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.

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.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-9226 2026 Unraveling the structural features of Dion–Jacobson-type layered perovskite-related material HCa2Nb3O10·1.5H2O EN Zihao Zhang Faculty of Environmental, Life, Natural Science and Technology, Okayama University Jun Kano Faculty of Environmental, Life, Natural Science and Technology, Okayama University Shu Morita Institute of Materials and Systems for Sustainability (IMaSS), Nagoya University Hiromu Shimokawa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Minoru Osada Department of Materials Chemistry and Institute of Materials and Systems for Sustainability (IMaSS), Nagoya University Hydrated layered oxides are widely encountered, yet the presence of disordered interlayer water often complicates crystal structure determination from laboratory X-ray diffraction. Here, we report the crystal structure of the Dion–Jacobson-type layered perovskite-related material HCa2Nb3O10·1.5H2O, solved from synchrotron X-ray diffraction data by combining direct methods in reciprocal space, Le Bail whole-pattern fitting, and Rietveld refinement. The hydrate crystallizes in a tetragonal structure with space group P42212 (a = 7.7070(5) Å, c = 32.4870(3) Å). Incorporation of partially occupied interlayer water-oxygen sites on the (110) plane at z = 0 and 1/2 successfully reproduces the low-angle 00l reflections while preserving the Ca2Nb3O10 framework. The resulting crystallographic model explicitly resolves the arrangement of interlayer water molecules and provides a robust structural foundation for band-structure calculations as well as for the rational design of hydration-controlled intercalation, exfoliation, and composite materials based on layered perovskite-related materials. No potential conflict of interest relevant to this article was reported.

Castledown Publishers Acta Medica Okayama 2982-3749 2 1 2026 AI-assisted writing feedback in EFL: Tracking student performance and reflections 103382 EN Junko Otoshi Okayama University Naomi Fujishima Kawasaki Medical School This study explores how AI-assisted writing feedback supports English as a Foreign Language (EFL) learners' writing development and feedback literacy in a Japanese university. Twenty-one first-year students completed nine Write & Improve (W&I) tasks, progressing from descriptive to argumentative essays. Each task was revised following W&I feedback, and students were asked to write a short reflective log. An explanatory mixed-methods approach was adopted, combining quantitative analyses of writing performance and linguistic features with qualitative coding of students' reflections. Findings showed measurable gains in both higher- and lower-level groups, with particularly notable improvement among lower-level students in complexity, fluency, and sophistication. While the higher group consistently outperformed the lower group in Term 1, this gap narrowed in Term 2. Reflection logs provided important insights into feedback literacy: students initially valued W&I for surface-level corrections but later expressed frustration as tasks became more complex and scores plateaued. This tendency was especially evident among lower-level students, reflecting both the affordances and limitations of automated feedback. The study concludes that AI-assisted tools can foster writing development and emerging feedback literacy, but sustained progress requires teacher mediation. Integrating Automated Writing Evaluation (AWE) into ecological feedback environments - combining AI, teacher, and student reflection - offers a promising approach for sustainable L2 writing instruction. 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 HLA-matched versus haploidentical donor transplantation with post-transplant cyclophosphamide: a study on behalf of the donor/source working group of the Japanese society for transplantation and cellular therapy 255 EN Yosuke Nakaya Department of Hematology, Osaka Metropolitan University Graduate School of Medicine Hirohisa Nakamae Department of Hematology, Osaka Metropolitan University Graduate School of Medicine Junichi Sugita Department of Hematology, Sapporo Hokuyu Hospital Junya Kanda Department of Hematology, Graduate School of Medicine, Kyoto University Yuta Hasegawa Department of Hematology, Hokkaido University Hospital Tetsuya Eto Department of Hematology, Hamanomachi Hospital Takahiro Fukuda Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital Naoki Kurita Department of Hematology, University of Tsukuba Hospital Nobuhiro Hiramoto Department of Hematology, Kobe City Medical Center General Hospital Koji Nagafuji Division of Hematology and Oncology, Department of Medicine, Kurume University HospitalDepartment of Hematology, Sapporo Hokuyu Hospital Shuichi Ota Department of Hematology, Sapporo Hokuyu Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Toshihiko Ando Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University Toshiro Kawakita Department of Hematology, NHO Kumamoto Medical Center Takashi Akasaka Department of Hematology, Tenri Hospital Yasuo Mori Hematology, Oncology & Cardiovascular medicine, Kyushu University Hospital Tomohiko Kamimura Department of Hematology, Harasanshin Hospital Makoto Onizuka Department of Hematology/Oncology, Tokai University School of Medicine Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Hideki Nakasone Division of Hematology, Jichi Medical University Saitama Medical Center Post-transplant cyclophosphamide (PTCy) is now being increasingly applied to HLA-matched donor (MD) transplantation. Prior studies in Western countries have demonstrated that allogeneic hematopoietic cell transplantation (allo-HCT) employing PTCy yields better outcomes with HLA-matched donors (MDs) than with haploidentical donors (HIDs). However, the effect of HLA mismatch may differ among racial groups. We retrospectively analyzed adult patients with hematological malignancies who underwent their first allo-HCT with PTCy from MDs or HIDs registered to the Japanese registry database between 2013 and 2021. Among 63 (related, n = 33; unrelated, n = 30) and 1261 patients who received MD and HID allo-HCT with PTCy, 50 (related, n = 30; unrelated, n = 20) and 100 patients were assigned to MD and HID groups by 1:2 propensity score matching (PSM). The results showed that MD recipients had better neutrophil recovery (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.04–2.10; P = 0.031) and lower risk of non-relapse mortality (NRM) (HR, 0.19; 95% CI, 0.05–0.81; P = 0.024) than HID recipients. Multivariable analyses in the entire cohort before PSM confirmed these findings. Fatal infection was the primary cause of NRM in the HID group. This study is the first to demonstrate that, within a homogeneous Asian cohort, MD may have an advantage over HID in PTCy-based allo-HCT in facilitating neutrophil engraftment and reducing the risk of NRM. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2090-6447 2026 1 2026 A Case of Peripheral Odontogenic Myxofibroma Arising in the Palatal Gingiva of the Maxillary Second Premolar Region: A Case Report EN Masanori Masui Department of Oral and Maxillofacial Surgery , Faculty of Medicine , Dentistry and Pharmaceutical Sciences Okayama University Hirokazu Yutori Department of Oral and Maxillofacial Surgery , Kagawa Prefectural Central Hospital Ai Fujimura Department of Oral and Maxillofacial Surgery , Kagawa Prefectural Central Hospital Soichiro Ibaragi Department of Oral and Maxillofacial Surgery , Faculty of Medicine , Dentistry and Pharmaceutical Sciences Okayama University Odontogenic myxofibroma (OMF) is a rare benign mesenchymal odontogenic tumor characterized by myxoid stroma with a prominent fibrous component. Although it usually arises intraosseously within the jaws, the peripheral variant, peripheral odontogenic myxofibroma (POMF), which occurs in extraosseous soft tissues, is uncommon and may be clinically misdiagnosed as a reactive gingival lesion. We report a case of POMF in a 68-year-old man who was referred for evaluation of a painless, slowly enlarging swelling of the palatal gingiva in the left maxillary second premolar region, which had initially been diagnosed as chronic periodontitis at a local clinic. An intraoral examination revealed an elastic, firm mass with partial erythema on the palatal marginal gingiva. Panoramic radiography showed mild generalized horizontal bone loss without lesion-specific changes, and computed tomography revealed no bone resorption associated with the lesion. Exfoliative cytology was negative for intraepithelial lesions or malignancy. The lesion was excised with a 5-mm clinical margin, including periosteum, and superficial peripheral ostectomy of the adjacent cortical bone was performed. Histopathological examination revealed a myxoid stroma rich in mucinous matrix and collagen fibers, containing sparsely distributed spindle-shaped cells and scattered nests of odontogenic epithelium. Alcian blue staining revealed diffuse positivity, supporting the diagnosis of POMF. No recurrence was observed during a 2-year follow-up period. This case highlights a diagnostic pitfall in the tooth-bearing gingiva and underscores the importance of histopathological confirmation of persistent gingival masses. When imaging shows no apparent bone involvement, and clinical suspicion of malignancy is low, complete excision with an adequate soft-tissue margin and selective, limited bone removal may achieve local control while preserving the adjacent teeth; long-term follow-up remains advisable. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2026 Gemcitabine-Induced neutrophil extracellular traps via interleukin-8-CXCR1/2 pathway promote chemoresistance in pancreatic cancer EN Shohei NOGI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2026 亜鉛トランスポーター1の速度論とpH依存性を中心とした輸送特性の解明 EN Yuma YOSHIOKA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2026 Dynamin 2 is involved in osteoblast migration by regulating the organization of F-actin EN Takumi MORIYA 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.

岡山大学算数・数学教育学会 Acta Medica Okayama 1341-3155 32 2026 基準量を1とみる見方の様相－小学校第4学年「割合」の授業実践を通して－ 21 28 EN 　本研究の目的は，小学校算数科における割合の見方である基準量を1とみる見方の様相について第4学年の授業実践を通して考察することである．第4学年の割合の出発点の学習において重要なことは，2つの数量関係の比較を行う場合，数学的な見方として，「基準とする数量を1とみたとき，もう一方の数量が何倍にあたるか」という割合の見方をすることが大切である．しかし，その見方を働かせることは子どもには相当難解である．一般的な問題点は，どうせ難しいからと「基準量を1とみましょう」と安易に指導者が教え込むため，不十分な理解のまま学習が進むことである．「基準量を1とみるとは一体どういうことなのか」「なぜ，基準量を1とみなければならないのか」と子ども自らがニーズを発見し，強く意識的に考えることが不可欠である．そうしなければ，5・6学年で発展的に百分率や比について学ぶ際に，割合の考えを活性化して割合の考えを統合的･発展的に深められることはできないと考える．本研究では，どのような指導の工夫をすれば，第4学年の子ども自らが基準量を1とみる見方で2量を比較する割合の考えを創発するか，授業実践を通して実証的に検証する． No potential conflict of interest relevant to this article was reported.

岡山大学算数・数学教育学会 Acta Medica Okayama 1341-3155 32 2026 図形の概念を形成する数学的活動の工夫～第2学年「三角形と四角形」の学びを通して～ 1 8 EN 　令和7年9月、中央教育審議会の教育課程企画特別部会が論点整理（素案）を発表した。この中で、令和9年に告示が見込まれる次期学習指導要領に向けての基本的な考え方が示された。➀主体的・対話的で深い学びの実装、②多様性の包摂、③実現可能性の確保、を柱に「多様な子供たちの『深い学び』を確かなものに」というフレーズが示されている。これにより、次期学習指導要領も引き続き、「主体的・対話的で深い学び」という授業改善の視点を重視し子どもの資質・能力を育成する方向性は継続されることが示された。変化の激しい時代を生き抜く多様な子どもたちに必要となる資質・能力の中核は、思考力・判断力・表現力だと考える。自分の頭で考え、判断し、表現する力、相手を説得する力が求められている。 　本研究では、第2学年「三角形と四角形」において、三角形と四角形の概念を形成する数学的活動の在り方を探究する。図形を弁別する数学的活動に焦点を当て、図形の概念を形成し、根拠をもとに説明する力をいかに育成すべきかを提案する。 No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 16 3 2026 Protocol for an open-label, randomised, controlled trial to evaluate the efficacy and safety of sotatercept add-on therapy compared with pulmonary vasodilator-based standard of care for pulmonary vasodilator-resistant pulmonary arterial hypertension associated with unrepaired congenital shunts (atrial septal defect, ventricular septal defect or patent ductus arteriosus), including Eisenmenger syndrome: the SuMILE trial e113430 EN Keimei Yoshida Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University Kazuya Hosokawa Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University Takahiro Hiraide Department of Cardiology, Keio University School of Medicine Satoshi Akagi Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaro Ejiri Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yu Taniguchi Division of Cardiovascular Medicine, Kobe University Hospital Shiro Adachi Department of Cardiology, Nagoya University Hospital Takumi Inami Department of Cardiovascular Medicine, Kyorin University School of Medicine Naohiko Nakanishi Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Masaharu Kataoka The Second Department of Internal Medicine, University of Occupational and Environmental Health Taijyu Satoh Department of Medical Science and Innovation, SiRIUS Institute of Medical Research, Tohoku University Shunsuke Tatebe Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine Toshiro Shinke Division of Cardiology, Department of Medicine, Showa Medical University Hospital Hideshi Tomita Periatric Heart Disease and Adult Congenital Heart Disease Center, Showa Medical University Hospital Yusuke Akazawa Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Takashi Higaki Department of Pediatric and Adolescent Therapeutic and Developmental Education, Ehime University Graduate School of Medicine Koshiro Tagawa Center for Clinical and Translational Research, Kyushu University Hospital Ayako Ishikita Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University Soshun Asakawa Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University Kohtaro Abe Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University Introduction Eisenmenger syndrome and pulmonary arterial hypertension (PAH) due to unrepaired congenital shunts, including atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA), remain life-threatening conditions despite advances in congenital heart disease (CHD) care. In this population, vasodilator-based therapies effective in other forms of PAH have shown limited benefit, and no disease-modifying treatment has been established. Sotatercept, an activin-signalling inhibitor, improved exercise capacity and haemodynamics in phase 2/3 PAH trials; however, patients with unrepaired CHD, including Eisenmenger syndrome, were excluded. The efficacy and safety of sotatercept in this population remain unknown. Methods and analysis The SuMILE trial is a prospective, exploratory, multicentre, open-label, randomised, controlled trial conducted at 11 Japanese tertiary centres. 36 adults with vasodilator-resistant PAH due to unrepaired ASD, VSD or PDA, including Eisenmenger syndrome, will be randomised 2:1 to sotatercept add-on therapy plus vasodilator-based PAH therapy versus vasodilator-based PAH therapy alone. Sotatercept will be administered subcutaneously every 3 weeks in accordance with label-approved dose-modification rules for haemoglobin and platelet changes. The primary endpoint is the change in 6-min walk distance from baseline to week 24. Key clinical events will be independently adjudicated. Secondary endpoints include all-cause mortality or lung transplantation; pulmonary hypertension-related hospitalisation or initiation of parenteral prostacyclin and changes in WHO functional class, N-terminal pro-brain natriuretic peptide and emPHasis-10. Exploratory endpoints include genotype, right heart catheterisation and cardiac MRI parameters. The primary analysis will use ANCOVA, adjusting for baseline 6-min walk distance and randomisation stratum in the intention-to-treat population. Ethics and dissemination The protocol has been reviewed and approved by the certified central review board (Kyushu University Hospital Clinical Ethics Review Board) and participating institutions. Written informed consent will be obtained from all participants. Findings will be disseminated through peer-reviewed journals, scientific conferences and trial registries. Trial registration number Japan Registry of Clinical Trials no. 1071250069; ClinicalTrials.gov NCT07356778. Protocol version and date: V.1.3; 23 October 2025 No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0003-6862 2026 Effect of caffeine on life-history traits on the red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae) EN Shine Shane Naing Okayama University (Graduate School of Environmental, Life, Natural Science and Technology) Teruhisa Matsuura Okayama University (Graduate School of Environmental, Life, Natural Science and Technology) Takahisa Miyatake Okayama University (Graduate School of Environmental, Life, Natural Science and Technology) Nowadays, addressing insect pest infestation effectively requires environmentally sound and sustainable pest control methods that minimize environmental pollution. Caffeine (1, 3, 7-trimethylxanthine), a plant-derived secondary metabolite, has insecticidal, hormonal and antifeedant properties, making it a promising and more sustainable alternative for pest management. In this study, the red flour beetle Tribolium castaneum Herbst (Coleoptera: Tenebrionidae), a serious stored pest, was used to investigate the effects of different caffeine concentrations on life-history traits. We applied two delivery methods: 1) oral exposure through a caffeine–sucrose solution for adults, and 2) dietary incorporation of caffeine powder mixed with wheat flour and brewer’s yeast for adults and their larvae. To evaluate the effect of caffeine on life-history traits, adult longevity, pupation rate, larval period, pupal weight, adult body size and food consumption were examined. Results revealed higher caffeine concentrations (> 1%) significantly reduced longevity, delayed pupation, decreased pupal number, pupal weight and adult body size in both males and females. Lower caffeine concentration (0.01%) increased pupal number but resulted in lower offspring quality, such as smaller pupal weight and adult size. The results show that caffeine has negative effects on life-history traits of T. castaneum, suggesting its potential use as a natural pesticide in caffeine-based sustainable pest-management programs and integrated pest management (IPM). No potential conflict of interest relevant to this article was reported.

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

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.

岡山英文学会 Acta Medica Okayama 0389-7788 53 2026 Japanese Students’ Engagement with a Social Language Learning Space: Awareness, Anxiety, and Participation at L-café 1 13 EN Jingzhou Wang No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 138 1 2026 令和６年度岡山医学会賞　総合研究奨励賞（結城賞） 4 6 EN Ryosuke Sato Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0304-4203 276 2026 Determination of picomolar to sub-nanomolar trace metals in seawater using an alternative chelating resin 104642 EN Naoya Kanna Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hajime Obata Atmosphere and Ocean Research Institute, The University of Tokyo Yoshiko Kondo Graduate School of Fisheries and Environmental Sciences, Nagasaki University In this study, we investigated the potential use of a chelating resin that immobilizes an amine with an iminodiacetic acid group (InertSep ME-2) for trace-metal analysis in natural seawater. Seven trace metals (Mn, Fe, Co, Ni, Cu, Zn, and Pb) were quantitatively preconcentrated onto the InertSep ME-2 chelating resin, eluted with nitric acid, and analyzed using high-resolution inductively coupled plasma mass spectrometry. The blank values and detection limits obtained using our method were at the sub-nanomolar level for most trace metals. These blank values were generally comparable to, or lower than, those previously reported for other chelating resins, including NOBIAS Chelate PA-1 and Toyopearl AF-Chelate-650 M. The accuracy and precision of our method were confirmed by analyzing reference seawater samples, and the results for the open-water samples were consistent with those obtained in an independent laboratory. The established preconcentration procedure was successfully applied to determine trace metal concentrations in natural seawater collected from the northwestern Pacific Ocean. Our method, which employs the InertSep ME-2 chelating resin, is sufficiently accurate for studying trace metals in open-ocean water at picomolar- to sub-nanomolar-level concentrations. 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.

Puar THK, Stikkelbroeck NMML, Smans LCCJ, Zelissen PMJ and Hermus ARMM: Adrenal Crisis: Still a Deadly Event in the 21st Century. Am J Med (2016) 129: 339.e1-339.e9. Dineen R, Thompson CJ and Sherlock M: Adrenal crisis: prevention and management in adult patients. Ther Adv Endocrinol Metab (2019) 10: 2042018819848218. Lousada LM, Mendonca BB and Bachega TASS: Adrenal crisis and mortality rate in adrenal insufficiency and congenital adrenal hyperplasia. Arch Endocrinol Metab (2021) 65: 488-494. Worth C, Vyas A, Banerjee I, Lin W, Jones J, Stokes H, Komlosy N, Ball S and Clayton P: Acute Illness and Death in Children With Adrenal Insufficiency. Front Endocrinol (Lausanne) (2021) 12: 757566. White KG: A retrospective analysis of adrenal crisis in steroid-dependent patients: Causes, frequency and outcomes. BMC Endocr Disord (2019) 19: 129. Hahner S, Spinnler C, Fassnacht M, Burger-Stritt S, Lang K, Milovanovic D, Beuschlein F, Willenberg HS, Quinkler M and Allolio B: High Incidence of Adrenal Crisis in Educated Patients With Chronic Adrenal Insufficiency: A Prospective Study. J Clin Endocrinol Metab (2015) 100: 407-416. Çamtosun E and Sangün Ö: Treatment and Prevention of Adrenal Crisis and Family Education. J Clin Res Pediatr Endocrinol (2025) 17: 80-92. Simcoe S and Simcoe RA: Emergency department evaluation and management of patients with adrenal insufficiency. Emerg Med Pract (2025) 27: 1-20. Husebye ES, Pearce SH, Krone NP and Kämpe O: Adrenal insufficiency. Lancet (2021) 397: 613-629. Lentz S, Collier KC, Willis G and Long B: Diagnosis and Management of Adrenal Insufficiency and Adrenal Crisis in the Emergency Department. J Emerg Med (2022) 63: 212-220. Mushtaq T, Ali SR, Boulos N, Boyle R, Cheetham T, Davies JH, Elder CJ, Gan HW, Hindmarsh PC, Katugampola H, Krone N, Salomon Estebanez M, Shenoy S, Tollerfield S, Wong SC and Regan F; Developed by the Paediatric Adrenal Insufficiency Group on behalf of the British Society for Paediatric Endocrinology and Diabetes (BSPED): Emergency and perioperative management of adrenal insufficiency in children and young people: British Society for Paediatric Endocrinology and Diabetes consensus guidance. Arch Dis Child (2023) 108: 871-878. Venkatesh B, Cohen J and Cooper M: Ten false beliefs about cortisol in critically ill patients. Intensive Care Med (2015) 41: 1817-1819.

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.

Zago TM, Pereira BMT, Calderan TRA, Hirano ES and Fraga GP: Extrahepatic duct injury in blunt trauma: two case reports and a literature review. Indian J Surg (2014) 76: 303-307. Feliciano DV: Biliary injuries as a result of blunt and penetrating trauma. Surg Clin North Am (1994) 74: 897-907. Balzarotti R, Cimbanassi S, Chiara O, Zabbialini G and Smadja C: Isolated extrahepatic bile duct rupture: a rare consequence of blunt abdominal trauma. Case report and review of the literature. World J Emerg Surg (2012) 7: 16. Ishida T, Hayashi E, Tojima Y and Sakakibara M: Rupture of the common bile duct due to blunt trauma, presenting difficulty in diagnosis. BMJ Case Rep (2018) 11: e227400. Ghosh S, Kazi FN and Sharma JVP: Extrahepatic bile duct injury caused by blunt abdomen trauma: a case report. Cureus (2022) 14: e25748. Sanford Z, Abdolmaali K, Robinson D and Denning D: Blunt trauma: an uncommon cause of common bile duct injury. Trauma Case Rep (2015) 1: 44-48. Zakaria HM, Oteem A, Gaballa NK, Hegazy O, Nada A, Zakareya T, Omar H, Abdelkawy H, Abdeldayem H and Gad EH: Risk factors and management of different types of biliary injuries in blunt abdominal trauma: single-center retrospective cohort study. Ann Med Surg (Lond) (2020) 52: 36-43. Agarwal H, Gupta A and Kumar S: An overview of Pancreatic Trauma. J Pancreatol (2020) 3: 139-146. Iacono C, Zicari M, Conci S, Valdegamberi A, De Angelis M, Pedrazzani C, Ruzzenente A and Guglielmi A: Management of pancreatic trauma: a pancreatic surgeonʼs point of view. Pancreatology (2016) 16: 302-308. Krige JE, Nicol AJ and Navsaria PH: Emergency pancreatoduodenectomy for complex injuries of the pancreas and duodenum. HPB (Oxford) (2014) 16: 1043-1049. Leppäniemi A, Tolonen M, Tarasconi A, Segovia-Lohse H, Gamberini E, Kirkpatrick AW, Ball CG, Parry N, Sartelli M, Wolbrink D, van Goor H, Baiocchi G, Ansaloni L, Biffl W, Coccolini F, Di Saverio S, Kluger Y, Moore E and Catena F: 2019 WSES guidelines for the management of severe acute pancreatitis. World J Emerg Surg (2019) 14: 27. Turan ÖF, Çankaya Gökdere D, Genç M, Bulut B, Akkanöz M, Mutlu H and Yazıcı R: Predictive factors of mortality in patients with abdominal trauma. Ulus Travma Acil Cerrahi Derg (2025) 31: 276-282. van der Wilden GM, Yeh D, Hwabejire JO, Klein EN, Fagenholz PJ, King DR, de Moya MA, Chang Y and Velmahos GC: Trauma Whipple: do or donʼt after severe pancreaticoduodenal injuries? An analysis of the national trauma data bank (NTDB). World J Surg (2014) 38: 335-340. Ylimartimo AT, Koskela M, Lahtinen S, Kaakinen T, Vakkala M and Liisanantti J: Outcomes in patients requiring intensive care unit (ICU) admission after emergency laparotomy: a retrospective study. Acta Anaesthesiol Scand (2022) 66: 954-960.

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

Beck DB, Ferrada MA, Sikora KA, Ombrello AK, Collins JC, Pei W, Balanda N, Ross DL, Ospina Cardona D, Wu Z, Patel B, Manthiram K, Groarke EM, Gutierrez-Rodrigues F, Hoffmann P, Rosenzweig S, Nakabo S, Dillon LW, Hourigan CS, Tsai WL, Gupta S, Carmona-Rivera C, Asmar AJ, Xu L, Oda H, Goodspeed W, Barron KS, Nehrebecky M, Jones A, Laird RS, Deuitch N, Rowczenio D, Rominger E, Wells KV, Lee CR, Wang W, Trick M, Mullikin J, Wigerblad G, Brooks S, DellʼOrso S, Deng Z, Chae JJ, Dulau-Florea A, Malicdan MCV, Novacic D, Colbert RA, Kaplan MJ, Gadina M, Savic S, Lachmann HJ, Abu-Asab M, Solomon BD, Retterer K, Gahl WA, Burgess SM, Aksentijevich I, Young NS, Calvo KR, Werner A, Kastner DL and Grayson PC: Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. N Engl J Med (2020) 383: 2628-2638. Georgin-Lavialle S, Terrier B, Guedon AF, Heiblig M, Comont T, Lazaro E, Lacombe V, Terriou L, Ardois S, Bouaziz JD, Mathian A, Le Guenno G, Aouba A, Outh R, Meyer A, Roux-Sauvat M, Ebbo M, Zhao LP, Bigot A, Jamilloux Y, Guillotin V, Flamarion E, Henneton P, Vial G, Jachiet V, Rossignol J, Vinzio S, Weitten T, Vinit J, Deligny C, Humbert S, Samson M, Magy-Bertrand N, Moulinet T, Bourguiba R, Hanslik T, Bachmeyer C, Sebert M, Kostine M, Bienvenu B, Biscay P, Liozon E, Sailler L, Chasset F, Audemard-Verger A, Duroyon E, Sarrabay G, Borlot F, Dieval C, Cluzeau T, Marianetti P, Lobbes H, Boursier G, Gerfaud-Valentin M, Jeannel J, Servettaz A, Audia S, Larue M, Henriot B, Faucher B, Graveleau J, de Sainte Marie B, Galland J, Bouillet L, Arnaud C, Ades L, Carrat F, Hirsch P, Fenaux P, Fain O, Sujobert P, Kosmider O and Mekinian A: Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients. Br J Dermatol (2022) 186: 564-574. de Valence B, Delaune M, Nguyen Y, Jachiet V, Heiblig M, Jean A, Riescher Tuczkiewicz S, Henneton P, Guilpain P, Schleinitz N, Le Guenno G, Lobbes H, Lacombe V, Ardois S, Lazaro E, Langlois V, Outh R, Vinit J, Martellosio JP, Decker P, Moulinet T, Dieudonne Y, Bigot A, Terriou L, Vlakos A, de Maleprade B, Denis G, Broner J, Kostine M, Humbert S, Lifermann F, Samson M, Pechuzal S, Aouba A, Kosmider O, Dion J, Grosleron S, Bourguiba R, Terrier B, Georgin-Lavialle S, Fain O, Mekinian A, Morgand M, Comont T, Hadjadj J and French VG: Serious infections in patients with VEXAS syndrome: data from the French VEXAS registry. Ann Rheum Dis (2024) 83: 372-381. Drancourt M, Bollet C, Carta A and Rousselier P: Phylogenetic analyses of Klebsiella species delineate Klebsiella and Raoultella gen. nov., with description of Raoultella ornithinolytica comb. nov., Raoultella terrigena comb. nov. and Raoultella planticola comb. nov. Int J Syst Evol Microbiol (2001) 51: 925-932. Huang Q, Zhang J and Liao G: Abdominal abscess caused by Raoultella ornithinolytica secondary to postoperative gastric fistula: case report and review of literature. BMC Infect Dis (2024) 24: 363. Goodman DT, Murphy D and Dorairaj J: Case Study: Soft tissue infection with Raoultella ornithinolytica. JPRAS Open (2022) 33: 17-20. Shimizu T, Ide H, Tsuji Y, Koga T and Kawakami A: VEXAS syndrome complicated with severe infection. Rheumatology (Oxford) (2022) 61: e374-e376. Yoshida A, Ota T, Sasaoka S, Matsuura H, Fujimoto W and Morita Y; Necrotizing fasciitis in a patient with rheumatoid arthritis treated with tocilizumab: Mod Rheumatol (2012) 22: 317-318. van de Sande MG and van Slobbe-Bijlsma ER: Necrotizing fasciitis in a rheumatoid arthritis patient treated with tocilizumab. Rheumatology (Oxford) (2012) 51: 577-578. Seng P, Boushab BM, Romain F, Gouriet F, Bruder N, Martin C, Paganelli F, Bernit E, Le Treut YP, Thomas P, Papazian L, Raoult D and Stein A: Emerging role of Raoultella ornithinolytica in human infections: a series of cases and review of the literature. Int J Infect Dis (2016) 45: 65-71. Sekowska A, Dylewska K, Gospodarek E and Bogiel T: Catheter-related blood stream infection caused by Raoultella ornithinolytica. Folia Microbiol (Praha) (2015) 60: 493-495. Van Cleve JR, Boucher BA, Smith DV and Croce MA: Ventilator associated pneumonia caused by Raoultella ornithinolytica in two immunocompetent trauma patients. Respir Med Case Rep (2018) 24: 135-137. Wang S, Xu L, Chi X, Li Y, Kou Z, Hou P, Xie H, Bi Z and Zheng B: Emergence of NDM-1- and CTX-M-3-Producing Raoultella ornithinolytica in Human Gut Microbiota. Front Microbiol (2019) 10: 2678. Sekowska A, Bogiel T, Wozniak M and Gospodarek-Komkowska E: Raoultella spp. - reliable identification, susceptibility to antimicrobials and antibiotic resistance mechanisms. J Med Microbiol (2020) 69: 233-238.

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.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 80 2 2026 Consistent Clinical Outcomes of Anteroinferior Minimally Invasive Plate Osteosynthesis for Midshaft Clavicle Fractures Across AO/OTA Fracture Types 99 107 EN Nguyen Trung Thanh Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Nakamichi Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasunori Shimamura Department of Orthopaedic Surgery, Kousei Hospital Taichi Saito Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Ishihara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoki Furutani Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisakazu Shitozawa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Noda Department of Orthopaedic Surgery, Kawasaki Medical School General Medical Center Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/70452 Although the performance of minimally invasive plate osteosynthesis (MIPO) via the anteroinferior approach is increasingly adopted for midshaft clavicle fractures, the influence of fracture morphology on clinical outcomes under a standardized protocol is unclear. We retrospectively analyzed the cases of 54 patients who underwent anteroinferior MIPO for an acute midshaft clavicle fracture (AO/OTA types B1, B2, B3) performed by a single surgeon across three affiliated institutions (2009-2022). We evaluated the clinical outcomes, i.e., the surgical time, incision length, radiographic union, reduction accuracy, range of motion, pain (visual analog scale [VAS]), and complications and compared them among the three AO/OTA subtypes. The mean incision length (3.4 cm) and surgical time (71-79 min) were similar among the groups (both p>0.2). All fractures achieved radiographic union at a mean of 3.5 months. Postoperative alignment and clavicular length were maintained (length reduction −1.0±2.2 mm [B1], −0.5±2.0 mm [B2], −0.6±1.8 mm [B3]; p=0.825; angulation −0.8±3.4°, −1.1±3.1°, −0.3±3.3°; p=0.888). At 3 months, shoulder elevation and abduction were 169°-175° (p=0.079) and 164°-175° (p=0.324). Pain was minimal (100-mm VAS: ≤1 mm; p=0.782). One plate-fatigue failure occurred; no supraclavicular-nerve symptoms were recorded. Anteroinferior MIPO yielded consistent outcomes across AO/OTA types, with excellent union rates, functional recovery, and few complications, indicating that this technique is safe and reproducible for the surgical management of midshaft clavicle fractures. No potential conflict of interest relevant to this article was reported.

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

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Okayama University Medical School Acta Medica Okayama 0386-300X 80 2 2026 Involvement of ADAM12 in TGF-β1-Induced Proliferation of Rheumatoid Arthritis Synovial Fibroblasts 75 83 EN Deting Lin Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Horita Department of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama University Masahito Watanabe Department of Orthopaedic Surgery, Muscat Orthopaedic Clinic Joe Hasei Medical Information and Assistive Technology Development, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Ohtsuki Medical Technology, Graduate School of Health Sciences, Okayama University Noriaki Otsuka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chinatsu Ichikawa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Shimizu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuichi Naniwa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nishida Division of Chronic Pain Medicine and Division of Comprehensive Rheumatology, Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Original Article 10.18926/AMO/70450 A disintegrin and metalloproteinase 12 (ADAM12) is known to be involved in chondrocyte proliferation and is upregulated in the synovial tissue of osteoarthritis (OA). However, the underlying mechanisms of ADAM12 on rheumatoid arthritis (RA) synovial cell proliferation remain unknown. Here, we investigated the role of ADAM12 in the proliferation of RA synovial fibroblasts (RASFs). The expression and localization of ADAM12 in RA synovial tissues were examined by immunohistochemistry and compared with OA and healthy control (HC) synovial tissues. The effect of inflammatory cytokines (TNF-α, TGF-β1, and PDGF-BB) on ADAM12 expression in RASFs from RA patients was examined by real-time RT-PCR. The effect of ADAM12 knock-down by ADAM12 siRNA and ADAM12 overexpression on cell proliferation of RASFs were examined by WST-1 assay. ADAM12 was identified predominantly in RA synovial tissue rather than OA and HC synovial tissues. Stimulation with TGF-β1 upregulated the expression of ADAM12 and cell proliferation of RASFs. ADAM12 siRNA suppressed TGF-β1-induced cell proliferation of RASFs, while ADAM12 overexpression promoted the cell proliferation of RASFs. These findings demonstrate that ADAM12 may have a key role in TGF-β1-induced cell proliferation of synovial fibroblasts in patients with RA. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2190-5991 17 2 2026 Muscle Atrophy-Related Adverse Events of Antidiabetic Drug Classes: A Pharmacovigilance Analysis Using VigiBase Data e70251 EN Shiho Ueta Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Takahiro Niimura Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Mitsuhiro Goda Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Tomoaki Ishida Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University Naohiro Iwata Department of Pharmacy, Okayama University Hospital Tatsuaki Takeda Department of Pharmacy, Okayama University Hospital Kei Kawada Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Koji Miyata Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Fuka Aizawa Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Kenta Yagi Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Masayuki Chuma Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical University Yuki Izawa‐Ishizawa Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Yoshito Zamami Department of Pharmacy, Okayama University Hospital Keisuke Ishizawa Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Background: Diabetes mellitus—a chronic metabolic disorder associated with an increased risk of muscle atrophy—can significantly impact patients' quality of life and overall health outcomes. While antidiabetic medications are crucial for managing blood glucose levels, some have been linked to muscle-related adverse events, potentially exacerbating the already elevated risk of muscle deterioration in diabetic patients. However, a comprehensive analysis of muscle atrophy-related adverse events across different classes of antidiabetic drugs has been lacking. Therefore, this study investigates the profile of muscle atrophy-related adverse events across major antidiabetic drug classes using the World Health Organization's (WHO's) Individual Case Safety Reports database. Methods: A pharmacovigilance analysis was conducted using data from VigiBase, the WHO's global reporting database, from 1968 to September 2025. The study examined adverse event signals related to muscle atrophy, sarcopenia, muscular weakness and motor function decline for nine classes of antidiabetic medications. Reporting odds ratios (RORs) were calculated to assess signal detection, and co-occurrence patterns of adverse events were analysed. Results: Among 41 551 306 adverse event reports, 2 095 847 were related to antidiabetic medications. Safety signals for muscle atrophy were detected with sulfonylureas (ROR: 1.2, 95% CI: 1.01–1.43, p = 0.042), GLP-1 analogues (ROR: 1.2, 95% CI: 1.02–1.41, p = 0.031) and SGLT2 inhibitors (ROR: 1.5, 95% CI: 1.19–1.78, p < 0.001). SGLT2 inhibitors also showed a signal for sarcopenia (ROR: 6.2, 95% CI: 3.71–10.3, p < 0.001). Biguanides demonstrated signals for muscular weakness (ROR: 1.6, 95% CI: 1.54–1.71, p < 0.001) and motor function decline (ROR: 1.7, 95% CI: 1.41–2.13, p < 0.001). Thiazolidinediones, glinides, DPP-4 inhibitors and alpha-glucosidase inhibitors showed no safety signals for the examined adverse events. Additionally, co-occurrence analysis revealed frequent associations between muscle atrophy and nausea/vomiting, falls and decreased appetite across different drug classes. Conclusions: These findings indicate notable differences in the profiles of muscle atrophy–related adverse events among major classes of antidiabetic drugs, suggesting that drug selection may influence the risk of muscle function decline in patients. Clinicians should consider these safety profiles when prescribing antidiabetic therapies; however, causal relationships cannot be inferred solely from pharmacovigilance data. Further studies are warranted to establish causality between antidiabetic drug use and muscle-related adverse events and to elucidate the underlying mechanisms. No potential conflict of interest relevant to this article was reported.

American Astronomical Society Acta Medica Okayama 0067-0049 283 2 2026 The Simons Observatory: Detector Polarization Angle Calibration Using a Sparse Wire Grid with Initial Datasets of the Small-aperture Telescopes 78 EN Hironobu Nakata Department of Physics, Faculty of Science, Kyoto University Shunsuke Adachi Okayama University, Department of Physics Kyohei Yamada Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University Michael Randall Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University Yutaro Kasai Department of Physics, Faculty of Science, Kyoto University Kam Arnold Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University Bryce Bixler Department of Physics, University of California San Diego Yuji Chinone QUP (WPI), KEK Kevin T. Crowley Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University Nadia Dachlythra Department of Physics, University of Milano-Bicocca Samuel Day-Weiss Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University Nicholas Galitzki Department of Physics, University of Texas at Austin Serena Giardiello School of Physics and Astronomy, Cardiff University Bradley R. Johnson University of Virginia, Department of Astronomy Brian Keating Department of Physics, University of California San Diego Brian J. Koopman Wright Laboratory, Department of Physics, Yale University Akito Kusaka Kavli IPMU (WPI), UTIAS, The University of Tokyo Jack Lashner Wright Laboratory, Department of Physics, Yale University Federico Nati Department of Physics, University of Milano-Bicocca Lyman Page Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University Daichi Sasaki Department of Physics, The University of Tokyo Yoshinori Sueno Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University Junya Suzuki Department of Physics, Faculty of Science, Kyoto University Osamu Tajima Department of Physics, Faculty of Science, Kyoto University Tran Tsan Physics Division, Lawrence Berkeley National Laboratory Improved measurements of B-modes in the cosmic microwave background can be obtained through accurate calibration of the orientation of detector antennas as projected onto the sky. Miscalibration of the detector polarization angle leads to a leakage of E-modes into B-modes, which can bias the detection of the latter. To achieve a σ(r) of 0.003, the Simons Observatory small-aperture telescopes are required to calibrate the global polarization angle on the sky with an accuracy ≲0.°1. We demonstrate a fully remote-controllable calibration system using a “sparse wire grid,” which injects a rotatable linear polarized signal across the telescope’s focal plane. This calibration system is installed and operational on one of the small-aperture telescopes at its observing site at the Parque Astronómico in the Atacama desert in Chile. We developed a pipeline for the detector polarization angle calibration, and demonstrate it using initial data for 93 and 145 GHz frequency bands. The observed distribution of detector polarization angles is in agreement with the instrument design. Statistical uncertainties for the relatively calibrated polarization angles are 0.°02 and 0.°03 at 93 and 145 GHz, respectively. Systematic uncertainty was evaluated to be 0.°08 at the hardware development and fabrication stage. Their sum in quadrature is less than 0.°1. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0046-5755 220 3 2026 Knot surgered elliptic surfaces without 1- and 3-handles for a (2, 2h + 1)-torus knot 29 EN Naoyuki Monden Department of Mathematics, Faculty of Science, Okayama University Reo Yabuguchi Department of Mathematics, Faculty of Science, Okayama University For any positive integers h and n, we show that a knot surgered elliptic surface E(n)T(2,2h+1) for a (2, 2h + 1)-torus knot T (2, 2h + 1) admits a handle decomposition without 1- and 3-handles using a Kirby diagram derived from a Lefschetz fibration on it. As a corollary, an elliptic surface E(1)2,2h+1 has such a handle decomposition. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 0020-739X 2026 Triangulation in teaching probability: teaching materials for the theoretical foundations of probability in real-world applications EN Yusuke Uegatani Hiroshima University High School Ippo Ishibashi Faculty of Education, Okayama University Aya Sakota Hiroshima University High School This paper proposes using the concept of triangulation with probabilistic models as a means to enhance theoretical inversion for deepening students’ understanding of the nature of probability in real-world contexts. Triangulation refers to the combined application of multiple methodologies to investigate the same phenomenon, particularly in the social sciences. Theoretical inversion refers to a shift in focus from surprising outcomes to the theoretical foundations of probability. The paper introduces three types of problem-solving tasks designed to enhance one of four types of triangulations: theory triangulation. Theoretical inversion is expected to emerge through engaging in these tasks. The characteristics of the problems are as follows. Problem 1 promotes students to compare different probabilistic models of events under similar procedures. Problem 2 provides students with an opportunity to simplify an experiment by omitting steps that add no new information. Problem 3 enhances students’ ability to recognise how subtle differences in the experimental setup can affect the resulting probability. These tasks are designed to encourage students to view probabilistic reasoning as a form of modelling and to appreciate the importance of assumptions, definitions of elementary events, and clarity in procedural descriptions. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Liquid–liquid phase separation by caged coacervating peptides 10464 EN Akinari Bando Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mizuki Kitamatsu Department of Applied Chemistry, Kindai University Yuuki Kanazaki Department of Applied Chemistry, Kindai University Rika Tojo Department of Applied Chemistry, Kindai University Kazunori Watanabe Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Liquid–liquid phase separation is an important biomolecular process in the formation of membraneless intracellular organelles that has inspired the development of artificial droplet systems. We developed caged coacervating peptides (CCPs) based on a histidine-rich squid beak protein sequence. The peptides were caged with a photodeprotectable (7-diethylaminocoumarin-4-yl)methoxycarbonyl group. The CCPs formed coacervates in the caged state and were partially dispersed upon blue-light irradiation. Photo-uncaging occurred rapidly, inducing coacervate dispersion. A mutant CCP with reduced π–π interactions exhibited efficient photo-dependent disassembly and enabled the encapsulation and release of a fluorescently labeled adenosine 5′-triphosphate (Bodipy-ATP) upon irradiation. These CCPs offer an efficient light-controlled approach for biomolecular encapsulation within coacervates and targeted drug delivery. No potential conflict of interest relevant to this article was reported.

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

岡山大学算数・数学教育学会 Acta Medica Okayama 1341-3155 31 2025 小学校3年生のわり算の単元における二重に統合する場面の指導について～かけ算，等分除，包含除の統合的把握におけるかけ算の意味理解の重要性～ 1 11 EN 　平成29年度告示の学習指導要領では，小学校算数科の目標を(1)知識及び技能，(2)思考力，判断力，表現力等，(3)学びに向かう力，人間性等の三本の柱に基づいて示している．特に(2)思考力，判断力，表現力等の内容として，「基本的な数量や図形の性質などを見出し統合的・発展的に考察する力」を養うと記述され，統合を通して子どもの考える力の向上が目指されている． 　本稿は，第 3 学年のわり算の等分除と包含除の問題を様々な視点から比較し，児童に統合する体験をさせることを目的としたものである．授業分析の結果，統合に関しては，等分除と包含除を統合するだけでなく，さらにかけ算とわり算を大きくかけ算とみて統合すること，つまり二重に統合する必要がある場合があり，かけ算の意味理解がこの場面の理解を助けるとともに，二重の統合に起因する学びの困難を指摘することができる． No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1470-1626 171 2 2026 Rho kinase and RND3 regulate the direct effect of estradiol-17β on oviductal tonus xaag004 EN Sayaka Kubota Laboratory of Reproductive Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Risa Okawara School of Agriculture, Okayama University Kohei Kawano Laboratory of Reproductive Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koji Kimura Laboratory of Reproductive Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ensuring the timely transport of gametes and embryos within the oviduct is essential for the successful establishment of pregnancy. This study investigated the direct effect of estradiol-17β (E2) on bovine oviductal contractility and the differences in responsiveness to E2 during the estrous cycle. Bovine isthmic tissues from four estrous stages were analyzed using the Magnus method to assess contractile responses to E2 and related reagents. Protein expression of G-protein-coupled estrogen receptor 1 (GPER1) and components of the RhoA/Rho kinase (ROCK) signaling pathway were also evaluated. E2 and a GPER1 agonist significantly increased oviductal tonus at 1–4 days after ovulation. This effect was significantly suppressed by treatment with a GPER1 antagonist and a ROCK inhibitor. At 1–4 days after ovulation, both ROCK II expression and ROCK activity were elevated. E2 also enhanced phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and myosin light chain (MLC), key downstream targets of ROCK. Before ovulation, when endogenous E2 levels peak, the expression of RND3—a ROCK inhibitor—was upregulated. The application of an RND inhibitor restored E2 responsiveness in oviductal tonus, ROCK activity, and the phosphorylation of MYPT1 and MLC in oviductal tissues before ovulation. These findings suggest that E2 directly increases oviductal tonus via GPER1 and ROCK/MYPT1/MLC activation at 1–4 days after ovulation. Differences in oviductal responsiveness to E2 during the estrous cycle appear to be mediated by the expression of ROCK and RND3. This mechanism can enable sperm transport within the oviduct at an appropriate time. 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 A Self-Adaptive Framework for Deploying Machine Learning Systems Without Ground-Truth Data at Runtime 30309 30326 EN Kento Furukawa Graduate School of Information Science and Technology, Osaka University Hiroyuki Nakagawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tatsuhiro Tsuchiya Graduate School of Information Science and Technology, Osaka University In recent years, the practical application of machine learning technology has rapidly progressed, accelerating its adoption across various fields. In this context, studies into the effective operation of machine learning systems in real-world environments have become essential. In actual operational settings, the distribution of input data often changes over time, leading to a significant decline in the predictive performance of models. Additionally, the lack of ground-truth data for test data during operation can sometimes make adaptation through retraining difficult. This study proposes a framework that autonomously adapts to changes in input data distribution, even in environments where ground-truth data for test data is unavailable during operation. This framework analyzes the distribution of input data and selects the appropriate predictive model based on the state of the distribution. To ensure optimal model selection, the framework employs two complementary approaches: 1) dynamically switching between multiple pre-trained models with different feature sets according to environmental changes and 2) building ensemble models based on the distribution of the test data. These approaches enable the framework to autonomously adapt to shifts in data distribution, even in operational settings where ground-truth data is unavailable. Evaluation experiments using both simulated and real-world data assessed the predictive performance of the proposed method through metrics such as R2, RMSE, and MAE. Compared to conventional single model predictions, the proposed method consistently demonstrated higher accuracy. These results indicate that the proposed approach effectively adapts to data distribution shifts in operational environments where ground-truth data is unavailable. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0143-4160 135 2026 Regulation of brain-specific kinases 1 and 2 (BRSK1/2) by Ca2+/calmodulin 103134 EN Naoyuki Washida Moe Kataoka Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Anna R. Brun Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Uryu Takezaki Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ko Hijikawa Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Haruki Yamauchi Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Satomi Ohtsuka Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masaki Magari Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ryo Morishita CellFree Sciences Co., Ltd. Hiroshi Tokumitsu Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University We conducted a genome-wide calmodulin (CaM) interaction screening of 462 GST-fused human protein kinases to identify novel CaM-dependent protein kinases (CaMKs). In addition to known CaMKs, including myosin light chain kinases, CaMK2γ, and death-associated kinase 2, we identified the brain-specific protein kinase 2 (BRSK2, also known as SAD-A) as a novel CaM interactant. Proximity biotinylation and CaM–sepharose chromatography assays revealed that rat BRSK isoforms (BRSK1/2) interact with CaM in a Ca2+-dependent manner in vitro. We found that CaM suppresses the activation-loop phosphorylation of BRSK1 (at Thr189) and BRSK2 (at Thr175) by liver kinase B1 (LKB1), an activating kinase, in a Ca2+-dependent manner (IC50 of ∼7 µM), thereby inhibiting BRSK activation. LKB1-catalyzed phosphorylation of the catalytic domain mutant of BRSK1 (residues 1–294) at Thr189 was suppressed by the addition of Ca2+/CaM, consistent with direct CaM binding of the kinase domain, as well as wild-type BRSK1. We confirmed that the LKB1 activity was not directly suppressed by Ca2+/CaM, supporting the hypothesis that the direct interaction of Ca2+/CaM with the kinase domain blocks the phosphorylation/activation of BRSK1/2 by LKB1. The kinase activity and PP2Cα-catalyzed dephosphorylation of LKB1-phosphorylated BRSK1 were not altered by Ca2+/CaM, although it was demonstrated to bind to Ca2+/CaM like that of unphosphorylated BRSK1. This unrecognized mechanism of BRSK1/2 regulation, involving the direct role of Ca2+/CaM binding, which inhibits phosphorylation/activation by LKB1, may open a new Ca2+ signal transduction pathway in neurons. No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構教師教育開発センター Acta Medica Okayama 2186-1323 16 2026 地域社会とグローバルをつなぐ和楽器音楽次世代育成の実践研究（３）小中学生の質問紙調査に見る「異文化間能力」育成の可能性 91 105 EN Rinko HAYAKAWA Okayama University Yuko BEPPU Kurashiki City College Miho YAMAJI Part-time Lecturer at Okayama University Yoko HANAKUSA Research Student at the Joint Graduate School in Science of School Education Hyogo University of Teacher Education Noriko TAKESHITA Biwako-Gakuin University Hiromi TAKASU Okayama University Keiko MIYOSHI Research Student at the Joint Graduate School in Science of School Education Hyogo University of Teacher Education Naoko SHIMIZU Doctoral Student at the Joint Graduate School in Science of School Education Hyogo University of Teacher Education Chihiro TOSA Yamaha Corporation Ai NAKAMURA Doctoral Student at the Joint Graduate School in Science of School Education Hyogo University of Teacher Education Aki HIGUCHI Okayama Prefectural School for the Deaf 10.18926/CTED/70362 　本研究は，「おかやま国際和楽器学生フェスティバル」の実践における，異文化間能力育成の可能性について，参加した小中学生の質問紙調査結果から検討した。 　その結果，１）体験を通して形成された新たな認識により，和楽器音楽文化と自己との関係性を再認識・再構築し，和楽器音楽文化への積極的な関与を示す価値づけ・意味づけが行われ，内在化が促されたこと，２）越境文化としての和楽器音楽文化に対して，開放的・尊重的態度を示していたが，自己の文化的アイデンティティを意識する契機となったこと，３）和楽器音楽の共有を通して生じた共感の上に，相互理解や協働関係が構築されていたこと，４）「文化の共有の可能性についての認識」が形成されるなど，フェスティバルでの経験が，文化観の形成に影響を与える契機となっていたこと，が明らかになった。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構教師教育開発センター Acta Medica Okayama 2186-1323 16 2026 外国人幼児の就学支援における保育士の工夫と実践的課題 1 13 EN Yiwen CHEN The Joint Graduate School (Ph.D. Program) in Science of School Education, Hyogo University of Teacher, Hyogo University of Teacher Education Kazuki YANAGISAWA Graduate School of Education, Okayama University Xinyu REN Graduate School of Education, Okayama University Munehisa YOSHITOSHI Faculty of Education, Okayama University 10.18926/CTED/70356 　本研究は，外国人幼児が就学期に直面する困難に対応するため，保育士が行っている具体的な保育実践における支援の工夫と課題を明らかにすることを目的とした。外国人幼児の支援経験を有する保育士2 名に半構造化インタビューを行い，SCAT を用いた質的分析により，幼児および保護者への支援内容を整理した。その結果，言語面では視覚的支援ややさしい日本語を活用し，文化面では家庭文化と日本の園文化の調整が行われていた。発達支援においては，非認知的スキルの育成や医療機関との連携の必要性が指摘された。保護者支援では，参加型の関わりや丁寧な説明が実践されていたが，制度情報の提供や行政との連携には課題が残された。これらの結果を踏まえ，今後は保育士の個別的努力に依存しないためにも，多文化背景をもつ家庭への支援を制度的に支える地域連携体制の整備や，情報提供の標準化，日本語教育資源との接続を図る実践的仕組みの構築が求められる。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院ヘルスシステム統合科学研究科 Acta Medica Okayama 2436-3227 6 2026 The effects of cold compresses on itching in patients with atopic dermatitis: A cross-over controlled pilot trial 1 6 EN Yuki HIRAMI Former Department of Nursing, Graduate School of Health Sciences, Okayama University Nahoko HARADA Department of Nursing Science, Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Miho ONO Department of Nursing, Faculty of Health, Kagawa Prefectural University of Health Sciences Masahide KODA Co-learning Community Healthcare Re-innovation Office, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyoko FUKAI Professor Emeritus, Okayama University, Graduate School of Nursing, The Jikei University School of Medicine 10.18926/interdisciplinary/70325 This cross-over controlled trial aimed to evaluate the effectiveness and safety of two types of cold compresses (towels and ice packs) in alleviating itching among patients with atopic dermatitis. The study recruited 19 participants diagnosed with atopic dermatitis and suffering from chronic itching for over 6 months. Each participant received both types of cold compress interventions. Itching sensations were assessed repeatedly using a visual analogue scale before and after the application of the cold compress. The mean and standard deviation of itching scores for the towel intervention were 16.9 ± 19.1 (baseline) and 11.4 ± 16.1 (post-application). For the ice pack intervention, the scores were 13.6 ± 14.7 (baseline) and 6.2 ± 9.8 (post-application). Although there was a reduction in mean itching scores following the application of cold compresses, the differences were not statistically significant for either intervention. Despite the lack of statistical significance, this study suggests that cold compresses, which are user-friendly and inexpensive, may safely reduce subjective itching in patients with atopic dermatitis without causing pain or discomfort. However, further research with a larger sample size is needed to confirm these findings. No potential conflict of interest relevant to this article was reported.

岡山大学教育学部国語研究会 Acta Medica Okayama 2189-5414 40 2026 魯迅「故郷」論 ―〈高い壁〉の中の「私」― 1 17 EN No potential conflict of interest relevant to this article was reported.

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

The Company of Biologists Acta Medica Okayama 1754-8403 19 2 2026 A genetic model of congenital intestinal atresia implicates Mypt1 in epithelial organisation dmm052605 EN Daisuke Kobayashi Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Akihiro Urasaki Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Tetsuaki Kimura Medical Genome Center, Research Institute, National Center for Geriatrics and Gerontology Satoshi Ansai Ushimado Marine Institute, Okayama University Kazuhiko Matsuo Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Hayato Yokoi Graduate School of Agricultural Science, Tohoku University Shigeo Takashima Institute for Glyco-core Research (iGCORE)/Life Science Research Centre, Gifu University Tadao Kitagawa Program in Environmental Management, Graduate School of Agriculture, Kindai University Takahiro Kage Department of Biological Sciences, Graduate School of Science, The University of Tokyo Takanori Narita Laboratory of Molecular Biology, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University Tomoko Jindo Department of Biological Sciences, Graduate School of Science, The University of Tokyo Masato Kinoshita Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University Kiyoshi Naruse Laboratory of Bioresources, National Institute for Basic Biology Yoshiro Nakajima Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Masaki Shigeta Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Shinichiro Sakaki Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Satoshi Inoue Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Rie Saba Department of Radiology, Kyoto Prefectural University of Medicine Kei Yamada Department of Radiology, Kyoto Prefectural University of Medicine Takahiko Yokoyama Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Yuji Ishikawa Research Centre for Radiation Protection, National Institute of Radiological Sciences Kazuo Araki Research Center for Aquatic Breeding, National Research Institute of Aquaculture, Fisheries Research Agency Yumiko Saga Department of Biological Sciences, Graduate School of Science, The University of Tokyo Hiroyuki Takeda Department of Biological Sciences, Graduate School of Science, The University of Tokyo Kenta Yashiro Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Congenital intestinal atresia (IA) is a birth defect characterised by the absence or closure of part of the intestine. Although genetic factors are implicated, mechanistic understanding has been hindered by the lack of suitable animal models. Here, we describe a medaka (Oryzias latipes) mutant, generated by N-ethyl-N-nitrosourea (ENU) mutagenesis, that develops IA during embryogenesis. Positional cloning identified a nonsense mutation in mypt1, encoding myosin phosphatase target subunit 1. Mutant embryos exhibited ectopic accumulation of F-actin and phosphorylated myosin regulatory light chain (Mrlc) in the intestinal epithelium, consistent with disrupted actomyosin regulation. These cytoskeletal abnormalities were accompanied by epithelial disorganisation, without notable alterations in cell proliferation, motility or apoptosis. Inhibition of myh11a, encoding smooth muscle (SM) myosin heavy chain, ameliorated the IA phenotype, whereas blebbistatin treatment completely rescued the defect, suggesting a non-contractile role prior to SM maturation. Together, these findings demonstrate that mypt1 loss disrupts intestinal morphogenesis through actomyosin dysregulation. Given the recent clinical identification of IA associated with MYPT1 variants, this medaka model offers a valuable platform to investigate the developmental and molecular basis of MYPT1-associated IA in humans. No potential conflict of interest relevant to this article was reported.

岡山大学理学部地球科学科 Acta Medica Okayama 1340-7414 32 1 2026 2018年7月5日〜7日の西日本豪雨における広域降水特性 33 44 EN Kuranoshin KATO Faculty of Education, Okayama University Kengo MATSUMOTO Okayama Gakugeikan High School Kazuo OTANI TV Setouchi Broadcasting Co., LTD. 10.18926/ESR/70297 　Large-scale rainfall characteristics at the heavy rainfall event around the western Japan for 5–7 July 2018 were analyzed with use of the 10-mimute precipitation data at the surface meteorological observation stations of the Japan Meteorological Agency, and so on. In this case, the area with 3 days total precipitation of near or more than 300 mm was distributed widely from northern Kyushu to Shiga and Fukui Prefectures. As in the many heavy rainfall events around Kyushu District in the mature stage of the Baiu season, contribution of the intense rainfall with more than 4 mm/10-minute (24 mm/h) attained about one third of the areal mean total precipitation. However, it is noted that the "not so intense rain" with less than 2 mm/10-minute (12 mm/h) also contributed to about one third of the huge total precipitation in the wide area. In short, this case could be characterized by the mixture of the western Japan type heavy rainfall event and the eastern Japan type one. No potential conflict of interest relevant to this article was reported.

岡山大学理学部地球科学科 Acta Medica Okayama 1340-7414 32 1 2026 10分間降水量から大雨の特徴の多様性を捉える大学での授業の試み（防災気象リテラシー育成へ向けて） 21 31 EN Kuranoshin KATO Faculty of Education, Okayama University 10.18926/ESR/70296 　In the disaster prevention education on the heavy rainfall around Japan, it is also important to promote the meteorological literacy on the seasonal and regional differences of their rainfall characteristics such as the convective rain or stratiform rain, together with their total amount of precipitation and their occurrence frequency. As the first step toward the above purpose, the present study made a lesson practice for the university students by utilizing the 10-minute precipitation data for the four heavy rainfall events, in which the types of the heavy rainfall (although all the cases examined in the lesson are relating to the deep convective clouds) are rather different from each other, such as the differences of the rainfall intensity at the peak time, short-period variation of the rainfall intensity and the persistency of the rainfall including the "not so intense rainfall". The reports by the students seem to perceive the different features among these events briefly, but the students' attention to how long the intense rainfall with short-period variation or "not so intense rainfall" lasted was not so sufficient. No potential conflict of interest relevant to this article was reported.

岡山大学理学部地球科学科 Acta Medica Okayama 1340-7414 32 1 2026 Title Page EN No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 61 2026 『論語集注』訳注（子罕第九　（二）） (1) (20) EN Luyi SUN 10.18926/70285 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 61 2026 多文化共修のためのグループワークから学生は何を感じたのか？ ― GIS ソフトを使用した地域研究授業からの一考察 ― 1 20 EN Takao INAMORI 10.18926/70274 No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2572-1143 9 1 2026 Mechanosensitive Ion Channel PIEZO1 Suppresses BMP2-Induced Ossification of the Annulus Fibrosus Cells e70168 EN Hisakazu Shitozawa Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Nakamichi Department of Orthopaedic Surgery, Okayama University Graduate School Medicine, Dentistry, and Pharmaceutical Sciences Aki Yoshida Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masataka Ueda Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taichi Saito Department of Orthopaedic Surgery, Okayama University Hospital Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Yoshiaki Oda Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Takatori Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazutaka Yamashita Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective: Major cause of low-back pain is intervertebral disc degeneration (IVDD), with mechanical stress playing a crucial role in its progression. A mechanosensitive ion channel, PIEZO1, is involved in various musculoskeletal tissues, but its role in the annulus fibrosus (AF) remains unclear. This study aimed to elucidate the function of PIEZO1 in AF cells under mechanical stimulation. Methods: Primary rat AF cells were subjected to cyclic tensile strain (CTS) at low (2%) and high (12%) strain levels to investigate strain-dependent effects on osteogenic gene expression. We evaluated the effects of Piezo1, Piezo2, and Trpv4 knockdown by RNA interference to identify the upstream mechanotransducer. Furthermore, PIEZO1 was activated using the agonist Yoda1, followed by RNA-sequencing analysis and evaluation of its effects on BMP2-induced osteogenesis in rat AF cells. We also examined the effects of Yoda1 in primary human AF cells. Results: Low-strain CTS significantly suppressed osteogenic marker expression, which was not observed with high strain. Piezo1 knockdown reversed this suppression, whereas Piezo2 and Trpv4 had no effect. Piezo1 activation by Yoda1 produced similar anti-osteogenic effects in both rat and human AF cells. RNA sequencing revealed the enrichment of ossification and calcineurin signaling pathways in rat cells. Furthermore, Piezo1 activation inhibited BMP2-induced osteogenesis and nuclear translocation of p-Smad1/5/9. Conclusions: Piezo1 maintains AF cell homeostasis under mechanical stress by suppressing osteogenic changes via calcineurin-mediated inhibition of BMP signaling, which may represent a novel therapeutic target for IVDD. No potential conflict of interest relevant to this article was reported.

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

岡山大学経済学会 Acta Medica Okayama 2433-4146 57 3 2026 地域間での情報交流に関するネットワーク分析：高梁川流域圏での調査による 11 40 EN Ryohei Nakamura Natsumi Yokota 10.18926/OER/70262 　本稿では，岡山県の「高梁川流域連携中枢都市圏」で2014年から開催されている「高梁川流域経済成長戦略会議」における参加主体間の情報交流についてのネットワーク分析を行った。高梁川流域連携中枢都市圏（高梁川流域圏）とは，岡山県高梁川周辺に位置する現在の新見市，高梁市，総社市，早島町，倉敷市，矢掛町，井原市，浅口市，里庄町，笠岡市の10自治体が参加している連携中枢都市圏である。高梁川流域圏におけるネットワーク分析に際しては，同圏域内で展開されている事業を８つに分類し，それぞれの事業に関する参加主体間の情報交流についてアンケート調査を行った。ネットワーク指標については事業ごとに次数中心性と媒介中心性の中心性指標を，また事業別に密度，推移性，相互性を算出した。事業別にみると，観光事業についての情報交流が最も密なネットワーク構造をしており，ネットワークの視点では観光事業が高梁川流域圏内で最も勢力的に行われている事業といえる。また全事業において特定の行政主体や商工会議所をはじめとする地域経済団体等の中心性指標が全体的に大きな値をとっており，ネットワークにおいて情報交流のハブや情報の集中・分散主体として機能していることが明らかになった。分析結果を踏まえ，ネットワークの視点から高梁川流域圏の今度の地域振興について２点提言した。１つは事業によって情報交流のハブや情報の集中・分散主体を主体間で分担することによって，すべての事業で密なネットワークを築くことを目指すことである。もう１つは高梁川流域圏の情報交流ネットワークに全く参加していない主体をなくすことで，全体的に密なネットワークを目指すことである。 No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 57 3 2026 1998年の外国為替及び外国貿易管理法改正と外国通貨の譲渡による損益の所得区分 ―1998年の法改正は所得区分にどのような影響を与えたのか― 1 10 EN Yoshiyuki Nakagawa 10.18926/OER/70261 　1998年の外国為替及び外国貿易管理法の改正（以降，外国為替及び外国貿易法に改名）により，それまで外国為替公認銀行に原則として限られていた外国為替取引が，あらゆる企業及び個人に解放され，自由に行うことができるようになった。 　本稿は，まず課税当局の「外国通貨の譲渡による損益は雑所得に該当する」との見解の判断根拠を，国会における政府参考人答弁及び東京地裁令和５年３月９日判決から読み解き，そのうえで，1998年の法改正により外国通貨取引が対外及び国内において何人も自由に行うことができるようになったことから，外国通貨は支払手段として言わば価値の尺度として機能するようになり，資産の値上がり，値下がりを観念することができなくなった結果として，その譲渡による所得区分が譲渡所得から雑所得へと変化したとの結論を導くものである。 No potential conflict of interest relevant to this article was reported.

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

Oxford University Press (OUP) Acta Medica Okayama 2752-4191 5 6 2025 Sex differences in the progression of cardiovascular–kidney–metabolic syndrome oeaf162 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 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 Atsushi Mizuno Department of Cardiology, Medical Quality Management Office, QI Center, St. Luke's International Hospital Toshiyuki Ko Department of Cardiovascular Medicine, The University of Tokyo Takahiro Jimba Department of Cardiovascular Medicine, The University of Tokyo Tatsuhiko Azegami Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine 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 Kaori Hayashi Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine Koichi Node Department of Cardiovascular Medicine, Saga University Masaomi Nangaku Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine 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 Aims Cardiovascular–kidney–metabolic (CKM) syndrome is a novel disease concept; however, sex differences in its progression remain uncertain. This study aimed to quantify the risk of cardiovascular disease (CVD) events across CKM stages and to explore sex differences in this association. Methods and results We included 1 332 436 individuals (581 423 males and 751 013 females) from the DeSC database between 2014 and 2023 who had no prior CVD (i.e. CKM Stage 4). CKM stages were categorized as follows: Stage 0 (no CKM risk factors); Stage 1 (excess or dysfunctional adiposity); Stage 2 [metabolic risk factors and chronic kidney diseases (CKD)], and Stage 3 (subclinical CVD). We used Cox models to examine the association of CKM stages with the risk of CVD events (newly developed CKM Stage 4), including myocardial infarction, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The progression from CKM Stages 0 to 3 showed a dose-dependent increase in adjusted hazard ratios (HR) for developing CVD events, with the highest risk at Stage 3 [1.85 (95% CI: 1.80–1.90)]. A similar pattern was observed in both males and females. However, the magnitude of associations for CKM stages 1–3 differed between the sexes: HR by Stage 1, 1.12 (1.04–1.21) vs. 1.12 (1.07–1.16); by Stage 2, 1.78 (1.69–1.88) vs. 1.43 (1.39–1.48); by Stage 3, 1.99 (1.89–2.10) vs. 1.82 (1.76–1.88); and P-for-interaction values were 0.87, < 0.001, and 0.005, respectively. Conclusion In this large nationwide cohort, CKM stage progression was associated with higher CVD risk in both sexes, with modest sex-specific differences. These findings highlight the value of CKM staging for early risk assessment, regardless of sex. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-4889 16 1 2025 TRPV2 in muscle satellite cells is crucial for skeletal muscle remodelling 888 EN Yanzhu Chen Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kimiaki Katanosaka Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University Makoto Shibuya Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yubing Dong Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Lidan Zhang Laboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka Motoi Kanagawa Department of Cell Biology and Molecular Medicine, Ehime University Graduate School of Medicine So-ichiro Fukada Laboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Katanosaka Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Skeletal muscle remodelling relies on muscle stem cells (MuSCs) for regeneration after injury and hypertrophy in response to mechanical loading. However, the mechanisms that trigger MuSC activation and proliferation remain unclear. Transient receptor potential vanilloid 2 (TRPV2) ion channels respond to insulin-like growth factor-1 and mechanical stimuli to regulate the biological characteristics of various cells. Using a temporally inducible MuSC-specific conditional knockout (cKO) mouse, we show that TRPV2 regulates MuSC function and is essential for muscle remodelling. In cultured myofibre, MuSCs express TRPV2 and exhibit Ca2+ responses to the TRPV2 agonists 2-aminoethoxydiphenyl borate and probenecid, which are abolished upon TRPV2 deletion. TRPV2-deficient MuSCs exhibit reduced paired box 7 (Pax7) expression and impaired proliferation, suggesting TRPV2 is a factor that regulates the early stage of MuSC function. Myotube formation in MuSCs was enhanced by overexpression of TRPV2 and suppressed by TRPV2 deficiency, suggesting that TRPV2 is a factor that promotes myogenesis. Muscle-administered cardiotoxin promoted muscle regeneration and resulted in the appearance of numerous Pax7-positive MuSCs between myofibres. MuSC-specific TRPV2 cKO mice exhibit substantially impaired muscle regeneration after cardiotoxin-induced injury, drastically reducing Pax7-positive MuSCs between myofibres. In floxed mice, mechanical loading via synergist ablation induces hypertrophy and greatly increases the number of myonuclei per myofibre. In contrast, MuSC-specific TRPV2 cKO mice show no changes in myofibre thickness or nuclear number, either at baseline or after mechanical loading. Mechanical loading of floxed mice increased TRPV2+/Pax7+ double-positive MuSCs, but MuSC-specific TRPV2 cKO mice showed no change. Additionally, MuSCs exhibit Ca2+ responses to hypo-osmotic stimuli, which are suppressed by TRPV2 inhibitors and TRPV2 deletion, suggesting that MuSCs exhibit TRPV2-dependent mechanical responses. These results establish TRPV2 as a critical regulator of MuSC-mediated muscle remodelling, an important finding that may lead to therapeutic strategies for muscle repair and adaptation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1863-9941 52 1 2026 Preferential sacral fracture sites in fragility fractures of the pelvis type IVb and comparison of internal fixation methods: CT-based morphological mapping and finite element analysis 72 EN Shuichi Naniwa Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masanori Yorimitsu Department of Musculoskeletal Traumatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Tsubasa Hasegawa Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teruhiko Ando Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichiro Okuda Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shiro Fukuoka Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital Yusuke Mochizuki Department of Emergency Health Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuaki Yamakawa Department of Orthopaedic Surgery, Kochi Health Sciences Center Ryuichi Nakahara Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shiro Hanakawa Department of Orthopaedic Surgery, Okayama Saidaiji Hospital Toshifumi Ozaki Department of Orthopedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose Fragility fractures of the pelvis (FFP) classified as Rommens-Hoffman type IVb are associated with spinopelvic dissociation and are generally considered to require surgical intervention. This study aimed to clarify the localization patterns of FFP type IVb and compare the biomechanical stability of different internal fixation techniques. Methods In this retrospective study, morphologic mapping of sacral fracture lines was performed in 36 patients with FFP type IVb. Based on the mapping results, a finite element (FE) model of FFP type IVb was developed to evaluate the biomechanical stability of ilio-sacral screw (ISS) fixation, trans-sacral screw (TSS) fixation, spinopelvic fixation (SPF; On each side, L5 pedicle screw was connected to two iliac screws with a rod, and the bilateral constructs were linked using a cross-connector.), and bilateral triangular fixation (one TSS at S1 combined with SPF mentioned above) using finite element analysis (FEA). Results Morphologic mapping showed that the sacrum fracture transverse line tended to pass between the S1-2 transverse lines. Although bilateral triangular fixation and SPF provided the highest stability in both U-type and H-type fractures, a TSS for U-type and two TSSs for H-type also demonstrated comparable levels of stability. ISS-based methods showed greater displacements. Conclusion TSS-based fixation may provide stability comparable to bilateral triangular fixation and SPF in FFP type IVb, with less invasiveness when anatomy permits. Further studies are needed to optimize treatment strategies for this complex injury. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1613-6810 21 50 2025 Collagen Signaling via DDR1 Exacerbates Barriers to Macromolecular Drug Delivery in a 3D Model of Pancreatic Cancer Fibrosis e06926 EN Mayu Ohira Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Moe Kitamura Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyo Iwasaki Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruko Ohta‐Okano Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiyori Tsujii Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Reika Nakamura Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuya Nakazawa Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Akihiro Nishiguchi Biomaterials Field, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science Masaya Yamamoto Department of Materials Processing, Graduate School of Engineering, Tohoku University Kensuke Osada Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST) Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Horacio Cabral Department of Bioengineering, Graduate School of Engineering, The University of Tokyo Atsushi Masamune Division of Gastroenterology, Graduate School of Medicine, Tohoku University Mitsunobu R. Kano Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hiroyoshi Y. Tanaka Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fibrosis is a significant barrier to drug delivery in pancreatic ductal adenocarcinoma (PDAC) and contributes to its dismal prognosis. Pancreatic stellate cells (PSCs) drive fibrosis by excessively secreting extracellular matrix proteins such as collagen I. Collagen I is thought to physically obstruct the delivery of macromolecules, such as albumin, antibodies, and nanomedicines. Apart from its structural role, collagen signals through dedicated cell surface receptors, such as the discoidin domain receptors (DDR) 1/2. However, whether and how collagen signaling contributes to fibrotic barrier generation remains uncharacterized. Here, a 3D culture model of PDAC fibrosis constructed from patient PSCs is used to assess the contribution of DDR1/2-mediated collagen signaling. DDR1/2 inhibition diminishes collagen I expression in PSCs to enhance macromolecular delivery. Moreover, MEK inhibitors exacerbate the fibrotic barrier by up-regulating collagen I, an effect reversed by inhibiting DDR1/2. Through isoform-specific targeting, inhibiting DDR1, but not DDR2, is shown to be effective. Downstream of DDR, the involvement of the PI3K/AKT/mTOR pathway is demonstrated, particularly alternative mTOR complexes involving MEAK7 and GIT1. Altogether, the results show in vitro that DDR1-mediated collagen signaling exacerbates the fibrotic barrier and may be targeted to enhance macromolecular drug delivery in PDAC. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2688-4526 7 2 2026 Safety and efficacy of Rezūm water vapour energy therapy in BPH patients receiving antithrombotic therapy: A Japanese single‐centre experience e70170 EN Takatoshi Moriwake Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Tominaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Katayama Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruki Kaku Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ichiro Tsuboi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kasumi Yoshinaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoaki Yamanoi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsushi Kawada Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuya Sadahira Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takehiro Iwata Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shingo Nishimura Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kensuke Bekku Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Katayama Department of Urology, Okamura Isshindo Hospital Motoo Araki Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: The objective of this study is to evaluate the safety and efficacy of Rezūm water vapour energy therapy (WAVE) in Japanese patients with benign prostatic hyperplasia (BPH) continuing antithrombotic therapy and to validate the Okayama University Modified Clavien-Dindo classification (OU-mCD) for perioperative hematuria. Patients and Methods: We retrospectively analysed 80 consecutive patients who underwent WAVE from August 2023 to July 2024, including 37 (46.2%) continuing antithrombotic therapy perioperatively. Hematuria within 30 days was graded using conventional Clavien-Dindo classification and the OU-mCD, a novel classification focusing on intervention necessity. We assessed clinically significant hematuria (Grade ≥ Ib), catheter-free rate, prostate volume reduction and haemoglobin change. Results: Clinically significant hematuria occurred in 21.6% (8/37) of patients continuing antithrombotic therapy versus 4.7% (2/43) without (p = 0.038). All 10 Grade ≥ Ib cases occurred during hospitalization with the catheter in place and were managed conservatively with continuous bladder irrigation (median 1 day); none required transfusion or surgical reintervention. Only one patient required temporary drug discontinuation. Treatment efficacy did not differ by antithrombotic status: 86.2% achieved PVR < 50 ml with 44% mean prostate volume reduction. Multivariate analysis identified antithrombotic therapy as the sole independent risk factor for Grade ≥ Ib hematuria (OR 5.46, 95% CI 1.06–28.16, p = 0.042). Conclusion: WAVE can be safely performed with continued antithrombotic therapy. Whereas Grade ≥Ib hematuria occurred in 25% of antiplatelet/anticoagulant users (vs. 5% without), 75% had no significant bleeding, and all complications were managed conservatively without transfusion. The OU-mCD provides precise complication stratification. These findings suggest outpatient procedures may be feasible with appropriate patient selection. No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 78 2025 広島市方言におけるアクセントの継承と変容（1）─ 1 拍・2 拍・3 拍名詞のアクセントの世代的動態 ─ 39 50 EN Yasue NAKATO 10.18926/okadai-bun-kiyou/70219 No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 78 2025 非大都市圏小規模自治体の持続的発展と地域的対応の特徴 1 11 EN Hirofumi KITAGAWA 10.18926/okadai-bun-kiyou/70216 No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1556-0864 20 12 2025 Final Analysis Results and Patient-Reported Outcomes From DESTINY-Lung02—A Dose-Blinded, Randomized, Phase 2 Study of Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic NSCLC 1814 1828 EN Pasi A. Jänne Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute Yasushi Goto Department of Thoracic Oncology, National Cancer Central Hospital Toshio Kubo Center for Clinical Oncology, Okayama University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Sang-We Kim Oncology Department, Asan Medical Center, Seoul, and University of Ulsan College of Medicine, Ulsan David Planchard Department of Medical Oncology, Thoracic Cancer Group, Gustave Roussy, and Faculty of Medicine, Paris-Saclay University Myung-Ju Ahn Department of Hematology and Oncology, Samsung Medical Center Sungkyunkwan, and University School of Medicine Egbert Smit Department of Pulmonary Diseases, Leiden University Medical Center Adrianus Johannes de Langen Department of Thoracic Oncology, Netherlands Cancer Institute Maurice Pérol Department of Medical Oncology, Léon Berard Centre Elvire Pons-Tostivint Centre Hospitalier Universitaire Nantes, Nantes University Silvia Novello Department of Oncology, University of Turin, Turin, and Azienda Ospedaliero-Universitaria San Luigi Gonzaga Hidetoshi Hayashi Department of Medical Oncology, Kindai University Hospital Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Hospital Dong-Wan Kim Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital Kaline Pereira Daiichi Sankyo Fu-Chih Cheng Daiichi Sankyo Ayumi Taguchi Daiichi Sankyo Yingkai Cheng Daiichi Sankyo Kyle Dunton Daiichi Sankyo UK Ahmed Ali Daiichi Sankyo Europe GmbH Koichi Goto Department of Thoracic Oncology, National Cancer Center Hospital East Introduction: Trastuzumab deruxtecan (T-DXd) demonstrated strong and durable responses in patients with previously treated HER2 (ERBB2) mutant (HER2m) metastatic NSCLC (mNSCLC) in the DESTINY-Lung02 primary analysis (December 23, 2022, data cutoff). This final analysis evaluated T-DXd efficacy and safety after 8 additional months of follow-up, including clinically relevant subgroups and patient-reported outcomes. Methods: DESTINY-Lung02 was a randomized, dose-blinded, multicenter, phase 2 trial. Patients with previously treated HER2m mNSCLC were randomized 2:1 to receive T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. Primary end point was confirmed objective response rate by blinded independent central review. Results: As of August 25, 2023, 102 and 50 patients had received T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up (Q1–Q3) was 15.8 (8.2–20.7) months and 16.5 (9.4–20.8) months, respectively. Confirmed objective response rate (95% confidence interval) was 50.0% (51/102; 39.9%–60.1%) and 56.0% (28/50; 41.3%–70.0%), respectively. Safety profile was acceptable and generally manageable. Accordingly, median treatment duration (Q1–Q3) was 7.7 (3.7–14.4) months and 8.3 (2.8–13.1) months; drug-related grade 3 or higher treatment-emergent adverse events occurred in 39.6% (40/101) and 60.0% (30/50), with nausea most common (67.3% [68/101], 82.0% [41/50]). Adjudicated drug-related interstitial lung disease occurred in 14.9% (15/101) and 32.0% (16/50), mostly grade 1 or 2 with one grade 5 in each arm. Health-related quality of life was preserved for the duration of T-DXd treatment while sample size was sufficient for analysis, with no adverse effects on health-related quality of life observed at either dose. Conclusions: T-DXd demonstrated strong and durable responses at both doses, with no clinically significant changes in toxicity. The approved 5.4-mg/kg dose demonstrated a more favorable benefit-risk profile, including lower adjudicated drug-related interstitial lung disease incidence. ClinicalTrials.gov identifier: NCT04644237 No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0309-0167 88 5 2025 Claudin-18 expression in gastric type adenocarcinoma and HPV-associated adenocarcinoma of the uterine cervix 1003 1015 EN Nobuko Yasutake Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Yuki Yokawa Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Takehiro Tanaka Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Riri Mishima Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Misato Komamizu Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University Fukuoka Japan Ryosuke Kuga Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Rina Jiromaru Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Shinichiro Kawatoko Department of Medicine and Clinical Science, Kyushu University Beppu Hospital Kenzo Sonoda Department of Gynecology, Kyushu University Beppu Hospital Hideaki Yahata Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Kiyoko Kato Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Yoshinao Oda Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University Hidetaka Yamamoto Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Aims: Claudin-18 (CLDN18) is both a marker for the gastric phenotype and a therapeutic target. However, little is known about its immunoexpression in endocervical adenocarcinomas (ECAs), particularly as detected using the clone 43-14A antibody, or about the gene expression of its isoforms in ECAs. Methods and results: We examined CLDN18, HIK1083, p16 and Rb expression by immunohistochemistry and high-risk human papillomavirus (HR-HPV) mRNA by in situ hybridization (ISH) in 121 ECAs, including 35 HPV-independent adenocarcinomas (gastric type [GAS], n = 24; non-GAS, n = 11) and 86 HPV-associated ECAs. We also analysed mRNA expression of the CLDN18.1 (lung type) and CLDN18.2 (gastric type) isoforms by quantitative polymerase chain reaction (qPCR) in selected cases. CLDN18 positivity was detected in 8/24 (33%) GASs, 0/11 (0%) non-GASs and 2/86 (2%) HPV-associated ECAs, with positivity defined as staining in ≥75% of tumour cells, as in gastric cancer. When a 5% cut-off was used, CLDN18 positivity was detected in 22/24 (92%) GASs, 0/11 (0%) non-GASs and 6/86 (7%) HPV-associated ECAs; CLDN18 expression was thus significantly associated with GAS histology (P < 0.0001). Among the 6 cases of HPV-associated ECAs with CLDN18 expression (ranging from 5% to 80%), the histological patterns included a mix of usual and mucinous features in 4 cases, pure usual type in 1 and villoglandular variant in 1. Otherwise features such as p16 overexpression and the Rb partial loss pattern were consistent with those of HPV-associated ECAs. Six of 22 (27%) CLDN18-positive GASs were also positive for p16, but their other features—such as CLDN18 expression and the Rb preserved pattern—were the same as in p16 negative GASs. Expression of CLDN18.2 mRNA but not CLDN18.1 mRNA was confirmed in both GASs and HPV-associated ECAs. Conclusions: CLDN18 (43-14A) emerged as a potential diagnostic and therapeutic marker for GAS. A minor subset of HPV-associated ECAs also can be immunoreactive for CLDN18 and express CLDN18.2 mRNA, suggesting divergent gastric phenotypic differentiation. The caution is that GAS and HPV-associated ECAs can share overlapping histological features and similar expression of CLDN18 and p16. No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 191 2026 青年の肯定的自己理解を促す強み介入の実践報告 ― 発達支持的教育相談によるアプローチを通して ― 187 196 EN Tsuguyuki IZUMI Faculty of Education, Okayama University 10.18926/bgeou/70207 　本研究は，発達支持的教育相談として実施した強み認識授業が，青年の自己の強み選択の難易度に及ぼす影響を探索的に検討したものである。研究１では中国地方の公立中学校423名を対象にオンラインで，研究２では専門学校学生86名，大学生93名を対象に対面で，強み認識授業を実施し，授業後に，自己の強み選択の難易度を測定した。その結果，すべての群の強み選択の難易度の評価は，平野(2019)と比較して「容易である」との回答傾向を示した(Mdn = ７)。また，３群の強み選択の難易度の分布に統計的な有意差は認められなかった(p = .222)。この知見は，本授業が対象者の発達段階や実施形式(オンライン・対面)に関わらず，普遍的に強み特定を支援する機能を持つ可能性を示唆する。最後に，この知見をもとに，学校現場での教育相談の新たな展開を提言した。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 191 2026 Character Education の動向と児童の特性を生かした教育的介入の可能性について ― Character Education と Character Strengths Education を区別して ― 63 77 EN Minglu LI The Joint Graduate School in Science of School Education, Hyogo University of Teacher Education Tazuko AOKI Faculty of Education, Okayama University 10.18926/bgeou/70196 　児童の幸福や心理的 well-being を高める研究の1つが，よい character の育成を目指す教育研究である。Lavy（2020）は，これには2つの流れがあるとする。１つが character education，もう１つは character strengths education である。本稿では，まずこの2つの特徴について解説して世界の流れを示し，次にポジティブ心理学に基づく character strengths education の限界点を指摘した。具体的には，その原典となるVIA-IS（Peterson & Seligman, 2004）について，東アジアにおける強みと well-being の関連研究がほとんど成されていないこと，加えて児童期の教育的介入の成果がほとんど見られないことを指摘した。これらの検討を通して，児童期の認知特性や発達段階に応じた，児童の負荷の少ない身体活動量，習慣形成の視点で character の育成を目指す教育的介入の可能性について議論した。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 191 2026 教職員研修の高度化に果たす大学の役割と課題 ― NITS 岡山大学センターの活動を通して ― 1 16 EN Atsushi TAKASE Faculty of Education, Okayama University Akiko TSURUMI Okayama University Kindergarten Chiyo KUROSUMI Okayama University Kindergarten Tetsuo KIYOTA Faculty of Education, Okayama University Yoshihiko INADA Faculty of Education, Okayama University Ai MATSUURA Faculty of Education, Okayama University Kouji MIYAMOTO Faculty of Education, Okayama University Mutsumi MATSUEDA Faculty of Education, Okayama University Aiko TSUSHIMA Faculty of Education, Okayama University Yoshio MIYAZAKI Faculty of Education, Okayama University Toshiya TAKEMOTO Okayama University School for Special Needs Education Yoko SAWATANI Okayama University School for Special Needs Education Kazuaki KAJII Faculty of Education, Okayama University Makiko KANAGAWA Faculty of Education, Okayama University 10.18926/bgeou/70192 　本論文では，専門職としての教職員の学びを保障する研修のあり方を検討し，とくに大学が果たす役割と課題について考察する。教職員の学びは教育委員会での研修，勤務校園での研修，教職大学院での学修，研究団体での研修などにおいて展開される。大学が開発・実施する研修はこれらとどう関連し，どのような特色をもつか。独立行政法人教職員支援機構（以下，NITS）岡山大学センターの活動を通して検討する。そして，大学は教職員の学びのニーズに応える側にあるだけでなく，教職員の学びを再構成し，自律的協働的な学びを支援・促進していく側としての役割を果たすものであることを考察する。また，大学おけるアウトカム重視の研修開発の必要性を指摘し，今後の取組の課題として示す。 No potential conflict of interest relevant to this article was reported.

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

The Japanese Society for Neuroendovascular Therapy Acta Medica Okayama 1882-4072 19 1 2025 The Qualification Examination for Specialists and Instructors in the Japanese Society of Neuroendovascular Therapy: History and Current Status sr.2024-0099 EN Shinichi Yoshimura Department of Neurosurgery, Hyogo Medical University Kenji Sugiu Department of Neurological Surgery, Okayama University Graduate School of Medicine Masaru Hirohata Department of Neurosurgery, Kurume Medical University Yukiko Enomoto Department of Neurosurgery, Gifu University Graduate School of Medicine Hirotoshi Imamura Department of Neurosurgery, National Cerebral and Cardiovascular Center Wataro Tsuruta Department of Endovascular Neurosurgery, Toranomon Hospital Toshiyuki Fujinaka Department of Neurosurgery, National Hospital Organization Osaka National Hospital Hitoshi Hasegawa Department of Neurosurgery, Brain Research Institute, Niigata University Toshio Higashi Department of Neurosurgery, Fukuoka University Chikushi Hospital Takashi Izumi Department of Neurosurgery, Nagoya University of Graduate School of Medicine Hiro Kiyosue Department of Diagnostic Radiology, Kumamoto University Faculty of Life Sciences Yasushi Matsumoto Division of Development and Discovery of Interventional Therapy, Tohoku University Hospital Hidenori Oishi Oishi Neurosurgery Clinic, and Department of Neurosurgery, The Jikei University School of Medicine Tetsu Satow Department of Neurosurgery/Stroke Center, Kindai University Hospital Michihiro Tanaka Department of Neurosurgery and Neuroendovascular Surgery, Kameda Neurocenter, Kameda Medical Center Tomoyuki Tsumoto Department of Neurosurgery, Showa University Fujigaoka Hospital Hiroshi Yamagami Division of Stroke Prevention and Treatment, Institute of Medicine, University of Tsukuba Akira Ishii Department of Neurosurgery, Juntendo University Faculty of Medicine Yuji Matsumaru Department of Neurosurgery, Institute of Medicine, University of Tsukuba Shigeru Miyachi Department of Neurological Surgery, Aichi Medical Univeristy Neuroendovascular therapy is a key treatment for cerebrovascular disorders, driven by advancements in devices and techniques. The Japanese Society for Neuroendovascular Therapy (JSNET) established a certification system in 1997 to ensure operator competence and minimize complications, with the first examination in 2002. JSNET offers 2 main certifications: specialist and instructor. Specialists perform basic procedures, while instructors lead in practice, education, and research. In 2020, the mechanical thrombectomy practitioner qualification was added to promote mechanical thrombectomy. Applicants must have a JSNET membership, relevant certifications, training, and documented experience. The certification process includes rigorous written and practical examinations that now employ non-fluoroscopic models. Certification renewal every 5 years requires conference participation and a continuing education program. Public awareness and integration into stroke center designations have grown. Over 2200 specialists, including more than 500 instructors, have been certified, significantly advancing neuroendovascular therapy in Japan. JSNET aims to continue improving certification and education to maintain high standards. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1345-2630 2026 Tabtoxin biosynthetic gene cluster in Pseudomonas syringae pv. tabaci 6605 genomic island 1 (GI-1Pta6605) is required for severe disease symptoms EN Kotomi Kunishi The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Norika Fujisawa The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiteru Noutoshi The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University One of the genomic islands in Pseudomonas syringae pv. tabaci 6605 (GI-1Pta6605) has been identified as a pathogenicity island required for virulence because the deletion almost completely eliminated disease symptoms in inoculation tests at 4 × 105 CFU/ml. GI-1Pta6605 contains four cargo regions (CRs) named CR-1 to CR-4. The ∆CR-4 mutant did not produce tabtoxin like ∆GI-1 and disease symptoms did not develop in tobacco. However, it grew, although to a lesser extent than the wild-type strain. These results indicate that the tabtoxin biosynthetic gene cluster in GI-1 is required for virulence but not for establishment of compatibility. No potential conflict of interest relevant to this article was reported.

Japanese Society for Horticultural Science Acta Medica Okayama 2189-0102 95 1 2026 Comparison of Fruit Development, Ripening, and Transcriptome Dynamics in Taiwanese and Japanese Cultivars of Japanese Apricot (Prunus mume Sieb. et Zucc.) 10 20 EN Tomoaki Kashiwamoto Graduate School of Environmental and Life Science, Okayama University Takashi Kawai Graduate School of Environmental and Life Science, Okayama University Takaaki Oe Japanese Apricot Laboratory, Wakayama Fruit Tree Experiment Station Koji Numaguchi Japanese Apricot Laboratory, Wakayama Fruit Tree Experiment Station Yuto Kitamura Faculty of Agriculture, Setsunan University Yasutaka Kubo Graduate School of Environmental and Life Science, Okayama University Fumio Fukuda Graduate School of Environmental and Life Science, Okayama University Koichiro Ushijima Graduate School of Environmental and Life Science, Okayama University In this study, we compared changes in traits associated with fruit development and ripening in Taiwanese and Japanese cultivars of Japanese apricot (Prunus mume Sieb. et Zucc.). We also analyzed transcriptome profiles to comprehensively examine different fruit development and ripening patterns between the two groups in terms of fruit characteristics and gene expression. Early fruit development in Taiwanese cultivars ‘ST’ and ‘Ellching’ and the Japanese cultivar ‘Hakuo’ was ahead of that in other three Japanese cultivars (P1). From late April to early May, around the stone-hardening stage, the developmental differences decreased to the same level. Thereafter, Japanese cultivars showed rapid growth, whereas Taiwanese cultivars showed slower growth, reversing the developmental differences between these lines (P2). Ethylene production was not detected until the full ripening stage and was detected for the first time at this stage in five cultivars, except for ‘Ellching’ (P3). In contrast, no ethylene production was observed during the entire duration of fruit development in ‘Ellching’. A multidimensional scaling plot showed that the overall transcriptome profile changed according to the three stages (P1–P3) of fruit development and ripening. At P1, gene ontologies (GOs) related to cell division, such as the cell cycle and regulation of cyclin-dependent protein serine/threonine kinase activity, were enriched for differentially expressed genes downregulated in Taiwanese cultivars as compared with their expression in Japanese cultivars. At P2, GOs related to fruit development were not enriched, but some genes related to phytohormones, such as auxin, abscisic acid, and cytokinin, which are associated with fruit development and ripening, were differentially expressed. At P3, the expression of genes such as ACS, ACO, and PG, which are involved in ethylene biosynthesis, increased in response to increased ethylene production, but not in ‘Ellching’, which showed no ethylene production. Expression analysis of 115 NAC (NAM-ATAF1/2-CUC2) family genes, which are related to fruit ripening and ripening date in other fruit species, in the ‘Ellching’ genome revealed changes in expression of NAC056 and NAC073 corresponding to fruit development and ripening in Taiwanese and Japanese cultivars. We discuss the differences in fruit development and ripening behaviors between Taiwanese and Japanese cultivars in terms of physiological and transcriptome changes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1746-6148 22 1 2026 Genetic and phenotypic identities of Staphylococcus coagulans isolated from pustules of dogs with superficial bacterial folliculitis 98 EN Takafumi Osumi Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology Yuuki Shinomiya Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology Thamonwan Wanganuttara Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ichiro Imanishi Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai Yotaro Shimazaki Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology Keita Iyori 1sec Co. Ltd. Yoichi Toyoda 1sec Co. Ltd. Kaori Ide Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Nishifuji Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology Background Staphylococcus coagulans, formerly called Staphylococcus schleiferi subsp. coagulans is the second most common isolate from skin lesions of dogs with superficial bacterial folliculitis (SBF). However, the clinical significance of S. coagulans in pustules of canine SBF remains uncertain. This study aimed to investigate the prevalence and genotypic and phenotypic diversity of S. coagulans isolated from pustules in two dogs with SBF. Results Two dogs with SBF were included in this study. S. schleiferi/coagulans was isolated as the sole organism from three pustules in case #1, whereas it coexisted with S. pseudintermedius in two of seven pustules in case #2. S. pseudintermedius was the sole organism in the remaining five pustules in case #2. Whole genome sequences revealed that all isolates tested were annotated as S. coagulans. The isolates from the same pustules exhibited identical genotypic and phenotypic profiles, indicating clonal multiplication. S. coagulans isolated from different pustules exhibited similar yet distinct genotypic and phenotypic profiles. Conclusions S. coagulans with identical genetic and phenotypic profiles can be identified as the sole pathogen or coexist with S. pseudintermedius in the pustules of the same dogs with SBF. No potential conflict of interest relevant to this article was reported.

岡山大学大学院法務研究科 Acta Medica Okayama 1881-1485 27 2026 成年後見制度　～中核機関の現状と課題～ 1 51 EN Kazuhiro NISHIDA Mika NISHIYAMA Okayama City Adult Gurdianship Center Case Ayaka NAGASHIO Okayama City Adult Gurdianship Center Case Kyosuke YOSHIOKA Soja City Case Tomono IMAI Chita Area Avocacy Center Case Yuji MIZUTA Oda City Case Daisuke UCHIDA Oda City Case 10.18926/OLR/70154 No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1758-5902 18 1 2025 Metachronous Pancreatic Metastasis of Myxoid Liposarcoma Successfully Treated With Robotic Spleen‐Preserving Distal Pancreatectomy With Splenic Vessels Resections: A Case Report e70069 EN Yumi Sota 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 Motohiko Yamada 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 Noriyuki Kanehira Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akari Masunaga 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 Pancreatic metastasis of myxoid liposarcoma (MLS) after primary resection is extremely rare. Herein, we present a case of metachronous pancreatic metastasis of MLS that was successfully treated with robotic spleen-preserving distal pancreatectomy (SPDP) using the Warshaw technique. A 60-year-old woman underwent radical resection of a 25-cm MLS in the right thigh after receiving neoadjuvant radiotherapy. The patient developed a 6-cm solitary pancreatic metastasis of the MLS 2 years later. Because no other distant metastases were detected, robotic SPDP (Warshaw technique) was performed. The operative time was 140 min with minimal blood loss. Follow-up at 3 months showed no recurrence. To our knowledge, this is the first report of a case of metachronous pancreatic metastasis of MLS successfully treated with robotic SPDP. Curative resection using minimally invasive surgery should be performed for solitary pancreatic metastases from MLS. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2589-5370 80 2025 Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): long-term results of a multicentre, single-arm, phase 2 trial 103078 EN Kazuyuki Shimada Department of Hematology and Oncology, Nagoya University Graduate School of Medicine Motoko Yamaguchi Department of Hematological Malignancies, Mie University Graduate School of Medicine Yachiyo Kuwatsuka Department of Advanced Medicine, Nagoya University Hospital Kosei Matsue Division of Hematology/Oncology, Internal Medicine, Kameda Medical Center Keijiro Sato Department of Hematology, Nagano Red Cross Hospital Shigeru Kusumoto Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences Hirokazu Nagai Department of Hematology, National Hospital Organization Nagoya Medical Center Jun Takizawa Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine Noriko Fukuhara Department of Hematology and Rheumatology, Tohoku University Hospital Koji Nagafuji Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine Kana Miyazaki Department of Hematology and Oncology, Mie University Graduate School of Medicine Eiichi Ohtsuka Department of Hematology, Oita Prefectural Hospital Akinao Okamoto Department of Hematology, Fujita Health University School of Medicine Yasumasa Sugita Department of Hematology, Oami Municipal Hospital Toshiki Uchida Department of Hematology and Oncology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital Satoshi Kayukawa Department of Clinical Oncology, Nagoya Memorial Hospital Atsushi Wake Department of Hematology, Toranomon Hospital Kajigaya Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital Yukio Kondo Department of Internal Medicine, Toyama Prefectural Central Hospital Akiko Meguro Division of Hematology, Tochigi Cancer Center Yoshihiro Kin Department of Hematology, Daini Osaka Police Hospital Yosuke Minami Department of Hematology, National Cancer Center Hospital East Daigo Hashimoto Department of Hematology, Hokkaido University Faculty of Medicine, Graduate School of Medicine Takahiro Nishiyama Division of Hematology, Ichinomiya Municipal Hospital Satoko Shimada Department of Pathology and Clinical Laboratories, Nagoya University Hospital Yasufumi Masaki Department of Hematology and Immunology, Kanazawa Medical University Masataka Okamoto Department of Hematology, Fujita Health University School of Medicine Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Hitoshi Kiyoi Department of Hematology and Oncology, Nagoya University Graduate School of Medicine Ritsuro Suzuki Department of HSCT Data Management and Biostatistics, Nagoya University School of Medicine Shigeo Nakamura Department of Pathology and Clinical Laboratories, Nagoya University Hospital Tomohiro Kinoshita Department of Hematology and Cell Therapy, Aichi Cancer Center Background Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma for which prognosis is typically poor without a timely diagnosis. To explore the safety and efficacy of standard chemotherapy combined with central nervous system (CNS)-directed therapy, we conducted a multicentre, single-arm, phase 2 trial in untreated IVLBCL patients without CNS involvement at diagnosis (PRIMEUR-IVL). In the primary analysis, the PRIMEUR-IVL study demonstrated 2-year progression-free survival (PFS) of 76% and 2-year overall survival (OS) of 92% with a low incidence (3%) of secondary CNS involvement (sCNSi). Methods We present a prespecified final analysis of the PRIMEUR-IVL study including 5-year PFS, OS and cumulative incidence of sCNSi. Participants were enrolled between June 2011 and July 2016, and the data cutoff date for the final analysis was 16 November 2021. The trial was registered in the UMIN Clinical Trial Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165). Findings With a median follow-up of 7.1 years (interquartile range 5.6–8.7), 5-year PFS in all 37 eligible patients was 68% (95% confidence interval [CI] 50%–80%) and OS was 78% (95% CI 61%–89%). No additional sCNSi was observed after the primary analysis. Severe adverse events after the primary analysis were grade 4 neutropenia (n = 1) and grade 4 myelodysplastic syndrome that did not require specific treatment (n = 1). Eight deaths occurred during the observation period after enrolment, due to primary disease (n = 6), sepsis (n = 1) and unknown sudden death (n = 1). Interpretation Long-term follow-up data demonstrated durable response for PFS and OS, and low cumulative incidence of sCNSi, indicating the efficacy of standard chemotherapy combined with CNS-directed therapy for untreated IVLBCL patients. Funding This study received financial support from the Japan Agency for Medical Research and Development, Center for Supporting Hematology-Oncology Studies, and National Cancer Center. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-7257 18 2 2025 Microsatellite-high intrahepatic cholangiocarcinoma with favorable treatment outcome using pembrolizumab 363 368 EN Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Kosaku Morimoto 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 Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Takehiro Tanaka Department of Pathology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Intrahepatic cholangiocarcinoma has a poor prognosis. In unresectable cases, the survival period is short despite combination therapy with cytotoxic anticancer agents and immune checkpoint inhibitors. The usefulness of immune checkpoint inhibitors against malignant tumors with microsatellite instability-high (MSI-H) mutations was shown in the KEYNOTE158 study; however, data for intrahepatic cholangiocarcinoma are insufficient. In the present case, a 65-year-old man with intrahepatic cholangiocarcinoma and lymph node metastasis could not be treated with a combination of gemcitabine, CDDP, and S-1. A comprehensive cancer genomic profiling (CGP) test showed MLH1 pathogenic mutation and MSI-H. When pembrolizumab was administered, the tumor shrinkage effect was rapidly observed, which was sustained even after 30 months. No pathogenic mutations were observed in the germline test, and MSI-high was considered to be due to the MLH1 pathogenic mutation occurring sporadically in somatic cells. MSI-H intrahepatic cholangiocarcinoma is extremely rare. However, because pembrolizumab is expected to be effective, CGP testing should be actively performed. No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 近代韓国の読本教科書『初等小学』の底本に関する再考 74 90 EN Ankoo LEE Institute for Promotion of Education and Campus Life, Okayama University 10.18926/70113 　本稿では、近代韓国の読本教科書『初等小学』（1906）の編纂において参照されたと思われる日本の明治期読本教科書について比較・考察を行った。まず、文部省編纂の検定『尋常小学読本』（1887）と第1期国定『尋常小学読本』（1903）、さらに金港堂出版の『尋常国語読本』（1900）及び『高等国語読本』（1900）との関連性について、先行研究の議論を再検討した。そのうえで、新たに金港堂の『新体読本尋常小学用』（1894）と普及舎の『尋常小学新読本』（1893）の2種を底本として確認することができた。『初等小学』において最も多く参照された明治期読本教科書は金港堂の『尋常国語読本』（1900）であり、『初等小学』は、金港堂と文部省の比較的新しい尋常小学用読本教科書を優先的に参照したと思われる。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 オンラインによるボランティア日本語教室における参加者間のインターアクションの分析 ―地域型日本語教育の実現に向けて― 31 40 EN Miwa SUESHIGE Institute for Promotion of Education and Campus Life, Okayama University 10.18926/70110 本研究では，地域型日本語教育のモデル構築に向け，地域型の特徴を有する教室内での支援者および参加者の発話や教授行動の傾向を明らかにすべく，外国語相互作用分析システムを用い，オンラインによるボランティア教室におけるインターアクションの分析を行った。分析の結果，（1）支援者の平均発話数が学習者より多いこと，（2）支援者の発話における間接的行動の割合が直接的行動よりもやや高いことが示された。「おしゃべり型の教育」では，学習者が伝えたいことを言語化していくプロセスの中で，間接的行動の下位分類の「質問」「学習者の意図の利用」「学習者の回答の繰り返し」等を支援者が積極的に使用し支援していることが分かった。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 心理臨床家同士のグループ体験における反省的実践 12 30 EN Ryosuke KOBASHI Institute for Promotion of Education and Campus Life, Okayama University Masashi TANAKA Tokai University Rin MURASE Graduate School of Education and Human Development, Nagoya University 10.18926/70109 　心理臨床家にとって反省的実践は重要であり，多様な形態のグループに参加をすることによって反省的実践を行っている。本研究では，全般的な心理臨床家同士のグループにおける体験（研究1）および継続的なグループにおける体験（研究2）を探索することを目的として，数名の心理臨床家による話し合いをKJ法を援用して分析した。その結果，心理臨床家同士のグループ体験における反省的実践には，【グループ体験が内省につながるかどうか】などの4つ側面が重要であることが示された。また，継続的なグループにおける体験では，《本来の人としての感覚や欲求》や《自分を不自由にしている要因》などの【会における気づき】が得られることが反省的実践として有意義であることが明らかになった。 No potential conflict of interest relevant to this article was reported.

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

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

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Metastatic Intraocular Tumor Likely from Hepatocellular Carcinoma Mimicking Panuveitis 63 67 EN Eri Takasu Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroya Kindo Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Kanzaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuro Morita Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Adachi Department of Gastroenterology and Hepatology, 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 Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/70074 A 77-year-old man undergoing treatment for hepatocellular carcinoma (HCC) presented with blurred vision in his right eye, persisting for 2 months. Slit-lamp microscopy and fundus examination revealed inflammatory cells in the anterior chamber, severe vitreous opacities, and retinal vasculitis in the right eye. The patient underwent vitreous surgery with biopsy, and vitreous cytology confirmed a metastatic intraocular tumor originating from the HCC. Radiotherapy was administered to the right eye, with no recurrence of intraocular inflammation observed at 10 months post-irradiation. No potential conflict of interest relevant to this article was reported.

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

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

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Kinesiophobia Is Associated with Disability, Poor Quality of Life, Psychological Morbidity, and Surgery Dissatisfaction in Patients with Lumbar Microdiscetomy: A Cross-Sectional Controlled Study 39 46 EN Nihal Tezel Department of Physical and Rehabilitation Medicine, Health Sciences University Aslı Gençay Can Department of Physical and Rehabilitation Medicine, Faculty of Medicine, Ankara Yıldırım Beyazıt University Original Article 10.18926/AMO/70071 The study aimed to determine the prevalence of kinesiophobia in patients who had undergone lumbar microdiscectomy and to examine its associations with pain intensity, disability, quality of life, depression, anxiety, and satisfaction with surgery. Forty-eight patients with microdiscectomy and 48 healthy controls were enrolled. The Tampa Scale for Kinesiophobia (TSK), Roland-Morris Disability Index (RMDI), Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively), and Short Form-36 Health Survey (SF-36) were administered to both groups. The scores of TSK, RMDI, HADS-A, and HADS-D were significantly higher and SF-36 scores were significantly lower in the microdiscectomy than the control group (p<0.001 for all). In the microdiscectomy group, median (min-max) RMDI, HADS-A, and HADS-D scores were 19 (4-34), 10 (0-18), and 9 (0-18), respectively, in kinesiophobic patients, and were significantly higher than 6 (2-20), 3 (0-11), 2.5 (0-11) in non-kinesiophobic patients (all p<0.001). The median (min-max) SF-36 PCS, SF-36 MCS, and VAS scores for surgery satisfaction were 36.5 (8.7-75), 52.1 (11-95), 5, 5 (0-10), respectively, in kinesiophobic patients and were significantly lower than 71 (28-95), 85.5 (9-93), 8.5 (3-10) in non-kinesiophobic patients (all p<0.05). TSK scores were significantly correlated with RMDI, HADS-A, HADS-D, SF-36, and surgery satisfaction scores (all p<0.05). Kinesiophobic patients with lumbar microdiscectomy therefore showed greater disability and psychological morbidity, poorer quality of life, and lower satisfaction with surgery. No potential conflict of interest relevant to this article was reported.

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

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

Elsevier BV Acta Medica Okayama 1349-0079 68 1 2026 Insights into the taste of organic acids via TAS1Rs 100731 EN Yuko Yamase Department of Dental Anesthesiology and Special Care Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Katsuki Takebe Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kengo Horie Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihiro Mitoh Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsuko Yamashita Institute for Protein Research, The University of Osaka Ryusuke Yoshida Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: Organic acids contribute significantly to the flavor of fermented foods by imparting sourness. Although mice generally avoid sour taste, previous studies have reported greater consumption of l-lactic acid than its d-enantiomer, suggesting enantiomer-specific recognition. This behavior is hypothesized to involve TAS1Rs, which consists of sweet/umami receptors. However, it remains unclear whether TAS1Rs additionally contribute to the recognition of other chiral organic acids. This study aimed to evaluate the role of TAS1Rs, particularly TAS1R3, in the modulation of enantiomer-dependent behavioral responses to organic acids in mice. Methods: Behavioral responses were evaluated using 48-h and 1-h 2-bottle tests. Binding of organic acids to TAS1Rs was investigated by differential scanning fluorimetry (DSF) with the ligand-binding domain (LBD) of medaka Tas1r2a/Tas1r3. Results: Wild-type mice consumed more d-malic acid than l-malic acid in the 48-h test, whereas Tas1r3-KO mice showed no such difference. This pattern was not observed in the short-term 1-h test, which minimized the contribution of post-ingestion and learned effects. DSF analysis revealed no binding of any of the tested organic acids to the LBD of medaka Tas1r2a/Tas1r3. Conclusions: Organic acids may elicit TAS1R3-dependent post-ingestion signals that contribute to enantiomer-selective consumption in mice. Electrostatic interactions and hydrogen-bonding networks within the orthosteric pocket of TAS1Rs may account for the differences in binding affinity to the LBD of medaka Tas1r2a/Tas1r3 between organic acids and L-alanine, a known ligand. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0031-9317 178 1 2026 Reactive Carbonyl Species Mediate Isothiocyanate Signaling Pathway in Arabidopsis thaliana Guard Cells e70775 EN Sumaiya Farzana Graduate School of Environmental and Life Science, Okayama University Md. Moshiul Islam Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Jun'ichi Mano Science Research Center, Yamaguchi University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Our previous results demonstrated that depletion of glutathione (GSH) rather than elevation of levels of reactive oxygen species (ROS) is highly correlated with the decrease in stomatal aperture induced by isothiocyanates (ITCs), although ROS is considered a key second messenger in stomatal closure, suggesting that another signal component regulates stomatal apertures along with GSH depletion. This study, using Arabidopsis, clarified that reactive carbonyl species (RCS), especially acrolein and 4-hydroxy-(E)-2-nonenal, are determinants of stomatal aperture responses to ITCs. All tested ITCs, allyl isothiocyanate (AITC), sulforaphane (SFN), benzyl isothiocyanate (BITC), and phenethyl isothiocyanate (PEITC), significantly induced stomatal closure, which was inhibited by the RCS scavengers, carnosine and pyridoxamine. The RCS scavengers suppressed ITC-induced depletion of GSH but not elevation of ROS levels. All tested ITCs (AITC, SFN, BITC, and PEITC) increased levels of RCS and non-RCS aldehydes in the epidermal tissues. However, acrolein, 4-hydroxy-(E)-2-nonenal, crotonaldehyde, and (E)-2-pentenal induced stomatal closure at 10 and 100 μM, whereas propionaldehyde, butyraldehyde, and n-pentanal did not at concentrations up to 100 μM. Acrolein and 4-hydroxy-(E)-2-nonenal more effectively induced stomatal closure and GSH depletion than crotonaldehyde and (E)-2-pentenal did. The contents of RCS were more strongly correlated with GSH levels and stomatal closure than with ROS levels. These results suggest that RCS, especially acrolein and 4-hydroxy-(E)-2-nonenal, acts as key regulators of stomatal closure in guard cells in response to ITCs. No potential conflict of interest relevant to this article was reported.

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

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

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 大田植の分布と種類に関する検討（3）―岡山県・広島県の自治体史等における記述・資料― 1 18 EN Hiroshi TAKANO 10.18926/70017 No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 0385-5414 70 1 2006 Synthesis of 6- and 7-(1,2,3-Trihydroxy-1,2-O-isopropylidenepropyl)pteridines and Deoxygenation of Their 3’-Hydroxy Groups 355 365 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Daisuke Takayama Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University Treatment of 3,4-O-isopropylidene-L-threo-pentos-2-ulose (7) with 5,6-diamino-1,3-dimethyluracil (8) afforded 1,3-dimethyl-6-[(1R,2S)-1,2,3-trihydroxy-1,2-O-isopropylidenepropyl]lumazine (9a) and its 7-substituted isomer (9b). Deoxygenation of 3’-hydroxy groups of 9a,b was investigated in connection with a practical transformation of neopterin into biopterin. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-152X 62 12 2025 An Improved Synthesis of a Key Intermediate for Glycosylation of Biopterin and Its Application for the First Synthesis of Microcystbiopterin B 2021 2029 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Yuta Maeda Department of Chemistry, Faculty of Science, Okayama University Katsuya Iwasaki Department of Chemistry, Faculty of Science, Okayama University A key intermediate for the selective 2′-O-glycosylation of biopterin, N2-(N,N-dimethylaminomethylene)-1′-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]biopterin (12), was efficiently synthesized via a novel route starting from d-glucose, leading to an improved overall yield. This new pathway involves the preparation of a 5-deoxy-l-arabinose phenylhydrazone derivative (9) as a crucial intermediate in the construction of the pteridine ring. Utilizing compound 12, the first synthesis of microcystbiopterin B (4) was accomplished by glycosylation of 12 with 4,6-di-O-acetyl-2-O-(4-methoxybenzyl)-3-O-methyl-α-d-glucopyranosyl bromide (19) in the presence of silver triflate and tetramethylurea, followed by stepwise deprotection. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1349-4147 54 1 2026 Mycobacterium mageritense-associated refractory cutaneous infection and lymphadenitis in an immunocompetent adult: insights from genomic sequencing 19 EN Shinnosuke Fukushima Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Jumpei Uchiyama Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshio Kawakami Department of Dermatology, Okayama University Hospital Yoshiko Matsuura Konohana Dermatology Clinic Satoru Sugihara Department of Dermatology, Okayama University Hospital Shin Morizane Department of Dermatology, Okayama University Hospital Poowadon Muenraya Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background Nontuberculous mycobacteria are increasingly recognized as causes of chronic and refractory skin and soft tissue infections, even in individuals without immunodeficiency. Among them, Mycobacterium mageritense is a rare, rapidly growing species that can lead to persistent lesions requiring prolonged antimicrobial therapy. Reports of M. mageritense infections involving both the skin and regional lymph nodes are limited, and this case adds new clinical and genomic insights. Case presentation A 48-year-old previously healthy man presented with a slowly enlarging cutaneous lesion on his lower leg and ipsilateral inguinal lymphadenitis. Empirical antibacterial therapy with β-lactams and macrolides was ineffective. Wound cultures subsequently grew M. mageritense, confirmed by whole-genome sequencing. Several antimicrobial regimens were attempted, and the final successful therapy consisted of oral levofloxacin and minocycline for 4 months, leading to complete clinical resolution. Genomic analysis identified resistance-related genes, including erm(40), aac(2′)-Ib, tet(V), and RbpA, although in vitro minimum inhibitory concentrations showed variable susceptibility. Phylogenetic comparison revealed that the isolate was closely related to previously reported M. mageritense strains from Japan. Conclusions This case demonstrates that M. mageritense can cause cutaneous infection with secondary lymphadenitis in an immunocompetent host. Accurate species identification using molecular or genomic methods and selection of appropriate combination antibiotic therapy based on susceptibility testing are crucial for successful management of such infections. No potential conflict of interest relevant to this article was reported.

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

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

Oxford University Press (OUP) Acta Medica Okayama 2328-8957 13 1 2025 Impact of Candida Care Bundle Compliance on the Prognosis of Patients With Candidemia: A Multicenter Retrospective Cohort Study With Propensity Score Matching Analysis (2016–2023) ofaf790 EN Hidemasa Akazawa Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Toshie Higuchi Department of General Internal Medicine, Okayama Red Cross Hospital Tomoko Miyoshi Center for Medical Education and Internationalization, Kyoto University Graduate School of Medicine Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Yukinobu Akamatsu Department of General Medicine, Tottori Municipal Hospital Yuto Haruki Department of Pharmacy, Tsuyama Chuo Hospital Yoshitaka Iwamoto Department of General Medicine, NHO Okayama Medical Center Shuichi Tanaka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shun Fujisato Department of Pharmacy, Okayama Rousai Hospital Soichiro Ako Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background. Candidemia is a life-threatening infection with high mortality, and appropriate management is essential to improve patient outcomes. The Candida Care Bundle aims to standardize hospital management for patients with candidemia and reduce mortality. Methods. This retrospective multicenter cohort study included candidemia cases from 9 hospitals in Japan between 2016 and 2023. Compliance to the Candida Care Bundle was evaluated based on 5 elements: central venous catheter removal within 24 hours, appropriate antifungal therapy, ophthalmologic examination, follow-up blood cultures, and antifungal treatment for ≥2 weeks after clearance. Patients were categorized into high (4–5 items) and low (0–3 items) compliance groups. The primary and secondary outcomes were defined as 30-day survival and the development of endophthalmitis, with propensity score matching used to adjust for potential confounders. Results. Among 230 patients, 160 (69.5%) were classified into the high compliance group, which exhibited significantly lower 30-day mortality than the low compliance group (8.8% vs 57.1%, P < .01). Even after matching, the high compliance group remained independently associated with improved survival (hazard ratio [HR]: 0.15; 95% confidence interval [CI]: .08–.30). C. albicans (HR: 1.95; 95% CI: 1.01–3.52) and central line-associated bloodstream infection (HR: 2.63; 95% CI: 1.35–5.12) were associated with the fatal outcome. Endophthalmitis involved 23.6% of the patients, being associated with C. albicans (odds ratio [OR]: 8.18; 4.46–19.30) and central line-associated bloodstream infection (OR: 2.69; 1.08–6.70). Conclusions. Strict compliance to the Candida Care Bundle significantly improves survival, underscoring its importance in candidemia management. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Single cell spatial transcriptomics links Wnt signaling disruption to extracellular matrix development in a cleft palate model 29639 EN Jeremie Oliver Piña Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Resmi Raju Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Evan Stipano Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Aye Chan Myo Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Ziyi Wang Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Department of Molecular Biology and Biochemistry, Okayama University Mitsuaki Ono Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Department of Molecular Biology and Biochemistry, Okayama University Parna Chattaraj Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Masae Furukawa Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Rena N. D’Souza Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Despite advances in understanding the morphological disruptions that lead to defects in palate formation, the precise perturbations within the signaling microenvironment of palatal clefts remain poorly understood. To explore in greater depth the genomic basis of palatal clefts, we designed and implemented the first single cell spatial RNA-sequencing study in a cleft palate model, utilizing the Pax9−/− murine model at multiple developmental timepoints, which exhibits a consistent cleft palate defect. Visium HD, an emerging platform for true single-cell resolution spatially resolved transcriptomics, was employed using custom bins of 2 × 2 μm spatial gene expression data. Validation of spatial gene expression was then validated using custom designed Xenium In Situ mRNA spatial profiling and RNAscope Multiplex assays. Functional enrichment analysis revealed a palate cell-specific perturbation in Wnt signaling effector function in tandem with disrupted expression of extracellular matrix genes in developing mesenchyme. As a key step toward laying the framework for identifying key molecular targets these data can be used for translational studies aimed at developing effective therapies for human palatal clefts. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2694-2445 5 6 2025 Electronic Structure of the S1 State Manganese Cluster in Photosystem II Investigated Using Q-Band Selective Hole-Burning 660 671 EN Shinya Kosaki Department of Physics, Graduate School of Science, Nagoya University Naohiko Nakamura Department of Physics, Graduate School of Science, Nagoya University Yoshiki Nakajima Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jian-Ren Shen Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyuki Mino Department of Physics, Graduate School of Science, Nagoya University The electronic structure of the S1 state of photosystem II (PSII) was investigated using selective hole burning of Q-band pulsed electron paramagnetic resonance. The free induction decay and spin–echo signals of the tyrosine radical YD• in the plant PSII oscillated because of the magnetic dipole–dipole interaction with the S1 state Mn cluster. The initial period was 410 ns (2.44 MHz) and was assigned to the S = 1 spin state. Based on the oscillation analysis, both Mn1 and Mn4 and both Mn2 and Mn3 were assigned as Mn(III) and Mn(IV), respectively, which is consistent with the quantum chemical calculations. The 410 ns period was accounted for in the simplified model using the isotropic spin density distribution ratio [1.6:–1.1:–1.1:1.6] for Mn1–4 ions. This oscillation was identical with that observed in the presence of methanol. The oscillation decreased in PsbP/Q- and PsbO/P/Q-depleted PSII. In Thermosynechococcus vulcanus, two periods, 390 ns (2.56 MHz) and 630 ns (1.59 MHz), were detected, indicating that the cyanobacterial S1 state includes two isomers, S = 1 and S ≥ 2 spins. The S ≥ 2 spin was not detected in PsbO/U/V-depleted PSII without polyethylene glycol. The S ≥ 2 state was consistent with the reported quantum chemical calculation using S = 3. A simplified model accounted for the S = 1 state as the spin density distribution [1.8:–1.3:–1.3:1.8] and for the S ≥ 2 state as the isotropic spin density distribution [−0.5:0.5:0.5:0.5] for Mn1–4 ions. In combination with quantum chemical calculations, the most probable protonated structure is W1 = H2O, W2 = H2O, O4 = O2–, and O5 = O2– for the S1 state. These results demonstrate that the selective hole burning method is a powerful tool to complement X-ray studies to determine the valence and protonation structure of manganese clusters, not only in the S1 state but also in higher S-states and general metal clusters, which would provide important insights into the water oxidation mechanism. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 2049-9450 23 5 2025 Prolonged exposure to axitinib alters the molecular profile of Caki‑2 renal cell carcinoma cells 101 EN Yuko Nakayama Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University Aya Ino Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohji Takara Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University Axitinib, an oral second‑generation multitargeted tyrosine kinase inhibitor, is used as a second‑line treatment for metastatic renal cell carcinoma (RCC). However, patients often develop resistance after initial responsiveness, necessitating the elucidation of the underlying resistance mechanisms. Therefore, the present study aimed to investigate the mechanisms underlying axitinib resistance using the Caki‑2 human papillary RCC model cells. Cells tolerating 0.1 µM axitinib were designated as Caki/AX cells. Cell viability was assessed using the water‑soluble tetrazolium salt assay. Notably, the 50% inhibitory concentration (IC50) values of axitinib and sunitinib were significantly higher in Caki/AX cells than those in Caki‑2 cells, indicating 2.83‑ and 1.2‑fold resistance, respectively. By contrast, the IC50 values of sorafenib and erlotinib were decreased in Caki/AX cells. Moreover, Caki/AX cells showed resistance to everolimus, temsirolimus and rapamycin, and decreased sensitivity to vinblastine, vincristine, paclitaxel, doxorubicin and SN‑38 compared with Caki‑2 cells. Notably, etoposide, 5‑fluorouracil, cisplatin and carboplatin sensitivities were comparable in both cell types. Reverse transcription‑quantitative polymerase chain reaction (PCR) analysis revealed that the mRNA levels of the ATP‑binding cassette subfamily B member 1 and subfamily G member 2 were significantly higher in Caki/AX cells than those in Caki‑2 cells. A PCR array related to vascular endothelial growth factor signalling showed that the mRNA levels of FIGF (also known as vascular endothelial growth factor D) and sphingosine kinase 1 were upregulated, whereas those of Rac family small GTPase 2 were downregulated in Caki/AX cells. Overall, these findings suggested that the upregulation of the ATP‑binding cassette subfamily B member 1, FIGF and sphingosine kinase 1 mRNA levels, and downregulation of the Rac family small GTPase 2 mRNA levels may contribute to acquired resistance in Caki/AX cells. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2025 Atezolizumab + Chemotherapy for Advanced Non-Small Cell Lung Cancer in Japanese Clinical Practice (J-TAIL-2) EN Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University 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 Ichiro Yoshino 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 Akito Hata Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center Akira Kisohara Department of Respiratory Medicine, Kasukabe Medical Center Shoichi Kuyama Department of Respiratory Medicine, NHO Iwakuni Clinical Center Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Asako Miwa Chugai Pharmaceutical Co., Ltd. Shunichiro Iwasawa Chugai Pharmaceutical Co., Ltd. Misa Tanaka Chugai Pharmaceutical Co., Ltd. Akihiko Gemma Nippon Medical School First-line atezolizumab combination therapies were approved for the treatment of metastatic non-small cell lung cancer (NSCLC) based on results from the global phase 3 trials IMpower130, IMpower132, and IMpower150. These trials reported 12-month overall survival (OS) rates of 60%–67% with atezolizumab combination therapy. J-TAIL-2 (NCT04501497), a prospective, multicenter, observational study, evaluated atezolizumab combination therapy in routine clinical practice in Japan. Patients ≥ 20 years old with NSCLC received atezolizumab plus carboplatin and nab-paclitaxel (atezo + CnP), atezolizumab plus carboplatin or cisplatin plus pemetrexed (atezo + PP), or atezolizumab plus bevacizumab plus carboplatin and paclitaxel (atezo + bev + CP) in clinical practice. The primary endpoint was the 12-month OS rate. Secondary endpoints included OS, progression-free survival, and subgroup analyses, including IMpower-unlike (did not meet the main eligibility criteria of each IMpower trial) and IMpower-like patients. In total, 814 patients were enrolled (atezo + CnP, n = 217; atezo + PP, n = 211; atezo + bev + CP, n = 386). The IMpower-unlike group included patients with Eastern Cooperative Oncology Group performance status ≥ 2, autoimmune disease, or interstitial lung disease. Twelve-month OS rates (95% confidence interval [CI]) were 62.9% (55.8–69.2), 72.1% (65.2–77.9), and 68.3% (63.2–72.9) with atezo + CnP, atezo + PP, and atezo + bev + CP, respectively. OS hazard ratios (95% CI) in the IMpower-unlike vs. -like subgroups were 1.36 (0.91–2.05), 1.08 (0.70–1.68), and 1.49 (1.09–2.06), respectively. No new safety signals were observed. Real-world efficacy and safety for each atezolizumab combination were comparable to those in the relevant IMpower trials. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2366-1070 13 4 2025 Asian Subgroup Analysis of Patients in the Phase 2 DeLLphi-301 Study of Tarlatamab for Previously Treated Small Cell Lung Cancer 1041 1054 EN Myung-Ju Ahn Hematology-Oncology Department, Samsung Medical Center (SMC), Sungkyunkwan University School of Medicine Byoung Chul Cho Medical Oncology Department-501, ABMRC, Yonsei University Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Hiroki Izumi Thoracic Oncology, National Cancer Center Hospital East Jong-Seok Lee Hematology/Oncology, Seoul National University Bundang Hospital Ji-Youn Han Center for Lung Cancer, National Cancer Center-Graduate School of Cancer Science and Policy Chi-Lu Chiang Department of Chest Medicine, Taipei Veterans General Hospital Shuang Huang Amgen Inc. Ali Hamidi Amgen Inc. Sujoy Mukherjee Amgen Inc. Krista Lin Xu Amgen Asia Pacific Pte. Ltd. Hiraoki Akamatsu Internal Medicine III, Wakayama Medical University Introduction: Tarlatamab is a bispecific T-cell engager (BiTE®) immunotherapy that binds delta-like ligand 3 on the surface of small cell lung cancer (SCLC) cells and CD3 on T cells, facilitating T cell-mediated cancer cell lysis. In the primary analysis of the phase 2 DeLLphi-301 study (NCT05060016), tarlatamab showed a favourable benefit-to-risk profile with durable objective responses and promising survival outcomes in patients with previously treated SCLC. Here, phase 2 data for the Asia region subgroup are presented. Methods: Patients with previously treated, advanced SCLC received 10 mg tarlatamab every 2 weeks. The primary endpoint was objective response rate (ORR) by blinded independent central review (RECIST version 1.1). Key secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. The present analysis includes patients enrolled at sites in Asia. Results: A total of 43 patients were enrolled at sites in Asia. ORR was 46.3% (95% confidence interval [CI], 30.7–62.6) and median DOR was 7.2 months (95% CI 3.9 to not estimable). The median follow-up was 16.6 months for PFS and 21.2 months for OS. Median PFS was 5.4 months (95% CI 3.0–8.1) and median OS was 19.0 months (95% CI 11.4 to not estimable). The most common treatment-emergent adverse event (AE) was cytokine release syndrome (48.8%), and all such events were grade 1 or 2. There were no discontinuations due to treatment-related AEs. Conclusions: Tarlatamab demonstrated durable responses and promising survival outcomes with a manageable safety profile in this post hoc analysis of patients from Asia with previously treated SCLC. Trial Registration: ClinicalTrials.gov, NCT05060016. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0301-486X 190 6 2025 Prognostic Value of Serum (1→3)-β-D-Glucan Levels in Patients with Candidemia Stratified by Compliance with Candida Bundle: A Multicenter Retrospective Cohort Study (2016–2023) 90 EN Hidemasa Akazawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Toshie Higuchi Department of General Internal Medicine, Okayama Red Cross Hospital Tomoko Miyoshi Center for Medical Education and Internationalization, Kyoto University Graduate School of Medicine Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Yukinobu Akamatsu Department of General Medicine, Tottori Municipal Hospital Yuto Haruki Department of Pharmacy, Tsuyama Chuo Hospital Yoshitaka Iwamoto Department of General Medicine, NHO Okayama Medical Center Shuichi Tanaka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shun Fujisato Department of Pharmacy, Okayama Rousai Hospital Soichiro Ako Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background Candidemia is a severe systemic infection with a high mortality risk. While β-D-glucan (BDG) serves as a diagnostic biomarker, its prognostic value in candidemia, particularly in association with Candida bundle compliance, remains unclear. Methods In this retrospective multicenter cohort study, we evaluated 96 patients with candidemia across nine Japanese hospitals between 2016 and 2023. Candida bundle compliance was assessed using five key components: central venous catheter removal within 24 h of diagnosis, appropriate initial antifungal therapy, ophthalmologic examination, follow-up blood cultures until clearance, and antifungal therapy for at least two weeks post-clearance. Analyses stratified patients by serum BDG status (positive/negative) and compliance with the Candida bundle (high: 4–5 points; low: 0–3 points). The primary outcome was 30-day mortality, and the secondary outcome was defined as endophthalmitis incidence. Results Of 96 eligible patients with candidemia, 70 (72.9%) were BDG-positive and 26 (27.1%) were BDG-negative. The overall 30-day mortality was 17.7%. Among BDG-positive patients, 15 (21.4%) died, while 2 (7.7%) died in BDG-negative cohorts (p = 0.09). Serum BDG positivity demonstrated a statistically significant association with decreased survival rates in the low bundle adherence group (p = 0.02), whereas this correlation was not observed among patients in the high-compliance cohort (p = 0.66). Endophthalmitis occurred in 25.0% of patients, without significant correlation to serum BDG status. C. albicans was associated with a significantly higher incidence of endophthalmitis compared with non-albicans species (45.7% vs. 8.9%). Conclusions Serum BDG positivity potentially correlates with worse survival in candidemia, particularly in patients with low bundle compliance. This emphasizes the importance of adherence to standardized Candida management protocols for optimizing patient outcomes. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0006-2960 64 20 2025 Characterization of Autonomous and Ca2+/Calmodulin-Dependent Activities of CaMKK Isoforms In Vitro and in Mouse Tissues 4309 4317 EN Satomi Ohtsuka Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yerun Chen Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masaki Magari Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Teruhiko Ishikawa Department of Science Education, Graduate School of Education, Okayama University Hiroyuki Sakagami Department of Anatomy, Kitasato University School of Medicine Futoshi Suizu Clinical Examination Department, Kagawa Prefectural University of Health Sciences Hiroshi Tokumitsu Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ca2+/CaM-dependent protein kinase kinase (CaMKK) phosphorylates and activates downstream kinases, including CaMKI, CaMKIV, PKB, and AMPK, regulating various cellular functions such as neuronal morphogenesis, metabolic control, and pathophysiological pathways, such as cancer progression. CaMKKα/1 is tightly regulated by an autoinhibitory mechanism. CaMKKβ/2 activity is highly Ca2+/CaM-independent (autonomous activity) in vitro and Ca2+/CaM-dependent in cultured cells. Whether these two activity states of CaMKKβ/2 exist in vivo and the detailed regulatory mechanisms for the transition of both activity states remain unclear due to the difficulty in distinguishing the two activity states. In this study, we detected Ca2+-dependent and autonomous CaMKK activity in HeLa cells and successfully separated both activity states of CaMKKβ/2 in mouse brain and testis extracts using a recently developed CaMKK inhibitor (TIM-063)-coupled sepharose, which binds to the catalytic domain in the active state but not in the autoinhibited state. Furthermore, lambda protein phosphatase treatment converted the Ca2+/CaM-dependent form to the autonomous form of CaMKKβ/2, which was not affected by Ala mutation of Ser128, Ser132, and Ser136. The two activity forms of CaMKKβ/2 had equivalent Ca2+/CaM-binding ability. The findings demonstrate the presence of autonomous and Ca2+/CaM-dependent forms of CaMKKβ/2 independently in mouse tissues and cultured cells. The transition of these states of CaMKKβ/2 may be dynamically regulated by the phosphorylation/dephosphorylation of serine residues in the N-terminal regulatory domain. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0378-4371 684 2026 Longitudinal-field fidelity susceptibility analysis of the 𝐽1-𝐽2 transverse-field Ising model around 𝐽2∕𝐽1 ≈ 0.5 131245 EN Yoshihiro Nishiyama Department of Physics, Faculty of Science, Okayama University The square-lattice 𝐽1-𝐽2 transverse-field (TF) Ising model was investigated with the exact diagonalization (ED) method. In order to analyze the TF-driven phase transition, we applied the longitudinal-field fidelity susceptibility 𝜒(ℎ)𝐹, which is readily evaluated via the ED scheme. Here, the longitudinal field couples with the absolute value of the magnetic moment |𝑀| rather than the raw 𝑀 so that the remedied fidelity susceptibility exhibits a peak around the critical point; note that the spontaneous magnetization does not appear for the finite-size systems. As a preliminary survey, the modified fidelity susceptibility 𝜒(ℎ)𝐹 is applied to the analysis of criticality for 𝐽2 = 0, where a number of preceding results are available. Thereby, properly scaling the distance from the multi-criticality, 𝜂 = 0.5−𝐽2, the 𝜒(ℎ)𝐹 data were cast into the crossover-scaling formula, and the multi-critical exponent for 𝜒(ℎ)𝐹 is estimated. The result is cross-checked by the numerically evaluated 𝛽-function behavior. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0250-7005 46 1 2025 P53-Armed Oncolytic Virotherapy Promotes the Efficacy of PD1 Blockade in Murine Osteosarcoma Tumors 69 84 EN MIHO KURE Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HIROSHI TAZAWA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KOJI DEMIYA Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HIROYA KONDO Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences YUSUKE MOCHIZUKI Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TADASHI KOMATSUBARA Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences AKI YOSHIDA Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KOJI UOTANI Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences JOE HASEI Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOMOHIRO FUJIWARA Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOSHIYUKI KUNISADA Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences YASUO URATA 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 TOSHIFUMI OZAKI Department of Orthopaedic 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: Osteosarcoma (OS) is refractory to immune checkpoint inhibitors targeting programmed cell death 1 (PD1)/PD ligand 1 (PD-L1) due to poor immune response. We previously developed telomerase-specific, replication-competent oncolytic adenoviruses non-armed OBP-301 and P53-armed OBP-702 that exert antitumor efficacy against human OS cells. Recently, we demonstrated that P53-armed OBP-702 induces more profound immunogenic cell death and antitumor immune response against human and murine OS cells than does non-armed OBP-301. In the present study, we assessed the combined efficacy of PD1 blockade and P53-armed OBP-702 against murine OS cells. Materials and Methods: Three murine OS cell lines (K7M2, NHOS, NHOS-LM4) were used to assess the cytopathic effect of non-armed OBP-301 and P53-armed OBP-702 by XTT assay. Virus-induced immunogenic cell death was assessed by analyzing the levels of extracellular adenosine triphosphate and high-mobility group box protein B1. The expression of PD-L1 and PD-L2 was analyzed by flow cytometry. The malignant potential of NHOS-LM4 cells was analyzed by a migration and invasion assay. An orthotopic NHOS-LM4 tumor model was used to evaluate the antitumor efficacy of combination therapy with P53-armed OBP-702 and anti-PD1. Results: P53-armed OBP-702 exhibited antitumor potential for the induction of immunogenic cell death, apoptosis, autophagy, and PD-L1/2 upregulation in K7M2 and NHOS cells. NHOS-LM4 cells showed increased migratory and invasive ability compared to NHOS cells. P53-armed OBP-702 significantly suppressed the malignant potential of NHOS-LM4 cells. Combination dosing showed that P53-armed OBP-702 significantly promoted the antitumor effect of PD1 blockade against NHOS-LM4 tumors. Conclusion: Our results suggest that P53-armed OBP-702 is a promising agent for improving the antitumor effect of PD1 blockade in treating invasive OS. No potential conflict of interest relevant to this article was reported.

eLife Sciences Publications, Ltd Acta Medica Okayama 2050-084X 13 2025 Redistribution of fragmented mitochondria ensures symmetric organelle partitioning and faithful chromosome segregation in mitotic mouse zygotes RP99936 EN Haruna Gekko Department of Animal Science, Graduate School of Environment and Life Science, Okayama University Ruri Nomura Department of Animal Science, Graduate School of Environment and Life Science, Okayama University Daiki Kuzuhara Reproductive Centre, Mio Fertility Clinic Masato Kaneyasu Department of Animal Science, Graduate School of Environment and Life Science, Okayama University Genpei Koseki Department of Animal Science, Graduate School of Environment and Life Science, Okayama University Deepak Adhikari Development and Stem Cell Program and Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University Yasuyuki Mio Reproductive Centre, Mio Fertility Clinic John Carroll Development and Stem Cell Program and Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University Tomohiro Kono Department of Bioscience, Tokyo University of Agriculture Hiroaki Funahashi Department of Animal Science, Graduate School of Environment and Life Science, Okayama University Takuya Wakai Department of Animal Science, Graduate School of Environment and Life Science, Okayama University In cleavage-stage embryos, preexisting organelles partition evenly into daughter blastomeres without signiﬁcant cell growth after symmetric cell division. The presence of mitochondrial DNA within mitochondria and its restricted replication during preimplantation development makes their inheritance particularly important. While chromosomes are precisely segregated by the mitotic spindle, the mechanisms controlling mitochondrial partitioning remain poorly understood. In this study, we investigate the mechanism by which Dynamin-related protein 1 (Drp1) controls the mitochondrial redistribution and partitioning during embryonic cleavage. Depletion of Drp1 in mouse zygotes causes marked mitochondrial aggregation, and the majority of embryos arrest at the 2 cell stage. Clumped mitochondria are located in the center of mitotic Drp1-depleted zygotes with less uniform distribution, thereby preventing their symmetric partitioning. Asymmetric mitochondrial inheritance is accompanied by functionally inequivalent blastomeres with biased ATP and endoplasmic reticulum Ca2+ levels. We also find that marked mitochondrial centration in Drp1-depleted zygotes prevents the assembly of parental chromosomes, resulting in chromosome segregation defects and binucleation. Thus, mitochondrial fragmentation mediated by Drp1 ensures proper organelle positioning and partitioning into functional daughters during the first embryonic cleavage. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 2 2025 Maturity-Onset Diabetes of the Young (MODY) With HNF1B p.Glu105Lys Mutation Achieving Significant Insulin Reduction on Tirzepatide: A Case Report e70173 EN Mihiro Sue Department of Diabetology and Metabolism, NHO Okayama Medical Center Mayu Watanabe Department of Diabetology and Metabolism, NHO Okayama Medical Center Ayumi Inoue Department of Diabetology and Metabolism, NHO Okayama Medical Center Akihiro Katayama Department of Diabetology and Metabolism, NHO Okayama Medical Center Sanae Teshigawara Department of Internal Medicine, Diabetes Center, Okayama Saiseikai General Hospital Yuichi Matsushita Department of Diabetology and Metabolism, NHO Okayama Medical Center Masaya Takeda Department of Diabetology and Metabolism, NHO Okayama Medical Center Izumi Iseda Department of Diabetology and Metabolism, NHO Okayama Medical Center Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazuyuki Hida Department of Diabetology and Metabolism, NHO Okayama Medical Center This report describes the first case of maturity-onset diabetes in young (MODY) with HNF1B mutation started administration of the dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, tirzepatide. A 26-year-old female with a 15-year history of diabetes mellitus was diagnosed with MODY, which is characterized by decreased insulin secretion. She was treated with tirzepatide, which significantly improved her glycemic management; insulin secretion increased the fasting serum C-peptide immunoreactivity from 0.36 to 1.09 ng/mL. The patient discontinued glimepiride, and her total daily insulin dose was reduced from 88 to 4 units. This report highlights the glucose-lowering effects of tirzepatide in a patient with MODY who has the HNF1B p.Glu105Lys mutation. No potential conflict of interest relevant to this article was reported.

岡山大学法学会 Acta Medica Okayama 0386-3050 75 2 2025 表紙・目次 EN No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1873-9601 19 4 2025 Interaction between nuclear‐translocated cellular communication network factor 2 and purine‐rich box 1 regulates the expression of fibrosis‐related genes e70051 EN Xuan Thi Nguyen Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaharu Takigawa Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan Takashi Nishida Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Cellular communication network factor 2 (CCN2) with a nuclear localization signal-like peptide is known to promote fibrosis. However, translocation of CCN2 into the nucleus and its role in fibrosis remain unclear. We hypothesized that nuclear-translocated CCN2 is associated with purine-rich box 1 (PU.1), which is a transcription factor regulating the differentiation of myofibroblasts. Western blot analysis of the cytoplasmic and nuclear fractions of cell lysate and immunofluorescence analysis revealed that CCN2 was detectable in both the cytoplasm and nuclei of murine fibroblastic NIH3T3 cells. Additionally, chromatin immunoprecipitation (IP)-PCR and an electrophoretic mobility shift assay revealed that recombinant CCN2 protein bound to the regulatory region of Spi1, which encodes PU.1. Furthermore, IP-Western blot analysis showed that CCN2 interacted with PU.1. Finally, the forced expression of both Ccn2 and Spi1 significantly promoted the production of angiotensin II, and increased fibrosis-related molecules, such as Col1a1 and Acta2, at the gene and protein levels. These findings indicate that CCN2 translocated to the nucleus interacts with PU.1 and that the complex promotes the markers of myofibroblast differentiation, suggesting that CCN2 plays an important role in fibrosis via cooperation with PU.1, as a transcription co-factor. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Recurrence of FVIII Inhibitor during Surgery in a Patient with Severe Hemophilia A Receiving Emicizumab Prophylaxis 451 455 EN Moe Hagihara Department of Hematology and Oncology, Okayama University Hospital Keisuke Seike Department of Hematology and Oncology, Okayama University Hospital Kenta Hayashino Department of Hematology and Oncology, Okayama University Hospital Takao Yasuhara Department of Neurological Surgery, Okayama University Hospital Kyohei Kin Department of Neurological Surgery, Okayama University Hospital Yuichi Hirata Department of Neurological Surgery, Okayama University Hospital Hiroki Kobayashi Department of Hematology and Oncology, Okayama University Hospital Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Division of Transfusion and Cell Therapy, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Case Report 10.18926/AMO/69848 Emicizumab, a bispecific monoclonal antibody, benefits patients with severe hemophilia A. It alters laboratory assessments of coagulation activity, requiring anti-idiotype monoclonal antibodies for accurate monitoring. A 64-year-old man, receiving emicizumab regularly, was admitted for laminoplasty. We planned to use FVIII replacement during the perioperative period after confirming the disappearance of inhibitors, monitoring coagulation activity with anti-idiotype monoclonal antibodies. Activated partial thromboplastin time was prolonged on postoperative day 2, prompting an immediate switch to eptacog alfa. The patient recovered without bleeding. This case underscores the necessity of anti-idiotype monoclonal antibodies for accurate monitoring. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Effects of Thoron Inhalation and Cyclosporin A Treatment on Dextran Sulfate Sodium-Induced Oxidative Damage in Mice 421 429 EN Ayumi Tanaka Graduate School of Health Sciences, Okayama University Shota Naoe Graduate School of Health Sciences, Okayama University Reiju Takenaka Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/69844 Radon (222Rn; Rn) and thoron (220Rn; Tn) inhalation have been reported to enhance antioxidant activity in various organs. However, the effects of Tn on the colon have not been investigated. This study aimed to clarify the effects of Tn inhalation, alone and in combination with cyclosporin A (CsA), on dextran sulfate sodium (DSS)-induced colitis, and the accompanying oxidative stress, in mice. Male BALB/c mice were subjected to continuous 8-day Tn inhalation (c-Tn, 533±128 Bq/m3) or alternate-day Tn inhalation over the same period (f-Tn, 577±63Bq/m3), followed by treatment with 3% DSS and either CsA or vehicle for 7 days. Although the disease activity index (DAI) decreased significantly by day 2 in the c-Tn group, scores remained significantly higher than those in the f-Tn group. In the c-Tn group, superoxide dismutase and catalase activity in the colon were significantly elevated compared with those in sham controls. Thus, DSS-induced damage was effectively inhibited in the earlier stages by the c-Tn mode of inhalation than by the f-Tn mode. These findings suggest that continuous Tn inhalation more effectively attenuated early colitis symptoms than alternate-day inhalation, potentially through upregulation of antioxidant defenses. Tn and CsA showed no combined effects. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 COVID-19 and the Risks of Migraine and Headache: A Mendelian Randomization Study 413 419 EN Zhiyun Jiang Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University Ying Xi Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University Original Article 10.18926/AMO/69843 Several observational studies suggested that migraine headache attacks were associated with coronavirus disease 2019 (COVID-19). We investigated genetic causal links between COVID-19 phenotypes and the development of headache and migraine, including migraine with aura (MA) and migraine without aura (MO). We conducted a two-sample Mendelian randomization (MR) analysis to estimate the genetic association in European populations. The inverse-variance weighted (IVW) method was used as the main approach in the MR analyses, together with weighted median and MR-Egger methods. We also performed a series of sensitivity tests to assess the robustness of the MR results. The MR results demonstrated that COVID-19 severity, hospitalization, and susceptibility had no causal effect on the risks of headache, migraine, MA, or MO. No horizontal pleiotropy was detected, and the results were robust as supported by the sensitivity analysis findings. Our analyses identified no casual effect of COVID-19 severity, hospitalization, or susceptibility on the risks of headache or migraine in European populations. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Real-World Outcomes of Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration in Patients Aged 85 or Older 405 412 EN Chihiro Ouchi Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Morizane Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuro Morita Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/69842 We investigated the treatment outcomes of patients aged ≥85 years with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (anti-VEGF) therapy using either treat-and-extend (TAE) or pro re nata (PRN) regimens for 1 year in real-world clinical practice. Eighty-five eyes from 85 patients were included. Among them, types 1, 2, and 3 macular neovascularization and polypoidal choroidal vasculopathy were present in 27.1%, 17.6%, 18.8%, and 36.5%, respectively. TAE and PRN regimens were used in 43.5% and 56.5% of patients, respectively. At baseline, the PRN group was older and had worse best-corrected visual acuity (BCVA), greater central retinal thickness, and more intraretinal fluid than the TAE group. In the TAE group, the mean number of injections was 7.6, BCVA improved significantly, and all retinal fluid rates decreased. In the PRN group, the mean number of injections was 3.9, BCVA remained unchanged, and the rates of macular fibrosis and atrophy increased. No serious adverse events were observed in either group. Anti-VEGF therapy was safe for patients aged ≥ 85 years with nAMD, and the TAE regimen effectively improved BCVA in this population. BCVA remained unchanged in the PRN-treated patients, with baseline disease severity and/or undertreatment potentially influencing the outcomes. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-3425 15 11 2025 Sensory Modality-Dependent Interplay Between Updating and Inhibition Under Increased Working Memory Load: An ERP Study 1178 EN Yuxi Luo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ao Guo Department of Psychology, Institute of Education, China West Normal University Jinglong Wu Faculty of Biomedical Engineering, Shenzhen University of Advanced Technology Jiajia Yang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Background/Objectives: Working memory (WM) performance relies on the coordination of updating and inhibition functions within the central executive system. However, their interaction under varying cognitive loads, particularly across sensory modalities, remains unclear. Methods: This study examined how sensory modality modulates flanker interference under increasing WM loads. Twenty-two participants performed a visual n-back task at three load levels (1-, 2-, and 3-back) while ignoring visual (within-modality) or auditory (cross-modality) flankers. Results: Behaviorally, increased WM load (2- and 3-back) led to reduced accuracy (AC) and prolonged reaction times (RTs) in both conditions. In addition, flanker interference was observed under the 2-back condition in both the visual within-modality (VM) and audiovisual cross-modality (AVM) tasks. However, performance impairment emerged at a lower load (2-back) in the VM condition, whereas in the AVM condition, it only emerged at the highest load (3-back). Significant performance impairment in the AVM condition occurred at higher WM loads, suggesting that greater WM load is required to trigger interference. Event-related potential (ERP) results showed that N200 amplitudes increased significantly for incongruent flankers under the highest WM load (3-back) in the visual within-modality condition, reflecting greater inhibitory demands. In the cross-modality condition, enhanced N200 was not observed across all loads and even reversed at low load (1-back). Moreover, the results also showed that P300 amplitude increased with load in the within-modality condition but decreased in the cross-modality condition. Conclusions: These results demonstrated that the interaction between updating and inhibition is shaped by both WM load and sensory modality, further supporting a sensory modality-specific resource allocation mechanism. The cross-modality configurations may enable more efficient distribution of cognitive resources under high load, reducing interference between concurrent executive demands. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 30 8 2025 Phase-Ib dose-finding and pharmacokinetic trial of metformin combined with nivolumab for refractory/recurrent solid tumors 1537 1544 EN Toshio Kubo Department of Allergy and Respiratory Medicine, Okayama University Hospital Hironari Kato Department of Gastroenterology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology, Okayama University Hospital Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center Akinori Asagi Department of Gastrointestinal Medical Oncology, NHO Shikoku Cancer Center Michihiro Yoshida Center for Innovative Clinical Medicine, Okayama University Hospital 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 Katsuyuki Hotta Department of Allergy and Respiratory Medicine, Okayama University Hospital Background Our previous findings showed that the addition of metformin to nivolumab resulted in remarkable tumor regression and increased the number of tumor-infiltrating T cells in mouse models. Therefore, we conducted a phase Ib study using combination therapy with nivolumab and metformin in patients with refractory/recurrent solid tumors. Methods This study consisted of two parts: 1, evaluating the maximum tolerated dose (MTD), safety, pharmacokinetics in solid tumors, and 2, principally investigating the safety at the recommended dose limited to thoracic and pancreatic cancers. Metformin and nivolumab were administered orally at doses of 750–2,250 mg/day and biweekly at a fixed intravenous dose of 3 mg/kg, respectively. Dose-limiting toxicity was evaluated within the first 4 weeks. Both metformin and nivolumab were continued until disease progression or discontinued because of toxicity. Results In total, 17 and 24 patients were enrolled in parts 1 and 2, respectively. One patient experienced increased pancreatic enzyme levels (grade 4) and lactic acidosis (grade 3). No Grade 5 adverse events were observed. MTD was not reached up to 2,250 mg/day of metformin, 2,250 mg/day was selected for part 2. An objective response was observed in 4 of 41 patients. One-year progression-free and overall survival rates were 9.8% and 56.8%, respectively. Two patients remained alive without disease progression for more than three years. Conclusions Nivolumab and metformin combination therapy was well-tolerated and showed preliminary signals of efficacy in a subset of patients. Further verification of the underlying mechanism in cases where treatment is effective is required. Trial registration numbers UMIN registration number 000028405 https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031915. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0883-2927 187 2025 Nitrogen distribution and nitrogen isotope fractionation in synthetic 2:1 phyllosilicates under hydrothermal conditions at 200 °C and saturated vapor pressure 106403 EN Jaeguk Jo Graduate School of Natural Science and Technology, Okayama University Toshiro Yamanaka Graduate School of Natural Science and Technology, Okayama University Youko Miyoshi Research Institute for Geo-Resources and Environment, Geological Survey of Japan, National Institute of Advanced Industrial Science and Technology (AIST) Masaya Suzuki Research Institute for Geo-Resources and Environment, Geological Survey of Japan, National Institute of Advanced Industrial Science and Technology (AIST) Yoshihiro Kuwahara Department of Environmental Changes, Faculty of Social and Cultural Studies, Kyushu University Isao Kadota Graduate School of Natural Science and Technology, Okayama University Hitoshi Chiba Graduate School of Natural Science and Technology, Okayama University Bum Han Lee Critical Minerals Research Center, Korea Institute of Geoscience & Mineral Resources (KIGAM) This study investigates nitrogen distribution and isotope fractionation within synthetic 2:1 phyllosilicates, simulating submarine hydrothermal environments at 200 °C and saturated vapor pressure. XRD and EDS results revealed the potential coexistence of multiple cations in the interlayer of synthetic 2:1 phyllosilicate, concurrently suggesting cation substitution in the tetrahedral and/or octahedral sheets. Meanwhile, the iron-enriched 25-5 sample exhibited restricted interlayer expansibility. NH4+ absorptions were identified in the NH4-stretching (3200–2800 cm−1) and NH4-bending (1450–1400 cm−1) regions, with wavenumber shifts indicating the influence of interlayer water removal. At pH 10.56, over 95% of nitrogen was released into the gas phase, while at pH 8.88, nitrogen proportions in the liquid and gas phases were comparable (average 48–49%). Experiments with iron at pH ∼8.80 showed that the nitrogen proportion in the gas phase (average 28%) was more than twofold lower than that in the liquid phase (average 68%). Equilibrium isotope fractionation factors indicated discernible preference for heavier nitrogen isotopes in the solid phase (αsolid-liquid = 1.009–1.021 and αsolid-gas = 1.011–1.027). The αliquid-gas range for sample 25–2 was 1.001–1.008, while that for the iron-enriched composite 25–5 was 0.997–1.010. Our experimental studies have confirmed that, in the absence of exchange interactions with external substances possessing different nitrogen isotope ratios, nitrogen isotope fractionation between ammonium and ammonia, controlled by variations in temperature and pH during mineralization, plays a crucial role in the variation of nitrogen isotope ratios. Additionally, we confirmed that metal-amines influence nitrogen isotope fractionation by modulating ammonia gas emission. These findings enhance our understanding of nitrogen cycling across the gas, liquid, and solid phases in submarine hydrothermal systems. No potential conflict of interest relevant to this article was reported.

British Editorial Society of Bone & Joint Surgery Acta Medica Okayama 2633-1462 6 8 2025 Long-term functional and quality of life outcomes after cementless minimally invasive extendable endoprosthesis replacement in skeletally immature patients with bone sarcomas at the lower limb a Japanese Musculoskeletal Oncology Group (JMOG) study 954 963 EN Yusuke Tsuda Department of Orthopaedic Surgery, The University of Tokyo Hospital Yoshihiro Nishida Department of Rehabilitation, Nagoya University Hospital Akio Sakamoto Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University Koichi Ogura Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tetsuya Sekita Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital Hirotaka Kawano Department of Orthopaedic Surgery, Teikyo University School of Medicine Hiroshi Kobayashi Department of Orthopaedic Surgery, The University of Tokyo Hospital Aims Extendable endoprostheses are utilized to reconstruct segmental defects following resection of bone sarcomas in skeletally immature children. However, there remains a paucity of data regarding long-term functional and quality of life outcomes. Methods We conducted a retrospective, multicentre study and reviewed 45 children who underwent cementless minimally invasive extendable endoprosthetic replacement. Anatomical sites included the distal femur (n = 29), proximal femur (n = 4), proximal tibia (n = 11), and total femur (n = 1). The mean follow-up period was 12 years. The mean age at extendable endoprosthetic replacement was ten years (5 to 15). Most patients (96%, 43/45) had reached skeletal maturity at the final follow-up. Results The ten-year endoprosthetic failure-free survival rate was 60%. Of the 45 patients, 25 (56%) had 42 complications which were frequently related to structural failure (45%, 19/42), with extension mechanism jamming being the most common (n = 7, 17%). Excluding lengthening procedures, 20 patients (44%) underwent additional surgery with a mean of two surgeries per patient. The mean limb-length discrepancy at the final follow-up was 2.3 cm. Limb salvage was achieved in 44 (98%) patients. The mean Musculoskeletal Tumor Society (MSTS) scores, Toronto Extremity Salvage Score (TESS), and EuroQol five-dimension five-level questionnaire (EQ-5D-5L) were 78%, 92%, and 92% at the last follow-up, respectively. Multiple additional surgeries (≥ 2 times) for complications were associated with worse MSTS scores compared with those without multiple additional surgeries (p = 0.009). Moreover, limb-length discrepancy > 3 cm showed significantly worse MSTS scores compared with those ≤ 3 cm (p = 0.019). Conclusion Extendable endoprostheses were associated with a high complication rate and need for additional surgeries over time, especially for structural-related complications. Despite this, successful limb salvage with reasonable function/quality of life and small limb-length discrepancy were achievable in the long term. Patients’ function in the long term depended on the experience of postoperative complications and limb-length discrepancy. No potential conflict of interest relevant to this article was reported.

American Society of Clinical Oncology (ASCO) Acta Medica Okayama 0732-183X 2025 Amivantamab Plus Lazertinib in Atypical EGFR-Mutated Advanced Non–Small Cell Lung Cancer: Results From CHRYSALIS-2 JCO-24-02835 EN Pascale Tomasini Aix Marseille University - CNRS, INSERM, CRCM; CEPCM - AP-HM Hôpital de La Timone Yongsheng Wang Division of Thoracic Tumor Multimodality Treatment, Cancer Center and Clinical Trial Center, West China Hospital, Sichuan University Yongsheng Li Chongqing University Cancer Hospital Enriqueta Felip Medical Oncology Service, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona Lin Wu Department of Thoracic Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University Jiuwei Cui The First Hospital of Jilin University Benjamin Besse Paris-Saclay University, Institut Gustave Roussy Alexander I. Spira Virginia Cancer Specialists Joel W. Neal Stanford Cancer Institute, Stanford University Koichi Goto National Cancer Center Hospital East Christina S. Baik University of Washington Fred Hutchinson Cancer Research Center Melina E. Marmarelis Perelman School of Medicine, University of Pennsylvania Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Yiping Zhang Zhejiang Cancer Hospital Jong-Seok Lee Seoul National University College of Medicine and Seoul National University Hospital Se-Hoon Lee Samsung Medical Center, Sungkyunkwan University School of Medicine James Chih-Hsin Yang National Taiwan University Cancer Center Sebastian Michels Department I for Internal Medicine, Faculty of Medicine and University Hospital Cologne, Lung Cancer Group Cologne, Center for Integrated Oncology Aachen Köln Bonn Düsseldorf, University of Cologne Zacharias Anastasiou Johnson & Johnson Joshua C. Curtin Johnson & Johnson Xuesong Lyu Johnson & Johnson Janine Mahoney Johnson & Johnson Levon Demirdjian Johnson & Johnson Craig S. Meyer Johnson & Johnson Youyi Zhang Johnson & Johnson Isabelle Leconte Johnson & Johnson Patricia Lorenzini Johnson & Johnson Roland E. Knoblauch Johnson & Johnson Leonardo Trani Johnson & Johnson Mahadi Baig Johnson & Johnson Joshua M. Bauml Johnson & Johnson Byoung Chul Cho Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine Purpose For patients with advanced non–small cell lung cancer (NSCLC) harboring atypical epidermal growth factor receptor (EGFR) mutations (eg, S768I, L861Q, G719X), efficacy of current treatment options is limited. Patients and Methods CHRYSALIS-2 Cohort C enrolled participants with NSCLC harboring atypical EGFR mutations (G719X, S768I, L861Q, etc) and ≤2 previous lines of therapy. Participants were treatment-naïve or previously received first- or second-generation EGFR tyrosine kinase inhibitors. Coexisting exon 20 insertions, exon 19 deletions, or exon 21 L858R mutations were exclusionary. Participants received 1,050 mg (1,400 mg if ≥80 kg) intravenous amivantamab once weekly for the first 4 weeks and then once every 2 weeks plus 240 mg oral lazertinib once daily. The primary end point was investigator-assessed objective response rate (ORR). Results As of January 12, 2024, 105 participants received amivantamab-lazertinib. Most common atypical mutations were G719X (56%), L861X (26%), and S768I (23%), including single and compound mutations. In the overall population (median follow-up: 16.1 months), the ORR was 52% (95% CI, 42 to 62). The median duration of response (mDoR) was 14.1 months (95% CI, 9.5 to 26.2). The median progression-free survival (mPFS) was 11.1 months (95% CI, 7.8 to 17.8); median overall survival (mOS) was not estimable (NE; 95% CI, 22.8 to NE). Adverse events were consistent with previous studies and primarily grade 1 and 2. Among treatment-naïve participants, the ORR was 57% (95% CI, 42 to 71). The mPFS was 19.5 months (95% CI, 11.2 to NE), the mDoR was 20.7 months (95% CI, 9.9 to NE), and mOS was NE (95% CI, 26.3 to NE). Solitary or compound EGFR mutations had no major impact on ORR. The ORR in participants with P-loop and αC-helix compressing, classical-like, and T790M-like mutations was 45% (n = 38), 64% (n = 14), and 67% (n = 3), respectively. Conclusion In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals. No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2158-4001 2025 A Linear Search Algorithm for Resource Allocation in Frequency Domain Non-Orthogonal Multiple Access EN Satoshi Denno Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yuto Ohba Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yafei Hou Faculty of Environmental, Life, Natural Science and Technology, Okayama University This paper proposes a linear search algorithm for resource allocation in frequency domain non-orthogonal multiple access based on the low-density signature (LDS). Although the proposed linear search enables the non-orthogonal multiple access to achieve superior transmission performance, the proposed linear search makes the resource allocation implemented with lower and fixed computational complexity. The performance of the non-orthogonal access based on the proposed linear search is evaluated by computer simulation. The proposed linear search algorithm makes the non-orthogonal multiple access achieve a gain of about 6 dB at the BER of 10–5 when the overloading ratio is set to 2. The complexity of the non-orthogonal access based on the proposed linear search algorithm is approximately half as much as that of the conventional low complexity resource allocation when the overloading ratio is 2, if the complexity is evaluated in terms of the number of additions. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2078-2489 16 10 2025 A Comparative Study of Authoring Performances Between In-Situ Mobile and Desktop Tools for Outdoor Location-Based Augmented Reality 908 EN Komang Candra Brata Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Htoo Htoo Sandi Kyaw Department of Information and Communication Systems, Okayama University Prismahardi Aji Riyantoko Department of Information and Communication Systems, Okayama University Noprianto Department of Information and Communication Systems, Okayama University Mustika Mentari Department of Information and Communication Systems, Okayama University In recent years, Location-Based Augmented Reality (LAR) systems have been increasingly implemented in various applications for tourism, navigation, education, and entertainment. Unfortunately, the LAR content creation using conventional desktop-based authoring tools has become a bottleneck, as it requires time-consuming and skilled work. Previously, we proposed an in-situ mobile authoring tool as an efficient solution to this problem by offering direct authoring interactions in real-world environments using a smartphone. Currently, the evaluation through the comparison between the proposal and conventional ones is not sufficient to show superiority, particularly in terms of interaction, authoring performance, and cognitive workload, where our tool uses 6DoF device movement for spatial input, while desktop ones rely on mouse-pointing. In this paper, we present a comparative study of authoring performances between the tools across three authoring phases: (1) Point of Interest (POI) location acquisition, (2) AR object creation, and (3) AR object registration. For the conventional tool, we adopt Unity and ARCore SDK. As a real-world application, we target the LAR content creation for pedestrian landmark annotation across campus environments at Okayama University, Japan, and Brawijaya University, Indonesia, and identify task-level bottlenecks in both tools. In our experiments, we asked 20 participants aged 22 to 35 with different LAR development experiences to complete equivalent authoring tasks in an outdoor campus environment, creating various LAR contents. We measured task completion time, phase-wise contribution, and cognitive workload using NASA-TLX. The results show that our tool made faster creations with 60% lower cognitive loads, where the desktop tool required higher mental efforts with manual data input and object verifications. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 2766-0400 5 1 2025 Linking structure and process in dendritic growth using persistent homology with energy analysis 2475735 EN Misato Tone Department of Material Science and Technology, Tokyo University of Science Shunsuke Sato Department of Material Science and Technology, Tokyo University of Science Sotaro Kunii Department of Material Science and Technology, Tokyo University of Science Ippei Obayashi Center for Artificial Intelligence and Mathematical Data Science, Okayama University Yasuaki Hiraoka Kyoto University Institute for Advanced Study, Kyoto University Yui Ogawa NTT Basic Research Laboratories, NTT Corporation Hirokazu Fukidome Research Institute of Electrical Communication, Tohoku University Alexandre Lira Foggiatto Department of Material Science and Technology, Tokyo University of Science Chiharu Mitsumata Department of Material Science and Technology, Tokyo University of Science Ryunosuke Nagaoka Department of Material Science and Technology, Tokyo University of Science Arpita Varadwaj Department of Material Science and Technology, Tokyo University of Science Iwao Matsuda Institute for Solid State Physics, The University of Tokyo Masato Kotsugi Department of Material Science and Technology, Tokyo University of Science We present a material analysis method that links structure and process in dendritic growth using explainable machine learning approaches. We employed persistent homology (PH) to quantitatively characterize the morphology of dendritic microstructures. By using interpretable machine learning with energy analysis, we established a robust relationship between structural features and Gibbs free energy. Through a detailed analysis of how Gibbs free energy evolves with morphological changes in dendrites, we uncovered specific conditions that influence the branching of dendritic structures. Moreover, energy gradient analysis based on morphological feature provides a deeper understanding of the branching mechanisms and offers a pathway to optimize thin-film growth processes. Integrating topology and free energy enables the optimization of a range of materials from fundamental research to practical applications. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 20 8 2025 Risk stratification for the prediction of skeletal-related events in patients with castration-resistant prostate cancer with bone metastases e0328792 EN Masanori Hamada Eiji Nakata Ryuichi Nakahara Shinsuke Sugihara Haruyoshi Katayama Takuto Itano Tomohiro Inoue Shota Takihira Yoshiteru Akezaki Toshifumi Ozaki Skeletal-related events (SREs) are common in patients with bone metastases from castration-resistant prostate cancer (CRPC). Despite advances in prostate cancer treatment, clinically validated predictive models for SREs in CRPC patients with bone metastases remain elusive. This gap in prognostic tools hinders optimal patient management and treatment planning for this high-risk population. This study aimed to develop a prediction model for SRE by investigating potential risk factors and classifying them into different groups. This model can be used to identify patients at high risk of SREs who need close follow-up. Between 2004 and 2013, 68 male patients with bone metastases from CRPC who were treated at our institute were evaluated for survival without SREs and survival without SREs of the spinal cord. The study analyzed clinical data at enrollment to identify risk factors for initial and spinal SREs. Multivariate analysis revealed that a high count of metastatic vertebrae, along with visceral or lymph node metastases, were significant risk factors. Patients were categorized into four subgroups based on the number of vertebral metastases and presence of visceral or lymph node metastases: 1) extensive vertebral and both types of metastases, 2) extensive vertebral without additional metastases, 3) some vertebral with other metastases, 4) some vertebral without additional metastases. The first SRE and spinal SRE occurred significantly sooner in the first subgroup compared to others. Incidence rates at 12 months for the first SRE were 56%, 40%, 27%, and 5%, and for the first spinal SRE were 47%, 40%, 27%, and 0% respectively. Patients with extensive vertebral and additional metastases require vigilant monitoring to mitigate SREs. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Association between gestational age and child health and neurodevelopment in twins from a nationwide longitudinal survey in Japan 40608 EN Kei Tamai Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihito Takeuchi Division of Neonatology, NHO Okayama Medical Center Makoto Nakamura Division of Neonatology, NHO Okayama Medical Center Misao Kageyama Division of Neonatology, NHO Okayama Medical Center Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Despite previous research, evidence on the relationship between gestational age and long-term health and neurodevelopmental outcomes among twins remains limited. Using data from the Longitudinal Survey of Babies in the 21st Century, we analyzed 549 twins born in Japan in 2010. The twins were grouped by gestational age: <32 weeks (very preterm), 32–36 weeks (moderately and late preterm), and 37–38 weeks (early term). The health status was evaluated by hospitalization between 0.5 and 5.5 years, and behavioral development was assessed using questionnaires at 2.5 and 5.5 years. Binomial log-linear regression with generalized estimating equations accounted for within-pair correlations and adjusted for child and parental variables. Moderately and late preterm children showed a higher risk of all-cause hospitalization during infancy than early-term children (adjusted risk ratio, 1.7; 95% CI, 1.0–2.6). Very preterm children showed a higher point estimate of the risk ratio, but a wide CI (risk ratio, 2.3; 95% CI, 0.8–6.8). Behavioral delays were more common in preterm groups at 2.5 years but not at 5.5 years. Preterm twins have a higher risk of hospitalization during infancy and developmental delay at 2.5 years than early-term twins. These risks show an increasing trend as gestational age decreases. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Long intervals between repetitive concussions reduce risk of cognitive impairment and limit microglial activation, astrogliosis, and tauopathy in adolescent rats 40522 EN Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital Kyohei Kin Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital Takayuki Nagase Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital Tatsuya Sasaki Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital Susumu Sasada Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital Chiaki Sugahara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital Takahiro Hirayama Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hospital Koji Kawai Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital Shun Tanimoto Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital Hayato Miyake Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital Tomoya Saijo Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hospital Kaori Masai Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Yasuhara Yasuhara Clinic Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital Although previous studies have demonstrated the effects of concussions do not accumulate as the time interval between injuries increases, little is known about the relationship between this interval and the effects of repetitive concussions. The objective of this study is to explore the relationship between the time interval and changes in behavior and histology following repetitive concussions. Male adolescent rats received concussions by weight drop and were randomly assigned to one of five experimental groups, receiving concussions three times either daily, every other day, once per week, once every 2 weeks, or receiving sham procedures. Only rats that received daily concussions exhibited cognitive impairment, while the other groups did not. No groups showed motor or anxiety-like impairments. Histological analysis revealed accumulation of microglia, as well as astrogliosis, in the prefrontal cortex, corpus callosum, dentate gyrus, and cornu Ammonis 1 region of the hippocampus in rats subjected to daily concussions. Accumulation of phosphorylated tau was also observed in the prefrontal cortex and cornu Ammonis 1. Longer intervals between concussions may reduce the risk of cognitive impairment and limit microglial activation, astrogliosis, and phosphorylated tau accumulation. These findings may help guide decisions on the appropriate timing for return to play in humans. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1349-0079 68 1 2026 Dynamin 2 is involved in osteoblast migration by regulating the organization of F-actin 100720 EN Takumi Moriya Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University A. Surong Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nanami Tatsumi Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Yamada Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumiko Takemoto Department of Orthodontics, Okayama University Hospital Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirohiko Okamura Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mika Ikegame Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: Dynamin, a GTPase that regulates membrane dynamics, has recently been implicated in actin cytoskeletal remodeling. This study aimed to elucidate the role of dynamin in osteoblast migration by examining the effects of dynamin inhibition on the localization and organization of F-actin and dynamin 2 in MC3T3-E1 cells. Methods: MC3T3-E1 cells were treated with dynamin inhibitors (Dyngo 4a and Dynole 34-2), and cell migration was assessed using a wound-healing assay. Fluorescent staining was performed to analyze the intracellular localization of F-actin and dynamin 2. Results: Dynamin inhibition significantly reduced the migration of MC3T3-E1 cells. Fluorescence analysis revealed a marked decrease in the accumulation and colocalization of F-actin and dynamin 2 at the protrusion edge. Additionally, dynamin inhibition suppressed the formation of lamellipodia and stress fibers while promoting the appearance of abnormal F-actin clusters in the cytoplasm. Conclusions: These findings suggest that dynamin plays an essential role in osteoblast migration by regulating actin cytoskeletal remodeling, particularly through the formation of lamellipodia and stress fibers. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0944-1174 60 5 2025 Diagnostic accuracy and cut-off values of serum leucine-rich alpha-2 glycoprotein for Crohn’s disease activity in the small bowel 573 582 EN Muneyori Okita Department of Biostatistics, Nagoya University Graduate School of Medicine Kento Takenaka Department of Gastroenterology and Hepatology, Institute of Science Tokyo Fumihito Hirai Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine Shinya Ashizuka Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine Hideki Iijima Osaka International Medical & Science Center, Osaka Keisatsu Hospital Shigeki Bamba Department of Fundamental Nursing, Shiga University of Medical Science Toshimitsu Fujii Department of Gastroenterology and Hepatology, Institute of Science Tokyo Kenji Watanabe Department of Internal Medicine for Inflammatory Bowel Disease, Toyama University Yosuke Shimodaira Department of Gastroenterology and Neurology, Akita University Graduate School of Medicine Hisashi Shiga Division of Gastroenterology, Tohoku University Graduate School of Medicine Sakiko Hiraoka Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshihiro Inokuchi Research Center for Intestinal Health Science, Okayama University Takeshi Yamamura Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine Ryo Emoto Department of Biostatistics, Nagoya University Graduate School of Medicine Shigeyuki Matsui Department of Biostatistics, Nagoya University Graduate School of Medicine Background Small bowel (SB) lesions in Crohn’s disease (CD) are often asymptomatic despite being highly active. Fecal calprotectin (FC) is the most widely used biomarker of CD activity, but its drawbacks include a large intra-individual sample variability and the burden of collecting stool samples. Meanwhile, serum leucine-rich alpha-2 glycoprotein (LRG) has recently attracted attention as a biomarker that can address the limitations of FC. This study determined the diagnostic accuracy of LRG and its cut-off values for diagnosing CD activity in SB. Methods This was a retrospective, multi-center study of CD patients undergoing retrograde balloon-assisted endoscopy. For ileal- and ileocolonic-type patients with a colon SES-CD score of 0, we estimated the receiver operating characteristic curve of LRG and determined the cut-off value to achieve a target sensitivity level of 80%. Results Among 285 patients with SB lesions, LRG had an area under the curve (AUC) of 0.72 (95% CI 0.67–0.78) with a sensitivity of 80.2% and specificity of 47.2% for a cut-off value of 10.5 when diagnosing endoscopic remission (modified SES-CD ≤ 3), while it had an AUC of 0.72 (95% CI 0.65–0.78) with a sensitivity of 81.2% and specificity of 46.2% for a cut-off value of 10.1 when diagnosing complete ulcer healing (modified SES-CD ≤ 1). Conclusion LRG was effective for diagnosing CD activity in SB, specifically with cut-off values of 10.5 and 10.1 for endoscopic remission and complete ulcer healing, respectively. A future prospective validation study will assess its clinical utility. No potential conflict of interest relevant to this article was reported.

Japanese Society of Radiological Technology Acta Medica Okayama 0369-4305 82 2 2026 放射線治療装置の回転座標系誤差が軸外targetの照射精度に及ぼす影響とTG142のトレランスの評価 26-1566 EN Takahiro Nakayama Department of Radiology, Public Mutual Aid Association Chugoku Central Hospital Yoshinori Tanabe Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Yasushi Fujii Department of Radiology, Public Mutual Aid Association Chugoku Central Hospital 【目的】放射線治療装置の回転座標系の誤差が軸外targetの照射精度に及ぼす影響を定量的に評価し，TG142における回転座標系誤差（±1.0°）のトレランスの妥当性を検討する．【方法】Elekta社製放射線治療装置（Elekta, Stockholm, Sweden）とMultiMet-WL QAファントム（Sun Nuclear, Melbourne, FL, USA）を用いて，6個のtargetに対してoff isocenterのWinston–Lutz test（WL test）を実施した．Baselineの測定に加え，意図的にcollimator，gantry，couchに+0.5°, +1.0°回転誤差を加えた6条件で測定を行い，照射野中心とtarget中心のベクトル距離（S値）および各方向（gantry-target: GT, left-right: LR, anterior-posterior: AP）の位置ずれを解析した．【結果】Isocenterからの距離が大きいtargetほど位置ずれが顕著であった．特にcollimator回転誤差の影響が最も大きく，isocenterから7 cm離れたtargetでは0.5°の回転誤差でもS値が最大1.24 mmに達した．次に影響が大きかったのはcouch回転であり，gantry回転はtargetの配置が回転軸に近いものが多く相対的に影響が少なかった．回転座標系の誤差は幾何学的誤差の影響が強く，位置ずれに方向依存性があった．【結語】Collimatorやcouchの影響が大きく，0.5°の誤差でも1 mm以上の位置ずれが生じることがあった．Gantryの影響はtargetの配置依存があり，相対的に小さかった．軸外targetの照射において，TG142の±1.0°のトレランスは放射線治療装置の種類にかかわらず最低限遵守するべき基準であり，targetの配置次第では臨床的に十分なマージンを保証できない可能性が示された．Target配置に応じたより厳格な基準と定期的quality assurance（QA）の重要性が示唆された． No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 1 2025 Mid-term Clinical and Radiographic Outcomes of the Actis Total Hip System: A Retrospective Study e77632 EN Yasutaka Masada Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomonori Tetsunaga Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Yamada Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Koura Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Inoue Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichiro Okuda Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoko Tetsunaga Department of Orthopaedic Surgery, Okayama University Hospital Yusuke Yokoyama Department of Orthopaedic Surgery, Okayama University Hospital Yuki Okazaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Introduction Implant technology for total hip arthroplasty (THA) was developed to improve hip function and patient satisfaction. Actis (DePuy Synthes, Warsaw, IN, USA) is a short fit-and-fill titanium stem, with a medial-collared and triple-taper (MCTT) geometry, that is fully coated with hydroxyapatite (HA). We evaluated the radiographic and clinical outcomes of the Actis Total Hip System during a mean follow-up of five years. Patients and methods We retrospectively analyzed data from 80 patients (14 male and 66 female, mean age: 65 ± 8.4 years) who underwent primary THA using Actis stems (anterolateral approach, 60 hips; posterior approach, 20 hips). Radiographs were obtained postoperatively and at the time of the final examination. Radiographic assessments included the alignment of the femoral stem, spot welds, stress shielding, cortical hypertrophy, subsidence (>2 mm), radiolucent line, pedestal formation, Dorr type, canal fill ratio (CFR), and stem fixation. Clinical evaluation included the Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ) and Harris Hip Score (HHS). Results The mean follow-up period was 64.0 ± 6.0 months. No significant differences were observed in the alignment of the femoral components between approaches. Of the 80 hips, 53 (66.3%) showed radiographic signs of stem osseointegration, predominantly in the mid-distal region of the stem at the final follow-up. Multiple logistic regression analysis revealed that younger age and a higher CFR (20 mm proximal to the lesser trochanter) were associated with the presence of spot welds. Mild stress shielding occurred in 25 hips (31.3%), and no patient experienced severe stress shielding. All stems were fixed by bone on growth. The JHEQ and HHS significantly improved at the final assessment. Conclusion At the five-year follow-up, patients who received the Actis Total Hip System during THA had good radiographic and clinical outcomes. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Coherence Generation in Atomic Cesium for Cosmic Dark Matter Detection EN JING WANG Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Changes of leucine-rich alpha 2 glycoprotein could be a marker of changes of endoscopic and histologic activity of ulcerative colitis EN Yuki AOYAMA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1869-6953 16 12 2025 A Multicenter, Prospective, Observational, and Single-Arm Interventional Study of Mirogabalin in Diabetic Peripheral Neuropathic Pain: Rationale and Design of Dia-NeP 2351 2363 EN Hideki Kamiya Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine Ryo Suzuki Department of Diabetes, Metabolism and Endocrinology, Tokyo Medical University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Takahisa Deguchi Department of Diabetes, Metabolism and Endocrinology, Kagoshima University Graduate School of Medical and Dental Sciences Tatsuhito Himeno Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine Shuhei Yamamoto Data Intelligence Department, Daiichi Sankyo Co., Ltd. Taiki Toyama Primary Medical Science Department, Daiichi Sankyo Co., Ltd. Jiro Nakamura Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine Background/Objectives: The exact prevalence of and recent changes in diabetic polyneuropathy (DPN) and diabetic peripheral neuropathic pain (DPNP) in Japan are unclear. The oral gabapentinoid, mirogabalin besylate (mirogabalin), is effective with a good safety profile for DPNP with moderate-to-severe pain (numerical rating scale [NRS] scores ≥ 4). However, clinical evidence for mild pain (NRS scores ≤ 3) is unclear. The Dia-NeP study aims to examine: (1) the prevalences of DPN and DPNP and background factors in patients with type 2 diabetes mellitus (T2DM); and (2) the efficacy and safety of mirogabalin in patients with DPNP, including those with mild pain. Methods: The Dia-NeP study is a multicenter, prospective study consisting of two parts, a baseline survey and an interventional study, to be conducted from March 2025 to August 2026 in patients with T2DM in Japan. The baseline survey is the observational study investigating the epidemiology of DPN and DPNP, and the interventional study is an exploratory, single-arm, open-label study of 12-week mirogabalin treatment. Of patients with T2DM enrolled in the baseline survey, those diagnosed with DPNP who have an NRS score for pain ≥ 1 will be included in the interventional study. The target sample size is 1000 to 3000 patients for the baseline survey and 100 for the interventional study. Planned Outcomes: The primary endpoint is the change from baseline in the NRS score at week 12 in the interventional study. The safety endpoint is adverse events. This study will not only show the latest prevalence of DPN and DPNP in Japan, but is also the first study to investigate the efficacy and safety of mirogabalin in patients with DPNP having mild pain, as well as moderate-to-severe pain, and is expected to provide useful evidence for future DPN and DPNP treatment. Trial Registration: Japan Registry of Clinical Trials (jRCTs031240623, registered 20/January/2025, https://jrct.mhlw.go.jp/en-latest-detail/jRCTs031240623). No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Elucidation of puberulic acid–induced nephrotoxicity using stem cell-based kidney organoids 42195 EN Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Soichiro Haraguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Recent cases of acute kidney injury (AKI) in Japan have been linked to Beni-koji CholesteHelp supplements, with puberulic acid identified as a potential nephrotoxic contaminant. To address the need for a reliable in vitro nephrotoxicity testing platform, we developed a screening model using kidney organoids derived from adult rat kidney stem (KS) cells. The organoids were exposed to known nephrotoxicants, including cisplatin and gentamicin, to validate the system. Puberulic acid toxicity was evaluated in both KS cell-derived organoids and wild-type mice. The organoids recapitulated tubular injury induced by known nephrotoxins and showed significant Kim-1 mRNA upregulation. Puberulic acid-treated organoids and mice exhibited morphological features of acute tubular necrosis (ATN), mitochondrial damage, and reduced cytochrome c oxidase subunit IV (COX-IV) expression. Markers of oxidative stress and apoptosis, such as 8-hydroxy-2’-deoxyguanosine (8-OHdG) and cleaved caspase-3, were also elevated. These findings suggest that puberulic acid induces mitochondrial dysfunction and oxidative stress, leading to tubular cell death. Puberulic acid-induced nephrotoxicity was demonstrated using our kidney organoid model. KS cell-derived kidney organoids may provide a simple, reproducible, and rapid platform for nephrotoxicity assessment, which may complement conventional animal experiments. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1467-7881 26 11 2025 Missing the Target: A Scoping Review of the Use of Percent Weight Loss for Obesity Management e13960 EN Diana Sherifali McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University Megan Racey McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University Donna Fitzpatrick‐Lewis McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University Michelle Greenway McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University Sanjeev Sockalingam Obesity Canada Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Soo Huat Teoh Department of Clinical Medicine, Advanced Medical and Dental Institute, Universiti Sains Malaysia Ian Patton Obesity Canada David Macklin Temerty Faculty of Medicine, University of Toronto Elizabeth F. C. van Rossum Department of Internal Medicine, Division of Endocrinology, and Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam Luca Busetto Department of Medicine, University of Padova Deborah Bade Horn Center of Obesity Medicine and Metabolic Performance, Department of Surgery, University of Texas McGovern Medical School J. D. Patricia Nece Obesity Action Coalition Morgan Emile Gabriel Salmon Leguede ABHispalis Spain, Alianza Hispana de Personas con Obesidad Latin America Nicole Pearce Obesity Canada Carel Le Roux School of Medicine, University College Dublin Jamy Ard School of Medicine, Wake Forest University Angela S. Alberga Department of Health, Kinesiology, and Applied Physiology, Concordia University Lee Kaplan Obesity, Metabolism and Nutrition Institute Massachusetts General Hospital and Harvard Medical School Arya M. Sharma Department of Medicine, University of Alberta Sean Wharton Temerty Faculty of Medicine, University of Toronto Introduction: To co-create comprehensive targets for obesity management, we need to understand the genesis and current use of percent weight loss targets in research. The goals of our scoping review are to (1) synthesize the literature on percent weight loss targets for adults with obesity and (2) discuss the percent weight loss targets in context with their health benefits. Methods: We searched Cochrane, MEDLINE, and EMBASE for English language, pharmaceutical, and/or behavioral intervention studies in adults with obesity where the explicit aim of the study was weight reduction defined as a percent of body weight. Reviewers screened citations and extracted data including study characteristics. Results: From 16,164 abstracts, we included 30 citations which were mostly randomized controlled trials (RCTs) (n = 17) or quasi-experimental studies (n = 12) published between 1992 and 2024. Most of the studies had target weight loss goals between 3% and 10% of body weight (n = 28), while n = 2 had body weight loss goals of 15% or 30%. The proportion of participants who met the percent weight loss target ranged from 5.9% (nutrition only study) to 85% (pharmaceutical study). The studies reported different reasons for targeting a percentage of weight loss such as disease-specific outcomes, reduced risk of disease, or patient-reported outcomes. Conclusion: Percent weight loss targets were based on similar research and were often not feasible nor sustainable for most participants. The design of these interventions and evaluation of obesity management would benefit from more patient-focused parameters which could help to co-design comprehensive targets for research and practice. No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 190 2025 中山間地域における人口移動の動向 ― 岡山県苫田郡鏡野町の事例 ― 95 108 EN Masao NOBE Faculty of Education, Okayama University 10.18926/bgeou/69614 　本稿の目的は，2006 年以降の岡山県鏡野町の人口動態を明らかにすることである。分析によって，次の4 点を明らかにした。(1) 鏡野町の人口は2006 年以降一貫して減少しているが，近年はその減少幅が拡大している。2006 年以降は自然減が続き，2010 年代後半からは社会減も拡大した。両効果が働いたために，2010 年代後半から人口減少が加速した。(2) 2006 年以降，鏡野町の人口移動はおおむね安定した傾向が見られた。そして，その人口移動は，津山圏との間における集中的かつ均衡した人口移動，近畿地方・岡山圏・関東地方への転出超過，真庭圏・阿新圏からの小規模な転入超過と特徴づけることができる。(3) 2010 年代後半から，鏡野町は岡山圏への転出超過が顕著となり，近畿地方および関東地方への転出もそれに続いた。その結果，鏡野町は社会減が大きくなった。農林業・製造業・商業の停滞や都市部との賃金格差が若年層の流出を促進し，社会減の拡大に繋がった。(4) 人口移動の中心は一貫して20 歳代と30 歳代であった。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 190 2025 教職員研修の評価と改善に関する予備的考察 ― NITS 岡山大学センターの学校事務職員研修の事例から ― 1 11 EN Kazuaki KAJII Faculty of Education，Okayama University Makiko KANAGAWA Faculty of Education，Okayama University Atsushi TAKASE Faculty of Education，Okayama University 10.18926/bgeou/69607 　教職員研修を研修転移という問題関心から検討し，学習内容の現場実践を促す研修に向けた評価と改善について予備的考察を行う。NITS 岡山大学センターで実施する学校事務職員研修を事例に検討を試みるものである。事例では，受講者は研修に対する反応として，高い満足度や関連度，有用度，自己効力感を示していた。その反応と学習の転移として，現場での行動の変化が重要となる。管理職へのアンケートから，受講者における現場での研修内容の具体的活用は，部分的にとどまるが，実践例が認められた。そして，研修が受講者の行動変化や現場での成果創出を促すものとなるため，教職員と管理職による協働探究的関係の形成が重要となることを展望的に論じる。 No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Hypoglycemia and hyperinsulinemia induced by phenolic uremic toxins in CKD and DKD patients 5762 EN Yoshiyasu Tongu Tohoku University School of Medicine Tomoko Kasahara Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Yasutoshi Akiyama Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences Takehiro Suzuki Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Hsin-Jung Ho Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Yotaro Matsumoto Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences Ryota Kujirai Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences Koichi Kikuchi Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Koji Nata Department of Medical Biochemistry, School of Pharmacy, Iwate Medical University Makoto Kanzaki Department of Biomedical Engineering, Tohoku University Kenshin Suzuki Tohoku University School of Medicine Shun Watanabe Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Chiharu Kawabe Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Yui Miyata Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Shun Itai Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Takafumi Toyohara Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Chitose Suzuki Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Tetsuhiro Tanaka Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Tomioka Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences Takaaki Abe Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Patients with end-stage renal disease have lower fasting plasma glucose and HbA1c levels, with significantly higher insulin levels. For a long time, it has been believed that this higher insulin level in renal failure is due to decreased insulin clearance caused by reduced renal function. However, here we reported that accumulation of the gut microbiota-derived uremic toxin, phenyl sulfate (PS) in the renal failure, increased insulin secretion from the pancreas by enhanced glucose-stimulated insulin secretion. Other endogenous sulfides compounds which accumulated as in the renal failure also increased glucose-stimulated insulin secretion from β-cell. With RNA-seq analyses and gene knock down, we demonstrated that insulin secretion evoked by PS was mediated by Ddah2. In addition, we also found that PS increased insulin resistance through lncRNA expression and Erk phosphorylation in the adipocytes. To confirm the relationship between PS and glucose metabolism in human, we recruited 2 clinical cohort studies (DKD and CKD) including 462 patients, and found that there was a weak negative correlation between PS and HbA1c. Because these trials did not measure fasting insulin level, we alternatively used the urinary C-peptide/creatinine ratio (UCPCR) as an indicator of insulin resistance. We found that PS may induce insulin resistance in patients with eGFR < 60 mL/min/1.73 m2. These data suggest that the accumulation of uremic toxins modulates glucose metabolism and induced insulin resistance in CKD and DKD patients. Considering HbA1c as a reflection of chronic hyperglycemia and UCPCR as a reflection of chronic hyperinsulinemia, our findings indicate that PS is negatively associated with hyperglycemia independent of CKD, and positively associated with hyperinsulinemia in DKD patients. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 14 1 2024 Association between proteinuria and mineral metabolism disorders in chronic kidney disease: the Japan chronic kidney disease database extension (J-CKD-DB-Ex) 27481 EN Sho Shimamoto Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Takako Nakahara Department of Medical Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare Shunsuke Yamada Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Hajime Nagasu Department of Nephrology and Hypertension, Kawasaki Medical School Seiji Kishi Department of Nephrology and Hypertension, Kawasaki Medical School Naoki Nakashima Department of Medical Informatics, Graduate School of Medical Science, Kyushu University Kazuhiko Tsuruya Department of Nephrology, Nara Medical University Hirokazu Okada Department of Nephrology, Faculty of Medicine, Saitama Medical University Kouichi Tamura Department of Medical Science and Cardiorenal Medicine, Graduate School of Medicine, Yokohama City University Ichiei Narita Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences Shoichi Maruyama Department of Nephrology, Nagoya University Graduate School of Medicine Yuichiro Yano Department of General Medicine, Juntendo University Faculty of Medicine Takashi Yokoo Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine Takashi Wada Department of Nephrology and Rheumatology, Kanazawa University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Eiichiro Kanda Department of Health Data Science, Kawasaki Medical School Hiromi Kataoka Department of Medical Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare Masaomi Nangaku Division of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine Naoki Kashihara Department of Nephrology and Hypertension, Kawasaki Medical School Toshiaki Nakano Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Chronic kidney disease-mineral and bone disorder (CKD-MBD) are recognized as a systemic disease affecting the prognosis of patients with CKD. Proper management of CKD-MBD is important to improve the prognosis of patients with CKD. Although proteinuria is recognized as a poor prognostic factor in these patients, few reports have examined its association with CKD-MBD. We examined the association between proteinuria and CKD-MBD using data from the Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex). Among the patients registered in the J-CKD-DB-Ex, 30,977 with CKD stages G2–G5 who had serum creatinine, albumin, calcium, and phosphate concentrations measured at least once and urinalysis performed were included. The patients were divided into four groups (negative, 1+, 2+, and 3+) according to the degree of proteinuria. The association between proteinuria and CKD-MBD was examined by a logistic regression analysis. In a model adjusted for age, sex, diabetes, and the estimated glomerular filtration rate (eGFR), the odds ratio of the 3 + group compared with the negative group significantly increased to 2.67 (95% confidence interval, 2.29–3.13) for hyperphosphatemia, 2.68 (1.94–3.71) for hypocalcemia, and 1.56 (1.24–1.98) for hypomagnesemia. Proteinuria is associated with hyperphosphatemia, hypocalcemia, and hypomagnesemia in patients with CKD independently of eGFR. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 10 2025 Bladder Trigone as a Sensory Hub: A Narrative Review e94951 EN Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Maruyama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Mitsui Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takanori Sekito Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomofumi Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The bladder trigone is an anatomically and functionally distinct region within the lower urinary tract (LUT), characterized by a dense network of afferent sensory fibers, specialized urothelial interactions, and prominent mechanotransduction mechanisms. Its intricate neuroarchitecture enables precise detection of bladder filling and coordination of micturition, whereas dysregulation of these pathways contributes to lower urinary tract symptoms (LUTS), including urgency, frequency, and bladder pain. Despite its recognized clinical relevance, the structural and functional basis of trigonal sensory signaling - and its role - remain incompletely understood. This review synthesizes current evidence on trigonal afferent organization, integrating data from anatomical mapping, receptor profiling, electrophysiological characterization, and translational research. Seminal anatomical observations are combined with recent advances in mechanotransduction and purinergic, peptidergic, and transient receptor potential (TRP) signaling to provide a comprehensive perspective. The trigone exhibits three principal afferent classes: (1) intraepithelial fibers penetrating umbrella cells, marked by P2X purinoceptor 3 (P2X3), transient receptor potential vanilloid 1 (TRPV1), calcitonin gene-related peptide (CGRP), and substance P (SP); (2) subepithelial plexuses surrounding microvasculature, enriched in vasoactive neuropeptides and exhibiting plastic hypertrophy in overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS); and (3) encapsulated corpuscular endings at the lamina propria-detrusor junction, expressing PIEZO1/2 and acid-sensing ion channels (ASICs) for rapid adaptation. In trigeminal dorsal root ganglion (DRG) neurons, high expression of PIEZO2, P2RX3, and voltage-gated sodium channel, type 1.8 (Nav1.8) was observed, revealing their role as the foundation for multisensory information processing. Functional assays highlight distinct mechanotransductive and chemosensory pathways, with aging, inflammation, and neurotrophic factors driving afferent plasticity underlying abnormal bladder sensation, such as urgency, frequency, and pain. Early clinical trials of P2X3 antagonists and intravesical TRPV1 inhibitors demonstrate promising symptomatic benefits. Collectively, evidence positions the bladder trigone as a critical sensory hub where neuronal, urothelial, and immune signals converge to regulate bladder sensation. Understanding its molecular and structural specialization may inform the development of region-specific neuromodulatory therapies targeting sensory urgency and afferent-driven bladder dysfunction. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0006-291X 786 2025 Hydrogen-rich gas enhances mitochondrial membrane potential and respiratory function recovery in Caco-2 cells post-ischemia-reperfusion injury 152753 EN Mizuki Seya Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Aokage Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology Ying Meng Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Hirayama Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takafumi Obara Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuyoshi Nojima Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosaki Yoshinori Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Yumoto Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Watanabe Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University Taihei Yamada Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University Hiromichi Naito Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Ischemia-reperfusion (I/R) injury induces oxidative stress, leading to damage in highly susceptible intestinal tissues. Molecular hydrogen (H2) has shown therapeutic potential in I/R injuries, with our prior research showing its efficacy in improving outcomes in rat intestinal transplantation models. However, its impact on mitochondrial function remain insufficiently understood. This study aims to elucidate how H2 modulates mitochondrial function impaired by I/R injury. Methods: To assess the effects of H2 on I/R injury, cells were divided into three groups: a control group, a hypoxic group (99 % N2, 1 % O2, without H2 for 3, 6, or 24 h), and a hypoxic-H2 group (99 % H2, 1 % O2, for the same durations). After treatment, cells were reoxygenated under normoxic conditions (21 % O2) for 1, 2, 4, or 6 h. Mitochondrial membrane potential, oxygen consumption, and ATP production were measured. Reactive oxygen species production and apoptotic and metabolic regulators were also assessed. Results: H2 markedly promoting mitochondrial recovery following I/R injury, by enhancing ATP production, restoring mitochondrial membrane potential, and improving oxygen consumption. It also reduced ROS levels and suppressed pro-apoptotic signaling. Notably, H2 suppressed the expression of HIF1α and PDK1, suggesting that H2 may act upstream of hypoxia-driven signaling pathways. These changes promoted oxidative phosphorylation and overall cellular function during reperfusion. Conclusions: Our findings reveal that H2 therapy supports mitochondrial function, suppresses ROS, and modulates hypoxia-driven pathways in I/R injury. These insights advance the understanding of H2's potential in addressing I/R injury and provide a foundation for its application in other hypoxia-related conditions. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1085-3278 2025 Enhancing Soil Aggregation and Water Retention by Applying Kaolinite Clay to Post‐Tin‐Mined Land on Belitung Island, Indonesia EN Hirmas F. Putra Graduate School of Environmental and Life Science, Okayama University Yasushi Mori Graduate School of Environmental and Life Science, Okayama University Post-mining sandy soils have low water retention, which causes soil particle separation and persistent soil erosion. Although organic matter is commonly used for soil restoration, it is lightweight, washes away during heavy rain, and decomposes under strong sunlight. The high potential for extreme rainfall events in tropical regions poses significant challenges to restoration projects. Therefore, we investigated the impact of kaolinite clay particles on enhancing soil stability in post-mining sandy soils. Soil samples were collected from three sites representing different succession stages of post-mined land (0, 1, and 6 years since mining cessation) and an adjacent natural forest as the reference site on Belitung Island, Indonesia. Soil samples were treated with 1% or 5% kaolinite or left untreated (control) and incubated at 34°C to mimic the local conditions of the study area. The samples were then analyzed to determine the soil aggregate distribution, water holding capacity, and soil erodibility, and SEM imaging was performed to examine the soil particle morphology. The results revealed an increasing trend in the silt-sized aggregate content and a 2%–5% increase in water retention in the 6-year soils relative to the untreated soils. The highest water retention was observed in the 6-year post-mining soil sample. Kaolinite amendment significantly reduced soil erodibility by 40%–50% compared to the untreated soils, even in the early restoration period (0–1 year post-mining). Kaolinite improved soil aggregation and water retention in post-mining sandy soils while reducing soil erodibility—highlighting its potential for accelerating land restoration in mining-affected areas. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-1380 18 1 2025 Tattoo-associated toxic shock syndrome: a case report 185 EN Takuya Kubo 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 Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Koji Iio Microbiology Division, Clinical Laboratory, 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 Background: Toxic shock syndrome (TSS) is a rare but life-threatening complication occasionally reported after tattooing. Case presentation: : A 29-year-old Japanese man was admitted to Okayama University Hospital, Okayama, Japan, in early spring 2025, one week after receiving a tattoo on his right shoulder and upper arm in Osaka. He presented with fever, gastrointestinal symptoms, hypotension, and multi-organ failure. Despite a failure to isolate a causative pathogen, he met clinical criteria for TSS. Supportive care and broad-spectrum antibiotics led to full recovery. Conclusions: TSS can occur after tattooing, even in individuals without apparent immunodeficiency. Pathogenic organisms may be unidentifiable; however, clinical diagnosis should not be delayed, and early therapeutic interventions are essential to improve outcomes. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0007-1048 2025 Efficacy of ciclosporin monotherapy in non-severe aplastic anaemia not requiring transfusions: Results from a multicentre phase II study EN Ken Ishiyama Department of Hematology, Kanazawa University Hospital Masahide Yamazaki Department of Internal Medicine, Keiju Medical Center Hiroyuki Maruyama Department of Hematology, Kanazawa University Hospital Naoko Hosono Department of Hematology and Oncology, University of Fukui Hospital Hiroki Yamaguchi Department of Hematology, Nippon Medical School Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Kazuki Tanimoto Department of Hematology and Oncology, Japanese Red Cross Fukuoka Hospital Hiroyuki Sugiura Department of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School Teachers Kensuke Usuki Department of Hematology, NTT Medical Center Tokyo Kenichi Yoshimura Department of Biostatistics and Health Data Science, Graduate School of Medical Science, Nagoya City University Seishi Ogawa Department of Pathology and Tumor Biology, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University Yuzuru Kanakura Sumitomo Hospital Itaru Matsumura Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Koichi Akashi Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences Shinji Nakao Department of Hematology, Kanazawa University Hospital The efficacy of ciclosporin (CsA) to treat transfusion-independent non-severe aplastic anaemia (TI-NSAA) has not yet been systematically evaluated. We conducted a prospective trial in patients with TI-NSAA treated with CsA monotherapy. CsA (3.5 mg/kg/day) was administered to patients with TI-NSAA aged ≥16. The CsA dose was adjusted to maintain a blood CsA level of ≥600 ng/mL at 2 h post-administration. Blood cell counts were assessed after 8, 16 and 52 weeks of therapy. Thirty-two evaluable patients from 21 institutions were enrolled. The median age was 63.5 (range: 16–83) years. At 8 weeks, haematological improvement, with increases in haemoglobin (Hb) ≥1.5 g/dL (haematological improvement in erythrocytes [HI-E]) and platelet count ≥30 × 109/L (haematological improvement in platelets [HI-P]), was observed in 0/25 (0%) and 6/32 (19%) evaluable cases respectively. HI-E and HI-P occurred in 1/25 (4%) and 10/32 (31%) patients at 16 weeks, respectively, and at 52 weeks in 5/25 (20%) and 16/32 (50%) patients respectively. Nine grade 3 adverse events (AEs) occurred in six patients, but there were no grade ≥4 AEs. Ten of the 32 patients experienced grade 2 renal toxicity. Low-dose CsA is effective in TI-NSAA patients and demonstrates minimal renal toxicity. However, at least 16 weeks are necessary to adequately evaluate its efficacy. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 15 6 2025 Protocol for a multicentre, open-label, dose-escalation phase I/II study evaluating the tolerability, safety, efficacy and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with aggressive natural killer cell leukaemia e098532 EN Noriko Fukuhara Hematology, Tohoku University Graduate School of Medicine Makoto Onizuka Department of Hematology and Oncology, Tokai University School of Medicine Graduate School of Medicine Junya Kanda Department of Hematology, Graduate School of Medicine, Kyoto University Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Koji Kato Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University Kiyoshi Ando Department of Hematology, Hiroshima University Introduction Aggressive natural killer cell leukaemia (ANKL) is a rare form of NK cell lymphoma with a very low incidence and poor prognosis. While multi-agent chemotherapy including L-asparaginase has been used to treat ANKL patients, they often cannot receive adequate chemotherapy at diagnosis due to liver dysfunction. PPMX-T003, a fully human monoclonal antibody targeting the transferrin receptor 1, shows promise in treating ANKL by helping patients recover from fulminant clinical conditions, potentially enabling a transition to chemotherapy. This study aimed to evaluate the tolerability, safety, efficacy, and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with ANKL. Methods and analysis This multicentre, open-label, dose-escalation phase I/II study will be conducted at nine hospitals in Japan. Patients diagnosed with ANKL (whether as a primary or recurrent disease) and exhibiting abnormal liver function or hepatomegaly due to the primary disease will be included. The primary endpoint is the tolerability and safety of repeated continuous intravenous administration of PPMX-T003 in the first course, based on adverse events and dose-limiting toxicities. PPMX-T003 will be administered as a continuous intravenous infusion every 24 hours for five consecutive days, followed by a 2-day break. Pretreatment will be provided to minimise the risk of infusion-related reactions. Initial doses of PPMX-T003 will be 0.5, 1.0 or 2.0 mg/kg, with subsequent dose increases determined by the Data and Safety Monitoring Committee. The sample size is set at seven participants, with enrolment increased to up to 12 participants if dose-limiting toxicities occur, based on feasibility due to the rarity of ANKL. Descriptive statistics will summarise data according to initial dose, and pharmacokinetic analysis will be conducted based on administered dose. Ethics and dissemination This study was approved by the institutional review boards at participating hospitals. The results will be disseminated in peer-reviewed journals. Trial registration number jRCT2061230008 (jRCT); NCT05863234 (ClinicalTrials.gov). No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0040-8166 98 2026 The vicious cycle between nutrient deficiencies and antibiotic-induced nutrient depletion at the host cell-pathogen interface: Coenzyme Q10 and omega-6 as key molecular players 103224 EN Darab Ghadimi Department of Microbiology and Biotechnology, Max Rubner-Institut Sophia Blömer Faculty of Medicine, Christian-Albrechts-University of Kiel Aysel Şahi̇n Kaya Department of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim University Sandra Krüger Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein Christoph Röcken Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein Heiner Schäfer Laboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus Kiel Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shigenobu Matsuzaki Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University Wilhelm Bockelmann Department of Microbiology and Biotechnology, Max Rubner-Institut The increasing prevalence of antibiotic resistance and pathological inflammation underscores the importance of understanding the underlying biochemical and immune processes that govern the host-pathogen interface. Nutrient deficiency, compounded by antibiotic-induced nutrient depletion, forms a vicious cycle of overt inflammation, contributing to bacterial toxin translocation in human inter-organ and intra-organs milieus. Coenzyme Q10 (CoQ10) and omega-6 linoleic acid (LA 18:2ω6) are integral to cellular membrane integrity and immune defense. However, the complex enzymatic steps at the host cell-pathogen interface remain poorly understood. This study is particularly timely, as it explores these knowledge gaps, which can inform the development of nutritional and therapeutic strategies that modulate or target these mechanisms. Using an infectious-inflamed cell co-culture model of the gut-liver axis, we exposed triple cell co-cultures of human intestinal epithelial cells (T84), macrophage-like THP-1 cells, and hepatic cells (Huh7) to linoleic acid-producing Lactobacillus casei (L. casei) and Pseudomonas aeruginosa strain PAO1 (PAO1). The cultures were incubated for 6 h in medium with or without ceftazidime antibiotic. PAO1 and L. casei exerted opposing effects on the secretion of Th1 cytokines IL-1β, IL-6, and the Th 2-type cytokine IL-10. Inoculation with PAO1 decreased CoQ10 and linoleic acid levels compared to uninfected controls. L. casei restored cellular health and biofunctionality impaired by PAO1, indicating its benefit to the host's well-being. The antibiotic ceftazidime exerted dual effects, alleviating PAO1 toxicity while marginally disrupting the beneficial effects of L. casei. Our results show how the vicious cycle of nutrient deficiency and antibiotic-induced nutrient loss reinforces pathological inflammation at the host cell-pathogen interface and highlights the need for more appropriate targeted antibiotic use that preserves essential nutrients like CoQ10 and omega-6 fatty acids. Inflammatory responses driven by opportunistic pathogens and LA-producing bacteria represent opposing immunometabolic pathways that may provide insights into novel approaches for treating infection and reducing antibiotic resistance. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 11 2025 Long-Term Outcome of Xenon-Arc Photocoagulation for Retinopathy of Prematurity in the 1970s in Japan: Eleven Patients With 32- to 49-Year Follow-Up e97797 EN Toshihiko Matsuo Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Nobuhiko Matsuo Ophthalmology, Okayama University Medical School Objectives: Photocoagulation or cryocautery, or their combinations, are the standard of care for retinopathy of prematurity at the recommended timing, which is based on the International Classification of Retinopathy of Prematurity. In Japan, the effectiveness of xenon-arc photocoagulation and cryocautery in retinopathy of prematurity was reported on an empirical basis first in 1968, and became the standard of care in retinopathy of prematurity in the 1970s, 10 years earlier compared with the other countries. In this study, we reported the up to 49 years visual outcome of 11 patients with retinopathy of prematurity who underwent xenon-arc photocoagulation and cryocautery in the 1970s. Methods: A retrospective review was made on the medical records of 11 consecutive patients who underwent xenon-arc photocoagulation for retinopathy of prematurity in the years 1974 to 1980, and were followed up until the period from 2009 to 2025. The birthweight ranged from 865 g to 2300 g at a median of 1350 g, and the gestational age at birth ranged from 27 weeks to 36 weeks at a median of 30 weeks. The corrected gestational age at the time of photocoagulation ranged from 32 weeks to 53 weeks, with a median of 37 weeks. Oxygen was given to all 11 patients, except for one who was born in the earliest year 1974. The retinopathy of prematurity was at stage 3 in both eyes of seven patients, with plus disease signs in four patients, at stage 2 with and without plus disease in two patients, at stage 2 and stage 3 in each eye of one patient, and at stage 1 with plus disease in both eyes of one patient. The entire 360-degree photocoagulation was given in seven patients, while partial photocoagulation was applied in four patients. Additional cryocautery was applied in six patients. Results: The age at the last visit ranged from 32 to 49 years with a median of 46 years. At the last visit, seven patients showed the best-corrected visual acuity in decimals of 0.8 or better in both eyes. One dizygotic twin showed no light perception in the phthisic right eye and 0.1 in the left eye with macular degeneration and nystagmus after he underwent cataract surgery at the age of 34 years. The other twin had the best-corrected visual acuity of 0.5 in the right eye and 0.02 in the left eye due to macular degeneration after he underwent cataract surgeries in both eyes at the age of 36 years. Two patients developed rhegmatogenous retinal detachment in one eye at the age of 44 and 41 years, respectively, and underwent vitrectomy with silicone oil tamponade, resulting in visual acuity of 0.1 and 0.3, respectively. Two patients experienced vitreous hemorrhage in one eye, which was absorbed spontaneously at the ages of 37 years and 42 years, respectively. One patient underwent partial scleral buckling for localized rhegmatogenous retinal detachment. No patient used intraocular pressure-lowering eyedrops. Conclusion: Most patients with xenon-arc photocoagulation for retinopathy of prematurity in the 1970s maintained standard levels of visual acuity up to 49 years in the follow-up. Cataract, retinal detachment, and vitreous hemorrhage were noted as late complications and were coped with on an individual basis. The conclusion would have a meaning, even though not novel, that the patients with retinopathy of prematurity would have benefited from the xenon-arc photocoagulation and cryocautery. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2662-4729 2025 Evaluation of the small-field output factor in eclipse modeling methods using representative beam and measured data with averaged ionization chamber and diode detector measurements EN Kunio Nishioka Department of Radiology, Tokuyama Central Hospital Yuki Kunii Department of Radiology, Tokuyama Central Hospital Yoshinori Tanabe Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Yuichi Sakamoto Department of Radiology, Tokuyama Central Hospital Akira Nakamoto Department of Radiology, Tokuyama Central Hospital Shotaro Takahashi Department of Radiology, Tokuyama Central Hospital Beam modeling for radiotherapy treatment planning systems (RTPS) can be performed using representative beam data (RBD) or direct measurements. However, RBD typically excludes output factor (OPF) measurements for fields smaller than 3 × 3 cm2. The Eclipse treatment planning system addresses this limitation by incorporating measured OPF data for fields as small as 1 × 1 cm2. Although existing studies have primarily examined the accuracy of small-field OPFs for plastic scintillator detectors, studies directly comparing the OPF values obtained through RBD modeling with and without OPF measurements for small field sizes are limited. Therefore, this study proposes a novel measurement approach using data averaged from an ion chamber and diode detector for small-field dosimetry to provide critical insights into the integration of OPFs for these small field sizes in RBD-based beam modeling. We systematically evaluated the impact of small-field OPF measurements on beam modeling accuracy by comparing three distinct approaches: (1) RBD-based modeling without small-field OPF data, (2) RBD-based modeling incorporating measured small-field OPF data, and (3) modeling based solely on measured data, with and without the inclusion of 1 × 1 cm2 field sizes. In addition, we compared OPF values obtained from a W2 plastic scintillator detector with the averaged OPF values from a PinPoint 3D ion chamber and EDGE diode detector across multiple beam energies and flattening filter-free (FFF) configurations. Our analysis included field sizes ranging from 1 × 1 cm2 to 40 × 40 cm2. The results demonstrated that for square fields, OPF calculation differences between RBD modeling with and without measured data were < 1.5%, < 4.5%, and < 4.5% at 1 × 1 cm2, and < 0.5%, < 1.5%, and < 1.5% at 2 × 2 cm2, respectively. The RBD group exhibited a trend in which the OPF difference increased with the expansion of the irradiation field size. Notably, the most significant variations between modeling approaches occurred along the upper jaw expansion direction in rectangular fields. This suggests that a thorough evaluation is necessary for modeling results with an OPF ≤ 1 × 1 cm2. This study highlights the advantages and disadvantages of beam modeling using measured OPF and RBD, providing valuable insights for future facilities that rely solely on RBD for beam modeling. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1279-8517 47 1 2025 A case of a large venous ring around the mandibular condyle 95 EN Keitaro Nishi Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima University Tatsuo Okui Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima University Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingo Kusukawa Dental and Oral Medical Center, Kurume University School of Medicine R. Shane Tubbs Department of Neurosurgery, Clinical Neuroscience Research Center, Tulane University School of Medicine Joe Iwanaga Dental and Oral Medical Center, Kurume University School of Medicine Anatomical details regarding venous drainage of the head and neck are an important matter for surgeons to avoid unnecessary complications such as hemorrhage. This report describes a case of the large venous ring around the mandibular condyle found in the cadaver. The left maxillofacial region of a latex-injected embalmed male cadaver (82 years of age at death) was dissected. The large two maxillary veins ran lateral to the capsule and superior to the mandibular notch and coursed posteroinferiorly to merge, and one trunk was formed at the posterior border of the ramus. It then received the superficial temporal vein superiorly to form the retromandibular vein (RMV). In addition, three maxillary veins were drained from the pterygoid venous plexus (PVP), medial to the ramus, one maxillary vein drained from the PVP into the RMV trunk, while two maxillary veins drained from the PVP into the anterior division of the RMV. All five large veins lateral and medial to the condyle drained from the PVP into the RMV. The knowledge of such an anatomical variation might prevent intraoperative bleeding in the temporomandibular joint region. No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 57 2 2025 金銭債権の譲渡による損益が雑所得に区分される理由―金利に該当するからなのか，それとも貸倒損失処理に伴う問題への対処なのか― 31 47 EN Yoshiyuki Nakagawa 10.18926/OER/69552 　金銭債権の譲渡による損益は，所得税基本通達33-1により譲渡所得の基因となる資産から除外される。この理由について課税当局は50年もの長きにわたり，①「金銭債権の譲渡による利益は金利に該当するからである」，との説明と，②「金銭債権の譲渡による損失を貸倒処理して税制上の恩典を受けることから生ずる不合理に対処するためである」，とする2つの異なる説明を行ってきている。 　本稿は課税当局によるこの2つの説明の比較検討を行い，②の「金銭債権の譲渡による損失を貸倒処理して税制上の恩典を受けることから生ずる不合理に対処するためである」，との説明の方がより優れていることを明らかにするものである。 　また「金銭債権の譲渡による利益は金利に該当する」との説明に根本的な疑問を感じたことから，この点について深い検討を行い，この説明は適切でないことを明らかにするものである。 No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 57 2 2025 介護離職の社会的損失―アップデートと時系列推移― 1 16 EN Kensaku Kishida 10.18926/OER/69550 　Kishida（2020）estimated the number of labor force exiters unemployed due to family care and their lost income. We updated the result of Kishida（2020）and modified the estimation method of the lost income. We defined labor force exiters as those who were out of work 2 years after they exited. The results using the latest Employment Status Survey for 2022 are as follow. Among the 10.6 thousand annual care leavers, 35.9％ restarted work and the remaining 64.1％ exited the labor market. Three-fourths of returned to the exiters were non-regular workers. Among the care leavers previously in regular employment who returned to the labor market, 34.4％ of them restarted work as regular workers and the remainder restarted work as non-regular workers. Among the exiters, the ratio of care leavers to all exiters was 3.8％ . More than 10％ of women exiters of 40-50 years of age were care leavers. Hence, the loss of middle-aged employment due to care leavers is significant. 　The wages of care leavers' previous jobs are indispensable for calculating the loss of income. However, our data did not contain the necessary information. Hence, as a proxy variable, we used the wages of workers whose attributes are similar to the ones of the care leavers. Additionally, in the loss of income calculation, we considered the income accrued from restarting work. 　The total loss of income during one year after care leave was 187.4 billion yen. We decomposed the income loss into the loss incurred by being unemployed and the loss incurred by getting a job that pays less than the previous one. The former loss was 77.1％ and the latter one was 22.9％ . Approximately 70％ of the income loss due to wage declines was due to previous full-time employment, and 86.3％ of that was due to resuming work as non-full-time employment with significantly lower wages. If the separation period lasts for more than one year, the income loss for society as a whole is the sum of the income losses in the years when the separation period is different. Based on our calculations, the annual income loss was at least 403.2 billion yen. 　The number of people leaving the labor market was 74,400 in 2012, 63,700 in 2017, and 68,100 in 2022. In 2012, when the unemployment rate was high, the return to work rate was lower than in 2017 and 2022, and the number of people leaving the labor market was relatively high. Income losses were 382.1 billion yen in 2012, 363.9 billion yen in 2017, and 399.2 billion yen in 2022. The breakdown of income losses by cause was roughly the same. No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 57 2 2025 表紙・目次 EN No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2363-9024 11 1 2025 Venous air embolism induced by burr hole drilling before dural incision in craniotomy: two case reports 59 EN Yohei Motoi Department of Anesthesiology and Resuscitology, Okayama University Hospital Shuji Okahara Department of Anesthesiology and Resuscitology, Okayama University Hospital Makiko Tani Department of Anesthesiology and Resuscitology, Okayama University Hospital Nobushige Tsuboi Department of Neurosurgery, Okayama Red Cross Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Hospital Background: Venous air embolism (VAE) is a rare but potentially fatal complication in neurosurgery typically caused by injury to dura mater, especially venous sinuses, during craniotomy. We report two cases of VAE that occurred before dural incision. Case presentation: Both patients underwent craniotomy under general anesthesia in a head-up position. Hemodynamic and respiratory deterioration occurred during or immediately after burr hole drilling with abnormal vital signs and transesophageal echocardiography findings, raising suspicion for VAE. Immediate management, including surgical field protection and cardiopulmonary support, stabilized the patients’ conditions. The procedure was subsequently discontinued in case 1 and modified to limited resection in case 2. Postoperative computed tomography revealed intracranial venous air within the internal jugular vein, cavernous sinus, and diploic veins. Conclusion: These cases highlight that VAE can occur even before dural incision. Vigilant intraoperative monitoring and prompt intervention are essential for preventing potentially fatal outcomes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0913-8668 39 2 2025 T2 high-signal-intensity zone of the spinal cord dorsal horn in patients treated with spinal cord stimulation for herpes zoster-associated pain: a retrospective case–control study 273 281 EN Kyosuke Arakawa Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masayuki Nakagawa Department of Pain Management Clinic, NTT Medical Center Tokyo Yoichiro Abe Department of Pain Management Clinic, NTT Medical Center Tokyo Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose In patients with herpes zoster-associated pain (ZAP), magnetic resonance imaging (MRI) has revealed T2 high-signal intensity zones (MRI T2 HIZ) in the dorsal horn of the spinal cord, associated with postherpetic neuralgia (PHN). We retrospectively analyzed the relationship between PHN and MRI T2 HIZ in patients with refractory ZAP in the subacute phase who underwent temporary spinal cord stimulation therapy (tSCS). Methods This single-center, case–control study included patients who underwent tSCS for refractory ZAP between 2010 and 2018. MRIs were re-assessed for the presence of T2 HIZ in the dorsal horn of the spinal cord. Patients were divided into T2 HIZ( +) and T2 HIZ(−) groups. Patients with a numerical rating score (NRS) ≥ 3 at the last visit were defined as PHN. The NRS values and the incidence rate of PHN were compared between the two groups. Results Of the 67 cases extracted, 38 were included in the analysis: 22 in T2 HIZ( +) group and 16 in T2 HIZ(−) group. No significant differences were observed in background factors between the two groups. However, the T2 HIZ( +) group had a significantly higher NRS at the final visit (T2 HIZ( +):3.8 ± 2.1, T2 HIZ(−):1.4 ± 1.5; P < 0.05) and had significantly more patients with PHN than the T2 HIZ(−) group (T2 HIZ( +) vs. T2 HIZ(−), 15/22 (68%) vs. 3/16 (19%); odds ratio = 8.67; 95% confidence interval, 1.7–63.3). Conclusion T2HIZ is detected in more than half of refractory ZAP, and pain is more likely to remain after tSCS treatment in the T2HIZ( +) group. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 15 8 2025 Neurological outcomes with hypothermia versus normothermia in patients with moderate initial illness severity following resuscitation from out-of-hospital cardiac arrest: protocol for a multicentre randomised controlled trial (R-CAST OHCA) e101809 EN Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Mitsuaki Nishikimi Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Yohei Okada Department of Preventive Services, School of Public Health, Graduate School of Medicine, Kyoto University Hiroki Maeyama Department of Emergency and Critical Care Medicine, Tsuyama Chuo Hospital Takeyuki Kiguchi Division of Trauma and Surgical Critical Care, Osaka General Medical Center Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kazuki Nishida Department of Biostatistics, School of Public Health, Graduate School of Medicine, Kyoto University Shigeyuki Matsui Department of Biostatistics, School of Public Health, Graduate School of Medicine, Kyoto University Yasuhiro Kuroda Emergency and Critical Care Center, TMG Asaka Medical Center Kei Nishiyama Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science Taku Iwami Department of Preventive Services, School of Public Health, Graduate School of Medicine, Kyoto University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences JAAM R-CAST OHCA Trial Group Introduction Temperature control is a fundamental intervention for neuroprotection following resuscitation from cardiac arrest. However, evidence regarding the efficacy of hypothermia in post-cardiac arrest syndrome (PCAS) remains unclear. Retrospective studies suggest that the clinical effectiveness of hypothermia may depend on the severity of PCAS. The R-CAST OHCA trial aims to compare the efficacy of hypothermia versus normothermia in improving 30-day neurological outcomes in patients with moderately severe PCAS following out-of-hospital cardiac arrest. Methods and analysis The multicentre, single-blind, parallel-group, superiority, randomised controlled trial (RCT) is conducted with the participation of 35 emergency and critical care centres and/or intensive care units at academic and non-academic hospitals. The study enrols moderately severe PCAS patients, defined as those with a revised post-Cardiac Arrest Syndrome for induced Therapeutic Hypothermia score of 5.5–15.5. A target number of 380 participants will be enrolled. Participants are randomised to undergo either hypothermia or normothermia within 3 hours after return of spontaneous circulation. Patients in the hypothermia group are cooled and maintained at 34°C until 28 hours post-randomisation, followed by rewarming to 37°C at a rate of 0.25°C/hour. Patients in the normothermia group are maintained at normothermia (36.5°C–37.7°C). Total periods of intervention, including the cooling, maintenance and rewarming phases, will occur 40 hours after randomisation. Other treatments for PCAS can be determined by the treating physicians. The primary outcome is a favourable neurological outcome, defined as Cerebral Performance Category 1 or 2 at 30 days after randomisation and compared using an intention-to-treat analysis. Ethics and dissemination This study has been approved by the Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital, Ethics Committee (approval number: R2201-001). Written informed consent is obtained from all participants or their authorised surrogates. Results will be disseminated via publications and presentations. Trial registration number jRCT1062220035. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2198-3844 2025 A Viral RNA Silencing Suppressor Modulates Reactive Oxygen Species Levels to Induce the Autophagic Degradation of Dicer‐Like and Argonaute‐Like Proteins e06572 EN Shiyu Zhai State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Tianxing Pang State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Shiyu Peng State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Shenshen Zou Department of Plant Pathology, College of Plant Protection, Shandong Agricultural University Zhiping Deng Institute of Virology and Biotechnology, Zhejiang Academy of Agricultural Sciences Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Zhensheng Kang State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Ida Bagus Andika State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Liying Sun State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Mounting evidence indicates that viruses exploit elevated reactive oxygen species (ROS) levels to promote replication and pathogenesis, yet the mechanistic underpinnings of this viral strategy remain elusive for many viral systems. This study uncovers a sophisticated viral counter-defense mechanism in the Cryphonectria hypovirus 1 (CHV1)-Fusarium graminearum system, where the viral p29 protein subverts host redox homeostasis to overcome antiviral responses. That p29 directly interacts with and inhibits the enzymatic activity of fungal NAD(P)H-dependent FMN reductase 1 (FMR1), leading to increased ROS accumulation and subsequent autophagy activation is demonstrated. Strikingly, this ROS-induced autophagy selectively targets for degradation two core antiviral RNA silencing components against CHV1 in F. graminearum, Dicer-like 2 (DCL2) and Argonaute-like 1 (AGL1), thereby compromising the host's primary antiviral defense system. Genetic analysis confirms this coordinated hijacking of host machineries, as CHV1 shows enhanced accumulation in the FMR1 knockout and reduced accumulation in autophagy-deficient fungal strains. This work reveals a tripartite interplay among oxidative stress, autophagy, and RNA silencing that CHV1 manipulates through p29 multifunctional activity. These findings provide a model for how viruses coordinately regulate distinct host defense systems to optimize infection. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1328-8067 67 1 2025 Early-life exposures and child health outcomes: A narrative review of LSN21 research in Japan e70258 EN Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rumi Matsuo Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuka Yamamura Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Tsuge Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoka Kadowaki Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Uraguchi Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Tamai Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazue Nakamura Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihito Takeuchi Division of Neonatology, NHO Okayama Medical Center Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: The Longitudinal Survey of Newborns in the 21st Century (LSN21) tracks two Japanese national birth cohorts—2001 (baseline n = 47,010) and 2010 (n = 38,554)—from infancy through young adulthood, capturing parenting practices and family environments. Most studies analyze single exposures or outcomes. We conducted a narrative review summarizing the findings published by the Okayama University group on diverse health and developmental outcomes. Methods: We reviewed 59 LSN21 papers (2013–2025), extracting data on exposures, outcomes, and methods. Evidence was categorized into four exposure types (infant feeding, sleep, environmental, and perinatal) and three outcome domains (obesity, allergies/respiratory tract infections, and neurobehavioral development), including cohort comparisons. Results: Exclusive breastfeeding was associated with a lower obesity risk at ages 7 (adjusted odds ratio 0.55, 95% confidence interval 0.39–0.78) and 15, later puberty, and fewer hospitalizations. Short or irregular sleep before age 3 was linked to behavioral problems and injuries. Maternal smoking and prenatal air pollution were associated with respiratory conditions and developmental challenges. Preterm birth and small-for-gestational-age predicted delays, especially without catch-up growth by age 2. Pneumococcal vaccination likely contributed to declining otitis media after 2010. Additional findings included associations between outdoor play and reduced obesity risk, and complex relationships between breastfeeding and food allergies that varied by infantile eczema status. Conclusions: LSN21 findings highlight modifiable early-life factors (breastfeeding, sleep patterns, and smoke-free environments) and identify preterm and growth-restricted children for priority monitoring. While LSN21's strength lies in longitudinal social assessments, complementary perspectives from other Japanese cohorts could enhance understanding of biological mechanisms and intergenerational effects. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Serum extracellular vesicles containing adenoviral E1A-DNA as a predictive biomarker for liquid biopsy in oncolytic adenovirus therapy 38590 EN Chiaki Yagi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shinji Kuroda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunya Hanzawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Daisuke Kadowaki Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yusuke Yoshida Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masaki Sakamoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuki Hamada Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ryoma Sugimoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomoko Ohtani Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kento Kumon Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masashi Hashimoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Nobuhiko Kanaya Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoru Kikuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunsuke Kagawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroshi Tazawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Oncolytic adenoviruses replicate selectively in tumor cells and induce immunogenic cell death, but predictive biomarkers for early therapeutic response are lacking. This study evaluated extracellular vesicle-encapsulated adenoviral E1A-DNA (EV-E1A-DNA) as a minimally invasive biomarker for monitoring responses to telomerase-specific oncolytic adenoviruses OBP-301 and OBP-502. EVs were isolated from human and murine cancer cell lines and from the serum of treated mice using ultracentrifugation. EV-associated E1A-DNA levels were measured by quantitative polymerase chain reaction and found to correlate with cytotoxicity in vitro and tumor regression in vivo. In xenograft models, serum EV-E1A-DNA levels at 2 days post-treatment showed strong correlations with final tumor volume and survival, supporting their utility as an early predictive biomarker. In immunocompetent mice pre-immunized with wild-type adenovirus, free viral DNA was undetectable in serum due to neutralizing antibodies, whereas EV-E1A-DNA remained detectable. This “stealth effect” indicates that EVs protect viral components from immune clearance. These results demonstrate that EV-E1A-DNA is a sensitive and virus-specific biomarker that enables early assessment of therapeutic efficacy, even in the presence of antiviral immunity. This strategy offers a promising liquid biopsy approach for personalized monitoring of oncolytic virotherapy and may be applicable to other virus-based therapies. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0007-0920 2025 Gemcitabine-induced neutrophil extracellular traps via interleukin-8-CXCR1/2 pathway promote chemoresistance in pancreatic cancer EN Shohei Nogi 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 Atsuki Taniguchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiko Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi 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 Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiyasu Kono Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoru Kikuchi 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 Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, and chemoresistance poses a significant challenge in its treatment. Neutrophil extracellular traps (NETs) have emerged as key players in the tumour microenvironment, but their role in chemoresistance remains unclear. Methods: We investigated the involvement of NETs in PDAC chemoresistance using patient tumour samples, in vitro assays with gemcitabine (GEM)-treated PDAC cells, and in vivo mouse models. We evaluated cytokine production, NET formation and tumour response to GEM, with or without the CXCR1/2 inhibitor navarixin. Results: NETs are significantly accumulated in the tumours of PDAC patients exhibiting poor response to chemotherapy. GEM-treated PDAC cells secrete pro-inflammatory cytokines such as interleukin-8 (IL-8). IL-8 promote the formation of chemotherapy-induced NETs (chemoNETosis) through activation of CXCR 1/2 on neutrophils. Importantly, treatment with navarixin significantly suppressed chemoNETosis, restored sensitivity to GEM, and significantly reduced tumour growth in vivo. Conclusions: Our findings reveal that NETs contribute to chemoresistance in PDAC and that IL-8–mediated chemoNETosis plays a pivotal role in this process. Inhibition of CXCR1/2-mediated NET formation enhances the efficacy of GEM. This approach may represent a promising therapeutic strategy for overcoming chemoresistance in PDAC. These results support further clinical investigation of anti-NETs therapies. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 iTRAQ-based quantitative proteomics reveals reduced expression of KRT19, KRT7, and PTGDS in cutaneous specimens after kidney transplantation 33014 EN Ichiro Tsuboi Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yosuke Mitsui Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kasumi Yoshinaga Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomoaki Yamanoi Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takanori Sekito Department of Inflammation and Immunity, Lerner Research Institute Cleveland Clinic Yuki Maruyama Department of Inflammation and Immunity, Lerner Research Institute Cleveland Clinic Takuya Sadahira Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shingo Nishimura Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kensuke Bekku Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Motoo Araki Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Clinical improvement in pigmentation is frequently observed after kidney transplantation. However, the underlying molecular and histological mechanisms remain unclear. We conducted a study to quantify the skin color change using a handheld reflected light colorimeter and to investigate protein expression changes in the skin before and after kidney transplantation. Paired skin biopsies were obtained from three patients who underwent kidney transplantation before and one month after transplantation. Protein expression was analyzed using iTRAQ-based quantitative proteomics. Differentially expressed proteins were identified and visualized using hierarchical clustering and volcano plots. Histopathological evaluation included hematoxylin and eosin (H&E), Masson’s trichrome, and immunohistochemical (IHC) staining for keratin (KRT) 7, KRT19, and MelanA. Skin pigmentation of the arms, ankles, and abdomen had significant L-value improvement after kidney transplantation. Proteomic profiling identified 2148 proteins, with six proteins showing significant differential expression after transplantation. Among them, KRT7, KRT19, and prostaglandin D2 synthase (PTGDS) were significantly downregulated, potentially reflecting reduced epithelial stress and systemic inflammation. H&E and Masson’s trichrome staining revealed a post-transplantation reduction in dermal pigmentation and collagen content. IHC showed decreased KRT7, KRT19, and MelanA expression after transplantation. Our results suggest that targeting KRT or prostaglandin pathways may offer new treatments for ESRD-related skin symptoms. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 0194-911X 82 10 2025 Redefining AT1 Receptor PET Imaging: Introducing the Radiotracer [18F]DR29 1626 1637 EN Xinyu Chen Nuclear Medicine, Faculty of Medicine, University of Augsburg Hiroyuki Kimura Agency for Health, Safety and Environment, Kyoto University Takanori Sasaki Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Konrad Klimek Goethe University Frankfurt, University Hospital, Clinic for Radiology and Nuclear Medicine, Department of Nuclear Medicine Saskia Mühlig Department of Nuclear Medicine and Comprehensive Heart Failure Center (DZHI), University Hospital Würzburg Anahi Paula Arias-Loza Department of Nuclear Medicine and Comprehensive Heart Failure Center (DZHI), University Hospital Würzburg Naoko Nose Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Yagi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Steven P Rowe Molecular Imaging and Therapeutics, Department of Radiology, School of Medicine, University of North Carolina, Chapel Hill Constantin Lapa Nuclear Medicine, Faculty of Medicine, University of Augsburg Rudolf A. Werner Department of Nuclear Medicine, LMU Hospital, Ludwig-Maximilians-University of Munich Takahiro Higuchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University BACKGROUND: AT1R (angiotensin II type 1 receptors) are central to the renin-angiotensin system and are involved in regulating blood pressure and renal physiology. This study introduces [18F]DR29, a fluorine-18-labeled radiotracer for positron emission tomography imaging, to enable noninvasive visualization of AT1R expression. Its potential applications in understanding AT1R-associated renal processes are explored in healthy and hypertensive rat models. METHODS: Radiolabeling was established, and biodistribution studies were conducted on healthy Wistar rats with and without the AT1R antagonist candesartan and transporter inhibitors. Dynamic positron emission tomography imaging assessed tracer specificity, and feasibility for renal AT1R quantification was explored using a hypertensive rat model. RESULTS: [18F]DR29 was radiolabeled with a yield of 36±6%. High kidney uptake was observed, significantly reduced by candesartan (kidney-to-blood ratio, 0.43±0.01 versus 4.54±1.59 in vehicle, where vehicle refers to saline without any treatment). Transporter inhibition protocols targeting organic anion transporting polypeptides (liver) and organic anion transporters (kidneys) successfully reduced radiotracer clearance, increasing the specific accumulation of [18F]DR29 in the kidneys and improving renal imaging contrast. Positron emission tomography imaging revealed rapid kidney uptake and stable retention over 2 hours. In hypertensive rats, kidney uptake was higher, aligning with AT1R expression levels. CONCLUSIONS: These results support [18F]DR29 as a promising tool for the noninvasive evaluation of renal AT1R expression in healthy and diseased states. The findings lay the groundwork for clinical translation, offering potential applications in diagnosing and managing kidney-related diseases, including hypertension and other conditions involving AT1R dysregulation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1439-0108 2025 Coupling effects of biochar and sediment microbial fuel cells on CH4 and CO2 emissions from straw-amended paddy soil EN Adhena Tesfau Bekele Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Morihiro Maeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nozomi Nakahara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ayumi Hashiguchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroaki Somura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Satoshi Akao Faculty of Science and Engineering, Doshisha University Chiyu Nakano Department of Comprehensive Technical Solutions, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Purpose The independent incorporation of biochar and sediment microbial fuel cells (SMFCs) into paddy soil has been shown to reduce methane (CH4) emissions. However, the application of rice straw into paddy soil enhances the availability of labile carbon that stimulates methanogen growth, counteracting the mitigation effects of both methods. This study, therefore, aimed to investigate the effect of coupling biochar and SMFC on CH4 and CO2 emissions from straw-amended paddy soil. Materials and methods Single chamber SMFC setups constructed using acrylic columns (height, 25 cm; inner diameter, 9 cm) with six treatments were established using soil amended with 0% (0BC), 1% (1BC), and 2% (2BC) biochar: with and without SMFC conditions. Stainless steel mesh (15 × 3 cm) and graphite felt (6 × 5 cm) were used as anode and cathode materials, respectively. Results Cumulative emission of CH4 in the 0BC treatment with SMFC was 39% less than in that without SMFC. Biochar addition and SMFC operation together further reduced CH4 emission by 57% and 60% in 1BC and 2BC treatments, respectively, compared to that in the 0BC treatment without SMFC operation. The relative abundance of microbial communities indicated methane-oxidizing bacteria were enriched in the presence of biochar and hydrogenotrophic Methanoregula were suppressed by SMFC operation. This suggested that SMFC mainly inhibited CH4 production by outcompeting hydrogenotrophic archaea. Conclusion The use of biochar made from leftover rice straw has an interactive effect on SMFC operation and both methods can be used to reduce CH4 emission from straw-amended paddy soil. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 7 2025 Prevalence of Locomotive Syndrome in Perioperative Patients With Localized Cancer e88699 EN Yoshimi Katayama Department of Rehabilitation Medicine, Okayama University Hospital Eiji Nakata Department of Orthopaedic Surgery, Okayama University Hospital Takuto Itano Department of Orthopaedic Surgery, Okayama University Hospital Yoshiteru Akezaki Division of Physical Therapy, Kochi Professional University of Rehabilitation Masanori Hamada Department of Rehabilitation Medicine, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Introduction Many patients with cancer experience reduced activities of daily living due to muscle weakness and fatigue caused by underlying symptoms and treatment side effects. However, the incidence of locomotive syndrome, which may reduce mobility due to motor dysfunction in patients with cancer, has not been sufficiently explored. Therefore, we aimed to investigate the incidence of locomotive syndrome and identify its risk factors in perioperative patients with cancer. Methods We included 636 perioperative patients with localized cancer who were treated between 2020 and 2023. The severity of locomotive syndrome was classified into stages 1, 2, and 3. Results The overall locomotive syndrome rate was 88.1%, with distribution across stages: stage 1 (56.8%), stage 2 (17.5%), and stage 3 (13.8%). Among men, the overall incidence was 86.5%, with stage 1 (60.3%), stage 2 (15.5%), and stage 3 (10.7%). Among women, the overall incidence was 90.6%, with stage 1 (50.6%), stage 2 (20.9%), and stage 3 (19.1%). Half of patients in their 20s and two-thirds in their 30s had locomotive syndrome. The rates were 58.6%, 80.4%, 81.8%, 93.2%, and 97.8% in the 40s, 50s, 60s, 70s, and 80s age groups, respectively. Individuals in their 40s had significantly lower rates than those in older groups. Age, grip strength, and percent vital capacity were identified as risk factors. Conclusion A high prevalence of locomotive syndrome was observed among patients with localized cancer. Age, reduced grip strength, and lower respiratory capacity were identified as associated factors. While the findings suggest possible implications for postoperative recovery, further validation through longitudinal studies is required. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 1109-6535 22 6 2025 C1orf50 Accelerates Epithelial-Mesenchymal Transition and the Cell Cycle of Hepatocellular Carcinoma 836 849 EN ATSUSHI TANAKA Department of Pathology, Beth Israel Deaconess Medical Center YUSUKE OTANI Department of Pathology, Beth Israel Deaconess Medical Center MASAKI MAEKAWA Department of Pathology, Beth Israel Deaconess Medical Center ANNA ROGACHEVSKAYA Department of Pathology, Beth Israel Deaconess Medical Center TIRSO PEÑA Department of Pathology, Beth Israel Deaconess Medical Center VANESSA D. CHIN UMass Chan Medical School, UMass Memorial Medical Center SHINICHI TOYOOKA Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences MICHAEL H. ROEHRL Department of Pathology, Beth Israel Deaconess Medical Center ATSUSHI FUJIMURA Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aim: Hepatocellular carcinoma (HCC) is a heterogeneous liver cancer with limited treatment options and a poor prognosis in advanced stages. To identify novel biomarkers and therapeutic targets, we investigated the role of chromosome 1 open reading frame 50 (C1orf50), a gene with a previously uncharacterized function in HCC. Materials and Methods: We performed a comprehensive transcriptome data analysis of the human hepatocellular carcinoma project from The Cancer Genome Atlas (TCGA) and subsequently validated the oncogenic roles of C1orf50 using HCC cell lines. Results: Using transcriptomic and clinical data from TCGA, we stratified 355 primary HCC samples based on C1orf50 expression levels. Patients with high C1orf50 expression exhibited significantly shorter overall survival, suggesting its association with aggressive tumor behavior. Differential expression and enrichment analyses revealed that C1orf50-high tumors were enriched in oncogenic pathways, including epithelial-mesenchymal transition (EMT), cell cycle activation, and stemness-related properties. Transcriptional regulatory network analysis detected 456 significantly dysregulated regulons, including ZEB1/2 and E2F2, key drivers of EMT and cell cycle, in the C1orf50-high group. In addition, we observed increased YAP1/TAZ signaling, further linking C1orf50 to stemness and therapeutic resistance. Functional data from CRISPR-based dependency screening suggested that several transcription factors up-regulated in the C1orf50-high state, such as ZBTB11 and CTCE, are essential for the survival of HCC cells. These findings indicate potential therapeutic vulnerabilities and support the rationale for targeting C1orf50-associated pathways. Conclusion: C1orf50 is a novel biomarker of poor prognosis in HCC and a key regulator of oncogenic features such as EMT, cell cycle progression, and stemness. This study highlights the therapeutic potential of targeting C1orf50-related networks in aggressive subtypes of liver cancer. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2376-7839 11 5 2025 Vanishing White Matter Disease With EIF2B2 c.254T >A Variant e200293 EN Toshiyuki Kakumoto Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Ryo Tokimura Department of Neurology, Graduate School of Medicine, The University of Tokyo Yoko Tsuboyama Department of Neurology, Graduate School of Medicine, The University of Tokyo Yasufumi Hayashi Department of Neurology, Graduate School of Medicine, The University of Tokyo Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Atsushi Iwata Department of Neurology, Graduate School of Medicine, The University of Tokyo Meiko Hashimoto Maeda Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Shimizu Department of Neurology, Graduate School of Medicine, The University of Tokyo Wataru Gonoi Department of Radiology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Mitsui Department of Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Objectives Typical MRI findings of vanishing white matter disease (VWM) include diffuse white matter lesions with cystic degeneration. However, mild cases may lack these typical features, posing diagnostic challenges. Methods We describe 2 of 3 individuals carrying the homozygous c.254T >A variant in EIF2B2 identified at our hospital, excluding 1 previously reported case.1 Genetic analyses were performed using whole-genome sequence or whole-exome sequence analysis, and detected variants were confirmed by direct nucleotide sequence analysis. Brain MRI findings and clinical features were reviewed for the 2 individuals along with other cases in the literature with the same variant. Results A 69-year-old woman presented with recurrent transient dizziness and secondary amenorrhea. MRI of the brain revealed small T2-hyperintense lesions confined to the subcortical white matter with hyperintensities on diffusion-weighted images and mildly elevated apparent diffusion coefficient values. A 28-year-old woman presented with transient dizziness and secondary amenorrhea. MRI of the brain showed mild T2-hyperintense lesions in the cerebral white matter with frontal predominance. Discussion This report highlights the clinically mild cases of VWM with subtle abnormalities on brain MRI who had the homozygous c.254T >A in EIF2B2, further expanding the clinical spectrum of VWM and underscoring the importance of genetic assessments in the diagnosis of individuals with mild clinical and MRI findings. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2328-9503 2025 INF2-Related Charcot–Marie–Tooth Disease in a Japanese Cohort: Genetic and Clinical Insights EN Chikashi Yano Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences 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 Jun‐Hui Yuan Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Akiko Yoshimura Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Takahiro Hobara Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Risa Nagatomo Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Fumikazu Kojima Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Yu Hiramatsu Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Satoshi Nozuma Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Tomonori Nakamura Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Yusuke Sakiyama Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Chika Matsuoka 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 Takashi Kimura Department of Neurology, Hyogo Medical University Ayako Miyazaki Department of Clinical Genetics, Hyogo Medical University Chinatsu Kinjo Department of Clinical Genetics, Hyogo Medical University Kenji Yokochi Department of Pediatrics, Toyohashi Municipal Hospital Nanami Yamanaka Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine Nozomu Matsuda Department of Neurology, Fukushima Medical University School of Medicine Tomoki Suichi Department of Neurology, Graduate School of Medicine, Chiba University Yoshiyuki Hanaoka Department of Pediatrics, Kurashiki Central Hospital Haruka Kojima Department of Neurology, Tokyo Women's Medical University Kenichi Todo Department of Neurology, Tokyo Women's Medical University Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Department of Neurology, The University of Tokyo Hospital Hiroshi Takashima Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Background: INF2 mutations cause focal segmental glomerulosclerosis (FSGS) and Charcot–Marie–Tooth disease (CMT). Accurate genetic diagnosis is critical, as INF2-related FSGS is typically resistant to immunotherapy yet rarely recurs after transplantation, and its associated neuropathy can mimic treatable immune-mediated disorders such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods: We performed a multicenter study investigating 3329 Japanese patients with inherited peripheral neuropathies/CMT who underwent gene panel sequencing or whole-exome analysis between 2007 and 2024. Clinical data, including electrophysiological assessments, were obtained from the patients' medical records. Results: We identified six pathogenic INF2 variants in eight patients, all of which were located within the diaphanous inhibitory domain. Structural modeling revealed clustering of variants near the diaphanous autoregulatory domain-binding pocket, which is critical for INF2 autoinhibition. Clinically, all cases were sporadic, with a median age at neurological onset of 9 years. All patients exhibited lower limb weakness, and 6/8 (75%) had sensory disturbances. All patients also developed kidney dysfunction, with 7/8 (88%) progressing to end-stage renal disease at a median age of 15 years. Furthermore, all patients showed demyelinating neuropathy, and 2/8 (25%) received immunotherapy due to suspected immune-mediated neuropathy. Conclusion: Although INF2 variants are a rare cause of CMT in Japan, they should be considered in pediatric patients with demyelinating neuropathy and early-onset proteinuria, even in the absence of a family history. Blood and urine tests assessing renal dysfunction can provide guidance for appropriate genetic testing. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 20 2025 Impact of Neoadjuvant Chemotherapy with Gemcitabine Plus S-1 in Patients with Resectable Pancreatic Ductal Adenocarcinoma 3287 EN Kazuya Yasui 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 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 Kazuyuki Matsumoto 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, Yuki Fujii Department of Gastroenterology and Hepatology, 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Although neoadjuvant chemotherapy (NAC) is not universally recommended for resectable pancreatic ductal adenocarcinoma (PDAC), NAC with gemcitabine plus S-1 (NAC-GS) has become a commonly used regimen for resectable PDAC in Japan. Furthermore, the impact of achieving textbook outcomes (TO) in patients receiving NAC-GS remains unclear. Methods: This retrospective study included 265 patients who were diagnosed with resectable PDAC at our institution between January 2009 and December 2023. Patients were categorized into two groups: the NAC-GS group (n = 81; 2019–2023) and the upfront surgery (UFS) group (n = 164; 2009–2018). After comparing the clinical outcomes between groups, multivariate analyses for survival were performed. Additionally, outcomes stratified by the achievement of the modified TO were analyzed in the NAC-GS group. Results: The completion rate of NAC-GS was 90.1%. Patients in the NAC-GS group exhibited significantly longer survival than those in the UFS group (2-year recurrence-free survival: 61.4% vs. 37.9%, p < 0.01; 2-year overall survival: 83.2% vs. 61.2%, p < 0.01). Multivariate analyses identified lymph node metastasis, NAC-GS induction, and completion of adjuvant chemotherapy as factors significantly associated with improved survival. Moreover, among patients who received NAC-GS, those who achieved modified TO demonstrated significantly longer survival than those who did not. Conclusions: This study demonstrated the clinical efficacy of NAC-GS in patients with resectable PDAC. Induction of NAC-GS was significantly associated with improved long-term outcomes. In multidisciplinary treatment strategies for PDAC, achieving a modified TO may lead to improved survival of patients undergoing NAC-GS. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1752-1947 19 1 2025 The safety and efficacy of finasteride for transgender men with androgenetic alopecia: a case series 468 EN Yusuke Tominaga Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomoko Kobayashi Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuko Matsumoto Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomoko Sako Department of Urology, Hiroshima City Hiroshima Citizens Hospital Takatoshi Moriwake Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoshi Horii Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takuya Sadahira Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoshi Katayama Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takehiro Iwata Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shingo Nishimura Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kensuke Bekku Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kohei Edamura Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masami Watanabe Center for Innovative Clinical Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Motoo Araki Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background Testosterone replacement therapy is commonly used in transgender men for masculinization. One of the most common adverse effects of testosterone replacement therapy is androgenetic alopecia. In Japan, finasteride is approved exclusively for cisgender men and is not indicated for transgender men. The aim of this clinical trial was to evaluate the safety and efficacy of finasteride in transgender men with androgenetic alopecia. Case presentation This study included three transgender men (assigned female at birth, identifying as male), aged 44, 43, and 29 years. All participants were of Asian ethnicity. A clinical trial was conducted from October 2021 to December 2023. Transgender men aged 20–60 years who had not undergone hysterectomy, were undergoing testosterone replacement therapy, and who had been diagnosed with stage ≥ II androgenetic alopecia on the basis of the Norwood–Hamilton scale were recruited. The participants initiated treatment with 0.2 mg of finasteride per day for 3 months (phase 1). If no adverse events above grade 2 occurred, the dose was increased to 1.0 mg per day for an additional 3 months (phase 2). The primary endpoints were the incidence of treatment-related adverse events at 1 week, 1 month, and 3 months, as well as the rate of participants continuing treatment at 3 months. None of the patients experienced serious adverse events at 3 months, and all the patients extended their treatment to a total of 6 months. Improvements of at least one stage on the N–H scale were observed, but two participants experienced resumption of menstruation. Conclusion Finasteride appears to be a safe and effective treatment for androgenetic alopecia in transgender men undergoing testosterone replacement therapy. However, its potential for reducing some of the effects of testosterone replacement therapy warrants further investigation. Trial registration: jRCT, jRCTs061210040, registered 7 October 2021, https://jrct.mhlw.go.jp/latest-detail/jRCTs061210040. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Epstein-Barr Virus-Associated Early Gastric Carcinoma with Lymphoid Stroma Mimicking a Submucosal Tumor: A Typical Case Diagnosed by Endoscopic Resection and Treated by Local Resection with Sentinel Node Navigation 399 404 EN Hiroshi Isozaki Department of Surgery, Oomoto Hospital Sasau Matsumoto Department of Surgery, Oomoto Hospital Takehiro Takama Department of Surgery, Oomoto Hospital Yuka Isozaki Department of Surgery, Oomoto Hospital Shigeki Murakami Department of Surgery, Oomoto Hospital Case Report 10.18926/AMO/69442 Gastric cancer with lymphoid stroma (GCLS) accounts for 1%-7% of gastric cancers; ~80% are Epstein-Barr virus (EBV)-positive. The rate of lymph node metastasis is relatively low, even when an early GCLS has invaded the submucosa. We report an early GCLS with massive submucosal invasion mimicking a submucosal tumor (SMT), diagnosed by endoscopic submucosal resection (ESD) and treated with local resection and sentinel node navigation surgery (SNNS). The patient was a 40-year-old Japanese man. A protruding lesion on the greater curvature of the middle part of his stomach was detected by X-ray, and an endoscopic examination revealed a 2.5-cm protruding tumor covered with a normal mucosa and small ulcers at the apex. ESD was performed for a diagnosis. The pathological diagnosis was lymphoepithelioma-like gastric cancer (GCLS), pT1b(SM2), Ly0, V0, pHM1, pVM1. EBV infection in the cancer cells was confirmed pathologically by EBV-encoded RNA. The local resection was performed using SNNS. The patient has had no recurrence or post-gastrectomy syndrome 4 years postsurgery. EBV-associated early GCLS resembling an SMT is relatively rare, and clinicians need to be aware of this disease. Local resection using SNNS may be a surgical option for GCLS cases with a low rate of lymphatic metastasis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Blood Pressure and Heart Rate Patterns Identified by Unsupervised Machine Learning and Their Associations with Subclinical Cerebral and Renal Damage in a Japanese Community: The Masuda Study 369 379 EN Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Minako Kinuta Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sosuke Munetomo Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mari Fukuda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuhide Kojima Department of Radiology, Okayama University Hospital Kaori Taniguchi Department of Environmental Medicine and Public Health, Izumo, Shimane University Faculty of Medicine Noriko Nakahata Department of Health and Nutrition, The University of Shimane Faculty of Nursing and Nutrition Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/69438 We applied unsupervised machine learning to analyze blood pressure (BP) and resting heart rate (HR) patterns measured during a 1-year period to assess their cross-sectional relationships with subclinical cerebral and renal target damage. Dimension reduction via uniform manifold approximation and projection, followed by K-means++ clustering, was used to categorize 362 community-dwelling participants (mean age, 56.2 years; 54.9% women) into three groups: Low BP and Low HR (Lo-BP/Lo-HR), High BP and High HR (Hi-BP/Hi-HR), and Low BP and High HR (Lo-BP/Hi-HR). Cerebral vessel lesions were defined as the presence of at least one of the following magnetic resonance imaging findings: lacunar infarcts, white matter hyperintensities, cerebral microbleeds, or intracranial artery stenosis. A high urinary albumin-to-creatinine ratio (UACR) was defined as the top 10% (≥ 12 mg/g) of the mean value from ≥2 measurements. Poisson regression with robust error variance, adjusted for demographics, lifestyle, and medical history, showed that the Hi-BP/Hi-HR group had relative risks of 3.62 (95% confidence interval, 1.75-7.46) for cerebral vessel lesions and 3.58 (1.33-9.67) for high UACR, and the Lo-BP/Hi-HR group had a relative risk of 3.09 (1.12-8.57) for high UACR, compared with the Lo-BP/Lo-HR group. These findings demonstrate the utility of an unsupervised, data-driven approach for identifying physiological patterns associated with subclinical target organ damage. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Inhibition of Air-Exposure Stress–Induced Autolysis in Clostridium perfringens by Zn2+ 345 352 EN Nozomu Matsunaga Department of Life Science, Faculty of Science, Okayama University of Science Seira Egusa Department of Life Science, Faculty of Science, Okayama University of Science Riyo Aono Department of Medical Technology, Kagawa Prefectural University of Health Sciences Eiji Tamai Department of Infectious Disease, College of Pharmaceutical Science, Matsuyama University Yasuo Hitusmoto Department of Life Science, Faculty of Science, Okayama University of Science Seiichi Katayama Department of Life Science, Faculty of Science, Okayama University of Science Original Article 10.18926/AMO/69435 Clostridium perfringens is a pathogenic anaerobe that causes gas gangrene and food poisoning. Although autolysin-mediated reorganization of the bacterial cell wall is crucial for cell division, excessive autolysin activity induced by stressors can lead to cell lysis. In C. perfringens, air exposure is a significant stressor that causes cell lysis, and Acp (N-acetylglucosaminidase) is known to be a major autolysin. To further facilitate C. perfringens research, a technology to prevent air-induced cell lysis must be developed. This study investigated the role of Acp in air-induced autolysis and explored potential inhibitors that would prevent cell lysis during experimental procedures. Morphological analyses confirmed that Acp functions as an autolysin in C. perfringens, as acpdeficient strains exhibited filamentous growth. The mutants exhibited negligible autolysis under air-exposure stress, confirming the involvement of Acp in the autolytic process. We also evaluated the effects of various divalent cations on Acp activity in vitro and identified Zn2+ as a potent inhibitor. Brief treatment with a Zn2+- containing buffer induced dose-dependent cell elongation and autolysis inhibition in C. perfringens. These findings demonstrate that simple Zn2+ treatment before experiments stabilizes C. perfringens cells, reducing autolysis under aerobic conditions and facilitating various biological studies, except morphological analyses. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 A Review of the Endoscopic Treatment for Bile Leak Following Cholecystectomy and Hepatic Surgery 321 328 EN Taisuke Obata Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Review 10.18926/AMO/69432 Bile leak occurs in 2-25% of liver transplant, 3-27% of hepatic resection, and 0.1-4% of cholecystectomy cases. The clinical course of bile leak varies depending on the type of surgery that caused the fistula, as well as the type, severity, and timing of bile duct injury. Although infections resulting from bile leak can be life-threatening, the introduction of endoscopic treatment has enabled some patients to avoid reoperation and has reduced the negative impact on quality of life associated with external fistulas for percutaneous drainage. Endoscopic interventions, such as sphincterotomy and stent placement, reduce the pressure gradient between the bile duct and duodenum, facilitating bile drainage through the papilla and promoting the closure of the leak. We reviewed the literature from 2004 to 2024 regarding bile leak following cholecystectomy and liver surgery, examining recommended techniques, timing, and treatment outcomes. In cases of bile leak following cholecystectomy, clinical success was achieved in 72-96% of cases, while success rates for bile leak following liver surgery ranged from 50% to 100%. Although endoscopic treatment is effective, it is not universally applicable, and its limitations must be carefully considered. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 14 17 2025 Risk Factors for Perioperative Urinary Tract Infection After Living Donor Kidney Transplantation Characterized by High Prevalence of Desensitization Therapy: A Single-Center Analysis 6102 EN Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Inoue 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 Ichiro Tsuboi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Moto Tokunaga Department of Urology, NHO Okayama Medical Center 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 Yosuke Mitsui 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 Risa Kubota Department of Urology, NHO Okayama Medical Center Takuya Sadahira 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 Takehiro Iwata 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 Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Edamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Wada Department of Urology, Shimane University Faculty of Medicine Yasuyuki Kobayashi Department of Urology, Hiroshima City Hiroshima Citizens Hospital Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Limited research exists on risk factors for urinary tract infections (UTIs) in kidney transplant recipients, particularly in high-risk groups such as ABO-incompatible or donor-specific antibody (DSA)-positive cases. Early UTIs, especially within the first month post-transplant, impact on acute rejection and long-term graft outcomes, highlighting the need for risk factor identification and management. Methods: Among 157 living donor kidney transplant cases performed at our institution between 2009 and 2024, 128 patients were included after excluding cases with >72 h of perioperative prophylactic antibiotics or urological complications. UTI was defined as the presence of pyuria and a positive urine culture, accompanied by clinical symptoms requiring antibiotic treatment, occurring within one month post-transplantation. Results: The median onset of UTI was postoperative day 8 (interquartile range, IQR: 6.8–9.3). No subsequent acute rejection episodes were observed. The median serum creatinine at 1 month postoperatively was 1.3 mg/dL (IQR: 1.1–1.7), and this was not significantly different from those who did not develop UTI. In univariate analysis, low or high BMI (<20 or >25), longer dialysis duration (>2.5 years), desensitization therapy (plasmapheresis + rituximab), elevated preoperative neutrophil-to-lymphocyte ratio (NLR) (≥3), and longer warm ischemic time (WIT) (≥7.8 min) were significantly associated with an increased infection risk of UTI (p = 0.010, 0.036, 0.028, 0.015, and 0.038, respectively). Multivariate analyses revealed that abnormal BMI, longer dialysis duration, desensitization therapy, and longer WIT were independent risk factors for UTI (p = 0.012, 0.031, 0.008, and 0.033, respectively). The incidence of UTI increased with the number of risk factors: 0% (0/16) for zero, 10% (5/48) for one, 31% (16/51) for two, 45% (5/11) for three, and 100% (2/2) for four risk factors. Conclusions: Desensitization therapy, BMI, dialysis duration, and WIT were identified as independent risk factors for perioperative UTI. In patients with risk factors, additional preventive strategies should be considered, with extended antibiotic prophylaxis being one potential option. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 2352-3727 11 2 2025 Advancements in systemic therapy for muscle-invasive bladder cancer: A systematic review from the beginning to the latest updates 1 13 EN Takafumi Yanagisawa Department of Urology, The Jikei University School of Medicine Akihiro Matsukawa Department of Urology, The Jikei University School of Medicine Jeremy Yuen-Chun Teoh Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Keiichiro Mori Department of Urology, The Jikei University School of Medicine 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 Paweł 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 Marco Moschini Department of Urology, San Raffaele Hospital and Scientific Institute Shahrokh F. Shariat Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Jun Miki Department of Urology, The Jikei University School of Medicine Takahiro Kimura Department of Urology, The Jikei University School of Medicine Context: Several phase III randomized controlled trials (RCTs) have shown the importance of perioperative systemic therapy, especially for the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings for muscle-invasive bladder cancer (MIBC). Objective: To synthesize the growing evidence on the efficacy and safety of systemic therapies for MIBC utilizing the data from RCTs. Evidence acquisition: Three databases and ClinicalTrials.gov were searched in October 2024 for eligible RCTs evaluating oncologic outcomes in MIBC patients treated with systemic therapy. We evaluated pathological complete response (pCR), disease-free survival (DFS), progression-free survival (PFS), event-free survival (EFS), overall survival (OS), and adverse events (AEs). Evidence synthesis: Thirty-three RCTs (including 14 ongoing trials) were included in this systematic review. Neoadjuvant chemotherapy improved OS compared to radical cystectomy alone. Particularly, the VESPER trial demonstrated that dd-MVAC provided oncological benefits over GC alone in terms of pCR rates, OS (HR: 0.71), and PFS (HR: 0.70). Recently, the NIAGARA trial showed that perioperative durvalumab plus GC outperformed GC alone in terms of pCR rates, OS (HR: 0.75), and EFS (HR: 0.68). Despite the lack of data on overall AE rates in the VESPER trial, differential safety profiles in hematologic toxicity were reported between dd-MVAC and durvalumab plus GC regimens. In the adjuvant setting, no study provided the OS benefit from adjuvant chemotherapy. However, only adjuvant nivolumab had significant DFS and OS benefits compared to placebo. Conclusions: Neoadjuvant chemotherapy remains the current standard of care for MIBC. Durvalumab shed light on the promising impact of ICIs added to neoadjuvant chemotherapy. Nivolumab is the only ICI recommended as adjuvant therapy in patients who harbored adverse pathologic outcomes. Ongoing trials will provide further information on the impact of combination therapy, including chemotherapy, ICIs, and enfortumab vedotin, in both neoadjuvant and adjuvant settings. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2624-831X 6 3 2025 An Extension of Input Setup Assistance Service Using Generative AI to Unlearned Sensors for the SEMAR IoT Application Server Platform 52 EN I Nyoman Darma Kotama Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Yohanes Yohanie Fridelin Panduman Graduate School of Information Science and Technology, The University of Osaka Komang Candra Brata Graduate School of Natural Science and Technology, Okayama University Anak Agung Surya Pradhana Graduate School of Natural Science and Technology, Okayama University Noprianto Graduate School of Natural Science and Technology, Okayama University Nowadays, Internet of Things (IoT) application systems are broadly applied to various sectors of society for efficient management by monitoring environments using sensors, analyzing sampled data, and giving proper feedback. For their fast deployment, we have developed Smart Environmental Monitoring and Analysis in Real Time (SEMAR) as an integrated IoT application server platform and implemented the input setup assistance service using prompt engineering and a generative AI model to assist connecting sensors to SEMAR with step-by-step guidance. However, the current service cannot assist in connections of the sensors not learned by the AI model, such as newly released ones. To address this issue, in this paper, we propose an extension to the service for handling unlearned sensors by utilizing datasheets with four steps: (1) users input a PDF datasheet containing information about the sensor, (2) key specifications are extracted from the datasheet and structured into markdown format using a generative AI, (3) this data is saved to a vector database using chunking and embedding methods, and (4) the data is used in Retrieval-Augmented Generation (RAG) to provide additional context when guiding users through sensor setup. Our evaluation with five generative AI models shows that OpenAI’s GPT-4o achieves the highest accuracy in extracting specifications from PDF datasheets and the best answer relevancy (0.987), while Gemini 2.0 Flash delivers the most balanced results, with the highest overall RAGAs score (0.76). Other models produced competitive but mixed outcomes, averaging 0.74 across metrics. The step-by-step guidance function achieved a task success rate above 80%. In a course evaluation by 48 students, the system improved the student test scores, further confirming the effectiveness of our proposed extension. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2078-2489 16 7 2025 A Map Information Collection Tool for a Pedestrian Navigation System Using Smartphone 588 EN Kadek Suarjuna Batubulan Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Komang Candra Brata Graduate School of Natural Science and Technology, Okayama University I Nyoman Darma Kotama Graduate School of Natural Science and Technology, Okayama University Htoo Htoo Sandi Kyaw Graduate School of Natural Science and Technology, Okayama University Shintami Chusnul Hidayati Department of Informatics, Institut Teknologi Sepuluh Nopember Nowadays, a pedestrian navigation system using a smartphone has become popular as a useful tool to reach an unknown destination. When the destination is the office of a person, a detailed map information is necessary on the target area such as the room number and location inside the building. The information can be collected from various sources including Google maps, websites for the building, and images of signs. In this paper, we propose a map information collection tool for a pedestrian navigation system. To improve the accuracy and completeness of information, it works with the four steps: (1) a user captures building and room images manually, (2) an OCR software using Google ML Kit v2 processes them to extract the sign information from images, (3) web scraping using Scrapy (v2.11.0) and crawling with Apache Nutch (v1.19) software collects additional details such as room numbers, facilities, and occupants from relevant websites, and (4) the collected data is stored in the database to be integrated with a pedestrian navigation system. For evaluations of the proposed tool, the map information was collected for 10 buildings at Okayama University, Japan, a representative environment combining complex indoor layouts (e.g., interconnected corridors, multi-floor facilities) and high pedestrian traffic, which are critical for testing real-world navigation challenges. The collected data is assessed in completeness and effectiveness. A university campus was selected as it presents a complex indoor and outdoor environment that can be ideal for testing pedestrian navigations in real-world scenarios. With the obtained map information, 10 users used the navigation system to successfully reach destinations. The System Usability Scale (SUS) results through a questionnaire confirms the high usability. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1999-5903 17 5 2025 An Improved Reference Paper Collection System Using Web Scraping with Three Enhancements 195 EN Tresna Maulana Fahrudin Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Komang Candra Brata Department of Information and Communication Systems, Okayama University Inzali Naing Department of Information and Communication Systems, Okayama University Soe Thandar Aung Department of Information and Communication Systems, Okayama University Amri Muhaimin Department of Data Science, Universitas Pembangunan Nasional Veteran Jawa Timur Dwi Arman Prasetya Department of Data Science, Universitas Pembangunan Nasional Veteran Jawa Timur Nowadays, accessibility to academic papers has been significantly improved with electric publications on the internet, where open access has become common. At the same time, it has increased workloads in literature surveys for researchers who usually manually download PDF files and check their contents. To solve this drawback, we have proposed a reference paper collection system using a web scraping technology and natural language models. However, our previous system often finds a limited number of relevant reference papers after taking long time, since it relies on one paper search website and runs on a single thread at a multi-core CPU. In this paper, we present an improved reference paper collection system with three enhancements to solve them: (1) integrating the APIs from multiple paper search web sites, namely, the bulk search endpoint in the Semantic Scholar API, the article search endpoint in the DOAJ API, and the search and fetch endpoint in the PubMed API to retrieve article metadata, (2) running the program on multiple threads for multi-core CPU, and (3) implementing Dynamic URL Redirection, Regex-based URL Parsing, and HTML Scraping with URL Extraction for fast checking of PDF file accessibility, along with sentence embedding to assess relevance based on semantic similarity. For evaluations, we compare the number of obtained reference papers and the response time between the proposal, our previous work, and common literature search tools in five reference paper queries. The results show that the proposal increases the number of relevant reference papers by 64.38% and reduces the time by 59.78% on average compared to our previous work, while outperforming common literature search tools in reference papers. Thus, the effectiveness of the proposed system has been demonstrated in our experiments. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 0003-2719 58 2 2024 Influence of Dilution Upon the Ultraviolet-Visible Peak Absorbance and Optical Bandgap Estimation of Tin(IV) Oxide and Tin(IV) Oxide-Molybdenum(IV) Sulfide Solutions 196 212 EN Chin Khai Ong School of Engineering and Physical Sciences, Heriot-Watt University Malaysia Weng Nam Lee Heriot-Watt Global College, Heriot-Watt University Malaysia Mohammad Khalid Sunway Centre for Electrochemical Energy and Sustainable Technology (SCEEST), School of Engineering and Technology, Sunway University Muhammad Amirul Aizat Mohd Abdah Sunway Centre for Electrochemical Energy and Sustainable Technology (SCEEST), School of Engineering and Technology, Sunway University Patrik Ohberg Institute of Photonics and Quantum Sciences, School of Engineering and Physical Sciences, Heriot-Watt University Ling Hong Lim Heriot-Watt Global College, Heriot-Watt University Malaysia Yasuhiko Hayashi Graduate School of Natural Science and Technology, Faculty of Engineering, Okayama University Takeshi Nishikawa Graduate School of Natural Science and Technology, Faculty of Engineering, Okayama University Yuenkiat Yap Heriot-Watt Global College, Heriot-Watt University Malaysia The study investigated the constraints associated with the dilution technique in determining the optical bandgap of nanoparticle dispersion and modified nanocomposites, utilizing ultraviolet-visible absorbance spectra and Tauc plot analysis. A case study involving SnO2 dispersion and SnO2-MoS2 nanocomposite solutions, prepared through the direct solution mixing method, was conducted to assess the implications of dilution upon the absorbance spectra and bandgap estimation. The results emphasize the considerable impact of the dilution technique on the measured optical bandgap, demonstrating that higher dilution factors lead to shift in bandgap values. Furthermore, the study highlights that dilution can induce variations in the average nanoparticle sizes due to agglomeration, thereby influencing bandgap estimation. In the context of nanocomposites, the interaction between SnO2 nanoparticles and exfoliated MoS2 nanosheets diminishes with increasing dilution, leading to the estimated optical bandgap being primarily attributable to SnO2 nanoparticles alone. These observations underscore the necessity for caution when employing the dilution technique for bandgap estimation in nanoparticles dispersion and nanocomposites, offering valuable insights for researchers and practitioners in the field. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0781 66 7 2025 Oxygen supply is a prerequisite for response to aluminum in cultured cells of tobacco (Nicotiana tabacum) 1044 1060 EN Yoshiyuki Tsuchiya Institute of Plant Science and Resources, Okayama University Maki Katsuhara Institute of Plant Science and Resources, Okayama University Takayuki Sasaki Institute of Plant Science and Resources, Okayama University Yoko Yamamoto Institute of Plant Science and Resources, Okayama University Responses to aluminum (Al) were investigated in tobacco cells (cell line SL) in a calcium-sucrose solution for up to 24 h under shaking (aerobic) condition. Microarray analysis of upregulated and downregulated genes under Al exposure and following Gene Ontology (GO) enrichment analysis of biological process category revealed only one GO term to be enriched for the upregulated genes, “response to chitin,” annotated with genes encoding transcription factors (NtERF1 and NtMYB3) and MAP kinase (WIPK), and nine GO terms for the downregulated genes, including “cell wall loosening” and “lipid transport,” annotated with genes encoding expansin (NtEXPA4) and lipid transfer protein (LTP)/LTP-like (NtLTP3 and NtEIG-C29), respectively. Al triggered the production of nitric oxide (NO) then reactive oxygen species (ROS). Addition of NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide decreased the levels of NO and a part of the transcriptional changes described above, but increased the levels of ROS and a loss of growth capacity, suggesting a role of the NO to induce the transcriptional changes partly and to repress these toxic responses under Al exposure. Under non-shaking (anaerobic) condition, the cells exhibited upregulation of several hypoxia-responsive genes. The cells exposed to Al exhibited the same level of Al accumulation but much lower levels of the Al responses including NO production, ROS production, a loss of growth capacity, citrate secretion, and a part of the transcriptional changes described above, compared with the cells under shaking condition. These results suggest that coexistence of oxygen with Al is necessary to trigger the Al responses related to toxicity and tolerance. No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science (AAAS) Acta Medica Okayama 2375-2548 11 38 2025 Polymeric microwave rectifiers enabled by monolayer-thick ionized donors eadv9952 EN Nobutaka Osakabe Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Jeongeun Her Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Takahiro Kaneta Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Akiko Tajima Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Elena Longhi School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology Kan Tang Renewable and Sustainable Energy Institute, University of Colorado Boulder Kazuhiro Fujimori Faculty of Environmental, Life, Natural Science and Technology, Okayama University Stephen Barlow School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology Seth R. Marder School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology Shun Watanabe Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Jun Takeya Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Yu Yamashita Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Solution processing of polymeric semiconductors provides a facile way to fabricate functional diodes. However, energy barriers at metal-semiconductor interfaces often limit their performance. Here, we report rectifying polymer diodes with markedly modified energy-level alignments. The gold electrode surface was treated with a dimeric metal complex, which resulted in a shallow work function of 3.7 eV by forming a monolayer-thick ionized donor layer. When a polymeric semiconductor was coated on the treated electrode, most of the ionized donors remained at the metal-semiconductor interface. The confined ionized donors with the ideal thickness enabled fabrication of a polymer diode with a forward current density of over 100 A cm−2. Furthermore, a power conversion efficiency of 7.9% was observed for rectification at a microwave frequency of 920 MHz, which is orders of magnitude higher than that reported for organic diodes. Our findings will pave a way to solution-processed high-frequency and high-power devices. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0014-4800 142 2025 Cross-feeding between beneficial and pathogenic bacteria to utilize eukaryotic host cell-derived sialic acids and bacteriophages shape the pathogen-host interface milieu 104967 EN Darab Ghadimi Department of Microbiology and Biotechnology, Max Rubner-Institut Regina Fölster-Holst Clinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-Holstein Sophia Blömer Clinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-Holstein Michael Ebsen Städtisches MVZ Kiel GmbH (Kiel City Hospital), Department of Pathology Christoph Röcken Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shigenobu Matsuzaki Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University Wilhelm Bockelmann Department of Microbiology and Biotechnology, Max Rubner-Institut Under an inflamed-intestinal milieu, increased free sialic acids are associated with the overgrowth of some pathogenic bacterial strains. Recently, the protective immunomodulatory activity of gut bacteriophages (phages) has also been highlighted. However, the role of phages in triple reciprocal interactions between pathogenic bacteria, beneficial bacteria, and their host cell sialic acids has not been studied so far. We established a sialidase-explicit model in which beneficial and pathogenic bacteria interact through cross-feeding and competition for free sialic acid using a human triple co-culture cell model incorporating colonocytes (T84 cells), monocytes (THP-1 cells), and hepatocytes (Huh7 cells). Triple co-cultured cells were challenged with Gram-positive Bifidobacterium bifidum (B. bifidum) and Gram-negative Pseudomonas aeruginosa PAO1 (P. a PAO1) in the absence or presence of its KPP22 phage in two different cell culture mediums: 1) standard Dulbecco's Modified Eagle Medium (DMEM) and 2) DMEM with 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). Changes in physiological, functional, and structural health markers of stimulated cocultured cells were evaluated. The concentrations of sialic acid and pro-inflammatory cytokines in the cell culture supernatants were quantified. P. a PAO1 triggered the release of interleukin 6 and 8 (IL-6 and IL-8), accompanied by increased levels of free sialic acid, reduced viability of co-cultured cells, and disrupted the integrity of the cellular monolayer. These disruptive effects were markedly attenuated by KPP22 phage and B. bifidum. In addition to well-documented differences in the structure and composition of the bacterial cell walls of Gram-negative pathogenic bacteria and bifidobacteria, two distinct factors seem to be pivotal in modulating the pathogen-host interface milieu: (i) the presence of phages and (ii) the utilization of free sialic acids secreted from host cells by bifidobacteria. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0021-8901 2025 Urbanised landscape and microhabitat differences can influence flowering phenology and synchrony in an annual herb EN Hinata Fujiwara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroto Yamaguchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuyoshi Nakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koki R. Katsuhara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University 1. Flowering phenology, a crucial determinant of plant reproductive success and biotic interactions, is susceptible to urbanisation. Numerous studies have shown the impact of urbanised landscapes on flowering phenology based on comparisons along urban–rural gradients. Phenological patterns among microenvironments in the urban ecosystem have received less attention, although they often offer unique habitats with varying artificial influences, such as roadsides, drainage ditches and vacant lots. If differences in microenvironments diversify flowering phenology, the urban matrix might reduce flowering synchrony with neighbouring populations, limiting outcrossing opportunities and therefore reducing reproductive success. 2. We investigated the flowering phenology and synchrony of the native annual herb Commelina communis in approximately 250 populations at two rural and two urban sites over 3 years. To determine the effect of microhabitat differences, we categorised the microhabitats of C. communis populations into five types: drains, roadsides, vacant land, farmland and forest edge. In some study populations, we investigated reproductive success (seed set) to estimate the degree of outcross pollination limitation. 3. Our findings revealed that populations in urban sites exhibited earlier flowering onset and longer flowering duration compared to rural locations. Besides, we did not detect consistent patterns of flowering onset, peak and duration among the different microhabitat types. For flowering synchrony, we found that the population in urban sites, growing in drain habitats, and with artificial disturbances exhibited relatively lower interpopulation flowering synchrony, suggesting their phenology differed from neighbouring populations within the same landscape. Additionally, populations in urban sites, especially those growing in drain and roadside habitats, suffered severe outcross pollen limitation compared to those in rural landscapes. 4. Synthesis and applications. In conclusion, our results indicate that in addition to landscape changes associated with urbanisation, variations in local microhabitats also influence the flowering phenology and synchrony of C. communis populations. Urbanised landscapes and differences in microhabitats could contribute to the diversification of phenological patterns between populations, potentially having a negative impact on the reproductive success of native plant species. These findings highlight the need to consider not only spatial but also temporal fragmentation from diversified flowering phenology when addressing conservation in the urban matrix. No potential conflict of interest relevant to this article was reported.

Ceramic Society of Japan Acta Medica Okayama 1348-6535 133 1 2025 Comparative study of the effects of fluoride treatment with cyclic variations in pH on the structures of stoichiometric, calcium-deficient, and carbonated hydroxyapatites 15 24 EN Satoshi Hayakawa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yu Okada Graduate School of Natural Science and Technology, Okayama University Tomohiko Yoshioka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University The primary objective of this study was to analyze the effects of fluoride treatment with cyclic variations in pH on the structure of stoichiometric hydroxyapatite (HAp), calcium-deficient HAp (CDHAp), and carbonated HAp (CHAp) powders. The structures of HAp, CDHAp, and CHAp before and after fluoride treatment were investigated using X-ray diffraction, Fourier-transform infrared, Raman, and nuclear magnetic resonance spectroscopic analyses. The fluoride treatment with cyclic variations in pH increased the calcium deficiency in HAp and CHAp but decreased in CDHAp. During fluoride treatment, fluoridated CDHAp or fluoridated calcium-deficient CHAp was formed on the surface of the HAp samples via dissolution and crystal growth, accompanied by the selective elution of component ions and partial substitution of OH− groups in the HAp hexagonal lattice with F− ions. No evidence of the formation of Ca(OH)2 and OH− groups outside the HAp crystal lattice was obtained. A new perspective on the formation of structured water at the surface termination of the OH columns (disordered region), with possible interactions with adsorbed water molecules or nonspecifically adsorbed F− ions was provided. The top surface of the fluoridated CDHAp consisted of an amorphous fluoride-rich hydrated layer, which included calcium phosphate and CaF2. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0003-6072 118 10 2025 Duganella hordei sp. nov., Duganella caerulea sp. nov., and Duganella rhizosphaerae sp. nov., isolated from barley rhizosphere 146 EN Katsumoto Kishiro Institute of Plant Science and Resources, Okayama University Nurettin Sahin Egitim Fakultesi, Mugla Sitki Kocman University Daisuke Saisho Institute of Plant Science and Resources, Okayama University Naoki Yamaji Institute of Plant Science and Resources, Okayama University Jun Yamashita Institute of Plant Science and Resources, Okayama University Yuki Monden Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tomoyuki Nakagawa Faculty of Applied Biological Sciences, Gifu University Keiichi Mochida RIKEN Center for Sustainable Resource Science Akio Tani Institute of Plant Science and Resources, Okayama University Duganella sp. strains R1T, R57T, and R64T, isolated from barley roots in Japan, are Gram-stain-negative, motile, rod-shaped bacteria. Duganella species abundantly colonized barley roots. Strains R1T, R57T, and R64T were capable of growth at 4 °C, suggesting adaptation to colonize winter barley roots. Strains R57T and R64T formed purple colonies, indicating violacein production, while strain R1T did not. Based on 16S rRNA gene sequence similarities, strains R1T, R57T, and R64T were most closely related to D. violaceipulchra HSC-15S17T (99.10%), D. vulcania FT81WT (99.45%), and D. violaceipulchra HSC-15S17T (99.86%), respectively. Their genome sizes ranged from 7.05 to 7.38 Mbp, and their genomic G+C contents were 64.2–64.7%. The average nucleotide identity and digital DNA–DNA hybridization values between R1T and D. violaceipulchra HSC-15S17T, R57T and D. vulcania FT81WT, R64T and D. violaceipulchra HSC-15S17T were 86.0% and 33.2%, 95.7% and 67.9%, and 92.7% and 52.6%, respectively. Their fatty acids were predominantly composed of C16:0, C17:0 cyclo, and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). Based on their distinct genetic and phenotypic characteristics, and supported by chemotaxonomic analyses, we propose that strains R1T, R57T, and R64T represent novel species within the Duganella genus, for which the names Duganella hordei (type strain R1T = NBRC 115982 T = DSM 115069 T), Duganella caerulea (type strain R57T = NBRC 115983 T = DSM 115070 T), and Duganella rhizosphaerae (type strain R64T = NBRC 115984 T = DSM 115071 T) are proposed. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0016-7037 400 2025 Lithium- and oxygen-isotope compositions of a Si-rich nebular reservoir determined from chondrule constituents in the Sahara 97103 EH3 chondrite 51 71 EN Torii Douglas-Song The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Tsutomu Ota The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Masahiro Yamanaka The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Hiroshi Kitagawa The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Ryoji Tanaka The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Christian Potiszil The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Tak Kunihiro The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Here we report the in situ ion-microprobe analyses of the Li- and O-isotope compositions of enstatite, FeO-rich pyroxene, olivine, glass, and cristobalite grains from six chondrule-related objects from the Sahara 97103 EH3 chondrite. The O-isotope composition of the enstatite grains scattered around the intersection between the terrestrial fractionation and primitive chondrule minerals lines. Whereas, that of olivine varied along the primitive chondrule minerals line. Based on the mineralogy, we found cristobalite formed as a result of Si saturation, instead of the reduction of FeO-rich silicates, consistent with Si-enrichment of whole rock enstatite chondrites. Based on the mineralogy and O-isotope compositions, we infer that olivines in some chondrules are relict grains. In chondrules that contained olivine, no abundant niningerite [(Mg,Fe,Mn)S] was observed. Thus, enstatite formation can be explained by the interaction of an olivine precursor with additional SiO2 (Mg2SiO4 + SiO2 → Mg2Si2O6), instead of sulfidation (Mg2SiO4 + S → 1/2 Mg2Si2O6 + MgS + 1/2 O2). Using the equation Mg2SiO4 + SiO2 → Mg2Si2O6 and the O-isotope compositions of enstatite and olivine, the O-isotope composition of the additional SiO2 was estimated. Based on the O-isotope composition, we infer that there could be a Si-rich gas with an elevated Δ17O value similar to, or greater than the second trend line (Δ17O = 0.9 ‰) suggested by Weisberg et al. (2021), during chondrule formation. The variation in the Li-isotope compositions of enstatite and olivine grains from EH3 chondrules is smaller than that for the same phases from CV3 chondrules. The variation in the Li-isotope compositions of the enstatite and olivine grains from EH3 chondrules is also smaller than that of their O-isotope compositions. During the recycling of enstatite-chondrite chondrules, both Li- and O-isotope compositions were homogenized. Although enstatite is the major carrier of Li in EH3 chondrules, the Li-isotope composition (δ7Li) of enstatite is lower than that of whole rock EH3 chondrites, suggesting the existence of a phase with higher δ7Li. Meanwhile, the Li-isotope composition and concentration (δ7Li, [Li]) of enstatite is higher than that of olivine. The Li-isotope composition of the Si-rich gas was estimated to be δ7Li = 1 ‰, using a similar mass-balance calculation as applied for the O-isotope composition. The Li-isotope composition of the Si-rich gas from the enstatite-chondrite-chondrule forming-region, is consistent with that of whole rock EH3 chondrites, and differs significantly from that of the Si-rich gas from the carbonaceous-chondrite-chondrule forming-region (δ7Li = −11 ‰) determined by a previous study. We speculate that the Si-rich gas in the carbonaceous-chondrite-chondrule forming-region maintained the Li-isotope heterogeneity inherited from light lithium synthesized by galactic cosmic-ray spallation in the interstellar medium. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0889 198 1 2025 The thylakoid membrane remodeling protein VIPP1 forms bundled oligomers in tobacco chloroplasts kiaf137 EN Sarah W Gachie Institute of Plant Science and Resources, Okayama University Alexandre Muhire Institute of Plant Science and Resources, Okayama University Di Li Institute of Plant Science and Resources, Okayama University Akihiro Kawamoto Institute for Protein Research, Osaka University Noriko Takeda-Kamiya Mass Spectrometry and Microscopy Unit, RIKEN Center for Sustainable Resource Science Yumi Goto Mass Spectrometry and Microscopy Unit, RIKEN Center for Sustainable Resource Science Mayuko Sato Mass Spectrometry and Microscopy Unit, RIKEN Center for Sustainable Resource Science Kiminori Toyooka Mass Spectrometry and Microscopy Unit, RIKEN Center for Sustainable Resource Science Ryo Yoshimura Institute of Plant Science and Resources, Okayama University Tsuneaki Takami Institute of Plant Science and Resources, Okayama University Lingang Zhang School of Life Sciences, Inner Mongolia University/Key Laboratory of Herbage and Endemic Crop Biotechnology Genji Kurisu Institute for Protein Research, Osaka University Toru Terachi Faculty of Life Sciences, Kyoto Sangyo University Wataru Sakamoto Institute of Plant Science and Resources, Okayama University The thylakoid membrane (TM) serves as the scaffold for oxygen-evolving photosynthesis, hosting the protein complexes responsible for the light reactions and ATP synthesis. Vesicle inducing protein in plastid 1 (VIPP1), a key protein in TM remodeling, has been recognized as essential for TM homeostasis. In vitro studies of cyanobacterial VIPP1 demonstrated its ability to form large homo-oligomers (2 MDa) manifesting as ring-like or filament-like assemblies associated with membranes. Similarly, VIPP1 in Chlamydomonas reinhardtii assembles into rods that encapsulate liposomes or into stacked spiral structures. However, the nature of VIPP1 assemblies in chloroplasts, particularly in Arabidopsis, remains uncharacterized. Here, we expressed Arabidopsis thaliana VIPP1 fused to GFP (AtVIPP1-GFP) in tobacco (Nicotiana tabacum) chloroplasts and performed transmission electron microscopy (TEM). A purified AtVIPP1-GFP fraction was enriched with long filamentous tubule-like structures. Detailed TEM observations of chloroplasts in fixed resin-embedded tissues identified VIPP1 assemblies in situ that appeared to colocalize with GFP fluorescence. Electron tomography demonstrated that the AtVIPP1 oligomers consisted of bundled filaments near membranes, some of which appeared connected to the TM or inner chloroplast envelope at their contact sites. The observed bundles were never detected in wild-type Arabidopsis but were observed in Arabidopsis vipp1 mutants expressing AtVIPP1-GFP. Taken together, we propose that the bundled filaments are the dominant AtVIPP1 oligomers that represent its static state in vivo. No potential conflict of interest relevant to this article was reported.

岡山大学法学会 Acta Medica Okayama 0386-3050 75 1 2025 併行給付・重複填補論の検討 84 57 EN K. Hamaguchi No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 14 17 2025 Evaluation of the Diagnostic Performance of the Brush/Biopsy Rapid On-Site Evaluation (B-ROSE) in Cases of Bile Duct Stricture: A Prospective, Pilot Study 6207 EN Nao Hattori Department of Gastroenterology, Okayama University Hospital Daisuke Uchida Department of Gastroenterology, Okayama University Hospital Kei Harada Department of Gastroenterology, Okayama University Hospital Ryosuke Sato Department of Gastroenterology, Okayama University Hospital Taisuke Obata Department of Gastroenterology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology, Okayama University Hospital Hiroyuki Terasawa Department of Gastroenterology, Okayama University Hospital Yuki Fujii Department of Gastroenterology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology, Okayama University Hospital settingsOrder Article Reprints Open AccessArticle Evaluation of the Diagnostic Performance of the Brush/Biopsy Rapid On-Site Evaluation (B-ROSE) in Cases of Bile Duct Stricture: A Prospective, Pilot Study by Nao Hattori 1,Daisuke Uchida 1,2,*,Kei Harada 1,Ryosuke Sato 1ORCID,Taisuke Obata 1,Akihiro Matsumi 1ORCID,Kazuya Miyamoto 1ORCID,Hiroyuki Terasawa 1ORCID,Yuki Fujii 1,Koichiro Tsutsumi 1ORCID,Shigeru Horiguchi 1,Kazuyuki Matsumoto 1ORCID andMotoyuki Otsuka 1 1 Department of Gastroenterology, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan 2 Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan * Author to whom correspondence should be addressed. J. Clin. Med. 2025, 14(17), 6207; https://doi.org/10.3390/jcm14176207 Submission received: 23 June 2025 / Revised: 21 August 2025 / Accepted: 26 August 2025 / Published: 2 September 2025 (This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine) Downloadkeyboard_arrow_down Browse Figures Versions Notes Abstract Background: Biliary strictures are diagnosed using endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology and biopsy. However, brush cytology shows a sensitivity of 9–56.1% and a diagnostic accuracy of 43–65.4%, while biopsy demonstrates a sensitivity of 48%. Both methods exhibit high specificity but limited sensitivity. While rapid on-site evaluation (ROSE) is effective in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), its application in ERCP-obtained samples remains underexplored. Methods: This prospective pilot study was conducted at Okayama University Hospital from April 2019 to July 2024. Patients requiring ERCP-guided sampling for bile duct strictures were included. ROSE was applied to brush cytology with up to three additional attempts and to imprint cytology from biopsy samples with up to two attempts. Diagnostic accuracy was assessed based on pathology and clinical course. Results: Among 37 patients (median age: 73 years, add range, and male–female ratio: 27:10), 18 had hilar and 19 had distal bile duct strictures. Brush cytology required one, two, or three attempts in twenty-six, six, and five cases, respectively, whereas biopsy required one or two attempts in thirty-five and two cases, respectively. Among the thirty-seven cases, thirty-five were malignant and two were benign. The B-ROSE group showed a sensitivity, specificity, and accuracy of 71.4%, 100.0%, and 73.0%, respectively, compared to lower accuracy in the conventional group, where single brush cytology attempts yielded a sensitivity of 48.6% and an accuracy of 48.6%, and single biopsy attempts showed a sensitivity of 68.6% and an accuracy of 70.3%. Conclusions: B-ROSE improves diagnostic accuracy, reduces repeat sampling, and minimizes patient burden in ERCP-based diagnosis of bile duct strictures, making it a valuable addition to current diagnostic protocols. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 1071-5762 2025 Pseudohypoxia induced by iron chelator activates tumor immune response in lung cancer EN Yusuke Hamada 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 Yuehua Chen Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Manato Terada Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuze Wang Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masayoshi Fujisawa 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 Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hypoxia-inducible factor (HIF) signaling plays a critical role in immune cell function. Pseudohypoxia is characterized as iron-mediated stabilization of HIF-1α under normoxic conditions, which can be induced by iron chelators. This study explored whether iron chelators exert antitumor effects by enhancing tumor immune responses and elucidating the underlying mechanisms. The iron chelators Super–polyphenol 10 (SP10) and Deferoxamine (DFO) were used to create iron-deficient and pseudohypoxia conditions. Pseudohypoxia induced by iron chelators stimulates IL-2 secretion from T cells and from both human and murine nonsmall cell lung cancer (NSCLC) cell lines (A549, PC-3, and LLC). Administration of SP10 reduced tumor growth when LLC tumors were implanted in C57BL/6 mice; however, this was not observed in immunodeficient RAG1-deficient C57BL/6 mice. SP10 itself did not directly inhibit LLC cells proliferation in vitro, suggesting an activation of the tumor immune response. SP10 synergistically enhanced the efficacy of PD-1 antibody therapy in lung cancer by increasing the number of tumor-infiltrating lymphocytes (TILs). In conclusion, iron chelation-induced pseudohypoxia activates tumor immune responses by directly upregulating HIF-1α, augmenting T cell function, and inducing IL-2 secretion from T cells, and cancer cells, thereby amplifying the immune efficacy of the PD-1 antibody in lung cancer treatment. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-7080 13 4 2025 An Implementation of Creep Test Assisting System with Dial Gauge Needle Reading and Smart Lighting Function for Laboratory Automation 139 EN Dezheng Kong Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shihao Fang Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Noprianto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mitsuhiro Okayasu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pradini Puspitaningayu Department of Electrical Engineering, Universitas Negeri Surabaya For decades, analog dial gauges have been essential for measuring and monitoring data at various industrial instruments including production machines and laboratory equipment. Among them, we focus on the instrument for creep test in a mechanical engineering laboratory, which evaluates material strength under sustained stress. Manual reading of gauges imposes significant labor demands, especially in long-duration tests. This burden further increases under low-lighting environments, where poor visibility can lead to misreading data points, potentially compromising the accuracy of test results. In this paper, to address the challenges, we implement a creep test assisting system that possesses the following features: (1) to save the installation cost, a web camera and Raspberry Pi are employed to capture images of the dial gauge and automate the needle reading by image processing in real time, (2) to ensure reliability under low-lighting environments, a smart lighting mechanism is integrated to turn on a supplementary light when the dial gauge is not clearly visible, and (3) to allow a user to stay in a distant place from the instrument during a creep test, material break is detected and the corresponding message is notified to a laboratory staff using LINE automatically. For evaluations, we install the implemented system into a material strength measuring instrument at Okayama University, Japan, and confirm the effectiveness and accuracy through conducting experiments under various lighting conditions. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 2 2025 令和６年度岡山医学会賞　胸部・循環研究奨励賞（砂田賞） 43 45 EN Takahiro Nishihara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0956-5663 287 2025 A plant-insertable multi-enzyme biosensor for the real-time monitoring of stomatal sucrose uptake 117674 EN Shiqi Wu Graduate School of Information, Production and Systems, Waseda University Wakutaka Nakagawa Graduate School of Information, Production and Systems, Waseda University Yuki Mori Faculty and Graduate School of Environmental Engineering, The University of Kitakyushu Saman Azhari Graduate School of Information, Production and Systems, Waseda University Gábor Méhes Graduate School of Information, Production and Systems, Waseda University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Tomonori Kawano Faculty and Graduate School of Environmental Engineering, The University of Kitakyushu Takeo Miyake Graduate School of Information, Production and Systems, Waseda University Monitoring sucrose transport in plants is essential for understanding plant physiology and improving agricultural practices, yet effective sensors for continuous and real-time in-vivo monitoring are lacking. In this study, we developed a plant-insertable sucrose sensor capable of real-time sucrose concentration monitoring and demonstrated its application as a useful tool for plant research by monitoring the sugar-translocating path from leaves to the lower portion of plants through the stem in living plants. The biosensor consists of a bilirubin oxidase-based biocathode and a needle-type bioanode integrating glucose oxidase, invertase, and mutarotase, with the two electrodes separated by an agarose gel for ionic connection. The sensor exhibits a sensitivity of 6.22 μA mM−1 cm−2, a limit of detection of 100 μM, a detection range up to 60 mM, and a response time of 90 s at 100 μM sucrose. Additionally, the sensor retained 86 % of its initial signal after 72 h of continuous measurement. Day-night monitoring from the biosensor inserted in strawberry guava (Psidium cattleianum) showed higher sucrose transport activity at night, following well the redistribution of photosynthetically produced sugars. In addition, by monitoring the forced translocation of sucrose dissolved in the stable isotopically labeled water, we demonstrated that a young seedling of Japanese cedar known as Sugi (Cryptomeria japonica) can absorb and transport both water and sucrose through light-dependently opened stomata, which is the recently revealed path for liquid uptake by higher plants. These findings highlight the potential of our sensor for studying dynamic plant processes and its applicability in real-time monitoring of sugar transport under diverse environmental conditions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 8 2025 Craniofacial Fibrous Dysplasia to Affect or Not the Optic Nerve in Long-Term Follow-Up of Three Cases e91072 EN Toshihiko Matsuo Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama University Hospital Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kiyoshi Yamada Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mitsuhiro Okano Department of Otorhinolaryngology, School of Medicine, International University of Health and Welfare Fibrous dysplasia of the bone is characterized by immature fibrous bones of trabeculae and fibrovascular proliferation in the medulla. In this study, we report three consecutive patients with craniofacial fibrous dysplasia with or without optic nerve involvement. In Case 1, a 43-year-old man with blurred vision in the right eye at the first visit was well until the age of 54 years, when he came back with symptoms suggestive of paranasal sinusitis. Computed tomography scans disclosed a mucocele in the right sphenoid sinus and thickened bilateral ethmoid, sphenoid, and frontal bones. He underwent an emergency nasal endoscopic surgery to make a drainage opening to the sphenoid and ethmoid sinuses on the right side with incomplete success. The pathology of the resected tissue confirmed fibrous dysplasia. With intravenous antibiotics, he recovered from blepharoptosis, complete ophthalmoplegia, and visual acuity decrease on the right side. He was well until the age of 71 years when he had a self-limiting episode of visual field cloudiness caused by the right sphenoid sinus mucocele. At the age of 75 years, he developed abrupt vision loss to no light perception in the right eye. He underwent an open skull surgery to extirpate the sphenoid mucocele on the right side and died of an unknown cause two years later. In Case 2, a 29-year-old man had a two-week-long headache, and computed tomography scans revealed fibrous dysplasia in the bilateral sphenoid bones. Nasal biopsy at the spheno-ethmoid recess proved a pathological diagnosis of fibrous dysplasia. Goldmann perimetry showed normal visual fields in both eyes. He was followed every year by magnetic resonance imaging to maintain normal visual fields until the latest visit at the age of 41 years. In Case 3, a 12-year-old girl was referred to an ophthalmologist to check her vision. She had been diagnosed with fibrous dysplasia of the left maxillary bone at the age of six years by a dentist. She had a gingival resection on the left maxilla at the age of 15 years and had a left maxillary bone resection at 18 years at another hospital. One month after the resection, Goldmann perimetry showed superior peripheral field depression in the left eye, in contrast with the normal visual field in the right eye. She maintained the visual acuity of 1.5 in both eyes until the last visit at the age of 21 years. In fibrous dysplasia as a rare disease, functional and cosmetic problems, including vision problems, should be considered in a case-based approach. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 4 3 2025 Occupational therapist‐guided exercise increased white blood cell and neutrophil counts during clozapine treatment: A case report e70167 EN Kenji Hinotsu Department of Neuropsychiatry, Okayama University Hospital Shinji Sakamoto Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshio Ohya Department of Neuropsychiatry, Okayama University Hospital Akiyoshi Yokode Department of Neuropsychiatry, Okayama University Hospital Takahiro Asada Department of Neuropsychiatry, Okayama University Hospital Yuko Okahisa Department of Neuropsychiatry, Okayama University Hospital Manabu Takaki Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background: Moderate exercise increases white blood cells and neutrophils. However, there are no reports on the relationship between exercise intensity and these cells. We observed a patient taking clozapine whose white blood cell and neutrophil counts were borderline. Supervised exercise therapy with an occupational therapist stabilized these counts. Case Presentation: A 50-year-old woman with treatment-resistant schizophrenia was prescribed clozapine. By Day 63, the clozapine dosage had been increased to 450 mg/day. Additionally, she was advised to perform a 30-min walking exercise program 1 h before blood tests. Exercise therapy supervised by an occupational therapist was performed eight times, and self-training was performed five times. Exercise intensity was monitored using the Borg Scale for subjective evaluation and the Karvonen formula for objective evaluation. Supervised exercise therapy with an occupational therapist resulted in greater increases on the Borg Scale and Karvonen formula than did self-training. It also induced increases in white blood cells and neutrophils. Her psychiatric symptoms improved, and she was discharged on Day 71. A blood test taken after discharge revealed that her white blood cell and neutrophil counts were within the normal range and she continued to take clozapine for 2 years. She has since been able to enjoy a calm and relaxed life at home. Conclusion: Exercise involving subjective and objective evaluation by an occupational therapist effectively increased white blood cells and neutrophils during clozapine treatment. Supervised exercise therapy by an occupational therapist is important when self-exercise is insufficient for continuing clozapine treatment. No potential conflict of interest relevant to this article was reported.

Japan Surgical Society Acta Medica Okayama 2198-7793 11 1 2025 Obese Patient with Gastric Diverticulum Undergoing Laparoscopic Sleeve Gastrectomy Guided by Preoperative Endoscopic Measurement: A Case Report and Literature Review cr.25-0141 EN Kensuke Hirosuna Center for Graduate Medical Education, Okayama University Hospital Hajime Kashima 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 Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshihiko Kakiuchi 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 Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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 INTRODUCTION: Gastric diverticulum is a rare condition, often asymptomatic and incidentally detected. Laparoscopic sleeve gastrectomy (LSG) is a widely performed bariatric procedure, but a gastric diverticulum complicates surgical planning. In this case, careful preoperative assessment allowed safe execution of LSG despite the diverticulum’s proximity to the esophagogastric junction. CASE PRESENTATION: A 45-year-old woman (BMI: 46.8 kg/m2) with hypertension, dyslipidemia, and glucose intolerance was referred for bariatric surgery after unsuccessful weight loss with conservative management. Preoperative endoscopy revealed an 18 × 14 mm gastric diverticulum on the posterior wall of the gastric fundus, 40 mm from the esophagogastric junction. LSG was performed using a surgical stapler, ensuring complete diverticulum resection while preserving gastric tube integrity. The surgery was uneventful, with minimal blood loss and a duration of 2 hours and 52 minutes. The patient had an uneventful postoperative course and was discharged on day 9. Her BMI decreased to 39.3 kg/m2 at the 1-year follow-up, with improved metabolic parameters. CONCLUSIONS: This case highlights the importance of thorough preoperative evaluation when performing LSG in patients with gastric diverticulum. Accurate endoscopic measurement of the diverticulum’s location aids in determining the optimal resection line, ensuring surgical safety and efficacy. Surgeons should remain vigilant when encountering such anatomical variations to optimize outcomes in bariatric surgery. No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 189 2025 大学院生が自らの造形行為を省察する事例研究 ─保育者としての学びをつくるオートエスノグラフィー─ 75 85 EN Shuya OHIRA Faculty of Education，Okayama University Sayaka SEGIRI Okayama University Graduate School of Education Master's Course Kyogo KURIHARA Menoto childcare center Miho AOE Okayama University Graduate School of Education Master's Course Akiko TSURUMI Okayama University Kindergarten 10.18926/bgeou/69239 　本研究では，造形行為と，その造形行為の記録を振り返ることによって「自己省察」する学びの過程をオートエスノグラフィーとし，保育者を目指す大学院生である第3 筆者，及び現職の保育者の大学院生である第2 筆者と第4 筆者にもたらしたオートエスノグラフィーの学びの作用を検討した。第1 筆者，第2 筆者，第3 筆者，第4 筆者が協働した造形行為では，個々の造形物が自ずと繋がり合い1 つになっていく過程がビデオ記録された。また，造形行為の過程で見たり，感じたり，気付いたりしたことと，ビデオ記録を振り返ることで見たり，感じたり，気付いたりしたことの差異を学びとして第2 筆者，第3 筆者，第4 筆者が「自己省察」した。この「自己省察」は，保育者にとっての新たな視点を導き出す契機となり,保育における省察の在り方とも深く共通する点で，保育者養成にて経験する意義がある。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 189 2025 ウィトゲンシュタイン哲学に基づく授業分析研究 ―理科の授業を支える「信用」の基底性― 1 17 EN Yoshitsugu HIRATA Faculty of Education，Okayama University 10.18926/bgeou/69234 　本研究は、小学校4 年生の単元「月と星」（50 分×3 回）の授業に会話分析を施したうえで、ウィトゲンシュタインの『確実性について』における信用概念に依拠した考察を加えた。ここで言う信用とは、子どもが教師や教材を端的に信じることを指しており、言語ゲームの学習を基底において支えているものである。理科の授業は科学的条件を重視しようとすればするほど、授業が成立しなくなってしまうという逆説を抱えているが、この逆説による破綻を回避するものとして、科学的でも合理的でもない信用があることを指摘した。本研究は、先行研究において理論的に指摘されるに留まっていた非合理的な概念変容の過程を、実践的に明らかにしたものである。 No potential conflict of interest relevant to this article was reported.

American Physiological Society Acta Medica Okayama 1040-0605 329 1 2025 Activated factor X inhibition ameliorates NF-κB-IL-6-mediated perivascular inflammation and pulmonary hypertension L183 L196 EN Satomi Imakiire Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Keiji Kimuro Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Keimei Yoshida Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Kohei Masaki Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Ryo Izumi Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Misaki Imabayashi Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Takanori Watanabe Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Tomohito Ishikawa Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Kazuya Hosokawa Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Shouji Matsushima Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Toru Hashimoto Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Keisuke Shinohara Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Shunsuke Katsuki Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Tetsuya Matoba Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Katsuya Hirano Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University Hiroyuki Tsutsui Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Kohtaro Abe Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Activated factor X (FXa) induces inflammatory response and cell proliferation in various cell types via activation of proteinase-activated receptor-1 (PAR1) and/or PAR2. We thus aimed to investigate the impact of FXa on the development of pulmonary arterial hypertension (PAH) and the mechanisms involved. The effects of edoxaban, a selective FXa inhibitor, on hemodynamic, right ventricular (RV) hypertrophy, and vascular remodeling were evaluated in a monocrotaline (MCT)-exposed pulmonary hypertension (PH) rat model. At 21 days after a single subcutaneous injection of MCT of 60 mg/kg, right ventricular systolic pressure (RVSP) and total pulmonary vascular resistance index (TPRI) were elevated concomitant with the increased plasma FXa and lung interleukin-6 (IL-6) mRNA. Daily administration of edoxaban (10 mg/kg/day, by gavage) starting from the day of MCT injection for 21 days ameliorated RVSP, TPRI, RV hypertrophy, pulmonary vascular remodeling, and macrophage accumulation. Edoxaban reduced nuclear factor-kappa B (NF-κB) activity and IL-6 mRNA level in the lungs of MCT-exposed rats. mRNA levels of FXa, PAR1, and PAR2 in cultured pulmonary arterial smooth muscle cells (PASMCs) isolated from patients with PAH were higher than those seen in normal PASMCs. FXa stimulation increased cell proliferation and mRNA level of IL-6 in normal PASMCs, both of which were blunted by edoxaban and PAR1 antagonist. Moreover, FXa stimulation activated extracellularly regulated kinases 1/2 in a PAR1-dependent manner. Inhibition of FXa ameliorates NF-κB-IL-6-mediated perivascular inflammation, pulmonary vascular remodeling, and the development of PH in MCT-exposed rats, suggesting that FXa may be a potential target for the treatment of PAH. NEW & NOTEWORTHY This study demonstrated that chronic treatment with activated factor X (FXa) inhibitor ameliorated NF-κB-IL-6-mediated perivascular inflammation in a rat model with pulmonary arterial hypertension, which is associated with elevated FXa activity. FXa may act on pulmonary arterial smooth muscle cells, inducing cell proliferation and inflammatory response via upregulated PAR1, thereby contributing to pulmonary vascular remodeling. Understanding the patient-specific pathophysiology is a prerequisite for applying FXa-targeted therapy to the treatment of pulmonary arterial hypertension. 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 Evaluation of a novel central venous access port for direct catheter insertion without a peel-away sheath 282 289 EN Toshihiro Iguchi Department of Radiology, Okayama University Hospital Takahiro Kawabata Department of Radiology, Okayama University Hospital Yusuke Matsui Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Tomita Department of Radiology, Okayama University Hospital Mayu Uka Department of Radiology, Okayama University Hospital Noriyuki Umakoshi Department of Radiology, Okayama University Hospital Soichiro Okamoto Department of Radiology, Okayama University Hospital Kazuaki Munetomo Department of Radiology, Okayama University Hospital Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose This study retrospectively evaluated the feasibility and safety of implanting a newly developed central venous access port (CV-port) that allows catheter insertion into a vein without the use of a peel-away sheath, with a focus on its potential to minimize risks associated with conventional implantation methods. Materials and methods All procedures were performed using a new device (P-U CelSite Port™ MS; Toray Medical, Tokyo, Japan) under ultrasound guidance. The primary endpoint was the implantation success rate. The secondary endpoints were the safety and risk factors for infection in the early postprocedural period (< 30 days). Results We assessed 523 CV-port implantations performed in a cumulative total of 523 patients (240 men and 283 women; mean age, 61.6 ± 13.1 years; range, 18–85 years). All implantations were successfully performed using an inner guide tube and over-the-wire technique through 522 internal jugular veins and one subclavian vein. The mean procedural time was 33.2 ± 10.9 min (range 15–112 min). Air embolism, rupture/perforation of the superior vena cava, or hemothorax did not occur during catheter insertion. Eleven (2.1%) intraprocedural complications occurred, including Grade I arrhythmia (n = 8) and subcutaneous bleeding (n = 1), Grade II arrhythmia (n = 1), and Grade IIIa pneumothorax (n = 1). Furthermore, 496 patients were followed up for ≥ 30 days. Six early postprocedural complications were encountered (1.1%), including Grade IIIa infection (n = 4), catheter occlusion (n = 1), and skin necrosis due to subcutaneous leakage of trabectedin (n = 1). These six CV-ports were withdrawn, and no significant risk factors for infection in the early postprocedural period were identified. Conclusion The implantation of this CV-port device demonstrated comparable success and complication rates to conventional devices, with the added potential benefit of eliminating complications associated with the use of a peel-away sheath. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 15 1 2024 Neurotransmitter recognition by human vesicular monoamine transporter 2 7661 EN Dohyun Im Department of Cell Biology, Graduate School of Medicine, Kyoto University Mika Jormakka Department of Cell Biology, Graduate School of Medicine, Kyoto University Narinobu Juge Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University Jun-ichi Kishikawa Department of Applied Biology, Kyoto Institute of Technology Takayuki Kato Institute for Protein Research, Osaka University Yukihiko Sugita Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University Takeshi Noda Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University Tomoko Uemura Department of Cell Biology, Graduate School of Medicine, Kyoto University Yuki Shiimura Department of Cell Biology, Graduate School of Medicine, Kyoto University Takaaki Miyaji Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University Hidetsugu Asada Department of Cell Biology, Graduate School of Medicine, Kyoto University So Iwata Department of Cell Biology, Graduate School of Medicine, Kyoto University Human vesicular monoamine transporter 2 (VMAT2), a member of the SLC18 family, plays a crucial role in regulating neurotransmitters in the brain by facilitating their uptake and storage within vesicles, preparing them for exocytotic release. Because of its central role in neurotransmitter signalling and neuroprotection, VMAT2 is a target for neurodegenerative diseases and movement disorders, with its inhibitor being used as therapeutics. Despite the importance of VMAT2 in pharmacophysiology, the molecular basis of VMAT2-mediated neurotransmitter transport and its inhibition remains unclear. Here we show the cryo-electron microscopy structure of VMAT2 in the substrate-free state, in complex with the neurotransmitter dopamine, and in complex with the inhibitor tetrabenazine. In addition to these structural determinations, monoamine uptake assays, mutational studies, and pKa value predictions were performed to characterize the dynamic changes in VMAT2 structure. These results provide a structural basis for understanding VMAT2-mediated vesicular transport of neurotransmitters and a platform for modulation of current inhibitor design. No potential conflict of interest relevant to this article was reported.