Wiley Acta Medica Okayama 0018-019X 85 9 2002 A New Route for Preparation of 5-Deoxy-5-(hydroxyphosphinyl)- D-mannopyranose and -L-gulopyranose Derivatives 2608 2618 EN Tadashi Hanaya Center of Instrumental Analysis, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University Starting from methyl 2,3-O-isopropylidene-α-D-mannofuranoside (5), methyl 6-O-benzyl-2,3-O-isopropylidene-α-D-lyxo-hexofuranosid-5-ulose (12) was prepared in three steps. The addition reaction of dimethyl phosphonate to 12, followed by deoxygenation of 5-OH group, provided the 5-deoxy-5-dimethoxyphosphinyl-α-D-mannofuranoside derivative 15a and the β-L-gulofuranoside isomer 15b. Reduction of 15a and 15b with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by the action of HCl and then H2O2, afforded the D-mannopyranose (17) and L-gulopyranose analog 21, each having a phosphinyl group in the hemiacetal ring. These were converted to the corresponding 1,2,3,4,6-penta-O-acetyl-5-methoxyphosphinyl derivatives 19 and 23, respectively, structures and conformations (4C1 or 1C4, resp.) of which were established by 1H-NMR spectroscopy. 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?<br> Methods: We interviewed 21 Peruvian mothers who had lived in Japan for 17–35 years.<br> Results: The analysis identified four identity positions to this cultural friction. The first is holding firmly to Peruvian maternal scripts (“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”).<br> Discussion: This study helps us understand that migrant mothers do not simply choose between their home and new cultures. Instead, they actively work to create a way of mothering through a process we call Reflexive Continuity that makes sense for their unique situations. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 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.

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 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.

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.

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.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 5 2025 Phase II Study of Platinum Re-administration in Non-small Cell Lung Cancer Following Chemoimmunotherapy Resistance e84709 EN Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Shinobu Hosokawa Respiratory Medicine, Japanese Red Cross Okayama Hospital Toshihide Yokoyama Respiratory Medicine, Kurashiki Central Hospital Masaaki Inoue Chest Surgery, Shimonoseki City Hospital Keisuke Sugimoto Respiratory Medicine, Japanese Red Cross Kobe Hospital Kenichiro Kudo Respiratory Medicine, National Hospital Organization Okayama Medical Center Toshiaki Okada Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Tadashi Maeda Respiratory Medicine, National Hospital Organization Yamaguchi Ube Medical Center Haruyuki Kawai Internal Medicine, Okayama Saiseikai General Hospital Masayuki Yasugi Respiratory Medicine, Chugoku Central Hospital Koji Inoue Respiratory Medicine, Ehime Prefectural Central Hospital Shoichi Kuyama Respiratory Medicine, Iwakuni Medical Center Takashi Ninomiya Respiratory Medicine, National Hospital Organization Shikoku Cancer Center Isao Oze Division of Molecular Medicine, Aichi Cancer Center Research Institute Yoshinobu Maeda Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Platinum compounds represent standard treatments for various cancers. However, the efficacy of re-administrating platinum compounds has been demonstrated only in ovarian cancer and small cell lung cancer (SCLC), with its utility in non-small cell lung cancer (NSCLC) remaining unclear. Given that the prognosis of NSCLC has improved with effective treatments such as immune checkpoint inhibitors (ICIs), we propose a multicenter, single-arm, prospective phase II trial of re-administrating platinum-based combination therapy for NSCLC. Patients with NSCLC who have progressed after chemoimmunotherapy and exhibit a platinum-free interval of 85 days or more will receive carboplatin combination therapy. The drugs combined with carboplatin - pemetrexed, nab-paclitaxel, or gemcitabine - must not have been administered previously. The primary endpoint is progression-free survival (PFS), assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Assuming a threshold PFS of 4.2 months and an expected hazard ratio of 0.60, the required sample size is calculated as 40 patients to achieve 70% power with a 5% alpha error. Secondary endpoints included objective response rate, toxicity, and overall survival. This study will clarify the efficacy of re-administrating platinum compounds to patients with NSCLC who have developed resistance to chemoimmunotherapy. No potential conflict of interest relevant to this article was reported.

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

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

Oxford University Press (OUP) Acta Medica Okayama 1465-3621 2026 Early progression after immune checkpoint inhibitor therapy in recurrent or metastatic head and neck squamous cell carcinoma: association with disease distribution in a single-center retrospective study hyag167 EN Hiroki Noda Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuma Makino Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuto Naoi Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Fujimoto Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology—Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Immune checkpoint inhibitors (ICIs) are an important treatment option for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, some patients experience rapid disease progression shortly after ICI initiation, potentially resulting in deterioration of general condition and limited opportunities for subsequent treatment. This study investigated clinicopathological factors associated with early progression after ICI initiation in patients with R/M HNSCC.<br> Methods: We retrospectively analyzed 207 patients with R/M HNSCC treated with nivolumab or pembrolizumab at a single institution. Early progression was defined as disease progression within 90 days after ICI initiation. Associations between clinicopathological factors and early progression were evaluated using logistic regression analyses.<br> Results: Early progression was observed in 80 patients (38.6%). In an exploratory survival comparison, patients with early progression had significantly shorter overall survival than those without early progression. Early progression rates increased from distant-only disease to locoregional-only disease and combined locoregional and distant disease. In multivariable analysis, combined locoregional, and distant disease showed the strongest independent association with early progression. Elevated neutrophil-to-lymphocyte ratio and hypoalbuminemia were also independently associated with early progression. In contrast, treatment regimen, treatment line, number of lesions, and bulky disease were not significantly associated with early progression.<br> Conclusion: Disease distribution was associated with early progression after ICI initiation in patients with R/M HNSCC, with combined locoregional and distant disease showing the strongest independent association. These findings suggest that both disease status and host condition may influence failure to achieve adequate disease control shortly after ICI initiation. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2210-6014 15 1 2025 Relationship Between Heated Tobacco Products and Placental Abruption: A Prospective Cohort Study Using Online Questionnaire 30 EN Hikaru Ooba Center for Innovative Clinical Medicine, Okayama University Hospital Jota Maki Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Tabuchi Division of Epidemiology, School of Public Health, Tohoku University Graduate School of Medicine Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Placental abruption (PA) is a critical obstetric complication, with maternal smoking recognized as a key risk factor. Despite the increased use of heated tobacco products (HTPs), the impact of HTPs remains unclear. This study investigated whether pregnant women using HTPs are at a higher risk of PA than non-users.<br> Methods: We analyzed data from “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.<br> Results: We found the robust aRD of 0.07 (95% confidence interval (CI): 0.06, 0.09) and the rRR of 11.3 (95% CI: 7.5, 17.0). Multiple bias analyses showed that unmeasurable confounders would need to have at least an rRR = 14 relationship with both exposure and outcome to disprove the observed association. There has not been post hoc analysis or secondary use of data.<br> Conclusion: Early pregnancy use of HTPs is associated with an increased risk of PA. No potential conflict of interest relevant to this article was reported.

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

SAGE Publications Acta Medica Okayama 1758-8359 17 2025 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.<br> Objectives: We examined this prognostic effect in patients with LSCC, and the usefulness of minocycline administration.<br> Design: This was a sub-analysis of the retrospective multicenter NINJA study.<br> Methods: We performed a landmark survival analysis according to the presence of skin disorders at Day 30 of treatment and examined the usefulness of minocycline for treating skin disorders.<br> Results: Among the 93 patients, 62 (66.7%) had a skin disorder at Day 30. Nineteen, 30, and 13 patients experienced Grade 1, 2, and 3 skin disorders, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with skin disorders at Day 30 were longer than those of patients without skin disorders (median OS: 434 vs 278 days, p = 0.0201; median PFS: 148 vs 82 days, p = 0.0835). Multivariable analysis showed that a skin disorder at Day 30 was an independent prognostic factor for both OS (p = 0.0044) and PFS (p = 0.0514). Of the 62 patients with skin disorders at Day 30, 38 (61.3%) were taking minocycline, and their time to treatment failure (TTF) was better than that in patients not taking minocycline (median TTF: 148 vs 101 days, p = 0.0495).<br> Conclusion: A skin disorder within 30 days was a favorable prognostic factor for patients with LSCC administered Neci + GC. Additionally, minocycline administration may be beneficial in patients who develop skin disorders within 30 days. No potential conflict of interest relevant to this article was reported.

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

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.<br> Highlight: This review summarizes historical and ultrastructural studies describing synaptic vesicles in taste bud cells across a range of animal species. The classical mechanisms of chemical synaptic transmission in the central nervous system are then outlined, followed by review studies demonstrating the expression of synapse-associated proteins in taste bud cells, with particular emphasis on the putative mechanisms of synaptic transmission in Type III taste cells. Finally, the current evidence for candidate neurotransmitters, including 5-hydroxytryptamine, gamma-aminobutyric acid, noradrenaline, acetylcholine, and ATP, is discussed.<br> Conclusion: Although several proteins related to conventional chemical synapses in the central nervous system and some candidate neurotransmitters have been identified in Type III cells, their contributions to sour taste transmission have not been fully elucidated. Further molecular and physiological studies are required to establish their roles in the synaptic transmission of sour taste signals from Type III cells. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 1362-1017 31 6 2026 Bridging the Awareness–Action Gap in Disaster Preparedness: A Qualitative Study of Immersive Virtual Reality Learning Among Nursing Students e70681 EN Keiko Mori Graduate School of Health Sciences, Okayama University Miina Yamazaki Kobe University Hospital Yoshiyuki Haruna Snowlion. Inc. Background: Disasters increasingly challenge healthcare systems, highlighting the need to strengthen preparedness among future healthcare professionals. Although disaster risk awareness is important, it does not consistently translate into preparedness behaviours, reflecting the awareness–action gap. Immersive virtual reality (VR) may enhance experiential disaster learning, but how it influences preparedness processes remains insufficiently understood, particularly in healthcare and critical care education.<br> Aims: To explore how immersive VR-based disaster simulations influence disaster risk perception and preparedness among nursing students, with particular attention to the awareness–action gap and implications for future healthcare and critical care practice.<br> Study Design: A qualitative descriptive study using immersive VR-based disaster simulations followed by semi-structured interviews. Twelve undergraduate and graduate nursing students in Japan experienced immersive VR simulations depicting floods and landslides. Individual semi-structured interviews explored emotional responses, disaster risk perception, preparedness awareness and anticipated behavioural responses. Data were analysed using Krippendorff's content analysis with researcher triangulation.<br> Results: Five categories were identified: (1) heightened vulnerability and psychological burden through immersion; (2) persistence of the awareness–action gap despite increased risk perception; (3) enhanced risk recognition and preparedness intentions; (4) recognition of the need for social and structural support systems; and (5) emerging responsibility accompanied by perceived limitations. VR transformed abstract disaster risk into emotionally salient experiences, strengthening threat appraisal and preparedness awareness; however, awareness did not consistently translate into preparedness behaviours, reflecting insufficient coping appraisal and self-efficacy.<br> Conclusions: Immersive VR may strengthen disaster risk perception and preparedness awareness, but immersive experiences alone may be insufficient to bridge the awareness–action gap. Combining VR with reflective learning, skills-based training and collaborative simulation may strengthen coping appraisal and preparedness action.<br> Relevance to Clinical Practice: Immersive VR combined with reflective and skills-based learning may support psychological readiness, situational awareness and disaster preparedness competencies among future nurses, including those preparing for critical care practice. No potential conflict of interest relevant to this article was reported.

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

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

Wiley Acta Medica Okayama 1058-8388 2026 MIT/TFE family transcription factors, Mitf and Tfec, redundantly promote pigment cell differentiation and retinal epithelium pigmentation in teleosts 1 15 EN James Lister Department of Human and Molecular Genetics and Massey Cancer Center, Virginia Commonwealth University School of Medicine Keisuke Sugiwaka Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Tetsuaki Kimura Department of Basic Biology, School of Life Science, Graduate University of Advanced Studies (SOKENDAI) & Laboratory of Bioresources, National Institute for Basic Biology Rieko Tanaka World Medaka Aquarium, Nagoya Higashiyama Zoo and Botanical Gardens Makoto Goda Institute of Photonics Medicine, Hamamatsu University School of Medicine Hikaru Kobayashi Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Chikako Inoue R&D Fish Breeding Group, Regional Fish Institute, Ltd. Kawilarang W. A. Masengi Faculty of Fisheries and Marine Science, Sam Ratulangi University Kazunori Yamahira Tropical Biosphere Research Center, University of the Ryukyus Kiyoshi Naruse Department of Basic Biology, School of Life Science, Graduate University of Advanced Studies (SOKENDAI) & Laboratory of Bioresources, National Institute for Basic Biology Satoshi Ansai Ushimado Marine Institute, Graduate School of Natural Science and Technology, Okayama University Robert N. Kelsh Department of Life Sciences, University of Bath Masahiko Hibi Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Hisashi Hashimoto Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Background: Transcription factors of the MIT/TFE family—mitfa, mitfb, and tfec—play essential roles in specifying pigment cells derived from neural crest cells in vertebrates. In teleosts, which possess multiple pigment cell types, these factors exhibit partially redundant but largely distinct functions across different pigment lineages. We previously reported that the combined loss of mitfa and mitfb leads to a complete absence of melanophores, xanthophores, and leucophores in medaka.<br> Results: Here, we describe newly generated hypomorphic alleles of mitfa and mitfb, which result in delayed melanophore development. Using these hypomorphic mutants in combination with a newly generated null allele of tfec, we show that Tfec can partially compensate for the loss of Mitfa and Mitfb in melanophore, xanthophore, and leucophore differentiation. Consistent with previous findings in zebrafish, loss of tfec alone results in the complete absence of iridophores. Importantly, simultaneous null mutations in all three genes cause a complete loss of all four chromatophore types and lead to defective pigmentation of the retinal pigmented epithelium (RPE), which is not derived from the neural crest in both Oryzias species and in zebrafish. Using an RPE-specific marker, we further show that the RPE is specified and structurally intact but fails to melanize.<br> Conclusions: These findings indicate that the redundant functions of Mitfa, Mitfb, and Tfec are not only essential for the specification of diverse pigment cell types but also critical for RPE pigmentation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-3751 604 18 2026 Integrative simulation analysis of myocardial ischaemia–reperfusion injury 7640 7662 EN Takao Shimayoshi Center for Artificial Intelligence and Mathematical Data Science, Okayama University Ayako Takeuchi Department of Physiology and Biophysics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Matsuoka Department of Integrative and Systems Physiology, Faculty of Medical Sciences, University of Fukui Cardiac ischaemia, reduced coronary blood flow, causes significant damages to the heart, and paradoxically reperfusion, restored flow after ischaemia, often results in more severe injury. Although the mechanisms underlying cardiac ischaemia–reperfusion injury have been intensively investigated, effective therapeutic strategies applicable during reperfusion to mitigate this damage have not been established yet. To obtain more insights into the mechanisms underlying ischaemia–reperfusion injury, and to explore effective methods to relieve reperfusion injury, we developed a comprehensive mathematical model of ventricular myocyte, implementing excitation–contraction (E–C) coupling, cytosolic and mitochondrial pH regulation, pH dependence of major components of E–C coupling and cellular energy metabolism, including mitochondrial oxidative phosphorylation. The mathematical model successfully reproduced experimentally observed findings on cardiac ischaemia–reperfusion injury, such as intracellular and extracellular acidosis, cytosolic Na+ overload, cytosolic Ca2+ overload, mitochondrial dysfunction, action potential shortening and contraction failure. It was found that the reperfusion-induced exacerbation of Na+i, Ca2+i overloads was mainly caused by insufficient production of NADH, which is used in mitochondrial oxidative phosphorylation to synthesize ATP for Na+/K+ pump and sarcoplasmic/endoplasmic reticulum Ca2+ pump (SERCA) to expel accumulated cytosolic Na+ and Ca2+, respectively. It was suggested that the preservation of mitochondrial NADH production, attenuation of ATP consumption via SERCA or contraction for a short period or activation of the Na+/K+ pump during reperfusion mitigates reperfusion injury. 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.

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

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 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 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.

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.

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.

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

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.

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.<br> 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.<br> 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 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.

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

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

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.<br> 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.<br> 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.<br> 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.

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.

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.

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.

Elsevier BV Acta Medica Okayama 0009-2541 713 2026 Tungsten(VI) speciation in aqueous fluids at high pressures and high temperatures: in-situ Raman spectroscopy supported by DFT calculations 123411 EN Naoko Takahashi Department of Earth Science, Graduate School of Science, Tohoku University Michihiko Nakamura Department of Earth Science, Graduate School of Science, Tohoku University Shigeru Yamashita Institute for Planetary Materials, Okayama University Hiroyuki Kagi Geochemical Research Center, Graduate School of Science, The University of Tokyo Tungsten (W) is mobile in magmatic–hydrothermal and deep subduction zone fluids, and its stable isotopes offer potential as tracers of fluid-rock interactions. We investigated W behavior in aqueous fluids using in-situ Raman spectroscopy on slightly acidic to alkaline Na2WO4 solutions (10−3–10−1 M W) and WO3–H2O/D2O ± NaCl systems up to 1.4 GPa and ∼800 °C, with the band assignments supported by density functional theory (DFT) calculations. Raman spectra showed that the ν1 mode of WO42− persisted to the highest P–T conditions in alkaline fluids, while additional high-frequency bands near 950 or 973 cm−1 appeared at elevated T in the studied fluids. Their relative intensities depended on T, pH, and NaCl content; the 973 cm−1 band was only observed above 650 °C in Na-free fluids. Substitution of H2O with D2O did not significantly affect the band frequencies. Based on analogous molybdenum experiments, previous in-situ studies, and thermodynamic models, these high-T bands are assigned to mononuclear species rather than polynuclear species, consistent with the stepwise formation of hydrogentungstate anion, HWO4−, and then neutral tungstic acid, H2WO4, as T increases. DFT vibrational frequency calculations for HWO4−, H2WO4, and their D-substituted species support this interpretation, suggesting tetrahedral HWO4− and higher-coordinated H2WO4 as plausible species. The present study clarifies Raman band assignments for HWO4− and paratungstate A (W7O246−) to address previous ambiguities in the literature, and confirms that polynuclear species play a negligible role in high-T ore-forming fluids. The tetrahedral HWO4− appears to be a predominant transport species in NaCl-bearing metamorphic fluids and may govern stable W isotope fractionation during deep fluid-rock interactions. No potential conflict of interest relevant to this article was reported.

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

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

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

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

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.<br> 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.<br> 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.<br> 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 1612-9059 2026 Incidental detection of cancers during population-based endoscopic gastric cancer screening in Japan EN Kensuke Uraguchi Department of Otolaryngology–Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kenta Hamada Department of Practical Gastrointestinal Endoscopy, Okayama University Naomi Matsumoto Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Mizuo Ando Department of Otolaryngology–Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kenji Fujimoto Occupational Health Data Science Center, University of Occupational and Environmental Health Shunsaku Hayase Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takashi Yorifuji Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background Upper gastrointestinal endoscopy traverses the full upper aerodigestive tract, unlike radiography, potentially enabling incidental detection of non-gastric malignancies. However, its population-level incidental detection rate for non-gastric upper aerodigestive tract cancers has not been systematically quantified. The aim of this study was to compare endoscopic screening with radiography and quantify detection of non-gastric upper aerodigestive tract cancers in a population-based setting.<br> Methods This population-based cohort study was conducted by linking the Okayama City municipal gastric cancer screening registry with the Kokuho Database (KDB) for fiscal years 2016–2021. Among 36,326 participants contributing 64,822 screening examinations (40,832 radiography; 23,990 endoscopy), diagnoses of oral cavity, pharyngeal, laryngeal, and esophageal cancer occurring within 2 months of screening were ascertained from the KDB. Generalized estimating equations with modified Poisson regression were used to estimate adjusted risk ratios (aRRs) comparing endoscopy with radiography.<br> Results Endoscopic screening was significantly associated with higher composite incidental detection rates for non-gastric upper aerodigestive tract cancers (95.9 vs. 34.3 per 100,000 examinations; aRR 2.94, 95% confidence interval [CI] 1.50–5.76; p = 0.002). Specifically, esophageal cancer detection was markedly higher with endoscopy (83.4 vs. 17.1 per 100,000; aRR 5.16, 95% CI 2.16–12.32; p < 0.001). No statistically significant differences were observed for oral cavity, pharyngeal, or laryngeal cancers.<br> Conclusions Endoscopic gastric cancer screening is associated with substantially higher incidental detection of non-gastric upper aerodigestive tract cancers, particularly esophageal cancer. These findings suggest an additional detection value for endoscopy that extends beyond its primary gastric cancer target in organized screening programs. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2673-9801 6 3 2026 The Antioxidant Activity of 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.

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 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.

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.

Elsevier BV Acta Medica Okayama 2666-5174 11 2026 Interbacterial antagonism mediates plant growth modulation by rhizosphere synthetic communities in barley 100639 EN Md Asif Mahamud Institute of Plant Science and Resources, Okayama University Rungnapa Pichaikarn School of Science, Walailak University Muhammad Ammar Latif Institute of Plant Science and Resources, Okayama University Takakazu Matsuura Institute of Plant Science and Resources, Okayama University Izumi C Mori Institute of Plant Science and Resources, Okayama University Daisuke Saisho Institute of Plant Science and Resources, Okayama University Pakpimol Ungcharoenwiwat School of Science, Walailak University Akio Tani Institute of Plant Science and Resources, Okayama University Microbial communities in plant roots are shaped by complex interbacterial interactions, yet how these interactions translate into plant fitness remains poorly understood. In this study, 127 bacterial isolates were obtained from barley (Hordeum vulgare L.) roots of two cultivars grown in a non-fertilized field, representing 45 genera and 72 species. Screening identified isolates with growth-promoting, growth-reducing, and neutral phenotypes. Co-inoculation experiments using synthetic communities (SynComs) demonstrated that growth-promoting isolates effectively cancelled the inhibitory effects of growth-reducing isolates on barley seedling growth. Mechanistic investigation revealed that growth-promoting isolates Variovorax sp. 14F-2.1 and Pseudomonas sp. 37A kill growth-reducing isolates Flavobacterium sp. 2D-1 through direct cell-to-cell contact. Deletion of the Type VI secretion system (T6SS) gene tssA in Variovorax sp. 14F-2.1 substantially reduced this activity, implicating T6SS as a key antagonistic mechanism. Phytohormone profiling revealed that growth-promoting and neutral isolates, but not growth-reducing isolates, produce cytokinins, and only Variovorax sp. 14F-2.1 could degrade IAA, suggesting a potential hormonal basis for differential growth effects. A two-year field microbiome study showed that fertilization regimen and seasonal sampling times were dominant drivers of rhizosphere community composition, while bacterial inoculation had limited and inconsistent effects on microbial diversity and plant growth under field conditions. These results demonstrate that interbacterial antagonism is a key determinant of community-level plant growth outcomes and highlight the complexity of translating laboratory inoculant effects to field settings. No potential conflict of interest relevant to this article was reported.

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

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.

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.

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 自然脱落した子宮原発 DLBCL に対して Pola-R-CHP 療法と CNS 再発予防を行った１例 58 61 EN Hikaru Osada Department of Hematology, Japanese Red Cross Okayama Hospital Maiko Kimura Department of Hematology, Japanese Red Cross Okayama Hospital Manaka Muneishi Department of Hematology, Japanese Red Cross Okayama Hospital Kozo Murayama Department of Hematology, Japanese Red Cross Okayama Hospital Daigo Niiya Department of Hematology, Japanese Red Cross Okayama Hospital Makoto Takeuchi Department of Hematology, Japanese Red Cross Okayama Hospital Soichiro Fujii Department of Hematology, Japanese Red Cross Okayama Hospital 　A 55-year-old woman presented to her local physician with the chief complaint of genital bleeding. A 22×19-mm mass was noted on the patient's cervix, and during the internal examination the mass auto-amputated. The pathological examination of the auto-amputated mass revealed diffuse large B-cell lymphoma (DLBCL). An examination by F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) showed FDG uptake at physiological levels in the cervix, with no abnormal uptake in other organs. Cervical tissue was sampled after the spontaneous detachment of the cervical mass, and the biopsy of the cervical mass did not reveal findings suggestive of lymphoma. Six courses of chemotherapy with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisolone (Pola-R-CHP) plus an intramedually injection of methotrexate, cytarabine, and predonisolone (IT-triple), followed by two courses of high-dose intrathecal methotrexate (HD-MTX) were adiministered, and the patient has remained recurrence-free for the more than 8 months since the completion of this treatment. Primary uterine DLBCL is an extremely rare disease with a high rate of recurrence in the central nervous system and a poor prognosis. Our search of the relevant literature identified very few reports describing the prognoses of cases with spontaneous tumor detachment. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0360-3199 270 2026 Synergistic effects of gas-to-liquid pilot ignition and high rates of nitrogen-based simulated EGR on PREMIER combustion in dual-fuel hydrogen engines 157237 EN Nirendra Nath Mustafi Graduate School of Natural Science and Technology, Okayama University Nobuyuki Kawahara Graduate School of Natural Science and Technology, Okayama University Yoshimitsu Kobashi Graduate School of Natural Science and Technology, Okayama University Hydrogen-fueled compression-ignition engines offer a pathway to decarbonize heavy-duty propulsion but face a trade-off between thermal efficiency, NOx emissions, and narrow knock-free windows. Although EGR dilution and pilot-fuel reactivity control have each been studied independently, their combined effect on hydrogen PREMIER (PREmixed Mixture Ignition in the End-gas Region) combustion has not been systematically characterized. This study addresses that gap by comparing diesel and high-cetane Gas-to-Liquid (GTL) pilot fuels in a supercharged hydrogen dual-fuel engine, while varying nitrogen addition to isolate the inert dilution effect of simulated EGR (0–50%). GTL's superior ignitability shortened ignition delay and enhanced combustion stability versus diesel. Increasing inert EGR (nitrogen) dilution suppressed NOx by over 90% (360 to 30 ppm) via reduced peak temperatures, while sustaining knock-free PREMIER combustion and achieving a peak indicated thermal efficiency of 43.55% at ∼0.80 MPa IMEP. Coupling pilot-fuel reactivity control with EGR dilution enables safe, clean, high-efficiency hydrogen dual-fuel. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 31 6 2026 Efficacy of bepotastine compared with hydroxyzine in preventing rituximab-induced infusion-related reactions in non-hodgkin lymphoma patients: a phase II, double-blind, multicenter, and randomized trial 979 988 EN Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Hironobu Minami Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kimikazu Yakushijin Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Keiji Kurata Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Rina Sakai Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Miki Saeki Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Yuri Okazoe-Hirakawa Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Kotaro Iida Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Natsuko Murase Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Isamu Harima Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine Naoko Kitamura Department of Pharmacy, Kobe University Hospital Kotaro Itohara Department of Pharmacy, Kobe University Hospital Tomohiro Omura Department of Pharmacy, Kobe University Hospital Takeshi Sugimoto Department of Hematology and Oncology, Kita-Harima Medical Center Hidetomo Takakura Department of Hematology and Oncology, Kita-Harima Medical Center Akihito Kitao Department of Hematology and Oncology, Kita-Harima Medical Center Masako Takahashi Department of Pharmacy, Kita-Harima Medical Center Manabu Shimoyama Department of Hematology and Oncology, Kohnan Medical Center Mamoru Okuno Department of Pharmacy, Kohnan Medical Center Ikuko Yano Department of Pharmacy, Kobe University Hospital Background This study evaluated the efficacy of hydroxyzine and bepotastine, first- and second-generation H1 receptor antagonists (H1RA), as pretreatments to prevent infusion-related reactions (IRRs) during the initial rituximab infusion in patients with non-Hodgkin lymphoma.<br> Methods In this double-blind, multicenter, randomized phase II study, 40 patients received hydroxyzine or bepotastine with acetaminophen 30 min before rituximab infusion. Primary endpoint was incidence of ≥ grade 2 IRRs based on the National Cancer Institute Common Terminology Criteria for Adverse Events. Secondary endpoints included IRRs severity, time to IRR onset, and H1RA-induced drowsiness.<br> Results Incidence of ≥ grade 2 IRRs was 52.4% and 31.6% for the hydroxyzine (n = 21) and bepotastine (n = 19) groups, respectively (P = 0.184). Distribution of initial and maximum IRR grades in the two groups was not statistically significant (P = 0.846 and 0.555). Median time (range) to IRR onset in the two groups was 67 (12–112) and 62 (10–119) min, respectively (P = 0.981). Median visual analog scale score (range and 75th percentile) for drowsiness was 37 (0–100, 46) and 12 (0–100, 29) mm in the two groups, respectively (P = 0.138). Incidence of ≥ grade 2 IRRs in the absence of bone marrow infiltration was 43.8% and 14.3% in the two groups, respectively (P = 0.118), and no group differences were observed with bone marrow infiltration.<br> Conclusions Bepotastine did not show significant superiority over hydroxyzine in preventing rituximab-induced IRRs due to the small sample size. Nevertheless, this exploratory study provides insight for further confirmatory studies.<br> Trial registration number and date of registration jRCTs051220169; February 14, 2023. No potential conflict of interest relevant to this article was reported.

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.

Elsevier BV Acta Medica Okayama 2589-0042 29 6 2026 Posterior shift of Shh-Fgf signaling in axolotl limb regeneration drives sequential digit formation 116256 EN Saya Furukawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sakiya Yamamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haruki Nakayama Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ayaka Ohashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akira Satoh Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Do conserved morphogen modules generate a given form only via a single spatiotemporal deployment, or can alternative deployments yield the same morphology? Axolotl limb regeneration provides a tractable test bed. SHH and FGF8, universally used in limb formation across vertebrates, also operate in axolotl, although the spatial domain of Fgf8 differs markedly from that in amniotes. A mutual Shh/Fgf feedback loop is likewise conserved. Here, we show that, in axolotl, the active domain of this loop shifts progressively posterior as digit formation proceeds. In step with this anterior-to-posterior displacement, digit-forming regions are sequentially induced posteriorly, explaining the axolotl’s reversed order relative to the amniote posterior-to-anterior sequence. These findings indicate that conserved molecular toolkits can overcome differences in spatial deployment to produce equivalent final limb architectures, demonstrating that there is not a single route to a target morphology. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2589-0042 29 8 2026 Brain circadian clock neurons drive fitness advantages in Drosophila 117125 EN Sae Aikawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shoichiro Tamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Makiko Mimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taishi Yoshii Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The adaptive significance of circadian clocks is widely assumed due to their ubiquity; yet, direct empirical evidence remains scarce. Evaluating these benefits is often confounded by pleiotropic effects in conventional circadian null mutants. To address this, we selectively altered the circadian period exclusively within brain clock neurons in Drosophila melanogaster. Multi-generational competition assays revealed that flies with aberrant rhythms exhibit a significant fitness disadvantage under standard light-dark (LD 12:12) cycles. This disadvantage was abolished under constant light, confirming that the selection pressure is specifically mediated by the circadian clock. Furthermore, paternity assays conducted under LD 12:12 indicated that the timing of brain clock neurons influences male reproductive success, providing a potential mechanistic link between clock-controlled behavior and fitness. Intriguingly, we found that these fitness costs are highly photoperiod-dependent. Under short-day conditions (LD 8:16), the short-period strain (dbtS) maintained a significantly higher overall frequency than the long-period strain (dbtL). Our behavioral observations suggest that this difference may be associated with the quality of activity rhythms; specifically, dbtS lacked defined morning peaks and showed suppressed nocturnal activity, potentially narrowing its window for reproductive interactions compared to dbtL. These findings illustrate that the circadian system does not merely track a 24-h cycle but functions as a flexible feature that enables flies to cope with changing day lengths by aligning their mating behavior with the most favorable time of day. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1939-5981 2026 Micro-segregation of Primary Si in ADC14 (Al–17Si–4Cu) Alloy Produced by Unidirectional Continuous Casting 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 An upgrading approach for hypereutectic Al–Si alloys was investigated through controlled segregation of Si using a unidirectional casting process. The precipitation behavior and spatial distribution of primary Si in the hypereutectic ADC14 (Al–17Si–4Cu) alloy were systematically examined at different casting speeds (0.06, 1.9, and 10 mm/s). Microstructural observations revealed that high casting speed suppresses primary Si formation due to rapid solidification, whereas intermediate speed leads to a relatively uniform distribution of primary Si. In contrast, low casting speed combined with a holding period for 2 min promotes pronounced segregation and coarsening of primary Si in localized regions. Energy-dispersive X-ray spectroscopy analysis confirmed significant fluctuations in Si concentration along the casting direction, particularly after process interruption. Based on these results, a preliminary upgrading process was proposed, involving the selective removal of Si-enriched regions followed by remelting. This approach resulted in a reduction of Si content to approximately 13.9 wt.%, corresponding to a decrease of about 3%. The results demonstrate that controlling solidification behavior to induce phase separation provides a promising and energy-efficient strategy for upgrading recycled Al–Si alloys. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 0016-6480 384 2026 Alternative transcription of the mouse Gh gene identifies an immune-associated transcript with species-specific structural divergence 114996 EN Ai Fukushima Graduate School of Natural Science and Technology, Okayama University Yu Takeuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hibiki Fukuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sakura Egoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hirotaka Sakamoto Graduate School of Natural Science and Technology, Okayama University Sayaka Aizawa Graduate School of Natural Science and Technology, Okayama University Sakae Takeuchi Graduate School of Natural Science and Technology, Okayama University Growth hormone (GH) in mice is primarily expressed in the anterior pituitary, although Gh expression has been reported in extrapituitary tissues, including immune organs. However, the structure of immune-associated Gh transcripts remains poorly characterized. To determine whether splenic Gh transcripts differ from pituitary Gh mRNA, 5′- and 3′-rapid amplification of cDNA ends (RACE) analyses were performed. While 3′ RACE showed a shared polyadenylation site, 5′ RACE identified a novel exon located approximately 2 kb upstream of the conventional exon 1, generating a transcript (spl-Gh mRNA) with a distinct first exon but shared downstream exons with pituitary Gh mRNA (pit-Gh mRNA). RT-PCR analysis revealed that spl-Gh mRNA is predominantly expressed in immune tissues such as spleen and bone marrow, and its distribution did not correlate with Pit-1 mRNA expression. Quantitative RT-PCR further demonstrated that spl-Gh mRNA was expressed at levels comparable to those of pit-Gh mRNA in the mouse spleen, indicating that spl-Gh is one of the major Gh transcript forms in this tissue. Sequence analysis indicated that spl-Gh mRNA is predicted to retain coding potential for a GH protein. Comparative genomic analyses further demonstrated that genomic features associated with the spl-Gh transcriptional unit are conserved only in a subset of closely related Mus species. In contrast, although a spl-Gh–related transcript was detected in rat spleen, no properly spliced mouse-like transcript was identified under the present experimental conditions. The detected transcript exhibited intron retention and an in-frame stop codon, suggesting that it is unlikely to produce a functional GH protein. These findings identify a distinct immune-associated Gh transcript generated through alternative transcription of the mouse Gh gene and suggest that immune-associated Gh transcriptional mechanisms have undergone species-specific divergence among rodents. Together, these findings reveal previously unrecognized complexity in Gh gene regulation and highlight species-specific differences in immune-associated Gh transcripts. No potential conflict of interest relevant to this article was reported.

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

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

Wiley Acta Medica Okayama 1356-9597 30 3 2025 Polished Rice Regulates Maturation but Not Survival of Secondary Cells in Drosophila Male Accessory Gland e70025 EN Shinichi Otsune Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mirai Matsuka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Chisato Shirakashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Xuanshuo Zhang Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hideki Nakagoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University In Drosophila males, the accessory gland is responsive to nutrient signal-dependent regulation of fertility/fecundity. The accessory gland is composed of two types of binucleated epithelial cells, about 1000 main cells and 60 secondary cells (SCs). The transcription factors Defective proventriculus (Dve), Abdominal-B, and Ecdysone receptors (EcRs) are strongly expressed in adult SCs. In response to nutrient conditions during development, coordinated action between Dve and ecdysone signaling determines the optimal number of SCs and regulates their maturation. A downstream effector of ecdysone signaling, Ftz-F1, is crucial in this process. Another downstream effector, Polished rice (Pri), is small peptides of 11 or 32 amino acids. Here we show that pri is required for maturation of SCs and for male fecundity, whereas it is not involved in determination of the number of SCs. We provide evidence that Pri acts downstream of Ftz-F1 to regulate maturation but not survival of SCs. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1467-7644 2026 Identification of Critical Amino Acid Residues Required for the Polar Localization of a Rice Manganese Transporter EN Noriyuki Konishi Institute of Plant Science and Resources, Okayama University Jian Feng Ma Institute of Plant Science and Resources, Okayama University Rice has developed an efficient system for manganese (Mn) uptake, mediated by two distinct transporters, OsNramp5 and OsMTP9. These transporters exhibit polar localization at the root exodermis and endodermis; however, the mechanisms underlying their polar localization and their role in Mn uptake remain unclear. Here, we identified key amino acid residues critical for the polar localization of OsNramp5 at the distal side. Through analysis of chimeric proteins between OsNramp5 and its non-polar homologues, we found that the C-terminal cytosolic region of OsNramp5 is essential for its polar localization. Site-directed mutagenesis further revealed that aspartate 500 and four valine residues at positions 494, 495, 498 and 506 are crucial for polarity. Substitution of these valine residues with isoleucine, leucine, phenylalanine, or threonine partially or fully maintained polar localization, whereas substitution with alanine, serine, or asparagine resulted in loss of polarity. These findings suggest that β-branching and high hydrophobicity of amino acid side chains are likely required for OsNramp5 polarity. Furthermore, we found that adaptor protein 2-dependent clathrin-mediated endocytosis is not involved in the polar localization of OsNramp5. Finally, we provided experimental evidence showing the significant role of OsNramp5 polarity in efficient Mn uptake in rice; plants expressing non-polarly localized OsNramp5 exhibited reduced Mn uptake compared to those with polarly localized OsNramp5. In addition, we found that cadmium accumulation in shoots could be reduced by manipulating OsNramp5 polarity in combination with its overexpression, without a growth penalty. No potential conflict of interest relevant to this article was reported.

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

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

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

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

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

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

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

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

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

Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 66 2 2026 RHOA G17V mutation analysis redirecting diagnosis: nodal T-follicular helper cell lymphoma with classic Hodgkin lymphoma feature 122 129 EN Rio Yamada Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Takuya Fukumi Department of Hematology, Okayama City Hospital Kumiko Ohsawa Department of Pathology, Saitama Medical Center, Saitama Medical University Shuji Momose Department of Pathology, Saitama Medical Center, Saitama Medical University Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Nodal T-follicular helper cell lymphoma (nTFHL) may present with Hodgkin/Reed–Sternberg (HRS)-like cells and can morphologically mimic classic Hodgkin lymphoma (CHL), although these entities are usually distinguishable. We report an unusual case showing marked morphologic and molecular overlap with CHL, creating a diagnostic challenge but ultimately considered biologically consistent with nTFHL.<br> An 81-year-old woman presented with stage IV disease involving the bone marrow and markedly elevated serum soluble interleukin-2 receptor levels. Excisional lymph node biopsy revealed scattered HRS cells in a T-cell–rich background, with strong CD30 and PD-L1 expression and weak PAX5 positivity, findings consistent with CHL. Fluorescence in situ hybridization demonstrated copy-number alterations at the 9p24.1 locus in HRS cells, further supporting molecular features characteristic of CHL.<br> However, the presence of two T-follicular helper markers, detection of the RHOA p.Gly17Val (G17V) mutation, and oligoclonal T-cell receptor rearrangements with shared peaks in lymph node and bone marrow indicated an underlying nTFHL. The differential therapeutic response also supported a diagnosis of nTFHL, which could not have been established on morphology alone.<br> In this case, although the HRS cells displayed morphological, immunophenotypic, and molecular features highly suggestive of CHL, the biological nature of the lesion was consistent with nTFHL. Compared with previously reported cases of nTFHL with HRS-like cells, this case more closely resembled CHL and may represent a distinct subset best described as “nTFHL with CHL features,” a concept warranting greater recognition among pathologists and clinicians. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 3 2025 Effects of Pemafibrate and Eicosapentaenoic Acid Ethyl Ester on Endothelial Function in Patients With Hypertriglyceridemia and Coronary Artery Disease: A Study Protocol for a Multicenter, Open-Label Randomised Controlled Trial e81104 EN Trou Miyoshi Cardiovascular Medicine, Okayama University Yasushi Matsuzawa Cardiovascular Medicine, Kumamoto University Masayuki Doi Cardiology, Kagawa Prefectural Central Hospital Shinsuke Yuasa Cardiovascular Medicine, Okayama University Seigo Sugiyama Cardiovascular Medicine, Jinnouchi Hospital Despite intensive low-density lipoprotein cholesterol-lowering therapies effectively reducing cardiovascular events, residual cardiovascular risks remain significant, with hypertriglyceridemia being an important contributing factor. Pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, has shown strong triglyceride-lowering effects and potential vascular benefits. Similarly, eicosapentaenoic acid ethyl ester (EPA) has demonstrated cardiovascular protective effects, particularly in patients with hypertriglyceridemia. However, the comparative impact of these agents on endothelial function, a key marker of atherosclerotic progression, has not been thoroughly evaluated in patients with coronary artery disease (CAD). The PRIME (PRospective comparIson of peMafibrate and Eicosapentaenoic acid ethyl ester on vascular functions for hypertriglyceridemia) trial is a multi-center, open-label, randomised trial designed to compare the effects of pemafibrate and EPA on endothelial function in patients with CAD and hypertriglyceridemia. Patients receiving statin therapy with fasting triglyceride levels ≥150 mg/dL will be randomised into two groups: pemafibrate (0.2 mg/day, with possible dose escalation to 0.4 mg/day) or EPA (1800 mg/day, with possible dose escalation to 2700 mg/day). Endothelial function will be assessed with reactive hyperemia index (RHI). The primary endpoint is the change in RHI at 12 weeks. The secondary endpoints include the changes in RHI at 24 weeks, correlations between changes in RHI and changes in lipid biomarkers, and changes in biochemical parameters at 12 and 24 weeks. This study investigates the comparative effects of pemafibrate and EPA on endothelial function, addressing an unmet need in managing residual cardiovascular risk in patients with CAD. The findings will contribute to the optimisation of treatment strategies in patients with CAD and hypertriglyceridemia. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 5 2025 Association Between Initial Symptoms and Clinical Outcomes in COVID-19 e84919 EN Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Mitsuru Tsuge Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kou Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenichiro Kudo Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Yasushi Tanimoto Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Kazuhiro Nouso Department of Gastroenterology, Okayama City Hospital Naohiro Oda Department of Internal Medicine, Fukuyama City Hospital Sho Mitsumune Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Goro Kimura Department of Respiratory Medicine, National Hospital Organization (NHO) Okayama Medical Center Haruto Yamada Department of Infectious Diseases, Okayama City Hospital Ichiro Takata Department of Internal Medicine, Fukuyama City Hospital Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akihiko Taniguchi Department of Internal Medicine, Fukuyama City Hospital Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyuki Aokage Department of Emergency Medicine, Tokyo Metropolitan Institute for Geriatrics and Gerontology Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: The clinical presentation of coronavirus disease 2019 (COVID-19) ranges from localized respiratory symptoms such as cough and sore throat to systemic symptoms such as fever and fatigue. To our knowledge, no study has assessed severe disease risk by dividing onset symptoms into localized respiratory and other symptoms. We aimed to determine whether the risk of severe COVID-19 differs depending on whether the symptoms at onset are limited to local respiratory symptoms.<br> Method: This was a multicenter prospective cohort study. The patients were classified into localized respiratory or systemic symptom groups based on the symptoms at onset. Demographic data, blood biomarkers, and clinical outcomes, including mortality, intubation, admission to the intensive care unit, and time to discharge, were compared. This study included 100 adult patients diagnosed with COVID-19 between July 2020 and August 2021.<br> Result: Twelve patients were classified into the localized respiratory symptom group and the remaining 88 into the systemic symptom group. No significant differences between the groups were observed in the baseline characteristics, blood biomarkers, or clinical outcomes. The mortality rates were 0.0% and 4.6%, respectively. The median durations to discharge were 11 and 10 days, respectively (p=0.512). The levels of inflammatory and oxidative stress biomarkers, including interleukin-6 and hydroperoxides, were similar between the groups.<br> Conclusion: The symptom type at disease onset was not significantly associated with differences in clinical outcomes. Comprehensive assessments beyond initial symptoms are crucial for predicting disease progression and optimizing management strategies. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 14 8 2026 Black Hairy Tongue in a 54‐Day‐Old Infant: A Case Report e73170 EN Masanori Masui Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumi Sakamoto Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Black hairy tongue is a benign condition caused by elongation and defective desquamation of the filiform papillae, and it is uncommon in neonates and infants. We report a case in a 54-day-old girl who presented with a black lesion on the tongue dorsum. The lesion had first been noted at the 1-month medical checkup and persisted despite observation. At presentation, a localized blackish-brown lesion with accentuated filiform papillae was observed on the tongue dorsum and could not be wiped off with gauze. Oral candidiasis was considered in the differential diagnosis, but microbiological examination detected no Candida species. A clinical diagnosis of black hairy tongue was made, and the parents were instructed to gently clean the tongue dorsum with gauze and a sponge brush. The lesion resolved within 2 weeks without recurrence. Recognition of this benign entity may help avoid unnecessary treatment in infants. No potential conflict of interest relevant to this article was reported.

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

Oxford University Press (OUP) Acta Medica Okayama 0032-0781 66 12 2025 ABA receptor isoforms differently regulate stomatal movements and generation of reactive oxygen species in ABA signaling in Arabidopsis guard cells 1811 1822 EN Ye Yin Graduate School of Environmental and Life Science, Okayama University Yuki Hayashi Graduate School of Science, Nagoya University Monira Sirajam Graduate School of Environmental and Life Science, Okayama University Oumayma Shaiek Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Toshinori Kinoshita Graduate School of Science, Nagoya University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Izumi C Mori Institute of Plant Science and Resources, Okayama University ABA signaling in stomatal guard cells is crucial for plants to cope with abiotic stress condition. Pyrabactin is a synthetic agonist of ABA that has a selective affinity to limited isoforms of ABA receptors. Here, we investigated the differential utilization of downstream signaling events in guard cell ABA signaling under specific receptor isoforms taking advantage of pyrabactin affinity. Pyrabactin-induced stomatal closure as well as ABA, while it did not inhibit stomatal opening. Plasma membrane inwardly rectifying K+ channel was not regulated by pyrabactin, while H+-ATPase activation was negatively regulated by pyrabactin. Pharmacological and molecular genetic evidence supported that reactive oxygen species production occurred differentially between the closure-inducing and opening-inhibiting signals in guard cells. These findings offer a previously unidentified mechanism for ABA signaling events promoting closure induction and opening inhibition of stomata, which were distinct from each other and governed by different ABA receptor isoforms discriminable by their affinity for pyrabactin. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 1473-0502 65 5 2026 Association of initial interface formation time with CD34+ collection efficiency in continuous mononuclear cell collection: A retrospective study 104504 EN Hiroyuki Murakami Department of Hematology, Okayama University Hospital Keiko Fujii Department of Hematology, Okayama University Hospital Wataru Kitamura Department of Hematology, Okayama University Hospital Kazuhiro Ikeuchi Department of Hematology, Okayama University Hospital Joji Shimono Department of Hematology, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Okayama University Hospital Nobuharu Fujii Department of Hematology, Okayama University Hospital Background: Factors influencing CD34+ cell collection efficiency (CE) during peripheral blood stem cell harvesting have been investigated; however, the impact of procedural management remains unclear. In continuous mononuclear cell (CMNC) collection, a stable cell–plasma interface (IF) is formed through channel priming, initial IF establishment, and mononuclear cell (MNC) collection. Although IF instability is known to impair CE, the adequacy of initial IF formation has not been examined as an independent factor. Therefore, we focused on the time required for initial IF formation and its association with CE.<br> Methods: We retrospectively analyzed 291 Spectra Optia CMNC procedures (52 autologous and 239 allogeneic) performed between 2016 and 2025. Initial interface formation time (IFT) was defined as the interval from the start of the procedure to transition to MNC collection. CE2 was defined as the ratio of collected CD34+ cells to the product of pre-apheresis peripheral blood CD34+ cell concentration and processed blood volume. Results: CE2 was lower in autologous than in allogeneic collections (41.3% vs. 59.2%) and was associated with longer IFT (median, 18 vs. 15 min). CE2 correlated with white blood cell count (r = −0.24), hematocrit (r = 0.36), and IFT (r = −0.23; all p < 0.001). In multivariable analysis, these factors remained independently associated with CE2, and IFT was inversely correlated with hematocrit (r = −0.44, p < 0.001).<br> Conclusion: IFT is independently associated with CE2 and provides insight into the early dynamics of IF formation during leukapheresis, highlighting an underexplored procedural aspect of CE. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0170-0839 83 10 2026 Osmotic pressure, correlation lengths and viscosity of aqueous pullulan solutions beyond the overlap concentration 565 EN Lingzi Meng Department of Materials Science and Engineering, The Pennsylvania State University Rene Iwato Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Takaichi Watanabe Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Carlos G. Lopez Department of Materials Science and Engineering, The Pennsylvania State University We investigate the thermodynamic, scattering, and flow properties of pullulan, a flexible non-ionic polysaccharide in aqueous solution, focusing on semidilute and concentrated solutions. We review dilute solution data for the intrinsic viscosity and radius of gyration and hydrodynamic radius of aqueous pullulan and find the Kuhn length and thermal blob size, below which the polymer chain is nearly ideal, to be 3 nm and 20 nm, respectively. We establish the scaling laws for static correlation length, specific viscosity, osmotic pressure, and osmotic compressibility across dilute, semidilute, and concentrated regions, finding that the scaling exponents align well with theoretical predictions but the crossover concentrations obtained from different methods are not consistent. The ratio between the osmotic and Ornstein–Zernike correlation lengths ξΠ/ξOZ is approximately 2.5 for aqueous solutions, similar to that observed in polystyrene in a theta solvent. This similarity may arise because the crossover concentration between the semidilute and concentrated regions c∗∗ is close to the overlap concentration c∗. No potential conflict of interest relevant to this article was reported.

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

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

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

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

Wiley Acta Medica Okayama 2045-8940 16 2 2026 Recurrence of Pulmonary Hypertension After Unilateral Lung Transplantation: Histological Evidence of Vasoconstrictive Mechanism e70289 EN Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Megumi Kondo Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichi Ichimura Department of Pathology, Hiroshima City Hiroshima Citizens Hospital Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Center for Advanced Heart Failure, Okayama University Hospital Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pulmonary hypertension (PH) is widely recognized as a disease driven by both vasoconstriction and vascular remodeling. Vasoconstriction is thought to play a predominant role in the early stages of PH, whereas the contribution of vascular remodeling increases as the disease progresses. However, clinical or histological evidence of this pathological progression has not been reported. We describe a case of recurrent PH after unilateral right lung transplantation, ultimately requiring bilateral transplantation 9 years later, and discuss the pathogenesis of PH based on histological findings in the transplanted normal lungs and changes in pulmonary blood flow observed by lung perfusion scintigraphy. Serial lung perfusion scintigraphy revealed a dynamic shift in pulmonary blood flow, initially favoring the transplanted lung, followed by a gradual decline. Histological examination demonstrated that the right lung of the second transplantation showed minimal vascular remodeling. These findings provide compelling evidence that vasoconstriction was the predominant contributor to PH after the first transplantation, offering unique insight into early PH pathobiology. No potential conflict of interest relevant to this article was reported.

Japan Atherosclerosis Society Acta Medica Okayama 1340-3478 33 2 2026 A Case of Acquired LCAT Deficiency with the Discrepancy between Spontaneous Resolution of Proteinuria and Continually Low HDL Cholesterol Levels 228 236 EN Miki Matsuo Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center Masatsune Ogura Department of Clinical Laboratory Technology, Faculty of Medical Science, Juntendo University Masayuki Kuroda Center for Advanced Medicine, Chiba University Hospital, Chiba University Tetsuya Arisato Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center Masatsugu Kishida Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center Mariko Harada-Shiba Cardiovascular Center, Osaka Medical and Pharmaceutical University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koutaro Yokote Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine Fumiki Yoshihara Department of Nephrology and Hypertension, National Cerebral and Cardiovascular Center A 79-year-old Chinese man was referred for nephrotic syndrome (proteinuria 4.4 g/day). In blood tests, serum high-density lipoprotein (HDL) cholesterol was undetectable, and the esterified cholesterol to total cholesterol ratio was very low. Lecithin: cholesterol acyltransferase (LCAT) activity was also undetectable. Since he had neither corneal opacity nor pathological mutations in the LCAT gene and anti-LCAT antibodies were detected in serum, a diagnosis of acquired LCAT deficiency was made. Renal biopsy revealed glomerulopathy associated with LCAT deficiency and membranous nephropathy (MN). Since the patient’s proteinuria did not improve despite prescribing an angiotensin II receptor blocker (ARB), we suggested the prescription of prednisolone, but he returned to China due to the expiration of his residence visa for Japan. One year after the initial visit, his proteinuria had improved to 0.9 g/day without immunosuppressive therapy. However, his HDL cholesterol level was still low at around 3 mg/dL, indicating a discrepancy between remission of nephrotic syndrome and lack of improvement in lipid levels.<br> Of the 11 patients with acquired LCAT deficiency reported to date, 4 with undetectable LCAT activity and MN on renal biopsy required immunosuppressive therapy to alleviate proteinuria. The present patient was prescribed only an ARB according to his preference, which happened to be consistent with the MN treatment guideline that states, “Wait 6 months for spontaneous remission while using maximal antiproteinuric therapy.” The clinical course of acquired LCAT deficiency varies, and further case reports are needed to determine the necessity of immunosuppressive therapy. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0914-5087 87 5 2026 Cardio-ankle vascular index as a screening tool for coronary artery disease in patients with metabolic dysfunction-associated steatotic liver disease 429 433 EN Mitsutaka Nakashima 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 Yuta Ueki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Nishihara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Hara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keishi Ichikawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Centre Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common hepatic disorder that significantly increases cardiovascular risk. However, no established screening method exists for detecting subclinical coronary artery disease (CAD) in this high-risk population. The cardio-ankle vascular index (CAVI), a blood pressure–independent measure of arterial stiffness, may offer a non-invasive tool for early detection of coronary atherosclerosis.<br> Methods: We retrospectively analyzed 295 patients with MASLD who underwent both CAVI measurement and coronary computed tomography angiography at a single center. Significant CAD was defined as ≥50 % luminal stenosis. Receiver operating characteristic (ROC) analysis was used to evaluate diagnostic performance. Multivariable logistic regression was performed to identify independent associations between elevated CAVI and CAD. The incremental predictive value of CAVI was assessed using net reclassification improvement (NRI).<br> Results: Of the 295 patients, 110 (37.3 %) had significant CAD. Patients with CAD had significantly higher CAVI values (9.0 vs. 8.7, p = 0.007). The area under the ROC curve for CAVI predicting CAD was 0.614. A CAVI cut-off of 8.6 provided a sensitivity of 66.4 % and a specificity of 56.8 %. CAVI ≥8.0 was independently associated with CAD (OR 3.44, 95 % CI: 1.06–11.2, p = 0.040). Adding CAVI to a conventional risk model improved risk reclassification (NRI 0.4236, p < 0.001), although the C-statistic change was not significant (from 0.724 to 0.725, p = 0.835).<br> Conclusions: CAVI is independently associated with significant coronary stenosis in MASLD patients and may serve as a non-invasive screening tool to enhance cardiovascular risk stratification. Its moderate diagnostic accuracy suggests utility as a component of a multifactorial risk assessment strategy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0289-0771 2026 Sex differences and contest experience shape walking patterns in the broad-horned flour beetle EN Kentarou Matsumura Graduate School of Arts and Sciences, The University of Tokyo Sora Hashioka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Naohisa Nagaya Faculty of Information Science and Engineering, Kyoto Sangyo University Ryusuke Fujisawa Faculty of Environmental Engineering, University of Kitakyushu, Takahisa Miyatake Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Animal movement patterns vary widely across species, and sex differences are often expected because males typically need to encounter multiple females and acquire resources. In species where males engage in male–male combat using exaggerated weapons, variation in weapon size and contest outcomes is known to influence male reproductive strategies, and may therefore also affect movement behavior. However, sex-specific and male-specific differences in locomotor behavior, particularly in relation to weapon size and social interactions, remain poorly understood. Here, we investigated walking trajectories in the broad-horned flour beetle (Gnatocerus cornutus) to test for (1) sex differences, (2) associations between male weapon size and movement behavior, and (3) the effects of male–male combat. Males exhibited more tortuous and localized movement, whereas females showed straighter and more spatially extensive trajectories. Following contests, all males showed a reduction in activity regardless of contest outcome; however, winners and losers exhibited divergent changes in movement patterns, with winners showing straighter and more spatially extensive trajectories and losers showing more tortuous and localized trajectories. In contrast, body-size-corrected weapon size was not associated with any aspect of walking behavior. These results indicate that locomotor behavior in G. cornutus varies with sex and contest experience, and that variation in walking behavior is more closely associated with social experience than with weapon morphology. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 65 8 2026 Autopsy Case of a Disseminated Cytomegalovirus Infection with a Cutaneous Ulcer Mimicking Rheumatoid Vasculitis 1172 1177 EN Kohei Oguni Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Yukichika Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoharu Ishida Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoka Ohki Department of Pathology, 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 A 60-year-old woman with rheumatoid arthritis and an impaired consciousness was referred to our hospital. Prior to transfer, the patient underwent intensified immunosuppressive therapy under a diagnosis of rheumatoid vasculitis that had developed in her buttocks. Upon hospitalization, she developed severe multiorgan failure and hemophagocytic syndrome. Four days after admission, both blood cytomegalovirus (CMV) antigenemia and the DNA load were markedly elevated. Despite intensive care, the patient died. Later, a histopathological examination revealed that the cutaneous manifestation represented CMV disease, not rheumatoid vasculitis, as was initially suspected. Failure to identify CMV as the underlying cause may result in the inappropriate administration of immunosuppressive therapy, potentially worsening the patient's condition. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1572-1000 58 2026 Pathological features of residual head and neck cancer after near-infrared photoimmunotherapy: implications of an unfavorable tumor immune microenvironment 105422 EN Takuma Makino Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Department of Hematopathology, Okayama University Graduate School of Health Sciences Asami Nishikori Department of Hematopathology, Okayama University Graduate School of Health Sciences Yuto Naoi 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 Purpose: Near-infrared photoimmunotherapy has been approved in Japan for unresectable locally advanced or recurrent head and neck cancer. While this therapy theoretically induces selective necrosis of epidermal growth factor receptor-expressing tumor cells following administration of cetuximab sarotalocan sodium and irradiation with 690-nm light, residual disease is not uncommon in clinical practice. The mechanisms underlying such persistence remain poorly understood.<br> Methods: We examined two patients with head and neck squamous cell carcinoma who underwent salvage resection due to residual disease after four cycles of near-infrared photoimmunotherapy. Resected specimens were subjected to histopathological evaluation, including immunohistochemistry for epidermal growth factor receptor, cluster of differentiation 8, programmed cell death protein 1, and forkhead box P3 proteins.<br> Results: In both cases, residual tumor cells were predominantly localized in the superficial mucosal layers, while deeper layers were replaced by fibrosis. All residual tumors retained expression of epidermal growth factor receptor. Lymphocytic infiltration was sparse, with scattered cluster of differentiation 8-positive cells but few programmed cell death protein 1-positive or forkhead box P3-positive lymphocytes. These findings suggest that the tumor microenvironment surrounding residual tumors may have been unfavorable for the induction of robust antitumor immune responses.<br> Conclusion: Residual tumors after near-infrared photoimmunotherapy can occur despite adequate laser irradiation and epidermal growth factor receptor expression. Our observations imply that insufficient immune activation within the tumor microenvironment may contribute to treatment resistance. Further characterization of the post-photoimmunotherapy tumor microenvironment will be essential to better understand treatment mechanisms and to optimize therapeutic efficacy. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2399-3642 9 1 2026 In vivo activities of E1 elements in the insulin promoter 838 EN Hirofumi Noguchi Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus Chika Miyagi-Shiohira Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Issei Saitoh Department of Pediatric Dentistry, Asahi University School of Dentistry In this study, we evaluated the in vivo activity of the E1 element within the insulin promoter region. While we successfully obtained mice carrying a deletion exclusively in the E1 element of Ins2 (2E mice), we were unable to obtain mice with a deletion limited to the E1 element of Ins1. To assess the role of the E1 element in Ins1, we compared the mice carrying deletions in the GG2-GG1/A2-C1 elements with or without an additional E1 element deletion (1GC/1GCE mice). 1GCE2E mice developed diabetes. In contrast, 1GCE23 mice (without deletion in the E1 element of Ins2) did not develop diabetes, suggesting that the E1 element of Ins2 is critical for transcriptional regulation. Furthermore, 1GC2E mice (presence of the E1 element of Ins1) developed diabetes. However, the severity of the disease was milder in 1GC2E mice than in 1GCE2E mice, indicating that the E1 element of Ins1 also contributes to transcriptional regulation. These data suggest that the E1 elements in both Ins1/2 promoters are regulated for the in vivo transcription of insulin genes in mice. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1472-6831 26 1 2026 Differences in understanding of explanations and risk perception between dental staff and patients: a questionnaire study at a university hospital 1050 EN Shiho Otomo School of Environment and Society, Institute of Science Tokyo Maoko Fujisaki School of Environment and Society, Institute of Science Tokyo Risako Yanagase School of Environment and Society, Institute of Science Tokyo Kanako Noritake Institute of Science Tokyo Hospital, Institute of Science Tokyo Yoshinobu Yanagi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taro Sugihara School of Environment and Society, Institute of Science Tokyo Background and purpose: Proper self-care necessitates behavioral changes, underpinned by correct knowledge. Oral health literacy (OHL) research constitutes a fundamental foundation for fostering effective self-care practices. However, the extent of the awareness gap between patients and dental staff regarding explanations provided during treatment remains unknown. This descriptive study was conducted to serve as an initial step in bridging this gap.<br> Methods: Questionnaires were distributed to 92 dental staff members and 205 patients at university hospitals, with responses from 72 staff members and 157 patients.<br> Results: In the category assessing understanding of explanations (patient vs. dental staff), patients’ self-assessed understanding exceeded the dental staff’s estimates in three aspects: disease name (p = 0.03, r = 0.17), treatment period (p = 0.01, r = 0.21), and pain relief (p = 0.01, r = 0.19). Regarding health self-awareness, the high-scoring group significantly outperformed the low-scoring group in explaining treatment risks (p = 0.03, r = 0.21) and understanding (p = 0.01, r = 0.23). Nevertheless, patients’ risk recognition was higher than that of dental staff in three aspects: root canal treatment (p < 0.01, r = 0.23), holes in the teeth (p < 0.01, r = 0.24), and bleeding during toothbrushing (p = 0.02, r = 0.17). Questions on “crack” (p = 0.02, r = 0.21) by sex, holes in one’s own teeth (p = 0.05, r = 0.03), and feeling one’s own teeth wobble (p < 0.01, r = 0.07) in the intergenerational comparison showed significant differences.<br> Conclusion: Dental staff should not be satisfied merely with having "explained" something to the patient; they must engage in a confirmation process to verify the patient's correct understanding of the information or to identify excessive anxiety. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1022-5536 34 1 2026 Similar functional outcomes but different remodeling patterns: A minimum 5-years radiographic comparison of short fit-and-fill stem and quadrangular taper stem 1 10 EN Yasutaka Masada Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomonori Tetsunaga Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuo Fujiwara Department of Orthopaedic Surgery, Okayama City General Medical Center, Okayama City Hospital Kazuki Yamada Department of Orthopaedic Surgery, Okayama University Hospital Tomohiro Inoue Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichiro Okuda Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoko Tetsunaga Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Okazaki Center for Education in Medicine and Health Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose: ACTIS and CORAIL are cementless titanium femoral stems with hydroxyapatite (HA) coating but differing macro-geometries: ACTIS features a variable triple-taper with a medial collar, whereas CORAIL is a straight double-tapered design available with or without a collar. We compared mid-term clinical and radiographic outcomes of these stems with a minimum 5-years follow-up.<br> Methods: We retrospectively reviewed 114 primary total hip arthroplasties using ACTIS (63 hips) or CORAIL (51 hips). Clinical outcomes and standardized radiographic parameters were assessed and compared between groups.<br> Results: The canal-fill ratio (CFR) was significantly greater at the proximal, middle, and distal levels in the ACTIS group. Spot-weld formation was more frequent with ACTIS than with CORAIL (58.7% vs 35.3%). In logistic regression, proximal CFR significantly predicted spot-weld formation for ACTIS, with an optimal cutoff of 66.2% (sensitivity 91.9%, specificity 72.0%). Rates of subsidence, radiolucent lines, and pedestal formation did not differ significantly between groups. No severe stress shielding was observed with ACTIS, whereas three CORAIL hips demonstrated severe stress shielding (0% vs 5.9%). Clinical scores improved significantly in both groups, with no significant between-group differences at final follow-up.<br> Conclusions: Both stems yielded favorable radiographic and clinical mid-term outcomes. In ACTIS, greater proximal canal fill was associated with radiographic osseointegration, suggesting proximal CFR as a probabilistic radiographic marker of stem ingrowth. 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 The role of Pth1r in posterior cranium cartilage regulation and craniosynostosis 5862 EN Katsuhiko Amano Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Okuzaki Laboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of Osaka Yuji Fujimoto Laboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of Osaka Yu-Chen Liu Laboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of Osaka Mikihiko Kogo The First Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry Seiji Iida Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Craniosynostosis is a major craniofacial congenital disorder that causes developmental complications. During normal cranial development, intramembranous ossification forms the flat bones and sutures, while cartilage appears transiently in the posterior calvarial region. However, in craniosynostosis, premature suture fusion disturbs normal calvarial morphogenesis. To clarify the role of transient cartilage in this morphogenetic disruption, we investigated its molecular regulation and pathology in mice, focusing on parathyroid hormone 1 receptor (Pth1r) signaling. Conditional deletion of Pth1r in the cranial mesenchyme unexpectedly caused acrocephalic dysmorphology and craniosynostosis, with altered cartilage differentiation. Occipito–interparietal synostosis consistently occurred in Pth1r-ablated Gli1+ and Acan+ lineages, but not after adult Gli1-CreERT2 deletion, indicating a developmental role. Bulk and single-cell RNA-seq analysis revealed nine mesenchymal subsets, with mutant cells showing abnormal chondrocyte differentiation and upregulated Indian hedgehog (Ihh) signaling. These findings indicate that Pth1r maintains proper chondrogenic regulation during calvarial development, and its loss induces craniosynostosis through Ihh overactivation. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0278-0372 46 3 2026 Estimating the distributional expansion of the invasive crayfish Procambarus clarkii (Girard, 1852) (Decapoda: Astacidea: Cambaridae) in South Korea using environmental DNA analysis ruag033 EN Seong-Nam Ham Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kaito Moriuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mayuko Hamada Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuyoshi Nakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The red swamp crayfish Procambarus clarkii (Girard, 1852) is a globally invasive species that poses serious threats to native biodiversity and ecosystem functioning. In South Korea, established populations of P. clarkii have been documented from the Jiseokcheon River in the Yeongsangang River basin since 2018; however, information on its current nationwide distribution remains limited. We conducted environmental DNA (eDNA) surveys at 19 sites across 11 river systems in South Korea, including sites with no prior distributional records, to evaluate the current distribution and potential range expansion of P. clarkii. Water samples collected during July-August 2024 were analyzed using quantitative real-time PCR (qPCR) with two species-specific primer-probe sets targeting the mitochondrial COI gene. Procambarus clarkii eDNA was detected at three sites in the Yeongsangang River basin, whereas no eDNA was detected in the other surveyed river systems. Notably, P. clarkii eDNA was not detected at a site in the Mangyeonggang River system despite previous reports of individuals and eDNA data sampled there, indicating a possible local population decline or very low abundance. By contrast, detections within the Yeongsangang River basin, together with elevated eDNA concentrations at some sites, are consistent with localized upstream expansion and increased local abundance. The concordant results from the two primer-probe sets, together with Sterivex-based on-site filtration, support the reliability of the applied eDNA framework. These findings identify the Yeongsangang River basin as the current primary focus of the P. clarkii invasion in South Korea, with evidence consistent with localized upstream expansion and increasing abundance, and provide baseline data for early detection and long-term monitoring, as well as for developing management strategies. No potential conflict of interest relevant to this article was reported.

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

American Society for Clinical Investigation Acta Medica Okayama 1558-8238 136 10 2026 Spatial single-cell proteotyping reveals immunotherapy-resistant features within the complex tumor microenvironment of metastatic NSCLC e195021 EN Kohsuke Isomoto Department of Medical Oncology, Kindai University Faculty of Medicine Koji Haratani Department of Medical Oncology, Kindai University Faculty of Medicine Takahiro Tsujikawa Department of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of Medicine Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Yusuke Makutani Department of Surgery, Kindai University Faculty of Medicine Masayuki Takeda Department of Medical Oncology, Kindai University Faculty of Medicine Kimio Yonesaka Department of Medical Oncology, Kindai University Faculty of Medicine Kaoru Tanaka Department of Medical Oncology, Kindai University Faculty of Medicine Tsutomu Iwasa Department of Medical Oncology, Kindai University Faculty of Medicine Kazuko Sakai Department of Genome Biology, Kindai University Faculty of Medicine Kazuto Nishio Department of Genome Biology, Kindai University Faculty of Medicine Akihiko Ito Department of Pathology, Kindai University Faculty of Medicine Kazuhiko Nakagawa Department of Medical Oncology, Kindai University Faculty of Medicine Hidetoshi Hayashi Department of Medical Oncology, Kindai University Faculty of Medicine BACKGROUND. Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1 axis have revolutionized metastatic non–small cell lung cancer (mNSCLC) treatment. However, disease progression remains a concern, and the role of the complex tumor microenvironment (TME) in treatment failure is not fully understood.<br> METHODS. In this biomarker study involving 103 patients with mNSCLC, including 81 patients who received ICI treatment, we evaluated the association between heterogeneous immune cell subsets and ICI efficacy through single-cell spatial profiling of pretreatment tumor tissue, using a 29-marker multiplex IHC platform built for in-depth dissection of the TME.<br> RESULTS. Among various types of intratumoral lymphocytes, including Th1, Treg, and NK cells, only CD8+ T cells (tumor-infiltrating lymphocytes [TILs]) were associated with ICI efficacy. Computational tissue segmentation underscored the importance of direct physical interactions between CD8+ TILs and cancer cells for ICI efficacy. TIL phenotyping identified CD39/CD103/Ki-67 positivity as a hallmark of exhausted yet functional tumor-reactive CD8+ TILs. Immunosuppressive tumor-associated macrophages (TAMs) and cancer-associated fibroblasts were independent unfavorable adversaries. High CD73 expression on cancer cells was suggested to confer tolerance to ICI in EGFR/ALK-oncogene+ NSCLC, potentially through M2-TAM accumulation and aberrant angiogenesis.<br> CONCLUSION. Our study delineates the clinical relevance of heterogeneous immune cell subsets in ICI-treated mNSCLC, aiding the development of targeted therapeutic strategies. 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 Dual-calibration RT-qPCR reveals distinct dnaK1/2/3 and groEL1/2 expression dynamics under heat and acid stress in the sinefungin producer Streptomyces incarnatus 19282 EN Zhao Xiao-Hui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mao Kubo Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haruka Yamagata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuriko Nakashima Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tomohisa Hasunuma Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tadayoshi Kanao Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takashi Tamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Streptomyces incarnatus NRRL8089 produces sinefungin, a nucleoside antibiotic whose yield is enhanced under defined environmental stresses. Here, dual-calibration RT-qPCR was used to resolve paralogue-specific expression dynamics of the dnaK and groE chaperone systems under heat and acid stress conditions that increase sinefungin titres. The canonical dnaK1–dnaJ1 and groES–groEL1 operons exhibited moderate induction, whereas monocistronic paralogues (dnaK2, dnaK3 and groEL2) showed markedly higher inducibility, with up to ~ 125-fold increases relative to baseline expression. Promoter analyses revealed conserved inverted repeats and differences in predicted secondary-structure stability, suggesting that promoter architecture contributes to paralogue-specific responsiveness. Structural modelling indicated divergence among DnaK paralogues in regions associated with substrate interaction, whereas GroEL paralogues retained a conserved overall scaffold, consistent with kinetic rather than structural differentiation. Together, these findings indicate that duplicated paralogues are not functionally redundant but are differentially regulated to partition proteostasis capacity under stress. This paralogue-specific regulation may provide a framework linking environmental perturbation to secondary-metabolite production in actinomycetes. No potential conflict of interest relevant to this article was reported.

Japanese Society of Veterinary Science Acta Medica Okayama 0916-7250 87 6 2025 Effects of heat stress on gene expression associated with antioxidant capacity of bovine early antral follicles 680 684 EN Kohei KAWANO Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kenichiro SAKAGUCHI Laboratory of Veterinary Theriogenology, Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University Eri FURUKAWA National Institute of Animal Health, National Agriculture and Food Research Organization Nattapong NINPETCH Department of Animal Science, Faculty of Agriculture at Kamphaeng Saen, Kasetsart University Yojiro YANAGAWA Laboratory of Theriogenology, Department of Clinical Sciences, Division of Veterinary Medicine, Faculty of Veterinary Medicine, Hokkaido University Seiji KATAGIRI Laboratory of Theriogenology, Department of Clinical Sciences, Division of Veterinary Medicine, Faculty of Veterinary Medicine, Hokkaido University Heat exposure at the physiological level of oocyte-cumulus-granulosa cell complexes (OCGCs) during in vitro growth (IVG) culture decreases the reduced glutathione (GSH) level of oocytes, an antioxidant, but its mechanism has been unclear. We subjected OCGCs to IVG for 4, 8, or 12 days and investigated the effects of heat exposure on the gene expression of cumulus-granulosa cells associated with antioxidant capacity. Heat exposure did not alter the expression of genes related to GSH synthesis or reuse. Conversely, heat exposure increased mRNA expression of superoxide dismutase 2 and decreased that of glutathione peroxidase 1, which are antioxidant enzymes. Ultimately, heat exposure alters the gene expression of antioxidant enzymes in growing follicles, which may indirectly decrease the GSH level of oocytes. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0021-9193 206 10 2024 Overexpression of diglucosyldiacylglycerol synthase leads to daptomycin resistance in Bacillus subtilis e00307-24 EN Ryogo Yamamoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuya Ishikawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuyuki Furuta Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin-Ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikara Kaito Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The lipopeptide antibiotic daptomycin exhibits bactericidal activity against Gram-positive bacteria by forming a complex with phosphatidylglycerol (PG) and lipid II in the cell membrane, causing membrane perforation. With the emergence of daptomycin-resistant bacteria, understanding the mechanisms of bacterial resistance to daptomycin has gained great importance. In this study, we aimed to identify the genetic factors contributing to daptomycin resistance in Bacillus subtilis, a model Gram-positive bacterium. Our findings demonstrated that overexpression of ugtP, which encodes diglucosyldiacylglycerol synthase, induces daptomycin resistance in B. subtilis. Specifically, overexpression of ugtP resulted in increased levels of diglucosyldiacylglycerol (Glc2DAG) and decreased levels of acidic phospholipids cardiolipin and PG, as well as the basic phospholipid lysylphosphatidylglycerol. However, ugtP overexpression did not alter the cell surface charge and the susceptibility to the cationic antimicrobial peptide nisin or the cationic surfactant hexadecyltrimethylammonium bromide. Furthermore, by serial passaging in the presence of daptomycin, we obtained daptomycin-resistant mutants carrying ugtP mutations. These mutants showed increased levels of Glc2DAG and a >4-fold increase in the minimum inhibitory concentration of daptomycin. These results suggest that increased Glc2DAG levels, driven by ugtP overexpression, modify the phospholipid composition and confer daptomycin resistance in B. subtilis without altering the cell surface charge of the bacteria. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0304-8608 171 1 2025 Novel Escherichia coli phages representing a distinct genus within the subfamily Stephanstirmvirinae: genome and host range characteristics 18 EN Tomoyoshi Kaneko Department of Life Science and Medical Bioscience, Waseda University Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Osaka Department of Microbiology and Immunology, Tokyo Women’s Medical University Satoshi Tsuneda Department of Life Science and Medical Bioscience, Waseda University Bacteriophages play crucial roles in microbial ecosystems and have potential for biotechnological applications. However, our understanding of culturable phages remains limited. In this study, we characterized six novel Escherichia coli phages isolated from pig farm wastewater and urban sewage, using comprehensive genomic, morphological, and host-range analysis. Using multiple comparative approaches, including gene-sharing network analysis, average nucleotide identity (ANI), and nucleotide intergenomic similarity (NIS), we demonstrated that five of these phages form a distinct group within the subfamily Stephanstirmvirinae, potentially representing a novel genus, for which we propose the name "Wecvirus”. We further propose that these phages, each of which exhibits a unique host range pattern, should be classified in two distinct species within the proposed genus. This host specificity is reflected in differences in the amino acid sequences of tail fibers, which are crucial for infection. The remaining phage, which was not classified as a wecvirus, exhibited characteristics that challenged the current classification criteria, highlighting the need for more-flexible taxonomic approaches. These findings expand our understanding of phage diversity within the subfamily Stephanstirmvirinae and contribute to the evolving phage taxonomy framework. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0012-1606 520 2025 Tunicate-specific protein Epi-1 is essential for conferring hydrophilicity to the larval tunic in the ascidian Ciona 41 52 EN Kazu Kuroiwa Shimoda Marine Research Center, University of Tsukuba Kaoru Mita-Yoshida Shimoda Marine Research Center, University of Tsukuba Mayuko Hamada Ushimado Marine Institute, Okayama University Akiko Hozumi Shimoda Marine Research Center, University of Tsukuba Atsuo S. Nishino Department of Biology, Faculty of Agriculture and Life Science, Hirosaki University Yasunori Sasakura Shimoda Marine Research Center, University of Tsukuba Animals must avoid adhesion to objects in the environment to maintain their mobility and independence. The marine invertebrate chordate ascidians are characterized by an acellular matrix tunic enveloping their entire body for protection and swimming. The tunic of ascidian larvae consists of a surface cuticle layer and inner matrix layer. Hydrophilic substances coat the cuticle; this modification is thought to be for preventing adhesion. However, the molecule responsible for regulating this modification has not been clarified. We here found that the tunicate-specific protein Epi-1 is responsible for preventing adhesiveness of the tunic in the ascidian Ciona intestinalis Type A. Ciona mutants with homozygous knockouts of Epi-1 exhibited adhesion to plastic plates and to other individuals. The cuticle of the Epi-1 mutants was fragile, and it lost the glycosaminoglycans supplied by test cells, the accessory cells that normally attach to the tunic surface. Although it has an apparent signal peptide for membrane trafficking, we showed that the Epi-1 protein is localized to the cytosol of the epidermal cells. Our study suggests that the emergence of the tunicate-specific protein Epi-1 made the tunic less adhesive, providing a selective advantage for the last common tunicate ancestor. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1347-6947 88 10 2024 Evaluation of quercetin as a potential cytoprotector against acetaldehyde using the cultured hepatocyte model with aldehyde dehydrogenase isozyme deficiency 1199 1202 EN Yuhang Xu Graduate School of Environmental and Life Science, Okayama University Takeshi Sawamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ruitong Sun Graduate School of Environmental and Life Science, Okayama University Aki Ishikura 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 Ayano Satoh Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Akiko Matsumoto Department of Social and Environmental Medicine, Saga University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Protective effect of quercetin against acetaldehyde was evaluated using the cultured hepatocyte models with aldehyde dehydrogenase (ALDH) isozyme deficiency (aldh2-kd and aldh1a1-kd). The quercetin-induced cytoprotection against acetaldehyde in the ALDH1A1-deficient mutant (aldh1a1-kd) was weaker than that in the wild type. Furthermore, quercetin did not enhance the ALDH activity in aldh1a1-kd cells, suggesting that ALDH1A1 is involved in quercetin-induced cytoprotection. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 2050-7488 13 11 2025 Enhanced capacity of aluminum-ion batteries by adjusting the average pore size of the porous carbon cathode 8052 8058 EN Yifeng Chen Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Hiroo Suzuki Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Shu Fukumoto Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Chiyu Nakano Department of Comprehensive Technical Solutions, Okayama University Takeshi Nishikawa Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Shigeyuki Umezawa Seiwa Electric Mfg. Co., Ltd Yasuhiko Hayashi Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Lithium-ion batteries (LIBs) are widely used but with the increasing scarcity and uneven distribution of global lithium resources, there is a need to explore alternative battery technologies. Due to its abundance, low cost, and high theoretical capacity, aluminum is a strong candidate for metal anodes, making aluminum-ion batteries (AIBs) an area of considerable interest. Current mainstream research focuses on ionic liquid electrolytes, which offer a wide electrochemical window and high ionic conductivity. Carbon materials are ideal cathode candidates due to their low cost, abundance, and high voltage platform. AIBs using carbon materials typically exhibit low discharge capacity. This study addressed the challenge of improving the discharge capacity of carbon-based cathodes in AIBs. By using porous carbon (PC) materials with varying specific surface areas, average pore sizes, and total pore volumes as cathodes, average pore size was found to impact capacity. This contradicts the contention that larger specific surface areas result in higher capacities. There is a key difference in ion behavior: whereas aluminum chloride ions intercalate into layered graphite structures, they do not intercalate into PC materials but are adsorbed to the surface. By adjusting the average pore size, it is possible to increase the discharge capacity of AIBs, challenging the traditional emphasis on specific surface area. This research does not fully solve the problem of low discharge capacity in carbon-based cathodes, but provides a new perspective on the role of pore size in enhancing battery performance, offering valuable insights for future electrode design. No potential conflict of interest relevant to this article was reported.

American Society of Clinical Oncology (ASCO) Acta Medica Okayama 0732-183X 43 16 2025 Methotrexate, Doxorubicin, and Cisplatin Versus Methotrexate, Doxorubicin, and Cisplatin + Ifosfamide in Poor Responders to Preoperative Chemotherapy for Newly Diagnosed High-Grade Osteosarcoma (JCOG0905): A Multicenter, Open-Label, Randomized Trial 1886 1897 EN Hiroaki Hiraga Musculoskeletal Oncology, NHO Hokkaido Cancer Center Ryunosuke Machida Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Akira Kawai Musculoskeletal Oncology, National Cancer Center Hospital Toshiyuki Kunisada Orthopaedic Surgery, Faculty of Medicine, Okayama University Tsukasa Yonemoto Orthopaedic Surgery, Chiba Cancer Center Makoto Endo Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University Yoshihiro Nishida Department of Rehabilitation Medicine, Nagoya University Hospital Akihito Nagano Orthopaedic Surgery, Gifu University School of Medicine Keisuke Ae Orthopaedic Surgery, Cancer Institute Hospital Shinichirou Yoshida Orthopaedic Surgery, Tohoku University Graduate School of Medicine Kunihiro Asanuma Orthopaedic Surgery, Mie University Junya Toguchida Department of Tissue Regeneration, Center for Induced Pluripotent Stem Cell Research and Application, Institute for Frontier Medical Sciences, Kyoto University Taisuke Furuta Orthopaedic Surgery, Hiroshima University Robert Nakayama Department of Orthopaedic Surgery, Keio University School of Medicine Toshihiro Akisue Orthopaedic Surgery, Kobe University Toru Hiruma Bone and Soft Tissue Tumour Surgery, Kanagawa Cancer Center Takeshi Morii Orthopaedic Surgery, Kyorin University Hideki Nishimura Orthopaedic Surgery, Kagawa University Hospital Koji Hiraoka Orthopaedic Surgery, Kurume University Hospital Masanobu Takeyama Orthopaedic Surgery, Yokohama City University Hospital Makoto Emori Orthopaedic Surgery, Sapporo Medical University Hospital Satoshi Tsukushi Orthopaedic Surgery, Aichi Cancer Center Hiroshi Hatano Musculoskeletal Oncology, Niigata Cancer Center Hospital Hiroyuki Kawashima Orthopaedic Surgery, Niigata University Medical & Dental Hospital Kazuo Isu Orthopaedic Surgery, Higashi Sapporo Hospital Kazuhiro Tanaka Advanced Medical Sciences, Oita University Faculty of Medicine Tomoko Kataoka Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Haruhiko Fukuda Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Yukihide Iwamoto Orthopaedic Surgery, Kyushu Rosai Hospital Toshifumi Ozaki Orthopaedic Surgery, Faculty of Medicine, Okayama University Purpose Our previous NECO phase II studies on high-grade osteosarcoma suggested that administering ifosfamide (IF; 16 g/m2 [4g/m2 once on day 1, then 2g/m2 once on days 2-7] × six) to patients showing a poor response (PrRsp) to preoperative chemotherapy with methotrexate, doxorubicin, and cisplatin (MAP) improves their prognoses. In this Japan Clinical Oncology Group (JCOG) study, JCOG0905, we aimed to investigate the efficacy and safety of IF in patients with PrRsp.<br> Methods JCOG0905 is a multicenter, open-label, multi-institutional, randomized trial. Eligible patients (50 years and younger) had resectable, high-grade osteosarcoma (stage II or III, Union for International Cancer Control TNM) of the extremities, limb girdles, and thoracic wall. After two MAP cycles and tumor resection, patients with PrRsp were randomly assigned to either the MAP or MAP plus 15 g/m2 (3g/m2 once daily on days 1-5) × six IF (MAP + IF [MAPIF]) group. The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The planned sample size was 100 patients with a one-sided α of .1 and a power of 0.7, assuming a 3-year DFS of 50% and 65% for MAP and MAPIF, respectively. This trial is registered with the Japan Registry of Clinical Trials (jRCT; jRCTs031180126).<br> Results Of the 287 patients registered between February 2010 and August 2020, 51 and 52 patients with PrRsp were assigned to the MAP and MAPIF groups, respectively. As of March 2022, DFS did not differ between groups (hazard ratio [HR], 1.05 [95% CI, 0.55 to 1.98]) and OS was numerically inferior in the MAPIF group (HR, 1.48 [95% CI, 0.68 to 3.22]). Nine and zero patients in the MAPIF and MAP groups discontinued treatment because of adverse events, respectively.<br> Conclusion Evidence from JCOG0905 does not support the addition of IF for patients with PrRsp. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0025-5831 392 1 2025 Global well-posedness and scattering in weighted space for nonlinear Schrödinger equations below the Strauss exponent without gauge-invariance 1051 1097 EN Masaki Kawamoto Research Institute for Interdisciplinary Science, Okayama University Satoshi Masaki Department of Mathematics, Hokkaido University Hayato Miyazaki Teacher Training Courses, Faculty of Education, Kagawa University In this paper, we consider the nonlinear Schrödinger equation (NLS) with a general homogeneous nonlinearity in dimensions up to three. We assume that the degree (i.e., power) of the nonlinearity is such that the equation is mass-subcritical and short-range. We establish global well-posedness (GWP) and scattering for small data in the standard weighted space for a class of homogeneous nonlinearities, including non-gauge-invariant ones. Additionally, we include the case where the degree is less than or equal to the Strauss exponent. When the nonlinearity is not gauge-invariant, the standard Duhamel formulation fails to work effectively in the weighted Sobolev space; for instance, the Duhamel term may not be well-defined as a Bochner integral. To address this issue, we introduce an alternative formulation that allows us to establish GWP and scattering, even in the presence of poor time continuity of the Duhamel term. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1279-8517 46 10 2024 Radiological assessment of the dissection area in supraomohyoid neck dissection 1643 1652 EN Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Joe Iwanaga Clinical Anatomy Research Association in Oral and Maxillofacial Surgery Yoshio Ohyama Clinical Anatomy Research Association in Oral and Maxillofacial Surgery Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Matsushita Clinical Anatomy Research Association in Oral and Maxillofacial Surgery R. Shane Tubbs Clinical Anatomy Research Association in Oral and Maxillofacial Surgery Norio Kitagawa Clinical Anatomy Research Association in Oral and Maxillofacial Surgery Toshiyuki Kawazu Miki Hisatomi Department of Oral and Maxillofacial Radiology, Okayama University Hospital Shunsuke Okada Department of Oral and Maxillofacial Radiology, Okayama University Hospital Mamiko Fujikura Department of Oral and Maxillofacial Radiology, Okayama University Hospital Junichi Asaumi Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose The current supraomohyoid neck dissection (SOHND) is performed above the omohyoid muscle to dissect levels I, II, and III in the levels of cervical lymph nodes. However, the anatomical boundary between levels III and IV is the inferior border of the cricoid cartilage. We investigated the anatomical relationship between the omohyoid muscle and cricoid cartilage using contrast-enhanced CT (CE-CT) images to assess the validity of the current SOHND.<br> Methods CE-CT images of the head and neck regions in patients were reviewed. The patients were divided into two groups: “malignant tumors” and “others”. The vertebral levels corresponding to the positions of anatomical structures such as the intersection of the omohyoid muscle and internal jugular vein (OM-IJ), and the inferior border of the cricoid cartilage (CC), were recorded.<br> Results The OM-IJ was located around the seventh cervical to the first thoracic vertebra. There was a significant difference between the malignant tumor and others groups in females (p = 0.036). The CC was located around the sixth to seventh cervical vertebrae. There was a significant sex difference in each group (malignant tumor: p < 0.0001; others: p = 0.008). Both sexes tended to have lower OM-IJ than CC, and females had significantly lower OM-IJ than males.<br> Conclusion This study provides clear anatomical evidence showing the difference between the SOHND dissection area and levels I, II, and III. It could be considered that in most cases SOHND invades level IV, not just levels I, II, and III, especially in female patients. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0361-8609 100 1 2024 Different impacts of granulocyte colony‐stimulating factor administration on allogeneic hematopoietic cell transplant outcomes for adult acute myeloid leukemia according to graft type 66 77 EN Takaaki Konuma Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo Kazuaki Kameda Division of Hematology, Jichi Medical University Saitama Medical Center Kaoru Morita Division of Hematology, Jichi Medical University Tadakazu Kondo Department of Hematology, Kobe City Medical Center General Hospital Fumihiko Kimura Division of Hematology, Department of Internal Medicine, National Defense Medical College Hideki Nakasone Division of Hematology, Jichi Medical University Saitama Medical Center Fumihiko Ouchi Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Naoyuki Uchida Department of Hematology, Toranomon Hospital Masatsugu Tanaka Department of Hematology, Kanagawa Cancer Center Tetsuya Nishida Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Takahiro Fukuda Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital Yuta Hasegawa Department of Hematology, Hokkaido University Hospital Mamiko Sakata‐Yanagimoto Department of Hematology, University of Tsukuba Hospital Makoto Onizuka Department of Hematology and Oncology, Tokai University School of Medicine Masashi Sawa Department of Hematology and Oncology, Anjo Kosei Hospital Shuichi Ota Department of Hematology, Sapporo Hokuyu Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Shin‐Ichiro Fujiwara Division of Hematology, Jichi Medical University Satoshi Yoshihara Department of Hematology, Hyogo Medical University Hospital Fumihiko Ishimaru Technical Department, Japanese Red Cross Society Blood Service Headquarters Makoto Yoshimitsu Department of Hematology and Rheumatology, Kagoshima University Hospital Yoshinobu Kanda Division of Hematology, Jichi Medical University Marie Ohbiki Japanese Data Center for Hematopoietic Cell Transplantation Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Masamitsu Yanada Department of Hematology and Oncology, Nagoya City University East Medical Center We retrospectively evaluated the impacts of using granulocyte colony-stimulating factor (G-CSF) and its timing on posttransplant outcomes for 9766 adults with acute myeloid leukemia (AML) between 2013 and 2022 using a Japanese database. We separately evaluated three distinct cohorts based on graft type: 3248 received bone marrow transplantation (BMT), 3066 received peripheral blood stem cell transplantation (PBSCT), and 3452 received single-unit cord blood transplantation (CBT). Multivariate analysis showed that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT. However, it was associated with a higher risk of grades II–IV acute graft-versus-host disease (GVHD) across all graft types. Moreover, an increased incidence of overall chronic GVHD was observed with G-CSF administration in BMT and CBT patients, but not in PBSCT patients. G-CSF administration significantly improved overall survival (OS) and leukemia-free survival (LFS) only following CBT. Regarding the timing of G-CSF, in comparison with late initiation of G-CSF (Days 5–10), early initiation (Days 0–4) did not provide benefits for hematopoietic recovery regardless of graft type. In contrast, late initiation was significantly associated with a lower risk of grades II–IV acute GVHD and better OS and LFS in CBT patients. These data demonstrated that G-CSF administration accelerated neutrophil recovery and increased the risk of grades II–IV acute GVHD across all graft types, but significantly improved survival outcomes but only following CBT. Therefore, routine use of G-CSF should be considered for CBT in adult patients with AML. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 30 3 2025 Five-year outcomes with gefitinib induction and chemoradiotherapy in EGFR-mutant stage III non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study 497 503 EN Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Sho Saeki Department of Respiratory Medicine, Kumamoto University Hospital Shinya Sakata Department of Respiratory Medicine, Kumamoto University Hospital Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Daijiro Harada Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center Akihiro Bessho Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Kentaro Tanaka Department of Respiratory Medicine, Kyushu University Hospital Koji Inoue Department of Respiratory Medicine, Kitakyushu Municipal Medical Center Koji Inoue Department of Respiratory Medicine, Ehime Prefectural Central Hospital Kenichi Gemba Department of Respiratory Medicine, Chugoku Central Hospital Toshio Kubo Department of Respiratory Medicine, Okayama University Hospital Akiko Sato Department of Respiratory Medicine, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Hiromi Watanabe Department of Respiratory Medicine, Okayama University Hospital Junji Kishimoto Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University Yoshiyuki Shioyama Radiation Oncology, Ion Beam Therapy Center, SAGA HIMAT Foundation Kuniaki Katsui Department of Radiology, Kawasaki Medical School Kenji Sugio Division of Radiation Oncology, Department of Thoracic and Breast Surgery, Oita University Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Background We previously showed the 2-year OS rate, the primary endpoint, of 90% in a phase II trial of gefitinib induction followed by chemoradiotherapy (CRT) in unresectable, stage III, EGFR-mutant, non-small-cell lung cancer (NSCLC). However, neither long-term survival data nor late-phase adverse event profiles have been presented.<br> Patients and methods Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy for 8 weeks. After confirming no disease progression during induction therapy, cisplatin and docetaxel on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy were subsequently administered.<br> Results In the enrolled twenty patients, the 5-year OS rate and median survival time were 70.0% [95% confidence interval: 45.1–85.3] and 5.5 years [4.91-NE], respectively, whereas 5-year PFS rate and median PFS time were 15.0% (3.7–33.5) and 1.4 years [0.69–2.29], respectively. Efficacy did not seem influenced even if radiation field was re-planed in response to the effect of gefitinib induction. As for late adverse events, pulmonary fibrosis occurred in 7 patients (35%). The median time from completion of CRT to the occurrence of the event was 245 days. All were grade 1, and there was no evidence of cavitation of the lesions or chronic infections such as Aspergillus infection during the course of the disease. One case of small cell lung cancer occurred during the period.<br> Conclusions With longer follow-up time, we demonstrated favorable efficacy with tolerable toxicity profiles in the EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III, NSCLC.<br> Trial registration numbers UMIN00005086. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000006047&type=summary&language=EjRCTs071180036. https://jrct.niph.go.jp/latest-detail/jRCTs071180036 No potential conflict of interest relevant to this article was reported.

John Wiley & Sons Ltd Acta Medica Okayama 0364-2313 2026 Indicators for Monitoring Recovery From Surgery to Discharge Using Accelerometer in Patients With Esophageal Cancer 1 4 EN Takahiro Yamane Department of Biomedical Informatics, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Yoshikazu Kimura Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Manami Tetsutani Faculty of Health Sciences, Okayama University Medical School Shota Yamamura Faculty of Health Sciences, Okayama University Medical School Airu Ito Faculty of Health Sciences, Okayama University Medical School Moe Tanuma Faculty of Health Sciences, Okayama University Medical School Mina Honjoh Faculty of Health Sciences, Okayama University Medical School Yoshiko Moriwaki Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshikazu Matsuoka Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mizuki Morita Department of Biomedical Informatics, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Esophageal cancer is a highly invasive malignancy necessitating esophagectomy, which is associated with considerable postoperative morbidity and prolonged hospitalization. Enhanced Recovery After Surgery (ERAS) protocols recommend early mobilization to facilitate recovery; however, objectively assessing physical activity during hospitalization remains challenging. Traditional methods, such as the 6-min walk test or patient-reported questionnaires can be burdensome, or may not accurately reflect recovery. Accelerometer-based measurement provides a low-burden, objective approach, but previous studies focused on the immediate postoperative period or long after discharge, leaving the recovery trajectory from surgery to discharge underexplored. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0960-9822 36 5 2026 Compound starch granule formation in grass seeds is associated with distinct temporal patterns of gene expression 1142 1155.e6 EN Alexander Watson-Lazowski John Innes Centre, Norwich Research Park Doreen Feike John Innes Centre, Norwich Research Park Qi Yang Ngai John Innes Centre, Norwich Research Park Lara Esch John Innes Centre, Norwich Research Park Naoko Fujita Department of Biological Production, Akita Prefectural University Ryo Matsushima Institute of Plant Science and Resources, Okayama University Alison M. Smith John Innes Centre, Norwich Research Park David Seung John Innes Centre, Norwich Research Park There is extensive interspecies variation in starch granule morphology in the endosperm of grass species, but the factors underpinning this variation are poorly understood. The two major granule morphology types among species are simple and compound granules, where simple granules arise from a single initiation per amyloplast, and compound granules form from multiple granule initiations. Here, we carried out an extensive survey of seed starch morphology, examining specimens from 105 species within the Pooideae using electron microscopy. This not only expanded our current knowledge of the diversity of starch granule types but also confirmed the homoplasy of simple and compound starch granules. We then selected species representing independent origins of simple (Brachyelytrum japonicum, Phaenosperma globosa, and Brachypodium distachyon) and compound granules (Nardus stricta, Melica altissima, and Calamagrostis brachytricha) for analysis of starch structure and gene expression. There were no clear patterns in starch content, amylopectin structure, or amylose content that could distinguish the two granule types. However, comparative transcriptomics over seed development revealed gene expression patterns associated with granule type, most notably increasing expression of STARCH SYNTHASE 3a (SS3a), STARCH BRANCHING ENZYME 1 (SBE1), and limit dextrinases (LDAs) between 3 and 9 days post anthesis in species with compound granules. Mutation of these genes in rice, which natively produces compound granules, resulted in altered granule shape and/or size. Our work highlights differences in gene expression that could contribute to natural variation in granule morphology within the Pooideae while providing important new starch phenotype and gene expression datasets that can be widely used to study endosperm development. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0021-9193 208 5 2026 Knockout of tusA confers cationic antimicrobial resistance via fur and omp genes in Escherichia coli e00103-26 EN Kazuya Ishikawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiho Nakata Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koichiro Yamada Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mio Uneme Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuyuki Furuta Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikara Kaito Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University tRNA 2-thiouridine synthesizing protein A (TusA), a sulfur-carrier protein, plays a crucial role in tRNA sulfur modification. Several studies have reported that tusA deficiency affects iron–sulfur (Fe–S) homeostasis in addition to tRNA sulfur modification, resulting in pleiotropic phenotypes. In this study, we analyzed the phenotype of tusA-deficient Escherichia coli and its underlying mechanisms. Although the Keio tusA knockout strain showed increased swimming motility and flagellar biosynthesis, these phenotypes were not restored by tusA complementation. Genome resequencing of the original Keio tusA knockout strain identified an unintended secondary mutation in lrhA, a transcriptional regulator of flagellar and chemotaxis genes. This secondary mutation impaired lrhA function, contributing to enhanced flagellar synthesis and swimming motility, as well as altered global gene expression. A tusA knockout strain in which the secondary mutation was corrected (ΔtusA) exhibited reduced swimming motility compared with the wild-type strain, despite showing no abnormalities in flagellar formation. Furthermore, ΔtusA displayed increased resistance to cationic antibacterial agents, including cetyltrimethylammonium bromide, cetylpyridinium chloride, and protamine sulfate. The reduced motility caused by tusA deletion was observed independently of Fur, a global regulator of iron homeostasis, whereas resistance to cationic antibacterial agents was abolished in the fur knockout background. In addition, altered expression of outer membrane protein (omp) genes was observed in ΔtusA, and deletion of these omp genes abolished resistance to cationic antibacterial agents. Together, these results indicate that, by disentangling the phenotypic effects of tusA deletion from those of the unintended secondary mutation, loss of tusA confers resistance to cationic antibacterial agents through a Fur-dependent and Omp-dependent mechanism. No potential conflict of interest relevant to this article was reported.

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

Microbiology Society Acta Medica Okayama 2057-5858 11 4 2025 Whole-genome-based characterization of Escherichia albertii strains isolated from paediatric diarrhoeal cases in Kolkata, India 001363 EN Goutam Chowdhury Collaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute of Cholera and Enteric Diseases Yuki Hoshiko Division of Microbiology, Department of Infectious Medicine, School of Medicine, Kurume University Miki Okuno Division of Microbiology, Department of Infectious Medicine, School of Medicine, Kurume University Kei Kitahara Collaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute of Cholera and Enteric Diseases M John Albert Department of Microbiology, College of Medicine, Kuwait University Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshitoshi Ogura Division of Microbiology, Department of Infectious Medicine, School of Medicine, Kurume University Shanta Dutta Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases Thandavarayan Ramamurthy Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases Asish K. Mukhopadhyay Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases Escherichia albertii is a Gram-negative facultative anaerobic bacterium that causes diarrhoea in humans. This study shows the isolation of E. albertii from hospitalized paediatric diarrhoeal cases and genome-based characteristics with putative virulence factors and antimicrobial resistance. E. albertii isolates were identified by species-specific PCR, targeting the gene encoding cytolethal distending toxin (Ea-cdt). The genome of E. albertii was sequenced to identify (i) genes encoding virulence factors (ii) antibiotic resistance-encoding genes, including the mobile genetic elements and (iii) core gene-based phylogenetic relationships and pan-genome features. A total of 10 (1.2%) E. albertii isolates were isolated from 854 faecal samples, of which 6 (60%) were found as the sole pathogen and the remaining 4 (40%) were identified along with other pathogens, such as enteroaggregative Escherichia coli, rotavirus and adenovirus. Patients from whom E. albertii was isolated presented cholera-like diarrhoea, i.e. with watery stool (60%) with moderate dehydration (100%), fever (20%) and abdominal pain (20%). The antimicrobial susceptibility testing of E. albertii showed that most of the isolates were susceptible or reduced susceptible to most of the antibiotics except resistance to erythromycin (80%), tetracycline (50%), nalidixic acid (40%), ampicillin (40%), doxycycline (30%) and ceftriaxone (20%). In the whole-genome sequence, E. albertii isolates revealed several virulence-encoding genes, namely the intimin (eae, E. coli attaching and effacing), the cytolethal distending toxin type II subunit A (cdt-IIA), adhesion (paa, porcine attaching- and effacing-associated), non-LEE (locus of enterocyte effacement) encoded effector A (nleA) and antimicrobial resistance genes (ARGs) conferring resistance to tetracycline (tetA, tetR), sulphonamides (sul2), fluoroquinolones (qnrS) and beta-lactamases (blaCTX-M, blaTEM). The SNP-based phylogenetic analysis of 647 whole genomes of E. albertii isolates from the National Center for Biotechnology Information databases did not reveal any comparable clustering pattern based on the biological source and place of isolation. The genome of some of the E. albertii was closely related to those of the isolates from China and the United Kingdom. The PFGE patterns revealed that most of the E. albertii isolates were distinct clones. This study reports on the extensive genome analysis of diarrhoea-associated E. albertii harbouring multiple virulence and ARGs. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0021-9258 301 3 2025 Taste receptor type 1 member 3 in osteoclasts regulates osteoclastogenesis via detection of glucose 108273 EN Anna Yoshimura Division of Molecular Signaling and Biochemistry, Kyushu Dental University Takuma Matsubara Division of Molecular Signaling and Biochemistry, Kyushu Dental University Nao Kodama Division of Molecular Signaling and Biochemistry, Kyushu Dental University Yoshimitsu Kakuta Laboratory of Structural Biology, Graduate School of Systems Life Sciences, Kyushu University Kazuma Yasuda Division of Molecular Signaling and Biochemistry, Kyushu Dental University Ryusuke Yoshida Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Osamu Kaminuma Department of Disease Model, Research Institute of Radiation Biology and Medicine, Hiroshima University Shuhei Hosomi Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University Hiroji Shinkawa Department of Hepatobiliary-Pancreatic Surgery, Graduate School of Medicine, Osaka Metropolitan University Quan Yuan State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University Tatsuo Kawamoto Division of Orofacial Functions and Orthodontics, Kyushu Dental University Shoichiro Kokabu Division of Molecular Signaling and Biochemistry, Kyushu Dental University The taste system extends beyond the oral cavity, with various taste receptors found in extraoral organs. Mice deficient in the taste receptor type 1 (TAS1R) family member, TAS1R3, and fed a high-fat, high-sugar diet showed high bone mass without altering food consumption. However, the underlying mechanisms, including the cell types responsible for TAS1R3 expression, remain unclear. Here, we demonstrate the expression and function of TAS1R3 in osteoclasts, which are responsible for bone resorption. The expression of Tas1r3, but not Tas1r1 or Tas1r2, is evoked during osteoclast differentiation. Osteoclastogenesis-related genes were downregulated in TAS1R3-deficient mice, whereas the opposite phenotypes were elicited by TAS1R3 overexpression. Contrary to the common heterodimerization with TAS1R1 or TAS1R2, TAS1R3 formed a homodimer that functioned to detect glucose, enhance p38 phosphorylation, and induce osteoclastogenesis. These results provide novel insights into the role of TAS1R3 in bone metabolism and suggest that TAS1R3 may be a viable target for therapeutic agents in bone metabolic diseases. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0969-8043 236 2026 An algorithm to calculate physical density of biomedical objects having 3 ≤ Zeff ≤ 20: an application study using clinical photon-counting computed tomography equipment 112768 EN Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Mana Mitani Division of Radiological Technology, Medical Support Department, Okayama University Hospital Noriaki Akagi Division of Radiological Technology, Medical Support Department, Okayama University Hospital Fumiyo Higaki Department of Radiology, Medical Development Field, Okayama University Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Recently, photon-counting computed tomography (PC-CT) devices have become clinically available for X-ray diagnosis, and developments of analysis algorithms to generate various quantitative images have focused attention. This study proposes an algorithm to calculate the effective physical density (ρeff) of biological objects having an effective atomic number (Zeff) of 3–20. In our procedure, ρeff was determined when fitting the interaction cross sections (σs) to the measured linear attenuation coefficients (μs), which were determined from virtual monochromatic images (VMIs). In this process, the Zeff was analyzed in advance, and this information was fed back to the ρeff analysis. A key feature of our procedure is that it does not require calibration processes based on specific substances, which allow us to analyze any substance without making assumptions.<br> To validate the availability of the proposed algorithm, we conducted an experiment using a clinical PC-CT scanner. A multi-energy CT phantom, a water phantom, an in-house low-density phantom, food samples, and a chest phantom were scanned. The results showed that our procedure can calculate ρeff of water with an uncertainty of 4.5%. The academic significance of the present research results lies in demonstrating that the factors contributing to contrast, previously obtained from CT values, can be physically interpreted using information from Zeff and ρeff. This analysis cannot be performed with conventional single-energy CT scanners and is possible with PC-CT and dual-energy CT scanners. Our novel procedure is expected to provide useful additional information in X-ray diagnosis. No potential conflict of interest relevant to this article was reported.

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

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

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

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 Oral Eicosapentaenoic Acid and Paclitaxel-Associated Peripheral Neuropathy: A Retrospective Study at Okayama University Hospital 179 184 EN Ayako Morita Center for Clinical Oncology, Okayama University Hospital Hideki Katayama Center for Clinical Oncology, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Original Article 10.18926/AMO/70853 This retrospective study investigated whether eicosapentaenoic acid (EPA) reduces paclitaxel-associated chemotherapy-induced peripheral neuropathy (CIPN) and acute neuropathic pain in dyslipidemic cancer patients. The medical records of cancer patients treated with paclitaxel or nab-paclitaxel at Okayama University Hospital between January 2018 and December 2022 were reviewed. Patients receiving concomitant therapy for dyslipidemia were categorized as EPA users or non-EPA users. Numbness and pain severity were extracted from medical records. The primary endpoint was the change from baseline in Common Terminology Criteria for Adverse Events (CTCAE) grade for peripheral neuropathy and pain; groups were analyzed using the Mann–Whitney U test. Of 184 eligible patients, 18 received EPA. Bleeding events were more frequent in the EPA group; however, changes in numbness and pain did not differ significantly between groups at any time point. Overall, EPA did not show a preventive effect on paclitaxel-associated CIPN or acute neuropathic pain. Future studies should evaluate EPA in combination with other neuroprotective agents to better define its potential role in CIPN prevention. No potential conflict of interest relevant to this article was reported.

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

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

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

American Physiological Society Acta Medica Okayama 0022-3077 135 4 2026 Characteristics of cross-modal negative BOLD responses in the human sensory subcortex and cortex 747 759 EN Toshikazu Miyata Division of Sensory and Cognitive Brain Mapping, Department of System Neuroscience, National Institute for Physiological Sciences Masaki Fukunaga Section of Brain Function Information, National Institute for Physiological Sciences Junxiang Luo Division of Sensory and Cognitive Brain Mapping, Department of System Neuroscience, National Institute for Physiological Sciences Isao Yokoi National Institute for Physiological Sciences Tetsuya Yamamoto Section of Brain Function Information, National Institute for Physiological Sciences Ayumi Yoshioka Section of Brain Function Information, National Institute for Physiological Sciences Jiajia Yang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tomoyo Morita Center for Information and Neural Networks (CiNet), Advanced ICT Research Institute, National Institute of Information and Communications Technology (NICT) Hiromasa Takemura Division of Sensory and Cognitive Brain Mapping, Department of System Neuroscience, National Institute for Physiological Sciences Functional magnetic resonance imaging (fMRI) is a noninvasive method for measuring human brain activity based on blood oxygenation level-dependent (BOLD) responses. Although many studies have reported positive BOLD responses evoked by sensory stimuli, others have reported negative BOLD responses (NBRs) in the sensory cortex when stimuli from different sensory modalities are presented (i.e., cross-modal NBRs). We conducted an fMRI experiment to better understand the characteristics of cross-modal NBRs in subcortical and cortical regions. Auditory and visual stimuli were presented unilaterally to one ear and to either the left or right visual field, respectively. The lateral geniculate nucleus and medial geniculate nucleus did not show a significant cross-modal NBR. In contrast, the primary auditory cortex showed a significant cross-modal NBR when visual stimuli were presented in either the contralateral or ipsilateral visual fields. Finally, we found that the cross-modal NBR in the early visual cortex was highly variable across subjects and did not exhibit consistent trends. However, each subject’s data exhibited considerable split-half reliability. Our results suggest that cross-modal NBR in the auditory cortex likely reflects mechanisms such as interhemispheric suppression, rather than those coordinated within the same hemisphere.<br> NEW & NOTEWORTHY This study demonstrated that the human primary auditory cortex showed a significant cross-modal negative BOLD response bilaterally, regardless of the visual field in which the visual stimuli were presented. This result suggests that the cross-modal negative BOLD response is not an epiphenomenon of visual cortex activation predominantly observed in the contralateral hemisphere, but is more likely to reflect interhemispheric suppression mechanisms. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1574-7891 2026 Stimulator of interferon genes agonist augmented antitumor immunity of osimertinib in <i>Egfr</i> ‐mutated lung cancer EN Jun Nishimura Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadahiro Kuribayashi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Johannes Brägelmann Department of Translational Genomics Faculty of Medicine and University Hospital Cologne, University of Cologne Germany Sachi Okawa Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masataka Taoka Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunta Mori Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoka Nishimura Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaaki Tanaka Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Go Makimoto Department of Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Kammei Rai Center for Innovative Clinical Medicine, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Ryohei Katayama Division of Experimental Chemotherapy, Cancer Chemotherapy Centre, Japanese Foundation for Cancer Research Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Masahiro Tabata Center for Clinical Oncology, Okayama University Hospital Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Martin L. Sos Department of Translational Genomics Faculty of Medicine and University Hospital Cologne, University of Cologne Germany Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers (NSCLCs) lack effective immunotherapy due to a noninflamed tumor microenvironment (TME). We previously reported that EGFR tyrosine-kinase-inhibitor (TKI) induced CD8+ T-cell immunity, which was insufficient for tumor eradication. We evaluated the potential of combining EGFR-TKI with stimulator of interferon genes (STING) agonists in activating a systemic antitumor response. Using a syngeneic mouse model of genetically engineered Egfr-mutant NSCLC, we evaluated the antitumor effects of STING agonist ADU-S100, alone and combined with osimertinib. Immunohistochemistry and flow cytometry were used to assess the TME. Osimertinib alone enhanced CD8+ T-cell infiltration but not Natural Killer (NK) cell infiltration. ADU-S100 injection alone modestly suppressed tumor growth with increasing CD8+/NK cell infiltration in the TME, but lacked an abscopal effect. Combining ADU-S100 with osimertinib significantly enhanced the antitumor effects and CD8+/NK cell infiltration. Depletion of either CD8+ or NK cells reduced the combination effect. Crucially, the combination induced an abscopal effect accompanied by PD-1+/CD8+ cell infiltration. Combining osimertinib with a STING agonist augmented innate and adaptive immunity, inducing systemic antitumor responses in EGFR-mutant NSCLC. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 2732-7787 6 3 2026 Predictors for Recurrences Within One Year Following Radical Nephrectomy for Non-metastatic Renal Cell Carcinomas 419 427 EN KENSUKE BEKKU 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 YUSUKE TOMINAGA 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 TAKEHIRO IWATA 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 MOTOO ARAKI Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background/Aim: This study aimed to identify predictors of rapid recurrence following radical nephrectomy for non-metastatic renal cell carcinomas.<br> Patients and Methods: Patients with non-metastatic renal cell carcinoma who underwent radical nephrectomy between 2014 and 2024 at Okayama University Hospital were included. Rapid recurrence was defined as local or distant metastasis occurring within one year after radical nephrectomy, whereas recurrences occurring beyond one year were classified as non-rapid.<br> Results: Among a total of 194 patients, 37 (19%) experienced recurrence during a median follow-up of 37 months, with 16 (43%) being classified as experiencing rapid recurrence. The multivariate Cox hazard model revealed that microscopic venous invasion and a size of 60 mm or larger were predictors of rapid recurrence (hazard ratio=4.1, 95% confidence interval=1.5-11.4, p=0.006, and hazard ratio=8.0, 95% confidence interval=2.6-25.0, p<0.001, respectively). Dividing the entire cohort into four groups based on the presence of the two risk factors (0, 1: venous invasion, 1: tumor size, and 2), the median PFS was not estimable, 87, 67, and 7 months, respectively (p<0.001).<br> Conclusion: Microscopic venous invasion and tumor size of 60 mm or larger were identified as independent predictors of rapid recurrence following radical nephrectomy for non-metastatic renal cell carcinoma. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2753-670X 41 5 2026 Lung Segmental Perfusion Defect Is Associated With Airway Complications After Living-Donor Lobar Lung Transplantation ivag139 EN Kentaro Imanishi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuyoshi Ryuko Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuaki Tomioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences PURPOSE: Airway complications (ACs) are potentially fatal after lung transplantation (LT). Although bronchial blood flow to the graft is supplied mainly from the pulmonary circulation after LT, lung segmental perfusion defects (LSPDs) are occasionally identified on lung perfusion scintigraphy (Q-scinti) after living-donor lobar LT (LDLLT). Lung segmental perfusion defects may impair bronchial healing and contribute to the development of ACs. This study aimed to evaluate the relationship between LSPD and AC after LDLLT.<br> METHODS: We retrospectively reviewed 86 recipients who underwent LDLLT and 163 living donors at our institution from October 1998 to December 2023. Transplanted lungs that developed AC were classified as the AC group, whereas those without AC were classified as the non-AC group. Blood flow in the transplanted lungs was evaluated using Q-scinti after LDLLT.<br> RESULTS: AC developed in 8 (4.9%) of 163 transplanted lungs after LDLLT. Although there were no significant differences in recipient-related variables between the 2 groups, LSPD was detected significantly more frequently in the AC group (n = 8) than in the non-AC group (n = 155) (50.0% vs 6.5%, P = .002). Furthermore, transplanted lungs showing LSPD were associated with significantly higher grades of the pulmonary interlobar fissures at the time of living-donor lobectomy (P = .025). Overall survival did not differ between patients with and without AC after LDLLT.<br> CONCLUSIONS: LSPD on Q-scinti, which may develop in grafts with incomplete interlobar fissures during living-donor lobectomy, is associated with the development of AC after LDLLT.<br> CLINICAL REGISTRATION NUMBER: This study was approved by the Institutional Review Board of Okayama University Hospital (approval date: August 23, 2024; 2409-027). No potential conflict of interest relevant to this article was reported.

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

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

Wiley Acta Medica Okayama 0012-1592 68 4-5 2026 Computer‐Aided Sperm Analysis Protocol for Evaluating Sperm Motility in Japanese Medaka e70061 EN Miwa Kuroyanagi Department of Advanced Aquaculture Science, Faculty of Marine Bioscience and Technology, Fukui Prefectural University Satoshi Ansai Ushimado Marine Institute, Faculty of Science, Okayama University Keigo Okamoto Laboratory of Aquatic Molecular Developmental Biology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University Ai Kato Interuniversity Bio-Backup Project Center, National Institute for Basic Biology (NIBB) Touko Yamazaki Laboratory of Bioresources, National Institutes of Natural Sciences Yasuhiro Kamei Optics and Bioimaging Facility, NIBB Eiji Watanabe Basic Biology Program, Graduate University for Advanced Studies (SOKENDAI) Kiyoshi Naruse Laboratory of Bioresources, National Institutes of Natural Sciences Yukiko Ogino Laboratory of Aquatic Molecular Developmental Biology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University Changes in sperm motility can serve as an early indicator of reproductive effects caused by environmental chemicals or genetic perturbations. However, sperm motility is highly sensitive to external factors such as osmolarity, ionic composition, and the timing of measurement after activation, making it challenging to obtain consistent and reproducible measurements. Here, we present a standardized protocol for assessing sperm motility in Japanese medaka (Oryzias latipes) using a sperm motility analysis system (SMAS), an application for computer-aided sperm motility analysis (CASA). This protocol details the procedures for sperm collection, activation, and quantitative motility assessment, with particular focus on changes in the percentage of motile sperm post activation and the effects of sperm cryopreservation. We demonstrate time-dependent declines in sperm motility and velocity, and highlight the importance of early post-activation measurements to accurately capture peak motility. Notably, cryopreservation significantly accelerated the decline in sperm motility rate without affecting the initial proportion of motile sperm. To enable reliable comparisons among experimental groups, we recommend standardizing the initiation time after sperm activation by using CASA, and show that measurements should be initiated within 1 min after activation to obtain consistent and reliable data. This standardized SMAS-based protocol provides a robust and reproducible framework for sperm motility analysis in medaka and will be valuable not only for studies in reproductive biology, toxicology, and environmental risk assessment but also for applied research, such as breeding of aquacultural fishes. No potential conflict of interest relevant to this article was reported.

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

Portland Press Ltd. Acta Medica Okayama 0144-8463 46 6 2026 Tubulogenesis of bovine uterine glands by epidermal growth factor and collagen I in 3D culture systems BSR20260010 EN Yosuke Sugino Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Rei Ichikawa Graduate School of Bioagricultural Sciences, Nagoya University Shuichi Matsuyama Graduate School of Bioagricultural Sciences, Nagoya University Yuki Yamamoto Department of Veterinary Medicine, Tokyo University of Agriculture and Technology Kohei Kawano Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koji Kimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Uterine glands are endometrial exocrine epithelia that support early embryo development. Their secretions are particularly essential for conceptus elongation in cattle. Uterine glands develop from the luminal epithelium and elongate into the stromal layer toward the myometrium. This process is regulated by growth factors, WNT proteins, and the surrounding extracellular matrix (ECM); however, the precise mechanisms that govern bovine uterine gland morphogenesis remain unclear. In this study, we determined how these signaling factors and ECM components affect the tubular formation of bovine uterine gland fragments in 3D culture systems. Uterine gland fragments were enzymatically isolated from bovine endometria and 3D-cultured in Matrigel with or without growth factors (EGF, FGF1, FGF2, FGF7, FGF10, and IGF-1) and WNT (WNT3A, WNT5A, and WNT7A) proteins. Of these, only EGF stimulated the elongation of uterine gland fragments and eventually induced the formation of uterine gland-like structures. EGF-induced tubulogenesis was accompanied by a rapid increase in cell proliferation and alterations in cell–ECM interactions. The supplementation of collagen I with Matrigel further promoted the elongation of the tubular structures. Although the addition of collagen I did not alter the gene expression profiles of the uterine gland-like structures, the integrin-ROCK pathway contributed to the collagen-induced enhancement of elongation. Our findings clarified that EGF and collagen I, but not FGFs, IGF-1, or WNTs, are key regulators for the tubular formation of 3D-cultured bovine uterine gland fragments. This 3D culture system provides a new platform to examine the cellular and molecular mechanisms underlying bovine uterine gland morphogenesis. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1359-7345 2026 Switchable photoluminescence of europium(iii) complexes with chromonylhydrazones EN Asahi Kamei Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Daisuke Saito Graduate School of Science, Hokkaido University Kazuma Takahara Graduate School of Science, University of Hyogo Keito Nose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hideki Okamoto Department of Chemistry, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Masaki Yoshida Graduate School of Science, The University of Osaka Masako Kato School of Biological and Environmental Sciences, Kwansei Gakuin University Takayoshi Suzuki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Europium(III) complexes bearing 4-hydroxy- or 4-methyl-N′-((6-methyl-4-oxo-4H-chromen-3-yl)methylene)benzohydrazide (HL1 or HL2) showed characteristic EuIII 5D0 → 7FJ (J = 0–4) luminescence both in acetonitrile and in solid states with relatively high Φtot values. The luminescence was quenched not only by adding triethylamine in acetonitrile, but also by heating the solid sample, and recovered by adding perchloric acid in solution or by diffusion of HCl vapor to the resulting solid sample. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2090-6528 2026 1 2026 Selective ARID1A Loss Restricted to the Undifferentiated Component of a Mismatch Repair‐Deficient Gastric Carcinoma: A Case Report 8863202 EN Rika Omote Department of Diagnostic Pathology, NHO Fukuyama Medical Center Ryosuke Hamano Department of Surgery, NHO Fukuyama Medical Center Shinya Otsuka Department of Surgery, NHO Fukuyama Medical Center Takehiro Tanaka Department of Pathology, Okayama University Hospital Hiroyuki Yanai Department of Pathology, Okayama University Hospital Mismatch repair-deficient (dMMR) gastric carcinomas often harbor ARID1A alteration, but a sharply demarcated undifferentiated/rhabdoid component with selective ARID1A loss is uncommon and may create a diagnostic dilemma. An 80-year-old man underwent esophagogastroduodenoscopy for anemia, which revealed a circumferential Borrmann Type 3 lesion in the gastric body, and distal gastrectomy was performed. Histologically, the tumor was composed predominantly of undifferentiated carcinoma with focal rhabdoid features and a minute well-differentiated adenocarcinoma component, with an abrupt transition between the two. Immunohistochemistry showed loss of nuclear MLH1 and PMS2 in both components, whereas loss of ARID1A expression was confined to the undifferentiated component; SMARCB1 (INI1), SMARCA2 (BRM), and SMARCA4 (BRG1) were retained. EBER in situ hybridization was negative. Because gene-level testing, MSI testing, and MLH1 promoter methylation analysis were not performed, the molecular basis of the dMMR phenotype and ARID1A loss could not be determined. The restricted scope of molecular testing limits the ability to draw broad or generalizable conclusions and to fully establish clinicopathological correlations. The value of this report is, therefore, not mechanistic proof but recognition of a practical morphologic-immunophenotypic observation: When a gastric carcinoma shows a sharply demarcated shift from differentiated to undifferentiated/rhabdoid morphology, dMMR should be considered, and selective ARID1A loss in the undifferentiated component may be associated with dedifferentiation. These findings should be interpreted with caution as preliminary, hypothesis-generating observations that require validation in larger studies with more extensive molecular profiling. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2667-2421 20 2026 Behavioral effects of a chronic envy-like stress paradigm in mice using an adjacent cage model 148 159 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yoshihiro Tanaka Department of Psychiatry, Kawasaki Medical School Eriko Kitano Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Background: Social comparison and envy are significant psychosocial stressors in humans and are known to be involved in the onset and persistence of psychiatric disorders. However, animal models capable of experimentally reproducing the effects of indirect social comparison without physical contact are limited. In this study, we used a newly developed "adjacent-cage paradigm" to investigate whether chronic vicarious exposure to conspecifics in different environments induces envy-like stress in mice.<br> Methods: Male C57BL/6 N mice served as observers, while demonstrator mice were assigned to one of four conditions: (1) an environment enriched with objects, (2) an igloo, (3) a tube, or (4) social isolation. Observers were continuously exposed to these adjacent cages for 21 days. Subsequently, a comprehensive battery of behavioral tests was conducted to assess general health, anxiety-like behavior, spatial memory, social behavior, and depression-like behavior.<br> Results: In the objects condition, a decrease in time spent in the light compartment of the light/dark box indicated an increase in anxiety-like behavior. In the isolation condition, the mean duration per social interaction was shortened, suggesting a qualitative change in social behavior. The igloo condition resulted in reduced immobility time in the forced swim test, suggesting a possible alteration in stress coping behavior. Furthermore, increased nociceptive sensitivity was observed in the hot plate test under both the objects and isolation conditions.<br> Conclusion: Although the envy-like stress paradigm did not affect many behavioral indices, it did cause condition-dependent and limited behavioral changes. This suggests that the paradigm may serve as a novel model for capturing psychological and context-dependent social stress, which differs from conventional physical stress models. Elucidating the neural basis of this paradigm is expected to contribute to the understanding of how social comparison affects mental health in modern society. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 0006-291X 827 2026 Staphylococcus aureus activates dendrite elongation in dendritic cells 154001 EN Kai Kobata Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuyuki Furuta Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuki Ikeya Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yohei Chishaki Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuya Ishikawa Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Chikara Kaito Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Dendritic cells (DCs) are thought to extend dendrites to enhance the efficiency of antigen uptake and presentation. We previously reported that short-chain fatty acids (SCFAs), such as butyrate and valerate, promote dendrite extension in DCs. In this study, we found that the human pathogen Staphylococcus aureus also induces dendrite extension in DCs and investigated the underlying mechanisms. Dendrite extension in DC2.4 cells was induced not only by live S. aureus but also by heat-killed bacteria and purified peptidoglycan (PGN). DC2.4 cells lacking TLR2 or its adaptor protein MyD88 extend dendrites in response to SCFAs, but failed to extend dendrites in response to S. aureus. Furthermore, inhibitors of ERK, PI3K, and Cdc42 suppressed dendrite extension triggered by S. aureus. Co-stimulation with S. aureus and butyrate enhanced dendrite extension beyond either stimulus alone. DC2.4 cells co-stimulated with S. aureus and butyrate also showed increased uptake of insoluble beads and, upon co-culture with T cells, induced elevated production of IL-17 and IL-10 by T cells. Collectively, these findings suggest that S. aureus activates ERK/PI3K/Cdc42 signaling through TLR2 recognition of PGN to drive dendrite extension in DCs. In addition, S. aureus promotes dendrite extension in DCs via a pathway distinct from that of SCFAs, thereby acting cooperatively with SCFAs to enhance immune responses. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2730-7182 26 1 2026 Revised taxonomy reveals sustained introgression and secondary contact in ancient lake ricefishes 46 EN Yuki Yashima Tropical Biosphere Research Center, University of the Ryukyus Andy B. Nofrianto Tropical Biosphere Research Center, University of the Ryukyus Handung Nuryadi Tropical Biosphere Research Center, University of the Ryukyus Ryo Kakioka Department of Applied Aquabiology, National Fisheries University Hirozumi Kobayashi The Natural History Museum and Institute Satoshi Ansai Ushimado Marine Institute, Okayama University Ixchel F. Mandagi Faculty of Fisheries and Marine Science, Sam Ratulangi University Kawilarang W. A. Masengi Faculty of Fisheries and Marine Science, Sam Ratulangi University Sjamsu A. Lawelle Faculty of Fisheries and Marine Science, Halu Oleo University Atsushi J. Nagano Bioscience and Biotechnology Center, Nagoya University Junko Kusumi Faculty of Social and Cultural Studies, Kyushu University Kazunori Yamahira Tropical Biosphere Research Center, University of the Ryukyus Background Biotic diversification in ancient lakes is shaped by complex geological histories and genetic exchange among populations. The Malili Lake system on Sulawesi Island represents a classic natural laboratory for studying freshwater fish evolution and harbors multiple endemic Oryzias species that diversified under repeated hydrological reorganizations. Previous genomic analyses inferred that two sympatric species in Lake Towuti (O. profundicola and O. loxolepis) experienced a single ancient introgression event from a “ghost lineage” derived from O. marmoratus inhabiting another lake. However, recent taxonomic re-evaluation has revealed the presence of an extant O. marmoratus population within Lake Towuti itself. This finding suggests that the putative ghost lineage may in fact represent a living population co-occurring in the lake, calling for a re-examination of the introgression history and speciation mode in Lake Towuti.<br> Results By incorporating newly generated ddRAD-seq data from the true O. marmoratus in Lake Towuti, we reanalyzed phylogenetic relationships and population genetic structure among Malili Lake Oryzias. Previously reported major phylogenetic relationships and inter-lake introgression patterns were largely reproduced. In contrast, TreeMix and f4-statistic analyses revealed that introgression signals previously attributed to a “ghost lineage” into O. profundicola and O. loxolepis instead originated from the extant O. marmoratus population coexisting within Lake Towuti. Demographic model comparisons explicitly incorporating within-lake gene flow further supported a scenario in which O. profundicola and O. loxolepis diverged in allopatry, subsequently came into secondary contact within Lake Towuti, and later experienced additional gene flow following secondary contact with O. marmoratus that entered the lake.<br> Conclusion Our results demonstrate that introgression from the O. marmoratus lineage into O. profundicola and O. loxolepis was not a single ancient event, but rather a more sustained process. This finding highlights the critical importance of taxonomic resolution for accurately inferring introgression and divergence history. Comparative studies across other ancient lakes on Sulawesi will be valuable for understanding how the timing and nature of gene flow from third lineages influence patterns of population divergence and the strength of reproductive isolation. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 2169-3536 14 2026 Programmable Clock Distribution Using Switching Matrices for Field Programmable Gate Arrays 52641 52653 EN Ayumu Ogura Okayama University Minoru Watanabe Okayama University Nobuya Watanabe Okayama University Every digital systems using very large scale integration require clock distributions, for which a dedicated clock tree or a mesh clock is frequently used. Field programmable gate arrays have numerous general-purpose programmable wires based on switching matrices to connect the outputs and inputs of look-up tables and input–output ports. However, field programmable gate arrays never use numerous general-purpose programmable wires for their clock distributions to satisfy the clock skew margin similarly to very large scale integrations. Field programmable gate arrays also use dedicated clock trees, although their programmability is not high. Currently, field programmable gate arrays can support multiple dedicated clock routing or multiple clock trees. Unfortunately, the number of clock trees is fixed. They remain limited to a small number. Even if an application requires many clock distributions, such a clock distribution cannot be supported in current field programmable gate arrays. This paper therefore presents a proposal of a more flexible clock distribution method based on wiring channels and switching matrices. The method uses general-purpose programmable wires. In addition, to resolve clock skew increase difficulties, we have introduced a new flip-flop with a two-phase clock signal. This paper presents simulation results obtained using the proposed clock distribution method on an originally designed field programmable gate array. In addition, experimentally obtained results indicate that the proposed clock distribution method can function correctly on a Cyclone V field programmable gate array. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 3 2026 Bortezomib Induces Apoptosis via Upregulation of Abhd4 in Peripheral Nerve Cells 496 502 EN Yusuke Konishi Department of Pharmacy, Kobe University Hospital Tomohiro Omura Department of Pharmacy, Kobe University Hospital Takeshi Ijichi Department of Pharmacy, Kobe University Hospital Hiroki Nishiguchi Department of Pharmacy, Kobe University Hospital Ryunosuke Hayakawa Education and Research Center for Clinical Pharmacy, Kobe Pharmaceutical University Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Kotaro Itohara Department of Pharmacy, Kobe University Hospital Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ikuko Yano Department of Pharmacy, Kobe University Hospital Bortezomib, a first-in-class proteasome inhibitor, is widely used to treat multiple myeloma and other hematological malignancies. Despite its therapeutic efficacy, bortezomib causes peripheral neuropathy (PN) in approximately 20–30% of patients, often leading to dose reduction or discontinuation. Preventive or therapeutic approaches to bortezomib-induced PN are currently unavailable, as its precise mechanism remains unclear. In this study, we compared the effects of bortezomib and the second-generation proteasome inhibitor carfilzomib on peripheral nerve cells to identify candidate molecules involved in PN development. Transcriptome profiling of differentiated F11 cells, a hybridoma of a rat embryonic dorsal root ganglion and mouse neuroblastoma cell line N18TG2, revealed that bortezomib selectively upregulated α/β-hydrolase containing domain 4 (Abhd4), whereas carfilzomib did not. This finding was confirmed by quantitative RT-PCR and immunoblotting, which demonstrated consistent increases in Abhd4 mRNA and protein levels following bortezomib treatment. Functional analysis further revealed that Abhd4 overexpression promoted early apoptosis, suggesting a mechanistic link between bortezomib-induced Abhd4 elevation and neuronal vulnerability. Therefore, these results suggest that Abhd4 represents a candidate molecular signature associated with bortezomib-induced PN. Although further in vivo validation is needed, these findings warrant further investigation of Abhd4 as a potential contributor to bortezomib-induced PN. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0250-7005 46 1 2025 Impact of Polymeric Formula on Outcomes in Robotic Pancreatectomy: A Randomized Controlled Trial 407 414 EN KOSEI TAKAGI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TOMOKAZU FUJI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KAZUYA YASUI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences MOTOHIKO YAMADA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TAKEYOSHI NISHIYAMA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences YASUO NAGAI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences MASASHI HASHIMOTO Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TOSHIHARU MITSUHASHI Center for Innovative Clinical Medicine, Okayama University Hospital TOSHIYOSHI FUJIWARA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background/Aim: Evidence regarding the benefits of nutritional therapy after robotic pancreatectomy is limited. This randomized controlled trial aimed to investigate the effects of a polymeric formula (PF) on preventing body weight loss (BWL) following robotic pancreatectomy.<br> Patients and Methods: This single-center, open-label, randomized trial was conducted to assign 46 patients undergoing robotic pancreatectomy in a 1:1 ratio to either the PF (ISOCAL Clear) or control group. The primary endpoint was the percentage of BWL on postoperative days 14 and 28. The secondary endpoints were postoperative outcomes.<br> Results: Of the 52 eligible patients between December 2023 and November 2024, 46 were analyzed using intention-to-treat principles: 23 in the ISOCAL group and 23 in the control group. The %BWL was significantly lower in the ISOCAL group compared with that in the control group on postoperative days 14 (4.8±3.5% vs. 6.6±3.2%, p=0.02) and 28 (6.4±3.0% vs. 8.4±3.5%, p=0.047). Postoperative outcomes, including major complications (p=0.55) and hospital stay (p=0.83), did not differ significantly between the groups.<br> Conclusion: This study demonstrates the safety and feasibility of administering PF to patients undergoing robotic pancreatectomy. The results showed the beneficial effects of PF on mitigating BWL without compromising short-term outcomes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 3 2026 Septic Arthritis of the Temporomandibular Joint Complicated by Dislocation e105091 EN Hideka Kanemoto Department of Oral Surgery, Kochi Health Sciences Center Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koki Umemori Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine Septic arthritis of the temporomandibular joint (SATMJ) is a rare but potentially serious condition, and standardized diagnostic and therapeutic strategies have not been established. We present the case of a 70-year-old man who developed acute right temporomandibular joint (TMJ) pain, swelling, mandibular deviation, and inability to achieve mouth closure. Computed tomography and magnetic resonance imaging revealed right TMJ dislocation, joint effusion, degenerative changes, and anterior disc displacement with effusion. Aspiration of the joint yielded neutrophil-predominant purulent fluid, although bacterial cultures were negative. The patient was treated empirically with intravenous ceftriaxone followed by oral clindamycin and amoxicillin, resulting in rapid symptom resolution, and the dislocation spontaneously reduced without surgical intervention. No recurrence was observed during three months of follow-up. This case highlights the diagnostic challenges associated with culture-negative SATMJ, supports the role of early empirical antibiotic therapy, and suggests that chronic joint instability due to habitual dislocation may predispose the TMJ to infection. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 75 4 2026 Immunological effects of amivantamab in EGFR or MET-expressing non-small cell lung cancer 121 EN Ryo Yoshichika Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumiaki Mukohara Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kotaro Yamada Department of Respiratory Medicine, Okayama University Hospital Joji Nagasaki Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroko Watanabe Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Youki Ueda Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Takamasa Ishino Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Epidermal growth factor receptor (EGFR) mutations represent one of the most frequent oncogenic driver in non-small cell lung cancer (NSCLC). Amivantamab, a bispecific antibody targeting EGFR and MET proto-oncogene, receptor tyrosine kinase (MET), has demonstrated clinical benefit in EGFR-mutant NSCLC through dual blockade, but its immunological role in human clinical specimens, especially tumor-infiltrating lymphocytes (TILs), has not been directly evaluated.<br> Methods We analyzed surgically resected tumor samples from 40 patients with NSCLC to investigate immune responses and their associations with EGFR and MET expression. TILs were characterized by flow cytometry (FCM) and immunohistochemistry (IHC). To assess the immunomodulatory potential of amivantamab, fresh tumor digests containing live tumor cells and TILs were cultured ex vivo with CD3 and CD28 stimulation in the absence or presence of amivantamab, followed by FCM. EGFR and MET expression were also evaluated by IHC.<br> Results EGFR mutations and high EGFR protein expression were associated with a trend toward reduced CD8⁺ T-cell and dendritic cell (DC) infiltration. In ex vivo TIL assays, exposure to amivantamab significantly activated CD8⁺ T cells, such as programmed cell death-1 expression and cytokine production, and promoted DC maturation. These effects were most pronounced in tumors with high EGFR or MET protein expression rather than EGFR mutations.<br> Conclusions This study provides the first direct evidence from ex vivo fresh TIL assays using human NSCLC clinical specimens that amivantamab can activate immune responses. EGFR and MET expression may serve as potential biomarkers for amivantamab-induced immune responses. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 1347-9032 117 5 2026 TGF-β Inhibitor Potentiates Osimertinib-Induced Anti-Tumor Immunity in Egfr-Mutant Lung Cancer 1260 1272 EN Tadahiro Kuribayashi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Nishimura Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sachi Okawa Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masataka Taoka Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunta Mori Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaaki Tanaka Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoka Nishimura Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayako Morita Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naofumi Hara Department of Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Go Makimoto Department of Respiratory Medicine, Okayama University Hospital 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 Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Immunotherapy for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) remains challenging. We previously found that EGFR-tyrosine kinase inhibitors induced antitumor immunity but also triggered immunosuppressive cytokines, including transforming growth factor-β (TGF-β), in Egfr-mutant lung cancer. Here, we investigate whether TGF-β inhibition potentiates osimertinib-induced antitumor immunity using a syngeneic mouse model of Egfr-mutated lung cancer, with cancer cells subcutaneously transplanted into wild-type C57BL/6J mice. We evaluated the antitumor effect of the combination therapy with osimertinib and either nintedanib (an indirect TGF-β inhibitor) or vactosertib (a specific TGF-β type I receptor kinase inhibitor). Changes in the tumor microenvironment during treatment were assessed using immunohistochemical staining, western blot analysis, and flow cytometry. We found that TGF-β expression was upregulated in the tumor treated with osimertinib. Nintedanib monotherapy showed no significant antitumor effect, whereas osimertinib combined with nintedanib significantly potentiates the antitumor effect compared with osimertinib monotherapy in vivo. Crucially, no additive effect of nintedanib on osimertinib monotherapy was observed in vitro. Combination therapy with osimertinib and nintedanib significantly increased effector T cells (CD8+CD44+CD62L−) and Granzyme B+ areas and decreased CD206+ cells, while significantly decreasing TGF-β and SMAD2/3 expression. Similar effects were observed with vactosertib but not with a vascular endothelial growth factor receptor 2 inhibitor. In conclusion, combination therapy with osimertinib and TGF-β inhibitors potentiates osimertinib-induced antitumor immunity. These findings highlight a novel therapeutic strategy for EGFR-mutated NSCLC and warrant further clinical investigation. No potential conflict of interest relevant to this article was reported.

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

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

Public Library of Science (PLoS) Acta Medica Okayama 1932-6203 21 3 2026 Early administration of renin–angiotensin system inhibitors improves survival and cardiac remodeling in heart failure with preserved ejection fraction e0339600 EN Yuka Kono Department of Medical Technology, Graduate School of Health Sciences, Okayama University Kunihiro Sonoda Collage of Human Life and Environment, Kinjo Gakuin University Kazuo Ohtake School of Pharmacy, Faculty of Pharmaceutical Science, Josai University Akinobu Ota Collage of Human Life and Environment, Kinjo Gakuin University Shusei Yamamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Hinako Nakayama Department of Medical Technology, Graduate School of Health Sciences, Okayama University Taketo Fukuoka Department of Medical Technology, Graduate School of Health Sciences, Okayama University Yuki Kawai Department of Medical Technology, Graduate School of Health Sciences, Okayama University Haruka Tago Department of Medical Technology, Graduate School of Health Sciences, Okayama University Nobuhisa Watanabe Department of Medical Technology, Graduate School of Health Sciences, Okayama University Ikumi Sato Academic Field of Health Science, Okayama University Satoshi Hirohata Academic Field of Health Science, Okayama University Kazuya Kitamori Collage of Human Life and Environment, Kinjo Gakuin University Shogo Watanabe Academic Field of Health Science, Okayama University Heart failure with preserved ejection fraction (HFpEF) is a major cardiovascular disease that accounts for 50% of all cases of heart failure. Patients with HFpEF have limited therapeutic options because of the complex pathogenesis of this disease. Decreased nitric oxide (NO) levels and increased renin–angiotensin system (RAS) activity may be associated with HFpEF pathogenesis. However, whether soluble guanylate cyclase (sGC) stimulators and RAS inhibitors protect against HFpEF remains unclear. This study aimed to evaluate the preventive effects of RAS inhibitors captopril (Cap) and/or sacubitril/valsartan (Sac/Val) and sGC stimulator vericiguat (Ver) on HFpEF progression. HFpEF was induced in 8-week-old male Wistar rats through intake of L-arginine methyl ester and a high-fat diet. Results showed that the survival rate after 8 weeks of treatment was 100% in the normal diet (Cont group), Cap, and Sac/Val groups, whereas it was approximately 20% in the HFpEF and Ver groups. No significant differences in the left ventricular systolic function were found. In addition, histochemistry revealed that myocardial hypertrophy and interstitial fibrosis obviously increased in the HFpEF group but not in the Cap and Sac/Val groups compared with the Cont group. Furthermore, RNA sequencing analysis showed that the expression of genes related to inflammatory response, hypertrophy, and extracellular matrix–receptor interaction increased in the HFpEF group and decreased in the Cap and Sac/Val groups. In conclusion, early administration of Cap or Sac/Val may reduce the risk of developing HFpEF by inhibiting the RAS pathway rather than the NO-sGC-cGMP pathway. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 2673-253X 8 2026 Development of a generative AI agent for family support in implementing family-based treatment for children and adolescents with anorexia nervosa 1759690 EN Mana Hanzawa Department of Pediatrics, Okayama University Hospital Medical Center for Children Joe Hasei Department of Medical Informatics and Clinical Support Technology Development, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Ayumi Okada Department of Pediatrics, Okayama University Hospital Medical Center for Children Chie Tanaka Department of Pediatrics, Okayama University Hospital Medical Center for Children Yoshie Shigeyasu Department of Pediatrics, Okayama University Hospital Medical Center for Children Chikako Fujii Department of Pediatrics, Okayama University Hospital Medical Center for Children Makiko Horiuchi Clinical Psychology Section, Department of Medical Support, Okayama University Hospital Akiko Sugihara Department of Pediatrics, Okayama University Hospital Medical Center for Children Koichi Takeuchi Life Natural Science and Technology, Graduate School of Environmental, Okayama University Ryuichi Nakahara Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hideki Katayama Department of Palliative and Supportive Care, Okayama University Hospital Yasushi Takahashi NEC Corporation Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Tsukahara Department of Pediatrics, Okayama University Hospital Medical Center for Children Introduction: Family-based treatment (FBT) is a first-line psychotherapy for children and adolescents with anorexia nervosa (AN). However, families must understand the principles of FBT, provide meal support, and manage their children's pathological behaviors. Difficulties occur outside clinic hours when it is impossible to consult professionals. This “support gap” increases caregivers’ psychological distress and threatens their treatment continuity. To the best of our knowledge, this is the first domain-specific generative artificial intelligence (AI) agent designed to provide situation-specific, FBT-concordant advice and psychological support.<br> Methods: The system integrates three components: (1) an FBT-specific knowledge base constructed from treatment manuals, family guides, guideline-compliant resources, and a clinical Q&A corpus; (2) a multistage natural language processing pipeline using Retrieval-Augmented Generation (RAG), with intent and sentiment analyses; and (3) safety guardrails that prohibit unsolicited numerical goals or direct hospitalization recommendations and standardized escalation to clinicians. When strong negative emotions are detected, empowerment messages are dynamically incorporated to maintain caregivers’ confidence. Six clinicians with expertise with pediatric mental health authored queries that simulated common FBT-related concerns and evaluated each response for clinical appropriateness and safety, and classified problems as information insufficiency, not FBT concordant, or escalation insufficiency.<br> Results: Of the 477 queries, 57.0% were FBT-related, 24.5% were general AN, 16.5% were parental psychological distress, and 1.8% were related to other topics. The clinically appropriate response rate was 91.6% (437/477), including 92.3% for FBT-related questions, 88.0% for general knowledge, 93.7% for psychological distress, and 100.0% for other questions. Clinically inappropriate responses (8.4%) were mainly attributable to information insufficiency; not FBT concordant (1.8% of FBT-related responses) and escalation insufficiency (0.6% of all dialogs) rarely occurred.<br> Discussion: In this expert review, the safety-gated RAG system predominantly generated FBT-concordant responses that provided meal-level guidance and empathic empowerment-oriented support to families. By proceduralizing complex FBT concepts and presenting multiple response options for pathological behaviors, the system translates FBT principles into practical guidance supporting refeeding adherence, preserving family self-efficacy, and suggesting that domain-specific AI may help bridge structural limitations in FBT. Usability studies and randomized controlled trials are warranted to determine their impact on caregiver burden, self-efficacy, treatment adherence, and clinical outcomes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0010-7999 181 7 2026 Electrical conductivity of geikielite (MgTiO3) at lunar mantle conditions: the role of metastable defect states and thermal history 55 EN Takashi Yoshino Institute for Planetary Materials, Okayama University Daisuke Yamazaki Institute for Planetary Materials, Okayama University The electrical conductivity of geikielite (MgTiO3), the Mg endmember of the ilmenite group, was investigated at mantle pressures of 2 and 4.3 GPa and temperatures up to 1850 K using a Kawai-type multi-anvil apparatus. Electrical conductivity increases by more than seven orders of magnitude between 800 and 1700 K and exhibits two distinct conduction regimes separated by a transition at ~ 1500–1700 K. The high-temperature regime is characterized by large activation enthalpies (ΔH ≈ 1.8–2.3 eV), whereas the low-temperature regime shows much lower values (ΔH ≈ 0.19–0.31 eV). Stepwise annealing experiments reveal a pronounced thermal-history dependence: repeated heating to progressively higher maximum temperatures (Tmax) produces metastable conductivity states, enhancing low-temperature conductivity by up to six orders of magnitude and systematically reducing activation enthalpy. This behavior indicates activation and freezing-in of defect-related charge carriers. Negative activation volumes further support a hopping-type conduction mechanism. Although Ti³⁺ was not directly detected, the combination of reducing experimental conditions, Al³⁺ impurities (~ 0.35 wt% Al₂O₃), low activation energies, and strong thermal memory is most consistent with small-polaron hopping involving Ti³⁺–Ti⁴⁺ pairs. At lunar core–mantle boundary temperatures, geikielite reaches conductivities of 10¹–10² S/m, exceeding those of olivine and overlapping estimates for the lunar low-velocity zone. Our results demonstrate that solid-state Ti-rich oxides can produce high electrical conductivity without partial melting, providing new constraints on the thermochemical evolution and electromagnetic structure of the lunar interior. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0781 2026 Involvement of tRNA thiolation in uORF-mediated translational regulation during Xylogenesis in Arabidopsis thaliana pcag055 EN Yuichi Nishii Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Daichi Araki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mitsuru Saraumi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taku Takahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Post-transcriptional modification of tRNAs is an important mechanism for regulating translation efficiency and cellular homeostasis, yet its contribution to upstream open reading frame (uORF)-mediated translational control remains largely unexplored. In this study, we investigated the role of tRNA thiolation in thermospermine-dependent regulation of xylem development in Arabidopsis thaliana. Using a suppressor screen of the thermospermine-deficient mutant acaulis5 (acl5), which exhibits dwarfism and excessive xylem differentiation, we identified suppressor-of-acl502 (sac502) as a recessive loss-of-function allele of CTU2, a gene encoding a key enzyme in the biosynthesis of the wobble uridine modification 5-methoxycarbonylmethyl-2-thiouridine. Mutations in other components of the same modification pathway, including ROL5 and TRM9, similarly suppressed the acl5 phenotype. Translational analyses using 5′ leader-GUS reporter constructs revealed that the ctu2 mutation did not enhance translation of the mRNA containing a thermospermine-responsive uORF of SAC51, but instead significantly reduced translation of that of SACL3, a member of the SAC51 family, and that of LONESOME HIGHWAY (LHW), which contains another conserved uORF in the 5′ leader region. Polysome profiling further demonstrated decreased association of SACL3 and LHW mRNAs with actively translating ribosomes in ctu2. Genetic interaction analyses supported the conclusion that the suppression of excessive xylem formation in acl5 by ctu2 is attributable to reduced LHW activity. In addition, ctu2 mutants displayed increased sensitivity to exogenous thermospermine, resembling the response of lhw mutants. Together, our results reveal that tRNA thiolation contributes to uORF-mediated translational regulation of key developmental regulators and identify tRNA modification as an important regulatory layer controlling vascular development. No potential conflict of interest relevant to this article was reported.

Hrvatski Sumarski Institut (Croatian Forest Research) Acta Medica Okayama 1849-0891 17 1 2026 Understory Vegetation Structure in Remnant Natural Forests and Acacia Plantations on Coastal Sand Dunes in North Central Vietnam 26007 EN Tuan Quoc Doan Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Tetsuya K. Matsumoto Ibaraki University, Graduate School of Science and Engineering Tai Tien Dinh Hue Union of Science and Technology Associations (HUSTA) Hung Thai Le Hue University, University of Agriculture and Forestry Tuan Ngoc Anh Ho Hue Union of Science and Technology Associations (HUSTA) Naoko H. Miki Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Hoang Thai Dac Ho Hue Union of Science and Technology Associations (HUSTA) Muneto Hirobe Okayama University, Graduate School of Environmental, Life, Natural Science and Technology In the coastal sand dune forests of North Central Vietnam, vegetation has been seriously damaged by war and overexploitation. To recover ecosystem functions, including sand stabilisation under harsh environments, exotic species like Acacia spp. have been planted as a monoculture. However, the long-term sustainability of this practice remains unclear. To assess the long-term effectiveness of revegetation with Acacia spp., this study aims to understand the differences and similarities in ecological characteristics of remnant natural forests and Acacia plantations on the coastal sand dune of North Central Vietnam by comparing understory vegetation structure and environmental conditions. We investigated the understory vegetation (height < 130 cm) in a total of 54 quadrants (1 m × 1 m), including nine natural forests and nine Acacia plantations. We compared diversity indices by mixed ANOVA and examined the differences in the understory vegetation structure between the two forest types through PERMANOVA. We also determined some abiotic environmental factors (e.g. light and soil water availability, and soil pH). We identified 951 individuals, with 792 found in natural forests and 159 in plantations. The species found in natural forests were well-distributed among Liana phanerophytes (Lp), Microphanerophytes (Mi), Mega-Mesophanerophytes (MM), and Cryptophytes (Cr). In contrast, species found in plantations were predominantly Cr, Hemicryptophytes (Hm), and MM. All diversity indices were significantly higher in natural forests (P < 0.05), and the NMDS analysis confirmed significant differences in the understory vegetation structure between natural forests and plantations. Only soil pH was significantly lower in natural forests (P < 0.05), while none of the environmental factors had a statistically significant impact on the variations in understory vegetation structure. Our results indicate that succession by native tree species does not seem to occur naturally in Acacia plantations. Hence, to restore and sustainably develop coastal sand dune forests in North Central Vietnam, it is essential to establish a scientifically based strategy for managing and protecting the remaining natural remnant forest areas. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0584 105 5 2026 Donor selection for patients with HLA-homozygous haplotypes in allogeneic hematopoietic stem cell transplantation 244 EN Noriyoshi Yoshinaga Department of Hematology, Graduate School of Medicine, Kyoto University Makoto Iwasaki Department of Hematology, Graduate School of Medicine, Kyoto University Koji Kato Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences Fumihiko Kimura Division of Hematology, Department of Internal Medicine, National Defense Medical College Masahiro Hirayama Department of Pediatrics, Mie University Graduate School of Medicine Minoru Kanaya Blood Disorders Center, Aiiku Hospital Satoko Morishima Central Japan Cord Blood Bank Naoyuki Uchida Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital Noriko Doki Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Takahiro Fukuda Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital Yoshinobu Kanda Division of Hematology, Jichi Medical University Tetsuya Nishida Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Yuta Hasegawa Department of Hematology, Hokkaido University Hospital Shinichi Kako Division of Hematology, Jichi Medical University Saitama Medical Center Masatsugu Tanaka Department of Hematology, Kanagawa Cancer Center Mineo Kurokawa Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Toshiro Kawakita Department of Hematology, NHO Kumamoto Medical Center Keisuke Kataoka Division of Hematology, Department of Medicine, Keio University School of Medicine Yukio Kondo Department of Hematology, Toyama Prefectural Central Hospital Kazunori Imada Department of Hematology, Japanese Red Cross Osaka Hospital Tatsuo Ichinohe Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University Makoto Onizuka Department of Hematology/Oncology, Tokai University School of Medicine Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Junya Kanda Department of Hematology, Graduate School of Medicine, Kyoto University HLA homozygous haplotypes occur worldwide, but outcomes after allogeneic hematopoietic stem cell transplantation using alternative donor sources remain uncertain. We retrospectively analyzed the Japanese national transplantation registry to compare outcomes after first allogeneic hematopoietic stem cell transplantation in patients with HLA homozygous haplotypes. Donors were classified as homo-to-homo, defined as HLA-matched, or hetero-to-homo, defined as allele-level mismatches at HLA-A, -B, -C, and/or -DRB1 restricted to the host-versus-graft direction. The unrelated donor homo-to-homo group served as the reference. We included 691 patients: related donor homo-to-homo (n = 121), related donor hetero-to-homo (n = 76), unrelated donor homo-to-homo (n = 374), unrelated donor hetero-to-homo (n = 22), cord blood homo-to-homo (n = 40), and cord blood hetero-to-homo (n = 58). Compared with the unrelated donor homo-to-homo group, overall survival was inferior in the cord blood homo-to-homo group (adjusted hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.11–2.64; P = 0.015), whereas the unrelated donor hetero-to-homo group showed a nonsignificant trend toward inferior overall survival (adjusted HR, 1.77; 95% CI, 0.97–3.22; P = 0.061). In this Japanese cohort, cord blood homo-to-homo transplantation was associated with inferior overall survival, whereas related donor hetero-to-homo and cord blood hetero-to-homo transplantation were not. These findings should be interpreted cautiously given the retrospective design and long study period, and require validation in contemporary, ethnically diverse cohorts. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1342-1751 2026 Optimizing low-dose rituximab protocol for ABO-mismatched kidney transplantation: long-term outcomes in a single-center retrospective cohort study EN Tomoaki Yamanoi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takanori Sekito Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Moto Tokunaga Department of Urology, NHO Okayama Medical Center 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 Yuki Maruyama Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Risa Kubota Department of Urology, NHO Okayama Medical Center Yusuke Tominaga 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 Takehiro Iwata 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 Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidemi Takeuchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morinaga Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Wada Department of Urology, Shimane University Faculty of Medicine Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background ABO-mismatched kidney transplantation (KTx) expands donor availability but increases risks of antibody-mediated rejection and passenger lymphocyte syndrome (PLS). While rituximab (Rit) potentially mitigates these complications, conventional high-dose regimens (375 mg/m2) elevate infectious and hematologic toxicity. We implemented low-dose Rit induction (200 mg/body) for desensitization in minor/major ABO-mismatched and DSA-positive KTx, evaluating its efficacy and safety over 15-years.<br> Methods This single-center retrospective cohort (May 2009–April 2024) analyzed 161 adult KTx recipients: Rit (n = 107) and Non-Rit (n = 54) groups. All received tacrolimus, mycophenolate mofetil, prednisolone, and basiliximab; high-risk patients also underwent plasmapheresis. Outcomes included graft survival, biopsy-proven acute rejection, de novo donor-specific antibody (DSA) formation, infection, severe neutropenia, and PLS.<br> Results 1-year graft survival was 100% in both groups. 5-year death-censored graft survival was 95.8% (Rit) vs 95.9% (Non-Rit), respectively (log-rank P = 0.43). Biopsy-proven acute rejection (7.5% vs 3.7%, P = 0.50) and de novo DSA production were equivalent (Class I: 5.5% vs 2.2%; Class II: 6.6% vs 8.7%; both P = 1.00), with lower mean fluorescent intensity (MFI) in the Rit group. Cytomegalovirus disease, urinary tract infection and fungal infection rates were comparable between both groups. Grade 4 neutropenia was not associated with Rit (OR 2.65; 95% CI 0.63–11.0; P = 0.18). Blood transfusion for hemoglobin declines occurred in 5.6% vs 7.4%, with preserved haptoglobin in all cases, indicating no PLS.<br> Conclusions Low-dose Rit induction achieves excellent graft survival and effective PLS prevention, without increasing toxicity, supporting its adoption as an optimal desensitization strategy. No potential conflict of interest relevant to this article was reported.

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

Acta Medica Okayama 2026 Long intervals between repetitive concussions reduce risk of cognitive impairment and limit microglial activation, astrogliosis, and tauopathy in adolescent rats EN Yuichi HIRATA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2026 Induction of IL-9-producing CD8+ T cells by ascochlorin derivatives EN Natsumi IMANO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2026 TRPV2 in muscle satellite cells is crucial for skeletal muscle remodelling　 EN YANZHU CHEN Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 0094-8276 53 2026 Discovery of Repeating Shallow Moonquakes in the Apollo Lunar Seismic Data e2026GL122541 EN Keisuke Onodera Institute for Planetary Materials, Okayama University Shallow moonquakes have been considered unique due to their large magnitudes and affinities with intraplate earthquakes. However, the small number of detections (<80 events) has prevented detailed characterization. In this study, I identified a pair of repeating shallow moonquakes by analyzing a recently updated moonquake data set. Relative-phase assessment revealed that these events exhibit a consistent fault-slip direction despite their occurrence at opposite tidal phases. This differs from what was observed for repeating deep moonquakes, which are closely related to tides, implying that tidal stress does not dominantly control fault-slip initiation of the repeating shallow moonquakes. Also, the identified repeating shallow moonquakes exhibit a similar relationship between seismic moment and the spatial scale of the slip area to earthquakes. This may indicate that earthquake-like fault physics operates on the Moon, albeit with a different driving mechanism than on Earth. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1756-2848 19 2026 Second-look endoscopy does not reduce delayed bleeding after endoscopic papillectomy: a multicenter propensity score-matched analysis EN Yuki Fujii Department of Endoscopy, Okayama University Hospital Kazuyuki Matsumoto Department of Endoscopy, Okayama University Hospital Toru Ueki Department of Gastroenterology, Fukuyama City Hospital Hitomi Himei Department of Gastroenterology, Hiroshima City Hiroshima Citizens Hospital Ichiro Sakakihara Department of Gastroenterology, Kagawa Prefectural Central Hospital Eijiro Ueta Department of Gastroenterology, National Hospital Organization Iwakuni Clinical Center Tatsuya Toyokawa Department of Gastroenterology, NHO Fukuyama Medical Center Ryo Harada Department of Gastroenterology, Japanese Red Cross Okayama Hospital Taiji Ogawa Department of Gastroenterology, Tsuyama Chuo Hospital Takeshi Tomoda Department of Gastroenterology, Okayama City Hospital Hironari Kato Department of Gastroenterology, Okayama City Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Ryosuke Sato Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Background: Delayed bleeding is a frequent and serious complication after endoscopic papillectomy (EP). Second-look endoscopy (SLE) is often scheduled on the following day for wound assessment and prophylactic hemostasis, but its clinical value remains unclear.<br> Objectives: This study evaluated the effectiveness of SLE in preventing delayed bleeding after EP.<br> Design: This study was a multicenter, retrospective cohort study.<br> Methods: We retrospectively reviewed 132 consecutive patients who underwent EP at nine high-volume centers between 2003 and 2024 (SLE group, n = 73; non-SLE group, n = 59). Propensity score matching was performed to balance baseline characteristics. The primary outcome was delayed bleeding, and secondary outcomes were risk factors, the impact of prophylactic hemostasis during SLE, and hospital stay.<br> Results: After matching, 43 patients were included in each group. The incidence of delayed bleeding did not differ between the SLE and non-SLE groups (14% vs 9%, p = 0.50). Multivariate analysis identified a lack of preventive clipping closure as the only independent risk factor (odds ratio 15, 95% confidence interval 1.3–177, p = 0.030). Prophylactic hemostasis during SLE did not reduce bleeding but was associated with prolonged hospitalization (13 vs 9 days, p = 0.012).<br> Conclusion: Routine SLE after EP does not reduce delayed bleeding. Moreover, prophylactic hemostasis in asymptomatic patients may unnecessarily prolong hospitalization. Hemostasis should be reserved for patients who develop clinical signs of bleeding. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1574-6968 373 2026 Intercellular signal transduction within the mother cell compartment during Bacillus subtilis sporulation fnag055 EN Nobuki Kuwabara Department of Frontier Bioscience, Hosei University Masato Anzue Department of Frontier Bioscience, Hosei University Shin-ichi Miyoshi Research Center for Intestinal Health Science, Okayama University Tsutomu Sato Department of Frontier Bioscience, Hosei University Daisuke Imamura Research Center for Intestinal Health Science, Okayama University Intercellular signaling contributes to the spatiotemporal regulation of gene expression during sporulation in Bacillus subtilis. The mother cell transcription factor σE is initially produced as an inactive precursor protein pro-σE and activated by the processing enzyme SpoIIGA in response to the forespore-produced putative signaling molecule SpoIIR. However, the mechanism underlying the SpoIIR-mediated signal transduction remains poorly understood. In this study, we showed that the spoIIR-positive, spoIIGA-deleted strain was able to induce SpoIIGA-dependent pro-σE processing in co-cultured spoIIR-deleted, spoIIGA-positive strains. This signaling was dependent on SpoIIR expression and did not involve DNA transfer. Extracellular materials including secreted proteins and membrane vesicles were unlikely to be involved in this signaling pathway. Interestingly, cessation of co-incubation shaking enhanced the signaling, while the addition of membrane-solubilizing detergent abolished it. In addition, SpoIIR signaling did not necessitate release from the forespore membrane or extracellular translocation. A SpoIIR variant lacking the putative signal peptide-like hydrophobic domain produced solely in the mother cell compartment was still able to activate pro-σE. Overall, the study findings suggested that the forespore-produced SpoIIR is neither secreted nor externally translocated. Instead, SpoIIR appeared to be transferred into the mother cell compartment and interacts with the SpoIIGA cytoplasmic domain to trigger pro-σE processing. No potential conflict of interest relevant to this article was reported.

The Japanese Society for Neuroendovascular Therapy Acta Medica Okayama 1882-4072 20 1 2026 Current Status of Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: An International Perspective Including Japan ra.2025-0153 EN Masato Kawakami Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Sugiu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Hiramatsu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Haruma Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryu Kimura Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Soutome Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Juntaro Fujita Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fukiko Baba Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Middle meningeal artery embolization (MMAE) for chronic subdural hematoma (CSDH) is gaining global prevalence as a minimally invasive treatment aimed at serving as an adjunct to or method of avoiding surgery; however, its optimal positioning remains unclear. This study outlines the current status of MMAE in Japan, Germany, and the United States based on nationwide survey reports, recently published consensus guidelines, and meta-analyses including randomized controlled trials (RCTs) reported in the New England Journal of Medicine (NEJM; EMBOLISE, STEM, and MAGIC-MT) and examines its efficacy and limitations. Real-world clinical data from Japan, Germany, and the United States indicate that MMAE is primarily used as an adjunctive therapy following surgery for older and high-risk or recurrent cases, or as a stand-alone therapy in selected cases to safely reduce the risk of recurrence and reoperation. While a multidisciplinary consensus statement takes a cautious stance that limits MMAE to recurrent or inoperable cases such as those at high risk associated with interrupting antithrombotic medication, the Society of Vascular and Interventional Neurology guidelines published after the RCTs strongly recommend the concurrent use of MMAE with standard therapy in de novo cases. Meta-analyses integrating the 3 NEJM trials and other RCTs showed that MMAE suppressed recurrence and reoperation versus standard treatment, with particularly pronounced effects in the nonsurgical (conservative treatment) group; however, the additive effect was limited in the surgical adjunct group. No improvement in functional outcomes (modified Rankin Scale score) was observed. Cost-effectiveness analyses suggest that, while MMAE reduces reoperations, routine implementation for all cases is difficult to justify economically because of high procedural costs, indicating the need to narrow the indication to populations at high risk of recurrence. In conclusion, although MMAE is an effective treatment option, the current evidence does not support its uniform introduction in all patients with CSDH. Thus, it is necessary to individualize and adapt the indications for specific patient subgroups, such as those at high risk of recurrence or those for whom surgery is difficult. Finally, we propose a pragmatic treatment strategy for MMAE stratified by disease stage (de novo vs. recurrent) and clinical severity to guide the individualized selection of adjunctive and stand-alone embolization. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1867-1071 2026 Appropriate dose reduction using photon-counting detector CT for temporal bone imaging: phantom and clinical studies with helical acquisition EN Yuka Takahashi Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumiyo Higaki Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Nakamura Department of Diagnostic Radiology, Hiroshima University Toru Higaki Graduate School of Advanced Science and Engineering, Hiroshima University Akiko Sugaya Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Takahiro Kitayama Department of Radiology, Medical Development Field, Okayama University Yusuke Morimitsu Department of Radiological Technology, Okayama University Hospital Tomohiro Inoue Department of Radiological Technology, Okayama University Hospital Noriaki Akagi Department 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 Kazuo Awai Department of Diagnostic Radiology, Hiroshima University Takao Hiraki Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose: To determine the extent of possible dose reduction with photon-counting detector computed tomography (PCD-CT) while maintaining image quality equivalent to that of energy-integrating detector CT (EID-CT) images at standard dose in the temporal bone.<br> Materials and methods: PCD-CT and EID-CT imaging quality were compared by visual evaluation of clinical temporal bone images and visual scores with Welch’s t-test at standard dose. A head phantom was used to evaluate imaging quality under dose reduction. The detectability index (d’) of the PCD-CT images at various dose levels and the EID-CT images at standard dose was evaluated. Dose reduction limit with PCD-CT used in the subsequent clinical evaluation was determined as the lowest dose with image quality equal to or better than EID-CT. The clinical equivalence of PCD-CT image quality at the determined reduced dose to that with EID-CT at standard dose was evaluated using visual scores. Equivalence was determined if the 95% confidence intervals of differences did not exceed the equivalence margin of ±1.<br> Results: At standard doses, PCD-CT images demonstrated significantly higher visual scores than EID-CT images (3.73 vs. 2.56 for incudomalleolar joint, 3.75 vs. 2.63 for stapes, 3.54 vs. 2.52 for cochlea, and 3.58 vs. 2.46 for facial nerve canal; all P 0.001). In the phantom study, the d’ value was 0.15 with EID-CT at standard dose and was 0.12 and 0.17 with PCD-CT at 25% and 50% of the standard dose, respectively. Clinically, the mean visual scores of PCD-CT images at 50% of the standard dose were equivalent to EID-CT images at standard dose in all regions (3.58 vs. 3.12 for incudomalleolar joint, 3.46 vs. 3.19 for stapes, 3.50 vs. 3.08 for cochlea, 3.58 vs. 3.27 for facial nerve canal).<br> Conclusion: PCD-CT may preserve image quality even at 50% of the standard dose in the temporal bone. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 8756-3282 209 2026 PPy-coated wire actuators for micromechanostimulation of cells – identification of immediate-early responsive mechanoregulatory genes in osteoblasts 117914 EN Jiamin Chen Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Amaia B. Ortega-Santos Department of Physics, Chemistry and Biology (IFM), Linköping University Satoru Hayano Department of Orthodontics, Okayama University Hospital Ziyi Wang Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jose G. Martinez Department of Physics, Chemistry and Biology (IFM), Linköping University Emilio Satoshi Hara Department of Advanced International and Information Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Edwin W.H. Jager Department of Physics, Chemistry and Biology (IFM), Linköping University Hiroshi Kamioka Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mechanotransduction, i.e., the conversion of mechanical cues into biochemical signals, is essential for bone development, remodeling, and adaptation. Although mechanical loading is known to regulate osteoblast function and bone homeostasis, dissecting the early and sustained mechanotransductive responses at the microscale remains challenging due to limitations of existing in vitro models. Here, we report the development and application of a mechanostimulation system comprising a polypyrrole (PPy)-based wire actuator that expands and contracts (4 μm in radius) upon electrical actuation and enables precise, localized micromechanical stimulation of a small number of cells within standard culture formats. Using this system, we applied short-term (30 min) cyclic (Cyc30) or static (Stat30), as well as prolonged (120 min) cyclic (Cyc120) stimulations to two osteoblast-like cells (MC3T3-E1 or KUSA-A1). Subsequent transcriptomic profiling and computational network analyses revealed that Cyc30 was not capable of inducing significant changes in mRNA expression, suggesting cellular adaptation to short-term cyclic loading. In contrast, Stat30 induced the upregulation of Fos, Btg2, Egr1, and Fosl1, all known genes associated with mechanotransduction, supporting the validity and reproducibility of our experimental mechanostimulation system. Notably, two long non-coding RNAs (B930036N10Rik and 5430431A17Rik) were identified for the first time as being upregulated in response to Stat30 stimuli. Among the differentially expressed genes (DEGs) upregulated by Cyc120 stimuli, Hmox1, a stress-inducible enzyme known for its roles in maintaining cellular homeostasis and promoting survival, was the only DEG repeatedly observed across the Cyc30/Cyc120 and Stat30/Cyc120 comparisons in both cell types, potentially emerging as a key stress-response gene under prolonged mechanical loading. Collectively, these results establish the PPy-based microactuator as a powerful tool for microscale mechanobiology, and provide molecular insight into immediate-early responsive transcriptional programs underlying osteoblastic mechanoadaptation conserved across different cell types. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-1076 185 6 2026 Drug-induced sarcoidosis-like reaction following IL-4/IL-13 receptor blockade by dupilumab 391 EN Kozo Yasui Department of Pediatrics, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Masato Yashiro Okayama University Hospital Center for Innovative Clinical Medicine The purpose of the study is to review reported cases of dupilumab-associated drug-induced sarcoidosis-like reaction (DISR) and consider possible immunologic mechanisms. This short review aims to raise awareness of dupilumab-associated DISR and discuss safety considerations in pediatric patients.<br> Conclusion: Dupilumab is a human monoclonal antibody that reduces inflammation driven by T helper 2 (Th2) cells and is used to treat type 2 inflammatory disorders, including atopic dermatitis. The most common adverse reactions during the first year of treatment are local reactions at the injection site, conjunctivitis, and headache. Although DISR is rare, it has been documented in dupilumab-treated patients. We hypothesized that dupilumab shifts the Th1/Th2 equilibrium toward Th1 and granulomatous inflammation, which may present as DISR. We identified and reviewed 10 recently reported DISR cases and observed that reported features of DISR—including uveitis, optic neuritis and meningoencephalitis, bilateral hilar lymphadenopathy, and histopathologically noncaseating granulomas—can mimic systemic sarcoidosis. Discontinuation of dupilumab resulted in favorable outcomes in most reported DISR cases; however, symptoms worsened in some cases and sequelae became a concern. Case reports of DISR have so far been limited to adults or adolescents, but awareness of potential adverse effects of dupilumab remains important in pediatric patients. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 2948-216X 3 1 2026 Compact potential sensor for spacecraft based on a silicon photonic waveguide 10 EN Kosei Otsuka Department of Physics and Electronics, Osaka Metropolitan University Wataru Takahama Faculty of Environmental, Life, Natural Science and Technology, Okayama University Rikuto Hojo Department of Space Systems Engineering, Kyushu Institute of Technology Takeki Higashiguchi Department of Physics and Electronics, Osaka Metropolitan University Kazuya Kikunaga Sensing Technology Research Institute, National Institute of Advanced Industrial Science and Technology Tomofumi Mogami Electrostatic Engineering DEPT, Kasuga Denki INC Kazuhiro Toyoda Department of Space Systems Engineering, Kyushu Institute of Technology Yasushi Takahashi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Satellites charge up due to incoming electrons and ions, resulting in an electrical potential difference (ΔV) between the satellite and outer space. This can cause electrostatic discharge (ESD) events, damaging electronic devices. To reduce failures due to ESD, sensors monitoring the ΔV can be helpful. Due to spacecraft’s restrictions, the sensors should be as small as possible. While small potential sensors in terrestrial applications are often based on electrical conduction in semiconductors, such sensors are not suitable for space application due to a weak resistance to cosmic radiation and ESD. Here, we report a compact sensor based on another sensing method: the utilization of light absorption in a silicon photonic waveguide. We performed experiments in a vacuum chamber simulating the space plasma environment to demonstrate that the light attenuation in the waveguide depends on the ΔV. Our results further indicate that our sensor exhibits a high resistance to ESD. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2589-0042 29 4 2026 Human iPSC cardiomyocyte patch transplantation modifies extracellular matrix and fibroblast behavior after myocardial infarction 115341 EN Kosuke Torigata Cuorips Inc. Ryohei Matsuura Max Planck Institute for Heart and Lung Research, Laboratory for Cell Polarity and Organogenesis Fumiya Nagatomo Department of Mechanical Engineering, School of Engineering, The University of Tokyo Moe Thiha Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Takao Hikita Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Hiroko Iseoka Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine Hiromitsu Takagi Daiichi Sankyo Co., Ltd. Uichi Koshimizu Daiichi Sankyo Co., Ltd. Hiroki Sakakima Department of Mechanical Engineering, School of Engineering, The University of Tokyo Satoshi Izumi Department of Mechanical Engineering, School of Engineering, The University of Tokyo Asuka Hatano Department of Mechanical Engineering, School of Engineering, The University of Tokyo Thomas Braun MaxPlanck Institute for Heart and Lung Research, Department of Cardiac Development and Remodeling Yoshiki Sawa Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine Shigeru Miyagawa Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine Masanori Nakayama Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Myocardial infarction (MI) followed by chronic heart failure is the main cause of mortality of heart diseases. Although reparative cell transplantation therapies with pluripotent stem cell-derived cardiomyocytes (CMs) represent a promising therapeutic strategy, molecular mechanisms of the therapy remain elusive. Here, we show that transplantation of the human induced pluripotent stem cell (hiPSC)-derived CM patch onto the damaged heart after MI increases the ratio of collagen type I against collagen type III to modulate alignment of the collagen fibers at the infarcted zone. As a result, tissue elasticity of the heart is improved, and fibrosis at the remote zone is reduced. Mechanistically, we find that hiPSC-derived CM patches secrete TGF-β1, directly inducing collagen type I production in fibroblasts but not collagen type III. Our results suggest the direct effect of the transplanted CM patch on the cardiac fibroblasts to improve elasticity of the damaged heart, resulting in functional recovery after MI. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 2 2026 Complete Transection of the Common Bile Duct Caused by Blunt Abdominal Trauma: A Rare Case Report 147 152 EN Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Akira Hamada Department of Intensive Care Medicine, Kochi Health Sciences Center Rika Yoshimatsu Department of Radiology, Kochi Health Sciences Center Yuichi Saisaka Department of Emergency and Critical Care Medicine, Kochi Health Sciences Center Manabu Matsumoto Department of Diagnostic Pathology, Kochi Health Sciences Center Jun Iwata Department of Diagnostic Pathology, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Case Report 10.18926/AMO/70457 Common bile duct (CBD) injury after blunt abdominal trauma is rare and difficult to diagnose. Delayed recognition leads to severe morbidity. A 70-year-old Japanese man was admitted after sustaining blunt abdominal trauma. Ultrasonography revealed intra-abdominal fluid, suggesting bleeding. Contrast-enhanced computed tomography revealed pancreatic head injury, intra-abdominal bleeding, and pseudoaneurysm of the anterior superior pancreatoduodenal artery (ASPDA). Bile duct injury was not evident. The application of transarterial embolization (TAE) controlled the bleeding. Canulation into the pancreatic or biliary duct was not possible during endoscopic retrograde cholangiopancreatography. An emergency laparotomy revealed severe pancreatic head and extrahepatic bile duct injuries. Pancreaticoduodenectomy/Child reconstruction was performed. Complete CBD transection was confirmed. The patient was ultimately discharged without complications. Early recognition, timely surgical management, and intensive care are essential for favorable outcomes in patients who have sustained abdominal trauma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 2 2026 Necrotizing Fasciitis Caused by ESBL-Producing Raoultella ornithinolytica in an Immunocompromised Patient with VEXAS Syndrome 141 145 EN Moe Sakamoto-Tokunaga Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaki Matoba Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomokazu Tamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Natsuki Kubota Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuya Terajima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenta Shidahara Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Hirose Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoichi Nawachi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takato Nakadoi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Hayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshia Miyawaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eri Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruki Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Takano-Narazaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-Ei Sada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuma Tsuji Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University Kazuyoshi Gotoh Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/70456 VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory somatic) syndrome has a poor prognosis, with infections being a major cause of death. Raoultella ornithinolytica is an environmental bacterium found predominantly in soil and water. Although R. ornithinolytica can cause various infections, necrotizing fasciitis due to this bacterium has not been reported. We describe the case of an 84-year-old Japanese male with VEXAS syndrome who developed septic shock and necrotizing fasciitis while he was under immunosuppressive therapy. The pathogen was initially misidentified as R. planticola by mass spectrometry but later confirmed by whole-genome sequencing as extended spectrum β-lactamase (ESBL) produced by R. ornithinolytica. Although a life-saving leg amputation was required, the patient recovered with appropriate antibiotic therapy. R. ornithinolytica is thus able to cause severe skin infections in immunocompromised individuals. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 2212-5345 64 3 2026 Short- and long-term outcomes of anti-thymocyte globulin-based regimen for acute antibody-mediated rejection after lung transplantation 101428 EN Kentaroh Miyoshi Department of Thoracic Surgery, Okayama University Hospital Shinji Otani Department of Thoracic Surgery, Okayama University Hospital Seiichiro Sugimoto Department of Thoracic Surgery, Okayama University Hospital Shin Tanaka Department of Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Background: Antibody-mediated rejection (AMR) remains a major barrier to successful lung transplantation (LTx). Despite advances in donor-specific alloantibody (DSA) detection, effective treatments are limited, with current management largely empirical. Acute clinical AMR, marked by rapid graft dysfunction, demands urgent intervention. In Japan, where approved therapies for AMR were historically limited, rabbit anti-thymocyte globulin (rATG) has been adopted as a treatment option.<br> Methods: This retrospective study analyzed 11 patients who developed acute AMR within three months after LTx at Okayama University Hospital between 2013 and 2023. Diagnosis (ISHLT possible AMR) was based on acute graft dysfunction unresponsive to steroids, positive DSA, and exclusion of infection, without histological confirmation due to procedural risk. rATG (1.5 mg/kg/day for 7 days) was administered, along with intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and rituximab when indicated. Outcomes included DSA clearance, clinical response, survival, and adverse events.<br> Results: Remission was achieved in 64% of patients, with 36% not requiring PLEX and 64% not receiving rituximab. Early rATG treatment correlated with favorable outcomes, whereas delayed therapy resulted in poorer responses. Six patients (55%) survived without chronic lung allograft dysfunction (CLAD) for over one year. Adverse events included cytomegalovirus infection (91%), bacterial pneumonia (36%), fungal infection (18%), and malignancy (18%).<br> Conclusions: rATG was effective for acute possible AMR management, particularly when initiated early. Some patients achieved remission without adjunct therapy, indicating rATG's potent immunosuppressive activity. However, frequent infectious complications emphasize the need for optimized dosing and further studies to validate its safety and long-term efficacy. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 1434-193X 2026 Informatics‐Driven and Automated Optimization in Flow Electrochemical Synthesis e202501237 EN Eisuke Sato Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akine Tani Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tomohiro Nakahama Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koichi Mitsudo Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Seiji Suga Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Electrochemical synthesis has emerged as a powerful platform for environmentally sustainable chemical transformations. When integrated with flow chemistry, electrosynthetic processes exhibit enhanced scalability, making them suitable for industrial applications. Recently, the integration of electrochemical flow systems with informatics techniques has accelerated the optimization of reaction conditions. Data-driven strategies facilitate rapid exploration of multidimensional parameter spaces, enabling identification of optimal reaction conditions with high efficiency. These advances have enabled the development of automated optimization systems. This review highlights recent progress in combining electrosynthesis, flow chemistry, and computational tools, focusing on representative examples that illustrate efficient optimization protocols and autonomous reaction development. By showcasing these developments, we discuss how the integration of these technologies is driving innovation in electrochemical synthesis. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0016-6480 380 2026 Constitutive activation of MC1R in the large-billed crow (Corvus macrorhynchos) and its potential role in black plumage 114924 EN Saya Nakano Graduate School of Natural Science and Technology, Okayama University Yuichi Tashiro Graduate School of Natural Science and Technology, Okayama University Hibiki Fukuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sayaka Aizawa Graduate School of Natural Science and Technology, Okayama University Sakae Takeuchi Graduate School of Natural Science and Technology, Okayama University Melanin-based plumage coloration in birds is largely regulated by the melanocortin 1 receptor (MC1R), a G protein–coupled receptor that promotes eumelanin synthesis via cAMP signaling. In domestic chickens, constitutively activating mutations such as the MC1R^E (E92K) allele cause melanistic phenotypes, demonstrating that persistent MC1R activation can drive generalized darkening. However, to our knowledge, no experimental study has directly demonstrated constitutive MC1R activation in wild birds exhibiting uniformly black plumage. We investigated the sequence and signaling properties of MC1R from the Large-billed Crow (Corvus macrorhynchos), a species with strongly eumelanin-dominant plumage. Crow MC1R exhibited elevated basal cAMP signaling and minimal responsiveness to α-melanocyte-stimulating hormone (α-MSH) in both stable Chinese hamster ovary (CHO-K1) cells and transient CRE-luciferase assays in HEK293T cells, demonstrating ligand-independent activation comparable to that observed in the melanizing chicken MC1R^E (E92K) allele. Comparative sequence analysis identified multiple substitutions conserved across Corvus species. Among these, E12K and E18K were functionally evaluated based on prior associations with melanism in other birds. Although E12K modestly increased basal signaling in chicken MC1R, E18K alone or in combination with E12K did not reproduce crow-level constitutive activity, and reciprocal substitutions in crow MC1R failed to abolish ligand-independent activation. These findings demonstrate that crow MC1R possesses constitutive activity and suggest that this phenotype reflects lineage-specific modifications rather than a single activating substitution. Our results provide experimental evidence that constitutive MC1R activation is a plausible molecular mechanism that may contribute to the black plumage in the Large-billed Crow, although a direct causal relationship remains to be established. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2589-0042 29 4 2026 Multifaceted role of POU5F1P1 in regulating its parental stem cell gene, POU5F1 115137 EN Kyohei Irie Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuko Kosaka Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Mizuno Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Omae Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshimasa Nakatani Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sandi Myat Noe Oo Department of Human Morphology, 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 Ayano Kawaguchi Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The human-specific retrogene POU5F1P1 (OCT4-Pseudogene1; OCT4-PG1), derived from stem cell factor POU5F1 (OCT4A), is predicted to encode an OCT4A-like protein; however, its function remains unclear. This study investigated OCT4-PG1 expression, translational control, and its role in endometrial cancer and stem cell regulation. Quantitative analyses revealed that elevated OCT4A, but not OCT4-PG1, expression correlated with clinical risk factors associated with poor prognosis in patients with endometrial cancer. OCT4-PG1 is under strong translational suppression mediated by its untranslated region and does not function as a protein under normal conditions. Instead, it acts as a non-coding RNA that suppresses OCT4A translation. Structural analyses showed that a single amino acid deletion (Gln259) destabilizes the OCT4-PG1 protein, thereby preventing its tumorigenic and transcriptional functions. Nevertheless, OCT4-PG1 forms heterodimers with OCT4A or SOX2, enhancing the regulatory activity of OCT4A. These findings highlight the regulatory role of pseudogenes in cancer and stem cell biology, with implications for therapies targeting OCT4A-related pathways. No potential conflict of interest relevant to this article was reported.

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

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

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 2 2026 Functional Transport Properties of Human Zinc Transporter 1: Kinetics and pH-Dependency 364 370 EN Yuma Yoshioka Department of Molecular Membrane Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takaaki Miyaji Department of Molecular Membrane Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Intracellular zinc (Zn2+) homeostasis is essential for physiological and pathological processes and is strictly regulated by Zn2+ transporters. Zinc transporter 1 (ZnT1) is a ubiquitously expressed plasma membrane-localized Zn transporter that exports Zn2+ from the cytoplasm to the extracellular space. However, the functional transport properties regarding kinetics and driving forces of ZnT1 remain debatable. In this study, we established a cell-free proteoliposome assay system and demonstrated that ZnT1 transports Zn2+ with high affinity in pH-dependent and pH-independent manners. The Km and Vmax of pH-dependent Zn2+ transport were 0.40 μM and 15.13 nmol/min/mg protein, and those of pH-independent Zn2+ transport were 0.52 μM and 8.88 nmol/min/mg protein (low concentrations of Zn2+), 3.02 μM and 17.59 nmol/min/mg protein (high concentrations of Zn2+), respectively, suggesting biphasic kinetic components of Zn2+ transport. Even without pH gradient formation, ZnT1 exhibits potent Zn2+ transport activity. In pH dependency, Zn2+ transport activity was higher at an inside pH of 6.0 than at 6.5–7.5 for proteoliposomes, despite the same ΔpH of 0.5–1.5. The Zn2+ transport activity decreased at an outside pH of 8.0, despite an increase in ΔpH. Although previous studies have proposed that ZnT1-mediated Zn2+ transport activity is driven by a calcium (Ca2+) gradient and not by a pH gradient, Ca2+ does not enhance Zn2+ transport activity in the presence or absence of a pH gradient. These results strongly suggest that ZnT1 protein transports Zn2+ optimally at a specific pH and exports excess intracellular Zn2+ even without ΔpH. No potential conflict of interest relevant to this article was reported.

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

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

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