Kazakhstan Society of Geneticists and Breeders Acta Medica Okayama 3134-6359 1 3 2026 Advances and Future Perspectives of Targeted Mutagenesis in Barley 202615 EN Hiroshi Hisano Institute of Plant Science and Resources, Okayama University Targeted mutagenesis technologies, commonly referred to as “genome editing”, have rapidly become transformative tools in crop breeding. Modern crop production faces mounting challenges such as climate change, emerging diseases, and shifting quality demands, creating an urgent need for breeding approaches that enable more precise genetic improvement within shorter timeframes. Targeted mutagenesis capable of introducing mutations accurately and efficiently began with the development of meganucleases and subsequently evolved through ZFNs, TALENs, and CRISPR/Cas systems. Recent technological advances, including multiplex editing and DNA-free genome editing, have made direct modification of elite cultivars increasingly feasible, helping to overcome long-standing barriers associated with genotype dependency and the complexity of polyploid genomes. Targeted mutagenesis has now been applied to a wide range of breeding targets, including disease resistance, tolerance to abiotic stresses, yield-related traits, and quality traits. Moreover, machine learning and AI are beginning to support target selection and phenotype prediction, ushering in an era in which genome editing can be integrated into breeding programs more rationally and efficiently. These scientific developments coincide with regulatory shifts in many countries toward easing restrictions on new genomic techniques (NGTs), particularly by treating SDN-1 genome-edited crops equivalently to those produced through conventional breeding. Such changes are expected to accelerate field trials, commercialization, and international collaboration. Nevertheless, several challenges remain, including bottlenecks in transformation efficiency, off-target assessment, the control of complex traits, societal acceptance, and unresolved regulatory details. Even so, genome editing is poised to become a central technology in next-generation cereal breeding, enabling the development of cultivars with greater resilience, productivity, and adaptability to diverse industrial needs. 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 μM)-induced cytotoxicity, with an effective concentration (EC50) of 0.54 μM, 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 μM. 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 “intensive surveillance” within Japan's structural norms of autonomy: maternal identity negotiation among long-term Peruvian migrant mothers (1990–2025) 1944754 EN Katia Sara Huaman Palomino Graduate School of Humanities and Social Sciences, Okayama University Yoshitsugu Hirata Faculty of Education, Okayama University Introduction: This study examines how Peruvian mothers who have settled in Japan for decades rework their identities as mothers. These women were raised with the belief that being a good mother means constantly watching over and protecting their children. But in Japan, child-rearing pushes children toward independence from a young age. This study asks: What happens when these two different approaches of mothering meet? Methods: We interviewed 21 Peruvian mothers who had lived in Japan for 17–35 years. Results: The analysis identified four identity positions to this cultural friction. The first is holding firmly to Peruvian maternal scripts (“Ideological Retention”). The second is following Japanese conventions in public while keeping Peruvian ways at home (“Compartmentalization”). The third is moving away from inherited protective scripts and adopting Japanese norms of independence (“Assimilation”). The fourth is blending elements of both into a maternal self that is “neither the one nor the other” (a “Third Space”). Discussion: This study helps us understand that migrant mothers do not simply choose between their home and new cultures. Instead, they actively work to create a way of mothering through a process we call Reflexive Continuity that makes sense for their unique situations. No potential conflict of interest relevant to this article was reported.

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

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

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.

Elsevier BV Acta Medica Okayama 0008-6215 340 1 2005 Synthesis and structural analysis of 6-deoxy-6-hydroxyphosphinyl-d-fructopyranose derivatives 31 37 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Kumiko Imai Department of Chemistry, Faculty of Science, Okayama University Yurij V. Prikhod’ko Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University 3,4-Di-O-benzyl-6-deoxy-6-diethoxyphosphinyl-1,2-O-isopropylidene-β-d-fructofuranose (13) was prepared from the known 1,2-O-isopropylidene-6-O-tosyl-β-d-fructofuranose in five steps. Reduction of 13 with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by the action of hydrochloric acid and then hydrogen peroxide, afforded the 6-deoxy-6-hydroxyphosphinyl-d-fructopyranose derivative. This was converted into the 1,2,3,4,5-penta-O-acetyl-6-deoxy-6-methoxyphosphinyl-d-fructopyranoses, whose structure and conformation were established by 1H NMR spectroscopy. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Cinnamyl alcohol dehydrogenase (CAD) underlies the orange lemma trait and lignin reduction in barley 30805 EN Kazuhiro Sato Institute of Plant Science and Resources, Okayama University Maho Morita Institute of Plant Science and Resources, Okayama University Nami Yamaji Institute of Plant Science and Resources, Okayama University Rinka Kako Graduate School of Agricultural Science, Setsunan University Tomokazu Ushijima Graduate School of Agricultural Science, Setsunan University Hiroshi Hisano Institute of Plant Science and Resources, Okayama University Barley (Hordeum vulgare L.) is one of the world’s major cereal crops and is widely used for feed, brewing, and food. Reducing lignin content in barley grain and straw is beneficial for improving forage digestibility and enhancing the efficiency of bioethanol production. The orange lemma mutation―characterized by orange pigmentation of husks and nodes―has long been associated with altered lignin metabolism; however, its genetic basis has remained unclear. We show that Cinnamyl Alcohol Dehydrogenase (CAD) is the causal gene underlying the orange lemma phenotype in barley. Genetic mapping using a ‘Haruna Nijo’ × ‘L053’ F₂ population and the Barley 50 K SNP array defined a candidate region on chromosome 6H containing the CAD gene. Sequence analysis revealed that all orange lemma mutants, including both naturally occurring and EMS-induced lines, carried nucleotide changes in the CAD gene, resulting in amino acid substitutions or premature stop codons. Furthermore, CRISPR/Cas9-mediated knockout of CAD in the cultivar ‘Golden Promise’ reproduced the orange lemma phenotype, providing functional validation. The knockout plants also showed significantly lower lignin content than wild-type plants. These findings resolve a long-standing question regarding the genetic basis of the orange lemma trait and demonstrate that disruption of CAD alters lignin accumulation in barley. This work provides a valuable genetic resource for breeding barley cultivars with improved biomass utilization for feed and bioenergy applications. No potential conflict of interest relevant to this article was reported.

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

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

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 0385-5414 55 7 2001 Synthesis of 5-Deoxy-5-phosphinyl-D-galactopyranose Derivatives: New Phospha-Sugar Analogs of D-Galactose 1301 1309 EN Hiroshi Yamamoto Center of Instrumental Analysis, Okayama University Tadashi Hanaya Department of Chemistry, Okayama University Ken-ichi Sugiyama Department of Chemistry, Okayama University Yasushi Fujii Department of Chemistry, Okayama University Akihito Akamatsu Department of Chemistry, Okayama University The addition reaction of dimethyl phosphonate to 3,6-di-O-benzyl-1,2-O-isopropylidene-α-L-arabino-hexofuranos-5-ulose (11), followed by deoxygenation of 5-hydroxyl group, provided 5-deoxy-5-dimethoxyphosphinyl-D-galactofuranose derivative (13a). Reduction of 13a with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by the action of hydrochloric acid and then hydrogen peroxide, afforded the first D-galactopyranose analog (15) having a phosphinyl group in the hemiacetal ring. This was converted into the 1,2,4-tri-O-acetyl-5-methoxyphosphinyl derivatives (16), whose structure and conformation were established by 1H-NMR spectroscopy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0289-0771 2026 Experimental evolution of female mating responses to infertile males in Tribolium castaneum EN Yui Fujii Faculty of Environmental, Natural Science and Technology, Okayama University Yui Asano Faculty of Environmental, Natural Science and Technology, Okayama University Kenta Kori Faculty of Environmental, Natural Science and Technology, Okayama University Kentarou Matsumura Graduate School of Arts and Sciences, The University of Tokyo Yukio Yasui Faculty of Agriculture, Kagawa University Chihiro Himuro Okinawa Prefectural Plant Protection Center Yutaka Nakamoto Okinawa Prefectural Plant Protection Center Yoshitaka Sokei Okinawa Prefectural Plant Protection Center Takahisa Miyatake Faculty of Environmental, Natural Science and Technology, Okayama University In many animal populations, infertile males―those unable to reproduce―are commonly present. If females mate exclusively with such males, they fail to produce offspring. How, then, do females deal with this situation? Distinguishing infertile from fertile males both before and after copulation is difficult for females. Here, we tested the hypothesis of bet-hedging polyandry, in which females mitigate the risk of reproductive failure by mating with multiple males, using experimental evolution in the red flour beetle (Tribolium castaneum). Females were cohabited with males artificially sterilized by sublethal radiation and with untreated males at a 1:1 ratio (sterile:untreated). After more than 15 generations, females from the treatment strains did not avoid mating with infertile males, leading to reduced reproductive success. However, compared with the control strains, females from the treated strains tended to mate with a greater number of males. The results raise the possibility that increased polyandry (mating with multiple males) may evolve rather than relying on pre- or post-copulatory discrimination to mitigate the risk posed by infertile males. Bet-hedging is a strategy that spreads or minimizes risk under uncertainty, and these results are consistent with the hypothesis that polyandry can function as a bet-hedging strategy against uncertain male fertility. 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.

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

Springer Science and Business Media LLC Acta Medica Okayama 2662-4435 7 1 2026 Rapid fluvial response to meter-scale coseismic coastal uplift during the 2024 Noto Peninsula earthquake 742 EN Takayuki Takahashi International Research Institute of Disaster Science, Tohoku University Takuro Ogura Graduate School of Social Sciences, Hitotsubashi University Kotaro Iizuka Center for Spatial Information Science, The University of Tokyo Yoshiya Iwasa Faculty of Education, University of Teacher Education Fukuoka Yuichi S. Hayakawa Center for Spatial Information Science, The University of Tokyo Tatsuto Aoki Institute of Human and Social Sciences, Kanazawa University Nobuhisa Matta Graduate School of Education, Okayama University The response of river profiles to relative base-level change is a key topic in earth surface processes, but observations capturing these changes on unconsolidated deposits at a 1–10 years timescales are scarce. We monitored geomorphic changes at the Hakka River mouth after the 3.5-meter base-level fall caused by coseismic uplift of the 2024 Noto Peninsula earthquake, Japan. Utilizing uncrewed aerial vehicle surveys, we documented a maximum vertical riverbed lowering of 2 m and knickpoint upstream migration of 770-m within the first-year post-earthquake, primarily triggered by erosion during major floods that followed the earthquake. Our findings demonstrate that fluvial terraces can develop within a year or less, following co-seismic coastal uplift. However, the river has not yet reached a renewed graded stage because riverbed armoring resulting from sediment sorting during incision currently inhibits further incision. We suggest that the abandonment of alluvial plains and lowering and widening of the riverbed in the lower 10-km segment will continue over the next decade. 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.

IEEE Acta Medica Okayama 2026 A Novel Iterative Method for Principal Component Analysis 1 6 EN Qiuyun Cao Okayama University Kotaro Hattori Okayama University Tsuyoshi Migita Okayama University Norikazu Takahashi Okayama University Principal Component Analysis (PCA) is a statistical method used for identifying key patterns from a given dataset and reducing its dimensions, while retaining most of the original information. The power method, which is one of the most well-known algorithms for PCA, is simple and easy to implement. However it obtains the specified number of principal components one by one. In this paper, we propose a novel iterative method for PCA, which is expressed as a system of nonlinear difference equations. Unlike the power method, the proposed method can obtain the specified number of principal components in parallel. We also show results of numerical experiments and theoretical analysis to verify the validity of the proposed method. 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.

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

Elsevier BV Acta Medica Okayama 0959-8049 248 2026 Molecular characteristics and clinical outcomes of ERBB2-activating mutation-positive non-small cell lung cancer: A Japanese nationwide real-world cohort 117443 EN Masahiro Yamashita Department of Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Department of Respiratory Medicine, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Eiji Nakata Center for Comprehensive Genomic Medicine, Okayama University Hospital Ayako Morita Department of Respiratory Medicine, Okayama University Hospital Naofumi Hara Department of Respiratory Medicine, Okayama University Hospital Kenji Takada Department of Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Respiratory Medicine, Okayama University Hospital Toshio Kubo Department of Respiratory Medicine, Okayama University Hospital Eiki Ichihara Department of Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Department of Respiratory Medicine, Okayama University Hospital Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Background: Erb-b2 receptor tyrosine kinase 2 (ERBB2)-activating mutations are well-documented oncogenic drivers in non-small cell lung cancer (NSCLC), occurring in approximately 1–4% of cases. These alterations include a heterogeneous spectrum of variant subtypes; however, the clinicogenomic characteristics and clinical significance of the individual variants have yet to be elucidated. Methods: We searched the nationwide Center for Cancer Genomics and Advanced Therapeutics database, which integrates comprehensive genome profiling data generated in routine clinical practice across Japan, to investigate the molecular landscape and clinical outcomes of patients with ERBB2-mutated NSCLC. Results: A total of 319 patients with ERBB2-activating mutations were included in this retrospective analysis. Although 74% of the patients harbored canonical tyrosine kinase domain (TKD) in-frame insertions, 26% carried noncanonical variants, including TKD missense (8%), transmembrane/juxtamembrane domain (10%), and extracellular domain (ECD) mutations (8%). Co-occurring oncogenic driver alterations were identified in only 18 cases (5.6%) and were largely restricted to noncanonical variants, whereas no co-occurring driver alterations were detected among patients with TKD in-frame mutations. Noncanonical variants―TKD missense and ECD mutations in particular―were associated with an increased tumor mutational burden. Among 288 patients with available survival data, 78 (27%) received trastuzumab deruxtecan (T-DXd) during their clinical course. After excluding patients who had started treatment with T-DXd before undergoing comprehensive genome profiling testing, time-dependent T-DXd exposure was associated with a reduced risk of death (adjusted hazard ratio, 0.63; 95% confidence interval, 0.39–1.01; P = 0.057). Conclusions: ERBB2-mutated NSCLC exhibited substantial molecular heterogeneity, with canonical TKD in-frame insertions characterized by a low frequency of co-occurring oncogenic driver alterations. Among patients harboring ERBB2-activating mutations, exposure to T-DXd was associated with improved overall survival. 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. 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. 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. 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. 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. 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′s role in drug tolerance. Notably, ULK1 inhibition showed modest efficacy even after cells transitioned to the DTP or acquired resistance states. 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.

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

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. Methods: AYAME enrolled patients prescribed durvalumab for unresectable stage III non-small cell lung cancer (NSCLC) after chemoradiotherapy (CRT) from July 2019 to December 2020 in Japan. Patients received durvalumab for ≤ 12 months and were prospectively followed for 3 years. Incidence, severity, and management of ILD were examined. Multivariable logistic regression analysis was conducted to investigate the association of patient characteristics with grade ≥ 2 ILD occurrence. Results: Of 511 patients in the safety analysis population, ILD occurred in 383 patients (75.0%) from durvalumab initiation to subsequent treatment start; median time to occurrence was 44.0 days. ILD led to permanent durvalumab discontinuation in 121/383 patients (31.6%), dose interruption in 111/383 (29.0%), and corticosteroid intervention in 168/383 (43.9%). Grade ≥ 2 ILD occurrence was higher in patients with volume of lung parenchyma that received 20 Gy (V20) ≥ 25% versus < 25% (60.3% vs. 29.4%; adjusted odds ratio 2.20, 95% confidence interval 1.08–4.48), 5 Gy (V5) ≥ median (37.85%) versus < median (51.5% vs. 27.2%; 1.79, 1.07–3.00), and grade 1 ILD before durvalumab administration versus no ILD (50.0% vs. 37.6%; 2.11, 1.07–4.17). Conclusions: This study of durvalumab for NSCLC after CRT in a real-world setting indicated factors associated with grade ≥ 2 ILD and provided valuable insights into ILD management strategies. These findings may contribute to establishing effective approaches to minimize ILD risk in practice. Trial Registration: UMIN000037090/NCT03995875 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. Methods: This multicenter, noninterventional study (AYAME) enrolled patients who were prescribed durvalumab for unresectable stage III NSCLC after CRT (July 2019–December 2020; 52 sites; Japan). Patients received durvalumab for a maximum of 12 months and were prospectively followed up for 3 years, including the post-durvalumab treatment period. Primary end points were real-world progression-free survival (rwPFS), the incidence of interstitial lung disease (ILD), and adverse events of special interest (AESIs). Results: Of the 529 enrolled patients, 512 received durvalumab and 511 comprised the safety analysis population. The median time to onset of the first presentation or occurrence of ILD was 45.0 days. ILD of any grade occurred in 387 patients (75.7%) over the 3-year study period: grade 3, 57 (11.2%); grade 4, none (0.0%); and grade 5, 9 (1.8%). The most common AESIs of any grade during durvalumab treatment were thyroid dysfunction (12.5%), hepatic dysfunction (7.2%), and colitis (2.0%). No durvalumab treatment-related ILD or AESIs occurred during the post-treatment period. The median [95% confidence interval] rwPFS was 23.2 [18.2, 27.2] months in the effectiveness analysis population (n = 495). rwPFS rates were 62.5%, 54.6%, 49.4%, and 40.4% at 12, 18, 24, and 36 months, respectively. Conclusions: This first and largest prospective, observational study demonstrated the long-term safety and effectiveness of durvalumab for unresectable stage III NSCLC after CRT in a real-world clinical setting. Clinical Trial Registration: UMIN000037090 and NCT03995875 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.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 2 2025 Elevated Plasma Progastrin-Releasing Peptide Levels Associated With the Diagnosis of Pulmonary Carcinoid Tumors: A Report of Two Cases e79601 EN Takashi Yamaoka Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital Kiichiro Ninomiya Department of Allergy and Respiratory Medicine, Okayama University Hospital Taku Noumi Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital Chiaki Matsumoto Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital Keisuke Sugimoto Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital Pulmonary carcinoids are the type of thoracic malignant tumors classified as neuroendocrine tumors. Case 1 involved a 59-year-old woman with a nodular shadow in the left upper pulmonary field observed on chest radiography. Chest computed tomography (CT) scan revealed a nodule in the left upper lobe and a soft tissue tumor near the left third rib. Given her elevated plasma progastrin-releasing peptide (ProGRP) level, a CT-guided biopsy was performed, confirming a diagnosis of pulmonary carcinoid with solitary bone metastasis. She subsequently underwent partial resection of the left upper lobe and the rib tumor. Case 2 involved a 67-year-old woman referred to our hospital after a chest CT scan revealed a nodule in the left lingular region. Her plasma ProGRP level was elevated, and a CT-guided biopsy confirmed a diagnosis of pulmonary carcinoid. As no lymph node metastases were detected, she underwent segmental resection of the left upper lobe. In both cases, plasma ProGRP levels decreased following surgical resection. These findings suggest that plasma ProGRP levels may serve as a useful diagnostic marker for pulmonary carcinoids. No potential conflict of interest relevant to this article was reported.

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

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.

Elsevier BV Acta Medica Okayama 0008-6215 306 1-2 1998 Effect of a phosphorus atom upon vicinal – coupling constants in pyranose derivatives having a C–P bond: Additivity rule for the effect of phosphorus substituents 157 162 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University Additivity constants for phosphorus were estimated for the prediction of vicinal 1H–1H coupling constants by means of an additivity rule in a series of pyranose analogs having phosphorus as the ring heteroatom. The experimental J values were well reproduced by employing the proposed additivity constants with a small overall root-mean-square difference of 0.32 Hz. The prediction of coupling constants was employed for the investigation of conformational equilibria of pyranose analogs having a phosphinyl group in the ring or on the ring-carbon. 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. Methods: We retrospectively analyzed 207 patients with R/M HNSCC treated with nivolumab or pembrolizumab at a single institution. Early progression was defined as disease progression within 90 days after ICI initiation. Associations between clinicopathological factors and early progression were evaluated using logistic regression analyses. Results: Early progression was observed in 80 patients (38.6%). In an exploratory survival comparison, patients with early progression had significantly shorter overall survival than those without early progression. Early progression rates increased from distant-only disease to locoregional-only disease and combined locoregional and distant disease. In multivariable analysis, combined locoregional, and distant disease showed the strongest independent association with early progression. Elevated neutrophil-to-lymphocyte ratio and hypoalbuminemia were also independently associated with early progression. In contrast, treatment regimen, treatment line, number of lesions, and bulky disease were not significantly associated with early progression. Conclusion: Disease distribution was associated with early progression after ICI initiation in patients with R/M HNSCC, with combined locoregional and distant disease showing the strongest independent association. These findings suggest that both disease status and host condition may influence failure to achieve adequate disease control shortly after ICI initiation. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 0140-7791 2026 Natural Variation in Brachypodium distachyon Primarily Links Lignin Reinforcement to Rhizoctonia solani Resistance EN Rozi Fernanda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Niranjan Mahadevan Tea Research Institute of Sri Lanka Megumi Watanabe Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiteru Noutoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1867-1071 43 2 2024 Cranial and spinal computed tomography (CT) angiography with photon-counting detector CT: comparison with angiographic and operative findings 143 151 EN Fumiyo Higaki Department of Radiology, Okayama University Hospital Masafumi Hiramatsu Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takao Yasuhara Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Susumu Sasada Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yoshihiro Otani Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Jun Haruma Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tomohiro Inoue Division of Radiological Technology, Okayama University Hospital Yusuke Morimitsu Division of Radiological Technology, Okayama University Hospital Noriaki Akagi Division of Radiological Technology, Okayama University Hospital Yusuke Matsui Department of Radiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, 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 The clinical imaging features of photon-counting detector (PCD) computed tomography (CT) are mainly known as dose reduction, improvement of spatial resolution, and reduction of artifacts compared to energy-integrating detector CT (EID-CT). The utility of cranial and spinal PCD-CT and PCD-CT angiography (CTA) has been previously reported. CTA is a widely used technique for noninvasive evaluation. Cranial CTA is important in brain tumors, especially glioblastoma; it evaluates whether the tumor is highly vascularized prior to an operation and helps in the diagnosis and assessment of bleeding risk. Spinal CTA has an important role in the estimation of feeders and drainers prior to selective angiography in the cases of spinal epidural arteriovenous fistulas and spinal tumors, especially in hemangioblastoma. So far, EID-CTA is commonly performed in an adjunctive role prior to selective angiography; PCD-CTA with high spatial resolution can be an alternative to selective angiography. In the cases of cerebral aneurysms, flow diverters are important tools for the treatment of intracranial aneurysms, and postoperative evaluation with cone beam CT with angiography using diluted contrast media is performed to evaluate stent adhesion and in-stent thrombosis. If CTA can replace selective angiography, it will be less invasive for the patient. In this review, we present representative cases with PCD-CT. We also show how well the cranial and spinal PCD-CTA approaches the accuracy of angiographic and intraoperative findings. 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. 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. 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. 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.

Elsevier BV Acta Medica Okayama 0300-2896 61 5 2025 Histological Features and Gene Expression Profiling in Lung Transplantation From Donation After Circulatory Death 299 302 EN Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohisa Sakaue Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yujiro Kubo Department of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-Majadahonda Tatsuya Hayashi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Elvira Ramil Sequencing and Molecular Biology Unit, Hospital Universitario Puerta de Hierro-Majadahonda Antonio J. Sánchez-López Biobank, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana María Jose Coronado Confocal Microscopy Unit, Hospital Universitario Puerta de Hierro-Majadahonda Lucas Hoyos Department of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-Majadahonda Alejandra Romero Department of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-Majadahonda Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences David Gomez-de-Antonio Department of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-Majadahonda 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. Methods: We analyzed data from “the Japan COVID-19 and Society Internet Survey,” a prospective, self-reported online survey cohort. Questionnaires were randomly distributed between July 28, 2021, and August 30, 2021. Pregnant respondents in 2021 were invited to complete an additional survey from February 14, 2022, to February 28, 2022. We set the outcome as the absolute risk difference (aRD) and relative risk ratio (rRR) of PA incidence due to smoking HTPs in the first trimester of pregnancy. The sample size included 12 836 participants. We calculated outcomes using a generalized linear model (GLM) and inverse probability of treatment weighting (IPTW). We also performed a Bayesian approach and multiple-bias analysis for sensitivity analysis. Results: We found the robust aRD of 0.07 (95% confidence interval (CI): 0.06, 0.09) and the rRR of 11.3 (95% CI: 7.5, 17.0). Multiple bias analyses showed that unmeasurable confounders would need to have at least an rRR = 14 relationship with both exposure and outcome to disprove the observed association. There has not been post hoc analysis or secondary use of data. Conclusion: Early pregnancy use of HTPs is associated with an increased risk of PA. 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. 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). 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. 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’s 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. Objective: We aimed to evaluate the clinical characteristics and survival impact of hypomagnesemia induced by this therapy. Design: This was a sub-analysis of the retrospective multicenter NINJA study. Methods: Among the 93 patients enrolled in the NINJA study, this subanalysis included 75 patients with baseline serum magnesium concentrations. Results: The incidence of grade ⩾2 hypomagnesemia was 18.0% in the patients with normal baseline serum magnesium concentrations and 42.8% in those with low concentrations (p = 0.073). The discontinuation rates of GCN treatment owing to hypomagnesemia in each group were 0% and 7.1%, respectively (p = 0.187). The number of necitumumab doses and severity of hypomagnesemia were positively correlated (r = 0.389, p < 0.001). Patients who developed hypomagnesemia in fewer than 21 days after the first dose of GCN (n = 12) had significantly poorer progression-free survival (PFS) than those without the condition (n = 63; median: 4.1 vs 4.4 months, p = 0.048). A similar trend was observed for OS (median: 9.7 vs 15.7 months, p = 0.062). These results were maintained after multivariate analyses (PFS: hazard ratio (HR) 2.46, p = 0.014; OS: HR 2.78, p = 0.021). Conclusion: GCN as a second-line or later therapy may be tolerable regardless of the patient’s baseline serum magnesium concentration. On the other hand, early serum magnesium reduction with this therapy is associated with a poor prognosis. However, caution should be needed because our results lacked sufficient information for confounding variables other than those analyzed here that may influence the correlation between hypomagnesemia and survival. No potential conflict of interest relevant to this article was reported.

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

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

Wiley Acta Medica Okayama 0009-0352 102 3 2025 A Curve Fitting Method for Analyzing Starch Granule Size Distributions in Cereals 438 450 EN Rose McNelly John Innes Centre Amy Briffa John Innes Centre Georgia Yiasoumi John Innes Centre Cristobal Uauy John Innes Centre Ryo Matsushima Institute of Plant Science and Resources, Okayama University David Seung John Innes Centre Background and Objectives: The size distribution of starch granules is an important factor in determining the functional and nutritional properties of starch. However, a simple, standardized method for their analysis is lacking. Here, we developed an approach for estimating granule size parameters using a Python script that fits curves to volumetric granule size distributions generated using a Coulter counter. Findings: The bimodal size distribution of starch from most wheat and barley cultivars could be best described with a mixed distribution curve. A log-normal distribution was fitted to the small B-type granules, and a normal distribution was fitted to the large A-type granules, allowing estimation of their relative abundance and size parameters despite their overlapping size distributions. However, the optimal fitting is altered in wheat mutants with large perturbations in B-type granule content. In maize and rice, which have unimodal granule size distributions, size parameters were calculated by fitting a single normal distribution. Conclusions: Curve fitting is an effective approach for estimating starch granule size parameters in diverse cereals, particularly the Triticeae with A- and B-type granules. Significance and Novelty: We provide new tools and guidelines for the quantitative analysis of granule size in cereals. No potential conflict of interest relevant to this article was reported.

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

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

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’s 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. Objectives: We examined this prognostic effect in patients with LSCC, and the usefulness of minocycline administration. Design: This was a sub-analysis of the retrospective multicenter NINJA study. Methods: We performed a landmark survival analysis according to the presence of skin disorders at Day 30 of treatment and examined the usefulness of minocycline for treating skin disorders. Results: Among the 93 patients, 62 (66.7%) had a skin disorder at Day 30. Nineteen, 30, and 13 patients experienced Grade 1, 2, and 3 skin disorders, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with skin disorders at Day 30 were longer than those of patients without skin disorders (median OS: 434 vs 278 days, p = 0.0201; median PFS: 148 vs 82 days, p = 0.0835). Multivariable analysis showed that a skin disorder at Day 30 was an independent prognostic factor for both OS (p = 0.0044) and PFS (p = 0.0514). Of the 62 patients with skin disorders at Day 30, 38 (61.3%) were taking minocycline, and their time to treatment failure (TTF) was better than that in patients not taking minocycline (median TTF: 148 vs 101 days, p = 0.0495). Conclusion: A skin disorder within 30 days was a favorable prognostic factor for patients with LSCC administered Neci + GC. Additionally, minocycline administration may be beneficial in patients who develop skin disorders within 30 days. 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.

Wiley Acta Medica Okayama 0961-8368 35 10 2026 Conformational stability and domain‐specific structural features of tumor autoantigens regulate autoantibody epitope propensity e70808 EN Ai Miyamoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Rika Yamamoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ryui Sakaguchi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Rikako Kutsuma Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takeru Mori Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mirei Masui Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tomoko Honjo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Midori Futami Department of Bioscience, Faculty of Life Science, Okayama University of Science Mariko Morii Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hiromi Watanabe Department of Respiratory Medicine, Okayama University Hospital Tadahiro Kuribayashi Department of Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Junichiro Futami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Autoantibodies against tumor-associated autoantigens are clinically valuable biomarkers for cancer diagnosis; however, the structural determinants governing epitope selectivity remain unknown. Here, we investigated whether the intrinsic conformational stability of target autoantigens regulates the epitope propensity of tumor-associated autoantibodies in non-small cell lung cancer. Using a dual-antigen Luminex bead-based assay that presents each autoantigen in both native and S-cationized denatured forms, we directly compared IgG autoantibody reactivity toward conformational and linear epitopes across 11 autoantigens. Intrinsically disordered aggregation-prone autoantigens, including cancer/testis antigens, NY-ESO-1, and XAGE-1b, predominantly elicit linear epitope-directed responses, whereas thermodynamically stable soluble autoantigens generally drive conformational epitope recognition. Intriguingly, for autoantigens harboring both ordered and disordered segments, the immune response is strictly guided by domain-specific biophysics: while p53-specific antibodies preferentially target their flanking disordered regions, the Wilms' tumor protein 1 exceptionally drives conformational recognition directed toward its structured zinc-finger domains. Recombinant solubility in Escherichia coli broadly correlated with epitope class across all 11 autoantigens, confirming that prokaryotic folding efficiency generally reflects intrinsic conformational stability in vivo for autonomously folding monomeric cytosolic proteins. Independent computational validation was provided by the concordance between the experimental solubility ratios and AlphaFold3-derived Rosetta energy unit/solvent-accessible surface area values, demonstrating the convergence of thermodynamic estimates and patient-derived immune data within a unifying biophysical framework. These findings establish that the autoantibody epitope propensity is closely associated with the thermodynamic stability of the target autoantigen and provide a rational basis for tailoring antigen preparation strategies for autoantibody-based cancer diagnosis. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 0094-8276 53 18 2026 Hydrogen-Bond Symmetrization in Hydrous Aluminous Silica Enhances Deep-Mantle Water Cycle e2026GL123823 EN Chaoshuai Zhao State Key Laboratory of Precision Geodesy, University of Science and Technology of China Zhu Mao State Key Laboratory of Precision Geodesy, University of Science and Technology of China Yingxin Yu Department of Earth Sciences, University of Oxford Ningyu Sun State Key Laboratory of Precision Geodesy, University of Science and Technology of China Yunhua Fu SKLab‐DeepMinE, MOEKLab‐OBCE, School of Earth and Space Sciences, Peking University Jianbo Zhang Center for High‐Pressure Science and Technology Advance Research Hanns‐Peter Liermann Deutsches Elektronen‐Synchrotron DESY Renbiao Tao Center for High‐Pressure Science and Technology Advance Research Takayuki Ishii Institute for Planetary Materials, Okayama University (Al, H)-bearing CaCl2-type SiO2 serves as a key water carrier in Earth's deep-water cycle. Evolution of hydrogen-bond symmetrization in this phase was measured up to 62 GPa and 800 K by synchrotron infrared and Raman spectroscopy, and X-ray diffraction. It undergoes symmetrization at ∼30 GPa and 300 K, while elevated temperature to 800 K lowers the onset pressure to ∼12 GPa. This implies that the symmetrized phase will form directly near the base of the transition zone in (Al, H)-rich subducted slabs, and deeper in (Al, H)-poor slabs via transformation from stishovite. More importantly, this symmetrization state stiffens the crystal lattice and immobilizes hydrogen within the structure, enhancing water retention and preventing hydrogen loss during subduction to the lower mantle. Our findings suggest that this phase acts as an important deep-water reservoir capable of transporting water to the lower mantle, thereby linking the deep-water cycle from Earth's surface to core-mantle boundary. 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. Gap Statement. Interpretation of mCIM results for isolates with reduced carbapenem susceptibility remains challenging. 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. 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. 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-β-lactamase (MBL) activity. MIC reductions in the presence of CVA were consistent with inhibition of a class A β-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 β-lactamase gene encoding a class A enzyme. No novel β-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. 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.

Wiley Acta Medica Okayama 2751-1219 5 9 2026 Proton‐Radiation‐Tolerant Silicon Photonic Charge Sensor for Spacecraft Applications e70208 EN Wataru Takahama Department of Physics and Electronics, Osaka Metropolitan University Kosei Otsuka Department of Physics and Electronics, Osaka Metropolitan University Ayumi Ishihara Department of Physics and Electronics, Osaka Metropolitan University Rikuto Hojo Department of Space Systems Engineering, Kyushu Institute of Technology Tomofumi Mogami ElectrostaticEngineering DEPT, Kasuga Denki INC Kazuhiro Toyoda Department of Space Systems Engineering, Kyushu Institute of Technology Kohtaku Suzuki Research and Development, The Wakasa Wan Energy Research Center Yasushi Takahashi Faculty of Environmental, Life, Natural Science and Technology,Okayama University Silicon waveguides are promising platforms for spacecraft potential sensing owing to their compactness and immunity to electromagnetic interference. However, proton-induced optical absorption in operating silicon waveguides has not been quantitatively clarified, despite their direct exposure to the space radiation environment during spacecraft operation. Here, we present a systematic elucidation of proton-radiation effects on a photonic charge sensor based on silicon photonic crystal waveguides. During proton irradiation at 20 keV, we quantitatively evaluate the increase in optical absorption under device operation and find that a fluence of 1.0 ×1014 cm－ 2 induces an additional absorption coefficient of approximately 0.41 cm－ 1 . We further demonstrate that the sensor retains its ability to measure spacecraft potential even after exposure to a high proton fluence of 1.0 ×1015 cm－ 2 , confirming its intrinsic radiation tolerance. These results establish the radiation robustness of silicon-waveguide- based sensing mechanisms and provide the first quantitative basis for implementing photonic charge sensors in radiation-rich spacecraft environments. 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. 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. 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.

American Physical Society (APS) Acta Medica Okayama 0031-9007 137 9 2026 Strain-Tuned Nodal Superconductivity in the Charge-Ordered Kagome Metal CsV3⁢Sb5 096003 EN Yusuke Takeuchi Department of Physics, Okayama University Akito Kobayashi Department of Physics, Okayama University Saki Uchida Department of Physics, Okayama University Takumi Nagao Department of Physics, Okayama University Seigo Ogawa Department of Physics, Okayama University Rui Zhou Institute of Physics, Chinese Academy of Sciences, and Beijing National Laboratory for Condensed Matter Physics Shinji Kawasaki Department of Physics, Okayama University Fei Song Fujian Provincial Collaborative Innovation Center for Advanced High-Field Superconducting Materials and Engineering, College of Physics and Energy, Fujian Normal University Hao Ni Fujian Provincial Collaborative Innovation Center for Advanced High-Field Superconducting Materials and Engineering, College of Physics and Energy, Fujian Normal University Yong Zhao Fujian Provincial Collaborative Innovation Center for Advanced High-Field Superconducting Materials and Engineering, College of Physics and Energy, Fujian Normal University Guo-qing Zheng Department of Physics, Okayama University The nature of the superconducting pairing symmetry in the kagome metal CsV3⁢Sb5 and its relationship with the charge density wave (CDW) order are central unresolved issues. Here, we investigate the evolution of superconductivity in CsV3⁢Sb5 under in situ uniaxial pressure using 121Sb nuclear quadrupole resonance (NQR). We find that tensile strain significantly enhances the superconducting transition temperature, 𝑇c, while the CDW remains unchanged, demonstrating that superconductivity can be tuned independently of the bulk charge order. At a tensile strain of 𝜖 =+0.90%, the nuclear spin-lattice relaxation rate reveals a remarkable double transition: an upper transition at 𝑇c⁢1=3.6 K to a nodal gap state, and a lower one at 𝑇c⁢2=3.0 K characterized by a nodeless gap. These results evidence degenerate superconducting states with different gap symmetry in the kagome metal at ambient pressure which split under strain. Our Letter demonstrates a high tunability of superconductivity by uniaxial pressure. 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. Methods We performed a retrospective cohort study including patients diagnosed neoplasm and 18 and older when receiving ICI therapy from 1/1/2011 to 12/31/2022. Queried ICD 9/10 codes identified patients experiencing myocarditis, pericarditis, pericardial effusion, and cardiac tamponade within 1 year of ICI initiation. Survival analyses compared one-year overall survival (OS) of patients experiencing cardiac irAEs against propensity score matched populations not experiencing them. Results In 88,928 identified ICI patients, the incidence of myocarditis(0.48%), pericarditis(0.22%), and cardiac tamponade(0.47%) were less than 1% while pericardial effusion occurred in 4.71% of patients. Hazard ratios (HRs) were significantly higher in all cardiac irAE groups: myocarditis (HR:1.26, 95% CI:1.04–1.54, p = 0.02), pericarditis (HR:1.36, 95% CI:1.02–1.82, p = 0.04), pericardial effusion (HR:1.49, 95% CI:1.39–1.59, p < 0.0001), cardiac tamponade (HR:2.15, 95% CI:1.79–2.57, p < 0.0001), and overall pericardial disease (HR:1.46, 95% CI:1.37–1.56, p < 0.0001). There was no significant difference in OS between myocarditis and pericarditis or overall pericardial diseases. Discussion/conclusion Utilizing a uniquely large cohort of ICI patients, this study further shows the rarity of cardiac inflammatory irAEs and highlights their significant impact on patient survival. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0008-6215 338 16 2003 Stereoselectivity in deoxygenation of 5-hydroxy-5-phosphinyl-hexofuranoses (α-hydroxyphosphonates) 1641 1650 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Ken-ichi Sugiyama Department of Chemistry, Faculty of Science, Okayama University Heizan Kawamoto Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University The addition of dimethyl phosphonate to six different hexofuranos-5-uloses in the presence of DBU, followed by esterification with methoxalyl chloride and then radical reduction, afforded 5-deoxy-5-dimethoxyphosphinyl-d- and l-hexofuranoses. The stereoselectivity of the deoxygenation and possible transition-state models are discussed. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2198-3844 2026 SPRED2 Negatively Regulates CD8+ T Cell-Mediated Antitumor Immunity in Breast Cancer e77909 EN Miao Tian Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kun Zhao Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tong Gao Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ziyi Wang Department of Advanced International and Information Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Activation of the RAS/RAF/ERK pathway is crucial for adaptive immunity. Here, we provide evidence that Sprouty-related EVH1 domain containing 2 (SPRED2), an endogenous inhibitor of this pathway, negatively regulates CD8+ T cell-mediated antitumor immunity in breast cancer. In EO771 and 4T1 mouse models, Spred2－/－ mice exhibit reduced tumor growth, with lower endpoint lung metastatic burden in the 4T1 model, accompanied by increased T-cell infiltration and activation. Spred2－/－ T cells show enhanced cytokine expression, proliferation,survival, in vitro cytotoxicity, and memory-like phenotypes, particularly among CD8+ T cells. Adoptive transfer of Spred2－/－ CD8+ T cells into tumor-bearing wild-type hosts similarly reduces endpoint lung metastatic burden. MEK inhibition with U0126 attenuates increased interferon-gamma and granzyme B expression in Spred2－/－ CD8+ T cells. Transcriptomic analyses reveal an inverse correlation between SPRED2 expression and antitumor CD8+ T cell states in both humans and mice. In tumor-infiltrating T cells from patients with breast cancer, SPRED2low T cells show enriched effector and cytotoxicity programs and are associated with “immune-hot” tumors, whereas survival associations vary with CD8+ T cell context. Collectively, these findings suggest that SPRED2 functions as a cell-intrinsic negative regulator of CD8+ T-cell activation and highlight its potential as a therapeutic target to enhance T cell–based cancer immunotherapy. 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.

Elsevier BV Acta Medica Okayama 2212-5345 63 3 2025 Practical Guidelines for Asthma Management (PGAM): Digest edition 405 421 EN Jun Tamaoki Department of Respiratory Medicine, Tokyo Women's Medical University Hiroyuki Nagase Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine Hiroyuki Sano Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Takeshi Kaneko Department of Pulmonology, Yokohama City University Graduate School of Medicine Yasuhiro Gon Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital Hironori Sagara Department of Medicine, Division of Allergology and Respiratory Medicine, School of Medicine, Showa University Akihiko Tanaka Department of Medicine, Division of Allergology and Respiratory Medicine, School of Medicine, Showa University Takahiko Horiguchi Department of Respiratory Medicine, Toyota Regional Medical Center Etsuko Tagaya Department of Respiratory Medicine, Tokyo Women's Medical University Tomohiro Akaba Department of Respiratory Medicine, Tokyo Women's Medical University Yuji Tohda Kindai University Hospital The international and national guidelines for asthma management are typically comprehensive and designed for respiratory specialists, making them less practical for primary care physicians who handle most asthma cases. Recognizing the need for more accessible guidelines, the Japan Asthma Society developed the Practical Guidelines for Asthma Management (PGAM). PGAM aims to provide a concise summary of key asthma management principles, increasing awareness, education, and support among nonspecialists and patients alike. It includes user-friendly tables and lists outlining common symptoms, triggers, diagnostic criteria, and basic management strategies, along with frequently encountered treatable traits and comorbidities. These elements are presented through simple, clinically relevant algorithms. A notable feature of PGAM is the “Basic Roadmap for Asthma Management,” which outlines a clear sequence for patient assessment, diagnosis, and treatment from initial consultation onward, offering an easy-to-follow visual guide. Additionally, the guidelines include methods for assessing airway inflammation, enabling patient phenotyping and endotyping. This supports a personalized treatment approach, particularly with biologics, aimed at achieving clinical remission. No potential conflict of interest relevant to this article was reported.

Japan Medical Association Acta Medica Okayama 2433-3298 8 2 2025 Unraveling Causality: Innovations in Epidemiologic Methods 323 337 EN Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University For several decades, the counterfactual model and the sufficient cause model have shaped our understanding of causation in biomedical science and, more recently, the link between these two models has enabled us to obtain a deeper understanding of causality. In this article, I provide a brief overview of these fundamental causal models using a simple example. The counterfactual model focuses on one particular cause or intervention and gives an account of the various effects of that cause. By contrast, the sufficient cause model considers sets of actions, events, or states of nature which together inevitably bring about the outcome under consideration. In other words, the counterfactual framework addresses the question “what if?” while the sufficient cause framework addresses the question “why does it happen?” Although these two models are distinct and address different causal questions, they are closely related and used to elucidate the same cause-effect relationships. Importantly, the sufficient cause model makes clear that causation is a multifactorial phenomenon, and it is a “finer” model than the counterfactual model; an individual is of one and only one response type in the counterfactual framework, whereas an individual may be at risk of none, one, or several sufficient causes. Understanding the link between the two causal models can provide greater insight into causality and can facilitate the use of each model in appropriate contexts, highlighting their respective strengths. I will briefly present three topics of interest from our research: the relationship between the concepts of confounding and of covariate balance; distinctions between attributable fractions and etiologic fractions; and the identification of operating mediation and mechanism. It is important to scrutinize observed associations in a complementary manner, using both the counterfactual model and the sufficient cause model, employing both inductive and deductive reasoning. This holistic approach will better help us to unravel causality. No potential conflict of interest relevant to this article was reported.

Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 0385-5414 66 1 2005 Synthesis of Phospholane 1-Oxide Having Oxygen Functional Groups from a 4-Bromobutylphoshinate Derivative 251 261 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Shigeru Kawase Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University Ethyl 4-bromo-2,3-dimethoxybutyl(phenyl)phosphinate (10a) was prepared from 2,3-di-O-methyl-L-threitol (12) in five steps. Reduction of 10a with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by the action of hydrogen peroxide, afforded 3,4-dimethoxy-1-phenylphospholane 1-oxide (3), while the reaction of 10a with magnesium in boiling THF resulted in the formation of ethyl 2-methoxy-3-butenyl(phenyl)phosphinate (26). No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1328-8067 67 1 2025 A case of fetal myocardial calcification with hyperechoic area in fetal echocardiography e15868 EN Takeshi Sato Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yosuke Washio Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hotaka Kawai Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Baba Department of Pediatrics, 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 Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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-κB 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-κB mediates transcriptional regulation crucial to many biological functions, and elevated NF-κB 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-κB 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-κB signal in breast cancer. Studies with 35 human breast cancer cell lines reveal that Tob expression is negatively correlated with NF-κB activity. Analysis of The Cancer Genome Atlas (TCGA) database of clinical samples reveals an inverse correlation between Tob expression and NF-κB activity. Tob knockdown in human breast cancer cells promoted overactivation of NF-κB upon TNF-α treatment, whereas overexpression of Tob inhibited TNF-α stimulation-dependent NF-κB activation. Mechanistically, Tob associates with the TNF receptor complex I and consequently inhibits RIPK1 polyubiquitylation, leading to possible prevention of overwhelming activation of NF-κB. 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. Aims: To explore how immersive VR-based disaster simulations influence disaster risk perception and preparedness among nursing students, with particular attention to the awareness–action gap and implications for future healthcare and critical care practice. Study Design: A qualitative descriptive study using immersive VR-based disaster simulations followed by semi-structured interviews. Twelve undergraduate and graduate nursing students in Japan experienced immersive VR simulations depicting floods and landslides. Individual semi-structured interviews explored emotional responses, disaster risk perception, preparedness awareness and anticipated behavioural responses. Data were analysed using Krippendorff's content analysis with researcher triangulation. Results: Five categories were identified: (1) heightened vulnerability and psychological burden through immersion; (2) persistence of the awareness–action gap despite increased risk perception; (3) enhanced risk recognition and preparedness intentions; (4) recognition of the need for social and structural support systems; and (5) emerging responsibility accompanied by perceived limitations. VR transformed abstract disaster risk into emotionally salient experiences, strengthening threat appraisal and preparedness awareness; however, awareness did not consistently translate into preparedness behaviours, reflecting insufficient coping appraisal and self-efficacy. Conclusions: Immersive VR may strengthen disaster risk perception and preparedness awareness, but immersive experiences alone may be insufficient to bridge the awareness–action gap. Combining VR with reflective learning, skills-based training and collaborative simulation may strengthen coping appraisal and preparedness action. Relevance to Clinical Practice: Immersive VR combined with reflective and skills-based learning may support psychological readiness, situational awareness and disaster preparedness competencies among future nurses, including those preparing for critical care practice. 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. 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. 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. Methods: This multicenter, retrospective cohort study is an analysis of data collected from the JAPAN Registry of Self-harm and Suicide Attempts. Patients were divided into two groups, the OHCA group and the non-OHCA group. The primary outcome was death at 30 days. Results: Among 1,960 self-harm and suicide attempts patients, 213 patients (10.9 %) were assigned to the OHCA group and 1,747 (89.1%) were in the non-OHCA group. Patients in the OHCA group were older (44 vs. 33 years old, p < 0.001), and the OHCA group had a higher proportion of males compared to the non-OHCA group (122 [57.3%] vs. 604 [34.6%], p < 0.001). Despite missing and unknown data, lower proportions of psychiatric consultation history (54 [30.8%] vs. 1177 [70.5%], p < 0.001), psychiatric hospitalization history (9 [5.1%] vs. 386 [23.1%], p < 0.001), and previous suicide attempts (16 [9.2%] vs. 807 [48.4%], p < 0.001) were observed in the OHCA group. Risk of death at 30 days was significantly higher in the OHCA group (200 [93.9%] vs. 31 [1.8%], p < 0.001). Conclusion: Suicide-related OHCA was rare and associated with poorer prognosis compared to patients without OHCA. It was more common in middle-aged men without a history of psychiatric care or prior suicide attempts, although the study was limited by missing data. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 16 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. Design Observational study. Setting A single-centre retrospective observational study in Okayama, Japan. Participants We retrospectively analysed consecutive patients who underwent AF ablation under deep propofol sedation with adaptive servo-ventilation. A total of 686 patients were included. Patients were managed using a standardised sedation protocol with or without low-dose pentazocine. Patients treated with conventional manual compression for haemostasis (n=383) were compared with those treated using a venous access-site closure device (n=303). Interventions Postprocedural bed rest duration and the incidence and timing of PONV were compared between groups. Associations between closure device use and PONV were evaluated using logistic regression analysis. Primary outcome measure The primary outcome was the occurrence of PONV following AF ablation. Results All procedures were completed under propofol sedation without conversion to general anaesthesia. The duration of postprocedural bed rest was shorter in the device group than in the conventional-compression group (mean difference －14.7 hours, 95% CI －15.2 to －14.0). PONV occurred in 6/303 patients (2.0%) in the device group and 20/383 patients (5.2%) in the conventional-compression group, corresponding to a relative risk of 0.38 (95% CI 0.15 to 0.93), an OR 0.25 (95% CI 0.10 to 0.62) and a risk difference of －3.2% (95% CI －6.0% to －0.5%). In multivariable analysis, use of a venous closure device was associated with a lower likelihood of PONV. Conclusions In this single-centre observational study, use of a venous access-site closure device was associated with a lower occurrence of PONV after AF ablation under propofol sedation. These findings suggest that postprocedural management strategies enabling earlier mobilisation may be associated with improved patient comfort; however, causal inference is limited by the observational design. No potential conflict of interest relevant to this article was reported.

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

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. 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. 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). 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.

American Society for Microbiology Acta Medica Okayama 2576-098X 2026 Complete genome sequence of Helicobacter pylori strain NY43 harboring bacteriophage KHP30 e00747-26 EN Michiko Takahashi Department of Surgery, Kochi Medical School, Kochi University Hiromichi Maeda Department of Surgery, Kochi Medical School, Kochi University Satoru Seo Department of Surgery, Kochi Medical School, Kochi University Hiroaki Takeuchi Department of Medical Laboratory Sciences, Health and Science, International University of Health and Welfare Graduate School Jumpei Uchiyama Department of Infectious Diseases, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University Shigenobu Matsuzaki Department of Surgery, Kochi Medical School, Kochi University The Helicobacter pylori NY43 strain spontaneously releases the bacteriophage (phage) KHP30. Here, we report the complete genome sequence of H. pylori NY43. In addition to the chromosome of H. pylori NY43, we successfully obtained the complete sequence of the episomal prophage KHP30. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 17 1 2026 RNase-mediated defence and its association with SCCmec in Staphylococcus aureus 9986 EN Kohei Kondo Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Aa Haeruman Azam Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Junzo Hisatsune Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Shinjiro Ojima Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Kotaro Chihara Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Tomohiro Nakamura Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Azumi Tamura Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Wakana Yamashita Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Satoshi Nakano Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Shoko Kutsuno 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 Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Masayuki Amagai Department of Dermatology, Keio University School of Medicine Tetsuo Yamaguchi Department of Microbiology and Infectious Diseases, Toho University School of Medicine Yoshikazu Ishii Department of Microbiology and Infectious Diseases, Toho University School of Medicine Koichi Watashi Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Yoshimasa Takahashi Research Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security Kotaro Kiga Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Motoyuki Sugai Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security The rise of antibiotic resistance in Staphylococcus aureus is a major threat to global health. Resistance often emerges when bacteria acquire foreign DNA elements, such as the SCCmec cassette that makes strains resistant to nearly all β-lactam antibiotics. Yet, not all S. aureus lineages take up these elements equally, raising the question of what prevents some strains from becoming drug-resistant. Here we identify a previously unknown defence factor that explains this mystery in a common skin lineage (ST188), frequently isolated from patients with atopic dermatitis. Such defence factor is encoded by a gene, which we name sadR, that is present in methicillin-susceptible ST188 strains but absent from resistant counterparts. SadR exhibits RNase activity that provides anti-bacteriophage and anti-plasmid defence, thus acting as a barrier to the uptake of mobile genetic elements. Gene sadR is found in methicillin-susceptible strains in S. aureus lineages other than ST188, and is consistently located adjacent to rlmH, the canonical SCCmec integration site. Moreover, SadR homologues are widespread across staphylococci and other bacteria suggesting a previously unrecognised family of RNase-based defence systems. 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. Methods: This repeated cross-sectional study included 40,898 3-year-olds who underwent checkups in Okayama City, Japan. We compared children examined before (2017–2019) and during the pandemic (2020–2023). The primary outcome was physician-determined risk of language difficulties. The secondary outcome was children’s infrequent questions using words such as “what,” “who,” and “where.” Modified Poisson regression estimated RRs adjusted for confounders. Subgroup analyses examined effect modification by sex, childcare setting, and family size. Results: The COVID-19 pandemic was associated with increased risk of language difficulties (RR 1.52, 95% CI 1.35–1.72). The association peaked in fiscal year 2021 and remained elevated throughout the pandemic. Secondary outcome showed elevated risk (RR 1.16, 95% CI 1.05–1.29). Girls and home-care children showed higher RRs than boys and preschool attendees. Conclusions: The COVID-19 pandemic was associated with risk of language difficulties among 3-year-old children, with associations varying by sex and childcare setting. These findings suggest the importance of maintaining social interaction opportunities for young children during public health crises. No potential conflict of interest relevant to this article was reported.

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

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

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

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

Elsevier BV Acta Medica Okayama 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 (ρ) and amount-of-substance concentration (mol) were determined. The product of these values produced a ρ×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 ρ×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.

AIP Publishing Acta Medica Okayama 0021-9606 165 10 2026 Scaled-charge ion force field optimized for individual ion partial molar volumes in water 104508 EN Aoi Taira Department of Chemistry, Faculty of Science, Okayama University Hiroyuki Katsuto Department of Chemistry, Faculty of Science, Okayama University Kanon Nakao Department of Chemistry, Faculty of Science, Okayama University Tomonari Sumi Graduate School of Engineering, Muroran Institute of Technology Kenichiro Koga Department of Chemistry, Faculty of Science, Okayama University We present an ion partial molar volume force field for common monovalent and divalent ionic species, including Li+, Na+, K+, Cs+, Mg2+, Ca2+, F－, Cl－, Br－, I－, OH－, and H3O+. When combined with the TIP4P/2005 water model, the force field enables quantitative investigations of ion-specific effects in both bulk and interfacial properties. The iPMV force field is developed based on a single guiding principle: the ion–water interaction parameters are optimized such that the experimental partial molar volume of each individual ion at infinite dilution―determined via the ultrasonic vibrational potential method―is reproduced by construction. An exception is made for the hydronium ion, for which we also provide an alternative interface-optimized model. The force field employs a charge scaling factor of 0.75 and adopts the Lorentz–Berthelot combining rules for cross-Lennard-Jones interactions, with specific modifications for divalent cations. A distinctive feature of the iPMV force field is that, despite its straightforward design, a single set of ion parameters consistently reproduces a wide range of experimental properties―from volumetric and interfacial properties to salting-out/in effects and transport coefficients. This robust performance suggests a fundamental correlation between the partial molar volumes of individual ions and the broader physical properties of aqueous electrolyte solutions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2197-4284 13 1 2026 Carbon solubility and liquid–liquid immiscibility in Fe–C–S ternary system up to 6 GPa: implications for the core of small planetary bodies 60 EN Bin Zhao Institute for Planetary Materials, Okayama University Guillaume Morard UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université Geeth Manthilake Laboratoire Magmas et Volcans, Université Clermont-Auvergne Paraskevas Parisiades UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université Jing Yang Earth and Planets Laboratory, Carnegie Institution for Science Yingwei Fei Earth and Planets Laboratory, Carnegie Institution for Science Yann Le Godec UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université Nozomi Kondo Institute for Planetary Materials, Okayama University Takashi Yoshino Institute for Planetary Materials, Okayama University Daniele Antonangeli UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université High-pressure, high-temperature experiments were conducted in a multi-anvil press using seven different starting compositions to investigate the phase relations of Fe–C–S liquids at pressures up to 6 GPa and temperatures up to 2000 K. Quenched samples revealed immiscible C-rich and S-rich metallic liquids at 2 and 4 GPa, manifesting as either large immiscible zones or emulsified smaller droplets. On the contrary, no immiscibility was observed at 5 or 6 GPa. At these higher pressures, the carbon solubility limit, significantly reduced by increasing sulfur content in the ternary liquid, prevents the formation of a liquid phase rich in both C and S. Our findings thus indicate that super-liquidus immiscibility in Fe-rich compositions does not occur at pressures above 5 GPa, due to the differential pressure dependence of C solubility and miscibility. The limited C solubility in S-rich liquids at higher pressures effectively suppresses immiscibility. Based on these results, terrestrial planetary bodies with fluid cores at pressures exceeding 5 GPa are unlikely to experience liquid–liquid immiscibility, even when both carbon and sulfur are abundant, as sulfur limits carbon solubility and promotes its exsolution. For the Moon, immiscibility-induced core stratification is not expected, though local emulsification could occur near the core–mantle boundary (CMB). In smaller bodies, a two-liquid Fe–C–S core may form at high temperatures, but progressive cooling may lead to graphite crystallization and the potential development of a graphitic crust. 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 1010-6030 478 2026 Deep-blue solid-state emission from Ternaphthalene: Photophysical tuning via multi-chromophore architectures 117156 EN Minoru Yamaji Division of Molecular Science, Graduate School of Science and Engineering, Gunma University Kengo Suzuki Hamamatsu Photonics K.K. Hideki Okamoto Department of Chemistry, Faculty of Environment, Life, Natural Sciences and Technology, Okayama University We report the synthesis and photophysical characterization of a series of “all-naphthalene” multi-chromophore systems, ternaphthalenes (TNps), designed for efficient deep-blue solid-state emission. Unlike planar polycyclic aromatic hydrocarbons that suffer from aggregation-caused quenching (ACQ), the twisted molecular architecture of TNps effectively inhibits π-π stacking interactions. Consequently, several TNps exhibit crystallization-induced emission enhancement (CIEE) or retain high quantum yields (up to 0.94) in the solid state. Kinetic analysis revealed that this efficiency stems from the significant suppression of non-radiative rates (knr) due to the restricted intramolecular rotation in the rigid crystal lattice. Furthermore, a decisive topological effect on the radiative rate (kf) was demonstrated. The 1,4-, 1,5- and 2,6-linked isomers display allowed transitions with large oscillator strengths (f) and fast radiative rate (kf = ca. 5 × 108 s－1), whereas the 2,7-linked isomers exhibit forbidden-like character with prolonged lifetimes. A distinct linear correlation between the experimental and calculated values empirically supports the applicability of the Strickler-Berg relationship in both solution and solid states. These findings demonstrate that controlling the chromophore connectivity is a powerful strategy to tune excited-state dynamics for developing high-performance deep-blue organic emitters. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2367-0932 10 3 2026 Substitution‐Dependent Modulation of Photophysical Properties of 2,7‐ and 3,6‐Dinaphthyl‐9‐phenylcarbazoles in Solution and Solid State e202500335 EN Minoru Yamaji Division of Molecular Science, Graduate School of Science and Engineering, Gunma University Tadashi Mori Research Center for Environmental Preservation and Graduate School of Engineering, The University of Osaka Hideki Okamoto Department of Chemistry, Faculty of Environment, Life, Natural Sciences and Technology, Okayama University The photophysical properties of two positional isomers of dinaphthyl-9-phenylcarbazoles (2,7-DNpPCz and 3,6-DNpPCz) were systematically investigated in solution and solid states. Experimental measurements revealed a pronounced positional dependence, although both compounds exhibit fluorescence in solution and the solid state. On average, the 2,7-isomers exhibit larger fluorescence rate values than the 3,6-isomers, although the magnitude of this difference varies among individual compounds. To gain mechanistic insight, density function theory (DFT) and time-dependence DFT calculations were performed at the (TD)-B3LYP/6-31+G(d) level. The results show that 2,7-DNpPCz derivatives possess delocalized frontier orbitals and large oscillator strengths for the S1 ← S0 transition, whereas 3,6-DNpPCz derivatives exhibit smaller oscillator strengths with mixed orbital contributions, leading to weaker transition probabilities. These combined findings demonstrate that substitution geometry critically governs radiative decay dynamics in carbazole-based luminophores and provide valuable guidelines for the molecular design of efficient solid-state organic emitters. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2238-7854 45 2026 Enhancement of mechanical properties in a cast hypereutectic Al–Si alloy via rapid cooling in heated mold continuous casting 485 494 EN Shuhei Takeuchi Graduate School of Environment, Life, Natural Science and Technology, Okayama University Shota Nakagawa UACJ Corporation Yoshifumi Shinzato UACJ Corporation Tadashi Minoda UACJ Corporation Naotaka Ohtsuka UACJ Corporation Mitsuhiro Okayasu Department of Mechanical and Systems Engineering, Okayama University To enhance mechanical properties in cast hypereutectic Al–Si alloys, Al–14.5Si samples were produced by the heated mold continuous casting (HMC). The HMC process was conducted under unidirectional solidification at cooling rates (CRs) ranging from 4.6 × 10－1 to 1.3 × 103 K/s, which were obtained by controlling the casting speed (CS). The microstructure basically consisted of α-Al dendrite, Al–Si eutectic and primary Si, while their area fractions (fα-Al, fe, and fp-Si) varied depending on the CR. At the low CR of 4.6 × 10－1 K/s, their area fractions were as follows: fα-Al = 0.2%, fe = 97.3%, and fp-Si = 2.5%, which is the typical microstructural morphology of a hypereutectic Al-Si alloy. In contrast, at the high CR of 1.3 × 103 K/s, those area fractions were altered to fα-Al = 32.3% and fe = 67.7%, while primary Si was strongly suppressed (fp-Si ≈ 0%) despite the hypereutectic Al–14.5Si alloy. Moreover, at the high CR, the aluminum matrix appears to exhibit a nearly uniform crystal orientation along <101>. These microstructural changes may be related not only to high CR but also the difference in growth kinetics between primary Si and α-Al dendrites. Accordingly, an apparent eutectic composition shifted from 12.6 to 19.7 wt% Si. The atypical microstructural formation led to a significant improvement in the tensile properties: the ultimate tensile strength of 400 MPa and fracture strain of 17%. These tensile properties are more than twice those of the conventional cast hypereutectic Al–14.5Si alloy. No potential conflict of interest relevant to this article was reported.

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

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

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.

Elsevier BV Acta Medica Okayama 0005-2728 1868 1 2027 Structural and functional analysis of a photosystem II mutant PsbA3-S264V 149607 EN Songbo Fan Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiki Nakajima Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koji Kato Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haowei Jiang Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pi-Cheng Tsai Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Anqi Jia Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Miwa Sugiura Proteo-Science Research Center, Ehime University Jian-Ren Shen Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Photosystem II (PSII) catalyzes water oxidation and oxygen evolution by a light-induced electron transfer chain, leading to the generation of electrons, protons and dioxygen. D1-S264 is a residue located close to the QB-binding site, and mutation of this residue has been shown to bring significant effects on the electron transfer and oxygen-evolving activities. Here we analyzed the structure of a Thermosynechococcus elongatus mutant PsbA3-S264V by cryo-electron microscopy at 1.96 Å resolution, which showed significant changes in the structure surrounding the bicarbonate and QB-binding region. Due to change of Ser to Val, the hydrogen-bond between the QB carbonyl oxygen and S264 is altered, which changed the protonation pathway of QB from the original route of D1-H252 through D1-S264 to QB, to a new, longer and less efficient route of D1-H252 through D1-F265 to QB. Two residues, D1-E244 and D2-E242, changed their side chain orientations significantly. Among them, D2-E242 adopted two conformations, and both are largely deviated from the original structure. All these changes led to alterations in hydrogen-bonding networks of two channels, channel A and channel B, that connect the stromal surface to QB and may function to transport protons to protonate QB. Furthermore, isothermal titration calorimetry experiments showed a diminished 3-(3,4-dichlorophenyl)-1, 1-dimethylurea (DCMU) binding affinity of the mutated PSII, which may be explained by a structural rotation of D1-F255 in the mutant based on structural analysis of DCMU-bound PSII. These findings offer valuable insights into the functions of D1-S264 in QB protonation and function, as well as in the DCMU-binding. 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.

Wiley Acta Medica Okayama 1758-5902 19 1 2026 Transcystostomal Bladder Tumor Resection in a Transgender Man After Phalloplasty e70330 EN Takatoshi Moriwake Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Tominaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nariaki Ozaki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Matsumoto Department of Urology, Miyakekai Good Life Hospital Tomoko Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ichiro Tsuboi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kasumi Yoshinaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoaki Yamanoi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira 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 Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuzaburo Namba Gender Center, Okayama University Hospital Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction Phalloplasty in transgender men is frequently complicated by a neourethral stricture, precluding standard transurethral access for bladder tumor resection. We describe the first reported case of a transcystostomal bladder tumor resection in a transgender man after a radial forearm free flap (RFFF) phalloplasty. Materials and Surgical Technique A 65-year-old transgender man, 23 years after an RFFF phalloplasty, presented with gross hematuria and a 15-mm posterior bladder tumor. A 7.95 Fr flexible ureteroscope reached the bladder but with markedly limited maneuverability. A two-stage transcystostomal approach was used: a 14 Fr suprapubic cystostomy (SPC) was placed 1 month before resection for tract maturation, followed by balloon dilation and insertion of a 24 Fr resectoscope. The modified Valdivia position enabled simultaneous transcystostomal and transurethral access with gravity-assisted irrigation drainage. Complete tumor resection was achieved without complications, and pathology confirmed noninvasive papillary urothelial carcinoma (pTa, low-grade) with negative margins. A single immediate intravesical instillation of pirarubicin was administered. Surveillance cystoscopy via the cystostomy tract at 3 and 6 months revealed no recurrence; the patient continues to void while standing with the cystostomy catheter capped. Discussion The two-stage transcystostomal approach, combining prior SPC placement, balloon tract dilation, and the modified Valdivia position, enabled safe oncological control while preserving phallic anatomy and standing voiding function. This technique offers a reproducible option for bladder tumor resection in patients with functionally inadequate transurethral access after phalloplasty. No potential conflict of interest relevant to this article was reported.

日本健康教育学会 Acta Medica Okayama 1340-2560 34 2 2026 中・高・大学生の健診結果活用の促進要因―ヘルスリテラシースキルフレームワークを用いた検討― 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’s University Takehiko ITO Graduate School of Education, Okayama University 目的：学校健康診断結果活用（以下，活用）と関連要因及び相互の関連性をヘルスリテラシースキルフレームワークを用いて明らかにすることを目的とした． 方法：中学生493名，高校生360名，大学1年生297名を対象に無記名自記式質問紙調査を行った．調査内容は活用と，健康への関心，ヘルスリテラシー（以下，HL），健診結果に対する認識，健診結果の読解力（以下，読解力），意思決定バランスとした．これらの関連性を示す仮説モデルを校種，性別の多母集団同時パス解析で検証した． 結果：仮説モデルに4つのパスを追加した修正モデルで，校種，性別いずれにおいても配置不変モデルで良好な適合度を得た．健診結果に対する認識から読解力，読解力から意思決定バランス，意思決定バランスから活用，健康への関心から読解力，意思決定バランス，活用へのパス及び，HLから活用へのパスは全ての校種において有意であった．健康への関心と結果に対する認識からHL，HLから読解力，意思決定バランスへのパスは中・高校生のみで有意であった． 結論：中・高・大学生の健診結果活用を促すためには，健診結果を分かりやすくすること，健診結果の読解力及び意思決定バランスの向上，すなわち恩恵の認識の向上と，負担の認識の軽減が有効であり，その際に対象者の健康への関心とHLの程度を考慮する必要性が示唆された． No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2577-171X 9 4 2026 Varicocelectomy Restores Spermatogenesis in Fontan‐Associated Varicocele: A Two‐Case Series e70206 EN Yusuke Tominaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Matsumoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takatoshi Moriwake Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nariaki Ozaki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira 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 Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Fontan circulation may cause chronic venous hypertension and predispose patients to varicocele and infertility,but the clinical significance of surgical treatment remains unclear. Case Presentation: We describe two patients with Fontan circulation who developed Fontan-associated varicocele (FAVC). A42-year-old man presented with secondary infertility, bilateral varicocele, and progression to azoospermia after Fontan surgery.A 28-year-old man had asthenozoospermia, bilateral varicocele, and repeated failure of assisted reproductive technology. Bothunderwent bilateral microsurgical varicocelectomy with perioperative heparin bridging. Postoperative semen parameters im-proved in both patients, with sperm reappearing in the first case. Conclusion: Varicocelectomy for FAVC may restore spermatogenesis in selected cases, but the risk of postoperative recurrencemay be increased. 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. 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. 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. 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. Methods This multicenter retrospective study included 44 patients with 48 lesions who underwent initial NIR-PIT between January 2021 and March 2026. The primary analysis compared outcomes according to prior ICI exposure. An exploratory analysis evaluated outcomes according to treatment sequence and timing of ICI administration. The primary endpoint was local control. Secondary endpoints were objective response rate and disease control rate, while overall survival was assessed exploratorily. Results Median local control duration was 253 days, but was 174 days in the prior ICI exposure group and 342 days in the non-prior ICI exposure group (log-rank P = 0.031). Local progression occurred in 69.2–37.1% of lesions, respectively (P = 0.059). Among 45 evaluable lesions, the objective response rate and disease control rate were 60.0–93.3%, respectively. Median overall survival was 866 days. Exploratory analyses suggested potential differences in clinical outcomes according to treatment sequence and ICI timing. Conclusions Prior ICI exposure was associated with poorer local control after NIR-PIT. Exploratory analyses suggested that ICI timing and treatment sequencing may influence clinical outcomes. Treatment sequencing may represent an important consideration when integrating NIR-PIT and ICIs for recurrent or metastatic head and neck cancer. 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’s disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Tetrabenazine (TBZ), a vesicular monoamine transporter 2 inhibitor, is commonly used to manage chorea; however, it may exhibit fluctuating plasma levels and elicit frequent adverse events. In this study, we aimed to clarify the effects of TBZ deuteration on its safety profile. We compared the safety profiles of TBZ and deutetrabenazine (DTBZ) in real-world clinical practice using disproportionality analysis and the large-scale pharmacovigilance database, VigiBase―the WHO’s global database of adverse drug reactions. Adverse event signals were assessed using the information component (IC). Seriousness was classified according to clinical outcome, and time to onset (TTO) was analyzed for selected events. TBZ showed signals for disorientation, dystonia, and sleep disorders (IC025 > 0), whereas DTBZ did not. Serious adverse events were reported in 54.7% of TBZ cases and 37.9% of DTBZ cases. The TTO of sleep disorder was also evaluated; however, the number of cases with available TTO information was limited. DTBZ showed fewer adverse event signals and a lower proportion of serious adverse events than TBZ. These findings suggest potential differences in the safety profiles of the two drugs, which may influence tolerability in the treatment of HD. 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. Methods A cohort of patients receiving ICI therapy from 2010 to 2023 was identified from the TriNetX database. Cardiac irAEs were defined as the occurrence of relevant diagnosis codes within 90 days of ICI initiation, with corresponding hospital visits. We created ML models to predict these events, including elastic net logistic regression and multiple tree-based approaches (gradient boosted trees and random forest). We evaluated model performance with different performance measures and utilized assigned risk scores to stratify risk of cardiac irAEs into low, medium, and high-risk tiers. Results We identified 61,117 patients receiving ICI therapy, with nearly 2% of patients experiencing cardiac irAEs. Model performance on testing data was comparable with all approaches (AUC = 0.71–0.72, balanced accuracy = 65–66%). Each model emphasized distinct features to make classifications, as observed with feature importance and SHAP values. Comparing cardiac irAE rates among assigned risk strata, patients identified as high risk were significantly more likely to experience cardiac irAEs compared to lower tiers. Conclusion Our preliminary exploration of ML methods demonstrated the potential for risk assessment tools to predict rare cardiac irAEs in patients receiving ICI therapy. Follow-up studies can implement time series approaches to harness longitudinal data that incorporates real-time labs, new diagnoses, and new therapy, to refine predictions further. 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. Design: A pharmacovigilance–pharmacodynamic analysis using a spontaneous reporting system. Methods: This pharmacovigilance study used VigiBase, an adverse drug reaction database maintained by the World Health Organization. Drug–drug interactions (DDIs) between clozapine and other antipsychotics were assessed using the Ω 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 Ω shrinkage measure model (β = 0.295, 95% confidence interval: 0.119–0.471, p = 0.002) and replicated across all frequency statistical models. Conclusions: These findings suggest a potential role of dopamine D4 receptor occupancy in seizures associated with clozapine augmentation by other antipsychotics. Further large-scale epidemiological studies are needed to validate these findings. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 2026 Stereoselective synthesis of β,β-diborylalanine (AlaBB) and its incorporation into oligopeptides EN Naoyuki Nitta Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kenshin Nakai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haruki Mizoguchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akira Sakakura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University We report the stereoselective synthesis of β,β-diborylalanine (AlaBB), a compact amino acid scaffold designed to introduce a gem-diboronic acid motif as a branched connector in peptides. Pinacol-protected AlaBB derivatives, denoted as AlaBB(pin)2, were prepared from an Ellman imine, incorporated into short peptides, and converted to the corresponding gem-diboronic acid form. No potential conflict of interest relevant to this article was reported.

Japan Surgical Society Acta Medica Okayama 2198-7793 12 1 2026 Single-Incision Laparoscopic Hartmann’s Reversal Using the Stoma Site in a Patient with Perioperative Anaphylaxis cr.26-0206 EN Tsubasa Yanagihara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama, Japan Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshitaka Kondo 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 INTRODUCTION: Reversal of Hartmann’s procedure is associated with substantial morbidity, and further reduction of surgical invasiveness may be beneficial in selected patients. Perioperative anaphylaxis caused by anesthetic agents or skin antiseptics poses a significant challenge to surgical management. We report a case of stoma-site single-incision laparoscopic Hartmann’s reversal (HR) performed in a patient with severe perioperative allergies. CASE PRESENTATION: A 73-year-old woman underwent an emergency open Hartmann’s procedure with partial cystectomy for perforated sigmoid colon cancer with bladder invasion. After adjuvant chemotherapy, she developed a progressively enlarging giant parastomal hernia that significantly impaired daily activities. Two attempts at HR were aborted because of perioperative anaphylactic shock. Subsequent allergy evaluations suggested rocuronium and chlorhexidine as causative agents, and povidone-iodine was also avoided based on clinical history. Approximately 14 months after the initial surgery, single-incision laparoscopic HR using the stoma site was successfully performed under general anesthesia without neuromuscular blocking agents. Preoperative skin antisepsis was performed using benzalkonium chloride, avoiding both chlorhexidine and povidone-iodine. No additional abdominal incisions were required. The operative time was 2 h 56 min, with minimal blood loss. The postoperative course was uneventful and she was discharged on POD 9. CONCLUSIONS: Stoma-site single-incision laparoscopic HR may represent a useful surgical option for selected patients with severe perioperative allergies to anesthetic agents and skin antiseptics, in whom minimizing abdominal approach and wound-related risks is particularly important. 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. Methods: This multi-institutional retrospective study included 584 patients undergoing initial hepatectomy for CRLM. The impact of KRAS mutation was assessed according to primary tumor sidedness and tumor burden score (TBS). A nomogram predicting overall survival (OS) was constructed using independent prognostic factors and compared with established clinical risk scores. Results: KRAS mutation was identified in 36.8% of patients and was associated with worse OS (median survival: 47.3 vs. 70.6 months, p = 0.0006) and recurrence-free survival. This adverse impact was observed in left-sided tumors but not in right-sided tumors. TBS stratified prognosis in KRAS wild-type but not in mutant cases, suggesting that tumor biology may outweigh morphology. A nomogram incorporating KRAS status, TBS, CA19-9, primary nodal status, and extrahepatic disease demonstrated improved discriminatory ability compared with conventional models and stratified recurrence patterns, including extrahepatic recurrence. Conclusions: The prognostic impact of KRAS mutation depends on tumor sidedness and is independent of tumor morphology. Our nomogram provides a continuous biological risk assessment and may facilitate biological risk stratification and support future refinement of the concept of biologically borderline resectable CRLM. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2165-0497 14 8 2026 High-throughput screening system for antimycobacterial compounds using in vitro infected cells: construction and application to compounds in the Ōmura Natural Compound Library e00484-26 EN Takemasa Takii Department of Mycobacterium Reference and Research, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Aoi Kimishima Ōmura Satoshi Memorial Institute, Kitasato University Masato Iwatsuki Ōmura Satoshi Memorial Institute, Kitasato University Yoshihiro Watanabe Ōmura Satoshi Memorial Institute, Kitasato University Naoya Ohara Department of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University Yukihiro Asami Ōmura Satoshi Memorial Institute, Kitasato University The global increase in multidrug-resistant tuberculosis strains poses a major threat; consequently, there is an urgent need to identify and develop novel drugs. We have previously presented a simple fibroblast assay (SFA) screening method that enables the simultaneous assessment of antibacterial activity and cytotoxicity toward host cells. This method was developed based on our finding that live (but not dead) Mycobacterium tuberculosis bacilli exhibit cytotoxic activity against human lung fibroblasts, and that this cytotoxicity, which is proportional to the number of viable bacterial cells, is inhibited by known antimycobacterial drugs. While conventional methods to measure M. tuberculosis growth require 2–4 weeks to detect antibacterial activity; the SFA method enables detection within 2–3 days and can detect compounds that are active within host cells. Here, we applied high-throughput screening, based on assessment of cytotoxicity, to identify candidate antimycobacterial agents. In parallel, by comparing the direct antibacterial activity of compounds in liquid medium (using the broth dilution test) with that observed via SFA, we developed a new SFA-based screening system to select compounds with low cytotoxicity that are active outside or inside the host cells. Using this dual system, we screened 742 compounds from the Ōmura Natural Compound Library (Kitasato University, Japan), with 62 hits. Of these, 19 were excluded owing to their toxicity, and six exhibited antibacterial activity only via SFA screening. Four promising antimycobacterial candidates with no cytotoxicity at the 10 μg/mL threshold―aridicin A, lankamycin, streptovaricin, and lariatin A―were identified. identified.This novel system supports the rapid identification of low-cytotoxicity antimycobacterial compounds that are active inside or outside the host cells. 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.

Walter de Gruyter GmbH Acta Medica Okayama 2195-4720 7 3 2013 An Efficient Synthesis of Limipterin [2'-O-(2-Acetamido-2-deoxy-β- D-glucopyranosyl) -L- biopterin] via N2 - (N ,N -Dimethylamino )-methylene- 3-[2-(4-nitrophenyl)ethyl]-L-biopterin 110 112 EN Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Koichiro Harada Department of Chemistry, Faculty of Science, Okayama University Heizan Kawamoto Department of Chemistry, Faculty of Science, Okayama University Wolfgang Pfleiderer Universitat Konstanz, Fakultat fur Chemie No potential conflict of interest relevant to this article was reported.

Japan Surgical Society Acta Medica Okayama 2198-7793 12 1 2026 Successful Lung Transplantation after Plasma Exchange in a Patient with High Thermal Amplitude Cold Agglutinins: A Case Report cr.26-0502 EN Yuya Miyoshi Department of General Thoracic Surgery, Okayama University Hospital Kentaroh Miyoshi Department of General Thoracic Surgery, Okayama University Hospital Naomi Asano Division of Transfusion and Cell Therapy, Okayama University Hospital Haruchika Yamamoto Department of General Thoracic Surgery, Okayama University Hospital Shin Tanaka Department of General Thoracic Surgery, Okayama University Hospital Shuji Okahara Department of General Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of General Thoracic Surgery, Okayama University Hospital, Okayama, Okayama, Japan Seiichiro Sugimoto Department of General Thoracic Surgery, Okayama University Hospital Nobuharu Fujii Division of Transfusion and Cell Therapy, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery, Okayama University Hospital INTRODUCTION: Cold agglutinins (CAs) are immunoglobulin M autoantibodies that induce red blood cell agglutination at low temperatures and may cause hemolytic or thrombotic complications during procedures associated with hypothermia. In lung transplantation (LT), blood may be exposed to low temperatures within the reperfused lung graft and the extracorporeal circulation circuit, potentially increasing the risk of CA-mediated complications. However, the perioperative significance of CAs in this setting remains unclear, and optimal management has not been established. We report a case of successful bilateral LT in a patient with high-thermal-amplitude CAs managed with preoperative plasma exchange (PLEX) and strict intraoperative temperature control. CASE PRESENTATION: A 55-year-old man with diffuse panbronchiolitis and secondary pulmonary hypertension was listed for bilateral LT. Preoperative testing incidentally revealed clinically significant CAs, with a titer of 1:128 at 4°C and a thermal amplitude of 30°C. Because intraoperative blood temperature might approach this threshold despite active warming, a single preoperative session of PLEX using 36 units of fresh frozen plasma was performed to reduce the risk of a CA-mediated complication. Bilateral LT was subsequently completed under meticulous temperature management, including extracorporeal circulation maintained at 37.5°C, continuous systematic warming, avoidance of topical ice application, and rewarming of the donor lungs before reperfusion. After surgery, the CA titer decreased to 1:32. The postoperative course was uneventful, without thromboembolic events, primary graft dysfunction, or bronchial complications. CONCLUSIONS: LT may be performed safely in selected patients with high-thermal-amplitude CAs when careful perioperative temperature control is combined with preoperative PLEX. PLEX should be considered when the anticipated intraoperative temperature is expected to approach the patient’s thermal amplitude threshold. 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 μm 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.

Oxford University Press (OUP) Acta Medica Okayama 0366-7022 54 6 2025 Vesicle-combined PtBi/C catalyst for base-free conversion of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid upaf104 EN Toshinori Shimanouchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koji Deguchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuma Yasuhara Division of Materials Science, Nara Institute of Science and Technology (NAIST) Yukitaka Kimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University A conversion of 5-hydroxymethylfurfural to 2,5-frandicarboxylic acid (FDCA) was catalyzed by using a catalyst of PtBi-activated carbon (PtBi/C) combined with vesicles made of phospholipid. No alteration of the electron state of the PtBi/C by vesicles was observed. However, FDCA was obtained under mild-temperature and base-free conditions. The yield of FDCA depended on the hydration nature of vesicles. It was therefore suggested that vesicles gave bound water as a novel driving force for the reaction. The present finding would explore an application of vesicles to new catalytic reactions that are different from conventional biochemical reactions. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0376-7388 757 2026 Multi-criteria evaluation of graphene oxide nanofiltration membranes for decaffeination 125992 EN Yihan Tian School of Materials Science and Engineering, University of New South Wales Tongxi Lin School of Materials Science and Engineering, University of New South Wales Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Xiaojun Ren School of Materials Science and Engineering, University of New South Wales Rakesh Joshi School of Materials Science and Engineering, University of New South Wales Nanofiltration (NF) offers a promising low-energy approach for producing decaffeinated instant coffee, while requires membranes that balance caffeine removal, water permeance, and retention of key coffee matrix compounds. Here, graphene oxide membranes (GOMs) were modified by sodium alginate (SA) intercalation, Ca2+ crosslinking, and their combined strategy to tune nanochannel structure and separation performance. The results show that membrane modification does not follow a simple monotonic trend; instead, small structural and chemical changes generate competing effects on permeance and selectivity through coupled transport, adsorption, and confinement mechanisms. To identify the most suitable membrane, a multi-criteria evaluation framework (MCEF) combining entropy weighting and TOPSIS was established using five key performance indicators: caffeine removal, flavour-related marker retention index, choline retention, water permeance, and concentration increase. This framework identified CGSM-1 as the best-performing flat membrane, which also showed promising performance in hollow-fibre form. In coffee filtration tests, CGSM-1 reduced caffeine concentration from 24.64 to 12.95 μg/mg, corresponding to a 47.4% reduction, while retaining measurable levels of HMF, trigonelline, NMP, and choline. These findings demonstrate the potential of engineered GOMs for selective caffeine reduction in coffee liquor and provide a practical evaluation strategy for membrane-based decaffeination. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1880-6546 76 3 2026 Effects of serotonin transporters on myocardial cell injury during ischemia/reperfusion in rats 100085 EN Yoshimasa Kishi Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Shuji Shimizu Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Yosuke Kuroko 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 Tsuyoshi Akiyama Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Serotonin (5-HT) reuptake in the heart is mediated by the platelet serotonin reuptake transporter (SERT) and the cardiomyocyte plasma membrane monoamine transporter (PMAT). However, the specific roles of these transporters in myocardial cell injury during ischemia/reperfusion remain unclear. Sprague-Dawley rats underwent left coronary artery occlusion followed by reperfusion. Using cardiac microdialysis technique, fluoxetine (SERT inhibitor, 900 μM) or decynium 22 (PMAT inhibitor, 100 μM) was administered locally to the ischemic region. Myoglobin concentrations in the dialysate were measured during ischemia followed by reperfusion. In the fluoxetine-treated group, peak myoglobin concentration (14,889 ± 1364 ng/mL) during 0–15 min of reperfusion was significantly higher compared to both the control group (9800 ± 1627 ng/mL) and the decynium 22-treated group (8172 ± 877 ng/mL) (P < 0.01 for both). Local SERT inhibition exacerbated myocardial cell injury during ischemia/reperfusion. However, co-inhibition of PMAT reduced myocardial cell injury under SERT inhibition to the control level. 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. Methods: We conducted a retrospective cohort study on patients with FALD who were referred to our gastroenterology department. The cumulative incidence of HCC after FALD diagnosis was calculated, and multivariate analysis was used to identify independent risk factors. Overall survival after FALD diagnosis was compared between patients who developed HCC and those who did not. Results: A total of 120 patients with FALD were followed up for a median period of 50.0 months. The cumulative incidence rates of HCC at 1, 2, and 3 years after FALD diagnosis were 0.9%, 2.7%, and 3.9%, respectively. Elevated alpha-fetoprotein (AFP) at FALD diagnosis was independently associated with HCC development (hazard ratio, 1.29; 95% confidence interval, 1.04–1.60; p=0.01). There was no significant difference in overall survival between patients with and without HCC in this cohort (log-rank test, p=0.50). Conclusions: Patients with FALD face a non-negligible risk of developing HCC, thus supporting the need for surveillance. Elevated AFP levels at the time of FALD diagnosis may aid in risk stratification, which enables the targeted monitoring and early detection of HCC. Furthermore, routine surveillance contributes to the excellent prognosis of patients with FALD who develop HCC, thus making their prognosis comparable to that of patients without HCC. No potential conflict of interest relevant to this article was reported.

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

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

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.

Wiley Acta Medica Okayama 2052-8817 13 1 2026 Clinical and Microbiological Characteristics of Invasive Group A Streptococcus Infection: Four Case Series of Re‐Emerging Pathogens e70160 EN Shuji Okahara Department of Intensive Care, Okayama University Hospital Shinnosuke Fukushima Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuto Hamaguchi Department of Anesthesiology and Resuscitology, Okayama University Hospital Masanobu Hishiike Department of Anesthesiology and Resuscitology, Okayama University Hospital Yohei Motoi Department of Anesthesiology and Resuscitology, Okayama University Hospital Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Introduction: Group A Streptococcus (GAS), particularly the M1UK lineage, has re-emerged as a major global public health concern following the COVID-19 pandemic, with a rise in invasive GAS (iGAS) and streptococcal toxic shock syndrome (STSS). Although STSS is under national surveillance in Japan, comprehensive molecular monitoring of iGAS infections remains limited, and the clinical characteristics of M1UK-associated iGAS have not been fully elucidated. Methods: We retrospectively reviewed four consecutive iGAS cases requiring intensive care between March and May 2024. Detailed clinical, microbiological, and genomic investigations were performed to characterize the causative strains and their associated virulence profiles. Results: All patients required respiratory and/or circulatory support with surgical debridement. Three cases involved necrotizing fasciitis, and one involved intra-abdominal infection secondary to ovarian tumor rupture. All four patients received penicillin G and clindamycin as definitive antimicrobial therapy, with two developing severe drug-related adverse events. Genotypic analysis identified three isolates as emm1 strains, including two M1UK lineage strains. The two M1UK isolates commonly harbored multiple superantigen genes. All isolates remained susceptible to β-lactam, clindamycin, and macrolide antibiotics. Conclusion: This case series documents the identification of the M1UK lineage among critically ill patients with iGAS infections in Japan. Our findings support the need for continued molecular surveillance while reinforcing the importance of prompt surgical source control and appropriate antimicrobial therapy in the management of severe iGAS. No potential conflict of interest relevant to this article was reported.

Georg Thieme Verlag KG Acta Medica Okayama 0936-5214 2006 13 2006 Novel Preparation of a 2′-O-Acetyl-1′-O-(4-methoxybenzyl)-l-biopterin Derivative, a Versatile Precursor for a Selective Synthesis of l-Biopterin Glycosides 2075 2078 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Hiroki Toyota Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University l-Rhamnose was converted, over a 13-step-sequence, into 2′-O-acetyl-N 2-(N,N-dimethylaminomethylene)-1′-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]-l-biopterin, an appropriately protected precursor of 1′-O- and 2′-O-monoglycosyl-l-biopterin. Thus, the first selective synthesis of these l-biopterin glycosides was accomplished by treatment of the precursor with either DDQ or sodium methoxide, then with tetra-O-benzoyl-α-d-glucopyranosyl bromide in the presence of silver triflate and tetramethylurea, followed by removal of the remaining protecting groups. No potential conflict of interest relevant to this article was reported.

American Astronomical Society Acta Medica Okayama 0004-637X 999 2 2026 Constraining the Effects of Pre- and Post-accretionary Processes on Ryugu Insoluble Organic Matter 187 EN Christian Potiszil Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Masahiro Yamanaka Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Tsutomu Ota Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Chie Sakaguchi Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Hiroshi Kitagawa Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Ryoji Tanaka Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Tak Kunihiro Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Katsura Kobayashi Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Eizo Nakamura Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Asteroidal and cometary fragments have been indicated as possible sources of the building blocks of life for the early Earth. Samples returned from the asteroid Ryugu are uncontaminated and contain organic matter. Such samples enable an investigation of the processes that formed and altered extraterrestrial organic matter. Here, the FTIR and Raman responses of insoluble organic matter (IOM) isolated from Ryugu particles and carbonaceous chondrites are reported. Several relationships were observed: (1) a strong positive correlation of CH2/CH3 plotted against aliphatics/C=C; (2) a strong negative correlation of CH2/CH3 plotted against δ15N and δ13C; and (3) strong negative correlations of FTIR band ratios plotted against Raman band parameters and D/G values. The data are not consistent with even moderate heating of the IOM, as indicated by CH2/CH3 ratios that are consistent with unheated carbonaceous chondrites. The C and N isotope data previously collected for each Ryugu particle preclude aqueous alteration based on our understanding of its effects on carbonaceous chondrite IOM. Mixing of several IOM endmembers was considered, but due to the similarities of the particle with the lowest CH2/CH3 ratio to the other particles in terms of its other spectroscopic parameters, this scenario was considered unlikely. Finally, the effects of irradiation were considered, and UV irradiation, in particular, was hypothesised to be the best explanation for the trends observed. Overall, the data highlight the importance of comprehensive data sets for revealing extraterrestrial processes, which could define the nature of organic matter reaching habitable environments, such as those of the Early Earth. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 0094-8276 53 13 2026 Limits of Water Storage in Stishovite at Deep Mantle Conditions e2025GL120078 EN Fei Wang Bayerisches Geoinstitut, University of Bayreuth Artem Chanyshev Bayerisches Geoinstitut, University of Bayreuth Lianjie Man Bayerisches Geoinstitut, University of Bayreuth Yunke Song Bayerisches Geoinstitut, University of Bayreuth Lin Wang Bayerisches Geoinstitut, University of Bayreuth Takayuki Ishii Institute for Planetary Materials, Okayama University Noriyoshi Tsujino Japan Synchrotron Radiation Research Institute Shrikant Bhat Deutsches Elektronen‐Synchrotron DESY Robert Farla Deutsches Elektronen‐Synchrotron DESY Tomoo Katsura Bayerisches Geoinstitut, University of Bayreuth The deep Earth water cycle is a key process in Earth's evolution. Stishovite has been proposed as a major carrier of water from the surface into the lower mantle. However, its role remains unclear because its water solubility is controversial. We investigated the water solubility of Al-free stishovite at pressures of 33–38 GPa and temperatures of 700–1200 K using in situ X-ray diffraction in an advanced multianvil apparatus. Water solubility is high, around 3 wt%, at 700 K but decreases rapidly with increasing temperature and becomes negligible (<1,000 ppm), at temperatures above 1000 K. These results suggest that pure stishovite is unlikely to transport significant amounts of water into Earth's lower mantle under comparable pressure-temperature conditions. Previously reported high water contents in pure stishovite under deep Earth conditions likely reflect the solubility of post-stishovite or experimental artifacts. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-152X 63 8 2026 First Total Synthesis and Structural Elucidation of Microcystbiopterin C, a Pterin Glycoside From a Microcystis Bloom 1278 1287 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Katsuya Iwasaki Department of Chemistry, Faculty of Science, Okayama University The first total synthesis and unambiguous structural elucidation of microcystbiopterin C, a pterin glycoside isolated from a Microcystis bloom, has been achieved. Two candidate biopterin glycosides (5a and 5b) corresponding to the proposed structures of microcystbiopterin C were synthesized by glycosylation of a suitably protected biopterin derivative 10 with 2,4-di-O-benzoyl-6-deoxy-3-O-methyl-α-L-mannopyranosyl bromide (9) and the corresponding α-D-mannopyranosyl bromide (22), respectively, followed by stepwise deprotection. Detailed comparison of the NMR data and the specific rotation of compounds 5a and 5b with those of the natural product established that microcystbiopterin C possesses the structure of 2′-O-(6-deoxy-3-O-methyl-α-D-mannopyranosyl)biopterin (5b). No potential conflict of interest relevant to this article was reported.

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

AME Publishing Company Acta Medica Okayama 2304-3865 15 2 2026 First-line fulvestrant vs. anastrozole in hormone receptor-positive advanced breast cancer: insights from the final FALCON trial results 22 EN Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Maki Tanioka Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2667-2421 19 2025 Chronic fluoxetine modulates perineuronal nets and inhibitory neuronal function in relation to behavioral outcomes 781 791 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Eriko Kitano Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Chronic fluoxetine administration has been reported to enhance neural plasticity in the adult brain, but the underlying structural correlates remain incompletely understood. In particular, the impact of fluoxetine on aggrecan-positive perineuronal nets (PNNs)―critical regulators of plasticity―is largely unknown. We investigated whether chronic fluoxetine treatment (20 mg/kg/day, i.p., 21 days) alters behavior and PNN expression in adult male C57BL/6 N mice. Behavioral assessments included grip strength, hot plate, light/dark transition, elevated plus-maze, open field, Y-maze, social interaction, tail suspension, Porsolt forced swim, and passive avoidance tests. To evaluate structural plasticity, we performed immunohistochemical analyses of parvalbumin (PV)-positive neurons and PNNs using aggrecan-specific antibodies (Cat-315, AB1031) in the primary somatosensory cortex and hippocampus. Fluoxetine-treated mice exhibited increased exploration and reduced anxiety-like behavior in light/dark transition and elevated plus-maze tests, with no significant changes in grip strength or nociception. They also showed increased locomotor activity (distance and entries) in the Y-maze, but did not significantly alter spontaneous alternation performance, and increased social interaction, the latter possibly reflecting abnormal social behavior. No significant differences were observed in depression-like behavior as assessed by tail suspension and forced swim tests. Passive avoidance performance was impaired, suggesting a decline in cognitive function. Immunohistochemical analysis revealed a significant reduction in aggrecan-positive PNN density, particularly in layer 4 of the primary somatosensory cortex and in the CA1 and CA3 regions of the hippocampus. Our results indicate that chronic fluoxetine administration induces behavioral and structural changes indicative of reactivated neuroplasticity. Importantly, these changes are associated with a region- and layer-specific reduction of aggrecan-positive PNNs, underscoring their critical role in modulating adult cortical plasticity. 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 1086-9379 61 4 2026 The effects of pressure on immiscibility in metallic, core‐forming liquids: Implications for protoplanetary differentiation 720 738 EN Geoffrey David Bromiley School of GeoSciences, University of Edinburgh, Grant Institute Hidenori Terasaki Department of Earth Sciences, Okayama University Matthew Varnam School of GeoSciences, University of Edinburgh, Grant Institute Mechanisms for metal core formation in rocky planetesimals and planetary embryos remain poorly constrained, in part due to complexities arising from immiscibility in core-forming liquids at low pressures. To assess the pressure dependence of immiscibility and its role in protoplanetary differentiation, we performed experiments at 3 and 5 GPa in the system Fe0.9Ni0.1 + S, P, C. Immiscibility arises due to the highly non-ideal nature of light element mixing in Fe liquids, and results in separation of Fe-rich (S-depleted, C-rich, P-rich) and FeS-rich (S-rich, C-rich, P-depleted) liquids. For a broad range of core-forming liquid compositions, a miscibility gap is only present at pressures <5 GPa. With increasing pressure, the behavior of complex systems converges on that of the Fe-S-C ternary, although S-P-C interactions continue to influence metal liquid compositions and stability. Comparison with planetary core compositions derived from meteorite data suggests that immiscibility can play a significant role during melting in planetesimals, and up to medium-sized planetary embryos. In turn, the importance of immiscibility during differentiation depends on the extent of melting, mechanisms for core formation, and corollary degree of light element loss from planetary bodies. No potential conflict of interest relevant to this article was reported.

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

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. Patients and Methods: This multicenter retrospective study included patients with HCC who started therapy with atezolizumab plus bevacizumab between September 2020 and December 2023. The primary outcome was the time to exacerbation of proteinuria from baseline within 6 months after treatment initiation according to SGLT2i use. Secondary outcomes included the development of grade ≥2 proteinuria. Results: A total of 188 patients were included, of whom 29 received SGLT2i. No significant difference in the time to exacerbation of proteinuria was observed between the SGLT2i and non-SGLT2i groups considering the overall population (median: 157 vs. 116 days, p=0.95). Multivariate analysis identified diabetes with systolic blood pressure ≥130 mmHg as an independent risk factor for proteinuria exacerbation (hazard ratio=2.19, 95% confidence interval=1.18-4.06, p=0.013), whereas SGLT2i use was not significantly associated with proteinuria exacerbation. In patients with both diabetes and systolic blood pressure ≥130 mmHg, SGLT2i significantly prolonged the time to proteinuria exacerbation. Conclusion: SGLT2i may suppress proteinuria progression only in high-risk patients with HCC complicated by diabetes and hypertension. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 17 1 2026 Water exchange process and bulk composition regulate slab dynamics and deep earthquakes 8291 EN Jintao Zhu Institute for Planetary Materials, Okayama University Renbiao Tao Center for High Pressure Science and Technology Advanced Research (HPSTAR) Lifei Zhang SKLab-DeepMinE, MOEKLab-OBCE, School of Earth and Space Sciences, Peking University Takayuki Ishii Institute for Planetary Materials, Okayama University Water strongly influences deep mantle processes, including geochemical cycles, slab dynamics, and deep-focus earthquakes. Yet the stability and interactions of hydrous minerals with nominally anhydrous minerals (NAMs) under the water-undersaturated conditions of subducting slabs remain unclear. Here we show, using high-pressure and high-temperature experiments on MgO–SiO2–H2O systems (~2 wt% H2O), that hydrous minerals progressively dehydrate in the mantle transition zone, transferring water to NAMs such as wadsleyite and ringwoodite, while the cold slab core stays nearly dry. Rapid dehydration near the top of the lower mantle may generate fluids linked to the deepest earthquakes. Our results indicate that dry olivine transformations, rather than dehydration embrittlement, likely trigger most deep-focus earthquakes, and that hydration variations in NAMs influence slab deformation and stagnation above 660 km. The bulk Mg/Si ratio controls hydrous mineral stability, suggesting harzburgite transports water more efficiently than peridotite. 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. 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. 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.

Elsevier BV Acta Medica Okayama 2950-1334 14 2026 Clinical phenotypes and the risk factors of mild pulmonary hypertension 100628 EN Satoshi Taya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshitake Fukuda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Misaki Kanezawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: The definition of pulmonary hypertension (PH) was revised as mean pulmonary arterial pressure (mPAP) >20 mmHg from ≥25 mmHg in the recent PH guidelines; however, the characteristics of PH patients with mPAP 21–24 mmHg have not been well described. Methods: A total of 1080 individuals who underwent right heart catheterization (2018–2022) was categorized into 3 groups by mPAP: no PH with mPAP ≤20 mmHg, mild PH with mPAP 21–24 mmHg, and conventional PH with mPAP ≥25 mmHg. We assessed PH subtypes of hemodynamic and clinical classification and compared survival outcomes (all-cause mortality, heart failure hospitalization, lung transplant) using Cox models. Results: Of them, 391 patients (36.2%) were diagnosed as PH including mild PH (n = 137) and conventional PH (n = 254). Phenotypically, mild PH was predominantly characterized by pre-capillary hemodynamics and Group 2 clinical classification. Mild PH is associated with an intermediate prognosis: outcomes are more favorable than in conventional PH but inferior to no PH (HR 1.74 [95% CI 1.15–2.61]). While the two PH phenotypes appear to share comorbidity-related factors, hemodynamic parameters were associated with survival outcomes not in mild PH but in conventional PH. Conclusions: The observation that mild PH constitutes approximately one-third of overall PH cases carries substantial clinical weight. The newly identified mild PH cohort was characterized mainly by pre-capillary and Group 2 subtypes. While mild PH is associated with an intermediate prognosis, comorbidities appear to be the primary determinant of outcomes in this group, unlike in conventional PH where hemodynamics play a larger role. No potential conflict of interest relevant to this article was reported.

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

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. Methods We retrospectively analyzed 233 patients who underwent curative-intent surgery for locally advanced HNSCC. Event-free survival (EFS) and overall survival (OS) were evaluated. Unresectable recurrence-free survival (URFS) was explored as an additional endpoint to capture post-recurrence treatment feasibility. Prognostic factors were assessed using Cox proportional hazards models. Results The median follow-up duration was 18.2 months. The 1-year EFS and OS rates were 67.1% and 89.4%, respectively. pN2 or higher disease, venous invasion, and perineural invasion were identified as independent adverse prognostic factors. Recurrence occurred in 34.8% of patients; among these, disease control at the last follow-up was achieved in 61.7% following curative-intent salvage treatment. Salvage surgery was associated with significantly improved post-recurrence survival (p < 0.001). Conclusions This study provides real-world surgical outcome data for resectable locally advanced HNSCC prior to the introduction of perioperative immunotherapy. Recurrence remains a major clinical challenge, with heterogeneous post-recurrence outcomes influenced by treatment feasibility. These findings may help inform interpretation of treatment outcomes and clinical decision-making in the evolving era of perioperative immunotherapy. 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. Methods This population-based cohort study was conducted by linking the Okayama City municipal gastric cancer screening registry with the Kokuho Database (KDB) for fiscal years 2016–2021. Among 36,326 participants contributing 64,822 screening examinations (40,832 radiography; 23,990 endoscopy), diagnoses of oral cavity, pharyngeal, laryngeal, and esophageal cancer occurring within 2 months of screening were ascertained from the KDB. Generalized estimating equations with modified Poisson regression were used to estimate adjusted risk ratios (aRRs) comparing endoscopy with radiography. Results Endoscopic screening was significantly associated with higher composite incidental detection rates for non-gastric upper aerodigestive tract cancers (95.9 vs. 34.3 per 100,000 examinations; aRR 2.94, 95% confidence interval [CI] 1.50–5.76; p = 0.002). Specifically, esophageal cancer detection was markedly higher with endoscopy (83.4 vs. 17.1 per 100,000; aRR 5.16, 95% CI 2.16–12.32; p < 0.001). No statistically significant differences were observed for oral cavity, pharyngeal, or laryngeal cancers. 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 α-Tocopherol Metabolites in Comparison with the Parent Compound in Hepatocytes 26 EN Tomoka Nishio Graduate School of Environmental and Life Science, Okayama University Kasumi Amako Graduate School of Environmental and Life Science, Okayama University Daiki Moriya Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University α-Tocopherol (αT) is the major form of vitamin E. Although it is metabolized in the liver when high levels of αT are present, the function of its metabolites has not yet been fully elucidated. This study aimed to evaluate the antioxidant activities of the αT metabolites, α-carboxyethyl hydroxychroman (αCEHC) and α-carboxymethylbutyl hydroxychroman (αCMBHC), in comparison with their parent compound. The pretreatment with αT and its metabolites showed a cytoprotective effect on the cytotoxicity induced by hydrogen peroxide in the mouse hepatoma Hepa1c1c7 cells. To elucidate the mechanism underlying the effect, in vitro assays and assessments of antioxidant-related genes and proteins were conducted. The in vitro assays showed that these compounds showed little scavenging activity against hydrogen peroxide but exhibited scavenging activity against DPPH radicals. On the other hand, assessments of antioxidant-related genes and proteins showed that αT and its metabolites significantly upregulated the expression of heme oxygenase-1 (HO-1) possibly through activation of the transcript factor Nrf2. Moreover, the cytoprotective effects of αT and its metabolites against hydrogen peroxide were counteracted by HO-1 inhibitors. These results suggest that not only αT but also its metabolites are potential cytoprotective factors against oxidative stress-induced cytotoxicity, and that their effects are exerted not through a direct action of scavenging hydrogen peroxide in the body, but rather through the regulation of gene expression. No potential conflict of interest relevant to this article was reported.

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

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.

Elsevier BV Acta Medica Okayama 1078-8174 32 7 2026 Patient-centred communication in radiographer education: A five-country comparative document analysis of curriculum and competency standards 103553 EN Y. Komatsu Division of Radiological Technology, Graduate School of Health Sciences, Okayama University Y. Chikamoto Independent Researcher K. Tsukano Department of Psychosomatic Medicine, Yokohama Rosai Hospital 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 Division of Radiological Technology, Graduate School of Health Sciences, Okayama University Introduction: Patient-centred communication is fundamental to radiographic practice, particularly when patients experience anxiety or uncertainty during imaging or treatment. However, it remains unclear whether broad communication expectations in radiography education and professional standards are translated into explicit, observable behaviours and integrated into education and assessment. This comparative document analysis examined the representation of patient-centred communication in selected national-level documents from five countries, using listening-related behaviours as an illustrative example. Methods: Selected national-level curriculum, accreditation, registration, capability, and competency documents from the United States, the United Kingdom, Australia, Canada, and Japan were analysed deductively using a predefined extraction framework. The framework assessed communication competence, listening-related behaviours, patient-centred care, patient/family relationships, interprofessional collaboration, education, and assessment. Results: Communication was addressed in all five selected national-level document sets, although institutional framing differed. It was framed as a professional competency or capability in the United Kingdom and Australia, a role-based competency framework in Canada, clinical competency and accreditation requirements in the United States, and primarily as curriculum content in Japan. Explicit observable behavioural expectations, such as listening-related behaviours, were uncommon. Listening was explicitly defined only in the Australian capability standards; elsewhere, it was represented indirectly through broader concepts, such as patient interaction, information gathering, and interpersonal communication. Conclusion: The selected documents differed in the explicitness, structure, and educational integration of communication-related standards, without implying differences in education quality or clinical outcomes. Defining patient-centred communication through observable behaviours may strengthen alignment among professional expectations, learning outcomes, feedback, and assessment. Implications for practice: Operationalising patient-centred communication as observable behaviours may enhance curriculum mapping, feedback, and assessment in radiographer education. 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 Iα 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 CaMKIα in HeLa cells upon physiological stimulation that elevates intracellular Ca²⁺. ATP induced CaMKIα 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 CaMKIα 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. CaMKIα was then rapidly dephosphorylated to basal levels within 10 min. Consistently, histamine-induced (but not ATP-induced) CaMKIα phosphorylation was absent in triple IP₃ receptor-knockout HeLa cells. Dephosphorylation of CaMKIα 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 CaMKIα dephosphorylation activity that was insensitive to ANS and ANDS. Furthermore, co-expression of PP2Cα fully abolished ATP-, histamine-, or ionomycin-stimulated CaMKIα phosphorylation, which is consistent with in vitro dephosphorylation of CaMKIα at Thr177 by recombinant PP2Cα. Taken together, these results reveal that agonist-induced Ca²⁺ influx from the extracellular space or release from intracellular stores transiently activates CaMKK-CaMKIα signaling in HeLa cells, which is shut off by dephosphorylation catalyzed by PP2Cα as a promising candidate for CaMKIα 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 “Biological Function and Evolution through Interactions between Hosts and Transposable Elements,” 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.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 裏表紙・英文目次 EN No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 奥付 EN No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 マット運動の側方倒立回転に関する認識の実態 ― 素朴概念に基づく調査と考察 ― 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 　本研究の目的は，小学校体育科，および中学校・高等学校保健体育科の器械運動領域で取り扱われる「側方倒立回転」に関する認識の実態を素朴概念に基づく調査を通して明らかにすることであった。素朴概念とは学習者が日常生活において経験的に獲得した知識，もしくは学校の授業等で学習する科学的概念とは必ずしも一致しない知識を指し示す用語である。本研究にて側方倒立回転という技を取り上げた理由とは，運動の形態上4パターンの実施方法が存在しているにも関わらず，合理的，かつ行い易い実施方法はそのうちの2パターンに限定されるという特殊性にある。本研究では側方倒立回転に対する素朴概念を明らかにするために，その認識を問うためのアンケート調査を実施した。調査期間は2023年6月7月，調査対象はA大学小学校教員養成課程に在籍する学生140名であった。調査の結果140名中35名，割合にすると32.1％が誤った知識を素朴概念として保有していたということが明らかとなった。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 ダンスを通じた共生社会の実現に向けた地域協働プロジェクト ― 岡山うらじゃ祭りにおけるインクルーシブダンス実践 ― 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 　障がい者の文化芸術活動では，障がい者が創造や発信に主体的に関わることが重視されている。しかし，その一形態であるインクルーシブダンスを地域社会に開かれた文化活動へと展開する事例の分析は十分ではない。そこで本稿では，岡山県の「うらじゃ」祭りにおいて発足したインクルーシブ踊り連「一期一会～輪舞温羅」を対象に，インクルーシブうらじゃダンスの開発および実践過程を整理した。活動記録，映像記録，活動資料をもとに分析した結果，表現内容や実施方法，演舞環境が，参加者の心身の特性を踏まえて段階的に調整されていたことが明らかとなった。また，参加者の主観的運動強度は主に「楽」から「ややきつい」の範囲に分布し，活動満足度も高い傾向を示した。以上より，本プロジェクトは，地域文化を基盤としたインクルーシブな身体表現活動に関する基礎的知見を提供するものであると考えられる。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 岡山大学教育学部初等家庭科必修科目を通した学生の教科観の深化 ―2024-2025年度のアンケート調査の結果から― 137 146 EN Chiharu MORI Faculty of Education, Okayama University Miyuki HISANARI Faculty of Education, Okayama University Yoko SHINOHARA Faculty of Education, Okayama University Kyoungwon LEE Faculty of Education, Okayama University 10.18926/bgeou/71150 　本研究では，岡山大学教育学部新カリキュラムにおける，初等家庭科の必修科目「内容構成基礎」，「指導法基礎」，「指導法Ⅰ」の3科目を通して，履修学生の家庭科に対する教科観（イメージや考え方）がどのように変化したのかを，アンケート調査を用いて明らかにすることを目的とした。「指導する立場から小学校家庭科を学修して，家庭科のイメージや考え方が変化した」に対する5件法の回答では，「あてはまる」，「ややあてはまる」を合わせた肯定的な回答の割合は，「内容構成基礎」90.1%，「指導法基礎」88.5%，「指導法Ⅰ」95.0%と，「指導法基礎」でやや下がったものの，「指導法Ⅰ」で最も高い割合を示した。自由記述のテキスト分析では，必修科目の学修を通した学生の教科観は，「教科の学習内容の理解」→「教科理念の理解」→「教科指導の理解」の段階を踏むことにより，徐々に深化したと推察された。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 「創造性が社会と出会う美術教育」による教員の学びに関する基礎研究Ⅲ ― 中学校美術科教員の授業記録と追跡インタビューに基づく事例研究― 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 　本論は，学校外の他者との対話経験が，中学校美術科教員の授業実践においてどのように意味づけられていたのかを明らかにすることを目的とする。市井プロジェクトに参加した教諭Bを対象に，市井インタビュー後に実施された表現活動の授業記録と，授業実践後の追跡インタビューを照合した。その結果，教諭Bは，学校外の他者との対話経験を，授業方法の直接的な変更としてではなく，授業中の判断，生徒理解，題材・表現理解，生活実践との関係において意味づけていたことが確認された。特に，生徒の行動や表現を統制する見方から，その背景や生成過程を見取る見方への移行があった可能性が高い。以上のことから，本論により教師の学びを学校内の研修や同僚性に限定せず学校外の生活世界との関係から捉える意義が示唆された。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 中国地方広域中心都市における人口移動の動向 ―岡山県岡山市の事例― 109 124 EN Masao NOBE Faculty of Education, Okayama University 10.18926/bgeou/71148 　本稿の目的は，2006年から2025年までの岡山市における人口移動を分析し，その動向を明らかにすることである。21世紀に入って以降，岡山市では中心市街地の再開発や分譲マンション供給の拡大により，都心回帰が進展してきた。また，リーマンショックや東日本大震災，新型コロナウイルス感染症の拡大といった出来事も，人口移動に一定の影響を及ぼしたと考えられる。しかし，こうした外部要因にもかかわらず，人口移動の基本的な趨勢に大きな変化はみられなかった。すなわち，岡山市は県内の大部分の圏域および県外の周辺地域から人口を吸収する一方で，三大都市圏を含む関東・近畿・中部地方へ人口を送り出している。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 ウィーン体制における勢力圏 ―1820年代の露墺関係を中心に― 91 107 EN Hiroaki YAGUCHI Faculty of Education, Okayama University 10.18926/bgeou/71147 　国際政治上，頻繁に言及される現象にもかかわらず，「勢力圏」とその概念は十分に整理されていない。本稿では，1820年代ロシアのイタリア半島におけるオーストリアの勢力範囲に対する認識を事例に，19世紀前半のヨーロッパ国際社会における勢力圏のあり方を検討した。とりわけロシアは，1820年代を通じてバルカン半島で継続したギリシア独立革命への干渉を認めさせるべく，1820年代初頭のナポリ立憲革命を鎮圧したオーストリアの干渉の先例に繰り返し言及していた。その結果としてロシアの政策決定者たちは，1820年代初頭には完全に受け入れていなかった，イタリア半島におけるオーストリアの特別な利益の存在を認めるに至った。そして1830年のフランス七月革命の結果として，露墺両国は，バルカン半島とイタリア半島における双方の利益と勢力範囲をお互いに受け入れた。19世紀前半のウィーン体制期の勢力圏は，長期的な交渉の繰り返しで形成・構築されるものであり，認識のすり合わせが成功した場合には，大国間の外交的協力を可能にした。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 法に基づく初等社会科内容構成に関する研究 ―米国法教育教材『民主主義の基礎(FOUNDATIONS of DEMOCRACY)』を手掛かりにして― 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 　本研究は，法に基づいて構成される初等教育段階の社会科の内容構成原理を明らかにするため，米国の初等法教育教材『民主主義の基礎（FOUNDATIONS of DEMOCRACY）』を分析したものである。日本における法教育研究は，1990年代後半から，米国の法教育研究を紹介する形で始まり，その後，数多くの米国の法関連教育教材が日本に紹介され，その分析に基づく研究成果が蓄積されてきた。しかし，それらの研究の多くは，中等教育段階のものであり，初等教育を対象とする法教育の研究は多くはない。本研究は，初等社会科としての法教育に焦点を当て，その内容構成を明らかにしようとする点に独自性がある。本研究で取り上げる『民主主義の基礎』は，日本でも注目され，複数の研究者によって分析されている。本研究では，それらの先行研究をふまえつつ，これまでの研究では十分解明されていなかった内容構成原理の解明を目指す。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 子どもの自己が立ち上がる造形行為についての文献研究 ― 木村敏の文献に基づいた子どもの学びを捉える視点 ― 69 77 EN Shuya OHIRA Faculty of Education, Okayama University 10.18926/bgeou/71145 　本研究では，造形行為において，子どもの「自己」が立ち上がることをその子ども自身の学びとして捉える視点について，木村の文献を手掛かりに検討した。まず，「自我」，「無意識」，「自己」の概念を整理し，造形行為において個々の子どもに経験される学びを考察した。次に，個々の子どもに経験される学びが，活動場所や造形行為を共有する他の子どもへと知られ受容されていく関係が，造形行為の過程で形成されることを考察した。最後に，造形行為において形成される子ども同士の関係へと参与し，同じ経験を共有していくあり方が，子どもの「自己」が立ち上がる学びを捉える視点そのものであることを示した。今後は，芸術教育や芸術実践を対象とした研究により，本研究の知見を深めていく。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 ０歳児クラスにおける負の情動調整を支える保育実践の構造 ―保育者へのグループインタビューの SCAT 分析― 53 67 EN Mika KATAYAMA Faculty of Education, Okayama University Sachiyo OKAMURA Tachibanaima Nursery School of the Tachibana Social Welfare Association 10.18926/bgeou/71144 　本研究の目的は，０歳児クラスにおける乳児の負の情動調整を支える保育実践の構造を明らかにすることである。０歳児クラス担当保育者２名を対象にフォーカス・グループ・インタビューを実施し，逐語録をSCAT により分析した。その結果，【受容的共同調整による情緒的安全基地の形成】【子どもの心情の理解に基づく見立ての深化】【子どもの心情の予測に基づく情動調整】【保育者間協働による情動調整の実践の共有】【好みや文化的媒介を活用した情動安定化】の５つの統合カテゴリーが導出された。保育者が子どもの心情変化を見取りながら，待機・見守り・最小限の介入を調整する「子どもの心情の予測に基づく情動調整」が特徴的であった。情動調整支援が保育者間の協働的実践で支えられていることも明らかになった。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 聴覚障害学生支援のための初学者向け大学ノートテイカー共同養成研修の効果・課題・あり方 ―多様な人的リソースを活用した養成研修モデルの検討― 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 　本研究は，多様な人的リソースを活用した聴覚障害学生支援のための初学者向けノートテイカー共同養成研修の効果と課題を明らかにし，今後の共同養成研修のあり方について検討することを目的とした。共同養成研修の効果として，【他大学との交流の有効性】，【研修順序の有効性】，【研修内容の充実】などが見られ，今後の研修の生かし方として，【研鑽や活動拡大】，【支援・研修の充実】などが挙げられており，研修の有効性が明らかになった。一方で，共同養成研修の課題として，交流プログラムの満足度が相対的に最も低く，【時間不足】が背景にあると考えられた。これらのことを踏まえて，共同養成研修のあり方として，学生・教職員が交流する十分な時間の確保や，各講義時間の増加のために，動画を視聴するオンデマンド形式を基本として，交流や演習などを対面，またはリアルタイムオンラインで実施するなどの研修方法が考えられる。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 大学生の主観的幸福感，幸福への動機づけを規定する心理的要因 ―本来感，対人関係，エンゲージメントに着目して― 27 36 EN Tazuko AOKI Faculty of Education, Okayama University Miki HARADA Elementary School teacher in Okayama Prefecture 10.18926/bgeou/71142 　本研究は，大学生の幸福感を規定する心理的要因を明らかにすることを目的とし，主観的幸福感（SHS）および幸せへの動機づけ（HEMA）を従属変数として，本来感，対人関係（被受容感・被拒絶感），エンゲージメント（感情・認識）との関連を検討した。大学生139名を対象に質問紙調査を実施し，相関分析および重回帰分析を行った。その結果，主観的幸福感には本来感と感情エンゲージメントが正の影響を，被拒絶感が負の影響を与えていた。幸せへの動機づけのうち，幸福追求と喜び追求には本来感が正の影響を示し，幸福追求には感情エンゲージメントと認識エンゲージメントも関連していた。一方，くつろぎ追求にはいずれの要因も有意な影響を示さなかった。以上より，大学生の幸福感は，自分らしく行動できている感覚や活動への積極的関与によって高まり，他者からの拒絶感は幸福感を低下させることが示唆された。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 集団活動での協働経験を通じて培われるリーダーシップ効力感 ― 経験を振り返る習慣がもつ意味 ― 13 26 EN Ryo MISAWA Faculty of Education, Okayama University Shunta KANEMI Benesse Corporation Naoko HASEGAWA Faculty of Human Sciences, Department of Psychology, Bunkyo University 10.18926/bgeou/71141 　本研究では，日常的な集団活動での協働経験および経験学習習慣が，リーダーシップ効力感とどのように関連するのかを検討した。大学生を対象に質問紙調査を実施し，99名の有効回答を分析対象とした。因子分析により，協働経験について「協働的問題解決」，「集団内責任遂行」，「意思決定参画」の3因子が抽出された。リーダーシップ効力感（鼓舞力，変革力，共感力）との関連を階層的重回帰分析で検討した結果，集団内責任遂行の経験は変革力と，意思決定参画の経験は鼓舞力と関連し，経験学習習慣は変革力および共感力と正の関連を示した。また，協働的問題解決の経験が少ない場合には，経験学習習慣が鼓舞力と変革力を補完的に高める可能性が示唆された。得られた知見に基づき，大学生のリーダーシップ育成における協働経験の内容に応じた支援と，経験を省察する習慣形成の重要性を議論した。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 19世紀後半日本における一斉教授法の受容の一断面 ― 近世・近代転換期の教育状況の視野 ― 1 12 EN Kazuaki KAJII Faculty of Education, Okayama University 10.18926/bgeou/71140 　近代日本における西洋教育の日本教育への影響を考察し，とくに世界で伝播のあったモニトリアル・システム（助教法）の日本教育における位置を検討する。19世紀後半は，近世の寺子屋の時代から近代の小学校の時代への転換期であった。国民教育の場としての小学校が整い，男女が就学する状況の形成があった。この過程において，日本がアメリカ経由で受容した一斉教授は，教師が教室で教授する方法であった。助教を用いる方法ではなかった。本稿は，近代日本ではモニトリアル･システムを基本的には経験しない展開と，一斉教授を行う教師の養成があったことを論じるものである。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 表紙・目次 EN 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.

Springer Science and Business Media LLC Acta Medica Okayama 0934-9723 2026 Streptococcal toxic shock syndrome caused by ST525 Streptococcus dysgalactiae subsp. equisimilis with genomic characterization of virulence and antimicrobial resistance EN Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Maki Tanioka Clinical Oncology Center, Okayama University Hospital Hideharu Hagiya Research Center for Intestinal Health Science, Okayama University Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of severe invasive infections. We describe the clinical course of an immunocompromised patient with advanced breast cancer who developed streptococcal toxic shock syndrome, necrotizing fasciitis, and disseminated intramuscular abscesses caused by a multidrug-resistant Lancefield group G SDSE isolate, alongside a comprehensive genomic characterization of its virulence and antimicrobial resistance profiles. Genomic analysis identified the isolate as emm subtype stG840.0 and sequence type 525 (ST525), harboring genes encoding several virulence-associated factors, including an emm-like gene encoding an M-like surface protein, streptokinase, streptolysin O, streptolysin S, and SpeG. Through comprehensive genomic analysis of the highly virulent SDSE isolate, we provided insights into its underlying genetic background. Further accumulation of genomic data is expected to fully elucidate the mechanisms of virulence and antimicrobial resistance in SDSE. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0300-8126 54 4 2026 Rectal syphilis: a great imitator of rectal malignancy 2155 2156 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University A 48-year-old transgender woman presented with a sudden onset of bloody stool. Colonoscopy revealed an ulcerated, circumscribed mass in the lower rectum, closely resembling a Borrmann type 2 malignancy. The patient lacked classic signs of syphilis, such as anal pain, primary genital chancres, or localized lymphadenopathy. However, serological assays were highly reactive, and immunohistochemical analysis of the biopsy specimen confirmed the presence of Treponema pallidum, establishing the diagnosis of syphilitic proctitis. A four-week oral amoxicillin regimen (1,500 mg/day) led to complete clinical and serological resolution. This elusive condition must be considered when evaluating anorectal mucosal abnormalities. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1523-7060 28 1 2025 Optimization of the External Directing Group Depending on the Substrates for the Regioselective C–H Alkenylation of Phenyl Ethers 94 99 EN Koki Yano Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Sawada Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Using an external directing group (externalDG), we have succeeded in ortho-selective C–H alkenylation of various DG-free phenyl ethers, including bulky silyl ethers. Also, we demonstrated a strategy to develop regioselective C–H activation by optimizing externalDG depending on the substrate. The means for optimizing externalDG include the selection of the precursor, the addition of a Lewis acid, and changing the ratio of the precursor/Pd, to control the reactivity and regioselectivity. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 0172-0643 2026 Fenestration Re-creation for Early Fontan Deterioration: Long-Term Hemodynamic and Clinical Outcomes EN Thi Hai Yen Tran Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshihiko Kurita Department of Pediatrics, Kochi Health Sciences Center Maiko Kondo Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yosuke Fukushima Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yusuke Shigemitsu Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuya Kawamoto Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Mayuko Hara Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hirokazu Tsukahara Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tatsuo Iwasaki Department of Pediatric anesthesiology, Okayama University Hospital Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Hospital Kenji Baba Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Spontaneous closure of a Fontan fenestration may precipitate early hemodynamic deterioration in vulnerable patients. In such situations, fenestration re-creation may be considered as a rescue strategy when medical therapy is insufficient. However, the long-term hemodynamic consequences of this intervention remain poorly defined. We retrospectively reviewed 62 patients who underwent the Fontan procedure between January 2011 and December 2020 and subsequently experienced spontaneous fenestration closure. Patients were divided into two groups according to management strategy: those who underwent fenestration re-creation (Group 1, n = 19) and those managed without re-creation (Group 2, n = 43). Longitudinal hemodynamic data were analyzed using linear mixed models over a median follow-up of 10.2 years. Fenestration closed spontaneously at a median of 12 days (IQR 2.5–26.5) and initial re-creation was performed at the median of 42 days (IQR 11–213) postoperatively. Early and mide-term hemodynamic trends were broadly similar between groups, however, clear divergence emerged in the late follow-up. fenestration re-created patients demonstrated persistently higher central venous pressure and pulmonary vascular resistance, lower systemic vascular resistance, progressive increases in cardiac index, and declining oxygen saturation. Survival in this group remained above 80% during the mid-term follow-up but declined substantially in the late phase compared with patients without re-creation (52% vs. 85%, p = 0.043). This was accompanied by higher incidences of protein-losing enteropathy/plastic bronchitis, thromboembolism, and severe cyanosis. Fenestration re-creation may provide temporary hemodynamic stabilization in early Fontan deterioration; however, its benefits appear to diminish in the late phase. These findings highlight the need for hemodynamically tailored management strategies and alternative therapeutic options for patients with deteriorating Fontan circulation. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0005-2728 1867 4 2026 Cryo-EM structure of photosystem II D1-V185T mutant from Thermosynechococcus vestitus 149598 EN Haowei Jiang Research Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiki Nakajima Research Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Fusamichi Akita Research Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hongjie Li Center for Transformative Science, School of Life Science and Technology and Shanghai Clinical Research and Trial Center, ShanghaiTech University Koji Kato Research Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Miwa Sugiura Proteo-Science Research Center, Ehime University Jian-Ren Shen Research Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Photosystem II (PSII) catalyzes water oxidation into electrons, protons and dioxygen at its catalytic center, a Mn4CaO5 cluster, utilizing light energy. An amino acid residue D1-V185 in the D1 protein is located close to the Mn4CaO5 cluster, and plays a critical role in its catalytic function. In this research we purified PSII dimers from a D1-V185T mutant of Thermosynechococcus vestitus and analyzed its structure using low-damage cryo-electron microscopy (cryo-EM) at a resolution of 1.88 Å. The results revealed the presence of multi-conformations at the mutation site. Unlike the wild-type valine, which does not allow water molecules to be able to form hydrogen-bonds with it, both conformations of the mutant formed hydrogen bonds with nearby water molecules, which leads to rearrangement of the hydrogen bond networks in the O1 and Cl-1 channels. In conformation-A, the mutated Thr residue forms a hydrogen bond with a water molecule W6, which creates a new channel that bypasses the original O1 channel. Due to the hydrophilic OH group of Thr, the side-chain of D1-Glu189 was attracted and shifted toward the mutant Thr residue. In conformation-B, it forms a hydrogen bond with a water molecule W9 in the Cl-1 channel, bringing W9 closer and thereby disrupting the hydrogen bond network of the Cl-1 channel. In addition, multi-conformations of D2-K317, which is a ligand of Cl-1, were found in the mutant. These changes alter the environment surrounding the Cl-1 ion and Mn4CaO5, thereby affecting the PSII water-oxidation activity. 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. 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. 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.

Frontiers Media SA Acta Medica Okayama 1662-5110 20 2026 New mechanistic insight into SARM1 activation: TRIM32-mediated ubiquitination is a key lever that actuates SARM1’s catalytic action, leading to axon degeneration and cell death 1842408 EN Hitoshi Murata Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-ichi Yamamoto Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sterile alpha and TIR motif-containing protein 1 (SARM1) is an enzyme that cleaves nicotinamide adenine dinucleotide (NAD+) and plays a role in disrupting neural circuits through axon degeneration and cell death. SARM1 is activated by changes in the nicotinamide mononucleotide (NMN)/NAD+ ratio and by various post-translational modifications, but its complete regulatory mechanism remains poorly understood. Here, we report that tripartite motif-containing protein 32 (TRIM32) activates SARM1 through specific ubiquitination triggered by anticancer drug treatment. TRIM32 promotes the attachment of Lys27-linked ubiquitin chains to Lys173 and Lys375 within the ARM domain, which is an autoinhibitory region of SARM1. This ubiquitination by TRIM32 increases SARM1’s NAD+-cleaving catalytic activity and enhances its ability to induce neurite degeneration and cell death. A mutant form of TRIM32 lacking the enzymatically active RING domain fails to promote SARM1 ubiquitination, and reducing TRIM32 levels decreases SARM1 ubiquitination. Additionally, ubiquitin-specific peptidase 13 (USP13), a known negative regulator of SARM1, can deubiquitinate SARM1. These findings suggest that TRIM32 is a key regulator of axon degeneration and cell death through its ubiquitination of SARM1. 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, ξ and ε, were estimated. The ξ-ε 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. Methods In this double-blind, multicenter, randomized phase II study, 40 patients received hydroxyzine or bepotastine with acetaminophen 30 min before rituximab infusion. Primary endpoint was incidence of ≥ grade 2 IRRs based on the National Cancer Institute Common Terminology Criteria for Adverse Events. Secondary endpoints included IRRs severity, time to IRR onset, and H1RA-induced drowsiness. Results Incidence of ≥ grade 2 IRRs was 52.4% and 31.6% for the hydroxyzine (n = 21) and bepotastine (n = 19) groups, respectively (P = 0.184). Distribution of initial and maximum IRR grades in the two groups was not statistically significant (P = 0.846 and 0.555). Median time (range) to IRR onset in the two groups was 67 (12–112) and 62 (10–119) min, respectively (P = 0.981). Median visual analog scale score (range and 75th percentile) for drowsiness was 37 (0–100, 46) and 12 (0–100, 29) mm in the two groups, respectively (P = 0.138). Incidence of ≥ grade 2 IRRs in the absence of bone marrow infiltration was 43.8% and 14.3% in the two groups, respectively (P = 0.118), and no group differences were observed with bone marrow infiltration. Conclusions Bepotastine did not show significant superiority over hydroxyzine in preventing rituximab-induced IRRs due to the small sample size. Nevertheless, this exploratory study provides insight for further confirmatory studies. Trial registration number and date of registration jRCTs051220169; February 14, 2023. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1616-301X 2026 Biomineral-Inspired Organic/Inorganic Colloidal Liquid-Crystalline Hybrids for Photoresponsive Adhesion e77420 EN Junya Uchida Research Institute for Interdisciplinary Science, Okayama University Ryuta Kiguchi Department of Chemistry and Biotechnology School of Engineering, The University of Tokyo Riki Kato Research Institute for Interdisciplinary Science, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Takashi Kato Research Institute for Interdisciplinary Science, Okayama University Bioinspired hybrid nanostructures offer a promising strategy for developing dynamic functional materials. Herein, we report a new class of photoresponsive liquid-crystalline (LC) adhesives based on organic/inorganic nanostructured colloidal hybrids. These LC materials are composed of a biomineral-inspired hydroxyapatite (HAp) nanorod and azobenzene-based forklike molecules. The organic/inorganic LC hybrids exhibit unusual photo-enhanced adhesion upon photoinduced order–disorder phase transitions of these LC materials. The photoresponsive adhesion functions of the colloidal LC hybrids are tuned by spacer moieties of the forklike molecules as well as mixing of the hybrids with the forklike molecules. The reversible photo-enhanced adhesion of the LC hybrids is achieved when the forklike molecule having oligooxyethylene spacers is hybridized with the HAp nanorod. The flexible oligooxyethylene spacers of the forklike molecule are effective for the formation of less ordered packing of the azobenzene units in the LC hybrids, which enables the dynamic photoresponsive functions. We propose an approach to the development of bioinspired photoresponsive LC materials through self-assembly of functional organic molecules and biomineral-based colloidal hybrids. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2328-8957 13 6 2026 Digital Tattoos in Infectious Diseases Management ofag338 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital The widespread adoption of electronic medical records (EMRs) has improved continuity and efficiency in healthcare; however, the permanence of digital documentation may unknowingly and unintentionally disadvantage patients. Certain infectious disease–related labels, particularly those denoting colonization of antimicrobial-resistant organisms, status of stigmatized diseases, or antibiotic drug allergy, frequently persist long after their clinical relevance has expired. These Digital Tattoos silently influence clinical decision-making and impose multifaceted burdens, leading to unnecessary isolation, excessive use of broad-spectrum antimicrobials, psychological distress, higher healthcare costs, and reinforcement of stigma. A critical mismatch exists between static (unchanged) EMRs and the dynamic (changeable) nature of clinical conditions. To mitigate the harms of Digital Tattoos, we must urgently move beyond passive documentation toward proactive management of healthcare data. Decoupling the permanence of digital records from systemic inequities in patient care hinges on the robust synthesis of Digital Humility and patient-oriented risk evaluation. No potential conflict of interest relevant to this article was reported.

Optica Publishing Group Acta Medica Okayama 2026 Demonstration of a Raman Silicon Nanocavity Laser Emitting in the L-Band with S-band excitation FM4B.2 EN Rikuto Ichinose Department of Physics and Electronics, Osaka Metropolitan University Shoei Yamasaki Department of Physics and Electronics, Osaka Metropolitan University Ayumi Ishihara Department of Environmental, Life, and Natural Sciences, Okayama University Yuta Kanemaru Department of Physics and Electronics, Osaka Metropolitan University Takashi Asano Department of Electronic Science and Engineering, Kyoto University Susumu Noda Department of Electronic Science and Engineering, Kyoto University Yasushi Takahashi Department of Environmental, Life, and Natural Sciences, Okayama University We demonstrated a Raman silicon nanocavity laser that enables wavelength conversion from the S-band to the L-band. Compared with Raman lasers operating from the E-band to the C-band, a degradation in lasing threshold was observed. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1759-9954 17 29 2026 Effect of graphene oxide sheet size on pickering miniemulsion polymerization of styrene 3226 3236 EN Yue Zhang Cluster for Advanced Macromolecular Design, School of Chemical Engineering, The University of New South Wales Yasemin Fadil Cluster for Advanced Macromolecular Design, School of Chemical Engineering, The University of New South Wales Yuta Nishina Research Core for Interdisciplinary Sciences, Okayama University Vipul Agarwal Cluster for Advanced Macromolecular Design, School of Chemical Engineering, The University of New South Wales Per B. Zetterlund Cluster for Advanced Macromolecular Design, School of Chemical Engineering, The University of New South Wales The effect of graphene oxide (GO) sheet size on the progression of Pickering miniemulsion polymerization of styrene was systematically investigated using two GO samples with lateral dimensions (∼500 nm and 5–10 µm). Key parameters, including the presence of the conventional surfactant sodium dodecyl sulfate (SDS), GO loading, and initiator concentration, were investigated individually. Miniemulsion polymerization with GO was successfully conducted both in the absence and presence of SDS, with the addition of SDS leading to a significant rate enhancement attributed to SDS-induced secondary nucleation. In the presence of SDS, GO sheet size influenced polymerization behavior, and its effect on polymerization rate and monomer conversion exhibited opposite trends at different GO loadings. Small GO (∼500 nm) led to higher conversion and faster rates at high GO loading (5 wt%), whereas large GO (5–10 µm) resulted in higher conversion and faster rates at low GO loading (0.5 wt%). This size-dependent effect became more pronounced at lower initiator concentration. Overall, while GO sheet size exhibited a measurable influence on polymerization behavior, the overall kinetics were primarily governed by SDS-induced secondary nucleation. These findings provide new insights into the role of GO lateral dimensions in miniemulsion polymerization and offer guidance for the design and synthesis of polymer/graphene (oxide) nanocomposites with tunable properties. No potential conflict of interest relevant to this article was reported.

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

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’s Medical University Hiroo Kawarazaki Department of Internal Medicine, Teikyo University Hospital Mizonokuchi Tsutomu Sakurada Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine Background: Patients on maintenance hemodialysis (HD) have reduced health-related quality of life (HRQoL). Structured exercise therapy is recommended, but domain-specific effects and the influence of intervention duration remain uncertain. This study evaluated the impact of structured exercise therapy on multiple HRQoL domains, including fatigue and depression, stratified by intervention duration. Methods: We conducted a systematic review and meta-analysis, searching MEDLINE (PubMed) through November 2024. The protocol was registered in PROSPERO (CRD42025642273). We included trials comparing structured exercise with non-exercise controls in adult HD patients. Primary outcomes were Short Form (SF)-36 Physical and Mental Component Summaries (PCS, MCS), fatigue, pain, general health, and depression (Beck Depression Inventory). Data were synthesized using random-effects models, stratified by intervention duration (≤ 3 versus > 3 months). Risk of bias was assessed using the Cochrane RoB 2 tool. Results: We identified 94 randomized controlled trials (5228 participants); 22 reported HRQoL outcomes and were meta-analyzed. Exercise significantly improved fatigue (mean difference [MD] + 7.27, 95% confidence interval [CI] 4.75–9.80) and reduced depressive symptoms in > 3-month trials (MD －7.62, 95% CI －8.34 to －6.90); no ≤ 3-month depression data were available. In overall analyses, general health (MD + 11.59, 95% CI 6.98–16.21) and PCS (MD + 5.83, 95% CI 0.71–10.94) improved, whereas MCS (MD + 7.60, 95% CI －3.75 to 18.94) and pain (MD + 2.19, 95% CI －4.41 to 8.79) showed no clear benefit. Short-term interventions (≤ 3 months) yielded significant improvements in pain and general health. In longer-term interventions (> 3 months), general health estimates were similar in magnitude but statistically nonsignificant, and pain effects were also nonsignificant with substantial heterogeneity. Fatigue improved in both duration strata. Conclusions: Structured exercise therapy appears to improve fatigue in patients on maintenance HD and may provide additional gains in PCS and general health with interventions longer than 3 months. Improvements in depressive symptoms were observed from limited evidence, and duration-specific effects remain uncertain because no trials assessed depression at ≤ 3 months. Effects on pain and MCS remain uncertain owing to substantial heterogeneity. Larger long-term trials are needed to clarify the sustainability of HRQoL benefits beyond 3 months. No potential conflict of interest relevant to this article was reported.

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