 54), respectively, received prior brain metastasis treatment. In patients with and without brain metastases, systemic confirmed objective response rates (ORRs) were 47% (15 of 32; 95% CI, 29%-65%) and 50% (35 of 70; 95% CI, 38%-62%), respectively, with the T-DXd 5.4-mg/kg dose, and 50% (27 of 54; 95% CI, 36%-64%) and 59% (51 of 87; 95% CI, 48%-69%) with the T-DXd 6.4-mg/kg dose. Median progression-free survival was 7.1 (95% CI, 5.5-9.7) months in the T-DXd 5.4-mg/kg dose group and 7.1 (95% CI, 4.5-9.6) months in the T-DXd 6.4-mg/kg dose group of patients with baseline brain metastases. Among patients with measurable baseline brain metastases, intracranial confirmed ORRs were 50% (7 of 14; 95% CI, 23%-77%) with the T-DXd 5.4-mg/kg dose and 30% (9 of 30; 95% CI, 15%-49%) with the T-DXd 6.4-mg/kg dose. At both doses, the safety profile of T-DXd was generally manageable, regardless of baseline brain metastases, favoring the T-DXd 5.4 mg/kg dose. Conclusions and Relevance In this secondary analysis, T-DXd at the approved dose of 5.4 mg/kg showed antitumor activity in patients with previously treated ERBB2-mutant metastatic NSCLC with or without brain metastases. This finding supports T-DXd 5.4 mg/kg use in this population. No potential conflict of interest relevant to this article was reported.

American Association for Cancer Research (AACR) Acta Medica Okayama 2767-9764 6 2 2026 Clinical Characteristics and Spatial Transcriptome Analysis of Non–Small Cell Lung Cancers Exhibiting Early Alectinib Resistance: A Retrospective OLCSG Study 284 293 EN Tadahiro Kuribayashi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Go Makimoto Department of Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Hirofumi Inoue Center for Comprehensive Genomic Medicine, Okayama University Hospital Toshihide Yokoyama Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital Shoichi Kuyama Department of Respiratory Medicine, NHO Iwakuni Clinical Center Yuka Kato Department of Thoracic Oncology and Medicine, National Hospital Organization, Shikoku Cancer Center Kenichiro Kudo Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center Naokatsu Horita Department of Respiratory Medicine, Kure Kyosai Hospital Hiroe Kayatani Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Masaaki Inoue Department of Chest Surgery, Shimonoseki City Hospital Keisuke Sugimoto Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Some anaplastic lymphoma kinase (ALK) gene rearrangement–positive lung cancers show early resistance, within 3 months, to alectinib. This study investigated the clinical and molecular characteristics of these patients. We analyzed patients with unresectable stage III/IV disease without indications for radical radiotherapy and recurrent ALK-positive lung cancer who received alectinib as the primary ALK tyrosine kinase inhibitor between 2013 and 2021 at nine hospitals. In total, 103 patients were included. The median age was 65 years; 44 were male and 22 had brain metastases. The median progression-free survival and overall survival (OS) were 28.7 and 80.6 months. Nineteen patients treated for ≤3 months and 84 treated for >3 months were categorized into the early resistance and responder groups, respectively. The early resistance group had significantly shorter OS (8.4 months vs. not estimable, P < 0.001) and was significantly more likely to have brain metastases (42% vs. 17%, P = 0.027). They also showed elevated inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR). Univariate analysis identified brain metastases and high NLR as significant predictors of early resistance. Spatial transcriptome analysis and immunohistochemical staining revealed upregulation of annexin A1 (ANXA1), a calcium-dependent phospholipid-binding protein involved in inflammation and cancer progression, in the early resistance group. Interleukin 6 stimulation, prompted by elevated inflammatory markers, increased ANXA1 expression and reduced alectinib sensitivity. Knockdown of ANXA1 improved alectinib sensitivity in alectinib-resistant cells. In conclusion, brain metastases and high NLR are associated with early resistance. ANXA1 may play an important role in mediating early resistance. New treatment options for the early resistance group are required. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0916-9636 2026 Distinct associations of blood pressure phenotypes with subclinical cerebrovascular disease and coronary artery calcification in Japanese men EN Nomin Bayaraa NCD Epidemiology Research Center, Shiga University of Medical Science Yuichiro Yano NCD Epidemiology Research Center, Shiga University of Medical Science Aya Kadota NCD Epidemiology Research Center, Shiga University of Medical Science Nazar Mohd Azahar Tran Ngoc Hoang Phap National Institutes of Biomedical Innovation, Health and Nutrition Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiko Kondo NCD Epidemiology Research Center, Shiga University of Medical Science Sayuki Torii NCD Epidemiology Research Center, Shiga University of Medical Science Akira Fujiyoshi Department of Hygiene, School of Medicine, Wakayama Medical University Takayoshi Ohkubo Department of Hygiene and Public Health, Teikyo University School of Medicine Akihiko Shiino Molecular Neuroscience Research Center, Shiga University of Medical Science Kazuhiko Nozaki Department of Neurosurgery, Shiga University of Medical Science Katsuyuki Miura NCD Epidemiology Research Center, Shiga University of Medical Science Hypertension, encompassing white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH), is an established risk factor for cardiovascular diseases (CVDs), including atherosclerosis. However, among the general population, findings on which target organ is affected by the different phenotypes of hypertension remain unclear. In this community-based observational study of Shiga Epidemiological Study of Subclinical Atherosclerosis, 740 Japanese men underwent brain magnetic resonance imaging to assess the presence of lacunar infarction, white-matter hyperintensities, microbleeds, and intracranial artery stenosis (ICAS) between 2012 and 2015. They also underwent office blood pressure (BP) measurements, home BP monitoring for at least five consecutive days, and coronary artery calcification (CAC) assessments between 2010 and 2014. The final analysis included 686 participants without a history of CVDs. Of the 686 participants, the mean age ( ± SD) was 68.0 ( ± 8.3) years, and 39.3% were taking antihypertensive medication. In multivariable-adjusted models, each of WCH, MH, and SH was significantly associated with a higher risk of microbleeds compared to normotension. However, the association of WCH with microbleeds was evident only among those on antihypertensive medication (adjusted odds ratio [OR] 6.75 [95% CI 1.83–24.86]) and absent in those not on such medication (adjusted OR 1.20 [95% CI 0.31–4.73]). SH was associated with lacunar infarction, ICAS, and CAC. Among Japanese men, WCH, MH, SH were associated with subclinical cerebrovascular diseases, whereas only SH was associated with CAC. Moreover, any elevated BP phenotype increased the risk of microbleeds. Our findings suggest that different hypertension phenotypes distinctly affect target organs, particularly the brain and heart. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1123-6337 29 1 2025 Safety and feasibility of D3 lymph node dissection in oldest-old patients undergoing colorectal cancer surgery: a multi-institutional, retrospective analysis 146 EN R. Inada Department of Surgery, Kochi Health Sciences Center F. Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences T. Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital S. Takanaga Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences T. Toshima Department of Surgery, Kagawa Rosai Hospital T. Ohtani Department of Surgery, Saiseikai Okayama Hospital R. Yoshida Department of Surgery, Okayama Rosai Hospital N. Hori Department of Surgery, Tottori Municipal Hospital K. Shigemitsu Department of Surgery, Tsuyama Chuo Hospital S. Yamamoto Department of Surgery, Okayama City Hospital T. Kubota Department of Surgery, Kobe Red Cross Hospital Y. Okano Department of Surgery, Onomichi City Hospital T. Nobuhisa Department of Surgery, Himeji Red Cross Hospital F. Taniguchi Department of Surgery, National Hospital Organization Iwakuni Clinical Center W. Ishikawa Department of Surgery, Fukuyama City Hospital R. Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences T. Matsuda Department of Surgery, Matsuda Hospital T. Umeoka Department of Surgery, Matsuyama City Hospital T. Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Setouchi Colorectal Neoplasm Registration Study Group Collaborators Background Colorectal cancer (CRC) is a significant health burden, with lymph node dissection (LND) playing a critical role in staging and guiding treatment. However, the optimal extent of LND for the oldest-old population (aged ≥ 90 years) remains undefined because of insufficient targeted clinical data. This study aimed to compare the short-term outcomes of D3 versus non-D3 LND in Stage II–III CRC in oldest-old patients. Methods This retrospective cohort study utilized data from the Setouchi Colorectal Neoplasm Registration database, including 282 oldest-old patients with CRC treated between 2011 and 2022. Patients were stratified into D3 and non-D3 LND groups, with inverse-probability-weighted regression adjustment implemented to address potential confounding factors. Postoperative complications and hospital stays were analyzed using regression models and descriptive statistics. Results D3 LND resulted in significantly higher lymph node harvests in both Stage II and Stage III patients (p < 0.01). There were no significant differences in overall or major postoperative complications between D3 and non-D3 groups. Hospital stays were comparable for Stage II patients but shorter for Stage III patients in the D3 group (p < 0.01). Complication rates ranged from 28% to 47.7%, with surgical site infections and pneumonia being the most common. Conclusions D3 LND can be safely performed in oldest-old patients with CRC without increasing postoperative complications or extending hospital stays. These findings support the feasibility of extensive LND in this age gr No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 3 2026 A Rare Association of Congenital Glaucoma and Retinitis Pigmentosa: A 22-Year Follow-Up Case e105012 EN Toshihiko Matsuo Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Primary congenital glaucoma is a rare congenital disease with a genetic background that shows high intraocular pressure due to ocular outflow anomalies. Retinitis pigmentosa is a predominant form of inherited retinal disorders. In this study, we present the case of a patient with primary congenital glaucoma in association with retinitis pigmentosa. A four-month-old female baby was brought to the emergency department due to corneal opacity in the left eye. The intraocular pressure measured by a hand-held applanation tonometer was 40 mmHg in the right eye and 36 mmHg in the left eye. She was otherwise healthy and diagnosed with primary congenital glaucoma. She immediately underwent trabeculotomy ab externo in both eyes under general anesthesia, and the intraocular pressure was lowered to 15 mmHg in the right eye and 12 mmHg in the left eye three weeks later. At the age of nine months, she was found to have retinal degeneration along the upper and lower vascular arcades of the fundus in both eyes and was diagnosed with retinitis pigmentosa. At the age of one year and 10 months, the visual acuity was measured at 0.2 in the right eye and 0.2 in the left eye for the first time by a preferential looking procedure. The intraocular pressure was 9 mmHg in both eyes under sedation, and she did not use any topical medication. At the age of three years and three months, the uncorrected visual acuity and best-corrected visual acuity with myopic astigmatism correction were 0.1 and 0.15, respectively, in the right eye and 0.6 and 0.7, respectively, in the left eye. Occlusion therapy with an eye patch over the left eye for one hour daily was started. At the age of four years and 10 months, the best-corrected visual acuity was 0.7 in both eyes. At the age of six years, occlusion therapy was discontinued, and full-correction glasses were prescribed, based on cycloplegic refraction. The visual acuity in the right eye decreased to 0.3 at the age of 11 years and further to 0.1 at the age of 12 years, while the visual acuity in the left eye remained 0.8. Afterwards, she maintained a visual acuity of 0.1 in the right eye and 0.8 in the left eye until the age of 22 years. An incidental presence of primary congenital glaucoma in this patient led to the detection of retinitis pigmentosa in earlier years and allowed long-term follow-up for 22 years. Even though genetic testing was not performed for this patient, the abnormal function of primary cilia, designated as ciliopathy, might explain the co-occurrence of primary congenital glaucoma and retinitis pigmentosa. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1999-4923 18 1 2026 Streamlined Radiosynthesis of [18F]Fluproxadine (AF78): An Unprotected Guanidine Precursor Enables Efficient One-Step, Automation-Ready Labeling for Clinical Use 123 EN Xinyu Chen Nuclear Medicine, Faculty of Medicine, University of Augsburg Kaito Ohta Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Kimura Agency for Health, Safety and Environment, Kyoto University Yusuke Yagi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Sasaki Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoko Nose Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaru Akehi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiko Yamane Department of Molecular Imaging Research, Kobe City Medical Center General Hospital Rudolf A. Werner Department of Nuclear Medicine, LMU Hospital, and German Cancer Consortium (DKTK), Partner Site Munich, Ludwig-Maximilians-University of Munich Takahiro Higuchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: [18F]Fluproxadine (formerly [18F]AF78) is a PET radiotracer targeting the norepinephrine transporter (NET) with potential applications in cardiac, neurological, and oncological imaging. Its guanidine moiety, while essential for NET binding, presents major radiosynthetic challenges due to high basicity and the harsh deprotection conditions required for protected precursors. Previous methods relied on multistep procedures, strong acids, and complex purification, limiting clinical translation. This study aimed to develop a practical one-step radiosynthesis suitable for routine and automated production. Methods: A direct SN2-type nucleophilic [18F]fluorination was performed using an unprotected guanidine precursor to eliminate deprotection steps. Reaction parameters, including the base system, solvent composition, precursor concentration, and temperature, were optimized under conventional and microwave heating. Radiochemical conversion (RCC) and operational robustness were evaluated, and purification strategies were assessed for automation compatibility. Results: Direct [18F]fluorination using the unprotected precursor reduced the total synthesis time to 60–70 min. Optimal conditions employed a tert-butanol/acetonitrile (4:1) solvent system with K2CO3/Kryptofix222, affording RCC up to 33% under conventional heating. Microwave irradiation further improved efficiency, achieving RCC of up to 64% within 1.5 min at 140 °C. The method showed broad tolerance to variations in the base molar ratio and precursor concentration and enabled isocratic HPLC purification. Conclusions: This one-step radiosynthesis overcomes longstanding challenges in [18F]fluproxadine production by eliminating harsh deprotection and enabling high-yield, automation-ready synthesis, thereby improving clinical feasibility. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 5 2026 Fgf10 Gene Dosage from a Single Allele Is Insufficient for Forming Multilayered Epithelial Cells in the Murine Lacrimal Gland 2113 EN Shiori Ikeda Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Keita Sato Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuki Tajika Department of Radiological Technology, Gumma Prefectural College of Health Sciences Hirofumi Fujita Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Bando Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsutomu Nohno Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Satoru Miyaishi Department of Legal Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hideyo Ohuchi Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mutations in the fibroblast growth factor 10 (FGF10) gene in humans cause aplasia of the lacrimal and salivary glands (ALSG). In patients with ALSG, heterozygous loss-of-function mutations are found, and FGF10 haploinsufficiency results in the absence of these secretory organs. Lacrimal glands (LGs) are formed through epithelial thickening, budding, and branching morphogenesis. To compare the variable phenotypes of the Fgf10+/− Harderian glands (HGs) previously reported, we examined the development of LGs in wild-type (WT), Fgf10+/−, and Fgf10-null mice. Pax6 immunostaining was performed to visualize the LG primordia from embryonic day 15.5 (E15.5) onwards. In situ hybridization of the genes encoding the epithelial receptor of FGF10, FGFR2b, and its other ligands was performed to determine their potential involvement in LG development. LG primordia were not observed in Fgf10+/− mice bilaterally at E16.5 or later stages. At E15.5, budding from the developing conjunctival epithelium (CE) was observed in a small fraction of the Fgf10+/− LG primordia. In contrast, the Fgf10-null CE failed to promote budding. Among Fgf1, Fgf3, Fgf7, Fgf10, and Fgf22, Fgf10 was expressed in the mesenchyme surrounding developing LG epithelial cells, whereas Fgf1 was expressed in the LG epithelium of WT mice. Fgf7 was initially expressed in the mesenchyme surrounding the nascent LG epithelium, but its expression subsequently became diffused. Thus, we conclude that among the FGFR2b ligands, initial LG formation is dependent on the mesenchymal factors FGF10 and FGF7, and FGF1 is likely to function as an epithelial factor in the LG primordia. A single allele of Fgf10 was found to be insufficient to support the budding process during LG morphogenesis. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 1350-4622 2026 Towards place-responsive climate change education: Mongolian primary teachers’ pedagogical judgement across urban and rural contexts EN Shinetsetseg Gerelkhuu Graduate School of Humanities and Social Sciences, Okayama University Khalifatulloh Fiel’ardh Graduate School of Education, Okayama University Hiroki Fujii Graduate School of Education, Okayama University Batchuluun Yembuu Geography Department, Mongolian National University of Education Uuriintuya Dembereldorj Lifelong Learning and Distance Education Department, Mongolian National University of Education Climate change education (CCE) in primary schools is increasingly recognised as essential, yet how teachers interpret and enact CCE across diverse local contexts remains underexplored. This study examines how Mongolian primary school teachers working with students aged 6–11 in urban and rural contexts interpret and teach climate change, with particular attention to the role of place. Drawing on semi-structured interviews with 20 teachers across contrasting contexts, the study explores how environmental, cultural, and institutional conditions shape teachers’ pedagogical interpretations and classroom practices. Data were analysed using reflexive thematic analysis, informed by conceptual frameworks that position place as an active mediator of teaching and learning. Findings show that rural teachers frequently integrated traditional ecological knowledge and lived environmental experience to connect global climate processes with locally observable ecological change, emphasising livelihood impacts and intergenerational ecological memory. Urban teachers, by contrast, framed climate change through anthropogenic pressures such as air pollution, waste, and infrastructure constraints, foregrounding feasible individual actions within everyday school contexts. Across both settings, teachers exercised place-responsive pedagogical judgement by selectively adapting climate content to local realities while navigating curriculum constraints and workload pressures. The study contributes a place-responsive account of teachers’ pedagogical judgement in CCE, demonstrating how place functions not only as context but as a condition shaping pedagogical feasibility. No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 セクシュアリティのゆらぎと発達障害のADHDとの関連 1 11 EN Megumi MATSUI Institute for Promotion of Education and Campus Life, Okayama University 10.18926/70108 　セクシュアリティのゆらぎと発達障害のADHDとの関連を明らかにするため，WEBによる縦断調査を行った。18歳以上の成人を対象とし，第1回目の調査は11,018人，1年後の第2回目の調査では5,474人から回答を得た。性自認，性的指向，性表現の様々なセクシュアリティについて，2回の調査での該当・非該当で4群に分け，ADHD得点について1要因の被験者間分散分析を行った。「デミロマンティック」「デミセクシュアル」以外で群の主効果が有意であり，「異性愛」「ゲイ」を除くセクシュアリティで，2回とも「非該当」群よりも「該当→非該当」群のADHD得点が有意に高かった。これによりセクシュアリティのゆらぎとADHDとの関連が示唆された。 No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 15 5 2026 Effect of Surgical Procedures for Rheumatoid Forefoot Deformities on Radiographic Foot Length and Width Variations 1877 EN Masahiro Horita Department of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama University Yohei Kiso Department of Orthopaedic Surgery, Kurashiki Sweet Hospital Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama City Hospital Ryuichi Nakahara Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenta Saiga Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Nishida Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Background: The number of patients with rheumatoid arthritis (RA) undergoing forefoot arthroplasty has increased to better control the disease. Despite patients frequently expressing concerns regarding postoperative foot appearance and footwear-related expectations, no study has investigated postoperative changes in foot length and width in patients with RA. The aim of this study was to evaluate the effect of surgical procedures for rheumatoid forefoot deformities on variations in radiologically determined foot length and width. Methods: In total, 72 feet of 50 women and 3 men (average age: 66.7 years) underwent joint-preserving arthroplasty (n = 33) and arthrodesis of the first metatarsophalangeal joint with shortening osteotomy of the lesser metatarsals or resection arthroplasty of the lesser metatarsal heads (n = 39); procedures were carried out in our institute from August 2013 to February 2020. The mean disease duration was 23.5 years, and the average follow-up period was 17.5 months. Pre- and postoperative hallux valgus angle (HVA), intermetatarsal angle (IMA) of the first and second metatarsals (M1M2A), and IMA of the first and fifth metatarsals (M1M5A) were measured on weightbearing radiographs as well as foot length and width. We also evaluated the correlation between changes in radiographic parameters and variations in radiologically determined foot length and width. Results: Radiologically determined foot width changed significantly from 10.1 cm to 9.7 cm (p < 0.01), while no significant difference was found between pre- and postoperative radiologically determined foot length. HVA, M1M2A, and M1M5A were significantly improved after the surgery (p < 0.01, p < 0.01, and p < 0.01, respectively). A significant negative correlation was found between the variation in radiologically determined foot length and changes in HVA (r = −0.29, p = 0.02) and M1M5A (r = −0.23, p < 0.05), while a significant positive correlation was found between the variation in the foot width and changes in HVA (r = 0.34, p < 0.01), M1M2A (r = 0.55, p < 0.01), and M1M5A (r = 0.45, p < 0.01). There were no significant differences between operative procedures regarding variation in radiologically determined foot length and width. Conclusions: Surgical procedure for rheumatoid forefoot deformity improved radiographic parameters and reduced radiographic foot width while maintaining foot length. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-1380 19 1 2026 Association of Wet-Bulb Globe Temperature with heat-related illness hospitalizations in Japan: a time-stratified, case-crossover study 11 EN Yuka Yamamura Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Fumiya Sasai Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Kohei Tokioka Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Jun Kanda Emergency and Critical Care Medicine, Nippon Medical School Musashikosugi Hospital Shoji Yokobori Department of Emergency and Critical Care Medicine, Nippon Medical School Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Background Heat-related illnesses are a serious public health concern and are exacerbated by global warming. Wet-Bulb Globe Temperature (WBGT) is widely used as a heat stress indicator, but its clinical impact remains unclear. This study aimed to investigate the association between hourly variations in WBGT and the incidence of hospitalizations for heat-related illness in Japan using a nationwide database. By incorporating individual-level clinical data and performing stratified analyses, we sought to provide a more granular understanding of how heat exposure affects the risk of heat-related illness requiring hospitalization. Methods We conducted a time-stratified, case-crossover study using data collected from July to September in 2020 and 2021 in the Heatstroke STUDY registry. The inclusion criteria were patients registered in the Heatstroke STUDY registry, specifically hospitalized patients with heat-related illness who were transported to participating hospitals during the study period. Hourly WBGT values were assigned based on the nearest monitoring station to each hospital. Conditional logistic regression and distributed lag models were used to estimate associations between WBGT and the risk of hospitalization. Results A total of 1,653 heat-related illness hospitalizations were analyzed. The mean patient age was 67.9 years; 67.6% were male. Each 1 °C increase in WBGT at onset (hospital arrival) was associated with a significantly increased risk of hospitalization (OR 1.10, 95% CI: 1.05–1.15). The cumulative effect over the prior six hours was also significant (OR 1.56, 95% CI: 1.50–1.62). Compared with WBGT < 25 °C, adjusted ORs were 3.39 (25–27 °C), 8.81 (28–30 °C), and 22.10 (≥ 31 °C). Stratified analyses suggested stronger associations among several subgroups; however, only patients with mental disorders showed statistically significant effect modification, whereas elevated WBGT posed a risk across all groups. Conclusions Higher WBGT levels were associated with an increased risk of heat-related hospitalization. Although the effect appeared greater in some subgroups, only patients with mental disorders demonstrated statistically significant effect modification, suggesting elevated WBGT confers risk broadly. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-4418 16 4 2026 Recent Advances in Kidney Disease Diagnosis and Treatment: Bridging Molecular Insights and Clinical Practice 549 EN Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2079-7737 15 5 2026 Alpha-Ketoglutarate Drives an Osteogenic and Extracellular Matrix Gene Program in Periodontal Ligament Fibroblasts via Selective Reduction of H3K27me3 372 EN Ryu Hasegawa Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Shigeki Suzuki Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences Rahmad Rifqi Fahreza Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Shin-Ho Tsai Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences Yoshino Daidouji Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Masato Omori Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Tetsuhiro Kajikawa Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Satoru Yamada Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Periodontal disease damages the tissues that support teeth and can ultimately lead to tooth loss, yet effective treatments to regenerate these tissues are still limited. Recent studies have shown that substances produced during normal cellular metabolism can influence how genes are regulated, but their role in periodontal regeneration has not been fully clarified. In this study, we investigated whether alpha-ketoglutarate, a naturally occurring metabolite involved in energy production, could promote periodontal tissue regeneration. We found that alpha-ketoglutarate enhanced bone-related and extracellular matrix-related gene expression in human periodontal ligament cells by reducing a repressive gene-regulatory signal that normally suppresses these genes. Importantly, alpha-ketoglutarate did not broadly alter chromatin accessibility, indicating that its effects were mediated through selective gene regulation. Furthermore, oral administration of alpha-ketoglutarate promoted alveolar bone regeneration and collagen-rich tissue formation in a mouse model of periodontal disease. Because alpha-ketoglutarate is a naturally occurring molecule in the body, these findings suggest that metabolite-based regulation of gene activity may represent a promising and safe approach for periodontal tissue regeneration. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 18 4 2026 Antigen Remodeling in Colorectal Cancer: How Radiotherapy and Chemotherapy Enhance Immunotherapy Responsiveness 715 EN Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiaki Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Moriwake Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masashi Kayano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Colorectal cancer (CRC) is traditionally considered a “cold tumor” characterized by low immunogenicity and limited responsiveness to immune checkpoint inhibitors (ICIs). However, recent findings reveal that cytotoxic modalities can reprogram this immunologically inert landscape. This review integrates these evolving concepts to guide the optimization of future treatments. Radiotherapy induces extensive DNA double-strand breaks, which may generate de novo mutations through error-prone repair while simultaneously exposing cryptic antigens via increased transcriptional instability, alternative splicing, and enhanced proteasomal processing. Chemoradiation also amplifies epigenetic and epitranscriptomic sources of neoepitope diversity, including RNA editing and stress-induced splicing alterations, expanding the immunopeptidome beyond canonical mutation-driven neoantigens. These changes collectively enhance antigen presentation and facilitate T-cell priming. Chemotherapy further reduces immunosuppressive cell populations and promotes dendritic cell activation, creating a permissive milieu for subsequent immune engagement. Clinically, the VOLTAGE studies demonstrated that long-course chemoradiotherapy can sensitize even mismatch repair–proficient rectal cancers to PD-1 blockade, yielding clinically meaningful pathological responses. In contrast, mismatch repair–deficient rectal tumors may respond completely to ICIs alone. Short-course radiotherapy combined with chemotherapy and ICIs has also shown encouraging activity in the setting of total neoadjuvant therapy. Collectively, these findings support a paradigm in which radiotherapy, chemotherapy, and epigenetic/epitranscriptomic alterations—including RNA editing—act as potent modulators of tumor antigenicity. By expanding the neoantigen repertoire and reshaping the tumor microenvironment, these strategies can transform CRC from a cold tumor into one that is increasingly responsive to immunotherapy. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2073-445X 15 2 2026 A Study on the Development of an Image Classification System for Urban Sprawl Areas in Japan 275 EN Ryota Hemmi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takehito Ujihara Faculty of Environmental, Life, Natural Science and Technology, Okayama University Ryosuke Ando National Institute for Land and Infrastructure Management, Ministry of Land, Infrastructure Transport and Tourism Seiji Hashimoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University In Japan, unlike in many other countries, urbanization has progressed while original rural road structures have been retained, leading to distinctive urban sprawl areas with intermingling residential lots and farmland. Currently, much of Japan’s urban areas consist of urban sprawl areas, posing considerable challenges for infrastructure development. However, for such urban sprawl areas in Japan, it is difficult to say that methods have been established to identify their spatial distribution based on quantitative evaluation. Therefore, for this study, we used machine learning to investigate a system that extracts sprawling urban areas from aerial photographs divided into meshes. In the system’s design, we prioritized precision to ensure the reliable detection of urban sprawl areas. Consequently, the accuracy of identifying sprawl areas achieved precision of 0.81, recall of 0.63, and an F-score of 0.71. Examination of the classification results of sprawl areas revealed that most misclassifications occurred near class boundaries. By contrast, areas with particularly high levels of urban sprawl showed few misclassifications. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2730-664X 6 1 2026 Effects of an oral exercise intervention on pre-frailty or frailty in older people: a randomized clinical trial 96 EN Noriko Takeuchi Department of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama University Nanami Sawada Section of Preventive and Public Health Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University Sakura Inada Division of Health Promotion, Okayama-City Health Center Manabu Morita Department of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health Care Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Frailty is often experienced by older adults, which can lead to long-term health problems. We aimed to examine associations with improvements in nutritional status, sarcopenia (age-related loss of skeletal muscle mass and strength), and frailty in four groups with different oral exercise frequencies. Methods: We conducted a prospective, parallel multi-arm randomized controlled trial (Japan Registry of Clinical Trials (jRCT) 1062210063) to test the effects of oral exercise on frailty in older adults. Each intervention consisted of a standardized oral exercise protocol including neck exercises, lip exercises, and tongue movements, designed to improve oral function and reduce frailty. The primary outcome was the change in the number of frailty criteria from baseline to follow-up. Individuals aged ≥60 years were screened for frailty status using standardized criteria at the Department of Preventive Dentistry at Okayama University Hospital between October 2022 and December 2023. Those identified as pre-frailty or frailty were eligible and enrolled in the study. After screening 60 individuals, 58 eligible participants were randomly assigned using block randomization to one of four oral exercise frequency groups: 3 times/day & everyday, 3 times/day & 3 days/week, once/day & everyday, and once/day & 3 days/week. A two-way repeated measures analysis of variance was used to evaluate the impact of the four frequencies of oral exercise methods on frailty in older adults. Outcome assessors were blinded; participants were not. Results: Here we show the results of the 58 participants. Group sizes are: 3 times/day & everyday (n = 14), 3 times/day & 3 days/week (n = 15), once/day & everyday (n = 14), once/day & 3 days/week (n = 15). The trial is completed as planned, and all randomized participants are analyzed. The main effect of time is significant for the number of frailty criteria (F = 14.803, p < 0.001, partial eta squared = 0.215). The mean changes from baseline to follow-up are −0.357 (95% Confidence Interval −0.787 to 0.073) in the 3 times/day & everyday group, −0.600 (95% Confidence Interval −1.255 to 0.055) in the 3 times/day & 3 days/week group, −0.571 (95% Confidence Interval −1.379 to 0.236) in the once/day & everyday group, and −0.600 (95% Confidence Interval −1.008 to −0.192) in the once/day & 3 days/week group. The main effect of time is also significant for the number of oral hypofunction criteria (F = 16.456, p < 0.001, partial eta squared = 0.234). No important adverse events or side effects related to the intervention were observed. Conclusions: After conducting oral exercises for 3 months on older adults with pre-frailty or frailty, improvements in frailty are observed. Overall, these exercises could be a simple, low-cost way to support healthy aging in the community. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1201-9712 164 2026 Global trends in Clostridioides difficile infection–related mortality, 2001-2023: An observational study 108315 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Yoshito Nishimura Division of Hematology/Oncology, Mayo Clinic Ko Harada Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai Maki Yamamoto Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuaki Takeda Quynh Thi Vu Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keith Pardillada Belangoy Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hanane Ouddoud Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: Clostridioides difficile infection (CDI) is a major public health concern, particularly in aging populations. The aim of this study was to evaluate global trends in CDI-related mortality to inform sustainable and cost-effective management strategies. Methods: We conducted an observational study using mortality data from the World Health Organization (WHO) database spanning 2001 to 2023. Sixty-three countries with satisfactory data quality and at least 12 years of data between 2001 and 2023 were included. Crude and age-standardized CDI-related mortality rates per 1,000,000 individuals were calculated after stratification by age, sex, WHO region, and sociodemographic index (SDI). Global trends were analyzed using locally weighted regression. Results: The global age-standardized CDI-related mortality rate was 0.76 per 1,000,000 individuals in 2001, peaked at 4.08 in 2010, and declined to 2.44 in 2023. The most notable downward trends were observed in the Americas and high-SDI countries. These improvements may reflect the impact of multidisciplinary efforts in CDI prevention and management. Conclusions: Although CDI-related mortality has declined globally over the past decade, the disease remains a significant threat, especially in older populations. Ongoing global efforts are essential to further reduce CDI-related deaths. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1341-321X 32 3 2026 Tick-borne pathogens in ticks collected from Humans: A prospective clinical pilot study 102931 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaomi Sumida Numakuma Hospital Osamu Kawamata Numakuma Hospital Yoshimi Hidani Numakuma Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Tick-borne diseases (TBDs), particularly Japanese spotted fever, are an increasing public health concern in Japan. Data on pathogens carried by ticks removed directly from patients and their associated clinical outcomes remain limited. This prospective study investigated pathogen carriage in patient-derived ticks and evaluated the clinical risk of TBDs. Between April and October 2025, ticks were collected from patients presenting with tick bites at two medical institutions in Western Japan. Ticks were morphologically identified and spotted fever group rickettsiae (SFGR) was detected by nested PCR targeting the 17-kDa antigen gene, followed by sequence analysis. Clinical data, including patient background, antibiotic prescriptions, and outcomes, were reviewed. Clinical information was available for 70 patients (median age; 75 years), of whom 88.6% were prescribed prophylactic antibiotics. Ticks were collected from 60 patients (85.7%), and seven adults without antibiotic prophylaxis were followed for disease onset. Sixty-two ticks, predominantly Amblyomma testudinarium (88.7%), were analyzed. SFGR was detected in eight ticks (12.9%), including seven A. testudinarium and one Ixodes nipponensis, collected from seven patients. Two patients bitten by Rickettsia tamurae–carrying ticks were observed for one month without antibiotics and remained asymptomatic. In this prospective analysis, no clinically apparent rickettsiosis was observed following bites from R. tamurae–positive ticks without antibiotic prophylaxis; however, subclinical infection could not be excluded. Despite the small sample size, our findings suggest that the clinical risk associated with R. tamurae infection may be low. Direct analysis of removed ticks from patients may help characterize pathogen reservoirs and inform targeted approaches to TBDs. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1424-8220 26 4 2026 A Generative AI–Based Technical Data Extraction Tool for IoT Application Systems 1081 EN Dezheng Kong Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Htoo Htoo Sandi Kyaw Department of Information and Communication Systems, Okayama University I Nyoman Darma Kotama Department of Information and Communication Systems, Okayama University Zihao Zhu Department of Information and Communication Systems, Okayama University Alfiandi Aulia Rahmadani Department of Information and Communication Systems, Okayama University Nowadays, Internet of Things (IoT) application systems play an essential role in smart cities, industry, healthcare, agriculture, and smart homes. For non-expert users, designing and implementing IoT application systems remains challenging, especially when configuring sensors, edge devices, and server platforms. To support configuration tasks of IoT application systems, we have developed an AI-based setup assistance tool. However, AI models still fail to reliably support newly released or previously unseen devices, sometimes producing incomplete or erroneous outputs that may lead to configuration failures. Incorporating their technical-document information into Retrieval-Augmented Generation (RAG) is an effective way to supplement AI knowledge and improve reliability. In this paper, we propose a generative AI-based technical data extraction tool to address the challenges. It extracts essential technical information using the schema-based extraction from given PDF or HTML datasheets and converts it into a structured format suitable for AI-supported configurations. A local vector database is used to enable semantic similarity retrieval and provide document-grounded evidence for RAG-based answering, ensuring consistent support for previously unseen IoT devices. For evaluations, we applied the proposal to several sensor and device datasheets and compared extracted specifications with ground-truth values to measure accuracy and completeness. Then, we compared end-to-end configuration QA reliability against a commercial baseline (ChatPDF) using the golden benchmark. The results show that the proposed tool reliably acquires key specifications and significantly improves end-to-end configuration QA reliability. Across 960 golden QA pairs, the proposed method improves Recall from 0.636 to 0.926 and Accuracy from 0.595 to 0.807 compared with ChatPDF. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1999-4893 19 2 2026 A Slide Annotation System with Multimodal Analysis for Video Presentation Review 110 EN Amma Liesvarastranta Haz Department of Information and Communication Systems, Okayama University Komang Candra Brata Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Htoo Htoo Sandi Kyaw Department of Information and Communication Systems, Okayama University Evianita Dewi Fajrianti Human Centric Multimedia Research Laboratory, Department of Informatic and Computer Engineering, Politeknik Elektronika Negeri Surabaya Sritrusta Sukaridhoto Human Centric Multimedia Research Laboratory, Department of Informatic and Computer Engineering, Politeknik Elektronika Negeri Surabaya With the rapid growth of online presentations, there has been an increasing need for efficient review of recorded materials. In typical presentations, speakers verbally elaborate on each slide, providing details not captured in the slides themselves. Automatically extracting and embedding these verbal explanations at their corresponding slide locations can greatly enhance the review process for audiences. This paper presents a Slide Annotation System that employs a robust hybrid two-stage detector to identify slide boundaries, extracts slide text through Optical Character Recognition (OCR), transcribes narration, and employs a multimodal Large Language Model (LLM) to generate concise, context-aware annotations that are added to their corresponding slide locations. For evaluations, the technical performance was validated on five recorded presentations, while the user experience was assessed by 37 participants. The results showed that the system achieved a macro-average 𝐹1 score of 0.879 (𝑆𝐷=0.024, 95% 𝐶𝐼[0.849,0.909]) for slide segmentation and 90.0% accuracy (95% 𝐶𝐼[74.4%,96.5%]) for annotation alignment. Subjective evaluations revealed high annotation validity and usefulness as rated by presenters, and a high System Usability Scale (SUS) score of 80.5 (𝑆𝐷=6.7, 95% 𝐶𝐼[78.3,82.7]). Qualitative feedback further confirmed that the system effectively streamlined the review process, enabling users to locate key information more efficiently than standard video playback. These findings demonstrate the strong potential of the proposed system as an effective automated annotation system. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2078-2489 17 1 2026 An SQL Query Description Problem with AI Assistance for an SQL Programming Learning Assistant System 65 EN Ni Wayan Wardani Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Htoo Htoo Sandi Kyaw Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Zihao Zhu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University I Nyoman Darma Kotama Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Putu Sugiartawan Graduate School of Environmental, Life, Natural Science and Technology, Okayama University I Nyoman Agus Suarya Putra Faculty of Business and Creative Design, Indonesian Institute of Business and Technology Today, relational databases are widely used in information systems. SQL (structured query language) is taught extensively in universities and professional schools across the globe as a programming language for its data management and accesses. Previously, we have studied a web-based programming learning assistant system (PLAS) to help novice students learn popular programming languages by themselves through solving various types of exercises. For SQL programming, we have implemented the grammar-concept understanding problem (GUP) and the comment insertion problem (CIP) for its initial studies. In this paper, we propose an SQL Query Description Problem (SDP) as a new exercise type for describing the SQL query to a specified request in a MySQL database system. To reduce teachers’ preparation workloads, we integrate a generative AI-assisted SQL query generator to automatically generate a new SDP instance with a given dataset. An SDP instance consists of a table, a set of questions and corresponding queries. Answer correctness is determined by enhanced string matching against an answer module that includes multiple semantically equivalent canonical queries. For evaluation, we generated 11 SDP instances on basic topics using the generator, where we found that Gemini 3.0 Pro exhibited higher pedagogical consistency compared to ChatGPT-5.0, achieving perfect scores in Sensibleness, Topicality, and Readiness metrics. Then, we assigned the generated instances to 32 undergraduate students at the Indonesian Institute of Business and Technology (INSTIKI). The results showed an average correct answer rate of 95.2% and a mean SUS score of 78, which demonstrates strong initial student performance and system acceptance. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2813-2203 5 1 2025 A Threshold Selection Method in Code Plagiarism Checking Function for Code Writing Problem in Java Programming Learning Assistant System Considering AI-Generated Codes 2 EN Perwira Annissa Dyah Permatasari Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mustika Mentari Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Safira Adine Kinari Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Soe Thandar Aung Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Htoo Htoo Sandi Kyaw Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Khaing Hsu Wai Graduate School of Engineering Science, Akita University To support novice learners, the Java programming learning assistant system (JPLAS) has been developed with various features. Among them, code writing problem (CWP) assigns writing an answer code that passes a given test code. The correctness of an answer code is validated by running it on JUnit. In previous works, we implemented a code plagiarism checking function that calculates the similarity score for each pair of answer codes based on the Levenshtein distance. When the score is higher than a given threshold, this pair is regarded as plagiarism. However, a method for finding the proper threshold has not been studied. In addition, AI-generated codes have become threats in plagiarism, as AI has grown in popularity, which should be investigated. In this paper, we propose a threshold selection method based on Tukey’s IQR fences. It uses a custom upper threshold derived from the statistical distribution of similarity scores for each assignment. To better accommodate skewed similarity distributions, the method introduces a simple percentile-based adjustment for determining the upper threshold. We also design prompts to generate answer codes using generative AI and apply them to four AI models. For evaluation, we used a total of 745 source codes of two datasets. The first dataset consists of 420 answer codes across 12 CWP instances from 35 first-year undergraduate students in the State Polytechnic of Malang, Indonesia (POLINEMA). The second dataset includes 325 answer codes across five CWP assignments from 65 third-year undergraduate students at Okayama University, Japan. The applications of our proposals found the following: (1) any pair of student codes whose score is higher than the selected threshold has some evidence of plagiarism, (2) some student codes have a higher similarity than the threshold with AI-generated codes, indicating the use of generative AI, and (3) multiple AI models can generate code that resembles student-written code, despite adopting different implementations. The validity of our proposal is confirmed. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2079-9292 14 24 2025 An AI-Driven System for Learning MQTT Communication Protocols with Python Programming 4967 EN Zihao Zhu Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Htoo Htoo Sandi Kyaw Department of Information and Communication Systems, Okayama University I Nyoman Darma Kotama Department of Information and Communication Systems, Okayama University Anak Agung Surya Pradhana Department of Information and Communication Systems, Okayama University Alfiandi Aulia Rahmadani Department of Information and Communication Systems, Okayama University Noprianto Department of Information and Communication Systems, Okayama University With rapid developments of wireless communication and Internet of Things (IoT) technologies, an increasing number of devices and sensors are interconnected, generating massive amounts of data in real time. Among the underlying protocols, Message Queuing Telemetry Transport (MQTT) has become a widely adopted lightweight publish–subscribe standard due to its simplicity, minimal overhead, and scalability. Then, understanding such protocols is essential for students and engineers engaging in IoT application system designs. However, teaching and learning MQTT remains challenging for them. Its asynchronous architecture, hierarchical topic structure, and constituting concepts such as retained messages, Quality of Service (QoS) levels, and wildcard subscriptions are often difficult for beginners. Moreover, traditional learning resources emphasize theory and provide limited hands-on guidance, leading to a steep learning curve. To address these challenges, we propose an AI-assisted, exercise-based learning platform for MQTT. This platform provides interactive exercises with intelligent feedback to bridge the gap between theory and practice. To lower the barrier for learners, all code examples for executing MQTT communication are implemented in Python for readability, and Docker is used to ensure portable deployments of the MQTT broker and AI assistant. For evaluations, we conducted a usability study using two groups. The first group, who has no prior experience, focused on fundamental concepts with AI-guided exercises. The second group, who has relevant background, engaged in advanced projects to apply and reinforce their knowledge. The results show that the proposed platform supports learners at different levels, reduces frustrations, and improves both engagement and efficiency. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Changes in Prescribing Patterns of Antiviral Drugs before and after Public Coverage Termination among Hospitalized COVID-19 Patients in Regional Hospitals in Japan: A Retrospective, Multicenter Study 55 62 EN Hidemasa Akazawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Shohei Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Original Article 10.18926/AMO/70073 In Japan, antiviral agents for COVID-19 were freely available until September 2023 as part of national policy. This study evaluated changes in these agents’ prescribing patterns and the patient outcomes following the policy shift. We conducted a multicenter retrospective study at four hospitals in Japan’s Okayama and Kagawa prefectures from January 2022 to March 2024. The study period was divided into the public-expenditure phase (January 2022 to September 2023) and the post-expenditure phase (October 2023 to March 2024). We extracted the hospitalized patients’ clinical data from the electronic database. The study’s primary outcome was the antiviral prescription rate; the secondary outcome was in-hospital mortality. Among the 302 hospitalized patients (median age 85 years), 52.0% were classified as having a mild condition. Of the patients with mild conditions, 37.7% were diagnosed in outpatient settings prior to hospitalization. During the public-expenditure phase, 47.4% of the patients received antivirals as outpatients, mainly molnupiravir (80.9%). In the post-expenditure period, 80.0% of the patients were prescribed antivirals, mostly molnupiravir (91.7%). The antiviral prescription rate was significantly higher after the policy change. The overall in-hospital mortality was 15.8%, with no significant difference between the two periods (17.0% vs. 10.5%). Despite the termination of government funding, antiviral prescriptions remained frequent at community hospitals located in highly aging regions of western Japan such as Okayama and Kagawa prefectures. Mortality remains high among the elderly, highlighting the need for continued antiviral therapy and booster vaccinations. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Time Course of the Development and Loss of Delta-9-tetrahydrocannabinol Tolerance: Effects on Hypothermia and Spontaneous Locomotor Activity in Mice 47 54 EN Yukiomi Eguchi Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Soichiro Ushio Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Keiichi Irie Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Yuta Yamashita Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Miyu Eguchi Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Takafumi Nakano Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Kenichi Mishima Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Original Article 10.18926/AMO/70072 Deregulation of cannabis use is gradually expanding in Europe and the United States. However, the biological processes driving tolerance to delta-9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component of cannabis, remain unclear. Thus, this study aimed to investigate the mechanisms and time course of tolerance development and loss to Δ9-THC in mice. Male ICR mice (7 weeks old) were administered Δ9-THC once daily for 3 days and then divided into three groups according to the washout period (3-, 10-, and 17-day washout groups). After each washout, changes in body temperature and locomotor activity were measured following re-exposure to Δ9-THC. Furthermore, the mRNA expression levels of CB1 and CB2 receptors in the brain were evaluated using real-time PCR. On day 1, significant hypothermia and reduced spontaneous locomotor activity were observed in the Δ9-THC-treated mice compared with the vehicle-treated mice. Tolerance to the hypothermic and locomotor-suppressing effects of Δ9-THC developed on days 2 and 3, respectively, and dissipated after 3 and 11 days of washout, respectively. These differences in the rates of tolerance development and recovery may reflect distinct underlying mechanisms. No significant changes in receptor mRNA expression were observed. These findings highlight the complexity of Δ9-THC tolerance and its potential implications for long-term cannabis use. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 The Preoperative Anterior Pelvic Plane Angle Predicts Cup Anteversion Changes at 1 Year after Total Hip Arthroplasty 31 37 EN Kyota Ishibashi Department of Orthopedic Surgery, Hachinohe City Hospital Hirotaka Oishi Department of Orthopedic Surgery, Hachinohe City Hospital Ryo Araki Department of Orthopedic Surgery, Hachinohe City Hospital Kosuke Kawamura Department of Orthopedic Surgery, Hachinohe City Hospital Isamu Sasaki Department of Orthopedic Surgery, Hachinohe City Hospital Eiji Sasaki Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine Hikaru Kamada Department of Orthopedic Surgery, Hachinohe City Hospital Masakazu Kogawa Department of Orthopedic Surgery, Hachinohe City Hospital Sunao Tanaka Department of Orthopedic Surgery, Hachinohe City Hospital Takuya Numasawa Department of Orthopedic Surgery, Hachinohe City Hospital Yasuyuki Ishibashi Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine Original Article 10.18926/AMO/70070 We investigated global alignment changes following total hip arthroplasty (THA) and predictive alignment parameters for increased cup anteversion (CA) by retrospectively analyzing the primary THA data of 75 patients treated at our hospital (49 women, 26 men; age 65.1±5.7 years, BMI 28.3±3.4 kg/m2). Global alignment parameters, i.e., the anterior pelvic plane angle (APPa) and proximal femoral shaft angle (PFSa) and other alignment parameters were measured. CA was evaluated based on the patients’ standing coronal radiographs. ΔCA was defined as the difference in CA from 2 weeks before to 1 year after each THA. We classified the cases as stable (S) (CA < 10°; n=63) and pelvic retroversion (R) (CA ≥ 10°; n=12) groups. Associations between ΔCA and alignment parameters were evaluated by linear regression and a receiver operating characteristic (ROC) analysis. A significant decrease in the PFSa occurred between the 2-week and 1-year post-THA timepoints (7.8±4.3° vs. 4.2±3.6°, p<0.001), with no notable change in other alignment parameters. At 1-year post-THA, the CA of 12 (16%) patients had increased to 4.5±4.4°. Only the preoperative APPa was positively associated with ΔCA (β=0.165, p=0.020). The ROC analysis revealed that the optimal cut-off value for increased CA in the APPa is 2.1° (area under the curve, 0.700; p=0.020; odds ratio, 4.80). The APPa change predicted increased CA, which emphasizes the importance of the use of preoperative standing radiography for identifying the optimal cup positioning for post-THA changes in CA. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 A Novel Nomogram that Predicts Chronic Hemodialysis Patients’ Survival Based on Their Sedentary Behavior 9 16 EN Kentaro Sugahara Department of Hygiene, Faculty of Medicine, Kagawa University Takashi Kondo Innoshima General Hospital Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Hiroyuki Nishi Innoshima General Hospital Kazuhiro Ujike Innoshima General Hospital Kiichi Koumoto Innoshima General Hospital Keiichi Namio Department of Hygiene, Faculty of Medicine, Kagawa University Shuhei Hishii Department of Hygiene, Faculty of Medicine, Kagawa University Akihiko Katayama Faculty of Social Studies, Shikokugakuin University Hiromi Suzuki Department of Hygiene, Faculty of Medicine, Kagawa University Yorimasa Yamamoto Innoshima General Hospital Original Article 10.18926/AMO/70068 Appropriate treatments for chronic hemodialysis patients are a public health challenge in Japan. Sedentary behavior appears to be closely associated with these patients’ survival. We thus sought to develop a nomogram that predicts survival based on the duration of chronic hemodialysis patients’ sedentary behavior. One hundred twenty-four patients under chronic hemodialysis (73 men, 51 women, age 71.7±11.1 years) were enrolled in this cohort study. The patients wore a triaxial accelerometer that measured both their sedentary behavior, i.e., total sedentary behavior (minutes) and their maximum sedentary bouts (min) on non-hemodialysis days. We obtained the Kaplan-Meier curve and used the log-rank test and a Cox proportional hazards model to evaluate the relationship between the patients’ sedentary behavior and their survival. We also used a Cox proportional hazards model to develop a nomogram for the patients’ 5-year survival rate. Forty-six patients died during the follow-up period. When we stratified the patients by the medians of total sedentary behavior and maximum sedentary bouts, we observed significant between-group differences. After adjustment for confounding factors in a Cox proportional hazards model, total sedentary behavior and maximum sedentary bouts were identified as critical survival factors, and we generated a nomogram using an index of sedentary behavior. Our analysis results demonstrated that sedentary behavior on non-dialysis days was closely associated with the survival of the chronic hemodialysis patients, suggesting that a decrease in sedentary behavior would prolong their survival. The nomogram developed herein based on sedentary behavior may be useful for predicting the outcomes of chronic hemodialysis patients. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0001-690X 153 3 2026 Impact of Schizophrenia Spectrum Disorders on the Receipt of Invasive and Systemic Therapy for Colorectal Cancer: A Nationwide Multicenter Retrospective Cohort Study in Japan 191 199 EN Masaki Fujiwara Department of Neuropsychiatry, Medical Development Field, Okayama University Yuto Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Taisuke Ishii Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center Tomone Watanabe Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center Maiko Fujimori Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center Naoki Nakaya Tohoku Medical Megabank Organization, Tohoku University Toshihiko Kawamura Department of Medical Informatics, Shimane University Hospital Koji Otsuki Department of Psychiatry, Faculty of Medicine, Shimane University Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Medical Development Field, Okayama University Taichi Shimazu Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center Shiro Hinotsu Department of Biostatistics and Data Management, Sapporo Medical University Yosuke Uchitomi Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine Masatoshi Inagaki Department of Psychiatry, Faculty of Medicine, Shimane University Introduction: This study examined treatment disparities for colorectal cancer among patients diagnosed with schizophrenia spectrum disorders (SSD), focusing on invasive treatments and stage-appropriate systemic therapy within a universal healthcare system. Method: In this nationwide retrospective cohort study (2018–2021), we identified 248,966 colorectal cancer patients, including 2337 diagnosed with SSD, using linked cancer registry and insurance claims data in Japan. The presence of SSD was classified according to ICD-10 codes F20–29. We used multivariable logistic regression to compare the odds of receiving stage-appropriate adjuvant chemotherapy and systemic therapy, as well as the odds of receiving surgical or endoscopic treatments, between the two groups. The analysis adjusted for age, sex, clinical stage, and scores on the Charlson Comorbidity Index and Barthel Index. Results: The clinical stage distribution at diagnosis for colorectal cancer differed significantly between patients with SSD and those without psychiatric disorders (p < 0.001). After adjusting for clinical stage and other covariates, patients with SSD demonstrated significantly lower odds of receiving surgical or endoscopic treatment (adjusted odds ratio [aOR], 0.83; 95% CI, 0.73–0.94). The disparities were more pronounced for systemic therapy; patients with SSD had substantially lower odds of receiving adjuvant chemotherapy for stage III disease (aOR, 0.33; 95% CI, 0.26–0.41) and systemic therapy for stage IV disease (aOR, 0.23; 95% CI, 0.17–0.31). Conclusion: Patients with SSD encounter substantial disparities in accessing standard colorectal cancer care, particularly systemic therapies. These findings highlight the urgent need for interventions to ensure equitable cancer treatment for this vulnerable population. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 15 4 2026 Perioperative Ozoralizumab Management for Patients with Rheumatoid Arthritis Who Underwent Orthopaedic Surgery: A Retrospective Case Series 1422 EN Keiichiro Nishida Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama City Hospital Ryozo Harada Department of Orthopaedic Surgery, Kurashiki Sweet Hospital Ryuichi Nakahara Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Masahiro Horita Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Masamitsu Natsumeda Rheumatic Disease Center, Mabi Memorial Hospital Shuichi Naniwa Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Launched in Japan in 2022, ozoralizumab (OZR) is a novel, anti-tumour necrosis factor (TNF)-α inhibitor for treating rheumatoid arthritis (RA) that is refractory to conventional therapies. However, there is a lack of evidence regarding its perioperative management. Methods: This retrospective case series included nine patients with RA who underwent a total of 12 either RA-related (n = 9) or unrelated (n = 3) orthopaedic procedures. We reviewed patient demographics, surgical procedures, perioperative OZR discontinuation periods, and postoperative complications. Results: The mean preoperative OZR discontinuation period was 15.8 days (range, 2–25 days). Sutures were removed at a mean of 12.8 days postoperatively (range, 11–14 days) after adequate wound healing had been confirmed. The mean total discontinuation period was 34.9 days (range, 27–43 days). No cases of surgical site infection (SSI) or delayed wound healing (DWH) were observed during a minimum follow-up period of three months. One patient experienced a disease flare before OZR was restarted. Conclusions: Preoperative OZR discontinuation for up to four weeks appeared to be safe in this cohort. These findings may assist orthopaedic surgeons in determining an appropriate perioperative discontinuation strategy for OZR that minimises SSI and DWH risk while reducing the likelihood of RA flare. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2221-3759 14 1 2026 The Influence of Fluidic Flow Stress on the Development of the Secondary Palate 9 EN Masayo Nagata Department of Orthodontics, Okayama University Hospital Satoru Hayano Department of Orthodontics, Okayama University Hospital Ziyi Wang Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Kosami Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Craniofacial development is orchestrated by a finely regulated interplay of numerous genes and signaling pathways. Palatogenesis proceeds through a complex, stepwise process, in which endogenous mechanical stresses within tissues have been implicated. However, the impact of exogenous fluidic flow mechanical stress derived from maternal movement on palatal development remains unclear. In this study, we investigated the effect of exogenous fluidic flow mechanical stress on palatal morphogenesis, focusing on the horizontal outgrowth of palatal shelves after elevation. Palatal tissues dissected from mouse embryos were subjected to organ culture with or without mechanical loading (loaded and unloaded groups, respectively). Stress magnitude was quantified by calculating wave energy, and morphometric and molecular analyses were performed. Compared with the unloaded group, palatal shelves in the loaded group showed significant increases in thickness and volume, accompanied by enhanced cell proliferation, nuclear translocation of YAP and β-catenin, and upregulation of the osteogenic markers Osterix and Osteocalcin. No significant difference in apoptosis was observed. These findings indicate that exogenous mechanical stress promotes cell proliferation and osteogenic differentiation through the Hippo and WNT/β-catenin pathways in palate explants. Our results suggest that moderate maternal movement-induced mechanical stress contributes to normal palatogenesis, providing new insights into the mechanisms underlying cleft palate. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1996-1944 19 3 2026 Effect of Surface Morphology Formed by Additive Manufacturing on the Adhesion of Dental Cements to Zirconia 563 EN Kumiko Yoshihara National Institute of Advanced Industrial Science and Technology (AIST), Health and Medical Research Institute Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Sungho Lee National Institute of Advanced Industrial Science and Technology (AIST) Yukinori Maruo Department of Prosthodontics, Okayama University Fiona Spirrett Joining and Welding Research Institute, Osaka University Soshu Kirihara Joining and Welding Research Institute, Osaka University Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Bart Van Meerbeek Department of Oral Health Sciences, BIOMAT, KU Leuven Background: Durable bonding to zirconia remains difficult because its chemically inert surface resists acid etching. Additive manufacturing (AM) enables controlled surface morphology, which may enhance micromechanical retention without additional treatments. Methods: Zirconia specimens with three AM-derived surface designs—(1) concave–convex hemispherical patterns, (2) concave hemispherical patterns, and (3) as-printed surfaces—were fabricated using a slurry-based 3D printing system and sintered at 1500 °C. Zirconia specimens fabricated by subtractive manufacturing using CAD/CAM systems, polished with 15 µm diamond lapping film and with or without subsequent alumina sandblasting, served as controls. Surface morphology was analyzed by FE-SEM, and shear bond strength (SBS) was tested after cementation with a resin-based luting agent. Results: SEM revealed regular layered textures and designed hemispherical structures (~300 µm) in AM specimens, along with step-like irregularities (~40 µm) at layer boundaries. The concave–convex AM group showed significantly higher SBS than both sandblasted and polished subtractive-manufactured zirconia (p < 0.05). Vertically printed specimens demonstrated greater bonding strength than those printed parallel to the bonding surface, indicating that build orientation affects resin infiltration and interlocking. Conclusion: AM-derived zirconia surfaces can provide superior and reproducible micromechanical retention compared with conventional treatments. Further optimization of printing parameters and evaluation of long-term durability are needed for clinical application. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 12 2025 Specific Heat-Killed Lactic Acid Bacteria Enhance Mucosal Aminopeptidase N Activity in the Small Intestine of Aged Mice 5742 EN Takeshi Tsuruta Faculty of Environmental, Life, Natural Science and Technology, Okayama University Mami Wakisaka Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takumi Watanabe Bio-Lab Co., Ltd. Aoi Nishijima Faculty of Environmental, Life, Natural Science and Technology, Okayama University Akihito Ikeda Faculty of Environmental, Life, Natural Science and Technology, Okayama University Mao Teraoka Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tianyang Wang Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kuiyi Chen Faculty of Environmental, Life, Natural Science and Technology, Okayama University Naoki Nishino Faculty of Environmental, Life, Natural Science and Technology, Okayama University Aminopeptidase N (APN), an enzyme expressed in the small intestinal mucosa, is involved in dietary protein digestion. Previous studies have shown that oral administration of fermented milk containing lactic acid bacteria (LAB) enhances mucosal APN activity in young mice. This study aimed to investigate whether LAB strains stimulate mucosal APN activity in aged mice and to evaluate its relevance to age-related changes in body composition. The underlying molecular mechanisms were also explored in vitro. Experiment 1: Aged C57BL/6J mice were fed diets supplemented with heat-killed LAB strains—Enterococcus faecalis OU-23 (EF), Leuconostoc mesenteroides OU-03 (LM), or Lactiplantibacillus plantarum SNK12 (LP). Compared to the aged Control group, the ileal APN activity was significantly higher in the LP group. LP administration also elevated serum Gla-osteocalcin levels and decreased serum CTX-1 levels. Experiment 2: IEC-6 cells were co-cultured with LP that had been treated with RNase, DNase, or lysozyme. APN activity was significantly lower in cells co-cultured with DNase- or lysozyme-treated LP compared to those co-cultured with untreated LP. A specific LAB strain may enhance mucosal APN activity in the aged intestine, potentially contributing to improved bone metabolism. This effect may be mediated by bacterial DNA and peptidoglycan. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-3492 2026 A retrospective cohort study comparing periodontal regeneration using fibroblast growth factor‐2 versus autologous bone graft EN Toshiki Matsumoto Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Nakamura Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Ito‐Shinoda Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mai Sakamoto Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Ishii Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuki Nonomura Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetaka Ideguchi Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Okubo Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazu Takeuchi‐Hatanaka Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazuhiro Omori Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto The Center for Graduate Medical Education (Dental Division), Okayama University Hospital Shogo Takashiba Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Fibroblast growth factor-2 (FGF-2) is a novel agent utilized in periodontal regeneration therapy. However, its clinical efficacy compared with autologous bone graft (ABG), a long-established treatment, remains unclear. This study aimed to compare the clinical outcomes of FGF-2 and ABG and to assess the impact of patient background factors on outcomes when using FGF-2. Methods: We collected the subjects from January 2013 to September 2023. Clinical outcomes included the vertical bone defect improvement rate (VBDIR) and the probing pocket depth improvement (PPDI). Clinical outcomes between the two groups were compared using analysis of covariance (ANCOVA), adjusting for age, sex, smoking history, and hypertension. Additionally, a multilevel linear analysis was performed to assess factors influencing outcomes in FGF-2. Results: A total of 180 sites from 141 patients (FGF-2: 150 sites; ABG: 30 sites) were evaluated. Both VBDIR and PPDI significantly improved postoperatively in both groups. There were no significant differences in clinical outcomes between FGF-2 and ABG. In FGF-2, smoking history was positively associated, while the preoperative bone defect angle (BDA) was negatively associated with clinical outcomes. Conclusions: FGF-2 might exhibit clinical outcomes comparable to those of ABG, suggesting it is a clinically viable alternative for vertical bone defects. When using FGF-2, patient-specific factors such as smoking history and preoperative BDA should be considered carefully. The name in the trial registry: A survey of clinical practice and evaluation of treatment outcomes of periodontal regenerative therapy using REGROTH at Okayama University Hospital No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 1 2026 Central Serous Chorioretinopathy in Parallel With Onset and Relapses of Minimal Change Nephrotic Syndrome: A 28-Year Case Follow-Up e102426 EN Toshihiko Matsuo Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Central serous chorioretinopathy is an idiopathic disease that manifests as one or several localized, small, dome-shaped serous retinal detachments on fundus examination. The pathophysiology involves fluid leakage from the choroidal capillaries, known as the choriocapillaris, into the subretinal space through sites of damage in the retinal pigment epithelium. This case report discusses the underlying causes of central serous chorioretinopathy-like findings in minimal change nephrotic syndrome. The patient was a 33-year-old woman who developed nephrotic syndrome that was confirmed to be minimal change disease by renal biopsy. She experienced two major relapses of nephrotic syndrome at the ages of 36 and 41 years. She also had a minor relapse at the age of 37 years, five months after the first major relapse at the age of 36 years, as well as four additional minor relapses at the ages of 44, 46, 50, and 51 years. The onset of central serous chorioretinopathy-like manifestations, which were localized to the left eye, occurred three months after the initial onset of nephrotic syndrome at the age of 33 years. Two subsequent episodes of relapse of central serous chorioretinopathy-like manifestations were observed in both eyes at intervals of five months and one month, respectively, after major relapses of nephrotic syndrome at the ages of 36 and 41 years. Thereafter, she did not develop further central serous chorioretinopathy-like manifestations. She discontinued oral prednisolone at the age of 54 years and experienced no further relapses of nephrotic syndrome through her latest visit at the age of 61 years. She maintained normal renal function and good visual acuity in both eyes. The long-term, consistent temporal association between episodes of central serous chorioretinopathy and the onset and relapses of minimal change nephrotic syndrome is strongly supported by longitudinal clinical observations spanning 28 years. This parallel course suggests a possible shared pathophysiological mechanism or common triggering factors underlying both diseases. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-2615 16 3 2026 Impact of the July 2018 Heavy Rain Disaster on the Endangered Nagoya Daruma Pond Frog (Pelophylax porosus brevipodus) in Rice Fields of Mabi Town, Kurashiki City, Western Japan: Changes in Population Structure over Five Years 369 EN Ryo Nakajima Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Daisuke Azumi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Masakazu Tada Okayama Prefectural Public Interest Incorporated Foundation for Environmental Conservation Junya Nakaichi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koki R. Katsuhara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuyoshi Nakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Rice paddy fields (referred to below as rice fields) are important not only for food production, but also as habitats for various species. The Nagoya Daruma Pond Frog (Pelophylax porosus brevipodus) is an endangered frog species endemic to Japan, mainly living in and around rice field areas. In July 2018, heavy rainfall caused severe flooding in Mabi Town of Okayama Prefecture, western Japan, submerging numerous rice fields and affecting local frog populations, including P. porosus brevipodus. To clarify whether the population structure of P. porosus brevipodus changed following the flood disaster in the rice fields of Mabi Town, we conducted quantitative field surveys in a rice fallow field in mid-October before (2017) and after (2018, 2020–2022, excluding 2019) the flood. The number of frogs declined sharply after the 2018 flood, reaching only a few individuals by 2020, but showed a substantial recovery in 2021 following the resumption of rice cultivation, although numbers decreased again in 2022. This recovery, despite fluctuations, indicates that habitat restoration through rice farming played a key role in enabling the population to rebound. Our findings underscore the importance of maintaining and restoring rice field environments after natural disasters for the survival and long-term recovery of P. porosus brevipodus. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1687-8728 2026 1 2026 Experimental Analysis of Automatic Discrimination Performance Between Simulated Bruxism and Non‐Bruxism Under Conscious Conditions Using Electromyography and Machine Learning 7874254 EN Hajime Minakuchi Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuhiro Nagasaki Department of Electrical Engineering and Information Systems, Graduate School of Engineering, The University of Tokyo Lộc Hoàng Đình Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruna Miki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ko Omori Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tazuko Nishimura Department of Electrical Engineering and Information Systems, Graduate School of Engineering, The University of Tokyo Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuaki Minematsu Department of Electrical Engineering and Information Systems, Graduate School of Engineering, The University of Tokyo Purpose: This study aimed to evaluate the potential use of machine learning to automatically classify electromyography (EMG) data into bruxism simulated movement with tooth contact (BMwTC), bruxism simulated movement without tooth contact (BMwoTC), and non-bruxism movement (non-BM). Methods: Twelve eligible healthy participants (female/male: 2/10, mean age: 35.3 ± 8.4 years) were asked to perform the simulated movements (all the tasks were performed five times for 5 s each with a 30-s rest interval). The electrodes were placed on the masseter, infrahyoid, inframandibular, and chin muscles. A sound sensor was placed adjacent to the masseter. The EMG and sound data were sampled at 1 and 44.1 kHz, respectively. Single- and multi-stream hidden Markov models (HMMs) were used to automatically discriminate the tested behavior from the others using a hamming window with 100 ms and shift length of 50 ms. The leave-one-out method was used for training and testing the model, with data from 11 participants used for training and one for testing. Each participant was evaluated, and the final performance was measured by averaging the results of 12 classification trials. The validity of the discrimination was assessed by calculating the harmony mean values using six EMG signals and the sound data. Results: The masseter EMG demonstrated significantly higher discrimination accuracy in the single-stream model (p < 0.05, One-way ANOVA, Tukey HDS). The multi-stream model also demonstrated higher accuracy; however, no significant difference was observed. Notably, the accuracy of BMwoTC was less than 0.5. Conclusion: The machine-learning-based discriminative system accurately discriminates BMwTC from non-BM using masseter EMG. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1873-149X 33 1 2026 Bridging the Gap Between Static Histology and Dynamic Organ-on-a-Chip Models 10 EN Zheyi Wang Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Takahashi Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University For more than a century, pathology has served as a cornerstone of modern medicine, relying primarily on static microscopic assessment of tissue morphology—such as H&E staining—which remains the “gold standard” for disease diagnosis. However, this conventional paradigm provides only a snapshot of disease states and often fails to capture their dynamic evolution and complex functional mechanisms. Moreover, animal models are constrained by marked interspecies differences, creating a persistent gap in translational research. To overcome these limitations, we propose the concept of New Pathophysiology, a research framework that transcends purely morphological descriptions and aims to resolve functional dynamics in real time. This approach integrates Organ-on-a-Chip (OOC) technology, multi-omics analyses, and artificial intelligence to reconstruct the entire course of disease initiation and to enable personalized medicine. In this review, we first outline the foundations and limitations of traditional pathology and animal models. We then systematically summarize more than one hundred existing OOC disease models across multiple organs—including the kidney, liver, and brain. Finally, we elaborate on how OOC technologies are reshaping the study of key pathological processes such as inflammation, metabolic dysregulation, and fibrosis by converting them into dynamic, mechanistic disease models, and we propose future perspectives in the field. This review adopts a relatively uncommon classification strategy based on pathological mechanisms (mechanism-based), rather than organ-based categorization, allowing readers to recognize shared principles underlying different diseases. Moreover, the focus of this work is not on emphasizing iteration or replacement of existing approaches, but on preserving past achievements from a historical perspective, with an emphasis on overcoming current limitations and enabling new advances. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 15 12 2025 Effectiveness of education programme to increase competency of health cadres in Indonesia: a cluster non-randomised controlled trial e095428 EN Dewie Sulistyorini Graduate School of Biomedical and Health Sciences, Hiroshima University K A T M Ehsanul Huq Graduate School of Biomedical and Health Sciences, Hiroshima University Abdulfatai Olamilekan Babaita Graduate School of Biomedical and Health Sciences, Hiroshima University Sadia A Aivey Graduate School of Biomedical and Health Sciences, Hiroshima University Gao Huiying Graduate School of Biomedical and Health Sciences, Hiroshima University Kana Kazawa Faculty of Health Sciences, Okayama University Yasuko Fukushima Graduate School of Biomedical and Health Sciences, Hiroshima University Mayumi Kako Graduate School of Biomedical and Health Sciences, Hiroshima University Michiko Moriyama Graduate School of Biomedical and Health Sciences, Hiroshima University Objectives Health cadres, who assist midwives in supporting pregnant women in community settings, need to enhance their competencies in identifying risk factors and referring high-risk pregnant women to midwives for further care. Since the capabilities of these health cadres are influenced by maternal complications, an educational programme was implemented to strengthen their skills. Therefore, this study aimed to evaluate the competency of health cadres by providing a researcher-developed educational programme. Design An open-label, cluster non-randomised controlled trial. Setting and participants Health cadres with at least 1 year of work experience were recruited at six public health centres (PHCs) in Banjarnegara Regency, Indonesia. Interventions Six PHCs were selected and allocated into intervention group (IG=3 PHCs) and control group (CG=3 PHCs) groups. A total of 133 female health cadres were enrolled across the selected PHCs. At each PHC, a systematic random sampling method was used to select the participants. The researchers and health professionals provided a 3-week period of theoretical and scenario-based simulations to the IG, while the CG received no education. Outcome measures Researcher-developed questionnaires and checklists were used to assess the knowledge, skills (health assessment, communication, attitude) and confidence. The primary endpoint was competency, a total score of knowledge and skills. The outcome domains were compared between the two groups, and a linear mixed-effect model was used to account for cluster-level variation. Results A total of 130 (97.7%) completed the study (IG:64, CG:66). The competency score showed significant improvement at endline (CG=49.5 and IG=52.5; p=0.002). The median scores for health assessment skills (CG=12 vs IG=14; p<0.001) and communication skills (CG=7 vs IG=8; p<0.001) were increased in the IG compared with the CG. Mixed-effect model indicated that groups (β (95% CI) 2.49 (0.57 to 4.41), p=0.012), baseline knowledge (β(95% CI) 0.73 (0.54 to 0.92), p<0.001) and midline health assessment skills (β (95% CI) 0.54 (0.25 to 0.82), p<0.001) were significant positive predictors, while age was negatively associated with competency (β (95% CI) −0.20 (−0.30 to −0.10), p<0.001)). Conclusion Education effectively increased the competency of health cadres. A well-structured education programme is necessary for health cadres to improve and maintain their competencies in monitoring high-risk pregnant women. Trial registration number NCT06134518. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0029-6473 2026 1 2026 Knowledge and Attitudes Toward Pain Management Among Nurses in University-Affiliated Hospitals in Western Japan: A Cross-Sectional Study 9991157 EN Mengyao Xi Graduate School of Health Sciences, Okayama University, Yuki Kajiwara Faculty of Health Sciences, Okayama University Takako Hiramatsu Department of Nursing, Kawasaki Medical School Hospital Michiko Morimoto Faculty of Health Sciences, Okayama University Background: Pain is a major global concern. Nurses’ knowledge and attitudes toward pain management are critical determinants of pain care quality and patient outcomes, making them essential for effective clinical practice. Objective: This study aimed to assess nurses’ pain management knowledge and attitudes using the Japanese version of the Knowledge and Attitudes Survey Regarding Pain (J-KASRP), applied for the first time in Japan, and to examine how background factors affect these aspects. Methods: A descriptive, cross-sectional survey was conducted with 1589 nurses in three university-affiliated hospitals in Western Japan. Data were collected using a questionnaire capturing sociodemographic information and the J-KASRP. Descriptive statistics, t-tests, one-way ANOVA, and effect size were used to analyze J-KASRP scores and subdomains. Tukey’s honestly significant difference test was applied for post hoc comparisons across clinical experience patterns. Results: Of 1001 respondents, 856 valid responses (85.5%) were analyzed. The mean age was 30.1 years (SD = 8.3), and the mean total correct response rate for the J-KASRP was 59.8%; only 1.3% scored ≥ 80%. Cancer-related pain had the lowest J-KASRP subdomain score (42.5%, SD = 20.3%). Higher total J-KASRP scores were found for those with a higher level of education, prior clinical pain education, and recent opioid administration experience (all p < 0.001, effect size > 0.2). In an exploratory pattern analysis, regardless of education level, respondents with both education and opioid administering experience had the highest total and pharmacology subdomains’ scores. No significant differences in cancer-related pain subdomain were observed across patterns of clinical experiences. Conclusions: This first application of the J-KASRP in Japan revealed that nurses’ pain management knowledge and attitudes need to be strengthened, especially for cancer-related pain and opioid pharmacology. The study findings highlight the importance of pain management strengthening education and training to enhance nurses’ evidence-based knowledge and clinical competence. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2313-433X 12 1 2025 FluoNeRF: Fluorescent Novel-View Synthesis Under Novel Light Source Colors and Spectra 16 EN Lin Shi Department of Artificial Intelligence, Kyushu Institute of Technology Kengo Matsufuji Department of Artificial Intelligence, Kyushu Institute of Technology Michitaka Yoshida Department of Computer Science, Okayama University Ryo Kawahara Graduate School of Informatics, Kyoto University Takahiro Okabe Department of Computer Science, Okayama University Synthesizing photo-realistic images of a scene from arbitrary viewpoints and under arbitrary lighting environments is one of the important research topics in computer vision and graphics. In this paper, we propose a method for synthesizing photo-realistic images of a scene with fluorescent objects from novel viewpoints and under novel lighting colors and spectra. In general, fluorescent materials absorb light with certain wavelengths and then emit light with longer wavelengths than the absorbed ones, in contrast to reflective materials, which preserve wavelengths of light. Therefore, we cannot reproduce the colors of fluorescent objects under arbitrary lighting colors by combining conventional view synthesis techniques with the white balance adjustment of the RGB channels. Accordingly, we extend the novel-view synthesis based on the neural radiance fields by incorporating the superposition principle of light; our proposed method captures a sparse set of images of a scene from varying viewpoints and under varying lighting colors or spectra with active lighting systems such as a color display or a multi-spectral light stage and then synthesizes photo-realistic images of the scene without explicitly modeling its geometric and photometric models. We conducted a number of experiments using real images captured with an LCD and confirmed that our method works better than the existing methods. Moreover, we showed that the extension of our method using more than three primary colors with a light stage enables us to reproduce the colors of fluorescent objects under common light sources. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2673-7086 5 4 2025 An Integrated QGIS-Based Evacuation Route Optimization Approach for Disaster Preparedness Against Urban Flood in Japan 74 EN Wenliang Pan Graduate School of Environmental and Life Science, Okayama University Shijun Pan Graduate School of Environmental and Life Science, Okayama University Junko Kaneto Graduate School of Environmental and Life Science, Okayama University Keisuke Yoshida Graduate School of Environmental and Life Science, Okayama University Satoshi Nishiyama Graduate School of Environmental and Life Science, Okayama University Urban inland flooding has become a serious problem in many cities because heavy rain often exceeds the capacity of drainage systems. In Japan, GIS-based evacuation maps are commonly used to support disaster preparedness, but they still have several limitations. In particular, they do not avoid flooded road segments and cannot generate multiple evacuation options at the same time. This study proposes an improved evacuation route method using the free and open-source software QGIS. The method combines flood-depth data with road network processing to remove roads where the predicted water depth is higher than 0.5 m. It also provides several evacuation paths to different shelters at the same time. A case study in Kurashiki City, Okayama Prefecture, demonstrates that about 1.37% of the road network becomes unusable during an inland-flood scenario. Several existing evacuation routes also pass through hazardous areas, but the QGIS-based method avoids these areas in most cases. Since the workflow uses only built-in QGIS functions and does not require programming or plug-ins, it is easy to reproduce and apply in other regions. This study offers a practical and low-cost method to support inland-flood evacuation planning for local governments. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0919-8172 2025 Daytime Bladder Control Status in Toddlerhood Is Associated With Subsequent Bedwetting in Preschool Years: A Nationwide Cohort Study of Over 30 000 Japanese Children EN Takatoshi Moriwake Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Tominaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kensuke Uraguchi Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoko Kobayashi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ichiro Tsuboi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kasumi Yoshinaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoaki Yamanoi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsushi Kawada Department of Urology Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama Japan Takuya Sadahira Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Katayama Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takehiro Iwata Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shingo Nishimura Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kensuke Bekku Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Edamura Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soshi Takao Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoo Araki Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: Nocturnal enuresis is common in early childhood. While daytime bladder control typically precedes nighttime continence, the temporal relationship between early daytime bladder control and subsequent bedwetting remains unclear. We investigated whether daytime bladder control status at age 2.5 years—as indicated by diaper use—is associated with bedwetting at age 4.5 years in a Japanese nationwide cohort. Methods: We analyzed data from the Japanese Longitudinal Survey of Newborns in the 21st Century (2010 cohort). Daytime bladder control was assessed at age 2.5 years through caregiver-reported diaper use, and bedwetting frequency at age 4.5 years through parental questionnaires. Modified Poisson regression estimated risk ratios (RRs), adjusting for birth-related factors, socioeconomic status, daycare attendance, and developmental milestones. Results: Among 32 168 children, 26 651 (82.8%) still used diapers at 2.5 years. Bedwetting prevalence at 4.5 years was 42.2%: 34.5% in children who achieved daytime bladder control at 2.5 years versus 43.9% in those still using diapers. After multivariable adjustment, incomplete daytime bladder control at 2.5 years was associated with higher bedwetting risk (adjusted RR 1.25; 95% CI, 1.20–1.31). Multinomial regression revealed dose–response relationships: odds ratios 1.41 (95% CI, 1.30–1.52) for “sometimes” and 1.58 (95% CI, 1.42–1.77) for “often” bedwetting. Conclusions: Daytime bladder control status at 2.5 years was associated with a 25% increased bedwetting risk at 4.5 years. This association likely reflects individual differences in bladder control maturation rather than causal effects. While daytime bladder control may serve as a developmental marker, its validity as an intervention target remains unestablished. No potential conflict of interest relevant to this article was reported.

European Respiratory Society (ERS) Acta Medica Okayama 2312-0541 11 6 2025 Global trends in idiopathic pulmonary fibrosis mortality rates during 2001–2022 00362-2025 EN Ko Harada Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai Yoshito Nishimura Division of Hematology/Oncology, Mayo Clinic Quynh Thi Vu Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Maki Yamamoto Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and ultimately fatal lung disease. Updated global mortality data, especially from underexplored countries, are limited. This study aimed to understand the current global trends in IPF-associated mortality rates. Methods This observational study used the World Health Organization Mortality Database to analyse data stratified by sex, age and geographic region, encompassing 64 countries between 2001 and 2022. IPF was defined according to the International Code for Diseases-10 code J84.1. Crude and age-standardised mortality rates per 100 000 individuals were calculated to estimate long-term mortality trends. Mortality rates were calculated by dividing IPF-associated deaths by the corresponding population, with age-specific rates determined for each 5-year age group. Trends in the 2001–2022 period were analysed using a locally weighted regression model, and the average annual percentage change in mortality rates between 2010 and 2022 was estimated using joinpoint regression analysis. Results Overall, 874 998 deaths associated with IPF were analysed. The LOESS-smoothed crude mortality rate increased from 2.10 (95% confidence interval (CI) 1.77–2.43) per 100 000 in 2001 to 3.14 (95% CI 2.71–3.57) per 100 000 by 2022. The LOESS-smoothed age-standardised mortality rates increased overall, peaking at 1.59 (95% CI 1.51–1.67) per 100 000 in 2018 and declining slightly to 1.57 (95% CI 1.35–1.79) per 100 000 in 2022. Mortality was higher among males than females; furthermore, 87.5% of deaths occurred in individuals aged ≥65 years. Mortality rates were highest among the American population, with a notable increase in Latin American countries. Conclusion IPF-associated mortality rates have increased globally, particularly in males. Significant geographical, age and sex disparities were observed, emphasising the need for targeted public health measures and improved disease management. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0925-5710 122 5 2025 Intravenous umbilical cord-derived mesenchymal stromal cell therapy may improve overall survival in Japanese patients with idiopathic pneumonia syndrome after hematopoietic stem cell transplantation: a multicenter, single-arm, phase II trial 733 743 EN Noriko Doki Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Shinichi Kako Division of Hematology, Jichi Medical University Saitama Medical Center Emiko Sakaida Department of Hematology, Chiba University Hospital Yoshinobu Kanda Division of Hematology, Department of Medicine, Jichi Medical University Idiopathic pneumonia syndrome (IPS) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) and has a poor prognosis. Although IPS is often treated with steroids, the disease can become resistant to or dependent on steroid treatment, and there is no effective cure for patients with refractory or steroid-dependent IPS. This multicenter, open-label, single-arm, phase II clinical trial investigated the efficacy and safety of HLC-001 (allogeneic umbilical cord-derived mesenchymal stromal cells) in patients with progressive steroid-dependent or refractory IPS after HSCT. Seven male patients (all male; mean age: 43.3 years) received HLC-001 and three completed the trial. The survival rate at day 56 (primary endpoint) was 71.4% (5/7 patients; 95% confidence interval: 29.0%–96.3%) and was sustained at day 100, suggesting that HLC-001 was more effective than previously reported treatment. Three of the five patients with ≥ 100 days of follow-up died. Five patients experienced at least one adverse drug reaction, none of which were serious. These findings indicate that HLC-001 was potentially effective and generally well tolerated in Japanese patients with steroid-dependent or refractory IPS after HSCT. Given there is no effective cure for steroid-dependent or refractory IPS, HLC-001 may be a promising treatment option and further clinical evaluation is warranted. Trial registration: Japan Registry of Clinical Trials identifier: jRCT2063220014. No potential conflict of interest relevant to this article was reported.