Springer Science and Business Media LLC Acta Medica Okayama 2662-2963 7 6 2026 A simple proof for the existence of V-form fronts in reaction–diffusion equations 48 EN Satomu Nagashima Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Masaharu Taniguchi Research Institute for Interdisciplinary Science, Advanced Research Field, Okayama University George Taylor Graduate School of Environmental, Life, Natural Science and Technology, Okayama University This paper studies V-form traveling fronts to a bistable reaction–diffusion equation. V-form traveling fronts have been studied so far for many reaction–diffusion equations. The proof of its existence is often based on the multi-scale method. In this paper we present a new simple proof for the existence of V-form traveling fronts based on estimates by inscribed balls. No potential conflict of interest relevant to this article was reported.

Japanese Society of Toxicology Acta Medica Okayama 0388-1350 51 10 2026 Integration of QSAR modeling and in vitro validation for identification of food-derived Nrf2 activators against arsenic-induced toxicity 533 547 EN Ngo Thanh Huong Laboratory of Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Susumu Kodama Laboratory of Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Ono Laboratory of Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Arsenic exposure is a major public health concern due to its toxicity and carcinogenicity, largely mediated by oxidative stress, and activation of the Nrf2 signaling pathway is considered a promising strategy to mitigate such damage. In this study, a quantitative structure–activity relationship (QSAR) model was developed to identify potential Nrf2 activators from food-derived compounds. Machine learning algorithms, including Random Forest (RF), Support Vector Machine (SVM), Linear Discriminant Analysis (LDA), and a stacking model, were developed and optimized. The optimized RF, SVM, and LDA models were subsequently integrated into a stacking framework, which was selected as the final predictive model for virtual screening based on its robust and balanced predictive performance. The stacking model achieved the highest accuracy during five-fold cross-validation (0.77) and demonstrated competitive performance on the independent test set (0.742 �} 0.040), with balanced precision, sensitivity, and F-measure. Consequently, the stacking model was selected as the final model for virtual screening. A total of 70,926 compounds retrieved from a food-derived database were filtered based on physicochemical criteria, and QSAR-based virtual screening predicted 920 compounds as potential activators of the Nrf2 signaling pathway, from which 5,7-Dimethylchrysin (FooDB ID: FDB015537) and Demethylvestitol (FooDB ID: FDB012218) were selected for experimental validation. In vitro assays using HepG2 cells demonstrated that 5,7-Dimethylchrysin significantly enhanced cell viability against sodium arsenite (150 ƒÊM)-induced cytotoxicity, with an effective concentration (EC50) of 0.54 ƒÊM, whereas Demethylvestitol exhibited only limited protective effects. Furthermore, luciferase reporter assays confirmed that 5,7-Dimethylchrysin activated antioxidant response element (ARE)-driven transcription in a concentration-dependent manner, producing a 1.5 to 2.4-fold increase at concentrations ranging from 0.78 to 6.25 ƒÊM. Overall, these findings highlight the effectiveness of integrating QSAR modeling with experimental validation to identify food-derived compounds with protective potential against arsenic-induced toxicity, with 5,7-Dimethylchrysin emerging as a promising candidate for further investigation. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 2297-7775 11 2026 Navigating inherited �gintensive surveillance�h 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?<br> Methods: We interviewed 21 Peruvian mothers who had lived in Japan for 17–35 years.<br> Results: The analysis identified four identity positions to this cultural friction. The first is holding firmly to Peruvian maternal scripts (�gIdeological Retention�h). The second is following Japanese conventions in public while keeping Peruvian ways at home (�gCompartmentalization�h). The third is moving away from inherited protective scripts and adopting Japanese norms of independence (�gAssimilation�h). The fourth is blending elements of both into a maternal self that is �gneither the one nor the other�h (a �gThird Space�h).<br> 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�fs 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�fs 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.

IOP Publishing Acta Medica Okayama 0021-4922 65 7 2026 Study of preload mechanism for small piezoelectric transducers with hollow structure for cryogenic environments 07SP13 EN Souta Mimura Graduate School of Environment, Life, Natural Science and Technology, Okayama University Takefumi Kanda Graduate School of Environment, Life, Natural Science and Technology, Okayama University Daisuke Yamaguchi Graduate School of Environment, Life, Natural Science and Technology, Okayama University Kazuki Kubo Graduate School of Environment, Life, Natural Science and Technology, Okayama University Shuichi Wakimoto Graduate School of Environment, Life, Natural Science and Technology, Okayama University In various industrial fields, cryogenic fluids such as liquid hydrogen and liquid nitrogen are increasingly used as fuels and refrigerants. To control the flow rate of those fluids, valves that can be operated in cryogenic environments are needed. In general, the miniaturization of the valve can be achieved by using a piezoelectric ceramic as an actuator to drive the mechanism. Additionally, the properties degradation can be suppressed by applying a preload to the piezoelectric ceramic. To miniaturize the piezoelectric actuator applying preload at low temperature conditions, we use differences in thermal expansion coefficients to apply preload to the piezoelectric ceramics. In this study, we have designed and fabricated a small piezoelectric transducer with a hollow structure for cryogenic environments by using this proposed structure. To evaluate the fabricated transducer, we have measured vibration velocity and estimated the acceleration in cryogenic environments. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0289-0771 2026 Temporally structured plasticity in death-feigning behavior in response to nutritional conditions in Tribolium castaneum EN Kohjiro Shibuya Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kentarou Matsumura Department of General Systems Studies, Graduate School of Arts and Sciences, The University of Tokyo Takahisa Miyatake Faculty of Environmental, Life, Natural Science and Technology, Okayama University Investment in antipredator behavior and foraging both directly influence fitness, yet these investments are often subject to trade-offs. In income-breeding species, individuals may initially prioritize foraging after adult emergence and subsequently increase investment in antipredator behavior as their nutritional condition improves. In this study, we investigated temporal changes in death-feigning behavior, an antipredator response, in the red flour beetle Tribolium castaneum from immediately after adult emergence. Both fed and starved individuals exhibited an increase in death-feigning duration with time after emergence. However, in starved individuals, this trend reversed after approximately 15 days, with a marked decline in duration. These results suggest that the increase in investment in death-feigning behavior early in adulthood is relatively inflexible, whereas behavioral responses become highly plastic in response to environmental conditions around day 15. Furthermore, individuals that were fed until day 18 before starvation showed a less pronounced behavioral change than those subjected to starvation from the beginning of the experimental period, suggesting that the timing of environmental exposure may influence subsequent behavioral responses. Together, these findings suggest that behavioral plasticity is not constant over time but is instead structured across developmental stages. We propose a novel conceptual framework, termed temporally structured plasticity (TSP), to describe this pattern. 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�fs 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�fs 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.<br> 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.<br> 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.

Springer Science and Business Media LLC Acta Medica Okayama 0340-5443 80 11 2026 No evidence for differential allocation or sex ratio adjustment in response to male attractiveness in the broad-horned flour beetle 132 EN Kensuke Okada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Katsuya Kiyose Seibukasei Co., Ltd Masako Katsuki Graduate School of Bioagricultural Sciences, Nagoya University Sexual selection theory predicts that females can enhance the benefits of mate choice by increasing reproductive investment (differential allocation) or by biasing offspring sex ratios toward sons (sex ratio adjustment) when mating with attractive males. Clear empirical support for these hypotheses has been documented in many vertebrate taxa, whereas relatively few studies have tested them in invertebrates. Here, we investigated whether females adjust reproductive investment and offspring sex ratio in response to male attractiveness in the beetle Gnatocerus cornutus. We assessed male attractiveness using copulation latency and examined its associations with female lifetime reproductive success, egg size, and offspring sex ratio under single-mating conditions. Our results, however, provide no support for either the differential allocation or sex ratio adjustment hypotheses: females did not alter reproductive investment or offspring sex ratio according to mate quality. In this species, male sexual phenotypes are strongly influenced by environmental conditions. Such phenotype–genotype mismatches may reduce the reliability of male traits as indicators of genetic quality and increase the likelihood of assessment errors by females. This may explain the absence of maternal allocation in relation to mate attractiveness in G. cornutus. Instead, previous work on this beetle indicates that females can secure genetic benefits by remating with more attractive males and biasing fertilization toward their sperm. Our findings therefore suggest that postcopulatory mechanisms, rather than differential maternal allocation, provide a more effective route for females to secure the benefits of mate choice in G. cornutus. No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2026 Tourism Demand Forecasting Using Machine Learning with Cross-Model Feature Ranking 11689307 EN Yomei Hendra Okayama University Tsuyoshi Migita Okayama University Norikazu Takahashi Okayama University This study proposes a machine learning (ML) framework for forecasting tourist visits to a destination, leveraging feature ranking consistency across heterogeneous models. The proposed framework uses a unified stepwise feature selection pipeline to systematically determine a subset of given features that reduces prediction error of an ML model. The transferability of feature rankings is demonstrated through experiments using ML models including Random Forest, XGBoost, LightGBM, and Support Vector Regression (SVR), and a dataset related to tourist visits to West Sumatra, Indonesia. Experimental results show that i) SVR using top four features in the feature ranking based on SHAP achieves the highest accuracy and ii) application of the feature ranking based on XGBoost improves performance stability across other models, reducing error fluctuations. These findings reveal that an optimized feature subset combined with cross-model ranking transfer can outperform more complex ensembles, highlighting the importance of ranking robustness in tourism forecasting. The proposed framework provides a methodological foundation for building interpretable and dataefficient decision support systems for tourism management and policy planning. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0308-8146 526 2026 Flavor encapsulation capacities of amphiphilic polyvinylpyrrolidone as a carrier for amorphous solid dispersions 150819 EN Haruna Sato Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nao Honda Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takato Hasegawa Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Chika Araga Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyuki Imanaka Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Naoyuki Ishida Department of Chemical Engineering and Material Sciences, Faculty of Science and Engineering, Doshisha University Koreyoshi Imamura Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University This study investigates the characteristics of amorphous solid dispersions (ASDs) formed using an amphiphilic carrier polymer, focusing on the effects of source solution conditions on flavor retention. Cinnamaldehyde and polyvinylpyrrolidone (PVP) were dissolved as flavor and carrier components in methanol or ethanol under different conditions and subsequently spray-dried into fine powders. The amount of cinnamaldehyde retained in the spray-dried ASDs was quantified to assess the impact of solution conditions. The results indicate that cinnamaldehyde molecules were physically entrapped within the entangled PVP chains during the spray-drying process. The flavor encapsulation capacity of PVP reached a maximum of approximately 4 mmol/g-PVP under specific conditions. This maximum capacity implies that each cinnamaldehyde molecule is associated with approximately two PVP monomer units, which is higher than those reported for selected cyclodextrin-based systems in comparable contexts of cinnamaldehyde encapsulation. Additionally, the dissipation of cinnamaldehyde from the ASD samples during storage under vacuum was examined. No potential conflict of interest relevant to this article was reported.

American Association for Cancer Research (AACR) Acta Medica Okayama 1078-0432 32 17 2026 Sequential Immune Activation of Effector T Cells as Biomarkers of Response to Durvalumab in Patients with Locally Advanced NSCLC 3880 3890 EN Atsuto Mouri Department of Respiratory Medicine, International Medical Center, Saitama Medical University Hirotsugu Kenmotsu Division of Thoracic Oncology, Shizuoka Cancer Center Hiroshi Kagamu Department of Respiratory Medicine, International Medical Center, Saitama Medical University Koichi Azuma Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine Ryota Saito Department of Respiratory Medicine, Tohoku University Graduate School of Medicine Hiroaki Akamatsu Internal Medicine III, Wakayama Medical University Kimio Yonesaka Department of Medical Oncology, Kindai University Faculty of Medicine Mikiko Kakegawa Department of Respiratory Medicine, Kitasato University School of Medicine Hiromi Nagashima Department of Respiratory Medicine, Iwate Medical University School of Medicine Satoshi Takahashi Department of Thoracic Surgery, Tokyo Medical University Hospital Masaki Fujita Department of Respiratory Medicine, Fukuoka University Hospital Noriko Yanagitani Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yasuhiko Nishioka Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University Keita Mori Department of Biostatistics, Clinical Research Support Center, Shizuoka Cancer Center Shigehisa Kitano Department of Advanced Medical Development, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Koji Tamada Department of Immunology, Yamaguchi University Graduate School of Medicine Nobuyuki Yamamoto Internal Medicine III, Wakayama Medical University Akihiko Gemma Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Tetsuya Mitsudomi Division of Thoracic Surgery, Izumi City General Hospital Purpose: Durvalumab therapy following concurrent chemoradiotherapy (cCRT) improves progression-free survival (PFS) in patients with unresectable locally advanced non–small cell lung cancer. In this prospective observational study, we evaluated the changes in peripheral blood immune cell counts to elucidate the immunologic mechanisms underlying cCRT and durvalumab therapy.<br> Experimental Design: Peripheral blood mononuclear cell (PBMC) samples were collected at four time points: before cCRT, after cCRT, at the start of durvalumab, and 8 weeks after the start of durvalumab, and analyzed by multicolor flow cytometry.<br> Results: Of the 149 enrolled patients, 115 received durvalumab consolidation therapy after cCRT. The median PFS in the overall population was 24.2 months, and the 3-year PFS rate was 38.9%. PBMC analysis showed an increased effector fraction of CD4+ T cells before and after cCRT but no change in CD8+ T cells. Following durvalumab therapy, the effector fraction ratio of CD8+ T cells (CD62Llow CD8+ T cells) increased and positively correlated with increased CD62Llow CD4+ T cells during cCRT. Patients whose proportion of CD62Llow CD4+ T cells exceeded the threshold for cCRT had better PFS than those below the threshold. Patients whose CD62Llow CD8+ T-cell proportion exceeded the threshold after durvalumab therapy showed prolonged PFS compared with those below the threshold.<br> Conclusions: cCRT promotes an increase in effector CD4+ T cells, and the subsequent increase in CD8+ T cells following durvalumab therapy prolongs PFS. Peripheral blood effector–type CD4+ and CD8+ T cells are potential biomarkers for evaluating the immune status of patients and predicting treatment efficacy. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0169-5002 218 2026 ULK1, a novel therapeutic target to delay drug tolerance to EGFR–TKIs in an EGFR-mutant non-small cell lung cancer model 109516 EN Ayako Morita Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kammei Rai Center for Innovative Clinical Medicine, Okayama University Hospital Tadahiro Kuribayashi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Tatsuya Nishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naofumi Hara Department of Allergy and Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Allergy and Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Toshio Kubo Center for Innovative Clinical Medicine, Okayama University Hospital Kadoaki Ohashi Center for Innovative Clinical Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Nobuaki Ochi Department of General Internal Medicine 4, Kawasaki Medical School Yosuke Togashi Department of Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Background: The presence of drug-tolerant persister (DTP) cells reduces the effectiveness of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC). Although autophagy is a potential target for eliminating DTP cells, clinical trials targeting autophagy in EGFR-mutant NSCLC have been unsuccessful�\likely because most trials have utilized chloroquine, non-specifically inhibiting autophagy targeting lysosomes with dose limitations. This study focused on unc-51-like autophagy activating kinase 1 (ULK1), a more specific target for autophagy inhibition, to assess whether ULK1 inhibition delays the emergence of tolerance to EGFR-tyrosine kinase inhibitors in EGFR-mutant NSCLC cells.<br> Methods: DTP cells were generated by treating EGFR-mutant NSCLC cell lines with osimertinib. Autophagy status and ULK1 expression were evaluated using immunofluorescence, western blotting, and quantitative real-time PCR. The effects of both pharmacological and genetic inhibition of ULK1 were examined in vitro and in vivo.<br> Results: ULK1 and LC3-II, markers of autophagy, were upregulated in DTP cells. Inhibition of ULK1, either pharmacologically or genetically, suppressed autophagy, prevented the formation of DTP cells, and enhanced the antitumor activity of osimertinib in both in vitro and in vivo models. Furthermore, upregulation of ULK1 expression through serum starvation conferred tolerance to osimertinib, reinforcing ULK1�Œs role in drug tolerance. Notably, ULK1 inhibition showed modest efficacy even after cells transitioned to the DTP or acquired resistance states.<br> Conclusion: ULK1 plays a critical role in mediating drug tolerance in EGFR-mutant NSCLC. Targeting ULK1 represents a promising therapeutic approach to enhance the efficacy of EGFR-TKIs and to delay the development of drug tolerance. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1759-7706 17 10 2026 Interstitial Lung Disease in Patients With Unresectable Stage III NSCLC Treated With Chemoradiotherapy Followed by Durvalumab in Japan: Analysis From the Multicenter Prospective AYAME Study e70299 EN Nobuyuki Yamamoto Internal Medicine III, Wakayama Medical University Hirotsugu Kenmotsu Division of Thoracic Oncology, Shizuoka Cancer Center Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Burak Akdemir Oncology Medical, AstraZeneca K.K Shinya Uematsu Oncology Medical, AstraZeneca K.K Ayako Fukui Evidence and Observational Research, Medical, AstraZeneca K.K Ryo Koto Evidence and Observational Research, Medical, AstraZeneca K.K Masakazu Fujiwara Evidence and Observational Research, Medical, AstraZeneca K.K Chikako Iwao Oncology Medical, AstraZeneca K.K Hiroshi Kitagawa Oncology Medical, AstraZeneca K.K Ichiro Yoshino Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital Akihiko Gemma Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Tetsuya Mitsudomi Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine Yoshinobu Saito Department of Pulmonary Medicine, Nippon Medical School Musashi Kosugi Hospital Introduction: Interstitial lung disease (ILD) is a concerning adverse event associated with immune checkpoint inhibitors, including durvalumab. This analysis of the multicenter AYAME study assessed the longterm safety of durvalumab, focusing on ILD.<br> Methods: AYAME enrolled patients prescribed durvalumab for unresectable stage III non-small cell lung cancer (NSCLC) after chemoradiotherapy (CRT) from July 2019 to December 2020 in Japan. Patients received durvalumab for ≤ 12 months and were prospectively followed for 3 years. Incidence, severity, and management of ILD were examined. Multivariable logistic regression analysis was conducted to investigate the association of patient characteristics with grade ≥ 2 ILD occurrence.<br> Results: Of 511 patients in the safety analysis population, ILD occurred in 383 patients (75.0%) from durvalumab initiation to subsequent treatment start; median time to occurrence was 44.0 days. ILD led to permanent durvalumab discontinuation in 121/383 patients (31.6%), dose interruption in 111/383 (29.0%), and corticosteroid intervention in 168/383 (43.9%). Grade ≥ 2 ILD occurrence was higher in patients with volume of lung parenchyma that received 20 Gy (V20) ≥ 25% versus < 25% (60.3% vs. 29.4%; adjusted odds ratio 2.20, 95% confidence interval 1.08–4.48), 5 Gy (V5) ≥ median (37.85%) versus < median (51.5% vs. 27.2%; 1.79, 1.07–3.00), and grade 1 ILD before durvalumab administration versus no ILD (50.0% vs. 37.6%; 2.11, 1.07–4.17).<br> Conclusions: This study of durvalumab for NSCLC after CRT in a real-world setting indicated factors associated with grade ≥ 2 ILD and provided valuable insights into ILD management strategies. These findings may contribute to establishing effective approaches to minimize ILD risk in practice.<br> Trial Registration: UMIN000037090/NCT03995875 No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1556-0864 21 1 2026 Long-Term Safety and Effectiveness of Durvalumab in Unresectable Stage III NSCLC in Japan: A Multicenter Prospective Study (AYAME) 160 173 EN Hirotsugu Kenmotsu Division of Thoracic Oncology, Shizuoka Cancer Center Yoshinobu Saito Department of Respiratory Medicine, Nippon Medical School, Musashi Kosugi Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Shinya Uematsu Oncology Medical, AstraZeneca K.K. Burak Akdemir Oncology Medical, AstraZeneca K.K. Ayako Fukui Evidence and Observational Research, Medical, AstraZeneca K.K. Ryo Koto Evidence and Observational Research, Medical, AstraZeneca K.K. Masakazu Fujiwara Evidence and Observational Research, Medical, AstraZeneca K.K. Chikako Iwao Oncology Medical, AstraZeneca K.K. Hiroshi Kitagawa Oncology Medical, AstraZeneca K.K. Ichiro Yoshino Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital Akihiko Gemma Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Tetsuya Mitsudomi Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine and Faculty of Medicine & Hospital Nobuyuki Yamamoto Internal Medicine III, Wakayama Medical University Introduction: Based on the PACIFIC trial results, durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III NSCLC. However, few large-scale studies have prospectively evaluated its long-term effectiveness and safety, including subsequent treatment.<br> Methods: This multicenter, noninterventional study (AYAME) enrolled patients who were prescribed durvalumab for unresectable stage III NSCLC after CRT (July 2019–December 2020; 52 sites; Japan). Patients received durvalumab for a maximum of 12 months and were prospectively followed up for 3 years, including the post-durvalumab treatment period. Primary end points were real-world progression-free survival (rwPFS), the incidence of interstitial lung disease (ILD), and adverse events of special interest (AESIs).<br> Results: Of the 529 enrolled patients, 512 received durvalumab and 511 comprised the safety analysis population. The median time to onset of the first presentation or occurrence of ILD was 45.0 days. ILD of any grade occurred in 387 patients (75.7%) over the 3-year study period: grade 3, 57 (11.2%); grade 4, none (0.0%); and grade 5, 9 (1.8%). The most common AESIs of any grade during durvalumab treatment were thyroid dysfunction (12.5%), hepatic dysfunction (7.2%), and colitis (2.0%). No durvalumab treatment-related ILD or AESIs occurred during the post-treatment period. The median [95% confidence interval] rwPFS was 23.2 [18.2, 27.2] months in the effectiveness analysis population (n = 495). rwPFS rates were 62.5%, 54.6%, 49.4%, and 40.4% at 12, 18, 24, and 36 months, respectively.<br> Conclusions: This first and largest prospective, observational study demonstrated the long-term safety and effectiveness of durvalumab for unresectable stage III NSCLC after CRT in a real-world clinical setting.<br> Clinical Trial Registration: UMIN000037090 and NCT03995875 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 Phase II Study of Platinum Re-administration in Non-small Cell Lung Cancer Following Chemoimmunotherapy Resistance e84709 EN Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Shinobu Hosokawa Respiratory Medicine, Japanese Red Cross Okayama Hospital Toshihide Yokoyama Respiratory Medicine, Kurashiki Central Hospital Masaaki Inoue Chest Surgery, Shimonoseki City Hospital Keisuke Sugimoto Respiratory Medicine, Japanese Red Cross Kobe Hospital Kenichiro Kudo Respiratory Medicine, National Hospital Organization Okayama Medical Center Toshiaki Okada Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Tadashi Maeda Respiratory Medicine, National Hospital Organization Yamaguchi Ube Medical Center Haruyuki Kawai Internal Medicine, Okayama Saiseikai General Hospital Masayuki Yasugi Respiratory Medicine, Chugoku Central Hospital Koji Inoue Respiratory Medicine, Ehime Prefectural Central Hospital Shoichi Kuyama Respiratory Medicine, Iwakuni Medical Center Takashi Ninomiya Respiratory Medicine, National Hospital Organization Shikoku Cancer Center Isao Oze Division of Molecular Medicine, Aichi Cancer Center Research Institute Yoshinobu Maeda Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Platinum compounds represent standard treatments for various cancers. However, the efficacy of re-administrating platinum compounds has been demonstrated only in ovarian cancer and small cell lung cancer (SCLC), with its utility in non-small cell lung cancer (NSCLC) remaining unclear. Given that the prognosis of NSCLC has improved with effective treatments such as immune checkpoint inhibitors (ICIs), we propose a multicenter, single-arm, prospective phase II trial of re-administrating platinum-based combination therapy for NSCLC. Patients with NSCLC who have progressed after chemoimmunotherapy and exhibit a platinum-free interval of 85 days or more will receive carboplatin combination therapy. The drugs combined with carboplatin - pemetrexed, nab-paclitaxel, or gemcitabine - must not have been administered previously. The primary endpoint is progression-free survival (PFS), assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Assuming a threshold PFS of 4.2 months and an expected hazard ratio of 0.60, the required sample size is calculated as 40 patients to achieve 70% power with a 5% alpha error. Secondary endpoints included objective response rate, toxicity, and overall survival. This study will clarify the efficacy of re-administrating platinum compounds to patients with NSCLC who have developed resistance to chemoimmunotherapy. 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�fs 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.

Wiley Acta Medica Okayama 1347-9032 2026 Clinical Significance of a Cell-Of-Origin-Based Classification in Pancreatic Ductal Adenocarcinoma EN Tatsuya Kikuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ako Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironari Kato Department of Gastroenterology, Okayama City Hospital Hideaki Kinugasa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaki Uchida Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Oda Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Hirai Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Terasawa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shigeru Horiguchi Department of Gastroenterology and Hepatology, 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 Tomokazu Fuji 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 Hirokazu Kato Bioinformatics Analysis Center, Kagawa University Tomoyuki Honda Department of Virology, 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 Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited therapeutic options and poor clinical outcomes. Although PDAC has traditionally been thought to arise from ductal epithelial cells, recent studies using genetically engineered mouse models have demonstrated that acinar cells can also serve as a cell of origin, giving rise to tumors with distinct biological properties. Here, we investigated whether such lineage-specific differences are preserved in human PDAC. RNA sequencing was performed on resected specimens from 40 treatment-naïve patients with PDAC, and tumors were classified into Acinar- and Ductal-subtypes using lineage-specific gene expression signatures derived from mouse models. This classification strategy was further applied to human PDAC cell lines, followed by in vitro drug sensitivity assays. Patients with Acinar-subtype tumors had significantly longer overall survival than those with Ductal-subtype tumors (median, 54.0 vs. 26.5 months; p < 0.01), and multivariate analysis identified the ductal cell-derived tumor signature as an independent predictor of poor prognosis (HR, 3.74 [95% CI, 1.41–9.97]; p = 0.01). Among patients who developed postoperative recurrence, Acinar-subtype tumors were associated with more durable disease control (≥ 10 months) following gemcitabine-based chemotherapy than Ductal-subtype tumors (63.6% vs. 16.7%; p = 0.02). Consistently, pancreatic cancer cell lines classified as Acinar-subtype showed greater sensitivity to gemcitabine (p < 0.01) and paclitaxel (p < 0.05). These findings extend the clinical relevance of cell-of-origin signatures beyond prognostic stratification, highlighting the potential of cell-of-origin-based classification for treatment stratification and precision medicine in PDAC. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0366-7022 55 9 2026 Size-dependent reflection behavior of graphene oxide-based photonic crystals upag176 EN Daisuke Ogawa Department of Chemistry and Materials, Faculty of Textile Science and Technology, Shinshu University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Koki Sano Department of Chemistry and Materials, Faculty of Textile Science and Technology, Shinshu University Graphene oxide (GO) nanosheets can spontaneously self-assemble into photonic crystals in water, exhibiting structural colors based on Bragg reflection. In this study, we systematically investigated the effect of GO lateral size on the reflection behavior of GO-based photonic crystals. Reflection spectroscopy revealed that both the reflection peak intensity and its time-dependent evolution strongly depended on the GO lateral size, suggesting the existence of an optimal size range for maximizing their reflection intensity. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0931-2250 212 6 2026 Validation and Fine Mapping of Quantitative Trait Loci Associated With Salinity Tolerance at Reproductive Stage on Chromosome 6 in the Rice Variety Nona Bokra e70252 EN M M Emam Ahmed Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koki Maeoka Graduate School of Environment and Life Science, Okayama University Yuki Sakata 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 Soil salinity is a major abiotic stress affecting rice production globally. Previously, one promising salinity-tolerant line (SL535) was identified through screening of Nona Bokra-CSSLs with a Koshihikari background. In 2016, 102 F2 individuals derived from SL535/Koshihikari were evaluated under long-term salt stress, with salt treatment imposed from the active tillering stage to maturity to investigate salt tolerance at the reproductive stage. Three QTLs for plant dry weight, panicle number, and panicle weight were detected on chromosome 6. This genomic region was further validated in 2019 and 2020 for plant dry weight, tiller number, and Na+ and Cl�| contents using homozygous lines with or without the Nona Bokra allele in a Koshihikari background. As expected, significantly higher tiller number and lower Na+ and Cl�| contents were maintained in plants carrying the Nona Bokra allele (NIL) at the full-heading stage. In 2023, seven newly developed NILs were evaluated for agronomic traits under control and salt stress conditions. Based on their performance, the QTL for plant dry weight, qPDW6.1, was narrowed down to a 390 kb region ranging from 4.78 to 5.17 Mb on chromosome 6. Within this region, several stress-related candidate genes were predicted based on annotation information and variant effect prediction analysis. Among them, two genes, Os06g0196700 (Auxin response factor 1) and Os06g0199100 (P-type pentatricopeptide repeat protein), were considered the most likely candidate genes associated with salt tolerance. These findings provide a foundation for future gene cloning and functional validation studies, which may help elucidate the genetic and molecular mechanisms underlying salt tolerance at the reproductive stage. No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2026 Multi-Objective Optimization for Decision Support for Supply Warehouse Location Under Earthquake Disaster Conditions �\ A Case Study in Okayama City, Japan �\ 684 689 EN Atsushi Kuroda Okayama University Takaki Kawamoto Okayama University In this study, we consider a Nankai Trough earthquake scenario and examine the optimal location of a new emergency supply warehouse to strengthen the emergency supply chain. Conventional facility location studies have primarily emphasized accessibility to demand points. In contrast, this study also incorporates safety based on disaster risk. We formulate an extended p-median model as a multi-objective optimization problem that simultaneously considers accessibility and safety as two evaluation criteria. Multiple scalarization methods are applied to obtain solutions under different preference settings. Numerical experiments using real-world data reveal a clear trade-off between accessibility and safety. The results also show that differences in scalarization methods affect the characteristics of the obtained solutions. Furthermore, by comparing our results with the previous study, we show that the proposed approach can flexibly derive a wide range of solutions, from distance-oriented to safety-oriented configurations. These findings provide useful insights for proposing resilient supply locations in disaster preparedness planning. 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.

Springer Science and Business Media LLC Acta Medica Okayama 0021-8820 2026 Amino acid mapping–guided scaffold selection and hit identification of histidine kinase inhibitors from a virtual library of over 12 million compounds EN Teruhiko Ishikawa Graduate School of Education, Okayama University Yoko Eguchi Department of Science and Technology on Food Safety, Faculty of Biology-Oriented Science and Technology, Kindai University Toshihide Okajima SANKEN, The University of Osaka Masayuki Igarashi Institute of Microbial Chemistry (BIKAKEN) Shino Ohira Analysis Technology Center, FUJIFILM Corporation Kyosuke Tsumura Analysis Technology Center, FUJIFILM Corporation Kazumasa Sakurai High Pressure Protein Research Center, Institute of Advanced Technology, Kindai University Yoshimasa Ishizaki Institute of Microbial Chemistry (BIKAKEN) Chigusa Hayashi Institute of Microbial Chemistry (BIKAKEN) Shammi Akter Laboratory of Microbial Technology, Division of Systems Bioengineering, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University Jiro Nakayama Laboratory of Microbial Technology, Division of Systems Bioengineering, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University Chie Kohayakawa Department of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, The University of Osaka Akiyoshi Tani Department of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, The University of Osaka Naoki Sawa Graduate School of Education, Okayama University Takaomi Katsumoto Graduate School of Education, Okayama University Fumiya Matsumoto Graduate School of Education, Okayama University Jun-Ichi Haruta Department of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, The University of Osaka Ryutaro Utsumi SANKEN, The University of Osaka Waldiomycin is a natural product originally isolated from actinomycete extracts. It inhibits histidine kinases (HKs), which are essential components of bacterial two-component signal transduction systems, by targeting the conserved H-box region and suppressing autophosphorylation. Here, we identified novel HK inhibitors using amino acid mapping (AAM)-based virtual screening. We compared the AAM descriptor of the naphthoquinone moiety of waldiomycin, which directly interacts with the H-box region, with those of approximately 12 million commercially available compounds and identified 714 candidates with similar descriptor values. From these candidates, we selected 9-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one as a promising and structurally distinct scaffold and synthesized 15 derivatives. The inhibitory activities of these derivatives were evaluated against the HKs WalK, VicK, and EnvZ. Three 4H-pyrido[1,2-a]pyrimidin-4-one derivatives (FF-054, FF-055, and FF-060) exhibited potent inhibitory activity, with IC50 values ranging from 4.39 to 259 µM. Notably, the IC50 values of these compounds increased three- to six-fold against the EnvZ S242A mutant, in which the conserved H-box residue is substituted. Furthermore, nuclear magnetic resonance (NMR) analysis using the EnvZ DHp domain (residues 223–289, encompassing the H-box region) confirmed direct interaction with this domain. Taken together, these results demonstrate that pyrido[1,2-a]pyrimidin-4-one derivatives FF-054, FF-055, and FF-060 are novel HK inhibitors that target the H-box region. This study represents the first successful application of AAM-based screening to identify HK inhibitors targeting this highly conserved region. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1465-3621 2026 Early progression after immune checkpoint inhibitor therapy in recurrent or metastatic head and neck squamous cell carcinoma: association with disease distribution in a single-center retrospective study hyag167 EN Hiroki Noda Department of Otolaryngology�\Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuma Makino Department of Otolaryngology�\Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuto Naoi Department of Otolaryngology�\Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Fujimoto Department of Otolaryngology�\Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology�\Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Immune checkpoint inhibitors (ICIs) are an important treatment option for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, some patients experience rapid disease progression shortly after ICI initiation, potentially resulting in deterioration of general condition and limited opportunities for subsequent treatment. This study investigated clinicopathological factors associated with early progression after ICI initiation in patients with R/M HNSCC.<br> Methods: We retrospectively analyzed 207 patients with R/M HNSCC treated with nivolumab or pembrolizumab at a single institution. Early progression was defined as disease progression within 90 days after ICI initiation. Associations between clinicopathological factors and early progression were evaluated using logistic regression analyses.<br> Results: Early progression was observed in 80 patients (38.6%). In an exploratory survival comparison, patients with early progression had significantly shorter overall survival than those without early progression. Early progression rates increased from distant-only disease to locoregional-only disease and combined locoregional and distant disease. In multivariable analysis, combined locoregional, and distant disease showed the strongest independent association with early progression. Elevated neutrophil-to-lymphocyte ratio and hypoalbuminemia were also independently associated with early progression. In contrast, treatment regimen, treatment line, number of lesions, and bulky disease were not significantly associated with early progression.<br> Conclusion: Disease distribution was associated with early progression after ICI initiation in patients with R/M HNSCC, with combined locoregional and distant disease showing the strongest independent association. These findings suggest that both disease status and host condition may influence failure to achieve adequate disease control shortly after ICI initiation. 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.<br> 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.<br> 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).<br> 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.

Frontiers Media SA Acta Medica Okayama 1664-2392 16 2025 Efficacy in Japanese adults with growth hormone deficiency receiving weekly somapacitan or daily growth hormone: results from phase 3 REAL 1 trial 1534891 EN Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Michael Højby Rasmussen Clinical Drug Development, Novo Nordisk A/S Takaaki Endo Medical Affairs Department, Novo Nordisk Pharma Ltd. Claus Sværke Clinical Drug Development, Novo Nordisk A/S Shigeyuki Tahara Department of Neurological Surgery, Nippon Medical School, Musashikosugi Hospital Gudmundur Johannsson Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg and Department of Endocrinology, Diabetology, and Metabolism, Sahlgrenska University Hospital Introduction: Somapacitan is a long-acting growth hormone (GH) derivative approved for once-weekly treatment of adult GH deficiency (AGHD). This study aimed to evaluate the efficacy and safety of somapacitan and daily GH in Japanese individuals with AGHD.<br> Methods: This subgroup study included the 34-week main period of the multinational, randomized, parallel-group, phase 3 trial, REAL 1 (NCT02229851). Participants received once-weekly somapacitan or daily GH (Norditropin®), both administered subcutaneously. Investigators and trial sites were blinded. A total of 36 Japanese GH-naïve individuals with AGHD were allocated to somapacitan or daily GH (excluding the placebo group of the global trial). Endpoints included change in truncal fat percentage to week 34 measured using dual-energy x-ray absorptiometry, as well as other body composition measures. Insulin-like growth factor I standard deviation score values were used for dose titration.<br> Results: In total, 36 Japanese individuals were included (18 and 18 in the somapacitan and daily GH group, respectively). 35 completed the main period (34 weeks). Mean (SD) change from baseline to week 34 in truncal fat percentage was -2.23 (2.50) %-points in the somapacitan group and -2.12 (4.21) %-points in the daily GH group. Other body composition measures also improved in both groups, including reduced visceral fat and increased lean body mass. Somapacitan was well tolerated, with a safety profile similar to daily GH.<br> Conclusions: In Japanese treatment-naïve individuals with AGHD, once-weekly somapacitan demonstrated similar efficacy and safety to daily GH after 34 weeks of treatment. Somapacitan provides an effective alternative to daily GH in AGHD. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1012-2443 94 1 2025 An XAI-based meta-parameter tuning for time-series forecasting 1 18 EN Hiroyuki Nakagawa Okayama University Shimon Sumita Osaka University Ryuichi Iida Okayama University Tatsuhiro Tsuchiya Osaka University How can we efficiently determine meta-parameter values for deep learning-based time-series forecasting given a time-series dataset? This paper introduces Xtune, an efficient and novel meta-parameter tuning method for deep learning-based time-series forecasting, leveraging explainable AI techniques. In particular, this study focuses on optimizing the window size for time-series forecasting. Xtune determines the optimal meta-parameter value for these methods and can also be applied to tune the window size for anomaly detection methods that utilize deep learning-based time-series forecasting. Extensive experiments on real-world datasets and forecasting methods demonstrate that Xtune efficiently identifies the optimal meta-parameter value and consistently outperforms the existing methods in terms of execution speed. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 74 3 2025 Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis 76 EN Takafumi Yanagisawa Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Keiichiro Mori Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Akihiro Matsukawa Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ekaterina Laukhtina Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Pawel Rajwa Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Fahad Quhal Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Benjamin Pradere Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Wataru Fukuokaya Department of Urology, The Jikei University School of Medicine Kosuke Iwatani Department of Urology, The Jikei University School of Medicine Renate Pichler Department of Urology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck Jeremy Yuen-Chun Teoh S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong Marco Moschini Department of Urology, San Raffaele Hospital and Scientific Institute Wojciech Krajewski Department of Minimally Invasive and Robotic Urology, Wrocław Medical University Jun Miki Department of Urology, The Jikei University School of Medicine Shahrokh F. Shariat Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Takahiro Kimura Department of Urology, The Jikei University School of Medicine European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU) Recent phase 3 randomized controlled trials (RCTs) demonstrate the promising impact of immune checkpoint inhibitor (ICI)-based combination therapies on locally advanced or metastatic urothelial carcinoma (UC). However, comparative data on the efficacy and toxicity of different ICI-based combinations are lacking. This study aims to compare the efficacy of first-line ICI-based combination therapies for locally advanced or metastatic UC using phase 3 RCT data. In November 2023, three databases were searched for RCTs evaluating oncological outcomes in patients with locally advanced or metastatic UC who were treated with first-line ICI-based combination therapies. Network meta-analysis (NMA) was conducted to compare outcomes, including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), and treatment-related adverse events (TRAEs). Subgroup analyses were based on PD-L1 status and cisplatin eligibility. The NMA included five RCTs. Enfortumab vedotin (EV) + pembrolizumab ranked the highest for improving OS (100%), PFS (100%), ORR (96%), and CRR (96%), followed by nivolumab + chemotherapy. EV + pembrolizumab combination superiority held across PD-L1 status and cisplatin eligibility. In patients who are cisplatin-eligible, EV + pembrolizumab significantly improved OS (HR: 0.68, 95%CI 0.47–0.99) and PFS (HR: 0.67, 95%CI 0.49–0.92) compared to nivolumab + chemotherapy. Durvalumab + tremelimumab was the safest combination for severe TRAEs, and EV + pembrolizumab ranked second. Our analyses support EV + pembrolizumab combination as a first-line treatment for locally advanced or metastatic UC. Thus, EV + pembrolizumab may become a guideline-changing standard treatment. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2210-6014 15 1 2025 Relationship Between Heated Tobacco Products and Placental Abruption: A Prospective Cohort Study Using Online Questionnaire 30 EN Hikaru Ooba Center for Innovative Clinical Medicine, Okayama University Hospital Jota Maki Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Tabuchi Division of Epidemiology, School of Public Health, Tohoku University Graduate School of Medicine Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Placental abruption (PA) is a critical obstetric complication, with maternal smoking recognized as a key risk factor. Despite the increased use of heated tobacco products (HTPs), the impact of HTPs remains unclear. This study investigated whether pregnant women using HTPs are at a higher risk of PA than non-users.<br> Methods: We analyzed data from �gthe Japan COVID-19 and Society Internet Survey,�h a prospective, self-reported online survey cohort. Questionnaires were randomly distributed between July 28, 2021, and August 30, 2021. Pregnant respondents in 2021 were invited to complete an additional survey from February 14, 2022, to February 28, 2022. We set the outcome as the absolute risk difference (aRD) and relative risk ratio (rRR) of PA incidence due to smoking HTPs in the first trimester of pregnancy. The sample size included 12 836 participants. We calculated outcomes using a generalized linear model (GLM) and inverse probability of treatment weighting (IPTW). We also performed a Bayesian approach and multiple-bias analysis for sensitivity analysis.<br> Results: We found the robust aRD of 0.07 (95% confidence interval (CI): 0.06, 0.09) and the rRR of 11.3 (95% CI: 7.5, 17.0). Multiple bias analyses showed that unmeasurable confounders would need to have at least an rRR = 14 relationship with both exposure and outcome to disprove the observed association. There has not been post hoc analysis or secondary use of data.<br> Conclusion: Early pregnancy use of HTPs is associated with an increased risk of PA. No potential conflict of interest relevant to this article was reported.

American Astronomical Society Acta Medica Okayama 0004-637X 980 1 2025 Observing Supernova Neutrino Light Curves with Super-Kamiokande. V. Distance Estimation with Neutrinos 117 EN Yudai Suwa Department of Earth Science and Astronomy, The University of Tokyo Akira Harada Interdisciplinary Theoretical and Mathematical Sciences Program (iTHEMS), RIKEN Masamitsu Mori Division of Science, National Astronomical Observatory of Japan Ken�fichiro Nakazato Faculty of Arts and Science, Kyushu University Ryuichiro Akaho Faculty of Science and Engineering, Waseda University Masayuki Harada Department of Physics, Okayama University Yusuke Koshio Department of Physics, Okayama University Fumi Nakanishi Department of Physics, Okayama University Kohsuke Sumiyoshi National Institute of Technology, Numazu College Roger A. Wendell Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU, WPI), Todai Institutes for Advanced Study, The University of Tokyo Neutrinos are pivotal signals in multimessenger observations of supernovae (SNe). Recent advancements in the analysis method of supernova (SN) neutrinos, especially in quantitative analysis, have significantly broadened scientific possibilities. This study demonstrates the feasibility of estimating distances to SNe using neutrinos. This estimation utilizes the direct relationship between the radius of a neutron star (NS) and the distance to the supernova, which is analogous to main-sequence fitting. The radius of an NS is determined with an approximate uncertainty of 10% through observations such as X-rays and gravitational waves. By integrating this information, the distance to the supernova can be estimated with an uncertainty of within 15% at a 95% confidence level. It has been established that neutrinos can pinpoint the direction of supernovae, and when combined with distance estimates, three-dimensional localization becomes achievable. This capability is vital for follow-up observations using multimessenger approaches. Moreover, more precise distance determinations to SNe through follow-up observations, such as optical observations, allow for accurate measurements of neutron-star radii. This data, via the neutron-star mass–radius relationship, could provide various insights into nuclear physics. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1556-0864 20 6 2025 A Single-Arm Phase 2 Study of Sotorasib Plus Carboplatin and Pemetrexed in Patients With Advanced Nonsquamous NSCLC With KRAS G12C Mutation (WJOG14821L, SCARLET) 775 785 EN Hiroaki Akamatsu Internal Medicine III, Wakayama Medical University Shinya Sakata Department of Respiratory Medicine, Kumamoto University Hospital Koichi Azuma Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Takehiro Uemura Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences Yuko Tsuchiya-Kawano Department of Respiratory Medicine, Kitakyushu Municipal Medical Center Seiya Esumi Respiratory Center, Matsusaka Municipal Hospital Takashi Kurosaki Department of Medical Oncology, Kindai University Faculty of Medicine Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Tomohiro Sakamoto Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Ryo Toyozawa Department of Thoracic Oncology, NHO Kyushu Cancer Center Yasuto Yoneshima Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University Takehito Shukuya Department of Respiratory Medicine, Juntendo University Graduate School of Medicine Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center Kana Watanabe Department of Respiratory Medicine, Miyagi Cancer Center Haruko Daga Department of Medical Oncology, Osaka City General Hospital Terufumi Kato Department of Thoracic Oncology, Kanagawa Cancer Center Toshiaki Takahashi Division of Thoracic Oncology, Shizuoka Cancer Center Mitsuo Osuga Center for Biomedical Sciences, Wakayama Medical University Yasuhiro Koh Internal Medicine III, Wakayama Medical University Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine Nobuyuki Yamamoto Internal Medicine III, Wakayama Medical University Introduction: The efficacy and safety of sotorasib plus platinum doublet chemotherapy in KRAS G12C-mutated nonsquamous NSCLC (nonsq NSCLC) have been previously reported with a limited follow-up period.<br> Methods: SCARLET is a single-arm phase 2 study involving chemotherapy-naive patients with KRAS G12C–mutated nonsq NSCLC. The participants received 960 mg daily plus four cycles of carboplatin (area under the curve = 5)/pemetrexed 500 mg/m2, followed by sotorasib/pemetrexed until disease progression. The primary end point was the overall response rate (ORR) and the secondary end points were progression-free survival (PFS), overall survival, and safety. Using plasma samples, next-generation sequencing was performed at baseline, 3 weeks, and during disease progression (the Japan Registry of Clinical Trials number 2051210086).<br> Results: Thirty patients were enrolled between October 2021 and July 2022 with a median follow-up of 14.8 months. ORR was 88.9% (80% confidence interval [CI]: 78.5%–94.8%, 95% CI: 70.8%–97.6%), median PFS was 6.6 months (95% CI: 5.3–16.7 mo), and median overall survival was 20.6 months (95% CI: 8.1 mo–not estimated). Among patients with programmed death-ligand 1 expression levels of 1% or higher and less than 1%, the ORRs were 82.3 and 100%, respectively, and the median PFS was 7.6 and 9.7 months, respectively. Using plasma samples, patients without KRAS G12C at baseline, without KRAS-related pathway co-alterations, or who cleared KRAS G12C at 3 weeks had better median PFS (16.7, 13.9, 8.7 mo, respectively). Tumor protein 53 mutations and EGFR and MET amplification were detected as acquired resistance.<br> Conclusions: In patients with KRAS G12C-mutated nonsq NSCLC, sotorasib plus carboplatin/pemetrexed reported favorable efficacy, particularly for patients with less than 1% programmed death-ligand 1, with manageable toxicity. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1758-8359 17 2025 Clinical impact of hypomagnesemia induced by necitumumab plus cisplatin and gemcitabine treatment in patients with advanced lung squamous cell carcinoma: a subanalysis of the NINJA study 1 16 EN Shigeru Tanzawa Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yasunori Murata Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Takeshita Department of Respiratory Medicine, Ichinomiya Nishi Hospital Fumihiko Kinoshita Department of Thoracic Oncology, NHO Kyushu Cancer Center Takatoshi Fujishita Department of Thoracic Oncology, NHO Kyushu Cancer Center Shunichi Sugawara Department of Pulmonary Medicine, Sendai Kousei Hospital Yosuke Kawashima Department of Pulmonary Medicine, Sendai Kousei Hospital Kazuki Hashimoto Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Masahide Mori Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Akihiko Miyanaga Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Anna Hayashi Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Hisashi Tanaka Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine Ryoichi Honda Department of Respiratory Medicine, Asahi General Hospital Masafumi Nojiri Department of Respiratory Medicine, Kanazawa Medical University Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Akito Hata Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center Nobuhisa Ishikawa Department of Respiratory Medicine, Hiroshima Prefectural Hospital Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center Takahisa Kawamura Department of Thoracic Oncology, Osaka International Cancer Institute Go Saito Department of Respirology, Graduate School of Medicine, Chiba University Teppei Yamaguchi Department of Thoracic Oncology, Aichi Cancer Center Hospital Kazuhiro Asada Department of Respiratory Medicine, Shizuoka General Hospital Satoshi Tetsumoto Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital Hiroshi Tanaka Department of Internal Medicine, Niigata Cancer Center Hospital Satoshi Watanabe Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Yukihiro Umeda Department of Respiratory Medicine, Faculty of Medical Sciences, University of Fukui Kakuhiro Yamaguchi Department of Respiratory Medicine, Hiroshima University Hospital Kazuya Nishii Department of Respiratory Medicine, NHO Iwakuni Clinical Center, Iwakuni, Yamaguchi, Japan Kosuke Tsuruno Department of Respiratory Medicine, Iizuka Hospital Yuki Misumi Department of Respiratory Medicine, Yokohama Municipal Citizen�fs Hospital Hiroshi Kuraishi Department of Pulmonary Medicine, Nagano Red Cross Hospital Ken Yoshihara Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Akira Nakao Department of Respiratory Medicine, Fukuoka University Hospital Akihito Kubo Department of Respiratory Medicine and Allergology, Aichi Medical University Toshihiko Yokoyama Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Kana Watanabe Department of Respiratory Medicine, Miyagi Cancer Center Nobuhiko Seki Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Background: The clinical impact of hypomagnesemia induced by necitumumab plus gemcitabine and cisplatin (GCN) as a second-line or later therapy is unclear.<br> Objective: We aimed to evaluate the clinical characteristics and survival impact of hypomagnesemia induced by this therapy.<br> Design: This was a sub-analysis of the retrospective multicenter NINJA study.<br> Methods: Among the 93 patients enrolled in the NINJA study, this subanalysis included 75 patients with baseline serum magnesium concentrations.<br> Results: The incidence of grade ⩾2 hypomagnesemia was 18.0% in the patients with normal baseline serum magnesium concentrations and 42.8% in those with low concentrations (p = 0.073). The discontinuation rates of GCN treatment owing to hypomagnesemia in each group were 0% and 7.1%, respectively (p = 0.187). The number of necitumumab doses and severity of hypomagnesemia were positively correlated (r = 0.389, p < 0.001). Patients who developed hypomagnesemia in fewer than 21 days after the first dose of GCN (n = 12) had significantly poorer progression-free survival (PFS) than those without the condition (n = 63; median: 4.1 vs 4.4 months, p = 0.048). A similar trend was observed for OS (median: 9.7 vs 15.7 months, p = 0.062). These results were maintained after multivariate analyses (PFS: hazard ratio (HR) 2.46, p = 0.014; OS: HR 2.78, p = 0.021).<br> Conclusion: GCN as a second-line or later therapy may be tolerable regardless of the patient�fs baseline serum magnesium concentration. On the other hand, early serum magnesium reduction with this therapy is associated with a poor prognosis. However, caution should be needed because our results lacked sufficient information for confounding variables other than those analyzed here that may influence the correlation between hypomagnesemia and survival. 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�fs University Miyuki Yokoro-Hisanari Faculty of Education, Okayama University Akira Ohtsubo Community Liaison Division for Education and Research, Mukogawa Women�fs University Tatsuya Fujii School of Education, Mukogawa Women�fs University Jotaro Kato School of Letters, Mukogawa Women�fs University Hitoshi Ogasawara School of Nursing, Mukogawa Women�fs 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�fs 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.

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�fs 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.

SAGE Publications Acta Medica Okayama 1758-8359 17 2025 Skin disorder within 30 days is a favorable prognostic factor in patients with lung squamous cell carcinoma treated with necitumumab plus gemcitabine and cisplatin: a sub-analysis of the NINJA study 1 13 EN Fumihiko Kinoshita Department of Thoracic Oncology, NHO Kyushu Cancer Center Shigeru Tanzawa Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yasunori Murata Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Takeshita Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Shunichi Sugawara Department of Pulmonary Medicine, Sendai Kousei Hospital Yosuke Kawashima Department of Pulmonary Medicine, Sendai Kousei Hospital Kazuki Hashimoto Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Masahide Mori Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Akihiko Miyanaga Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Anna Hayashi Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Hisashi Tanaka Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine Ryoichi Honda Department of Respiratory Medicine, Asahi General Hospital Masafumi Nojiri Department of Respiratory Medicine, Kanazawa Medical University Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Ken Yamamoto Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center Ken Masuda Department of Respiratory Medicine, Hiroshima Prefectural Hospital Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center Takahisa Kawamura Department of Thoracic Oncology, Osaka International Cancer Institute Takuji Suzuki Department of Respirology, Graduate School of Medicine, Chiba University Teppei Yamaguchi Department of Thoracic Oncology, Aichi Cancer Center Hospital Kazuhiro Asada Department of Respiratory Medicine, Shizuoka General Hospital Satoshi Tetsumoto Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital Hiroshi Tanaka Department of Internal Medicine, Niigata Cancer Center Hospital Satoshi Watanabe Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Yukihiro Umeda Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui Kakuhiro Yamaguchi Department of Respiratory Medicine, Hiroshima University Hospital Shoichi Kuyama Department of Respiratory medicine, NHO Iwakuni Clinical Center Kosuke Tsuruno Department of Respiratory Medicine, Iizuka Hospital Yuki Misumi Department of Respiratory Medicine, Yokohama Municipal Citizen�fs Hospital Hiroshi Kuraishi Department of Respiratory Medicine, Nagano Red Cross Hospital Ken Yoshihara Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine Akira Nakao Department of Respiratory Medicine, Fukuoka University Hospital Akihito Kubo Department of Respiratory Medicine and Allergology, Aichi Medical University School of Medicine Toshihiko Yokoyama Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Kana Watanabe Department of Respiratory Medicine, Miyagi Cancer Center Nobuhiko Seki Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Background: Skin disorders are major adverse events associated with necitumumab plus gemcitabine and cisplatin (Neci + GC) administration. However, the prognostic effect of skin disorders in patients with lung squamous cell carcinoma (LSCC) administered Neci + GC is unclear.<br> Objectives: We examined this prognostic effect in patients with LSCC, and the usefulness of minocycline administration.<br> Design: This was a sub-analysis of the retrospective multicenter NINJA study.<br> Methods: We performed a landmark survival analysis according to the presence of skin disorders at Day 30 of treatment and examined the usefulness of minocycline for treating skin disorders.<br> Results: Among the 93 patients, 62 (66.7%) had a skin disorder at Day 30. Nineteen, 30, and 13 patients experienced Grade 1, 2, and 3 skin disorders, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with skin disorders at Day 30 were longer than those of patients without skin disorders (median OS: 434 vs 278 days, p = 0.0201; median PFS: 148 vs 82 days, p = 0.0835). Multivariable analysis showed that a skin disorder at Day 30 was an independent prognostic factor for both OS (p = 0.0044) and PFS (p = 0.0514). Of the 62 patients with skin disorders at Day 30, 38 (61.3%) were taking minocycline, and their time to treatment failure (TTF) was better than that in patients not taking minocycline (median TTF: 148 vs 101 days, p = 0.0495).<br> Conclusion: A skin disorder within 30 days was a favorable prognostic factor for patients with LSCC administered Neci + GC. Additionally, minocycline administration may be beneficial in patients who develop skin disorders within 30 days. 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.

Microbiology Society Acta Medica Okayama 0022-2615 75 3 2026 Investigation of carbapenem-hydrolysing Klebsiella oxytoca strains lacking detectable carbapenemase genes 002139 EN Hiroshi Teraguchi Department of Clinical Laboratory, Kindai University Nara Hospital Ayaka Oda Dental School, Okayama University Satoyo Wakai Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Sayoko Kawakami Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Koki Yoshida Department of Clinical Laboratory, Kindai University Nara Hospital Wataru Hayashi Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Norikazu Kitamura Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Yo Sugawara Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Naoya Ohara Dental School, Okayama University Motoyuki Sugai Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Koji Yahara Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Aki Hirabayashi Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Introduction. Carbapenemase-producing Enterobacterales (CPE) pose a clinical concern due to limited treatment options and plasmid-mediated spread of carbapenemase genes. The modified carbapenem inactivation method (mCIM) is increasingly used in clinical settings to detect CPE.<br> Gap Statement. Interpretation of mCIM results for isolates with reduced carbapenem susceptibility remains challenging.<br> Aim. To assess the interpretation of positive mCIM results in Klebsiella oxytoca isolates lacking detectable carbapenemase genes and exhibiting reduced carbapenem susceptibility and to propose a phenotypic testing strategy for accurate evaluation.<br> Methodology. Antimicrobial susceptibility testing with clavulanic or dipicolinic acid supplementation, phenotypic carbapenemase assays, carbapenem hydrolysis assays and whole-genome sequencing (WGS) were conducted on K. oxytoca strains.<br> Results. K. oxytoca strains were isolated from both blood and urine samples of a patient in a Japanese hospital. Although classified as susceptible by clinical breakpoints, these isolates exhibited reduced susceptibility to carbapenems. Although these strains were mCIM-positive, the zinc-supplemented carbapenem inactivation method did not support the presence of metallo-ƒÀ-lactamase (MBL) activity. MIC reductions in the presence of CVA were consistent with inhibition of a class A ƒÀ-lactamase. In contrast, dipicolinic acid supplementation did not reduce the meropenem MIC, ruling out MBL production. Furthermore, WGS revealed that both K. oxytoca strains lacked known carbapenemase genes, with blaOXY-2-4 being the only identifiable ƒÀ-lactamase gene encoding a class A enzyme. No novel ƒÀ-lactamase genes were identified; however, an enhanced blaOXY-2-4 expression-associated point mutation was found in the promoter region. Both K. oxytoca strains exhibited carbapenem-hydrolysing activity, although to a lesser extent than that of the MBL-producing strain.<br> Conclusion. We identified K. oxytoca strains that lacked known carbapenemase genes but that yielded positive mCIM results, possibly due to OXY-2 overproduction. Our study findings emphasize the need for cautious mCIM result interpretation for K. oxytoca and highlight the diagnostic value of combined susceptibility testing with clavulanic and dipicolinic acids to distinguish the underlying resistance mechanisms. Combining complementary clinical laboratory tests will enable clarification of the factors underlying mCIM positivity and guide clinical decision-making. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0781 2026 Disrupted FLOWERING LOCUS C alleles from weedy radish enhance the florigenic potential of rootstocks for graft-mediated floral induction in Brassicaceae pcag119 EN Ko Motoki Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Saki Kobayashi Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Kazusa Nishimura Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Yu Kinoshita Graduate School of Agriculture, Kyoto University Makoto Kashima Faculty of Science, Department of Biomolecular Science, Toho University Koichiro Ushijima Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Tanjuro Goto Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Ken-ichiro Yasuba Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Munetaka Hosokawa Faculty of Agriculture, Kindai University Graft-mediated floral induction is a classical yet promising breeding technique that accelerates seed production and shortens generation time in crops. However, its application remains limited to a few species because floral induction is often unstable. Even among florally induced rootstocks, grafted scions can differ in their flowering response depending on rootstock genotype, but the genetic basis of this variation remains unclear. Here, using a Brassicaceae grafting model, we investigated two early-bolting radish (Raphanus sativus) accessions differing in their ability to induce flowering. We focused on a significant difference in FLOWERING LOCUS T (FT) expression between these accessions and identified two quantitative trait loci (QTLs) associated with FT levels. Transcriptomic and genomic analyses revealed that both QTLs harbored previously unreported disrupted alleles of FLOWERING LOCUS C (FLC) homologs, key floral repressors involved in vernalization, which showed reduced expression and produced defective transcripts. Grafting experiments demonstrated that these disrupted FLC alleles enhanced floral induction, with RsFLC1 having a major effect. Our results indicate that the FT expression threshold required for graft-mediated floral induction is higher than that for rootstock flowering itself and that this threshold is reached when FLC-mediated repression is substantially reduced. These alleles were inferred to have originated from weedy radish (Raphanus raphanistrum), likely contributing to early flowering in disturbed environments. This study suggests that exploring genetic variations in FT expression is an effective strategy to develop highly florigenic rootstocks, thereby broadening the application of graft-mediated floral induction in crop breeding. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1349-0079 68 6 2026 Synaptic transmission in Type III taste cells 100819 EN Hinata Tatsukawa Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kengo Horie Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryusuke Yoshida Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Type III taste cells are the primary taste receptor cells that form conventional chemical synapses with gustatory nerve fibers. Since the first ultrastructural identification of synaptic vesicles in Type III cells, numerous studies have demonstrated that these cells have synapse-associated proteins and vesicular release machinery that is similar to that in the central nervous system.<br> Highlight: This review summarizes historical and ultrastructural studies describing synaptic vesicles in taste bud cells across a range of animal species. The classical mechanisms of chemical synaptic transmission in the central nervous system are then outlined, followed by review studies demonstrating the expression of synapse-associated proteins in taste bud cells, with particular emphasis on the putative mechanisms of synaptic transmission in Type III taste cells. Finally, the current evidence for candidate neurotransmitters, including 5-hydroxytryptamine, gamma-aminobutyric acid, noradrenaline, acetylcholine, and ATP, is discussed.<br> Conclusion: Although several proteins related to conventional chemical synapses in the central nervous system and some candidate neurotransmitters have been identified in Type III cells, their contributions to sour taste transmission have not been fully elucidated. Further molecular and physiological studies are required to establish their roles in the synaptic transmission of sour taste signals from Type III cells. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2057-3804 11 1 2025 Incidence and survival outcomes of myocarditis and pericardial diseases associated with immune checkpoint inhibitor therapy 26 EN Aya F. Ozaki School of Pharmacy & Pharmaceutical Sciences, University of California Michael Sayer School of Pharmacy & Pharmaceutical Sciences, University of California Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Misako Nagasaka Division of Hematology and Oncology, University of California Benjamin J. Lee Department of Pharmacy, University of California Jean Doh Department of Pharmacy, University of California Ali Naqvi Division of Cardiology, Department of Medicine, University of California Nareh Nowrouzi School of Pharmacy & Pharmaceutical Sciences, University of California Yoshito Zamami Department of Pharmacy, Okayama University Hospital Pranav M. Patel Division of Cardiology, Department of Medicine, University of California Introduction Immune checkpoint inhibitor(ICI) induced cardiac immune related adverse events are challenging to study; Leveraging large data bases like TriNetX global health network may provide needed insights.<br> Methods We performed a retrospective cohort study including patients diagnosed neoplasm and 18 and older when receiving ICI therapy from 1/1/2011 to 12/31/2022. Queried ICD 9/10 codes identified patients experiencing myocarditis, pericarditis, pericardial effusion, and cardiac tamponade within 1 year of ICI initiation. Survival analyses compared one-year overall survival (OS) of patients experiencing cardiac irAEs against propensity score matched populations not experiencing them.<br> Results In 88,928 identified ICI patients, the incidence of myocarditis(0.48%), pericarditis(0.22%), and cardiac tamponade(0.47%) were less than 1% while pericardial effusion occurred in 4.71% of patients. Hazard ratios (HRs) were significantly higher in all cardiac irAE groups: myocarditis (HR:1.26, 95% CI:1.04–1.54, p = 0.02), pericarditis (HR:1.36, 95% CI:1.02–1.82, p = 0.04), pericardial effusion (HR:1.49, 95% CI:1.39–1.59, p < 0.0001), cardiac tamponade (HR:2.15, 95% CI:1.79–2.57, p < 0.0001), and overall pericardial disease (HR:1.46, 95% CI:1.37–1.56, p < 0.0001). There was no significant difference in OS between myocarditis and pericarditis or overall pericardial diseases.<br> Discussion/conclusion Utilizing a uniquely large cohort of ICI patients, this study further shows the rarity of cardiac inflammatory irAEs and highlights their significant impact on patient survival. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0361-8609 100 4 2025 Exploring the Clinical Diversity of Castleman Disease and TAFRO Syndrome: A Japanese Multicenter Study on Lymph Node Distribution Patterns 592 605 EN Mizuna Otsuka Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Tomohiro Koga Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Remi Sumiyoshi Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Shoichi Fukui Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Yuko Kaneko Division of Rheumatology, Department of Internal Medicine Keio University School of Medicine Tokyo Japan Takayuki Shimizu Division of Hematology, Department of Medicine, Keio University School of Medicine Atsushi Katsube Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine Shingo Yano Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine Yasufumi Masaki Department of Hematology and Immunology, Kanazawa Medical University Makoto Ide Department of Hematology, Takamatsu Red Cross Hospital Hajime Yoshifuji DDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University Masayasu Kitano Department of Collagen Disease and Rheumatology, Sumitomo Hospital Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Naoki Sawa Nephrology Center and Department of Rheumatology, Toranomon Hospital Kajigaya Hiroaki Niiro Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University Hospital Naoya Nakamura Department of Pathology, Tokai University School of Medicine David C. Fajgenbaum Center for Cytokine Storm Treatment & Laboratory, University of Pennsylvania Frits van Rhee Myeloma Center, University of Arkansas for Medical Sciences Atsushi Kawakami Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Individuals diagnosed with Castleman disease (CD) and TAFRO syndrome (characterized by thrombocytopenia, anasarca, fever, bone marrow fibrosis, and organomegaly) displays a wide range of clinical symptoms, including varying patterns of lymph node enlargement, systemic inflammation, and impaired organ function. Some patients may present with both CD and TAFRO syndrome concurrently. A retrospective study conducted across multiple centers in Japan examined 321 cases to determine if the quantity and position of swollen lymph nodes could forecast the clinical progression and intensity of these conditions. Interestingly, the study revealed that patients with TAFRO syndrome exhibited lymphadenopathy across all ranges of lymph node region counts. Moreover, no specific clinical patterns were associated with the number of affected lymph node regions in CD patients, regardless of whether they also had TAFRO syndrome. These results enhance our understanding of the clinical variability in CD and TAFRO syndrome, suggesting that a comprehensive clinical evaluation, rather than relying solely on lymph node count, is crucial for effectively managing these conditions. Additional studies are required to establish reliable diagnostic markers and to predict disease severity at the time of diagnosis, ultimately improving patient outcomes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0929-1903 32 5 2025 Tob negatively regulates NF-ƒÈB activation in breast cancer through its association with the TNF receptor complex 573 583 EN Miho Tokumasu Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsuko Sato Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University Taku Ito-Kureha Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University Mizuki Yamamoto Research Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo Nao Ohmine Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University Kentaro Semba Department of Life Science and Medical Bioscience, Waseda University Jun-ichiro Inoue The University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA) Tadashi Yamamoto Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University NF-ƒÈB mediates transcriptional regulation crucial to many biological functions, and elevated NF-ƒÈB activity leads to autoimmune and inflammatory diseases, as well as cancer. Since highly aggressive breast cancers have few therapeutic molecular targets, clarification of key molecular mechanisms of NF-ƒÈB signaling would facilitate the development of more effective therapy. In this report, we show that Tob, a member of the Tob/BTG family of antiproliferative proteins, acts as a negative regulator of the NF-ƒÈB signal in breast cancer. Studies with 35 human breast cancer cell lines reveal that Tob expression is negatively correlated with NF-ƒÈB activity. Analysis of The Cancer Genome Atlas (TCGA) database of clinical samples reveals an inverse correlation between Tob expression and NF-ƒÈB activity. Tob knockdown in human breast cancer cells promoted overactivation of NF-ƒÈB upon TNF-ƒ¿ treatment, whereas overexpression of Tob inhibited TNF-ƒ¿ stimulation-dependent NF-ƒÈB activation. Mechanistically, Tob associates with the TNF receptor complex I and consequently inhibits RIPK1 polyubiquitylation, leading to possible prevention of overwhelming activation of NF-ƒÈB. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1362-1017 31 6 2026 Bridging the Awareness–Action Gap in Disaster Preparedness: A Qualitative Study of Immersive Virtual Reality Learning Among Nursing Students e70681 EN Keiko Mori Graduate School of Health Sciences, Okayama University Miina Yamazaki Kobe University Hospital Yoshiyuki Haruna Snowlion. Inc. Background: Disasters increasingly challenge healthcare systems, highlighting the need to strengthen preparedness among future healthcare professionals. Although disaster risk awareness is important, it does not consistently translate into preparedness behaviours, reflecting the awareness–action gap. Immersive virtual reality (VR) may enhance experiential disaster learning, but how it influences preparedness processes remains insufficiently understood, particularly in healthcare and critical care education.<br> Aims: To explore how immersive VR-based disaster simulations influence disaster risk perception and preparedness among nursing students, with particular attention to the awareness–action gap and implications for future healthcare and critical care practice.<br> Study Design: A qualitative descriptive study using immersive VR-based disaster simulations followed by semi-structured interviews. Twelve undergraduate and graduate nursing students in Japan experienced immersive VR simulations depicting floods and landslides. Individual semi-structured interviews explored emotional responses, disaster risk perception, preparedness awareness and anticipated behavioural responses. Data were analysed using Krippendorff's content analysis with researcher triangulation.<br> Results: Five categories were identified: (1) heightened vulnerability and psychological burden through immersion; (2) persistence of the awareness–action gap despite increased risk perception; (3) enhanced risk recognition and preparedness intentions; (4) recognition of the need for social and structural support systems; and (5) emerging responsibility accompanied by perceived limitations. VR transformed abstract disaster risk into emotionally salient experiences, strengthening threat appraisal and preparedness awareness; however, awareness did not consistently translate into preparedness behaviours, reflecting insufficient coping appraisal and self-efficacy.<br> Conclusions: Immersive VR may strengthen disaster risk perception and preparedness awareness, but immersive experiences alone may be insufficient to bridge the awareness–action gap. Combining VR with reflective learning, skills-based training and collaborative simulation may strengthen coping appraisal and preparedness action.<br> Relevance to Clinical Practice: Immersive VR combined with reflective and skills-based learning may support psychological readiness, situational awareness and disaster preparedness competencies among future nurses, including those preparing for critical care practice. 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.

Walter de Gruyter GmbH Acta Medica Okayama 2294-1932 2026 Direct evidence for water-filled yet hydraulically isolated xylem vessels in two temperate tree species 1 14 EN Mayumi Y. Ogasa Kansai Research Center, Forestry and Forest Products Research Institute Yasuhiro Utsumi Ashoro Research Forest, Kyushu University Kenichi Yazaki Hokkaido Research Center, Forestry and Forest Products Research Institute Naoko H. Miki Faculty of Environmental, Life, Natural Science and Technology Kenji Fukuda Graduate School of Agricultural and Life Sciences, The University of Tokyo Xylem vessels in sapwood are typically interpreted as either conductive or non-functional following embolism or occlusion, implicitly assuming that the presence of water within the lumen reflects participation in the transpiration stream. However, the relationship between lumen water content and hydraulic connectivity has rarely been examined directly at the cellular level. In this study, we combined cryo-scanning electron microscopy and fluorescence microscopy to compare lumen water status with hydraulic connectivity on the same xylem surface in current-year xylem of Carpinus tschonoskii and Aria alnifolia, using tension-driven dye uptake to identify conductive vessels. Most vessels were stained and water-filled, consistent with functional conduits, whereas unstained gas-filled vessels corresponded to embolized conduits. Notably, certain vessels retained water despite lacking dye signals, indicating hydraulic isolation from the conductive xylem network. Although these vessels represented a minor fraction of the conduit population, their occurrence suggests that the traditionally binary classification should be expanded to incorporate an additional conduit function. These vessels were observed in both species, suggesting that hydraulically disconnected vessels represent a common phenomenon across species. These findings reveal previously underrecognized heterogeneity in xylem hydraulic organisation and demonstrate that conduit status cannot always be inferred from the presence of water alone. Recognising this intermediate condition refines current interpretations of xylem function and highlights the value of integrating high-resolution imaging with hydraulic measurements. No potential conflict of interest relevant to this article was reported.

John Benjamins Publishing Company Acta Medica Okayama 0019-0829 2026 Making alliterative collocations memorable: Does vocalisation help? EN Satoshi Yamagata Okayama University Mariko Abe Okayama University Anna Siyanova-Chanturia Victoria University of Wellington Collocations are a key component of second language (L2) mastery. Yet, their acquisition poses major challenges to L2 learners. One potential solution to this difficulty is employing the mnemonic effect of alliteration (e.g., professional practice). In the present study, 230 Japanese EFL university students learnt alliterative and non-alliterative collocations (e.g., primary purpose vs. primary care) under vocalised and non-vocalised conditions in a within-subject design. Vocalisation frequencies were operationalised (none, once, three, and five times) over four weeks to examine potential differences across repetition frequencies. Immediate and delayed productive recall post-test assessed collocational uptake. Results showed that alliterative collocations yielded greater gains than non-alliterative ones when vocalisation was involved, suggesting a conditional benefit of vocalisation in combination with phonological salience. A modest advantage was observed in the three-times vocalisation condition in the immediate post-test; however, it was not reliably maintained at the delayed post-test. No potential conflict of interest relevant to this article was reported.

Association for Computing Machinery (ACM) Acta Medica Okayama 2474-9567 9 3 2025 Presentation Quality Assessment through Audience 3D Facial and Head Direction Using Conventional Cameras 1 15 EN Goshi Imamura Okayama University Atsushi Nakazawa Okayama University This paper shows the method for evaluating the quality of presentations using information from the audience's facial and head behavior. Existing studies have focused on assessing presentation skills by analyzing presentation materials and the presenter's verbal and non-verbal cues, however, since a presentation is an interaction between the presenter and the audience, the presentation quality is not only influenced by presenter's information but also audience's information such as their background knowledge. This means that the presenter's output alone is not enough for a comprehensive evaluation of the presentation. To address this, we show a method that utilizes videos of the audience recorded during presentations using two cameras: one capturing from the presenter's point of view and the other from around the presentation screen. The 3D position and direction of the audience's face were detected using face detection techniques, which were then used to predict gaze targets, such as the presenter and the presentation screen. The number of times these targets were looked at during the presentation served as feature values for evaluating presentation quality. Using a dataset of 18 presenters and 32 audience members, this paper shows a significant correlation between subjective ratings and behavioral characteristics. It also demonstrates an algorithm that infers the quality of a presentation from these feature values. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1058-8388 2026 MIT/TFE family transcription factors, Mitf and Tfec, redundantly promote pigment cell differentiation and retinal epithelium pigmentation in teleosts 1 15 EN James Lister Department of Human and Molecular Genetics and Massey Cancer Center, Virginia Commonwealth University School of Medicine Keisuke Sugiwaka Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Tetsuaki Kimura Department of Basic Biology, School of Life Science, Graduate University of Advanced Studies (SOKENDAI) & Laboratory of Bioresources, National Institute for Basic Biology Rieko Tanaka World Medaka Aquarium, Nagoya Higashiyama Zoo and Botanical Gardens Makoto Goda Institute of Photonics Medicine, Hamamatsu University School of Medicine Hikaru Kobayashi Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Chikako Inoue R&D Fish Breeding Group, Regional Fish Institute, Ltd. Kawilarang W. A. Masengi Faculty of Fisheries and Marine Science, Sam Ratulangi University Kazunori Yamahira Tropical Biosphere Research Center, University of the Ryukyus Kiyoshi Naruse Department of Basic Biology, School of Life Science, Graduate University of Advanced Studies (SOKENDAI) & Laboratory of Bioresources, National Institute for Basic Biology Satoshi Ansai Ushimado Marine Institute, Graduate School of Natural Science and Technology, Okayama University Robert N. Kelsh Department of Life Sciences, University of Bath Masahiko Hibi Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Hisashi Hashimoto Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Background: Transcription factors of the MIT/TFE family�\mitfa, mitfb, and tfec�\play essential roles in specifying pigment cells derived from neural crest cells in vertebrates. In teleosts, which possess multiple pigment cell types, these factors exhibit partially redundant but largely distinct functions across different pigment lineages. We previously reported that the combined loss of mitfa and mitfb leads to a complete absence of melanophores, xanthophores, and leucophores in medaka.<br> Results: Here, we describe newly generated hypomorphic alleles of mitfa and mitfb, which result in delayed melanophore development. Using these hypomorphic mutants in combination with a newly generated null allele of tfec, we show that Tfec can partially compensate for the loss of Mitfa and Mitfb in melanophore, xanthophore, and leucophore differentiation. Consistent with previous findings in zebrafish, loss of tfec alone results in the complete absence of iridophores. Importantly, simultaneous null mutations in all three genes cause a complete loss of all four chromatophore types and lead to defective pigmentation of the retinal pigmented epithelium (RPE), which is not derived from the neural crest in both Oryzias species and in zebrafish. Using an RPE-specific marker, we further show that the RPE is specified and structurally intact but fails to melanize.<br> Conclusions: These findings indicate that the redundant functions of Mitfa, Mitfb, and Tfec are not only essential for the specification of diverse pigment cell types but also critical for RPE pigmentation. 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.<br> 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.<br> 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).<br> 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 6 2026 Association between venous access-site closure device use and postoperative nausea and vomiting after atrial fibrillation ablation under propofol sedation: a single-centre retrospective observational study in Okayama, Japan e117719 EN Haruna Sakanoue Department of Nursing, Okayama Heart Clinic Hirosuke Yamaji Heart Rhythm Centre, Okayama Heart Clinic Sayaka Okamoto Department of Nursing, Okayama Heart Clinic Kumi Okano Department of Nursing, Okayama Heart Clinic Yuka Fujita Department of Nursing, Okayama Heart Clinic Shunichi Higashiya Heart Rhythm Centre, Okayama Heart Clinic Takashia Murakami Heart Rhythm Centre, Okayama Heart Clinic Satoshi Hirohata Graduate School of Health Sciences, Department of Medical Technology, Okayama University Shozo Kusachi Heart Rhythm Centre, Okayama Heart Clinic Objectives To examine whether the use of a venous access-site closure device is associated with the occurrence of postoperative nausea and vomiting (PONV) after atrial fibrillation (AF) ablation under propofol sedation.<br> Design Observational study.<br> Setting A single-centre retrospective observational study in Okayama, Japan.<br> Participants We retrospectively analysed consecutive patients who underwent AF ablation under deep propofol sedation with adaptive servo-ventilation. A total of 686 patients were included. Patients were managed using a standardised sedation protocol with or without low-dose pentazocine. Patients treated with conventional manual compression for haemostasis (n=383) were compared with those treated using a venous access-site closure device (n=303).<br> Interventions Postprocedural bed rest duration and the incidence and timing of PONV were compared between groups. Associations between closure device use and PONV were evaluated using logistic regression analysis.<br> Primary outcome measure The primary outcome was the occurrence of PONV following AF ablation.<br> Results All procedures were completed under propofol sedation without conversion to general anaesthesia. The duration of postprocedural bed rest was shorter in the device group than in the conventional-compression group (mean difference �|14.7 hours, 95% CI �|15.2 to �|14.0).<br> PONV occurred in 6/303 patients (2.0%) in the device group and 20/383 patients (5.2%) in the conventional-compression group, corresponding to a relative risk of 0.38 (95% CI 0.15 to 0.93), an OR 0.25 (95% CI 0.10 to 0.62) and a risk difference of �|3.2% (95% CI �|6.0% to �|0.5%).<br> In multivariable analysis, use of a venous closure device was associated with a lower likelihood of PONV.<br> Conclusions In this single-centre observational study, use of a venous access-site closure device was associated with a lower occurrence of PONV after AF ablation under propofol sedation. These findings suggest that postprocedural management strategies enabling earlier mobilisation may be associated with improved patient comfort; however, causal inference is limited by the observational design. 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.<br> 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).<br> 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.<br> Trial registration number jRCT2031240586, No potential conflict of interest relevant to this article was reported.

Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, Japan Society of Gynecologic Oncology Acta Medica Okayama 2005-0380 37 5 2026 Examining the relationship between cesarean section scar and endometrial cancer e96 EN Keiichiro Nakamura 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 Hironori Itou Department of Obstetrics and Gynecology, National Hospital Organization Iwakuni Clinical Center Miyuki Shimizu Department of Obstetrics and Gynecology, Kagawa Rosai Hospital Thi Hai Ly Dao 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 Kazuhiro Okamoto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chikako Ogawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eriko Eto 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 Objective: The incidence of endometrial cancer (EC) has been increasing annually. Studies have reported that cesarean section (CS) is associated with a higher risk of developing EC than vaginal delivery (VD). However, few studies have examined the relationship between CS and EC development.<br> Methods: Data were extracted from the medical records of patients with EC and a history of childbirth who underwent EC treatment at 3 institutions. Factors contributing to EC development were analyzed between April 2010 and December 2024.<br> Results: Among patients EC and a history of childbirth, 8.7% (69/794) had undergone CS, and 50.7% (35/69) developed a CS scar. Compared with patients who had a VD or those without a CS scar, patients with a CS scar showed significantly shorter intervals from delivery to EC onset (VD: p=0.013; non-CS scar: p=0.031). A narrower residual myometrial thickness/adjacent myometrial thickness (RMT/AMT) ratio of the CS scar was significantly associated with a shorter interval from the last delivery to EC onset (p=0.034) and was independently associated with earlier EC onset after the last delivery in both univariate and multivariate analyses (p<0.001 and p=0.030, respectively).<br> Conclusion: A narrower RMT/AMT ratio in the CS scar was considerably associated with a shorter interval from the last delivery to EC onset. 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 1345-2630 2026 Macroscopic and microscopic visualization of Pseudomonas syringae pv. tabaci infection using complementary bioluminescent and fluorescent reporter systems EN Kana Kuroe Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yasuhiro Ishiga Faculty of Life and Environmental Sciences, University of Tsukuba Yoshiteru Noutoshi 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 Hidenori Matsui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The development of bioluminescent and fluorescent reporter systems has enabled visualization of plant-pathogenic bacterial infection dynamics, providing insights into detailed mechanisms of infection and potential applications for disease control. Pseudomonas syringae pv. tabaci 6605 (Pta) possesses quorum sensing systems and produces fluorescent pigments, which make it difficult to directly apply commonly used reporter systems. In this study, we first constructed a homologous recombination-based genomic insertion system for stable chromosomal integration of reporter genes in Pta. Using this system, we established a LuxCDABE bioluminescent system driven by the nptII promoter, which successfully enabled macroscale tracking of bacterial populations during infection. We then attempted to construct an sGFP fluorescent reporter using the same nptII promoter. However, the endogenous autofluorescence of Pta masked the sGFP signal, making quantitative detection difficult. To overcome this autofluorescence problem, we screened constitutively highly expression promoters based on transcriptome data and identified two effective promoters suitable for fluorescent monitoring of Pta infection. Together with the LuxCDABE system, this integrated platform provides comprehensive spatiotemporal analysis of virulence mechanisms and plant defense responses in the Pta pathosystem, with potential applicability to other plant-pathogenic bacteria. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 8756-758X 2026 Fatigue Life Evaluation Using the Damage�]Equivalent Strain for 7075�]T6 Aluminum Alloy Under Bending and Torsion Bending Vibrations EN Junji Sakamoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Naoya Tada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takeshi Uemori Faculty of Environmental, Life, Natural Science and Technology, Okayama University The vibrations caused by external factors (such as fluids) or internal factors often pose strength-related problems in mechanical and structural components. Although several studies have investigated the material fatigue characteristics during vibration, reports on complex vibration modes such as torsion bending are limited. In this study, we addressed this gap by conducting experiments and finite element analyses on I- and L-shaped aluminum alloy specimens under bending and torsion bending vibrations, respectively. We established a reliable method to estimate the strain at the notch by utilizing the strain measured at a position outside the notch and a ratio derived from finite element analysis. This method allows for accurate assessment of the critical strain history without interfering with crack observation. Using the strain range at the crack initiation site effectively unified the fatigue life evaluation for both specimens. 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.<br> 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�fs infrequent questions using words such as �gwhat,�h �gwho,�h and �gwhere.�h Modified Poisson regression estimated RRs adjusted for confounders. Subgroup analyses examined effect modification by sex, childcare setting, and family size.<br> 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.<br> 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<br> 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.<br> 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.<br> Results<br> 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.<br> Conclusion<br> 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.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 8 2026 Impact of Adjusted Creatinine Clearance on Carboplatin Dosing in Endometrial Cancer: A Retrospective Study 1285 1290 EN Kentaro Katayama Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Makio Imamura Department of Clinical Support, Kurashiki Medical Center Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Carboplatin (CBDCA) dosing is commonly determined using the Calvert formula, with creatinine clearance (Ccr) estimated by the Cockcroft–Gault formula. In Japan, where serum creatinine (sCr) is usually measured enzymatically, unadjusted Ccr may overestimate glomerular filtration rate and lead to CBDCA overdosing. We retrospectively compared treatment exposure, hematologic toxicity, and exploratory oncologic outcomes in patients with endometrial cancer who received postoperative paclitaxel plus CBDCA therapy. Patients were grouped according to whether CBDCA dosing was based on the conventional Cockcroft–Gault formula (CG group) or on adjusted Ccr calculated by adding 0.2 mg/dL to sCr (adjusted group). The incidence of Grade ≥3 neutropenia was significantly lower in the adjusted group than in the CG group. The 5-year progression-free survival (PFS) rate was numerically lower in the adjusted group than in the CG group, although no statistically significant difference was observed between the groups. Because the number of PFS events was limited, the effect of adjusted Ccr-based dosing on oncologic outcomes remains uncertain. These findings suggest that adjusted Ccr-based dosing may reduce hematologic toxicity in routine clinical practice. However, given the limited number of PFS events and the wide uncertainty in survival estimates, further studies are needed to clarify its impact on oncologic outcomes. 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<br> 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.<br> Methods<br> 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.<br> Results<br> 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.<br> Conclusions<br> 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 0969-806X 251 2027 A rule-based calculation approach to derive bone-suppressed chest X-ray images using photon-counting techniques 114493 EN Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Mana Mitani Division of Radiology, Medical Support Department, Okayama University Hospital Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Noriaki Akagi Division of Radiology, Medical Support Department, Okayama University Hospital Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Improving the visibility of lung nodules, which are often hidden by bone shadows and difficult to identify, remains a challenge in chest radiography. This study aims to develop an algorithm for generating novel bone-suppressed images using photon-counting techniques. The core idea of our algorithm is to fit photon interaction cross-sections to X-ray attenuation data measured with photon-counting detectors. Based on further calculations using the derived fitting coefficients, both density (ƒÏ) and amount-of-substance concentration (mol) were determined. The product of these values produced a ƒÏ�~mol image exhibiting a clear bone-suppression effect. We conducted a virtual chest imaging simulation using 10 patient datasets acquired via clinical photon-counting computed tomography (PC-CT). The CT images were converted into ƒÏ�~mol images following the proposed processing procedure, and two-dimensional chest images were generated through projection. Quantitative evaluations confirmed that the proposed images achieved sufficient bone suppression. Furthermore, commercial software provided by a vendor was used to generate bone-suppressed images from conventional images projected from CT data. A comparable bone-suppression effect on the ribs was observed between the vendor-generated images and our proposed images, while lesion visibility (e.g., lung nodules) was preserved. Additionally, bone-suppression effects in our images were observed in the vertebrae and clavicles located outside the lung fields. Our research demonstrates the value of constructing general X-ray imaging systems using photon-counting detectors. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0739-7240 98 2027 Transcriptional remodeling of local thyroid hormone metabolism is associated with feather growth termination in chicken wing feathers 107057 EN Masamichi Shinohara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuri Nozawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hibiki Fukuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yu Takeuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sayaka Aizawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sakae Takeuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Feather elongation is sustained by continuous cell proliferation within the feather follicle; however, the molecular mechanisms responsible for feather growth termination remain poorly understood. In this study, we investigated molecular changes associated with feather growth termination by comparing two chicken wing feather types with contrasting growth characteristics: primary wing feathers and primary coverts. Histological and bromodeoxyuridine incorporation analyses demonstrated that primary wing feathers remained in an active growth phase, whereas primary coverts exhibited pulp regression, reduced cell proliferation, and characteristics of growth termination. Gene expression analyses showed that primary coverts exhibited reduced expression of prolactin receptor (PRLR), type 2 iodothyronine deiodinase (DIO2), and insulin-like growth factor 2 (IGF2), together with marked induction of the thyroid hormone (TH)-inactivating enzyme type 3 iodothyronine deiodinase (DIO3). In contrast, primary wing feathers exhibited relatively higher expression of PRLR, DIO2, and IGF2 than primary coverts, while maintaining consistently low DIO3 expression. Reporter assays showed increased IGF2 promoter activity following triiodothyronine (T3) treatment in all three independent experiments, although the increase did not reach statistical significance. Thus, the reporter assay provides only tentative support for T3 responsiveness of the IGF2 promoter, consistent with our previous in vivo and primary-culture findings showing T3-dependent increases in IGF2 expression. These coordinated transcriptional changes are consistent with remodeling of local TH metabolism during the transition from active feather growth to growth termination. While local TH concentrations and direct deiodinase activities remain to be quantified, and the causal relationship between PRL/PRLR signaling and DIO3 induction remains unresolved, this study provides a molecular framework for understanding how local endocrine regulation translates systemic hormonal signals into feather type-specific growth responses during avian feather development. Graphical abstract No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0099-2240 2026 Interaction with the N-acetylgalactosamine moiety facilitates pore formation by Cry4Aa toxin, thereby increasing its toxicity e00714-26 EN Mohammad Tofazzal Hossain Howlader Department of Entomology, Bangladesh Agricultural University Taiyo Tsutsui Applied Chemistry and Biotechnology Program, School of Engineering, Okayama University Kouichi Saito Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tohru Hayakawa Applied Chemistry and Biotechnology Program, School of Engineering, Okayama University Cry4Aa is a mosquito-larvicidal toxin produced by Bacillus thuringiensis serovar israelensis. Cry4Aa exhibits a characteristic architecture comprising three domains (I, II, and III) and functions as a pore-forming toxin, consistent with many previously reported insecticidal Cry toxins. However, the mechanism preceding pore formation by Cry4Aa, including receptor recognition, remains to be elucidated. The present study examined the potential involvement of sugar moieties in the Cry4Aa mode of action, with a particular focus on the process of pore formation. Cry4Aa and the sugar N-acetylgalactosamine exhibited considerably increased binding affinity. Furthermore, N-acetylgalactosamine treatment significantly enhanced the toxicity of Cry4Aa against Culex pipiens mosquito larvae. In the presence of N-acetylgalactosamine, the binding of Cry4Aa to phosphatidylcholine liposomes increased by 1.4-fold. The presence of this sugar did not affect the single-channel conductance of Cry4Aa pores formed in artificial lipid bilayers; however, it did appear to increase the number of Cry4Aa pores per designated area. In silico molecular docking analysis revealed promising binding sites within the cavity, surrounded by the Cry4Aa domains. These results suggest that the interaction of Cry4Aa with N-acetylgalactosamine moieties is a vital step in the process of pore formation. This interaction may induce a conformational change in the Cry4Aa molecule that facilitates its insertion into the target membrane. 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.

Springer Science and Business Media LLC Acta Medica Okayama 1866-6299 85 13 2026 Intensity of chemical weathering and its implications for soil erosion across lithological and climatic gradients in the Chemoga watershed, Upper Blue Nile Basin 317 EN Alebachew Tareke Kehali The United Graduate School of Agricultural Sciences, Tottori University Hiroshi Kitagawa Institute for Planetary Materials, Okayama University Nigussie Haregeweyn International Platform for Dryland Research and Education, Tottori University Mitsuru Tsubo International Platform for Dryland Research and Education, Tottori University Zelalem Leyew Anteneh Department of Geology, School of Earth Sciences, Bahir Dar University Belay Tesfa Ayalew Department of Geology, School of Earth Sciences, Bahir Dar University Zena Tessema Terefe The United Graduate School of Agricultural Sciences, Tottori University Ashebir Sewale Belay Department of Geology, School of Earth Sciences, Bahir Dar University Ayele Almaw Fenta Institute for Planetary Materials, Okayama University Atsushi Tsunekawa Institute for Planetary Materials, Okayama University The geochemistry of rocks, regolith/soil, surficial and core sediments, and clay mineral assemblages from these sediments was analyzed to elucidate the transition from fresh to chemically altered materials. These data were used to evaluate the intensity of chemical weathering and its implications for erosion across contrasting lithological and climatic gradients in the Chemoga watershed of the Upper Blue Nile Basin, Ethiopia. Our findings show depletion of Na+, Ca2+, Mg2+, and K+, and enrichment of Al3+, Fe3+, Ti4+, and Mn2+ in the regolith/soil, upper part of surficial sediment, and upper layer of the core sediment (10 m). Chemical Index of Alteration (CIA) values are rocks 35–47, regolith/soil 75–96, surficial river sediments 45–96, and core sediments 50–90. River sediments in the highland area are dominated by kaolinite (39%), illite (34%), and chlorite (27%), while the lower study area has illite (76%), chlorite (11%), and kaolinite (12%). Geochemistry, ternary plots, and clay mineralogy show that the highland region underwent intensive chemical weathering, while the midland experienced intermediate to high weathering, and the lowland had weak weathering. The highlands experience severe weathering due to a humid, bimodal precipitation climate; despite having younger, weathering-resistant rocks (basalt, andesite, trachyte), the lower regions consist of older, more mafic rocks (basalt and trachybasalt). Like the surficial river sediment, core sediment showed intense chemical weathering and kaolinite dominance in the upper layers (0–10 m depth, CIA > 80). Weathering intensity decreased with depth, suggesting changes in weathering and in clay mineral formation that reflect past climate. The high weathering gradient from highland to lowland correlates with erosion, indicating that weathering strongly influences soil erosion variability in the watershed. This work provides a reasonable basis for improving our understanding of the degree of weathering across contrasting environments and its implications for soil erosion by connecting the relationship between parent materials and chemically altered samples with the degree of soil erosion. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1520-541X 28 3 2026 Sexual Dimorphism in Vertebral Number: Developmental Implications Inferred From Vertebral and Body Proportions e70062 EN Kazunori Yamahira Tropical Biosphere Research Center, University of the Ryukyus V. K. Anoop Tropical Biosphere Research Center, University of the Ryukyus Rajeev Raghavan Department of Fisheries Resource Management, Kerala University of Fisheries and Ocean Studies Yoshitaka Tanaka Ushimado Marine Institute, Okayama University Satoshi Ansai Ushimado Marine Institute, Okayama University Segmentation is a fundamental feature of vertebrate body plans, and variation in vertebral number contributes substantially to morphological diversity. Although sexual dimorphism in vertebral number has been documented in several vertebrate lineages, its developmental basis remains poorly understood. Here, we report pronounced sexual dimorphism in vertebral number in the western Indian endemic ricefish Oryzias setnai, distributed across ~1800 km. Radiographic analyses of individuals collected throughout its range revealed that vertebral number increased with latitude in both sexes, while males consistently possessed more vertebrae than females irrespective of geographic origin. Size-adjusted analyses showed that this dimorphism is associated with sex differences in head size and position-dependent variation in vertebral length. However, positional allometric analyses demonstrated that both the magnitude and direction of these sex differences vary markedly during growth. In particular, among smaller individuals, posterior vertebrae were relatively shorter in males than in females, suggesting reduced somite length in the posterior body axis of male embryos and potentially reflecting sex-specific differences in the dynamics of somitogenesis. Given that this variation arises between males and females within a single species sharing an essentially identical genetic background, O. setnai provides a rare empirical system not only for linking early developmental processes to intraspecific sexual variation in vertebrate body plans but also as a powerful model to investigate the developmental basis of body plan variation across species. No potential conflict of interest relevant to this article was reported.

“ú–{Œ’�N‹³ˆçŠw‰ï Acta Medica Okayama 1340-2560 34 2 2026 ’†�E�‚�E‘åŠw�¶‚ÌŒ’�fŒ‹‰ÊŠˆ—p‚Ì‘£�i—vˆö�\ƒwƒ‹ƒXƒŠƒeƒ‰ƒV�[ƒXƒLƒ‹ƒtƒŒ�[ƒ€ƒ��[ƒN‚ð—p‚¢‚½ŒŸ“¢�\ 118 129 EN Hitomi ONISHI The Joint Graduate School (Ph.D. Program) in Science of School Education, Hyogo University of Teacher Education Nobuki NISHIOKA Faculty of Psychology and Collaboration, Kyoto Women�fs University Takehiko ITO Graduate School of Education, Okayama University –Ú“I�FŠw�ZŒ’�N�f’fŒ‹‰ÊŠˆ—p�iˆÈ‰º�CŠˆ—p�j‚ÆŠÖ˜A—vˆö‹y‚Ñ‘ŠŒÝ‚ÌŠÖ˜A�«‚ðƒwƒ‹ƒXƒŠƒeƒ‰ƒV�[ƒXƒLƒ‹ƒtƒŒ�[ƒ€ƒ��[ƒN‚ð—p‚¢‚Ä–¾‚ç‚©‚É‚·‚邱‚Æ‚ð–Ú“I‚Æ‚µ‚½�D<br> •û–@�F’†Šw�¶493–¼�C�‚�Z�¶360–¼�C‘åŠw1”N�¶297–¼‚ð‘Î�Û‚É–³‹L–¼Ž©‹LŽ®Ž¿–⎆’²�¸‚ð�s‚Á‚½�D’²�¸“à—e‚ÍŠˆ—p‚Æ�CŒ’�N‚Ö‚ÌŠÖ�S�Cƒwƒ‹ƒXƒŠƒeƒ‰ƒV�[�iˆÈ‰º�CHL�j�CŒ’�fŒ‹‰Ê‚ɑ΂·‚é”FŽ¯�CŒ’�fŒ‹‰Ê‚̓ljð—Í�iˆÈ‰º�C“ljð—Í�j�CˆÓŽvŒˆ’èƒoƒ‰ƒ“ƒX‚Æ‚µ‚½�D‚±‚ê‚ç‚ÌŠÖ˜A�«‚ðŽ¦‚·‰¼�àƒ‚ƒfƒ‹‚ð�ZŽí�C�«•Ê‚Ì‘½•ê�W’c“¯ŽžƒpƒX‰ð�Í‚ÅŒŸ�Ø‚µ‚½�D<br> Œ‹‰Ê�F‰¼�àƒ‚ƒfƒ‹‚É4‚‚̃pƒX‚ð’ljÁ‚µ‚½�C�³ƒ‚ƒfƒ‹‚Å�C�ZŽí�C�«•Ê‚¢‚¸‚ê‚É‚¨‚¢‚Ä‚à”z’u•s•Ïƒ‚ƒfƒ‹‚Å—Ç�D‚È“K�‡“x‚𓾂½�DŒ’�fŒ‹‰Ê‚ɑ΂·‚é”FŽ¯‚©‚ç“ljð—Í�C“ljð—Í‚©‚çˆÓŽvŒˆ’èƒoƒ‰ƒ“ƒX�CˆÓŽvŒˆ’èƒoƒ‰ƒ“ƒX‚©‚犈—p�CŒ’�N‚Ö‚ÌŠÖ�S‚©‚ç“ljð—Í�CˆÓŽvŒˆ’èƒoƒ‰ƒ“ƒX�CŠˆ—p‚ւ̃pƒX‹y‚Ñ�CHL‚©‚犈—p‚ւ̃pƒX‚Í‘S‚Ä‚Ì�ZŽí‚É‚¨‚¢‚Ä—LˆÓ‚Å‚ ‚Á‚½�DŒ’�N‚Ö‚ÌŠÖ�S‚ÆŒ‹‰Ê‚ɑ΂·‚é”FŽ¯‚©‚çHL�CHL‚©‚ç“ljð—Í�CˆÓŽvŒˆ’èƒoƒ‰ƒ“ƒX‚ւ̃pƒX‚Í’†�E�‚�Z�¶‚Ì‚Ý‚Å—LˆÓ‚Å‚ ‚Á‚½�D<br> Œ‹˜_�F’†�E�‚�E‘åŠw�¶‚ÌŒ’�fŒ‹‰ÊŠˆ—p‚𑣂·‚½‚ß‚É‚Í�CŒ’�fŒ‹‰Ê‚𕪂©‚è‚â‚·‚­‚·‚邱‚Æ�CŒ’�fŒ‹‰Ê‚̓ljð—Í‹y‚шӎvŒˆ’èƒoƒ‰ƒ“ƒX‚ÌŒü�ã�C‚·‚È‚í‚¿‰¶Œb‚Ì”FŽ¯‚ÌŒü�ã‚Æ�C•‰’S‚Ì”FŽ¯‚ÌŒyŒ¸‚ª—LŒø‚Å‚ ‚è�C‚»‚Ì�Û‚É‘Î�ÛŽÒ‚ÌŒ’�N‚Ö‚ÌŠÖ�S‚ÆHL‚Ì’ö“x‚ð�l—¶‚·‚é•K—v�«‚ªŽ¦�´‚³‚ꂽ�D No potential conflict of interest relevant to this article was reported.

XMLink Acta Medica Okayama 2005-0380 37 2026 Nationwide survey of hereditary breast and ovarian cancer–related clinical practice in gynecologic oncology in Japan: a joint study by the Japan Society of Gynecologic Oncology (JSGO) and the Japan Society of Obstetrics and Gynecology (JSOG) e122 EN Kenta Masuda Department of Obstetrics and Gynecology, Keio University School of Medicine Katsutoshi Oda Division of Integrative Genomics, Graduate School of Medicine, The University of Tokyo Hidemichi Watari Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine and Faculty of Medicine Akira Hirasawa Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinya Sato Department of Obstetrics and Gynecology, Tottori University School of Medicine Kenichi Harano Department of Medical Oncology, National Cancer Center Hospital East Satoru Nagase Department of Obstetrics and Gynecology, Faculty of Medicine, Yamagata University Kazuhiro Takehara Department of Gynecologic Oncology, NHO Shikoku Cancer Center Masaki Mandai Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University Yuko Sasajima Department of Pathology, Teikyo University Hospital Tamotsu Sudo Department of Cancer Genetics & Genomics, Fujita Health University, School of Medicine Hiroyuki Yanai Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hitoshi Tsuda Department of Basic Pathology, National Defense Medical College Yusuke Kobayashi Department of Obstetrics and Gynecology, Institute of Medicine, University of Tsukuba Kei Kawana Department of Obstetrics and Gynecology, Nihon University School of Medicine Mikio Mikami Department of Medical Science, Shonan University of Medical Science Kiyoko Kato Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Daisuke Aoki International University of Health and Welfare Graduate School Aikou Okamoto Department of Obstetrics and Gynecology, The Jikei University School of Medicine Objective: To evaluate the current status of hereditary breast and ovarian cancer (HBOC)–related clinical practice in Japan, including genetic testing, risk-reducing surgery, and surveillance systems, and to identify institutional gaps and unmet needs.<br> Methods: A nationwide questionnaire survey was conducted between February and April 2024 targeting 647 Japan Society of Obstetrics and Gynecology–affiliated training facilities and gynecologic oncology centers. Institutional-level data on genetic testing, homologous recombination deficiency (HRD) testing, risk-reducing salpingo-oophorectomy (RRSO), postoperative management, surveillance practices, and healthcare infrastructure were collected. Responses from 248 institutions (response rate, 38.3%) were analyzed descriptively.<br> Results: BRCA1/2 genetic testing was performed in 83% of institutions, and HRD testing using the myChoice® CDx system in 87%. However, only 30% offered universal BRCA1/2 testing for ovarian, fallopian tube, or peritoneal cancer, and testing indications varied widely. Genetic counseling resources were uneven, with 29% lacking on-site genetic specialists, driven mainly by institutional characteristics rather than geographic location. RRSO was performed in 50% of institutions, predominantly laparoscopically. While management of occult carcinoma after RRSO was largely consistent, postoperative management of serous tubal intraepithelial carcinoma (STIC) and positive peritoneal cytology varied substantially. Over 70% of institutions reported a need for expanded insurance coverage for genetic services and preventive care.<br> Conclusion: Although HBOC-related genetic testing and preventive strategies are widely implemented in Japan, this nationwide survey revealed critical structural and evidence gaps, particularly in institutional capacity and the management of evidence-limited scenarios such as STIC, underscoring the need for system-level improvement. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2026 Clinical outcomes of near-infrared photoimmunotherapy according to immune checkpoint inhibitor timing and treatment sequence: a multicenter retrospective study EN Takuma Makino Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shohei Fujimoto Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yorihisa Orita Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kumamoto University Tomoyasu Tachibana Department of Otolaryngology Head and Neck Surgery, Japanese Red Cross Society Himeji Hospital Yuto Naoi Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mizuo Ando Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Near-infrared photoimmunotherapy (NIR-PIT) is a novel local treatment for recurrent or metastatic head and neck cancer. However, the clinical significance of immune checkpoint inhibitor (ICI) timing and treatment sequencing remains unclear. This study investigated their association with clinical outcomes after NIR-PIT.<br> Methods This multicenter retrospective study included 44 patients with 48 lesions who underwent initial NIR-PIT between January 2021 and March 2026. The primary analysis compared outcomes according to prior ICI exposure. An exploratory analysis evaluated outcomes according to treatment sequence and timing of ICI administration. The primary endpoint was local control. Secondary endpoints were objective response rate and disease control rate, while overall survival was assessed exploratorily.<br> Results Median local control duration was 253 days, but was 174 days in the prior ICI exposure group and 342 days in the non-prior ICI exposure group (log-rank P = 0.031). Local progression occurred in 69.2–37.1% of lesions, respectively (P = 0.059). Among 45 evaluable lesions, the objective response rate and disease control rate were 60.0–93.3%, respectively. Median overall survival was 866 days. Exploratory analyses suggested potential differences in clinical outcomes according to treatment sequence and ICI timing.<br> Conclusions Prior ICI exposure was associated with poorer local control after NIR-PIT. Exploratory analyses suggested that ICI timing and treatment sequencing may influence clinical outcomes. Treatment sequencing may represent an important consideration when integrating NIR-PIT and ICIs for recurrent or metastatic head and neck cancer. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 6 2026 Effect of Deuterated Drugs on Safety: Insights from Pharmacovigilance Data Analysis 983 988 EN Kohei Kitagawa Department of Neuropsychiatry, Okayama Psychiatric Medical Center Hideki Nawa Department of Pharmacy, Faculty of Pharmacy, Shujitsu University Shota Asai Department of Pharmacy, Faculty of Pharmacy, Shujitsu University Naohiro Iwata Department of Pharmacy, Okayama University Hospital Takahiro Niimura Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Mitsuhiro Goda Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Keisuke Ishizawa Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Huntington�fs disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Tetrabenazine (TBZ), a vesicular monoamine transporter 2 inhibitor, is commonly used to manage chorea; however, it may exhibit fluctuating plasma levels and elicit frequent adverse events. In this study, we aimed to clarify the effects of TBZ deuteration on its safety profile. We compared the safety profiles of TBZ and deutetrabenazine (DTBZ) in real-world clinical practice using disproportionality analysis and the large-scale pharmacovigilance database, VigiBase�\the WHO�fs global database of adverse drug reactions. Adverse event signals were assessed using the information component (IC). Seriousness was classified according to clinical outcome, and time to onset (TTO) was analyzed for selected events. TBZ showed signals for disorientation, dystonia, and sleep disorders (IC025 > 0), whereas DTBZ did not. Serious adverse events were reported in 54.7% of TBZ cases and 37.9% of DTBZ cases. The TTO of sleep disorder was also evaluated; however, the number of cases with available TTO information was limited. DTBZ showed fewer adverse event signals and a lower proportion of serious adverse events than TBZ. These findings suggest potential differences in the safety profiles of the two drugs, which may influence tolerability in the treatment of HD. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0941-4355 34 8 2026 Machine learning approaches to predict early cardiac immune-related adverse events in patients receiving immune checkpoint inhibitors 809 EN Michael Sayer School of Pharmacy & Pharmaceutical Sciences, University of California Peter D. Chang School of Medicine, Pathology & Laboratory Medicine, University of California Hirofumi Hamano Department of Pharmacy, Medical Development Field, Okayama University Reina Yamamoto Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Misako Nagasaka Division of Hematology and Oncology, University of California Ali A. Naqvi Mary & Steve Wen Cardiovascular Division, Department of Medicine, University of California Pranav M. Patel Mary & Steve Wen Cardiovascular Division, Department of Medicine, University of California Yoshito Zamami Department of Pharmacy, Medical Development Field, Okayama University Aya F. Ozaki School of Pharmacy & Pharmaceutical Sciences, University of California Purpose Immune checkpoint inhibitor (ICI)–induced cardiac immune-related adverse events (cardiac irAEs) are rare yet serious complications. Clinical assessment tools to identify at-risk patients would allow for more effective prevention strategies, thus improving clinical outcomes. We constructed various machine learning (ML) models to predict these events among patients receiving ICI therapy.<br> Methods A cohort of patients receiving ICI therapy from 2010 to 2023 was identified from the TriNetX database. Cardiac irAEs were defined as the occurrence of relevant diagnosis codes within 90 days of ICI initiation, with corresponding hospital visits. We created ML models to predict these events, including elastic net logistic regression and multiple tree-based approaches (gradient boosted trees and random forest). We evaluated model performance with different performance measures and utilized assigned risk scores to stratify risk of cardiac irAEs into low, medium, and high-risk tiers.<br> Results We identified 61,117 patients receiving ICI therapy, with nearly 2% of patients experiencing cardiac irAEs. Model performance on testing data was comparable with all approaches (AUC = 0.71–0.72, balanced accuracy = 65–66%). Each model emphasized distinct features to make classifications, as observed with feature importance and SHAP values. Comparing cardiac irAE rates among assigned risk strata, patients identified as high risk were significantly more likely to experience cardiac irAEs compared to lower tiers.<br> Conclusion Our preliminary exploration of ML methods demonstrated the potential for risk assessment tools to predict rare cardiac irAEs in patients receiving ICI therapy. Follow-up studies can implement time series approaches to harness longitudinal data that incorporates real-time labs, new diagnoses, and new therapy, to refine predictions further. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 2045-1253 16 2026 Seizures associated with clozapine augmentation by other antipsychotics: a pharmacovigilance–pharmacodynamic analysis using VigiBase EN Masakazu Hatano Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Masaya Kanda Department of Pharmacy, Asahikawa Medical University Hospital Takenao Koseki Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Tsuyoshi Nakai Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Rina Horii Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Nozomi Yoshihara Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Takeo Saito Department of Psychiatry, Fujita Health University School of Medicine Kenshi Takechi Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University Satoru Esumi The Faculty of Pharmaceutical Sciences, Kobe Gakuin University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Shigeki Yamada Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Background: Clozapine is associated with a high risk of central nervous system abnormalities. However, seizure risk related to interactions between clozapine and other antipsychotics remains poorly characterized, and the pharmacological mechanisms underlying these seizures are unclear. Objectives: We aimed to evaluate safety signals for seizures associated with clozapine augmentation by other antipsychotics and analyze the relationship between these signals and neurotransmitter receptor occupancy profiles.<br> Design: A pharmacovigilance–pharmacodynamic analysis using a spontaneous reporting system.<br> Methods: This pharmacovigilance study used VigiBase, an adverse drug reaction database maintained by the World Health Organization. Drug–drug interactions (DDIs) between clozapine and other antipsychotics were assessed using the ƒ¶ shrinkage measure model. The association between DDI signals and neurotransmitter receptor occupancy was evaluated using linear regression. Robustness was tested using four frequency statistical models: additive, multiplicative, combination risk ratio, and chi-square statistic models. Results: Of 38,758,077 reports in VigiBase between 1990 and 2024, 230,371 involved clozapine. Among antipsychotics classified under ATC code N05A, DDIs with clozapine were detected for amisulpride, chlorpromazine, haloperidol, lurasidone, olanzapine, penfluridol, risperidone, sulpiride, zotepine, and zuclopenthixol. A significant association between dopamine D4 receptor occupancy and the point estimates of signal values was observed in the ƒ¶ shrinkage measure model (ƒÀ = 0.295, 95% confidence interval: 0.119–0.471, p = 0.002) and replicated across all frequency statistical models.<br> Conclusions: These findings suggest a potential role of dopamine D4 receptor occupancy in seizures associated with clozapine augmentation by other antipsychotics. Further large-scale epidemiological studies are needed to validate these findings. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2475-0328 2026 Biological Resectability in Colorectal Liver Metastases: A Nomogram�]Based Continuous Risk Model to Define Borderline Disease EN Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Kojima Department of Surgery, Okayama Saiseikai General Hospital Takeshi Koujima Department of Surgery, Himeji Red Cross Hospital Tatsuo Matsuda Department of Surgery, Tenwakai Matsuda Hospital Daisuke Satoh Department of Surgery, Hiroshima Citizens Hospital Masaru Inagaki Department of Surgery, National Hospital Organization Fukuyama Medical Center Kosei Takagi 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: Resectability in colorectal liver metastases (CRLM) is traditionally defined by technical feasibility; however, a biologically based definition of borderline resectable disease has not been established. We evaluated the prognostic impact of KRAS mutation and developed a model for biological risk stratification.<br> Methods: This multi-institutional retrospective study included 584 patients undergoing initial hepatectomy for CRLM. The impact of KRAS mutation was assessed according to primary tumor sidedness and tumor burden score (TBS). A nomogram predicting overall survival (OS) was constructed using independent prognostic factors and compared with established clinical risk scores.<br> Results: KRAS mutation was identified in 36.8% of patients and was associated with worse OS (median survival: 47.3 vs. 70.6 months, p = 0.0006) and recurrence-free survival. This adverse impact was observed in left-sided tumors but not in right-sided tumors. TBS stratified prognosis in KRAS wild-type but not in mutant cases, suggesting that tumor biology may outweigh morphology. A nomogram incorporating KRAS status, TBS, CA19-9, primary nodal status, and extrahepatic disease demonstrated improved discriminatory ability compared with conventional models and stratified recurrence patterns, including extrahepatic recurrence.<br> Conclusions: The prognostic impact of KRAS mutation depends on tumor sidedness and is independent of tumor morphology. Our nomogram provides a continuous biological risk assessment and may facilitate biological risk stratification and support future refinement of the concept of biologically borderline resectable CRLM. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1462-5814 2026 1 2026 Phenotypic Characterization of Porphyromonas gulae Fimbria Mutants 1926696 EN Hiroaki Inaba Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sho Yoshida Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoya Ohara Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryota Nomura Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University Kazuhiko Nakano Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Michiyo Matsumoto-Nakano Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Porphyromonas gulae has been established as a pathogen in animal periodontal disease and expresses several virulence factors, including fimbriae, lipopolysaccharide, and proteases. P. gulae fimbriae are classified into three genotypes (A, B, and C) based on the fimbrillin (fimA) gene encoding a fimbrial subunit protein. We previously reported that P. gulae organisms with type C fimbriae were clearly more virulent as compared to those with other fimbria types, though the basic function of this is not fully understood. Here, we investigated the function of fimbriae using fimA-deficient mutants. In the present study, bacterial fimbriae were related to biofilm tenacity, whereas biofilm formation was not. Also, P. gulae fimbriae are involved in bacterial adhesion and entry into gingival epithelial cells. The role of P. gulae fimbriae in bacterial pathogenicity was then determined using fimA-deficient mutants with a silkworm infection model. Additionally, P. gulae infection can induce inflammatory responses in gingival epithelial cells and also inhibit cell migration and proliferation. In contrast, a P. gulae fimA-deficient mutant did not cause several of those cellular responses. Together, the results show that fimbriae contribute to the pathogenicity of P. gulae by affecting bacterial functions and host cell interactions. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2590-1230 32 2026 Prediction of tool-path and cycle time errors of CNC machining using a transformer-based deep learning model 112872 EN Kazuki Kaneko Graduate School of Environmental, Life, Natural Science and Tech, Okayama University Zongze Li Graduate School of Advanced Science and Engineering, Hiroshima University The prediction of tool-path and cycle time errors of computer numerical control (CNC) machining is important in manufacturing field. In this study, these errors are considered as sequential data corresponding to the lines of G-code, i.e., the error prediction is a sequence-to-sequence task, and a Transformer-based deep learning model was constructed to predict the tool-path and cycle time errors simultaneously, taking the positional increments and feed rate as the input. The training datasets were created by running a randomly generated G-code on a real CNC machine tool and subsequently tracking the actual errors, where the motion and feed rate are stochastically defined. The model is validated by conducting the error prediction on six sets of G-code. In addition, the comparison with a Bi-LSTM-based deep learning model is conducted. The results show that the prediction accuracy of the Transformer model can achieve the mean prediction accuracies of �}1 ƒÊm and �}1 ms in tool-path and cycle time error predictions, respectively. Furthermore, the Transformer model has a smaller prediction uncertainty than the Bi-LSTM model. Compared with conventional methods only analyzing tool-path errors or cycle-time errors, the utilized model has an advantage in its ability to simultaneously predict tool-path errors and cycle time errors. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2471-254X 10 3 2026 Hepatocellular carcinoma in Fontan-associated liver disease: Incidence, risk stratification, and surveillance implications e0910 EN Hideki Onishi Department of Gastroenterology and Hepatology, Medical Development Field, Okayama University Norihisa Toh Department of Cardiovascular Medicine, Medical Development Field, Okayama University, Okayama, Japan Kenji Baba Department of Pediatric Cardiology, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Kotani Department of Cardiovascular Surgery, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shingo Kasahara Department of Cardiovascular Surgery, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoyuki Otsuka Department of Gastroenterology and Hepatology, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Hepatocellular carcinoma (HCC) is a serious complication of Fontan-associated liver disease (FALD). However, data on its incidence, risk factors, and outcomes in this rare population are limited. We aimed to assess the incidence and predictors of HCC and evaluate the utility of surveillance in patients with FALD.<br> Methods: We conducted a retrospective cohort study on patients with FALD who were referred to our gastroenterology department. The cumulative incidence of HCC after FALD diagnosis was calculated, and multivariate analysis was used to identify independent risk factors. Overall survival after FALD diagnosis was compared between patients who developed HCC and those who did not.<br> Results: A total of 120 patients with FALD were followed up for a median period of 50.0 months. The cumulative incidence rates of HCC at 1, 2, and 3 years after FALD diagnosis were 0.9%, 2.7%, and 3.9%, respectively. Elevated alpha-fetoprotein (AFP) at FALD diagnosis was independently associated with HCC development (hazard ratio, 1.29; 95% confidence interval, 1.04–1.60; p=0.01). There was no significant difference in overall survival between patients with and without HCC in this cohort (log-rank test, p=0.50).<br> Conclusions: Patients with FALD face a non-negligible risk of developing HCC, thus supporting the need for surveillance. Elevated AFP levels at the time of FALD diagnosis may aid in risk stratification, which enables the targeted monitoring and early detection of HCC. Furthermore, routine surveillance contributes to the excellent prognosis of patients with FALD who develop HCC, thus making their prognosis comparable to that of patients without HCC. 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�fs Hospital, Boston Harvard Medical School David Zurakowski Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children�fs 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.<br> 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.<br> 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%).<br> 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.

Fuji Technology Press Ltd. Acta Medica Okayama 1883-8022 20 5 2026 Real-Time Estimation of Temperature Field and Thermal Displacement in Machine Tool Linear Motion Systems Using Servo Data 466 477 EN Ryoji Kondo YASDA PRECISION TOOLS K.K. Kazuhito Ohashi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Heat generated in machine tools during operation causes thermal deformation and deteriorates machining accuracy. To suppress thermal deformation and the resulting displacement, strategies such as reducing heat generation, cooling machine elements that generate heat, and compensating for thermal displacement are generally adopted. However, existing methods for estimating and compensating for thermal deformation and displacement can only be adopted in limited situations. In particular, there are few reports on real-time estimation methods that take into account moving parts and actual machine operating conditions. For high-accuracy machining, it is important to understand the temperature field and the associated displacement. In this study, real-time estimation of the temperature field and displacement is carried out on a test apparatus equipped with a ball screw drive system and a linear guideway system. In the estimation process, heat generation values are first calculated from servo data corresponding to the machine operation. Using these calculated values, the temperature field is then derived through the finite volume method. Finally, the thermal displacement is obtained from the temperature field using a simplified estimation method. The results are validated by comparison with experimental data and with results from commercial finite element method software, demonstrating the effectiveness and real-time performance of the proposed approach. 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�fs Clinic Women�fs 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�fs Clinic Motomi Yukawa Department of Radiology, Okayama Couple�fs Clinic Women�fs Health Checkup Center Shizuka Okuda Department of Radiology, Okayama Couple�fs Clinic Women�fs Health Checkup Center Miyu Hirano Department of Medical Technology, Okayama Couple�fs Clinic Toshihiro Habara Department of Reproductive Medicine, Okayama Couple�fs Clinic Nobuyoshi Hayashi Department of Reproductive Medicine, Okayama Couple�fs 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.<br> 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.<br> 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.<br> 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 1341-9625 30 7 2025 Guidance on the short hydration method for cisplatin administration 1287 1293 EN Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Kei Kunimasa Department of Thoracic Oncology, Osaka International Cancer Institute Yasuko Kurata Department of Pharmacy, Okayama University Hospital Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Yasuhito Fujisaka Department of Medical Oncology, Osaka Medical and Pharmaceutical University Hitoshi Ishikawa QST Hospital, National Institutes for Quantum Science and Technology Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Cisplatin is currently used as the central agent in several cancer chemotherapy protocols because of its broad antitumor spectrum and potent antitumor effects; however, preventing cisplatin-induced renal damage and other adverse events is challenging. Recently, several clinical studies have shown that a short hydration method could prevent cisplatin-induced renal damage. In addition, appropriate magnesium supplementation and administration of forced diuretics have been shown to be renoprotective. The Japanese Lung Cancer Society Guidelines Committee has summarized the evidence of renal protection regarding cisplatin administration to provide optimal administration guidance for the cisplatin short hydration method. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0953-8194 38 9 2026 Marine flatworms as windows into the evolution of bilaterian neuropeptide signalling e70259 EN Ryo Nakamura Ushimado Marine Institute, Faculty of Science, Okayama University Mayuko Hamada Ushimado Marine Institute, Faculty of Science, Okayama University Xavier Bailly Multicellular Marine Models Team, CNRS – Sorbonne University – Station Biologique de Roscoff Hirotaka Sakamoto Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tatsuya Sakamoto Ushimado Marine Institute, Faculty of Science, Okayama University The evolutionary origin(s) of neuropeptide signalling is still largely unknown. It has been hypothesised that signal transmission via neuropeptides played a crucial role in the regulation of nervous systems in the bilaterian ancestor. Identification, expression and functional analyses of neuropeptides and their receptors across different taxonomic groups are important for better understanding the origin(s) of bilaterian neuropeptide signalling. An example is flatworms belonging to the Platyhelminthes (spiralian protostomes) and Xenacoelomorpha (sister to all Bilateria or sister to Ambulacraria). Despite their simple morphology (i.e., a body plan lacking a coelom and circulatory system), they often possess brain-like central nervous systems and a number of bilaterian-conserved neuropeptides. This feature makes them useful models for analyses of neuropeptides and their links to nervous systems. Although previous studies have revealed orthologous relationships between vertebrate neuropeptides and those found in both marine Platyhelminthes and Xenacoelomorpha, our work suggests possible ancestral functions of vasopressin/oxytocin (VP/OT) peptides (platytocin) in these groups. 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.<br> 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).<br> 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.<br> 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.

Elsevier BV Acta Medica Okayama 0009-2541 713 2026 Tungsten(VI) speciation in aqueous fluids at high pressures and high temperatures: in-situ Raman spectroscopy supported by DFT calculations 123411 EN Naoko Takahashi Department of Earth Science, Graduate School of Science, Tohoku University Michihiko Nakamura Department of Earth Science, Graduate School of Science, Tohoku University Shigeru Yamashita Institute for Planetary Materials, Okayama University Hiroyuki Kagi Geochemical Research Center, Graduate School of Science, The University of Tokyo Tungsten (W) is mobile in magmatic–hydrothermal and deep subduction zone fluids, and its stable isotopes offer potential as tracers of fluid-rock interactions. We investigated W behavior in aqueous fluids using in-situ Raman spectroscopy on slightly acidic to alkaline Na2WO4 solutions (10�|3–10�|1 M W) and WO3–H2O/D2O �} NaCl systems up to 1.4 GPa and ∼800 �‹C, with the band assignments supported by density functional theory (DFT) calculations. Raman spectra showed that the ƒË1 mode of WO42�| persisted to the highest P–T conditions in alkaline fluids, while additional high-frequency bands near 950 or 973 cm�|1 appeared at elevated T in the studied fluids. Their relative intensities depended on T, pH, and NaCl content; the 973 cm�|1 band was only observed above 650 �‹C in Na-free fluids. Substitution of H2O with D2O did not significantly affect the band frequencies. Based on analogous molybdenum experiments, previous in-situ studies, and thermodynamic models, these high-T bands are assigned to mononuclear species rather than polynuclear species, consistent with the stepwise formation of hydrogentungstate anion, HWO4�|, and then neutral tungstic acid, H2WO4, as T increases. DFT vibrational frequency calculations for HWO4�|, H2WO4, and their D-substituted species support this interpretation, suggesting tetrahedral HWO4�| and higher-coordinated H2WO4 as plausible species. The present study clarifies Raman band assignments for HWO4�| and paratungstate A (W7O246�|) to address previous ambiguities in the literature, and confirms that polynuclear species play a negligible role in high-T ore-forming fluids. The tetrahedral HWO4�| appears to be a predominant transport species in NaCl-bearing metamorphic fluids and may govern stable W isotope fractionation during deep fluid-rock interactions. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1738-5733 59 1 2027 Impact of correcting beam hardening and detector response function in photon-counting X-ray imaging when using anti-coincidence mode 104678 EN Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Takuya Kasue Graduate School of Medical Sciences, Kanazawa University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University X-ray imaging using photon-counting detectors (PCDs) allows for the calculation of quantitative images such as the effective atomic number (𝑍eff). However, physical phenomena such as characteristic X-ray emission and charge sharing can cause incomplete total absorption events during signal generation, which reduces the accuracy of X-ray penetration analysis. To solve the problem, an anti-coincidence mode (ACM) has been developed, but complete correction has not been established. We aimed to investigate the accuracy of 𝑍eff image when the proposed software-based corrections, namely beam hardening and response function corrections, are added to the hardware-based correction of the ACM. The response function was calculated using the Monte-Carlo simulation code. In a simulation study, we analyzed a phantom composed of virtual materials with 𝑍eff values of 4–16. While sufficient accuracy cannot be achieved by applying only the ACM, it was demonstrated that low-noise 𝑍eff images can be obtained by applying our correction. Furthermore, it was demonstrated that 𝑍eff images of food samples can be generated by using actual non-destructive testing equipment with a 10 m/min transportation speed. In conclusion, our correction procedure can maximize the performance of PCDs, and our findings are essential for promoting imaging techniques concerning quantitative images. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 0094-8276 52 17 2025 Phase Relations in the MgSiO3 System Associated With Hot Mantle Upwelling Across the 660 km Depth e2025GL115385 EN Artem Chanyshev Bayerisches Geoinstitut, University of Bayreuth Narangoo Purevjav Bayerisches Geoinstitut, University of Bayreuth Dmitry Bondar Bayerisches Geoinstitut, University of Bayreuth Hu Tang Bayerisches Geoinstitut, University of Bayreuth Hongzhan Fei Bayerisches Geoinstitut, University of Bayreuth Lin Wang Bayerisches Geoinstitut, University of Bayreuth Fei Wang Bayerisches Geoinstitut, University of Bayreuth Eun Jeong Kim Bayerisches Geoinstitut, University of Bayreuth Dan Liu Bayerisches Geoinstitut, University of Bayreuth Takayuki Ishii Institute for Planetary Materials, Okayama University Shrikant Bhat Deutsches Elektronen�]Synchrotron DESY Robert Farla Deutsches Elektronen�]Synchrotron DESY Tomoo Katsura Bayerisches Geoinstitut, University of Bayreuth The phase transformations of MgSiO3 bridgmanite control the structure, dynamics and chemistry of the Earth's mantle. Formation of bridgmanite occurs at a depth of about 660 km causing the strong and abrupt seismic discontinuity. Previous experimental studies have revealed that this discontinuity is caused by ringwoodite dissociation in the average mantle. However, the cause of the 660-km seismic discontinuity beneath hotspots remains unclear. Here we determine the phase relations in the MgSiO3 system near the 660-km seismic discontinuity conditions. At 2,200–2,350 K with decreasing pressure, MgSiO3 bridgmanite first transforms to akimotoite and then to garnet. The akimotoite-bridgmanite boundary has almost no temperature dependence, whereas the garnet–akimotoite transition has a very steep positive boundary slope. Based on these slopes, we calculated the garnet–bridgmanite boundary slope. Depending on the temperature regime, the akimotoite-bridgmanite or the garnet–bridgmanite transition may occur in ascending plume beneath hotspots near the 660 km depth. No potential conflict of interest relevant to this article was reported.

Ceramic Society of Japan Acta Medica Okayama 1348-6535 134 9 2026 Preparation of chitosan/apatite composite particles with core–shell structure 676 681 EN Takuya Kataoka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ryo Ikeda Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Eiji Fujii Industrial Technology Center of Okayama Prefecture Tomohiko Yoshioka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Satoshi Hayakawa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University In this study, a novel sequential preparation process of core–shell particles with chitosan (CS) cores and hydroxyapatite (HAp) shells is presented. This process involved the formation of phosphorylated CS particles, followed by HAp precipitation. Importantly, the precipitation of HAp on the surface of phosphorylated CS was confirmed. Different CaCl2 concentrations during the HAp precipitation step resulted in different HAp contents in the particles. To confirm the formation of the core–shell structure, the particles were immersed in hydrochloric acid (pH 2) for 5, 10, and 30 min. Notably, samples with higher HAp content (59 wt % and 84 wt %) retained their core morphology after 30 min of immersion, whereas samples with lower HAp content (28 wt %) rapidly lost their morphology. These results indicate that higher HAp content contributes to improved morphological stability under acidic conditions, leading to the formation of more stable core–shell particles. Overall, these findings clarify the role of phosphorylated CS in inducing HAp precipitation and show that the proposed preparation process leads to the formation of CS/HAp core–shell structures. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0250-7005 46 9 2026 Antiproteinuric Effect of SGLT2 Inhibitors in Patients With Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab 5141 5154 EN TOMOKI HORI Department of Pharmacy, Nara Prefecture General Medical Center KAZUHIRO YAMAMOTO Department of Integrated Clinical and Basic Pharmaceutical Science, Okayama University HIROSHI AOI Department of Pharmacy, Nara Medical University Hospital YUSUKE KOIZUMI Department of Pharmacy, Nara Medical University Hospital MAKOTO KUROMATSU Department of Pharmacy, Tenri Hospital AIKO FUKUI Department of Pharmacy, Kindai University Nara Hospital HIROYO OKAMOTO Department of Pharmacy, Kindai University Nara Hospital ATSUSHI HIRATA Department of Pharmacy, Kindai University Nara Hospital KENTARO SHINMORI Department of Pharmacy, Yamatotakada Municipal Hospital YUKI IMANAKA Department of Pharmacy, Yamatotakada Municipal Hospital MIYU NAMBA Department of Pharmacy, Nara Prefecture General Medical Center SYUNSUKE KITAMURA Department of Nephrology, Nara Medical University Hospital KEISUKE NAKANISHI Department of Gastroenterology, Nara Prefecture General Medical Center HIDEO TSUSHIMA Department of Nephrology, Nara Prefecture General Medical Center IKUKO YANO Department of Pharmacy, Kobe University Hospital KEI MORIYA Department of Gastroenterology, Nara Prefecture General Medical Center MASARU MATSUI Department of Nephrology, Nara Medical University Hospital SHIGEKI IKUSHIMA Department of Pharmacy, Nara Prefecture General Medical Center Background/Aim: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce proteinuria in patients with diabetes mellitus and chronic kidney disease. However, their effect on vascular endothelial growth factor inhibitor-induced proteinuria remains unclear. This study evaluated the prophylactic effect of SGLT2i on bevacizumab-induced proteinuria in patients with hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab.<br> Patients and Methods: This multicenter retrospective study included patients with HCC who started therapy with atezolizumab plus bevacizumab between September 2020 and December 2023. The primary outcome was the time to exacerbation of proteinuria from baseline within 6 months after treatment initiation according to SGLT2i use. Secondary outcomes included the development of grade ≥2 proteinuria.<br> Results: A total of 188 patients were included, of whom 29 received SGLT2i. No significant difference in the time to exacerbation of proteinuria was observed between the SGLT2i and non-SGLT2i groups considering the overall population (median: 157 vs. 116 days, p=0.95). Multivariate analysis identified diabetes with systolic blood pressure ≥130 mmHg as an independent risk factor for proteinuria exacerbation (hazard ratio=2.19, 95% confidence interval=1.18-4.06, p=0.013), whereas SGLT2i use was not significantly associated with proteinuria exacerbation. In patients with both diabetes and systolic blood pressure ≥130 mmHg, SGLT2i significantly prolonged the time to proteinuria exacerbation.<br> Conclusion: SGLT2i may suppress proteinuria progression only in high-risk patients with HCC complicated by diabetes and hypertension. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2198-4034 12 1 2026 Development of a preoperative accuracy prediction model using machine learning for implant placement in static-guided surgery: retrospective observational study 44 EN Takuya Mino Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University Yurina Matsuoka Department of Semiconductor, Computer Science and Applied Mathematics, Graduate School of Science and Technology, Kumamoto University Ken�fichi Morooka Division of Biomedical Engineering, Faculty of Advanced Science and Technology, Kumamoto University Kana Tokumoto Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University Hiroaki Shimizu Shimizu Dental Clinic Yoko Kurosaki Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University Aya Kimura-Ono Center for Innovative Clinical Medicine, Okayama University Hospital Hiromitsu Kishimoto Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenji Maekawa Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University Purpose This study aimed to develop a machine learning model capable of preoperatively predicting three-dimensional implant placement errors at the implant apex in static-guided surgery and to identify the clinical features associated with placement accuracy.<br> Methods Clinical data partially derived from a previous observational study were analyzed. In total, 181 patients and 480 implants placed using fully static-guided surgery were included in this study. The outcome variable was defined as three-dimensional implant placement error at the implant apex relative to the preoperative simulation, dichotomized as less than 0.5 mm or ≥ 0.5 mm. Twenty-one clinical and radiographic factors previously suggested to influence the placement accuracy were used as explanatory variables. The feature importance was evaluated using three gradient boosting decision tree models. Furthermore, a stacking model combining multiple classifiers was constructed, and the classification performance was assessed using ten-fold cross-validation.<br> Results The feature importance analysis identified 12 features associated with implant placement errors. The stacking model demonstrated superior classification performance compared to individual classifiers. The true positive rate was 0.73, false negative rate was 0.27, false positive rate was 0.14, and true negative rate was 0.86.<br> Conclusions The proposed stacking model correctly classified 86% of cases with implant placement error less than 0.5 mm and 73% of cases with implant placement error of ≥ 0.5 mm. These findings suggest that the proposed model may support the preoperative evaluation of implant placement accuracy in static-guided surgeries. 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.

Elsevier BV Acta Medica Okayama 2212-8778 112 2026 Adaptive oligodendrogenesis regulates blood-hypothalamus barrier permeability, hypothalamic glucose sensing and systemic glucose homeostasis in male mice 102428 EN Sophie Buller Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Emily O. Staricoff Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Christine Riches Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Anthony Tsang Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Giada Giavara Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Masa Josipovic Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Kentaro Ikemura Department of Medical Technology, Graduate School of Health Sciences, Okayama University Gabriel Opoku Department of Medical Technology, Graduate School of Health Sciences, Okayama University Ikumi Sato Department of Medical Technology, Graduate School of Health Sciences, Okayama University Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Saskia Stenzel Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Stuart G. Nayar Wolfson Institute for Biomedical Research, University College London Marta Ramos Vega GUBRA Jacob Hecksher-Sørensen GUBRA Sebastian Timmler Cambridge Stem Cell Institute, University of Cambridge Georgina K.C. Dowsett Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Brian Y.H. Lam Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Giles S.H. Yeo Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Kimberly M. Alonge Diabetes Institute, University of Washington Huiliang Li Wolfson Institute for Biomedical Research, University College London William D. Richardson Wolfson Institute for Biomedical Research, University College London Mark L. Evans Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Clemence Blouet Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Objective: Brain glucose sensing is critical for survival during hypoglycaemia, yet how glucose-sensing neurons access circulating glucose concentrations to maintain glucose homeostasis remains poorly understood. Here we tested the hypothesis that adult oligodendrogenesis in the median eminence (ME) is responsive to changes in blood glucose levels and contributes to hypothalamic glucose sensing through regulation of the blood-hypothalamus barrier.<br> Methods: We used glycemic challenges and hypoinsulinaemic clamp studies to identify the effect of systemic changes in glycaemia on hypothalamic oligodendrocyte lineage cells. We used conditional knockout mouse models to dissect the respective contributions of adult oligodendrogenesis and new myelin formation to glucose homeostasis in adult male mice. Analyses combined immunofluorescence, serial electron microscopy, whole-brain tissue clearing, and transcriptomic analyses.<br> Results: We found that adult oligodendrogenesis in the median eminence (ME) is modulated by changes in circulating glucose levels and rapidly upregulated by hypoglycaemia. Genetic blockade of new oligodendrocyte production in adult male mice impairs the regulation of glucose homeostasis, the integrity of the ME blood-hypothalamus barrier, and hypothalamic glucose sensing. Unexpectedly, functional integrity of adult-formed myelin is not required for the maintenance of glucose homeostasis. Instead, we show that blockade of adult oligodendrogenesis disrupts hypothalamic expression of A disintegrin and metallopeptidase with thrombospondin motifs 4 (ADAMTS4), a metallopeptidase whose brain expression is restricted to the oligodendrocyte lineage and whose ME expression requires ongoing adult oligodendrogenesis. We show that ADAMTS4 regulates hypothalamic perineuronal net deposition, vascular permeability and glucose sensing. Finally, we show that ME ADAMTS4 expression is regulated by changes in peripheral glycaemia and is dysregulated in diabetes, providing a mechanism by which ME oligodendrocytes contribute to the regulation of glucose homeostasis. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 31 9 2026 Event-free survival and recurrence patterns after curative resection for locally advanced head and neck squamous cell carcinoma: single-institution real-world outcomes prior to the introduction of perioperative immunotherapy 1890 1900 EN Takuma Makino Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuto Naoi Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Go Hasegawa Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuto Yamasaki Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Noda Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Fujimoto Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junya Matsumoto Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Perioperative immune checkpoint inhibitors have improved outcomes for resectable locally advanced head and neck squamous cell carcinoma (HNSCC). However, real-world surgical outcome data based on contemporary endpoints remain limited.<br> Methods We retrospectively analyzed 233 patients who underwent curative-intent surgery for locally advanced HNSCC. Event-free survival (EFS) and overall survival (OS) were evaluated. Unresectable recurrence-free survival (URFS) was explored as an additional endpoint to capture post-recurrence treatment feasibility. Prognostic factors were assessed using Cox proportional hazards models.<br> Results The median follow-up duration was 18.2 months. The 1-year EFS and OS rates were 67.1% and 89.4%, respectively. pN2 or higher disease, venous invasion, and perineural invasion were identified as independent adverse prognostic factors. Recurrence occurred in 34.8% of patients; among these, disease control at the last follow-up was achieved in 61.7% following curative-intent salvage treatment. Salvage surgery was associated with significantly improved post-recurrence survival (p < 0.001).<br> Conclusions This study provides real-world surgical outcome data for resectable locally advanced HNSCC prior to the introduction of perioperative immunotherapy. Recurrence remains a major clinical challenge, with heterogeneous post-recurrence outcomes influenced by treatment feasibility. These findings may help inform interpretation of treatment outcomes and clinical decision-making in the evolving era of perioperative immunotherapy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1612-9059 2026 Incidental detection of cancers during population-based endoscopic gastric cancer screening in Japan EN Kensuke Uraguchi Department of Otolaryngology–Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kenta Hamada Department of Practical Gastrointestinal Endoscopy, Okayama University Naomi Matsumoto Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Mizuo Ando Department of Otolaryngology–Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kenji Fujimoto Occupational Health Data Science Center, University of Occupational and Environmental Health Shunsaku Hayase Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takashi Yorifuji Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background Upper gastrointestinal endoscopy traverses the full upper aerodigestive tract, unlike radiography, potentially enabling incidental detection of non-gastric malignancies. However, its population-level incidental detection rate for non-gastric upper aerodigestive tract cancers has not been systematically quantified. The aim of this study was to compare endoscopic screening with radiography and quantify detection of non-gastric upper aerodigestive tract cancers in a population-based setting.<br> Methods This population-based cohort study was conducted by linking the Okayama City municipal gastric cancer screening registry with the Kokuho Database (KDB) for fiscal years 2016–2021. Among 36,326 participants contributing 64,822 screening examinations (40,832 radiography; 23,990 endoscopy), diagnoses of oral cavity, pharyngeal, laryngeal, and esophageal cancer occurring within 2 months of screening were ascertained from the KDB. Generalized estimating equations with modified Poisson regression were used to estimate adjusted risk ratios (aRRs) comparing endoscopy with radiography.<br> Results Endoscopic screening was significantly associated with higher composite incidental detection rates for non-gastric upper aerodigestive tract cancers (95.9 vs. 34.3 per 100,000 examinations; aRR 2.94, 95% confidence interval [CI] 1.50–5.76; p = 0.002). Specifically, esophageal cancer detection was markedly higher with endoscopy (83.4 vs. 17.1 per 100,000; aRR 5.16, 95% CI 2.16–12.32; p < 0.001). No statistically significant differences were observed for oral cavity, pharyngeal, or laryngeal cancers.<br> Conclusions Endoscopic gastric cancer screening is associated with substantially higher incidental detection of non-gastric upper aerodigestive tract cancers, particularly esophageal cancer. These findings suggest an additional detection value for endoscopy that extends beyond its primary gastric cancer target in organized screening programs. 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 ƒ¿-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 ƒ¿-Tocopherol (ƒ¿T) is the major form of vitamin E. Although it is metabolized in the liver when high levels of ƒ¿T are present, the function of its metabolites has not yet been fully elucidated. This study aimed to evaluate the antioxidant activities of the ƒ¿T metabolites, ƒ¿-carboxyethyl hydroxychroman (ƒ¿CEHC) and ƒ¿-carboxymethylbutyl hydroxychroman (ƒ¿CMBHC), in comparison with their parent compound. The pretreatment with ƒ¿T 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 ƒ¿T 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 ƒ¿T and its metabolites against hydrogen peroxide were counteracted by HO-1 inhibitors. These results suggest that not only ƒ¿T 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.

Wiley Acta Medica Okayama 1873-9601 20 3 2026 Critical role of cellular communication network factor 1 in early osteogenesis of mesenchymal stem cells primed by low�]intensity pulsed ultrasound and bone morphogenetic protein 2 e70101 EN Hsu Myat Paing Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Masaharu Takigawa Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Faculty of Medicine Dentistry and Pharmaceutical Sciences Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Takashi Nishida Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences There is a known reciprocal inhibitory relationship between adipogenesis and osteogenesis in mesenchymal stem cells (MSCs). Our previous study showed that low-intensity pulsed ultrasound (LIPUS) did not promote osteogenesis of a murine MSC line C3H10T1/2, although LIPUS treatment suppressed adipogenesis. Therefore, we investigated the effect of a combination of an osteoinductive factor such as bone morphogenic protein-2 (BMP-2) and LIPUS treatment on osteogenesis. This combination significantly upregulated the gene expressions of BMP receptors and RUNX2, which is a key early osteogenic transcription factor. Interestingly, cellular communication network factor 1 (CCN1) was significantly increased at the mRNA and protein levels. Additionally, Runx2 expression was increased by a recombinant CCN1 protein and decreased in CRISPR-Cas9-generated Ccn1 knockout (KO) cells treated with the combination of LIPUS treatment and BMP-2. Moreover, Runx2 expression was recovered through the transfection of a Ccn1 expression plasmid into Ccn1 KO cells. These findings indicate that treatment with the combination of LIPUS treatment and BMP-2 promoted CCN1 production, and the CCN1 regulates the Runx2 expression in C3H10T1/2 cells, thus suggesting that CCN1 induced by mechanical stimulation and an osteoinductive factor plays a pivotal role in osteogenesis of MSCs. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1873-9601 20 2 2026 Species�]specific roles of cellular communication network proteins in cartilage development: A comparative study using in vitro chondrogenic models e70089 EN Zhangzheng Wang Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen Judit Vágó Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen Roland Takács Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen Szilárd Póliska Genomic Medicine and Bioinformatics Core Facility Department of Biochemistry and Molecular Biology Faculty of Medicine, University of Debrecen Ee Hyun Kim Department of Biomedical Materials Science Graduate School of JABA, Wonkwang University Eun�]Jung Jin Department of Biomedical Materials Science Graduate School of JABA, Wonkwang University Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University, Faculty of Medicine, Dentistry and Pharmaceutical Science Celina G Kleer Department of Pathology, University of Michigan Medical School Bernard Perbal International CCN Society Csaba Matta Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen Cellular communication network (CCN) proteins are key matricellular regulators of cartilage development, yet their species-specific roles and network-level context remain unclear. This study integrated bulk RNA sequencing from chicken and mouse embryonic limb bud micromass cultures and human mesenchymal stem cell chondrogenesis with co-expression, protein–protein interaction, and ortholog analyses to construct CCN-centered regulatory networks across models. CCN1 and CCN2 emerged as dominant, conserved hubs enriched in collagen-containing extracellular matrix, cartilage development, and growth factor signaling modules, whereas CCN3–CCN6 showed lower context-dependent expression and connectivity. Functional and ortholog analyses revealed moderate pathway conservation, with high conservation of IGF, EGFR, and HIF-1 signaling, but reduced overlap in hypoxia and mechanosensing/Hippo categories, indicating species-specific tuning of environmental sensing. A focused ortholog screen identified multifunctional conserved hubs, including COL2A1, TGFBR1, SMAD3, RUNX2, HIF1A, IGF1, SPP1, and CD44. Single-cell RNA-seq meta-analysis of human iPSC-derived chondrogenesis and embryonic limb datasets showed CCN1/2 expression and homologous network activity peaking in mesenchymal and early chondrocyte populations, consistent with model-dependent persistence into hypertrophic and ossification stages in vivo. Overall, this work defines a conserved CCN1/2-centered axis integrating extracellular matrix formation with growth factor and mechanical cues, providing a framework for model selection and CCN-targeted cartilage regeneration strategies. No potential conflict of interest relevant to this article was reported.

The Society for Free Radical Research Japan Acta Medica Okayama 0912-0009 79 2 2026 Organ-specific modulation of antioxidant functions by combined voluntary exercise and radon inhalation in mice 141 149 EN Reiju Takenaka Graduate School of Health Sciences, Okayama University Ayumi Tanaka Graduate School of Health Sciences, Okayama University Shogo Miyanaga Graduate School of Health Sciences, Okayama University Shota Naoe Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Shuna Goto Graduate School of Health Sciences, Okayama University Mitsuki Nagano Graduate School of Health Sciences, Okayama University Kotaro Tano Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Radon inhalation as well as voluntary exercise increase anti­oxidant function in experimental animals. However, the combined effects of radon inhalation and exercise on antioxidant functions have not yet been investigated. In this study, we examined the effects of combined voluntary wheel running (VWR) and radon inhalation on antioxidant functions in various organs of mice. Mice were individually housed in cages equipped with running wheels, and allowed voluntary exercise for 5, 15, or 25 days, followed by radon inhalation at 2,000 Bq/m3 for 24 ‍‍h. Antioxidant function was enhanced by the combined treatment in the kidneys, pancreas, spleen, and stomach, with responses varying according to exercise duration. In contrast, antioxidant function was reduced in the lungs and heart. No clear interaction effects of the combined treatment were observed in the liver, small intestine, colon, and brain. These findings suggest that the combined effects of voluntary exercise and radon inhalation on antioxidant functions are organ-specific and can be categorized into distinct response patterns across tissues. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1939-8425 19 1 2026 GWAS and Candidate Gene Prediction of Elemental Accumulation Traits in Rice Using a Multiparental Population 44 EN Qian Zhang Institute of Plant Science and Resources, Okayama University Tomoyuki Furuta Institute of Plant Science and Resources, Okayama University Kazunari Kashihara Institute of Plant Science and Resources, Okayama University Daisuke Ogawa Institute of Crop Science, National Agriculture and Food Research Organization Junichi Yonemaru Research Center for Agricultural Information Technology, National Agriculture and Food Research Organization Jian Feng Ma Institute of Plant Science and Resources, Okayama University Toshio Yamamoto Institute of Plant Science and Resources, Okayama University Rice plants accumulate essential elements to sustain physiological processes during growth and development and to ensure the nutritional quality of the grain as a food source. However, the genetic basis of elemental accumulation and the interrelationships among elemental concentrations across different tissues remain poorly understood. To conduct breeding aimed at improving the absorption characteristics of multiple interrelated elements, genetic analysis using experimental populations that retain diversity while sharing the genetic background of cultivated varieties is effective. Here we show genetic variations in the concentrations of 13 elements (P, K, Ca, Mg, As, Cd, Cr, Cu, Fe, Mo, Mn, Ni, and Zn) in rice straw at the flowering stage and grain at the mature stage using a multi-parent advanced generation inter-cross (MAGIC) population that derived from eight cultivars including both Japonica and Indica. Comprehensive evaluation of the correlation coefficients revealed divergences in the association between grain and straw for several combinations of elements. Haplotype-based genome-wide association studies (GWAS) identified 51 and 53 quantitative trait loci (QTLs) in straw and grain, respectively. In total, the 104 QTLs were grouped into 19 clusters and 60 independent QTLs. By leveraging the haplotype information from the MAGIC population, 52 candidate genes associated with the accumulation of Ca, Mg, Cd, Cu, Fe, and Mo were efficiently predicted from these QTLs, including both previously reported and novel genes. Among them, OsMOT1;1 encoding a molybdenum transporter, was predicted to be within a QTL associated with Mo accumulation in grain on chromosome 8. OsACA9, a homolog of autoinhibited Ca²⁺-ATPases, was predicted within a QTL related to Ca accumulation in straw on chromosome 2. In addition, an unidentified gene, OsCML6, which is presumed to be involved in calcium signaling, was predicted to be a candidate for a Ca-accumulation QTL on chromosome 11. These findings offer insights into haplotypes and putative genes associated with element accumulation and trait interrelationships, providing valuable information for optimizing plant growth and enhancing grain nutritional quality in rice breeding programs. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0143-4160 137 2026 Activation phosphorylation and dephosphorylation dynamics of Ca2+/Calmodulin-dependent protein kinase Iƒ¿ in HeLa cells 103183 EN Yerun Chen Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masao Miki Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masaki Magari Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Satomi Ohtsuka Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masumi Eto Graduate School of Veterinary Science, Okayama University of Science Atsuhiko Ishida Laboratory of Molecular Brain Science, Graduate School of Integrated Sciences for Life, Hiroshima University Futoshi Suizu Clinical Examination Department, Kagawa Prefectural University of Health Sciences Akihiro Mizutani Department of Pharmacotherapeutics, Showa Pharmaceutical University Hideaki Ando Laboratory for Developmental Neurobiology, RIKEN Center for Brain Science Katsuhiko Mikoshiba Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University Hiroshi Tokumitsu Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ca²⁺/calmodulin-dependent protein kinase I (CaMKI), a multifunctional CaM-activated protein kinase, is involved in various Ca²⁺ signaling pathways including neuronal development. Here, we characterize the phosphorylation at Thr177 (an activation Thr residue) and subsequent dephosphorylation dynamics of CaMKIƒ¿ in HeLa cells upon physiological stimulation that elevates intracellular Ca²⁺. ATP induced CaMKIƒ¿ phosphorylation within 5–10 min; phosphorylation was then blocked by CaMKK inhibitor TIM-063, or by the depletion of extracellular Ca²⁺. This was followed by gradual dephosphorylation to basal levels within 30–60 min. Histamine induced CaMKIƒ¿ phosphorylation, peaking within 3–4 min; this process was abolished by treatment with either TIM-063 or intracellular Ca²⁺ chelation using BAPTA-AM and thapsigargin; however, not by extracellular Ca²⁺ depletion. CaMKIƒ¿ was then rapidly dephosphorylated to basal levels within 10 min. Consistently, histamine-induced (but not ATP-induced) CaMKIƒ¿ phosphorylation was absent in triple IP₃ receptor-knockout HeLa cells. Dephosphorylation of CaMKIƒ¿ after ATP-induced phosphorylation was unaffected by okadaic acid or CaMK phosphatase (CaMKP, known as PPM1F) inhibitors (ANS and ANDS). We found that HeLa cell extracts contained Mg2+/Mn2+-dependent CaMKIƒ¿ dephosphorylation activity that was insensitive to ANS and ANDS. Furthermore, co-expression of PP2Cƒ¿ fully abolished ATP-, histamine-, or ionomycin-stimulated CaMKIƒ¿ phosphorylation, which is consistent with in vitro dephosphorylation of CaMKIƒ¿ at Thr177 by recombinant PP2Cƒ¿. Taken together, these results reveal that agonist-induced Ca²⁺ influx from the extracellular space or release from intracellular stores transiently activates CaMKK-CaMKIƒ¿ signaling in HeLa cells, which is shut off by dephosphorylation catalyzed by PP2Cƒ¿ as a promising candidate for CaMKIƒ¿ phosphatase. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1759-8753 17 1 2026 Report on the seventh Japanese meeting on biological function and evolution through interactions between hosts and transposable elements 6 EN Kenji Ichiyanagi Laboratory of Genome and Epigenome Dynamics, Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University Yoko Ikeda Institute of Plant Science and Resources, Okayama University Kuniaki Saito Invertebrate Genetics Laboratory, National Institute of Genetics The seventh Japanese meeting on host–transposon interactions, titled �gBiological Function and Evolution through Interactions between Hosts and Transposable Elements,�h was held on September 1st and 2nd, 2025, at the National Institute of Genetics, as well as online. This meeting was supported by the National Institute of Genetics and aimed to bring together researchers studying the diverse roles of transposable elements (TEs) in genome function and evolution, as well as host defense systems against TE mobility, TE bursts during evolution, and intron mobility in mammals, insects, land plants, fungi, and protozoa. Here, we present the highlights of these discussions. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2165-0497 14 9 2026 Combinations of long terminal repeat and tax protein substitutions influence bovine leukemia virus transmission through altered viral productivity e0086926 EN Hironobu Murakami School of Veterinary Medicine, Azabu University Reiichiro Sato Graduate School of Medicine and Veterinary Medicine, University of Miyazaki Jumpei Uchiyama Department of Infectious Diseases, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Kazuyuki Sogawa School of Life and EnvironmentaScience, Azabu University Hiroho Ishida School of Veterinary Medicine, Azabu University Makoto Nagai School of Veterinary Medicine, Azabu University Bovine leukemia virus (BLV) infection imposes a substantial economic burden on the global cattle industry. Although proviral load (PVL) in blood influences transmission, the effects of viral genetic variations, including the high viral production-associated long terminal repeat (LTR) substitution at nucleotide position 175 (LTR175), on herd-level dynamics remain unclear. This study investigated the effects of specific substitutions on the regulation of viral productivity and transmission. Longitudinal monitoring of a single farm (herd size: 50–68 cows; 438 samples collected) over a 7-year period revealed that viral strains carrying cytosine at LTR175 (LTR175C) significantly increased in frequency, becoming dominant over wild-type strains carrying thymidine. In contrast, amino acid substitutions in the Tax protein at positions 69 (Tax69) and 73 (Tax73) modified viral transactivation independent of LTR175. Structural modeling via AlphaFold2 predicted that Tax69 and Tax73 mutations alter protein properties, suggesting modulation of transactivation activity. Consistent with this prediction, in vitro assays confirmed that the substitutions modified viral production by regulating transactivation independent of LTR175. Moreover, high viral-productivity haplotypes containing LTR175C and Tax73Q (glutamine at amino acid residue 73) exhibited a transmission advantage within the herd, even when host PVL levels were not significantly elevated. These findings suggest that cellular-level viral productivity is one of the key determinants of transmission fitness. Overall, this study revealed a regulatory interaction between the LTR and Tax protein that optimizes viral spread and highlights the need for control strategies that account for viral genetic substitutions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0918-9440 139 2 2026 Knockout of a single aquaporin, OsPIP2;4, decreases root water permeability in rice 255 265 EN Aya Onishi Institute of Plant Science and Resources, Okayama University Tomoaki Horie Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University Ryo Ishitsuka Institute of Plant Science and Resources, Okayama University Shizuka Sasano Institute of Plant Science and Resources, Okayama University Rie Horie Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University Yunosuke Mito Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University Shigeko Utsugi Institute of Plant Science and Resources, Okayama University Junko Ishikawa Institute of Crop Science, NARO Majid Mahdieh Institute of Plant Science and Resources, Okayama University Maki Katsuhara Institute of Plant Science and Resources, Okayama University Aquaporins (AQPs) are membrane proteins that facilitate water transport and are present in nearly all bacterial, animal, and plant cells. In plants, AQPs are classified into four or more subfamilies, with plasma membrane intrinsic proteins (PIPs) playing a key role in root water uptake and cellular water regulation. Previous studies have demonstrated that PIPs contribute to root hydraulic conductivity (Lpr) in various plant species. In this study, we examined the specific role of OsPIP2;4, one of the PIP-type aquaporins among 11 rice (Oryza sativa) PIP2s, in regulating Lpr. Transgenic rice plants, including OsPIP2;4-knockout (KO) and overexpressing (Ox) lines, were used for this investigation. Two independent KO lines, generated via the CRISPR-Cas9 system and T-DNA insertion mutagenesis, respectively, showed significantly lower Lpr compared to wild-type rice plants. The decrease in Lpr in the T-DNA KO line was associated with reduced OsPIP2;4 transcript levels, measured by real-time PCR, and lower OsPIP2;4 protein levels, as shown by immunohistochemical analysis. Conversely, no notable increase in Lpr was observed in the Ox lines. These results suggest that OsPIP2;4 is expressed in appropriate tissues in rice roots and is a key factor influencing Lpr. This research represents a significant step toward further understanding the physiological functions of OsPIP2;4 in rice. No potential conflict of interest relevant to this article was reported.

ˆê”ÊŽÐ’c–@�l “d‹CŠw‰ï Acta Medica Okayama 0385-4221 146 9 2026 ‘½—l‚È“d—Í�Á”ïŒ`‘Ô‚ð�l—¶‚µ‚½ƒXƒ}�[ƒgƒOƒŠƒbƒh‰^—p‚Ì�Å“K‰» 864 876 EN Takaki Kawamoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yuriko Toda School of Creative Science and Engineering, Waseda University Takashi Hasuike School of Creative Science and Engineering, Waseda University �@This study examines an optimal operation model for a smart grid composed of multiple microgrids to promote renewable energy use in Japan. In Japan, about 70% of electricity is still supplied by fossil fuel power, while renewables account for only 18% despite a 36–38% target for 2030. Using demand and photovoltaic data from Setagaya Ward, we construct a system model with factory/office and residential microgrids and formulate a mathematical optimization model that considers power interchange, batteries and heat storage. Numerical experiments based on several case studies show the effectiveness of smart grid operation designed according to the proposed model in promoting renewable energy utilization and reducing total generation cost. In particular, the results show that increasing photovoltaic capacity, increasing the number of microgrids, and considering heat demand are all effective measures. However, these benefits depend on the season. Future work should extend the system model to account for seasonal variability and associated investment costs. No potential conflict of interest relevant to this article was reported.

‰ªŽR‘åŠw‘åŠw‰@‹³ˆçŠwŒ¤‹†‰È Acta Medica Okayama 1883-2423 192 2026 ƒ}ƒbƒg‰^“®‚Ì‘¤•û“|—§‰ñ“]‚ÉŠÖ‚·‚é”FŽ¯‚ÌŽÀ‘Ô �\ ‘f–pŠT”O‚ÉŠî‚­’²�¸‚Æ�lŽ@ �\ 161 169 EN Toru TAKAHASHI Faculty of Education, Okayama University Kousuke SAKAMOTO International Pacific University Ken HIRONO UCHIDA YOKO CO., LTD. 10.18926/bgeou/71152 �@–{Œ¤‹†‚Ì–Ú“I‚Í�C�¬Šw�Z‘̈ç‰È�C‚¨‚æ‚Ñ’†Šw�Z�E�‚“™Šw�Z•ÛŒ’‘̈ç‰È‚ÌŠíŠB‰^“®—̈æ‚ÅŽæ‚舵‚í‚ê‚é�u‘¤•û“|—§‰ñ“]�v‚ÉŠÖ‚·‚é”FŽ¯‚ÌŽÀ‘Ô‚ð‘f–pŠT”O‚ÉŠî‚­’²�¸‚ð’Ê‚µ‚Ä–¾‚ç‚©‚É‚·‚邱‚Æ‚Å‚ ‚Á‚½�B‘f–pŠT”O‚Æ‚ÍŠw�KŽÒ‚ª“ú�í�¶Šˆ‚É‚¨‚¢‚ÄŒoŒ±“I‚ÉŠl“¾‚µ‚½’mŽ¯�C‚à‚µ‚­‚ÍŠw�Z‚ÌŽö‹Æ“™‚ÅŠw�K‚·‚é‰ÈŠw“IŠT”O‚Æ‚Í•K‚¸‚µ‚àˆê’v‚µ‚È‚¢’mŽ¯‚ðŽw‚µŽ¦‚·—pŒê‚Å‚ ‚é�B–{Œ¤‹†‚É‚Ä‘¤•û“|—§‰ñ“]‚Æ‚¢‚¤‹Z‚ðŽæ‚è�ã‚°‚½—�—R‚Æ‚Í�C‰^“®‚ÌŒ`‘Ô�ã4ƒpƒ^�[ƒ“‚ÌŽÀŽ{•û–@‚ª‘¶�Ý‚µ‚Ä‚¢‚é‚É‚àŠÖ‚í‚炸�C�‡—�“I�C‚©‚Â�s‚¢ˆÕ‚¢ŽÀŽ{•û–@‚Í‚»‚Ì‚¤‚¿‚Ì2ƒpƒ^�[ƒ“‚ÉŒÀ’肳‚ê‚é‚Æ‚¢‚¤“ÁŽê�«‚É‚ ‚é�B–{Œ¤‹†‚Å‚Í‘¤•û“|—§‰ñ“]‚ɑ΂·‚é‘f–pŠT”O‚𖾂炩‚É‚·‚邽‚ß‚É�C‚»‚Ì”FŽ¯‚ð–₤‚½‚߂̃Aƒ“ƒP�[ƒg’²�¸‚ðŽÀŽ{‚µ‚½�B’²�¸ŠúŠÔ‚Í2023”N6ŒŽ7ŒŽ�C’²�¸‘Î�Û‚ÍA‘åŠw�¬Šw�Z‹³ˆõ—{�¬‰Û’ö‚É�Ý�Ђ·‚éŠw�¶140–¼‚Å‚ ‚Á‚½�B’²�¸‚ÌŒ‹‰Ê140–¼’†35–¼�CŠ„�‡‚É‚·‚é‚Æ32.1�“‚ªŒë‚Á‚½’mŽ¯‚ð‘f–pŠT”O‚Æ‚µ‚Ä•Û—L‚µ‚Ä‚¢‚½‚Æ‚¢‚¤‚±‚Æ‚ª–¾‚ç‚©‚Æ‚È‚Á‚½�B No potential conflict of interest relevant to this article was reported.

‰ªŽR‘åŠw‘åŠw‰@‹³ˆçŠwŒ¤‹†‰È Acta Medica Okayama 1883-2423 192 2026 ƒ_ƒ“ƒX‚ð’Ê‚¶‚½‹¤�¶ŽÐ‰ï‚ÌŽÀŒ»‚ÉŒü‚¯‚½’nˆæ‹¦“­ƒvƒ�ƒWƒFƒNƒg �\ ‰ªŽR‚¤‚炶‚á�Õ‚è‚É‚¨‚¯‚éƒCƒ“ƒNƒ‹�[ƒVƒuƒ_ƒ“ƒXŽÀ‘H �\ 147 159 EN Risako YOSHIMURA The Joint Graduate School in Science of School Education, Hyogo University of Teacher Education Aito ODA Resorttrust, Inc. Wing In CHIU The Joint Graduate School in Science of School Education, Hyogo University of Teacher Education Sayaka TANIGAWA The Joint Graduate School in Science of School Education, Hyogo University of Teacher Education Haruko SAKO Faculty of Education, Okayama University 10.18926/bgeou/71151 �@�Ⴊ‚¢ŽÒ‚Ì•¶‰»Œ|�pŠˆ“®‚Å‚Í�C�Ⴊ‚¢ŽÒ‚ª‘n‘¢‚â”­�M‚ÉŽå‘Ì“I‚ÉŠÖ‚í‚邱‚Æ‚ª�dŽ‹‚³‚ê‚Ä‚¢‚é�B‚µ‚©‚µ�C‚»‚̈êŒ`‘Ô‚Å‚ ‚éƒCƒ“ƒNƒ‹�[ƒVƒuƒ_ƒ“ƒX‚ð’nˆæŽÐ‰ï‚ÉŠJ‚©‚ꂽ•¶‰»Šˆ“®‚Ö‚Æ“WŠJ‚·‚鎖—á‚Ì•ª�Í‚Í�\•ª‚Å‚Í‚È‚¢�B‚»‚±‚Å–{�e‚Å‚Í�C‰ªŽRŒ§‚Ì�u‚¤‚炶‚á�v�Õ‚è‚É‚¨‚¢‚Ä”­‘«‚µ‚½ƒCƒ“ƒNƒ‹�[ƒVƒu—x‚è˜A�uˆêŠúˆê‰ï�`—Ö•‘‰·—…�v‚ð‘Î�Û‚É�CƒCƒ“ƒNƒ‹�[ƒVƒu‚¤‚炶‚áƒ_ƒ“ƒX‚ÌŠJ”­‚¨‚æ‚ÑŽÀ‘H‰ß’ö‚ð�®—�‚µ‚½�BŠˆ“®‹L˜^�C‰f‘œ‹L˜^�CŠˆ“®Ž‘—¿‚ð‚à‚Æ‚É•ª�Í‚µ‚½Œ‹‰Ê�C•\Œ»“à—e‚âŽÀŽ{•û–@�C‰‰•‘ŠÂ‹«‚ª�CŽQ‰ÁŽÒ‚Ì�S�g‚Ì“Á�«‚𓥂܂¦‚Ä’iŠK“I‚É’²�®‚³‚ê‚Ä‚¢‚½‚±‚Æ‚ª–¾‚ç‚©‚Æ‚È‚Á‚½�B‚Ü‚½�CŽQ‰ÁŽÒ‚ÌŽåŠÏ“I‰^“®‹­“x‚ÍŽå‚É�uŠy�v‚©‚ç�u‚â‚â‚«‚‚¢�v‚͈̔͂ɕª•z‚µ�CŠˆ“®–ž‘«“x‚à�‚‚¢ŒXŒü‚ðŽ¦‚µ‚½�BˆÈ�ã‚æ‚è�C–{ƒvƒ�ƒWƒFƒNƒg‚Í�C’nˆæ•¶‰»‚ðŠî”Õ‚Æ‚µ‚½ƒCƒ“ƒNƒ‹�[ƒVƒu‚È�g‘Ì•\Œ»Šˆ“®‚ÉŠÖ‚·‚éŠî‘b“I’mŒ©‚ð’ñ‹Ÿ‚·‚é‚à‚Ì‚Å‚ ‚é‚Æ�l‚¦‚ç‚ê‚é�B No potential conflict of interest relevant to this article was reported.

‰ªŽR‘åŠw‘åŠw‰@‹³ˆçŠwŒ¤‹†‰È Acta Medica Okayama 1883-2423 192 2026 �u‘n‘¢�«‚ªŽÐ‰ï‚Æ�o‰ï‚¤”ü�p‹³ˆç�v‚É‚æ‚鋳ˆõ‚ÌŠw‚Ñ‚ÉŠÖ‚·‚éŠî‘bŒ¤‹†‡V �\ ’†Šw�Z”ü�p‰È‹³ˆõ‚ÌŽö‹Æ‹L˜^‚Æ’Ç�ÕƒCƒ“ƒ^ƒrƒ…�[‚ÉŠî‚­Ž–—ጤ‹†�\ 125 135 EN Ai MATSUURA Faculty of Education, Okayama University Yusuke SENOO Okayama Prefectural Tamashima High School Hitoshi KIMURA Shiga University Faculty of Education Elementary School Soichiro TAKEDA Okayama University Junior High School Chande SON Osaka Kyoiku University Tennoji Junior High School Tetsuo KIYOTA Faculty of Education, Okayama University 10.18926/bgeou/71149 �@–{˜_‚Í�CŠw�ZŠO‚Ì‘¼ŽÒ‚Ƃ̑ΘbŒoŒ±‚ª�C’†Šw�Z”ü�p‰È‹³ˆõ‚ÌŽö‹ÆŽÀ‘H‚É‚¨‚¢‚Ăǂ̂悤‚ɈӖ¡‚¯‚ç‚ê‚Ä‚¢‚½‚Ì‚©‚𖾂炩‚É‚·‚邱‚Æ‚ð–Ú“I‚Æ‚·‚é�BŽsˆäƒvƒ�ƒWƒFƒNƒg‚ÉŽQ‰Á‚µ‚½‹³—@B‚ð‘Î�Û‚É�CŽsˆäƒCƒ“ƒ^ƒrƒ…�[Œã‚ÉŽÀŽ{‚³‚ꂽ•\Œ»Šˆ“®‚ÌŽö‹Æ‹L˜^‚Æ�CŽö‹ÆŽÀ‘HŒã‚Ì’Ç�ÕƒCƒ“ƒ^ƒrƒ…�[‚ð�Æ�‡‚µ‚½�B‚»‚ÌŒ‹‰Ê�C‹³—@B‚Í�CŠw�ZŠO‚Ì‘¼ŽÒ‚Ƃ̑ΘbŒoŒ±‚ð�CŽö‹Æ•û–@‚Ì’¼�Ú“I‚È•Ï�X‚Æ‚µ‚Ä‚Å‚Í‚È‚­�CŽö‹Æ’†‚Ì”»’f�C�¶“k—�‰ð�C‘è�Þ�E•\Œ»—�‰ð�C�¶ŠˆŽÀ‘H‚Æ‚ÌŠÖŒW‚É‚¨‚¢‚ĈӖ¡‚¯‚Ä‚¢‚½‚±‚Æ‚ªŠm”F‚³‚ꂽ�B“Á‚É�C�¶“k‚Ì�s“®‚â•\Œ»‚ð“��§‚·‚錩•û‚©‚ç�C‚»‚Ì”wŒi‚â�¶�¬‰ß’ö‚ðŒ©Žæ‚錩•û‚ւ̈Ú�s‚ª‚ ‚Á‚½‰Â”\�«‚ª�‚‚¢�BˆÈ�ã‚Ì‚±‚Æ‚©‚ç�C–{˜_‚É‚æ‚苳Žt‚ÌŠw‚Ñ‚ðŠw�Z“à‚ÌŒ¤�C‚⓯—»�«‚ÉŒÀ’肹‚¸Šw�ZŠO‚Ì�¶Šˆ�¢ŠE‚Æ‚ÌŠÖŒW‚©‚瑨‚¦‚éˆÓ‹`‚ªŽ¦�´‚³‚ꂽ�B No potential conflict of interest relevant to this article was reported.

‰ªŽR‘åŠw‘åŠw‰@‹³ˆçŠwŒ¤‹†‰È Acta Medica Okayama 1883-2423 192 2026 ’†�‘’n•û�Lˆæ’†�S“sŽs‚É‚¨‚¯‚é�lŒûˆÚ“®‚Ì“®Œü �\‰ªŽRŒ§‰ªŽRŽs‚ÌŽ–—á�\ 109 124 EN Masao NOBE Faculty of Education, Okayama University 10.18926/bgeou/71148 �@–{�e‚Ì–Ú“I‚Í�C2006”N‚©‚ç2025”N‚܂ł̉ªŽRŽs‚É‚¨‚¯‚é�lŒûˆÚ“®‚ð•ª�Í‚µ�C‚»‚Ì“®Œü‚𖾂炩‚É‚·‚邱‚Æ‚Å‚ ‚é�B21�¢‹I‚É“ü‚Á‚ĈÈ�~�C‰ªŽRŽs‚Å‚Í’†�SŽsŠX’n‚Ì�ÄŠJ”­‚╪�÷ƒ}ƒ“ƒVƒ‡ƒ“‹Ÿ‹‹‚ÌŠg‘å‚É‚æ‚è�C“s�S‰ñ‹A‚ª�i“W‚µ‚Ä‚«‚½�B‚Ü‚½�CƒŠ�[ƒ}ƒ“ƒVƒ‡ƒbƒN‚â“Œ“ú–{‘å�k�Ð�C�VŒ^ƒRƒ�ƒiƒEƒCƒ‹ƒXŠ´�õ�Ç‚ÌŠg‘å‚Æ‚¢‚Á‚½�o—ˆŽ–‚à�C�lŒûˆÚ“®‚Ɉê’è‚̉e‹¿‚ð‹y‚Ú‚µ‚½‚Æ�l‚¦‚ç‚ê‚é�B‚µ‚©‚µ�C‚±‚¤‚µ‚½ŠO•”—vˆö‚É‚à‚©‚©‚í‚炸�C�lŒûˆÚ“®‚ÌŠî–{“I‚È�–�¨‚É‘å‚«‚ȕω»‚Í‚Ý‚ç‚ê‚È‚©‚Á‚½�B‚·‚È‚í‚¿�C‰ªŽRŽs‚ÍŒ§“à‚Ì‘å•”•ª‚ÌŒ—ˆæ‚¨‚æ‚ÑŒ§ŠO‚ÌŽü•Ó’nˆæ‚©‚ç�lŒû‚ð‹zŽû‚·‚éˆê•û‚Å�CŽO‘å“sŽsŒ—‚ðŠÜ‚ÞŠÖ“Œ�E‹ß‹E�E’†•”’n•û‚Ö�lŒû‚ð‘—‚è�o‚µ‚Ä‚¢‚é�B No potential conflict of interest relevant to this article was reported.

‰ªŽR‘åŠw‘åŠw‰@‹³ˆçŠwŒ¤‹†‰È Acta Medica Okayama 1883-2423 192 2026 –@‚ÉŠî‚­�‰“™ŽÐ‰ï‰È“à—e�\�¬‚ÉŠÖ‚·‚錤‹† �\•Ä�‘–@‹³ˆç‹³�Þ�w–¯ŽåŽå‹`‚ÌŠî‘b(FOUNDATIONS of DEMOCRACY)�x‚ðŽèŠ|‚©‚è‚É‚µ‚Ä�\ 79 90 EN Toshinori KUWABARA Faculty of Education, Okayama University Shinnosuke FUKUNAGA Okayama University Graduate School of Education Master's Course 10.18926/bgeou/71146 �@–{Œ¤‹†‚Í�C–@‚ÉŠî‚¢‚Ä�\�¬‚³‚ê‚é�‰“™‹³ˆç’iŠK‚̎Љï‰È‚Ì“à—e�\�¬Œ´—�‚𖾂炩‚É‚·‚邽‚ß�C•Ä�‘‚Ì�‰“™–@‹³ˆç‹³�Þ�w–¯ŽåŽå‹`‚ÌŠî‘b�iFOUNDATIONS of DEMOCRACY�j�x‚ð•ª�Í‚µ‚½‚à‚Ì‚Å‚ ‚é�B“ú–{‚É‚¨‚¯‚é–@‹³ˆçŒ¤‹†‚Í�C1990”N‘ãŒã”¼‚©‚ç�C•Ä�‘‚Ì–@‹³ˆçŒ¤‹†‚ð�Љ‚éŒ`‚ÅŽn‚Ü‚è�C‚»‚ÌŒã�C�”‘½‚­‚Ì•Ä�‘‚Ì–@ŠÖ˜A‹³ˆç‹³�Þ‚ª“ú–{‚É�Љ‚ê�C‚»‚Ì•ª�Í‚ÉŠî‚­Œ¤‹†�¬‰Ê‚ª’~�Ï‚³‚ê‚Ä‚«‚½�B‚µ‚©‚µ�C‚»‚ê‚ç‚ÌŒ¤‹†‚Ì‘½‚­‚Í�C’†“™‹³ˆç’iŠK‚Ì‚à‚Ì‚Å‚ ‚è�C�‰“™‹³ˆç‚ð‘Î�Û‚Æ‚·‚é–@‹³ˆç‚ÌŒ¤‹†‚Í‘½‚­‚Í‚È‚¢�B–{Œ¤‹†‚Í�C�‰“™ŽÐ‰ï‰È‚Æ‚µ‚Ä‚Ì–@‹³ˆç‚É�Å“_‚ð“–‚Ä�C‚»‚Ì“à—e�\�¬‚𖾂炩‚É‚µ‚悤‚Æ‚·‚é“_‚É“ÆŽ©�«‚ª‚ ‚é�B–{Œ¤‹†‚ÅŽæ‚è�ã‚°‚é�w–¯ŽåŽå‹`‚ÌŠî‘b�x‚Í�C“ú–{‚Å‚à’�–Ú‚³‚ê�C•¡�”‚ÌŒ¤‹†ŽÒ‚É‚æ‚Á‚Ä•ª�Í‚³‚ê‚Ä‚¢‚é�B–{Œ¤‹†‚Å‚Í�C‚»‚ê‚ç‚Ì�æ�sŒ¤‹†‚ð‚Ó‚Ü‚¦‚‚Â�C‚±‚ê‚Ü‚Å‚ÌŒ¤‹†‚Å‚Í�\•ª‰ð–¾‚³‚ê‚Ä‚¢‚È‚©‚Á‚½“à—e�\�¬Œ´—�‚̉𖾂ð–ÚŽw‚·�B No potential conflict of interest relevant to this article was reported.

‰ªŽR‘åŠw‘åŠw‰@‹³ˆçŠwŒ¤‹†‰È Acta Medica Okayama 1883-2423 192 2026 ’®Šo�áŠQŠw�¶Žx‰‡‚Ì‚½‚ß‚Ì�‰ŠwŽÒŒü‚¯‘åŠwƒm�[ƒgƒeƒCƒJ�[‹¤“¯—{�¬Œ¤�C‚ÌŒø‰Ê�E‰Û‘è�E‚ ‚è•û �\‘½—l‚È�l“IƒŠƒ\�[ƒX‚ðŠˆ—p‚µ‚½—{�¬Œ¤�Cƒ‚ƒfƒ‹‚ÌŒŸ“¢�\ 37 51 EN Takeshi SHIMONAKAMURA Faculty of Education, Okayama University Hiroko INOUE Child Consultation Center, Kumamoto city Yuka TAKAGI Student Accessibility Support Room, Kumamoto University Hirofumi SOEJIMA Student Accessibility Support Room, Kumamoto University Noboru FUJISE Kumamoto Prefecture Mental Health Welfare Center 10.18926/bgeou/71143 �@–{Œ¤‹†‚Í�C‘½—l‚È�l“IƒŠƒ\�[ƒX‚ðŠˆ—p‚µ‚½’®Šo�áŠQŠw�¶Žx‰‡‚Ì‚½‚ß‚Ì�‰ŠwŽÒŒü‚¯ƒm�[ƒgƒeƒCƒJ�[‹¤“¯—{�¬Œ¤�C‚ÌŒø‰Ê‚Ɖۑè‚𖾂炩‚É‚µ�C�¡Œã‚Ì‹¤“¯—{�¬Œ¤�C‚Ì‚ ‚è•û‚ɂ‚¢‚ÄŒŸ“¢‚·‚邱‚Æ‚ð–Ú“I‚Æ‚µ‚½�B‹¤“¯—{�¬Œ¤�C‚ÌŒø‰Ê‚Æ‚µ‚Ä�C�y‘¼‘åŠw‚Ƃ̌𗬂̗LŒø�«�z�C�yŒ¤�C�‡�˜‚Ì—LŒø�«�z�C�yŒ¤�C“à—e‚Ì�[ŽÀ�z‚È‚Ç‚ªŒ©‚ç‚ê�C�¡Œã‚ÌŒ¤�C‚Ì�¶‚©‚µ•û‚Æ‚µ‚Ä�C�yŒ¤èr‚⊈“®Šg‘å�z�C�yŽx‰‡�EŒ¤�C‚Ì�[ŽÀ�z‚È‚Ç‚ª‹“‚°‚ç‚ê‚Ä‚¨‚è�CŒ¤�C‚Ì—LŒø�«‚ª–¾‚ç‚©‚É‚È‚Á‚½�Bˆê•û‚Å�C‹¤“¯—{�¬Œ¤�C‚̉ۑè‚Æ‚µ‚Ä�CŒð—¬ƒvƒ�ƒOƒ‰ƒ€‚Ì–ž‘«“x‚ª‘Š‘ΓI‚É�Å‚à’á‚­�C�yŽžŠÔ•s‘«�z‚ª”wŒi‚É‚ ‚é‚Æ�l‚¦‚ç‚ꂽ�B‚±‚ê‚ç‚Ì‚±‚Ƃ𓥂܂¦‚Ä�C‹¤“¯—{�¬Œ¤�C‚Ì‚ ‚è•û‚Æ‚µ‚Ä�CŠw�¶�E‹³�Eˆõ‚ªŒð—¬‚·‚é�\•ª‚ÈŽžŠÔ‚ÌŠm•Û‚â�CŠe�u‹`ŽžŠÔ‚Ì‘�‰Á‚Ì‚½‚ß‚É�C“®‰æ‚ðŽ‹’®‚·‚éƒIƒ“ƒfƒ}ƒ“ƒhŒ`Ž®‚ðŠî–{‚Æ‚µ‚Ä�CŒð—¬‚≉�K‚È‚Ç‚ð‘ΖÊ�C‚Ü‚½‚̓ŠƒAƒ‹ƒ^ƒCƒ€ƒIƒ“ƒ‰ƒCƒ“‚ÅŽÀŽ{‚·‚é‚È‚Ç‚ÌŒ¤�C•û–@‚ª�l‚¦‚ç‚ê‚é�B No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-5174 11 2026 Interbacterial antagonism mediates plant growth modulation by rhizosphere synthetic communities in barley 100639 EN Md Asif Mahamud Institute of Plant Science and Resources, Okayama University Rungnapa Pichaikarn School of Science, Walailak University Muhammad Ammar Latif Institute of Plant Science and Resources, Okayama University Takakazu Matsuura Institute of Plant Science and Resources, Okayama University Izumi C Mori Institute of Plant Science and Resources, Okayama University Daisuke Saisho Institute of Plant Science and Resources, Okayama University Pakpimol Ungcharoenwiwat School of Science, Walailak University Akio Tani Institute of Plant Science and Resources, Okayama University Microbial communities in plant roots are shaped by complex interbacterial interactions, yet how these interactions translate into plant fitness remains poorly understood. In this study, 127 bacterial isolates were obtained from barley (Hordeum vulgare L.) roots of two cultivars grown in a non-fertilized field, representing 45 genera and 72 species. Screening identified isolates with growth-promoting, growth-reducing, and neutral phenotypes. Co-inoculation experiments using synthetic communities (SynComs) demonstrated that growth-promoting isolates effectively cancelled the inhibitory effects of growth-reducing isolates on barley seedling growth. Mechanistic investigation revealed that growth-promoting isolates Variovorax sp. 14F-2.1 and Pseudomonas sp. 37A kill growth-reducing isolates Flavobacterium sp. 2D-1 through direct cell-to-cell contact. Deletion of the Type VI secretion system (T6SS) gene tssA in Variovorax sp. 14F-2.1 substantially reduced this activity, implicating T6SS as a key antagonistic mechanism. Phytohormone profiling revealed that growth-promoting and neutral isolates, but not growth-reducing isolates, produce cytokinins, and only Variovorax sp. 14F-2.1 could degrade IAA, suggesting a potential hormonal basis for differential growth effects. A two-year field microbiome study showed that fertilization regimen and seasonal sampling times were dominant drivers of rhizosphere community composition, while bacterial inoculation had limited and inconsistent effects on microbial diversity and plant growth under field conditions. These results demonstrate that interbacterial antagonism is a key determinant of community-level plant growth outcomes and highlight the complexity of translating laboratory inoculant effects to field settings. 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.<br> 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 ƒÀ-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.<br> 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�fs 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�fs 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.

American Chemical Society (ACS) Acta Medica Okayama 2643-6728 7 4 2026 Graphene Oxide: Designing a Functional Smarter Material for Advanced Biomedicine 399 409 EN Cécilia Ménard-Moyon CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Alberto Bianco Research Institute for Interdisciplinary Science, Okayama University Graphene oxide (GO) has emerged as one of the most extensively studied two-dimensional (2D) materials, thanks to its large surface area and abundance of functional groups, which enable applications across energy, catalysis, electronics, construction, and mobility. Its exceptional dispersibility in water further expands its use in the biomedical field. However, researchers have consistently expressed concerns about the limited control over GO chemical composition and structural heterogeneity. These factors are often overlooked, strongly affecting the reproducibility in both synthesis and applications. Because GO is considered a promising platform for advanced drug delivery, achieving reproducible preparation and precise structural control is essential to make it a reliable alternative to the many nanomaterials currently being explored for nanomedicine.<br> Motivated by these challenges, we have focused our work on identifying and controlling the key parameters that govern GO structure and surface chemistry. Over the past decade, we have developed methods to produce GO with controlled and tunable chemical structures, clarified the reactivity of its major functional groups, and developed robust strategies for postfunctionalizing GO with therapeutic agents, targeting ligands, and imaging dyes. In parallel, we have established systematic approaches to evaluate GO biocompatibility and biodegradability, revealing how specific physicochemical features influence biological responses and clearance pathways.<br> Together, these findings provide a unified framework linking GO synthesis, chemical modification, and biological behavior. By integrating chemical control, functional performance, and safety assessment, our work outlines a coherent strategy for the rational design of GO-based biomedical materials. We believe that this Account offers a solid foundation for the targeted exploitation of GO in nanomedicine and will help facilitate its eventual clinical translation. 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 Microstructural changes in irradiated teeth revealed by swept-source optical coherence tomography 22258 EN Kumiko Matsuzaki Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital Hidenobu Matsuzaki Department of Oral Diagnosis and Dentomaxillofacial Radiology, Okayama University Hospital Tomoko Tabata Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Hideki Aoyama Central Division of Radiology, Okayama University Hospital Kotaro Yoshio Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirotaka Kosaki Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital Naoko Ohara Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Alireza Sadr Biomimetics Biomaterials Biophotonics Biomechanics & Technology Laboratory, Department of Restorative Dentistry, Magnuson Health Sciences Center, University of Washington Yoshihiko Soga Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital Yasushi Shimada Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Radiation-induced caries is a late complication of radiotherapy for head and neck cancers. Although direct irradiation-induced changes in tooth structure may contribute to its development, these changes have not been fully characterized. This study evaluated irradiation-associated microstructural alterations and tissue density changes in human teeth using swept-source optical coherence tomography (SS-OCT). Eight extracted fully impacted human third molars were assigned to irradiated and non-irradiated groups (n = 4 each). The irradiated group received X-rays at a total dose of 70 Gy, a clinically relevant dose in definitive radiotherapy for head and neck cancer. A total of 64 SS-OCT cross-sectional images were obtained and analyzed, with 32 images from each group, including 16 from the coronal area on the occlusal side and 16 from the cervical area. Microcrack-like features were observed in 100% (16/16) of irradiated and 31.3% (5/16) of non-irradiated images in the coronal area on the occlusal side, and in 43.8% (7/16) and 0% (0/16) of images in the cervical area, respectively. Attenuation coefficients were significantly higher in irradiated enamel and dentin. These findings suggest that irradiation-induced microstructural changes in extracted human teeth in vitro may contribute to increased susceptibility to radiation-induced caries. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0360-3199 270 2026 The effect of end-gas auto-ignition flame properties on the knocking intensity of a dual-fuel hydrogen engine 157103 EN Riku Okamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuyuki Kawahara Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yoshimitsu Kobashi Faculty of Environmental, Life, Natural Science and Technology, Okayama University This study sought to elucidate the mechanism governing PRE-mixed mixture ignition in end-gas region (PREMIER) combustion in a dual-fuel hydrogen engine. Both knocking and PREMIER combustion are induced by end-gas auto-ignition, but differ in terms of the subsequent development of pressure waves. Knocking is accompanied by strong waves, whereas PREMIER combustion is characterized by the absence of, or very few, such waves. End-gas auto-ignition of hydrogen–air mixtures was visualized while in-cylinder pressure was measured using an optical compression and expansion machine. The visualization data indicate that KI increased as the spread velocity of the end-gas auto-ignition front rose. That velocity remained below 100 m/s during PREMIER combustion, but attained approximately 400 m/s in severe knocking cycles. The theory proposed by Bradley was used to evaluate the experimental results, and two dimensionless parameters, ƒÌ and ƒÃ, were estimated. The ƒÌ-ƒÃ diagram showed a distinct transition from PREMIER combustion to knocking. (150 words). No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0360-3199 270 2026 Synergistic effects of gas-to-liquid pilot ignition and high rates of nitrogen-based simulated EGR on PREMIER combustion in dual-fuel hydrogen engines 157237 EN Nirendra Nath Mustafi Graduate School of Natural Science and Technology, Okayama University Nobuyuki Kawahara Graduate School of Natural Science and Technology, Okayama University Yoshimitsu Kobashi Graduate School of Natural Science and Technology, Okayama University Hydrogen-fueled compression-ignition engines offer a pathway to decarbonize heavy-duty propulsion but face a trade-off between thermal efficiency, NOx emissions, and narrow knock-free windows. Although EGR dilution and pilot-fuel reactivity control have each been studied independently, their combined effect on hydrogen PREMIER (PREmixed Mixture Ignition in the End-gas Region) combustion has not been systematically characterized. This study addresses that gap by comparing diesel and high-cetane Gas-to-Liquid (GTL) pilot fuels in a supercharged hydrogen dual-fuel engine, while varying nitrogen addition to isolate the inert dilution effect of simulated EGR (0–50%). GTL's superior ignitability shortened ignition delay and enhanced combustion stability versus diesel. Increasing inert EGR (nitrogen) dilution suppressed NOx by over 90% (360 to 30 ppm) via reduced peak temperatures, while sustaining knock-free PREMIER combustion and achieving a peak indicated thermal efficiency of 43.55% at ∼0.80 MPa IMEP. Coupling pilot-fuel reactivity control with EGR dilution enables safe, clean, high-efficiency hydrogen dual-fuel. 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 Efficacy of bepotastine compared with hydroxyzine in preventing rituximab-induced infusion-related reactions in non-hodgkin lymphoma patients: a phase II, double-blind, multicenter, and randomized trial 979 988 EN Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Hironobu Minami Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kimikazu Yakushijin Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Keiji Kurata Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Rina Sakai Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Miki Saeki Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Yuri Okazoe-Hirakawa Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Kotaro Iida Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Natsuko Murase Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Isamu Harima Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Naoko Kitamura Department of Pharmacy, Kobe University Hospital Kotaro Itohara Department of Pharmacy, Kobe University Hospital Tomohiro Omura Department of Pharmacy, Kobe University Hospital Takeshi Sugimoto Department of Hematology and Oncology, Kita-Harima Medical Center Hidetomo Takakura Department of Hematology and Oncology, Kita-Harima Medical Center Akihito Kitao Department of Hematology and Oncology, Kita-Harima Medical Center Masako Takahashi Department of Pharmacy, Kita-Harima Medical Center Manabu Shimoyama Department of Hematology and Oncology, Kohnan Medical Center Mamoru Okuno Department of Pharmacy, Kohnan Medical Center Ikuko Yano Department of Pharmacy, Kobe University Hospital Background This study evaluated the efficacy of hydroxyzine and bepotastine, first- and second-generation H1 receptor antagonists (H1RA), as pretreatments to prevent infusion-related reactions (IRRs) during the initial rituximab infusion in patients with non-Hodgkin lymphoma.<br> Methods In this double-blind, multicenter, randomized phase II study, 40 patients received hydroxyzine or bepotastine with acetaminophen 30 min before rituximab infusion. Primary endpoint was incidence of ≥ grade 2 IRRs based on the National Cancer Institute Common Terminology Criteria for Adverse Events. Secondary endpoints included IRRs severity, time to IRR onset, and H1RA-induced drowsiness.<br> Results Incidence of ≥ grade 2 IRRs was 52.4% and 31.6% for the hydroxyzine (n = 21) and bepotastine (n = 19) groups, respectively (P = 0.184). Distribution of initial and maximum IRR grades in the two groups was not statistically significant (P = 0.846 and 0.555). Median time (range) to IRR onset in the two groups was 67 (12–112) and 62 (10–119) min, respectively (P = 0.981). Median visual analog scale score (range and 75th percentile) for drowsiness was 37 (0–100, 46) and 12 (0–100, 29) mm in the two groups, respectively (P = 0.138). Incidence of ≥ grade 2 IRRs in the absence of bone marrow infiltration was 43.8% and 14.3% in the two groups, respectively (P = 0.118), and no group differences were observed with bone marrow infiltration.<br> Conclusions Bepotastine did not show significant superiority over hydroxyzine in preventing rituximab-induced IRRs due to the small sample size. Nevertheless, this exploratory study provides insight for further confirmatory studies.<br> Trial registration number and date of registration jRCTs051220169; February 14, 2023. 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�fs 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.<br> 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).<br> 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.<br> 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.<br> Trial registration Registered in the PROSPERO database (CRD42025642273). 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 Duration-stratified effects of exercise therapy on health-related quality of life in hemodialysis patients: a systematic review and meta-analysis 13 EN Yu Honda Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine Daisuke Uchida Department of Internal Medicine, Teikyo University Hospital Mizonokuchi 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 Department of Nephrology, Tokyo Women�fs 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: Patients on maintenance hemodialysis (HD) have reduced health-related quality of life (HRQoL). Structured exercise therapy is recommended, but domain-specific effects and the influence of intervention duration remain uncertain. This study evaluated the impact of structured exercise therapy on multiple HRQoL domains, including fatigue and depression, stratified by intervention duration.<br> Methods: We conducted a systematic review and meta-analysis, searching MEDLINE (PubMed) through November 2024. The protocol was registered in PROSPERO (CRD42025642273). We included trials comparing structured exercise with non-exercise controls in adult HD patients. Primary outcomes were Short Form (SF)-36 Physical and Mental Component Summaries (PCS, MCS), fatigue, pain, general health, and depression (Beck Depression Inventory). Data were synthesized using random-effects models, stratified by intervention duration (≤ 3 versus > 3 months). Risk of bias was assessed using the Cochrane RoB 2 tool.<br> Results: We identified 94 randomized controlled trials (5228 participants); 22 reported HRQoL outcomes and were meta-analyzed. Exercise significantly improved fatigue (mean difference [MD] + 7.27, 95% confidence interval [CI] 4.75–9.80) and reduced depressive symptoms in > 3-month trials (MD �|7.62, 95% CI �|8.34 to �|6.90); no ≤ 3-month depression data were available. In overall analyses, general health (MD + 11.59, 95% CI 6.98–16.21) and PCS (MD + 5.83, 95% CI 0.71–10.94) improved, whereas MCS (MD + 7.60, 95% CI �|3.75 to 18.94) and pain (MD + 2.19, 95% CI �|4.41 to 8.79) showed no clear benefit. Short-term interventions (≤ 3 months) yielded significant improvements in pain and general health. In longer-term interventions (> 3 months), general health estimates were similar in magnitude but statistically nonsignificant, and pain effects were also nonsignificant with substantial heterogeneity. Fatigue improved in both duration strata.<br> Conclusions: Structured exercise therapy appears to improve fatigue in patients on maintenance HD and may provide additional gains in PCS and general health with interventions longer than 3 months. Improvements in depressive symptoms were observed from limited evidence, and duration-specific effects remain uncertain because no trials assessed depression at ≤ 3 months. Effects on pain and MCS remain uncertain owing to substantial heterogeneity. Larger long-term trials are needed to clarify the sustainability of HRQoL benefits beyond 3 months. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1386-1425 359 2026 Discrimination of nanovesicles using two-color laser-induced fluorescence detection 127928 EN Shunsuke Asahi Department of Chemistry, Okayama University Takashi Kaneta Department of Chemistry, Okayama University A two-color fluorescence-detection system was developed to distinguish between two types of nanovesicles labeled with different fluorescent dyes. This system employs two lasers emitting at distinct wavelengths (488 and 635 nm). These lasers are reshaped into sheet-like beams and focused at separate positions within a square capillary. As vesicles flow through the capillary, they pass through the laser beams and emit fluorescence when excited by the corresponding wavelength. This technique allows for the counting of vesicles and identification of the specific fluorophores on the vesicles based on their emission positions. The system was validated using liposomes labeled with fluorophores excited by the 488 and 635 nm lasers. It was then applied to differentiate CD63-positive extracellular vesicles (EVs) from other types of EVs in a culture media consisting of HeLa and A549 cells. Additionally, the system was used to study the effect of the anticancer drug doxorubicin on EV secretion in these cancer cells. 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.

Wiley Acta Medica Okayama 1356-9597 31 5 2026 Transforming Life Science Through Chromosome�]Level Genome Assemblies e70145 EN Tetsuo Kon Department of Neurosciences and Developmental Biology, University of Vienna Kosuke Kataoka Graduate School of Engineering, Tokyo University of Agriculture and Technology Yi�]Jyun Luo Biodiversity Research Center, Academia Sinica Johannes Nicolaus Wibisana Genomics and Regulatory Systems Unit, Okinawa Institute of Science and Technology Graduate University Kouhei Toga Laboratory of BioDX, PtBio Co�]Creation Research Center, Genome Editing Innovation Center, Hiroshima University Narumi Uno Laboratory of Bioengineering, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences Yuki Monden Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Mayuko Hamada Ushimado Marine Institute, Okayama University Advances in long-read sequencing and Hi–C scaffolding have made chromosome-level genome assembly increasingly accessible to individual laboratories, shifting genome research from large consortium-led projects toward investigator-driven studies across diverse taxa. This transition allows researchers to select organisms based on biological questions rather than the prior availability of genomic resources. In this review, we summarize the core experimental and computational steps for generating, evaluating, and annotating chromosome-level assemblies, and examine how they have advanced research in non-model organisms and genetically complex systems. Representative case studies illustrate four major contributions: resolving structural variation and lineage-specific genome architecture, linking genome organization to phenotypic innovation and plasticity, reconstructing deep chromosome evolution and macrosynteny, and distinguishing homologous and homoeologous chromosomes in polyploid genomes. These examples show that chromosome-level assemblies provide more than complete reference sequences. They establish a continuous genomic coordinate system through which genes, regulatory elements, transposable element insertions, sequence variants, and cellular states can be interpreted within broader chromosomal, population, and evolutionary contexts. We describe this integrative perspective as �gglocal biology.�h Future progress will require pangenomic, population-scale, and haplotype-resolved resources integrated with multi-omics and functional analyses. Collectively, chromosome-level genomics is reshaping life science by embedding molecular functions within chromosomal and evolutionary contexts. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2056-306X 12 1 2026 Knockout analysis of period and timeless and EGFP-based visualization of per-expressing clock cells in the cricket circadian clock 12 EN Kenji Tomioka Graduate School of Natural Science and Technology, Okayama University Shintaro Inoue Bio-Innovation Research Center, Tokushima University Taro Mito Bio-Innovation Research Center, Tokushima University Yoshiyuki Moriyama Department of Natural Sciences, Kawasaki Medical School Taishi Yoshii Graduate School of Environmental, Life, Natural Science and Technology, Okayama University In the present study, we generated crickets with knockout of either period (per) or timeless (tim) gene by CRISPR/Cas9-based genome editing. We also identified a naturally occurring per- mutant lacking a large coding region including PAS domains. To examine possible synergistic effects, a per- and timKO double mutant was generated by applying genome editing to the per- crickets. Under constant darkness (DD), timKO crickets exhibited a locomotor rhythm with a free-running period of 23.06 �} 0.20 h (mean �} SD), which was significantly shorter than that of the parental strain (23.78 �} 0.12 h). By contrast, perKO and per- crickets showed basically similar phenotype of locomotor rhythm: they exhibited an arrhythmic pattern during the first two to three weeks after transfer to DD but subsequently showed a complex rhythmic pattern with one or multiple components with significantly longer free-running periods (33.35 �} 10.72 h). In the per-;timKO double mutants, approximately 60% of individuals became arrhythmic, while the remaining 40% exhibited complex rhythms with extremely longer free-running periods (37.0 �} 9.17 h) under DD. These results suggest the existence of an underlying oscillatory mechanism that is responsible for regulating locomotor rhythms independently of the canonical per/tim feedback loop. Furthermore, we generated a reporter line on a per�| background by knocking egfp into exon 1 of the per gene, allowing egfp expression to report per transcription. EGFP expression was detected in three distinct clusters of cells within the optic lobe: two located along the dorsal and ventral boundaries between the lamina and medulla neuropils, and one situated near the accessory medulla. These findings raise the possibility that these form part of the circadian clock network that governs circadian locomotor rhythms. No potential conflict of interest relevant to this article was reported.

Œö‰vŽÐ’c–@�l “ú–{•úŽË�ü‹Z�pŠw‰ï Acta Medica Okayama 0369-4305 82 10 2026 ƒxƒCƒY�„’è‚ð—p‚¢‚½ƒ‰ƒWƒIƒNƒ�ƒ~ƒbƒNƒtƒBƒ‹ƒ€‚ÌADC’l–�ü—Ê•ÏŠ·–@ 26-1707 EN Yuki Tanimoto Department of Radiology, NHO Iwakuni Clinical Center Kohei Sugimoto Department of Radiological Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare Masahide Tamori Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Miho Yatsuki Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Shohei Yoshida Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Kazuma Sugahara Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Masataka Oita Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University �y–Ú“I�zƒ‰ƒWƒIƒNƒ�ƒ~ƒbƒNƒtƒBƒ‹ƒ€‚Í�‚‚¢‹óŠÔ•ª‰ð”\‚ð—L‚·‚邱‚Æ‚©‚ç�CŠ³ŽÒ•ÊIMRT•iŽ¿•Û�Ø�iIMRT QA�j‚É�L‚­—˜—p‚³‚ê‚Ä‚¢‚é�Dˆê•û�CƒsƒNƒZƒ‹’l‚ð�ü—Ê‚Ö•ÏŠ·‚·‚邽‚߂̃LƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“‚É‚Í�C•¡�”‚ÌŠù’m�ü—Ê‚Å�ÆŽË‚µ‚½ƒtƒBƒ‹ƒ€‚ª•K—v‚Å‚ ‚è�C�ì‹Æ•‰’S‚ª‘å‚«‚¢‚±‚Æ‚©‚ç�CŽ{�Ý‚É‚æ‚Á‚Ă̓tƒBƒ‹ƒ€ƒ�ƒbƒg•Ï�XŽž‚È‚Ç‚ÉŒÀ’肵‚ÄŽÀŽ{‚³‚ê‚é�ê�‡‚ª‚ ‚é�D–{Œ¤‹†‚Å‚Í�C‰ß‹Ž‚̃LƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“ƒf�[ƒ^ƒZƒbƒg‚Æ‘Î�ÛƒtƒBƒ‹ƒ€‚Ì–¢�ÆŽËŽžƒsƒNƒZƒ‹’l‚ð—p‚¢‚ăLƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“‹È�ü‚ð�„’è‚·‚éƒxƒCƒY�„’胂ƒfƒ‹‚ð�\’z‚µ�CƒLƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“�ì‹Æ‚ÌŒø—¦‰»‚ð–Ú“I‚Æ‚µ‚Ä‚»‚Ì—L—p�«‚ðŒŸ�Ø‚µ‚½�D�y•û–@�zTomoHD‚ð—p‚¢‚Ď擾‚µ‚½93‘g‚̃LƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“ƒf�[ƒ^ƒZƒbƒg‚ð‰ð�Í‘Î�Û‚Æ‚µ‚½�D�ü—Ê‚¨‚æ‚Ñ�ÆŽË‚©‚çƒXƒLƒƒƒ“‚Ü‚Å‚ÌŒo‰ßŽžŠÔ‚ð�à–¾•Ï�”‚Æ‚·‚é“ñŽŸ‘½�€Ž®‰ñ‹Aƒ‚ƒfƒ‹‚ð�\’z‚µ‚½�Dƒ‚ƒfƒ‹‚̓XƒLƒƒƒi‚Ì“Ç‚ÝŽæ‚è•ûŒü�i�c•ûŒü�E‰¡•ûŒü�j‚²‚Æ‚É�ì�¬‚µ�C‘Î�ÛƒtƒBƒ‹ƒ€‚Ì–¢�ÆŽËŽžƒsƒNƒZƒ‹’l‚ð�Ø•Ð�€‚Æ‚µ‚Ä�„’肵‚½�DƒxƒCƒY�„’è‚É‚ÍStan‚ð—p‚¢�CƒgƒŒ�[ƒXƒvƒ�ƒbƒg‚¨‚æ‚ÑRhat“�Œv—Ê‚É‚æ‚èŽû‘©�«‚ð•]‰¿‚µ‚½�D�X‚Ƀ‚ƒfƒ‹�«”\‚Ì•]‰¿‚É‚Í�CˆÙ‚È‚éƒ�ƒbƒg‚ÌEBT4ƒtƒBƒ‹ƒ€10–‡‚ð—p‚¢‚Ä—\‘ªƒsƒNƒZƒ‹’l‚ÆŽÀ‘ª’l‚ð”äŠr‚·‚é‚Æ‚Æ‚à‚É�C�ü—ÊŒë�·‚ð•]‰¿‚µ‚½�D�yŒ‹‰Ê�z‚·‚ׂẴ‚ƒfƒ‹‚ÅRhat‚Í1.01–¢–ž‚ðŽ¦‚µ�C—Ç�D‚ÈŽû‘©�«‚ªŠm”F‚³‚ꂽ�DŒŸ�Ø—pƒtƒBƒ‹ƒ€‚Å‚Í�CƒsƒNƒZƒ‹’l‚ÌŒë�·‚Í3.6%–¢–ž�CŒˆ’èŒW�”�iR2�j‚Í0.99ˆÈ�ã‚Å‚ ‚Á‚½�D‚Ü‚½�C�ü—ÊŒë�·‚Í24 cGy‚Å•½‹Ï2.7 cGy�iSD 1.3�j�C868.2 cGy‚Å•½‹Ï37.5 cGy�iSD 12.8�j‚Å‚ ‚è�C�Å‘å�ü—ÊŒë�·‚Í710.6 cGy‚É‚¨‚¢‚Ä66.6 cGy‚Å‚ ‚Á‚½�D�yŒ‹Œê�z–{Žè–@‚Í�C‰ß‹Ž‚̃LƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“ƒf�[ƒ^ƒZƒbƒg‚Æ‘Î�ÛƒtƒBƒ‹ƒ€‚Ì–¢�ÆŽËŽžƒsƒNƒZƒ‹’l‚ð—p‚¢‚ăLƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“‹È�ü‚ð�„’è‚Å‚«‚é‰Â”\�«‚ðŽ¦‚µ‚½�D‚Ü‚½�Cƒ‰ƒWƒIƒNƒ�ƒ~ƒbƒNƒtƒBƒ‹ƒ€‚̃LƒƒƒŠƒuƒŒ�[ƒVƒ‡ƒ“�ì‹Æ‚ÌŒø—¦‰»‚ÉŠñ—^‚·‚é‰Â”\�«‚ªŽ¦�´‚³‚ꂽ�D�¡Œã‚ÍŠ³ŽÒ•ÊIMRT QA‚É“K—p‚µ�C�ü—Ê•ª•z•]‰¿‚ւ̉e‹¿‚ðŒŸ�Ø‚·‚é•K—v‚ª‚ ‚é�D No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0960-7412 127 3 2026 AHG1–AFP interaction as a regulatory node in the ABA response during seed germination e71081 EN Noriyuki Nishimura Institute of Agrobiological Sciences, National Agriculture and Food Research Organization Sho Ushiyama Institute of Plant Science and Resources, Okayama University Masato Otagiri Institute of Plant Science and Resources, Okayama University Kouji Satoh Institute of Agrobiological Sciences, National Agriculture and Food Research Organization Nahomi Suzuki Institute of Agrobiological Sciences, National Agriculture and Food Research Organization Tomoko Irisa Institute of Agrobiological Sciences, National Agriculture and Food Research Organization Nobutaka Mitsuda Biomanufacturing Process Research Center, National Institute of Advanced Industrial Science and Technology Taishi Umezawa Graduate School of Advanced Interdisciplinary Science, Tokyo University of Agriculture and Technology Hideki Nishimura Institute of Plant Science and Resources, Okayama University Keiichirou Nemoto Proteo-Science Center, PIAS, Ehime University Wataru Tsuchiya Research Center for Advanced Analysis, National Agriculture and Food Research Organization Ryoichi Yano Research Center for Advanced Analysis, National Agriculture and Food Research Organization Tatsuya Sawasaki Proteo-Science Center, PIAS, Ehime University Toshimasa Yamazaki Research Center for Advanced Analysis National Agriculture and Food Research Organization Tsukuba Ibaraki 305�]8518 Japan Takashi Hirayama Research Center for Advanced Analysis, National Agriculture and Food Research Organization Seed dormancy and germination are tightly regulated by complex signaling networks that integrate internal and external cues, including the endogenous phytohormone abscisic acid (ABA). ABA HYPERSENSITIVE GERMINATION 1 (AHG1), a group A type 2C protein phosphatase (PP2C), is thought to modulate the activity of transcription factors such as ABA INSENSITIVE 5 (ABI5) in seeds and during germination. AHG1 is regulated by DELAY OF GERMINATION 1 (DOG1), a key regulator of seed dormancy, through physical interaction. We previously reported that AHG1 also interacts with ABI FIVE BINDING PROTEIN 2 (AFP2), a member of the AFP family; however, the molecular basis of AHG1–AFP coordination has remained unclear. In this study, we show that AHG1 interacts with all AFP family members and that AFP3 binds AHG1 and ABI5 through adjacent but distinct amino acid residues within its C-domain, allowing simultaneous association with both proteins. In addition, AHG1 modulates the phosphorylation status of AFP3 at Ser60 in a DOG1-dependent manner, suggesting that DOG1–AHG1 regulates AFP3 post-translationally. Transcriptomic analyses of AHG1- or AFP3-overexpressing lines revealed that these factors are associated with the regulation of a shared set of ABA-responsive genes, including AFPs, and that AFP3 overexpression is predominantly associated with altered expression of genes involved in transcriptional regulation. Large-scale protein interaction analyses showed that AFPs interact with multiple classes of transcription factors, suggesting their involvement in diverse regulatory pathways, including ABA signaling. Together, these findings demonstrate that DOG1 regulates ABI5 function and modulates ABA responses, at least in part, by controlling AHG1-mediated dephosphorylation of AFPs. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0021-9606 165 7 2026 High-resolution analysis of the S1–S0 transition of magnesium phthalocyanine: Rotational structure and electronic angular momentum 074308 EN Yuki Miyamoto Research Institute for Interdisciplinary Science, Okayama University Katsunari Enomoto Department of Physics, University of Toyama Kana Iwakuni Institute for Laser Science, University of Electro-Communications Susumu Kuma Department of Physics, Rikkyo University Koichi M. T. Yamada Institute for Laser Science, University of Electro-Communications We report a high-resolution spectroscopic analysis of the S1–S0 transition of magnesium phthalocyanine (MgPc), obtained by probing buffer-gas-cooled molecules with a narrow-linewidth laser. The observed spectrum exhibits a characteristic three-peak pattern, which is well reproduced by modeling MgPc as an oblate symmetric top with D4h symmetry. A key result of this work is that the spectrum is strongly influenced by electronic Coriolis coupling, which is associated with electronic angular momentum. The electronic Coriolis constant is determined to be ∼2, indicating an effective orbital angular momentum of about 2 in the excited S1 state, originating from the ƒÎ-conjugated ring excitation. This provides a direct spectroscopic signature of electronic angular momentum in a large polyatomic molecule. The presence of nonzero electronic orbital angular momentum is qualitatively consistent with the perimeter model of phthalocyanines. The value lies within the range inferred from previous magnetic circular dichroism (MCD) studies. Compared with the previous MCD estimate, the present analysis provides a more state-specific and narrower constraint, demonstrating that high-resolution spectroscopy enables direct access to electronic and magnetic properties beyond conventional structural characterization. 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.<br> 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.<br> 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.<br> 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.

AME Publishing Company Acta Medica Okayama 2304-3865 13 5 2024 Primary angiosarcoma of the breast: a literature review 68 EN Yidan Zhu Department of Breast Surgery, Liaoning Cancer Hospital & Institute Shogo Nakamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Yoko Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Tsuguo Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Xinfeng Zhang Department of Breast Surgery, Liaoning Cancer Hospital & Institute Maki Tanioka Department of Clinical AI Human Resources Development Program, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Background and Objective: Primary angiosarcoma of the breast (PBA) is an extremely rare and heterogeneous disease. PBA is difficult to diagnose and has a poor prognosis. In order to better understand the disease and provide evidence-based treatment for PBA patients, a review of the published literature in the English language was conducted.<br> Methods: A literature review in agreement with the PRISMA protocol was conducted. Medline and Cochrane databases were searched for English articles on PBA patients in September 2023 with a predetermined strategy. The articles were categorized and assessed based on hierarchical levels of scientific evidence.<br> Key Content and Findings: A total of 255 articles were identified, among these 137 publications which included 1,888 patients met the criteria for inclusion in the final analysis. No prospective, randomized trials exclusive to PBA have been recognized. This article provides an overview of the most current and comprehensive evidence concerning the epidemiology, etiology, genomic features, clinical presentations, diagnosis, treatment, and prognosis of PBA.<br> Conclusions: Despite the fact that current evidence is largely derived from retrospective studies, database analyses, and case reports, we utilized this information to tackle important clinical questions concerning optimal patient management practices for PBA. Complete surgical excision continues to be the mainstay treatment for PBA. However, the effectiveness of adjuvant therapies is still unclear. This narrative review highlights the urgent need for more rigorously designed research to enhance the management and treatment strategies for PBA. 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 ƒÊm is emitted with a 0.916 radiant ratio, and the measured emitted radiant energy is 3.69 �~ 102 W/m2·ƒÊm. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Amyloid-forming property of the N-terminal 1�|70 residues of human apolipoprotein A-IV 13203 EN Norihiro Namba Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University Tokiko Danjo Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University Yuichiro Kitagawa Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University Yoshito Naito Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University Takashi Ohgita Center for Instrumental Analysis, Kyoto Pharmaceutical University Toshinori Shimanouchi Graduate School of Environmental and Life Science, Okayama University Hiroyuki Saito Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University Apolipoprotein A-IV (apoA-IV), the largest member of the exchangeable apolipoprotein family, is a common constituent of amyloid deposits in renal and cardiac amyloidosis. In this study, we characterized the aggregation propensity of the apoA-IV N-terminal fragment to form amyloid fibrils using a variety of biophysical techniques. Thioflavin T fluorescence assay, circular dichroism measurement, and microscopic observations revealed that the N-terminal 1�|70 amino acid fragment of apoA-IV readily forms amyloid fibrils by a transition from a random coil to a ƒÀ-sheet-rich structure. Sequence-based analysis indicated that residues 7�|16 and 38�|42 are the major aggregation-prone segments within the N-terminal 1�|70 residues of apoA-IV. Consistent with this, deletion of these residues strongly inhibited the ƒÀ-transition and fibril formation of apoA-IV 1�|70. Kinetic and thermodynamic analyses of fibril formation by the apoA-IV 1�|70 fragment demonstrated that primary nucleation is the dominant step in fibril formation, for which the activation energy barrier is entirely entropic. In addition, we found that the presence of heparin, a representative glycosaminoglycan, accelerated fibril formation kinetics and enhanced the yield of apoA-IV 1�|70 fibrils, and the positively charged residues K58-K59 play a critical role in heparin interaction. Overall, our results suggest that the strong amyloid-forming propensity of the N-terminal fragment of apoA-IV may play a key role in amyloid deposition associated with apoA-IV amyloidosis. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 2296-634X 14 2026 Prolonged TNF-ƒ¿ stimulation induces a PD-1–associated exhaustion-like phenotype in mesenchymal stromal cells 1680076 EN Naoya Matsunaga Department of Oral Rehabilitation and Regenerative Medicine, 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 Aung Ye Mun Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tinling Zou Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Ito Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ruji Tagashira Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mesenchymal stromal cells (MSCs) have emerged as promising therapeutic agents for inflammatory diseases because of their potent immunomodulatory properties. Although acute inflammation transiently enhances MSC functionality, the impact of chronic inflammatory exposure remains poorly defined. In this study, we investigated the effects of sustained TNF-ƒ¿ stimulation and indirect co-culture with M1 macrophages on MSC behavior. Comprehensive gene expression profiling was performed to assess the changes in immunoregulatory, apoptotic, and metabolic pathways. To determine functional reversibility, we also evaluated MSCs following the withdrawal of TNF-ƒ¿. Short-term exposure led to upregulation of Tgf-ƒÀ, Il-10, and Fasl, whereas prolonged stimulation suppressed these genes and significantly increased the expression of immune checkpoint genes Pd-1 and Ctla-4, indicative of an exhaustion-like phenotype. This phenotypic shift was associated with sustained NF-ƒÈB activation, upregulation of Stat3 and Ap-1, suppression of mTORC1/2 components, decreased Pd-l1 expression, and increased Pd-1 expression, raising the possibility that PD-1 upregulation is associated with MSC dysfunction under chronic inflammatory stress. These findings revealed that prolonged stimulation (48 h) induces an exhaustion-like dysfunction state in MSCs, characterized by checkpoint activation, transcriptional repression, and metabolic dysfunction. PD-1 may serve as a biomarker associated with inflammation-induced MSC impairment. 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�fs Medical University Teppei Omori Institute of Gastroenterology, Tokyo Women�fs 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.

Elsevier BV Acta Medica Okayama 2452-302X 10 10 2025 Inhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-Induced Heart Failure Progression 101308 EN Toshiomi Katsuki Department of Cardiology, Keio University School of Medicine Dai Kusumoto Department of Cardiology, Keio University School of Medicine Yohei Akiba Department of Cardiology, Keio University School of Medicine Mai Kimura Department of Cardiology, Keio University School of Medicine Jin Komuro Department of Cardiology, Keio University School of Medicine Takahiro Nakamura Department of Cardiology, Keio University School of Medicine Hisayuki Hashimoto Department of Cardiology, Keio University School of Medicine Thukaa Kouka Department of Cardiology, Keio University School of Medicine Kazuhisa Sugai Institute for Integrated Sports Medicine, School of Medicine, Keio University Yoshinori Katsumata Department of Cardiology, Keio University School of Medicine Masaki Miyasaka Department of Computational Biology and Medical Sciences, the University of Tokyo Yutaka Suzuki Department of Computational Biology and Medical Sciences, the University of Tokyo Junko Kuramoto Department of Pathology, Keio University School of Medicine Yoshiaki Kubota Department of Anatomy, Keio University School of Medicine Keiichi Fukuda Department of Cardiology, Keio University School of Medicine Shinsuke Yuasa Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaki Ieda Department of Cardiology, Keio University School of Medicine Inappropriate endothelial cell (EC) interactions contribute to heart failure; however, their precise mechanisms remain poorly understood. This study investigated EC-fibroblast interactions mediated by Scarb1 using single-cell RNA-sequencing analysis in a mouse heart failure model. ECs exhibited inflammatory and fibrotic gene expression, with Scarb1-mediated fibroblast-EC interactions driving disease progression. EC-specific Scarb1 knockout and systemic SCARB1 inhibition attenuated heart failure progression. In vitro and spatial omics analyses confirmed the role of SCARB1 in ECs and cell-cell interaction during heart failure progression. These findings highlight SCARB1 as a promising therapeutic target for EC-focused interventions. 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.<br> 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.<br> 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.<br> 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.

Copernicus GmbH Acta Medica Okayama 1816-3459 35 2 2026 An interdisciplinary approach to sampling hard rock cores of the oceanic crust for microbiological and biogeochemical research 159 169 EN William J. Brazelton School of Biological Sciences, University of Utah Oscar Cavazos International Ocean Discovery Program, Texas A&M University Jordyn A. Robare School of Molecular Sciences, Arizona State University Gordon Southam School of the Environment and Sustainable Minerals Institute, University of Queensland Johanna Suhonen International Ocean Discovery Program, Texas A&M University Fengping Wang School of Oceanography, Shanghai Jiao Tong University Susan Q. Lang Dept. of Geol. and Geophys., Woods Hole Oceanographic Institution Andrew McCaig School of Earth and Environment, University of Leeds Peter Blum International Ocean Discovery Program, Texas A&M University Natsue Abe Japan Agency for Marine-Earth Science and Technology Rémi Coltat ISTO, UMR 7327, Univ. Orleans, CNRS, BRGM, OSUC Jeremy R. Deans School of Biological, Environmental, and Earth Sciences, University of Southern Mississippi Kristin L. Dickerson Dept. of Earth and Planetary Sciences, University of California Marguerite Godard Geosciences Montpellier, CNRS, University of Montpellier Barbara E. John Dept. of Geology and Geophysics, University of Wyoming, Laramie Frieder Klein Dept. of Geol. and Geophys., Woods Hole Oceanographic Institution, Rebecca Kuehn Institute of Geosciences and Geography, Martin Luther University Halle-Wittenberg Kuan-Yu Lin Electron Microscopy Core Facility, Purdue University C. Johan Lissenberg School of Earth and Environmental Sciences, Cardiff University Haiyang Liu Center of Deep Sea Research, Institute of Oceanology, Chinese Academy of Sciences Ethan L. Lopes Dept. of Geophysics, Stanford University Toshio Nozaka Dept. Earth Sciences, Okayama University Andrew J. Parsons School of Geography, Earth and Environmental Sciences, University of Plymouth Vamdev Pathak Dept. Geology, Central University of Punjab Mark K. Reagan Dept. of Earth and Environmental Sciences, University of Iowa C. Geoffrey Wheat Global Undersea Research Unit, University of Alaska Fairbanks Studying life in the deep, rocky subseafloor involves many layers of technological and methodological challenges, and each drilling project or expedition must make a series of choices to address these challenges. We report on the workflow for sampling hard rock cores for microbiological and biogeochemical research that was developed and optimized during International Ocean Discovery Program (IODP) Expedition 399. All steps of the workflow, including selection of the sample and its shipboard homogenization and subsampling for specific analyses, were designed to maximize the potential for interdisciplinary collaborations and syntheses of results. Furthermore, multiple strategies to minimize and detect potential microbial and organic chemical contamination of the core samples were employed, including the shipboard detection of a fluorescent chemical tracer pumped into the drill fluid. Contamination tracer levels were detectable on the exterior surfaces of the core but absent in the homogenized interiors of most core samples. Based on the experiences and preliminary results of this expedition, recommendations for processing samples on future expeditions are presented. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 2169-9313 131 8 2026 Effect of Fluorine on the Stability of Dense Hydrous Mg Silicates With Implications for the Deep Water Cycle e2025JB033593 EN Takashi Yoshino Institute for Planetary Materials, Okayama University Yunfan Miao Institute for Planetary Materials, Okayama University Satheesh T. Saji Institute for Planetary Materials, Okayama University Daijo Ikuta Institute for Planetary Materials, Okayama University Nozomi Kondo Institute for Planetary Materials, Okayama University Takayuki Ishii Institute for Planetary Materials, Okayama University Xuejing He Geochemical Research Center Graduate School of Science, The University of Tokyo Tsutomu Ota Institute for Planetary Materials, Okayama University Takuya Kunihiro Institute for Planetary Materials, Okayama University Water is believed to be transported, at least locally, into the Earth's deep mantle via hydrous minerals. Fluorine not only tends to interact with water but also influences the stability of hydrous minerals. Thus, knowledge of its stability could be important in understanding the deep-water cycle. In this study, we conducted high-pressure experiments to investigate the stability of dense hydrous Mg silicates in the presence of fluorine at pressures ranging from 9 to 23 GPa. In the presence of even small amounts of fluorine, clinohumite or phase E survives up to approximately 17 GPa, allowing it to exist without dehydration at temperatures by about 200�‹C higher than a fluorine-free system. At pressures above 18 GPa, superhydrous phase B stabilizes as a major fluorine host. Fluorine partitions very little into phase D, leaving its stability field unchanged, but the stability field of superhydrous phase B extends to temperatures above 1400�‹C, thereby enabling the hydrous phase in the dragged wedge mantle just above the slab to have transport potential into the lower mantle. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 Post-Tracheostomy Fistula Formation Between the Trachea and Left Common Carotid Artery in a Pediatric Patient with Trisomy 18 247 252 EN Tsuyoshi Shiina Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Watanabe Department of Pediatrics, Fukuyama City Hospital Junko Yoshimoto Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takeshi Sato Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisaku Morimoto Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoka Okamura Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Terutaka Tanimoto Department of Pediatric Surgery, Okayama University Hospital Yosuke Washio Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Oyama Department of Pediatric Surgery, Fukuyama City Hospital Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuo Noda Department of Pediatric Surgery, Japanese Red Cross Society Himeji Hospital Case Report 10.18926/AMO/71068 The long-term survival of individuals with trisomy 18 has improved, and the need for tracheostomy in this population has thus increased. We describe the case of a 3-year-old Japanese boy with trisomy 18 who developed a tracheoarterial fistula involving the left common carotid artery (LCCA). He underwent an emergency tracheostomy for respiratory failure secondary to pneumonia. Massive hemorrhage from the tracheostoma occurred on postoperative day 31, leading to his death. The autopsy revealed that the LCCA originated from the brachiocephalic trunk and coursed medially, forming a fistulous connection with the trachea. This case highlights the clinical importance of preoperative vascular mapping in patients with chromosomal abnormalities. 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�fs 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 ƒÀ-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.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 The Impact of Migraine on Cerebral Artery Dissection 227 231 EN Kenichi Kashihara Okayama Neurology Clinic Toshikazu Hamaguchi Department of Neurology, Okayama Kyokuto Hospital Yasuko Takeda Okayama Neurology Clinic Original Article 10.18926/AMO/71065 The impact of migraines as a risk factor for cervicocerebral artery dissection was retrospectively investigated in patients who had a cervicocerebral artery dissection. We first evaluated the patients�f medical records and history of migraine and then calculated the proportion of patients with migraine as well as the relevant vascular risk factors. The prevalence of migraine with respect to the location of the cervicocerebral artery dissection was also identified. Sixty-two patients (37 men, 25 women) had both a cerebral artery dissection and a record of migraine. Among them, 93.5% presented with an isolated headache, and 6.5% presented with a related stroke. Regarding the locations of the artery dissection, 56 (90.3%) were in the intracranial vertebral artery (VA), three (4.8%) were in the internal carotid artery, and one case each (1.6%) was in an anterior cerebral artery, basilar artery (BA), and both the VA and BA. Among the patients with VA dissection, 42 (73.7%) presented with migraines. Among the four patients with dissection of an artery of anterior circulation, only one (25%) had a migraine history. The frequency of migraines tended to be higher in the patients with VA dissection compared to those with a dissection of arteries of anterior circulation. These data suggest that (i) migraine is a potent risk factor for cerebral artery dissection, especially intracranial VA dissection, and (ii) the intracranial VA may be more susceptible to dissection compared to arteries of anterior circulation. No potential conflict of interest relevant to this article was reported.

Japanese Society of Veterinary Science Acta Medica Okayama 0916-7250 88 8 2026 Comparison of three irradiation ways with Monte Carlo calculation for the feline lymphoma with orthovoltage radiation therapy 1239 1245 EN Yuki NEMOTO Department of Veterinary Radiology, Joint Faculty of Veterinary Medicine, Yamaguchi University Yoshinori TANABE Faculty of Medicine, Graduate School of Health Sciences, Okayama University Ryouta ONIZUKA Department of Radiology, Kokura Memorial Hospital Munekazu NAKAICHI Department of Veterinary Radiology, Joint Faculty of Veterinary Medicine, Yamaguchi University Although orthovoltage radiation therapy remains widely used in veterinary medicine in Japan due to its affordability and operational simplicity, accurate calculation of dose distribution is challenging. Treatment planning varies between practitioners and tends to rely on empirical methods. This study aimed to compare the effects of three different orthovoltage beam directions on dose distribution in feline nasal lymphoma using Monte Carlo simulations. CT images from five clinical cases were analyzed using three irradiation plans: Plan A (beam directed perpendicularly to the hard palate), Plan B (perpendicularly to the nasal bridge), and Plan C (from the oral cavity). Each plan used a 4 �~ 4 cm field and delivered a 10 Gy dose at 280 kVp. Doses to the tumor, brain, and both eyes were calculated. Mean dose for the tumor did not significantly differ among the three plans. Plan B resulted in significantly higher doses to the ipsilateral eye compared to Plan C, but delivered the lowest brain dose. Depth-dose analysis revealed a peak just above the bone at the beam entrance, followed by a sharp attenuation in all plans. These findings suggest that beam direction substantially affects dose distribution in orthovoltage therapy, particularly for organs at risk including superficial bones and overlying skin. Meticulous planning is essential to ensure sufficient tumor dose coverage while mitigating and distributing adverse effects, especially in complex regions like the feline nasal cavity. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 2169-9313 131 8 2026 Spin Transition of Ferric Iron in Silicate Glasses Inferred by High�]Pressure Electrical Conductivity Measurements e2026JB034225 EN Izumi Mashino Institute for Planetary Materials, Okayama University Takashi Yoshino Institute for Planetary Materials, Okayama University Shinji Kitao Institute for Integrated Radiation and Nuclear Science, Kyoto University Takaya Mitsui Synchrotron Radiation Research Center, Kansai Photon Science Institute, Quantum Beam Science Research Directorate, National Institutes for Quantum Science and Technology Ryo Masuda Graduate School of Science and Technology, Hirosaki University Makoto Seto Institute for Integrated Radiation and Nuclear Science, Kyoto University Silicate melt has been proposed to exist near the base of the mantle and has been invoked to explain seismic and electrical conductivity anomalies observed near the core-mantle boundary; however, its presence and stability under lowermost-mantle conditions remain uncertain. Here we report high-pressure electrical conductivity measurements of Fe2+- and Fe3+-bearing pyroxene glasses (Fe3+/ƒ°Fe ≈ 0.5), used as analogs of silicate melts, up to megabar pressures at room temperature. At lower pressures, conductivity increases with pressure and iron content, consistent with electron-hole hopping between Fe2+ and Fe3+. Above 77–85 GPa, all samples show a marked conductivity decrease, suggesting a pressure-induced spin transition of Fe3+. Previous studies have suggested that lower-mantle silicate melts may be enriched in Fe3+, and iron spin-state changes may modify iron partitioning between silicate melts and coexisting crystalline phases. Therefore, the Fe3+ spin transition inferred here may affect the evolution of deep-mantle melts through pressure-dependent changes in iron partitioning behavior. 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<br> 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.<br> Methods <br> 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.<br> Results<br> 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.<br> Conclusions <br> 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.

Elsevier BV Acta Medica Okayama 1059-1311 141 2026 Transient loss of wakefulness with falls in temporal lobe epilepsy: A retrospective single-centre study 254 261 EN Kohei Izumihara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsuya Sasaki Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Okazaki Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shun Tanimoto Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoya Saijo Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kyohei Kin Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Focal impaired awareness seizures in temporal lobe epilepsy (TLE) typically involve behavioural arrest and automatisms with preserved posture. However, some patients can exhibit a transient loss of wakefulness with fall without any overt motor manifestations, a phenomenon previously described as �gtemporal lobe syncope.�h However, previous reports did not always rigorously exclude FBTCS or ictal asystole. Herein, we aimed to reappraise this semiology by excluding these conditions using simultaneous video-electroencephalogram (VEEG) and electrocardiogram (ECG), clarifying its clinical characteristics.<br> Methods: We retrospectively analysed 65 patients with drug-resistant TLE who underwent surgery between April 2017 and December 2025. Seizures with transient loss of wakefulness with fall were defined as events without generalized motor manifestations or ECG changes, such as bradycardia or asystole. Outcomes were assessed using the ILAE seizure outcome classification.<br> Results: Three of 65 patients exhibited seizures characterised by transient loss of wakefulness with fall. All patients were clinically diagnosed with left TLE, and these seizures developed at least 10 years after epilepsy onset. Simultaneous VEEG and ECG excluded ictal asystole and FBTCS as the causes of the falls. One patient achieved seizure freedom after anterior temporal lobectomy, whereas the other two patients did not achieve seizure freedom after surgery.<br> Conclusion: Our findings suggest that transient loss of wakefulness in TLE patients may represent a distinct seizure semiology that should be differentiated from impaired awareness and from other causes of fall. Although the underlying mechanism remains uncertain, distinguishing wakefulness from awareness may provide a useful conceptual framework for understanding disorders of consciousness during epileptic seizures. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2026 Workforce and institutional factors associated with comprehensive genomic profiling utilization in gynecologic oncology: a nationwide questionnaire survey in Japan EN Tamotsu Sudo Department of Cancer Genetics and Genomics, School of Medicine, Fujita Health University Kenta Masuda Department of Obstetrics and Gynecology, Keio University School of Medicine Katsutoshi Oda Division of Integrative Genomics, Graduate School of Medicine, The University of Tokyo Hidemichi Watari Department of Obstetrics and Gynecology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University Akira Hirasawa Department of Clinical Genomic Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shinya Sato Department of Obstetrics and Gynecology, Tottori University School of Medicine Kenichi Harano Department of Medical Oncology, National Cancer Center Hospital East Satoru Nagase Department of Obstetrics and Gynecology, Faculty of Medicine, Yamagata University Kazuhiro Takehara Department of Gynecologic Oncology, NHO Shikoku Cancer Center Masaki Mandai Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine Yuko Sasajima Department of Pathology, Teikyo University Hospital Hirouki Yanai Department of Pathology, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hitoshi Tsuda Department of Basic Pathology, National Defense Medical College Yusuke Kobayashi Department of Obstetrics and Gynecology, Institute of Medicine, University of Tsukuba Kei Kawana Department of Obstetrics and Gynecology, Nihon University School of Medicine Mikio Mikami Department of Medical Science, Shonan University of Medical Science Kiyoko Kato Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Daisuke Aoki International University of Health and Welfare Graduate School Aikou Okamoto Department of Obstetrics and Gynecology, The Jikei University School of Medicine Background Comprehensive genomic profiling (CGP) has been widely introduced into precision oncology; however, its real-world implementation in gynecologic oncology remains unclear. This study evaluated nationwide CGP utilization, treatment translation, and management of secondary germline findings in Japanese gynecologic oncology.<br> Methods A nationwide survey was conducted across 98 institutions participating in gynecologic oncology training and/or Japan�fs cancer genomic medicine network. Institutional characteristics, workforce composition, treatment translation, and management of germline findings were assessed. Associations between institutional factors and CGP utilization or trial-related treatment translation were analyzed using incidence rate ratios (IRRs) with 95% confidence intervals.<br> Results Among 68 institutions with complete CGP volume data, 6,964 CGP tests were performed, including 922 for gynecologic malignancies. The median number of gynecologic CGP tests per institution was 10. In multivariate analysis, the number of board-certified obstetrician–gynecologists was associated with CGP utilization (IRR, 1.05; 95% CI 1.01–1.08). CGP-guided therapy was delivered to 80 patients (8.7%). Trial-related treatment translation was associated with the number of board-certified obstetrician–gynecologists (IRR, 1.09; 95% CI 1.02–1.16) and the presence of a medical oncology department (IRR, 7.93; 95% CI 1.41–44.72). Presumed germline pathogenic variants were identified in 100 cases (10.8%); however, confirmatory germline testing was performed in only 38 cases.<br> Conclusion CGP utilization in Japanese gynecologic oncology was associated with gynecologic workforce capacity and multidisciplinary genomic infrastructure. Collaboration between gynecologic oncology and medical oncology may facilitate treatment translation. CGP may also serve as an entry point for hereditary cancer evaluation despite incomplete downstream germline evaluation. 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.<br> 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.<br> 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.<br> Conclusions Preoperative MUL on MRI independently predicted QOL recovery and continence after HoLEP. 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.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 0885-8993 41 11 2026 Structural Design of Litz Wires for Reducing AC Transport Current Loss Using an Equivalent Circuit Model Considering the Path of All Strands 19516 19529 EN Ryota Inoue Graduate School of Environment, Life, Natural Science, and Technology, Okayama University Hiroshi Ueda Graduate School of Environment, Life, Natural Science, and Technology, Okayama University SeokBeom Kim Graduate School of Environment, Life, Natural Science, and Technology, Okayama University Litz wires are generally fabricated based on the proprietary know-how of wire manufacturers. Therefore, the design guidelines for the conductor structure of low-loss Litz wires have not been clearly established. In this study, we investigated the effect of differences in the conductor structure on the AC resistance using the equivalent circuit model considering the path of all strands. Moreover, we proposed design guidelines for the conductor structure of Litz wires to reduce AC resistance originating from strand paths. Furthermore, we prototyped Litz wires according to the proposed design guidelines and compared the AC resistance of the proposed Litz wires with that of commercial Litz wires. As a result, the AC resistance of the prototyped Litz wires according to the proposed design guidelines was reduced compared to that of the commercial Litz wires. Moreover, the quality factor of the spiral coil using the proposed Litz wire was higher than that using the commercial Litz wire. From the above results, we experimentally clarified that the proposed design guidelines for the conductor structure of Litz wires are effective in reducing the AC resistance originating from strand paths. No potential conflict of interest relevant to this article was reported.

Public Library of Science (PLoS) Acta Medica Okayama 1932-6203 21 1 2026 Fertility-sparing surgery with neoadjuvant chemotherapy in early and locally advanced cervical cancer: A clinical protocol e0340963 EN Momoko Tanioka Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shoji Nagao 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 Yui Tanaka 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 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 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 Keiichiro Nakamura 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 Fertility preservation remains a critical concern in young women with early or locally advanced cervical cancer, as standard radical treatments compromise reproductive potential. This study aims to evaluate the feasibility, oncological safety, and reproductive outcomes of fertility-sparing treatment involving neoadjuvant chemotherapy followed by cervical conization and laparoscopic pelvic lymphadenectomy. This single-center, prospective, open-label, single-arm, Phase II interventional study will assess patients with FIGO stage IB2–IB3 cervical cancer (FIGO stage 2018) desiring fertility preservation. Eligible patients will receive three cycles of dose-dense paclitaxel and carboplatin (dd-TC), followed by conization and laparoscopic lymphadenectomy. The primary endpoint is successful uterine preservation. Patients requiring concurrent chemoradiotherapy due to inadequate treatment response will not be considered successful. Secondary endpoints include 2-year recurrence-free survival (RFS), overall survival (OS), quality of life assessments, menstrual and ovulatory resumption, pregnancy, live birth, miscarriage, and preterm birth. Adverse events will be graded according to CTCAE v5.0. No potential conflict of interest relevant to this article was reported.

Public Library of Science (PLoS) Acta Medica Okayama 1932-6203 21 8 2026 Study protocol: Effect of inulin supplementation on gut microbiota in patients with oral lichen planus �\ A double-blind, randomised, placebo-controlled parallel-group trial e0356180 EN Koki Nambu Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Naoki Kaneko Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Shiho Yokomizo Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Hu Chen Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Lijing Yan Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Wang Shiyao Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Ryusei Shizuma Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Eiji Iwata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yukiko Ohyama Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Shohei Akagawa Department of Pediatrics, Kansai Medical University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shintaro Kawano Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Masafumi Moriyama Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Oral lichen planus is a chronic inflammatory disease of the oral mucosa characterised by immune dysregulation, but its pathogenesis remains incompletely understood and no curative treatment has been established. Our previous work showed that patients with oral lichen planus exhibit gut dysbiosis, including reduced microbial diversity and depletion of butyrate-producing bacteria. Because butyrate promotes regulatory T-cell differentiation and supports immune homeostasis, targeting this dysbiosis may represent a microbiota-directed approach for immune modulation in oral lichen planus. This study aims to investigate the effects of inulin supplementation on the gut microbiota and related immune markers in patients with oral lichen planus. This multicentre, double-blind, randomised, placebo-controlled parallel-group trial will enrol 80 patients with oral lichen planus. Participants will be randomly assigned in a 1:1 ratio to receive either inulin (8 g/day) or a maltose placebo for 4 weeks, in addition to standard care. The primary outcome is the change in the relative abundance of prespecified butyrate-producing gut bacteria from baseline to the end of intervention at Week 6. Secondary outcomes include changes in gut microbiota diversity, salivary microbiota composition, faecal short-chain fatty acid concentrations, peripheral blood regulatory T-cell counts, blood test parameters, and clinical symptoms of oral lichen planus. Analyses will follow the intention-to-treat principle, and between-group differences will be assessed using appropriate statistical methods. This trial is designed to evaluate, in a randomised placebo-controlled setting, whether a microbiota-directed intervention can modify gut microbial profiles and related immune markers in patients with oral lichen planus. The findings are expected to clarify whether inulin supplementation can modify gut microbial profiles and related immunological markers in patients with oral lichen planus. Trial registration: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000060840, registered on 1 April 2026 (https://rctportal.mhlw.go.jp/detail/um?trial_id=UMIN000060840#). No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2662-9984 7 1 2026 Diversity of hymenopteran assemblages prevailed during reproductive stage of cotton�\implications for natural control 1039 EN Md Mizanur Rahman Insect Biotechnology and Biopesticide Laboratory, Department of Entomology, Bangladesh Agricultural University Tohru Hayakawa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mohammad Tofazzal Hossain Howlader Insect Biotechnology and Biopesticide Laboratory, Department of Entomology, Bangladesh Agricultural University Hymenoptera is one of the most important insect orders contributes to pollination, biocontrol and natural control largely unexplored from Bangladesh. We, therefore, assess the diversity and relative abundance of hymenopteran insects in cotton fields from five locations of Bangladesh using five types of traps (Malaise, Yellow Pan, Fluorescent Yellow Pan, Pitfall, and Sweep Net). Analysis of samples revealed presence of diverse type of hymenopteran insects from the studied locations, with a total of 1642 insects collected, representing 28 morphospecies and 16 families of the Hymenoptera. Formicidae, Braconidae, Diapridae, Figitidae, Ichneumonidae, Scelionidae constitutes the major families comprises of 36.37, 25.09, 5.36, 5.24, 5.18 and 4.93% of the populations respectively. Among the locations, cotton fields of Rangpur showed the highest species richness, diversity indices (Simpson, and Shannon values), while cotton fields located at Jashore had the lowest. Yellow and fluorescent pan traps captured insects from nearly all families, indicating broad sampling effectiveness. Malaise traps also sampled a wide range of families except for low captures of Formicidae. Pitfall traps primarily targeted Formicidae, consistent with their ground-dwelling hymenopterans. Sweep nets captured fewer families, reflecting a more selective sampling role. Among functional guilds, parasitoids were the most abundant, followed by predators, pollinators, and herbivores of hymenopteran insects. Overall, the hymenopteran community in cotton agroecosystems from Bangladesh was dominated by parasitoid families, indicating strong potential for natural biological control. Leveraging this natural enemy dominance could significantly reduce dependence on chemical insecticides. These findings support the integration of parasitoid conservation strategies into national Integrated Pest Management (IPM) programs and landscape-level pest management policies. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0275-5319 91 2026 Does ESG performance enhance investment efficiency and firm performance? Evidence from Japan 103582 EN Yusra Nazir Graduate School of Humanities and Social Sciences, Okayama University Xiaojing Cai Graduate School of Humanities and Social Sciences, Okayama University Tatsumasa Tennojiya Graduate School of Humanities and Social Sciences, Okayama University This study examines the association between investment sensitivity to growth opportunities, firm performance, and environmental, social, and governance (ESG) performance in Japanese listed firms. To determine whether ESG performance is associated with a firm�fs investment sensitivity to growth opportunities rather than directly increasing investment levels, panel data covering the period from 2002 to 2023 and an investment-Q sensitivity framework are employed. To evaluate robustness and reduce endogeneity issues, high-dimensional fixed effects (HDFE), the System Generalized Method of Moments (GMM), and a difference-in-differences (DID) design based on Japan�fs post-2015 governance and disclosure environment are added to the baseline fixed-effects estimations. The findings show a positive association between investment-Q sensitivity and ESG performance, indicating a conditional association wherein firms with higher ESG performance are more receptive to expansion prospects. The findings, however, contradict the hypothesis that ESG performance and investment intensity are consistently associated. Stricter identification techniques diminish positive baseline associations, demonstrating sensitivity to model specification and cross-sectional firm variations. As a result, firm performance results are mixed. Governance-related factors are comparatively more consistently associated with investment outcomes across all ESG components. By focusing on ESG performance and capital allocation behavior under various economic scenarios rather than on whether ESG generally enhances firm outcomes, this study expands the ESG literature. The results imply that ESG serves more as a governance and information mechanism associated with investment sensitivity than as a reliable indicator of firm performance or investment efficiency. No potential conflict of interest relevant to this article was reported.

American Society for Horticultural Science Acta Medica Okayama 0018-5345 61 9 2026 Stomatal Traits in Strawberry Cultivars: Variation among Plant Parts and Associations with Growth and Yield 1988 1991 EN Minori Hikawa-Endo Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Ryosuke Yamanaka Western Region Agricultural Research Center, NARO Takayoshi Yano Western Region Agricultural Research Center, NARO Stomatal traits are important determinants of photosynthesis and water use; however, their variation among plant parts and cultivars and their relationships with growth and yield in strawberry remain unclear. This study characterized stomatal density and guard cell length among plant parts and across 34 cultivars and examined their associations with growth and yield. Stomata were found not only on the abaxial leaf surface but also on petioles and calyces and occasionally on the adaxial surface of leaves. Both traits varied widely among cultivars and decreased between November and May. Stomatal density was significantly negatively correlated with plant height, estimated leaf area, and total yield in both seasons, whereas guard cell length showed no significant association with these traits. These results suggest that stomatal density may be a more relevant indicator of growth and yield in strawberries and that characterizing stomatal traits across plant parts and cultivars may support breeding and cultivation research. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0449-3060 67 4 2026 Enhancement of antioxidant function in various organs in mice using combined thermal and radon inhalation treatment 538 549 EN Shogo Miyanaga Graduate School of Health Sciences, Okayama University Ayumi Tanaka Graduate School of Health Sciences, Okayama University Reiju Takenaka Graduate School of Health Sciences, Okayama University Shota Naoe Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Shuna Goto Graduate School of Health Sciences, Okayama University Mitsuki Nagano Graduate School of Health Sciences, Okayama University Kotaro Tano Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Enhancing antioxidant function is a key strategy for preventing and treating oxidative stress-related diseases. Radon inhalation and thermal treatment (TT) increase the levels of antioxidant enzymes, such as superoxide dismutase (SOD). The positive effects of this combination on pain-related diseases have been reported; however, few studies have elucidated the underlying mechanisms. In this study, we examined the enhancement of antioxidant function in various organs of mice subjected to combined TT and radon inhalation. The mice were placed in an incubator once daily for 40 min at 38.5 �} 0.5�‹C and treated for 1, 3 and 7 days. The mice then inhaled radon at a concentration of 2000 Bq/m3 for 24 h. The characteristic changes in antioxidant function following combined TT and radon inhalation could be categorized into four groups: (i) increased antioxidant function in the brain and colon; (ii) increased or decreased antioxidant function, as observed in the kidney; (iii) decreased antioxidant function, such as in the lungs and (iv) no changes, such as in the small intestine, spleen, pancreas, heart, liver and stomach. Additionally, SOD may be the antioxidant enzyme most sensitive to combined TT and radon treatment. Collectively, the combined treatment may be the most effective in activating antioxidative functions in the brain and colon. This study provides new insights into the effects of combined TT and radon inhalation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 1 2025 Association Between Dinner-to-Bed Time and Gastroesophageal Reflux-Related Diseases in Children e77709 EN Kensuke Uraguchi Department of Epidemiology, 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 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 Seiichiro Makihara Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mizuo Ando Department of Otolaryngology- Head and Neck Surgery, 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 Introduction: Gastroesophageal reflux disease (GERD) is characterized by esophageal mucosal injury due to the reflux of gastroduodenal contents. Typical symptoms include heartburn and acid regurgitation. In addition, gastroesophageal reflux (GER) can influence conditions such as otitis media, rhinitis, and asthma. This study aimed to examine the association between dinner-to-bed time and GER-related diseases, such as otitis media, allergic rhinitis, and asthma.<br> Methods: This was a longitudinal cohort study using secondary data. Data were collected from a large-scale birth cohort study conducted in Japan including babies born in 2001 and 2010. Dinner-to-bed time was categorized as �glonger dinner-to-bed time" (>120 minutes), �gshorter dinner-to-bed time" (≤120 minutes or less), and �girregular dinner-to-bed time.�h Modified Poisson regression with robust variance was used to estimate risk ratios (RRs).<br> Results: A total of 60,392 children were included in this study. Children with shorter dinner-to-bed time had a higher risk of asthma (adjusted RR (aRR) = 1.10; 95% confidence interval (CI), 1.03-1.18) than those with longer dinner-to-bed time. However, no significant association was observed between shorter dinner-to-bed time and otitis media or allergic rhinitis. Furthermore, supplementary analyses revealed that the risk of asthma was significantly higher in children born in 2001 (aRR = 1.13; 95% CI, 1.04-1.22).<br> Conclusion: This study showed that dinner-to-bed time within 120 minutes after dinner increases the risk of developing asthma. This underscores the importance of considering lifestyle modifications, as certain pediatric asthma cases may be influenced by behaviors that promote GER. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 2 2025 Short-Term and Long-Term Outcomes of Robotic Gastrectomy for Gastric Cancer: A Single-Center, Single-Arm Prospective Study e79063 EN Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshihiko Kakiutchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hajime Kashima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masahiko Nishizaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunsuke Kagawa 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: Robotic gastrectomy (RG) has emerged as a promising approach for gastric cancer (GC) treatment, offering advantages such as enhanced dexterity, improved visualization, and increased precision. However, its widespread adoption remains limited due to technical complexity, high costs, limited applications, and insufficient evidence.<br> Methods: We conducted a single-center, prospective study to evaluate the safety and feasibility of RG, including robotic total gastrectomy (RTG), robotic proximal gastrectomy (RPG), and robotic distal gastrectomy (RDG) with D1+ or D2 lymphadenectomy, in clinical stage I/II GC. The primary endpoint was the incidence of intraoperative and postoperative complications, while the secondary endpoints included surgical outcomes and long-term prognosis.<br> Results: Seven patients were enrolled. No intraoperative complications or conversions to open surgery occurred. The primary endpoint was met, with no major postoperative complications. RTG had a longer operative time and more lymph nodes dissected than RDG and RPG. The median postoperative hospital stay was 10 days. Recurrence was observed in two cases, one of which achieved long-term survival without chemotherapy.<br> Conclusion: Our findings demonstrate the safety and feasibility of RG for early and advanced GC. Further multicenter studies with larger cohorts are needed to establish its oncological benefits and cost-effectiveness, facilitating broader clinical adoption. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 3 2025 Cholecystectomy Is Linked to Worse Clinical Outcomes in Primary Sclerosing Cholangitis e80184 EN Nozomi Miyake Department of Gastroenterology and Hepatology, Okayama University Kengo Yasugi Department of Gastroenterology and Hepatology, Okayama University Akinobu Takaki Department of Gastroenterology and Hepatology, Okayama University Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Recent findings have suggested that gallbladder-derived retinoic acid signaling plays a crucial role in the regeneration of damaged intrahepatic biliary ducts. This retrospective cohort study analyzed the clinical records of 20 patients with primary sclerosing cholangitis (PSC) treated at our hospital between 2013 and 2024. We investigated the clinical implications of gallbladder removal in patients with PSC, a progressive cholangiopathy with limited therapeutic options. We retrospectively analyzed the data of patients with PSC and compared patients with and without prior cholecystectomy to assess the impact on disease progression using the Mayo risk score, Fibrosis-4 (FIB4) index, and other clinical parameters. Our findings indicated that cholecystectomy was associated with worse Mayo risk scores (p = 0.0004) and an elevated FIB4 index (p = 0.021), suggesting a potential link between gallbladder removal and accelerated disease progression. Furthermore, mortality and transplant-free survival analysis revealed significantly worse outcomes in the cholecystectomy group (odds ratio = 21.0, p = 0.032). However, given the retrospective nature and small sample size of this study, selection bias cannot be excluded, and further research is needed to confirm these findings. These findings support the hypothesis that gallbladder-derived factors, such as retinoic acid, may influence PSC progression and highlight the need for further research into therapeutic interventions targeting this pathway. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 2 2025 A Rare Course of Chiari Malformation With Large Syringomyelia Presenting at 54 Years Old e78399 EN Masato Tanaka Orthopedic Surgery, Okayama University Hospital Sneha Sharma Orthopedics, North Delhi Municipal Corporation (DMC) Medical College Kushal H Gori Orthopedic Surgery, Okayama Rosai Hospital Md Shohidullah Orthopedic Surgery, Okayama Rosai Hospital Koji Uotani Orthopedic Surgery, Okayama University Hospital Chiari malformation type 1 (CM1) is considered a congenital condition. The symptoms include severe headache, hypalgesia, and loss of temperature sensation. It constitutes a significant burden among children and young adults. The onset of symptoms of CM1 is more commonly observed in relatively young children and is very rare in those over 50 years old. This study aims to present a rare surgical case of CM1 associated with a large syringomyelia in a 54-year-old man.<br> A 54-year-old man with low back pain was introduced to our department. He had slight hyperreflexia of the extremities, slight muscle weakness in both legs, and numbness in the right leg (3/10). He also had urinary and bowel incontinence and spastic gait. Cervical magnetic resonance imaging (MRI) showed CM1 with large syringomyelia extending from C1 to T11. The cervical canal was widened because of a long history of spinal cord expansion.<br> The patient was successfully treated surgically by foramen magnum decompression and syringosubarachnoid shunting under the guidance of O-arm navigation. The muscle weakness and sensory function recovered almost entirely on the one-year follow-up. The patient's cervical Japanese Orthopedic Association (JOA) score had improved from 11/17 to 16/17.<br> Gradually enlarging syringomyelia with slight CM1 is rare, but surgeons should consider this condition's possibility. Foramen magnum decompression achieves good results even in cases with a long history of syringomyelia. This new navigation technique provides an excellent result for a large syringomyelia with CM1. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 16 8 2024 Navigation-Guided C-arm-Free Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Comparative Study of Cage Orientation and Screw Insertion Accuracy Against the Conventional C-arm-Assisted Technique e66070 EN Koji Uotani Navigation-Guided C-arm-Free Minimally Invasive Transforaminal Masato Tanaka Department of Orthopaedic Surgery, Okayama Rosai Hospital Chetan Kumawat Department of Orthopaedic Surgery, Okayama Rosai Hospital Sharvari Gunjotikar Department of Orthopaedic Surgery, Okayama Rosai Hospital Yoshiaki Oda Navigation-Guided C-arm-Free Minimally Invasive Transforaminal Kensuke Shinohara Navigation-Guided C-arm-Free Minimally Invasive Transforaminal Tadashi Komatsubara Department of Orthopaedic Surgery, Okayama Rosai Hospital Shinya Arataki Department of Orthopaedic Surgery, Okayama Rosai Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a widely utilized technique in spine surgery. This study compares the efficacy and safety of MIS-TLIF performed with traditional C-arm fluoroscopy and C-arm-free O-arm navigation. To the best of our knowledge, our study is the first to compare cage positioning between C-arm-free and C-arm techniques for MIS- TLIF.<br> Methods: A retrospective, comparative analysis was conducted on 43 patients undergoing MIS-TLIF. The group was divided based on the utilization of C-arm fluoroscopy or C-arm-free O-arm navigation. Key parameters analyzed included cage orientation, screw insertion accuracy, operative efficiency, and postoperative recovery. Radiographic measurements were used to assess surgical precision and perioperative complications were documented.<br> Results: The study encompassed 43 patients, with no significant differences in demographic characteristics between the two groups. Surgical time and blood loss were comparable between C-arm-free and C-arm groups. O-arm navigation significantly reduced pedicle screw misplacement (p=0.024). Cage positioning differed between groups (p=0.0063): O-arm cages were mostly mid-center, while C-arm cages were more anterior-center. Such differences in the cage location did not cause any impact on clinical outcome. No significant differences were observed in postoperative complications (screw loosenings, dural tears, surgical site infections) between groups. The Oswestry Disability Index scores at the final follow-up showed no significant difference between the O-arm and C-arm groups, indicating similar levels of postoperative disability.<br> Conclusion: Despite the clinically insignificant difference in cage placement between C-arm-free and C-arm dependent, C-arm-free MIS-TLIF significantly improves screw placement accuracy and reduces radiation exposure to operating stuff. This suggests its potential as a valuable tool for safer and more precise spinal fusion surgery. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1523-7060 2026 Cathodic AziridinationUsing Dichloramine-Tas a Nitrogen Source EN Eisuke Sato Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kanon Nagamine Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koichi Mitsudo Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Seiji Suga Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Aziridines are valuable motifs in organic synthesis due to their biological activities and their utility as synthetic intermediates. Although electrochemical methods have been developed for aziridine synthesis, these approaches rely on anodic oxidation. This study reports the first cathodic reduction-promoted aziridine formation using dichloramine-T as a nitrogen source. The reaction conditions were optimized via Gaussian process regression. Overall, this strategy enables aziridine formation with broad substrate scope, providing a practical platform that expands the electrochemical synthesis toolbox. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 3 2025 Effects of Pemafibrate and Eicosapentaenoic Acid Ethyl Ester on Endothelial Function in Patients With Hypertriglyceridemia and Coronary Artery Disease: A Study Protocol for a Multicenter, Open-Label Randomised Controlled Trial e81104 EN Trou Miyoshi Cardiovascular Medicine, Okayama University Yasushi Matsuzawa Cardiovascular Medicine, Kumamoto University Masayuki Doi Cardiology, Kagawa Prefectural Central Hospital Shinsuke Yuasa Cardiovascular Medicine, Okayama University Seigo Sugiyama Cardiovascular Medicine, Jinnouchi Hospital Despite intensive low-density lipoprotein cholesterol-lowering therapies effectively reducing cardiovascular events, residual cardiovascular risks remain significant, with hypertriglyceridemia being an important contributing factor. Pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, has shown strong triglyceride-lowering effects and potential vascular benefits. Similarly, eicosapentaenoic acid ethyl ester (EPA) has demonstrated cardiovascular protective effects, particularly in patients with hypertriglyceridemia. However, the comparative impact of these agents on endothelial function, a key marker of atherosclerotic progression, has not been thoroughly evaluated in patients with coronary artery disease (CAD). The PRIME (PRospective comparIson of peMafibrate and Eicosapentaenoic acid ethyl ester on vascular functions for hypertriglyceridemia) trial is a multi-center, open-label, randomised trial designed to compare the effects of pemafibrate and EPA on endothelial function in patients with CAD and hypertriglyceridemia. Patients receiving statin therapy with fasting triglyceride levels ≥150 mg/dL will be randomised into two groups: pemafibrate (0.2 mg/day, with possible dose escalation to 0.4 mg/day) or EPA (1800 mg/day, with possible dose escalation to 2700 mg/day). Endothelial function will be assessed with reactive hyperemia index (RHI). The primary endpoint is the change in RHI at 12 weeks. The secondary endpoints include the changes in RHI at 24 weeks, correlations between changes in RHI and changes in lipid biomarkers, and changes in biochemical parameters at 12 and 24 weeks. This study investigates the comparative effects of pemafibrate and EPA on endothelial function, addressing an unmet need in managing residual cardiovascular risk in patients with CAD. The findings will contribute to the optimisation of treatment strategies in patients with CAD and hypertriglyceridemia. 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<br> 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.<br> Methodology<br> 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.<br> Results<br> 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).<br> Conclusions<br> 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 9 2024 Decreased CD3+CD56+ Natural Killer T Lymphocytes and Increased Human Leukocyte Antigen-DR+ Cells in the Inflamed Area of Pouchitis in Ulcerative Colitis Patients e70066 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Hospital Masahiro Takahara Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshihiro Inokuchi 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 Background: Pouchitis is an inflammatory condition that affects the ileal pouch during ileal pouch-anal anastomosis surgery. Despite its clinical significance, precise immunological mechanisms underlying pouchitis remain unclear. This study aimed to investigate the lymphocyte profile in the ileal pouch of patients with pouchitis compared to those with familial adenomatous polyposis (FAP) and ulcerative colitis without pouchitis using flow cytometry and immunohistochemical techniques.<br> Methods: We prospectively analyzed endoscopic biopsy specimens from the ileal pouches of 15 patients and categorized them into three groups: FAP, ulcerative colitis with an inflammation-free pouch (UC-I), and ulcerative colitis with ulcers and/or erosions in the pouch (UC-UE). Flow cytometry was used to assess various T-lymphocyte markers, including cluster of differentiation (CD) 4, CD8, CD56, and human leukocyte antigen (HLA)-DR. Immunohistochemistry was performed to visualize the spatial distribution of CD3+, CD56+, and HLA-DR+ cells in the pouch mucosa.<br> Results: We observed significantly reduced CD56+/CD3+ and CD8+/CD3+ ratios in the UC-UE group compared to those in the FAP group, indicating a disruption in natural killer T-cell populations. Immunohistochemical analysis revealed that the spatial distribution of lymphocytes differed among the non-inflamed mucosa, dense lymphocyte infiltration, and lymphoid follicles, with these components frequently intermingling. CD56 + cells were less abundant in areas with dense lymphocyte infiltration, whereas HLA-DR+ cells were more abundant.<br> Conclusion: Our study revealed a decrease in CD56+ natural killer T cells and an increase in HLA-DR+-activated T cells in areas with dense lymphocyte infiltration, suggesting an association between these cells and pouchitis in ulcerative colitis. The distinct patterns observed in non-inflamed mucosa, areas with dense lymphocyte infiltration, and lymphoid follicles underscore the need for further analyses of these three segments to elucidate the immunological mechanisms underlying pouchitis. 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.<br> 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.<br> 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.<br> 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 2168-8184 17 5 2025 Association Between Initial Symptoms and Clinical Outcomes in COVID-19 e84919 EN Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Mitsuru Tsuge Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kou Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenichiro Kudo Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Yasushi Tanimoto Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Kazuhiro Nouso Department of Gastroenterology, Okayama City Hospital Naohiro Oda Department of Internal Medicine, Fukuyama City Hospital Sho Mitsumune Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Goro Kimura Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Haruto Yamada Department of Infectious Diseases, Okayama City Hospital Ichiro Takata Department of Internal Medicine, Fukuyama City Hospital Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akihiko Taniguchi Department of Internal Medicine, Fukuyama City Hospital Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyuki Aokage Department of Emergency Medicine, Tokyo Metropolitan Institute for Geriatrics and Gerontology Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: The clinical presentation of coronavirus disease 2019 (COVID-19) ranges from localized respiratory symptoms such as cough and sore throat to systemic symptoms such as fever and fatigue. To our knowledge, no study has assessed severe disease risk by dividing onset symptoms into localized respiratory and other symptoms. We aimed to determine whether the risk of severe COVID-19 differs depending on whether the symptoms at onset are limited to local respiratory symptoms.<br> Method: This was a multicenter prospective cohort study. The patients were classified into localized respiratory or systemic symptom groups based on the symptoms at onset. Demographic data, blood biomarkers, and clinical outcomes, including mortality, intubation, admission to the intensive care unit, and time to discharge, were compared. This study included 100 adult patients diagnosed with COVID-19 between July 2020 and August 2021.<br> Result: Twelve patients were classified into the localized respiratory symptom group and the remaining 88 into the systemic symptom group. No significant differences between the groups were observed in the baseline characteristics, blood biomarkers, or clinical outcomes. The mortality rates were 0.0% and 4.6%, respectively. The median durations to discharge were 11 and 10 days, respectively (p=0.512). The levels of inflammatory and oxidative stress biomarkers, including interleukin-6 and hydroperoxides, were similar between the groups.<br> Conclusion: The symptom type at disease onset was not significantly associated with differences in clinical outcomes. Comprehensive assessments beyond initial symptoms are crucial for predicting disease progression and optimizing management strategies. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 8 2025 Efficacy of Ibuprofen Gargle for Oral Lichen Planus: A Single-Center, Placebo-Controlled, Double-Blind, Randomized Crossover Study Trial e91242 EN Yasumasa Kakei Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine Yumi Kitahiro Pharmacy, Kobe University Graduate School of Medicine Takeshi Ioroi Pharmacy, Kobe University Graduate School of Medicine Masahiko Kashin Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine Masaki Kobayashi Oral and Maxillofacial Surgery, Shin-suma General Hospital Asami Morioka Pharmacy, Kobe University Graduate School of Medicine Kazuhiro Yamamoto Integrated Clinical and Basic Pharmaceutical Sciences, Okayama University Takumi Hasegawa Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine Ikuko Yano Pharmacy, Kobe University Graduate School of Medicine Masaya Akashi Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine Purpose: Oral lichen planus (OLP) is a chronic, refractory type of stomatitis characterized by abnormal keratinization and often accompanied by pain. The best treatment for OLP, particularly for pain management, remains unclear. This study focuses on the short-term efficacy of ibuprofen gargle for pain relief in patients with OLP.<br> Methods: In this crossover study, 24 patients with painful OLP were enrolled. One group received an ibuprofen gargle (0.6%) on days one and three to five and a placebo on day two. The other group received a placebo on day one and ibuprofen on days two to five. The primary outcome was the change in pain level, measured by a Visual Analogue Scale (VAS) before and after gargling on days one and two. Additionally, changes in each domain of the Patient-Reported Oral Mucositis Symptom (PROMS) scale were evaluated from days one to five.<br> Results: There was no significant difference in the degree of reduction in pain VAS values between the ibuprofen and placebo groups before and five and 15 minutes after use of the gargle. However, the PROMS scale showed a significant reduction in dietary restrictions (p = 0.032) in favor of the ibuprofen gargle compared to baseline.<br> Conclusion: Ibuprofen gargle may help alleviate dietary restrictions associated with oral intake in patients with OLP who experience pain.<br> Trial registration: This study was registered with the Japan Registry of Clinical Trials (jRCT) (jRCTs051220009). 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.<br> 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.<br> 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.<br> 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.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 16 11 2024 Curve Progression After the Termination of Bracing for Adolescent Idiopathic Scoliosis: Usefulness of Combining the Proximal Femur Maturity Index (PFMI) and Risser Staging e73395 EN Hisakazu Shitozawa Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruo Misawa Department of Orthopaedic Surgery, Ryusou Orthopaedic Hospital Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Tomoko Tetsunaga Department of Orthopaedic Surgery, Okayama University Hospital Kensuke Shinohara Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Oda Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masataka Ueda Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Takatori Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazutaka Yamashita Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background<br> The brace therapy for adolescent idiopathic scoliosis (AIS) typically ends upon the end of growth. However, determining the timing of growth cessation can be challenging. The purpose of this study was to evaluate the utility of the proximal femur maturity index (PFMI), which can be assessed simultaneously with Risser staging without requiring additional radiation exposure, in determining the appropriate timing to terminate bracing. To achieve this, we investigated the relationship between skeletal maturity at the end of bracing, post-bracing curve progression, and height growth in patients who had been successfully treated with a brace.<br> Methods<br> Between April 2010 and March 2021, a total of 84 female patients with AIS who started bracing at our hospital with an initial Cobb angle of 20-40 degrees were included. All patients were followed for at least one year after brace termination. Height and radiographic parameters (Risser staging, PFMI, Cobb angle) were retrospectively collected.<br> Results<br> At the end of the bracing period, patients were categorized into Risser stage 4 (85.7%) and 5 (14.3%). By the last follow-up, patients with Risser stage 4 experienced an average main curve progression of 1.8�‹, whereas those with Risser stage 5 had an average progression of �|0.3�‹ (P = 0.03). Patients with Risser stage 4 were further divided into PFMI grade 5 (59.7%) and 6 (40.3%). Significant curve progression was observed in patients with PFMI grade 5 (average: 3.0�‹) compared to grade 6 (average: -0.6�‹) (P < 0.0001). The mean height growth was 1.9 cm/year for PFMI grade 5, and 0.3 cm/year for grade 6, with significant differences between these groups (P < 0.001).<br> Conclusions<br> PFMI allowed further categorization within Risser stage 4: PFMI grade 5 indicated remaining growth potential and risk of postbracing curve progression, whereas grade 6 indicated growth cessation. The combined use of Risser staging and PFMI, both evaluable through the same whole-spine radiograph, may provide a more accurate prediction of growth cessation. 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 Assessment of All-Inside Sutures to the Posteromedial Capsule in Medial Meniscus Posterior Root Repair: Findings From a Retrospective Three-Dimensional Magnetic Resonance Imaging Study e73778 EN Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Furumatsu Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Keisuke Kintaka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yokoyama Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Tamura Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koki Kawada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsubasa Hasegawa Department of Orthopaedic 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 Purpose: Medial meniscus (MM) posterior root tears (PRT) cause pathological medial extrusion (MMME) and posterior extrusion (MMPE), particularly during knee flexion, leading to rapidly progressive knee osteoarthritis. We investigated pre- and postoperative MM extrusion using three-dimensional open magnetic resonance imaging (MRI) following two pullout repair techniques: two simple stitches (TSS) and TSS with an additional all-inside suture to the posteromedial capsule (TSS-PM). We hypothesized that TSS-PM would decrease MM extrusion more effectively than TSS.<br> Methods: Thirty patients who underwent MM posterior root repair were retrospectively evaluated. TSS and TSS-PM techniques were used for pullout repair. Open MRI was performed at 10/90�‹ of knee flexion preoperatively and three months postoperatively. MMME, MMPE, and MM extrusion volume (MMEV) were measured and compared between groups.<br> Results: At 90�‹ of knee flexion, postoperative MMPE and MMEV were significantly decreased compared to preoperative values in both the TSS and TSS-PM groups. Furthermore, a significantly decreased ƒ¢MMPE was observed in the TSS group compared to the TSS-PM group, whereas no significant difference was observed in ƒ¢MMEV.<br> Conclusion: TSS and TSS-PM repair techniques helped decrease MMEV at 90�‹ of knee flexion, whereas a significantly decreased ƒ¢MMPE was observed in the TSS group at 90�‹ of knee flexion. An additional all-inside suture at the posteromedial capsule may be insufficient to decrease MMEV and may negatively affect the decrease in ƒ¢MMPE at 90�‹ of knee flexion. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1526-9914 27 7 2026 Potential of quantitative X�]ray imaging from photon�]counting CT: A novel analysis based on effective atomic number and physical density e70673 EN Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Mana Mitani Division of Radiological Technology, Medical Support Department, Okayama University Hospital Yusuke Morimitsu Division of Radiological Technology, Medical Support Department, Okayama University Hospital Noriaki Akagi Division of Radiological Technology, Medical Support Department, Okayama University Hospital Fumiyo Higaki Department of Radiology, Medical Development Field, Okayama University Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation Kanazawa University Kanazawa Ishikawa Japan Background: Conventional CT assessment of lung lesions is based mainly on morphological features. CT values represent relative X-ray attenuation that does not directly reflect tissue composition and/or physical density. Quantitative imaging using photon-counting CT (PC-CT) has the potential to provide quantitative parameters, such as effective atomic number (Zeff) and effective physical density (ƒÏeff).<br> Purpose: The purpose is to develop and demonstrate the potential of an algorithm that generates both the Zeff and ƒÏeff images, derived directly from virtual monoenergetic images (VMIs) acquired with a clinical PC-CT system.<br> Methods: The ƒÏeff image was generated by fitting a database of mass attenuation coefficients (ƒÊ/ƒÏ) to the measured linear attenuation coefficients (ƒÊ), which were obtained from two VMIs at 70 and 100 keV. As an effective material, Zeff information was also determined and fed back into the ƒÏeff calculation. An in-house low-density phantom was scanned for quantitative evaluation of ƒÏeff. In addition, to demonstrate the applicability of our procedure to actual clinical imaging, representative chest PC-CT images from patients were analyzed.<br> Results: In experiments using low-density phantoms, the CT values did not necessarily correlate with Zeff values, but they showed a very good correlation with the ƒÏeff values. The ƒÏeff values calculated using our procedure correlated well with the correct values of ƒÏ. A relative root mean square error of ƒÏeff calculation was 5.5%. Furthermore, we found that in pulmonary diagnosis, image contrast information from ƒÏeff makes it easier to identify and distinguish lesions compared to that from Zeff.<br> Conclusions: The proposed procedure directly generated Zeff and ƒÏeff images from PC-CT data and enabled quantitative interpretation of CT value in terms of elemental composition and physical density. In this study, the feasibility of generating Zeff and ƒÏeff images was demonstrated. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0021-9258 302 8 2026 Proton pump rhodopsins for optogenetic manipulation of biological activities and beyond 113318 EN Keiichi Kojima Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miyu Inokuchi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Sudo Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Water (H2O), the principal component of living organisms including humans, dissociates into H+ and OH- in aqueous environments, and the resulting H+ concentration determines both cellular pH and the proton motive force (PMF) across cellular membranes. These physicochemical parameters are fundamental regulators of a wide range of biological processes. Optogenetics enables the manipulation of biological and cellular functions using light, typically through the ectopic expression of microbial rhodopsins as photoreceptive proteins in target cells or organs. This review provides a comprehensive overview of optogenetic studies employing H+ pump rhodopsins in diverse biological systems and highlights their growing relevance to neuroscience, cell biology, bioengineering, and therapeutic research. Notably, optical control of H+ concentration allows the precise modulation of neural and non-neural activities in animals and bacteria, highlighting the broad applicability and significant potential of H+ pump rhodopsins for optogenetics. Based on previous and current studies, we discuss how further expansion of the molecular toolkit of H+ pump rhodopsins could enable increasingly fine-tuned manipulation of intracellular pH dynamics and PMF for probing cellular physiology and designing next-generation therapeutic strategies and consider emerging directions that extend beyond classical optogenetics toward the optical control of bioenergetic and chemical processes. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0168-0102 229 2026 Enhanced calcium activity and transcriptomic alterations in iPSC-derived neurons from BAFME patients with repeat expansions 105080 EN Yuki Nagasako Department of Neurology, Graduate School of Medicine, The University of Tokyo Mitsuru Ishikawa Department of Physiology, Keio University School of Medicine Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sopak Supakul Department of Physiology, Keio University School of Medicine Sumihiro Maeda Department of Physiology, Keio University School of Medicine Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Hideyuki Okano Department of Physiology, Keio University School of Medicine Benign adult familial myoclonus epilepsy (BAFME) is caused by intronic TTTCA and TTTTA repeat expansions in SAMD12 and other genes; the neuronal basis of cortical hyperexcitability, however, remains unclear. We generated induced pluripotent stem cell (iPSC)-derived glutamatergic and GABAergic neurons from three BAFME1 patients and examined functional and transcriptomic phenotypes. Patient-derived neurons retained the pathogenic repeat expansions and showed a tendency toward upstream intronic RNA accumulation. Calcium imaging revealed increased spontaneous Ca2 + transient frequency in both neuronal subtypes, indicating heightened activity. Pharmacological profiling demonstrated attenuated responses to calcium-permeable ƒ¿-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor (CP-AMPAR) blockade and GABAA receptor antagonism in GABAergic neurons, suggesting altered inhibitory signaling. RNA sequencing revealed transcriptomic alterations without differential expression of ion channels and neurotransmitter receptors. In glutamatergic neurons, ATF4-regulated genes, including SLC7A5 encoding LAT1, a Kv1.2 channel modulator, were downregulated. Reduced SLC7A5 expression was validated at both mRNA and protein levels. In GABAergic neurons, synapse-associated genes PTPRD and GPC6 were upregulated. TCERG1L and NLRP2 were suppressed across both neuronal subtypes. These findings suggest subtype-specific alterations may contribute to neuronal hyperexcitability in BAFME and provide a platform for mechanistic studies of repeat expansion-associated epilepsies. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1473-0502 65 5 2026 Association of initial interface formation time with CD34+ collection efficiency in continuous mononuclear cell collection: A retrospective study 104504 EN Hiroyuki Murakami Department of Hematology, Okayama University Hospital Keiko Fujii Department of Hematology, Okayama University Hospital Wataru Kitamura Department of Hematology, Okayama University Hospital Kazuhiro Ikeuchi Department of Hematology, Okayama University Hospital Joji Shimono Department of Hematology, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Okayama University Hospital Nobuharu Fujii Department of Hematology, Okayama University Hospital Background: Factors influencing CD34+ cell collection efficiency (CE) during peripheral blood stem cell harvesting have been investigated; however, the impact of procedural management remains unclear. In continuous mononuclear cell (CMNC) collection, a stable cell–plasma interface (IF) is formed through channel priming, initial IF establishment, and mononuclear cell (MNC) collection. Although IF instability is known to impair CE, the adequacy of initial IF formation has not been examined as an independent factor. Therefore, we focused on the time required for initial IF formation and its association with CE.<br> Methods: We retrospectively analyzed 291 Spectra Optia CMNC procedures (52 autologous and 239 allogeneic) performed between 2016 and 2025. Initial interface formation time (IFT) was defined as the interval from the start of the procedure to transition to MNC collection. CE2 was defined as the ratio of collected CD34+ cells to the product of pre-apheresis peripheral blood CD34+ cell concentration and processed blood volume. Results: CE2 was lower in autologous than in allogeneic collections (41.3% vs. 59.2%) and was associated with longer IFT (median, 18 vs. 15 min). CE2 correlated with white blood cell count (r = �|0.24), hematocrit (r = 0.36), and IFT (r = �|0.23; all p < 0.001). In multivariable analysis, these factors remained independently associated with CE2, and IFT was inversely correlated with hematocrit (r = �|0.44, p < 0.001).<br> Conclusion: IFT is independently associated with CE2 and provides insight into the early dynamics of IF formation during leukapheresis, highlighting an underexplored procedural aspect of CE. 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 ƒÀ-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.

Elsevier BV Acta Medica Okayama 0022-1759 541 2025 Development of a novel histidine-rich glycoprotein measurement system as a biomarker for sepsis 113868 EN Takaoki Uchiumi Diagnostic Drug Office, Shionogi & Co., Ltd. Masahiro Nishibori Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoko Inoue Diagnostic Drug Office, Shionogi & Co., Ltd. Hiroshi Nishi Diagnostic Drug Office, Shionogi & Co., Ltd. Norio Ota Diagnostic Drug Office, Shionogi & Co., Ltd. The plasma histidine-rich glycoprotein concentration is a marker of sepsis severity. In this study, we generated selective and specific monoclonal antibodies against histidine-rich glycoprotein for use in a prototype enzyme-linked immunosorbent assay-based in vitro diagnostic system. First, we investigated the properties of monoclonal antibodies produced by 21 hybridomas that we developed using immunized mice, and we identified monoclonal antibodies 69-1A and 75-2D to be the most suitable combination for use in the sandwich enzyme-linked immunosorbent assay. Wild-type histidine-rich glycoprotein (Form-1, 75 kDa) with a proline residue at amino acid position 204 is the most common isoform of the protein in humans, followed by its variant (Form-2, 77 kDa), which has a serine residue at position 204.<br> The epitope mapping was examined for the HRG amino acid sequence with 69-1A and 75-2D mAbs to achieve the identification of respective specific binding domains, though the other kinds of mAbs showed considerably complex domains. The identified epitopes recognized by 69-1A and 75-2D monoclonal antibodies did not span position 204. Furthermore, immunoprecipitation-immunoblotting analysis showed that the 69-1A and 75-2D monoclonal antibodies could bind to both Form-1 and Form-2 in human plasma samples. Thus, these two new antibodies can be used to clearly detect both forms of histidine-rich glycoproteins in human plasma samples. In our analysis of clinical samples by enzyme-linked immunosorbent assays using various combinations of our newly synthesized antibodies, we found that the histidine-rich glycoprotein concentration was significantly lower in plasma samples from septic patients than in those from healthy volunteers (p < 0.01). Thus, our novel analysis system using the new antibodies is expected to be a useful tool for sepsis research, and it may be adapted as an in vitro diagnostic tool for many other kinds of diseases in the future. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1746-8094 127 2026 Outcome-aware and interpretable subtyping of chronic kidney disease: an analysis of the FROM-J study 111090 EN Tianyi Shi Department of Computer Science, University of Tsukuba Xiucai Ye Department of Computer Science, University of Tsukuba Wenyu Xi Department of Computer Science, University of Tsukuba Akira Imakura Department of Computer Science, University of Tsukuba Kaori Mase Department of Nephrology, Faculty of Medicine, University of Tsukuba Ryoya Tsunoda Department of Nephrology, Faculty of Medicine, University of Tsukuba Chie Saito Department of Nephrology, Faculty of Medicine, University of Tsukuba Akihiko Kato Blood Purification Unit, Hamamatsu University School of Medicine Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoichi Maruyama Department of Nephrology, Nagoya University Graduate School of Medicine Takashi Wada Department of Nephrology and Rheumatology, Kanazawa University Ichiei Narita Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences Kunihiro Yamagata Department of Nephrology, Faculty of Medicine, University of Tsukuba Tetsuya Sakurai Department of Computer Science, University of Tsukuba Chronic kidney disease (CKD) affects approximately 10% of the global population and exhibits substantial heterogeneity in disease progression and clinical outcomes. Despite ongoing efforts to develop new therapeutic strategies, the number of patients progressing to end-stage kidney disease (ESKD) and the incidence of cardiovascular disease (CVD) continue to rise. Although severity classification systems for CKD are well established and refined, they remain insufficient to capture prognostically relevant patient subtypes. In this study, we developed an outcome-aware and interpretable clustering framework for CKD subtyping using data from the FROM-J cohort with prognostic follow-up. A supervised XGBoost model was first trained to predict a ≥ 30% decline in estimated glomerular filtration rate (eGFR), a surrogate marker of CKD progression. SHAP (SHapley Additive exPlanations) values derived from this model were then used to quantify outcome-relevant feature contributions. Based on these feature attributions, a similarity graph was constructed, and spectral clustering was performed to identify patient subtypes driven by prognostic relevance. The proposed framework identified four CKD subtypes with distinct baseline clinical characteristics and significantly different risks of renal replacement therapy (RRT) and cardiovascular disease (CVD) events. Serum albumin, blood urea nitrogen (BUN), and smoking status consistently emerged as key features defining subtype structure and prognosis. Robust risk stratification was preserved even when clustering was restricted to these three routinely measured variables. Overall, our findings demonstrate that integrating outcome-driven feature attribution into clustering enables interpretable and clinically relevant CKD subtyping, providing a practical approach for characterizing disease heterogeneity and supporting risk stratification and personalized management. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2949-6780 8 2026 Immersion is not enough: Design quality as the key determinant of perceived effectiveness and usage intention in educational virtual reality 100152 EN Achmad Samsudin Universitas Pendidikan Indonesia Muhammad Zahran Okayama University Eki Nugraha Universitas Pendidikan Indonesia Hadi Nasbey Universitas Negeri Jakarta Mustafa Sozbilir Atatürk University Nor Farahwahidah Abdul Rahman Universiti Teknologi Malaysia Takashi Irie Okayama University Immersive technologies such as Virtual Reality (VR) are increasingly used to support conceptual understanding in science education, yet perceived learning benefits depend on the quality of system design rather than immersion alone. This study investigates how four design-quality dimensions�\Visual and Technological Design (VT), Aesthetic Quality (AQ), Curriculum Alignment (CA), and Digital Feasibility (DF)�\influence learners' Perceived Effectiveness (PE) and Intention to Use (IU) the VARIASI VR simulation, which visualizes particle behavior across phase states of matter. Using an explanatory sequential mixed-methods design, quantitative data from 60 participants were analyzed using PLS-SEM, followed by reflexive thematic analysis of open-ended responses. Results show that VT, AQ, CA, and DF each significantly predict PE, demonstrating that learners' perception of effectiveness depends on the coordinated alignment of conceptual clarity, emotional resonance, and system reliability. However, none of these dimensions directly predicted IU, and the PE �¨ IU relationship was positive but marginal, reflecting learners�f need for procedural guidance and comfort to sustain voluntary adoption. Qualitative findings reveal that while VR enhanced conceptual clarity and engagement, continued use depended on familiarity, scaffolding, and physical comfort. The study highlights that effective VR-based science learning experiences emerge when immersive environments are not only well-designed but pedagogically framed to support confidence and sustained use. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2165-0497 2026 Escalation of CTX-M-producing extensively drug-resistant Shigella spp. in Kolkata, India, following the COVID-19 pandemic e02824-25 EN Puja Bose Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Gourab Halder Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Pratanu Kayet Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections Goutam Chowdhury Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Surajit Basak Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections Deboleena Roy Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Daisuke Imamura Research Center for Intestinal Health Science, Okayama University Shin-ichi Miyoshi Research Center for Intestinal Health Science, Okayama University Masatomo Morita Department of Bacteriology I, National Institute of Infectious Diseases Thandavarayan Ramamurthy Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Hemanta Koley Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Santasabuj Das Division of Clinical Medicine, ICMR-National Institute for Research in Bacterial Infections Asish Kumar Mukhopadhyay Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Shigella spp. is recognized by the World Health Organization as a high-priority pathogen due to its global prevalence, unique pathogenic mechanisms, and growing antimicrobial resistance (AMR). Nearly half of all Shigella strains worldwide are now multidrug-resistant (MDR), and the emergence of extensively drug-resistant (XDR) variants�\resistant to ciprofloxacin, ceftriaxone, and azithromycin�\has severely limited effective treatment options. The present study is based on prospective laboratory surveillance involving 323 Shigella isolates collected during 2021–2023, with pre-COVID-19 pandemic data included from a previously published study solely for historical comparison. The presence of antibiotic resistance genes (ARGs) was investigated, and whole-genome sequencing (WGS) was performed on representative isolates to assess phylogenetic relatedness with global isolates. Approximately 10% of isolates exhibited resistance to third-generation cephalosporins. While only 3% of Shigella isolates carried the blaCTX-M-15 gene from 2013 to 2019, its prevalence increased to 26% by 2022–2023. Among 38 ceftriaxone-resistant S. sonnei isolates, 33 were also resistant to azithromycin, categorizing them as XDR. These isolates showed 48% clonal similarity and high phylogenetic resemblance to the isolates reported from England. Hybrid genome assembly revealed a plasmid harboring both the blaCTX-M-15 and mphA ARGs. Conjugation experiments and plasmid profiling confirmed the plasmid�fs transferability. We report a rising trend in third-generation cephalosporin resistance among Shigella spp., primarily driven by the spread of extended-spectrum ƒÀ-lactamase-producing S. flexneri and the emergence of XDR S. sonnei. These findings underscore the urgent need for strengthened national AMR containment strategies and enhanced international surveillance of cephalosporin-resistant Shigella to mitigate this growing public health threat. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0024-4937 542-543 2026 Serpentinization parageneses controlled by lithological variations among olivine gabbro and peridotite from the Atlantis Massif, Mid-Atlantic Ridge 108716 EN Toshio Nozaka Department of Earth Sciences, Okayama University Shun Kazumata Department of Earth Sciences, Okayama University Frieder Klein Department of Marine Chemistry and Geochemistry, Woods Hole Oceanographic Institution Serpentinization of olivine impacts the geochemical and ecological environment via molecular hydrogen production, promoted by iron oxidation to form magnetite and ferric iron in serpentine. Previous studies suggested that serpentinization proceeds with various reactions and the extent of iron oxidation is variable depending on the reaction pathways. To examine the effect of lithological variation on reactions at an incipient stage of serpentinization, we carried out microscopic observations, electron-probe analyses, and Raman spectroscopy of serpentine veins cutting olivine in gabbroic rocks and peridotites from the Atlantis Massif, Mid-Atlantic Ridge. The results indicate that the serpentine veins in the proximity of olivine dominantly comprise lizardite mixed with variable minor phases or components depending on igneous lithology: brucite in peridotites, troctolites, and primitive olivine gabbros; cronstedtite-bearing serpentine, commonly without brucite, in some troctolites and slightly evolved olivine gabbros; and neither brucite nor cronstedtite component in evolved olivine gabbros. This suggests that incipient-stage serpentinization paragenesis is dominantly controlled by silica activity reflecting lithological variation. In addition to magnetite, the formation of cronstedtite in gabbroic rocks has the potential to produce hydrogen. The presence or absence of brucite and cronstedtite could affect the timing and magnitude of iron oxidation and hydrogen production during serpentinization. Considering the predominance of gabbroic rocks in the lower oceanic crust, the variation in incipient-stage serpentinization paragenesis in gabbroic rocks may have an impact on the redox state and ecological environment around the (sub)seafloor. No potential conflict of interest relevant to this article was reported.

American Society for Horticultural Science Acta Medica Okayama 0018-5345 61 8 2024 Shoot-to-Root Ratio Serves as an Early Practical Indicator of Tipburn Risk in Lisianthus [Eustoma grandiflorum (Raf.) Shinn.] Seedlings 1884 1891 EN Nethone Samba Faculty of Food and Agricultural Sciences, Fukushima University Kureha Iki Fukushima Prefectural Iwaki Agriculture and Forestry Office Tanjuro Goto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Minori Hikawa-Endo Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ken-ichiro Yasuba Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoko Miyama Faculty of Food and Agricultural Sciences, Fukushima University, Fukushima, 960-1296, Japan; and The United Graduate School of Agricultural Sciences, Iwate University Tipburn is a calcium-related physiological disorder that reduces lisianthus seedling quality, yet the factors underlying cultivar differences remain unclear. This study evaluated 10 lisianthus cultivars to determine whether the shoot-to-root (S/R) ratio and key physiological traits influence tipburn susceptibility. Seedlings were grown in a closed production system with restricted root volume and once-daily irrigation to enhance symptom expression. The S/R ratio varied significantly among cultivars (2.82–4.02) and was strongly correlated with tipburn incidence (r = 0.744, P < 0.05) and severity (r = 0.706, P < 0.05). Cultivars with higher S/R ratios exhibited greater tipburn, whereas those with lower ratios showed little to no symptoms. Diurnal measurements of transpiration, stomatal conductance, leaf temperature, and electron transport rate revealed cultivar-specific physiological patterns; however, midday transpiration showed only a weak association with tipburn. These results indicate that biomass allocation, rather than physiological activity alone, is the primary factor governing tipburn susceptibility. The S/R ratio represents a simple and practical indicator for identifying high-risk cultivars in nursery production. Future studies should investigate the roles of calcium transport, developmental stage, and irrigation management in mitigating tipburn occurrence. 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�fs 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.

Frontiers Media SA Acta Medica Okayama 2296-4185 14 2026 High horizontal force and lateral force transmission induced by the twist of the Achilles tendon 1874501 EN Shota Enomoto Graduate School of Education, Okayama University Kohta Ito Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST) The Achilles tendon�\the largest and strongest of the many tendons in the human body�\consists of subtendons arising from each head of the triceps surae. These subtendons run helically and intertwine to form a twisted three-dimensional structure. More than a century has passed since the twisted structure of the Achilles tendon was first described, and numerous studies have investigated its functional morphology. However, it remains unclear how the presence or degree of twist affects the mechanical function of the lower limbs. Here, using finite element models of the Achilles tendon with and without twist, we show that the presence and degree of twist can modulate the forces transmitted from muscle to skeleton in a complex manner. In contrast to the model without twist, the twisted models clearly exhibit anterolaterally directed horizontal forces at the distal end under a simple proximal tensile load. The lateral and anterior components reach approximately 101 N and 63 N, respectively. Furthermore, the twisted structure induces inter-subtendon force transmission, and the magnitude of the transmitted force increases with increasing degree of twist. These results indicate that the uniaxial contractile force generated by the triceps surae is transformed into triaxial forces by the twisted Achilles tendon and is redistributed in a complex three-dimensional manner through inter-subtendon interactions. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1344-6223 84 2026 Factors that delay discovery in cases of death at home in Japan 102895 EN Yukie Yamasaki Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nanako Tamiya Department of Health Services Research, Faculty of Medicine, University of Tsukuba Hideki Yamamoto Department of Environmental Health, Faculty of Pharma-Science, Teikyo University Masanobu Miura Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaori Taniguchi Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chie Kobayashi Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Motomura Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ayako Himemiya-Hakucho Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Miyaishi Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences In Japan, solitary deaths have become a social issue, with an increasing number of cases in which the body is discovered long after death. This study aimed to clarify the factors underlying such delays. Cases of death at home were extracted from forensic autopsies. In each case, we collected information about the deceased and their living conditions. The postmortem interval until finding (PMI-f) was calculated by measuring the time between death and discovery. We classified the cases into long PMI-f (LPMI-f; having PMI-f of ≥3 days) and short PMI-f (SPMI-f; having PMI-f of <3 days), and examined the factors that lead to LPMI-f. The characteristics of the group living alone with a PMI-f of <24 h and living with family or acquaintances with an LPMI-f were also analyzed. Among the 420 cases included, 244 (58.1%) were in the LPMI-f group. The LPMI-f group had higher number of males; older individuals; those living alone; those found inside their homes; single, retired, or non-employed individuals; those without long-term care certification; and those with drinking habits. Forty-seven individuals lived alone and had PMI-f of <24 h. Regular visits from relatives living separately led to early detection after death. In the LPMI-f group, 56 individuals lived with family or acquaintances. The absence of regular visits can result in delayed discovery after death; however, the time between death and discovery could be shortened by implementing systems such as allowing neighbors to check the person's safety by noticing uncollected mail. 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.<br> 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.<br> 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).<br> 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.

Elsevier BV Acta Medica Okayama 1078-8174 32 6 2026 Students�f perceptions of an electronic one-minute paper in a radiography training programme: An exploratory cross-sectional questionnaire study 103486 EN Y. Komatsu Division of Radiological Technology, Graduate School of Health Sciences, Okayama University S. Abe Department of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care Sciences S. Tsudou Department of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care Sciences Y. Yamamoto Division of Radiological Technology, Graduate School of Health Sciences, Okayama University Y. Tanabe Faculty of Health Sciences, Department of Radiological Technology, Okayama University Medical School, Okayama University Introduction: Formative assessment can support health professions education; however, reports on electronic 1-min papers as classroom feedback and engagement tools in radiography programmes remain limited. This study explored radiography students�f perceptions of an electronic 1-min paper, focusing on in-class reflection, ease of asking questions, and instructor feedback.<br> Methods: An electronic 1-min paper was used in a radiotherapy course across 45 class sessions in the 2024 academic year for third-year students enrolled in a 4-year radiography programme. Each 90-min class comprised a 60-min lecture, 10-min completion of the paper, and 20-min instructor feedback. After the course, a de-identified online questionnaire was administered. Eleven 5-point Likert-scale items were analysed using descriptive statistics and Spearman's rank correlations. Free-text responses were analysed using inductive qualitative content analysis.<br> Results: Of the 77 eligible students, 74 responded (96.1%). Ease of use received the highest rating (mean, 4.76; standard deviation [SD], 0.52), followed by ease of asking questions (mean, 4.32), question resolution (mean, 4.16), and usefulness of instructor feedback (mean, 4.08). Motivation to review after class was lowest (mean, 3.04; SD, 1.16). Active participation showed a strong positive association with in-class concentration (rs = 0.815; P < 0.001). Free-text responses indicated reflection and improved understanding, anonymous sharing of questions, active listening and concentration, and suggestions for improvement.<br> Conclusion: The electronic 1-min paper was widely accepted and perceived to support in-class reflection, question expression, and immediate feedback. However, students�f perceptions of its influence on out-of-class review motivation were limited. The findings indicate perceived value and engagement rather than demonstrated educational effectiveness.<br> Implications for practice: Electronic 1-min papers may help instructors identify students�f questions and respond during class, providing a practical approach to in-class feedback. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0941-4355 34 8 2026 Incidence and impact of odontogenic infection-related febrile episodes during perioperative doxorubicin-cyclophosphamide or docetaxel-cyclophosphamide chemotherapy for breast cancer 747 EN Yoshihiko Soga Division of Hospital Dentistry, Okayama University Hospital Kumiko Matsuzaki Division of Hospital Dentistry, Okayama University Hospital Hirotaka Kosaki Division of Hospital Dentistry, Okayama University Hospital Tomoko Kishimoto Division of Hospital Dentistry, Okayama University Hospital Aiko Yoshitomi Division of Hospital Dentistry, Okayama University Hospital Makoto Kajizono Department of Pharmacy, Okayama University Hospital Takashi Makita Department of Pharmacy, Okayama University Hospital Yuta Tanaka Department of Pharmacy, Okayama University Hospital Yoshito Zamami Department of Pharmacy, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Department of Surgery, Kawasaki Medical School General Medical Center Background Doxorubicin-cyclophosphamide (AC) and docetaxel-cyclophosphamide (TC) are standard perioperative chemotherapy regimens for breast cancer. Febrile neutropenia (FN) is a common adverse event, and odontogenic infections may contribute to febrile episodes. This study was performed to investigate the incidence and impact of febrile episodes clinically associated with odontogenic infections during AC and TC chemotherapy.<br> Methods A total of 408 patients with breast cancer receiving 4 cycles of AC (n = 285) or TC (n = 123) between 2015 and 2020 were included in this single-center retrospective study. Patients recorded daily axillary temperatures and oral symptoms. Dental evaluations were performed when oral infection was suspected. Febrile episodes (≥ 37.5 �‹C) were assessed, and their clinical association with odontogenic infections was determined based on dental records and the documented clinical course. Relative dose intensity (RDI) was calculated to assess chemotherapy delivery.<br> Results Overall, 40.2% of patients experienced febrile episodes, and the frequency was higher in the TC group (48.8%) than the AC group (36.5%, P = 0.02). Febrile episodes associated with oral infections occurred in 9.1% of patients, of which 78.4% were clinically associated with odontogenic infections (7.1% of all patients). Most such episodes occurred during the first chemotherapy cycle (79.3%, P < 0.01). Chemotherapy RDI was reduced in three patients with febrile episodes clinically associated with odontogenic infection, but remained ≥ 85%.<br> Conclusions Febrile episodes clinically associated with odontogenic infections occurred in approximately 7%–8% of patients with breast cancer receiving perioperative AC or TC chemotherapy, predominantly during the first cycle. Odontogenic infections should be considered one possible source of febrile episodes during treatment. 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.

Elsevier BV Acta Medica Okayama 1323-8930 75 3 2026 Outcomes following the discontinuation of biologic therapy in patients with severe asthma 400 408 EN Tadao Nagasaki Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital Hisako Matsumoto Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Takashi Iwanaga Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Kazuto Matsunaga Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University Kiyoshi Sekiya Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital Tomoya Harada Department of Multidisciplinary Internal Medicine, Division of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University Shogo Sakurai Department of Respiratory Medicine, Shizuoka General Hospital Norihiro Harada Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine Toshiyuki Koya Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Koichi Fukunaga Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine Takeshi Kaneko Department of Pulmonology, Yokohama City University Graduate School of Medicine Kazuhisa Asai Department of Respiratory Medicine, Graduate School of Medicine, Osaka Metropolitan University Yuko Komase Department of Respiratory Medicine, St.Marianna University School of Medicine, Yokohama Seibu Hospital Yasuhiro Gon Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine Akihiko Tanaka Department of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of Medicine Hironori Sagara Department of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of Medicine Hironobu Sunadome Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University Tatsuya Nagano Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine Yoichi Nakamura Medical Center for Allergic and Immune Diseases, Yokohama City Minato Red Cross Hospital Akio Niimi Department of Respiratory Medicine, Allergy, and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences Noboru Hattori Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University Takashi Hajiro Department of Respiratory Medicine, Tenri Hospital Hajime Fujimoto Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine Masayuki Hojo Division of Respiratory Medicine, National Center for Global Health and Medicine Nobuaki Miyahara Department of Medical Technology, Okayama University Graduate School of Health Sciences Masafumi Yamaguchi Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science Kimiko Tsuji Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University Akiko Sano Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Ryuta Haraguchi Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Hiroyuki Sano Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Masato Muraki Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital Yuji Tohda Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Background: Biologic therapies are pivotal in managing severe asthma. Despite their efficacy, some patients discontinue biologics, with varying outcomes. Predictors of successful versus unsuccessful discontinuation remain poorly defined. This study aimed to identify clinical factors associated with post-discontinuation outcomes in a real-world practice.<br> Methods: This retrospective cohort included adults with severe asthma who had received biologics for at least 12 months and subsequently discontinued therapy for a minimum of three consecutive months. We assessed the effects of baseline blood eosinophilia (≥300 cells/ƒÊL), residual sputum symptoms during biologic therapy, treatment responsiveness, biologic class, and discontinuation reasons on post-discontinuation asthma exacerbation rates using multivariable Cox models.<br> Results: A total of 118 patients were analyzed. The Kaplan–Meier analysis estimated a 65 % exacerbation-free probability at 12 months after discontinuation. Factors associated with successful discontinuation included a robust clinical response and absence of exacerbations before cessation. Conversely, baseline eosinophilia, residual sputum symptoms during biologics, and discontinuation due to inadequate therapeutic response or financial burden were associated with post-discontinuation exacerbations. In class-stratified restricted models, persistent sputum remained significantly associated with post-discontinuation exacerbations after stopping anti-IL-5 therapies, while baseline eosinophilia was associated with post-discontinuation exacerbations after stopping anti-IgE or anti-IL-4Rƒ¿. Among patients with sputum symptoms or poor-response discontinuation, the overall frequency of exacerbations declined after discontinuation.<br> Conclusions: Baseline eosinophilia, persistent sputum during therapy, and discontinuation prompted by poor response or cost may serve as risk factors for post-discontinuation exacerbations; however, risk is phenotype- and class-dependent. Careful patient selection and monitoring are essential when considering the discontinuation of biologic treatment. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1745-6215 27 1 2025 Oral health care during pregnancy to prevent preterm birth and low birth weight: study protocol for a randomized controlled trial 35 EN Junko Yasuoka Division of Global Health Sciences, Graduate School of Public Health, St. Luke�fs International University Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunsuke Okada Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University Prodhan MD Rubayet Alam Department of Orthodontics, Dental Unit, TMSS Medical College & Rafatullah Community Hospital Akira Shibanuma Department of Community and Global Health, Graduate School of Medicine, The University of Tokyo Keiko Nanishi Office of International Academic Affairs, Graduate School of Medicine, The University of Tokyo Yoko Sato Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University Md. Zahid Hossain Department of Periodontology and Oral Pathology, Holy Family Red Crescent Medical College Hospital Musfiqa Aman Department of Periodontology, Dental Unit, TMSS Medical College & Rafatullah Community Hospital Fahmida Karim Department of Obstetrics & Gynecology, Holy Family Red Crescent Medical College Hospital Sultana Razia Department of Obstetrics & Gynecology, TMSS Medical College & Rafatullah Community Hospital Rifat Rezwana Department of Molecular and Cellular Biochemistry, Division of Oral Health, Brain Health and Total Health, Faculty of Dental Science, Kyushu University Md Mahmudur Rahman Global Communication Center, Grameen Communications Nusrat Jahan Khan Global Communication Center, Grameen Communications Naoki Nakashima Department of Medical Informatics, Graduate School of Medical Sciences, Kyushu University Rafiqul Islam Division of Healthcare Digital Transformation, Kyushu University Kimiyo Kikuchi Department of Research Promotion, Institute for Asian and Oceanian Studies, Kyushu University Background Periodontal disease during pregnancy has been associated with an increased risk of preterm birth (PTB) and low birth weight (LBW). However, most previous interventional studies have reported that scaling and root planing (SRP), a form of basic periodontal treatment, is insufficient to effectively prevent PTB and LBW. Recent systematic reviews and meta-analyses suggest that combining SRP with routine use of chlorhexidine gluconate (CHG) mouthwash may reduce the risk of these adverse birth outcomes by approximately half. This study will be among the first randomized controlled trials (RCTs) to evaluate the potential synergistic effects of this combined approach on improving birth outcomes.<br> Methods This multi-center, three-arm RCT will be conducted at two hospitals in Dhaka and Bogura, Bangladesh, between April 2025 and September 2026. A total of 480 pregnant women less than 20 weeks�f gestation attending antenatal checkups will be recruited. Participants diagnosed with periodontal disease will be randomly assigned to either an intervention group or a positive control group. Participants without periodontal disease will be assigned to a negative control group. The intervention consists of SRP combined with continued use of CHG mouthwash throughout pregnancy. The primary outcome will be the rate of PTB. Secondary outcomes include the birth weight of the newborn baby, maternal periodontal status, and oral health-related quality of life (OHRQoL). Effectiveness will be assessed by comparing outcomes across the study groups.<br> Discussion The oral health intervention is expected to improve both birth outcomes and maternal oral health. Demonstrating its effectiveness in a real-world setting may support the integration of oral health care into broader maternal, neonatal, and child health strategies, particularly in resource-limited settings.<br> Trial registration UMIN Clinical Trials Registry. UMIN000057519. Registered on April 4, 2025. https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000065719. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1756-0500 19 1 2025 Plasma expression levels of microRNA-101 are downregulated in patients with Parkinson�fs disease 19 EN Tomohiro Omura Department of Pharmacy, Kobe University Hospital Hiroki Nishiguchi Department of Pharmacy, Kobe University Hospital Haruka Kaneda Department of Pharmacy, Kobe University Hospital Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Kotaro Itohara Department of Pharmacy, Kobe University Hospital Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyasu Sakane Department of Pharmaceutical Technology, Kobe Pharmaceutical University Ikuko Yano Department of Pharmacy, Kobe University Hospital Objective Parkinson�fs disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons. Endoplasmic reticulum (ER) stress contributes to PD pathogenesis, with the ER-associated degradation (ERAD) system playing a protective role. HRD1, an ER-resident ubiquitin ligase, and its stabilizer SEL1L are involved in ERAD and neuronal survival. This study investigated alterations in the plasma levels of microRNA-101 (miR-101), which targets SEL1L, in patients with PD, and its potential role as a biomarker.<br> Results Plasma miR-101 levels in patients with PD significantly decreased compared with those in healthy controls. Receiver operating characteristic curve analysis demonstrated that miR-101 could moderately discriminate patients with PD from healthy individuals (area under the curve = 0.781, 95% confidence interval = 0.547–1.00). The optimal cutoff, as determined by the Youden index, was 0.737 (expression ratio relative to that in the healthy control group), yielding a sensitivity of 50% and specificity of 100%. These results suggested that reduced plasma miR-101 expression may reflect the pathophysiological state of PD, and miR-101 has potential as minimally invasive biomarker for PD. No potential conflict of interest relevant to this article was reported.

‰ªŽR‘åŠwŒo�ÏŠw‰ï Acta Medica Okayama 2433-4146 58 1 2026 ƒ‰ƒCƒuƒ‰ƒŠ�EƒXƒL�[ƒ}‚É‚æ‚é‘åŠw�}�‘ŠÙ�\‘¢‚̉Ž‹‰»‚Æ’mŽ¯‘n‘¢ �\‹¤—L”F’m‚ÌŒ`�¬‚ÉŠî‚­Œ¤‹†˜g‘g‚Ý‚Ì�\’z�\ 1 19 EN Kensuke Kobayashi Satoru Miyazaki 10.18926/OER/70973 �@This study proposes a theoretical framework for understanding the relationship between the structural representation of university libraries and knowledge creation. In recent years, university libraries have experienced significant transformations due to the digitization of scholarly information, the expansion of research data management, and the increasing importance of learning support services. As their functions diversify, it has become increasingly difficult to comprehensively understand the structure and roles of university libraries.<br> �@To address this issue, this study focuses on the concept of a library schema, which represents the structural relationships among the elements that constitute a library, including people, resources, services, and activities. While previous research has discussed methods for organizing library components, little attention has been paid to how structural understanding of libraries contributes to knowledge creation and service value.<br> �@Drawing on schema theory, shared cognition in organizational studies, and the knowledge creation theory of Nonaka and Takeuchi, this study constructs a conceptual framework linking library schema visualization, shared cognition, interaction, knowledge creation processes, and library service value. The framework proposes that visualization of library structure through a library schema promotes shared cognition among librarians and users, which in turn facilitates interactions that activate knowledge creation processes. These processes ultimately contribute to the creation of library service value that supports learning and research activities.<br> �@Furthermore, the framework introduces two moderating factors: schema representation methods and operational constraints of library management. Based on this framework, six research propositions are presented.<br> �@By integrating concepts from library and information science with knowledge management theory, this study contributes to the theoretical understanding of university libraries as knowledge infrastructures and provides a foundation for future empirical research on knowledge creation in library environments. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-6367 32 4 2026 Spatial Transcriptomics Analysis of Macrophage-to-Myofibroblast Transition in Bronchiolitis Obliterans Following Hematopoietic Stem Cell Transplantation 454 465 EN Akira Yamamoto Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Keisuke Seike Department of Hematology and Oncology, Okayama University Hospital Seiichiro Sugimoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Yusuke Naoi Center for Comprehensive Genomic Medicine, Okayama University Hospital Tomohiro Nagano Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Saya Kubota Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Kambara Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine Kanako Fujiwara Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiki Terao Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Oyama Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mari Kunihiro Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kobayashi Department of Hematology and Oncology, Okayama University Hospital Takumi Kondo Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Bronchiolitis obliterans (BO) is a severe, fibrotic manifestation of chronic graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Macrophage-derived TGF-ƒÀ is linked to GVHD-related fibrosis; however, its role in BO remains unclear. Given emerging evidence of macrophage-to-myofibroblast transition (MMT) in fibrosis, this study aimed to investigate whether MMT contributes to BO development. We analyzed lung samples from 3 HSCT recipients with BO who underwent lung transplantation, with tissues from 2 patients with lung cancer as controls. Immunofluorescent staining for CD68, CD206, and ƒ¿-SMA was used to identify cells undergoing MMT. Spatial transcriptomics was performed to profile gene expression in foamy macrophages across anatomical regions and histological stages, compared to control peribronchiolar regions. Immunostaining showed strong co-expression of CD68, CD206, and ƒ¿-SMA in foamy macrophages within and surrounding bronchioles in BO samples, with minimal expression in controls, suggesting MMT involvement. In BO, spatial transcriptomics revealed upregulation of macrophage- and TGF-ƒÀ signaling genes, with distinct stage- and region-specific gene expression patterns. Unsupervised clustering revealed a shift from inflammation to fibrosis. These findings indicate that MMT contributes to fibrosis in BO. Gene expression shifts from inflammation to fibrosis as the disease advances, underscoring the importance of early intervention. No potential conflict of interest relevant to this article was reported.

Fuji Technology Press Ltd. Acta Medica Okayama 1883-8030 21 1 2026 Developing and Implementing a Disaster Prevention Game to Enhance Local Understanding 128 135 EN Miri Shirokane Okayama University Airi Yamada Okayama University Ryo Misawa Okayama University Nobuhisa Matta Okayama University This study developed and implemented a local disaster prevention sugoroku-style game to address challenges in preserving and transmitting regional knowledge in areas with high population mobility. Many Japanese communities face both natural and social vulnerabilities, and effective disaster education requires linking hazard knowledge with local characteristics. Conducted at Sonan Junior High School in Okayama, the project combined lectures, workshops, and a community engagement event. Students learned about regional topography, land use, and disaster history and used this knowledge to design quizzes, rules, and disaster scenarios for the game. The final sugoroku set included a map-based board, thematic quiz areas, and preparedness item cards, enabling players to predict damage and consider appropriate actions. After creating the game, students shifted from identifying familiar landmarks to describing concrete disaster impacts such as liquefaction or infrastructure collapse. Interaction with local residents further enriched learning through shared experiences. The model proved feasible in terms of time and cost, and its structure is easily adaptable to other regions by incorporating local information. The findings suggest that this participatory, place-based approach enhances imagination, self-efficacy, and intergenerational knowledge transfer, contributing to community-wide disaster preparedness. Future studies will examine long-term educational impacts and broader regional applications. No potential conflict of interest relevant to this article was reported.

Japan Neurosurgical Society Acta Medica Okayama 0470-8105 66 3 2026 Full-endoscopic Laminotomy Is Effective for Lumbar Spinal Stenosis with Low-grade Spondylolisthesis: A Comparative Cohort Study 107 115 EN Kyohei KIN Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryoji TOMINAGA Department of Orthopaedics, Iwai Orthopaedic Medical Hospital Kento TAKEBAYASHI Department of Orthopaedics, Iwai Orthopaedic Medical Hospital Hiroki IWAI Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirohiko INANAMI Department of Orthopaedics, Iwai Orthopaedic Medical Hospital Hisashi KOGA Department of Orthopaedics, Iwai Orthopaedic Medical Hospital The optimal management of lumbar spinal canal stenosis with spondylolisthesremains controversial, particularly when choosing between decompression alone or decompression with fusion. Current evidence is based on conventional open or endoscopy-assisted surgeries, with limited data on full-endoscopic decompression. This study aimed to assess the impact of spondylolisthesis on outcomes after full-endoscopic laminotomy by evaluating back pain-related disability scores in patients with lumbar spinal canal stenosis, with and without spondylolisthesis. A retrospective analysis was conducted at Iwai Orthopaedic Hospital, Japan. Patients with lumbar spinal canal stenosis who underwent full-endoscopic laminotomy between January 2021 and December 2022 were included and categorized into those without spondylolisthesis and those with spondylolisthesis. Postoperative Oswestry Disability Index scores at 2 years were compared in the groups using multivariable linear regression, adjusting for confounding factors. Exploratory analyses were also conducted to identify factors affecting the Oswestry Disability Index in the patients with lumbar spinal canal stenosis with spondylolisthesis group. Statistical significance was set at p < 0.05. The study included 80 patients, with 40 in each group. Both groups showed improved postoperative Oswestry Disability Index. There was no significant association between spondylolisthesis and postoperative Oswestry Disability Index. However, cauda equina redundancy negatively affected postoperative Oswestry Disability Index improvement in the patients with lumbar spinal canal stenosis with spondylolisthesis group. Full-endoscopic laminotomy is an effective surgical option for lumbar spinal canal stenosis, leading to significant alleviation of disability and improvements in quality of life, regardless of spondylolisthesis. Full-endoscopic laminotomy may offer similar functional improvements regardless of the presence of low-grade spondylolisthesis, supporting its role as a less invasive alternative to fusion. No potential conflict of interest relevant to this article was reported.