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

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.

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

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

Elsevier BV Acta Medica Okayama 1556-0864 21 1 2026 Long-Term Safety and Effectiveness of Durvalumab in Unresectable Stage III NSCLC in Japan: A Multicenter Prospective Study (AYAME) 160 173 EN Hirotsugu Kenmotsu Division of Thoracic Oncology, Shizuoka Cancer Center Yoshinobu Saito Department of Respiratory Medicine, Nippon Medical School, Musashi Kosugi Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Shinya Uematsu Oncology Medical, AstraZeneca K.K. Burak Akdemir Oncology Medical, AstraZeneca K.K. Ayako Fukui Evidence and Observational Research, Medical, AstraZeneca K.K. Ryo Koto Evidence and Observational Research, Medical, AstraZeneca K.K. Masakazu Fujiwara Evidence and Observational Research, Medical, AstraZeneca K.K. Chikako Iwao Oncology Medical, AstraZeneca K.K. Hiroshi Kitagawa Oncology Medical, AstraZeneca K.K. Ichiro Yoshino Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital Akihiko Gemma Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Tetsuya Mitsudomi Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine and Faculty of Medicine & Hospital Nobuyuki Yamamoto Internal Medicine III, Wakayama Medical University Introduction: Based on the PACIFIC trial results, durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III NSCLC. However, few large-scale studies have prospectively evaluated its long-term effectiveness and safety, including subsequent treatment. Methods: This multicenter, noninterventional study (AYAME) enrolled patients who were prescribed durvalumab for unresectable stage III NSCLC after CRT (July 2019–December 2020; 52 sites; Japan). Patients received durvalumab for a maximum of 12 months and were prospectively followed up for 3 years, including the post-durvalumab treatment period. Primary end points were real-world progression-free survival (rwPFS), the incidence of interstitial lung disease (ILD), and adverse events of special interest (AESIs). Results: Of the 529 enrolled patients, 512 received durvalumab and 511 comprised the safety analysis population. The median time to onset of the first presentation or occurrence of ILD was 45.0 days. ILD of any grade occurred in 387 patients (75.7%) over the 3-year study period: grade 3, 57 (11.2%); grade 4, none (0.0%); and grade 5, 9 (1.8%). The most common AESIs of any grade during durvalumab treatment were thyroid dysfunction (12.5%), hepatic dysfunction (7.2%), and colitis (2.0%). No durvalumab treatment-related ILD or AESIs occurred during the post-treatment period. The median [95% confidence interval] rwPFS was 23.2 [18.2, 27.2] months in the effectiveness analysis population (n = 495). rwPFS rates were 62.5%, 54.6%, 49.4%, and 40.4% at 12, 18, 24, and 36 months, respectively. Conclusions: This first and largest prospective, observational study demonstrated the long-term safety and effectiveness of durvalumab for unresectable stage III NSCLC after CRT in a real-world clinical setting. Clinical Trial Registration: UMIN000037090 and NCT03995875 No potential conflict of interest relevant to this article was reported.

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

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

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. Methods: We retrospectively analyzed 207 patients with R/M HNSCC treated with nivolumab or pembrolizumab at a single institution. Early progression was defined as disease progression within 90 days after ICI initiation. Associations between clinicopathological factors and early progression were evaluated using logistic regression analyses. Results: Early progression was observed in 80 patients (38.6%). In an exploratory survival comparison, patients with early progression had significantly shorter overall survival than those without early progression. Early progression rates increased from distant-only disease to locoregional-only disease and combined locoregional and distant disease. In multivariable analysis, combined locoregional, and distant disease showed the strongest independent association with early progression. Elevated neutrophil-to-lymphocyte ratio and hypoalbuminemia were also independently associated with early progression. In contrast, treatment regimen, treatment line, number of lesions, and bulky disease were not significantly associated with early progression. Conclusion: Disease distribution was associated with early progression after ICI initiation in patients with R/M HNSCC, with combined locoregional and distant disease showing the strongest independent association. These findings suggest that both disease status and host condition may influence failure to achieve adequate disease control shortly after ICI initiation. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1867-1071 43 2 2024 Cranial and spinal computed tomography (CT) angiography with photon-counting detector CT: comparison with angiographic and operative findings 143 151 EN Fumiyo Higaki Department of Radiology, Okayama University Hospital Masafumi Hiramatsu Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takao Yasuhara Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Susumu Sasada Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yoshihiro Otani Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Jun Haruma Department of Neurological Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tomohiro Inoue Division of Radiological Technology, Okayama University Hospital Yusuke Morimitsu Division of Radiological Technology, Okayama University Hospital Noriaki Akagi Division of Radiological Technology, Okayama University Hospital Yusuke Matsui Department of Radiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University The clinical imaging features of photon-counting detector (PCD) computed tomography (CT) are mainly known as dose reduction, improvement of spatial resolution, and reduction of artifacts compared to energy-integrating detector CT (EID-CT). The utility of cranial and spinal PCD-CT and PCD-CT angiography (CTA) has been previously reported. CTA is a widely used technique for noninvasive evaluation. Cranial CTA is important in brain tumors, especially glioblastoma; it evaluates whether the tumor is highly vascularized prior to an operation and helps in the diagnosis and assessment of bleeding risk. Spinal CTA has an important role in the estimation of feeders and drainers prior to selective angiography in the cases of spinal epidural arteriovenous fistulas and spinal tumors, especially in hemangioblastoma. So far, EID-CTA is commonly performed in an adjunctive role prior to selective angiography; PCD-CTA with high spatial resolution can be an alternative to selective angiography. In the cases of cerebral aneurysms, flow diverters are important tools for the treatment of intracranial aneurysms, and postoperative evaluation with cone beam CT with angiography using diluted contrast media is performed to evaluate stent adhesion and in-stent thrombosis. If CTA can replace selective angiography, it will be less invasive for the patient. In this review, we present representative cases with PCD-CT. We also show how well the cranial and spinal PCD-CTA approaches the accuracy of angiographic and intraoperative findings. No potential conflict of interest relevant to this article was reported.

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

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

SAGE Publications Acta Medica Okayama 1758-8359 17 2025 Clinical impact of hypomagnesemia induced by necitumumab plus cisplatin and gemcitabine treatment in patients with advanced lung squamous cell carcinoma: a subanalysis of the NINJA study 1 16 EN Shigeru Tanzawa Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yasunori Murata Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Takeshita Department of Respiratory Medicine, Ichinomiya Nishi Hospital Fumihiko Kinoshita Department of Thoracic Oncology, NHO Kyushu Cancer Center Takatoshi Fujishita Department of Thoracic Oncology, NHO Kyushu Cancer Center Shunichi Sugawara Department of Pulmonary Medicine, Sendai Kousei Hospital Yosuke Kawashima Department of Pulmonary Medicine, Sendai Kousei Hospital Kazuki Hashimoto Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Masahide Mori Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Akihiko Miyanaga Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Anna Hayashi Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Hisashi Tanaka Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine Ryoichi Honda Department of Respiratory Medicine, Asahi General Hospital Masafumi Nojiri Department of Respiratory Medicine, Kanazawa Medical University Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Akito Hata Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center Nobuhisa Ishikawa Department of Respiratory Medicine, Hiroshima Prefectural Hospital Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center Takahisa Kawamura Department of Thoracic Oncology, Osaka International Cancer Institute Go Saito Department of Respirology, Graduate School of Medicine, Chiba University Teppei Yamaguchi Department of Thoracic Oncology, Aichi Cancer Center Hospital Kazuhiro Asada Department of Respiratory Medicine, Shizuoka General Hospital Satoshi Tetsumoto Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital Hiroshi Tanaka Department of Internal Medicine, Niigata Cancer Center Hospital Satoshi Watanabe Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Yukihiro Umeda Department of Respiratory Medicine, Faculty of Medical Sciences, University of Fukui Kakuhiro Yamaguchi Department of Respiratory Medicine, Hiroshima University Hospital Kazuya Nishii Department of Respiratory Medicine, NHO Iwakuni Clinical Center, Iwakuni, Yamaguchi, Japan Kosuke Tsuruno Department of Respiratory Medicine, Iizuka Hospital Yuki Misumi Department of Respiratory Medicine, Yokohama Municipal Citizen’s Hospital Hiroshi Kuraishi Department of Pulmonary Medicine, Nagano Red Cross Hospital Ken Yoshihara Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Akira Nakao Department of Respiratory Medicine, Fukuoka University Hospital Akihito Kubo Department of Respiratory Medicine and Allergology, Aichi Medical University Toshihiko Yokoyama Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Kana Watanabe Department of Respiratory Medicine, Miyagi Cancer Center Nobuhiko Seki Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Background: The clinical impact of hypomagnesemia induced by necitumumab plus gemcitabine and cisplatin (GCN) as a second-line or later therapy is unclear. Objective: We aimed to evaluate the clinical characteristics and survival impact of hypomagnesemia induced by this therapy. Design: This was a sub-analysis of the retrospective multicenter NINJA study. Methods: Among the 93 patients enrolled in the NINJA study, this subanalysis included 75 patients with baseline serum magnesium concentrations. Results: The incidence of grade ⩾2 hypomagnesemia was 18.0% in the patients with normal baseline serum magnesium concentrations and 42.8% in those with low concentrations (p = 0.073). The discontinuation rates of GCN treatment owing to hypomagnesemia in each group were 0% and 7.1%, respectively (p = 0.187). The number of necitumumab doses and severity of hypomagnesemia were positively correlated (r = 0.389, p < 0.001). Patients who developed hypomagnesemia in fewer than 21 days after the first dose of GCN (n = 12) had significantly poorer progression-free survival (PFS) than those without the condition (n = 63; median: 4.1 vs 4.4 months, p = 0.048). A similar trend was observed for OS (median: 9.7 vs 15.7 months, p = 0.062). These results were maintained after multivariate analyses (PFS: hazard ratio (HR) 2.46, p = 0.014; OS: HR 2.78, p = 0.021). Conclusion: GCN as a second-line or later therapy may be tolerable regardless of the patient’s baseline serum magnesium concentration. On the other hand, early serum magnesium reduction with this therapy is associated with a poor prognosis. However, caution should be needed because our results lacked sufficient information for confounding variables other than those analyzed here that may influence the correlation between hypomagnesemia and survival. No potential conflict of interest relevant to this article was reported.

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

SAGE Publications Acta Medica Okayama 1758-8359 17 2025 Skin disorder within 30 days is a favorable prognostic factor in patients with lung squamous cell carcinoma treated with necitumumab plus gemcitabine and cisplatin: a sub-analysis of the NINJA study 1 13 EN Fumihiko Kinoshita Department of Thoracic Oncology, NHO Kyushu Cancer Center Shigeru Tanzawa Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yasunori Murata Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Takeshita Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Shunichi Sugawara Department of Pulmonary Medicine, Sendai Kousei Hospital Yosuke Kawashima Department of Pulmonary Medicine, Sendai Kousei Hospital Kazuki Hashimoto Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Masahide Mori Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Akihiko Miyanaga Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Anna Hayashi Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Hisashi Tanaka Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine Ryoichi Honda Department of Respiratory Medicine, Asahi General Hospital Masafumi Nojiri Department of Respiratory Medicine, Kanazawa Medical University Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Ken Yamamoto Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center Ken Masuda Department of Respiratory Medicine, Hiroshima Prefectural Hospital Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center Takahisa Kawamura Department of Thoracic Oncology, Osaka International Cancer Institute Takuji Suzuki Department of Respirology, Graduate School of Medicine, Chiba University Teppei Yamaguchi Department of Thoracic Oncology, Aichi Cancer Center Hospital Kazuhiro Asada Department of Respiratory Medicine, Shizuoka General Hospital Satoshi Tetsumoto Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital Hiroshi Tanaka Department of Internal Medicine, Niigata Cancer Center Hospital Satoshi Watanabe Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Yukihiro Umeda Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui Kakuhiro Yamaguchi Department of Respiratory Medicine, Hiroshima University Hospital Shoichi Kuyama Department of Respiratory medicine, NHO Iwakuni Clinical Center Kosuke Tsuruno Department of Respiratory Medicine, Iizuka Hospital Yuki Misumi Department of Respiratory Medicine, Yokohama Municipal Citizen’s Hospital Hiroshi Kuraishi Department of Respiratory Medicine, Nagano Red Cross Hospital Ken Yoshihara Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine Akira Nakao Department of Respiratory Medicine, Fukuoka University Hospital Akihito Kubo Department of Respiratory Medicine and Allergology, Aichi Medical University School of Medicine Toshihiko Yokoyama Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Kana Watanabe Department of Respiratory Medicine, Miyagi Cancer Center Nobuhiko Seki Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Background: Skin disorders are major adverse events associated with necitumumab plus gemcitabine and cisplatin (Neci + GC) administration. However, the prognostic effect of skin disorders in patients with lung squamous cell carcinoma (LSCC) administered Neci + GC is unclear. Objectives: We examined this prognostic effect in patients with LSCC, and the usefulness of minocycline administration. Design: This was a sub-analysis of the retrospective multicenter NINJA study. Methods: We performed a landmark survival analysis according to the presence of skin disorders at Day 30 of treatment and examined the usefulness of minocycline for treating skin disorders. Results: Among the 93 patients, 62 (66.7%) had a skin disorder at Day 30. Nineteen, 30, and 13 patients experienced Grade 1, 2, and 3 skin disorders, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with skin disorders at Day 30 were longer than those of patients without skin disorders (median OS: 434 vs 278 days, p = 0.0201; median PFS: 148 vs 82 days, p = 0.0835). Multivariable analysis showed that a skin disorder at Day 30 was an independent prognostic factor for both OS (p = 0.0044) and PFS (p = 0.0514). Of the 62 patients with skin disorders at Day 30, 38 (61.3%) were taking minocycline, and their time to treatment failure (TTF) was better than that in patients not taking minocycline (median TTF: 148 vs 101 days, p = 0.0495). Conclusion: A skin disorder within 30 days was a favorable prognostic factor for patients with LSCC administered Neci + GC. Additionally, minocycline administration may be beneficial in patients who develop skin disorders within 30 days. No potential conflict of interest relevant to this article was reported.

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

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.

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

Wiley Acta Medica Okayama 2198-3844 2026 SPRED2 Negatively Regulates CD8+ T Cell-Mediated Antitumor Immunity in Breast Cancer e77909 EN Miao Tian Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kun Zhao Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tong Gao Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ziyi Wang Department of Advanced International and Information Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Activation of the RAS/RAF/ERK pathway is crucial for adaptive immunity. Here, we provide evidence that Sprouty-related EVH1 domain containing 2 (SPRED2), an endogenous inhibitor of this pathway, negatively regulates CD8+ T cell-mediated antitumor immunity in breast cancer. In EO771 and 4T1 mouse models, Spred2−/− mice exhibit reduced tumor growth, with lower endpoint lung metastatic burden in the 4T1 model, accompanied by increased T-cell infiltration and activation. Spred2−/− T cells show enhanced cytokine expression, proliferation,survival, in vitro cytotoxicity, and memory-like phenotypes, particularly among CD8+ T cells. Adoptive transfer of Spred2−/− CD8+ T cells into tumor-bearing wild-type hosts similarly reduces endpoint lung metastatic burden. MEK inhibition with U0126 attenuates increased interferon-gamma and granzyme B expression in Spred2−/− CD8+ T cells. Transcriptomic analyses reveal an inverse correlation between SPRED2 expression and antitumor CD8+ T cell states in both humans and mice. In tumor-infiltrating T cells from patients with breast cancer, SPRED2low T cells show enriched effector and cytotoxicity programs and are associated with “immune-hot” tumors, whereas survival associations vary with CD8+ T cell context. Collectively, these findings suggest that SPRED2 functions as a cell-intrinsic negative regulator of CD8+ T-cell activation and highlight its potential as a therapeutic target to enhance T cell–based cancer immunotherapy. No potential conflict of interest relevant to this article was reported.

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

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

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

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

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

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

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

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

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.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 8 2026 Impact of Adjusted Creatinine Clearance on Carboplatin Dosing in Endometrial Cancer: A Retrospective Study 1285 1290 EN Kentaro Katayama Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Makio Imamura Department of Clinical Support, Kurashiki Medical Center Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Carboplatin (CBDCA) dosing is commonly determined using the Calvert formula, with creatinine clearance (Ccr) estimated by the Cockcroft–Gault formula. In Japan, where serum creatinine (sCr) is usually measured enzymatically, unadjusted Ccr may overestimate glomerular filtration rate and lead to CBDCA overdosing. We retrospectively compared treatment exposure, hematologic toxicity, and exploratory oncologic outcomes in patients with endometrial cancer who received postoperative paclitaxel plus CBDCA therapy. Patients were grouped according to whether CBDCA dosing was based on the conventional Cockcroft–Gault formula (CG group) or on adjusted Ccr calculated by adding 0.2 mg/dL to sCr (adjusted group). The incidence of Grade ≥3 neutropenia was significantly lower in the adjusted group than in the CG group. The 5-year progression-free survival (PFS) rate was numerically lower in the adjusted group than in the CG group, although no statistically significant difference was observed between the groups. Because the number of PFS events was limited, the effect of adjusted Ccr-based dosing on oncologic outcomes remains uncertain. These findings suggest that adjusted Ccr-based dosing may reduce hematologic toxicity in routine clinical practice. However, given the limited number of PFS events and the wide uncertainty in survival estimates, further studies are needed to clarify its impact on oncologic outcomes. No potential conflict of interest relevant to this article was reported.

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

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

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

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

Wiley Acta Medica Okayama 2577-171X 9 4 2026 Varicocelectomy Restores Spermatogenesis in Fontan‐Associated Varicocele: A Two‐Case Series e70206 EN Yusuke Tominaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Matsumoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takatoshi Moriwake Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nariaki Ozaki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Fontan circulation may cause chronic venous hypertension and predispose patients to varicocele and infertility,but the clinical significance of surgical treatment remains unclear. Case Presentation: We describe two patients with Fontan circulation who developed Fontan-associated varicocele (FAVC). A42-year-old man presented with secondary infertility, bilateral varicocele, and progression to azoospermia after Fontan surgery.A 28-year-old man had asthenozoospermia, bilateral varicocele, and repeated failure of assisted reproductive technology. Bothunderwent bilateral microsurgical varicocelectomy with perioperative heparin bridging. Postoperative semen parameters im-proved in both patients, with sperm reappearing in the first case. Conclusion: Varicocelectomy for FAVC may restore spermatogenesis in selected cases, but the risk of postoperative recurrencemay be increased. No potential conflict of interest relevant to this article was reported.

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

Japan Surgical Society Acta Medica Okayama 2198-7793 12 1 2026 Single-Incision Laparoscopic Hartmann’s Reversal Using the Stoma Site in a Patient with Perioperative Anaphylaxis cr.26-0206 EN Tsubasa Yanagihara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama, Japan Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshitaka Kondo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences INTRODUCTION: Reversal of Hartmann’s procedure is associated with substantial morbidity, and further reduction of surgical invasiveness may be beneficial in selected patients. Perioperative anaphylaxis caused by anesthetic agents or skin antiseptics poses a significant challenge to surgical management. We report a case of stoma-site single-incision laparoscopic Hartmann’s reversal (HR) performed in a patient with severe perioperative allergies. CASE PRESENTATION: A 73-year-old woman underwent an emergency open Hartmann’s procedure with partial cystectomy for perforated sigmoid colon cancer with bladder invasion. After adjuvant chemotherapy, she developed a progressively enlarging giant parastomal hernia that significantly impaired daily activities. Two attempts at HR were aborted because of perioperative anaphylactic shock. Subsequent allergy evaluations suggested rocuronium and chlorhexidine as causative agents, and povidone-iodine was also avoided based on clinical history. Approximately 14 months after the initial surgery, single-incision laparoscopic HR using the stoma site was successfully performed under general anesthesia without neuromuscular blocking agents. Preoperative skin antisepsis was performed using benzalkonium chloride, avoiding both chlorhexidine and povidone-iodine. No additional abdominal incisions were required. The operative time was 2 h 56 min, with minimal blood loss. The postoperative course was uneventful and she was discharged on POD 9. CONCLUSIONS: Stoma-site single-incision laparoscopic HR may represent a useful surgical option for selected patients with severe perioperative allergies to anesthetic agents and skin antiseptics, in whom minimizing abdominal approach and wound-related risks is particularly important. No potential conflict of interest relevant to this article was reported.

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

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

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

Japan Surgical Society Acta Medica Okayama 2198-7793 12 1 2026 Successful Lung Transplantation after Plasma Exchange in a Patient with High Thermal Amplitude Cold Agglutinins: A Case Report cr.26-0502 EN Yuya Miyoshi Department of General Thoracic Surgery, Okayama University Hospital Kentaroh Miyoshi Department of General Thoracic Surgery, Okayama University Hospital Naomi Asano Division of Transfusion and Cell Therapy, Okayama University Hospital Haruchika Yamamoto Department of General Thoracic Surgery, Okayama University Hospital Shin Tanaka Department of General Thoracic Surgery, Okayama University Hospital Shuji Okahara Department of General Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of General Thoracic Surgery, Okayama University Hospital, Okayama, Okayama, Japan Seiichiro Sugimoto Department of General Thoracic Surgery, Okayama University Hospital Nobuharu Fujii Division of Transfusion and Cell Therapy, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery, Okayama University Hospital INTRODUCTION: Cold agglutinins (CAs) are immunoglobulin M autoantibodies that induce red blood cell agglutination at low temperatures and may cause hemolytic or thrombotic complications during procedures associated with hypothermia. In lung transplantation (LT), blood may be exposed to low temperatures within the reperfused lung graft and the extracorporeal circulation circuit, potentially increasing the risk of CA-mediated complications. However, the perioperative significance of CAs in this setting remains unclear, and optimal management has not been established. We report a case of successful bilateral LT in a patient with high-thermal-amplitude CAs managed with preoperative plasma exchange (PLEX) and strict intraoperative temperature control. CASE PRESENTATION: A 55-year-old man with diffuse panbronchiolitis and secondary pulmonary hypertension was listed for bilateral LT. Preoperative testing incidentally revealed clinically significant CAs, with a titer of 1:128 at 4°C and a thermal amplitude of 30°C. Because intraoperative blood temperature might approach this threshold despite active warming, a single preoperative session of PLEX using 36 units of fresh frozen plasma was performed to reduce the risk of a CA-mediated complication. Bilateral LT was subsequently completed under meticulous temperature management, including extracorporeal circulation maintained at 37.5°C, continuous systematic warming, avoidance of topical ice application, and rewarming of the donor lungs before reperfusion. After surgery, the CA titer decreased to 1:32. The postoperative course was uneventful, without thromboembolic events, primary graft dysfunction, or bronchial complications. CONCLUSIONS: LT may be performed safely in selected patients with high-thermal-amplitude CAs when careful perioperative temperature control is combined with preoperative PLEX. PLEX should be considered when the anticipated intraoperative temperature is expected to approach the patient’s thermal amplitude threshold. No potential conflict of interest relevant to this article was reported.

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

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

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

Wiley Acta Medica Okayama 1086-9379 61 4 2026 The effects of pressure on immiscibility in metallic, core‐forming liquids: Implications for protoplanetary differentiation 720 738 EN Geoffrey David Bromiley School of GeoSciences, University of Edinburgh, Grant Institute Hidenori Terasaki Department of Earth Sciences, Okayama University Matthew Varnam School of GeoSciences, University of Edinburgh, Grant Institute Mechanisms for metal core formation in rocky planetesimals and planetary embryos remain poorly constrained, in part due to complexities arising from immiscibility in core-forming liquids at low pressures. To assess the pressure dependence of immiscibility and its role in protoplanetary differentiation, we performed experiments at 3 and 5 GPa in the system Fe0.9Ni0.1 + S, P, C. Immiscibility arises due to the highly non-ideal nature of light element mixing in Fe liquids, and results in separation of Fe-rich (S-depleted, C-rich, P-rich) and FeS-rich (S-rich, C-rich, P-depleted) liquids. For a broad range of core-forming liquid compositions, a miscibility gap is only present at pressures <5 GPa. With increasing pressure, the behavior of complex systems converges on that of the Fe-S-C ternary, although S-P-C interactions continue to influence metal liquid compositions and stability. Comparison with planetary core compositions derived from meteorite data suggests that immiscibility can play a significant role during melting in planetesimals, and up to medium-sized planetary embryos. In turn, the importance of immiscibility during differentiation depends on the extent of melting, mechanisms for core formation, and corollary degree of light element loss from planetary bodies. No potential conflict of interest relevant to this article was reported.

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.

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

Springer Science and Business Media LLC Acta Medica Okayama 2198-4034 12 1 2026 Development of a preoperative accuracy prediction model using machine learning for implant placement in static-guided surgery: retrospective observational study 44 EN Takuya Mino Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University Yurina Matsuoka Department of Semiconductor, Computer Science and Applied Mathematics, Graduate School of Science and Technology, Kumamoto University Ken’ichi Morooka Division of Biomedical Engineering, Faculty of Advanced Science and Technology, Kumamoto University Kana Tokumoto Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University Hiroaki Shimizu Shimizu Dental Clinic Yoko Kurosaki Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University Aya Kimura-Ono Center for Innovative Clinical Medicine, Okayama University Hospital Hiromitsu Kishimoto Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenji Maekawa Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University Purpose This study aimed to develop a machine learning model capable of preoperatively predicting three-dimensional implant placement errors at the implant apex in static-guided surgery and to identify the clinical features associated with placement accuracy. Methods Clinical data partially derived from a previous observational study were analyzed. In total, 181 patients and 480 implants placed using fully static-guided surgery were included in this study. The outcome variable was defined as three-dimensional implant placement error at the implant apex relative to the preoperative simulation, dichotomized as less than 0.5 mm or ≥ 0.5 mm. Twenty-one clinical and radiographic factors previously suggested to influence the placement accuracy were used as explanatory variables. The feature importance was evaluated using three gradient boosting decision tree models. Furthermore, a stacking model combining multiple classifiers was constructed, and the classification performance was assessed using ten-fold cross-validation. Results The feature importance analysis identified 12 features associated with implant placement errors. The stacking model demonstrated superior classification performance compared to individual classifiers. The true positive rate was 0.73, false negative rate was 0.27, false positive rate was 0.14, and true negative rate was 0.86. Conclusions The proposed stacking model correctly classified 86% of cases with implant placement error less than 0.5 mm and 73% of cases with implant placement error of ≥ 0.5 mm. These findings suggest that the proposed model may support the preoperative evaluation of implant placement accuracy in static-guided surgeries. No potential conflict of interest relevant to this article was reported.

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

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

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

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.

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

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

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

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

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

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

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

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

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

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.

AIP Publishing Acta Medica Okayama 0021-9606 165 7 2026 High-resolution analysis of the S1–S0 transition of magnesium phthalocyanine: Rotational structure and electronic angular momentum 074308 EN Yuki Miyamoto Research Institute for Interdisciplinary Science, Okayama University Katsunari Enomoto Department of Physics, University of Toyama Kana Iwakuni Institute for Laser Science, University of Electro-Communications Susumu Kuma Department of Physics, Rikkyo University Koichi M. T. Yamada Institute for Laser Science, University of Electro-Communications We report a high-resolution spectroscopic analysis of the S1–S0 transition of magnesium phthalocyanine (MgPc), obtained by probing buffer-gas-cooled molecules with a narrow-linewidth laser. The observed spectrum exhibits a characteristic three-peak pattern, which is well reproduced by modeling MgPc as an oblate symmetric top with D4h symmetry. A key result of this work is that the spectrum is strongly influenced by electronic Coriolis coupling, which is associated with electronic angular momentum. The electronic Coriolis constant is determined to be ∼2, indicating an effective orbital angular momentum of about 2 in the excited S1 state, originating from the π-conjugated ring excitation. This provides a direct spectroscopic signature of electronic angular momentum in a large polyatomic molecule. The presence of nonzero electronic orbital angular momentum is qualitatively consistent with the perimeter model of phthalocyanines. The value lies within the range inferred from previous magnetic circular dichroism (MCD) studies. Compared with the previous MCD estimate, the present analysis provides a more state-specific and narrower constraint, demonstrating that high-resolution spectroscopy enables direct access to electronic and magnetic properties beyond conventional structural characterization. No potential conflict of interest relevant to this article was reported.

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

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

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.

Elsevier BV Acta Medica Okayama 0001-8686 358 2026 Revisiting particle formation beyond classical nucleation: A unified classification framework for nonclassical pathways 104018 EN Yuya Iida Faculty of Environmental, Life, Natural Science and Technology, Okayama University Satoshi Watanabe Department of Chemical Science and Engineering, Kyoto University Particle formation is pervasive in both nature and technology, shaping environmental and biological phenomena while underpinning a broad range of industrial products. A mechanistic understanding of particle formation is therefore important both for fundamental science and for the design of particle properties. It is now well established that particle formation can proceed through diverse pathways beyond classical one-step nucleation. At the same time, the proliferation of reported nonclassical pathways has blurred the distinctions among mechanistic categories and obscured their underlying relationships. In this review, we revisit the development of concepts in particle formation pathways and present a unified perspective on this increasingly complex mechanistic landscape. To this end, we classify the nonclassical features of particle formation along three conceptual axes: stepwise transitions between phases or phase-like fluctuations, chemically driven formation of structural units, and aggregation-dominant nucleation and growth processes. This framework places diverse pathways within a common three-dimensional space referenced to classical nucleation, providing a basis for comparing apparently distinct mechanisms within a single picture. We further discuss representative theoretical descriptions in relation to these axes and outline future challenges. No potential conflict of interest relevant to this article was reported.

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

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

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 Transcanal Cochlear Implantation Under Endoscopic Guidance with Canal Closure in a Pediatric Patient with CHARGE Syndrome: A Case Report and Surgical Technique 265 270 EN Takuto Yamasaki Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akiko Sugaya Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuto Naoi Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Kariya Department of Otolaryngology-Head and Neck Surgery, Kawasaki Medical School Mizuo Ando Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Case Report 10.18926/AMO/71071 Cochlear implantation (CI) in patients with CHARGE syndrome presents unique surgical challenges due to complex external, middle, and inner ear malformations. We describe the case of a 3-year-old Japanese boy for whom simultaneous transcanal CI under endoscopic guidance and external auditory canal closure were performed. This approach enabled safe electrode placement and resulted in favorable auditory outcomes, representing a potential novel surgical option for CI in patients with CHARGE syndrome. There are few reports of this type of surgical intervention, and the present case highlights the feasibility and clinical benefits of individualized surgical planning for CI in anatomically complex patients. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 Hemorrhage from a Jejunal Lymphangioma 253 257 EN Sachiko Ishikami Department of Gastroenterological Surgery, Kochi Health Sciences Center Shuta Tamura Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Nao Yamamoto Department of General Medicine, Kochi Health Sciences Center Yuki Okamoto Department of Gastroenterology and Hepatology, Kochi Health Sciences Center Rika Yoshimatsu Department of Radiology, 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/71069 Lymphangioma is a benign tumor arising from lymphatic vessel proliferation and most commonly occurs in the head, neck, or axilla. Involvement of the small intestine is rare and is often overlooked as a source of obscure gastrointestinal bleeding. Because jejunal lymphangiomas frequently present with nonspecific symptoms and may escape detection by conventional upper and lower gastrointestinal endoscopy or cross-sectional imaging, diagnosis is often delayed. Advances in balloon-assisted enteroscopy have enabled direct visualization of small intestinal lesions, facilitating accurate diagnosis and appropriate therapeutic decision-making. Here, we report a case of jejunal lymphangioma presenting with severe anemia due to active bleeding, which was detected by double-balloon endoscopy and successfully managed by laparoscopic-assisted resection. This case highlights the importance of considering small intestinal lymphangioma in the differential diagnosis of unexplained gastrointestinal bleeding and underscores the clinical utility of deep enteroscopy in identifying rare but clinically significant small bowel tumors. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 4 2026 Post-Tracheostomy Fistula Formation Between the Trachea and Left Common Carotid Artery in a Pediatric Patient with Trisomy 18 247 252 EN Tsuyoshi Shiina Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Watanabe Department of Pediatrics, Fukuyama City Hospital Junko Yoshimoto Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takeshi Sato Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisaku Morimoto Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoka Okamura Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Terutaka Tanimoto Department of Pediatric Surgery, Okayama University Hospital Yosuke Washio Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Oyama Department of Pediatric Surgery, Fukuyama City Hospital Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuo Noda Department of Pediatric Surgery, Japanese Red Cross Society Himeji Hospital Case Report 10.18926/AMO/71068 The long-term survival of individuals with trisomy 18 has improved, and the need for tracheostomy in this population has thus increased. We describe the case of a 3-year-old Japanese boy with trisomy 18 who developed a tracheoarterial fistula involving the left common carotid artery (LCCA). He underwent an emergency tracheostomy for respiratory failure secondary to pneumonia. Massive hemorrhage from the tracheostoma occurred on postoperative day 31, leading to his death. The autopsy revealed that the LCCA originated from the brachiocephalic trunk and coursed medially, forming a fistulous connection with the trachea. This case highlights the clinical importance of preoperative vascular mapping in patients with chromosomal abnormalities. No potential conflict of interest relevant to this article was reported.

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

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

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

Wiley Acta Medica Okayama 2050-0904 14 7 2026 A Biologically Dominant Trophoblastic Component Guiding Neoadjuvant EMA/CO in Endometrial Carcinoma: A Clinical Case Report e72982 EN Shinsuke Shirakawa Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shoji Nagao Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yui Tanaka Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Fujikawa Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryoko Imatani Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Momoko Tanioka Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Tani Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hanako Sugihara Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Okamoto Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoyuki Ida Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirofumi Matsuoka Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junko Haraga Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikako Ogawa Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Nakamura Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Yanai Department of Diagnostic Pathology, Okayama University Hisashi Masuyama Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Endometrial carcinoma with choriocarcinomatous components (ECCC) is a rare and aggressive malignancy for which optimal management remains undefined. We report a case illustrating how preoperative identification of a biologically dominant trophoblastic component can guide treatment sequencing and achieve durable remission. A 61-year-old postmenopausal woman presented with abnormal uterine bleeding. Endometrial biopsy revealed a mixed tumor composed predominantly of choriocarcinomatous elements with a minor grade 1 endometrioid carcinoma component. Despite only superficial myometrial invasion, imaging demonstrated multiple pulmonary nodules, and serum human chorionic gonadotropin (hCG) was markedly elevated (46,538 mIU/mL). This clinicopathological incongruity suggested that the trophoblastic component, rather than the low-grade endometrioid carcinoma, was driving disease progression. Neoadjuvant EMA/CO chemotherapy was therefore prioritized to achieve rapid systemic control. After six cycles, serum hCG normalized and pulmonary lesions completely resolved. The patient subsequently underwent total hysterectomy and bilateral salpingo-oophorectomy, which revealed no residual choriocarcinoma. She remains disease-free more than two years after completion of treatment. This case highlights the importance of recognizing clinicopathological incongruity and identifying the biologically dominant tumor component when determining treatment sequencing in rare mixed malignancies. No potential conflict of interest relevant to this article was reported.

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

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.

Frontiers Media SA Acta Medica Okayama 2234-943X 16 2026 Case Report: Multidisciplinary approach for complete resection of primary advanced low-grade serous ovarian carcinoma involving the iliac vessels and paraspinal region 1762009 EN Naoyuki Ida Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoji Nagao Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Fujikawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Tanaka Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Momoko Tanioka Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoko Imatani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Tani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hanako Sugihara Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirofumi Matsuoka Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Okamoto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Haraga Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chikako Ogawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Low-grade serous ovarian carcinoma (LGSC) is characterized by indolent progression and relative resistance to cytotoxic chemotherapy, making complete cytoreduction the key prognostic determinant. However, extra-pelvic invasion presents significant surgical and functional challenges requiring coordinated multidisciplinary management. Case presentation: A 62-year-old woman with FIGO stage IVB LGSC presented with right inguinal swelling infiltrating the femoral vein and abdominal wall. MRI and PET-CT revealed bilateral ovarian tumors and multiple lymph node metastases. A multidisciplinary operation involving gynecologic, orthopedic, plastic, and gastrointestinal surgeons was conducted. The procedures included total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic and para-aortic lymphadenectomy, en bloc resection of the right inguinal lesion, femoral vein repair, and anterolateral thigh flap reconstruction. Complete resection (R0) was achieved. Postoperative recovery was favorable, with transient leg edema resolving within 4 months. The patient remains disease-free at 13 months after surgery. Discussion: Strategic multidisciplinary collaboration enabled complete resection and functional preservation in this chemotherapy-resistant LGSC case. We propose the “Four Surgical Limits” framework—anatomical, oncological, functional, and interdisciplinary—as a structured concept guiding operative decision-making beyond conventional boundaries. Conclusion: Multidisciplinary collaboration can overcome traditional surgical and oncologic barriers, achieving both radicality and quality-of-life preservation in advanced LGSC. 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. 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. 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. 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 17 2 2025 Short-Term and Long-Term Outcomes of Robotic Gastrectomy for Gastric Cancer: A Single-Center, Single-Arm Prospective Study e79063 EN Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshihiko Kakiutchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hajime Kashima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masahiko Nishizaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: Robotic gastrectomy (RG) has emerged as a promising approach for gastric cancer (GC) treatment, offering advantages such as enhanced dexterity, improved visualization, and increased precision. However, its widespread adoption remains limited due to technical complexity, high costs, limited applications, and insufficient evidence. Methods: We conducted a single-center, prospective study to evaluate the safety and feasibility of RG, including robotic total gastrectomy (RTG), robotic proximal gastrectomy (RPG), and robotic distal gastrectomy (RDG) with D1+ or D2 lymphadenectomy, in clinical stage I/II GC. The primary endpoint was the incidence of intraoperative and postoperative complications, while the secondary endpoints included surgical outcomes and long-term prognosis. Results: Seven patients were enrolled. No intraoperative complications or conversions to open surgery occurred. The primary endpoint was met, with no major postoperative complications. RTG had a longer operative time and more lymph nodes dissected than RDG and RPG. The median postoperative hospital stay was 10 days. Recurrence was observed in two cases, one of which achieved long-term survival without chemotherapy. Conclusion: Our findings demonstrate the safety and feasibility of RG for early and advanced GC. Further multicenter studies with larger cohorts are needed to establish its oncological benefits and cost-effectiveness, facilitating broader clinical adoption. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 2 2025 Durable Response to Nivolumab Combined With Metformin in Advanced Pancreatic Cancer: A Case Report With Seven Years of Follow-Up e79001 EN Ryosuke Sato Department of Gastroenterology and Hepatology, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Toshio Kubo Department of Allergy and Respiratory Medicine, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Department of Gastroenterology, Okayama City Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Toshiyuki Kozuki Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University Heiichiro Udono Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital We report a case of poorly differentiated pancreatic cancer that showed an exceptional response to combination therapy with nivolumab and metformin. A 58-year-old man presented with epigastric pain and was diagnosed with locally advanced pancreatic cancer with para-aortic lymph node metastasis. After disease progression following modified FOLFIRINOX therapy (a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin), the patient was enrolled in a phase Ib clinical trial of nivolumab (3 mg/kg biweekly) combined with metformin (750 mg/day). Post-treatment imaging showed marked tumor shrinkage with normalization of the tumor markers. During treatment, the patient was diagnosed with early-stage lung cancer and underwent successful left S1+S2 segmentectomy with temporary suspension of immunotherapy. The therapeutic response of pancreatic cancer has been sustained for seven years, with minimal residual disease. This unprecedented response duration is particularly noteworthy considering his microsatellite stability, which typically predicts a limited response to immune checkpoint inhibition. This case demonstrates an exceptional response to nivolumab and metformin combination therapy in poorly differentiated pancreatic cancer. The remarkable durability of the response suggests the need for further investigation to identify patients most likely to benefit from this therapeutic approach. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 16 8 2024 A New Minimally Invasive Technique for Thoracolumbar/Lumbar Focal Kyphosis Due to Osteoporotic Vertebral Fracture: A Case Report e66069 EN Masato Tanaka Department of Orthopedic Surgery, Okayama University Hospital Abd El Kader Al Askar Department of Orthopedic Surgery, Okayama Rosai Hospital Chetan Kumawat Department of Orthopedic Surgery, Okayama Rosai Hospital Shashank J Ekade Department of Orthopedic Surgery, Okayama Rosai Hospital Koji Uotani Department of Orthopedic Surgery, Okayama University Hospital Osteoporotic vertebral fractures are common fractures in the elderly population and are often associated with low back pain and disruption in daily living activities. Reconstruction surgeries, such as corpectomy, are among the treatment options for these conditions. However, a corpectomy requires a longer surgical procedure and involves a significant amount of blood loss. We present the case of an 80-year-old woman with severe low back pain due to an L2 fracture and focal kyphosis treated with a novel minimally invasive technique. The patient underwent anterior and posterior surgery in the right decubitus position using a C-arm-free technique. Hyperlordotic cages were inserted in the upper and lower disc space via a lateral approach, while percutaneous pedicle screws were inserted from a posterior approach. These procedures were performed simultaneously under navigation guidance only. 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. 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. 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. 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. Methods Forty-eight AYA patients aged 15–39 years and 69 older patients aged ≥ 65 years with surgically treated stage I–II OSCC were retrospectively analyzed. Histological evaluation, survival analysis, immunohistochemistry for p53, p16, and MTAP, high-risk HPV RNA in situ hybridization, and fluorescence in situ hybridization for CDKN2A and MTAP were performed. Results Compared with older patients, OSCCs in AYAs were more frequently located on the tongue (93.7% vs. 47.8%) and more often exhibited a superficial spreading growth pattern (60.4% vs. 31.8%). AYA tumors more frequently showed modified WPOI-1, high tumor budding, and abnormal p53 immunophenotypes (85.4% vs. 68.1%). AYA patients showed significantly better overall and disease-free survival than older patients. Within the AYA group, depth of invasion (DOI) > 5 mm was associated with distant metastasis and poorer overall and disease-free survival. Postoperative lymph node metastasis occurred in 31.2% of AYAs. Univariable analysis suggested that clinical stage II, tumor thickness > 5 mm, DOI > 5 mm, and tumor budding scores 1–2 were associated with postoperative lymph node metastasis. Molecular status, including p53, p16/CDKN2A, and MTAP, did not provide robust prognostic stratification. Conclusion Early-stage AYA OSCC exhibits distinct clinicopathological features. DOI was the strongest prognostic indicator, whereas clinical stage, tumor thickness, and tumor budding may provide additional prognostic information regarding the risk of late nodal metastasis. No potential conflict of interest relevant to this article was reported.

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

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

Elsevier BV Acta Medica Okayama 1344-6223 84 2026 Factors that delay discovery in cases of death at home in Japan 102895 EN Yukie Yamasaki Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nanako Tamiya Department of Health Services Research, Faculty of Medicine, University of Tsukuba Hideki Yamamoto Department of Environmental Health, Faculty of Pharma-Science, Teikyo University Masanobu Miura Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaori Taniguchi Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chie Kobayashi Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Motomura Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ayako Himemiya-Hakucho Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Miyaishi Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences In Japan, solitary deaths have become a social issue, with an increasing number of cases in which the body is discovered long after death. This study aimed to clarify the factors underlying such delays. Cases of death at home were extracted from forensic autopsies. In each case, we collected information about the deceased and their living conditions. The postmortem interval until finding (PMI-f) was calculated by measuring the time between death and discovery. We classified the cases into long PMI-f (LPMI-f; having PMI-f of ≥3 days) and short PMI-f (SPMI-f; having PMI-f of <3 days), and examined the factors that lead to LPMI-f. The characteristics of the group living alone with a PMI-f of <24 h and living with family or acquaintances with an LPMI-f were also analyzed. Among the 420 cases included, 244 (58.1%) were in the LPMI-f group. The LPMI-f group had higher number of males; older individuals; those living alone; those found inside their homes; single, retired, or non-employed individuals; those without long-term care certification; and those with drinking habits. Forty-seven individuals lived alone and had PMI-f of <24 h. Regular visits from relatives living separately led to early detection after death. In the LPMI-f group, 56 individuals lived with family or acquaintances. The absence of regular visits can result in delayed discovery after death; however, the time between death and discovery could be shortened by implementing systems such as allowing neighbors to check the person's safety by noticing uncollected mail. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2090-6447 2026 1 2026 Carcinoma ex Pleomorphic Adenoma With an Epithelial‐Myoepithelial Carcinoma Component in the Submandibular Gland: A Case Report EN Tomohiro Yasuhara Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masanori Masui Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroaki Takakura Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiji Iwata Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koichi Kadoya Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koki Umemori Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Norie Yoshioka Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, 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 Background: Carcinoma ex pleomorphic adenoma (CXPA) is an uncommon malignant salivary gland tumor arising from pleomorphic adenoma, whereas epithelial-myoepithelial carcinoma (EMC) is a rare low-grade salivary gland malignancy. CXPA with an EMC component in the submandibular gland is uncommon. Case Report: A 65-year-old man presented with a painless, firm mass in the left submandibular region and weakness of the left lower lip. Computed tomography and magnetic resonance imaging demonstrated an irregular submandibular mass, and FDG-PET/CT showed increased uptake (maximum standardized uptake value, 9.2). Core biopsy suggested pleomorphic adenoma; however, the clinical and radiological findings strongly indicated malignancy. Incisional biopsy was therefore performed under general anesthesia, with a plan to proceed to definitive treatment if malignancy was confirmed. Intraoperative histopathological examination revealed a malignant salivary gland tumor, and tumor resection with neck dissection was completed during the same procedure. Histopathological examination showed invasive CXPA with an EMC component, accompanied by extracapsular invasion exceeding 6 mm, perineural invasion, and extension into adjacent muscle (pT3N0). Although surgical margins were negative, pulmonary metastases developed 12 months after surgery, followed by suspected pleural dissemination and spinal canal extension. The patient declined further aggressive treatment and died of the disease 48 months after surgery. Conclusion: This case highlights the importance of integrating clinical, radiological, and pathological findings for accurate diagnosis of salivary gland tumors, particularly when biopsy results are inconsistent with clinical suspicion. 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. 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 1323-8930 75 3 2026 Outcomes following the discontinuation of biologic therapy in patients with severe asthma 400 408 EN Tadao Nagasaki Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital Hisako Matsumoto Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Takashi Iwanaga Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Kazuto Matsunaga Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University Kiyoshi Sekiya Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital Tomoya Harada Department of Multidisciplinary Internal Medicine, Division of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University Shogo Sakurai Department of Respiratory Medicine, Shizuoka General Hospital Norihiro Harada Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine Toshiyuki Koya Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Koichi Fukunaga Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine Takeshi Kaneko Department of Pulmonology, Yokohama City University Graduate School of Medicine Kazuhisa Asai Department of Respiratory Medicine, Graduate School of Medicine, Osaka Metropolitan University Yuko Komase Department of Respiratory Medicine, St.Marianna University School of Medicine, Yokohama Seibu Hospital Yasuhiro Gon Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine Akihiko Tanaka Department of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of Medicine Hironori Sagara Department of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of Medicine Hironobu Sunadome Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University Tatsuya Nagano Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine Yoichi Nakamura Medical Center for Allergic and Immune Diseases, Yokohama City Minato Red Cross Hospital Akio Niimi Department of Respiratory Medicine, Allergy, and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences Noboru Hattori Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University Takashi Hajiro Department of Respiratory Medicine, Tenri Hospital Hajime Fujimoto Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine Masayuki Hojo Division of Respiratory Medicine, National Center for Global Health and Medicine Nobuaki Miyahara Department of Medical Technology, Okayama University Graduate School of Health Sciences Masafumi Yamaguchi Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science Kimiko Tsuji Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University Akiko Sano Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Ryuta Haraguchi Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Hiroyuki Sano Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Masato Muraki Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital Yuji Tohda Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine Background: Biologic therapies are pivotal in managing severe asthma. Despite their efficacy, some patients discontinue biologics, with varying outcomes. Predictors of successful versus unsuccessful discontinuation remain poorly defined. This study aimed to identify clinical factors associated with post-discontinuation outcomes in a real-world practice. Methods: This retrospective cohort included adults with severe asthma who had received biologics for at least 12 months and subsequently discontinued therapy for a minimum of three consecutive months. We assessed the effects of baseline blood eosinophilia (≥300 cells/μL), residual sputum symptoms during biologic therapy, treatment responsiveness, biologic class, and discontinuation reasons on post-discontinuation asthma exacerbation rates using multivariable Cox models. Results: A total of 118 patients were analyzed. The Kaplan–Meier analysis estimated a 65 % exacerbation-free probability at 12 months after discontinuation. Factors associated with successful discontinuation included a robust clinical response and absence of exacerbations before cessation. Conversely, baseline eosinophilia, residual sputum symptoms during biologics, and discontinuation due to inadequate therapeutic response or financial burden were associated with post-discontinuation exacerbations. In class-stratified restricted models, persistent sputum remained significantly associated with post-discontinuation exacerbations after stopping anti-IL-5 therapies, while baseline eosinophilia was associated with post-discontinuation exacerbations after stopping anti-IgE or anti-IL-4Rα. Among patients with sputum symptoms or poor-response discontinuation, the overall frequency of exacerbations declined after discontinuation. Conclusions: Baseline eosinophilia, persistent sputum during therapy, and discontinuation prompted by poor response or cost may serve as risk factors for post-discontinuation exacerbations; however, risk is phenotype- and class-dependent. Careful patient selection and monitoring are essential when considering the discontinuation of biologic treatment. No potential conflict of interest relevant to this article was reported.

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

岡山大学経済学会 Acta Medica Okayama 2433-4146 58 1 2026 ライブラリ・スキーマによる大学図書館構造の可視化と知識創造 ―共有認知の形成に基づく研究枠組みの構築― 1 19 EN Kensuke Kobayashi Satoru Miyazaki 10.18926/OER/70973 　This study proposes a theoretical framework for understanding the relationship between the structural representation of university libraries and knowledge creation. In recent years, university libraries have experienced significant transformations due to the digitization of scholarly information, the expansion of research data management, and the increasing importance of learning support services. As their functions diversify, it has become increasingly difficult to comprehensively understand the structure and roles of university libraries. 　To address this issue, this study focuses on the concept of a library schema, which represents the structural relationships among the elements that constitute a library, including people, resources, services, and activities. While previous research has discussed methods for organizing library components, little attention has been paid to how structural understanding of libraries contributes to knowledge creation and service value. 　Drawing on schema theory, shared cognition in organizational studies, and the knowledge creation theory of Nonaka and Takeuchi, this study constructs a conceptual framework linking library schema visualization, shared cognition, interaction, knowledge creation processes, and library service value. The framework proposes that visualization of library structure through a library schema promotes shared cognition among librarians and users, which in turn facilitates interactions that activate knowledge creation processes. These processes ultimately contribute to the creation of library service value that supports learning and research activities. 　Furthermore, the framework introduces two moderating factors: schema representation methods and operational constraints of library management. Based on this framework, six research propositions are presented. 　By integrating concepts from library and information science with knowledge management theory, this study contributes to the theoretical understanding of university libraries as knowledge infrastructures and provides a foundation for future empirical research on knowledge creation in library environments. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 65 7 2026 Nasal Mucosal Manifestation of Behçet's Disease 1069 1073 EN Hiroshi Akiyama 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 Yohei Masuda 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 Kenta Nakamoto Department of General Medicine, 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 Aki Sato Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Behçet's disease (BD) is a multisystem inflammatory condition that rarely affects the nasal mucosa. We report the case of a 25-year-old man presenting with prolonged fever, bilateral rhinalgia, and nasal obstruction, who was subsequently diagnosed with nasal ulcers associated with BD. These ulcers resolved along with the systemic symptoms following treatment with colchicine, apremilast, and prednisolone. Although there is no specific treatment strategy for nasal mucosal lesions in BD, standard systemic therapies may be effective. This case highlights nasal mucosal involvement as a rare but important manifestation of BD, emphasizing the importance of thorough evaluation and consideration of nasal symptoms for the diagnosis and treatment. No potential conflict of interest relevant to this article was reported.

American Society of Tropical Medicine and Hygiene Acta Medica Okayama 0002-9637 114 3 2026 A Case of Heavy Paragonimiasis Involving a Multi-Organ Presentation with Hypereosinophilia and Hepatic Migration 486 489 EN Hidemasa Akazawa Department of Infectious Diseases, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Kenta Nakamoto Department of Infectious Diseases, Okayama University Hospital Kohei Oguni Department of Infectious Diseases, Okayama University Hospital Yohei Manabe Department of Pharmacy, Okayama University Hospital Mio Kokubo-Tanaka Division of Parasitology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki Haruhiko Maruyama Division of Parasitology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki Fumio Otsuka Department of General Medicine, Okayama University Hospital Paragonimiasis is a parasitic disease caused by the genus Paragonimus, typically transmitted through the ingestion of raw or undercooked freshwater crabs. Although pulmonary involvement is typical, ectopic migration to subcutaneous or hepatic sites is rare and poses diagnostic challenges. A case of paragonimiasis in a 29-year-old Cambodian woman residing in Japan who presented with painless subcutaneous nodules on the chest and abdomen is reported in the current study. She had consumed raw crab 4 months before presentation. Laboratory findings revealed marked eosinophilia (21,000/µL) and elevated immunoglobulin E (5,049 IU/mL). Computed tomography scans revealed pleural effusion, club-shaped pulmonary consolidation, funicular hypodense lesions in the liver, and subcutaneous lesions. Stool and sputum test results were negative for parasite eggs; however, a microplate ELISA indicated a Paragonimus westermani infection. The patient responded well to 3 consecutive days of praziquantel (75 mg/kg/day) and was discharged a week later. This case highlights the importance of considering paragonimiasis in patients with unexplained subcutaneous nodules and eosinophilia, especially when supported by dietary risk factors. No potential conflict of interest relevant to this article was reported.

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

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

Wiley Acta Medica Okayama 2090-6447 2026 1 2026 A Rare Case of Hyperplastic Dental Follicle Presenting With an Unusually Large Radiolucent Area 2879891 EN Satoshi Otsuki Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koichi Kadoya Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chizuru Kobayashi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Kawazu Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hyperplastic dental follicle (HDF) is a rare odontogenic hamartomatous lesion typically associated with unerupted teeth in children and adolescents and is often found incidentally on radiographic imaging. HDF usually presents as a pericoronal radiolucency of 2–3 mm in diameter and is commonly difficult to distinguish from dentigerous cysts on radiographs. We report an unusual case of HDF in an 11-year-old male who was referred for evaluation of delayed eruption of the left maxillary canine. Panoramic radiography and cone-beam computed tomography (CBCT) revealed a remarkably large radiolucent area, with a maximum dimension of 25.3 mm. The initial clinical diagnosis was a dentigerous cyst; however, incisional biopsy revealed solid tissue characteristics, and histopathological examination confirmed HDF, with no evidence of cystic lining, neoplastic transformation, or inflammation. Following the patient′s and parents′ preference for complete removal, resection of the lesion together with extraction of the impacted canine was performed under general anesthesia. At the 6-month follow-up, no recurrence was observed and bone regeneration was confirmed on radiographic examination. This case underscores the diagnostic challenge posed by atypical radiographic findings and highlights the necessity of histopathological confirmation. Given the exceptional size and potential for recurrence, long-term follow-up is warranted. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0584 105 7 2026 WT1 mRNA in peripheral blood enables early prognostic stratification in AML patients receiving venetoclax and azacitidine therapy 105 EN Hiroyuki Sugiura Division of Internal Medicine, Fukuyama City Hospital Noboru Asada Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takeru Asano Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital Yasushi Hiramatsu Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital Tomohiro Urata Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Toshi Imai Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Makoto Nakamura Department of Hematology, Okayama City Hospital Kazuhiko Yamamoto Department of Hematology, Okayama City Hospital Tatsunori Ishikawa Department of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School Teachers Masanori Makita Department of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School Teachers Takanori Yoshioka Department of Hematology, NHO Okayama Medical Center Kazutaka Sunami Department of Hematology, NHO Okayama Medical Center Kyosuke Saeki Division of Hematology, Ehime Prefectural Central Hospital Yuichiro Nawa Division of Hematology, Ehime Prefectural Central Hospital Maiko Kimura Department of Hematology, Japanese Red Cross Okayama Hospital Makoto Takeuchi Department of Hematology, Japanese Red Cross Okayama Hospital Masaya Abe Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shoji Asakura Department of Internal Medicine, Okayama Rosai Hospital Tomofumi Yano Department of Internal Medicine, Okayama Rosai Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Venetoclax and azacitidine (VEN/AZA), which target BCL-2 and DNA methylation, have demonstrated substantial efficacy, particularly in older or unfit patients with acute myeloid leukemia (AML). Wilms’ Tumor-1 (WT1) mRNA, measurable in peripheral blood (PB), is an established biomarker for monitoring treatment response and predicting AML prognosis. We conducted a retrospective analysis of patients with AML treated with VEN/AZA within the Okayama Hematology Study Group (OHSG). Patients who showed a marked reduction in PB WT1 mRNA levels from baseline after the first or second treatment cycle had significantly improved overall survival (OS) and progression-free survival (PFS). Moreover, achieving PB WT1 mRNA negativity-regardless of whether this occurred early or later in the therapy།was consistently associated with superior OS and PFS. These findings suggest that PB WT1 mRNA is a sensitive and reliable biomarker for predicting treatment response and long-term outcomes in patients with AML receiving VEN/AZA. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 1471-2431 26 1 2026 Sebastidae-specific food allergy causing anaphylaxis: a pediatric case report and fish allergen analysis 628 EN Mitsuru Tsuge Department of Pediatric Acute Diseases, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Uda Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masanori Ikeda Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background Fish allergy affects approximately 0–0.3% of the population. Parvalbumin is the major allergen in fish allergy, and patients with fish allergy sensitized to parvalbumin demonstrate allergic reactions to various fish species. However, a subset of patients exhibits allergic responses to only specific fish species. Fish of the Sebastidae family, widely consumed in Asian, North American, and European countries, has rarely been reported as an allergenic trigger. Case presentation A 14-year-old Japanese boy visited our clinic for evaluation of fish allergy after experiencing allergic reactions to Sebastes alutus (Alaskan rockfish). He developed respiratory symptoms, eyelid edema, and skin erythema after consuming a meal containing Sebastes alutus, suggesting anaphylaxis; however, he was able to consume many other fish species without any issues. Skin prick tests and basophil activation tests using fish species from the Sebastidae family showed positive reactions, whereas other fish species that the patient could tolerate showed negative reactions. Immunoblot analysis performed to identify the causative allergen revealed two IgE-binding bands (17 and 110 kDa) in Sebastidae, distinct from parvalbumin. Mass spectrometry identified these proteins as alpha-actinin-3b, ATPase sarcoplasmic/endoplasmic reticulum Ca2 + transporting 1, and several myosin-related proteins. Conclusions This case highlights the need for clinicians to recognize fish allergy specific to the Sebastidae family. Identifying the causative non-parvalbumin allergens would improve understanding of fish allergy diversity and individualized dietary management for patients. Additional cases and detailed analyses are necessary to identify the specific allergens involved in Sebastidae allergy. No potential conflict of interest relevant to this article was reported.

American Society of Hematology Acta Medica Okayama 2473-9529 10 13 2026 Drivers of temporal improvement in CAR T-cell therapy for large B-cell lymphoma: a Japanese nationwide registry analysis 4427 4438 EN Yu Yagi Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Yusuke Kanemasa Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Toshiki Terao 2Department of Hematology, Okayama University Hospital, Okayama, Japan Motohiro Kato Department of Pediatrics, The University of Tokyo Tomoyasu Jo Department of Hematology, Kyoto University Hospital Tatsu Shimoyama Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Toshio Kitawaki Department of Hematology, Kyoto University Hospital Ryo Hanajiri Department of Hematology and Oncology, Nagoya University Graduate School of Medicine Noriko Doki Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Satoshi Yoshihara Department of Hematology, Hyogo Medical University Hospital Nobuharu Fujii Department of Hematology, Okayama University Hospital Noriko Iwaki Department of Hematology, National Cancer Center Hospital Go Yamamoto Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital Masatoshi Sakurai Division of Hematology, Department of Medicine, Keio University School of Medicine Toshihiro Matsukawa Department of Hematology, Hokkaido University Hospital Emiko Sakaida Department of Hematology, Chiba University Hospital Yasuhiro Nakashima Hematology and Hematopoietic Cell Transplantation, Osaka Metropolitan University Hospital Akiyo Yoshida Division of Transfusion Medicine, Kanazawa University Hospital Yoshihiro Umezawa Department of Hematology, Institute of Science Tokyo Hospital Haryoon Kim Division of Hematology, Department of Medicine, Keio University School of Medicine Keisuke Kataoka Division of Hematology, Department of Medicine, Keio University School of Medicine Hideki Goto 11Department of Hematology, Hokkaido University Hospital, Sapporo, Japan Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Koji Kato Department of Hematology, Oncology, and Cardiovascular Medicine, Kyushu University Hospital Real-world CD19 chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL) is characterized by expanded eligibility and evolving management practices. However, the prognostic impact of these changes remains inconsistent, and the specific drivers of outcomes remain unclear. This study analyzed 913 patients with relapsed/refractory (R/R) LBCL from a Japanese registry and compared the outcomes between 2 calendar periods (2019-2021 vs 2022-2024). The 2022-2024 cohort was older, had more adverse baseline features, and was less pretreated. Treatment patterns have shifted toward higher utilization of second-line therapy, a growing preference for axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel), and improved disease control before infusion. Accordingly, the 2022-2024 cohort achieved a longer progression-free survival (PFS; 6-month PFS, 63.2% vs 55.2%; P = .005), which persisted after adjusting for baseline characteristics using propensity score matching. Multivariable analysis identified second-line therapy, improved preinfusion disease control, and a shift in product selection from tisagenlecleucel to axi-cel or liso-cel as the primary drivers of this improvement. This benefit was pronounced in high-risk populations, including patients with stable or progressive disease at infusion (6-month PFS, 54.6% vs 43.8%; P = .012) and those who were refractory to first-line therapy (6-month PFS, 51.7% vs 40.3%; P = .013). Despite broader use in higher-risk populations and greater axi-cel exposure, 6-month nonrelapse mortality remained low (2.1% vs 1.5%). Real-world outcomes of CD19 CAR T-cell therapy for R/R LBCL have improved, predominantly driven by second-line therapy, enhanced preinfusion disease control, and increased use of more potent CAR T products. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 2169-9097 131 7 2026 Surface Geology and Evolution of Asteroid Ryugu: Insights From Hayabusa2 Global Mapping e2025JE009578 EN Lisa M. Vincent Department of Earth Sciences, Utrecht University Trishit Ruj Institute for Planetary Materials, Okayama University Goro Komatsu International Research School of Planetary Sciences, Università G. d'Annunzio Aditya Ray Department of Geology, Presidency University Hiroshi Kikuchi Gakushuin University Ryodo Hemmi Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Hideaki Miyamoto Department of Systems Innovation School of Engineering, The University of Tokyo Seiji Sugita Planetary Exploration Research Center, Chiba Institute of Technology the Hayabusa2 ONC science team Rubble-pile asteroids, characterized by loose aggregates of debris held together by gravity, represent both a significant planetary hazard and a key to understanding planetesimal formation. Geologic mapping of these bodies provides essential insights into their origins, evolution, and surface processes. This knowledge is crucial for advancing space mission capabilities, from precise navigation and safe sampling to assessing the feasibility of future asteroid mining. Here, we present the most comprehensive geologic map of Ryugu in comparison to previous early-stage and single-feature maps, integrating Optical Navigation Camera (ONC) mosaics, LIDAR-derived topography, Mobile Asteroid Surface Scout (MASCOT) descent images, and spectral slope data. The analysis includes reclassification of previously identified features and newly identified features from global to local scales. The geologic mapping technique followed United States Geological Survey (USGS) planetary cartography standards using the ArcGIS Pro platform. This global framework provides an essential geologic context for interpreting returned samples and constraining rubble-pile evolution. We identified geomorphological, structural, and surface texture units on Ryugu's unconsolidated rubble-pile surface using 0.2–0.7 m/pixel image mosaics. Elongated troughs at the poles and mirrored, oblique lineaments near the equatorial ridge are consistent with rotational strain. Compared with another rubble-pile asteroid Bennu, Ryugu shows a more uniform boulder distribution, and its immensely prominent equatorial ridge indicates a more intense period of rotational deformation. However, the western bulge deviates from this trend; its fewer boulders, underdeveloped ridges, and older degraded craters suggest selective resurfacing. These features show evidence of catastrophic disruption, rotational reshaping, and ongoing surface movement. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2977-0548 2 3 2026 Truncation by death in the sufficient-cause framework uuag021 EN Bronner P Gonçalves Faculty of Health and Medical Sciences, University of Surrey Eiji Yamamoto Okayama University of Science Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The sufficient-cause framework has been used for decades to improve our understanding of both basic and complex causal concepts in epidemiology, such as mediation and interaction. Here, we make use of this framework to provide a description of truncation by death, in which the outcome of interest is undefined for individuals who die before the assessment time at the end of follow-up. We explain the noncausal nature of the crude estimand that compares outcomes by treatment levels conditional on observed survival by showing that it corresponds to a comparison of distinct risk-status types, which are defined based on their susceptibility to sufficient causes. Further, expressions for the crude estimand and for the survivor average causal effect (SACE)—a causal estimand defined under the principal stratification approach—are provided in terms of population-level joint frequencies of the background factors of sufficient causes. Finally, we also describe conditions, based on background factors of sufficient causes, under which the SACE is null. Our description of this problem, which studies truncation by death from a new perspective, might encourage further analyses of principal stratification-based estimands using sufficient causes. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0019-9567 93 1 2025 A newly developed oral infection mouse model of shigellosis for immunogenicity and protective efficacy studies of a candidate vaccine e00346-2 EN Risha Haldar Division of Clinical Medicine, ICMR-National Institute of Cholera and Enteric Diseases Prolay Halder Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases Hemanta Koley Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases Shin-ichi Miyoshi Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Santasabuj Das Division of Clinical Medicine, ICMR-National Institute of Cholera and Enteric Diseases Shigella infection poses a significant public health challenge in the developing world. However, lack of a widely available mouse model that replicates human shigellosis creates a major bottleneck to better understanding of disease pathogenesis and development of newer drugs and vaccines. BALB/c mice pre-treated with streptomycin and iron (FeCl3) plus desferrioxamine intraperitoneally followed by oral infection with virulent Shigella flexneri 2a resulted in diarrhea, loss of body weight, bacterial colonization and progressive colitis characterized by disruption of epithelial lining, loss of crypt architecture with goblet cell depletion, increased polymorphonuclear infiltration into the mucosa, submucosal swelling (edema), and raised proinflammatory cytokines and chemokines in the large intestine. To evaluate the usefulness of the model for vaccine efficacy studies, mice were immunized intranasally with a recombinant protein vaccine containing Shigella invasion protein invasion plasmid antigen B (IpaB). Vaccinated mice conferred protection against Shigella, indicating that the model is suitable for testing of vaccine candidates. To protect both Shigella and Salmonella, a chimeric recombinant vaccine (rIpaB–T2544) was developed by fusing IpaB with Salmonella outer membrane protein T2544. Vaccinated mice developed antigen-specific serum IgG and IgA antibodies and a balanced Th1/Th2 response and were protected against oral challenge with Shigella (S. flexneri 2a, Shigella dysenteriae, and Shigella sonnei) using our present mouse model and Salmonella (Salmonella Typhi and Paratyphi) using an iron overload mouse model. We describe here the development of an oral Shigella infection model in wild-type mouse. This model was successfully used to demonstrate the immunogenicity and protective efficacy of a candidate protein subunit vaccine against Shigella. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 47 12 2024 Staphylococcus aureus δ-Toxin Induces Ca2+ Influx-Independent Degranulation of Murine Cultured Mast Cells 2058 2064 EN Kang Liu Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University Tomoaki Katayama Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hitomi Sato Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuho Hamaoka-Tamura Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University Michiko Saito Bioscience Research Center, Kyoto Pharmaceutical University Kazuyuki Furuta Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoshi Tanaka Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University Cutaneous colonization with Staphylococcus aureus (SA) is frequently observed in patients with atopic dermatitis. SA produces a wide variety of bacterial toxins, among which δ-toxin was found to induce degranulation of mast cells. Degranulation of mast cells could enhance bacterial clearance and protection from future SA infection but lead to exacerbation of atopic dermatitis. Because it remains to be determined how δ-toxin triggers degranulation, we investigated δ-toxin-induced changes in murine bone marrow-derived cultured mast cells in this study. We found that δ-toxin-induced degranulation could be classified into two phases, an early Ca2+-independent and a late Ca2+-dependent phase. Recent studies suggest that NOD-like receptor family, pyrin domain containing 3 is involved in the degranulation of mast cells, raising a possibility that leakage of K+ induced by δ-toxin is involved in the Ca2+-independent phase. However, Ca2+-independent degranulation remains unchanged although Ca2+-influx and degranulation induced by δ-toxin were significantly suppressed in the presence of high concentrations of K+. Because actin depolymerization was reported to induce degranulation in the absence of Ca2+ in the permeabilized rat peritoneal mast cells, a slow but steady decrease in the amount of filamentous actin observed here may be involved in Ca2+-independent degranulation induced by δ-toxin. Although Mas-related G protein-coupled receptor (MRGPR) X2 in humans and Mrgprb2 in mice are regarded as the receptors responsible for immunoglobulin E-independent degranulation, δ-toxin-induced degranulation remained unchanged in Mrgprb2−/− mast cells. Our findings pave the way for identification of the target receptors of δ-toxin. No potential conflict of interest relevant to this article was reported.

American Physical Society (APS) Acta Medica Okayama 2470-0010 113 5 2026 Analytical study of birefringent cavities for axionlike dark matter search 055009 EN Tadashi Kuramoto Research Institute for Interdisciplinary Science, Okayama University Yasutaka Imai Research Institute for Interdisciplinary Science, Okayama University Takahiko Masuda Research Institute for Interdisciplinary Science, Okayama University Yutaka Shikano Institute of Systems and Information Engineering, University of Tsukuba Sayuri Takatori Research Institute for Interdisciplinary Science, Okayama University Satoshi Uetake Research Institute for Interdisciplinary Science, Okayama University Light polarization plays a crucial role in optical-cavity experiments; however, mirror birefringence presents a significant challenge that must be addressed carefully. In this study, a rigorous, nonperturbative framework is developed to quantify birefringence effects by incorporating variations in reflectance and polarization misalignment. We analyze the impact of this framework on the sensitivity of axionlike particle (ALP) dark matter searches. The results show that both birefringence and misalignment contribute to sensitivity degradation in the low-mass regime; however, the adverse effects of misalignment can be mitigated by selecting a postselection angle greater than the misalignment angle. Furthermore, birefringence produces an additional resonance peak in the high-mass region, which remains largely unaffected by misalignment and postselection variations. This rigorous framework underscores the importance of considering birefringence in high-precision optical-cavity experiments for ALP detection. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0743-7463 40 52 2024 Formation of Nonspherical Cellulose Acetate Microparticles under Microflow 27314 27322 EN Kurumi Mori 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 Tsutomu Ono Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nonspherical particles have gained significant interest owing to their unique shapes and large specific surface areas, making them suitable for a wide range of applications, such as drug delivery, catalysis, and adsorption. However, conventional methods for preparing nonspherical particles face certain limitations. In this study, we propose a simple method for fabricating nonspherical cellulose acetate (CA) microparticles using a microfluidic device in which droplets undergo rapid diffusion in a continuous aqueous phase. The influence of variations in the flow rate ratio and continuous phase composition on the dimensionless Péclet number (Pe) within the droplet and shape of the resultant particles is investigated. Pe is critical, because it indicates the balance between polymer diffusion and droplet shrinkage dynamics. Our findings reveal that increasing the flow rate ratio and reducing the methyl acetate concentration in the continuous phase lead to faster droplet shrinkage and an increased Pe. A high Pe (>100) suggests that the reduction of the droplet interface predominates over polymer diffusion, resulting in the formation of a viscous layer near the droplet surface, which subsequently leads to nonspherical particle shapes (such as bowl-like or biconcave structures). In situ time-lapse observations of droplets from the top and side of a microchannel reveal that the formation of a viscous layer near the droplet surface and the deformation of the droplet, influenced by the z-axis location of the droplets during particle formation, ultimately determine the final particle shape. Based on these observations, a linear correlation between the initial conditions, i.e., the Pe and z-axis location at which the viscous layer formed, is established, enabling the prediction of the particle structure. In summary, the present study enhances the understanding of shape control in microfluidic particle formation and offers a novel guideline for the fabrication of spherical and nonspherical particles. No potential conflict of interest relevant to this article was reported.

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

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. 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). 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. 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 0911-6028 40 4 2024 Central dentinogenic ghost cell tumor of the maxilla: a case report with new imaging findings and review of the literature 561 568 EN Suzuka Yoshida Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Kawazu Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miki Hisatomi Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunsuke Okada Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mamiko Fujikura Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Hospital Kiyofumi Takabatake Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Saori Yoshida Preliminary Examination Room, Okayama University Hospital Junichi Asaumi Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences A dentinogenic ghost cell tumor (DGCT) is a rare benign odontogenic tumor that commonly shows characteristics of solid proliferation and has a relatively high risk of recurrence after surgical treatment. We herein report a case of a central DGCT that occurred in the maxilla and resulted in bone expansion. This study highlights new imaging findings (particularly magnetic resonance imaging) along with histopathological observations. In addition, we conducted a review of the existing literature on this rare tumor. A 37-year-old man developed swelling around the right cheek. A benign odontogenic tumor such as ameloblastoma was suspected based on the imaging examination findings (including bone expansion and the internal characteristics of the tumor) on panoramic imaging, computed tomography, and magnetic resonance imaging. The lesion was surgically excised from the right maxilla. Postoperative histopathological examination led to a definitive diagnosis of central DGCT. The tumor comprised epithelial neoplastic islands, resembling ameloblastoma, inside tight fibroconnective tissue; masses of ghost cells and formation of dentin were also observed. We had suspected that the minute high-density region around the molars on the imaging examinations represented alveolar bone change; however, it represented dentin formation. This led to difficulty diagnosing the lesion. Although DGCT may present characteristic findings on imaging examinations, its occurrence is infrequent, and in some cases, the findings may include the presence or absence of an impacted tooth without obvious calcification. The present case suggests that we should consider the possibility of an odontogenic tumor with calcification when high-density structures are observed inside the lesion. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 22 46 2024 A direct oxidative esterification of aldehydes with alcohols mediated by photochemical C–H bromination 9032 9035 EN Haru Ando Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Sakura Kodaki Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University The photochemical direct esterification of aldehydes with alcohols via in situ-generated acyl-bromides presented in this report is an attractive complementary addition to hitherto reported methods, as these are usually carried out in a two-step, one-pot procedure in order to avoid side reactions such as the oxidation of alcohols by halogen sources. 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. 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. 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. 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. 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.

Geological Society of America Acta Medica Okayama 0091-7613 53 11 2025 Long-term and multi-stage ice accumulation in the martian mid-latitudes during the Amazonian 945 950 EN Trishit Ruj Institute for Planetary Materials, Okayama University Hanaya Okuda Kochi Institute for Core Sample Research (X-star), JAMSTEC Goro Komatsu International Research School of Planetary Sciences, Università d’Annunzio Hitoshi Hasegawa Department of Global Environment and Disaster Prevention, Faculty of Science and Technology, Kochi University James W. Head Department of Earth, Environmental and Planetary Sciences, Brown University Tomohiro Usui Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Shun Mihira Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Makito Kobayashi Department of Systems Innovation, School of Engineering, University of Tokyo Subsurface ice in the mid-latitudes of Mars represents one of the largest present-day water ice reservoirs. While atmospheric models predict Late Amazonian (during the past hundreds of millions of years) obliquity-driven ice accumulation, its long-term variations, and the factors influencing accumulation remain unclear. Using geomorphological evidence and numerical modeling, we reveal a southwestern depositional trend within northern mid-latitudinal crater walls and floors. Detailed crater-fill deposit analyses indicate multiple glaciation stages, including an earlier, high-intensity stage followed by a later, lower-intensity stage, both exhibiting this southwestern trend (ca. 640–98 Ma). We conclude that persistent multiple-stage Amazonian glaciations were governed by atmospheric water availability and obliquity-driven climate cycles. No potential conflict of interest relevant to this article was reported.

Department of Mathematics, Faculty of Science, Okayama University Acta Medica Okayama 0030-1566 68 1 2026 Generator of the quadratic subextension of an odd dihedral extension 1 12 EN Toru Komatsu Department of Mathematics Faculty of Science and Technology Tokyo University of Science In this paper we present an algorithm to make a generator of the quadratic subextension of an odd dihedral extension. As an application we solve the Galois group problem for the quintic polynomials given by Kishi and Yamada. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 65 10 2026 Mycobacterium intracellulare Infection in a Japanese Patient with Signal Transducer and Activator of Transcription-3 Gain-of-function Syndrome 1421 1430 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Yoshiaki Soejima 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 Yoji Hirai Department of Dermatology, 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 Marina Kawaguchi Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Kenta Nakamoto Department of Infectious Diseases, Okayama University Hospital Kohei Oguni Department of Infectious Diseases, Okayama University Hospital Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Uda Department of Pediatrics, Okayama University Hospital Masato Yashiro Department of Pediatrics, Okayama University Hospital Kousei Hasegawa Department of Pediatrics, Okayama University Hospital Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Signal transducer and activator of transcription-3 (STAT3) gain-of-function (GOF) syndrome predisposes patients to autoimmunity diseases. Yet, nontuberculous mycobacterial (NTM) infections have rarely been described. We herein report a teenage Japanese patient with genetically confirmed STAT3-GOF syndrome who developed Mycobacterium intracellulare disease. Combination antimycobacterial chemotherapy reduced the bacterial burden; however, the refractory NTM infection relapsed after initiation of adjunctive tofacitinib therapy. The present case demonstrates that host-directed therapy must be combined with prolonged antimycobacterial regimens to control drug-resistant NTM in patients with inborn errors of immunity. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2056-3426 12 2025 Optimizing β-TCP with E-rhBMP-2-infused fibrin for vertical bone regeneration in a mouse calvarium model rbae144 EN Kun Zhao Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuaki Ono Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Xindi Mu Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ziyi Wang Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shichao Xie Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Yonezawa Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Okada Division of Dental Biomaterials, Tohoku University Graduate School of Dentistry Takuya Matsumoto Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshitaka Oohashi Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Effective reconstruction of large bone defects, particularly in thickness, remains one of the major challenges in orthopedic and dental fields. We previously produced an Escherichia coli-based industrial-scale GMP-grade recombinant human bone morphogenetic protein-2 (E-rhBMP-2) and showed that the combination of E-rhBMP-2 with beta-tricalcium phosphate (β-TCP/E-rhBMP-2) can effectively promote bone reconstruction. However, the limited mechanical strength and poor morphology retention of β-TCP granules are key points that need optimization to obtain more effective grafts and further expand its clinical applications. Therefore, we combined β-TCP/E-rhBMP-2 with fibrin gel to enhance its mechanical properties and usability for vertical bone regeneration. We investigated the mechanical properties and vertical bone regeneration effects of the materials applied, with or without fibrin containing E-rhBMP-2, in a calvarial defect model in mice. Compression tests were conducted to assess the initial stability of the materials. Scanning electron microscopy and Fourier transform infrared spectroscopy were conducted to characterize the presence of fibrin on the scaffold. After 4 and 12 weeks of implantation, micro-computed tomography and histological and immunofluorescent analyses were performed to assess the morphology and volume of the newly formed bone. The fibrin-containing groups had significantly higher initial mechanical strength and higher ability to maintain their morphology in vivo compared to the counterparts without fibrin. However, fibrin gel alone suppressed the bone formation ability of β-TCP/E-rhBMP-2 whereas the presence of high doses of E-rhBMP-2 in fibrin gel resulted in material resorption and enhanced new bone formation. In conclusion, fibrin gel significantly improved the mechanical strength and surgical manageability of the β-TCP/E-rhBMP-2 scaffold, and the addition of E-rhBMP-2 to the fibrin gel further enhanced the vertical bone regeneration and initial structural integrity of the scaffold. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2407 25 1 2025 Long-term outcomes of salvage high-dose-rate brachytherapy for localized recurrence of prostate cancer following definitive radiation therapy: a retrospective analysis 524 EN Kenta Watanabe Department of Radiology, Okayama University Hospital Nobuhiko Kamitani Department of Radiology, Kawasaki Medical School Naoki Ikeda Department of Radiology, Kawasaki Medical School Yujiro Kawata Department of Radiology, Kawasaki Medical School Ryoji Tokiya Department of Radiology, Kawasaki Medical School Takafumi Hayashi Department of Radiology, Kawasaki Medical School Yoshiyuki Miyaji Department of Urology, Kawasaki Medical School Tsutomu Tamada Department of Radiology, Kawasaki Medical School Kuniaki Katsui Department of Radiology, Kawasaki Medical School Background Salvage high-dose-rate brachytherapy (HDR-BT) is a potential treatment for localized recurrence of prostate cancer following definitive radiation therapy. This study aimed to evaluate the long-term safety and efficacy of HDR-BT alone, without androgen deprivation therapy (ADT), in this patient population. Methods We conducted a retrospective analysis of patients with prostate cancer who developed pathologically confirmed local recurrence after definitive radiation therapy and were treated with salvage HDR-BT alone at Kawasaki Medical School Hospital between 2007 and 2021. The prescribed HDR-BT dose was 22 Gy in 2 fractions. Biochemical relapse-free survival (bRFS), cause-specific survival (CSS), and overall survival (OS) were assessed using the Kaplan–Meier method. Adverse events were evaluated based on the Common Terminology Criteria for Adverse Events. Results Thirty-five patients were included, with a median follow-up of 66.0 months (range, 8.1–169.1). The 5-year bRFS, CSS, and OS rates were 29.7%, 100%, and 89.3%, respectively. Biochemical recurrence occurred in 21 patients (60.0%). Grade 2 adverse events were reported in eight patients (22.9%), while two (5.7%) experienced grade 3 adverse events. All grade 3 adverse events occurred in patients who had HDR-BT as their initial definitive radiation therapy. Conclusions Salvage HDR-BT without ADT is a safe and effective treatment option for localized prostate cancer recurrence after definitive radiation therapy. It provides excellent CSS rates with acceptable toxicity while potentially reducing the need for ADT. Further prospective studies are warranted to confirm these findings. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Boulder populations and orientation trends on asteroid Ryugu: implications for rubble-pile surface processes 14404 EN Aditya Ray Institute for Planetary Materials, Okayama University Trishit Ruj Institute for Planetary Materials, Okayama University Goro Komatsu International Research School of Planetary Sciences, Università G. d‘Annunzio Lisa M. Vincent Department of Earth Sciences, Utrecht University Hiroshi Kikuchi Gakushuin University Ryodo Hemmi Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Jens Ormö Centro de Astrobiología (CAB), CSIC-INTA Asteroid (162173) Ryugu is a spinning-top shaped, rubble-pile C-type asteroid with a surface dominated by boulders spanning a broad size-range. Using Hayabusa2 ONC-T mosaics for mapping, we present the most extensive global boulder dataset to date, representing an eleven-fold increase over the earliest survey and greater completeness than later AI-based estimates. Crucially, this work provides the first global boulder orientation dataset. The cumulative size-frequency distribution follows a power-law slope of − 2.665 ± 0.066 (boulders ≥ 3 m), indicating its fragmented nature. Boulder density is lower along the equatorial ridge, consistent with regolith accumulation during earlier YORP-driven spin-up and poleward migration of blocks during the present spin-down phase. Orientation analyses reveal systematic hemispheric trends in what we define as slope-breaker zones (i.e., regions of high slope differentials), with NW–SE alignment in the northern hemisphere and NE–SW in the southern hemisphere, but absent at the equatorial ridge and poles. We interpret these as reorientations that developed during downslope boulder migration, as despite ongoing spin-down, the current spin rate remains high enough to drive such motion. In addition, fresh craters exhibit locally heightened boulder densities, recording ongoing resurfacing by impact events that exhume buried subsurface boulders and segregate them from finer regolith via seismic shaking induced granular convection. Together, these results yield new insights into rubble-pile surface evolution, rotational dynamics, and impact-driven resurfacing, with boulder orientations providing critical evidence of spin-related downslope transport and establish a framework for comparative asteroid studies. 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. 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.

Elsevier BV Acta Medica Okayama 1931-5244 295 2026 A novel spontaneous rat model of chronic kidney disease with mitochondrial dysfunction driven by thioredoxin insufficiency 51 64 EN Iori K. Ohmori Section of Developmental Physiology and Pathology, Faculty of Education, Okayama University Mamoru Ouchida Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiko Hada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinya Toyokuni Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine Tomoji Mashimo Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo Background: Chronic kidney disease (CKD) is a global health burden with high prevalence and poor prognosis. Although oxidative stress and mitochondrial dysfunction have been implicated in its pathogenesis, in vivo causal evidence remains limited. Thioredoxin (Trx), encoded by Txn1, is a redox-active protein that plays a central role in controlling oxidative stress and maintaining intracellular redox homeostasis. Methods: To address this gap, we investigated the lifelong phenotypes of Txn1-F54L mutant rats harboring approximately one-third of the normal Trx activity. These rats were generated via N-ethyl-N-nitrosourea mutagenesis and validated by clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 genome editing. Comprehensive analyses included biochemical testing, histopathology, immunohistochemistry, transmission electron microscopy, RNA-sequencing, western blotting, and cytokine profiling. Results: Txn1-F54L mutant rats spontaneously developed progressive CKD, with median survival times of 110–119 days for homozygotes and 303–346 days for heterozygotes. Their clinical features—elevated blood urea nitrogen, hypoalbuminemia, hypercholesterolemia, hypertension, and arterial medial sclerosis—closely resembled those of human CKD. Histopathological evaluation revealed extensive tubular injury, interstitial fibrosis, and glomerulosclerosis. Transcriptomic profiling identified 3,418 differentially expressed genes significantly enriched in immune activation and fibrosis pathways. Mitochondrial dysfunction was prominent in proximal tubules, accompanied by oxidative stress accumulation and concurrent activation of regulated cell death pathways (apoptosis, necroptosis, and pyroptosis). Elevated serum levels of interleukin-1β, interleukin-6, and interferon-γ indicated systemic inflammation. Conclusions: Our findings demonstrate that lifelong Trx deficiency induces oxidative stress–mediated mitochondrial dysfunction and regulated cell death, leading to inflammation and progressive CKD. This study establishes the Txn1 mutant rat as a valuable spontaneous CKD model, providing translational insights and a platform for developing therapeutic strategies targeting oxidative stress–induced pathways. 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 Common Bile Duct Stone Formed Around an Ingested Fish Bone 219 223 EN Kaitaro Higashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Shuta Tamura Department of Gastroenterological Surgery, Kochi Health Sciences Center Sunao Uemura Department of Gastroenterological Surgery, Kochi Health Sciences Center Teppei Tokumaru Department of Gastroenterological Surgery, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Case Report 10.18926/AMO/70858 An 86-year-old man presented with epigastric pain. He had previously undergone distal gastrectomy with Roux-en-Y reconstruction. Computed tomography (CT) revealed a 32×17 mm common bile duct (CBD) stone with an internal 20 mm linear hyperdense component. Endoscopic removal was unsuccessful due to the size and impaction of the stone. Open choledochotomy retrieved multiple stones and a calcified fish bone, which was confirmed by infrared spectroscopy using the potassium bromide (KBr) wafer method. Although fish bone ingestion is relatively common, this case highlights that such foreign bodies can occasionally serve as a nidus for CBD stone formation, leading to unexpected and clinically significant pathologies. When CT demonstrates a linear high-attenuation intraductal structure, clinicians should suspect a bone fragment and follow a stepwise approach, considering early surgical intervention when endoscopic extraction is unsuccessful or likely to be challenging. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 HIP COMPASS®: A Mechanical Intraoperative Navigation Guide Associated with Improved Revision-Free Implant Survivorship after Ceramic-on-Ceramic Total Hip Arthroplasty at Minimum 10-Year Follow-up 195 202 EN Yoshiaki Tei Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Norio Imai Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Keishi Kimura Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Yuki Hirano Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Yoji Horigome Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Ken Suda Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Hiroyuki Kawashima Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Original Article 10.18926/AMO/70855 HIP COMPASS® has demonstrated improved accuracy in intraoperative support for the acetabular component insertion angle. We assessed long-term revision-free implant survivorship following total hip arthroplasty (THA) using HIP COMPASS, with ≥10 years of follow-up. We retrospectively analyzed 210 hips of 186 patients who underwent cementless THA with ceramic-on-ceramic bearing couples, with or without HIP COMPASS. The mean follow-up duration was 10.8 years in the HIp COMPASS group and 12.7 years in the control group. Overall, 86.0% and 78.2% of cups were placed within Lewinnek’s safe zone with and without HIP COMPASS, respectively. Variability in radiographic inclination and anteversion was greater in the control group than in the HIP COMPASS group. Dislocation rates were 3.2% in the control group and 1.2% in the HIP COMPASS group, with no significant difference between groups. The control group had a significantly higher revision rate than the HIP COMPASS group (7.3% vs. 1.2%). Use of HIP COMPASS was associated with improved long-term revision-free implant survivorship over ≥ 10 years and more consistent acetabular component positioning at an appropriate insertion angle, which may contribute to stable initial fixation. 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.

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. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 17 1 2026 Structural insights into YheS-mediated release of SecM-arrested ribosome 4963 EN Kaishi Iso Department of Biological Sciences, Graduate School of Science, The University of Tokyo Toma Ikeda School of Life Science and Technology, Institute of Science Tokyo Kohei Yamasaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yushin Ando Department of Biological Sciences, Graduate School of Science, The University of Tokyo Fumiya K. Sano Department of Biological Sciences, Graduate School of Science, The University of Tokyo Tadaomi Furuta School of Life Science and Technology, Institute of Science Tokyo Hideki Taguchi School of Life Science and Technology, Institute of Science Tokyo Osamu Nureki Department of Biological Sciences, Graduate School of Science, The University of Tokyo Yuhei Chadani Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yuzuru Itoh Department of Biological Sciences, Graduate School of Science, The University of Tokyo ATP-binding cassette subfamily F (ABCF) proteins interact with the ribosome to resolve translation defects near the peptidyl transferase center (PTC). In Escherichia coli, four ABCF proteins (EttA, Uup, YbiT, and YheS) selectively promote translation of distinct problematic nascent peptide sequences, but their molecular mechanisms remain unclear. Here, we present a 2.8 Å cryo-EM structure of the ribosome in complex with an ATPase-deficient mutant of YheS and investigate how it releases ribosomes arrested by the SecM nascent chain. YheS binds to the ribosomal E-site via the L1 stalk, and its P-site tRNA-interaction motif (PtIM) extends toward the PTC, displacing the CCA end of the P-site tRNA. Notably, the cryo-EM density corresponding to the SecM nascent chain within the exit tunnel is largely lost upon YheS binding. These observations suggest that YheS relieves peptide sequence-dependent stalling by perturbing nascent chain-tunnel interactions through P-site tRNA relocation. Steered molecular dynamics simulations provide qualitative support for this model. Together, our findings provide mechanistic insight into a mode of arrest release distinct from the translocon-mediated release mechanism. 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. 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. 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. 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. 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.

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

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

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

Springer Science and Business Media LLC Acta Medica Okayama 1068-9265 33 5 2026 Novel Arterial Reconstruction of the Left Gastric Artery Supplying the Replaced Left Hepatic Artery in Distal Pancreatectomy with Celiac Axis Resection 4118 4121 EN Kosei Takagi Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Atene Ito Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomokazu Fuji Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuya Yasui Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takeyoshi Nishiyama Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuo Nagai Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shohei Yokoyama Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background. Distal pancreatectomy with celiac axis resection (DP-CAR) with reconstruction of the left gastric artery (LGA) is a technically challenging procedure. The middle colic artery is commonly used for LGA reconstruction. This study highlights our novel arterial reconstruction of the LGA using the common hepatic artery (CHA) supplying the replaced left hepatic artery (rLHA) during DP-CAR. Patient and Methods. A 65-year-old man diagnosed with locally advanced unresectable pancreatic body cancer underwent DP-CAR following systemic chemotherapy. As a rLHA arising from the LGA was present, arterial reconstruction was necessary. Results. After confirming resectability, the CHA and LGA were encircled. Following division of the pancreas and radical lymphadenectomy, the origin of the celiac axis (CA) was divided. Subsequently, the CHA and LGA were transected and anastomosed. An indocyanine green fluorescence system was used to confirm adequate arterial blood supply and satisfactory tissue perfusion. Operative time was 215 min, with an estimated blood loss of 35 mL. Conclusions. This study demonstrated a novel arterial reconstruction of the LGA supplying the rLHA during DP-CAR. The CHA may be a candidate for the reconstruction of the LGA in DP-CAR. No potential conflict of interest relevant to this article was reported.

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

International Institute of Anticancer Research Acta Medica Okayama 0258-851X 40 1 2026 Modified Subtraction Technique for the Middle Hepatic Vein Tributary and Glissonean Pedicle in Right Lobe Graft Procurement 349 354 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 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 SHOHEI YOKOYAMA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences YUZO UMEDA Department of Hepatobiliary Pancreatic Surgery, Ehime University Graduate School of Medicine TOSHIYOSHI FUJIWARA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background/Aim: The procurement of right lobe grafts while preserving the middle hepatic vein (MHV) tributaries (V5 and V8) just before graft retrieval is technically challenging. Moreover, the safe isolation of the hepatic duct from the Glissonean pedicle is essential in living donor hepatectomy. To date, few studies have reported surgical techniques for preserving the MHV tributaries during right lobe graft procurement. Patients and Methods: This report presents our modified subtraction technique for managing the MHV tributaries and Glissonean pedicle during right lobe graft procurement. First, a subtraction technique for the MHV tributaries was initiated by isolating the right Glissonean pedicle. The lower tip of the tape was placed behind the caudate lobe and passed behind the right hepatic vein. Each end of the tape was then passed behind V5 and V8, followed by dissection of the remaining liver parenchyma between them. Subsequently, a subtraction technique for the Glissonean pedicle was applied to safely isolate the right hepatic duct and hilar plate. Results: Between September 2011 and May 2025, seven donors underwent right lobe graft procurement using the subtraction technique for the middle hepatic vein tributaries. The mean operative time was 381 min with an estimated blood loss of 217 ml. Using the subtraction technique, all middle hepatic vein tributaries were preserved just before graft retrieval. Conclusion: This study presents subtraction techniques used during living donor hepatectomy. The technique may facilitate liver parenchyma dissection while preserving MHV tributaries just before graft retrieval and isolating the Glissonean pedicle. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0258-851X 40 3 2026 Impact of Donor Cirrhosis Outcome Risk Estimator (CORE) Score on Recipient Outcomes Following Living-donor Liver Transplantation 1570 1576 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 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 NAOHIRO OKADA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences SHOHEI YOKOYAMA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TOSHIYOSHI FUJIWARA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background/Aim: Several studies have investigated predictive factors for outcomes of living-donor liver transplantation (LDLT). However, few have examined the clinical significance of the Cirrhosis Outcome Risk Estimator (CORE) score on prognosis following LDLT. This study aimed to investigate the impact of donor CORE scores in predicting the outcomes of patients undergoing LDLT. Patients and Methods: This single-center retrospective study included 362 adult LDLT recipients at our Institution between January 1998 and December 2024. Patient and graft survival rates were compared between the groups with low (≤0.05) and high (>0.05) CORE scores. Subsequently, multivariate analyses were performed to investigate prognostic factors for survival, including the CORE score. Results: Patients in the group with a low CORE score had significantly better survival (p=0.001; 5-year, 85.3% vs. 76.2%) and graft survival (p=0.001; 5-year, 84.1% vs. 74.6%) than those with a high CORE score. Multivariate analyses identified the CORE score (>0.05) as an independent predictor of patient survival (hazard ratio=1.70, 95% confidence interval=1.01-2.62, p=0.018) and graft survival (hazard ratio=1.66, 95% confidence interval=1.07-2.57, p=0.024). Conclusion: This study demonstrated the clinical significance of donor CORE scores in recipient outcomes after LDLT. Assessment of the donor CORE score may be useful for evaluating the quality of liver grafts and estimating recipient outcomes. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 1868-6974 32 11 2025 Risk Factors and Strategies for Failure to Rescue Following Hepatectomy: A Review 801 809 EN Jiro Kimura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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 Takeyoshi Nishiyama 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 Failure to rescue (FTR), defined as mortality after major postoperative complications, is a crucial indicator of surgical quality. Although mortality rates after hepatectomy have declined owing to improved surgical techniques and perioperative care, FTR remains a major concern. This review synthesizes the current evidence on the risk factors contributing to FTR after hepatectomy and explores multidisciplinary strategies to reduce its rate. Post-hepatectomy liver failure, hemorrhage, bile leakage, and sepsis commonly precede FTR. Risk factors for FTR are multifactorial and include patient-, procedure-, and system-related factors. Higher procedural volumes are associated with lower FTR rates, likely due to better infrastructure, experienced personnel, and access to rapid interventions. Strategies to reduce the FTR rate include preoperative optimization, intraoperative precision, and vigilant postoperative surveillance. System-level approaches, such as multidisciplinary rounds, standardized escalation protocols, and a robust institutional safety culture, are also pivotal. Future innovations, such as predictive analytics, artificial intelligence, and wearable monitoring devices, offer considerable potential for the early detection of complications. Centralization of complex liver surgeries to high-volume centers is recommended to enhance team preparedness. This review emphasizes the importance of adopting a comprehensive, proactive, and technologically integrated approach to reduce the FTR rate after hepatectomy and improve patient survival. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1068-9265 33 7 2026 Association of Preoperative Inspiratory Muscle Weakness and Respiratory Sarcopenia with Postoperative Pneumonia Following Esophagectomy: A Multicenter Retrospective Cohort Study 6296 6305 EN Kazuki Okura Department of Rehabilitation Medicine, Akita University Hospital Tomohiro Ikeda Department of Rehabilitation Medicine, Okayama University Hospital Hiroki Sato Department of Rehabilitation, Kawasaki University of Medical Welfare Sho Katayama Department of Rehabilitation Medicine, Okayama University Hospital Yusuke Takahashi Department of Rehabilitation Medicine, Akita University Hospital Yushi Nagaki Department of Esophageal Surgery, Akita University Hospital Akiyuki Wakita Department of Esophageal Surgery, Akita University Hospital Naoaki Maeda Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunsuke Tanabe Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Fujiwara Department of Digestive Surgery, Kawasaki Medical School Kazuhiro Noma Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Sato Department of Esophageal Surgery, Akita University Hospital Yuji Kasukawa Department of Rehabilitation Medicine, Akita University Hospital Naohisa Miyakoshi Department of Rehabilitation Medicine, Akita University Hospital Background Esophagectomy is associated with a high rate of postoperative pneumonia, which significantly impacts patient outcomes, including survival and quality of life. While some modifiable risk factors have been identified, the specific role of preoperative respiratory muscle function remains to be fully elucidated. Therefore, this study was designed to investigate the association of preoperative inspiratory muscle weakness (IMW) and respiratory sarcopenia (RS) with postoperative pneumonia in patients with esophageal cancer who underwent esophagectomy. Methods Patients with esophageal cancer who underwent esophagectomy between July 2021 and June 2023 were enrolled in this multicenter, retrospective, cohort study. The primary outcome was postoperative pneumonia, while preoperative IMW and RS were the main exposures. Respiratory sarcopenia was defined as the presence of both IMW and low skeletal muscle mass, which is assessed by using bioelectrical impedance analysis. Associations were analyzed by using G-computation within a Bayesian framework. Results A total of 213 patients were enrolled in this study. Postoperative pneumonia occurred in 42 patients (19.7%). Preoperative IMW was strongly associated with an increased risk of pneumonia, with a mean risk difference (RD) of 18.1% (95% credible interval [CrI] 5–33.6). The posterior probability that the RD exceeds 5% was > 98%. Respiratory sarcopenia also showed a potential association, although with greater uncertainty (mean RD, 11.2%; 95% CrI − 3.8 to 27.9). The posterior probability that the RD exceeds 5% was 76.7%. Conclusions Preoperative IMW is a notable risk factor for postoperative pneumonia following esophagectomy. While a potential link with RS was found, its role remains uncertain and requires further investigation. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 1347-9032 2026 Plasma Protein Analysis for Biomarker Discovery in Lung Cancer Treated With Atezolizumab Combination Therapy in J-TAIL-2 1 13 EN Yasushi Goto 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 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 Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Yasutaka Watanabe Department of Thoracic Oncology, Saitama Cancer Center Nobuyuki Katakami Department of Pulmonary Medicine and Medical Oncology Takarazuka City Hospital Takarazuka Japan Akira Kisohara Department of Respiratory Medicine, Kasukabe Medical Center Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Hirotaka Kuroki Chugai Pharmaceutical Co., Ltd. Masamichi Sugimoto Chugai Pharmaceutical Co., Ltd. Hisao Ashimura Chugai Pharmaceutical Co., Ltd. Misa Tanaka Chugai Pharmaceutical Co., Ltd. Akihiko Gemma Nippon Medical School J-TAIL-2 evaluated the efficacy and safety of atezolizumab, an anti–programmed death-ligand 1 (PD-L1), plus chemotherapy in patients with non-small cell lung cancer (NSCLC) and extensive-stage small cell lung cancer (ES-SCLC) in Japanese clinical practice, demonstrating comparable outcomes to those in the corresponding Phase 3 trials. Although PD-L1 expression is predictive of atezolizumab efficacy in some settings, additional minimally invasive, blood-based biomarkers are needed. This exploratory biomarker study included 359 J-TAIL-2 patients. The NSCLC cohort received atezolizumab combined with carboplatin and nab-paclitaxel (CnP, n = 42), cisplatin/carboplatin and pemetrexed (n = 72), or bevacizumab plus carboplatin and paclitaxel (bev + CP, n = 135). The ES-SCLC cohort received atezolizumab plus carboplatin and etoposide (n = 100). Approximately 560 cancer- or immune-related proteins were evaluated using the Proximity Extension Assay from blood plasma collected at three timepoints: baseline, before the second atezolizumab dose, and at the onset of immune-related adverse events (irAEs). Protein-wise comparisons were made to evaluate significant changes (P < 0.05 and > 0.5 log2 fold change) and linked to clinical outcomes reported in J-TAIL-2. IL-6, MUC-16, and KRT-19 were associated with shorter progression-free survival across multiple regimens. Granzyme A and B, immune activation markers, were elevated in responders who received atezolizumab + CnP and atezolizumab + bev + CP. High levels of baseline immune stimulation proteins were associated with irAEs across regimens. Protein expression changes were varied and regimen-dependent in subgroup analyses including older patients and those with EGFR-mutant tumors. These data warrant further investigation across different cancer types and atezolizumab-containing regimens to determine their relevance to efficacy and irAE occurrence of atezolizumab combination therapy. 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.

Frontiers Media SA Acta Medica Okayama 1663-9812 17 2026 Hochuekkito attenuates anxiety-like behavior associated with pulmonary inflammation induced by intratracheal lipopolysaccharides in mice 1774957 EN Yasuhisa Izushi Department of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu University Soichiro Ushio Department of Pharmaceutical Sciences for Health Crisis Management, Faculty of Pharmaceutical Sciences, Fukuoka University Teppei Ueda Department of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu University Yuichi Tasaka Laboratory of Clinical Pharmacy, School of Pharmacy, Shujitsu University Ikuko Miyazaki Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masato Asanuma Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihisa Kitamura Department of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu University Introduction: We have previously demonstrated that intratracheal lipopolysaccharide (LPS) injection induces significant pulmonary inflammation accompanied by hippocampal microglial activation, indicative of neuroinflammation. Hochuekkito (HET) is a traditional Japanese herbal medicine used to treat various conditions, including mental disorders and physical weakness. We have previously reported that HET ameliorates anxiety-like behaviors induced by intraperitoneal LPS injections in mice. However, its anxiolytic effects on anxiety-like behaviors due to pulmonary inflammation remain poorly understood. Therefore, in the present study, we aimed to investigate the effects of HET on anxiety-like behaviors induced by intratracheal LPS injection in mice. Methods: Mice received HET (1.0 g/kg) once daily for 2 weeks through oral gavage prior to LPS treatment. The light-dark box test was conducted 24 h following LPS injection to assess anxiety-like behaviors. Diazepam, a clinically used anxiolytic, served as a positive control. The lung wet-to-dry weight ratio was determined, and the concentrations of interleukin-6 (IL-6) in the lungs and serum were assessed. Results: Repeated administration of HET prevented the development of anxiety-like behaviors and reduced serum IL-6 concentrations and hippocampal Il6 mRNA expression levels in LPS-treated mice. Diazepam failed to exert significant effects in LPS-treated mice, whereas HET remained effective under inflammatory conditions. Moreover, LPS injections significantly increased the number of Iba-1-immunoreactive microglial cells in the CA1 region of the hippocampus, whereas this effect was suppressed by treatment with HET. In the bronchoalveolar lavage fluid (BALF), the LPS-induced increase in white blood cell count was significantly reduced by treatment with HET. Furthermore, HET alleviated LPS-induced pulmonary inflammation, as evidenced by decreased lung wet-to-dry weight ratios. Conclusion: This study suggests that inflammation induced by intratracheal LPS injection contributes to anxiety-like behaviors in mice and that IL-6 may play a key role in linking peripheral inflammation to neuroinflammatory responses. The anxiolytic effects of HET appear to be associated, at least in part, with the suppression of IL-6 elevation in both the periphery and the hippocampus, along with attenuation of microglial activation. Our findings suggest that HET may serve as a potential therapeutic agent for anxiety-like behaviors associated with pulmonary inflammation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0919-8172 33 5 2026 Comparative Efficacy of First-Line Immune Checkpoint Inhibitor-Based Combination Therapies in Patients With Sarcomatoid Renal Cell Carcinoma: A Japanese Multicenter Cohort Study e70494 EN Keita Tamura Department of Urology, Hamamatsu University School of Medicine Yuto Matsushita Department of Urology, Hamamatsu University School of Medicine Hiromitsu Watanabe Department of Urology, Hamamatsu University School of Medicine Takafumi Yanagisawa Department of Urology, Jikei University School of Medicine Keiichiro Mori Department of Urology, Jikei University School of Medicine Hirofumi Morinaka Department of Urology, Kawasaki Medical School Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shingo Toyoda Department of Urology, Kindai University Faculty of Medicine Takuhisa Nukaya Department of Urology, Fujita-Health University School of Medicine Ryoichi Maenosono Department of Urology, Osaka Medical and Pharmaceutical University Kazumasa Komura Department of Urology, Kawasaki Medical School Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazutoshi Fujita Department of Urology, Kindai University Faculty of Medicine Kiyoshi Takahara Department of Urology, Fujita-Health University School of Medicine Haruhito Azuma Department of Urology, Osaka Medical and Pharmaceutical University Teruo Inamoto Department of Urology, Hamamatsu University School of Medicine Objectives: Sarcomatoid renal cell carcinoma (sRCC) is an aggressive histological variant associated with a poor prognosis. While immune checkpoint inhibitor (ICI)-based combinations have become the standard of care, the optimal first-line regimen, specifically dual immunotherapy (IO-IO) vs. IO plus tyrosine kinase inhibitor (IO-TKI), remains controversial. We herein examined the real-world clinical outcomes of Japanese patients with sRCC. Methods: We conducted a retrospective multicenter study on 46 patients with advanced or metastatic sRCC receiving first-line ICI-based combination therapy between January 2018 and December 2024 (IO-IO: n = 18; IO-TKI: n = 28). In a comparative survival analysis, three favorable-risk patients in the IO-TKI group were excluded to align risk profiles, focusing on intermediate/poor-risk groups (n = 43). The primary endpoint was overall survival (OS). Results: In the entire cohort (n = 46), the objective response rate was numerically higher in the IO-TKI group (64.3%) than in the IO-IO group (50.0%) (p = 0.37). In the comparative analysis of intermediate/poor-risk patients (n = 43), progression-free survival (PFS) was slightly longer (p = 0.071), and OS was significantly longer (p = 0.016) in the IO-TKI group than in the IO-IO group. A multivariable analysis adjusted for IMDC risk categories showed favorable survival with the IO-TKI regimen (HR 0.37, p = 0.061). Conclusions: The present study indicates that first-line IO-TKI combination therapy represents a promising treatment option with a potential survival advantage over IO-IO therapy for Japanese patients with sRCC. However, due to the retrospective design and small sample size, reliably determining the comparative efficacy of these regimens remains challenging, and further validation is warranted. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2090-6749 2026 Arthroscopically Confirmed Complete Healing of Anterior Cruciate Ligament Avulsion Fracture Following Four‐Corner Pullout Repair Using Ultrahigh‐Molecular‐Weight Polyethylene Tapes: A Case Report 5671446 EN Toshiki Kohara Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Yuki Okazaki Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Shinichi Miyazawa Department of Orthopedic Surgery , NHO Fukuyama Medical Center Takayuki Furumatsu Department of Orthopedic Surgery , Japanese Red Cross Okayama Hospital Yusuke Yokoyama Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Masanori Tamura Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Koki Kawada Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Tsubasa Hasegawa Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Tomonori Tetsunaga Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Kazuki Yamada Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopedic Surgery , Okayama University Graduate School of Medicine , Dentistry , and Pharmaceutical Sciences We report a case of tibial insertion avulsion fracture of the anterior cruciate ligament (ACL). A 10-year-old boy who fell from a skateboard was diagnosed with a tibial insertion avulsion fracture of the ACL and was treated arthroscopically. The avulsed fragment was provisionally fixed with guide pins inserted into its four corners, and the lateral view was checked to avoid penetration of the growth plate. Two ultrahigh-molecular-weight polyethylene tapes were passed through the ACL just above its tibial insertion, pulled through the four-corner bone tunnels in an X-shaped configuration, and tightened. The patient was immobilized for 3 weeks, and partial weight bearing was initiated at 4 weeks. Bone union was confirmed at 6 months using plain radiographs, and second-look arthroscopy and implant removal were performed 8 months postoperatively. During arthroscopy, complete union with smooth continuity of the articular cartilage at the fracture site and a stable ACL were observed. The patient had a full knee range of motion and no pain at the final follow-up. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-7257 19 3 2026 Successful management and 10-year survival of a rectal neuroendocrine tumor with rare systemic metastases via a non-portal venous pathway 491 498 EN Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroyuki Terasawa Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Kosei Takagi Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takashi Kuise Department of Gastroenterological Surgery, Okayama Red Cross Hospital Takehiro Tanaka Department of Pathology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Metastatic neuroendocrine tumors (NETs) typically involve the liver and lymph nodes. Metastases in the orbit, heart, and ovary are rare and present unique clinical challenges. We report a woman who was 70 years old at the time of initial presentation with liver metastases from a rectal neuroendocrine tumor. Following a right hepatectomy for liver metastases, she remained free of hepatic recurrence for 10 years. Notably, four years after the right hepatectomy, she developed new metastases in the left orbit, right ventricle, and left ovary, with diplopia as the sole clinical symptom. This clinical course suggests a distinct metastatic pathway associated with the lower rectum that bypasses the portal circulation, consistent with the dual drainage system of the rectal region. Management involved a strategic multimodal approach that includes systemic therapy with everolimus and lanreotide as well as targeted surgical resectioning of the cardiac and ovarian lesions. The orbital lesion achieved a complete response through systemic therapy alone, preserving visual function. Currently, 10 years after the initial treatment, the patient maintains an excellent performance status (ECOG PS 0) while receiving peptide receptor radionuclide therapy (PRRT). This case demonstrates that recognizing atypical metastatic pathways and employing strategic multimodal therapies can achieve long-term survival and functional preservation in rectal NETs. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 33 4 2026 Differences in drug efficacy and prognosis between primary and metastatic sites for de novo stage IV breast cancer: an exploratory analysis of a phase III trial, JCOG1017 829 838 EN Kiyo Tanaka Department of Breast Surgery, Toranomon Hospital Akihiko Shimomura Department of Breast and Medical Oncology, National Center for Global Health and Medicine Makoto Ishitobi Department of Breast Surgery, Osaka Habikino Medical Center Takashi Yamanaka Department of Breast Surgery, Kanagawa Cancer Center Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroji Iwata Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences Fumikata Hara Department of Breast Oncology, Aichi Cancer Center Tomomi Fujisawa Department of Breast Oncology, Gunma Prefectural Cancer Center Keita Sasaki Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Ryo Sadachi Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Riku Kajikawa Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Takehiko Sakai Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Yasuaki Sagara Department of Breast Surgery, Sagara Hospital Hideo Shigematsu Department of Breast Surgery, Hiroshima University Hospital Yukinori Ozaki Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Kazuki Nozawa Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences Kazuki Sudo Department of Medical Oncology, National Cancer Center Hospital Yoichi Naito Department of General Internal Medicine, National Cancer Center Hospital East Kaori Terata Department of Breast and Endocrine Surgery, Akita University Hospital Toshiyuki Ishiba Department of Breast Surgery, Institute of Science Tokyo Hospital Haruhiko Fukuda Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Background Breast cancer is a highly heterogeneous disease, with biological factors like estrogen receptor, progesterone receptor, and HER2 receptor differing between primary and metastatic sites, potentially affecting treatment response. This exploratory analysis aims to differentiate drug efficacy and long-term prognosis between these sites in stage IV breast cancer. Methods Patients from JCOG1017, a phase III trial evaluating the role of primary tumor resection, who received primary systemic therapy (PST) were evaluated at three months. In this analysis, treatment response was assessed separately in primary and metastatic sites. Patients were categorized into four groups: discordant I (primary non-PD, metastatic PD), concordant I (both PD), discordant II (primary PD, metastatic non-PD), and concordant II (both non-PD). Results Among 271 patients, overall discordance proportion of treatment response between primary and metastatic sites was 25.1%. Group distribution was 24.7% (discordant I), 9.6% (concordant I), 0.4% (discordant II), and 65.3% (concordant II). Discordance was more frequent in luminal (28.9%), triple-negative (25.0%), and luminal-HER2 (22.0%) subtypes than in HER2-enriched (11.1%). Survival analysis showed prognostic differences: concordant II, with both sites non-PD, demonstrated the most favorable outcome compared with discordant I (HR 0.556; 95% confidence interval, 0.396–0.782). Conclusions One-fourth of patients exhibited discordant responses between primary and metastatic sites in early treatment phases. These discrepancies were associated with survival differences, emphasizing the importance of evaluating both primary and metastatic lesions when assessing efficacy and determining treatment strategies in de novo stage IV breast cancer. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 31 3 2026 Clinical complete response and predictive factors in HER2-positive early breast cancer treated with neoadjuvant chemotherapy aimed at omission of surgery: an exploratory analysis of the JCOG1806 trial 528 536 EN Hideo Shigematsu Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University Hospital Tomomi Fujisawa Gunma Prefectural Cancer Center Fumikata Hara Aichi Cancer Center Hiroji Iwata Graduate School of Medical Sciences, Nagoya City University Toshiyuki Ishiba Institute of Science Tokyo Hospital Yukinori Ozaki Cancer Institute Hospital of the Japanese Foundation for Cancer Research Takehiko Sakai Cancer Institute Hospital of the Japanese Foundation for Cancer Research Yasuaki Sagara Hakuaikai Sagara Hospital Akihiko Shimomura National Center for Global Health and Medicine Kazuki Sudo National Cancer Center Hospital Kaori Terata Akita University Hospital Yoichi Naito National Cancer Center Hospital East Kazuki Nozawa Graduate School of Medical Sciences, Nagoya City University Keita Sasaki Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Noriko Mitome Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Ryo Sadachi Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Taro Shibata Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital Tadahiko Shien Okayama University Hospital Purpose The JCOG1806 trial (jRCTs031190129) is underway to evaluate the omission of surgery in patients with human epidermal growth factor receptor (HER2)-positive early breast cancer who have a clinical complete response (cCR) after primary systemic therapy (PST). We aimed to assess the cCR rate in this trial and identify predictive factors. Methods HER2-positivity was defined as an immunohistochemistry (IHC) score of 3 + or in situ hybridization-positivity. A cCR was defined as the absence of detectable lesions upon palpation, contrast-enhanced magnetic resonance imaging, and ultrasonography; biopsy-based confirmation was optional in hormone receptor (HR)-negative cases and mandatory in HR-positive cases. Multivariate logistic regression analyses were used to identify predictors of a cCR. Results The cCR rate was 57.6% (196/340 patients; 95% confidence interval [CI]: 52.2–63.0%). Strongly estrogen-receptor (ER)-positive tumors (≥ 10%) were significantly less likely to have a cCR than ER-negative tumors (odds ratio [OR], 0.41; 95% CI: 0.20–0.81). IHC 3 + tumors had higher cCR rates than IHC 1 + or 2 + tumors (OR, 2.19; 95% CI: 1.01–4.74). Compared with histological grade I tumors, cCR odds were higher in grade II (OR: 2.92; 95% CI: 1.07–7.93) and III (OR: 4.90; 95% CI: 1.76–13.7) tumors. Among patients without a cCR patients undergoing surgery, 22.2% were diagnosed with ypT0 tumors upon analysis of surgical specimens. Conclusion ER-negativity, an IHC score of 3 + , and a higher histological grade were independent predictors of a cCR. Identifying these features may improve the feasibility and safety of surgery omission for patients with HER2-positive early breast cancer. 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.

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.

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

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.

Elsevier BV Acta Medica Okayama 1201-9712 166 2026 eConsult in infectious diseases: A narrative review 108524 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Hidemasa Akazawa Department of Infectious Diseases, Okayama University Hospital Kenta Nakamoto Department of Infectious Diseases, Okayama University Hospital Kohei Oguni Department of Infectious Diseases, Okayama University Hospital Objectives: Asynchronous electronic consultation, eConsult, is increasingly applied in infectious diseases (ID) management to improve access to specialty care and reduce unnecessary referrals. We aimed to integrate published studies to provide a comparative perspective and propose future directions for ID eConsult. Methods: To synthesize relevant findings and present a comprehensive overview of ID eConsult, we searched in MEDLINE database and identified 11 studies between 2017 and 2025 on ID eConsult programs. Structured data were extracted on study characteristics, mode of consultation, and outcomes. Results: Nine studies on outpatient ID eConsult demonstrated faster turnaround times, high rates of avoidance of in-person referrals (24-87%), improved antimicrobial optimization, and high provider satisfaction. Two studies on inpatient ID eConsult reported reductions in mortality, readmission rates, and broad-spectrum antibiotic use. Conclusions: Given its affordability and scalability, the ID eConsult model is particularly advantageous in resource-limited environments. Collectively, ID eConsult may replace traditional telephone or face-to-face consultations, reducing the need for informal curbside discussions. 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. 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. 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. 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. Methods: J-TAIL-2 (ClinicalTrials.gov ID, NCT04501497) was a multicenter observational study that enrolled patients receiving atezolizumab plus CE (ES-SCLC cohort) in clinical practice in Japan per local label and treatment guidelines. In this exploratory analysis, the association of CD8+ tumor-infiltrating lymphocyte (TIL) density and SCLC subtypes (SCLC-A [ASCL1 dominant], SCLC-N [NEUROD1 dominant], SCLC-P [ASCL1/NEUROD1 double-negative with POU2F3 expression], and SCLC-O [ASCL1/NEUROD1 double-negative not otherwise specified]) with overall survival (OS) and progression-free survival (PFS) was evaluated. SCLC subtyping was performed by immunohistochemistry. Results: SCLC samples (n = 100; data cutoff, February 3, 2023) were categorized as SCLC-A (73%), SCLC-N (16%), SCLC-P (8%), and SCLC-O (3%). Among 96 patients who received first-line atezolizumab plus CE, median age was 72 (range, 39–87) years and 81% were male. Furthermore, 56 patients were classified into the CD8+ TIL-high subgroup and 40 into the TIL-low subgroup. Median (m)PFS with atezolizumab plus CE was 6.1 months (95% confidence interval [CI]: 4.5–7.5) in the TIL-high versus 4.4 months (95% CI: 4.0–5.1) in the TIL-low subgroup (p = 0.01); mOS was 18.4 (95% CI: 11.8–not estimable) versus 10.8 months (95% CI: 7.7–16.2; p = 0.04). mOS and mPFS were not significantly different between SCLC subtypes but were numerically shorter in the SCLC-N group. Conclusions: CD8+ TIL density is a potential biomarker of clinical benefit in ES-SCLC and may facilitate patient selection for atezolizumab combination therapy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-1380 19 1 2026 Pseudoaneurysm of the thoracoacromial artery associated with habitual shoulder dislocation: a case report 139 EN Honoka Wada Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Aya Hamasaki Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Soichiro Okamoto Department of Radiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Shunki Yamamoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background Shoulder dislocation is one of the most common joint dislocations encountered in emergency departments, but vascular complications are rare and often underrecognized. Pseudoaneurysms of the thoracoacromial artery, a branch of the axillary artery, are extremely uncommon and may present with subtle symptoms, delaying diagnosis. Case presentation An 82-year-old woman with a history of habitual anterior shoulder dislocation presented with a 10-day history of progressive pain and swelling in the left shoulder. She was on edoxaban for atrial fibrillation. Examination revealed localized tenderness and swelling without neurological deficits. Computed tomography angiography showed a 30 × 35 × 35 mm pseudoaneurysm arising from the acromial branch of the thoracoacromial artery. Endovascular embolization was performed using a proximal oxidized regenerated cellulose sheet placement followed by injection of N-butyl cyanoacrylate and Lipiodol due to the risk of coil migration into the joint space. The procedure achieved complete exclusion of the lesion. At three-month follow-up, the patient remained asymptomatic with preserved left upper limb function. Computed tomography angiography demonstrated the pseudoaneurysm remains excluded. Conclusion Although rare, pseudoaneurysms of the thoracoacromial artery can occur after repeated shoulder dislocation and reduction, especially in elderly patients on anticoagulation therapy. Early recognition through imaging and prompt endovascular intervention can prevent serious vascular and neurological complications. No potential conflict of interest relevant to this article was reported.

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

American Association for Cancer Research (AACR) Acta Medica Okayama 2767-9764 6 4 2026 Constitutive EGFR Activation Induced by PTPRR Downregulation Confers Resistance to KRAS Inhibitors 728 741 EN Hiroaki Kanemura Department of Medical Oncology, Kindai University Faculty of Medicine Toshiyuki Takehara Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine Osamu Maenishi Department of Pathology, Kindai University Faculty of Medicine Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Natsumi Iwawaki Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine Kei Kunimasa Department of Thoracic Oncology, Osaka International Cancer Institute Tomohiro Nakayama Department of Medical Oncology, Kishiwada City Hospital Satomi Watanabe Department of Medical Oncology, Kishiwada City Hospital Shinichiro Suzuki Department of Medical Oncology, Kindai University Faculty of Medicine Kazuko Sakai Department of Genome Biology, Kindai University Faculty of Medicine Koichi Azuma Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine Keita Kudo Department of Medical Oncology, National Hospital Organization Osaka Minami Medical Center Kazuto Nishio Department of Genome Biology, 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 Takeshi Teramura Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine Kimio Yonesaka Department of Medical Oncology, Kindai University Faculty of Medicine KRASG12C inhibitors, such as sotorasib, show clinical efficacy for non–small cell lung cancer (NSCLC) positive for the G12C mutations of KRAS, but primary and acquired resistance to these drugs remains a clinical problem. In this study, we show that the development of resistance to sotorasib in KRASG12C-positive NSCLC cells was mediated by constitutive activation of EGFR resulting from downregulation of the protein tyrosine phosphatase receptor type R (PTPRR). PTPRR has been identified as a physiologic regulator of ERK signaling in several cancer types. In our study, PTPRR was demonstrated to bind directly to EGFR, facilitating its dephosphorylation on tyrosine residues. Resumption of PTPRR expression in the resistant cells attenuated EGFR phosphorylation and restored sotorasib sensitivity. PTPRR downregulation was associated with gene promoter hypermethylation in the sotorasib-resistant cells and NSCLC tissue samples. Furthermore, low PTPRR expression in tumor specimens was associated with shorter progression-free and overall survival for patients with NSCLC treated with sotorasib. In contrast to sotorasib, high PTPRR expression was associated with a poor response to EGFR tyrosine kinase inhibitors in EGFR-mutated NSCLC, suggesting that PTPRR may broadly regulate EGFR dependence in NSCLC. Finally, dual blockade of KRASG12C and EGFR showed a substantial antitumor effect in a xenograft model of sotorasib-resistant NSCLC. This approach is therefore a rational therapeutic strategy for KRASG12C-positive NSCLC, especially for tumors showing PTPRR downregulation. Significance: The current study shows that downregulation of PTPRR induces EGFR activation and resistance to KRASG12C inhibitors in NSCLC, suggesting dual KRAS-EGFR blockade as a rational therapy. PTPRR may help identify patient subgroups that would benefit from the addition of EGFR inhibitors to KRASG12C-targeted therapies. No potential conflict of interest relevant to this article was reported.

The Company of Biologists Acta Medica Okayama 0022-0949 229 2 2026 Insulin-like peptide has antagonistic pleiotropic effects on male combat traits and survival traits in an armed beetle jeb251318 EN Takumi Kato Graduate School of Science, Nagoya University Chiho Yoshimine Graduate School of Science, Tokyo Metropolitan University Haruna Fujioka Graduate School of Environmental, Natural Science and Technology, Okayama University Masako Katsuki Graduate School of Science, Nagoya University Kensuke Okada Graduate School of Environmental, Natural Science and Technology, Okayama University Yasukazu Okada Graduate School of Science, Nagoya University The expression of sexually selected traits, such as exaggerated weapons and ornaments, often entails trade-offs against life-history traits. While phenotypic trade-offs are well documented, the underlying molecular physiological mechanisms remain largely unexplored. In this study, we investigated the potential role of an insulin-like peptide, ILP2, in mediating the trade-off between sexually selected combat traits and survival traits in the broad-horned flour beetle, Gnatocerus cornutus. RNA interference (RNAi)-mediated knockdown (KD) of ILP2 during larval stages resulted in a reduction in the development of mandibular horns and overall body size. Interestingly, ILP2 KD males had increased lipid storage and enhanced starvation tolerance, indicating a shift in resource allocation from sexually selected traits to survival traits. Behaviorally, ILP2 KD males showed decreased locomotor activity and reduced aggression, leading to lower combat success. These findings suggest that ILP2 functions as a key mediator in the allocation of resources between combat and survival traits, highlighting its pleiotropic effects on morphology, metabolism and behavior. Our study provides novel insights into the molecular physiological mechanisms underlying life-history trade-offs associated with sexually selected traits. 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. 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. 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. 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.

Elsevier BV Acta Medica Okayama 2666-951X 19 2026 Heteroarylation of mono- and dichloroarenes via phenothiazine organophotoredox catalysis 100163 EN Masato Oishi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kenta Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University 2-Arylpyrroles are key structural motifs found in a wide range of pharmaceuticals and functional materials. Although the photocatalytic heteroarylation of pyrroles with aryl iodides and bromides has been extensively developed for the synthesis of 2-arylpyrroles, the corresponding reactions using aryl chlorides remain relatively unexplored owing to the high energy barrier associated with C(sp2)–Cl bond activation. Herein, we report a phenothiazine-based organophotoredox-catalyzed heteroarylation of aryl chlorides with pyrroles for the synthesis of diverse 2-arylpyrroles. Notably, dichloroarenes also efficiently undergo heteroarylation to afford the corresponding products. Therefore, the present reaction represents a versatile approach to heteroarylation and provides a valuable tool for the synthesis of pharmaceuticals and functional materials. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1463-9076 2026 Phase behaviour of liquid CO2 with an impurity of water: influence of CO2 hydrate EN Hideki Tanaka Research Institute for Interdisciplinary Science, Okayama University Masakazu Matsumoto Research Institute for Interdisciplinary Science, Okayama University Takuma Yagasaki Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University Munetaka Takeuchi Engineering Advancement Association of Japan Yoshihito Mori Ochanomizu University Takumi Kono Engineering Advancement Association of Japan The solubility of water in liquid CO2 coexisting with CO2 hydrate or liquid water is evaluated in order to investigate the thermodynamic conditions to avoid the formation of CO2 hydrate in the transportation processes of liquid CO2. To this end, theoretical calculations have been carried out to obtain the chemical potentials of water and CO2 in all the phases involved in their coexistence. The solubility of water in liquid CO2 coexisting with liquid water decreases with decreasing temperature over a wide range of temperature and pressure, except for in the vicinity of the critical point of CO2. The decrease in the solubility is further enhanced by the formation of hydrate. We estimate the Gibbs energy of hydrate formation, which is an important property for sequestration of CO2, for cases where the temperature or pressure of water-saturated liquid CO2 decreases. We also estimate the amount of water precipitated as hydrate during these processes, which has a direct bearing on flow assurance in CO2 transportation. The present study will contribute to the development of a low-energy, safe CO2 transport network aiming at achieving large-scale carbon neutrality. 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 Pathway Enrichment Analysis of Whole-Exome Sequencing Data from Formalin-Fixed, Paraffin-Embedded Enucleated Eyes with Retinoblastoma and Choroidal Malignant Melanoma e110548 EN Toshihiko Matsuo Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takehiro Tanaka Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Daisuke Ennishi Medical Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Akira Saito Genomic Statistics, Stagen Co. Ltd. Mitsuhiro Amemiya Genomic Statistics, Stagen Co. Ltd. Shigeo Kamitsuji Genomic Statistics, Stagen Co. Ltd. Objectives: Intraocular tumors are extremely rare, small in size, and difficult to approach by biopsy. In the era of cancer genome analysis, we designed a pilot study to perform whole-exome sequencing of formalin-fixed paraffin-embedded enucleated eyes of retinoblastoma and choroidal malignant melanoma as two major intraocular malignancies. Methodology: Genomic DNA was isolated from intraocular tumor areas of 105 paraffin sections with a 5 μm thickness of seven enucleated eyes with retinoblastoma and seven eyes with choroidal malignant melanoma. One of 7 samples of retinoblastoma and another of seven samples of choroidal malignant melanoma were excluded from the study since the sequencing output and depth of reads were lower compared with the other samples. The sequencing data after quality control were aligned to the reference genome sequence (hg38, GRCh38 Assembly, Genome Reference Consortium Human Build 38), and the mapped reads were processed to improve data quality. Somatic mutations (single nucleotide variants, insertions and deletions, and multiple nucleotide variants) in each sample were extracted after excluding variants reported in a Panel of Normals (PON) from the 1000 Genomes Project. Additional selection criteria included a mutation depth of ≥5 reads and either no registration in or an allele frequency of less than 5% in the Tohoku Medical Megabank of Japan (ToMMo 60KJPN-SNV/INDEL Allele Frequency Panel). Results: Candidate genes with somatic mutations were selected by three criteria: genes with the same mutation shared by two samples or more, recurrently mutated genes three times or over, and genes of driver candidates identified in combining several different driver mutation-detecting programs by Integrative OncoGenomics (IntOGen). Using candidate genes detected by any of the three criteria as input, enrichment analyses identified 28 pathways in Gene Ontology (GO) and 2 pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) for retinoblastoma, while 385 pathways in GO, 12 in KEGG, 2 in the Hallmark gene set of the Molecular Signatures Database (MSigDB), and 47 in Reactome were identified for choroidal malignant melanoma. The enrichment maps showed three major pathways differently in retinoblastoma and choroidal malignant melanoma: one with dynein in retinoblastoma and another with MET in choroidal malignant melanoma. Conclusions: Although there were limitations related to the small amounts of DNA available from formalin-fixed, paraffin-embedded small-sized tissues and the absence of matched normal control tissue, whole-exome sequencing provided clues to somatic mutations that were enriched in specific pathways and differed between retinoblastoma and choroidal malignant melanoma. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0178-8051 2026 Uniqueness of Dirichlet forms for random point fields in the absence of tail triviality EN Yosuke Kawamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama university We consider an infinite system of interacting Brownian motions that preserves a given random point field invariant. Such dynamics are constructed using Dirichlet form theory, which naturally leads to two Dirichlet forms for the random point field: the upper and the lower Dirichlet forms. A fundamental question is the uniqueness of the Dirichlet form: that is, whether these two forms coincide. This uniqueness has often been imposed as a key assumption in the Dirichlet form approach to the stochastic analysis for infinite particle systems. A sufficient condition for the uniqueness of the Dirichlet forms is known when the random point field is tail trivial. However, tail triviality has been established for only a limited class of random point fields. In this paper, we prove the uniqueness of the Dirichlet form without assuming tail triviality. The main contribution of this work is to establish the tail preserving property, which asserts that global properties of the system, such as particle density, are preserved under time evolution. As a consequence, our results also imply the strong uniqueness of solutions to the associated infinite-dimensional stochastic differential equations. 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.

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

Springer Science and Business Media LLC Acta Medica Okayama 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. 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. 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. 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.

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

Acta Medica Okayama 2026 Bioresorbable Membrane Composed of Sodium Hyaluronate and Carboxymethylcellulose (Seprafilm) Prevents Cancer Implantation at Peritoneal Defects in 3D‐Peritoneum and Murine Models EN Yuta UNE Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Japan Surgical Society Acta Medica Okayama 2198-7793 12 1 2026 Tailored Management of Anomalous Systemic Arterial Supply to the Basal Segment of the Lung: A Case Report and Literature Review cr.26-0288 EN Shunsuke Mori 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 Koji Tomita Department of Radiology, 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 Takao Hiraki Department of Radiology, 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 INTRODUCTION: Parenchyma-preserving strategies for anomalous systemic arterial supply to the basal segment of the lung have gained increasing attention. However, pulmonary infarction of the preserved lung has been reported, and clear criteria for selecting the optimal treatment have yet to be established. We report 2 cases in which detailed preoperative imaging informed tailored management—right posterior basal segmentectomy in 1 patient and endovascular embolization of the aberrant artery in the other—both without postoperative complications. A review of the relevant literature is also provided, with an emphasis on potential selection criteria. CASE PRESENTATION: Case 1: A 20-year-old asymptomatic woman was referred after an abnormal screening chest radiograph. CT demonstrated an aberrant artery arising from the abdominal aorta supplying the right posterior basal segment (S10) with a large intravascular thrombus. The pulmonary artery showed hypoplasia limited to A10, while the other branches were normal, and no parenchymal congestion was identified. Following resection of the aberrant artery, robot-assisted right S10 segmentectomy was performed. The postoperative course was uneventful, and the patient was discharged on POD 6. Case 2: A 27-year-old woman was incidentally diagnosed on CT for an unrelated indication. An aberrant artery arising from the descending thoracic aorta supplied the left basal segment. Pulmonary arterial branches were preserved, with only minimal congestion in S9-10. Angiography revealed no evidence of an arteriovenous fistula. As surgical lung resection was considered unnecessary, coil embolization of the aberrant artery was performed. No complications occurred, and the patient was discharged on day 3 after the procedure. CONCLUSIONS: In patients with anomalous systemic arterial supply to the basal segment of the lung, when pulmonary arterial branches are preserved and background parenchymal congestion is minimal, parenchyma-sparing approaches should be considered. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 2575-6265 7 2 2026 Exogenous Glutathione and Nitric Oxide Improve Waterlogging Stress Tolerance in Maize e70136 EN Prodipto Bishnu Angon Applied Plant Biology and Bioinformatics Lab, Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University Md. Tahjib‐Ul‐Arif Applied Plant Biology and Bioinformatics Lab, Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University Md. Sarwar Jahan Applied Plant Biology and Bioinformatics Lab, Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University Md. Mahadi Hasan Basic and Applied Scientific Research Centre, Imam Abdulrahman Bin Faisal University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Maize (Zea mays L.) is one of the major grain crops worldwide that is particularly vulnerable to waterlogging (WL) stress. Glutathione (GSH) and nitric oxide (NO) are known to protect plants from a variety of abiotic stresses; however, their potential for improving WL tolerance in maize remains unexplored. The present study examined the impact of exogenously applied GSH and NO on maize plants exposed to WL-stress. Our findings revealed that GSH + NO-treated waterlogged maize plants grew better and produced more biomass than only WL-stressed plants. The improved performance of GSH + NO-sprayed WL-stressed maize seedlings was supported by the increased root dry and fresh weight, shoot length, shoot dry and fresh weight, chlorophyll a, chlorophyll b, and carotenoid content. Exogenous GSH and NO treatments significantly enhanced the amounts of leaf proline, leaf soluble sugars, and total protein in maize seedlings, suggesting adaptive metabolic reprogramming under stress. The increased malondialdehyde (MDA) levels and accumulation of hydrogen peroxide (H2O2) in maize leaves and roots revealed that WL caused significant oxidative damage. Exogenous GSH, NO individually, and combinedly significantly decreased total H2O2 and MDA contents in both leaves and roots. Exogenous GSH and NO reduced oxidative stress by increasing peroxidase activity, ascorbic acid, and anthocyanin content in maize leaf and root tissues. Our findings emphasize the possible relevance of GSH and NO, simultaneously and individually, in enhancing adaptive mechanisms in maize seedlings for reducing WL-induced damage. Although the GSH + NO-mediated approach shows promise for mitigating WL-stress in maize under controlled conditions, further field-based investigations are required to validate its practical applicability. 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.

Elsevier BV Acta Medica Okayama 0168-1702 367 2026 Mycoviruses diversity in the black kōji mold, Aspergillus luchuensis (section Nigri) isolated from liquor-production environments in Japan 199724 EN Hideki Kondo Institute of Plant Science and Resources, Okayama University Misaki Nanaji Graduate School of Tokyo Kasei University Hitomi Sugahara Institute of Plant Science and Resources, Okayama University Miki Fujita Institute of Plant Science and Resources, Okayama University Ida Bagus Andika Northwest A&F University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University Fujimori Fumihiro Graduate School of Tokyo Kasei University Some fungal species in the genus Aspergillus are economically important due to their role in the production of liquors and various foods; however, their viromes, which may affect their performance, remain unexplored. Therefore, this study examined the viromes of nine strains of Aspergillus luchuensis (section Nigri), the black kōji mold used in the production of shochu (a traditional Japanese liquor) in Japan. It identified virus-like sequences related to alterna-, partiti-, curvula, botourmia-, narna-like, and umbra-like viruses. Some sequences appear to represent new variants (e.g., alterna- and gammapartitiviruses), while many others correspond to novel viral species within established or proposed mycoviral families. All A. luchuensis strains harbored multiple virus infections, with 2 to 7 viruses per strain. Three alternavirus strains with four-segmented double-stranded RNA (dsRNA) genomes were confirmed, along with minor variants co-present with the predominant strains. Notably, a gammapartitivirus appears to have two additional dsRNA genome segments, along with two satellite-like short dsRNA segments in some fungal isolates. Furthermore, at least five short RNAs (0.48–1.31 kb) were identified, three of which are possibly satellite-like RNAs associated with novel single-stranded RNA viruses (botourmia- and umbra-like viruses). These findings reveal the great diversity of mycoviruses in A. luchuensis populations and lay the foundation for further investigation into their impact on fungal phenotypes and liquor production. 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. 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.

Frontiers Media SA Acta Medica Okayama 2474-0896 83 2026 Clinical Utility of SARS-CoV-2 Antibody Titers in the Management of Patients With Long COVID Infected With the Omicron Variant 16255 EN Marina Kawaguchi 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 Kazuki Tokumasu 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 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 Daisuke Omura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuyoshi Matsuki Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Furukawa Department of Laboratory Medicine, Okayama University Hospital Akihito Higashikage Department of Laboratory Medicine, Okayama University Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Long COVID (LC) presents persistent symptoms that pose a major clinical challenge. Identification of reliable biomarkers to evaluate LC pathophysiology is needed. Objectives: To investigate whether serum S- and N-antibody titers against SARS-CoV-2 spike and nucleocapsid proteins reflect the clinical features of LC. Methods: This retrospective observational study included patients diagnosed with Omicron variant-related LC who attended a post-COVID-19 outpatient clinic between July 2023 and November 2024 and provided informed consent for antibody testing. Results: Among 275 patients (129 men and 146 women), 57 (21%) were unvaccinated. Median S- and N-antibody titers in vaccinated versus unvaccinated patients were 20,963 U/mL and 24.8 cut-off index (COI) versus 24 U/mL and 44.5 COI, respectively. S-antibody titers were associated with the number of vaccine doses received, whereas N-antibody titers correlated with disease severity during the acute phase of COVID-19 infection, with females having higher titers by multivariable analysis. N-antibody titers in unvaccinated patients with LC were negatively correlated with time interval from infection to clinic visit, with an estimated daily decline of 0.34% in measured N-antibody levels. Patients with LC having memory impairment had low S-antibody titers by multivariable logistic regression analysis, and low S-antibody levels were associated with reduced quality of life (QOL). Additionally, N-antibody titers positively correlated with lymphocyte counts and immunoglobulin levels. Conclusion: Serum N-antibody titers reflect immune responses to COVID-19, although they are affected by gender differences and interval between infection and evaluation. Lower S-antibody titers were associated with brain fog symptoms and reduced QOL in patients with LC. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0953-8194 38 4 2026 Type III CD38 is present in the membrane of neurosecretory vesicles and has a cytosol-facing catalytic domain in primate oxytocin neurons e70187 EN Tatsuki Miyamoto Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Akari Matsushima Department of Biology, Faculty of Science, Okayama University Akito Otubo Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Chihong Song Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences Kazuyoshi Murata Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences 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 CD38, an ADP-ribosyl cyclase that generates cyclic ADP-ribose (cADPR), is essential for Ca2+-dependent oxytocin release. However, its subcellular localisation and membrane topology within oxytocin neurones have remained unclear. We investigated the distribution and orientation of CD38 in oxytocin-producing neurones of Japanese macaques (Macaca fuscata) using immunoelectron microscopy combined with biochemical isolation of neurosecretory vesicles (NSVs). CD38 immunoreactivity was selectively detected on oxytocin-containing NSVs in axon terminals in the posterior pituitary and dendrites of the supraoptic nucleus, whereas vasopressin vesicles and the plasma membrane lacked detectable labelling. Cryo-electron microscopy confirmed the structural integrity of purified NSV fractions, and Western blotting verified the presence of CD38 protein within these fractions. Permeabilisation-dependent immunogold labelling further demonstrated that the NSV membrane localisation of CD38 and that the N-terminal region of CD38 is oriented toward the vesicle lumen, consistent with a type III membrane topology in which the catalytic domain faces the cytosol. This arrangement positions the active site near cytosolic NAD+, enabling localised cADPR production adjacent to Ca2+-mobilising channels that support regulated exocytosis. These findings identify, in primate oxytocin neurones, a previously unrecognised, vesicle-associated pool of CD38 with a cytosol-facing catalytic domain and provide a structural framework for understanding how intracellular type III CD38 contributes to neuropeptide release. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2051-3380 14 3 2026 An Atypical Surgical Case of Lung Cancer With Unilateral Absence of the Pulmonary Artery, With Only the Superior Branch Remaining e70554 EN Kazuhiro Okada Department of Thoracic Surgery, Okayama University Hospital Shin Tanaka Department of Thoracic Surgery, Okayama University Hospital Tsuyoshi Ryuko Department of Thoracic Surgery, Okayama University Hospital Yasuaki Tomioka Department of Thoracic Surgery, Okayama University Hospital Kazuhiko Shien Department of Thoracic Surgery, Okayama University Hospital Ken Suzawa Department of Thoracic Surgery, Okayama University Hospital Kentaroh Miyoshi Department of Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of Thoracic Surgery, Okayama University Hospital Seiichiro Sugimoto Department of Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital A 69-year-old woman was referred to our department for an abnormal shadow on chest radiography. Contrast-enhanced computed tomography (CT) revealed a solid nodule in the right lower lobe and defects in the branches of the middle and lower lobes of the pulmonary artery (PA). Furthermore, collateral circulation had developed via the right internal thoracic, bronchial, intercostal, inferior phrenic, and subdiaphragmatic arteries. The solid nodule was diagnosed as adenocarcinoma by CT-guided biopsy. The day before surgery, embolization was performed using interventional radiology (IVR) to mitigate the risk of bleeding during thoracotomy, resulting in minimal intraoperative bleeding during the subsequent right middle and lower lobectomies with lymph node dissection (ND2a-1). UAPA is a rare congenital abnormality characterized by unilateral pulmonary artery agenesis. The presence of recurrent infections, extensive intrathoracic adhesions, and developed collateral circulation may pose challenges during surgical procedures. No potential conflict of interest relevant to this article was reported.

American Physical Society (APS) Acta Medica Okayama 3070-2240 1 2026 Cryogenic buffer gas beam source with in situ ablation target replacement 000016 EN Zhen Han Department of Physics, University of Chicago Zack Lasner Department of Physics, Harvard University Collin Diver Center for Fundamental Physics, Northwestern University Peiran Hu Department of Physics, University of Chicago Takahiko Masuda Research Institute for Interdisciplinary Science, Okayama University Xing Wu Facility for Rare Isotope Beams, Michigan State University Ayami Hiramoto Research Institute for Interdisciplinary Science, Okayama University Maya Watts Center for Fundamental Physics, Northwestern University Satoshi Uetake Research Institute for Interdisciplinary Science, Okayama University Koji Yoshimura Research Institute for Interdisciplinary Science, Okayama University Xing Fan Department of Physics, Harvard University Gerald Gabrielse Center for Fundamental Physics, Northwestern University John M. Doyle Department of Physics, Harvard University David DeMille Department of Physics, University of Chicago The design and performance of a cryogenic buffer gas beam source with a load-lock system is presented. The third generation of advanced cold molecule electric dipole moment search (ACME III) uses this source to produce a beam of cold, slow thorium monoxide (ThO) molecules. A feature of the apparatus is the capability of replacing the ablation targets without interrupting the vacuum or cryogenic conditions, thus increasing the average signal in the eEDM search. The beam source produces 1.3×1011 ground-state ThO molecules per pulse on average, with rotational temperature of 4.8K, molecular beam solid angle of 0.31sr, and forward velocity of 200ms−1, parameters that are consistent with the performance of a traditional source (without a load lock) requiring time-consuming thermal cycles for target replacement. Long-term yield improvement of ∼40% is achieved when the load-lock system is employed to replace targets every two weeks. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0969-0239 2026 Counterion condensation, ion pairing and scattering properties of carboxymethyl cellulose with mono- and di-valent ions EN Elmira Abbasi GharehTapeh Materials Science and Engineering Department, The Pennsylvania State University Takaichi Watanabe Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Ferenc Horkay Section on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health Can Hou Institute of Physical Chemistry, RWTH Aachen University Carlos G. Lopez Materials Science and Engineering Department, The Pennsylvania State University Max Hohenschutz Institute of Physical Chemistry, RWTH Aachen University We study the scattering and conductometric properties of a semiflexible polyelectrolyte, carboxymethyl cellulose (CMC), with monovalent and divalent counterions in aqueous media without added salts. The scattering patterns for the magnesium salts of CMC display a broad shoulder instead of the scattering peak observed for the monovalent salts. This suggests weaker electrostatic repulsion between chains and a consequent loss of local order. The result is consistent with conductivity measurements, which reveal that the effective charge of the backbone for MgCMC is approximately half that of NaCMC. The decrease in charge density agrees with Oosawa–Manning condensation, which expects the charge density to be inversely proportional to the counterion valence. Alkali metal counterions show large differences in ion-pair formation but only a weak effect in counterion condensation. We suggest that paired ions are a subset of condensed ions. A review of different methods to evaluate counterion condensation, including potentiometry, osmometry and viscosity-based methods is presented. Qualitative agreement between these methods is found and possible reasons for the discrepancies are discussed. No potential conflict of interest relevant to this article was reported.

XMLink Acta Medica Okayama 2383-9309 26 2 2026 General anesthesia management for oral surgery in a patient with plastic bronchitis associated with Fontan circulation: a case report 175 180 EN Kaho Noda Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukiko Nishioka Department of Dental Anesthesiology, Okayama University Hospital Hitoshi Higuchi Department of Dental Anesthesiology, Okayama University Hospital Fumika Hashimoto Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Saki Miyake Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Miyawaki Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Plastic bronchitis is a rare condition in which mucus plugs obstruct the bronchi, potentially leading to fatal respiratory failure. It has been reported in some patients with congenital heart disease following Fontan surgery. We report the general anesthesia management of a 22-year-old female patient with Fontan circulation and type II plastic bronchitis that was controlled using regular intravenous heparin injections. In this case, concerns existed regarding airway obstruction by bronchial plugs and hemodynamic instability specific to the Fontan circulation. During endotracheal intubation, the absence of mucus plugs was confirmed using a flexible bronchoscope. Intraoperatively, ventilation was managed at low pressure to avoid an increase in intrathoracic pressure caused by high positive-pressure ventilation. Additionally, fluid overload was avoided to prevent elevations in the central venous pressure. Consequently, perioperative management can be safely performed without any respiratory or circulatory complications. As treatment outcomes improve, the number of dental and oral surgical procedures in adult patients with congenital heart disease is expected to increase. Therefore, knowledge of congenital heart disease and its sequelae, such as plastic bronchitis, is essential to perform appropriate risk assessment and management. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0341-8162 269 2026 Aeolian dust provenance across the Eurasian Asian steppe from grain-size dependent quartz δ18O in surface soils 110109 EN Geer Teni Graduate School of Science and Technology, University of Tsukuba Ryoji Tanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Maki Asano Faculty of Life and Environmental Sciences, University of Tsukuba Kenji Tamura Faculty of Life and Environmental Sciences, University of Tsukuba Aeolian dust from the Eurasian interior significantly impacts climate, ecosystems, and soil formation, but the role of the Eurasian steppe as a dust source remains uncertain. We present grain-size-sorted quartz δ18O values in topsoil at 24 sites across the Eurasian steppe, from Ukraine and Kazakhstan to Xinjiang, Mongolia, and Inner Mongolia. Quartz fractions were separated from four fine soil classes (<2, 2–10, 10–20, 20–50 μm) at all sites, with additional coarse classes (50–200, 200–500, 500–2000 μm) at lithologically distinct locations. Coarse quartz grains in the Mongolian–Inner Mongolian Highlands show a relatively low and narrow δ18O range (7.6–9.0‰) over plutonic bedrocks and more variable higher values (8.9–17.8‰) over sedimentary bedrocks, indicating dependence on local lithology. In contrast, fine quartz grains (2–50 μm) exhibit a δ18O trend independent of bedrock lithology, indicating the values of regionally homogenized dust components. The δ18O values of the finest quartz fractions, exhibiting the highest at each site, decreased from the Western Steppe Plain (19.0 ± 0.8‰) through the Central Upland Steppe (18.0 ± 0.7‰) to the Mongolian–Inner Mongolian Highlands (13.8 ± 1.0‰), reflecting the distal dust input. Comparison with published quartz δ18O values for Mongolian and Northern China deserts and East Asian soils suggests that variable mixtures of these steppe end-members with Gobi and northern Chinese desert sources, along different atmospheric pathways of the East Asian winter monsoon, mid-latitude westerlies, and subtropical jets, can explain the aerosol-sized quartz in Japan and Korea. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0304-4238 361 2026 Far-red-enriched ultra-long-day conditions induce constitutive FT expression and rapid flowering in radish rootstocks, promoting graft-mediated floral induction in Brassicaceae crops 114818 EN Ko Motoki Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Nami Kakita School of agriculture, Okayama University Tanjuro Goto Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Ken-ichiro Yasuba Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Efficient floral induction is essential for breeding and seed production in Brassicaceae crops, particularly for late-bolting cultivars and plant-vernalization–type species such as cabbage (Brassica oleracea L.), which require substantial time and labor for artificial flower induction. A graft-mediated floral induction method was recently developed for cabbage, enabling flowering without vernalization treatment by grafting cabbage scions onto radish (Raphanus sativus L.) rootstocks. Although high expression of florigen gene FLOWERING LOCUS T (FT) in the rootstocks is a key determinant of success, environmental conditions capable of inducing strong FT expression in radish have remained unclear. Here, we demonstrate that a far-red-enriched ultra-long-day photoperiod (ULD-FR) markedly upregulates expression of radish FT homolog RsFTa and greatly enhances graft-mediated floral induction in cabbage. Under the ULD-FR condition, RsFTa expression remained constitutively high throughout the day, with daily transcript abundance increasing more than tenfold compared with standard high red/far-red (R/FR) ratio long-day conditions that employed fluorescent lamps. FT protein accumulation in cabbage scions grafted onto radish rootstocks was also strongly elevated, resulting in rapid flowering approximately 30 days after grafting. ULD-FR also promoted flowering in rapid-cycling Brassica rapa and B. oleracea accessions, and induced flowering in a vernalization-requiring R. sativus cultivar without low temperature treatment, suggesting that the response may be broadly conserved across Brassicaceae. Because ULD-FR can be implemented using standard lighting equipment by adding an FR light source, it presents potential utility as a versatile tool for breeding-related applications, including generation advancement and flowering synchronization among divergent accessions. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 0022-510X 481 2026 The utility of Gold Coast criteria for amyotrophic lateral sclerosis 125733 EN Emi Nomura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuta Morihara Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Osakada Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taijun Yunoki Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Takemoto Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease. Current diagnostic criteria, including the revised El Escorial (rEE) and Awaji (AW) criteria, have limitations in sensitivity. The Gold Coast (GC) criteria were proposed to simplify diagnosis and improve early detection, but their real-world performance remains unclear. Methods: We retrospectively analyzed 260 patients suspected of ALS who were admitted to our department between 2013 and 2022. The GC, AW, and rEE criteria were applied to data from initial hospitalization. Final diagnoses were based on follow-up data, and sensitivity/specificity were compared using McNemar's test. Results: The GC criteria showed equivalent sensitivity (91.6 %), but higher specificity (75.9 %) compared to all combined AW and rEE categories. GC sensitivity was significantly higher than that of AW/rEE definite/probable categories. False negatives of GC criteria were often due to insufficient LMN signs, particularly in bulbar-onset cases. Subgroup analysis showed consistent trends. Conclusion: The GC criteria demonstrated high sensitivity and moderate specificity, supporting their clinical utility in early ALS diagnosis. However, variability in clinical presentation and retrospective limitations suggest the need for further prospective validation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 2 2026 Revisiting Adrenal Crisis Triggered by Influenza Infection: Lessons from Two Fatal Cases 153 157 EN Yoshiyuki Ueda Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kosei Hasegawa Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Natsuko Futagawa Department of Pediatrics, Okayama University Hospital Hiromichi Naito Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Case Report 10.18926/AMO/70458 Adrenal crisis is a life-threatening endocrine emergency that can progress within hours despite a prior diagnosis and maintenance therapy. We describe a fatal influenza-triggered adrenal crisis in two patients: a child with panhypopituitarism and an adult with prior pituitary surgery, both presenting in cardiac arrest. Despite resuscitation and intravenous hydrocortisone, a fatal hypoxic-ischemic injury or multiorgan failure occurred. These cases highlight the fulminant course of an adrenal crisis and underscore the importance of early recognition, clinician awareness, prompt parenteral hydrocortisone administration, and reinforcement of education for patients, caregivers, and healthcare providers to improve preparedness and prevent avoidable deaths. 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 Impact of Proteinuria on Postoperative Complications Following Colorectal Cancer Surgery 131 139 EN Shunsuke Nakata Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Fumiaki Takatsu Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Yoshihiro Mikuriya Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Tomokazu Kakishita Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Shinji Hato Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Koji Ohta Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Takaya Kobatake Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Original Article 10.18926/AMO/70455 Colorectal surgery is associated with a high incidence of postoperative complications regardless of the advances in surgical techniques and multidisciplinary treatment. Proteinuria is common in patients with malignancies, but few studies have investigated the association between preoperative proteinuria and patient prognoses, especially postoperative complications. We investigated the impact of proteinuria on patients undergoing colorectal surgery in a single-center, retrospective cohort study of 767 patients who underwent surgical resection for colorectal cancer between January 2016 and December 2022 at the National Hospital Organization Shikoku Cancer Center. Among them, 81 patients with preoperative proteinuria were compared with the control group of 686 patients without proteinuria. Our analyses revealed that the patients with proteinuria had malnutrition with a significantly lower prognostic nutritional index compared to the no-proteinuria control group (p<0.001). The proteinuria group had a significantly advanced tumor stage (p=0.005), experienced more bleeding during the surgery (p=0.002), and required more transfusions (p<0.001). Postoperative complications were significantly more frequent in the proteinuria group (p=0.03), thus demonstrating that proteinuria was independently associated with postoperative complications (p=0.045). Proteinuria in patients undergoing colorectal cancer surgery can therefore be considered a risk factor for postoperative complications. No potential conflict of interest relevant to this article was reported.

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

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. 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. 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%). 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.