The Company of Biologists Acta Medica Okayama 2046-6390 15 2 2026 Gap junction-mediated signaling coordinates Rhodopsin coupling for Drosophila color vision bio062463 EN Xuanshuo Zhang Division of Biological Sciences, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ryoki Shinjo Division of Biological Sciences, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Manabu Kitamata Division of Health Science, Advanced Comprehensive Research Organization, Teikyo University Shinichi Otsune Division of Biological Sciences, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hideki Nakagoshi Division of Biological Sciences, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The Drosophila compound eye is composed of approximately 800 ommatidia, and every ommatidium contains eight photoreceptor cells, six outer cells (R1-R6) and two inner cells (R7 and R8), and accessory cells (cone and pigment cells). The expression of rhodopsin genes in R7 and R8 is highly coordinated through an instructive signal from R7 to R8. The activity of the homeodomain protein Defective proventriculus in R1 is also required to transmit this instructive signal, suggesting that cell–cell communication between R7, R1, and R8 is important to generate the pattern of Rh expression in R7/R8 (Rhodopsin coupling). As cell junctions play crucial roles in maintaining the structural and functional integrity of tissues, we tested whether cell junction proteins are involved in the interactions between photoreceptor cells. Here, we demonstrate that gap junction proteins innexin 2 and innexin 7 in accessory cells are necessary for transmitting signals from R7 to R8. In addition, Notch-mediated accessory cell development and Rhodopsin coupling in R7/R8 are highly correlated. Our results provide evidence that functional coupling of two different neurons, R7 and R8, is established through gap junction-mediated signaling from adjacent accessory cells. 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 初任保育教諭の語りに見る園児の在園時間の違いによる実践上の課題 139 152 EN Kazuya HASUI Faculty of Health and Welfare， Kawasaki University of Medical Welfare Mika KATAYAMA Faculty of Education, Graduate School of Science, Okayama University 10.18926/CTED/70365 　本論では，幼保連携型認定こども園の特徴である園児の在園時間の違いに焦点を当て，初任保育教諭への面接調査により実践上の課題と対応について検討した。その結果，保育教諭が８つの課題を認識していることが明らかになった。また，『幼保連携型認定こども園教育・保育要領』に記述されている「遊びの連続性を保障する保育の展開」に関する課題に加えて，記述されていない「多様な在園時間や生活形態を考慮した園児理解」に関する新たな課題が見出された。認定区分による在園時間の違いは園生活における時間的スケジュールや場所，集団の違いを余儀なくされる。そのため，保育教諭が設定するねらいに基づいた園生活で何を共通経験とすべき内容として設定し，何を経験差として活かし，どのような保育を実践するか明確にすべく，これまで認定こども園で積み重ねられてきた好実践例を集積・整理し，指標を明示することが今後の課題である。 No potential conflict of interest relevant to this article was reported.

一般社団法人粉体粉末冶金協会 Acta Medica Okayama 0532-8799 73 3 2026 熱間静水圧加圧法を用いたイットリア安定化ジルコニア緻密層の低温形成 55 59 EN Kyohei MANABE Osaka Gas Co. Ltd. Mitsuaki ECHIGO Osaka Gas Co. Ltd. Akira KISHIMOTO Institute of Academic and Research, Faculty of Environmental, Life, Natural Science and Technology, Okayama University The sintering conditions using hot isostatic press (HIP) of yttria-stabilized zirconia (YSZ) were investigated to obtain a dense YSZ layer at low sintering temperature such as 1000°C for an electrolyte of metal-supported solid oxide fuel cell. It was found that a dense YSZ pellet with relative density of 93% could be obtained under a sintering condition of 1000°C-10 hours with HIP in 195 MPa. On the other hand, in X-ray diffraction analysis of the dense YSZ pellet, peaks of the monoclinic phase were slightly detected in addition to peaks of the cubic phase. From energy dispersive X-ray spectroscopy analysis, a small amount of boron was detected in the dense YSZ pellet. It is considered that the YSZ crystalline phase transformation of cubic to monoclinic phase was occurred by the boron diffusion from the diffusion barrier coating of metal foil capsule used for the HIP. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2192-4449 15 1 2026 A case of tubulointerstitial nephritis with infiltration of neutrophils and interleukin-17-positive cells associated with Behçet’s disease 35 EN Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Keiko Tanaka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Natsuki Kubota Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Behçet’s disease (BD) is a non-infectious inflammatory condition characterized by neutrophilic infiltration. In addition to primary symptoms, including oral and genital ulcers, ocular involvement, and skin lesions, BD can also affect various organs. However, renal involvement, particularly in tubulointerstitial nephritis, has rarely been described. Herein, a rare case of acute tubulointerstitial nephritis in a patient clinically diagnosed with BD is reported. The renal lesion presented with other symptoms of BD and fever, and was considered to be BD-related due to the presence of neutrophilic infiltration and its responsiveness to BD-directed therapy. Alterations in T-helper (Th) 1, Th2, and Th17 cytokine profiles are associated with BD activity. Interleukin (IL)-17 plays a central role in neutrophil activation, and recent studies have demonstrated a strong correlation between IL-17A levels and BD activity. In the present case, elevated serum IL-17A levels and infiltration of IL-17A-positive cells into the renal tissue reflected an active phase of BD and a BD-associated renal lesion. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1424-8220 25 21 2025 Integrated Authentication Server Design for Efficient Kerberos–Blockchain VANET Authentication 6651 EN Maya Rahayu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Md. Biplob Hossain Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Samsul Huda Interdisciplinary Education and Research Field, Okayama University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Vehicular Ad Hoc Network (VANET) is a fundamental component of the intelligent transportation systems (ITS), providing critical road information to users. However, the volatility of VANETs creates significant vulnerabilities from malicious actors. Thus, verifying joining entities is crucial to maintaining the VANET’s communication security. Authentication delays must stay below 100 ms to meet VANET requirements, posing a major challenge for security. Our previous research introduced a Kerberos–Blockchain (KBC) authentication system that contains two main components separately: Authentication Server (AS) and Ticket Granting Server (TGS). However, this KBC architecture required an additional server to accommodate increasing vehicle volumes in urban environments, leading to higher infrastructure costs. This paper presents an integrated authentication server that merges AS and TGS into a Combined Server (CBS) while retaining blockchain security. We evaluate it using OMNeT++ with SUMO for traffic simulation and Ganache for blockchain implementation. Results show that CBS removes the need for an extra server while keeping authentication delays under 100 ms. It also improves throughput by 104% and reduces signaling overhead by 45% compared to KBC. By optimizing authentication without compromising security, the integrated server greatly enhances the cost-effectiveness and efficiency of VANET systems. 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.

MDPI AG Acta Medica Okayama 2076-3417 16 5 2026 Concentration-Dependent Synergistic Interfacial Interactions Between Multifunctional Acrylate and Silane Coupling Agents in an Organic–Inorganic Nanohybrid Material 2339 EN Yukinori Maruo Department of Prosthodontics, Okayama University Kumiko Yoshihara Health Research Institute, National Institute of Advanced Industrial Science and Technology Masao Irie Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University Naoki Kodama Department of Prosthodontics, Okayama University Mai Yoshizane Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaro Akiyama Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Synergistic effects of a multifunctional acrylate and a long-chain silane coupling agent were investigated in an organic–inorganic nanohybrid material. We tested the bond strength of nanohybrid composites treated with experimental primers containing silane coupling agents―3-methacryloxypropyl trimethoxysilane (γ-MPTS) or 8-methacryloxyoctyl trimethoxysilane (8-MOTS)―with or without multifunctional acrylates―trimethylolpropane triacrylate (A-TMPT) or dipentaerythritol hexaacrylate (A-DPH). Shear bond strength was evaluated after 24 h of water storage at 37 °C. Untreated control and silane-only groups exhibited low shear bond strengths (e.g., control: 2.4 ± 2.0 MPa) and failed exclusively at the adhesive interface. While addition of A-TMPT did not significantly improve bond strength, addition of A-DPH produced significantly higher shear bond strengths. Highest strength was achieved with 30% 8-MOTS and A-DPH (22.4 ± 6.1 MPa), followed by 20% γ-MPTS and A-DPH (19.0 ± 7.0 MPa), and A-DPH groups produced cohesive failures. Regardless of the silane used (γ-MPTS or 8-MOTS), incorporating A-DPH in the primer consistently yielded superior bond strengths, indicating a promising strategy for improved adhesion for such nanohybrid systems. These findings provide new insights into optimizing resin–filler interfacial interactions and may contribute to the development of restorative materials with improved long-term clinical durability. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2218-273X 16 2 2026 Targeting the Gut in Sepsis: Therapeutic Potential of Medical Gases 199 EN Tetsuya Yumoto 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 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 Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, often resulting in multiorgan dysfunction. Among affected systems, the gastrointestinal tract plays a central role in sepsis progression by promoting systemic inflammation through impaired barrier function, immune imbalance, and microbiome alterations. Recent research has identified selected medical gases and gasotransmitters as promising therapeutic candidates for preserving gut integrity in sepsis. In particular, hydrogen, carbon monoxide, and hydrogen sulfide exhibit antioxidative, anti-inflammatory, and cytoprotective properties. These gases act through defined molecular pathways, including activation of Nrf2, inhibition of NF-κB, and preservation of tight junction integrity, thereby supporting intestinal barrier function. In addition, they influence immune cell phenotypes and autophagy, with indirect effects on the gut microbiome. Although most supporting evidence derives from preclinical models, translational findings and emerging safety data highlight the potential of gut-targeted gas-based strategies. This review summarizes current mechanistic and translational evidence for gut-protective medical gases in sepsis and discusses their integration into future organ-specific and mechanism-based therapeutic approaches. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2261 25 1 2025 Prognostic value of right atrial strain in patients with chronic heart failure 908 EN Rie Nakayama Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Yoichi Takaya Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Mitsutaka Nakashima Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Takahiro Nishihara Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Norihisa Toh Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Miyoshi Toru Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Kazufumi Nakamura Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Shinsuke Yuasa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Aims Right ventricular dysfunction is a well-established prognostic marker in patients with heart failure (HF). However, the prognostic significance of right atrial (RA) function remains unclear. Given its sensitivity to systemic congestion, RA function may provide additional insights into HF disease progression and management. This study aimed to investigate whether RA reservoir function serves as an independent prognostic indicator in patients with chronic HF. Methods A total of 613 patients with chronic HF and a left ventricular (LV) ejection fraction of less than 50% who underwent echocardiographic assessment at Okayama University Hospital between January 2018 and March 2023 were included (median age: 68 (58–76) years; 69% male). RA reservoir function was quantified using two-dimensional speckle-tracking echocardiography. The primary endpoint was cardiovascular death or HF-related hospitalization. Kaplan–Meier survival analysis was performed to examine the association between RA reservoir function and clinical outcomes. Results During a median follow-up period of 41 months (range: 12–91 months), 119 patients experienced cardiac events. Compared with event-free patients, those with cardiac events exhibited a significantly larger RA maximum volume index (38 mL/m2 vs. 31 mL/m2, P < 0.001) and a significantly lower RA reservoir longitudinal strain (RASr) (17% vs. 22%, P < 0.001). Kaplan–Meier analysis demonstrated that patients with RASr ≤ 20% had significantly poorer event-free survival than those with RASr > 20%, even without RA volume enlargement (log-rank test, P < 0.001). Multivariate Cox regression analysis identified RASr as an independent predictor of cardiac events (hazard ratio: 0.95, 95% confidence interval: 0.93 to 0.97, P < 0.001). Conclusions In patients who experienced adverse cardiac events, a reduced RASr and an increased RA maximum volume were observed. Furthermore, a reduced RASr was independently associated with an increased risk of cardiovascular death and HF-related hospitalization in patients with chronic HF and LV dysfunction. These findings indicate that RASr may serve as a valuable prognostic marker for the risk stratification and management of chronic HF. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 7 2025 The Challenge of Diagnosing Scirrhous Gastric Cancer by Endoscopic Biopsy: A Case Report e87334 EN Yuka Ikeda Department of Internal Medicine, Clinic IkedaDepartment of Internal Medicine, Clinic Ikeda Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Takehiro Tanaka Department of Pathology, Okayama University Hospital Nobumasa Ikeda Department of Internal Medicine, Clinic Ikeda Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Scirrhous gastric cancer, also known as linitis plastica, is a rare and aggressive subtype of gastric carcinoma that poses significant diagnostic challenges due to its submucosal infiltration and often normal-appearing mucosa. We report a case involving a 30-year-old Japanese woman who presented with a six-month history of epigastric pain and postprandial vomiting. Initial endoscopic examination revealed erythema and mucosal swelling, with limited antral distensibility and resistance during duodenal intubation. Despite 12 mucosal biopsies, histopathological examination revealed no evidence of malignancy. Given the strong clinical and endoscopic suspicion of scirrhous gastric cancer, additional deep sections and immunohistochemical staining were performed. These revealed scattered signet-ring cell carcinoma and poorly differentiated adenocarcinoma, with positive immunostaining for p53 and Ki67. The patient underwent total gastrectomy, and the diagnosis of scirrhous gastric cancer was confirmed on the resected specimen. This case highlights the importance of a high index of clinical suspicion, close collaboration between endoscopists and pathologists, and the utility of ancillary diagnostic tools, such as immunohistochemistry, in identifying subepithelial gastric malignancies that may be missed on conventional biopsy. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2577-171X 9 2 2026 Mitrofanoff Appendicovesicostomy With Boari Flap for Complete Female Urethral Transection: A Case Report e70154 EN Kohei Mori 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 Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Tominaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuichiro Yamasaki Department of Urology, Kanagawa Children's Medical Center Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Female urethral complete transection caused by pelvic trauma is extremely rare, and no standard management has been established when urethral reconstruction is not feasible. Case Presentation: A woman in her twenties sustained an open pelvic fracture with perineal injury due to a traffic accident. Complete urethral transection was identified, and a suprapubic cystostomy was placed. After staged vaginal reconstruction and bladder function evaluation, a Mitrofanoff appendicovesicostomy was performed. Because the appendix was not enough to reach the umbilicus, a Boari flap was created to compensate for the length. Urodynamic evaluation showed improvement from a preoperative high-pressure bladder to increased compliance postoperatively, though pharmacological management was still required. Postoperatively, the patient achieved stable clean intermittent catheterization without complications. Conclusion: The Mitrofanoff procedure can be an effective option in female urethral injuries where reconstruction is impossible. The addition of a Boari flap may expand its applicability by overcoming conduit length limitations. No potential conflict of interest relevant to this article was reported.

American Society for Horticultural Science Acta Medica Okayama 0018-5345 61 2 2026 Interactive Effects of Maximum Daytime and Minimum Nighttime Temperatures on Spinach Growth and Physiological Characteristics 444 451 EN Nethone Samba Faculty of Food and Agricultural Sciences, Fukushima University Hisao Akasaka The United Graduate School of Agricultural Sciences, Iwate University, Iwate, 020-8550, Japan; and Iwate Agricultural Research Center, Kenpoku Agricultural Research Institute Ken-ichiro Yasuba Graduate School of Environmental and Life Science, Okayama University Tanjuro Goto Graduate School of Environmental and Life Science, Okayama University Minori Hikawa-Endo Graduate School of Environmental and Life Science, Okayama University Yoko Miyama Faculty of Food and Agricultural Sciences, Fukushima University, Fukushima, 960-1296, Japan; and The United Graduate School of Agricultural Sciences, Iwate University High temperatures restrict spinach growth, and the plant’s growth and physiological responses to heat remain poorly understood. It remains unclear whether high daytime or elevated nighttime temperatures have a more negative impact on spinach growth. In addition, the interaction effect of maximum daytime and minimum nighttime temperatures on spinach growth remains unknown. This study was conducted to address these issues. Spinach was grown in controlled environments under four temperature treatments: 30 and 20 °C (T30/20), 30 and 25 °C (T30/25), 35 and 20 °C (T35/20), and 35 and 25 °C (T35/25). These treatments represent the maximum daytime temperature and minimum nighttime temperature, respectively, and were maintained for 45 days. Plant growth characteristics were monitored, and the physiological responses to temperature regimes were assessed. The results show that compared with T30/20, dry matter production decreased by 15.4% with increased nighttime temperature (T30/25), decreased by 42.3% with increased daytime temperature (T35/20), and decreased by 57.7% when both daytime and nighttime temperatures were increased (T35/25). However, there was no statistically significant interaction effect (P > 0.05) between daytime maximum and nighttime minimum temperatures on plant biomass production variables. In comparison with T30/20, the T35/25 treatment increased significantly plant stomatal conductance, stomatal apertures, transpiration rate, and leaf temperature during heat waves. The T35/25 treatment also decreased the quantum efficiency in light compared with the other treatments. Plant biomass production did not improve with the T35/20 and T35/25 treatments, likely as a result of a decoupling of photosynthesis and stomatal conductance during heat waves. Overall, these results reveal that maximum daytime and minimum nighttime temperatures exert additive effects on spinach growth. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1664-462X 16 2025 Structural analysis of PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte alga Rhodomonas sp. NIES-2332 1716939 EN Wenyue Zhang Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nozomi Yonehara Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mizuki Ishii Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haowei Jiang Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Romain La Rocca Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pi-Cheng Tsai Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hongjie Li Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koji Kato Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Fusamichi Akita Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jian-Ren Shen Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Light energy is converted to chemical energy by two photosystems (PSI and PSII) in complex with their light-harvesting complex proteins (LHCI and LHCII) in photosynthesis. Rhodomonas is a member of cryptophyte alga whose LHCs contain unique chlorophyll a/c proteins (ACPs) and phycobiliproteins. We purified PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte Rhodomonas sp. NIES-2332 and analyzed their structures at high resolutions of 2.08 Å and 2.17 Å, respectively, using cryo-electron microscopy. These structures are largely similar to those reported previously from two other species of cryptophytes, but exhibited some differences in both the pigment locations and subunit structures. A part of the antenna subunits of both photosystems is shifted compared with the previously reported structures from other species of cryptophytes, suggesting some differences in the energy transfer rates from the antenna to the PSI and PSII cores. Newly identified lipids are found to occupy the interfaces between the antennae and cores, which may be important for assembly and stabilization of the supercomplexes. Water molecules surrounding three iron-sulfur clusters of the PSI core are found in our high-resolution structure, some of which are conserved from cyanobacteria to higher plants but some are different. In addition, our structure of PSII-ACPII lacks the subunits of oxygen-evolving complex as well as the Mn4CaO5 cluster, suggesting that the cells are in the S-growth phase, yet the PSI-ACPI structure showed the binding of PsaQ, suggesting that it is in an L-phase. These results suggest that the S-phase and L-phase can co-exist in the cryptophytic cells. The high-resolution structures of both PSI-ACPIs and PSII-ACPIIs solved in this study provide a more solid structural basis for elucidating the energy transfer and quenching mechanisms in this group of the organisms. 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.

IOP Publishing Acta Medica Okayama 1742-6588 3027 1 2025 LES analysis to investigate a random-phase forcing scheme for steadying anisotropic turbulence fields 012009 EN Koki Minami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroki Suzuki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Toshinori Kouchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kento Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The aim of this study is to investigate the effect of phase randomization on forcing mechanisms that stabilize localized turbulence. A trigonometric forcing based on vector potential is combined with uniform random numbers to create a spatially homogeneous forcing field. The analysis is performed using large-eddy simulation (LES) with the Smagorinsky model as the subgrid scale model. The results demonstrate that steady flows are generated regardless of the presence of phase randomization, successfully forming isotropic turbulence. In contrast, for anisotropic turbulent fields, the addition of phase randomization reduces the degree of anisotropy, indicating a smoothing effect on the anisotropy of the flow. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2590-1230 27 2025 Inscribed-type spherical speed reducer with uniform reduction ratio in all directions 106742 EN Seiya Naramura Faculty of Environmental, Life, Natural Science and Technology, Okayama University Koichi Tonegawa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University So Shimooka Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tomoaki Yano Faculty of Environmental, Life, Natural Science and Technology, Okayama University Akio Gofuku Okayama Prefectural University Nagayoshi Kasashima National Institute of Advanced Industrial Science and Technology Tetsushi Kamegawa Faculty of Environmental, Life, Natural Science and Technology, Okayama University A spherical motor is an actuator that can generate rotational motion about all three orthogonal axes. However, it is difficult to obtain high output torque from most electromagnetic spherical motors, primarily due to limitations inherent in electromagnetic actuators, such as restricted magnetic force and thermal constraints. Since its torque cannot be increased using planar gears, spherical speed reducers that transmit rotational torque along three orthogonal axes through sphere-to-sphere contact are required. One major limitation of conventional spherical speed reducers is that their size increases significantly as the reduction ratio becomes higher. To address this issue, we propose a novel inscribed-type spherical speed reducer, in which the deceleration mechanism is integrated within the output sphere. This configuration enables a more compact design, reducing the overall size to approximately half that of conventional designs. To predict the angular velocity and transmitted torque, theoretical models for the rotation and torque transmission of the speed reducer were developed. According to the proposed model, the reduction ratio of the spherical speed reducer is 1/3. To verify the validity of these models, experiments were conducted to measure angular velocity and torque. The theoretical results agreed well with the experimental results. In addition, the theoretical torque exhibited an average relative error of 1.63 % compared to the experimental result. Therefore, it was confirmed that the rotation and torque transmission models were valid. These results demonstrate that a reduction ratio can be obtained in all directions of the 3-DOF of the spherical speed reducer, unlike conventional 1-DOF reducers. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0003-9861 779 2026 Comparison of bioavailability of quercetin and its structural analogs in mice 110775 EN Nozomi Maeda Graduate School of Environmental and Life Science, Okayama University Atsushi Hashimoto Graduate School of Environmental and Life Science, Okayama University Ryosei Morita Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Flavonoids are thought to provide beneficial effects on health. However, there are still uncertainties regarding their bioavailability. In this study, we investigated the bioavailability of 6 flavonoids, galangin, kaempferol, quercetin, myricetin, fisetin, and luteolin, by oral administration to mice. Analysis of plasma concentrations of free flavonoids after deconjugation by LC-MS/MS revealed that all flavonoids were rapidly absorbed after administration. Among 6 flavonoids, kaempferol and fisetin showed high absorbed amounts in blood plasma. With the LogP value of the two flavonoids as the maximum value, the amount absorbed decreased for both lower and higher LogP values. The results of the tissue distribution of galangin, kaempferol, and quercetin suggested that the order of fastest movement from the stomach to the small intestine was kaempferol > quercetin > galangin. In addition, the amount of kaempferol and quercetin distributed in the liver was greater than that of galangin. These results suggest that the bioavailability of flavonoids varies with the slight structural differences, possibly due to differences in their rapid accessibility to the small intestine that is the primary site of absorption and metabolism within the body. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2050-3911 2026 2 2026 Feedback-Controlled Beam Pattern Measurement Method Using a Power-Variable Calibration Source for Cosmic Microwave Background Telescopes 023F01 EN Haruaki Hirose Department of Physics, Graduate School of Engineering Science, Yokohama National University Masaya Hasegawa Institute of Particle and Nuclear Studies (IPNS), High Energy Accelerator Research Organization (KEK) Daisuke Kaneko International Center for Quantum-field Measurement Systems for Studies of the Universe and Particles (WPI-QUP), High Energy Accelerator Research Organization (KEK) Taketo Nagasaki Accelerator Laboratory (ACCL), High Energy Accelerator Research Organization (KEK) Ryota Takaku Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tijmen de Haan Institute of Particle and Nuclear Studies (IPNS), High Energy Accelerator Research Organization (KEK) Satoru Takakura Department of Physics, Faculty of Science, The University of Tokyo Takuro Fujino International Center for Quantum-field Measurement Systems for Studies of the Universe and Particles (WPI-QUP), High Energy Accelerator Research Organization (KEK) We demonstrate a novel beam pattern measurement method for the side lobe characterization of cosmic microwave background telescopes. The method employs a power-variable artificial microwave source under feedback control from the detector under test on the telescope. It enables us to extend the dynamic range of the beam pattern measurement without introducing nonlinearity effects from the detector. We conducted a laboratory-based proof-of-concept experiment, measuring the H-plane beam pattern of a horn antenna coupled to a diode detector at 81 GHz. We gained an additional dynamic range of 60.3 dB attributed to the feedback control. In addition, we verified the measurement by comparing it with other reference measurements obtained using conventional methods. The method is also applicable to general optical measurements requiring a high dynamic range to detect subtle nonidealities in the characteristics of optical devices. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 1 2026 Saliva as a Reliable and Non-invasive Sample for Detecting Influenza A in Severe Acute Respiratory Infection Cases e100872 EN Junko S Takeuchi Department of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health Security Nobuaki Matsunaga Antimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health Security Ai Tsukada Antimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health Security Noriko Iwamoto Disease Control and Prevention Center, Japan Institute for Health Security Noriko Fuwa Disease Control and Prevention Center, Japan Institute for Health Security Takahiro Ichikawa Department of Infectious Diseases, Sapporo City General Hospital Yasuyuki Kato Department of Infectious Diseases, International University of Health and Welfare (IUHW) Narita Hospital Yuka Tomita Department of Infectious Diseases, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital Hiroki Kitagawa Department of Infectious Diseases, Hiroshima University Hospital Masaya Yamato Department of General Internal Medicine and Infectious Diseases, Rinku General Medical Center Tetsuji Aoyagi Department of Clinical Infectious Diseases, Tohoku University Graduate School of Medicine Hideharu Hagiya Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryota Hase Department of Infectious Diseases, Japanese Red Cross Narita Hospital Shuji Hatakeyama Division of Infectious Diseases, Jichi Medical University Hospital Tohru Inaba Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine Koichi Izumikawa Yoshio Takesue Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences Moto Kimura Department of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health Security Norio Ohmagari Disease Control and Prevention Center, Japan Institute for Health Security Background Nasopharyngeal swab sampling remains the gold standard for influenza diagnosis; however, it has several limitations, including dependence on medical staff, invasiveness, potential for nosocomial transmission, and occupational exposure risk. Non-invasive alternatives, such as saliva and nasal vestibular swabs, may improve patient comfort and participation in clinical studies. In addition, diagnosis with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) is often delayed because it requires trained laboratory technicians and facilities with appropriate laboratory settings. Although rapid diagnostic devices such as the GenPad® offer potential alternatives to RT-qPCR, their performance with non-invasive samples remains insufficiently explored. This study addresses the two key questions for influenza detection in severe acute respiratory infection (SARI) cases: (i) whether saliva or nasal vestibular swab samples serve as suitable alternatives to nasopharyngeal swab samples, and (ii) whether the GenPad® provides a reliable option for detecting influenza using saliva samples. Methodology A prospective observational study was conducted with 16 inpatients classified as having SARIs and diagnosed with influenza between December 2024 and March 2025 in Japan. Paired saliva and nasal vestibular swab samples were collected 1-9 (median = 3.5) days after symptom onset. RT-qPCR testing was performed according to the National Institute of Infectious Diseases protocol. Saliva samples were also tested using the GenPad® system. Comparisons between sample types and diagnostic methods were analyzed using the exact McNemar's test. Results Among the 16 influenza-positive patients, saliva samples demonstrated higher sensitivity (87.5%) than nasal vestibular swabs (31.3%) in RT-qPCR when compared with the diagnostic results obtained from nasopharyngeal swabs. A comparison of RT-qPCR results between saliva and nasal vestibular swabs revealed a total agreement of 43.8%, with exact McNemar's test showing a significant difference (p = 0.0039). While nasal vestibular swabs showed inconsistent results, saliva samples consistently tested positive, particularly within seven days of symptom onset (100% positive agreement). The GenPad®, a rapid diagnostic device, showed promising performance (92.9%) using saliva samples compared to RT-qPCR. Conclusions Saliva is a reliable non-invasive alternative to nasopharyngeal swabs for influenza detection in SARI cases, particularly within seven days of symptom onset, whereas nasal vestibular swabs show lower sensitivity. Additionally, the GenPad® provides comparable performance to RT-qPCR using saliva samples, offering a rapid, portable diagnostic option. These approaches may mitigate discomfort, minimize infection risk for healthcare workers, and improve testing capacity. However, the absence of influenza-negative controls and the small sample size (n = 16) substantially limit the assessment of diagnostic accuracy and specificity. As a result, the broader applicability of our findings should be interpreted with caution, and further studies are required to validate these observations. 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 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 Usefulness of D-dimer Assay to Confirm the Course of Overt Venous Thromboembolism (VTE) in Cancer Patients 1 7 EN Hidenaru Yamaoka Department of Cardiovascular Medicine, IMS Tokyo Katsushika General Hospital Masashi Yoshida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Sarashina Seisukai Kuroda Clinic Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuru Munemasa Department of Cardiovascular Medicine, Okayama Rosai Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/70067 Venous thromboembolism (VTE) is a serious complication in patients with cancer. In this population, the presence of thrombi is often assessed at cancer diagnosis by measuring D-dimer levels, which have high sensitivity but low specificity for identifying VTE at this clinical time point. However, the usefulness of D-dimer measurement during anticoagulation therapy has not been fully established, despite its widespread use. In this retrospective observational study, we investigated whether D-dimer measurement during anticoagulation therapy in cancer patients could predict overt VTE at follow-up. The study included patients who underwent D-dimer testing and contrast-enhanced computed tomography between 30 and 100 days after initiation of anticoagulation therapy. Eighty-two patients were included: 60 with cancer and 22 without. The diagnostic performance of D-dimer for overt VTE was as follows: sensitivity, 85.7%; specificity, 87.2%; positive predictive value, 78.3%; and negative predictive value, 89.2%. These findings suggest that D-dimer measurement at follow-up has high sensitivity and specificity for overt VTE in cancer patients and may aid in assessing thrombotic status. Clinically, if anticoagulation therapy is continued until D-dimer levels become negative, the absence of overt VTE could be inferred without additional invasive testing. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2950-3299 33 4 2025 Collagen depletion by pirfenidone enhances antitumor effect of oncolytic adenovirus against peritoneal metastases of gastric cancer 201045 EN Tomohiro Okura 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 Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Mikane 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 Ema Mitsui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Une Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara 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 Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Ohtsuka Laboratory of Fundamental Oncology, National Cancer Center Research Institute Rieko Ohki Laboratory of Fundamental Oncology, National Cancer Center Research Institute Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Cancer-associated fibroblasts (CAFs) play a crucial role in collagen accumulation, which develops and promotes peritoneal metastasis (PM) in gastric cancer (GC). In addition, the abundant stromal collagens in the tumor microenvironment function as a physical barrier against penetration of antitumor drugs and oncolytic viruses. This study investigated whether collagen depletion by pirfenidone (PFD), an antifibrotic drug, enhances the antitumor effects of oncolytic adenoviruses. Analysis of the clinical samples revealed a significant association of high expression of collagen 1 and α-smooth muscle actin (α-SMA) with PM development and poor prognosis of advanced GC. Human and murine GC cells enhanced collagen production by fibroblasts, which was suppressed by PFD. Abundant fibroblasts and collagen inhibited the penetration of OBP-702, which reduced the antitumor effects of OBP-702 in the spheroid model. Intraperitoneal co-injection of GC cells and fibroblasts promoted the development of collagen-rich PM and reduced the antitumor effects of OBP-702 in vivo model. PFD suppressed collagen production in PM and improved viral penetration into the tumors, which enhanced the antitumor effects of OBP-702 against PM of GC. Collagen depletion by PFD enhances the penetration of OBP-702 into PM of GC, in turn enhancing the antitumor effects of OBP-702 against PM of GC. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 1 2026 Central Serous Chorioretinopathy in Parallel With Onset and Relapses of Minimal Change Nephrotic Syndrome: A 28-Year Case Follow-Up e102426 EN Toshihiko Matsuo Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takehiro Tanaka Department of Pathology, 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 Central serous chorioretinopathy is an idiopathic disease that manifests as one or several localized, small, dome-shaped serous retinal detachments on fundus examination. The pathophysiology involves fluid leakage from the choroidal capillaries, known as the choriocapillaris, into the subretinal space through sites of damage in the retinal pigment epithelium. This case report discusses the underlying causes of central serous chorioretinopathy-like findings in minimal change nephrotic syndrome. The patient was a 33-year-old woman who developed nephrotic syndrome that was confirmed to be minimal change disease by renal biopsy. She experienced two major relapses of nephrotic syndrome at the ages of 36 and 41 years. She also had a minor relapse at the age of 37 years, five months after the first major relapse at the age of 36 years, as well as four additional minor relapses at the ages of 44, 46, 50, and 51 years. The onset of central serous chorioretinopathy-like manifestations, which were localized to the left eye, occurred three months after the initial onset of nephrotic syndrome at the age of 33 years. Two subsequent episodes of relapse of central serous chorioretinopathy-like manifestations were observed in both eyes at intervals of five months and one month, respectively, after major relapses of nephrotic syndrome at the ages of 36 and 41 years. Thereafter, she did not develop further central serous chorioretinopathy-like manifestations. She discontinued oral prednisolone at the age of 54 years and experienced no further relapses of nephrotic syndrome through her latest visit at the age of 61 years. She maintained normal renal function and good visual acuity in both eyes. The long-term, consistent temporal association between episodes of central serous chorioretinopathy and the onset and relapses of minimal change nephrotic syndrome is strongly supported by longitudinal clinical observations spanning 28 years. This parallel course suggests a possible shared pathophysiological mechanism or common triggering factors underlying both diseases. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 1 2026 Exploratory Analysis for Development Predictive Models of Immune Checkpoint Inhibitor-Induced Myocarditis Using a Nationwide Claims Database 66 73 EN Reina Yamamoto Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Koki Nakagomi Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Miyu Uchiyama Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ayana Michihara Department of Pharmacy, Okayama University Hospital Aya F. Ozaki Department of Clinical Pharmacy Practice, School of Pharmacy & Pharmaceutical Sciences, University of California Pranav M. Patel Division of Cardiology, School of Medicine, University of California Maki Tanioka Medical AI Project, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Yoshito Zamami Department of Pharmacy, Okayama University Hospital Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Immune checkpoint inhibitors (ICIs), essential in cancer therapy, can cause severe immune-related adverse events (irAEs), including myocarditis with a high fatality rate. Currently, the pathogenesis, biomarkers, and risk factors of ICI-induced myocarditis (ICIM) are not fully understood. This exploratory study aimed to develop machine learning-based models to predict the onset of ICIM within 3 months of starting ICI therapy, using a large health insurance database. The models were constructed using the Light Gradient Boosting Machine (LightGBM) and Random Forest algorithms, incorporating clinical variables such as comorbidities and prior medication classifications. In this study, a strategy combining undersampling and bagging was used to minimize the impact of highly imbalanced datasets. The Random Forest model demonstrated superior performance compared with the LightGBM model, and the SHapley Additive exPlanations (SHAP) analysis for the Random Forest model revealed that the concurrent use of ICIs was the most important variable for predictions. Although predictive performance remains limited (AUROC ≈ 0.63), this exploratory framework demonstrates the feasibility of developing data-driven risk prediction models for ICIM. Future studies with expanded datasets and integration of laboratory parameters are warranted to improve predictive accuracy and potential clinical applicability. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0014-4800 145 2026 Assessing the role of folate syntrophy and folate cross-feeding in the pathobiology of infectious-inflamed milieu caused by Fusobacterium nucleatum 105021 EN Darab Ghadimi Department of Microbiology and Biotechnology, Max Rubner-Institut Sophia Blömer Faculty of Medicine, Christian-Albrechts-University of Kiel Aysel Şahin 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 Diet and nutrition affect almost every biological process, including multiple chronic diseases, diabetes, and some cancers. However, there are still significant gaps in our understanding of the importance of nutrition and healthy diets in syntrophy with respect to cross-feeding of the microbe-microbe and the microbe-host in the pathobiology of the infectious-inflamed intestinal milieu caused by anaerobic opportunistic bacteria such as Fusobacterium nucleatum (F. nucleatum). We examined the immune outcomes of three-member folate syntrophy and cross-feeding between F. nucleatum bacteria, endogenous folate-producing gut bacteria, and host cells at the host-pathogen interface using a triple co-culture model. T84, THP-1, and Huh7 cells were inoculated with F. nucleatum for 6 h in regular DMEM, DMEM with 9.5 μM folic acid, or with/without a mixture of Bifidobacterium longum subsp. infantis (B. infantis) and Escherichia coli Nissle 1917 (EcN). Cytokine secretion, cometabolite levels (ammonia, indoles), cell viability, and barrier integrity were assessed. F. nucleatum-induced folate depletion was associated with increased IL-1β and IL-6 and decreased IL-22, along with reduced transepithelial electrical resistance (TEER) and cell viability in T84 cells. Folate supplementation mitigated these effects. The mixture of B. infantis and EcN reduced F. nucleatum-induced pro-inflammatory cytokines, increased IL-22, and improved TEER and cell viability. These protective effects were enhanced by the addition of folate. F. nucleatum also elevated ammonia and reduced indoles, effects reversed by B. infantis and EcN. In addition to the intrinsic pathogenicity of harmful bacteria, folate deprivation, microbe–microbe folate syntrophy, and microbe–host folate cross-feeding contribute to the pathobiology of anaerobic opportunistic bacteria and influence the physiological fate of host cells. A combination of B. infantis and EcN modulates the infectious-inflamed interface through a cytoprotective effect and mechanical competitive extrusion of pathogenic F. nucleatum. These results provide potential insights into the mechanisms of early-onset colorectal cancer, and evidently, require future studies using patient-derived organoids and in vivo systems to improve clinical relevance. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1663-9812 16 2025 Regulatory considerations for developing phage therapy medicinal products for the treatment of antimicrobial resistant bacterial infections 1713471 EN Ai Fukaya-Shiba Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency Akiko Ogata Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency Ryosuke Kuribayashi Office of Cellular and Tissue-based Products, Pharmaceuticals and Medical Devices Agency Akira Sakurai Office of Cellular and Tissue-based Products, Pharmaceuticals and Medical Devices Agency Kanako Suzuki Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency Shunsuke Takadama Office of New Drug IV, Pharmaceuticals and Medical Devices Agency Jihei Nishimura Office of New Drug IV, Pharmaceuticals and Medical Devices Agency Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hiroki Ohge Department of Infectious Diseases, Hiroshima University Hospital Takamasa Takeuchi Pathogen Genomics Center, National Institute of Infectious Diseases, Japan Institute for Health Security Hideyuki Tamaki Biomanufacturing Process Research Center, National Institute of Advanced Industrial Science and Technology Tetsuya Matsumoto Department of Infectious Diseases, International University of Health and Welfare Kotaro Kiga Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Hidetomo Iwano Laboratory of Veterinary Biochemistry, Rakuno Gakuen University School of Veterinary Medicine Recently, there have been growing expectations that treatment of infections with bacteriophages (phages), viruses which specifically infect bacteria, can be used as a treatment option for antimicrobial resistant bacterial infections. In Europe and the United States, in addition to phage therapy as a form of personalized medicine, development of pre-defined phage therapy medicinal products (PTMPs) is progressing, and clinical trials are underway. From October 2024 to July 2025, the Pharmaceuticals and Medical Devices Agency exchanged opinions on trends and points to consider in drug development of PTMPs used for antimicrobial resistant bacterial infections with external experts. Development of PTMPs for regulatory approval requires quality control strategies, establishment of manufacturing methods, non-clinical evaluations, and clinical trial plans based on the characteristics of the phage. In this document, based on the regulatory and development trends in Europe and the United States, the current considerations on quality, non-clinical evaluation, and clinical trial planning including the Cartagena Act in the development of PTMPs in Japan are summarized. The basic concepts presented here are intended to be applied to antimicrobial resistant bacterial infections targeted by PTMPs but can be mostly applicable to bacterial infections in general. We hope that these findings will further accelerate more active development of PTMPs towards timely patient access to innovative products. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 0963-6897 35 2026 Addition of human platelet lysate to islet culture medium suppresses islet loss and improves transplantation outcomes EN Hirofumi Noguchi Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus Chika Miyagi-Shiohira Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Issei Saitoh Department of Pediatric Dentistry, Asahi University School of Dentistry No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1758-5902 18 1 2025 A Procedural Transhiatal Approach for the Thoracic Para‐Aortic Lymph Node: A Case Report e70066 EN Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushige Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hijiri Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe 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 The thoracic posterior para-aortic lymph node (TPAN) is classified as an extra-regional lymph node in esophageal cancer, with metastasis indicating poor prognosis. However, some cases with suspected TPAN metastasis may benefit from esophagectomy with lymph node dissection, including TPAN. This report presents the case of a 58-year-old man with upper thoracic esophageal squamous cell carcinoma and suspected simultaneous TPAN metastasis who underwent neoadjuvant chemotherapy followed by thoracoscopic subtotal esophagectomy and procedural transhiatal TPAN dissection. This transhiatal approach provided direct access to the lymph node without additional thoracic incisions, ensuring safe resection in coordination with the assistant and following anatomical landmarks systematically. Pathological examination showed a false-positive TPAN finding, though the patient later developed distant recurrence. Compared with conventional approaches, this transhiatal technique allows for procedural and reproducible lymphadenectomy while minimizing respiratory burden. This case highlights the feasibility of a transhiatal approach for TPAN dissection. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2025 Genotype–Phenotype Correlations of Li–Fraumeni Syndrome in Japan Children's Cancer Group LFS20 Study Cohort EN Fumito Yamazaki Department of Pediatrics, Keio University School of Medicine Yoshiko Nakano Department of Genetic Medicine and Services, National Cancer Center Hospital Masashi Sanada Department of Advanced Diagnosis, Clinical Research Center, NHO Nagoya Medical Center Hiroki Kurahashi Division of Molecular Genetics, Center for Medical Science, Fujita Health University Shunsuke Miyai Division of Molecular Genetics, Center for Medical Science, Fujita Health University Arisa Ueki Department of Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research Yuko Watanabe Department of Pediatric Oncology, National Cancer Center Hospital Daisuke Hasegawa Department of Pediatrics, St. Luke's International Hospital Shuhei Karakawa Department of Pediatrics, Hiroshima University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Akira Hirasawa Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akiko M. Saito Clinical Research Center, NHO Nagoya Medical Center Eisuke Inoue Showa Medical University Research Administration Center, Showa Medical University Motohiro Kato Department of Pediatrics, The University of Tokyo Hiroyoshi Hattori Department of Clinical Genetics, NHO Nagoya Medical Center Li–Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by germline pathogenic variants in the TP53 gene. With the increasing use of multi-gene panel testing, TP53 variants have been identified in individuals who do not meet established TP53 testing criteria, such as the Chompret criteria. The term “attenuated LFS” has been proposed for some of these cases, particularly those with adult-onset cancer. We analyzed participants of the Japanese nationwide prospective clinical trial of the cancer surveillance program (Japan Children's Cancer Group LFS-20), along with clinical information including their family histories, to better understand their genotypic and phenotypic characteristics. We identified 32 distinct TP53 variants from 41 families (45 participants), including four missense variants with conflicting classifications of pathogenicity in ClinVar. Among these families, 36 (88%) met the LFS criteria (hereafter referred to as “LFS” in contrast to attenuated LFS), while 5 (12%) were classified as attenuated LFS. Including 30 additional family members carrying the same variant, we analyzed 75 individuals with TP53 variants. Of these, 40 with LFS and 6 with attenuated LFS had cancer. Multiple primary cancers occurred in 22 individuals (21 LFS, 1 attenuated LFS). LFS-core tumors accounted for 66% (58/88) of cancers in the LFS group and 63% (5/8) in the attenuated LFS group; of note, all core tumors in the attenuated group were limited to breast cancer. Hotspot missense variants were detected in 11 of 36 LFS families and in none of 5 attenuated LFS families, and non-hotspot null variants were found in 14 and 1, respectively. Our study revealed genotype–phenotype correlations in several respects. UMIN-CTR: UMIN000045855. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 15 1 2026 Oral Health-Related Quality of Life and Self-Reported Oral Health Status Are Associated with Change in Self-Reported Depression Status: A Cohort Study 376 EN Noriko Takeuchi Department of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama University Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoki Toyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuzuki Katsube Dental School, Okayama University Takahiro Tabuchi Division of Epidemiology, School of Public Health, Tohoku University Graduate School of Medicine Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Oral health-related quality of life (OHRQoL) may influence mental health outcomes, yet longitudinal evidence on its association with depression remains limited. This study aimed to examine whether oral health status and OHRQoL are associated with a change in self-reported depression status among adults in Japan. Methods: We analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), conducted in 2022 and 2023. A total of 15,068 participants aged ≥20 years without depression at baseline were included. Depression status was identified by self-reported measures between the two survey waves. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for change in self-reported depression status in relation to OHRQoL and oral health status, adjusting for sociodemographic and behavioral factors. Results: During follow-up, 218 participants (1.45%) reported a change in self-reported depression status. Poorer OHRQoL was significantly associated with a change in self-reported depression status (OR: 1.018; 95% CI: 1.001–1.036; p = 0.039). Additional risk factors included younger age (OR: 0.974; 95% CI: 0.964–0.985), participation in hobbies and cultural activities (OR: 2.224; 95% CI: 1.498–3.302), habitual use of sleeping pills or anxiolytics (current use OR: 3.512; 95% CI: 2.267–5.442), increased loneliness (OR: 1.217; 95% CI: 1.140–1.299), lower life satisfaction (OR: 0.900; 95% CI: 0.836–0.969), and poor self-rated health (OR: 2.921; 95% CI: 1.810–4.715). Conclusions: Impaired OHRQoL was associated with a change in self-reported depression status, potentially through psychosocial mechanisms. These findings suggest that oral health and OHRQoL may be relevant factors to consider in integrated oral and mental health approaches in clinical practice. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2772-7076 14 2025 Genetic variability in Neisseria meningitidis strains isolated in a Japanese hospital 100511 EN Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Shinnosuke Fukushima Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Osamu Matsushita Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives: Neisseria meningitidis is a significant pathogen causing invasive meningococcal disease, posing clinical and public health concerns worldwide. This study aimed to investigate the genetic characteristics of N. meningitidis clinical isolates at Okayama University Hospital in Japan. Methods: Between 2018 and 2023, five clinical strains were isolated, of which three were subjected to the antimicrobial susceptibility testing and whole genetic analysis using MiSeq platform (Illumina, San Diego, CA, USA). Results: One non-groupable isolate, belonging to sequence types (STs)-11026 (ST-32 complex), exhibited non-susceptibility to penicillin G, with a five-mutation pattern (F504L, A510V, I515V, H541N, and I566V) in the penA amino acid sequence and additional mutations (XXXIV and N513Y) characteristic of a mosaic penA gene. The other two isolates, ST-1655 (ST-23 complex) with serogroup Y and ST-2057 with serogroup B, were susceptible to penicillin G, neither of which contained the five-mutation pattern. Levofloxacin resistance was observed in two isolates carrying the T91I mutation in the gyrA protein. Conclusion: Our findings suggest the presence of antimicrobial-resistant N. meningitidis in Japan, underscoring the necessity for continuous local surveillance. Additional research is crucial for clarifying the ongoing spread of resistance mechanisms and for establishing effective countermeasures to reduce the clinical burden of invasive meningococcal disease. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 0018-9456 74 2025 Small Distance Increment Method for Measuring Complex Permittivity With mmWave Radar 6009610 EN Hang Song Research Institute for Semiconductor Engineering, Hiroshima University Hyun Joon Kim Department of Transdisciplinary Science and Engineering, Institute of Science Tokyo Mingxia Wan Department of Transdisciplinary Science and Engineering, Institute of Science Tokyo Bo Wei Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takamaro Kikkawa Research Institute for Semiconductor Engineering, Hiroshima University Jun-Ichi Takada Department of Transdisciplinary Science and Engineering, Institute of Science Tokyo Measuring the complex permittivity of material is essential in many scenarios, such as quality checks in material manufacturing. Generally, measurement methods for characterizing the material are based on the use of a vector network analyzer (VNA), which is large and not easy for on-site measurement, especially in high-frequency range such as millimeter wave (mmWave). In addition, some measurement methods require the destruction of samples, which is not suitable for nondestructive inspection. In this work, a small distance increment (SDI) method is proposed to nondestructively measure the complex permittivity of a material. In SDI, the transmitter and receiver are formed as a monostatic radar, which is facing toward the material under test (MUT). During the measurement, the distance between the radar and the MUT changes with small increments, and the signals are recorded at each position. A mathematical model is formulated to depict the relationship among the complex permittivity, distance increment, and measured signals. By fitting the model, the complex permittivity of MUT is estimated. To implement and evaluate the proposed SDI method, a commercial off-the-shelf (COTS) mmWave radar is utilized, and the measurement system is developed. Then, the evaluation was carried out on the acrylic plate. With the proposed method, the estimated complex permittivity of the acrylic plate shows good agreement with the literature values, demonstrating the efficacy of the SDI method for characterizing the complex permittivity of the material. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 75 1 2025 Gut microbial metabolite butyrate boosts p53-expressing telomerase-specific oncolytic adenovirus efficacy by enhancing infectivity and activating MHC-I/cGAS-STING 10 EN Masaki Sakamoto 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 Tetsuya Katayama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Mikane Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunya Hanzawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Kadowaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Hamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoma Sugimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa 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 Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The gut microbiota plays an essential role in regulating host immunity, and its metabolites such as butyrate exert immunomodulatory effects by acting as histone deacetylase inhibitors. Oncolytic virotherapy has emerged as a promising approach for cancer treatment, and we have developed OBP-702, a telomerase-specific oncolytic adenovirus that expresses p53 and elicits strong systemic antitumor responses. In this study, the potential synergy between butyrate and OBP-702 was investigated in colorectal cancer models. Using human and murine colorectal carcinoma cell lines, butyrate was found to directly enhance the infectivity of OBP-702 by upregulating CAR and integrins, thereby promoting apoptosis and autophagy in tumor cells. In addition, butyrate indirectly boosted systemic antitumor immunity by upregulating MHC-I expression through activation of the cGAS-STING pathway and enhancing CD8 + T cell recruitment via CXCL10 secretion. These findings were supported by in vivo experiments using CT26 subcutaneous, bilateral, and orthotopic tumor models, in which the combination of oral butyrate and intratumoral OBP-702 administration produced synergistic antitumor effects. These results highlight the therapeutic potential of integrating gut microbial metabolites with oncolytic virotherapy as a novel immunotherapeutic strategy for colorectal cancer. No potential conflict of interest relevant to this article was reported.

Japanese Society of Breeding Acta Medica Okayama 1344-7610 75 3 2025 Polyphyletic domestication and inter-lineage hybridization magnified genetic diversity of cultivated melon, Cucumis melo L. 168 178 EN Katsunori Tanaka Faculty of Agriculture and Life Science, Hirosaki University Gentaro Shigita Graduate School of Environmental and Life Science, Okayama University Tran Phuong Dung Graduate School of Environmental and Life Science, Okayama University Phan Thi Phuong Nhi University of Agriculture and Forestry, Hue University Mami Takahashi Graduate School of Environmental and Life Science, Okayama University Yuki Monden Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidetaka Nishida Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ryuji Ishikawa Faculty of Agriculture and Life Science, Hirosaki University Kenji Kato Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Melon accessions with diverse geographical origins were classified into large and small seed-types by length of seed at the boundary of 9 mm, and into five populations based on polymorphisms in the nuclear genome. They were further divided into three maternal lineages, Ia, Ib, and Ic, by polymorphisms in the chloroplast genome. By combining these three classifications, the Europe/US subsp. melo and the East Asian subsp. agrestis were characterized as [large seed, Ib, PopA1 or A2] and [small seed, Ia, PopB1 or B2], respectively, indicating nearly perfect divergence. In South Asia, in addition to the Europe/US and East Asian types, recombinant types between the two types were detected and accounted for 34.8% of South Asian melon. The finding of such an intermixed structure of genetic variation supported the Indian origin of Ia and Ib types. As to Momordica popular in South Asia, seed length was intermediate between the large and small seed-types, and chloroplast type was a mixture of Ia and Ib, suggesting its origin from the recombinant type. In Africa, three lineages of melon were distributed allopatrically and showed distinct divergence. Subsp. agrestis of the Ic type proved to be endemic to Africa, indicating its African origin. No potential conflict of interest relevant to this article was reported.

Iron and Steel Institute of Japan Acta Medica Okayama 0915-1559 65 13 2025 Heat Transfer Enhancement by Forming Bridges among Reactive Particles in a Packed Bed Reactor of a Solid-gas Chemical Heat Storage System 2097 2104 EN Koichi Nakaso Faculty of Environmental, Life Natural Science and Technology, Okayama University Kenji Shimada Graduate School of Natural Science and Technology, Okayama University Yasushi Mino Faculty of Environmental, Life Natural Science and Technology, Okayama University Kuniaki Gotoh Faculty of Environmental, Life Natural Science and Technology, Okayama University In this study, the enhancement of the thermal output of solid-gas chemical heat storage systems was investigated. Bridges made of high-thermal conductivity materials were formed among reactive particles by drying a slurry which contained graphite powder as a thermal additive and dispersant in a packed-bed reactor. First, the effect of the volume ratio of the dispersant on effective thermal conductivity was investigated. The optimum volume ratio of dispersant to graphite powder was determined. Furthermore, repetitive bridge formation increased the effective thermal conductivity. Based on these results, we investigated the thermal response of the energy-discharge process. Consequently, the temperature distribution in the radial direction of the reactor decreased owing to the formation of bridges. In addition, the thermal energy generated by the adsorption of water vapor onto the adsorbent was effectively transferred to the reactor wall. The thermal output was estimated based on the experimental results. The thermal output was increased by the formation of bridges. No potential conflict of interest relevant to this article was reported.

Ceramic Society of Japan Acta Medica Okayama 1348-6535 134 1 2026 Structure and acid resistance of fluoride-treated hydroxyapatite particles 31 37 EN Satoshi Hayakawa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazuki Ando Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tomohiko Yoshioka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Topical fluoride is used in clinical dentistry to prevent dental caries. The primary reaction product formed on the tooth surface after topical fluoride application is calcium fluoride (CaF2). In this study, we investigated the effect of deposited CaF2 on the acid resistance of fluoride-treated hydroxyapatite (HAp). Commercial HAp particles were treated with two types of fluoride-containing acetic acid-sodium acetate (Ac-AcNa) buffer solutions, with and without the addition of phosphate ions. X-ray diffraction (XRD) and nuclear magnetic resonance (NMR) analyses confirmed the formation of fluorine-substituted hydroxyapatite (F-HAp), along with a hydration layer containing calcium phosphate and CaF2. Phase composition analysis revealed that the presence of phosphate ions in the fluoride treatment solution reduced the amount of CaF2 deposited. Acid resistance evaluation and phase composition analysis indicated that the initial dissolution rate of the fluoride-treated HAp in Ac-AcNa buffer solutions decreased on surfaces densely covered with CaF2 particles. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2405-8440 11 11 2025 Suppression of defect in plated film on AMed metal products by electron beam polishing e43440 EN Togo Shinonaga Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yuki Matsuda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akira Okada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Additively manufactured (AMed) metal products with high shape accuracy can be produced by laser powder bed fusion (LPBF). However, the AMed metal products have large surface roughness due to the arrangement of bead shape. Surface irregularities such as spatter and small cavity are also generated on the surface. Furthermore, elemental composition of AMed metal products may be changed from that of original metal powder due to oxidation of surface. On the other hand, electroless plating has been applied to improvement of surface functions. However, defect is often generated in the plated film due to surface irregularities and oxidation of base material. Therefore, surface smoothing methods are required for suppression of defect in plated film. In this study, surface smoothing and surface repairing of AMed aluminum (Al) alloy were performed by electron beam (EB) polishing with large-area EB. After the EB polishing, electroless plating was conducted on the AMed Al alloy, and suppression of defect in plated film was proposed. Experimental results show that surface smoothing, surface repairing and removal of oxidization layer of AMed Al alloy can be done simultaneously by the EB polishing. Furthermore, the plated film without defect can be successfully formed on the EB polished Al alloy. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0897-3806 38 2 2025 Ethical Use of Cadaveric Images in Anatomical Textbooks, Atlases, and Journals: A Consensus Response From Authors and Editors 222 225 EN Joe Iwanaga Department of Neurosurgery, Tulane University School of Medicine Hee‐Jin Kim Division in Anatomy & Development Biology, Department of Oral Biology, Yonsei University College of Dentistry Keiichi Akita Department of Clinical Anatomy, Tokyo Medical and Dental University (TMDU) Bari M. Logan UK Ralph T. Hutchings UK Nicolás Ottone Department of Integral Adult Dentistry, Center for Research in Dental Sciences (CICO), Dental School, Universidad de La Frontera Yoichi Nonaka Department of Neurosurgery, Tokai University School of Medicine Mahindra Anand Department of Anatomy, Rama Medical College & Research Centre Danny Burns Department of Anatomical Sciences, School of Medicine, St. George's University Vishram Singh Department of Anatomy, Kasturba Medical College Mangalore, Manipal Academy of Higher Education Maria Peris‐Celda Department of Neurologic Surgery, Mayo Clinic Francisco Martinez‐Soriano Department of Anatomy, University of Valencia Nihal Apaydin Department of Anatomy, Faculty of Medicine, Ankara University Amgad Hanna Department of Neurological Surgery, University of Wisconsin Nobutaka Yoshioka Department of Neuroplastic and Reconstructive Surgery Social Medical Corporation Kotobukikai Tominaga Hospital Juan Fernandez‐Miranda Department of Neurosurgery, Stanford University School of Medicine Mi‐Sun Hur Department of Anatomy, Daegu Catholic University School of Medicine Mohammadali M. Shoja Department of Medical Education, Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University (NSU) Farhood Saremi Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Ronald Reagan UCLA Medical Center Francisco Reina Medical Sciences Department, Faculty of Medicine, Clinical Anatomy, Embryology and Neuroscience Research Group, University of Girona Yoko Tabira Division of Gross and Clinical Anatomy, Department of Anatomy, Kurume University School of Medicine Anna Carrera Medical Sciences Department, Faculty of Medicine, Clinical Anatomy, Embryology and Neuroscience Research Group, University of Girona Jonathan D. Spratt University Hospital of North Durham S. Yen Ho Cardiac Morphology, Royal Brompton & Harefield Hospitals Shumpei Mori University of California Los Angeles (UCLA) Cardiac Arrhythmia Center, Cardiovascular and Interventional Programs, UCLA Health System, David Geffen School of Medicine at UCLA Noritaka Komune Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Koichi Watanabe Division of Gross and Clinical Anatomy, Department of Anatomy, Kurume University School of Medicine Alberto Prats‐Galino Laboratory of Surgical NeuroAnatomy (LSNA), director of the Body Donation and Dissection Rooms Service, Faculty of Medicine and Health of Science, University of Barcelona Jose De Andrés Surgery Specialties Department, University of Valencia Miguel Angel Reina CEU‐San‐Pablo University School of Medicine Peter H. Abrahams Warwick Medical School Robert H. Anderson Biosciences Institute, Newcastle University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Marios Loukas Department of Anatomical Sciences, School of Medicine, St. George's University R. Shane Tubbs Department of Neurosurgery, Tulane University School of Medicine Nowadays, consent to use donor bodies for medical education and research is obtained from the body donors and their families before the donation. Recently, the International Federation of Associations of Anatomists (IFAA) published guidelines that could restrict the appearance of cadaveric images in commercial anatomical resources such as textbooks and other educational products. These guidelines state that the donor must expressly consent to using such images for this purpose. Cadaveric photos and drawings made from dissections of cadavers have been used in anatomy textbooks and atlases for hundreds of years. They are invaluable for anatomy students and clinical/surgical practitioners. The IFAA guidelines should not restrict the use of those older books; to do so would infringe the rights of those seeking knowledge from these resources. As the images in such textbooks and atlases are anonymized and are used for teaching and research, and the donors and their families are informed about this before the donation, we believe no additional consent is needed. It is impossible to separate educational from “commercial” usage entirely in any situation, e.g., publications from publishers and the use of cadavers in medical schools. Therefore, our best efforts to avoid unethical use of cadaveric images by following traditional consent processes are still needed so that more people will reap the benefits from them. As senior textbook/atlas authors/editors from over 10 countries, we believe that using cadaveric images in anatomy textbooks is appropriate, and no additional consent should be necessary. Such usage falls within the good faith of professionals using these invaluable gifts. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 12 2025 Sequential Bilateral Central Retinal Vein Occlusion With Differential Long-Term Outcomes Following Cardiac Surgery e100045 EN Toshihiko Matsuo Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama University Hospital Zenichi Masuda Cardiovascular Surgery, Okayama University Hospital Hiroki Sugiyama Cardiovascular Medicine, Okayama University Hospital Kazufumi Nakamura Cardiovascular Medicine and Center for Advanced Heart Failure, Okayama University Hospital Bilateral central retinal vein occlusion (CRVO) is rare and is associated with systemic diseases such as hypertension, diabetes, dyslipidemia, and coagulopathy. In this study, we showed that the sequential development of bilateral CRVO in an elderly patient was related to increased venous pressure in the right heart system. A 71-year-old man developed CRVO in the right eye, and one year later, he developed CRVO in the left eye. He had undergone pacemaker implantation for sick sinus syndrome 10 years earlier and had started hemodialysis three months prior for chronic renal failure, probably caused by hypertensive nephrosclerosis. The right CRVO resulted in neovascular glaucoma and loss of light perception despite intensive treatment with panretinal laser photocoagulation, intravitreal bevacizumab injection, and additional laser therapy. In contrast, the left CRVO remained at an impending stage, was treated only with panretinal laser photocoagulation, and had a favorable outcome for 11 years until his death. In retrospect, half a year after the onset of left CRVO, the patient underwent open-heart surgery to repair aortic, mitral, and tricuspid valve regurgitation through aortic valve replacement, mitral valve annuloplasty, and tricuspid valve annuloplasty, respectively. Based on the temporal sequence of events, elevated venous pressure due to right heart dysfunction may have contributed to the poor outcome of the right CRVO, whereas improvement of venous stasis after cardiac surgery may have led to the better long-term outcome of the left CRVO. Venous stasis in the right heart system should therefore be considered an underlying factor in the development of bilateral CRVO. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2328-9503 2025 Dorsolateral Cervical Cord T2 Hyperintensity in KIF1C-Related Disease (Spastic Paraplegia 58): Two Long-Duration Cases EN Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Masao Osaki Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Miho Osako Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled Chisen Takeuchi Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled 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 Ryo Kurokawa Department of Radiology, Graduate School of Medicine, The University of Tokyo Harushi Mori Department of Radiology, School of Medicine, Jichi Medical University Yuji Takahashi Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Goto Department of Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Institute of Medical Genomics, International University of Health and Welfare Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Pathogenic variants in KIF1C cause Spastic Paraplegia 58 (SPG58), typically presenting with cerebellar ataxia and spastic paraparesis. We report two unrelated patients with spastic paraparesis, cerebellar ataxia, and tremor. Whole-exome sequence analysis identified novel homozygous variants in the motor domain of KIF1C (NM_006612.6): c.921G>A (p.Trp307Ter) and c.607C>T (p.Arg203Trp). In addition to the canonical brain MRI showing leukoencephalopathy with posterior dominance and hyperintensity along the corticospinal tracts, both patients showed symmetric T2 hyperintensity confined to the lateral and dorsal columns of the cervical cord. Given the long disease durations (22 and 51 years), these findings may represent late-emerging or previously overlooked spinal cord involvement and broaden the neuroradiological spectrum of SPG58. No potential conflict of interest relevant to this article was reported.

Japanese Society for Horticultural Science Acta Medica Okayama 2189-0102 94 3 2025 Effect of Storage Temperature and a Sugar-ester Edible Coating on Postharvest Quality and Storage Life of ‘Fuyu’ Persimmon (Diospyros kaki Thunb.) 401 407 EN Maqsood Muqadas Graduate School of Environmental, Life Science, Natural Science and Technology Okayama University Oscar W. Mitalo Faculty of Life and Environmental Sciences, University of Tsukuba Kyohei Ohashi Graduate School of Environmental, Life Science, Natural Science and Technology Okayama University Takumi Otsuki Graduate School of Environmental, Life Science, Natural Science and Technology Okayama University Chikara Yano Graduate School of Environmental, Life Science, Natural Science and Technology Okayama University Ziaurrahman Hejazi Graduate School of Agriculture, University of Miyazaki Natsuki Hira Shiga R&D Center, Mitsubishi Chemical Corporation Koichiro Ushijima Graduate School of Environmental, Life Science, Natural Science and Technology Okayama University Yasutaka Kubo Graduate School of Environmental, Life Science, Natural Science and Technology Okayama University In ‘Fuyu’ persimmons (Diospyros kaki Thunb.), crunchiness is a preferred postharvest attribute among both distributors and consumers. The present study first examined softening characteristics during storage at 0, 5, 10, 15, 20, and 25°C. Fruit stored at 0°C remained firm for 84 d, while that stored at 5°C had a 100% softening rate within 35 d. At 10 and 15°C, over 70% of fruit softened within 49 d and 63 d, respectively. The softening rate was relatively slower at 20 and 25°C, with only 27% softened fruit after 56 d at 25°C. The potential of a newly developed sugar-ester (SE) edible coating to delay fruit softening and maintain postharvest quality was then assessed during storage at 0 and 25°C. Uncoated fruit stored at 0°C for 56 d developed chilling injury (CI) symptoms (rapid fruit softening and peel browning) within 2 d of rewarming at 20°C. These CI symptoms were notably mitigated in SE-coated fruit. At 25°C, SE coating also delayed fruit softening and peel color change in addition to reducing fruit shrinkage. In conclusion, in ‘Fuyu’ persimmons ambient temperature (20–25°C) storage in combination with an edible SE coating is recommended for the high demand Christmas and new year seasons and 0°C storage with an edible SE coating is suitable for longer storage and distribution. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 63 13 2024 Activated CD4+ T Cell Proportion in the Peripheral Blood Correlates with the Duration of Cytokine Release Syndrome and Predicts Clinical Outcome after Chimeric Antigen Receptor T Cell Therapy 1863 1872 EN Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Shuntaro Ikegawa Department of Hematology and Oncology, Okayama University Hospital, Japan Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Chihiro Kamoi Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Division of Clinical Laboratory, Okayama University Hospital Nobuharu Fujii Division of Blood Transfusion, Okayama University Hospital Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Objective Chimeric antigen receptor (CAR) T cell therapy is an emerging and effective therapy for relapsed or refractory diffuse large B cell lymphoma (R/R DLBCL). The characteristic toxicities of CAR T cell therapy include cytokine release syndrome (CRS) and prolonged cytopenia. We investigated the factors associated with these complications after CAR T cell therapy by analyzing lymphocyte subsets following CAR T cell infusion. Methods We retrospectively analyzed peripheral blood samples on days 7, 14, and 28 after tisagenlecleucel (tisa-cel) infusion by flow cytometry at our institution between June 2020 and September 2022. Patients Thirty-five patients with R/R DLBCL who received tisa-cel therapy were included. Results A flow cytometry-based analysis of blood samples from these patients revealed that the proportion of CD4+CD25+CD127+ T cells (hereafter referred to as "activated CD4+ T cells" ) among the total CD4+ T cells on day 7 after tisa-cel infusion correlated with the duration of CRS (r=0.79, p<0.01). In addition, a prognostic analysis of the overall survival (OS) using time-dependent receiver operating characteristic curves indicated a significantly more favorable OS and progression-free survival of patients with a proportion of activated CD4+ T cells among the total CD4+ T cells <0.73 (p=0.01, and p<0.01, respectively). Conclusion These results suggest that the proportion of activated CD4+ T cells on day 7 after tisa-cel infusion correlates with the CRS duration and predicts clinical outcomes after CAR T cell therapy. Further studies with a larger number of patients are required to validate these observations. 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.

Frontiers Media SA Acta Medica Okayama 1662-453X 19 2025 Effects of visual spatial frequency on audiovisual interaction: an event-related potential study 1599114 EN Fengxia Wu School of Artificial Intelligence, Changchun University of Science and Technology Yanna Ren Department of Psychology, College of Humanities and Management, Guizhou University of Traditional Chinese Medicine Tengfei Hao School of Artificial Intelligence, Changchun University of Science and Technology Jingjing Yang School of Artificial Intelligence, Changchun University of Science and Technology Qiong Wu Department of Psychology, Suzhou University of Science and Technology Jiajia Yang Cognitive Neuroscience Laboratory, Graduate School of Natural Science and Technology, Okayama University Meng Wang School of Artificial Intelligence, Changchun University of Science and Technology Spatial frequency is a fundamental characteristic of visual signals that modulates the audiovisual integration behavior, but the neural mechanisms underlying spatial frequency are not well established. In the present study, the high temporal resolution of event-related potentials was used to investigate how visual spatial frequency modulates audiovisual integration. A visual orientation discrimination task was used, and the spatial frequency of visual stimuli was manipulated under three conditions. Results showed that the influence of visual spatial frequency on audiovisual integration is a dynamic process. The earliest audiovisual integration occurred over the left temporal-occipital regions in the early sensory stage (60–90 ms) for high spatial frequency conditions but was absent for low and middle spatial frequency conditions. In addition, audiovisual integration over fronto-central regions was delayed as spatial frequency increased (from 230–260 ms to 260–320 ms). The integration effect was also observed over parietal and occipital regions at 350–380 ms, and its strength gradually decreased at higher spatial frequencies. These discrepancies in the temporal and spatial distributions of audiovisual integration imply that the role of spatial frequency varies between early sensory and late cognitive stages. The findings of this study offer the first neural demonstration that spatial frequency modulates audiovisual integration, thus providing a basis for studying complex multisensory integration, especially in semantic and emotional domains. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0264-1275 260 2025 An entangled material made from fiber aerosol deposition method 115195 EN Hongwu Yu Faculty of Environmental, Life, Natural Science and Technology, University of Okayama Naoshi Ikeda Faculty of Environmental, Life, Natural Science and Technology, University of Okayama Masakazu Mori Ryukoku University Jun Kano Faculty of Environmental, Life, Natural Science and Technology, University of Okayama Jae-Hyuk Park School of Advanced Materials Science & Engineering, Sungkyunkwan University Jun Akedo National Institute of Advanced Industrial Science and Technology This study demonstrates the successful application of Aerosol Deposition (AD) technology to short carbon fibers (length < 1 mm), enabling the rapid, three-dimensional (3D) fabrication of objects with vertical growth rates up to 0.3 mm/s, a significant improvement over conventional additive manufacturing. Through a series of experiments using this novel Fiber Aerosol Deposition (FAD) technology, three fiber lengths (47, 85, and 111 μm) and four substrate materials (carbon, polypropylene, polyethylene, and acrylonitrile butadiene styrene (ABS)) were investigated. Our findings indicate that both carbon substrate entanglement and fiber length critically influence deposition efficiency. Scanning electron microscopy (SEM) and X-ray computed tomography (CT) analyses reveal that during formation, longer fibers (>100 μm) initially create a cage-like framework, which is subsequently filled by shorter fibers. Density measurements and fiber distribution analysis confirmed that structures predominantly composed of shorter fibers exhibit higher packing densities, consistent with their role as filler material. These results collectively suggest that the FAD method’s formation mechanism relies on frictional entanglement rather than the room-temperature impact consolidation (RTIC) effect characteristic of traditional AD. This breakthrough presents a promising new technique for forming short fibers into functional 3D architectures, with potential applications extending to proteins, polymer fibers, and biomaterial fibers. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0031-9317 177 4 2025 Comparative Transcriptome Reveals ART1-Dependent Regulatory Pathways for Fe Toxicity Response in Rice Roots e70398 EN Yoshiaki Ueda Crop, Livestock and Environment Division, Japan International Research Center for Agricultural Sciences Naoki Yamaji Institute of Plant Science and Resources, Okayama University Matthias Wissuwa Crop, Livestock and Environment Division, Japan International Research Center for Agricultural Sciences Iron (Fe) is an essential element for plants, but an excess supply can have detrimental effects. Fe toxicity induces complex physiological and genetic responses, and due to this complexity, the knowledge of transcriptional regulatory mechanisms under Fe toxicity is very limited. Previous studies suggested that plant responses to excess Fe involve oxidative stress caused by reactive oxygen species (ROS), which itself causes transcriptional changes. We hypothesized that dissecting these complex responses could lead to the identification of a novel factor and conducted a comparative transcriptome analysis using roots of rice plants exposed to nutrient solutions containing 1 or 5 mM of hydrogen peroxide (a major form of ROS) or 300 mg L－1 of Fe (as FeSO4). Genes induced by hydrogen peroxide overlapped with 62%, 49%, and 30% of Fe toxicity-upregulated genes at 3 h, 1 day, and 3 days following treatment initiation. Subsequent gene co-expression analyses classified genes into 21 groups with varying responsiveness to ROS and Fe toxicity. Genes in group 15 were specifically upregulated by Fe toxicity and overlapped significantly with aluminum (Al)-inducible genes and target genes of the Zn-finger transcription factor, ART1, which regulates Al response in rice roots. Additional experiments using the art1 knock-out mutant demonstrated that ART1 is crucial for upregulating genes such as STAR2 and FRDL4 in response to Fe toxicity. This study reveals the contribution of ART1-dependent regulatory pathways in rice roots under Fe toxicity. 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.

Wiley Acta Medica Okayama 1748-3735 21 1 2025 Japanese Adult Day Service Nurses' Bathing Decisions for Persons Requiring Long‐Term Care: A Focused Ethnography e70052 EN Kanako Miyoshi Graduate School of Health Sciences, Okayama University Keiko Mori Graduate School of Health Sciences, Okayama University Introduction: Adult day services in Japan operate under the Long-Term Care Insurance Law, and care is provided mainly by caregivers. However, because doctors are often not on site, nurses manage the health of the person requiring long-term care. Adult day services provide bathing and functional training; however, although Japanese-style bathing relieves fatigue and brings a sense of well-being, it also entails the risk of bathing accidents for those in need of care. To continue living at home, those in need of care who have difficulty bathing at home must be provided with safe bathing during adult day services and supported in returning home safely. Nurses are responsible for accurately assessing the health status of users and implementing safe bathing. This study aimed to identify how nurses working in adult day services make bathing decisions for home-dwelling persons requiring long-term care. Method: Qualitative manifest and latent content analyses were performed using a focused ethnography. Findings: Six themes were identified: ‘gather information to compare with baseline’, ‘make observations based on information from others to understand the big picture’, ‘give persons time to get in shape’, ‘consideration of life at home’, ‘determining the need for medical institutions’ and ‘devise ways to communicate to promote collaboration’. Conclusions: Adult day service nurses' decisions about whether to bathe persons requiring care are characterised by their emphasis on information from others, consideration of the home living conditions of persons requiring care and their wishes regarding bathing. In addition, based on their observations, they determine the need for cooperation with medical institutions and communicate this information to family members and multiple professions. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1465-3621 55 5 2025 Multicenter, open-label, randomized, controlled study to test the utility of electronic patient-reported outcome monitoring in patients with unresectable advanced cancers or metastatic/recurrent solid tumors 547 555 EN Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Naomi Kiyota Department of Medical Oncology and Hematology, Cancer Center, Kobe University Hospital Yuichiro Kikawa Department of Breast Surgery, Kansai Medical University Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Kyoko Kato Department of Medical Oncology, National Hospital Organization Nagoya Medical Center Kaoru Kubota Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Ryosuke Tateishi Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo Akinobu Nakata Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukiya Narita Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Hiroji Iwata Department of Advanced Clinical Research and Development, Nagoya City University Akihiko Gemma Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Kojiro Shimozuma Department of Biomed Sciences, College of Life Sciences, Ritsumeikan University Kei Muro Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Tetsuya Iwamoto Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Yuki Takumoto Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takeru Shiroiwa Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takashi Fukuda Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takuhiro Yamaguchi Division of Biostatistics, Tohoku University Graduate School of Medicine Yasuhiro Hagiwara Department of Biostatistics, Division of Health Sciences and Nursing, The University of Tokyo Graduate School of Medicine Hironobu Minami Division of Medical Oncology and Hematology, Department of Medicine, Kobe University Graduate School of Medicine Electronic patient-reported outcome (ePRO) monitoring for patients undergoing cancer chemotherapy may provide qualified and early detection of adverse events or disease-related symptoms, leading to improved patient care. The aim of this study is to examine whether addition of ePRO monitoring to routine medical care contributes to improved overall survival and quality of life of cancer patients undergoing chemotherapy. Patients with unresectable advanced cancers or metastatic/recurrent solid tumors receiving systemic chemotherapy will be randomized to an ePRO monitoring group and a usual care group. The ePRO group will conduct weekly symptom monitoring using an electronic device after study enrollment until the end of the study. Monitoring results will be returned to medical personnel and used as information for patient care. The primary endpoints are overall survival and health related quality of life. The initial target sample size for the study was 1500 patients. However, due to delays in enrollment, the target was readjusted to 500 patients. Enrollment has been completed, and the study is now in the follow-up phase. 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.

Springer Science and Business Media LLC Acta Medica Okayama 0944-1174 60 12 2025 Combination chemotherapy for older patients with unresectable biliary tract cancer: a prospective observational study using propensity-score matched analysis (JON2104-B) 1584 1595 EN Satoshi Kobayashi Department of Gastroenterology, Kanagawa Cancer Center Kohei Nakachi Department of Medical Oncology, Tochigi Cancer Center Kouji Yamamoto Department of Biostatistics, Yokohama City University School of Medicine Makoto Ueno Department of Gastroenterology, Kanagawa Cancer Center Yuta Maruki Kenji Ikezawa Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute Takeshi Terashima Department of Gastroenterology, Kanazawa University Hospital Satoshi Shimizu Department of Gastroenterology, Kanazawa University Hospital Kotoe Oshima Division of Gastrointestinal Oncology, Shizuoka Cancer Center Kunihiro Tsuji Department of Gastroenterology, Ishikawa Prefectural Central Hospital Yoshiharu Masaki Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine Hidetaka Tsumura Department of Gastroenterological Oncology, Hyogo Cancer Center Taro Shibuki Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East Masato Ozaka Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research Naohiro Okano Department of Medical Oncology, Kyorin University Faculty of Medicine Yukiyasu Okamura Division of Digestive Surgery, Department of Surgery, Nihon University School of Medicine Kumiko Umemoto Department of Clinical Oncology, St. Marianna University School of Medicine Tatsunori Satoh Department of Gastroenterology, Shizuoka General Hospital Yasushi Kojima Department of Gastroenterology, National Center for Global Health and Medicine Kazuhiko Shioji Department of Gastroenterology, Niigata Cancer Center Hospital Hiroko Nebiki Department of Gastroenterology, Osaka City General Hospital Toshifumi Doi Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine Atsushi Naganuma Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center Shigeki Kataoka Department of Clinical Oncology, Graduate School of Medicine Faculty of Medicine, Kyoto University Emiri Kita Department of Gastroenterology, Chiba Cancer Center Hiroyuki Asama Department of Gastroenterology, Fukushima Medical University Kaoru Tsuchiya Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital Michiaki Unno Department of Surgery, Tohoku University Graduate School of Medicine Reiko Ashida Second Department of Internal Medicine, Wakayama Medical University Kazuyuki Matsumoto Department of Gastroenterology, Okayama University Graduate School of Medicine Izumi Ohno Department of Gastroenterology, Chiba University Graduate School of Medicine Takao Itoi Department of Gastroenterology, Tokyo Medical University Yuji Negoro Department of Oncologial Medicine, Kochi Health Sciences Center Yasunari Sakamoto Department of Gastroenterology and Hepatology, International University of Health and Welfare Atami Hospital Shiho Arima Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences Akinori Asagi Department of Gastroenterology, National Hospital Organization Shikoku Cancer Center Hiroyuki Okuyama Department of Medical Oncology, Kagawa University Hospital Yoshito Komatsu Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center Noritoshi Kobayashi Department of Oncology, School of Medicine Graduate School of Medicine, Yokohama City University Hiroaki Nagano Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine Junji Furuse Department of Gastroenterology, Kanagawa Cancer Center Background: Systemic chemotherapy with gemcitabine plus S-1 (GEM + S-1), GEM + CDDP plus S-1 (GEM + CDDP + S-1), or gemcitabine plus cisplatin (GEM + CDDP) is standard treatment for advanced biliary tract cancer (aBTC). We aimed to evaluate the efficacy and safety of combination chemotherapy in older patients with aBTC. Methods: This multicenter prospective observational study (JON2104-B, UMIN000045156) included patients aged ≥ 70 years with aBTC. Inverse-probability weighting propensity-score analyses (IPW) were used to compare overall survival (OS) as the primary endpoint and progression-free survival (PFS) across treatment groups. Results: This study included 305 patients between August 2021 and January 2023. Of them, 75, 131, 26, 52, and 10 received GEM + CDDP + S-1, GEM + CDDP, GEM + S-1, gemcitabine, and S-1; their median ages were 74, 75, 77.5, 80, and 80 years, and approximately 24%, 16.8%, 23.1%, 9.6%, and 0% had G-8 scores of > 14, respectively. GEM + CDDP had a safety profile comparable to that of GEM + CDDP + S-1 but was more toxic than gemcitabine. Per IPW, the hazard ratio (HR) for GEM + CDDP + S-1 versus GEM + CDDP was 0.80 for OS (95% confidence interval [CI], 0.55–1.17) and 0.55 for PFS (95% CI 0.38–0.80). The HR for GEM + CDDP versus gemcitabine was 0.74 for OS (95% CI 0.42–1.29) and 0.79 for PFS (95% CI 0.42–1.49). Conclusions: GEM + CDDP + S-1 was associated with longer PFS without additional toxicity than GEM + CDDP for fit older patients. However, the OS for both were not statistically different. The efficacies of GEM + CDDP and gemcitabine for vulnerable older patients did not also differ significantly. These findings highlight the importance of vulnerability in patients with aBTC. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0915-5635 2025 EUS-Guided Versus Percutaneous Transhepatic Drainage of Liver Abscesses: A Multicenter Endohepatology Study in Western Japan (EPIC-LA Study) EN Takeshi Ogura Pancreatobiliary Advanced Medical Center, Osaka Medical and Pharmaceutical University Hospital Taira Kuroda Gastroenterology Center, Ehime Prefectural Hospital Takanori Matsuura Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine Jun Kitadai Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine Koh Kitagawa Department of Gastroenterology, Nara Medical University Masahiro Itonaga Second Department of Internal Medicine, Wakayama Medical University Kotaro Takeshita Department of Gastroenterology, Tane General Hospital Tomoaki Matsumori Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine Tomoya Emori Department of Gastroenterology, Wakayama Rosai Hospital Mamoru Takenaka Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine Graduate School of Medical Sciences Hajime Imai Department of Gastroenterology, Okanami General Hospital Koichiro Mandai Department of Gastroenterology, Kyoto Second Red Cross Hospital Shuhei Shintani Department of Gastroenterology, Shiga University of Medical Science Nao Fujimori Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University Hideyuki Shiomi Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University Masanori Asada Department of Gastroenterology and Hepatology, Japanese Red Cross Osaka Hospital Ryota Sagami Department of Gastroenterology, Faculty of Medicine, Oita University Hirotsugu Maruyama Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University Tsukasa Ikeura Division of Gastroenterology and Hepatology, Kansai Medical University Hospital Masaaki Shimatani Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center Hidefumi Nishikiori Department of Gastroenterology, Oita San-ai Medical Center Kazuyuki Matsumoto Department of Endoscopy, Okayama University Hospital Masahito Kokubu Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine Hideki Kamada Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University Yusuke Ishida Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University Akitoshi Hakoda 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University Masayuki Kitano Second Department of Internal Medicine, Wakayama Medical University Objective: Percutaneous transhepatic liver abscess drainage (PTAD) and endoscopic ultrasound-guided liver abscess drainage (EUS-LAD) have several limitations. Recently, because of technical improvements in echoendoscope maneuvers, EUS-guided access for the right hepatic lobe has been reported. The aim of this multicenter, retrospective study was to compare clinical outcomes of PTAD and EUS-LAD including the right hepatic lobe in West Japan. Method: This retrospective, multicenter study included consecutive patients with liver abscesses between January 2019 and November 2024. The primary outcome in this study was the clinical success rate compared between EUS-LAD and PTAD. Results: During the study period, 1012 consecutive patients developed liver abscesses. Of them, 734 patients were excluded, 43 underwent EUS-LAD and 235 patients underwent PTAD. After propensity score-matched analysis, the clinical success rate was significantly higher in the EUS-LAD group (97.7%, 42/43) than in the PTAD group (79.1%, 34/43) (p = 0.007). After a propensity score-matched analysis, 25 patients were included in each group. The clinical success rate was significantly higher in the EUS-LAD group (100%, 25/25) than in the PTAD group (84%, 21/25) (p = 0.037). Adverse events were also significantly higher in the PTAD group (16%, 5/25) than in the EUS-LAD group (p = 0.025). In addition, the median length of hospital stay was significantly shorter in the EUS-LAD group (15 days) than in the PTAD group (22 days) (p = 0.005). Conclusions: EUS-LAD using a metal stent might be one of the options, but further randomized, controlled trials are needed. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1350-4487 191 2026 Experimental approach of internal dose map visualization during helical CT examinations: importance of X-ray incident direction analysis and central internal dose estimation 107586 EN Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Kazuki Takegami Department of Radiological Technology, Yamaguchi University Hospital Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Sota Goto Faculty of Health Sciences, Kobe Tokiwa University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Masaki Takemitsu Department of Radiological Technology, Yamaguchi University Hospital Rin Ishii College of Transdisciplinary Sciences for Innovation, Kanazawa University Shinichi Morimoto Meditec Japan Co., Ltd. Motochika Maki Meditec Japan Co., Ltd. During computed tomography (CT) examination, radiation exposures should be appropriately managed taking into considering the effects of bowtie filter, the heel effect and over-beaming effect. Furthermore, the analysis of an X-ray incident direction is important. The purpose of this study is to develop a procedure to obtain two-dimensional (2D) internal dose distributions based on actual measurements of surface dose distribution and central internal dose data. Experiments were conducted using a clinical CT scanner and four cylindrical polyacetal resin (POM) phantoms having diameters of 15–30 cm. The entrance surface doses and the central internal dose were measured by placing the optically stimulated luminescence (OSL) dosimeters on the surface and inner part of the phantom, respectively, during helical CT scans. The X-ray incident direction at the slice containing the dosimeter was estimated based on the noise distribution analysis of the CT image. Then, circumferential surface dose distributions were determined as a function of the X-ray incident direction. Based on these experimental data, we succeeded in visualizing the 2D dose distributions. The obtained dose distribution was inhomogeneous, clearly reflecting the influence of factors such as the heel effect. The uncertainty due to our methodology was estimated to be from 4.3 % to 7.4 %. Our methodology needs central internal dose data, and the absence of this data introduced additional systematic uncertainties of +6.9 % to －11.4 %. In conclusion, correcting for the effect of the X-ray incident directions for entrance surface dose and adding the central inner dose data can improve the reliability of the internal dose distribution. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 1949-0976 17 1 2025 Asiatic acid, a novel ciprofloxacin adjuvant inhibits Shigella flexneri infection 2586329 EN Priyanka Maitra Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections Samhati Bhukta Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections Animesh Gope Division of Clinical Medicine, ICMR-National Institute for Research in Bacterial Infections Pratanu Kayet Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections Surajit Basak Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections Shin-Ichi Miyoshi Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kei Kitahara Collaborative Research Center of Okayama University for Infectious Diseases in India, ICMR-National Institute for Research in Bacterial Infections Shanta Dutta Department of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Sushmita Bhattacharya Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections Bacterial infection caused by intracellular pathogens such as Shigella flexneri is a rapidly increasing global health concern that requires urgent and necessary action. The dearth of licensed vaccines against shigellosis and the decline in susceptibility to conventional antibiotics has encouraged the development of new antibiotic principles and drugs. The treatment options are decreasing faster than the discovery rate of new antibacterial agents. Combinatorial approach of antibiotics with non-antibiotic adjuvants is a promising aspect to treat resistant bacterial infections. Asiatic acid, a membrane-disrupting triterpenoid with wide antimicrobial and immunomodulatory properties, can potentiate antibiotics, but the exact mechanisms remain broadly unexplored. Therefore, in this study, we screened the interaction of asiatic acid with several antibiotics. The results showed synergistic interactions of asiatic acid with antibiotics against susceptible and multidrug-resistant S. flexneri clinical isolates. Particularly important was the interaction of asiatic acid with the quinolone antibiotics ciprofloxacin and nalidixic acid. A detailed study showed that combined treatment of asiatic acid with ciprofloxacin inhibited S. flexneri biofilm formation and resistance development. An increase in membrane disruption and depolarization upon co-treatment was evident by surface electron and confocal microscopy. In addition, asiatic acid and ciprofloxacin synergism was identified to inhibit efflux activity and intracellular bacterial viability. However, asiatic acid showed no synergistic toxicity with ciprofloxacin towards mammalian cells. The antibacterial activity was further verified in a S. flexneri infected mice model. Therapeutic benefits were evident with reduced bacterial burden, recovery from intestinal tissue damage and increase in mice survivability. The results showed that this combination can target the bacterial membrane, efflux pump proteins and biofilm formation, thereby preventing resistance development. The combination treatment offers a proof of concept in targeting essential bacterial activities and might be developed into a novel and efficient treatment alternative against S. flexneri. 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.

Oxford University Press (OUP) Acta Medica Okayama 2730-6151 5 1 2025 Proliferation of a bloom-forming phytoplankton via uptake of polyphosphate-accumulating bacteria under phosphate-limiting conditions ycaf192 EN Seiya Fukuyama Institute of Plant Science and Resources, Okayama University Fumiko Usami Institute of Plant Science and Resources, Okayama University Ryuichi Hirota Graduate School of Integrated Sciences for Life, Hiroshima University Ayano Satoh Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Shizuka Ohara Graduate School of Integrated Sciences for Life, Hiroshima University Ken Kondo Research Institute of Environment, Agriculture and Fisheries , Osaka Prefecture Yuki Gomibuchi Department of Physics and Information Technology, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology Takuo Yasunaga Department of Physics and Information Technology, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology Toshimitsu Onduka Hatsukaichi Branch, Fisheries Technology Institute , Fisheries Research and Education Agency Akio Kuroda Graduate School of Integrated Sciences for Life, Hiroshima University Kazuhiko Koike Graduate School of Integrated Sciences for Life, Hiroshima University Shoko Ueki Institute of Plant Science and Resources, Okayama University Harmful algal blooms negatively impact the ecosystem and fisheries in affected areas. Eutrophication is a major factor contributing to bloom occurrence, and phosphorus is particularly important in limiting the growth of bloom-forming algae. Although algae efficiently utilize orthophosphate (Pi) as a phosphorous source over other molecular forms, Pi is often limited in the marine environment. While uptake and utilization of soluble inorganic and organic phosphorous by bloom-forming algae has been extensively studied, the details of geochemical and biological phosphorous cycling remain to be elucidated. Here, we report for the first time that the bloom-forming alga Heterosigma akashiwo can phagocytose bacteria and grow under phosphate-depleted conditions. The addition of Vibrio comitans to Pi-depleted H. akashiwo enabled the alga propagate to high cell densities, whereas other bacterial strains had only a minor effect. Importantly, V. comitans accumulates polyphosphate―a linear polymer of Pi―at high levels. The extent of algal proliferation induced by the addition of Vibrio species and polyphosphate-accumulating Escherichia coli correlated strongly with their polyphosphate content, indicating that bacterial polyphosphate served as an alternative PO43－ source for H. akashiwo. The direct uptake of polyphosphate-accumulating bacteria through algal phagocytosis may represent a novel biological phosphorous-cycling pathway in marine ecosystems. The role of polyphosphate-accumulating marine bacteria as a hidden phosphorous source required for bloom formation warrants further investigation. 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 1478-6362 27 1 2025 Does perioperative discontinuation of anti-rheumatic drugs increase postoperative complications in orthopedic surgery for rheumatoid arthritis? 219 EN Hiromu Ito Department of Orthopaedic Surgery, Kurashiki Central Hospital Hajime Ishikawa Department of Rheumatology, Niigata Rheumatic Center Shigeyoshi Tsuji Department of Orthopaedic Surgery, Osaka Minami Medical Center Masanori Nakayama Department of Orthopaedic Surgery, International University of Health and Welfare Keiichiro Nishida Locomotive Pain Center, Okayama University Hospital Takeshi Mochizuki Department of Orthopaedic Surgery, Kamagaya General Hospital Kosuke Ebina Department of Orthopaedic Surgery, Osaka University Faculty of Medicine Graduate School of Medicine Toshihisa Kojima Department of Orthopaedic Surgery, Nagoya University Hospital Takumi Matsumoto Department of Orthopaedic Surgery, University of Tokyo Ayako Kubota Department of Orthopaedic Surgery, Toho University Omori Medical Center Arata Nakajima Department of Orthopaedic Surgery and Rehabilitation, Toho University Sakura Medical Center Atsushi Kaneko Department of Orthopaedic Surgery, Nagoya Medical Center Isao Matsushita Department of Rehabilitation Medicine, Kanazawa Medical University Ryota Hara The Center for Rheumatic Diseases, Nara Medical University Koji Sakuraba Department of Orthopaedic Surgery, Kyushu Medical Center Yukio Akasaki Department of Orthopaedic Surgery, Kyushu University Tsukasa Matsubara Department of Orthopaedic Surgery, Matsubara Mayflower Hospital Yuichi Mochida Department of Orthopaedic Surgery, Yokohama City University Medical Center Katsuaki Kanbe Department of Orthopaedic Surgery, Nippori Orthopaedics and Rheumatic Clinic Natsuko Nakagawa Department of Orthopaedic Surgery, Kakogawa Medical Center Koichi Murata Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine Shigeki Momohara Endowed Course for Advanced Therapy for Musculoskeletal Disorders, Keio University School of Medicine Objective This study aimed to investigate whether discontinuation of biological or targeted synthetic antirheumatic disease-modifying drugs (bDMARDs or tsDMARDs) influences the incidence of postoperative complications in patients with rheumatoid arthritis (RA) undergoing orthopedic surgery. Methods A retrospective multicenter cohort study including patients receiving bDMARDs or tsDMARDs who underwent orthopedic surgery was conducted. Data collected encompassed the duration of drug discontinuation and postoperative adverse events, such as delayed wound healing, surgical site infection (SSI), disease flare-ups, and mortality. The association between drug discontinuation and these outcomes was analyzed. Multivariate analyses were conducted to identify potential risk factors for these events. Results A total of 2,060 cases were initially enrolled. After applying inclusion and exclusion criteria, data from 1,953 patients were analyzed. No significant differences were observed between the groups regarding delayed wound healing, SSI, or mortality. However, the incidence of disease flare-ups was substantially higher in the drug discontinuation group and in the interleukin (IL)-6 inhibitor group. Multivariate analysis identified that tumor necrosis factor α and IL-6 inhibitor use was associated with a higher risk of delayed wound healing relative to T-cell function modifiers. Conclusion In orthopedic surgery for patients with RA, maintaining the standard or the half of administration interval of bDMARD appears safe in the preoperative period. However, the drug discontinuation may increase the risk of postoperative flare-ups, particularly with IL-6 inhibitors. In addition, T-cell function modifiers may be associated with a lower risk of delayed wound healing, suggesting their safety profile in this context. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1433-7398 2025 A rare case of supratentorial ependymosarcoma harboring ZFTA::RELA fusion EN Yuji Matsumoto Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuki Suruga Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kaishi Satomi Department of Pathology, Faculty of Medicine, Kyorin University Yohei Inoue Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuhiko Hattori Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Joji Ishida Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuhiko Kurozumi Department of Neurosurgery, Hamamatsu University Hospital Sumihito Nobusawa Department of Human Pathology, Gunma University School of Medicine Junko Hirato Department of Pathology, Public Tomioka General Hospital Takehiro Tanaka Department of Pathology, Okayama University Hospital Hiroyuki Yanai Department of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kana Washio Department of Pediatrics, Okayama University Hospital Koichi Ichimura Department of Pathology, Faculty of Medicine, Kyorin University Tomotsugu Ichikawa Department of Neurosurgery, Kagawa Prefectural Central Hospital Yoshihiro Otani Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shota Tanaka Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ependymosarcoma is an exceedingly rare variant of ependymoma characterized by a mixture of ependymomatous and sarcomatous components. We report a case of supratentorial ependymosarcoma harboring a ZFTA::RELA fusion in a 10-year-old girl. Histologically, the tumor comprised an ependymomatous component resembling clear cell ependymoma and a sarcomatous component. ZFTA::RELA fusion was confirmed in both components. Genome-wide methylation profiling classified both components as supratentorial ependymoma, ZFTA fusion–positive by the German Cancer Research Center (DKFZ) CNS tumor classifier v12b8. However, their copy number alteration profiles were distinct. The ependymomatous component exhibited a gain of chromosome 1q and a loss of chromosomes 1p, 9, and 19q, while the sarcomatous component showed a loss of chromosome 14. These findings suggest that both components may have differentiated from a common precursor despite their distinct morphologies. The patient underwent gross total resection followed by adjuvant chemoradiotherapy and remains recurrence-free eight years post-treatment. Further investigation of additional cases is warranted to better understand the pathogenesis of this rare tumor. 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 1434-3916 145 1 2025 Changes in the anatomical positions of the femoral nerve and artery in the lateral and supine positions: a multicenter retrospective study 373 EN Ryuichiro Okuda Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine 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 Tomoko Tetsunaga Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Koura Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomohiro Inoue Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasutaka Masada Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tetsuya Yamamoto Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shin Matsumoto Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hisanori Ikuma Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital Tadashi Komatsubara Department of Orthopaedic Surgery, Okayama Rosai Hospital Yuki Okazaki Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Introduction Femoral nerve palsy and femoral artery injury are serious complications of total hip arthroplasty. However, few studies have compared the anatomical positions of these structures in different patient positions. This study aimed to compare the anatomical positions of the femoral nerve and artery in the lateral and supine positions. Materials and methods This multicenter retrospective study included 111 patients who underwent lateral and supine computed tomography (CT) from 2016 to 2023. CT images were reconstructed in the anterior pelvic plane. The horizontal distance from the anterior margin of the acetabulum to the femoral nerve (Distance N) and femoral artery (Distance A) was measured. The difference in Distance N between the two positions (ΔLateral–supine Distance N) was calculated by subtracting the supine value from the lateral value. Results The average Distance N was 26.5 ± 5.1 mm in the lateral position and 21.1 ± 4.4 mm in the supine position, with the nerve located significantly closer to the acetabulum in the supine position (P < 0.001). Similarly, the average Distance A was 26.8 ± 5.4 mm in the lateral position and 20.4 ± 4.9 mm in the supine position (P < 0.001). Multiple regression analysis showed that Distance N in the lateral position was significantly shorter in female patients and those with low body weight. In addition, low body weight correlated with a smaller ΔLateral–supine Distance N. Conclusions The femoral nerve and artery are located closer to the anterior margin of the acetabulum in the supine position than in the lateral position. Low body weight was an independent predictor of shorter Distance N in both positions and a smaller ΔLateral–supine Distance N. These findings underscore the importance of considering patient positioning during total hip arthroplasty, particularly in patients with low body weight, to reduce neurovascular risks. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1648-9144 61 6 2025 Accuracy Verification of a Computed Tomography-Based Navigation System for Total Hip Arthroplasty in Severe Hip Dysplasia: A Simulation Study Using 3D-Printed Bone Models of Crowe Types II, III, and IV 973 EN Ryuichiro Okuda Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomonori Tetsunaga Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Yamada Department of Orthopaedic Surgery, Okayama University Hospital Tomoko Tetsunaga Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Koura Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Inoue Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutaka Masada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Okazaki 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 Background and Objective: The use of computed tomography (CT)-based navigation systems has been shown to improve surgical accuracy in total hip arthroplasty. However, there is limited literature available about the application of CT-based navigation systems in severe hip dysplasia. This study aimed to evaluate the accuracy of a CT-based navigation system in patients with severe hip dysplasia using three-dimensional (3D)-printed bone models. Methods: 3D-printed bone models were generated from CT data of patients with severe hip dysplasia (Crowe type II, 10 hips; type III, 10 hips; and type IV, 10 hips). The accuracy of automatic segmentation, success rate, point-matching accuracy across different registration methods, and deviation values at reference points after registration were assessed. Results: For the combined cohort of Crowe II, III, and IV cases (n = 30), the Dice Similarity Coefficient and Jaccard Index were 0.99 ± 0.01 and 0.98 ± 0.02, respectively. These values indicate a high level of segmentation accuracy. The “Matching with true and false acetabulum + iliac crest” method achieved a 100% success rate across all groups, with mean deviations of 0.08 ± 0.28 mm in the Crowe II group, 0.12 ± 0.33 mm in the Crowe III group, and 0.14 ± 0.50 mm in the Crowe IV group (p = 0.572). In the Crowe IV group, the anterior superior iliac spine deviation was significantly lower using the “Matching with true and false acetabulum + iliac crest” method compared to the “Matching with true and false acetabulum” method (0.28 ± 0.49 mm vs. 3.29 ± 2.56 mm, p < 0.05). Conclusions: This study demonstrated the high accuracy of automatic AI-based segmentation, with a Dice Similarity Coefficient of 0.99 ± 0.01 and a Jaccard Index of 0.98 ± 0.02 in the combined cohort of Crowe type II, III, and IV cases (n = 30). The matching success rate was 100%, with additional points on the iliac crest, which improved matching accuracy and reduced deviations, depending on the case. 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 特別支援学校に通う中学2年生の学校生活での身体活動量の特徴 149 155 EN Minoru ADACHI Faculty of Education, Okayama University 10.18926/bgeou/69618 　In this study, data from a survey completed before the spread of COVID-19 were used to measure the amount of physical activity in school among eighth graders attending special-needs schools and compared with the WHO Guidelines for Physical Activity and Sedentary Behavior. The subjects were 16 eighth graders in public special-needs schools. In addition to height and weight, the physical activity survey during school life was measured using a uniaxial accelerometer (Kenz Lifecorder GS 4-second version: LC). 7534 ± 2275 steps/day for boys, 6411 ± 1614 steps/day for girls, and middle and high intensity activity time (MVPA) was 19.3 ± 10.3 minutes/day for boys and 16.7 ± 8.3 minutes/day for girls. These results suggest that eighth graders attending special needs schools are well below the WHO Guidelines for Physical Activity and Sedentary Behavior standard of 60 minutes/day for children and adolescents with disabilities (5-17 years old ) for both boys and girls. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1320-5358 30 5 2025 A Case of IgA Nephropathy With Membranoproliferative Glomerulonephritis-Like Features Miyu Kanazawa, e70057 EN Miyu Kanazawa Okayama University Medical School Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoya Aoki Okayama University Medical School Mihiro Sue Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Miyake Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences A 73-year-old man was referred due to the onset of nephrotic-range proteinuria. He had been diagnosed with rheumatoid arthritis 18 years prior and had achieved remission with treatment, including methotrexate and janus kinase (JAK) inhibitor. Although routine follow-ups had not revealed any urinary abnormalities, subsequent tests detected proteinuria and hematuria in the absence of infection or other symptoms. As the urinary abnormalities persisted, with a serum albumin decrease and proteinuria measuring 5.7 g/day, indicating nephrotic syndrome, the patient was referred to our hospital for further evaluation, and a renal biopsy was performed. Light microscopy revealed mesangial cell proliferation, endocapillary proliferation and double-contoured basement membranes. Immunofluorescence microscopy showed IgA-dominant deposits in both mesangial areas and glomerular capillary walls. Transmission electron microscopy demonstrated electron-dense deposits in the mesangium and subendothelial regions, leading to the diagnosis of membranoproliferative glomerulonephritis (MPGN)-type IgA nephropathy. Immunostaining with the Gd-IgA1 (galactose-deficient IgA1)-specific antibody (KM55) was positive, consistent with the diagnosis. Following the initiation of steroid therapy, proteinuria rapidly decreased, achieving complete remission within 5 months. IgA nephropathy with MPGN-like features often presents as nephrotic syndrome, differing from the typical pathological and clinical presentation of IgA nephropathy, making differentiation from secondary MPGN and other diseases sometimes challenging. This case suggests that KM55 staining may offer additional information in differentiating atypical IgA nephropathy with non-classical pathological features. 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.

Elsevier BV Acta Medica Okayama 0341-8162 254 2025 Cellulose nanofibers boost soil water availability, plant growth, and irrigation water use efficiency under deficit irrigation 108998 EN An Thuy Ngo Graduate School of Environmental and Life Science, Okayama University Manh Cong Nguyen Nong Lam University Morihiro Maeda Graduate School of Environmental and Life Science, Okayama University Yasushi Mori Graduate School of Environmental and Life Science, Okayama University Under climate change, even previously rainfall-prone areas may experience droughts, and effective strategies are vital for soil conservation. Owing to their cutting-edge water absorption and storage properties, cellulose nanofibers (CNF) are expected to increase soil water availability and help plants resist water stress. However, the role of CNF in improving plant growth and soil water retention under various irrigation regimes is not yet known. We evaluated the effects of CNFs on plant available water (PAW), germination, plant growth, and irrigation water use efficiency (IWUE) under both adequate and deficit irrigation conditions. Plant cultivation experiments were conducted using different CNF dosages (0%, 0.1%, 0.5%, and 1.0%), irrigation levels (I100, I50, and I25), and soil types (sandy and silty loam). The results indicated that CNF significantly increased field capacity (FC) and PAW in both soil types, with PAW in CNF-amended soils increasing by up to 110% and 88% in sandy and silty loam soil, respectively, at 1% CNF dosage. In germination tests, CNF showed no phytotoxicity and supported the germination process during water stress, with enhancements of up to 64% and 163% at I50 and up to 125% and 214% at I25 in germination percentage and germination index, respectively. Plant growth experiments revealed that CNF addition helped plants resist water stress, maintaining plant height and weight close to those under full irrigation, while using 50% less water. IWUE analyses demonstrated that CNF enhanced IWUE, with increases of up to 56% under sufficient watering (I100), 169% under moderate water stress (I50), and 120% under severe water stress (I25), at 1% CNF dosage. These findings highlight the potential of CNF as a multifaceted amendment, offering practical solutions for addressing water scarcity challenges and contributing to more resilient and sustainable agricultural practices. No potential conflict of interest relevant to this article was reported.

Bioscientifica Acta Medica Okayama 2052-0573 2025 1 2025 Adult hypophosphatasia presenting with recurrent acute joint pain e240121 EN Hayao Yoshida Department of Diabetes and Endocrinology, Shiga General Hospital Takaaki Murakami Department of Diabetes and Endocrinology, Shiga General Hospital Atsubumi Ogawa Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine Takashi Sunouchi Division of Nephrology and Endocrinology, The University of Tokyo Hospital Naoko Hidaka Division of Nephrology and Endocrinology, The University of Tokyo Hospital Nobuaki Ito Osteoporosis Center, The University of Tokyo Hospital Hiromi Murakami Department of Genomic Medicine, Kyoto University Graduate School of Medicine Hidenori Kawasaki Department of Genomic Medicine, Kyoto University Graduate School of Medicine Tomoyuki Akiyama Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsumi Nakajima Department of Diabetes and Endocrinology, Shiga General Hospital Daisuke Yabe Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine Taizo Yamamoto Department of Diabetes and Endocrinology, Shiga General Hospital Hypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees. Magnetic resonance imaging and joint ultrasonography showed joint effusions indicating chronic inflammation. Blood biochemical tests revealed a remarkably low serum ALP level, and repeated examination confirmed a sustained low ALP level; urine phosphoethanolamine, plasma inorganic pyrophosphate and plasma pyridoxal-5′-phosphate levels were elevated, raising concern for HPP. While the patient had no history of premature loss of primary teeth, fragility fractures, muscle weakness or abnormalities in growth, genetic testing revealed a likely pathogenic and a pathogenic heterozygous variant in the ALPL gene, i.e., c.979T>C (p.Phe327Leu) and c.1559del (p.Leu520Argfs), confirming HPP. Additional genetic testing of his parents showed a heterozygous c.1559del variant in his father and a heterozygous c.979T>C variant in his mother. A diagnosis of adult HPP due to compound heterozygous mutations was therefore confirmed. Enzyme replacement therapy with asfotase alfa was then introduced; no attacks of arthralgia occurred in the 1-year period since then. This case highlights the possibility of HPP in adults who present clinically with repeated joint symptoms and low serum ALP levels but without bone-related symptoms. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0007-1048 2025 Impact of methotrexate-dosing regimens for GVHD prophylaxis on clinical outcomes of HLA-matched allogeneic HSCT EN Tomotaka Suzuki Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences Tomoyasu Jo Department of Hematology, Graduate School of Medicine, Kyoto University Kota Yoshifuji Department of Hematology, Institute of Science Tokyo Tadakazu Kondo Department of Hematology, Graduate School of Medicine, Kyoto University Noriko Doki Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Centre, Komagome Hospital Yoshinobu Kanda Division of Hematology, Jichi Medical University Saitama Medical Centre Tetsuya Nishida Department of Hematology, Japanese Red Cross Aichi Medical Centre Nagoya Daiichi Hospital Yasushi Onishi Department of Hematology, Tohoku University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Takahiro Fukuda Department of Haematopoietic Stem Cell Transplantation, National Cancer Centre Hospital Masashi Sawa Department of Hematology and Oncology, Anjo Kosei Hospital Yuta Hasegawa Department of Hematology, Hokkaido University Hospital Kentaro Serizawa Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Shuichi Ota Department of Hematology, Sapporo Hokuyu Hospital Masatsugu Tanaka Department of Hematology, Kanagawa Cancer Centre Makoto Yoshimitsu Department of Hematology and Rheumatology, Graduate School of Medical and Dental Sciences, Kagoshima University Yoshiko Atsuta Japanese Data Centre for Haematopoietic Cell Transplantation Junya Kanda Department of Hematology, Graduate School of Medicine, Kyoto University Severe graft-versus-host disease (GVHD) remains a major complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT), necessitating optimal immunosuppressive strategies. This retrospective study used data from the Japanese Transplant Registry Unified Management Program to compare three methotrexate (MTX)-dosing regimens for GVHD prophylaxis in patients undergoing human leucocyte antigen (HLA)-matched allo-HSCT: a low-dose 3-day regimen (Ld3:10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6), a low-dose 4-day regimen (Ld4: Ld3 with an additional 7 mg/m2 on day 11) and an original-dose 3-day regimen (Od3: 15 mg/m2 on day 1, 10 mg/m2 on days 3 and 6). Among 2537 analysed patients, Ld3 was the most commonly used regimen. Multivariate analyses showed no significant differences in the cumulative incidence of grade II–IV acute GVHD among regimens. However, Od3 was associated with an increased risk of grade III–IV acute GVHD, and Ld4 was linked to delayed neutrophil engraftment. This study is the first large-scale retrospective analysis of the impact of different MTX-dosing regimens on the outcomes of HLA-matched allo-HSCT, providing valuable insights into optimal MTX-dosing strategies in clinical practice. No potential conflict of interest relevant to this article was reported.

American Society of Hematology Acta Medica Okayama 2473-9529 9 18 2025 Refinement of day 28 treatment response criteria for acute GVHD: a collaboration study of the JSTCT and MAGIC 4640 4653 EN Yu Akahoshi Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Yoshihiro Inamoto Department of Blood and Marrow Transplantation and Cellular Therapy, Fujita Health University School of Medicine Nikolaos Spyrou Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Hideki Nakasone Division of Hematology, Jichi Medical University Saitama Medical Center Marcio A. Diniz Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Francis Ayuk Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf Hannah K. Choe Division of Hematology, Blood and Marrow Transplantation Program, The Ohio State University Comprehensive Cancer Center Noriko Doki Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Tetsuya Eto Department of Hematology, Hamanomachi Hospital Aaron M. Etra Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Elizabeth O. Hexner Department of Medicine and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania Nobuhiro Hiramoto Department of Hematology, Kobe City Medical Center General Hospital William J. Hogan Division of Hematology, Mayo Clinic Ernst Holler Department of Hematology and Oncology, Internal Medicine III, University of Regensburg Keisuke Kataoka Division of Molecular Oncology, National Cancer Center Research Institute Toshiro Kawakita Department of Hematology, National Hospital Organization Kumamoto Medical Center Masatsugu Tanaka Department of Hematology, Kanagawa Cancer Center Takashi Tanaka Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital Naoyuki Uchida Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital Ingrid Vasova Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg and University Hospital Erlangen Satoshi Yoshihara Department of Hematology, Hyogo Medical University Hospital Fumihiko Ishimaru Technical Department, Japanese Red Cross Blood Service Headquarters Takahiro Fukuda Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital Yi-Bin Chen Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital Junya Kanda Department of Hematology, Graduate School of Medicine, Kyoto University Ryotaro Nakamura Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation James L. M. Ferrara Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Yoshinobu Kanda Division of Hematology, Jichi Medical University Saitama Medical Center John E. Levine Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Takanori Teshima Department of Hematology, Hokkaido University Faculty of Medicine and Graduate School of Medicine Overall response (OR) that combines complete (CR) and partial responses (PR) is the conventional end point for acute graft-versus-host disease (GVHD) trials. Because PR includes heterogeneous clinical presentations, reclassifying PR could produce a better end point. Patients in the primary treatment cohort from the Japanese Society for Transplantation and Cellular Therapy (JSTCT) were randomly divided into training and validation sets. In the training set, a classification and regression tree algorithm generated day 28 refined response (RR) criteria based on symptoms at treatment and day 28. We then evaluated RR for primary and second-line treatments, using the area under the receiver operating characteristic curve (AUC) and negative predictive value (NPV) for 6-month nonrelapse mortality as performance measures. RR considered patients with grade 0/1 at day 28 without additional treatment as responders. RR for primary treatment produced higher AUCs than OR with small improvement of NPVs in both validation sets: JSTCT (AUC, 0.73 vs 0.69 [P < .001]; NPV, 92.0% vs 89.6% [P < .001]) and the Mount Sinai Acute GVHD International Consortium (MAGIC; AUC, 0.71 vs 0.68 [P = .032]; NPV, 90.9% vs 89.8% [P = .009]). RR for second-line treatment produced similar AUCs but much higher NPVs than OR in both validation sets of JSTCT (AUC, 0.64 vs 0.63 [P = .775]; NPV, 74.5% vs 66.0% [P < .001]) and MAGIC (AUC, 0.67 vs 0.64 [P = .105]; NPV, 86.8% vs 76.1% [P = .004]). Classifying persistent but mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses were major drivers in improving the prognostic performance of RR. Our externally validated day 28 RR would serve as a better end point than conventional criteria in future first- and second-line treatment trials. 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.

Elsevier BV Acta Medica Okayama 0301-679X 214 2026 The influence of lubricant additives and surface roughness and hardness of material on the damage behavior of gears 111341 EN Takuya Ohno Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tadashi Shiota Faculty of Environmental, Life, Natural Science and Technology, Okayama University Masahiro Fujii Faculty of Environmental, Life, Natural Science and Technology, Okayama University This study investigates the influence of lubricant additives, surface roughness, and material hardness on gear damage behavior under boundary lubrication conditions. We conducted both the Short-term Test and the Standard Test using an FZG gear test machine to evaluate how lubricant additives and gear surface roughness influence damage progression when the surface roughness exceeds the oil-film thickness. Acid phosphate ester effectively suppressed micropitting through surface smoothing but led to severe damage such as pitting and scuffing during prolonged use. In contrast, sulfurized fatty oil promoted mild wear, delaying catastrophic failures and extending gear life. Higher surface roughness accelerated wear, while increased hardness reduced deformation but it expanded damage areas. The study found that initial surface roughness and its progress during load stages strongly correlate with gear durability. Measurement of arithmetic mean roughness after sufficient running-in under actual load conditions proved useful for predicting long-term performance. These findings highlight the importance of selecting lubricant formulations tailored to specific gear operating environments and damage modes. Understanding the interplay between lubrication chemistry and material properties enables the design of more durable gear systems. No potential conflict of interest relevant to this article was reported.

The Company of Biologists Acta Medica Okayama 0950-1991 152 22 2025 ROS produced by Dual oxidase regulate cell proliferation and haemocyte migration during leg regeneration in the cricket dev204763 EN Misa Okumura-Hirono Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Bando Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshimasa Hamada Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideyo Ohuchi Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Many animals regenerate lost body parts through several signalling pathways; however, the triggers that initiate regeneration remain unclear. In the present study, we focused on the role of reactive oxygen species (ROS) produced by the NADPH oxidase Dual oxidase (Duox) during cricket leg regeneration. The results showed that ROS levels were upregulated during leg regeneration and decreased by DuoxRNAi. In DuoxRNAi nymphs, wound closure and scab formation were incomplete 2 days after amputation, and hypertrophy occurred in the distal region of the regenerating legs at 5 days after amputation. In addition, the hypertrophic phenotype was induced by DuoxARNAi and NADPH oxidase inhibitor treatment. During hypertrophy, haemocytes, including plasmatocytes, oenocytoids and granulocytes, accumulated. Proliferation of haemocytes in regenerating legs was not increased by DuoxRNAi; however, haemocyte accumulation was regulated by the Spatzle (Spz) family molecules, which are Toll receptor ligands. As the exoskeleton of DuoxRNAi nymphs was thinner than that of the control, excessive haemocyte accumulation can cause hypertrophy in DuoxRNAi nymphs. Thus, Duox-derived ROS are involved in wound healing and haemocyte accumulation through the Spz/Toll signalling pathway during leg regeneration in crickets. 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.

Wiley Acta Medica Okayama 1354-523X 2025 The Role of the Mylohyoid Line in the Spread of Mandibular Odontogenic Deep Neck Infection EN Eiji Iwata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kyoichi Obata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Kikuta Dental and Oral Medical Center, Kurume University School of Medicine Naoki Kaneko Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Kotaro Sato Department of Oral and Maxillofacial Surgery, Nagoya University, Graduate School of Medicine Norio Kitagawa Department of Oral and Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Yohei Takeshita Department of Oral and Maxillofacial Radiology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuhisa Matsuo Dental and Oral Medical Center, Kurume University School of Medicine Junsei Sameshima Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Akira Tachibana Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital Shintaro Kawano Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Jingo Kusukawa Dental and Oral Medical Center, Kurume University School of Medicine Masaya Akashi Department of Oral and Maxillofacial Surgery, Kobe University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Joe Iwanaga Dental and Oral Medical Center, Kurume University School of Medicine Introduction: Although mandibular odontogenic deep neck infections are occasionally fatal, the transmission pathway has not been elucidated. Materials and Methods: This multicenter retrospective study was comprised of the patients of both sexes who were over 18 years of age and who had mandibular odontogenic deep neck abscesses. The patients' characteristics, laboratory tests, and radiographic findings were analyzed. Results: One hundred eighteen patients with mandibular odontogenic deep neck abscesses were included. Bone resorption superior to the mylohyoid line and the related abscess formation in submandibular space or submental space were both significantly associated with the presence of sublingual space abscess. In addition, the type of causative tooth was not a risk factor for abscess formation in both the sublingual space and “submandibular or submental” space. Conclusions: When an odontogenic lesion is located superior to the mylohyoid line, the abscess tends to initially form in the sublingual space and subsequently spread to the submandibular or submental space. Since any mandibular tooth can lead to abscess formation in these regions, oral and maxillofacial surgeons should carefully assess the anatomical position of the lesion and accurately identify the causative tooth. 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.

Spandidos Publications Acta Medica Okayama 1791-2997 33 1 2025 Protective impact of landiolol against acute lung injury following hemorrhagic shock and resuscitation in rats 22 EN Risa Sakamoto Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroko Shimizu Department of Anesthesiology and Resuscitology, Okayama University Medical School Ryu Nakamura Department of Anesthesiology and Resuscitology, Okayama University Medical School Yifu Lu Department of Human Anatomy, Shantou University Medical College Yaqiang Li Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Emiko Omori Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Takahashi Department of Anesthesiology, Okayama Saidaiji Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation, leading to acute lung injury (ALI). Notably, blocking β1 receptors can lead to organ protection through anti‑inflammatory and anti‑apoptotic effects. Additionally, although the β1 receptor pathway is blocked by the β1 blocker, the β2 receptor pathway may be preserved and activate the 5' adenosine monophosphate‑activated protein kinase (AMPK) pathway. The present study aimed to examine whether administration of the β1 blocker landiolol could achieve lung protection in a model of HSR‑ALI, alongside improvements in inflammation and apoptosis. Male Sprague‑Dawley rats underwent hemorrhage keeping their mean arterial pressure at 30 mmHg for 1 h. Resuscitation by reinfusion was initiated to restore blood pressure to pre‑hemorrhage levels for >15 min, followed by a 45‑min stabilization period to create the HSR‑ALI model. Landiolol (100 mg/kg/min) or saline was continuously administered after resuscitation. The lung tissues, which were collected for assessing inflammation and apoptosis‑related damage, underwent analyses, including histological examination, neutrophil count, assessment of lung wet/dry weight ratio, detection of the mRNA levels of tumor necrosis factor‑α (TNF‑α) and inducible nitric oxide synthase (iNOS), identification of terminal deoxynucleotidyl transferase dUTP nick‑end labeling (TUNEL)‑positive cells, and evaluation of caspase‑3 expression. In addition, phosphorylated AMPKα (pAMPKα) expression was tested via western blotting. Compared with the HSR/saline group, the HSR/landiolol group demonstrated a reduction in lung tissue damage score, and significant reductions in neutrophil count, lung wet/dry weight ratio, lung TNF‑α and iNOS mRNA levels, TUNEL‑positive cells and cleaved caspase‑3 expression. Furthermore, landiolol administration following HSR treatment increased pAMPKα expression. No significant hypotension occurred between the HSR/landiolol and HSR/saline groups; and blood loss did not differ significantly between the groups. In conclusion, landiolol administration after HSR reduced lung inflammation and apoptosis, suggesting a potential improvement in tissue damage. Furthermore, pAMPKα activation in the HSR/landiolol group may be the mechanism underlying the pulmonary protective effects of landiolol. No potential conflict of interest relevant to this article was reported.

Microbiology Society Acta Medica Okayama 0022-1317 106 7 2025 Virus taxonomy proposal summaries: a searchable and citable resource to disseminate virus taxonomy advances 002079 EN Richard Mayne Nuffield Department of Medicine, University of Oxford Peter Simmonds Nuffield Department of Medicine, University of Oxford Donald B. Smith Nuffield Department of Medicine, University of Oxford Evelien M. Adriaenssens Quadram Institute Bioscience Elliot J. Lefkowitz Department of Microbiology, University of Alabama at Birmingham Hanna M. Oksanen Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki Francisco Murilo Zerbini Departamento de Fitopatologia/BIOAGRO, Universidade Federal de Viçosa Poliane Alfenas-Zerbini Departamento de Microbiologia, Universidade Federal de Viçosa Frank O Aylward Department of Biological Sciences, Virginia Tech Juliana Freitas-Astúa Embrapa Cassava and Fruits, Cruz das Almas R. Curtis Hendrickson Department of Microbiology, University of Alabama at Birmingham Holly R. Hughes Centers for Disease Control and Prevention Mart Krupovic Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit Jens H. Kuhn Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health Małgorzata Łobocka Institute of Biochemistry and Biophysics of the Polish Academy of Sciences Arcady R. Mushegian Division of Molecular and Cellular Biosciences, National Science Foundation Judit Penzes Institute for Quantitative Biomedicine, Rutgers University Alejandro Reyes Muñoz Departamento de Ciencias Biológicas, Universidad de los Andes David L. Robertson MRC-University of Glasgow Centre for Virus Research Simon Roux Department of Energy, Joint Genome Institute, Lawrence Berkeley National Laboratory Luisa Rubino Consiglio Nazionale delle Ricerche, Istituto per la Protezione Sostenibile delle Piante, Sede Secondaria di Bari Sead Sabanadzovic Department of Agricultural Science and Plant Protection, Mississippi State University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University Dann Turner Molecular Biology, University of the West of England Koenraad Van Doorslaer Department of Immunobiology, School of Animal and Comparative Biomedical Sciences, BIO5 Institute, University of Arizona Cancer Center Arvind Varsani The Biodesign Center for Fundamental and Applied Microbiomics, School of Life Sciences, Center for Evolution and Medicine, Arizona State University Taxonomic classification of cellular organisms requires the publication of descriptions and proposed names of species and the deposition of specimens. Virus taxonomy is developed through a different system of annual submission of formal taxonomy proposals (TPs) that can be submitted by anyone but are typically prepared by a study group appointed by the International Committee on Taxonomy of Viruses (ICTV) and consisting of experts on a particular group of viruses. These are initially evaluated by an expert subcommittee and by the executive committee (EC) of the ICTV. EC-approved TPs are then submitted for evaluation and a ratification vote by the wider ICTV membership. Following ratification, the new taxonomy is annually updated in the Master Species List, associated databases and bioinformatic resources. The process is consistent, creates traceability in assignments and supports a fully evaluated, hierarchical classification and nomenclature of all taxonomic ranks from species to realms. The structure also facilitates large-scale and coordinated changes to virus taxonomy, such as the recent introduction of a binomial species nomenclature. TPs are available on the ICTV website after ratification, but they are not indexed in bibliographic databases and are not easily cited. Authors of TPs do not receive citation credit for adopted proposals, and their voluntary contributions are largely invisible in the published literature. For greater visibility of TPs and their authors, the ICTV will commence the annual publication of summaries of all TPs from each ICTV subcommittee. These summaries will provide a searchable compendium of all annual taxonomy changes and additions as well as direct links to the Master Species List and other ICTV bioinformatic resources. Their publication will provide due credit and citations for their authors, form the basis for disseminating taxonomy decisions and promote greater visibility and accessibility to taxonomy changes for the virology community. 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 2051-5960 13 1 2025 Rotenone targets midbrain astrocytes to produce glial dysfunction-mediated dopaminergic neurodegeneration 234 EN Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nami Isooka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Kikuoka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Imafuku Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaori Masai Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kana Tomimoto Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiharu Sogawa Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology Norio Sogawa Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Kitamura Department of Pharmacotherapy, School of Pharmacy, Shujitsu University Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Exposure to pesticides, such as rotenone or paraquat, is an environmental factor that plays an important role in the pathogenesis of Parkinson's disease (PD). Rotenone induces PD-like pathology and is therefore used to develop parkinsonian animal models. Dopaminergic neurotoxicity caused by rotenone has been attributed to the inhibition of mitochondrial complex I, oxidative stress and neuroinflammation; however, the mechanisms underlying selective dopaminergic neurodegeneration by rotenone remain unclear. To resolve this, we focused on glial diversity and examined whether the brain region-specific glial response to rotenone could determine the vulnerability of dopaminergic neurons using primary cultured neurons, astrocytes and microglia from the midbrain and striatum of rat embryos and rotenone-injected PD model mice. Direct neuronal treatment with low-dose rotenone failed to damage dopaminergic neurons. Conversely, rotenone exposure in the presence of midbrain astrocyte and microglia or conditioned media from rotenone-treated midbrain glial cultures containing astrocytes and microglia produced dopaminergic neurotoxicity, but striatal glia did not. Surprisingly, conditioned media from rotenone-treated midbrain astrocytes or microglia monocultures did not affect neuronal survival. We also demonstrated that rotenone targeted midbrain astrocytes prior to microglia to induce dopaminergic neurotoxicity. Rotenone-treated astrocytes produced secreted protein acidic and rich in cysteine (SPARC) extracellularly, which induced microglial proliferation, increase in IL-1β and TNF-α, and NF-κB (p65) nuclear translocation in microglia, resulting in dopaminergic neurodegeneration. In addition, rotenone exposure caused the secretion of NFAT-related inflammatory cytokines and a reduction in the level of an antioxidant metallothionein (MT)-1 from midbrain glia. Furthermore, we observed microglial proliferation and a decrease in the number of MT-positive astrocytes in the substantia nigra, but not the striatum, of low-dose rotenone-injected PD model mice. Our data highlight that rotenone targets midbrain astrocytes, leading to SPARC secretion, which promotes the neurotoxic conversion of microglia and leads to glial dysfunction-mediated dopaminergic neurodegeneration. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 14 17 2025 Potential of Kidney Exchange Programs (KEPs) in Japan for Donor-Specific Antibody-Positive Kidney Transplants: A Questionnaire Survey on KEPs and a Multi-Institutional Study Conducting Virtual Cross-Matching Simulations 6122 EN Taihei Ito Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Miki Ito Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Naohiro Aida Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Kei Kurihara Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Akihiro Terao Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Yoshihiko Watarai Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital Mitsuru Saito Division of Blood Purification, Akita University Hospital Keizo Kaku Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University Daisuke Ishii Department of Urology, Kitasato University of Medicine Satoshi Sekiguchi Transplantation Surgery, Japan Community Healthcare Organization Sendai Hospital Tatsuo Yoneda Unit of Dialysis, Department of Urology, Nara Medical University Kohei Unagami Organ Transplant Medicine, Tokyo Women’s Medical University Masayuki Tasaki Division of Urology, Department of Regenerative & Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University Hitoshi Iwamoto Department of Kidney Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Takahashi Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba Kazuaki Yamanaka Department of Urology, Osaka University Graduate School of Medicine Mikio Sugimoto Department of Urology, Faculty of Medicine, Adrenal Surgery and Renal Transplantation, Kagawa University Kouhei Nishikawa Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine Chikashi Seto Department of Urology, Toyama Prefectural Central Hospital Masaki Muramatsu Department of Nephrology, Toho University Faculty of Medicine Toshihiro Asai Department of Kidney Transplant and Dialysis, Osaka City General Hospital Daiki Iwami Division of Renal Surgery and Transplantation, Department of Urology, Jichi Medical University Yasutoshi Yamada Department of Blood Purification, Kagoshima University Hospital Shigeyoshi Yamanaga Department of Transplant Surgery, Japanese Red Cross Kumamoto Hospital Tomonori Komatsu Department of Urology, Chukyo Hospital, Japan Community Healthcare Organization Masayoshi Miura Department of Renal Transplantation Surgery and Urology, Sapporo Hokuyu Hospital Takahiro Nohara Department of Urology, Kanazawa University Hospital Michihiro Maruyama Department of Frontier Surgery, Chiba University School of Medicine Yuki Miyauchi Department of Urology, Ehime University Toshiaki Tanaka Department of Urology, Sapporo Medical University Michio Nakamura Department of Transplant Surgery, Tokai University School of Medicine Kiyohiko Hotta Department of Renal and Genitourinary Surgery, Faculty of Medicine, Hokkaido University Takashi Kenmochi Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Objectives: To clarify the need for a kidney exchange program (KEP) in Japan by conducting a questionnaire survey on KEPs and simulated KEPs by virtual cross-matching based on past cases of transplantation avoidance. Methods: In addition to the content regarding KEPs, an electronic survey was conducted to investigate the number of cases of kidney transplant abandonment due to “immunological” reasons over the past 10 years (2012–2021). Virtual cross-matching was conducted to simulate the feasibility of avoiding immunological risks and enabling kidney transplantation in patients who were previously unable to undergo the procedure. Results: The survey received responses from 107 facilities (response rate: 81.7%). In response to the question about the necessity of a KEP in Japan, 71 facilities (66.4%) indicated that KEPs are necessary. In addition, 251 living-donor kidney transplants were abandoned for “immunological” reasons over the past decade (2012–2021). Among the 80 pairs for which detailed information was available, virtual cross-matching simulations showed that 37/80 pairs (46.3%) were donor-specific antibody (DSA)-negative for blood type-matched combinations, and 41/80 pairs (51.3%) were DSA-negative for blood type-incompatible transplants. Conclusions: The need for a KEP in Japan and its potential usefulness were demonstrated. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2352-4928 50 2026 Effects of grain size and crystal orientation on tensile properties of pure titanium thin wires 114240 EN Junji Sakamoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Naoya Tada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takeshi Uemori Faculty of Environmental, Life, Natural Science and Technology, Okayama University To clarify the effects of the grain size and crystal orientation on the tensile properties of pure titanium thin wires, tensile and stepwise tensile tests were conducted on pure titanium wires with diameters of approximately 180 μm and different average grain sizes (52, 37, 23, and 3.8 μm). When the grain size was large, the fracture strain was significantly smaller, the variation in tensile strength was larger, and the grain size threshold for such properties was a grain-size ratio to wire diameter of 0.13 or greater. For larger grain sizes, the slip system with the highest modified Schmid factor (MSF), which is the Schmid factor divided by the critical resolved shear stress of each slip system, was activated in all 15 grains whereas for smaller grain sizes, the percentage of slip systems activated with the highest MSF was slightly lower. In addition, the fracture location in a thin wire with larger grain sizes was highly correlated with the average MSF of the grains in the cross-section. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1618-1247 2025 Admission prognostic nutritional index predicts prolonged hospitalization in severe odontogenic deep neck infections EN Eiji Iwata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kyoichi Obata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Kikuta Dental and Oral Medical Center, Kurume University School of Medicine Naoki Kaneko Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Kotaro Sato Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine Norio Kitagawa Department of Oral and Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Yohei Takeshita Department of Oral and Maxillofacial Radiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Katsuhisa Matsuo Dental and Oral Medical Center, Kurume University School of Medicine Junsei Sameshima Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Akira Tachibana Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital Shintaro Kawano Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Jingo Kusukawa Dental and Oral Medical Center, Kurume University School of Medicine Masaya Akashi Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine Joe Iwanaga Dental and Oral Medical Center, Kurume University School of Medicine Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives Severe odontogenic deep neck infections (DNIs) can be life threatening. This study investigated the nutritional status of affected patients and evaluated the usefulness of the Prognostic Nutritional Index (PNI) at admission in helping maxillofacial surgeons identify, at presentation, those likely to require extended hospitalization. Methods A total of 112 patients treated for odontogenic deep neck abscesses and necrotizing soft tissue infections at five hospitals in Japan. Patients were included. Patients were categorized by length of hospitalization duration and factors associated with prolonged hospitalization were analyzed using propensity score matching to minimize bias. Spearman’s rank correlation analysis was also performed to assess the relationship between PNI and hospitalization duration. Results Fifty patients (44.6%) required hospitalization for more than 14 days. Multivariate analysis identified PNI ≤ 41.2 (odds ratio [OR] = 2.79) and the presence of abscesses in multiple deep neck spaces (OR = 2.76) as significant predictors of prolonged hospitalization. Propensity score analysis confirmed the significant association between PNI and length of hospitalization duration (P = 0.048). In addition, Spearman’s rank correlation coefficient was r = － 0.471 (P < 0.001), indicating a moderate negative correlation. Conclusion The admission PNI may serve as a useful adjunctive indicator for predicting prolonged hospitalization in patients with severe odontogenic DNIs, as it reflects both nutritional status and systemic inflammation. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1096-4959 281 2026 N-terminal domains and site-specific glycosylation regulate the secretion of avian melanocortin inverse agonists, agouti signaling protein (ASIP) and agouti-related protein (AGRP) 111174 EN Hibiki Fukuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ryoya Watanabe Graduate School of Natural Science and Technology, Okayama University Yuna Iida Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Saya Nakano Graduate School of Natural Science and Technology, Okayama University Aya Mizutani Graduate School of Natural Science and Technology, Okayama University Tatsuhiko Abo Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sayaka Aizawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sakae Takeuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Agouti signaling protein (ASIP) and agouti-related protein (AGRP) are paralogous inverse agonists of melanocortin receptors with distinct physiological roles, but their structural and biochemical properties in birds remain poorly understood. Here, we characterized chicken ASIP and AGRP proteins. Analysis of available sequences revealed that a motif resembling the mammalian proprotein convertase 1/3 (PC1/3, also known as PCSK1) cleavage site is conserved across a broad range of avian orders, but Western blot analysis of transfected Chinese hamster ovary (CHO-K1) cells and chicken hypothalamus detected no cleavage, suggesting that avian AGRP may not be post-translationally processed at this site. Chicken ASIP mRNA contains an in-frame upstream ATG (uATG) and a putative N-linked glycosylation site at Asn-42, both conserved across multiple avian orders. Overexpression in CHO-K1 cells showed that ASIP translated from either ATG produces a mature protein of the same size that is N-glycosylated at Asn-42 and exhibits markedly lower secretion efficiency than AGRP. Domain-swapping experiments revealed that the N-terminal domain reduces secretion, whereas a naturally occurring ASIP-b variant with an additional N-glycan at Asn-47 shows enhanced secretion. Proteasome inhibition increased intracellular ASIP, and endoglycosidase H (Endo H) sensitivity indicated endoplasmic reticulum (ER) retention, suggesting that the N-terminal domain limits secretion via ER-associated proteasomal degradation. These findings reveal species-specific post-translational regulation of avian melanocortin inverse agonists, in which N-terminal features and site-specific N-glycosylation determine secretion efficiency, likely contributing to their distinct roles in pigmentation and hypothalamic energy balance. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 9 2025 The Intranasal Administration of Semaphorin 3A Inhibitor in a Mouse Model of Olfactory Disorder e92587 EN Aya Murai Otolaryngology - Head and Neck Surgery, Okayama University Hospital Minori Noda Otolaryngology - Head and Neck Surgery, Okayama University Hospital Aiko Shimizu Otolaryngology - Head and Neck Surgery, Okayama University Hospital Junko Takahara Division of Technical Support for Medical Science, Department of Comprehensive Technical Solutions, Okayama University Seiichiro Makihara Otolaryngology - Head and Neck Surgery, Okayama University Hospital Mizuo Ando Otolaryngology - Head and Neck Surgery, Okayama University This study investigated the effects of intranasal administration of a semaphorin 3A inhibitor (Sema3A-I) in a mouse model of olfactory disorder, where olfactory sensory neuron (OSN) axons had been severely damaged. We performed axotomy (transection of OSN axons) of the OSNs in mice and administered Sema3A‑I intranasally to seven mice and saline to another seven mice. Following treatment, we assessed the thickness of the olfactory epithelium and the regeneration ratio of OSN axons. Intranasal administration of Sema3A-I did not significantly promote OSN regeneration, axonal outgrowth, or improve axonal projection compared to saline administration. Although Sema3A-I administration showed some promotion of axonal outgrowth, the difference was not statistically significant. Continuous subcutaneous administration of Sema3A-I in rats after axotomy promotes OSN regeneration and axonal outgrowth. Given that intranasal administration is minimally invasive, we believe that it may still be a feasible route when combined with additional treatment strategies. Further investigation into administration methods and therapeutic combinations is warranted. 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 The significance of adding posterior decompression to spine stabilization in metastatic spinal surgery: a multicenter prospective study 27684 EN Hiroyuki Tominaga Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Ichiro Kawamura Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Hirofumi Shimada Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Hiromi Sasaki Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Noboru Taniguchi Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Yuki Shiratani Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University Akinobu Suzuki Department of Orthopaedic Surgery, Osaka Metropolitan University Hidetomi Terai Department of Orthopaedic Surgery, Osaka Metropolitan University Takaki Shimizu Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Kenichiro Kakutani Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Yutaro Kanda Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Masayuki Ishihara Department of Orthopaedic Surgery, Kansai Medical University Hospital Masaaki Paku Department of Orthopaedic Surgery, Kansai Medical University Hospital Yohei Takahashi Department of Orthopaedic Surgery, Keio University Toru Funayama Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba Kousei Miura Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba Eiki Shirasawa Department of Orthopaedic Surgery, Kitasato University School of Medicine Hirokazu Inoue Rehabilitation Center, Jichi Medical University Hospital Atsushi Kimura Department of Orthopaedics, Jichi Medical University Takuya Iimura Department of Orthopaedic Surgery, Dokkyo Medical University Hiroshi Moridaira Department of Orthopaedic Surgery, Dokkyo Medical University Hideaki Nakajima Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui Shuji Watanabe Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui Koji Akeda Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Norihiko Takegami Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Kazuo Nakanishi Department of Orthopaedic Surgery, Kawasaki Medical School Hirokatsu Sawada Department of Orthopaedic Surgery, Nihon University School of Medicine Koji Matsumoto Department of Orthopaedic Surgery, Nihon University School of Medicine Masahiro Funaba Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Hidenori Suzuki Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Haruki Funao Department of Orthopaedic Surgery, International University of Health and Welfare Narita Hospital Tsutomu Oshigiri Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine Takashi Hirai Department of Orthopedic Surgery, Institute of Science Tokyo Bungo Otsuki Department of Orthopaedic Surgery, Kyoto University Hospital Kazu Kobayakawa Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Hiroaki Manabe Department of Orthopedics, Tokushima University Shinji Tanishima Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University Ko Hashimoto Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine Chizuo Iwai Department of Orthopaedic Surgery, Gifu University Hospital Daisuke Yamabe Department of Orthopaedic Surgery, Iwate Medical University Akihiko Hiyama Department of Orthopaedic Surgery, Tokai University School of Medicine Shoji Seki Department of Orthopaedic Surgery, University of Toyama Yuta Goto Department of Orthopaedic Surgery, Nagoya City University Masashi Miyazaki Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Kazuyuki Watanabe Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine Toshio Nakamae Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Takashi Kaito Department of Orthopedic Surgery, Osaka University Graduate School of Medicine Hiroaki Nakashima Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Narihito Nagoshi Department of Orthopaedic Surgery, Keio University Satoshi Kato Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Kota Watanabe Department of Orthopaedic Surgery, Keio University Gen Inoue Department of Orthopaedic Surgery, Kitasato University School of Medicine Takeo Furuya Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University The usefulness of spine stabilization for treating metastatic spinal tumors with tumor-induced instability has been reported. However, no reports have prospectively evaluated the effectiveness of adding posterior decompression to stabilization surgery for improving symptoms. This multicenter prospective study aimed to determine whether adding posterior decompression to spine stabilization surgery for metastatic spinal tumors affects postoperative outcomes and complications. A total of 263 patients who underwent spine stabilization with (n = 189) or without (n = 74) decompression were analyzed. Patient demographics, the Spinal Instability Neoplastic Score (SINS), and the Epidural Spinal Cord Compression (ESCC) score were recorded. The outcomes were assessed preoperatively and at 1 and 6 months postoperatively in terms of neurological status, the Barthel Index, the EQ-5D-5 L, and the visual analog scale (VAS). Decompression was primarily performed in patients with severe neurological deficits and high-grade ESCC. Both groups showed postoperative improvement. Propensity score matching was applied to adjust for baseline differences. After matching, there were no significant differences in functional improvement between the decompression and nondecompression groups, and the complication rates were comparable. In matched patients presenting primarily with spinal instability and pain, the addition of decompression did not appear to confer a significant functional benefit within 6 months postoperatively. 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.

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.

Springer Nature Singapore Acta Medica Okayama 1865-0929 2025 Evaluation of a Startup Program Identification for Efficient and Accurate IoT Security Investigations 417 431 EN Yuta Shimamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jiratchaya Phinyodom School of Engineering, Okayama University Ryota Yoshimoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyuki Uekawa NTT Social Informatics Laboratories Mitsuaki Akiyama NTT Social Informatics Laboratories Toshihiro Yamauchi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Not all file in firmware are executed while using Internet of Things (IoT) devices and hundreds to approximately a thousand executable and linkable format files exist in one firmware. Therefore, security investigations without prioritization may lead to investigate programs that are not executed while using IoT devices first. This has resulted in inefficient security investigations. To perform efficient security investigations, we proposed a method that can identify programs executed during the startup process. However, only two firmware were used for the evaluation which can only evaluate one of the two startup sequences in the OpenWrt-based firmware. In addition, security investigations to validate whether the proposed method addresses the problem of inefficient security investigations were limited to OpenWrt-based firmware. In this study, we use more firmware data for evaluation and validation. We use nine firmware not used in previous studies including startup methods that have not previously been used for evaluation. In addition, we increase the number of firmware used for validation to 225. The evaluation results demonstrate that the proposed method can identify with only few false positives. The validation demonstrates that efficiency can be improved and prioritizing investigations by considering the proposed method result is worthwhile. No potential conflict of interest relevant to this article was reported.

American Physical Society (APS) Acta Medica Okayama 0031-9007 135 10 2025 Terahertz Field Control of Electronic-Ferroelectric Anisotropy at Room Temperature in LuFe2⁢O4 106504 EN Hirotake Itoh Tohoku University Ryusei Minakami Tohoku University Hongwu Yu Institute of Science Tokyo Ryohei Tsuruoka Tohoku University Tatsuya Amano Tohoku University Yohei Kawakami Tohoku University Shin-ya Koshihara Institute of Science Tokyo Kosuke Fujiwara Okayama University Naoshi Ikeda Okayama University Yoichi Okimoto Institute of Science Tokyo Shinichiro Iwai Tohoku University Electronic ferroelectrics, with polarization 𝑷 induced by strongly correlated charges, are expected to show ultrafast, huge, and flexible responses required in future optoelectronics. Although the challenges for ultrafast manipulation of such a polarization are ongoing, the expected advantages have been unclear. In this Letter, we demonstrate an unprecedentedly large increase by a factor of 2.7 in optical second harmonic generation at room temperature in the prototypical electronic ferroelectrics, the rare-earth ferrite LuFe2⁢O4, by applying a terahertz field of 260 kV/cm. The transient anisotropy indicates that the direction of macroscopic polarization can be controlled three dimensionally on subpicosecond timescales, offering additional degrees of freedom in controlling polarization. Although the polarization response is in phase concerning the terahertz field, its sensitivity increased with delay, indicating that cooperative interactions among microscopic domains play an important role in the unprecedented response. No potential conflict of interest relevant to this article was reported.

Japan Institute of Metals Acta Medica Okayama 0021-4876 89 11 2025 Ti-18Nb-xAl合金の構成相と材料特性に及ぼすAl添加量の影響 337 343 EN Yoshikazu Mantani Department of Materials Science and Engineering, National Institute of Technology (KOSEN), Suzuka College Yoshito Takemoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University The Ti-18mass%Nb alloy with a quenched α” martensitic structure exhibited a high damping capacity. However, there are issues such as lower strength than annealed α+β structure and decreasing damping capacity due to heating until 400 K. Therefore, in this study, to address these issues, we investigated the effect of Al addition on the constituent phases and material properties of Ti-18Nb-xAl alloys. The crystal structure was determined by examining the lattice constant and unit volume using X-ray diffraction, and optical microscopy was also performed. The material properties were investigated by Vickers hardness, Young’s modulus, internal friction, tensile tests, and DSC measurements. Vickers hardness and tensile strength increased with increasing Al content. This is thought to be due to the combined effects of the refinement of the microstructure and solid-solution strengthening due to Al addition. The Young’s modulus increased slightly from 0Al to 1Al, but increased significantly to 4Al. Internal friction was highest for 0Al and decreased for 4Al, whereas 7Al showed a higher value than 1Al. In the DSC heating curves, there was a decrease in the exothermic peak starting temperature and an increase in the phase-transformation heat with the addition of Al, except for 1Al. It was suggested that these changes in Ti-18Nb-xAl alloys were influenced by the structure of the quenched α” phase, texture, and pseudoelasticity or phase transformation by deformation. No potential conflict of interest relevant to this article was reported.

Japan Society on Water Environment Acta Medica Okayama 1348-2165 23 5 2025 Biochar-amended Sediment Microbial Fuel Cells for Water Quality Improvement in Intensive and Extensive Pond Drainages in Central Vietnam 234 249 EN Uyen Tu Nguyen Graduate School of Environmental and Life Science, Okayama University Morihiro Maeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroaki Somura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nozomi Nakahara Department of Comprehensive Technical Solutions, Okayama University Gamamada Liyanage Erandi Priyangika Perera Graduate School of Environmental and Life Science, Okayama University Chiyu Nakano Graduate School of Environmental and Life Science, Okayama University Huu Tien Le Department of Education, Science and Technology Quang Tri Branch, Hue University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University The use of nutrient-rich feed in shrimp farming in Central Vietnam has led to high nitrogen (N) and phosphorus (P) contents in the pond sediment. The objectives of the study were to assess the effectiveness of biochar-sediment microbial fuel cells (BC-SMFCs) in suppressing P and N release from two types of sediment in intensive (Int) and extensive (Ext) pond drainages in Central Vietnam. Single chamber SMFCs were set up and operated under open or closed-circuit (no SMFC or SMFC) conditions. Coconut shell biochar (BC) was amended to sediments at 1%. For Int-sediment, total phosphorus (TP) release was reduced by no BC-SMFCs through co-precipitation with Fe. On the other hand, BC-SMFCs did not suppress TP release because P was released from BC and organic matter decomposition was enhanced in the sediment. Application of BC enhanced organic N mineralization in the sediment. Nitrification and denitrification occurred in the overlying water, reducing mineral N concentrations. For Ext-sediment, BC addition and SMFC conditions did not affect TP and total nitrogen (TN) release because of low initial organic matter content, and less reductive condition. Our study suggested that the effect of SMFCs was masked by BC which released more P from Int-sediment to the water. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0921-8831 36 10 2025 Evaluating the effects of electrolytes on the interaction forces between alumina surfaces in polyacrylic acid solutions using atomic force microscopy 105028 EN Naoto Kishimoto Graduate School of Natural Science and Technology, Okayama University Ryota Kaji Faculty of Science and Engineering, Doshisha University Katsumi Tsuchiya Faculty of Science and Engineering, Doshisha University Koreyoshi Imamura Graduate School of Natural Science and Technology, Okayama University Naoyuki Ishida Faculty of Science and Engineering, Doshisha University Evaluation and control of ceramic slurry at the microscopic level are critical to ensure consistent quality in manufactured ceramics. Notably, metal ions such as Mg2+ and Al3+ are common in ceramic slurries and significantly influence the stability of particle. This study applied atomic force microscopy to investigate the interaction forces between alumina particle surfaces in the presence of different concentrations of three metal ions and polyacrylic acid (PAA), a widely used dispersant. The attractive forces observed at low PAA concentrations were attributed to polymer bridging between alumina surfaces, whereas the repulsive forces observed at high PAA concentrations were attributed to the domination of steric repulsion between adsorbed PAA molecules. The presence of multivalent metal ions, such as Mg2+ and Al3+, modulated these interactions; an increasing ion valence induced a transition from repulsive to attractive force, primarily owing to electrostatic screening, which caused conformational collapse of the PAA chains and diminished the range of steric repulsion. Similarly, increasing the concentration of these metal ions decreased the range of repulsive forces, eventually resulting in a net attraction driven by the same electrostatic and polymer conformation mechanisms. Notably, the addition of 0.1 M AlCl3 produced an anomalous long-range attraction between surfaces that could not be explained by conventional mechanisms, such as polymer bridging or electrostatic interactions between charge domains. 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 Evaluation of Scleral Adjustment Method: A Novel Adjustable Suture Technique in Strabismus Surgery 339 343 EN Ichiro Hamasaki Lino Eye Clinic Kiyo Shibata Lino Eye Clinic Original Article 10.18926/AMO/69434 To determine whether passing a pole suture through the sclera at two points provides fixation comparable to that of a sliding noose, we measured the tensile strength of the suture‒sclera interface during simulated traction. In this in vitro study, three suture patterns were evaluated in porcine eyeballs, using 6-0 polyglycolic acid sutures. Patterns A (control), B (second suture pass perpendicular), and C (second suture pass in the same direction) were compared. The tensile strength of each pattern was measured 20 times using a KANON TK300CN, and the results were analyzed using the Kruskal‒Wallis test. Pattern A showed a tensile strength of 2±4 gram-force (gf) (range: 0-12). Pattern B showed 112±38 gf (range: 61-184). Pattern C showed 139±31 gf (range: 97-204). Patterns B and C had significantly higher tensile strengths than Pattern A (p<0.001). Although Pattern C was not significantly different from Pattern B (p=0.363), it exhibited the highest tensile strength. Lifting the suture between the first and second suture passes allows for an adjustable suture length, suggesting that adjustability can be achieved using only the sclera. This scleral adjustment method with a second suture pass offers a durable means of securing extraocular muscles and may represent a valuable addition to adjustable suturing techniques. 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.

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 8 2025 A Phrase Fill-in-Blank Problem in a Client-Side Web Programming Assistant System 709 EN Huiyu Qi Department of Information and Communication Systems, Okayama University Zhikang Li 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 Wen Chung Kao Department of Electrical Engineering, National Taiwan Normal University Mastering client-side Web programming is essential for the development of responsive and interactive Web applications. To support novice students’ self-study, in this paper, we propose a novel exercise format called the phrase fill-in-blank problem (PFP) in the Web Programming Learning Assistant System (WPLAS). A PFP instance presents a source code with blanked phrases (a set of elements) and corresponding Web page screenshots. Then, it requests the user to fill in the blanks, and the answers are automatically evaluated through string matching with predefined correct answers. By increasing blanks, PFP can come close to writing a code from scratch. To facilitate scalable and context-aware question creation, we implemented the PFP instance generation algorithm in Python using regular expressions. This approach targets meaningful code segments in HTML, CSS, and JavaScript that reflect the interactive behavior of front-end development. For evaluations, we generated 10 PFP instances for basic Web programming topics and 5 instances for video games and assigned them to students at Okayama University, Japan, and the State Polytechnic of Malang, Indonesia. Their solution results show that most students could solve them correctly, indicating the effectiveness and accessibility of the generated instances. In addition, we investigated the ability of generative AI, specifically ChatGPT, to solve the PFP instances. The results show 86.7% accuracy for basic-topic PFP instances. Although it still cannot fully find answers, we must monitor progress carefully. In future work, we will enhance PFP in WPLAS to handle non-unique answers by improving answer validation for flexible recognition of equivalent responses. 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.

Springer Science and Business Media LLC Acta Medica Okayama 0167-6903 105 4 2025 Effect of environmental conditions on seed germination and seedling growth in Cuscuta campestris 1157 1167 EN Koki Nagao Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taku Takahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ryusuke Yokoyama Graduate School of Life Sciences, Tohoku University Dodder (Cuscuta) is an obligate parasitic plant that cannot survive without a host and causes significant damage to crop yields. To understand its growth characteristics before parasitism, we examined the effects of environmental conditions on seed germination and seedling growth in Cuscuta campestris Yunck. Among various factors, we focused on the effects of light, pH, temperature, sugars, salts, hormones, amino acids and polyamines on seeds sown on agar plates. Regarding the effect of light on germination, far-red light was preferable rather than red light and the reversible response of seeds to red and far-red light was confirmed, implicating a phytochrome-mediated signaling pathway opposite to that in many seed plants. Among the amino acids, aspartic acid and alanine had a promotive effect, while histidine had an inhibitory effect on germination. We further found that, in addition to gibberellic acid, methyl jasmonate stimulated both germination and shoot elongation. While 2,4-D extended the viability of trichomes around the root cap, kinetin induced the formation of scale leaves on the shoot and undifferentiated cell clusters at the base of the shoot and root tip. Real-time reverse transcriptase PCR (RT-PCR) experiments confirmed that the expression of a putative RbcS gene for photosynthesis showed no response to light, whereas that of a Phytochrome A homolog increased in the dark. Our results indicate that some of the molecular mechanisms involved in responding to light and hormone signals are uniquely modified in dodder seedlings, providing clues for understanding the survival strategy of parasitic plants. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1757-6512 16 1 2025 Specific induction of right ventricular-like cardiomyocytes from human pluripotent stem cells 519 EN Yukihiro Saito Department of Cardiovascular Medicine, Okayama University Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Hospital Yuki Katanosaka Department of Cardiovascular Physiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Iida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Dai Kusumoto Department of Biomedical Informatics and Molecular Biology, The Sakaguchi Laboratory, Keio University School of Medicine Ryushi Sato Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka Riki Adachi Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka Satoshi Shimizu Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka Junko Kurokawa Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshida Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Keiji Naruse Department of Cardiovascular Physiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Mikako Nishida Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Heiichiro Udono Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Jianhua Zhang Department of Medicine, University of Wisconsin School of Medicine and Public Health Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Timothy J. Kamp Department of Medicine, University of Wisconsin School of Medicine and Public Health Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background Applications employing human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) require well-characterized, chamber-specific hPSC-CMs. Distinct first heart field (FHF) and second heart field (SHF) cardiac progenitor populations give rise to the left ventricular (LV) and right ventricular (RV) cardiomyocytes, respectively. This developmental difference in cardiomyocyte origin suggests that chamber-specific cardiomyocytes have unique characteristics. Therefore, efficient strategies to differentiate human pluripotent stem cells (hPSCs) specifically to LV-like or RV-like cardiomyocytes are needed and it is still unknown whether there is a phenotypic difference between LV-like cardiomyocytes and RV-like cardiomyocytes derived from hPSCs. Methods An established hPSC cardiac differentiation protocol employing sequential GSK3β inhibition followed by Wnt inhibition (GiWi) was modified by addition of insulin or BMP antagonists during mesoderm formation. Cardiac progenitor populations were evaluated for FHF and SHF markers, and differentiated hPSC-CMs were characterized for chamber-specific markers. Results The GiWi protocol produced mainly FHF-like progenitor cells that gave rise to LV-like cardiomyocytes. Inhibition of endogenous BMP signaling during mesoderm induction using insulin or BMP antagonists reduced expression of FHF markers and increased expression of SHF markers in cardiac progenitor cells. hPSC-CMs arising from the SHF-like progenitor cells showed an RV-like gene expression pattern and exhibited phenotypic differences in spontaneous contraction rate, Ca2+ transients, and cell size compared to control LV-like cardiomyocytes. Conclusion This study establishes methodology to generate RV-like hPSC-CMs to support the development of disease modeling research using chamber-specific hPSC-CMs. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 1044-3983 36 6 2025 Causal Approaches to Disease Progression Analyses 732 740 EN Bronner P. Gonçalves Faculty of Health and Medical Sciences, University of Surrey Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Epidemiologic analyses that aim to quantify exposure effects on disease progression are not uncommon. Understanding the implications of these studies, however, is complicated, in part because different causal estimands could, at least in theory, be the target of such analyses. Here, to facilitate interpretation of these studies, we describe different settings in which causal questions related to disease progression can be asked, and consider possible estimands. For clarity, our discussion is structured around settings defined based on two factors: whether the disease occurrence is manipulable or not, and the type of outcome. We describe relevant causal structures and sets of response types, which consist of joint potential outcomes of disease occurrence and disease progression, and argue that settings where interventions to manipulate disease occurrence are not plausible are more common, and that, in this case, principal stratification might be an appropriate framework to conceptualize the analysis. Further, we suggest that the precise definition of the outcome of interest, in particular of what constitutes its permissible levels, might determine whether potential outcomes linked to disease progression are definable in different strata of the population. Our hope is that this paper will encourage additional methodological work on causal analysis of disease progression, as well as serve as a resource for future applied studies. 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.

Universitas Negeri Jakarta Acta Medica Okayama 2614-3984 18 2 2025 Data inventory, processing, and reporting on plant blindness among high school students in three schools in West Java 22 32 EN Puan Helwa Rezha Soraya Biology Education, Faculty of Mathematics and Science Education, Universitas Pendidikan Indonesia Rini Solihat Biology Education, Faculty of Mathematics and Science Education, Universitas Pendidikan Indonesia Yayan Sanjaya Biology Education, Faculty of Mathematics and Science Education, Universitas Pendidikan Indonesia Taro Harada Graduate School of Education, Okayama University Plant blindness is a problem related to a person's inability to realize, recognize, and know the benefits and roles of plants. After some research, there was a shift in the term, from Plant Blindness to Plant Awareness Disparity. This study aims to find out the prevalence of Plant Blindness in three high schools in West Java. The method used in this study is descriptive Cross sectional. The results of this study revealed that there were differences in the level of plant awareness in the three schools studied. One of the schools in the city of Bandung showed the highest plant awareness rate. In addition, it was also found that students who had a high level of plant awareness had a high perception of plant awareness. As a follow-up, further research can be carried out to collect more data so that it becomes a whole population. In addition, researchers can then use additional instruments so that more things can be revealed about plant blindness. 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.

Association for Research in Vision and Ophthalmology (ARVO) Acta Medica Okayama 2164-2591 13 12 2024 Disruption of the Enterococcus faecalis–Induced Biofilm on the Intraocular Lens Using Bacteriophages 25 EN Tatsuma Kishimoto Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University Ken Fukuda Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University Waka Ishida Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University Aozora Kuwana Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University Daisuke Todokoro Department of Ophthalmology, Gunma University Graduate School of Medicine 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 Kenji Yamashiro Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University Purpose: To compare the effects of bacteriophages (phages) and vancomycin on Enterococcus faecalis–induced biofilms on the intraocular lens. Methods: E. faecalis strains EF24, GU02, GU03, and phiEF14H1 were used. The expression of the enterococcus surface protein (esp) gene was analyzed using polymerase chain reaction. Phages or vancomycin was added to the biofilms formed on culture plates or acrylic intraocular lenses. The biofilms were quantified after staining with crystal violet. The structure of the biofilms was analyzed using scanning electron microscopy. Results: E. faecalis strains EF24, GU02, and GU03 formed biofilms on cell culture plates; however, the esp-negative GU03 strain had a significantly lower biofilm-forming ability than the esp-positive strains EF24 and GU02. The addition of phiEF14H1 resulted in a significant reduction in biofilm mass produced by both EF24 and GU02 compared with the untreated control. However, the addition of vancomycin did not degrade the biofilms. Phages significantly degraded biofilms and reduced the viable EF24 and GU02 bacteria on the intraocular lens. Conclusions: Phages can degrade biofilms formed on the intraocular lens and destroy the bacteria within it. Thus, phage therapy may be a new treatment option for refractory and recurrent endophthalmitis caused by biofilm-forming bacteria. Translational Relevance: Phage therapy, a novel treatment option for refractory and recurrent endophthalmitis caused by biofilm-forming bacteria, effectively lyses E. faecalis–induced biofilms. No potential conflict of interest relevant to this article was reported.

Ceramic Society of Japan Acta Medica Okayama 1348-6535 133 9 2025 Preparation and structural characterization of nanoporous silica/magnesium(II)-whitlockite composite particles 555 561 EN Takuya Kataoka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Daiki Hirota Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Eiji Fujii Industrial Technology Center of Okayama Prefecture Tomohiko Yoshioka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Satoshi Hayakawa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University The preparation of particles composed of nanoporous silica (NS) and Mg2+-whitlockite (Mg-WH) would provide valuable insights for designing particles for biomedical applications. In this study, NS and Mg-WH composite particles were successfully synthesized. The addition of chitosan during synthesis possibly promoted the crystallization of calcium phosphate phases in the composite particles. Pore size distribution analysis of the particles showed a maximum at 3.2 nm. Investigating the adsorption of methylene blue onto the particles in a phosphate buffer (pH 7.4) showed that the saturated adsorption amount of methylene blue on the particles was significantly higher than that on commercial hydroxyapatite. The composite particles provided important results for potential applications as drug carriers for bone regeneration and repair. No potential conflict of interest relevant to this article was reported.

Elsevier B.V. Acta Medica Okayama 0304-4165 1869 12 2025 The F54L mutation of Thioredoxin shows protein instability and increased fluctuations of the catalytic center 130860 EN Takumi Baba Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Go Ueno Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Chika Ohe Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Shuku Saji Structural Biology Division, Japan Synchrotron Radiation Research Institute Sachiko Yamamoto Structural Biology Division, Japan Synchrotron Radiation Research Institute Masaki Yamamoto Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Hiroshi Nakagawa Materials Sciences Research Center, Japan Atomic Energy Agency Nobuo Okazaki Neutron Science and Technology Center, Comprehensive Research Organization for Science and Society (CROSS) Mamoru Ouchida Department of Molecular Oncology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Iori Kawasaki-Ohmori Section of Developmental Physiology and Pathology, Faculty of Education, Okayama University Kohei Takeshita Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Thioredoxin is a ubiquitous redox protein that acts as an electron donor via its conserved dithiol motif (C32GPC35), catalyzing dithiol–disulfide exchange to regulate the redox state of target proteins. It supports antioxidant defense via peroxiredoxins, facilitates DNA synthesis by donating electrons to ribonucleotide reductase, and regulates redox-sensitive signaling pathways, including those controlling transcription and apoptosis. Neuronal degeneration and chronic kidney disease have been observed in Txn-F54L mutant rats; however, the details of why the Txn mutation causes these phenomena remain unknown. The present study aimed to elucidate the functional and structural changes caused by the F54L mutation. The Thioredoxin-F54L showed less insulin-reducing activity and more thermosensitivity to denaturation in the body temperature range compared to the wild type. The crystal structure revealed that F54 forms hydrophobic interactions with the surrounding hydrophobic amino acids. In addition, molecular dynamics simulation predicts increased fluctuations around the F54L mutation and a tendency for the distance between residues C32 and C35 at the catalytic center to be widened. The increased distance between residues C32 and C35 of the catalytic center may affect the reducing activity of the enzyme on the substrate. The finding that Thioredoxin-F54L is prone to denaturation at normal body temperature may reduce the normally functioning Thioredoxin. These molecular characteristics of Thioredoxin-F54L may be related to brain and kidney disease development in the Txn-F54L rats. 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.

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 0032-0781 2025 Thylakostasis: key factors in thylakoid membrane organization with emphasis on biogenesis and remodeling proteins in vascular plants pcaf098 EN Wataru Sakamoto Institute of Plant Science and Resources, Okayama University The thylakoid membrane (TM), a defining feature for almost all oxygen-evolving photosynthetic organisms, serves as the structural foundation for light-driven energy conversion. In vascular plants, the TM evolved into a complex architecture composed of single-layered stroma thylakoids and stacked grana thylakoids, enabling the spatial organization of two photosystems (PSII and PSI) to optimize light capture and energy transfer. In addition, two membrane regions, one connecting these two compartments (grana margin) and the other corresponding to the curvature domain in grana, function in dissipating excess energy, balancing electron transfer, and maintaining functional PSII. Recent advances in electron microscopy imaging and proteome analysis of membrane subcompartments have provided new insights into the structure and dynamic adaptations of the TM in response to diverse environmental conditions. To describe the mechanisms that govern TM architecture, dynamics, and integrity, I am introducing the concept of “thylakostasis” (thylakoid homeostasis). Here, I provide an overview of the molecular components and processes central to thylakostasis, including the biosynthesis of lipids, chlorophyll, and proteins. I focus particularly on the membrane remodeling proteins whose functions have been elucidated recently, such as VIPP1, a member of the evolutionarily conserved PspA/ESCRT-III superfamily; FZL, a dynamin-like GTPase; and CURT1, a curvature-inducing protein unique to photosynthetic organisms. Together, these factors orchestrate TM biogenesis, remodeling, and adaptive flexibility that is essential for photosynthetic efficiency. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1751-7362 18 1 2024 Cyanorhodopsin-II represents a yellow-absorbing proton-pumping rhodopsin clade within cyanobacteria wrae175 EN Masumi Hasegawa-Takano Atmosphere and Ocean Research Institute, The University of Tokyo Toshiaki Hosaka Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research Keiichi Kojima Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Nishimura Atmosphere and Ocean Research Institute, The University of Tokyo Marie Kurihara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yu Nakajima Atmosphere and Ocean Research Institute, The University of Tokyo Yoshiko Ishizuka-Katsura Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research Tomomi Kimura-Someya Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research Mikako Shirouzu Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research Yuki Sudo Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Susumu Yoshizawa Atmosphere and Ocean Research Institute, The University of Tokyo Microbial rhodopsins are prevalent in many cyanobacterial groups as a light-energy-harvesting system in addition to the photosynthetic system. It has been suggested that this dual system allows efficient capture of sunlight energy using complementary ranges of absorption wavelengths. However, the diversity of cyanobacterial rhodopsins, particularly in accumulated metagenomic data, remains underexplored. Here, we used a metagenomic mining approach, which led to the identification of a novel rhodopsin clade unique to cyanobacteria, cyanorhodopsin-II (CyR-II). CyR-IIs function as light-driven outward H+ pumps. CyR-IIs, together with previously identified cyanorhodopsins (CyRs) and cyanobacterial halorhodopsins (CyHRs), constitute cyanobacterial ion-pumping rhodopsins (CyipRs), a phylogenetically distinct family of rhodopsins. The CyR-II clade is further divided into two subclades, YCyR-II and GCyR-II, based on their specific absorption wavelength. YCyR-II absorbed yellow light (λmax = 570 nm), whereas GCyR-II absorbed green light (λmax = 550 nm). X-ray crystallography and mutational analysis revealed that the difference in absorption wavelengths is attributable to slight changes in the side chain structure near the retinal chromophore. The evolutionary trajectory of cyanobacterial rhodopsins suggests that the function and light-absorbing range of these rhodopsins have been adapted to a wide range of habitats with variable light and environmental conditions. Collectively, these findings shed light on the importance of rhodopsins in the evolution and environmental adaptation of cyanobacteria. 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.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 2169-3536 13 2025 Security in Post-Quantum Era: A Comprehensive Survey on Lattice-Based Algorithms 89003 89024 EN Hien Nguyen School of Informatics, Computing, and Cyber Systems, Northern Arizona University Samsul Huda Interdisciplinary Education and Research Field, Okayama University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tuy Tan Nguyen School of Informatics, Computing, and Cyber Systems, Northern Arizona University Lattice-based post-quantum cryptography (PQC) has attracted significant attention as a promising solution to the security challenges posed by quantum computing. Unlike traditional cryptographic algorithms, lattice-based schemes are expected to remain secure even in the presence of quantum attacks, making them essential for securing future data. Despite their strong theoretical foundations, lattice-based schemes face several practical challenges, particularly in optimizing performance and scalability for real-world applications. This survey provides a novel taxonomy that categorizes lattice-based PQC designs, with an emphasis on computational paradigms and security considerations. We systematically evaluate lattice-based PQC implementations across both software platforms, including central processing units and graphics processing units, as well as hardware platforms like field-programmable gate arrays and application-specific integrated circuits, highlighting their strengths and limitations. In addition, we explore the practical applications of lattice-based cryptography in fields such as secure communication, critical infrastructure, privacy-preserving data analytics, artificial intelligence, and trust and authentication systems. By offering a comprehensive overview of the current state of lattice-based PQC, this survey aims to provide valuable insights into the ongoing advancements and future research directions in the field as we transition to a post-quantum era. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0024-9297 58 3 2025 Synthesis and Postfunctionalization of Acrylate-Appended Poly(cyclohexene carbonate)s: Modulation of Properties of CO2-Based Polymers 1571 1577 EN Chihiro Maeda Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Hina Inoue Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tadashi Ema Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Functional CO2-based polycarbonates are expected to be sustainable materials. Herein, a bifunctional aluminum porphyrin catalyzed the terpolymerization of cyclohexene oxide (CHO), acrylate-appended CHO, and CO2 to provide poly(cyclohexene carbonate)s (PCHCs) with acrylate groups. Postfunctionalization of PCHCs via Michael addition or Heck reaction enabled the incorporation of thiol, amine, and aromatics into PCHCs with high selectivity and efficiency. PCHCs with the flexible long alkyl chains showed a glass-transition temperature (Tg) of down to 52 °C, which was much lower than that of PCHC (127 °C). In sharp contrast, PCHCs with rigid pyrenyl groups showed Tg values of up to 152 °C and fluorescence emission. Thus, a wide range of polymers were obtained by robust and sustainable synthetic methods, and the functional groups modulated the properties of the CO2-based polycarbonates. No potential conflict of interest relevant to this article was reported.

JMIR Publications Inc. Acta Medica Okayama 1929-0748 14 2025 Optimization of Preemptive Therapy for Cytomegalovirus Infections With Valganciclovir Based on Therapeutic Drug Monitoring: Protocol for a Phase II, Single-Center, Single-Arm Trial e72549 EN Naoki Tamura Department of Pharmacy, Kobe University Hospital Kotaro Itohara Department of Pharmacy, Kobe University Hospital Yo Ueda Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Omura Department of Pharmacy, Kobe University Hospital Toshiyasu Sakane Department of Pharmaceutical Technology, Kobe Pharmaceutical University Jun Saegusa Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine Ikuko Yano Department of Pharmacy, Kobe University Hospital Background: Valganciclovir (VGCV) is the first-line drug for preemptive therapy of cytomegalovirus (CMV) infections. However, even when administered at the dose specified in the package insert, there is significant interindividual variability in the plasma concentrations of ganciclovir (GCV). In addition, correlations have been reported between the area under the concentration–time curve and therapeutic efficacy or adverse events. Therefore, therapeutic drug monitoring (TDM) can be used to improve the efficacy and safety of preemptive VGCV therapy. Objective: This study aims to evaluate whether the dosage adjustment of VGCV based on TDM in patients undergoing preemptive therapy for CMV infections is associated with the successful completion rate of treatment without severe hematological adverse effects. Methods: This phase II, single-center, single-arm trial aims to enroll 40 patients admitted at the Department of Rheumatology and Clinical Immunology, Kobe University Hospital, who will receive oral VGCV as preemptive therapy for CMV infections. Participants will begin treatment with VGCV at the dose recommended in the package insert, with subsequent dose adjustments based on weekly TDM results. The primary end point will be the proportion of patients who achieve CMV antigenemia negativity within 3 weeks without severe hematological adverse events. The secondary end points will include weekly changes in CMV antigen levels, total VGCV dose, and duration of preemptive therapy. For safety evaluation, the occurrence, type, and severity of VGCV-related adverse events will be analyzed. Additionally, this study will explore the correlations between the efficacy and safety of preemptive therapy and the pharmacokinetic parameters of GCV, CMV-polymerase chain reaction values, and nudix hydrolase 15 (NUDT15) genetic polymorphisms. The correlation between GCV plasma concentrations obtained from regular venous blood and blood concentrations will be examined using dried blood spots. Results: This study began with patient recruitment in September 2024, with 5 participants enrolled as of June 16, 2025. The target enrollment is 40 participants, and the anticipated study completion is set for July 2027. Conclusions: This is the first study to investigate the impact of TDM intervention in patients receiving VGCV as preemptive therapy. The findings are postulated to provide valuable evidence regarding the utility of TDM in patients receiving VGCV as preemptive therapy. Trial Registration: Japan Registry of Clinical Trials jRCTs051240080; https://jrct.mhlw.go.jp/latest-detail/jRCTs051240080 International Registered Report Identifier (IRRID): DERR1-10.2196/72549 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.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 63 23 2024 Successful Treatment for Life Threatening Recurrent Non-traumatic Rectus Sheath Hematoma in a Case with Microscopic Polyangiitis with Rapidly Progressive Glomerulonephritis 3243 3248 EN Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hidemi Takeuchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shiho Morimoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yuya Terajima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shugo Okamoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Keiko Tanaka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morinaga Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Mayu Uka Department of Radiology, Okayama University Hospital Koji Tomita Department of Radiology, Okayama University Hospital Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences A 68-year-old woman was admitted to our hospital because of a rapid progression of renal dysfunction with positive myeloperoxidase antineutrophil cytoplasmic antibody and was diagnosed with rapidly progressive glomerulonephritis associated with microscopic polyangiitis (MPA). Severe right rectus sheath hematoma (RSH) bleeding from the inferior epigastric artery developed after starting hemodialysis, which required 4 transarterial embolizations due to recurrent bleeding. After additional treatment with methylprednisolone pulse therapy and rituximab, no rebleeding occurred. Although the giant hematoma reached the pelvis, it shrank spontaneously without any intervention. Nontraumatic RSH should therefore be considered when treating patients with multiple risk factors. 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.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 48 1 2025 An Underlying Mechanism for the Altered Hypoglycemic Effects of Nateglinide in Rats with Acute Peripheral Inflammation 51 59 EN Haruka Toko Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Manami Ogino Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akane Nishiwaki Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Moeko Kojina Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tetsuya Aiba Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The hypoglycemic effects of nateglinide (NTG) were examined in rats with acute peripheral inflammation (API) induced by carrageenan treatment, and the mechanisms accounting for altered hypoglycemic effects were investigated. NTG was administered through the femoral vein in control and API rats, and its plasma concentration profile was characterized. The time courses of the changes in plasma glucose and insulin levels were also examined. Although the plasma concentration profile of NTG in API rats was marginally distinguishable from that in control rats, the hypoglycemic effect of NTG was more persistent in API rats than in control rats. In addition, NTG elevated the plasma level of insulin more intensely in API rats than in control rats. Then, the islets of Langerhans were procured by perfusing the pancreas with collagenase solution in control and API rats, and the pancreatic mRNA expression of preproinsulin (Ins1), as well as that of sulfonylurea receptor ABCC8 (Abcc8), were examined. As a result, the expression of preproinsulin and ABCC8 mRNA increased in API rats. These findings suggest that the hypoglycemic effect of NTG was potentiated in API rats due to increased insulin secretion in the pancreas, which was caused by enhanced preproinsulin synthesis and expression of the sulfonylurea receptor. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 64 15 2025 Clinical and Genetic Analyses of SPG7 in Japanese Patients with Undiagnosed Ataxia 2290 2294 EN Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Rimi Hino Department of Neurology, Graduate School of Medicine, The University of Tokyo Go Fujino Department of Neurology, Graduate School of Medicine, The University of Tokyo Yuto Sakai Department of Neurology, International University of Health and Welfare Mita Hospital Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobue K. Iwata Department of Neurology, International University of Health and Welfare Mita Hospital Shoji Tsuji Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Objective Spastic paraplegia 7 (SPG7) is an autosomal recessive neurodegenerative disorder caused by biallelic pathogenic variants in SPG7. It is predominantly characterized by adult-onset slowly progressive spastic paraparesis. While SPG7 presenting with ataxia with or without spasticity is relatively common in Europe and North America, it is considered rare in Japan. This study aimed to identify SPG7 patients among those with undiagnosed ataxia within the Japanese population. Methods We retrospectively selected 351 patients with undiagnosed ataxia, excluding those with secondary and common spinocerebellar ataxia. Whole-exome sequence analysis was conducted, and homozygosity of the identified variants was confirmed using droplet digital polymerase chain reaction (ddPCR). Results Among the 351 patients, 2 were diagnosed with SPG7, and homozygosity was confirmed by ddPCR. Both patients carried homozygous pathogenic variants in SPG7: c.1948G>A, p.Asp650Asn, and c.1192C>T, p.Arg398Ter (NM_003119.4). Clinically, both patients presented with progressive ataxia. In addition, Patient 1 exhibited partial ophthalmoplegia and spastic paraparesis, whereas Patient 2 demonstrated cerebellar ataxia without spasticity. Conclusion The rarity of SPG7 in Japan may be attributed to variation in the minor allele frequency of the c.1529C>T, p.Ala510Val variant, which is more prevalent in Europe and North America than in other areas. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0094-2405 52 8 2025 Commissioning of respiratory‐gated 4D dynamic dose calculations for various gating widths without spot timestamp in proton pencil beam scanning e18026 EN Yuki Tominaga Department of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy Clinic Yushi Wakisaka Department of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy Clinic Takahiro Kato Department of Radiological Sciences, School of Health Sciences, Fukushima Medical University Masaya Ichihara Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka Keisuke Yasui School of Medical Sciences, Fujita Health University Motoharu Sasaki Graduate School of Biomedical Sciences, Tokushima University Masataka Oita Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Teiji Nishio Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka Background: Proton pencil beam scanning (PBS) is susceptible to dose degradation because of interplay effects on moving targets. For cases of unacceptable motion, respiratory-gated (RG) irradiation is an effective alternative to free breathing (FB) irradiation. However, the introduction of RG irradiation with larger gate widths (GW) is hindered by interplay effects, which are analogous to those observed with FB irradiation. Accurate estimation of interplay effects can be performed by recording spot timestamps. However, our machine lacks this feature, making it imperative to find an alternative approach. Thus, we developed an RG 4-dimensional dynamic dose (RG-4DDD) system without spot timestamps. Purpose: This study aimed to investigate the accuracy of calculated doses from the RG-4DDD system for PBS plans with varying breathing curves, amplitudes, and periods for 10%–50% GW. Methods: RG-4DDDs were reconstructed using in-house developed software that assigned timestamps to individual spots, integrated start times for spills with breathing curves, and utilized deformable registrations for dose accumulation. Three cubic verification plans were created using a heterogeneous phantom. Additionally, typical liver and lung cases were employed for patient plan validation. Single- and multi-field-optimized (SFO and IMPT) plans (ten beams in total) were created for the liver and lung cases in a homogeneous phantom. Lateral profile measurements were obtained under both motion and no-motion conditions using a 2D ionization chamber array (2D-array) and EBT3 Gafchromic films on the CIRS dynamic platform. Breathing curves from the cubic plans were used to assess nine patterns of sine curves, with amplitudes of 5.0–10.0 mm (10.0–20.0 mm target motions) and periods of 3–6 sec. Patient field verifications were conducted using a representative patient curve with an average amplitude of 6.4 mm and period of 3.2 sec. Additional simulations were performed assuming a ± 10% change in assigned timestamps for the dose rate (DR), spot spill (0.08-s), and gate time delay (0.1-s) to evaluate the effect of parameter selection on our 4DDD models. The 4DDDs were compared with measured values using the 2D gamma index and absolute doses over that required for dosing 95% of the target. Results: The 2D-array measurements showed that average gamma scores for the reference (no motion) and 4DDD plans for all GWs were at least 99.9 ± 0.2% and 98.2 ± 2.4% at 3%/3 mm, respectively. The gamma scores of the 4DDDs in film measurements exceeded 95.4% and 92.9% at 2%/2 mm for the cubic and patient plans, respectively. The 4DDD calculations were acceptable under DR changes of ±10% and both spill and gate time delays of ±0.18 sec. For the 4DDD plan using all GWs for all measurement points, the absolute point differences for all validation plans were within ±5.0% for 99.1% of the points. Conclusions: The RG-4DDD calculations (less than 50% GW) of the heterogeneous and actual patient plans showed good agreement with measurements for various breathing curves in the amplitudes and periods described above. The proposed system allows us to evaluate actual RG irradiation without requiring the ability to record spot timestamps. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0002-0729 54 8 2025 Oestrogen replacement combined with resistance exercise in older women with knee osteoarthritis: a randomised, double-blind, placebo-controlled clinical trial afaf224 EN Tomohiro Mitoma Medical Development Field, Center for Innovative Clinical Medicine, Okayama University Hikaru Ooba Medical Development Field, Center for Innovative Clinical Medicine, Okayama University Kasumi Takahashi Obstetrics and Gynecology, Ochiai Hospital Tsunemasa Kondo Obstetrics and Gynecology, Ochiai Hospital Tomohiro Ikeda Rehabilitation Medicine, Okayama University Hospital Yoko Sakamoto Medical Development Field, Center for Innovative Clinical Medicine, Okayama University Toshiharu Mitsuhashi Medical Development Field, Center for Innovative Clinical Medicine, Okayama University Jota Maki Medical Development Field, Center for Innovative Clinical Medicine, Okayama University Background: Interventions targeting physical function decline in older women with knee osteoarthritis (KOA) are vital for healthy ageing. The additive benefits of combining oestrogen replacement therapy (ERT) with resistance exercise remain unclear. Objective: To evaluate the additive effect of low-dose ERT on physical performance when combined with a muscle resistance exercise programme (MREP) in older women with KOA. Design: This is a placebo-controlled, double-blind, randomised clinical trial. Subjects: The subjects were community-dwelling women aged ≥65 years with chronic knee pain and KOA diagnosis. Methods: Participants completed a 3-month MREP and were randomised to receive daily low-dose transdermal ERT (oestradiol 0.54 mg/day) or placebo. Outcomes were assessed at baseline, postintervention and 12 months later. The primary outcome was change in 30-second chair stand test (CS-30) score. Secondary outcomes included muscle mass, knee extension strength, walking performance, metabolic indicators, knee pain scale and 12-item short-form health survey (SF-12). Between-group differences in CS-30 changes were analysed using a linear regression model based on the intention-to-treat principle. Results: Among 168 individuals screened, 75 participants (mean age 73.8 years, SD 5.8) were enrolled and randomised into an ERT group (n = 37) or a placebo group (n = 38). Baseline CS-30 scores were 14.81 (SD 3.95) in the ERT group and 15.58 (SD 3.48) in the placebo group. At 3 months, mean changes were 2.59 (SD 2.58) and 1.79 (SD 2.28) repetitions, respectively. The primary analysis showed no statistically significant between-group difference [regression coefficient: 0.81 (95% CI: －0.31, 1.92); P = .16]. Post hoc subgroup and sensitivity analyses suggested that benefits may exist among early-stage KOA participants. SF-12 mental health scores also improved significantly in the ERT group. No serious adverse events occurred. Conclusions: ERT did not confer significant additive benefits to resistance exercise overall but may improve outcomes in early-stage KOA and mental health domains. These exploratory findings warrant further investigation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1758-9193 16 1 2024 Impact of amyloid and tau positivity on longitudinal brain atrophy in cognitively normal individuals 77 EN Motonobu Fujishima Department of Radiology, Kumagaya General Hospital Yohei Kawasaki Department of Biostatistics, Graduate School of Medicine, Saitama Medical University Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Hiroshi Matsuda Department of Biofunctional Imaging, Fukushima Medical University Background Individuals on the preclinical Alzheimer's continuum, particularly those with both amyloid and tau positivity (A + T +), display a rapid cognitive decline and elevated disease progression risk. However, limited studies exist on brain atrophy trajectories within this continuum over extended periods. Methods This study involved 367 ADNI participants grouped based on combinations of amyloid and tau statuses determined through cerebrospinal fluid tests. Using longitudinal MRI scans, brain atrophy was determined according to the whole brain, lateral ventricle, and hippocampal volumes and cortical thickness in AD-signature regions. Cognitive performance was evaluated with the Preclinical Alzheimer's Cognitive Composite (PACC). A generalized linear mixed-effects model was used to examine group × time interactions for these measures. In addition, progression risks to mild cognitive impairment (MCI) or dementia were compared among the groups using Cox proportional hazards models. Results A total of 367 participants (48 A + T + , 86 A + T － , 63 A － T + , and 170 A － T － ; mean age 73.8 years, mean follow-up 5.1 years, and 47.4% men) were included. For the lateral ventricle and PACC score, the A + T － and A + T + groups demonstrated statistically significantly greater volume expansion and cognitive decline over time than the A － T － group (lateral ventricle: β = 0.757 cm3/year [95% confidence interval 0.463 to 1.050], P < .001 for A + T － , and β = 0.889 cm3/year [0.523 to 1.255], P < .001 for A + T + ; PACC: β = － 0.19 /year [－ 0.36 to － 0.02], P = .029 for A + T － , and β = － 0.59 /year [－ 0.80 to － 0.37], P < .001 for A + T +). Notably, the A + T + group exhibited additional brain atrophy including the whole brain (β = － 2.782 cm3/year [－ 4.060 to － 1.504], P < .001), hippocampus (β = － 0.057 cm3/year [－ 0.085 to － 0.029], P < .001), and AD-signature regions (β = － 0.02 mm/year [－ 0.03 to － 0.01], P < .001). Cox proportional hazards models suggested an increased risk of progressing to MCI or dementia in the A + T + group versus the A － T － group (adjusted hazard ratio = 3.35 [1.76 to 6.39]). Conclusions In cognitively normal individuals, A + T + compounds brain atrophy and cognitive deterioration, amplifying the likelihood of disease progression. Therapeutic interventions targeting A + T + individuals could be pivotal in curbing brain atrophy, cognitive decline, and disease progression. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0171-9335 104 2 2025 Tri-culture model of intestinal epithelial cell, macrophage, and bacteria for the triggering of inflammatory bowel disease on a microfluidic device 151495 EN Shiori Tamura School of Life Science and Technology, Institute of Science Tokyo Clarissa Ellice Talitha Pasang School of Life Science and Technology, Tokyo Institute of Technology Minami Tsuda School of Life Science and Technology, Tokyo Institute of Technology Shilan Ma School of Life Science and Technology, Institute of Science Tokyo Hiromasa Shindo School of Life Science and Technology, Tokyo Institute of Technology Noriyuki Nagaoka Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoki Ohkubo Biology-Chemistry Unit, Technology Research Laboratory, Shimadzu Corporation Yoichi Fujiyama Biology-Chemistry Unit, Technology Research Laboratory, Shimadzu Corporation Miho Tamai School of Life Science and Technology, Tokyo Institute of Technology Yoh-ichi Tagawa School of Life Science and Technology, Institute of Science Tokyo Inflammatory bowel disease (IBD) involves gastrointestinal inflammation, due to intestinal epithelial barrier destruction caused by excessive immune activation. Conventional cell culture systems do not provide a model system that can recapitulate the complex interactions between epithelial cells, immune cells, and intestinal bacteria. To address this, we developed a microfluidic device that mimics the inflammatory response associated with microbial invasion of the intestinal mucosa. The device consisted of two media channels, an upper and a lower channel, and a porous membrane between these channels on which C2BBe1 intestinal epithelial cells were seeded to form a tight junction layer. Each electrode was placed in contact with both channels to continuously monitor the tight junction state. Fresh medium flow allowed bacterial numbers to be controlled and bacterial toxins to be removed, allowing co-culture of mammalian cells and bacteria. In addition, RAW264 macrophage cells were attached to the bottom of the lower channel. By introducing E. coli into the lower channel, the RAW264 cells were activated and produced TNF-α, successfully recapitulating a culture model of inflammation in which the C2BBe1cell tight junction layer was destroyed. The main structure of the device was initially made of polydimethylsiloxane to facilitate its widespread use, but with a view to introducing anaerobic bacteria in the future, a similar phenomenon was successfully reproduced using polystyrene. When TPCA-1, an IκB kinase 2 inhibitor was added into this IBD culture model, the tight junction destruction was significantly suppressed. The results suggest that this IBD culture model also is useful as a screening system for anti-IBD drugs. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1434-5161 69 12 2024 Association study of GBA1 variants with MSA based on comprehensive sequence analysis -Pitfalls in short-read sequence analysis depending on the human reference genome- 613 621 EN Kenta Orimo Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Masaki Tanaka Institute of Medical Genomics, International University of Health and Welfare Junko Nomoto Institute of Medical Genomics, International University of Health and Welfare Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Omae Genome Medical Science Project, National Center for Global Health and Medicine Yosuke Kawai Genome Medical Science Project, National Center for Global Health and Medicine Katsushi Tokunaga Genome Medical Science Project, National Center for Global Health and Medicine NCBN Controls WGS Consortium Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by various combinations of autonomic failure, parkinsonism, and cerebellar ataxia. To elucidate variants associated with MSA, we have been conducting short-read-based whole-genome sequence analysis. In the process of the association studies, we initially focused on GBA1, a previously proposed susceptibility gene for MSA, to evaluate whether GBA1 variants can be efficiently identified despite its extraordinarily high homology with its pseudogene, GBA1LP. To accomplish this, we conducted a short-read whole-genome sequence analysis with alignment to GRCh38 as well as Sanger sequence analysis and compared the results. We identified five variants with inconsistencies between the two pipelines, of which three variants (p.L483P, p.A495P–p.V499V, p.L483_M489delinsW) were the results of misalignment due to minor alleles in GBA1P1 registered in GRCh38. The miscalling events in these variants were resolved by alignment to GRCh37 as the reference genome, where the major alleles are registered. In addition, a structural variant was not properly identified either by short-read or by Sanger sequence analyses. Having accomplished correct variant calling, we identified three variants pathogenic for Gaucher disease (p.S310G, p.L483P, and p.L483_M489delinsW). Of these variants, the allele frequency of p.L483P (0.003) in the MSA cases was higher than that (0.0011) in controls. The meta-analysis incorporating a previous report demonstrated a significant association of p.L483P with MSA with an odds ratio of 2.85 (95% CI; 1.05 – 7.76, p = 0.0400). No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0003-4975 120 1 2025 Comparable Clinical Outcomes Between Segmentectomy and Lobectomy for NSCLC With Unsuspected N1/N2: A Multicenter Real-World Data Study 87 98 EN Tsuyoshi Ryuko 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 Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuyoshi Ueno Okayama University Thoracic Surgery Study Group Toshiya Fujiwara Okayama University Thoracic Surgery Study Group Mototsugu Watanabe Okayama University Thoracic Surgery Study Group Hidetoshi Inokawa Okayama University Thoracic Surgery Study Group Takahiko Misao Okayama University Thoracic Surgery Study Group Hidejiro Torigoe Okayama University Thoracic Surgery Study Group Kazuhiro Washio Okayama University Thoracic Surgery Study Group Hiroyuki Tao Okayama University Thoracic Surgery Study Group Daisuke Okutani Okayama University Thoracic Surgery Study Group Makio Hayama Okayama University Thoracic Surgery Study Group Masashi Uomoto Okayama University Thoracic Surgery Study Group Eiji Yamada Okayama University Thoracic Surgery Study Group Shinji Otani Okayama University Thoracic Surgery Study Group Takeshi Kurosaki Okayama University Thoracic Surgery Study Group Yuji Yaginuma Okayama University Thoracic Surgery Study Group Eito Niman Okayama University Thoracic Surgery Study Group Osamu Kawamata Okayama University Thoracic Surgery Study Group Hitoshi Nishikawa Okayama University Thoracic Surgery Study Group Tomoaki Otsuka Okayama University Thoracic Surgery Study Group Takeshi Yoshikawa Okayama University Thoracic Surgery Study Group Tatsuro Hayashi Okayama University Thoracic Surgery Study Group Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Segmentectomy for lung cancer has been increasingly performed. However, evidence regarding the necessity of additional surgical resection after the diagnosis of unsuspected N1 or N2 lymph node metastasis is limited. Methods We conducted a multicenter, real-world data study of patients with any clinical T and N0 non-small cell lung cancer (NSCLC) who underwent lobectomy or segmentectomy between 2012 and 2021 and who subsequently received a diagnosis of pathologic N1 or N2 lymph node metastasis. Patients were categorized into lobectomy and segmentectomy groups. We analyzed overall survival (OS), recurrence-free survival (RFS), cumulative recurrence rates, and recurrence patterns using both unadjusted and propensity score–adjusted cohorts. Results A total of 736 patients were in the lobectomy group, and 70 were in the segmentectomy group. In the unadjusted cohort, segmentectomy-treated patients were older, had a lower preoperative percentage of vital capacity, had smaller tumors, and received less postoperative adjuvant chemotherapy. The 5-year OS was significantly worse in the segmentectomy group (P = .011), with no significant differences in 5-year RFS or cumulative recurrence rates. In the propensity score–adjusted cohort, there were no significant differences in OS, RFS, or recurrence rates; however, the segmentectomy group had a higher rate of local recurrence. Conclusions In patients with unsuspected N1 or N2 NSCLC, analysis using a cohort adjusted for patient background with propensity scores revealed no differences in OS, RFS, or cumulative recurrence rates between segmentectomy and lobectomy. This finding suggests that additional resection of the remaining segments may not be necessary for these patients. However, the higher rate of local recurrence in the segmentectomy group warrants careful consideration. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2197-1153 12 2 2025 Clinical outcomes following medial meniscus posterior root repairs: A minimum of 5‐year follow‐up study e70262 EN Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhisa Sugiu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yusuke Kamatsuki Department of Orthopaedic Surgery, Okayama Saiseikai General Hospital Masanori Tamura Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Koki Kawada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tsubasa Hasegawa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Purpose: This study assessed the clinical outcomes of the FasT-Fix dependent modified Mason-Allen suture (F-MMA) and two simple stitches (TSS) on mid-term postoperative outcomes following medial meniscus (MM) posterior root repair. Methods: Forty-three patients who underwent transtibial pullout repair for MM posterior root tear (PRT) between November 2016 and September 2018 were initially enrolled. Patients with a femorotibial angle ≤ 180°, Kellgren–Lawrence grade of 0–2, and modified Outerbridge grade I or II cartilage lesions were included. The Lysholm, Tegner activity, International Knee Documentation Committee score, pain visual analogue scale and Knee injury and Osteoarthritis Outcome scores were assessed as clinical outcomes. Conversion surgery to knee arthroplasty was considered as the endpoint. Surgeries other than second-look arthroscopy and plate or screw removal were also recorded. Results: The mean follow-up period was 5.9 years. All evaluated 5-year postoperative clinical outcomes were significantly improved compared to the preoperative outcomes (p < 0.001). Both the F-MMA and TSS significantly improved all clinical scores at 5 years postoperatively in patients with MMPRT, whereas the F-MMA and TSS groups showed no significant differences in the pre- and postoperative clinical scores. None of the patients required ipsilateral knee arthroplasty during the follow-up, and the survival rate after pullout repair was 100%. However, the progression of osteoarthritis could not be completely suppressed, although there were no Kellgren–Lawrence grade 4 cases. The rate of subsequent knee-related surgical treatment was 11.6% in pullout-repaired knees, including arthroscopic debridement for arthrofibrosis with a limited range of motion, an additional all-inside suture repair and partial meniscectomy. Conclusion: Both F-MMA and TSS pullout repairs yielded satisfactory clinical outcomes in patients with MMPRT with a mean follow-up of 5.9 years, and no conversion to knee arthroplasty was required. Further follow-up is warranted to assess long-term survival rates. Level of Evidence: Level III. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2304-6767 12 11 2024 Coronal Cementum and Reduced Enamel Epithelium on Occlusal Surface of Impacted Wisdom Tooth in a Human 348 EN Naohiro Horie Division of Reconstructive Surgery for Oral and Maxillofacial Region, School of Dentistry, Health Sciences University of Hokkaido Masaru Murata Division of Regenerative Medicine, School of Dentistry, Health Sciences University of Hokkaido Yasuhito Minamida Division of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido Hiroki Nagayasu Division of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido Tsuyoshi Shimo Division of Reconstructive Surgery for Oral and Maxillofacial Region, School of Dentistry, Health Sciences University of Hokkaido Toshiyuki Akazawa Industrial Technology and Environment Research Development, Hokkaido Research Organization Hidetsugu Tsujigiwa Department of Life Science, Faculty of Science, Okayama University of Science Youssef Haikel Department of Biomaterials and Bioengineering, Institut National de la Santé et de la Recherche médicale Unité Mixte de Recherche (INSERM UMR) _S 1121, University of Strasbourg Hitoshi Nagatsuka Department of Oral Pathology and Medicine Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: There is only limited research on the coronal cementum of a tooth, and the mechanisms of its forming process are not well-defined. This report presents a coronal cementum on the occlusal surfaces of enamel in an impacted wisdom tooth in a human, which is not nearly the cervical portion. Materials and Methods: The tooth (Tooth #1) was derived from a 46-year-old female. Histological analysis, including hematoxylin and eosin (HE) and toluidine blue (TB) staining, and Scanning Electron Microscopy and Energy Dispersive X-ray Spectrometer (SEM-EDS) analysis of the extracted tooth were conducted. Radiographic examination showed that Tooth #1 was horizontally impacted in the maxilla and had the apex of a single root placed between the buccal and palatal roots of Tooth #2. Results: Coronal cementum was distributed widely on the enamel, and reduced enamel epithelium was also found with enamel matrix proteins histologically. The formation of acellular cementum was observed to be more predominant than that of the cellular cementum in Tooth #1. SEM showed that the occlusal cementum connected directly with enamel. Calcium mapping revealed an almost similar occlusal cementum and enamel. In addition, the spectrum of elements in coronal cementum resembled the primary cementum according to SEM-EDS. Discussion: Thus, coronal cementogenesis in impacted human teeth might be related to the existence of reduced enamel epithelium. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0006-291X 779 2025 1,2-naphthoquinone enhances IFN-γ-induced MHC-I expression in dendritic cells, thereby inducing CD8 T cell activation 152453 EN Kazuyuki Furuta Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kanon Miyazato Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kai Kobata Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuya Ishikawa Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Chikara Kaito Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Dendritic cells play a crucial role in immune responses by capturing pathogens and presenting antigens to T cells via major histocompatibility complex (MHC) molecules, thus triggering adaptive immune responses. 1,2-naphthoquinone (1,2-NQ), a quinone found in diesel exhaust and cigarette smoke, has various physiological functions. In this study, we investigated the effect of 1,2-NQ on the expression of antigen presentation-related molecules in the dendritic cell line DC2.4. The results revealed that 1,2-NQ enhanced the IFN-γ-induced upregulation of MHC-I expression at the transcriptional level. Moreover, it upregulated the expression of NLRC5, a transcriptional activator of MHC-I. 1,2-NQ is a reactive oxygen species (ROS) producing reagent. The 1,2-NQ-induced upregulation of MHC-I expression and downregulation of MHC-II expression were abolished by the ROS scavenger N-acetylcysteine. Similar effects on MHC expression were also observed with ROS-inducing reagents, such as paraquat and diethyl maleate. In addition, dendritic cells stimulated with 1,2-NQ exhibited enhanced efficacy in CD8 T cell activation, which was accompanied by increased IFN-γ production by T cells. These findings demonstrate that 1,2-NQ enhances the IFN-γ-induced activation of dendritic cells and promotes the activation of CD8 T cells. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-1683 73 2025 Incidence, Management, and Prevention of Gynecomastia and Breast Pain in Patients with Prostate Cancer Undergoing Antiandrogen Therapy: A Systematic Review and Meta-analysis of Randomized Controlled Trials 31 42 EN Ichiro Tsuboi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Robert J. Schulz Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Ekaterina Laukhtina Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Koichiro Wada Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Pierre I. Karakiewicz Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shahrokh F. Shariat Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Background and objective: In patients with prostate cancer treated with antiandrogen monotherapy, gynecomastia and breast pain are relatively common. In the setting of androgen receptor pathway inhibitors (ARPIs), the incidence of these adverse events (AEs) remains unclear. In addition, the effect of prophylactic treatment on gynecomastia remains uncertain. We aimed to evaluate the incidence of gynecomastia and breast pain in prostate cancer patients treated with ARPIs compared with androgen deprivation therapy (ADT) and the effect of prophylactic treatment for these AEs due to antiandrogen therapy. Methods: In June 2024, we queried four databases―PubMed, Scopus, Web of Science, and Embase―for randomized controlled trials (RCTs) investigating prostate cancer treatments involving antiandrogen therapy. The endpoints of interest were the incidence of these AEs due to ARPIs and the effect of prophylactic treatment for these. Key findings and limitations: Eighteen RCTs, comprising 5036 patients, were included in the systematic review and meta-analysis. ARPIs included enzalutamide, darolutamide, and apalutamide. The results indicated that patients who received ARPI monotherapy had a significantly higher incidence of gynecomastia than those who received ADT monotherapy (risk ratio [RR]: 5.19, 95% confidence interval [CI]: 3.58–7.51, p < 0.001). There was no significant difference in the incidence of gynecomastia between ARPI plus ADT therapy and ADT monotherapy (RR: 1.27, 95% CI: 0.84–1.93, p = 0.2). Prophylactic tamoxifen or radiotherapy reduced significantly the incidence of gynecomastia and breast pain caused by bicalutamide monotherapy. Conclusions and clinical implications: We found that ARPI monotherapy increases the incidence of these AEs significantly compared with ADT. In contrast, ARPI plus ADT therapy did not result in a higher incidence of AEs. The use of either tamoxifen or radiotherapy was effective in reducing the incidence of these AEs due to bicalutamide monotherapy. These prophylactic treatments could reduce the incidence of AEs due to ARPI monotherapy. However, further studies are needed to clarify their efficacy. Patient summary: Although androgen deprivation therapy (ADT) improves overall survival in patients with prostate cancer, it is associated with several complications. Androgen receptor pathway inhibitor (ARPI) monotherapy has emerged as a promising strategy for improving oncological outcomes in these patients. However, ARPI monotherapy increases gynecomastia and breast pain in prostate cancer patients compared with ADT, while ARPI plus ADT did not result in a higher incidence of adverse events. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2637-6105 2025 Tailoring Mechanical Properties and Ionic Conductivity of Poly(ionic liquid)-Based Ion Gels by Tuning Anion Compositions EN Takaichi Watanabe Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Yuna Mizutani Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Carlos G. Lopez Material Science and Engineering Department, The Pennsylvania State University, 80 Pollock Road, State College Tsutomu Ono Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Poly(ionic liquid) (PIL)-based ion gels have emerged as promising materials for advanced electrochemical applications because of their excellent miscibility with ionic liquids (IL), tunable mechanical properties, and high ionic conductivity. Despite extensive studies on PIL-based ion gels, a comprehensive understanding of how different anion combinations in the system affect physicochemical properties is lacking. In this study, we systematically investigate the effect of different anion species, such as bis(trifluoromethanesulfonyl)imide (TFSI) and hexafluorophosphate (PF6), on the mechanical, viscoelastic, and ion conductive behaviors of PIL-based ion gels. We investigate the interplay between anion size, packing density, and polymer segmental dynamics by varying the anion composition in both the PIL network and IL component. Rheological analysis and uniaxial tensile testing results indicate that PF6-containing ion gels exhibit enhanced higher Young’s modulus because of their restricted chain mobility resulting in higher glass transition temperature (Tg). In addition, we confirm the anion exchange between PIL and IL during gel preparation and find that the mechanical and ion conductive properties of the gels are governed by the total molar ratio of anions in the gels. Our findings highlight that tuning the anion composition in PIL-based ion gels provides an effective strategy to tailor their performance, with potential applications for flexible electronics and solid-state electrochemical devices. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0002-9262 2025 Immortal time bias from selection: a principal stratification perspective kwaf146 EN Bronner P Gonçalves Faculty of Health and Medical Sciences, University of Surrey Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Immortal time bias due to post-treatment definition of eligibility criteria can affect experimental and observational studies, and yet, in contrast to the extensive literature on the classical form of immortal time bias, it has seldom been the focus of methodological discussions. Here, we propose an account of eligibility-related immortal time bias that uses the principal stratification framework to explain the noncomparability of treatment arms (or exposure groups) conditional on selection. In particular, we show that the statistical estimand that conditions on observed eligibility after time zero of follow-up can be interpreted using partially overlapping principal strata. Furthermore, we show that, under this perspective, as the timing of eligibility approaches time zero of follow-up, the probabilities of the outcome for eligible individuals monotonically approach the corresponding unconditional (in absence of selection) expected potential outcomes under different treatment levels. Our study provides a potential outcomes-based explanation of eligibility-related immortal time bias, and indicates that, in addition to the target trial emulation framework, principal effects might, for some studies, be useful causal estimands. No potential conflict of interest relevant to this article was reported.

JMIR Publications Inc. Acta Medica Okayama 2561-326X 9 2025 Usefulness of Interventions Using a Smartphone Cognitive Behavior Therapy Application for Children With Mental Health Disorders: Prospective, Single-Arm, Uncontrolled Clinical Trial e60943 EN Shinichiro Nagamitsu Department of Pediatrics, Faculty of Medicine, Fukuoka University Ayumi Okada Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoichi Sakuta Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Ryuta Ishii Department of Pediatrics & Child Health, Kurume University, School of Medicine Kenshi Koyanagi Nagasaki Prefectural Center of Medicine and Welfare for Children Chizu Habukawa Department of Pediatric Allergy, Minami Wakayama Medical Center Takashi Katayama L2B Inc Masaya Ito National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry Ayako Kanie National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry Ryoko Otani Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Takeshi Inoue Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Tasuku Kitajima Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Naoki Matsubara Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Chie Tanaka Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chikako Fujii Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshie Shigeyasu Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Michiko Matsuoka Department of Neuropsychiatry, Kurume University School of Medicine Tatsuyuki Kakuma Biostatistics Center, Kurume University Masaru Horikoshi National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry Background: The prevalence of mental health disorders among children in Japan has increased rapidly, and these children often show depressive symptoms and reduced quality of life (QOL). We previously developed a smartphone-based self-monitoring app to deliver cognitive behavioral therapy (CBT), implemented it in healthy children, and reported its effectiveness for health promotion. Objective: This study aims to examine the usefulness of the CBT app for improvement in depressive symptoms and QOL in children with mental health disorders. Methods: The participants were 115 children with mental health disorders (eg, school refusal, orthostatic hypotension, eating disorders, developmental disorders, among others) and aged 12‐18 years. The CBT app–based program comprised 1 week of psychoeducation followed by 1 week of self-monitoring. After reading story-like scenarios, participants created a self-monitoring sheet with 5 panels: events, thoughts, feelings, body responses, and actions. All participants received regular mental health care from physicians in addition to the app-based program. To evaluate the participants’ depressive symptoms and QOL, Patient Health Questionnaire for Adolescents (PHQ-9A), Depression Self-Rating Scale for Children (DSRS-C), and Pediatric Quality of Life Inventory (PedsQL) were measured at the beginning of the intervention, and at 2 and 6 months thereafter. Questionnaire for Triage and Assessment with 30 items (QTA30), and Rosenberg Self-Esteem Scale (RSES) were also used to measure their health and self-esteem. Participants were divided into 4 groups on the basis of the PHQ-9A score (above or below the cutoff; PHQ-9A≥5 or PHQ-9A<5) and completion or noncompletion of the CBT app–based program (app [+] or app [-]). The primary outcome was improvement in the DSRS-C score, and secondary outcomes were improvement in other psychometric scales including PedsQL, QTA30, and RSE. A paired-samples t test was used for statistical analysis. The Medical Ethics Committee of Fukuoka University Faculty of Medicine (approval U22-05-002) approved the study design. Results: There were 48, 18, 18, and 7 participants in the PHQ-9A≥5 app (+), PHQ-9A≥5 app (-), PHQ-9A<5 app (+), and PHQ-9A<5 app (-) groups, respectively. A total of 24 participants dropped out. No improvement in the DSRS-C score was observed in all groups. However, PedsQL scores improved significantly at 2 and 6 months in the PHQ-9A<5 app (+) group (t17=6.62; P<.001 and t17=6.11; P<.001, respectively). There was a significant positive correlation between the PHQ-9A scores and the number of self-monitoring sheets completed. Conclusions: The CBT app was useful for improving PedsQL scores of children with mental health disorders. However, a higher-intensity CBT program is necessary for more severely depressed children. Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000046775; center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053360 No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-3417 15 11 2025 Top-Down Stereolithography-Based System for Additive Manufacturing of Zirconia for Dental Applications 6155 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 Fiona Spirrett Joining and Welding Research Institute, Osaka University Yukinori Maruo Department of Prosthodontics, Okayama University Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Bart Van Meerbeek BIOMAT, Department of Oral Health Sciences, KU Leuven Soshu Kirihara Joining and Welding Research Institute, Osaka University This study investigated the feasibility and effectiveness of a commercial top-down stereolithography (SLA)-based system for the additive manufacturing of zirconia dental prostheses. Yttria-stabilized zirconia–resin slurries were prepared, and zirconia objects were fabricated using a top-down SLA system. Thermogravimetric–differential thermal analysis was used to examine the resin, while X-ray fluorescence spectroscopy and X-ray diffraction were used to analyze the printed samples. The microstructures of additively manufactured and subtractively manufactured zirconia were compared using field emission scanning electron microscopy (FE-SEM) before and after sintering. Biaxial flexural strength tests were also conducted to evaluate mechanical properties. The green bodies obtained via additive manufacturing exhibited uniform layering with strong interlayer adhesion. After sintering, the structures were dense with minimal porosity. However, compared to subtractively manufactured zirconia, the additively manufactured specimens showed slightly higher porosity and lower biaxial flexural strength. The results demonstrate the potential of SLA-based additive manufacturing for dental zirconia applications while also highlighting its current mechanical limitations. The study also showed that using a blade to evenly spread viscous slurry layers in a top-down SLA system can effectively reduce oxygen inhibition at the surface and relieve internal stresses during the layer-by-layer printing process, offering a promising direction for clinical adaptation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2431 24 1 2024 Body weight and eating attitudes influence improvement of depressive symptoms in children and pre-adolescents with eating disorders: a prospective multicenter cohort study 551 EN Yuichi Suzuki Department of Pediatrics, Fukushima Medical University School of Medicine Shinichiro Nagamitsu Department of Pediatrics, Fukuoka University Faculty of Medicine Nobuoki Eshima Department of Pediatrics, Kurume University School of Medicine Takeshi Inoue Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Ryoko Otani Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Ryoichi Sakuta Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Toshiyuki Iguchi Department of Pediatrics, Hoshigaoka Maternity Hospital Ryuta Ishii Department of Pediatrics and Child Health, Kurume University School of Medicine Soh Uchida Karamun`S Forest Children`S Clinic Ayumi Okada Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kitayama Himeji City Center for the Disabled Kenshi Koyanagi Nagasaki Prefectural Center of Medicine and Welfare for Children Yuki Suzuki Department of Pediatrics, National Hospital Organization Mie National Hospital Yoshino Sumi Mental and Developmental Clinic for Children “Elm Tree” Shizuo Takamiya Takamiya Psychiatry Clinic Chikako Fujii Department of Pediatrics/Child Psychosomatic Medicine, Okayama University Hospital Yoshimitsu Fukai Department of Pediatrics, St. Luke’s International Hospital Background Pediatric patients with eating disorders in a multicenter joint study on 11 facilities were enrolled and prospectively investigated to determine whether improvement in body weight, eating attitudes, and psychosocial factors in children with eating disorders would also improve depressive symptoms. Methods In this study, 91 patients were enrolled between April 2014 and March 2016. The severity of underweight was assessed using the body mass index-standard deviation score (BMI-SDS), eating behavior was assessed using the children's eating attitude test (ChEAT26), the outcome of childhood eating disorders was assessed using the childhood eating disorder outcome scale, and depressive symptoms were assessed using the Children's Depression Inventory (CDI) score. Results After 12 months of treatment, depressive symptoms were evaluated in 62 of the 91 cases where it was evaluated at the initial phase. There was no difference in background characteristics between the included patients and the 29 patients who dropped out. A paired-sample t-test revealed a significant decrease in CDI scores after 12 months of treatment (p < 0.001, 95% CI: 2.401–7.373) and a significant increase in the BMI-SDS (p < 0.001, 95% CI: － 2.41973–1.45321). Multiple regression analysis revealed that BMI-SDS and ChEAT26 scores at the initial phase were beneficial in CDI recovery. In addition, BMI-SDS at the initial phase was useful for predicting BMI-SDS recovery after 12 months of treatment. Conclusions Depressive symptoms in children with eating disorders improved with therapeutic intervention on body weight and eating attitudes. Trial registration The Clinical Trial Number for this study is UMIN000055004. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1880-4276 41 3 2025 Acute effect of multipoint pacing and fused AV delay in patients receiving cardiac resynchronization therapy e70085 EN Masakazu Miyamoto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomofumi Mizuno Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akira Ueoka Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuro Masuda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Saori Asada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoshi Kawada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure with dyssynchrony. However, one-third of patients do not respond positively to it. Recently, multipoint pacing (MPP), which involves pacing from two sites on the left ventricle, has been found to improve symptoms and hemodynamics compared to conventional CRT. An automatic fused atrioventricular (AV) delay that performs fused pacing for intrinsic conduction has also been introduced. However, the combined effect of MPP and fused AV delay on acute hemodynamics is unknown. Objective: To evaluate the acute hemodynamic effects of MPP and fused AV delay in patients undergoing CRT. Methods: A pressure wire was delivered to the left ventricle, and dp/dt was compared with single atrial stimulation pacing in 52 patients with various pacing configurations. Results: Delta dp/dt was greater in MPP than in conventional CRT (10.5 ± 1.0% vs. 8.2 ± 1.0%, p < 0.001) and in fused AV delay than in short AV delay (10.4 ± 0.8% vs. 8.3 ± 1.1, p < 0.001). Hemodynamic parameters significantly most improved with the combination of MPP and fused AV delay. Delta dp/dt was greater in LV pacing than in biventricular (BiV) pacing with MPP and fused AV delay; however, the delta QRS duration was shorter in LV pacing than in BiV pacing. Delta dp/dt and delta QRS duration were negatively correlated. The super-responder rate was 66%. Conclusion: Combining MPP and fused AV delay has an additional effect. Shortening the QRS duration can increase the dp/dt, but the estimated line differs between LV and BiV pacing. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2458 25 1 2025 Longitudinal changes and tracking of in-school physical activity in primary school children: four-year longitudinal study 1041 EN Kensaku Sasayama Faculty of Education, Mie University Jin Yasunebe Faculty of Education, Okayama University Minoru Adachi Graduate School of Education, Okayama University Background There is little evidence on the tracking of physical activity during school hours. In addition, tracking physical activity in schools provides important evidence for understanding children’s physical activity and conducting intervention studies. Therefore, this study examined longitudinal changes and tracking of in-school physical activity in primary school children. Methods In this study, physical activity was investigated longitudinally in primary school children for 4 years. The baseline participants consisted of 103 second-grade students (7–8 years old) who participated. Step counts and moderate-to-vigorous physical activity (MVPA) in school and during first recess and lunch/second recess were examined using an accelerometer (Kenz Lifecorder GS 4-second version; Suzuken Co. Ltd, Nagoya, Japan). Results After excluding missing data (moving school; n = 8, physical activity; n = 8), 87 (43 boys and 44 girls) of whom were included in the final analysis. Step counts and MVPA during school and physical education in boys did not decrease across the school years. By contrast, in girls, step counts during school did not decrease across the school years, however MVPA did decrease. In addition, for both sexes, step counts and MVPA during first recess decrease across the school years. During lunch/second recess, only step counts decrease across the school years in both sexes. In addition, the tracking coefficients for step counts and MVPA for boys in school and during first recess and lunch/second recess were found across many school years. Contrarily, girls had fewer significant tracking coefficients between school years than boys. There were also few significant tracking coefficients between grades for physical education step counts and MVPA for both boys and girls. Conclusions Our results suggested that in-school step counts for both boys and girls does not decrease across the school years. However, given that girls demonstrated reduced levels of in-school MVPA across the school years, it is important to promote strategies to increase MVPA in this group. No potential conflict of interest relevant to this article was reported.

Japan Society on Water Environment Acta Medica Okayama 1348-2165 22 6 2024 Effects of Sediment Microbial Fuel Cells on CH4 and CO2 Emissions from Straw Amended Paddy Soil 271 285 EN Adhena Tesfau Bekele Graduate School of Environmental and Life Science, Okayama University Morihiro Maeda Graduate School of Environmental and Life Science, Okayama University Satoshi Akao Faculty of Science and Engineering, Doshisha University Hiroaki Somura Graduate School of Environmental and Life Science, Okayama University Chiyu Nakano Organization for Research Strategy and Development, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Straw returning into paddy soil enhances soil organic matter which usually promotes the emission of greenhouse gases to the atmosphere. The application of sediment microbial fuel cells (SMFCs) to paddy soil activates power-generating microorganisms and enhances organic matter biodegradation. In the present study, rice straw addition in SMFCs was examined to determine its effect on CH4 and CO2 emissions. Columns (height, 25 cm; inner diameter, 9 cm) with four treatments: soil without and with rice straw under SMFC and without SMFC conditions were incubated at 25°C for 70 days. Anodic potential values at 7 cm depth sediment were kept higher by SMFCs than those without SMFCs. Cumulative CH4 emission was significantly reduced by SMFC with straw amendment (p < 0.05) with no significant effect on CO2 emission. 16S rRNA gene analysis results showed that Firmicutes at the phylum, Closteridiales and Acidobacteriales at order level were dominant on the anode of straw-added SMFC, whereas Methanomicrobiales were in the treatment without SMFC, indicating that a certain group of methanogens were suppressed by SMFC. Our results suggest that the anodic redox environment together with the enrichment of straw-degrading bacteria contributed to a competitive advantage of electrogenesis over methanogenesis in straw-added SMFC system. 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 1 2025 無申告加算税に関するケーススタディ―最高裁平成18 年９月21 日決定を題材に― 63 69 EN Hiroyuki Fuke 10.18926/OER/69005 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 1 2025 地域産業連関表における経済波及効果のNew Approach 35 50 EN Ryohei Nakamura 10.18926/OER/69003 　本稿では，まず経済波及効果の考え方について，産業連関表を用いたシミュレーションの結果が，しばしば過大評価になっていることを述べる。その理由として，経済波及効果をもたらす前提条件の考え方にしばしば誤解があることを指摘する。域内の居住者の消費はマネーの移転であり，真の経済効果ではない。波及効果とは，本来，所得が増えた結果の追加消費であって，所得が増えない状況では，代替消費や消費の先取りに過ぎないのである。また，一般にいう経済効果とは，売上高の積み上げであって同じマネーが何でも加算されているものであり，付加価値効果すなわち所得効果とは異なる。付加価値効果は，当初の域外から入ってきたマネー以上にはならない。こういった解釈の誤謬をもたらしているのは，大学での産業連関分析の教育が十分でないことも原因の1つであるが，シンクタンクや公的機関などで提供されている波及効果の計算ツールにも問題がある。そこで本稿では，これまで筆者が提唱してきた波及効果プロセスを見える化するモデルを更に精緻化し，イベントなど外生的インパクトが発生した後の事後的な産業連関表を構築する流れに関して実例を用いて説明を行う。特に自給率の変化の効果については，これまでの競争移入型連関表では効果が過大傾向になる問題点を解消するべく，「部分非競争移入型」の投入構造を提案し，新たな分析方法を提案する。 No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0960-7412 121 5 2025 Spider mite tetranins elicit different defense responses in different host habitats e70046 EN Yukiko Endo Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science Miku Tanaka Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science Takuya Uemura Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science Kaori Tanimura Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science Yoshitake Desaki Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science Rika Ozawa Center for Ecological Research, Kyoto University Sara Bonzano Department of Life Sciences and Systems Biology, Plant Physiology Unit, University of Turin Massimo E. Maffei Department of Life Sciences and Systems Biology, Plant Physiology Unit, University of Turin Tomonori Shinya Institute of Plant Science and Resources (IPSR), Okayama University Ivan Galis Institute of Plant Science and Resources (IPSR), Okayama University Gen‐ichiro Arimura Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science Spider mites (Tetranychus urticae) are a major threat to economically important crops. Here, we investigated the potential of tetranins, in particular Tet3 and Tet4, as T. urticae protein-type elicitors that stimulate plant defense. Truncated Tet3 and Tet4 proteins showed efficacy in activating the defense gene pathogenesis-related 1 (PR1) and inducing phytohormone production in leaves of Phaseolus vulgaris. In particular, Tet3 caused a drastically higher Ca2+ influx in leaves, but a lower reactive oxygen species (ROS) generation compared to other tetranins, whereas Tet4 caused a low Ca2+ influx and a high ROS generation in the host plants. Such specific and non-specific elicitor activities were examined by knockdown of Tet3 and Tet4 expressions in mites, confirming their respective activities and in particular showing that they function additively or synergistically to induce defense responses. Of great interest is the fact that Tet3 and Tet4 expression levels were higher in mites on their preferred host, P. vulgaris, compared to the levels in mites on the less-preferred host, Cucumis sativus, whereas Tet1 and Tet2 were constitutively expressed regardless of their host. Furthermore, mites that had been hosted on C. sativus induced lower levels of PR1 expression, Ca2+ influx and ROS generation, i.e., Tet3- and Tet4-responsive defense responses, in both P. vulgaris and C. sativus leaves compared to the levels induced by mites that had been hosted on P. vulgaris. Taken together, these findings show that selected tetranins respond to variable host cues that may optimize herbivore fitness by altering the anti-mite response of the host plant. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0781 66 5 2024 SHORT AND CROOKED AWN, encoding the epigenetic regulator EMF1, promotes barley awn development 705 721 EN Koki Nakamura Institute of Plant Science and Resources, Okayama University Yuichi Kikuchi Institute of Plant Science and Resources, Okayama University Mizuho Shiraga Institute of Plant Science and Resources, Okayama University Toshihisa Kotake Graduate School of Science and Engineering, Saitama University Kiwamu Hyodo Institute of Plant Science and Resources, Okayama University Shin Taketa Institute of Plant Science and Resources, Okayama University Yoko Ikeda Institute of Plant Science and Resources, Okayama University The awn is a bristle-like extension from the tip of the lemma in grasses. In barley, the predominant cultivars possess long awns that contribute to grain yield and quality through photosynthesis. In addition, various awn morphological mutants are available in barley, rendering it a useful cereal crop to investigate the mechanims of awn development. Here, we identified the gene causative of the short and crooked awn (sca) mutant, which exhibits a short and curved awn phenotype. Intercrossing experiments revealed that the sca mutant induced in the Japanese cultivar (cv.) “Akashinriki” is allelic to the independently isolated moderately short-awn mutant breviaristatum-a (ari-a). Map-based cloning and sequencing revealed that SCA encodes the Polycomb group–associated protein EMBRYONIC FLOWER 1. We found that SCA affects awn development through the promotion of cell proliferation, elongation, and cell wall synthesis. RNA sequencing of cv. Bowman backcross-derived near-isogenic lines of sca and ari-a6 alleles showed that SCA is directly or indirectly involved in promoting the expression of genes related to awn development. Additionally, SCA represses various transcription factors essential for floral organ development and plant architecture, such as MADS-box and Knotted1-like homeobox genes. Notably, the repression of the C-class MADS-box gene HvMADS58 by SCA in awns is associated with the accumulation of the repressive histone modification H3K27me3. These findings highlight the potential role of SCA-mediated gene regulation, including histone modification, as a novel pathway in barley awn development. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1068-9265 2025 Tumor Microvessels with Specific Morphology as a Prognostic Factor in Esophageal Squamous Cell Carcinoma EN Hnin Thida Tun Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seitaro Nishimura Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Noma Department of Gastroenterological Surgery, 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 Background Angiogenesis is essential for tumor progression. Microvessel density (MVD) is a widely used histological method to assess angiogenesis using immunostained sections, but its prognostic significance in esophageal cancer remains controversial. Recently, the evaluation of microvascular architecture has gained importance as a method to assess tumor aggressiveness. The present study aimed to identify the histological characteristics of tumor microvessels that are associated with the aggressiveness of esophageal squamous cell carcinoma. Patients and Methods A total of 108 esophageal squamous cell carcinoma tissues were immunohistochemically stained with blood vessel markers and angiogenesis-related markers, including CD31, alpha smooth muscle actin, vascular endothelial growth factor A (VEGF-A), CD206, and D2-40. MVD, microvessel pericyte coverage index (MPI), and tumor vascular morphology were evaluated by microscopy. Results MVD was significantly associated with patient outcomes, whereas neither MPI nor VEGF-A expression throughout the tumor showed a significant correlation. In addition, the presence of blood vessels encircling clusters of tumor cells, termed C-shaped microvessels, and excessively branching microvessels, termed X-shaped microvessels, was significantly associated with poor prognosis. These vessel types were also correlated with clinicopathological parameters, including deeper invasion of the primary tumor, presence of lymph node metastasis, advanced pathological stage, and distant metastasis. Focal VEGF-A immunoexpression in tumor cells was higher in areas containing C-shaped or X-shaped microvessels compared with areas lacking these vessel morphologies. Conclusions The data suggest that tumor microvessels with specific morphologies (C-shaped and X-shaped microvessels) may serve as a promising prognostic factor in esophageal squamous cell carcinoma. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0910-6340 41 7 2025 Direct insertion of an ion channel immobilized on a soft agarose gel bead into a lipid bilayer: an optimized method 1073 1082 EN Mami Asakura Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Shuyan Wang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Minako Hirano Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toru Ide Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University In this paper, we report the development of a device that improves the conventional artificial lipid bilayer method and can measure channel currents more efficiently. Ion channel proteins are an attractive research target in biophysics, because their functions can be measured at the single-molecule level with high time resolution. In addition, they have attracted attention as targets for drug discovery because of their crucial roles in vivo. Although electrophysiological methods are powerful tools for studying channel proteins, they suffer from low measurement efficiency and require considerable skill. In our previous paper, we reported that by immobilizing channel proteins on agarose gel beads and forming an artificial lipid bilayer on the bead surface, we simultaneously solved two problems that had been hindering the efficiency of the artificial bilayer method: the time-consuming formation of artificial lipid bilayers and the time-consuming incorporation of channels into artificial bilayers. Previous studies have utilized crosslinked hard beads; however, here we show that channel current measurement can be achieved more simply and efficiently using non-crosslinked soft beads. In this study, we detailed the process of immobilizing channel proteins on the surface of non-crosslinked beads through chemical modification, allowing us to measure their channel activity. This method enables current measurements without the need for stringent bead size selection or high negative pressure. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2079-7737 14 5 2025 Mutagenesis Targeting the S153 Residue Within the Transmembrane β-Hairpin of Mosquito-Larvicidal Mpp46Ab Affects Its Toxicity and the Synergistic Toxicity with Cry4Aa 489 EN Tohru Hayakawa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Syun Yamaoka Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mami Asakura Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Minako Hirano Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toru Ide Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University We constructed a library of Mpp46Ab mutants, in which S153 within the transmembrane β-hairpin was randomly replaced by other amino acids. Mutagenesis and subsequent primary screening yielded 10 different Mpp46Ab mutants in addition to the wild type. Remarkably, S153 was replaced with a more hydrophobic amino acid in most of the mutants, and the S153I mutant in particular exhibited significantly increased toxicity. Electrophysiologic analysis using artificial lipid bilayers revealed that the single-channel conductance and PK/PCl permeability ratio were significantly increased for S153I pores. This suggests that the formation of highly ion-permeable and highly cation-selective toxin pores increases the influx of cations and water into cells, thereby facilitating osmotic shock. In addition, the S153F, S153L, and S153I mutants exhibited significantly reduced synergistic toxicity with Cry4Aa. Electrophysiologic analysis showed that the S153F, S153L, and S153I mutants form toxin pores with a significantly reduced PK/PNa permeability ratio and a significantly increased PK/PCa permeability ratio compared to wild-type pores. Thus, our results suggest that pore formation is central to the insecticidal activity of Mpp46Ab and that the ion permeability of toxin pores is a potential indicator correlated with both toxicity and synergistic toxicity with other toxins. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2772-4174 13 2025 Photochemical internalization of mRNA using a photosensitizer and nucleic acid carriers 100242 EN Hayaki Maemoto Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ryohei Suzaki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazunori Watanabe Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Keiji Itaka Department of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University mRNA has great potential for therapeutic applications because it can encode a variety of proteins and antigens, in addition to advantages over DNA in terms of gene expression without genomic integration, nuclear localization, or transcription. However, therapeutic applications of mRNA require safe and effective delivery into target cells. Therefore, we aimed to investigate photochemical internalization (PCI) as a promising strategy for delivering mRNA to target cells. In this strategy, mRNA is taken up into cells by endocytosis, accumulates in endosomes, and is released in a light-dependent manner from the endosomes using an endosome-accumulating photosensitizer, aluminum phthalocyanine disulfonate (AlPcS2a), in combination with nucleic acid carrier molecules. We compared the efficacy of various nucleic acid carriers, including branched polyethyleneimine (bPEI) and poly{N'-[N-(2-aminoethyl)-2-aminoethyl] aspartamide} (PAsp(DET)) under the same conditions for PCI-based mRNA delivery. Our results indicated that bPEI and PAsp(DET) at low N/P ratios exhibited efficient light-enhancement of mRNA expression by PCI with AlPcS2a. Notably, bPEI exhibited the highest light-dependent mRNA delivery among the carriers evaluated (including cationic polymers, cationic peptides, and lipids), whereas PAsp(DET) showed promise for clinical use because of its lower toxicity compared with bPEI. This PCI strategy allows effective cytosolic mRNA delivery at low N/P ratios, thereby reducing cationic carrier molecule-induced cytotoxicity. This method allows spatiotemporal control of protein expression and holds potential for novel light-dependent mRNA therapies. Overall, this study provided valuable insights into optimizing mRNA delivery systems for therapeutic applications. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-3921 14 7 2025 Carnosol, a Rosemary Ingredient Discovered in a Screen for Inhibitors of SARM1-NAD+ Cleavage Activity, Ameliorates Symptoms of Peripheral Neuropathy 808 EN Hitoshi Murata Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Ogawa Tama Biochemical Co., Ltd. Yu Yasui Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiki Ochi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-Ichi Yamamoto Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoji Wada Tama Biochemical Co., Ltd. Hiromichi Nakamura Tama Biochemical Co., Ltd. Masahiro Nishibori Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1) is a nicotinamide adenine dinucleotide (NAD+) hydrolase involved in axonal degeneration and neuronal cell death. SARM1 plays a pivotal role in triggering the neurodegenerative processes that underlie peripheral neuropathies, traumatic brain injury, and neurodegenerative diseases. Importantly, SARM1 knockdown or knockout prevents the degeneration; as a result, SARM1 has been attracting attention as a potent therapeutic target. In recent years, the development of several SARM1 inhibitors derived from synthetic chemical compounds has been reported; however, no dietary ingredients with SARM1 inhibitory activity have been identified. Therefore, we here focused on dietary ingredients and found that carnosol, an antioxidant contained in rosemary, inhibits the NAD+-cleavage activity of SARM1. Purified carnosol inhibited the enzymatic activity of SARM1 and suppressed neurite degeneration and cell death induced by the anti-cancer medicine vincristine (VCR). Carnosol also inhibited VCR-induced hyperalgesia symptoms, suppressed the loss of intra-epidermal nerve fibers in vivo, and reduced the blood fluid level of phosphorylated neurofilament-H caused by an axonal degeneration event. These results indicate that carnosol has a neuroprotective effect via SARM1 inhibition in addition to its previously known antioxidant effect via NF-E2-related factor 2 and thus suppresses neurotoxin-induced peripheral neuropathy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 32 4 2025 Japanese translation of the Functional Assessment of Cancer Therapy-Breast + 4 (FACT-B + 4) following international guidelines: a verification of linguistic validity 773 782 EN Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Nozomu Takata Simpson Querrey Biomedical Research Center, Northwestern University Saya R. Dennis Department of Preventive Medicine Feinberg School of Medicine, Northwestern University Kaori Terata Department of Breast and Endocrine Surgery, Akita University Hospital Yasuaki Sagara Department of Breast Surgical Oncology, Social Medical Corporation Hakuaikai Sagara Hospital Takehiko Sakai Department of Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital of JFCR Shin Takayama Department of Breast Surgery, National Cancer Center Hospital Dai Kitagawa Department of Breast Surgical Oncology, National Center for Global Health and Medicine Yuichiro Kikawa Department of Breast Surgery, Kansai Medical University Hospital Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Tsuguo Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Fumikata Hara Department of Breast Oncology, Aichi Cancer Center Hospital Tomomi Fujisawa Department of Breast Cancer, Gunma Prefectural Cancer Center Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Background For breast cancer patients, postoperative lymphedema and upper limb movement disorders are serious complications that absolutely reduce their quality of life (QOL). To evaluate this serious complication, we used “Quick Dash” or “FACT-B”, which can assess a patient's physical, social, emotional, and functional health status. To evaluate their breast cancer surgery-related dysfunction correctly, “FACT-B + 4” was created by adding four questions about “arm swelling'' and “tenderness”. We have translated it into Japanese according to international translation guidelines. Methods At the beginning, we contacted FACT headquarters that we would like to create a Japanese version of FACT-B + 4. They formed the FACIT Trans Team (FACIT) following international translation procedures, and then, we began translating according to them. The steps are 1: perform “Forward and Reverse translations” to create a “Preliminary Japanese version”, 2: request the cooperation of 5 breast cancer patients and “conduct a pilot study” and “questionnaire survey”, and 3: amendments and final approval based on pilot study results and clinical perspectives. Result In Step1, FACIT requested faithful translation of the words, verbs, and nouns from the original text. In Step2, patients reported that they felt uncomfortable with the Japanese version words such as “numb'' and “stiffness'' and felt that it might be difficult to describe their symptoms accurately. In Step3, we readjusted the translation to be more concise and closer to common Japanese language, and performed “Step1” again to ensure that the translation definitely retained the meaning of the original. Conclusion A Japanese version of FACT has existed until now, but there was no Japanese version of FACT-B + 4, which adds four additional items to evaluate swelling and pain in the upper limbs. This time, we have created a Japanese version that has been approved by FACT. No potential conflict of interest relevant to this article was reported.

Springer International Publishing Acta Medica Okayama 0302-9743 2022 CyNER: Information Extraction from Unstructured Text of CTI Sources with Noncontextual IOCs 85 104 EN Shota Fujii Graduate School of Natural Science and Technology, Okayama University Nobutaka Kawaguchi Research & Development Group, Hitachi, Ltd. Tomohiro Shigemoto Research & Development Group, Hitachi, Ltd. Toshihiro Yamauchi Faculty of Natural Science and Technology, Okayama University Cybersecurity threats have been increasing and growing more sophisticated year by year. In such circumstances, gathering Cyber Threat Intelligence (CTI) and following up with up-to-date threat information is crucial. Structured CTI such as Structured Threat Information eXpression (STIX) is particularly useful because it can automate security operations such as updating FW/IDS rules and analyzing attack trends. However, as most CTIs are written in natural language, manual analysis with domain knowledge is required, which becomes quite time-consuming. In this work, we propose CyNER, a method for automatically structuring CTIs and converting them into STIX format. CyNER extracts named entities in the context of CTI and then extracts the relations between named entities and IOCs in order to convert them into STIX. In addition, by using key phrase extraction, CyNER can extract relations between IOCs that lack contextual information, such as those listed at the bottom of a CTI, and named entities. We describe our design and implementation of CyNER and demonstrate that it can extract named entities with the F-measure of 0.80 and extract relations between named entities and IOCs with the maximum accuracy of 81.6%. Our analysis of structured CTI showed that CyNER can extract IOCs that are not included in existing reputation sites, and that it can automatically extract IOCs that have been exploited for a long time and across multiple attack groups. CyNER is thus expected to contribute to the efficiency of CTI analysis. No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2832-1324 2023 Prevention Method for Stack Buffer Overflow Attack in TA Command Calls in OP-TEE 274 278 EN Kaito Shiba Graduate School of Natural Science and Technology, Okayama University Hiroki Kuzuno Graduate School of Engineering, Kobe University Toshihiro Yamauchi Faculty of Environmental, Life, Natural Science and Technology, Okayama University TEE systems provide normal world and secure world. It is impossible to gain access to the secure world directly from the normal world. However, vulnerabilities in the secure world can cause attacks to compromise the secure world. In this study, we investigate the security features applied to trusted applications (TA) in OP-TEE and clarify the lack of protection against stack buffer overflow in TA command calls. We also propose a method for preventing attacks that exploit stack buffer overflows in TA command calls. In addition, the experimental results show that attacks on the vulnerable TAs can be prevented with the proposed method and the overhead can be evaluated. No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2379-1896 2023 Evaluation of Effectiveness of MAC Systems Based on LSM for Protecting IoT Devices 161 167 EN Masato Miki Graduate School of Natural Science and Technology, Okayama University Toshihiro Yamauchi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Satoru Kobayashi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Numerous active attacks targeting Internet of Things (IoT) devices exist. They exploit the latest vulnerabilities discovered in IoT devices. Therefore, Mandatory Access Control (MAC) systems based on Linux Security Modules (LSM), such as SELinux and AppArmor, are effective security features for IoT devices because they can mitigate the impact of attacks even if software vulnerabilities are discovered. However, they are not adopted by most IoT devices. The existing approaches are insufficient for investigating the causes of this problem.In this study, we comprehensively investigated what factors can affect the applicability of MAC systems based on LSM in IoT devices. We focused on how frequently cases can occur where they cannot be adopted, owing to each factor. To increase the comprehensiveness of the factors affecting the adoption of MAC systems in IoT devices, we investigated the kernel version, CPU architecture, and support for BusyBox in addition to the investigation of resources, which conducted in previous studies. We also conducted simulated experiments based on the attack method of Mirai to investigate whether MAC systems can protect against IoT malware. Finally, we discuss the impact of a combination of these factors on MAC system adoption. No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2832-1324 2023 Supporting Multiple OS Types on Estimation of System Call Hook Point by Virtual Machine Monitor 267 273 EN Masaya Sato Okayama Prefectural University Taku Omori Okayama Prefectural University Toshihiro Yamauchi Okayama University Hideo Taniguchi Okayama University Methods to hook system calls issued by a guest operating system (OS) running on a virtual machine using a virtual machine monitor are proposed. The address of the hook point is derived from the guest OS’s source code and established prior to the kernel startup process. Due to changes in system call processing in OS updates and address space layout randomization, the addresses of these hook points cannot always be pre-determined before the kernel startup process. To address this challenge, a method for estimating the system call hook point is proposed in Linux by analyzing the guest OS memory on x86-64 CPUs rather than pre-calculation. Although the method supports Linux, the method can be extended to support other OS types. In this paper, we propose a method to extend the method to support additional OSes. Specifically, we present analysis results and a novel method for estimating hook points on FreeBSD, NetBSD, and OpenBSD. The effectiveness of our proposed method is also demonstrated through evaluation. No potential conflict of interest relevant to this article was reported.

Elmer Press, Inc. Acta Medica Okayama 1923-4155 16 5 2025 Nephronophthisis and Retinitis Pigmentosa (Senior-Loken Syndrome) After Living-Donor Kidney Transplantation: Twelve-Year Follow-Up in a Young Woman 164 173 EN Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiroshi Morinaga 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 Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Motoo Araki Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Senior-Loken syndrome is a hereditary ciliopathy with recessive trait that manifests as nephronophthisis and retinitis pigmentosa. This report described an 18-year-old woman who was referred to a University Hospital to set up a treatment plan for chronic renal failure of an unknown cause. She had experienced nocturnal polyurea from the age of 12 years and was found to have an elevated level of serum creatinine at 3 mg/dL at the age of 15 years. She underwent renal biopsy at a hometown regional hospital which showed global glomerulosclerosis in six of the 13 glomeruli examined, renal tubular dilation in irregular shape, and marked interstitial fibrosis with lymphocytic infiltration. At the age of 19 years, she received a living-donor kidney transplant from her 46-year-old father as a preemptive therapy. At surgery, biopsy of the father’s donor kidney showed two glomeruli with global sclerosis out of 24 glomeruli examined, in association with minimal interstitial fibrosis and lymphocytic infiltration. She began to have extended-release tacrolimus 4 mg daily and mycophenolate mofetil 1,000 mg daily. According to the standard protocol, she underwent biopsy of the transplanted donor kidney to reveal interstitial fibrosis and lymphocytic infiltration, in addition to no sign of rejection and no glomerular deposition of immunoglobulins and complements, both 4 weeks and 14 months after the kidney transplantation. At the age of 23 years, 4 years after the kidney transplantation, she was, for the first time, diagnosed retinitis pigmentosa, and hence, Senior-Loken syndrome. She was followed up in the stable condition with basal doses of tacrolimus 5 mg daily, mycophenolate mofetil 1,000 mg daily, and prednisolone 5 mg daily up until now in 12 years after the kidney transplantation. The interstitial fibrosis with lymphocytic infiltration in the donor kidney might be a milder presentation of the disease with recessive inheritance. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1523-7060 2025 Transformation of α,β-Unsaturated Aldehydes with a Small Amount of Electricity: Cyanosilylation, Isomerization, and Nucleophilic Addition EN Mayu Fujii Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanaho Ueno Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koichi Mitsudo Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Eisuke Sato Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Seiji Suga Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University An electrochemical method was developed to convert α,β-unsaturated aldehydes into carboxylic acid derivatives via cyanosilylation, isomerization, and nucleophilic addition. This reaction is more sustainable than the usual electrochemical organic reaction because this reaction proceeds catalytically with active species generated by a very small amount of electricity. Furthermore, scale-up synthesis with a flow reactor has been achieved. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0781 2025 Sulfur dioxide-induced guard cell death and stomatal closure are attenuated in nitrate/proton antiporter AtCLCa mutants EN Lia Ooi Institute of Plant Science and Resources, Okayama University Takakazu Matsuura Institute of Plant Science and Resources, Okayama University Izumi C. Mori Institute of Plant Science and Resources, Okayama University Guard cells surrounding the stomata play a crucial role in regulating the entrance of hazardous gases such as SO2 into leaves. Stomatal closure could be a plant response to mitigate SO2 damage, although the mechanism for SO2-induced closure remains controversial. Proposed mediators for SO2-induced stomatal closure include phytohormones, reactive oxygen species, gasotransmitters, and cytosolic acidification. In this study, we investigated the mechanism of stomatal closure in Arabidopsis in response to SO2. Despite an increment in auxin and jasmonates after SO2 exposure, the addition of auxin did not cause stomatal closure and jasmonate-insensitive mutants exhibited SO2-induced stomatal closure suggesting auxin and jasmonates are not mediators leading to the closure. In addition, supplementation of scavenging reagents for reactive oxygen species and gasotransmitters did not inhibit SO2-induced closure. Instead, we found that cytosolic acidification is a credible mechanism for SO2-induced stomatal closure in Arabidopsis. CLCa mutants coding H+/nitrate antiporter, involved in cytosolic pH homeostasis, showed less sensitive stomatal phenotype against SO2. These results suggest that cytosolic pH homeostasis plays a tenable role in SO2 response in guard cells. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0893-3952 38 8 2025 The Involvement of PI3K–Akt Signaling in the Clinical and Pathological Findings of Idiopathic Multicentric Castleman Disease–Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis, and Organomegaly and Not Otherwise Specified Subtypes 100782 EN Tomoka Haratake Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Michael V. Gonzalez Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital You Cheng Lai Department of Medical Biotechnology and Laboratory Science, Chang Gung University Sayaka Ochi Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Manaka Tsunoda Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences David C. Fajgenbaum Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania Frits van Rhee Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania Shuji Momose Department of Pathology, Saitama Medical Center, Saitama Medical University Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Idiopathic multicentric Castleman disease is a rare lymphoproliferative disorder that is clinically classified into idiopathic plasmacytic lymphadenopathy (IPL); thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO); and not otherwise specified (NOS). Although each subtype shows varying degrees of hypervascularity, no statistical data on the degree of vascularization have been reported. Additionally, the mechanisms underlying vascularization in each clinical subtype are poorly understood. Here, we aimed to clarify these mechanisms by evaluating the histopathological characteristics of each clinical subtype across 37 patients and performing a whole-transcriptome analysis focusing on angiogenesis-related gene expression. Histologically, TAFRO and NOS exhibited a significantly higher degree of vascularization than IPL (IPL vs TAFRO, P < .001; IPL vs NOS, P = .002). In addition, the germinal centers (GCs) were significantly more atrophic in TAFRO than in IPL. In TAFRO and NOS, “whirlpool vessels” in GCs were seen in most cases (TAFRO, 9/9, 100%; NOS, 6/8, 75%) but not in IPL (IPL vs TAFRO, P < .001; IPL vs NOS, P = .007). Likewise, immunostaining for Ets-related gene revealed higher levels in endothelial cells of GCs in TAFRO than in IPL (P = .014), and TAFRO and NOS were associated with a significantly higher number of endothelial cells in interfollicular areas compared with that in IPL (TAFRO vs IPL, P < .001; NOS vs IPL, P = .002). Gene expression analysis revealed that the PI3K–Akt signaling pathway was significantly enriched in the TAFRO and NOS (TAFRO/NOS) groups. This pathway, which may be activated by vascular endothelial growth factor A and some integrins, is known to affect angiogenesis by increasing vascular permeability, which may explain the clinical manifestations of anasarca and/or fluid retention in TAFRO/NOS. These results suggest that the PI3K–Akt pathway plays an important role in the pathogenesis of TAFRO/NOS. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0039-9140 295 2025 Using a microfluidic paper-based analytical device and solid-phase extraction to determine phosphate concentration 128303 EN Kaewta Danchana Department of Chemistry, Okayama University Haruka Namba Department of Chemistry, Okayama University Takashi Kaneta Department of Chemistry, Okayama University Phosphate is an essential nutrient, but in high concentrations it contributes to water pollution. Traditional methods for phosphate measurement, such as absorption spectrophotometry and ion chromatography, require expensive equipment and skilled operators. This study introduces a microfluidic paper-based analytical device (μPAD) that is designed to accomplish field-based, low-concentration phosphate measurements. This μPAD utilizes colorimetric detection based on the molybdenum blue method. Herein, we describe how the conditions were optimized in terms of design and sensitivity by adjusting reagent concentrations, paper thickness, and the time frames for sample introduction, and reaction. The operation consists of simply dipping the μPAD into a sample, capturing images in a home-made photo studio box, and processing the images with ImageJ software to measure RGB intensity. An additional preconcentration step involves solid-phase extraction with an anion exchange resin that achieves a 10-fold enrichment, which enables detection that ranges from 0.05 to 1 mg L－1 with a detection limit of 0.089 mg L－1 and a quantification limit of 0.269 mg L－1. The replicated measurements showed good reproducibility both intraday and interday (five different days) as 4.7 % and 3.0 % of relative standard deviations, respectively. After storage in a refrigerator for as long as 26 days, this μPAD delivered stable and accurate results for real-world samples of natural water, soil, and toothpaste. The results produced using this system correlate well with those produced via spectrophotometry. This μPAD-based method is a cost-effective, portable, rapid, and simple approach that allows relatively unskilled operators to monitor phosphate concentrations in field applications. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 A Case of Aniline Poisoning Manifesting as Cyanosis with Unknown Cause 209 212 EN Kenichi Taguchi Department of Gastroenterology, NHO Iwakuni Clinical Center Kazuya Nishii Department of Respiratory Medicine, NHO Iwakuni Clinical Center Sakura Hata Department of Gastroenterology, NHO Iwakuni Clinical Center Shoichi Kuyama Shoichi Tanaka Department of Gastroenterology, NHO Iwakuni Clinical Center Case Report 10.18926/AMO/68729 A 38-year-old man was brought to the hospital for emergency treatment of cyanosis. The patient exhibited generalized cyanosis and impaired consciousness despite adequate oxygen therapy. Arterial blood was black, and arterial blood gas analysis revealed an abnormally high methemoglobin level of 67.8%. We later interviewed his colleagues regarding his exposure to aniline while working at the factory and diagnosed him with methemoglobinemia due to aniline poisoning. The patient was administered methylene blue (MB) after being transferred to another hospital, where this treatment was available, resulting in an improvement in symptoms. Although rare, methemoglobinemia is serious. A good understanding of the circumstances at disease onset, characteristic findings, and abnormal values of methemoglobinemia is important. In addition, MB is an important therapeutic for the treatment of methemoglobinemia; if MB is not available at a particular hospital, transfer of the patient to a hospital that stocks MB should be considered. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0306-5251 2025 Comprehensive analysis of adverse event profile changes with pertuzumab addition to trastuzumab‐based breast cancer therapy: Disproportionality analysis using VigiBase EN Tatsuaki Takeda Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Jun Matsumoto Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Tomonori Sakai Department of Pharmacy, Okayama University Hospital Naohiro Iwata Department of Pharmacy, Okayama University Hospital Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Noritaka Ariyoshi Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Aims: Pertuzumab is used in combination with trastuzumab-based therapy for HER2-positive breast cancer. However, real-world safety information on pertuzumab remains limited. This study assessed the safety of adding pertuzumab to trastuzumab-based therapy for HER2-positive breast cancer using real-world data. Methods: VigiBase, the World Health Organization's global database of adverse events (AEs), containing reports from November 1967 to December 2023, was used. Signals for pertuzumab-associated AEs in breast cancer cases were detected using the reporting odds ratio (ROR). Results: Signals of trastuzumab plus pertuzumab relative to trastuzumab alone were detected in gastrointestinal disorders (ROR: 1.45, 95% confidence interval: 1.26–1.67), including diarrhoea (3.49, 2.83–4.30); infections and infestations (1.54, 1.24–1.91); and skin and subcutaneous tissue disorders (ROR: 1.63, 1.40–1.90), including pruritus (1.96, 1.51–2.55) and rash (1.63, 1.20–2.23). Further, signals of trastuzumab plus docetaxel plus pertuzumab relative to those of trastuzumab plus docetaxel were detected in gastrointestinal disorders (1.63, 1.38–1.93), including nausea (1.72, 1.24–2.39) and vomiting (1.48, 1.01–2.17), and in nervous system disorders (1.50, 1.20–1.87), including paraesthesia (2.60, 1.33–5.08) and peripheral sensory neuropathy (5.94, 1.79–19.71). The frequency of AEs causing or prolonging hospitalization was increased with trastuzumab plus pertuzumab compared to that with trastuzumab alone (1.18, 1.00–1.38). Conclusions: AE profiles after the addition of pertuzumab to trastuzumab-based therapy were comprehensively identified. The findings in this study highlight the importance of considering these AEs when selecting pertuzumab combination therapy to ensure the safety of patients with breast cancer. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2772-963X 4 5 2025 Prognostic Value of Pericoronary Fat Attenuation Index on Computed Tomography for Hospitalization for Heart Failure 101685 EN Mitsutaka Nakashima Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Nishihara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Hara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Nakayama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keishi Ichikawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Centre Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences BACKGROUND Pericoronary fat attenuation index (FAI) assessed on computed tomography is associated with the inflammation of the pericoronary artery. OBJECTIVES This study aimed to investigate whether pericoronary FAI predicts hospitalization for heart failure with preserved ejection fraction (HFpEF). METHODS This retrospective single-center study included 1,196 consecutive patients who underwent clinically indicated coronary computed tomography angiography (CCTA) and transthoracic echocardiography. We assessed the FAI of proximal 40-mm segments for each major epicardial coronary vessel. The primary outcome was the incidence of hospitalization for HFpEF. Patients were divided into groups based on the optimal cutoff value for predicting hospitalization for HFpEF by receiver operating characteristic curve analysis. RESULTS During a median follow-up of 4.3 years, 29 hospitalizations for HFpEF occurred. Multivariable Cox regression analysis revealed that a left anterior descending artery (LAD)-FAI >=-63.4 HU and a left circumflex artery-FAI >=-61.6 HU were significantly associated with hospitalization for HF after adjustment for age and sex (HR: 4.8; 95% CI: 2.1-10.8 and HR: 4.5; 95% CI: 2.1-9.4, respectively). The addition of LAD-FAI >-63.4 HU to a model incorporating other risk factors, including hypertension, estimated glomerular filtration rate <60 mL/min/1.73 m2, and significant stenosis on CCTA, increased the C-statistic for predicting hospitalization for HFpEF from 0.646 to 0.750 (P = 0.010). CONCLUSIONS LAD-and left circumflex artery-FAI can predict hospitalization for HFpEF in patients undergoing clinically indicated CCTA. Pericoronary inflammation may be useful for identifying patients at high risk of developing HFpEF. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1477-9560 23 1 2025 Anticoagulant effects of edoxaban in cancer and noncancer patients with venous thromboembolism 36 EN Masashi Yoshida Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Matsuo Department of General Internal Medicine 3, Kawasaki Medical School Takanori Naito Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Kuroda Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital Koji Tokioka Department of Cardiovascular Medicine, Okayama City Hospital Kunihiko Hatanaka Department of Cardiovascular Medicine, Japanese Red Cross Society Himeji Hospital Ryohei Fujimoto Department of Cardiovascular Medicine, Tsuyama Chuo Hospital Hidenaru Yamaoka Department of Cardiovascular Medicine, Okayama Rosai Hospital Yutaka Kajikawa Department of Cardiovascular Medicine, NHO Fukuyama Medical Center Kazuki Suruga Department of Cardiovascular Medicine, Okayama Medical Center Hiroki Sugiyama Department of Cardiovascular Medicine, Okayama Saiseikai General Hospital Tsuyoshi Miyaji Hosogi Hospital Yoshimasa Morimoto Department of Cardiovascular Medicine, Fukuyama City Hospital Nobuhiro Okamura Okamura Isshindow Hospital Toshihiro Sarashina Kuroda Clinic Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of General Internal Medicine 3, Kawasaki Medical School Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background Edoxaban, a direct oral anticoagulant (DOAC), is a first-line treatment for venous thromboembolism (VTE) and the suppression of VTE recurrence. In patients with cancer, however, recurrent VTE after DOAC treatment may be more common than in noncancer patients. To evaluate our hypothesis that the anticoagulation effect of edoxaban is lower in VTE patients with cancer than in noncancer patients. Methods This study was a prospective, multicenter, observational study including patients treated with edoxaban for VTE in Japan. The primary outcome was the difference in the prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer level at 5 h after initial edoxaban administration between the cancer and noncancer groups. An additional outcome was the longitudinal change in PT and APTT from 5 h to overnight after edoxaban administration. The incidence of adverse events was further investigated. Results PT and APTT at 5 h after initial edoxaban administration were not significantly different between the cancer (n = 84) and noncancer groups (n = 138) (e.g., log-transformed APTT 3.55 vs. 3.55, p = 0.45). However, D-dimer in the cancer groups was significantly greater than that in the noncancer groups (log-transformed 1.83 vs. 1.79, p = 0.009). PT and APTT significantly decreased from 5 h to overnight after edoxaban, but a similar pattern was observed in each group. All adverse events after edoxaban administration were also similar between patients with cancer and noncancer. Conclusion PT and APTT after edoxaban administration were similar between VTE patients with cancer and noncancer groups, suggesting that edoxaban has anticoagulation effects on cancer-associated VTE similar to those of noncancer patients. Trial registration UMIN000041973; Registration Date: 2020.10.5. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1435-0211 71 1 2025 Quantitative assessment of adhesive effects on partial and full compressive strength of LVL in the edge-wise direction 19 EN Ryutaro Sudo Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Kohta Miyamoto Forestry and Forest Products Research Institute Hirofumi Ido Forestry and Forest Products Research Institute Laminated wood-based materials have been widely developed, and the laminating process and adhesive itself have been reported to enhance performance beyond the sum of the individual layers' performance. This phenomenon is particularly notable under loads applied in the "edge-wise direction", where each layer bears stress collectively. These combined effects are referred to as the "adhesive effect". Strength under partial compressive loads is critical in timber engineering, as partial compressive stress generates complex stress distributions influenced by boundary conditions. The adhesive effect may also be impacted by these conditions. The aim of this study was to quantitatively and directly evaluate the adhesive effect under partial and full compressive loads using various parameters. The strength of laminated veneer lumber (LVL) with adhesive was compared to that of simply layered veneers without adhesive to assess the adhesive effect. Three mechanisms contributing to the adhesive effect were proposed: Mechanism I, caused by the deformation of the adhesive layer independently from the veneers; Mechanism II, resulting from the adhesive impregnating the veneers; and Mechanism III, arising from the reinforcement provided by adjacent veneers. The results suggested the following: (i) Mechanism I had minimal impact, as the fiber direction and the presence of additional length showed strong and slight effects on the adhesive effect, respectively; (ii) Mechanism II contributed to preventing crack propagation and altering the relationships among mechanical properties, with its effectiveness increasing as the adhesive weight increased; and (iii) Mechanism III functioned as a crossband effect, reinforcing weaknesses caused by the slope of the grain and the angle of the annual rings. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Potential for Radiation Dose Reduction in Temporal Bone CT Imaging Using Photon-Counting Detector CT 75 80 EN Fumiyo Higaki Department of Radiology, Okayama University Hospital Yusuke Morimitsu Department of Radiological Technology, Okayama University Hospital Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Sung Il Hwang Department of Radiology, Seoul National University Bundang Hospital Takahiro Kitayama Department of Radiology, Okayama University Hospital Yuka Takahashi Department of Radiology, Okayama University Hospital Mayu Uka Department of Radiology, Okayama University Hospital Noriaki Akagi Department of Radiological Technology, Okayama University Hospital Akiko Sugaya Department of Otolaryngology-Head and Neck Surgery, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Yusuke Matsui Department of Radiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takao Hiraki Department of Radiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/68645 Temporal bone computed tomography (CT) is frequently performed for pediatric patients with ear diseases. Advances in CT technology have improved diagnostic imaging quality, but reduction of radiation exposure remains a goal. We evaluated the potential for radiation dose reduction in temporal bone CT examinations using porcine ear ossicles and a photon-counting detector CT system. Three scans of the bilateral temporal bone were performed on each of three pig cadaver heads. In each of seven successive imaging sessions, the radiation dose was reduced by an additional one-seventh of the recommended dose (RD). Two board-certified radiologists independently scored the resulting images on a scale of 1 to 5 points, where 5 represented the image quality at the RD. Images scoring ≥4.5 points were considered acceptable. Noise was assessed in a 2-cm-diameter region near the ear ossicles, and standard deviation was measured for each of the seven decrements from the RD. As the radiation dose decreased, the noise progressively increased, and visual assessment scores progressively decreased. Acceptable image scores were obtained at six-sevenths (4.9), five-sevenths (4.8), four-sevenths (4.7), and three-sevenths (4.6) of the RD. Thus, acceptable porcine temporal bone CT images were obtained with a radiation dose reduction of approximately 50%. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0099-2240 2025 Enterobacterial common antigen repeat-unit flippase WzxE is required for Escherichia coli growth under acidic conditions, low temperature, and high osmotic stress conditions EN Saki Yamaguchi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuya Ishikawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuyuki Furuta Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikara Kaito Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Colanic acid and enterobacterial common antigen (ECA) are cell-surface polysaccharides that are produced by many Escherichia coli isolates. Colanic acid is induced under acidic, low temperature, and high-salt conditions and is important for E. coli resistance to these stresses; however, the role of ECA in these stresses is less clear. Here, we observed that knockout of flippase wzxE, which translocates lipid-linked ECA repeat units from the cytoplasmic side of the inner membrane to the periplasmic side, resulted in the sensitivity of E. coli BW25113 to acidic conditions. The wzxE-knockout mutant showed reduced growth potential and viable counts in vegetable extracts with acidic environments, including cherry tomatoes, carrots, celery, lettuce, and spinach. A double-knockout strain of wzxE and wecF (glycosyltransferase that adds the third-and-final sugar of the lipid-linked ECA repeat unit) was not sensitive to acidic conditions, with similar results obtained for a double-knockout strain of wzxE and wcaJ (glycosyltransferase that initiates colanic acid lipid-linked repeat-unit biosynthesis). The wzxE-knockout mutant was sensitive to low temperatures or high-salt conditions, which induced colanic acid synthesis, and these sensitivities were abolished by the additional knockout of wcaJ. These results suggest that lipid-linked ECA repeat units confer E. coli susceptibility to acidic, low temperatures, and high-salt conditions in a colanic acid-dependent manner and that wzxE suppresses this negative effect. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 14 7 2025 Comparison of Midazolam and Diazepam for Sedation in Patients Undergoing Double-Balloon Endoscopic Retrograde Cholangiopancreatography: A Propensity Score-Matched Analysis 2287 EN Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Objective: The sedation method used in double-balloon endoscopic retrograde cholangiopancreatography (DB-ERCP) varies across countries and between healthcare facilities. No previous studies have compared the effects of different benzodiazepines on sedation during endoscopic procedures. This study aimed to compare the effects of midazolam and diazepam sedation on DB-ERCP outcomes. Methods: This retrospective cohort study analyzed consecutive patients who underwent DB-ERCP between January 2017 and February 2024. A total of 203 patients who were sedated with diazepam (n = 94) or midazolam (n = 109) were analyzed. Propensity score matching was applied to adjust for baseline group differences. The primary outcome was the incidence of sedation-related adverse events (AEs). Secondary outcomes included inadequate sedation requiring additional sedatives and risk factors for sedation-related AEs. Results: Sedation-related AEs were more frequent with diazepam (28% [21/75]) than with midazolam (14% [11/75]; p = 0.046). Hypoxia occurred more frequently with diazepam (19% [14/75]) than with midazolam (5% [4/75]; p = 0.012). However, no significant differences were observed between the two groups for hypotension (p = 0.41) and bradycardia (p = 1.0). Poor sedation requiring other sedatives occurred significantly more often with diazepam (8% [6/75]) compared with midazolam sedation (0% [0/75], p = 0.012). Multivariate analysis identified diazepam sedation (odds ratio, 2.3; 95% confidence interval, 1.0-5.3; p = 0.048) as the sole risk factor for sedation-related AEs. Conclusions: Midazolam is safer and more effective than diazepam sedation in patients undergoing DB-ERCP. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 4 2025 Bilateral Scleritis and Neutrophilic Dermatosis With Cytogenetic Chromosomal Aberrancy Related to Pyoderma Gangrenosum: A Case Report of a 20-Year Follow-Up e82348 EN Toshihiko Matsuo Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Noboru Asada Department of Hematology and Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mikako Obika Department of General Internal Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ryotaro Omichi Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Keiji Iwatsuki Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Pyoderma gangrenosum is a non-infectious autoimmune disease with skin plaques and ulcers in the entity of neutrophilic dermatosis and may have a background of myelodysplastic syndromes. This study reported a 20-year follow-up of a patient with pyoderma gangrenosum and scleritis who showed chromosomal aberrancy from the initial phase and later in the course developed thrombocythemia. A 51-year-old man presented with widespread indurated erythematous plaques with scaling and pustules on the forehead, bilateral eyelids, and nasal bridge, in addition to nodular scleritis in the left eye and ulcer formation of the plaques in the lower legs. Skin biopsy revealed massive dermal infiltration mainly with neutrophils in the absence of neutrophilic vasculitis. Suspected of myelodysplastic syndromes, bone marrow biopsy was normal, while chromosomal aberrancy, 46, XY, del (20) (q11q13.3), was detected. In the diagnosis of neutrophilic dermatosis, probably of pyoderma gangrenosum, he began to have oral prednisolone 20 mg daily and colchicine 1 mg daily, leading to the subsidence of skin lesions. Four months later, he developed nodular scleritis in the right eye and began to use topical 0.1% betamethasone in both eyes. He was stable with only prednisolone 12.5 mg daily until the age of 55.5 years, when he showed an increase of serum lactate dehydrogenase. The bone marrow aspirate disclosed neither blast cell increase nor atypical cells. The same chromosomal aberrancy was repeatedly detected. One year later, he developed breathing difficulty and underwent tracheostomy. Laryngeal lesion biopsy disclosed squamous cell papilloma with human papillomavirus-6. At 60 years old, he showed marginal corneal infiltration in the left eye, and at 61 years old, hypopyon in the right eye. Platelets tended to increase up to 1000 × 103/µL, and bone marrow examinations were recommended but refused by the patient. At the latest follow-up at 71 years old, he was ambulatory in health and stable with a tracheostomy cannula. In conclusion, pyoderma gangrenosum with scleritis occurred in an undetermined hematological malignancy with chromosomal aberrancy. 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 5 2025 知の探索時間についての企業の意思決定プロセス 1 9 EN Takeshi SHIMIZU Graduate School of Interdisciplinary Science and Engineering in Health Systems Okayama University 10.18926/interdisciplinary/68620 In order for companies to innovate through business co-creation, it is necessary to explore a wide range of external knowledge and technologies. However, there is no clear answer as to how much time should be spent for exploration. Under these circumstances, companies must take into account constraints such as the amount of management resources that can be invested, and make decisions about the time to spend for exploration. The purpose of this paper is to clarify the process of how companies that have introduced corporate accelerator program recognize the relationship between the program period and the results of business co-creation, and how they make decisions about the program period. We conducted a case study of several companies that have introduced corporate accelerator program in Japan. In addition, this paper established a hypothesis about decision-making about the time for exploration from case studies. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2397-9070 9 4 2025 Induction Therapy With Oral Tacrolimus Provides Long-Term Benefit in Thiopurine-Naïve Refractory Ulcerative Colitis Patients Despite Low Serum Albumin Levels e70139 EN Shoko Igawa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Inokuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junki Toyosawa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Aoyama Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushi Yamasaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Kinugasa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Takahara Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada 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 Background and Aim: Oral tacrolimus is an effective treatment for refractory ulcerative colitis (UC). However, tacrolimus is underutilized because of the difficulties in transitioning to subsequent maintenance therapy and concerns about adverse events. Methods: We evaluated the clinical outcomes, adverse events, and accumulated medication costs in consecutive 72 UC patients treated with tacrolimus. Results: Fifty-five (76%) patients with pancolitis and 43 (60%) patients with acute severe disease were entered. Fifty-four (75%) achieved clinical remission 8 weeks after starting tacrolimus. At the last visit, 62 (86%) patients had colectomy-free remission, and 55 (76%) patients had corticosteroid-free remission. Eighteen (25%) patients maintained remission without additional treatment after tacrolimus discontinuation. Patients with continuous remission had a significantly lower history of thiopurine use and lower serum albumin levels at the induction of tacrolimus than patients with failure to induce or maintain remission. No severe adverse events due to tacrolimus treatment were observed. The accumulated medication costs over 3 years in patients with continuous remission after the start of tacrolimus were lower than those in patients with induction and maintenance of infliximab (p < 0.001). Conclusions: Tacrolimus could have an irreplaceable role in the era of biologic therapies, especially for refractory UC patients with thiopurine-na & iuml;ve and low serum albumin levels. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1999-4893 18 3 2025 A Hair Drawing Evaluation Algorithm for Exactness Assessment Method in Portrait Drawing Learning Assistant System 143 EN Yue Zhang Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Erita Cicilia Febrianti Department of Electrical Engineering, Politeknik Elektronika Negeri Surabaya Amang Sudarsono Department of Electrical Engineering, Politeknik Elektronika Negeri Surabaya Chenchien Hsu Department of Electrical Engineering, National Taiwan Normal University Nowadays, portrait drawing has become increasingly popular as a means of developing artistic skills and nurturing emotional expression. However, it is challenging for novices to start learning it, as they usually lack a solid grasp of proportions and structural foundations of the five senses. To address this problem, we have studied Portrait Drawing Learning Assistant System (PDLAS) for guiding novices by providing auxiliary lines of facial features, generated by utilizing OpenPose and OpenCV libraries. For PDLAS, we have also presented the exactness assessment method to evaluate drawing accuracy using the Normalized Cross-Correlation (NCC) algorithm. It calculates the similarity score between the drawing result and the initial portrait photo. Unfortunately, the current method does not assess the hair drawing, although it occupies a large part of a portrait and often determines its quality. In this paper, we present a hair drawing evaluation algorithm for the exactness assessment method to offer comprehensive feedback to users in PDLAS. To emphasize hair lines, this algorithm extracts the texture of the hair region by computing the eigenvalues and eigenvectors of the hair image. For evaluations, we applied the proposal to drawing results by seven students from Okayama University, Japan and confirmed the validity. In addition, we observed the NCC score improvement in PDLAS by modifying the face parts with low similarity scores from the exactness assessment method. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 26 6 2025 Vesicular Glutamate Transporter 3 Is Involved in Glutamatergic Signalling in Podocytes 2485 EN Naoko Nishii Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Kawai Department of Cell Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Yasuoka Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Abe Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nanami Tatsumi Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuika Harada Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University Takaaki Miyaji Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University Shunai Li Center for Innovative Clinical Medicine, Okayama University Hospital Moemi Tsukano Central Research Laboratory, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Center for Innovative Clinical Medicine, Okayama University Hospital Daisuke Ogawa Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohji Takei Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Yamada Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Glomerular podocytes act as a part of the filtration barrier in the kidney. The activity of this filter is regulated by ionotropic and metabotropic glutamate receptors. Adjacent podocytes can potentially release glutamate into the intercellular space; however, little is known about how podocytes release glutamate. Here, we demonstrated vesicular glutamate transporter 3 (VGLUT3)-dependent glutamate release from podocytes. Immunofluorescence analysis revealed that rat glomerular podocytes and an immortal mouse podocyte cell line (MPC) express VGLUT1 and VGLUT3. Consistent with this finding, quantitative RT-PCR revealed the expression of VGLUT1 and VGLUT3 mRNA in undifferentiated and differentiated MPCs. In addition, the exocytotic proteins vesicle-associated membrane protein 2, synapsin 1, and synaptophysin 1 were present in punctate patterns and colocalized with VGLUT3 in MPCs. Interestingly, approximately 30% of VGLUT3 colocalized with VGLUT1. By immunoelectron microscopy, VGLUT3 was often observed around clear vesicle-like structures in differentiated MPCs. Differentiated MPCs released glutamate following depolarization with high potassium levels and after stimulation with the muscarinic agonist pilocarpine. The depletion of VGLUT3 in MPCs by RNA interference reduced depolarization-dependent glutamate release. These results strongly suggest that VGLUT3 is involved in glutamatergic signalling in podocytes and may be a new drug target for various kidney diseases. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1083-351X 301 4 2025 Roles of basic amino acid residues in substrate binding and transport of the light-driven anion pump Synechocystis halorhodopsin (SyHR) 108334 EN Masaki Nakama Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoyasu Noji Department of Applied Chemistry, The University of Tokyo Keiichi Kojima Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Susumu Yoshizawa Atmosphere and Ocean Research Institute, The University of Tokyo Hiroshi Ishikita Department of Applied Chemistry, The University of Tokyo Yuki Sudo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Microbial rhodopsins are photoreceptive seventransmembrane a-helical proteins, many of which function as ion transporters, primarily for small monovalent ions such as Na+, K+, Cl-, Br-, and I-. Synechocystis halorhodopsin (SyHR), identified from the cyanobacterium Synechocystis sp. PCC 7509, uniquely transports the polyatomic divalent SO42- inward, in addition to monovalent anions (Cl- and Br-). In this study, we conducted alanine-scanning mutagenesis on twelve basic amino acid residues to investigate the anion transport mechanism of SyHR. We quantitatively evaluated the Cl-and SO42- transport activities of the WT SyHR and its mutants. The results showed a strong correlation between the Cl-and SO42- transport activities among them (R = 0.94), suggesting a shared pathway for both anions. Notably, the R71A mutation selectively abolished SO42- transport activity while maintaining Cl- transport, whereas the H167A mutation significantly impaired both Cl-and SO42- transport. Furthermore, spectroscopic analysis revealed that the R71A mutant lost its ability to bind SO42- due to the absence of a positive charge, while the H167A mutant failed to accumulate the O intermediate during the photoreaction cycle (photocycle) due to reduced hydrophilicity. Additionally, computational analysis revealed the SO42- binding modes and clarified the roles of residues involved in its binding around the retinal chromophore. Based on these findings and previous structural information, we propose that the positive charge and hydrophilicity of Arg71 and His167 are crucial for the formation of the characteristic initial and transient anion-binding site of SyHR, enabling its unique ability to bind and transport both Cl-and SO42-. No potential conflict of interest relevant to this article was reported.

American Association for Cancer Research (AACR) Acta Medica Okayama 0008-5472 85 6 2025 Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy 1082 1096 EN Toshifumi Ninomiya Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoya Kemmotsu Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumiaki Mukohara Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaki Magari Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ai Miyamoto Medical Protein Engineering, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Youki Ueda Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takamasa Ishino Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Joji Nagasaki Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Fujiwara Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hidetaka Yamamoto Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetoshi Hayashi Department of Medical Oncology, Kindai University Faculty of Medicine Kota Tachibana Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Joji Ishida Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihiro Otani Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shota Tanaka Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University Isamu Okamoto Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Brain metastasis is a poor prognostic factor in patients with cancer. Despite showing efficacy in many extracranial tumors, immunotherapy with anti–PD-1 mAb or anti–CTLA4 mAb seems to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti–PD-1 and anti–CTLA4 mAbs has a potent antitumor effect on brain metastasis, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies. In this study, we analyzed the tumor-infiltrating lymphocytes in murine models of brain metastasis that responded to anti–CTLA4 and anti–PD-1 mAbs. Activated CD4+ T follicular helper (TFH) cells with high CTLA4 expression characteristically infiltrated the intracranial TME, which were activated by combination anti–CTLA4 and anti–PD-1 treatment. The loss of TFH cells suppressed the additive effect of CTLA4 blockade on anti–PD-1 mAb. B-cell–activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) produced by abundant myeloid cells, particularly CD80hiCD206lo proinflammatory M1-like macrophages, in the intracranial TME induced B-cell and TFH-cell infiltration and activation. Furthermore, the intracranial TME of patients with non–small cell lung cancer featured TFH- and B-cell infiltration as tertiary lymphoid structures. Together, these findings provide insights into the immune cell cross-talk in the intracranial TME that facilitates an additive antitumor effect of CTLA4 blockade with anti–PD-1 treatment, supporting the potential of a combination immunotherapeutic strategy for brain metastases. Significance: B-cell and CD4+ T follicular helper cell activation via BAFF/APRIL from abundant myeloid cells in the intracranial tumor microenvironment enables a combinatorial effect of CTLA4 and PD-1 blockade in brain metastases. No potential conflict of interest relevant to this article was reported.

岡山大学教師教育開発センター Acta Medica Okayama 2186-1323 15 2025 小児がん患児に対する教育的支援とその研究動向 341 355 EN Yiwen CHEN Graduate School of Education Doctoral Programs, Hyogo University of Teacher Education Munehisa YOSHITOSHI Graduate School of Education, Okayama University 10.18926/CTED/68503 　本研究は、小児がん患児の教育的支援に関する研究の動向を明らかにし、今後の課題とその解決策を提起することを目的とした。「学習」、「自己管理」、「対人」、「心理」、「連携」の5つの視点から分析を行った。学習支援について、治療に伴う学習の遅れや集中力の低下に対し、個別の教育支援計画や体験的な学習、および遠隔教育の実施に期待されていた。自己管理支援では、患児が自身の病状や治療による副作用を理解し、自立的に管理できる能力を育成することが求められていた。対人支援について、患児の長期入院により、友人関係の構築が困難になり、入院中や復学後のコミュニケーションの支援が重要であることが確認された。心理支援においては、周囲への効果的ながん教育や大学生ボランティアによる支援が、患児の心理的安定を促すことが示された。最後に、学校と医療機関、保護者の連携不足が指摘されており、連携ツールの開発が求められている。 No potential conflict of interest relevant to this article was reported.

岡山大学教師教育開発センター Acta Medica Okayama 2186-1323 15 2025 主体的・自律的な学びを萌芽させる「授業と授業をつなぐ家庭学習」の探究 297 311 EN Junko TANAKA Okayama Municipal Hosen Junior High School Ryo MISAWA Faculty of Education, Okayama University 10.18926/CTED/68500 　生徒が自ら学習を進めていく力を身に付けるには，授業内だけでなく，家庭など授業外の場での学習経験を積む必要がある。つまり，学習は授業内だけで完結するのではなく，広範な活動を通して成立する。本研究では，公立中学校の第2学年を対象に授業と家庭学習を連携させる実践を行い，生徒の「主体的・自律的な学び」を萌芽させることを目指した。教師が学習方略や目標設定の重要性を伝え，メタ認知を促すことで，生徒は自己調整学習のサイクルを意識し，自分なりの学習方略を探求するようになった。また，家庭学習で授業につながる課題に取り組むことで，授業への主体的な参加と，授業外で自律的に学ぶ意欲が促されることも示唆された。 No potential conflict of interest relevant to this article was reported.

Taylor and Francis Group Acta Medica Okayama 1559-2316 20 1 2025 Specific enhancement of the translation of thermospermine-responsive uORF-containing mRNAs by ribosomal mutations in Arabidopsis thaliana 2480231 EN Koki Mutsuda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuichi Nishii Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tomohiko Toyoshima Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroko Fukushima Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyasu Motose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taku Takahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Auxin-induced xylem formation in angiosperms is negatively regulated by thermospermine, whose biosynthesis is also induced by auxin. In Arabidopsis thaliana, loss-of-function mutants of ACL5, which encodes thermospermine synthase, exhibit a dwarf phenotype accompanied by excessive xylem formation. Studies of suppressor mutants that recover from the acl5 dwarf phenotype suggest that thermospermine alleviates the inhibitory effect of an upstream open-reading frame (uORF) on the main ORF translation of SAC51 mRNA. Many suppressor mutations for acl5 have been mapped to the uORF conserved in the SAC51 family or to ribosomal protein genes, such as RPL10A, RPL4A, and RACK1A. In this study, we identified newly isolated acl5 suppressors, sac501, sac504, and sac506, which are additional alleles of RPL10A and the uORFs of SAC51 family members, SACL1 and SACL3, respectively. To investigate whether acl5-suppressor alleles of ribosomal genes broadly affect translation of uORF-containing mRNAs, we examined GUS activity in several 5'-GUS fusion constructs. Our results showed that these alleles enhanced GUS activity in SAC51 and SACL3 5'-fusion constructs but had no effect on other 5'-fusion constructs unrelated to thermospermine response. This suggests that these ribosomal proteins are specifically involved in the thermospermine-mediated regulation of mRNA translation. No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 56 3 2025 地方創生第１期における製造事業所の存続，発生，消失 15 33 EN Ryohei Nakamura 10.18926/OER/68444 　地方に位置する多くの自治体においては，従来からある事業所の活性化や新規事業所の誕生に加えて，製造工場の誘致は地域振興にとっていまも重要な政策となっている。今日，高度経済成長期における重厚長大型の産業の誘致とは異なり，地域優位性をできるだけ活用した企業誘致の傾向になっている。雇用創出効果は昔に比べて小さくなっているとはいえ，製造業の多くにおいて，地域の基盤産業としての位置づけは残っている。第1期の地方創生の期間で，どのような地域において，どのような製造工場が消失，撤退や出現，存続しているのかを識別し，それらの要因を分析する。 　2014年と2019年の事業所の比較において，付加価値生産性の平均と分布を見ると2014年，2019年ともに存在する事業所の労働生産性が最も高い。次いで高いのが2019年に存在する事業所で，最も低かったのが2014年には存在したが2019年には存在していない事業所であった。またロジット分析の結果から，生産性が高く事業所規模が大きいと消滅しない傾向があり，また都市化の程度が高いと消滅傾向にあることが推定された。他方，発生した製造事業所について，産業別に同業種集積と人口規模で測った都市集積を説明変数とした市町村単位の回帰分析からは正の効果が示された。 No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 56 3 2025 市場区分と決算発表に対する市場の反応 ―四半期データを利用した分析― 1 13 EN Toyotaka Nakagawa Yuki Yamanishi Hiroaki Kobayashi 10.18926/OER/68443 The purpose of this paper is to examine, using quarterly financial data, how the market reaction to earnings announcements in each market segment （prime market segment, standard market segment, and growth market segment） has changed after the revision of market segmentation at the Tokyo Stock Exchange. For the research design, the abnormal volume and residual returns for the 12 quarters around April 1, 2022, when the market segmentation was changed, were calculated using the analysis method of Beaver et al. ［2020］. The results of the analysis suggest that volume is significantly affected by changes in market segmentation. In addition, for the group of stocks in the growth market, there appears to have been some change in the trend of stock price fluctuations after the market segmentation revision. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1341-321X 31 3 2025 Intention and potential determinants of COVID-19 vaccination among healthcare workers at a single university hospital in Japan, 2024–2025 pre-season 102660 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Yasushi Fujita Division of Infection Prevention and Control, Okayama University Hospital Takashi Kiguchi Division of Infection Prevention and Control, Okayama University Hospital Yohei Manabe Division of Infection Prevention and Control, Okayama University Hospital Background: Financial accessibility has emerged as a significant barrier to vaccine uptake following the cessation of universal public funding for coronavirus disease 2019 (COVID-19) vaccination programs. This investigation assessed the intention and determinant factors of COVID-19 vaccination among healthcare workers in Japan in the 2024–2025 pre-season. Methods: A retrospective survey was conducted utilizing data collected from hospital staff at Okayama University Hospital, Japan, to inform the COVID-19 vaccination strategy in October 2024. The analysis evaluated demographic characteristics, vaccine intention, perceived barriers to vaccination, and maximum acceptable out-of-pocket expenditure. Results: The study population of 3417 respondents comprised 843 medical doctors (24.7 %), 1131 nurses (33.1 %), 320 other medical staff (9.4 %), 286 dental doctors (8.4 %), and 627 administrative officers (18.3 %). At full cost, 2109 (61.7 %) indicated no intention to receive vaccination, while only 4.4 % expressed willingness to be vaccinated and 33.9 % remained undecided. With total self-payment, the vaccination acceptance rates were the highest and lowest among medical doctors (11.4 %) and nurses (1.0 %), respectively. Cost (38.1 %), followed by safety issues (29.5 %) and concerns regarding efficacy or medical necessity (20.3 %), emerged as the primary barrier. The projected vaccination intention increased to 43.9 % and 54.9 % at reduced self-pay costs of 3000 JPY and 5000 JPY, respectively. Conclusions: Addressing financial constraints through policy interventions could be effective strategies in increasing overall vaccination coverage among healthcare workers. In addition, providing tailored education on vaccine safety, efficacy, and necessity may further facilitate increased vaccine uptake within this critical population. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0939-5555 2025 A randomized controlled trial of conventional GVHD prophylaxis with or without teprenone for the prevention of severe acute GVHD EN Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Mitsuru Tsuge Department of Pediatric Acute Diseases, Okayama University Academic Field of Medicine Dentistry, and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Hiroki Kobayashi Department of Hematology and Oncology, Okayama University Hospital Chihiro Kamoi Department of Hematology and Oncology, Okayama University Hospital Akira Yamamoto Department of Hematology and Oncology, Okayama University Hospital Takumi Kondo Department of Hematology and Oncology, Okayama University Hospital Keisuke Seike Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Therapies that effectively suppress graft-versus-host disease (GVHD) without compromising graft-versus-leukemia/lymphoma (GVL) effects is important in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic malignancies. Geranylgeranylacetone (GGA) is a main component of teprenone, a gastric mucosal protectant commonly used in clinical practice. In preclinical models, GGA suppresses proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), which are associated with GVHD as well as induces thioredoxin-1 (Trx-1), which suppresses GVHD while maintaining GVL effects. Here, we investigated whether the addition of teprenone to standard GVHD prophylaxis could reduce the cumulative incidence of severe acute GVHD (aGVHD) without attenuating GVL effects. This open-label, randomized clinical trial enrolled 40 patients (21 control and 19 teprenone group) who received allo-HSCT between May 2022 and February 2023 in our institution. Patients in the teprenone group received 50 mg of teprenone orally thrice daily for 21 days from the initiation of the conditioning regimen. The cumulative incidence of severe aGVHD by day 100 after allo-HSCT was not significantly different in the two groups (27.9 vs. 16.1%, p = 0.25). The exploratory studies revealed no obvious changes in Trx-1 levels, but the alternations from baseline in IL-1β and TNF-α levels at day 28 after allo-HSCT tended to be lower in the teprenone group. In conclusion, we could not demonstrate that teprenone significantly prevented the development of severe aGVHD. Discrepancy with preclinical model suggests that appropriate dose of teprenone may be necessary to induce the expression of antioxidant enzymes that suppress severe aGVHD. Clinical Trial Registration number:jRCTs 061210072. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 14 4 2025 Natural Course and Long-Term Outcomes of Gastric Subepithelial Lesions: A Systematic Review 1055 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Gastric subepithelial lesions (SELs) are often incidentally detected during endoscopic examinations, with most patients being asymptomatic and lesions measuring <20 mm. Despite their generally indolent nature, certain SELs, such as gastrointestinal stromal tumors, require resection. Current guidelines recommend periodic surveillance; however, the natural course and long-term outcomes of gastric SELs have not been sufficiently investigated. This systematic review aimed to synthesize evidence on the progression, growth rate, and risk factors associated with gastric SELs to inform clinical management strategies. Methods: A comprehensive search of PubMed was conducted for peer-reviewed studies published between January 2000 and November 2024. Eligible studies included original studies on the follow-up and progression of gastric SELs. Non-English articles, reviews, case reports, and unrelated topics were excluded. In total, 277 articles were screened, with 15 additional articles identified through manual screening. Ultimately, 41 articles were included in the analysis. The study protocol is registered in PROSPERO (CRD42024614865). Results: Large-scale studies reported low growth rates of 2.0-8.5% over 2.0-5.0 years, while smaller studies reported a broader range of growth rates of 5.4-28.4%. The factors contributing to these discrepancies include patient selection, follow-up duration, and growth criteria. Risk factors for lesion size increase include larger initial lesion size, irregular margins, heterogeneous echo patterns, and certain tumor locations. Conclusions: These findings underscore the need for individualized management strategies based on lesion size, imaging characteristics, and risk factors. The close monitoring of high-risk lesions is crucial for timely intervention. Standardized growth criteria and optimized follow-up protocols are essential for improving clinical decision making and patient outcomes. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2078-2489 16 2 2025 Implementation of Sensor Input Setup Assistance Service Using Generative AI for SEMAR IoT Application Server Platform 108 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 Natural Science and Technology, Okayama University 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 I. Gusti Made Ngurah Desnanjaya Department of Computer System Engineering, Institute of Business and Technology Indonesia For rapid deployments of various IoT application systems, we have developed Smart Environmental Monitoring and Analytical in Real-Time (SEMAR) as an integrated server platform. It is equipped with rich functions for collecting, analyzing, and visualizing various data. Unfortunately, the proper configuration of SEMAR with a variety of IoT devices can be complex and challenging for novice users, since it often requires technical expertise. The assistance of Generative AI can be helpful to solve this drawback. In this paper, we present an implementation of a sensor input setup assistance service for SEMAR using prompt engineering techniques and Generative AI. A user needs to define the requirement specifications and environments of the IoT application system for sensor inputs, and give them to the service. Then, the service provides step-by-step guidance on sensor connections, communicating board configurations, network connections, and communication protocols to the user, which can help the user easily set up the configuration to connect the relevant devices to SEMAR. For evaluations, we applied the proposal to the input sensor setup processes of three practical IoT application systems with SEMAR, namely, a smart light, water heater, and room temperature monitoring system. In addition, we applied it to the setup process of an IoT application system for a course for undergraduate students at the Insitut Bisnis dan Teknologi (INSTIKI), Indonesia. The results demonstrate the effectiveness of the proposed service for SEMAR. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0361-8609 96 10 2021 Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease 1241 1252 EN Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences David C. Fajgenbaum Center for Cytokine Storm Treatment & Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania Sheila K. Pierson Center for Cytokine Storm Treatment & Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania Noriko Iwaki Hematology/Respiratory Medicine, Kanazawa University Graduate School of Medical Science Asami Nishikori Division of Pathophysiology, Okayama University Graduate School of Health Sciences Mitsuhiro Kawano Department of Rheumatology, Kanazawa University Graduate School of Medical Science Naoya Nakamura Department of Pathology, Tokai University School of Medicine Koji Izutsu Department of Hematology, National Cancer Center Hospital Kengo Takeuchi Department of Pathology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Midori Filiz Nishimura Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuyuki Yoshizaki Department of Organic Fine Chemicals, Institute of Scientific and Industrial Research, Osaka University Eric Oksenhendler Department of Clinical Immunology, Hôpital Saint-Louis Frits van Rhee Myeloma Center, University of Arkansas for Medical Sciences Yasuharu Sato Division of Pathophysiology, Okayama University Graduate School of Health Sciences Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome is a heterogeneous entity manifesting with a constellation of symptoms described above that can occur in the context of idiopathic multicentric Castleman disease (iMCD) as well as infectious diseases, malignancies, and rheumatologic disorders. So, iMCD-TAFRO is an aggressive subtype of iMCD with TAFRO syndrome and often hyper-vascularized lymph nodes. Since we proposed diagnostic criteria of iMCD-TAFRO in 2016, we have accumulated new insights on the disorder and additional cases have been reported worldwide. In this systematic review and cohort analysis, we established and validated a definition for iMCD-TAFRO. First, we searched PubMed and Japan Medical Abstracts Society databases using the keyword “TAFRO” to extract cases. Patients with possible systemic autoimmune diseases and hematologic malignancies were excluded. Our search identified 54 cases from 50 articles. We classified cases into three categories: (1) iMCD-TAFRO (TAFRO syndrome with lymph node histopathology consistent with iMCD), (2) possible iMCD-TAFRO (TAFRO syndrome with no lymph node biopsy performed and no other co-morbidities), and (3) TAFRO without iMCD or other co-morbidities (TAFRO syndrome with lymph node histopathology not consistent with iMCD or other comorbidities). Based on the findings, we propose an international definition requiring four clinical criteria (thrombocytopenia, anasarca, fever/hyperinflammatory status, organomegaly), renal dysfunction or characteristic bone marrow findings, and lymph node features consistent with iMCD. The definition was validated with an external cohort (the ACCELERATE Natural History Registry). The present international definition will facilitate a more precise and comprehensive approach to the diagnosis of iMCD-TAFRO. No potential conflict of interest relevant to this article was reported.

Medknow Publications Acta Medica Okayama 0971-6203 49 4 2024 Backside Irradiation of Ultraviolet-A for Correcting Nonuniformity Error of Gafchromic XR-QA2 Films 563 567 EN Nobuyoshi Tanki Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Sachiko Goto Department of Radiological Technology, Faculty of Health Sciences, Okayama University Toshizo Katsuda Department of Medical Radiation Technology, Shizuoka College of Medicalcare Science Rumi Gotanda Department of Radiological Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare Tatsuhiro Gotanda Department of Radiological Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare Tadao Kuwano Department of Radiology, Osaka Center for Cancer and Cardiovascular Diseases Prevention Purpose: Radiochromic film is used for quality assurance and quality control of X-ray equipment in the diagnostic radiology. In addition, three-dimensional dose distribution of computed tomography (CT) is measured. To correct the nonuniformity and uncertainty of radiochromic films for dose measurement of CT, the films are preirradiated ultraviolet (UV)-A rays. There is a difference in the UV protection strength of radiochromic films. A concern exists about the effects of the UV-A irradiation intensity. We thus irradiated with UV-A rays from the backsides of the films to assess if backside irradiation was possible. Materials and Methods: Gafchromic XR-QA2 and RTQA2 were used in this study. The UV-A rays were simultaneously irradiated on the front and backsides of each film for 12 h. The yellow layer of each film was scanned and imaged. The average pixel values ± standard deviations (SDs) were compared. In the statistical analysis, a paired t-test was performed. To compare, the active-layer densities engendered by the UV-A rays. Calibration curve was created with 48 h of preirradiation of UV-A. Results: The mean pixel values ± SD for Gafchromic XR-QA2 on the front and backsides were 130.776 ± 0.812 and 81.015 ± 1.128, respectively. On the other hand, the mean pixel values ± SD for Gafchromic RTQA2 on the front and backsides were 62.299 ± 1.077 and 133.761 ± 1.365, respectively. The statistical results of the paired t-test were significantly different (P < 0.01) between both films. Fitting equation of the calibration curve is shown below. y = -390.47 ± 200 + (443.45 ± 10x80).5068 ± 0.0434. Conclusion: Based on the relationship between the sensitivity of the active layer to UV-A rays and the strength of UV protection on the surface, we concluded that backside irradiation is recommended for Gafchromic XR-QA2, and frontside irradiation is recommended for Gafchromic RTQA2. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 1 2025 Photoinitiators Induce Histamine Production in Human Mast Cells 51 58 EN Taro Miura Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Kawasaki Laboratory of Clinical Pharmacology and Therapeutics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University Hirofumi Hamano Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshito Zamami Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Sendo Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/68362 Photoinitiators are used in the manufacture of many daily products, and may produce harmful effects due to their cytotoxicity. They have also been detected in human serum. Here, we investigated the histamine-producing effects in HMC-1 cells and the inflammatory cytokine release effects in RAW264 cells for four photoinitiators: 1-hydroxycyclohexyl phenyl ketone; 2-isopropylthioxanthone; methyl 2-benzoylbenzoate; and 2-methyl-4´-(methylthio)-2-morpholinopropiophenone. All four promoted histamine production in HMC-1 cells; however, they did not significantly affect the release of inflammatory cytokines in RAW264 cells. These findings suggest that these four photoinitiators induce inflammatory cytokine-independent histamine production, potentially contributing to histamine-mediated chronic inflammation in vitro. No potential conflict of interest relevant to this article was reported.

Proceedings of the National Academy of Sciences Acta Medica Okayama 0027-8424 121 35 2024 Somatic mutations in tumor-infiltrating lymphocytes impact on antitumor immunity e2320189121 EN Fumiaki Mukohara Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuma Iwata Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takamasa Ishino Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Inozume Department of Dermatology, Chiba University Graduate School of Medicine Joji Nagasaki Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Youki Ueda Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Toshihide Ueno Division of Cellular Signaling, National Cancer Center Research Institute Hideki Ikeda Division of Cell Therapy, Chiba Cancer Research Institute Katsushige Kawase Division of Cell Therapy, Chiba Cancer Research Institute Yuka Saeki Department of Dermatology, Chiba University Graduate School of Medicine Shusuke Kawashima Department of Dermatology, Chiba University Graduate School of Medicine Kazuo Yamashita KOTAI Biotechnologies, Inc. Yu Kawahara Department of Dermatology, Chiba University Graduate School of Medicine Yasuhiro Nakamura Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center Akiko Honobe-Tabuchi Department of Dermatology, University of Yamanashi Hiroko Watanabe Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromichi Dansako Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuyoshi Kawamura Department of Dermatology, University of Yamanashi Yutaka Suzuki Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa Hiroaki Honda Department of Pathology, Tokyo Women's Medical University Hiroyuki Mano Division of Cellular Signaling, National Cancer Center Research Institute Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Masahito Kawazu Division of Cell Therapy, Chiba Cancer Research Institute Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Immune checkpoint inhibitors (ICIs) exert clinical efficacy against various types of cancers by reinvigorating exhausted CD8+ T cells that can expand and directly attack cancer cells (cancer-specific T cells) among tumor-infiltrating lymphocytes (TILs). Although some reports have identified somatic mutations in TILs, their effect on antitumor immunity remains unclear. In this study, we successfully established 18 cancer-specific T cell clones, which have an exhaustion phenotype, from the TILs of four patients with melanoma. We conducted whole-genome sequencing for these T cell clones and identified various somatic mutations in them with high clonality. Among the somatic mutations, an SH2D2A loss-of-function frameshift mutation and TNFAIP3 deletion could activate T cell effector functions in vitro. Furthermore, we generated CD8+ T cell–specific Tnfaip3 knockout mice and showed that Tnfaip3 function loss in CD8+ T cell increased antitumor immunity, leading to remarkable response to PD-1 blockade in vivo. In addition, we analyzed bulk CD3+ T cells from TILs in additional 12 patients and identified an SH2D2A mutation in one patient through amplicon sequencing. These findings suggest that somatic mutations in TILs can affect antitumor immunity and suggest unique biomarkers and therapeutic targets. No potential conflict of interest relevant to this article was reported.

Anticancer Research USA Inc. Acta Medica Okayama 0258-851X 39 1 2024 Effect of Oral Nutritional Supplements Composed of High Protein on Body Weight Loss After Gastrectomy 426 432 EN SATORU KIKUCHI Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences NOBUO TAKATA Department of Gastroenterological Surgery, Kochi Health Sciences Center YOSHIHIKO KAKIUCHI 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 HAJIME KASHIMA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SHUNSUKE TANABE Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KAZUHIRO NOMA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences AYAKO TAKAHASHI Department of Clinical Nutrition, Okayama University Hospital SHUNSUKE KAGAWA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOSHIYOSHI FUJIWARA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aim: Body weight loss (BWL) after gastrectomy for gastric cancer (GC) decreases postoperative quality of life and survival in patients with GC. This study aimed to evaluate the effect of oral nutritional supplements composed of high protein on BWL in the early period following gastrectomy. Patients and Methods: Pre- and postoperative body weight and skeletal muscle mass were measured using bioelectrical impedance analysis in patients undergoing radical gastrectomy for GC and analyzed retrospectively. Patients received either a regular diet (control group, n=43) or 250 ml (320 kcal) per day of a high-protein oral nutritional supplement (ONS) (22 g protein) in addition to their regular diet (ONS group, n=40) for four weeks after gastrectomy. The actual daily intake of ONS was recorded by patients themselves. The BWL and skeletal muscle loss (SML) at one month after surgery were compared between the two groups. Results: BWL and SML at one month after surgery were similar between the two groups. In the ONS group, patients were divided into two subgroups (ONS-H and ONS-L) according to whether their ONS intake amount was above or below the average value of 216 kcal. The ONS-H group (ONS intake ≥216 kcal) showed significantly lower BWL compared to the control group (－4.6±2.6% vs. －6.2±2.5%; p=0.03). Moreover, the ONS group showed significantly lower BWL at one month after surgery than the control group in cases of total or proximal gastrectomy (－5.9±3.0% vs. －7.8±1.9%; p=0.04), although no significant difference was observed between the two groups in distal gastrectomy. The hematological nutritional parameters were similar between the two groups. Conclusion: The administration of ONS composed of high protein for four weeks after gastrectomy did not improve BWL at one month after gastrectomy. However, adequate amount of ONS intake and ONS intake after total or proximal gastrectomy might improve BWL. No potential conflict of interest relevant to this article was reported.

American Physiological Society Acta Medica Okayama 1931-857X 326 6 2024 Preventive effects of vasohibin-2-targeting peptide vaccine for diabetic nephropathy F1054 F1065 EN Yuri Nakashima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomoyo Mifune 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 Hiroki Hayashi Department of Health Development and Medicine, Osaka University Graduate School of Medicine Hironori Nakagami Department of Health Development and Medicine, Osaka University Graduate School of Medicine Yasufumi Sato New Industry Creation Hatchery Center, Tohoku University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Diabetic nephropathy remains the leading cause of end-stage kidney disease in many countries, and additional therapeutic targets are needed to prevent its development and progression. Some angiogenic factors are involved in the pathogenesis of diabetic nephropathy. Vasohibin-2 (VASH2) is a novel proangiogenic factor, and our previous study showed that glomerular damage is inhibited in diabetic Vash2 homozygous knockout mice. Therefore, we established a VASH2-targeting peptide vaccine as a tool for anti-VASH2 therapy in diabetic nephropathy. In this study, the preventive effects of the VASH2-targeting peptide vaccine against glomerular injury were examined in a streptozotocin (STZ)-induced diabetic mouse model. The mice were subcutaneously injected with the vaccine at two doses 2 wk apart and then intraperitoneally injected with 50 mg/kg STZ for 5 consecutive days. Glomerular injury was evaluated 20 wk after the first vaccination. Treatment with the VASH2-targeting peptide vaccine successfully induced circulating anti-VASH2 antibody without inflammation in major organs. Although the vaccination did not affect blood glucose levels, it significantly prevented hyperglycemia-induced increases in urinary albumin excretion and glomerular volume. The vaccination did not affect increased VASH2 expression but significantly inhibited renal angiopoietin-2 (Angpt2) expression in the diabetic mice. Furthermore, it significantly prevented glomerular macrophage infiltration. The preventive effects of vaccination on glomerular injury were also confirmed in db/db mice. Taken together, the results of this study suggest that the VASH2-targeting peptide vaccine may prevent diabetic glomerular injury in mice by inhibiting Angpt2-mediated microinflammation. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 17 1 2024 The Three-Class Annotation Method Improves the AI Detection of Early-Stage Osteosarcoma on Plain Radiographs: A Novel Approach for Rare Cancer Diagnosis 29 EN Joe Hasei Department of Medical Information and Assistive Technology Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichi Nakahara Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yujiro Otsuka Department of Radiology, Juntendo University School of Medicine Yusuke Nakamura Plusman LCC Kunihiro Ikuta Department of Orthopedic Surgery, Graduate School of Medicine, Nagoya University Shuhei Osaki Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital Tamiya Hironari Department of Musculoskeletal Oncology Service, Osaka International Cancer Institute Shinji Miwa Department of Orthopedic Surgery, Kanazawa University Graduate School of Medical Sciences Shusa Ohshika Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine Shunji Nishimura Department of Orthopaedic Surgery, Kindai University Hospital Naoaki Kahara Department of Orthopedic Surgery, Mizushima Central Hospital Aki Yoshida Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Fujiwara Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiji Nakata Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Kunisada Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Developing high-performance artificial intelligence (AI) models for rare diseases is challenging owing to limited data availability. This study aimed to evaluate whether a novel three-class annotation method for preparing training data could enhance AI model performance in detecting osteosarcoma on plain radiographs compared to conventional single-class annotation. Methods: We developed two annotation methods for the same dataset of 468 osteosarcoma X-rays and 378 normal radiographs: a conventional single-class annotation (1C model) and a novel three-class annotation method (3C model) that separately labeled intramedullary, cortical, and extramedullary tumor components. Both models used identical U-Net-based architectures, differing only in their annotation approaches. Performance was evaluated using an independent validation dataset. Results: Although both models achieved high diagnostic accuracy (AUC: 0.99 vs. 0.98), the 3C model demonstrated superior operational characteristics. At a standardized cutoff value of 0.2, the 3C model maintained balanced performance (sensitivity: 93.28%, specificity: 92.21%), whereas the 1C model showed compromised specificity (83.58%) despite high sensitivity (98.88%). Notably, at the 25th percentile threshold, both models showed identical false-negative rates despite significantly different cutoff values (3C: 0.661 vs. 1C: 0.985), indicating the ability of the 3C model to maintain diagnostic accuracy at substantially lower thresholds. Conclusions: This study demonstrated that anatomically informed three-class annotation can enhance AI model performance for rare disease detection without requiring additional training data. The improved stability at lower thresholds suggests that thoughtful annotation strategies can optimize the AI model training, particularly in contexts where training data are limited. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2052-8817 11 1 2024 Characteristics and outcomes of subarachnoid hemorrhage from vertebral artery dissection: A comparative study with other non-traumatic etiologies e70031 EN Shu Oshita Okayama University Medical School Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunta Jinno Department of Emergency, Critical Care, and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ippei Matsuo Department of Emergency, Critical Care, and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masafumi Hiramatsu Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Haruma Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenji Sugiu Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shota Tanaka Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aim: Vertebral artery dissection (VAD) is a rare cause of non-traumatic subarachnoid hemorrhage (SAH) with significant clinical implications. This study compared the clinical characteristics and outcomes of SAH from intracranial VAD rupture to those from other etiologies, primarily aneurysmal rupture. Methods: This single-center retrospective cohort study at Okayama University Hospital included patients with non-traumatic SAH diagnosed between 2019 and 2023. Patients were categorized into "VAD rupture" and "other etiologies" groups. The main outcome was clinical presentation and symptoms. Additional outcomes included ICU mortality, in-hospital mortality, and unfavorable outcomes at discharge and 6 months, defined as a modified Rankin Scale score of 3-6. Results: A total of 66 patients were included, with 14 in the VAD rupture group and 52 in the other etiologies group. The VAD rupture group was younger (median age 49 vs. 64 years, p = 0.003) and had a higher incidence of out-of-hospital cardiac arrest (42.9% vs. 9.6%, p = 0.011). Preceding headache was more common in the VAD rupture group (78.6% vs. 11.5%, p < 0.001), with a median duration of 36 h before presentation. ICU and in-hospital mortality was higher in the VAD rupture group (both 50.0% vs. 19.3%, p = 0.019). No significant differences were found in unfavorable neurological outcomes at hospital discharge and 6 months. Conclusions: VAD-related SAH often presents with prodromal headaches, severe symptoms like out-of-hospital cardiac arrest, and higher ICU and in-hospital mortality than other SAH causes, though long-term outcomes are similar. Larger, prospective studies are needed to refine interventions. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0947-6539 31 14 2025 Graphene Oxide as a Self‐Carbocatalyst to Facilitate the Ring‐Opening Polymerization of Glycidol for Efficient Polyglycerol Grafting e202404400 EN Yajuan Zou Research Institute for Interdisciplinary Science, Okayama University Kentaro Ohkura Graduate School of Natural Science and Technology, Okayama University Israel Ortiz‐Anaya Research Institute for Interdisciplinary Science, Okayama University Ryota Kimura Graduate School of Natural Science and Technology, Okayama University Alberto Bianco Research Institute for Interdisciplinary Science, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Grafting carbon-based nanomaterials (CNMs) with polyglycerol (PG) improves their application potentials in biomedicine and electronics. Although “grafting from” method offers advantages over “grafting to” one in terms of operability and versatility, little is known about the reaction process of glycidol with the surface groups onto CNMs. By using graphene oxide (GO) as a multi-functional model material, we examined the reactivity of the surface groups on GO toward glycidol molecules via a set of model reactions. We reveal that carboxyl groups spontaneously react with the epoxide ring with no need of catalyst, while GO catalyzes the reactions of hydroxyl groups with the epoxide of glycidol. In addition, the hydroxyl group of glycidol can open the epoxide in the basal plane of GO. The subsequent polymerization of PG is supposed to propagate at the primary and/or the secondary hydroxyl groups, generating a ramified PG macromolecule with random branch-on-branch topology. In addition, ketones, benzyl esters and aromatic ethers are found not to react with glycidol even in the presence of GO, while the aldehydes are easily oxidized into carboxyl groups under ambient condition, behaving then as the carboxyl groups. Our findings pose the foundation for understanding the polymerization mechanism of PG on CNMs. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0013-9351 222 2023 Environmental water in Kolkata is suitable for the survival of Vibrio cholerae O1 115374 EN Eizo Takahashi Collaborative Research Center of Okayama University for Infectious Diseases in India Kei Kitahara Collaborative Research Center of Okayama University for Infectious Diseases in India Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences of Okayama University Goutam Chowdhury National Institute of Cholera and Enteric Diseases Asish K. Mukhopadhyay National Institute of Cholera and Enteric Diseases Shanta Dutta National Institute of Cholera and Enteric Diseases Sadayuki Ochi Department of Health Pharmacy, Yokohama University of Pharmacy Keinosuke Okamoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences of Okayama University Many patients with cholera emerge in Kolkata, India throughout the year. Such emergency indicates that cholera toxin-producing Vibrio cholerae O1 (toxigenic V. cholerae O1) are widespread in Kolkata. This suggests that the suitable conditions for replication of toxigenic V. cholerae O1 is provided in Kolkata. In previous studies, we found that the replication rate of toxigenic V. cholerae O1 is low in the low ionic aqueous solution. Then we measured the ion concentration in the environmental water of Kolkata. As a control, we measured them in Japanese environmental water. The ion concentration in the environmental water of Kolkata was significantly high. Then, we examined the survival of toxigenic V. cholerae O1 in groundwater from Kolkata and found that V. cholerae O1 survive for long time in the solution but not in the solution diluted with Milli Q water. In addition, we found that V. cholerae O1 proliferated in environmental water of Kolkata to which a small amount of nutrient was added, but did not grow in the environmental water diluted with water to which the same amount of nutrient was added. These results indicate that the environmental water from Kolkata is suitable for survival of V. cholerae O1. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1341-321X 31 2 2024 Clinical and microbiological characteristics of high-level daptomycin-resistant Corynebacterium species: A systematic scoping review 102575 EN Shinnosuke Fukushima Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Hidemasa Akazawa Department of Infectious Diseases, Okayama University Hospital Osamu Matsushita Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of Infectious Diseases, Okayama University Hospital Introduction: Corynebacterium species potentially develop high-level daptomycin resistance (HLDR) shortly after daptomycin (DAP) administration. We aimed to investigate the clinical and microbiological characteristics of HLDR Corynebacterium infections. Methods: We first presented a clinical case accompanied by the results of a comprehensive genetic analysis of the isolate, and then performed a systematic scoping review. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched for articles with related keywords, including “Corynebacterium”, “Daptomycin", and "Resistance”, in the MEDLINE and Web of Science databases from the database inception to October 25, 2024. Clinical case reports and research articles documenting the isolation of HLDR Corynebacterium species, defined by a minimum inhibitory concentration of DAP at ≥256 μg/mL, were deemed eligible for this review. Results: Of 80 articles screened, seven case reports detailing eight cases of HLDR Corynebacterium infections, as well as five research articles, were included. C. striatum was the most common species (7/9 cases, 77.8 %), and prosthetic device-associated infections accounted for 66.7 % of the cases. Duration of DAP administration before the emergence of HLDR isolates ranged from 5 days to 3 months; three-quarters of the cases developed within 17 days. Three HLDR isolates were genetically confirmed to have an alteration in pgsA2. The majority of the patients were treated with either glycopeptides or linezolid, with favorable outcomes. In vitro experiments confirmed that C. striatum strains acquire the HLDR phenotype at higher rates (71 %–100 %) within 24 h of incubation, compared to other Corynebacterium strains. Conclusion: DAP monotherapy, especially for prosthetic device-associated infections, can result in the development of HLDR Corynebacterium. Additional research is warranted to investigate the clinical implications of this potentially proliferating antimicrobial resistant pathogen. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0016-7037 391 2025 Magnesium isotope composition of volcanic rocks from cold and warm subduction zones: Implications for the recycling of subducted serpentinites and carbonates 158 176 EN Wei Zhang The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Hiroshi Kitagawa The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Fang Huang CAS Key Laboratory of Crust-Mantle Materials and Environments, School of Earth and Space Sciences, University of Science and Technology of China Magnesium (Mg) isotopes are regarded as a sensitive tracer to the contribution from subducted serpentinites and carbonates. However, the source, distribution, and controlling factors of the Mg isotope composition of arc magmas remain unclear. In this study, we investigated the intra-arc and inter-arc variations in Mg isotope compositions of volcanic rocks from two typical cold subduction zones [NE Japan (NEJ) and Izu arcs] and a typical hot subduction zone [SW Japan (SWJ) arc] to address the question. The volcanic rocks from the frontal-arc regions of NEJ and Izu have isotopically heavy Mg (δ26Mg = –0.20 to –0.08 ‰) compared to the mantle-like δ26Mg values of most of volcanic rocks from SWJ and the rear regions of NEJ and Izu arcs (–0.28 to –0.17 ‰). It is also worth noting that NEJ arc includes samples with δ26Mg values (–0.61 to –0.39 ‰) significantly lower than the mantle, but similar to the < 110 Ma intra-continental basalts from eastern China, which is the first observation in modern arc rocks. No obvious effects of post-eruptive alteration, fractional crystallization, partial melting, or the addition of silicate-rich sediment and oceanic crust components could be identified in the Mg isotope compositions of these volcanic rocks. By contrast, the correlations between the δ26Mg values and the proxy for serpentinite component (i.e., 11B/10B and Nb/B ratios) indicate that the component exerts a strong control on the Mg-isotopic signature of these arc rocks. Considering metamorphic reactions in subduction lithologies under P-T conditions postulated for these arcs, the variations in δ26Mg values of these arc magmas are unlikely to have been controlled by dehydration of serpentinites in subducted oceanic lithosphere (slab serpentinite). Instead, the high-δ26Mg values of frontal-arc rocks are delivered by the fluids from serpentinite formed in the lowermost part of the sub-arc mantle (mantle wedge serpentinite) in channelized flow. Comparatively, such a high-δ26Mg signature is invisible in volcanic rocks from rear-arc regions of NEJ and Izu, and the entire SWJ, suggesting that the major Mg carriers in subducted serpentinites (e.g., talc, chlorite, and serpentine) were broken down completely before subducted slabs reached the depth beneath these volcanoes. Moreover, the volcanic rocks with low δ26Mg values from the rear arc of NEJ are characterized by high La/Yb and U/Nb ratios as well as low Ti/Eu, Ti/Ti*, and Hf/Hf* ratios, suggesting the involvements of carbonates in their magma sources. The quantitative modeling suggests that < 20 % of sedimentary carbonate (dolomite) was recycled into their mantle source, revealing that Mg-rich carbonate could be incorporated into a deep mantle wedge at rear-arc depths of 150–400 km in subduction zones. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1544-6123 65 2024 Currency portfolios and global foreign exchange ambiguity 105534 EN Takao Asano Faculty of Economics, Okayama University Xiaojing Cai Faculty of Economics, Okayama University Ryuta Sakemoto Faculty of Economics and Business, Hokkaido University This study investigates whether cross-sectional global foreign exchange (FX) ambiguity impacts currency portfolios. We observe that, in contrast to FX volatility, high FX ambiguity leads to high currency carry returns. We also reveal that FX ambiguity is weakly associated with the highest interest rate portfolio, but strongly related to the second highest interest rate portfolio. These results suggest that FX ambiguity captures elements of uncertainty that are not captured by FX volatility. In addition, FX ambiguity is not linked to returns on currency momentum and value portfolios. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1444-1586 25 1 2024 Effectiveness of oral health care intervention for stroke patients following the introduction of Oral Health Assessment Tool 48 53 EN Kazuyuki Matsunaga Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Ayaka Yoshida‐Tsuboi Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Ken Inohara Brain Attack Center, Ota Memorial Hospital Yasuko Yoshida Brain Attack Center, Ota Memorial Hospital Kanako Nakahama Brain Attack Center, Ota Memorial Hospital Kazuki Sasaki Brain Attack Center, Ota Memorial Hospital Fumie Souda Brain Attack Center, Ota Memorial Hospital Yuka Terasawa Brain Attack Center, Ota Memorial Hospital Yutaka Shimoe Brain Attack Center, Ota Memorial Hospital Kazu Takeuchi‐Hatanaka Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Tadashi Yamamoto The Center for Graduate Medical Education (Dental Division), Okayama University Hospital Kazuhiro Omori Department of Pathophysiology – Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuo Kohriyama Brain Attack Center, Ota Memorial Hospital Shogo Takashiba Department of Pathophysiology – Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aim: This study aimed to evaluate the effectiveness of oral health assessment tools in facilitating oral health care interventions by dental care providers for acute stroke patients within 48 h of admission, following a reform of the nursing system. Methods: Data were gathered from a retrospective cohort study conducted at a stroke center, comparing 10 months before and after the implementation of the reformed system, with a 2-month interval. Parameters assessed included stroke type, severity measured using the National Institutes of Health Stroke Scale, stroke history, stroke-related factors, number of teeth, hospitalization cost and duration, occurrence of fever and pneumonia, stroke treatment, days from admission to dental intervention, and intervention frequency. Results: Implementation of the new system significantly reduced the time before dental intervention (P < 0.001), increased the frequency of interventions (P < 0.001), and allowed for the management of more severe cases (P = 0.007). However, there was a slight increase in the occurrence of fevers and the days of fever (P = 0.039 and P = 0.015, respectively). Multiple regression analysis showed that fever days were positively correlated with stroke severity and the number of days from admission to dental intervention (P < 0.001 and P = 0.013, respectively). Even after propensity score matching adjusting for stroke severity, these associations persisted. Additional multiple regression analysis was performed after this, but fever days were positively correlated with stroke severity and sex (P < 0.001 and P = 0.008, respectively), as well as with the presence of other factors affecting the occurrence of fever. Conclusions: Although the frequency and duration of fevers increased slightly, this approach, incorporating oral health assessment tools, made it possible to provide early dental intervention, particularly for patients with severe strokes. Geriatr Gerontol Int 2025; 25: 48–53. No potential conflict of interest relevant to this article was reported.