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.

Wiley Acta Medica Okayama 0309-0167 2026 Clinicopathological and transcriptomic profiles of 101 patients with diffuse large B-cell lymphoma/high-grade B-cell lymphoma with double-hit MYC and BCL2 or BCL6 and triple hit EN Masashi Miyaoka Department of Pathology, School of Medicine, Tokai University Joaquim Carreras Department of Pathology, School of Medicine, Tokai University Yara Yukie Kikuti Department of Pathology, School of Medicine, Tokai University Haruka Ikoma Department of Pathology, School of Medicine, Tokai University Shunsuke Nagase Department of Pathology, School of Medicine, Tokai University Atsushi Ito Department of Pathology, School of Medicine Tokai University Isehara Japan Makoto Orita Department of Pathology, School of Medicine, Tokai University Hiroshi Kawada Department of Hematology, School of Medicine, Tokai University Rika Sakai Department of Medical Oncology, Kanagawa Cancer Center Yasuharu Sato 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 Kunihiro Tsukasaki Department of Hematology, International Medical Center, Saitama Medical University Shuji Momose Department of Pathology, Saitama Medical Center, Saitama Medical University Yoshihiro Kameoka Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine Masahiro Yoshida Department of Hematology, Osaka City General Hospital Akira Satou Department of Surgical Pathology, Aichi Medical University Hospital Seiichi Kato Center for Clinical Pathology, Fujita Health University Hospital Naoki Oishi Department of Pathology, University of Yamanashi Akio Saito Department of Hematology, NHO Shibukawa Medical Center Ken Sadahira Division of Hematology, Kawasaki Municipal Kawasaki Hospital Yohei Masugi Department of Pathology, School of Medicine, Tokai University Naoya Nakamura Department of Pathology, School of Medicine, Tokai University Aims: Diffuse large B-cell lymphoma/high-grade B-cell lymphoma (DLBCL/HGBCL) with MYC and BCL2 rearrangements (double-hit lymphoma with BCL2, DHL-BCL2) is a mature aggressive B-cell lymphoma that also includes concurrent triple hit with BCL6 translocation (TH). DHL with MYC and BCL6 (DH-BCL6) can also occur. The differences among these three DLBCL/HGBCL subtypes have not yet been definitively determined. Methods and Results: This study characterized the clinicopathological features and transcriptomic profiles of a series of 101 cases of DLBCL/HGBCL that were subclassified according to MYC, BCL2 and BCL6 FISH data, including cell-of-origin (COO)-like, molecular high-grade (MHG)-like and double-hit/dark-zone (DHIT/DZsig)-like signatures. DLBCL/HGBCL-DH-BCL2 was characterized by higher HGBCL morphology, CD10 positivity, GCB Hans's, GCB COO and MHG molecular subtype. DLBCL/HGBCL-TH had higher LDH levels and worse overall survival. DLBCL/HGBCL-DH-BCL6 had higher MUM1 expression, non-GCB Hans', ABC/Unclassified COO, non-MHG and low DHIT/DZ signatures. Transcriptomic analysis showed that DLBCL/HGBCL-DH-BCL2 and DLBCL/HGBCL-TH were close but separated from DLBCL/HGBCL-DH-BCL6. Gene set enrichment analysis (GSEA) revealed different levels of enrichment between the subtypes. Conclusions: DLBCL/HGBCL-DH-BCL6 differs from the DLBCL/HGBCL-DH-BCL2, and the DLBCL/HGBCL-TH is associated with the worst survival. Analysis of all three genes of MYC, BCL2 and BCL6 is recommended in the context of DLBCL/HGBCL diagnosis. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1046-1310 45 6 2026 Adolescent screen use in the pre-internet era and subsequent health and well-being: an outcome-wide longitudinal study 657 EN Pedro Antonio de la Rosa Fernández-Pacheco Youth in Transition, Institute for Culture and Society, Universidad de Navarra Renae Wilkinson Human Flourishing Program, Institute for Quantitative Social Science, Harvard University Richard G. Cowden Human Flourishing Program, Institute for Quantitative Social Science, Harvard University Ying Chen Human Flourishing Program, Institute for Quantitative Social Science, Harvard University Brendan Case Human Flourishing Program, Institute for Quantitative Social Science, Harvard University Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tyler J. VanderWeele Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study used data from the National Longitudinal Study of Adolescent to Adult Health (Add Health, N = 11,054) to assess whether increases in screen-based leisure during adolescence (Wave II, from 1996) predicted adult well-being (Wave IV, from 2008-09), adjusting for a wide range of covariates (Wave I, from 1995). Using an outcome-wide analytic approach, we examined associations between screen time and 38 adult outcomes, adjusting for prior screen time, values of most outcomes, and confounders. Most associations were null. Modest evidence was found for links between screen time (continuous) and reduced sense of control, illicit drug use, and allostatic load. High screen time (14 h/week) or more also showed weak associations with lower depression and preventive care use. Because the data predate widespread internet use, the findings help establish a baseline for the long-term effects of non-internet screen activities, which appeared to behave had limited impact on adult health and well-being. No potential conflict of interest relevant to this article was reported.

JMIR Publications Inc. Acta Medica Okayama 2369-3762 12 2026 Prescription Support Practice for Pharmacy Students: Pre-Post Educational Intervention Study e79545 EN Fuka Aizawa Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Kenta Yagi Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Tsukasa Higashionna Department of Pharmacy, Okayama University Hospital Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Shimon Takahashi Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Kazuaki Shinomiya Department of Pharmaceutical Care and Clinical Pharmacy, Tokushima Bunri University Takahiro Niimura Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Mitsuhiro Goda Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Kei Kawada Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Keisuke Ishizawa Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Background: In the field of team-based care, pharmacists are vital for optimizing medication therapy. However, many medical professionals lack the opportunity to learn how to propose prescription changes with precision. Objective: This study aimed to address this knowledge gap by developing and assessing a new educational program for pharmacy students focused on prescription support and interprofessional collaboration. Methods: We recruited 191 fifth-year pharmaceutical students during the 2022‐2024 academic years. The program featured a 7-day intensive curriculum that included learning how to assist with prescriptions, analyzing clinical data, and engaging in role-playing exercises. A web-based questionnaire and a paper test were used to evaluate students’ awareness and knowledge both before and after the program. Statistical analyses were performed to verify the significance of changes; we utilized the Wilcoxon signed-rank test for the ordinal data derived from the specific behavioral objectives and 2-tailed paired t tests for the interval data from the knowledge tests. The magnitude of change was quantified using r for Wilcoxon tests and Cohen dz for 2-tailed t tests, with 95% CI calculated to ensure the stability and reliability of the observed results. Results: Analysis of the primary outcome specific behavioral objectives revealed statistically significant effects across all items (Wilcoxon signed-rank test; P<.001). Effect sizes (r=0.505‐0.835) ranged from moderate to large, with particularly large effects observed in identifying contents issue (r=0.835, 95% CI 0.126-0.330; P<.001). Knowledge test scores showed significant improvement in the following 3 subjects: pharmacology (r=－0.504, 95% CI –0.215 to 0.127; P<.001), organic chemistry (r=0.254, 95% CI –0.148 to –0.193; P=.004), and communication (r=0.221, 95% CI –0.151 to –0.190; P=.01). No significant changes were observed in pathology or pharmacokinetics. Conclusions: This program provides strong evidence that practical, hands-on learning with hospital pharmacists helps improve pharmacy students’ professional skills and optimize pharmaceutical therapies in interprofessional care. By teaching pharmacists to effectively propose prescription changes, the program equips them to become integral members of interprofessional care, ultimately leading to optimized pharmaceutical care for patients. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1435-2451 411 1 2025 The impact of liver transection depth on surgical difficulty in robotic versus laparoscopic limited liver resection (TAKUMI-5) 22 EN Tomokazu Fuji Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kosei Takagi Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuya Yasui Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Atene Ito Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takeyoshi Nishiyama Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuo Nagai Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shohei Yokoyama Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Purpose Although robotic liver resection (RLR) has gained popularity worldwide, limited liver resection remains the mainstay of RLR. This study aimed to investigate the effect of parameters, including liver transection depth (LTD), on surgical difficulty in limited RLR compared with limited laparoscopic liver resection (LLR). Methods This retrospective study included 105 patients who underwent limited RLR (n = 56) or LLR (n = 49) at our institution between January 2018 and December 2024. After comparing outcomes of RLR and LLR, multivariate analyses were performed to examine effect of LTD on surgical difficulty (defined as prolonged operative time). Moreover, outcomes stratified by LTD cut-off values were compared between the groups. Results Median LTD was similar between groups (RLR vs. LLR: 2.6 vs. 2.6 cm, P = 0.77). LTD was significantly correlated with operative time for both procedures (RLR, R² = 0.07, P = 0.042; LLR, R² = 0.08, P = 0.046). Multivariate analyses demonstrated that LLR (odds ratio, 6.9; P < 0.001) and LTD (odds ratio, 2.0; P = 0.004) were significant risk factors of surgical difficulty. Among patients with deeper LTD (> 2.5 cm), the RLR group had significantly shorter operative time (145 vs. 231 min, P < 0.001), less blood loss (nil vs. 100 mL, P = 0.006), and a higher rate of textbook outcomes (76.7% vs. 42.3%, P = 0.01). Conclusion This study investigated impact of LTD on surgical outcomes in patients who underwent limited RLR compared to those who underwent limited LLR. LTD may be a useful parameter for estimating surgical difficulty in limited RLR. Moreover, robotic surgery may be favorable for deeper and limited liver resections. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1462-8910 27 10 2025 D3 lymph node dissection in colon cancer patients aged 90 years and over: Is it justified? A multi‐institutional retrospective study e70269 EN Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Hospital Satoe Takanaga Department of Gastroenterological Surgery, Okayama University Hospital Ryo Inada Department of Surgery, Kochi Health Sciences Center Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Toshiaki Toshima Department of Surgery, Kagawa Rosai Hospital Tsuyoshi Ohtani Department of Surgery, Saiseikai Okayama Hospital Ryosuke Yoshida Department of Surgery, Okayama Rosai Hospital Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Hospital Setouchi Colorectal Neoplasm Registration study group collaborators Aim: The oncological benefit of D3 lymph node dissection (D3 LND) for colon cancer in patients aged ≥90 years remains unclear. This study aimed to evaluate the impact of D3 LND on outcomes in this specific, vulnerable population. Method: This retrospective cohort study evaluated 166 patients aged ≥90 years with pathological Stages II–III colon cancer undergoing non-D3 or D3 LND from a multicentre database (2011–2022). Postoperative complications, overall survival and cancer-specific survival were compared between LND groups using propensity score-weighted analyses. Results: D3 LND group had significantly more females and laparoscopic procedures. Operation time was longer, and blood loss was lower in the D3 LND group. Postoperative complications and severe complications were significantly fewer, and postoperative hospital stay was shorter in the D3 LND group. The number of harvested lymph nodes and distal margin was significantly higher in the D3 group. While unadjusted analysis showed better overall survival with D3 LND (p < 0.001), adjusted cancer-specific survival showed no significant difference (p = 0.10). Adjusted mortality risk was significantly higher in the non-D3 group (p = 0.001). Conclusion: In nonagenarian colon cancer patients, D3 LND is safe and feasible without increasing complications, but lacks survival benefit. Careful consideration is warranted, and high-quality D2 LND must be consistently ensured when limited surgery is chosen. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 6 2025 Severe Anemia Caused by a Colorectal Lipoma With Central Erosions: A Case Report e85768 EN Yusuke Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Hospital Ko Watanabe Department of Pathology, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Colorectal lipomas are benign tumors that are often asymptomatic and discovered incidentally. In most cases, they can be managed conservatively with observation. We report the case of a man in his 70s with a colorectal lipoma located in the cecum. An investigation into his severe anemia led to the suspicion that the cecal lipoma was the underlying cause. An ileocecal resection was performed. Erosions were observed at the center of the lipoma. Although small colorectal lipomas are generally asymptomatic and rarely cause anemia, periodic endoscopic examinations are recommended. These lesions should be considered in the differential diagnosis of lower gastrointestinal bleeding. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1435-2451 411 1 2025 Surgical outcomes and patient selection in nonagenarians with colon cancer: a comparative multi-institutional study of laparoscopic and open approaches 21 EN Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoe Takanaga Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Ryo Inada Department of Surgery, Kochi Health Sciences Center Toshiaki Toshima Department of Surgery, Kagawa Rosai Hospital Tsuyoshi Ohtani Department of Surgery, Saiseikai Okayama Hospital Ryosuke Yoshida Department of Surgery, Okayama Rosai Hospital Naoto Hori Department of Surgery, Tottori Municipal Hospital Kaoru Shigemitsu Department of Surgery, Tsuyama Chuo Hospital Sumiharu Yamamoto Department of Surgery, Okayama City Hospital Tetsushi Kubota Department of Surgery, Kobe Red Cross Hospital Yuka Okano Department of Surgery, Onomichi City Hospital Tetsuji Nobuhisa Department of Surgery, Himeji Red Cross Hospital Fumitaka Taniguchi Department of Surgery, National Hospital Organization Iwakuni Clinical Center Wataru Ishikawa Department of Surgery, Fukuyama City Hospital Tatsuo Matsuda Department of Surgery, Matsuda Hospital Tatsuo Umeoka Department of Surgery, Matsuyama City Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Setouchi Colorectal Neoplasm Registration study group collaborators Purpose The appropriate surgical approach for colon cancer (CC) in nonagenarian patients remains a subject of clinical debate. This study aimed to compare the short-term outcomes of laparoscopic (Lap) versus open (Open) surgery in patients aged ≥ 90 years with resectable colon cancer. Methods This multi-institutional retrospective cohort study included oldest-old patientswith pathological Stage II/III CC who underwent elective surgery at 15 hospitals between 2011 and 2022. Patients with rectal cancer, Stage 0/I/IV disease, or emergency surgery were excluded. To address selection bias, inverse-probability-weighted regression adjustment and stabilized inverse probability of treatment weighting (sIPTW) were applied. The primary outcome was postoperative complications; secondary outcomes included overall survival (OS). Results Median age was 92 years in both groups. Before adjustment, the Lap group had a higher proportion of female patients (p = 0.038) and lower ASA scores (p = 0.01). Laparoscopic surgery was associated with a significantly longer operative time (220 vs. 171 min, p = 0.046) but less intraoperative blood loss (10 vs. 78 mL, p < 0.01). Postoperative complication rates were comparable (Lap: 31.8%, Open: 33.8%), while the Lap group had a significantly shorter hospital stay (13 vs. 17 days, p < 0.01). D3 lymph node dissection was more frequently performed in the Lap group (p < 0.01). After sIPTW, overall survival did not differ significantly between groups (p = 0.61). Conclusion Both laparoscopic and open surgery are feasible options for selected nonagenarians with colon cancer. Laparoscopic surgery may offer benefits in terms of reduced blood loss and shorter hospitalization, despite longer operative times. Careful patient selection considering frailty and comorbidities is essential in determining the most appropriate surgical approach. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2038-131X 2025 Early C-reactive protein as a predictive biomarker for postoperative complications following robot-assisted surgery for rectal cancer EN Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryusei Takahashi Department of Surgery, NHO Fukuyama Medical Center Hiroki Okabayashi Department of Surgery, NHO Fukuyama Medical Center Masashi Utsumi Department of Surgery, NHO Fukuyama Medical Center Hideaki Miyaso Department of Surgery, NHO Fukuyama Medical Center Ryohei Shoji 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 Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Masaru Inagaki Department of Surgery, NHO Fukuyama Medical Center This retrospective cohort study aimed to assess the predictive value of early postoperative C-reactive protein (CRP) levels for complications following robot-assisted rectal surgery (RARS) for rectal cancer. We analyzed data from 117 consecutive patients who underwent elective RARS at Okayama University Hospital between September 2020 and January 2025. Serum CRP levels were routinely measured preoperatively and on postoperative days (POD) 1 and 4. The primary outcome was the occurrence of any postoperative complication within 30 days, classified according to the Clavien–Dindo grading system. Postoperative complications were observed in 26 patients, representing 22.2% of the cohort. Univariate analysis revealed that several factors were significantly associated with complications, including older age, higher ASA score, neoadjuvant therapy, stoma creation, prolonged operative time, and elevated CRP levels on POD1 and POD4. Notably, multivariate logistic regression analysis identified POD1 CRP as a robust independent predictor of overall postoperative complications (adjusted odds ratio 0.77, 95% confidence interval (CI) [0.63–0.93], p < 0.01). In the ROC analysis, the AUC was 0.735 (bootstrap bias-corrected 95% CI 0.544–0.848). The optimal cutoff value of POD1 CRP was 5.63 mg/dl, at which Youden’s index, yielding a sensitivity of 0.615 and specificity of 0.868. In conclusion, early postoperative measurement of CRP on POD1 serves as a valuable and independent biomarker for predicting complications following RARS for rectal cancer. Incorporating POD1 CRP into postoperative surveillance may facilitate the early identification of high-risk patients, thereby facilitating timely interventions and ultimately improving surgical outcomes in this patient population. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0964-2633 70 3 2025 Prevalence and Modifiable Risk Factors of Dementia in People With Down Syndrome: Cross‐Sectional Study of Japan in Collaboration With the Intellectual Diversity for Goodness Research Consortium (INDIGO‐2019) 329 336 EN Shintaro Takenoshita Department of Neuropsychiatry, Okayama University Hospital Seishi Terada Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomokazu Inoue Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Taku Kurozumi Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Manabu Takaki Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryozo Kuwano Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Shigeru Suemitsu Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Background: People with Down syndrome (DS) have a strong genetic predisposition to Alzheimer's disease (AD). However, the clinical burden and associated risk factors in diverse, non-Western populations remain less understood. This study aimed to investigate the prevalence of dementia in Japanese adults with DS and to identify modifiable clinical factors associated with dementia. Methods: This cross-sectional multicentre study surveyed 133 adults with DS (mean age 50.1 years) residing in 45 welfare facilities across Japan in 2019. Dementia was diagnosed by a consensus panel of physicians using established criteria (DSM-5, ICD-10, DC-LD) after comprehensive assessments, including the Japanese version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID-J). Logistic regression analysis was performed to identify factors independently associated with dementia. Results: Forty-six participants (34.6%) were diagnosed with dementia. The prevalence rose sharply with age: 0% in their 30s, 30.8% in their 40s, 31.6% in their 50s and 65.5% in their 60s. After adjusting for covariates, older age, female sex, dyslipidaemia and visual impairment were independently associated with dementia. Conclusions: This study, the largest of its kind in Asia, confirms a high prevalence of dementia in institutionalized Japanese adults with DS. Crucially, this study is the first to identify dyslipidaemia and visual impairment as independent and potentially modifiable risk factors in this population. These findings highlight tangible targets for clinical interventions aimed at mitigating dementia risk in people with DS. 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.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 0969-0239 32 16 2025 Development of sulfation for cellulose pulp to change its fiber morphology and appearance to transparent in water 9663 9677 EN Ayato Nishimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tetsuya Uchida Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Cellulose pulp (CP) is composed mainly of cellulose which is one of the most useful and sustainable natural polymers. Cellulose-based materials, such as completely dispersed nanofibers and water-soluble cellulose, are transparent in water. Additionally, chemical modification of CP has been employed as a pretreatment for the preparation of nanofibers and to impart absorption properties derived from anionic functional groups. However, little is known about chemically modified CPs comprising micron-scale fibers that are transparent in water.In this study, we synthesized transparent sulfated cellulose pulp (TSCP) that exhibits good dispersion stability, high transparency in water, and highly swollen fiber structures. The sulfation method involved heating sulfamic acid and urea supported on CP. TSCP synthesized using a sulfamic acid amount relative to CP (Q) of 18.5, a molar ratio of urea to sulfamic acid (R) of 0.80, and a reaction temperature of 140 °C exhibited the highest total light transmittance (94.7%) in water, a degree of polymerization (535), and amount of sulfate groups (1.73 mmol/g). Polarization microscopy confirmed that most TSCP fibers swelled in water along the fiber width direction. The structure of hydrous-state TSCP was further confirmed using low-vacuum scanning electron microscopy. The maximum fiber width of the swollen TSCP reached 122 μm, which was approximately six times than that of CP. The crystallinity was equivalent to that of the original CP with a Cellulose I-type crystalline structure. This transparent, hydrous-state TSCP, comprising predominantly swollen CP fibers, demonstrates potential for applications as a transparent material. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1123-6337 29 1 2025 Safety and feasibility of D3 lymph node dissection in oldest-old patients undergoing colorectal cancer surgery: a multi-institutional, retrospective analysis 146 EN R. Inada Department of Surgery, Kochi Health Sciences Center F. Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences T. Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital S. Takanaga Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences T. Toshima Department of Surgery, Kagawa Rosai Hospital T. Ohtani Department of Surgery, Saiseikai Okayama Hospital R. Yoshida Department of Surgery, Okayama Rosai Hospital N. Hori Department of Surgery, Tottori Municipal Hospital K. Shigemitsu Department of Surgery, Tsuyama Chuo Hospital S. Yamamoto Department of Surgery, Okayama City Hospital T. Kubota Department of Surgery, Kobe Red Cross Hospital Y. Okano Department of Surgery, Onomichi City Hospital T. Nobuhisa Department of Surgery, Himeji Red Cross Hospital F. Taniguchi Department of Surgery, National Hospital Organization Iwakuni Clinical Center W. Ishikawa Department of Surgery, Fukuyama City Hospital R. Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences T. Matsuda Department of Surgery, Matsuda Hospital T. Umeoka Department of Surgery, Matsuyama City Hospital T. Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Setouchi Colorectal Neoplasm Registration Study Group Collaborators Background Colorectal cancer (CRC) is a significant health burden, with lymph node dissection (LND) playing a critical role in staging and guiding treatment. However, the optimal extent of LND for the oldest-old population (aged ≥ 90 years) remains undefined because of insufficient targeted clinical data. This study aimed to compare the short-term outcomes of D3 versus non-D3 LND in Stage II–III CRC in oldest-old patients. Methods This retrospective cohort study utilized data from the Setouchi Colorectal Neoplasm Registration database, including 282 oldest-old patients with CRC treated between 2011 and 2022. Patients were stratified into D3 and non-D3 LND groups, with inverse-probability-weighted regression adjustment implemented to address potential confounding factors. Postoperative complications and hospital stays were analyzed using regression models and descriptive statistics. Results D3 LND resulted in significantly higher lymph node harvests in both Stage II and Stage III patients (p < 0.01). There were no significant differences in overall or major postoperative complications between D3 and non-D3 groups. Hospital stays were comparable for Stage II patients but shorter for Stage III patients in the D3 group (p < 0.01). Complication rates ranged from 28% to 47.7%, with surgical site infections and pneumonia being the most common. Conclusions D3 LND can be safely performed in oldest-old patients with CRC without increasing postoperative complications or extending hospital stays. These findings support the feasibility of extensive LND in this age gr 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.

Elsevier BV Acta Medica Okayama 2212-4292 71 2025 A cross-sectional study of the gut microbiota associated with urinary and serum equol production status in a general population of Japanese men 107048 EN Yukiko Okami NCD Epidemiology Research Center, Shiga University of Medical Science Hisatomi Arima Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University Shigeki Bamba Department of Fundamental Nursing, Shiga University of Medical Science Fu Namai Graduate School of Agricultural Science, Tohoku University Keiko Kondo NCD Epidemiology Research Center, Shiga University of Medical Science Yuki Ideno Gunma University Center for Food Science and Wellness Ayumi Soejima Nutraceuticals Research Institute, R&D Headquarters, Nutraceuticals Division, Otsuka Pharmaceutical Co., Ltd. Haruna Miyakawa Nutraceuticals Research Institute, R&D Headquarters, Nutraceuticals Division, Otsuka Pharmaceutical Co., Ltd. Sayuki Torii NCD Epidemiology Research Center, Shiga University of Medical Science Hiroyoshi Segawa NCD Epidemiology Research Center, Shiga University of Medical Science Mizuki Ohashi NCD Epidemiology Research Center, Shiga University of Medical Science Megumi Kawashima NCD Epidemiology Research Center, Shiga University of Medical Science Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aya Kadota NCD Epidemiology Research Center, Shiga University of Medical Science Akira Sekikawa Department of Epidemiology, School of Public Health, University of Pittsburgh Akira Fujiyoshi Department of Hygiene, Wakayama Medical University Katsuyuki Miura NCD Epidemiology Research Center, Shiga University of Medical Science SESSA Research Group Equol is a metabolite produced by the gut microbiota from the soy isoflavone daidzein. Previous studies identified bacteria capable of converting daidzein to equol. We investigated whether equol producers among Japanese with a high soy intake contained these bacteria. We also examined differences in equol production status between urine and serum and how the gut microbiota differs between these statuses. To minimize the potential confounding effects of hormonal variability in women, this cross-sectional study analyzed 853 Japanese men. Urinary and serum isoflavones were collected in the morning after fasting and were analyzed using LC-MS/MS. By applying a finite mixture model for each log10 equol/daidzein ratio, we defined equol producers and non-producers from urine and serum. Among 669 participants with fecal microbial measurements, the 16S rRNA gene was sequenced on a MiSeq System. The cut-off values for the log10 equol/daidzein ratio were －0.94 for urine and －0.95 for serum. Equol production status in urine and serum matched in 97 %, and equol producers from urine or serum were 42 %. The microbiota was more diverse in producers than in non-producers; the genus Senegalimassilia included strains with high sequence identity (>98 %) to daidzein reductase. The family Oscillospiraceae and class Clostridia also had approximately 46 %–48 % sequence identity. The equol production status of fasting urine and serum almost matched among a general population of Japanese men. Although we did not detect a microbiota with known daidzein reductase in equol producers, several shared similar sequences; these may include equol-producing bacteria that have not yet been identified. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 15 5 2026 Effect of Surgical Procedures for Rheumatoid Forefoot Deformities on Radiographic Foot Length and Width Variations 1877 EN Masahiro Horita Department of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama University Yohei Kiso Department of Orthopaedic Surgery, Kurashiki Sweet Hospital Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama City Hospital Ryuichi Nakahara Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenta Saiga Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Nishida Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Background: The number of patients with rheumatoid arthritis (RA) undergoing forefoot arthroplasty has increased to better control the disease. Despite patients frequently expressing concerns regarding postoperative foot appearance and footwear-related expectations, no study has investigated postoperative changes in foot length and width in patients with RA. The aim of this study was to evaluate the effect of surgical procedures for rheumatoid forefoot deformities on variations in radiologically determined foot length and width. Methods: In total, 72 feet of 50 women and 3 men (average age: 66.7 years) underwent joint-preserving arthroplasty (n = 33) and arthrodesis of the first metatarsophalangeal joint with shortening osteotomy of the lesser metatarsals or resection arthroplasty of the lesser metatarsal heads (n = 39); procedures were carried out in our institute from August 2013 to February 2020. The mean disease duration was 23.5 years, and the average follow-up period was 17.5 months. Pre- and postoperative hallux valgus angle (HVA), intermetatarsal angle (IMA) of the first and second metatarsals (M1M2A), and IMA of the first and fifth metatarsals (M1M5A) were measured on weightbearing radiographs as well as foot length and width. We also evaluated the correlation between changes in radiographic parameters and variations in radiologically determined foot length and width. Results: Radiologically determined foot width changed significantly from 10.1 cm to 9.7 cm (p < 0.01), while no significant difference was found between pre- and postoperative radiologically determined foot length. HVA, M1M2A, and M1M5A were significantly improved after the surgery (p < 0.01, p < 0.01, and p < 0.01, respectively). A significant negative correlation was found between the variation in radiologically determined foot length and changes in HVA (r = －0.29, p = 0.02) and M1M5A (r = －0.23, p < 0.05), while a significant positive correlation was found between the variation in the foot width and changes in HVA (r = 0.34, p < 0.01), M1M2A (r = 0.55, p < 0.01), and M1M5A (r = 0.45, p < 0.01). There were no significant differences between operative procedures regarding variation in radiologically determined foot length and width. Conclusions: Surgical procedure for rheumatoid forefoot deformity improved radiographic parameters and reduced radiographic foot width while maintaining foot length. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2079-7737 15 5 2026 Alpha-Ketoglutarate Drives an Osteogenic and Extracellular Matrix Gene Program in Periodontal Ligament Fibroblasts via Selective Reduction of H3K27me3 372 EN Ryu Hasegawa Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Shigeki Suzuki Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences Rahmad Rifqi Fahreza Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Shin-Ho Tsai Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences Yoshino Daidouji Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Masato Omori Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Tetsuhiro Kajikawa Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Satoru Yamada Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Periodontal disease damages the tissues that support teeth and can ultimately lead to tooth loss, yet effective treatments to regenerate these tissues are still limited. Recent studies have shown that substances produced during normal cellular metabolism can influence how genes are regulated, but their role in periodontal regeneration has not been fully clarified. In this study, we investigated whether alpha-ketoglutarate, a naturally occurring metabolite involved in energy production, could promote periodontal tissue regeneration. We found that alpha-ketoglutarate enhanced bone-related and extracellular matrix-related gene expression in human periodontal ligament cells by reducing a repressive gene-regulatory signal that normally suppresses these genes. Importantly, alpha-ketoglutarate did not broadly alter chromatin accessibility, indicating that its effects were mediated through selective gene regulation. Furthermore, oral administration of alpha-ketoglutarate promoted alveolar bone regeneration and collagen-rich tissue formation in a mouse model of periodontal disease. Because alpha-ketoglutarate is a naturally occurring molecule in the body, these findings suggest that metabolite-based regulation of gene activity may represent a promising and safe approach for periodontal tissue regeneration. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2073-445X 15 2 2026 A Study on the Development of an Image Classification System for Urban Sprawl Areas in Japan 275 EN Ryota Hemmi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takehito Ujihara Faculty of Environmental, Life, Natural Science and Technology, Okayama University Ryosuke Ando National Institute for Land and Infrastructure Management, Ministry of Land, Infrastructure Transport and Tourism Seiji Hashimoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University In Japan, unlike in many other countries, urbanization has progressed while original rural road structures have been retained, leading to distinctive urban sprawl areas with intermingling residential lots and farmland. Currently, much of Japan’s urban areas consist of urban sprawl areas, posing considerable challenges for infrastructure development. However, for such urban sprawl areas in Japan, it is difficult to say that methods have been established to identify their spatial distribution based on quantitative evaluation. Therefore, for this study, we used machine learning to investigate a system that extracts sprawling urban areas from aerial photographs divided into meshes. In the system’s design, we prioritized precision to ensure the reliable detection of urban sprawl areas. Consequently, the accuracy of identifying sprawl areas achieved precision of 0.81, recall of 0.63, and an F-score of 0.71. Examination of the classification results of sprawl areas revealed that most misclassifications occurred near class boundaries. By contrast, areas with particularly high levels of urban sprawl showed few misclassifications. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1341-321X 32 3 2026 Tick-borne pathogens in ticks collected from Humans: A prospective clinical pilot study 102931 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaomi Sumida Numakuma Hospital Osamu Kawamata Numakuma Hospital Yoshimi Hidani Numakuma Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Tick-borne diseases (TBDs), particularly Japanese spotted fever, are an increasing public health concern in Japan. Data on pathogens carried by ticks removed directly from patients and their associated clinical outcomes remain limited. This prospective study investigated pathogen carriage in patient-derived ticks and evaluated the clinical risk of TBDs. Between April and October 2025, ticks were collected from patients presenting with tick bites at two medical institutions in Western Japan. Ticks were morphologically identified and spotted fever group rickettsiae (SFGR) was detected by nested PCR targeting the 17-kDa antigen gene, followed by sequence analysis. Clinical data, including patient background, antibiotic prescriptions, and outcomes, were reviewed. Clinical information was available for 70 patients (median age; 75 years), of whom 88.6% were prescribed prophylactic antibiotics. Ticks were collected from 60 patients (85.7%), and seven adults without antibiotic prophylaxis were followed for disease onset. Sixty-two ticks, predominantly Amblyomma testudinarium (88.7%), were analyzed. SFGR was detected in eight ticks (12.9%), including seven A. testudinarium and one Ixodes nipponensis, collected from seven patients. Two patients bitten by Rickettsia tamurae–carrying ticks were observed for one month without antibiotics and remained asymptomatic. In this prospective analysis, no clinically apparent rickettsiosis was observed following bites from R. tamurae–positive ticks without antibiotic prophylaxis; however, subclinical infection could not be excluded. Despite the small sample size, our findings suggest that the clinical risk associated with R. tamurae infection may be low. Direct analysis of removed ticks from patients may help characterize pathogen reservoirs and inform targeted approaches to TBDs. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 1743-9159 112 2 2025 Total thymectomy is oncologically superior to partial thymectomy in patients with thymic carcinoma: insights from a multicenter real-world data analysis 2301 2310 EN Tatsuya Hayashi 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 of Innovative Clinical Medicine, Okayama University Hospital Hidetaka Yamamoto Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Habu Okayama University Thoracic Surgery Study Group (OUTSSG) Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Okayama University Thoracic Surgery Study Group (OUTSSG) Tomoaki Otsuka Okayama University Thoracic Surgery Study Group (OUTSSG) Mototsugu Watanabe Okayama University Thoracic Surgery Study Group (OUTSSG) Takeshi Kurosaki Okayama University Thoracic Surgery Study Group (OUTSSG) Eiji Yamada Okayama University Thoracic Surgery Study Group (OUTSSG) Eisuke Matsuda Okayama University Thoracic Surgery Study Group (OUTSSG) Tatsurou Hayashi Okayama University Thoracic Surgery Study Group (OUTSSG) Toshiya Fujiwara Okayama University Thoracic Surgery Study Group (OUTSSG) Makio Hayama Okayama University Thoracic Surgery Study Group (OUTSSG) Hiroyuki Tao Okayama University Thoracic Surgery Study Group (OUTSSG) Masaomi Yamane Okayama University Thoracic Surgery Study Group (OUTSSG) Hidetoshi Inokawa Okayama University Thoracic Surgery Study Group (OUTSSG) Yuji Hirami Okayama University Thoracic Surgery Study Group (OUTSSG) Kazuhiro Washio Okayama University Thoracic Surgery Study Group (OUTSSG) Takahiko Misao Okayama University Thoracic Surgery Study Group (OUTSSG) Motohiro Yamashita Okayama University Thoracic Surgery Study Group (OUTSSG) Yoshifumi Sano Okayama University Thoracic Surgery Study Group (OUTSSG) Masao Nakata Okayama University Thoracic Surgery Study Group (OUTSSG) Osamu Kawamata Okayama University Thoracic Surgery Study Group (OUTSSG) Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Although total thymectomy has been the standard surgical approach for thymic epithelial tumors, an increasing number of recent reports suggest that partial thymectomy for early-stage thymomas may yield outcomes comparable to those of total thymectomy. However, whether partial thymectomy is a viable alternative for thymic carcinoma remains unclear. Materials and methods: A total of 106 patients with thymic carcinoma underwent curative intended resection at 19 institutions between January 2010 and December 2021. Excluding 14 patients with incomplete resection, 92 patients with thymic carcinoma who underwent total (n = 73) or partial thymectomy (n = 19) were compared. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier curves and Cox proportional hazard models. Overlap weighting was applied to adjust for potential confounding factors. Results: Among patients with clinical stage I disease, 79.3% were upstaged to stage II or higher postoperatively. Unadjusted analyses revealed no statistically significant differences in OS and RFS between the total and partial thymectomy groups, although a trend toward poorer outcomes in the partial thymectomy group was observed. After overlap weighting, partial thymectomy was associated with significantly poorer OS (P = 0.0027) and higher recurrence risk (P < 0.0001). Early postoperative recurrence occurred more frequently in the partial thymectomy group. Conclusion: Partial thymectomy was associated with significantly worse survival and recurrence outcomes in thymic carcinoma. Given the limitations of preoperative diagnosis, total thymectomy should remain the preferred surgical approach for undiagnosed thymic epithelial tumors to achieve optimal oncologic control and minimize the risk of recurrence. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 2235-2988 15 2026 Binding of IgA1 and surface-expressed collagen-binding protein of Streptococcus mutans contributes to IgA nephropathy pathogenesis 1673581 EN Daiki Matsuoka Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kana Suehara Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Naka Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taro Misaki Division of Nephrology, Seirei Hamamatsu General Hospital Yasuyuki Nagasawa Department of General Internal Medicine, Hyogo Medical University Seigo Ito Department of Internal Medicine, Japan Self-Defense Force Iruma Hospital Yuto Suehiro Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Ryota Nomura Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University Kazuhiko Nakano Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Michiyo Matsumoto-Nakano Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: The present study was conducted to examine the interaction between collagen-binding protein (Cnm) of Streptococcus mutans and immunoglobulin (IgA) to clarify the possible involvement in IgA nephropathy (IgAN) development. Methods: The binding of Cnm to human immunoglobulins was examined using an enzyme-linked immunosorbent assay. A nephritis-induced rat model was employed to confirm the localization of Cnm. Results: IgA1 showed significantly greater binding ability to Cnm than to other bacterial surface proteins, and Cnm showed significantly greater binding ability to IgA1 than to other immunoglobulins. In rats administered Cnm, IgA deposition was observed in the glomerular mesangial region. Furthermore, biotin-labeled Cnm was observed in the same region as IgA deposition in the Cnm group. Conclusions: Taken together, it is considered that following invasion into the bloodstream, Cnm binds to and forms a complex with IgA1, leading to deposition of IgA1 in renal glomeruli. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Effective Treatment of Advanced Hepatocellular Carcinoma with Extensive Peritoneal Dissemination Using Lenvatinib 69 74 EN Shinya Wakatsuki Department of Obstetrics and Gynecology, Kochi Health Sciences Center Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Akiko Ueno Department of Obstetrics and Gynecology, Kochi Health Sciences Center Takaomi Namba Department of Obstetrics and Gynecology, Kochi Health Sciences Center Yorito Yamamoto Department of Obstetrics and Gynecology, Kochi Health Sciences Center Manabu Matsumoto Department of Diagnostic Pathology, Kochi Health Sciences Center Jun Iwata Department of Diagnostic Pathology, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Case Report 10.18926/AMO/70075 Patients with hepatocellular carcinoma (HCC) and extensive peritoneal dissemination generally have a poor prognosis and are often resistant to systemic therapy. We report the case of a 47-year-old woman with HCC and massive peritoneal dissemination who presented with malignant ascites requiring repeated cell-free and concentrated ascites reinfusion therapy and peritoneovenous shunt placement, as well as malignant pleural effusion requiring pleurodesis. Combined immunotherapy with durvalumab/tremelimumab was initiated;however, disease progression was observed after three treatment courses, prompting a switch to lenvatinib therapy. Two months after initiation of lenvatinib, CT imaging demonstrated complete disappearance of arterial enhancement in the primary hepatic lesion, along with reduction in the size of peritoneal dissemination nodules. Thirteen months after switching to lenvatinib (16 months after the initial diagnosis), the alpha-fetoprotein level continued to decrease, and the disease remained stable under treatment. Despite the extremely high tumor burden, lenvatinib achieved disease stabilization and symptomatic improvement. No potential conflict of interest relevant to this article was reported.

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

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

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

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

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Development of a Stroke Discharge Support Evaluation Scale for Ward Nurses in Acute Care Hospitals 17 30 EN Hideki Yano Department of Nursing, Faculty of Human Health Sciences, Niimi University Yoko Takahata Graduate School of Health Sciences, Okayama University Takeshi Yamaguchi Faculty of Nursing, Shikoku University Shinya Saito Graduate School of Health Sciences, Okayama University Original Article 10.18926/AMO/70069 This study aimed to develop a scale enabling nurses to objectively evaluate their own stroke discharge support, as a basis for enhancing its overall effectiveness. A draft scale was created based on a literature review, and consisted of a 51-item, 5-point Likert-type questionnaire administered to ward nurses engaged in stroke discharge support at acute care hospitals. Factor analysis was performed to refine the scale. Construct validity was assessed using the known-groups method, and reliability was evaluated through internal consistency analysis. The resulting Stroke Discharge Support Evaluation Scale comprises 29 items across 5 factors, each rated on a 5-point Likert scale. Analysis of the data collected from 237 valid responses demonstrated good internal consistency and supported the scale’s construct validity. The Stroke Discharge Support Evaluation Scale is a reliable and valid tool enabling ward nurses in acute care hospitals to evaluate their own stroke discharge support. No potential conflict of interest relevant to this article was reported.

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

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.

MDPI AG Acta Medica Okayama 2077-0383 15 4 2026 Perioperative Ozoralizumab Management for Patients with Rheumatoid Arthritis Who Underwent Orthopaedic Surgery: A Retrospective Case Series 1422 EN Keiichiro Nishida Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama City Hospital Ryozo Harada Department of Orthopaedic Surgery, Kurashiki Sweet Hospital Ryuichi Nakahara Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Masahiro Horita Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Masamitsu Natsumeda Rheumatic Disease Center, Mabi Memorial Hospital Shuichi Naniwa Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Launched in Japan in 2022, ozoralizumab (OZR) is a novel, anti-tumour necrosis factor (TNF)-α inhibitor for treating rheumatoid arthritis (RA) that is refractory to conventional therapies. However, there is a lack of evidence regarding its perioperative management. Methods: This retrospective case series included nine patients with RA who underwent a total of 12 either RA-related (n = 9) or unrelated (n = 3) orthopaedic procedures. We reviewed patient demographics, surgical procedures, perioperative OZR discontinuation periods, and postoperative complications. Results: The mean preoperative OZR discontinuation period was 15.8 days (range, 2–25 days). Sutures were removed at a mean of 12.8 days postoperatively (range, 11–14 days) after adequate wound healing had been confirmed. The mean total discontinuation period was 34.9 days (range, 27–43 days). No cases of surgical site infection (SSI) or delayed wound healing (DWH) were observed during a minimum follow-up period of three months. One patient experienced a disease flare before OZR was restarted. Conclusions: Preoperative OZR discontinuation for up to four weeks appeared to be safe in this cohort. These findings may assist orthopaedic surgeons in determining an appropriate perioperative discontinuation strategy for OZR that minimises SSI and DWH risk while reducing the likelihood of RA flare. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0028-646X 2026 Starch Synthase 3 isoforms are essential for normal starch granule initiation in wheat endosperm EN Jinjin Ding John Innes Centre, Norwich Research Park Brendan Fahy John Innes Centre, Norwich Research Park Ryo Matsushima Institute of Plant Science and Resources, Okayama University Qiantao Jiang State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Triticeae Research Institute, Sichuan Agricultural University David Seung John Innes Centre, Norwich Research Park No potential conflict of interest relevant to this article was reported.

Proceedings of the National Academy of Sciences Acta Medica Okayama 0027-8424 123 6 2026 A nuclear CobW/WW-domain factor represses the CO2-concentrating mechanism in the green alga Chlamydomonas reinhardtii e2518136123 EN Daisuke Shimamura Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Junko Yasuda Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Yosuke Yamahara Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Hirobumi Nakano Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Shin-Ichiro Ozawa Institute of Plant Science and Resources, Okayama University Ryutaro Tokutsu Graduate School of Science, Division of Biological Sciences, Kyoto University Ayumi Yamagami Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Tomonao Matsushita Graduate School of Science, Division of Biological Sciences, Kyoto University Yuichiro Takahashi Research Institute for Interdisciplinary Science, Okayama University Takeshi Nakano Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Hideya Fukuzawa Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Takashi Yamano Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Microalgae induce a CO2-concentrating mechanism (CCM) to maintain photosynthesis when CO2 is limited. Because this system consumes a substantial portion of photosynthetically generated ATP, its suppression when CO2 levels rise is critical for energy balance, yet the underlying mechanism remains unclear. Here, we identify a nuclear repressor of the CCM in the green alga Chlamydomonas reinhardtii. A pull-down screen for interacting partners of the master activator CCM1/CIA5 revealed an uncharacterized protein that tightly associates with CCM1. This protein, CCM1-binding protein 1 (CBP1), combines a CobW/CobW_C GTP-binding metallochaperone module with a WW-domain characteristic of protein–protein interactions. CBP1 colocalizes and interacts with CCM1 in the nucleus regardless of CO2 conditions. Disruption of CBP1 does not affect growth or CCM induction under CO2 limitation but derepresses 27 of 41 CCM1-dependent low-CO2 inducible genes under high-CO2 conditions. These include the periplasmic and intracellular carbonic anhydrases (CAH1 and LCIB) and inorganic carbon transporters/channels (LCIA, LCI1, BST1, and BST3). Consistently, cbp1 mutants accumulate CAH1 and LCIB proteins and exhibit 40% higher inorganic carbon affinity under high-CO2 conditions; this phenotype is rescued by CBP1 complementation or by acetazolamide treatment. Crucially, cbp1 mutants exhibit significant growth delays under high-CO2 conditions, especially when light is limiting, providing direct evidence that CBP1-mediated repression is essential for energy conservation. Thus, CBP1 prevents unnecessary CCM activity when CO2 is abundant, acting upstream of both transporter/channel and carbonic anhydrase modules. Our findings suggest a regulatory mechanism potentially linking zinc-dependent protein chemistry to CCM gene repression, providing insights into energy-efficient CO2 sensing in aquatic photosynthetic organisms. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0041-1132 2026 Pediatric autologous peripheral blood stem cell collection without heparin using a highly concentrated sodium citrate anticoagulant: A retrospective comparison with standard ACD-A EN Keiko Fujii Department of Hematology, Okayama University Hospital Wataru Kitamura Department of Hematology, Okayama University Hospital Kana Washio Department of Pediatrics, Okayama University Hospital Kazuhiro Ikeuchi Department of Hematology, Okayama University Hospital Joji Shimono Department of Hematology, Okayama University Hospital Hiroyuki Murakami Department of Hematology, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Okayama University Hospital Nobuharu Fujii Department of Hematology, Okayama University Hospital Background: Heparin combined with sodium citrate has been used in leukocytapheresis for pediatric patients. Since 2022, we have performed leukocytapheresis using a highly concentrated sodium citrate solution (HSC, 5.32%) instead of acid citrate dextrose solution A (ACD-A). We conducted this study to determine whether HSC use reduces run time and the total amount of anticoagulant solution in children. Study Design and Methods: We retrospectively analyzed data from consecutive autologous peripheral blood stem cell harvests (auto-PBSCHs) between June 2012 and May 2025, including patient characteristics, mobilization methods, protocol used, anticoagulant type, run time, total anticoagulant solution volume, and collection efficiency. Results: Auto-PBSCH was performed using the mononuclear cell collection (MNC) protocol in 28 procedures and the continuous MNC protocol in 20 procedures. ACD-A was used in 35 procedures and HSC in 13. The run time was significantly shorter (204 [range, 117–302] vs. 157 min [range, 103–227], p = .02) in the HSC group and also confirmed in multivariable regression analysis (coefficient, －55.6; 95% confidence interval, －106.2 to －5.04; p = .03). In a subgroup analysis of cMNC procedures, CD34+ collection efficiency showed a strong negative correlation with the proportion of run time devoted to establishing the initial interface (r = －.73, p = .0003). Conclusion: Delays in establishing the initial interface can reduce the duration of the effective MNC collection phase and may negatively affect collection efficiency. Careful attention to the initial interface phase is therefore warranted when using HSC. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2059-3635 11 1 2026 Osimertinib inhibits the MYLK4-mediated phosphorylation of CDKAL1 to suppress stemness and chemoresistance in rhabdomyosarcoma 26 EN Takuto Itano Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rongsheng Huang Department of Cellular Physiology, 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 Eiji Nakata Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Fujimura Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-2615 16 3 2026 Impact of the July 2018 Heavy Rain Disaster on the Endangered Nagoya Daruma Pond Frog (Pelophylax porosus brevipodus) in Rice Fields of Mabi Town, Kurashiki City, Western Japan: Changes in Population Structure over Five Years 369 EN Ryo Nakajima Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Daisuke Azumi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Masakazu Tada Okayama Prefectural Public Interest Incorporated Foundation for Environmental Conservation Junya Nakaichi 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 Kazuyoshi Nakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Rice paddy fields (referred to below as rice fields) are important not only for food production, but also as habitats for various species. The Nagoya Daruma Pond Frog (Pelophylax porosus brevipodus) is an endangered frog species endemic to Japan, mainly living in and around rice field areas. In July 2018, heavy rainfall caused severe flooding in Mabi Town of Okayama Prefecture, western Japan, submerging numerous rice fields and affecting local frog populations, including P. porosus brevipodus. To clarify whether the population structure of P. porosus brevipodus changed following the flood disaster in the rice fields of Mabi Town, we conducted quantitative field surveys in a rice fallow field in mid-October before (2017) and after (2018, 2020–2022, excluding 2019) the flood. The number of frogs declined sharply after the 2018 flood, reaching only a few individuals by 2020, but showed a substantial recovery in 2021 following the resumption of rice cultivation, although numbers decreased again in 2022. This recovery, despite fluctuations, indicates that habitat restoration through rice farming played a key role in enabling the population to rebound. Our findings underscore the importance of maintaining and restoring rice field environments after natural disasters for the survival and long-term recovery of P. porosus brevipodus. No potential conflict of interest relevant to this article was reported.

Open Library of the Humanities Acta Medica Okayama 2056-6700 12 1 2026 Racialized Contagion and Defensive Biopolitics in The Last of Us EN Robert Yeates Faculty of Humanities and Social Sciences, Okayama University In the opening moments of the video game The Last of Us Part I, players are introduced to an emerging pandemic via Austin’s Texas Herald newspaper. Below a headline warning of mass hospitalizations from a 'mysterious infection', players read of a recall of imported crops 'potentially tainted with mold': 'Initial lists distributed to vendors nationwide warned against crops imported from South America. However now the scope has extended to include Central America and Mexico'. This scene immediately suggests the racialization of the franchise’s Cordyceps brain infection (CBI), with the contagion germinating in the global South, invading the US via its southern border, and spreading fastest in the nation’s diverse urban centres. By highlighting tainted crops as the vector of dispersal in the US, however, rather than infected humans, the franchise resists making this a simple invasion-scare narrative and instead suggests that the spread of the infection is in part a result of the capitalist exploitation of cheap land and labour in the global South. Despite its inconsistent record on racial representation and the near-absence of discussion of race across the franchise, the structures reflecting the racialization of contagion and the perpetuation of racialized hierarchies through defensive biopolitics remain present. Drawing connections with the discourse around immigration and the southern border and contemporary pandemics and epidemics, this article makes the case for reading the franchise in terms of racialized contagion and defensive biopolitics, a reading that highlights how the games and their television adaptation reflect urgent contemporary issues around race in America. 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.

American Society for Microbiology Acta Medica Okayama 0099-2240 2025 Efficient resuscitation of early-stage viable but non-culturable cells of Vibrio cholerae using treatment with proteolytic enzymes EN Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mona Ogasawara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shiho Niwaki Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rena Sugihara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Basilua Andre Muzembo Research Institute of Nursing Care for People and Community, University of Hyogo Daisuke Imamura Research Center for Intestinal Health Science, Okayama University Vibrio cholerae, the etiological agent of cholera, is ubiquitous in environmental brackish waters. Exposure to low water temperatures induces the bacterium to enter a viable but non-culturable (VBNC) state. In this study, a stepwise decrease in water temperature to 4°C was found to delay the transition to the non-culturable state compared to an abrupt temperature drop, suggesting that V. cholerae cells partially adapt to low temperatures. V. cholerae VBNC cells maintained at 4°C gradually lost their ability to revert to a culturable state. However, VBNC cells in the early stage of dormancy were efficiently resuscitated following treatment with proteolytic enzymes, including proteinase K. The abundance of culturable V. cholerae cells in brackish estuarine waters was quantified using the most probable number (MPN)–quantitative polymerase chain reaction (qPCR) method. Although culturable cells were undetectable in samples treated with bovine serum albumin, they were estimated at 93 and 1,500 MPN/mL in two water samples collected on different days and pre-incubated with proteinase K. Similarly, the abundance of Vibrio species increased markedly following treatment with this enzyme. Additionally, cells of Vibrio species were enumerated by the plating method using CHROMagar Vibrio plates. Consistent with the results of the MPN–qPCR method, treatment with proteinase K resulted in over a 100-fold increase in colony formation. Collectively, these findings suggest that treatment with proteinase K is effective for resuscitating and quantifying V. cholerae VBNC cells in environmental water samples. No potential conflict of interest relevant to this article was reported.

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

MDPI AG Acta Medica Okayama 2313-433X 12 1 2025 FluoNeRF: Fluorescent Novel-View Synthesis Under Novel Light Source Colors and Spectra 16 EN Lin Shi Department of Artificial Intelligence, Kyushu Institute of Technology Kengo Matsufuji Department of Artificial Intelligence, Kyushu Institute of Technology Michitaka Yoshida Department of Computer Science, Okayama University Ryo Kawahara Graduate School of Informatics, Kyoto University Takahiro Okabe Department of Computer Science, Okayama University Synthesizing photo-realistic images of a scene from arbitrary viewpoints and under arbitrary lighting environments is one of the important research topics in computer vision and graphics. In this paper, we propose a method for synthesizing photo-realistic images of a scene with fluorescent objects from novel viewpoints and under novel lighting colors and spectra. In general, fluorescent materials absorb light with certain wavelengths and then emit light with longer wavelengths than the absorbed ones, in contrast to reflective materials, which preserve wavelengths of light. Therefore, we cannot reproduce the colors of fluorescent objects under arbitrary lighting colors by combining conventional view synthesis techniques with the white balance adjustment of the RGB channels. Accordingly, we extend the novel-view synthesis based on the neural radiance fields by incorporating the superposition principle of light; our proposed method captures a sparse set of images of a scene from varying viewpoints and under varying lighting colors or spectra with active lighting systems such as a color display or a multi-spectral light stage and then synthesizes photo-realistic images of the scene without explicitly modeling its geometric and photometric models. We conducted a number of experiments using real images captured with an LCD and confirmed that our method works better than the existing methods. Moreover, we showed that the extension of our method using more than three primary colors with a light stage enables us to reproduce the colors of fluorescent objects under common light sources. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1465-3249 27 8 2025 Clinical outcomes of Japanese patients treated with out-of-specification tisagenlecleucel in a phase 3b trial 938 943 EN Koji Kato Department of Hematology, Oncology, and Cardiovascular Medicine, Kyushu University Hospital Jun Kato Division of Hematology, Department of Medicine, Keio University School of Medicine Hideki Goto Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital Takeshi Kobayashi Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Yoshiyuki Takahashi Department of Pediatrics, Nagoya University Graduate School of Medicine Emiko Sakaida Department of Hematology, Chiba University Hospital Hidefumi Hiramatsu Department of Pediatrics, Graduate School of Medicine, Kyoto University Masahide Yamamoto Department of Hematology, Institute of Science Tokyo Hospital Satoshi Yoshihara Department of Hematology, Hyogo Medical University Hospital Jun Ando Department of Cell Therapy and Transfusion Medicine, Juntendo University Graduate School of Medicine Katsuyoshi Koh Department of Hematology/Oncology, Saitama Children’s Medical Center Kentaro Fukushima Department of Hematology and Oncology, Osaka University Graduate School of Medicine Fumiko Iwamoto Medical Affairs, Novartis Pharma K.K. Ranjan Tiwari Development Advance Quantitative Sciences, Novartis Healthcare Private Limited Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Background: The final manufactured tisagenlecleucel product should meet the commercial product release specifications to ensure the quality in terms of safety, purity, identity, and potency. However, it may occasionally fail to meet these specifications due to the nature of patient-derived cells with variable properties as starting material and the complex manufacturing process. The final product that does not meet at least one of the commercial release specifications is referred to as “out-of-specification” (OOS). However, the benefit-risk profile of OOS tisagenlecleucel has not yet been fully elucidated. Aims: To evaluate the safety and efficacy of OOS tisagenlecleucel in Japanese patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) and B-cell acute lymphoblastic leukemia (B-ALL). Methods: This is a single-arm, open-label, multicenter phase 3b study (NCT04094311). Patients consistent with label indication were enrolled and followed-up for 3 months. Results: Of the 29 patients enrolled between December 2019 and May 2022 across 13 qualified sites in Japan, 28 received tisagenlecleucel, and of these, 23 had r/r DLBCL and 5 had r/r B-ALL. The primary reasons for OOS were low cell viability (15 of 24 batches) and low dose (8 of 23 batches) tisagenlecleucel in the r/r DLBCL group, and high dose (4 of 5 batches) in the r/r B-ALL group. In patients with r/r DLBCL, the grade 3 or 4 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 3 and 1 patients, respectively. Response assessments were performed for 15 of 23 patients with r/r DLBCL: 6 achieved a complete response, and 1 achieved a partial response as the best response within 3 months. Conclusions: Despite the limited patient sample size, our findings affirm that the infusion of OOS tisagenlecleucel is a viable option, with no observed increase in toxicity and outcomes comparable to those of in-specification products in clinical and real-world studies. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0007-8506 74 1 2025 Improvement of anodic oxide film characteristics of Al-Cu alloy by refinement of IMCs with large-area electron beam irradiation 263 267 EN T. Shinonaga Faculty of Environmental, Life, Natural Science & Technology, Okayama University A. Sebe Graduate School of Environmental, Life, Natural Science & Technology, Okayama University M. Taniguchi Shimano Research Laboratories, R&D Strategy Dept., SHIMANO INC. T. Fujii Shimano Research Laboratories, R&D Strategy Dept., SHIMANO INC. A. Okada Faculty of Environmental, Life, Natural Science & Technology, Okayama University Al-Cu alloy has been widely applied to automobile products due to its light weight and high strength, but pitting corrosion easily occurs due to intermetallic compounds (IMCs) in Al-Cu alloy. Anodizing process has been conventionally performed to improve the corrosion resistance of Al-Cu alloy surface. However, IMCs in Al-Cu alloy lead to defects in anodic oxide film. In this study, refinement of IMCs in Al-Cu alloy surface by large-area EB irradiation was proposed. Experimental results show that reflectance and corrosion resistance of anodic oxide film formed on Al-Cu alloy surface are improved by refinement of IMCs with the EB irradiation. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2059-7029 10 11 2025 Association between adjuvant chemotherapy and outcomes in resected locoregional recurrence of hormone receptor-positive HER2-negative breast cancer: a multi-institutional retrospective study 105889 EN Y. Ozaki Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research E. Tokuda Department of Medical Oncology, Fukushima Medical University Y. Sagara Department of Breast Surgery, Social Medical Corporation Hakuaikai Sagara Hospital F. Hara Department of Breast Oncology, Aichi Cancer Center Hospital S. Sasada Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University M. Sawaki Department of Breast Oncology, Aichi Cancer Center Hospital C. Kanbayashi Department of Breast Oncology, Niigata Cancer Center Hospital T. Yamanaka Department of Breast Surgery and Oncology, Kanagawa Cancer Center T. Onishi Department of Breast Oncology, National Cancer Center Hospital East Y. Fujiki Department of Breast Surgery, Social Medical Corporation Hakuaikai Sagara Hospital A. Suto Department of Breast Oncology, National Cancer Center Hospital Y. Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital E. Tokunaga Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center T. Aruga Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital R. Nakamura Division of Breast Surgery, Chiba Cancer Center T. Fujisawa Department of Breast Oncology, Gunma Prefectural Cancer Center S. Saji Department of Medical Oncology, Fukushima Medical University H. Iwata Department of Advanced Clinical Research and Development, Nagoya City University T. Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Background: To evaluate the association of adjuvant chemotherapy and prognosis for locoregional recurrence (LRR) in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative subtype breast cancer. Patients and methods: We carried out a multi-institutional retrospective cohort study in patients with breast cancer who developed HR-positive HER2-negative LRR. Patients who underwent curative surgery for LRR between 2014 and 2018 were categorized based on whether they received adjuvant chemotherapy for LRR (CTx versus no-CTx). Invasive disease-free survival (iDFS) was evaluated between the groups by Cox proportional hazards analysis. The primary analysis used a double-robust Cox model incorporating inverse probability of treatment weighting, and a sensitivity analysis using propensity score matching was also carried out. Results: A total of 958 patients were included. The median time from the primary surgery to LRR diagnosis was 9.5 years (interquartile range 3.1-10.1 years). There were 235 patients (25%) in the CTx group and 722 (75%) in the no-CTx group. Among all patients, the 5-year iDFS rate was 75.4% [95% confidence interval (CI) 72.4% to 78.2%]. Multivariate analysis showed better iDFS in the CTx group (hazard ratio 0.70, 95% CI 0.49-0.99, P = 0.045). Sensitivity analysis supported these findings. Subgroup analyses showed that the CTx group had better iDFS in cases with non-ipsilateral breast tumor recurrence (IBTR), recurrences during adjuvant endocrine therapy for primary breast cancer, and without perioperative chemotherapy for primary breast cancer. Secondary analysis showed no significant difference with a worse trend toward overall survival in the CTx group with multivariate Cox proportional hazards analysis. Conclusion: Adjuvant chemotherapy for HR-positive HER2-negative LRR was associated with better iDFS, particularly in cases of non-IBTR, recurrences during adjuvant endocrine therapy, and no prior perioperative chemotherapy for their primary tumor. However, the retrospective design and inability to distinguish true recurrences from new primary tumors in IBTR warrant cautious interpretation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0312-5963 64 12 2025 Evaluation of Fentanyl-Emerged Adverse Events and Pharmacokinetics in Neonates: A Physiologically Based Pharmacokinetic Modeling Approach 1811 1825 EN Walaa Yousef Bassyouni Mahdy 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 Risa Joji Department of Pharmacy, Kobe University Hospital Mari Hashimoto Department of Pharmacy, Kobe University Hospital Ruka Nakasone Department of Pediatrics, Graduate School of Medicine, Kobe University Kazumichi Fujioka Department of Pediatrics, Graduate School of Medicine, Kobe University Kotaro Itohara Department of Pharmacy, Kobe University Hospital Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Tomohiro Omura Department of Pharmacy, Kobe University Hospital Ikuko Yano Department of Pharmacy, Kobe University Hospital Background Despite its common use for analgesia in neonatal intensive care units, the optimal dosing and safety profile of fentanyl, particularly regarding suspected fentanyl-emerged adverse events (FEAEs), such as hypotension, desaturation, and oliguria, are not well-defined. Objective This study aimed to develop an optimal therapeutic monitoring and dosing strategy for fentanyl for neonates. A physiologically based pharmacokinetic (PBPK) model for predicting fentanyl pharmacokinetics across various populations, including preterm and term neonates, was developed, and the relationship between predicted fentanyl exposure and FEAE incidence in neonates was assessed. Methods A PBPK model was developed and validated against the observed values in the literature. The model’s predictive accuracy for fentanyl pharmacokinetics and association with FEAE incidence in an external retrospective cohort of Japanese neonates was evaluated using the predicted concentrations and pharmacokinetic parameters estimated by PBPK simulation. Results The PBPK model exhibited reasonable predictive performance for serum fentanyl concentrations in actual neonatal patients (mean error: 9.27% [standard error: 5.06%], root mean squared error: 54.7%). The incidence of any FEAE, particularly oxygen desaturation, was associated with the fentanyl concentration-to-dose ratio, but not with some exposure parameters, such as the area under the curve and maximum concentration. The recommended reduced infusion rate allowed serum fentanyl concentrations to fall within the ranges established by the reported values and our data. Conclusions Our PBPK model and proposed dosing strategy may contribute to safer and more effective fentanyl use in neonates. 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 2399-3642 8 1 2025 A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS 1720 EN Ryoichi Nakamura Department of Neurology, Aichi Medical University School of Medicine Genki Tohnai Division of ALS Research, Aichi Medical University School of Medicine Naoki Atsuta Department of Neurology, Aichi Medical University School of Medicine Yumi Matsuda Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine Satoru Morimoto Keio University Regenerative Medicine Research Center, Kawasaki Daisuke Ito Department of Neurology, Nagoya University Graduate School of Medicine Masahisa Katsuno Department of Neurology, Nagoya University Graduate School of Medicine Yuishin Izumi Department of Neurology, Tokushima University Graduate School of Biomedical Sciences Mitsuya Morita Division of Neurology, Department of Internal Medicine, Jichi Medical University Ikuko Iwata Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Ichiro Yabe Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Tomoko Nakazato Department of Neurology, Juntendo University School of Medicine Nobutaka Hattori Department of Neurology, Juntendo University School of Medicine Takehisa Hirayama Department of Neurology, Toho University Faculty of Medicine Osamu Kano Department of Neurology, Toho University Faculty of Medicine Asako Tamura Department of Neurology, Mie University Graduate School of Medicine Naoki Suzuki Department of Neurology, Tohoku University Graduate School of Medicine Masashi Aoki Department of Neurology, Tohoku University Graduate School of Medicine Kazumoto Shibuya Department of Neurology, Graduate School of Medicine, Chiba University Satoshi Kuwabara Department of Neurology, Graduate School of Medicine, Chiba University Masaya Oda Department of Neurology, Vihara Hananosato Hospital Rina Hashimoto Department of Neurology, NHO Higashinagoya National Hospital Ikuko Aiba Department of Neurology, NHO Higashinagoya National Hospital Tomohiko Ishihara Department of Neurology, Brain Research Institute, Niigata University Osamu Onodera Department of Neurology, Brain Research Institute, Niigata University Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Bokuda Department of Neurology, Tokyo Metropolitan Neurological Hospital Toshio Shimizu Department of Neurology, Tokyo Metropolitan Neurological Hospital Yoshio Ikeda Department of Neurology, Gunma University Graduate School of Medicine Kazuko Hasegawa Division of Neurology, NHO Sagamihara National Hospital Fumiaki Tanaka Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine Takanori Yokota Department of Neurology and Neurological Science, NucleoTIDE and PepTIDE Drug Discovery Center (TIDE), Institute of Science Tokyo Kazuaki Kanai Department of Neurology, Fukushima Medical University School of Medicine Yu-ichi Noto Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Ryuji Kaji Department of Neurology, Tokushima University Graduate School of Biomedical Sciences Hirohisa Watanabe Department of Neurology, Fujita Health University Tomoko Konishi Division of ALS Research, Aichi Medical University School of Medicine Mikiko Hasegawa Division of ALS Research, Aichi Medical University School of Medicine Hozuki Fukaya Division of ALS Research, Aichi Medical University School of Medicine Jun-ichi Niwa Department of Neurology, Aichi Medical University School of Medicine Manabu Doyu Department of Neurology, Aichi Medical University School of Medicine Yohei Okada Department of Neurology, Aichi Medical University School of Medicine Shiho Nakamura Keio University Regenerative Medicine Research Center, Kawasaki Fumiko Ozawa Keio University Regenerative Medicine Research Center, Kawasaki Hideyuki Okano Keio University Regenerative Medicine Research Center, Kawasaki Masahiro Nakatochi Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine Gen Sobue Division of ALS Research, Aichi Medical University School of Medicine Amyotrophic lateral sclerosis (ALS) exhibits considerable clinical variability, such as differences in age at onset (AAO). Multiple factors, including genetic factors, may underlie this variability; however, the specific determinants remain unclear. To identify genes affecting AAO, we have conducted a genome-wide association study in Japanese patients with ALS (discovery cohort: n = 1808; replication cohort: n = 207). Here, we show that the minor A allele of rs113161727 at the ADAM29-GPM6A locus is associated with a younger AAO in the discovery cohort (effect, -4.27 years; p = 4.60 × 10-8); this finding has been confirmed in the replication cohort (p = 0.0068) and meta-analysis (p = 1.08 × 10－9). Among 65 ALS patients with a SOD1 mutation, the AAO has been found to be 10.2 years younger in those with the A allele than in those without it (p = 0.002). This variant correlates with GPM6A upregulation in iPSC-derived motor neurons, suggesting GPM6A as a candidate AAO modifier. Overall, our study highlights the impact of genetic modifiers on ALS heterogeneity and provides a potential target for delaying disease onset. 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.

SAGE Publications Acta Medica Okayama 1468-0874 2025 Effects of size factors and velocity of impinging diesel spray flames on wall heat transfer EN Yoshimitsu Kobashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ryoga Hirai Graduate School of Engineering, Hokkaido University Gen Shibata Graduate School of Engineering, Hokkaido University Hideyuki Ogawa Graduate School of Engineering, Hokkaido University To examine the effects of size and velocity of impinging diesel spray flames on wall heat transfer, this study conducted visualization of the spray flame and measurements of wall heat flux in a constant volume vessel. The impinging flame velocity was varied by adjusting the injection velocity. To vary the flame size independently of the flame velocity, the nozzle orifice diameter and the nozzle-to-wall distance were varied under similarity conditions, while maintaining a constant ratio of nozzle-to-wall distance to orifice diameter. Care was taken to minimize wall interference from the liquid phase and unburned regions of the spray flame by employing a high cetane number fuel and increasing the nozzle-to-wall distance. The experimental results showed that the wall heat flux increased as the impinging velocity increased, and the flame width decreased. The power-law correlations between the Nusselt and Reynolds numbers were determined based on the experimental results, revealing that the exponent of the Reynolds number reaches a local minimum at the impingement point. As the radial displacement from the impingement point increases, the exponent of the Reynolds number approaches approximately 0.8, which is a typical value for turbulent wall flow. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Ileus Tube-Related Intussusception: A Case Report and Review of 80 Previously Reported Cases 469 474 EN Teruyuki Tsujii Department of Surgery, Matsuda Hospital Tatsuo Matsuda Department of Surgery, Matsuda Hospital Yuji Kimura Department of Surgery, Matsuda Hospital Ryoichi Katsube Department of Surgery, Matsuda Hospital Hironori Iwadou Department of Surgery, Matsuda Hospital Sadami Funabiki Department of Surgery, Matsuda Hospital Yasuaki Kamikawa Department of Surgery, Matsuda Hospital Tadakazu Matsuda Department of Surgery, Matsuda Hospital Case Report 10.18926/AMO/69851 We report a rare case of ileus tube-related intussusception in an adult. A 56-year-old man with adhesive bowel obstruction was treated with a nasointestinal ileus tube. Although his condition initially improved, persistent abdominal pain led to the diagnosis of intussusception via CT imaging. Manual repositioning of the tube resolved the intussusception without the need for bowel resection. A review of 80 previously reported cases of ileus tube-associated intussusception (total 81 cases, 95 lesions) highlighted the timing of onset, treatment strategies, and precautions. Early detection and diagnosis are crucial to prevent severe complications and preserve bowel function. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 MRI Images of a Case of Adenocarcinoma, Human Papillomavirus-Independent, Mesonephric Type, of the Uterine Cervix 463 468 EN Yudai Asano Department of Radiology, Okayama University Hospital Chika Nishihara Department of Radiology, Okayama University Hospital Takahiro Kitayama Department of Radiology, Okayama University Hospital Nanako Okawa Department of Radiology, Okayama University Hospital Satoko Makimoto Department of Radiology, Okayama University Hospital Fumiyo Higaki Department of Radiology, Okayama University Hospital Katsuhide Kojima Department of Radiology, Okayama University Hospital Hanako Sugihara Department of Obstetrics and Gynecology, Okayama University Hospital Naoyuki Ida Department of Obstetrics and Gynecology, Okayama University Hospital Hiroyuki Yanai Department of Pathology, Okayama University Hospital Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Case Report 10.18926/AMO/69850 We present a case of a woman in her 70s who was diagnosed with mesonephric adenocarcinoma of the uterine cervix, following biopsy and surgery. Preoperative MRI revealed a 7-cm, well-defined circumferential cervical mass with left lateral wall predominance, bulging into the uterine cavity and vagina. The lesion showed intermediate signal intensity on T2-weighted images, diffusion restriction, and early contrast enhancement weaker than that of the myometrium, followed by washout on contrast-enhanced imaging. The circumferential growth pattern with the lateral wall predominance and its imaging characteristics may suggest this rare entity be routinely included in the differential diagnosis of cervical cancers. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Exacerbation of Proteinuria in a Patient with Behçet’s Disease and IgA Nephropathy Following Colchicine Discontinuation 457 461 EN Tomohiko Asakawa 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 Yu Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yoshimasa Sakurabu Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Katsuyoshi Katayama 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 Natsumi Matsuoka-Uchiyama 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 Keiko Tanaka 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 Ryoko Umebayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Rika Takemoto 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 Case Report 10.18926/AMO/69849 This case involves a 23-year-old male who was diagnosed with Behçet’s disease 5 years ago and managed with colchicine. Two months ago, he underwent renal biopsy due to abnormal urinalysis and kidney dysfunction, leading to a diagnosis of IgA nephropathy. He subsequently underwent tonsillectomy followed by glucocorticoid pulse therapy. However, after the tonsillectomy, discontinuing colchicine led to increased proteinuria, despite the glucocorticoid pulse therapy. Upon reintroducing colchicine, urinary protein excretion decreased, achieving incomplete remission. These findings suggest that colchicine may be effective in decreasing proteinuria in patients with Behçet’s disease complicated by IgA nephropathy. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Perioperative Team Management Was Beneficially Associated with Prolonged Postoperative Hospital Stays after Long Lower-Abdominal Surgeries 445 449 EN Junya Matsumi Department of Anesthesiology and Intensive Care Medicine, National Cancer Center Hospital Original Article 10.18926/AMO/69847 Our hospital began a PERIO program (perioperative patient management by a multi-disciplinary team from multiple departments) in 2016 to improve patient outcomes. We retrospectively analyzed the clinical effects of the PERIO program regarding the postoperative hospital stay (PHS) in the patients aged ≥ 18 years who underwent long lower-abdominal surgery at our hospital during the period April 2019 to March 2023. We excluded the cases of patients whose general anesthesia use was < 8 h, those for whom another surgery was performed simultaneously at another site, and emergency surgeries. The outcome was prolonged PHS, defined as exceeding the scheduled number of days specified in the patient’s clinical pathway. Among the 480 patients, prolonged PHS was observed for 270 patients (56.3%). In a multivariate logistic regression using advanced age, sex, high-risk general state, surgery requiring colon resection, serious adverse events (SAEs), and PERIO use, the following were associated with prolonged PHS: advance age (odds ratio [OR] 4.91, 95% confidence interval [CI]: 2.68-8.99, p=0.01), surgery requiring colon resection (OR 4.91, 95%CI: 2.68-8.99, p<0.001), SAE (OR 18.7, 95%CI: 7.22-48.2, p<0.001), and PERIO (OR 0.25, 95%CI: 0.13-0.47, p<0.001). The use of the PERIO program was thus beneficially associated with PHS after long lower-abdominal surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Frailty at 1 Month before ICU Admission Poses a Hospital Mortality Risk in Cancer Survivors whose Condition Has Deteriorated due to Medical Factors 437 444 EN Junya Matsumi Department of Anesthesiology and Intensive Care Medicine, National Cancer Center Hospital Tetsufumi Sato Department of Anesthesiology and Intensive Care Medicine, National Cancer Center Hospital Original Article 10.18926/AMO/69846 The optimal indications for intensive care unit (ICU) treatment for critically ill cancer survivors whose condition has deteriorated due to medical factors are unclear. To test our hypothesis that frailty before deterioration was associated with hospital mortality in this patient population, we retrospective analyzed the cases of the patients admitted to the ICU at the National Cancer Center Hospital, Japan (April 2014-March 2022). We excluded patients who underwent surgery within 28 days or were denied critical care within 24 h or admitted after cardiopulmonary arrest. Their Clinical Frailty Scale (CFS) scores at 1 month before ICU admission (Pre-ICU) were obtained. Frailty was defined as CFS scores ≥4 points. We analyzed 298 admissions and observed that the mortality rate at hospital discharge was significantly higher in the frailty group (n=119). A multivariate analysis demonstrated that the following factors were significantly associated with hospital mortality: Pre-ICU frailty (OR 2.00, 95%CI: 1.19-3.36, p=0.009), cancer type (hematological: OR 2.93, 95%CI: 1.42-6.05, p=0.004), and Sequential Organ Failure Assessment score at ICU admission (OR 0.88, 95%CI: 0.82-0.95, p=0.0008). Frailty retrospectively assessed using the CFS at 1 month pre-ICU admission is a risk factor for hospital mortality in these cancer survivors. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Association of Weekend Admission and In-Hospital Mortality in Adult Patients with Acute Myeloid Leukemia in Japan 431 436 EN Takahiro Inoue Healthcare Management Research Center, Chiba University Hospital Hiroyo Kuwabara Healthcare Management Research Center, Chiba University Hospital Koh Yamamoto Department of Hematology, Yokohama City Minato Red Cross Hospital Original Article 10.18926/AMO/69845 The effect of weekend admission on patient mortality has been investigated in several therapeutic areas, including acute myeloid leukemia (AML), but the investigations’ results are controversial. We evaluated the relationship between in-hospital mortality and weekend admission in adult patients with AML in Japan by conducting a retrospective observational study using administrative data from 144 acute care hospitals from which patients were discharged between April 2014 and March 2019. The primary endpoint was in-hospital mortality, compared between weekend and weekday admissions. Among the 1,340 eligible patients, 11% (150) were admitted during a weekend. The in-hospital mortality rates of the patients admitted during weekends and those admitted on a weekday were 28% (42/150) and 17% (204/1190), respectively. After an adjustment for covariates, weekend admission was associated with a significantly higher risk of in-hospital mortality than weekday admission (HR 1.70, 95%CI: 1.20-2.40; p=0.003). However, such an association was not observed in patients treated in a bio-clean room (HR 1.26, 95%CI: 0.65-2.42). Our results demonstrate that for patients with AML, weekend admission was independently associated with a higher risk of death during hospitalization. An appropriate system is necessary for these patients. No potential conflict of interest relevant to this article was reported.

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

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

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

MDPI AG Acta Medica Okayama 2077-0383 14 14 2025 Symptomatic Trends and Time to Recovery for Long COVID Patients Infected During the Omicron Phase 4918 EN Hiroshi Akiyama Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasue Sakurada Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Honda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yui Matsuda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Tokumasu Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Nakano Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryosuke Takase Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Omura Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keigo Ueda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumio Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Since the pathophysiology of long COVID is not yet fully understood, there are no specific methods for its treatment; however, its individual symptoms can currently be treated. Long COVID is characterized by symptoms that persist at least 2 to 3 months after contracting COVID-19, although it is difficult to predict how long such symptoms may persist. Methods: In the present study, 774 patients who first visited our outpatient clinic during the Omicron period from February 2022 to October 2024 were divided into two groups: the early recovery (ER) group (370 cases; 47.8%), who recovered in less than 180 days (median 33 days), and the persistent-symptom (PS) group (404 cases; 52.2%), who had symptoms that persisted for more than 180 days (median 437 days). The differences in clinical characteristics between these two groups were evaluated. Results: Although the median age of the two groups did not significantly differ (40 and 42 in ER and PS groups, respectively), the ratio of female patients was significantly higher in the PS group than the ER group (59.4% vs. 47.3%). There were no significant differences between the two groups in terms of the period after infection, habits, BMI, severity of COVID-19, and vaccination history. Notably, at the first visit, female patients in the PS group had a significantly higher rate of complaints of fatigue, insomnia, memory disturbance, and paresthesia, while male patients in the PS group showed significantly higher rates of fatigue and headache complaints. Patients with more than three symptoms at the first visit were predominant in the PS groups in both genders. Notably, one to two symptoms were predominant in the male ER group, while two to three symptoms were mostly reported in the female PS group. Moreover, the patients in the PS group had significantly higher scores for physical and mental fatigue and for depressive symptoms. Conclusions: Collectively, these results suggest that long-lasting long COVID is related to the number of symptoms and presents gender-dependent differences. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2691-1299 5 3 2025 Synthesis of Oligodeoxynucleotide Containing Pseudo‐Deoxycytidine and Its Triphosphate Derivative e70101 EN Ryo Miyahara Graduate School of Pharmaceutical Sciences, Kyushu University Yosuke Taniguchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This article describes a detailed synthetic protocol for the preparation of oligodeoxynucleotide (ODN) containing pseudo-deoxycytidine (ψdC) and its triphosphate derivative (ψdCTP). These molecules were synthesized as novel compounds that recognize iso-2'-deoxyguanosine (iso-dG) in DNA. Iso-dG is one of the tautomers of 2-hydroxy-2'-deoxyadenosine (2-OH-dA), which is known as an oxidatively damaged nucleobase, and its selective recognition in DNA is expected to play a very important role in the diagnosis and pathogenesis of diseases. The hydroxyl groups of the known glycal compound were protected with silyl groups, and then coupled with 5-iodouracil under Mizorogi-Heck reaction conditions, yielding ψdU after desilylation and diastereoselective reduction. The endocyclic amino group of ψdU was protected by the benzyl group. Subsequently, the carbonyl group at the 6-position of the nucleobase was activated and converted to an amino group through treatment with aqueous ammonia. The benzyl group was removed, and the exocyclic amino group was protected with a benzoyl group. On one hand, the silyl groups at the 3’ and 5’ positions were deprotected, converted into a phosphoramidite unit, and incorporated into an ODN. On the other hand, the hydroxyl group at the 5’ position was selectively deprotected and then directly converted into the triphosphate using Van Boom's reagent under acidic conditions. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0361-5995 89 3 2025 Autoclaved lightweight aerated concrete suppressed N2O and CO2 emissions from paddy soil e70091 EN Nagoda R. R. W. S. Rathnayake Department of Soil Science, Faculty of Agriculture, University of Ruhuna Morihiro Maeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Dewpura A. L. Leelamanie Department of Soil Science, Faculty of Agriculture, University of Ruhuna Atsushi Yatagai Clion Co. Ltd Autoclaved lightweight aerated concrete (AAC), a construction waste that is utilized as a soil amendment, can influence terrestrial carbon dioxide (CO2) emissions. Still, no evidence exists regarding its impact on the emission of nitrous oxide (N2O), which has a higher global warming potential. This study examined effects of AAC on CO2 and N2O emissions from paddy soil under compacted and non-compacted conditions, under 60% and 100% water-holding capacity (WHC). Samples were incubated in glass vials (25°C) for 21 days. Emissions of CO2 and N2O were measured on days 0, 1, 3, 7, 14, and 21 using gas chromatography. The results revealed that AAC significantly (p < 0.05) lowered N2O emission rate during the whole period of incubation, while it suppressed CO2 emission rate only at the early stages (∼7 days) of incubation. In compacted soil, the emissions of CO2 were significantly lower, while N2O was significantly higher than that in non-compacted soil, showing the influence of soil physical conditions. The emissions of CO2 and N2O were significantly lower at 100% WHC than those at 60% WHC. AAC suppressed both CO2 and N2O emissions under both compaction and WHC levels. The results confirm that AAC supports suppressing terrestrial emission of both CO2 and N2O, indicating that AAC has a potential as a sustainable soil amendment that enhances the climate change resilience. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1433-7851 64 13 2025 Conduction Band and Defect Engineering for the Prominent Visible‐Light Responsive Photocatalysts e202419624 EN Akira Yamakata Graduate School of Natural Science and Technology, Okayama University Kosaku Kato Graduate School of Natural Science and Technology, Okayama University Takafumi Ogawa Nanostructures Research Laboratory, Japan Fine Ceramics Center Kanta Ogawa Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Makoto Ogawa Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Daichi Kato Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Chengchao Zhong Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Akihide Kuwabara Nanostructures Research Laboratory, Japan Fine Ceramics Center Ryu Abe Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Hiroshi Kageyama Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Controlling trap depth is crucial to improve photocatalytic activity, but designing such crystal structures has been challenging. In this study, we discovered that in 2D materials like BiOCl and Bi4NbO8Cl, composed of interleaved [Bi2O2]2+ and Cl- slabs, the trap depth can be controlled by manipulating the slab stacking structure. In BiOCl, oxygen vacancies (VO) create deep electron traps, while chlorine vacancies (VCl) produce shallow traps. The depth is determined by the coordination around anion vacancies: VO forms strong σ bonds with Bi-6p dangling bonds below the conduction band minimum (CBM), while those around Cl are parallel, forming weak π-bonding. The strong re-hybridization makes the trap depth deeper. In Bi4NbO8Cl, VCl also creates shallow traps, but VO does not produce deep traps although Bi-6p orbitals are also forming strong σ bonding. This difference is attributed to the difference of the energy level of CBM. In both cases, the CBM consists of Bi-6p orbitals extending into the Cl layers. However, these orbitals are isolated in BiOCl, but those in Bi4NbO8Cl are bonded with each other between neighboring [Bi2O2]2+ layers. This unique bonding-based CBM prevents the formation of deep electron traps, and significantly enhances H2 evolution activity by prolonging the lifetime of highly reactive free electrons. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2574-0962 2025 Enhanced Charge-Transfer Kinetics Enabled by ZrO2–Based Dielectric Layers in Lithium-Ion Batteries EN Takashi Teranishi Graduate School of Natural Science and Technology, Okayama University Yusuke Higaki Graduate School of Natural Science and Technology, Okayama University Tomonori Imamura Graduate School of Natural Science and Technology, Okayama University Motoki Horibe Department of Advanced Ceramics, Nagoya Institute of Technology Shinya Kondo Department of Energy Engineering, Nagoya University Chinatsu Sasaoka R&D Laboratory, Nippon Denko Co., Ltd. Hikaru Hirabaru R&D Laboratory, Nippon Denko Co., Ltd. Shingo Katayama R&D Laboratory, Nippon Denko Co., Ltd. Masanobu Nakayama Department of Advanced Ceramics, Nagoya Institute of Technology Akira Kishimoto Graduate School of Natural Science and Technology, Okayama University The development of high-rate capability lithium-ion batteries (LIBs) requires suppression of charge-transfer resistance (RCT) at electrode–electrolyte interfaces. Here, zirconia-based dielectric oxides (MZ; M = Y, Gd, Sm, Er, etc.) were introduced onto LiCoO2 (LCO) surfaces as electronically and ionically insulating modifiers to accelerate interfacial ion transport. Electrochemical impedance spectroscopy showed that Y2O3 modified ZrO2 (YZ) decoration reduced RCT from 75.8 Ω in reference LCO to 38.3 Ω, accompanied by a 2.3-fold improvement in capacity retention at 20C. Density functional theory molecular dynamics (DFT–MD) simulations showed that solvated Li ions coordinate with surface oxygen atoms in discharging, and that adsorption energies are governed by local charge distributions determined by stabilizing cations. Optimal adsorption activity, and thus the lowest RCT, occurred when the surface charge corrugation was balanced. These findings provide design principles for dielectric interface engineering to enhance rate capability of LIBs. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2692-4609 6 1 2025 Japanese Multi‐Institution Study of Success Rates of Wire‐Guided Biliary Cannulation During Endoscopic Retrograde Cholangiopancreatography in Relation to Guidewire tip Length (JMIT Study) (With Video) e70144 EN Takeshi Ogura Endoscopy Center, Osaka Medical and Pharmaceutical University Yuki Tanisaka Gastroenterology, Saitama Medical University International Medical Center Masanari Sekine Department of Gastroenterology Jichi Medical University, Saitama Medical Center Katsumasa Kobayashi Department of Gastroenterology, Tokyo Metropolitan Bokutoh Hospital Hirotsugu Maruyama Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University Shinji Hirai Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine Hideyuki Shiomi Department of Gastroenterology, Division of Hepatobiliary and Pancreatic Diseases, Hyogo Medical University Minoru Shigekawa Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine Masaki Kuwatani Department of Gastroenterology and Hepatology, Hokkaido University Hospital Kenji Ikezawa Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute Masahiro Itonaga Second Department of Internal Medicine, Wakayama Medical University Mamoru Takenaka Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University Susumu Hijioka Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital Tsukasa Ikeura Third Department of Internal Medicine, Kansai Medical University Shinpei Doi Department of Gastroenterology, Teikyo University Mizonokuchi Hospital Nao Fujimori Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University Kazuya Koizumi Department of Gastroenterology, Medicine Center, Shonan Kamakura General Hospital Yousuke Nakai Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo Tadahisa Inoue Department of Gastroenterology, Aichi Medical University Shuntaro Mukai Department of Gastroenterology and Hepatology, Tokyo Medical University Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Ryuki Minami Department of Gastroenterology, Tenri Hospital Koichiro Mandai Department of Gastroenterology, Kyoto Second Red Cross Hospital Atsuhiro Matsuda Department of Internal Medicine, Toyama Prefectural Central Hospital Takuji Iwashita First Department of Internal Medicine, Gifu University Hospital Hiroki Kawashima Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine Takao Itoi Department of Gastroenterology and Hepatology, Tokyo Medical University Objective: Wire-guided cannulation (WGC) reportedly increases the successful biliary cannulation rate and reduces the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis. Currently, various types of guidewires are available. However, the effect of the length of flexible-tip guidewires on the success rate of biliary cannulation under WGC and the rate of adverse events, especially post-endoscopic retrograde cholangiopancreatography pancreatitis, is unclear. The aim of this study was to compare the influence of long-tapered and short-tapered tips of a 0.025-inch guidewire on outcomes in primary selective biliary cannulation. Methods: Consecutive patients who underwent biliary access under endoscopic retrograde cholangiopancreatography guidance using WGC at 27 high-volume centers in Japan were enrolled in this prospective registration study. The primary outcome was the technical success rate of biliary cannulation. The secondary outcomes were the rates of adverse events, biliary cannulation time, and number of guidewire insertions into the pancreatic duct. Results: A total of 530 patients underwent biliary cannulation for biliary disease with native papilla between April 2021 and December 2023. The technical success rate of biliary cannulation was 86.1% (161/187) in the long-tip group and 84.3% (289/343) in the short-tip group, indicating no significant differences between the two groups. Although the frequency of post-endoscopic retrograde cholangiopancreatography was not significantly different, the successful biliary cannulation rate without guidewire mis-insertion into the main pancreatic duct was significantly higher in the long tip group (64.7%, 121/187) compared with the short tip group (54.2%, 186/343p = 0.02). Conclusions: In conclusion, WGC using long-tip guidewires might reduce the risk of guidewire insertion into the main pancreatic duct. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0944-1174 2025 Mortality and cancer risk in patients with chronic pancreatitis in japan: insights into the importance of surveillance for pancreatic cancer EN Ryotaro Matsumoto Division of Gastroenterology, Tohoku University Graduate School of Medicine Kazuhiro Kikuta Division of Gastroenterology, Tohoku University Graduate School of Medicine Tetsuya Takikawa Division of Gastroenterology, Tohoku University Graduate School of Medicine Yousuke Nakai Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo Mamoru Takenaka Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine Kentaro Oki Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Eizaburo Ohno Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine Ken Ito Division of Gastroenterology and Hepatology, Toho University Omori Medical Center Nao Fujimori Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University Akio Katanuma Center for Gastroenterology, Teine-Keijinkai Hospital Atsuhiro Masuda Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine Yasuki Hori Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences Tsukasa Ikeura Department of Gastroenterology and Hepatology, Kansai Medical University Rei Suzuki Department of Gastroenterology, Fukushima Medical University School of Medicine Satoshi Yamamoto Department of Gastroenterology, Fujita Health University Bantane Hospital Yoshio Sogame Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Hiroki Kawashima Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine Tetsuhide Ito Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, International University of Health and Welfare Kosuke Okuwaki Department of Gastroenterology, Kitasato University School of Medicine Takao Itoi Department of Gastroenterology and Hepatology, Tokyo Medical University Yukiko Takayama Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University Akira Nakamura Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine Shuji Terai Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Masaki Kuwatani Department of Gastroenterology and Hepatology, Hokkaido University Hospital Masashi Kishiwada Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine Minoru Shigekawa Department of Gastroenterology and Hepatology, The University of Osaka Graduate School of Medicine Tomoaki Matsumori Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine Osamu Inatomi Department of Medicine, Shiga University of Medical Science Waku Hatta Division of Gastroenterology, Tohoku University Graduate School of Medicine Atsushi Irisawa Department of Gastroenterology, Dokkyo Medical University School of Medicine Michiaki Unno Department of Surgery, Tohoku University Graduate School of Medicine Yoshifumi Takeyama Department of Surgery, Kindai University Faculty of Medicine Atsushi Masamune Division of Gastroenterology, Tohoku University Graduate School of Medicine Japan Pancreatitis Study Group for Chronic Pancreatitis Background/Objective: Since the 2010s, Japan’s national health insurance system has covered key management for chronic pancreatitis (CP), including pancreatic enzyme replacement therapy. These therapies are expected to improve long-term prognosis; however, recent data are lacking. This study aimed to clarify the updated cancer risk and mortality among patients with CP in Japan. Methods: We conducted a multicenter, retrospective cohort study on 1,110 patients with CP treated at 28 institutions in 2011. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were calculated for comorbidities. Factors associated with the development of malignancy and overall survival were analyzed. Results: Patients with CP had an elevated SIR of 1.62 (95% confidence interval [CI], 1.43–1.83) for malignancy, with the highest risk observed for pancreatic cancer (SIR = 6.44 [95% CI, 4.64–8.90]). During follow-up, 143 patients (12.9%) died, most frequently from malignancy (47.5%). The SMR was elevated in all patients with CP (SMR = 1.20 [95% CI, 1.01–1.42]) and in those with alcohol-related CP (SMR = 1.49 [95% CI, 1.23–1.81]) but not in those with alcohol-unrelated CP. Pancreatic cancer was identified as the strongest factor associated with overall survival (hazard ratio, 48.92 in multivariate analysis). Overall survival of the patients with pancreatic cancer was significantly longer in those who underwent regular examinations for CP at least every three months (P = 0.011). Conclusions: Patients with alcohol-related CP have higher mortality than the general population in Japan. Pancreatic cancer remains a crucial prognostic factor in patients with CP. Regular surveillance for pancreatic cancer is important to improve their prognosis. 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.

MDPI AG Acta Medica Okayama 1422-0067 26 19 2025 Critical Requirement of Senescence-Associated CCN3 Expression in CD44-Positive Stem Cells for Osteoarthritis Progression 9630 EN Janvier Habumugisha Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichiro Okuda Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Hirose Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miho Kuwahara Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ziyi Wang Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuaki Ono Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Kamioka Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takako Hattori Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, synovial inflammation, and subchondral bone remodeling. Previous studies have shown that cellular communication network factor 3 (CCN3) expression increases with age in cartilage, and its overexpression promotes OA-like changes by inducing senescence-associated secretory phenotypes. This study aimed to investigate the effect of Ccn3 knockout (KO) on OA development using a murine OA model. Destabilization of the medial meniscus (DMM) surgery was performed in wild-type (WT) and Ccn3-KO mice. Histological scoring and staining were used to assess cartilage degeneration and proteoglycan loss. Gene and protein expressions of catabolic enzyme (Mmp9), hypertrophic chondrocyte marker (Col10a1), senescence marker, and cyclin-dependent kinase inhibitor 1A (Cdkn1a) were evaluated. Single-cell RNA sequencing (scRNA-seq) data from WT and Sox9-deficient cartilage were reanalyzed to identify Ccn3+ progenitor populations. Immunofluorescence staining assessed CD44 and Ki67 expression in articular cartilage. The effects of Ccn3 knockdown on IL-1β-induced Mmp13 and Adamts5 expression in chondrocytes were examined in vitro. Ccn3 KO mice exhibited reduced cartilage degradation and catabolic gene expression compared with WT mice post-DMM. scRNA-seq revealed enriched Ccn3-Cd44 double-positive cells in osteoblast progenitor, synovial mesenchymal stem cell, and mesenchymal stem cell clusters. Immunofluorescence showed increased CCN3+/CD44+ cells in femoral and tibial cartilage and meniscus. Ki67+ cells were significantly increased in DMM-treated Ccn3 KO cartilage, mostly CD44+. In vitro Ccn3 knockdown attenuated IL-1β-induced Mmp13 and Adamts5 expressions in chondrocytes. Ccn3 contributes to OA pathogenesis by promoting matrix degradation, inducing hypertrophic changes, and restricting progenitor cell proliferation, highlighting Ccn3 as a potential therapeutic target for OA. 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.

Acta Medica Okayama 2025 Accuracy of deep learning-based attenuation correction in 99mTc-GSA SPECT/CT hepatic imaging EN Masahiro MIYAI Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 The X-ray induced quenching of the thorium-229 isomer states in a CaF2 crystal host EN Ming Guan Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Importance of Blood Glucose Measurement for Predicting the Prognosis of Long COVID：A Retrospective Study in Japan EN Sho YOKOYAMA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Novel extracellular role of REIC/Dkk-3 protein in PD-L1 regulation in cancer cells EN Yuma GOHARA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Single-cell and spatial characterization of plasmablast-like lymphoma cells in primary central nervous system lymphoma EN Hiroki KOBAYASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Role of galectin-9 in the development of gestational diabetes mellitus EN ALBUAYJAN HAYA HAMED H Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Evaluation and processing of physical properties of anti-calcified glutaraldehyde-treated three-dimensional cultured cartilage tissues EN Yohei KITAGUCHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 LRP4 and Agrin Are Modulated by Cartilage Degeneration and Involved in β-Catenin Signaling in Human Articular Chondrocytes EN Shuichi NANIWA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 19 2025 Utility of Same-Modality, Cross-Domain Transfer Learning for Malignant Bone Tumor Detection on Radiographs: A Multi-Faceted Performance Comparison with a Scratch-Trained Model 3144 EN Joe Hasei Department of Medical Informatics and Clinical Support 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 Koichi Takeuchi Graduate School of Environmental, Life Natural Science and Technology, Okayama University 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 Hironari Tamiya Department of Musculoskeletal Oncology Service, Osaka International Cancer Institute, Shinji Miwa Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University 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 Hiroya Kondo 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 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 like malignant bone tumors is limited by scarce annotated data. This study evaluates same-modality cross-domain transfer learning by comparing an AI model pretrained on chest radiographs with a model trained from scratch for detecting malignant bone tumors on knee radiographs. Methods: Two YOLOv5-based detectors differed only in initialization (transfer vs. scratch). Both were trained/validated on institutional data and tested on an independent external set of 743 radiographs (268 malignant, 475 normal). The primary outcome was AUC; prespecified operating points were high-sensitivity (≥0.90), high-specificity (≥0.90), and Youden-optimal. Secondary analyses included PR/F1, calibration (Brier, slope), and decision curve analysis (DCA). Results: AUC was similar (YOLO-TL 0.954 [95% CI 0.937–0.970] vs. YOLO-SC 0.961 [0.948–0.973]; DeLong p = 0.53). At the high-sensitivity point (both sensitivity = 0.903), YOLO-TL achieved higher specificity (0.903 vs. 0.867; McNemar p = 0.037) and PPV (0.840 vs. 0.793; bootstrap p = 0.030), reducing ~17 false positives among 475 negatives. At the high-specificity point (~0.902–0.903 for both), YOLO-TL showed higher sensitivity (0.798 vs. 0.764; p = 0.0077). At the Youden-optimal point, sensitivity favored YOLO-TL (0.914 vs. 0.892; p = 0.041) with a non-significant specificity difference. Conclusions: Transfer learning may not improve overall AUC but can enhance practical performance at clinically crucial thresholds. By maintaining high detection rates while reducing false positives, the transfer learning model offers superior clinical utility. Same-modality cross-domain transfer learning is an efficient strategy for developing robust AI systems for rare diseases, supporting tools more readily acceptable in real-world screening workflows. 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.

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

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 0929-1903 2025 p53-armed oncolytic adenovirus induces apoptosis in pancreatic cancer-associated stellate cells via macropinocytosis EN Takeyoshi Nishiyama 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 Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Kajiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoyuki Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara 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 Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyoshi Y. Tanaka Department of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Mitsunobu R. Kano Department of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Atsushi Masamune Division of Gastroenterology, Tohoku University Graduate School of Medicine Yasuo Urata Oncolys BioPharma, Inc. 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 Pancreatic ductal adenocarcinoma (PDAC)-associated pancreatic stellate cells (PSCs) promote PDAC tumor progression. Notably, PDAC tumors display enhanced macropinocytosis, resulting in enhanced uptake of extracellular particles, including nutrients and viruses. We previously demonstrated the therapeutic potential of telomerase-specific oncolytic adenoviruses OBP-301 and p53-armed OBP-702 against human PDAC cells. However, it remains unclear whether macropinocytosis promotes the virus sensitivity of PDAC-associated PSCs. Here, we show that PSCs activated by human PDAC cells (Panc-1 and BxPC-3) exhibit enhanced sensitivity to wild-type and oncolytic adenoviruses via enhanced macropinocytosis. The virus sensitivity of PSCs was analyzed for the infectivity, replication, and cytopathic activity of wild-type and oncolytic adenoviruses. PDAC-associated PSCs were more sensitive to wild-type and oncolytic adenoviruses than were control PSCs; this sensitivity was mediated by activation of macropinocytosis. In three-dimensional (3D) culture models, p53-armed OBP-702 decreased the viability of PDAC-associated PSCs more strongly than did non-armed OBP-301, reflecting induction of p53-mediated apoptosis. Co-inoculation of PSCs enhanced the growth of PDAC tumors, an effect that was attenuated by OBP-702-mediated p53 activation in the tumor stroma. Our results suggest that p53-armed oncolytic adenovirus OBP-702 eliminates PDAC-associated PSCs via enhancement of macropinocytosis-mediated virus entry and induction of p53-mediated apoptosis. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 2470-9239 10 3 2025 Decreased homovanillic acid and 5‐hydroxyindoleacetic acid levels in the cerebrospinal fluid of patients with Dravet syndrome with parkinsonism 965 970 EN Ryo Sugiyama Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry Takashi Saito Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry Atsuko Katsumoto Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry Shota Yoneno Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry Tomoyuki Akiyama Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Hirofumi Komaki Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry Dravet syndrome (DS) is an early onset, developmental, and epileptic encephalopathy characterized by drug-resistant seizures and multiple comorbidities. It has been reported that in adulthood, it may be accompanied by parkinsonism, but the pathogenesis of this condition remains unclear. We performed dopamine transporter single-photon emission computed tomography (DAT SPECT) and measured monoamine metabolite levels in the cerebrospinal fluid (CSF) in two adult patients with DS who developed parkinsonism around the age of 30 years. DAT SPECT showed no abnormalities in either patient, whereas CSF tests revealed significant decreases in the levels of homovanillic and 5-hydroxyindoleacetic acids. One patient with severe symptoms was treated with levodopa–carbidopa, which improved parkinsonism manifestations. The other patient initiated treatment with a low dose and has been continuing the treatment without any reported side effects. In conclusion, CSF testing can detect a decrease in dopamine synthesis and may be useful in monitoring the efficacy of levodopa treatment in patients with DS and parkinsonism. Plain Language Summary: Dravet syndrome (DS) is an early onset, developmental, and epileptic encephalopathy. DS can lead to the development of parkinsonism in adulthood, a clinical syndrome characterized by tremor, slowed movements, and rigidity. Although parkinsonism is a significant issue for patients, its underlying pathology has not yet been elucidated. In this study, we confirmed that the levels of monoamine metabolites in the CSF were low in two patients, potentially shedding light on the pathology involved. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0925-5710 122 5 2025 Cytomegalovirus reactivation in patients with large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy 689 699 EN Kenta Hayashino Department of Hematology and Oncology, Okayama University Keisuke Seike Department of Hematology and Oncology, Okayama University Taro Masunari Department of Hematology, Chugoku Central Hospital Risa Hashida Division of Hematology, Ehime Prefectural Central Hospital Satoshi Oka Department of Hematology and Blood Transfusion, Kochi Health Science Center Yuki Fujiwara Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital Toshiki Terao Department of Hematology and Oncology, Okayama University Wataru Kitamura Department of Hematology and Oncology, Okayama University Hiroki Kobayashi Department of Hematology and Oncology, Okayama University Chihiro Kamoi Department of Hematology and Oncology, Okayama University Takumi Kondo Department of Hematology and Oncology, Okayama University Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Noboru Asada Department of Hematology and Oncology, Okayama University Daisuke Ennishi Department of Hematology and Oncology, Okayama University Keiko Fujii Department of Hematology and Oncology, Okayama University Nobuharu Fujii Department of Hematology and Oncology, Okayama University Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Chimeric antigen receptor (CAR) T-cell therapy has improved outcomes of relapsed and/or refractory large B-cell lymphoma (r/r LBCL). However, its off-tumor effects result in severe prolonged humoral immune deficiency. Cytomegalovirus (CMV) is a latent virus that can be life-threatening in immunosuppressed patients. In the setting of CAR T-cell therapy, Asian race is a risk factor for clinically significant CMV infection. However, the effect of CAR T-cell therapy on CMV reactivation in Japanese patients remains unclear. Previous reports used polymerase chain reaction (PCR), but we used the pp65 antigenemia assay to retrospectively investigate long-term effects in patients with r/r LBCL. The study included 46 patients. Nine (19.6%) developed CMV reactivation, with a median onset of 13 days. Six of these patients received preemptive therapy, and none developed CMV end-organ disease. Primary refractory disease, grade 2–4 cytokine release syndrome, and high-dose corticosteroids were risk factors for CMV reactivation. Long-term follow-up showed that CMV reactivation rarely occurred later than 28 days post-infusion. Our study using the pp65 antigenemia assay showed a similar incidence of CMV reactivation, onset, and risk factors to those in the previous reports using PCR. 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.

Springer Science and Business Media LLC Acta Medica Okayama 1618-1247 2025 Impact of CT-assessed sarcopenia on the severity of odontogenic deep neck infections: a retrospective cohort study EN Shogo Kikuta Dental and Oral Medical Center, Kurume University School of Medicine Eiji Iwata Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yohei Takeshita Department of Oral and Maxillofacial Radiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Chizuru Kobayashi Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroki Kimura Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuki Kinisada Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Akira Tachibana Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital 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 Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Sarcopenia is increasingly recognized as a key predictor of adverse health outcomes. This study aimed to evaluate the impact of computed tomography-assessed sarcopenia (CT–SP) on the clinical severity and hospitalization duration of odontogenic deep neck infections (DNIs). Total of 119 patients admitted for odontogenic DNI treatment were included. Patients were divided into two groups by DNI clinical severity (severe or mild) and the patients' characteristics, including CT–SP based on skeletal muscle index (SMI), were compared between two groups. Multivariable logistic regression analysis was performed to identify independent risk factors for severe DNI. The correlation between SMI and hospitalization duration was assessed using Spearman’s rank correlation coefficient. Of the 119 patients, 60 (50.4%) presented with severe DNIs, including deep neck abscesses and necrotizing soft tissue infections. After adjusting for potential confounders, multivariable analysis identified CT–SP as the sole independent risk factor associated with severe DNI (Odds Ratio = 3.04; 95% Confidence Interval, 1.20–7.71; p = 0.019). Furthermore, SMI demonstrated a significant, weak negative correlation with the hospitalization duration (r = － 0.331, p < 0.001). CT–SP is a powerful, independent risk factor associated with severity in patients with odontogenic DNIs. This finding underscores the critical role of systemic host factors in the clinical course of maxillofacial infections and highlights the potential of opportunistic CT screening as a factor to consider in risk stratification in this vulnerable population. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1999-4923 17 11 2025 Development of Propofol-Encapsulated Liposomes and the Effect of Intranasal Administration on Bioavailability in Rabbits 1446 EN Hitomi Ujita Department of Dental Anesthesiology, Okayama University Hospital Hitoshi Higuchi Department of Dental Anesthesiology, Okayama University Hospital Yukiko Nishioka Department of Dental Anesthesiology, Okayama University Hospital Saki Miyake Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate of Medicine, Dentistry and Pharmaceutical Sciences Riko Sato Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate of Medicine, Dentistry and Pharmaceutical Sciences Takuya Miyawaki Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Propofol is frequently used as an intravenous anesthetic and is rapidly metabolized. Therefore, if it could be administered non-invasively (e.g., orally) as premedication, it might hasten emergence from anesthesia, thereby improving patient safety. However, it undergoes extensive first-pass metabolism in the liver and intestines, limiting the route for premedication. We evaluated whether intranasal delivery of a propofol-encapsulated liposome solution improves systemic exposure and bioavailability in rabbits. Methods: A propofol-encapsulated liposome solution was administered to rabbits via the intravenous, oral, and intranasal routes. Blood propofol concentrations were measured for up to 60 min after administration and the area under the concentration–time curve (AUC0–60) and bioavailability of the propofol-encapsulated liposome solution were compared with those of the non-encapsulated propofol formulation. The differences were tested by two-way analysis of variance (ANOVA) with Šidák’s post hoc multiple-comparisons test and the Mann–Whitney test (α = 0.05). Results: The AUC0–60 for blood propofol concentrations after intravenous administration was significantly higher with the propofol-encapsulated liposome solution than with the non-encapsulated propofol formulation (3038.8 ± 661.5 vs. 1929.8 ± 58.2 ng·min/mL; p = 0.0286). By contrast, no increase in blood propofol concentrations was observed after oral administration, whereas intranasal administration increased blood propofol concentrations and yielded significantly higher bioavailability compared with the non-encapsulated propofol formulation (16.4 ± 7.3% vs. 2.0 ± 1.2%; p = 0.0286). Conclusions: The findings of the present study suggest that intranasal liposomal propofol increased systemic availability compared with a non-encapsulated formulation, supporting further evaluation as a candidate premedication approach for propofol. 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.

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

Wiley Acta Medica Okayama 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.

Journal of Neurosurgery Publishing Group (JNSPG) Acta Medica Okayama 2694-1902 10 13 2025 Endovascular treatment for a symptomatic dissecting ophthalmic artery aneurysm occurring in the orbit: illustrative case CASE25483 EN Kohei Izumihara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Haruma Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Sugiu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fukiko Baba Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Juntaro Fujita Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Sotome Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Kawakami Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryu Kimura Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Hiramatsu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences BACKGROUND: Peripheral ophthalmic artery aneurysms (POAAs) arising from the main trunk or branches of the ophthalmic artery (OphA) are extremely rare. However, their epidemiology and optimal management remain poorly understood. The authors report a rare case of a symptomatic POAA caused by arterial dissection that was successfully treated using endovascular therapy, leading to favorable visual recovery. OBSERVATIONS: A 77-year-old woman presented with sudden-onset visual impairment in the right eye. Ophthalmological examination revealed a defect in the right visual field. CT angiography revealed a fusiform aneurysm in the right intraorbital OphA. Digital subtraction angiography revealed a pearl and string sign, consistent with a dissecting aneurysm. A balloon test occlusion (BTO) of the OphA origin confirmed collateral circulation from the external carotid artery. Internal trapping of the OphA was performed under general anesthesia. Postoperatively, the patient’s visual function gradually improved, and complete recovery was achieved within 3 months. LESSONS: Although POAAs are exceptionally rare, they may lead to significant visual dysfunction owing to optic nerve compression. When visual symptoms are present, prompt intervention may reverse the symptoms. Preoperative assessment of collateral circulation using BTO is essential for treatment planning. Internal trapping may be an effective strategy when sufficient collateral flow is confirmed. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 8 2025 A Higher Liver Fibrosis-4 Index Is Associated With More Severe Hearing Loss in Idiopathic Sudden Sensorineural Hearing Loss e89864 EN Yukihide Maeda Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryotaro Omichi Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Liver fibrosis is an important medical issue increasing over time in developed countries. Aims/objectives This study aimed to investigate whether liver fibrosis, as indicated by routine blood test parameters, influences the risk and severity of idiopathic sudden sensorineural hearing loss (ISSNHL). Material and methods Sixty-six patients with ISSNHL and 198 patients with benign parotid gland tumors (BPTs) (controls) were enrolled. Indices for liver fibrosis (Liver Fibrosis-4 index (FIB-4 index) and aspartate aminotransferase-to-platelet ratio index (APRI)) were calculated from the blood laboratory data. The pure tone average (PTA) was calculated as the mean of hearing levels at the six frequencies at the onset of ISSNHL. Severe hearing loss was defined as PTA≥60 decibels Hearing Level (dB HL). Results In risk evaluation, the FIB-4 index did not differ significantly between ISSNHL patients and controls. Regarding the severity of ISSNHL, the FIB-4 index was significantly higher in ISSNHL patients with severe hearing loss than in those with PTA<60 dB HL (P<0.05) on univariate comparison. After adjusting for age, sex, and indices of inflammation, both the FIB-4 index and APRI showed a significant association with severe hearing loss (odds ratio (OR): 5.9, 95% confidence interval (CI): 1.3-25.7, and OR: 2.2, 95% CI: 1.1-4.7). Conclusions and significance Higher liver fibrosis indices (FIB-4 index and APRI), derived from routine blood laboratory data, are associated with a more severe phenotype of ISSNHL. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0250-832X 2025 Radiological assessment of dissected cervical lymph nodes in level III affected by the area of supraomohyoid neck dissection EN Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshio Ohyama Clinical Anatomy Research Association in Oral and Maxillofacial Surgery Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Matsushita Clinical Anatomy Research Association in Oral and Maxillofacial Surgery R Shane Tubbs Clinical Anatomy Research Association in Oral and Maxillofacial Surgery Norio Kitagawa Clinical Anatomy Research Association in Oral and Maxillofacial Surgery Toshiyuki Kawazu Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miki Hisatomi Department of Oral and Maxillofacial Radiology, Okayama University Hospital Shunsuke Okada Department of Oral and Maxillofacial Radiology, Okayama University Hospital Mamiko Fujikura Department of Oral and Maxillofacial Radiology, Okayama University Hospital Yoshinobu Yanagi Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Joe Iwanaga Clinical Anatomy Research Association in Oral and Maxillofacial Surgery Objectives: To compare the number of dissected cervical lymph nodes in the anatomical level III with that in supraomohyoid neck dissection (SOHND) level III affected by the anatomical relationship between the omohyoid muscle and cricoid cartilage using contrast-enhanced CT (CE-CT) images to assess the validity of the current SOHND. Methods: CE-CT images of the patients who suffered from malignant tumours in the oral and maxillofacial regions were reviewed. The number of cervical lymph nodes both in the anatomical level III (area between the centre of the inferior border of the hyoid bone [HB] and the inferior border of the cricoid cartilage [CC]) and SOHND level III (area between HB and the intersection of the omohyoid muscle and internal jugular vein [OM-IJ]) were recorded, respectively. Results: The rate of patients whose number of lymph nodes in level III was affected by the positional relationship between the OM-IJ and CC was almost equal in males and females. As for the patients with OM-IJ below the CC, the number of lymph nodes in SOHND level III increased from that of anatomical level III. Females showed significantly higher values than males (P < .05). Meanwhile, for patients with OM-IJ at or above the CC, the number of lymph nodes in SOHND level III decreased from that of anatomical level III. Conclusions: The number of dissected cervical lymph nodes differed between the SOHND dissection area and levels I, II, and III. In most cases, SOHND dissects more cervical lymph nodes, especially in female patients. No potential conflict of interest relevant to this article was reported.

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

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.

Springer Science and Business Media LLC Acta Medica Okayama 1434-3916 145 1 2025 Component placement angles in total knee arthroplasty affect mid- to long-term clinical results: an average 8-year follow-up study 457 EN Koki Kawada Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Yokoyama Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomonori Tetsunaga Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Yamada Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Okazaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiki Kohara Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Introduction Few studies have examined how the component placement angles in total knee arthroplasty (TKA) affect mid- to long-term clinical outcomes. This study investigated the influence of coronal and sagittal plane component placement angles on mid- to long-term outcomes in mechanical alignment TKA. Materials and Methods Forty-eight knees undergoing TKA using the FINE Total Knee System were evaluated for range of motion (ROM) preoperatively. Both ROM and clinical scores were evaluated at 3 and 5 years postoperatively and at the final follow-up (average 8-year). The valgus (alpha) and flexion (gamma) angles of the femoral component, and the varus (beta) and posterior tilt (sigma) angles of the tibial component were evaluated. Correlations between radiographic assessments, knee ROM, and clinical scores were assessed using Spearman's correlation coefficient. Results The alpha angle was negatively correlated with the knee flexion angle (r = － 0.323, p = 0.025) and ROM (r = － 0.352, p = 0.014), and the sigma angle was negatively correlated with the Knee Injury and Osteoarthritis Outcome Score (KOOS)-Symptoms at 3 years postoperatively (r = － 0.304, p = 0.036). The alpha angle was negatively correlated with the knee flexion angle (r = － 0.357, p = 0.013), ROM (r = － 0.337, p = 0.019), and KOOS-Sports and Recreation function (r = － 0.349, p = 0.015), and positively correlated with the Visual Analog Scare pain score (r = 0.307, p = 0.034) at the final follow-up. The beta angle was positively correlated with KOOS-Pain (r = 0.303, p = 0.036) and KOOS-Symptoms (r = 0.397, p = 0.005) at the final follow-up. Conclusions Valgus placement of the femoral component and varus placement of the tibial component in the FINE Total Knee System negatively impacted clinical scores at an average 8-year follow-up. No potential conflict of interest relevant to this article was reported.

The Royal Society Acta Medica Okayama 2054-5703 12 9 2025 On weapons allometry and the form of sexual selection 251152 EN Hironori Shinohara Center for Ecology and Conservation, University of Exeter, Cornwall Campus Manmohan D. Sharma Center for Ecology and Conservation, University of Exeter, Cornwall Campus Tanya M. Pennell Center for Ecology and Conservation, University of Exeter, Cornwall Campus Kensuke Okada Faculty of Environmental, Life, Natural Science and Technology, Okayama University David J. Hosken Center for Ecology and Conservation, University of Exeter, Cornwall Campus The study of trait scaling with body size (allometry) has a long history, and it has been argued that positive static allometry is an indicator of directional sexual selection. However, a range of allometries exists for sexually selected traits, and modelling shows this variation can be generated by altering the form of selection (fitness functions) on the trait and/or body size. Interestingly, in all models, positive allometry appears to emerge only when there is directional selection on trait size. Here, we report on a sexually selected trait that shows strong positive static allometry and yet appears to be under stabilizing selection. This surprising finding suggests the evolution of trait scaling is even more nuanced than currently appreciated. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Gastroduodenal Artery-Preserving Pancreatoduodenectomy after Esophagectomy with Gastric Conduit Reconstruction 393 398 EN Akari Masunaga Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Kanehira Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yumi Sota 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 Case Report 10.18926/AMO/69441 Pancreatoduodenectomy (PD) after esophagectomy with gastric conduit reconstruction is technically challenging. Preserving the blood supply of the gastric conduit is crucial in performing PD after esophagectomy. We report the case of a 66-year-old man who underwent gastroduodenal artery-preserving PD after esophagectomy with gastric conduit reconstruction for intraductal papillary mucinous neoplasm. The patient developed pseudoaneurysm rupture postoperatively, but was successfully treated with interventional radiology. Precise assessment is important in developing a surgical strategy depending on the patient’s specific anatomy and tumor characteristics. Moreover, special attention should be paid to avoid accidental injuries of the gastric conduit and gastric vessels during surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 The Utility of a Preoperative 3D Imaging Analysis System for Trigonal Meningioma 387 392 EN Yusuke Mori Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Omae Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuichiro Hirano Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joji Ishida Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Fujii Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Haruma Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Hiramatsu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshi Matsushita Division of Radiological Technology, Okayama University Hospital Fumiyo Higaki Department of Radiology, Medical Development Field, Okayama University Kenji Sugiu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/69440 Trigonal meningiomas are rare and pose surgical challenges due to their deep location and proximity to critical neuroanatomical structures. We present the case of a 67-year-old woman with a growing trigonal meningioma successfully resected with guidance by a preoperative 3D imaging analysis system. Integration of CT and MRI including diffusion tensor imaging (DTI) enabled precise mapping of the optic radiation, guiding a middle temporal gyrus approach. Preoperative embolization reduced tumor vascularity, facilitating gross total resection with minimal blood loss. This case highlights the effectiveness of preoperative 3D imaging systems in optimizing surgical planning and improving outcomes in complex neurosurgical cases. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Advantages of Single-Position Surgery over Posterior Fusion for Single-Level Degenerative Lumbar Diseases 359 368 EN Tomohiko Hirose Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Hisanori Ikuma Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Kazutoshi Otsuka Otsuka Orthopedic Clinic Keisuke Kawasaki Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Original Article 10.18926/AMO/69437 Single-position surgery with lateral lumbar interbody fusion (LLIF) and percutaneous pedicle screws (PPSs) is gaining attention for its reduced invasiveness. We developed SPAPS, a technique allowing two surgeons to perform anterior LLIF and posterior PPS insertion simultaneously in a single lateral decubitus position. This retrospective study compared SPAPS (SPAPS-LLIF, Group SL) and minimally invasive posterior/transforaminal lumbar interbody fusion (MIS-PLIF/TLIF, Group PT) in patients treated between 2016 and 2019 with a two-year follow-up. Operative time, estimated blood loss (EBL), length of hospital stay (LOS), JOABPEQ and VAS scores, segmental lordotic angle, lumbar lordotic angle, segmental Cobb’s angle, PPS misplacement, PPS loosening, fusion status, and muscle cross-sectional areas were compared. Fifty-two patients were analyzed (Group SL: 25; Group PT: 27). SPAPS significantly reduced operative time (118.0 vs. 165.3 min, p <0.01) and estimated blood loss (8.6 vs. 164.1 mL, p<0.01). While clinical outcomes and hospital stay were comparable, Group SL had significantly lower PPS loosening (0% vs. 13%, p<0.01) and non-union rates (0% vs. 22.2%, p=0.02). Multifidus muscle atrophy was also less in Group SL (－14.3 vs. －121.5 mm2, p<0.01). SPAPS demonstrated advantages in reducing surgical invasiveness without compromising clinical efficacy, offering a promising alternative to conventional posterior fusion surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Comparison of Extraocular Muscles in Patients with Exotropia and Healthy Participants Using Anterior Segment Optical Coherence Tomography 353 358 EN Yuki Chihara Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ichiro Hamasaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyo Shibata Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Morisawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Reika Kono Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keisuke Kanenaga Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/69436 To analyze and characterize the medial and lateral rectus muscles in patients with exotropia using anterior segment optical coherence tomography (AS-OCT). This study included 24 patients with exotropia (48 eyes) and 25 healthy individuals (50 eyes). Anterior segment optical coherence tomography was used to construct the en face images. The anterior chamber angle to the extraocular muscle insertion distance, muscle width, and muscle fiber angle from the muscle insertion sites were compared between the exotropia and the control groups. The correlation between these parameters and age or angle of deviation was evaluated. The mean ages were 13.2±4.1 years for the exotropia group and 17.6±7.2 years for the control group. The lateral rectus angle was significantly more inwardly rotated in the exotropia group than in the control group (1.6±6.3°, －1.4±4.0°, p=0.014). With increasing angle of deviation, the width of the lateral rectus increased (p=0.002). Our results indicate that the lateral rectus angle is significantly more inwardly rotated in patients with exotropia. These findings should contribute to a deeper understanding of the extraocular muscles in patients with this condition. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 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.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Current Status of Extracorporeal Membrane Oxygenation as a Treatment Strategy for Primary Graft Dysfunction after Lung Transplantation 329 337 EN Kei Matsubara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/69433 Primary graft dysfunction (PGD) is one of the major risk factors affecting patients’ short- and long-term survival after lung transplantation. No particular management strategy has been established for PGD; supportive care is the mainstay of PGD treatment. When a supportive strategy fails, the patient may require the introduction of extracorporeal membrane oxygenation (ECMO) as the last-resort measure for severe PGD. A variety of study of ECMO as a PGD treatment was reported and the management of PGD patients developed so far. Early recognition of a patient’s need for ECMO and its prompt initiation are critical to improved outcomes. The use of venovenous-ECMO became the preferred procedure for PGD rather than venoarterial-ECMO. However, the current ECMO strategy has limitations, and using ECMO to manage patients with PGD is not sufficiently effective. Further studies are required to develop this promising technology. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1471-2369 26 1 2025 Risk of malignant neoplasms of tacrolimus in kidney transplant patients: a retrospective cohort study conducted using the Japanese National Database of Health Insurance Claims 491 EN Risa Kubota Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-Ei Sada Department of Clinical Epidemiology, Kochi Medical School, Kochi University Moto Tokunaga Department of Urology, National Hospital Organization Okayama Medical Center Kasumi Yoshinaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoaki Yamanoi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Tominaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Edamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Nakagawa Department of Urology, Juntendo University Graduate School of Medicine Naotsugu Ichimaru Department of Urology, Kinki Central Hospital Koichiro Wada Department of Urology, Shimane University Faculty of Medicine Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Although the long-term survival of kidney transplant recipients has significantly improved, malignant neoplasms remain one of the leading causes of death in this population. The recipients face a 1.8-fold increased risk of developing malignant neoplasms compared with the general population. This risk increases with time after transplantation. Tacrolimus (TAC) is preferred over cyclosporine A (CyA) in terms of efficacy against organ rejection, but evidence on the risk of malignant neoplasms is lacking. We aimed to describe the incidence and types of malignant neoplasms in kidney transplant recipients and evaluate the association between malignant neoplasms development and the type of prescribed CNI. Methods: This retrospective cohort study was conducted using the Japanese National Database of Health Insurance Claims, including data covering 99% of kidney transplant patients in Japan. Patients who underwent kidney transplantation and were prescribed TAC or CyA between April and June 2011 were included. The primary outcome included the incidence of malignant neoplasms, and secondary outcomes included overall survival and graft survival. Results: A total of 7,590 patients were included, with 11.0% developing malignant neoplasms during the follow-up period. The most common malignant neoplasms were in the digestive organs and urinary tract. No statistically significant difference in malignant neoplasms incidence was observed between TAC and CyA users (hazards ratio: 0.97, 95% CI: 0.84 to 1.12; estimated average treatment effect: －24.05, 95% CI: －184.90 to 136.80). The patient and graft survival rates were also comparable between the groups. Conclusions: This large study suggests that TAC is not associated with an increased risk of malignant neoplasms compared to CyA in the late post-transplant period. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 1932-4537 22 5 2025 Topology-Driven Configuration of Emulation Networks With Deterministic Templating 3933 3946 EN Satoru Kobayashi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Ryusei Shiiba Department of Informatics, School of Multidisciplinary Sciences, The Graduate University of Advanced Studies, Sokendai Shinsuke Miwa StarBED Technology Center, Testbed Research, Development and Operations Laboratory, National Institute of Information and Communications Technology Toshiyuki Miyachi Strategic Planning Department, Strategic Planning Office, National Institute of Information and Communications Technology Kensuke Fukuda Department of Informatics, School of Multidisciplinary Sciences, The Graduate University of Advanced Studies, Sokendai Network emulation is an important component of a digital twin for verifying network behavior without impacting on the service systems. Although we need to repeatedly change network topologies and configuration settings as a part of trial and error for verification, it is not easy to reflect the change without failures because the change affects multiple devices, even if it is as simple as adding a device. We present topology-driven configuration, an idea to separate network topology and generalized configuration to make it easy to change them. Based on this idea, we aim to realize a scalable, simple, and effective configuration platform for emulation networks. We design a configuration generation method using simple and deterministic config templates with a new network parameter data model, and implement it as dot2net. We evaluate three perspectives, scalability, simplicity, and efficacy, of the proposed method using dot2net through measurement and user experiments on existing test network scenarios. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2078-2489 16 1 2025 Relay Node Selection Methods for UAV Navigation Route Constructions in Wireless Multi-Hop Network Using Smart Meter Devices 22 EN Shuto Ohkawa Graduate School of Engineering, Nihon University Kiyoshi Ueda Graduate School of Engineering, Nihon University Takumi Miyoshi College of Systems Engineering and Science, Shibaura Institute of Technology Taku Yamazaki College of Systems Engineering and Science, Shibaura Institute of Technology Ryo Yamamoto Graduate School of Informatics and Engineering, The University of Electro-Communications Nobuo Funabiki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Unmanned aerial vehicles (UAVs) offer solutions to issues like traffic congestion and labor shortages. We developed a distributed UAV management system inspired by virtual circuit and datagram methods in packet-switching networks. By installing houses with wireless terminals, UAVs navigate routes in a multi-hop network, communicating with ground nodes. UAVs are treated as network packets, ground devices are treated as routers, and their connections are treated as links. Activating all nodes as relays increases control message traffic and node load. To optimize connectivity, we minimize relay nodes, connecting non-relay nodes to the nearest relay. This study proposes four relay node selection methods: random selection, two adjacency-based methods, and our innovative approach using Multipoint Relay (MPR) from the Optimized Link State Routing Protocol (OLSR). We evaluated these methods according to their route construction success rates, relay node counts, route lengths, and so on. The MPR-based method proved most effective for UAV route construction. However, fewer relay nodes increase link collisions, and we identify the minimum relay density needed to balance efficiency and conflict reduction. 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.

Wiley Acta Medica Okayama 1367-2223 28 1 2024 Can online interactions reduce loneliness in young adults during university closures in Japan? The directed acyclic graphs approach e12658 EN Kohei Kambara Doshisha University Akihiro Toya Hiroshima University Sumin Lee Hiroshima University Haruka Shimizu Nishikyushu Univ. Junior College Kazuaki Abe Hiroshima University Jun Shigematsu Toyama University Qingyuan Zhang Hiroshima University Natsuki Abe Hiroshima Bunkyo University Ryo Hayase Chubu University Nobuhito Abe Kyoto University Ryusuke Nakai Kyoto University Shuntaro Aoki Fukushima Medical University Kohei Asano Kyoto University Ryosuke Asano Kurume University Makoto Fujimura Fukuoka Jo Gakuin University Ken’ichiro Fukui Kwassui Women's University Yoshihiro Fukumoto Kansai Medical University Kaichiro Furutani Kansai University Koji Hasegawa Komazawa University Hirofumi Hashimoto Osaka Metropolitan University Mikoto Hashimoto Chukyo Gakuin University Hiroki Hosogoshi Kansai University Hiroshi Ikeda Kyushu University Toshiyuki Ishioka Kobe University Chiharu Ito University of Human Environments Suguru Iwano Fukushima Medical University Masafumi Kamada Shujitsu Junior College Yoshihiro Kanai Tohoku Gakuin University Tomonori Karita Ehime University Yu Kasagi Rissho University Emiko S. Kashima La Trobe University Juri Kato Kanazawa Institute of Technology Yousuke Kawachi Tohoku University Jun‐ichiro Kawahara Hokkaido University Masanori Kimura Graduate School of Business Administration, Kobe University Yugo Kira Kurume University Yuko Kiyonaga (Sakoda) Kyushu Kyoritsu University Hiroshi Kohguchi Ryutsu Keizai University Asuka Komiya Hiroshima University Keita Masui Otemon Gakuin University Akira Midorikawa Chuo University Nobuhiro Mifune Kochi University of Technology Akimine Mizukoshi Asahi University Kengo Nawata Fukuoka University Takashi Nishimura Hiroshima International University Daisuke Nogiwa Seikei University Kenji Ogawa Hokkaido University Junko Okada Prefectural University of Hiroshima Aki Okamoto Okayama University Reiko Okamoto Osaka University Kyoko Sasaki Kanagawa University of Human Services Kosuke Sato Kurume University Hiroshi Shimizu Kwansei Gakuin University Atsushi Sugimura Tokai University Yoko Sugitani Sophia University Hitomi Sugiura Kindai University Kyoko Sumioka Okayama University Bumpei Sunaguchi Graduate School of Business Administration, Kobe University Masataka Takebe Otsuma Women's University Hiroki C. Tanabe Nagoya University Ayumi Tanaka Doshisha University Masanori Tanaka Hokkai‐Gakuen University Junichi Taniguchi Tezukayama University Namiji Tokunaga Ehime Prefectural University of Health Sciences Ryozo Tomita Musashino University Yumiko Ueda Asahi University Tomomi Yamashita Jumonji University Kazuho Yamaura Ritsumeikan University Masao Yogo Doshisha University Kenji Yokotani Tokushima University Ayano Yoshida Tohoku Fukushi University Hiroaki Yoshida Shinshu University Katsue Yoshihara Fukuoka Institute of Technology Junior College Ayumi Yoshikawa Osaka Dental University Faculty of Nursing Kuniaki Yanagisawa Kobe University Ken'ichiro Nakashima Hiroshima University As a countermeasure to the increased loneliness induced by the COVID-19 pandemic-related university closures, universities provided students with online interaction opportunities. However, whether these opportunities contributed to reducing loneliness during the university closures remains unclear, as previous studies have produced contradictory findings. We conducted a nationwide cross-sectional survey. Data were collected on demographics, social environment, social support, interactions, health and loneliness from 4949 students from 60 universities across Japan. We used psychological network and Directed Acyclic Graphs (DAGs) to examine the effect of online interactions on loneliness during university closures during COVID-19. The results showed that the frequency of online interactions with friends did not exert a significant influence on loneliness during university closures. A comparative examination of the DAGs further illuminated that the social environment exhibited fewer pathways for interpersonal interactions and social support during these closure periods. The psychosocial pathways influencing young adults' loneliness show variations contingent on the university's closure status. Notably, the impact of heightened online interactions with friends on loneliness appears to be less pronounced among young adults in the context of university closure. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6643 17 18 2025 Lacticaseibacillus rhamnosus Probio-M9 Alters the Gut Microbiota and Mitigates Pulmonary Hypertension in a Rat Model 2927 EN Zhixin Zhao Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University Gaopeng Li Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University Kiyomi Ohmichi Department of Diagnostic Pathology, Kagawa University Hospital Xiaodong Li Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University Feiyan Zhao Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University Kaori Ishikawa Department of General Medicine, Kagawa University Hospital Ryou Ishikawa Department of Diagnostic Pathology, Kagawa University Hospital Kazufumi Nakamura Center for Advanced Heart Failure, Okayama University Hospital Naoya Yokota Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University Zhihong Sun Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University Lin Hai Kurahara Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University Background: Intestinal microbiota plays an important role in the progression of pulmonary hypertension (PH). Colostrum-derived Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) has shown protective effects against inflammation and remodeling. We investigated whether Probio-M9 supplementation could improve the pathology of PH. Methods: The monocrotaline (MCT)-induced PH model rats are created followed by Probio-M9 treatment. Microbiota and pathological analyses were performed to investigate the therapeutic effects of Probio-M9. Results: Probio-M9 significantly suppressed cardiovascular remodeling and reduced mortality in rats. Analysis of the fecal microbiota revealed that Probio-M9 significantly altered the gut microbiota of MCT model rats. Specifically, Alistipes sp009774895 and Duncaniella muris populations increased, whereas Limosilactobacillus reuteri_D, Ligilactobacillus apodeme and Monoglobus sp900542675 decreased compared to those in the MCT group. Focusing on the expression of GPNMB in macrophages and the localization of CD44, we found that the number of these cells increased in the MCT group but significantly decreased with Probio-M9 treatment. In lung tissue from PH patients, more GPNMB-positive macrophages were found than non-PH lungs, and an increase in CD44-positive cells was confirmed in the vicinity of GPNMB. Conclusions: Probio-M9 had a significant impact on the intestinal microbiota and GPNMB/CD44 positive cells in the lungs of PH rats. 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 Pharmacokinetics and the effectiveness of pyrogen-free bioabsorbable wet adhesives 20056 EN Risa Oshima Department of Periodontology, Faculty of Dental Medicine, Hokkaido University Kumiko Yoshihara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ko Nakanishi Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Tsukasa Akasaka Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Shinji Shimoji Department of Periodontology, Faculty of Dental Medicine, Hokkaido University Teppei Nakamura Department of Applied Veterinary Science, Faculty of Veterinary Medicine, Hokkaido University Takumi Okihara Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Mariko Nakamura Department of Clinical Psychology, School of Clinical Psychology, Kyushu University of Medical and Science Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ikkei Tamada Department of Plastic and Reconstructive Surgery, Tokyo Metropolitan Children’s Medical Center Bart Van Meerbeek BIOMAT, Department of Oral Health Sciences, & UZ Leuven, Dentistry, KU Leuven Tsutomu Sugaya Department of Periodontology, Faculty of Dental Medicine, Hokkaido University Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Bioabsorbable materials are essential for advanced therapies, including surgical sealing, cell therapy, and drug delivery. Natural bioabsorbable materials, including collagen and hyaluronic acid, have better biocompatibility than synthetic bioabsorbable polymers; however, they are mainly derived from animals, presenting infection risks. Non-animal origin polymers have a lower molecular weight than those of animal origins. Their viscosity increases with increase in molecular weight, making endotoxin removal difficult. Here, using the phosphoryl chloride disposal method, we present a strategy for synthesizing pyrogen-free bioabsorbable adhesives with controlled molecular weight. Phosphopullulan, a polysaccharide derivative, had less than detectable endotoxin levels and controllable average molecular weight of approximately 300,000 to over 1,400,000. Furthermore, it is important to ensure the safety as well as efficacy of bio-implantable materials. We have evaluated the biosafety of polysaccharide derivatives we are developing, and have examined their cell phagocytosis and pharmacokinetics in vitro and in vivo, and have confirmed that they are safe. We have also evaluated their adhesion to wet tissue adhesions and confirmed that they leak less than existing materials. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 16 1 2025 Fully-gapped superconductivity with rotational symmetry breaking in pressurized kagome metal CsV3Sb5 3643 EN X. Y. Feng Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics Z. Zhao Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics J. Luo Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics Y. Z. Zhou Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics J. Yang Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics A. F. Fang H. T. Yang Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics H.-J. Gao Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics R. Zhou Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics Guo-qing Zheng Department of Physics, Okayama University The discovery of the kagome metal CsV3Sb5 has generated significant interest in its complex physical properties, particularly its superconducting behavior under different pressures, though its nature remains debated. Here, we performed low-temperature, high-pressure 121/123Sb nuclear quadrupole resonance (NQR) measurements to explore the superconducting pairing symmetry in CsV3Sb5. At ambient pressure, we found that the spin-lattice relaxation rate 1/T1 exhibits a kink at T ~ 0.4 Tc within the superconducting state and follows a T3 variation as temperature further decreases. This suggests the presence of two superconducting gaps with line nodes in the smaller one. As pressure increases beyond Pc ~ 1.85 GPa, where the charge-density wave phase is completely suppressed, 1/T1 shows no Hebel-Slichter peak just below Tc, and decreases rapidly, even faster than T5, indicating that the gap is fully opened for pressures above Pc. In this high pressure region, the angular dependence of the in-plane upper critical magnetic field Hc2 breaks the C6 rotational symmetry. We propose the s + id pairing at P > Pc which explains both the 1/T1 and Hc2 behaviors. Our findings indicate that CsV3Sb5 is an unconventional superconductor and its superconducting state is even more exotic at high pressures. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 0912-3814 40 4 2024 Nationwide diversity of symbolic “city flowers” in Japan is increasing 463 474 EN Yoichi Tsuzuki Health and Environmental Risk Division, National Institute for Environmental Studies Haruna Ohsaki Department of Biological Sciences, Tokyo Metropolitan University Yawako W. Kawaguchi Department of Biological Sciences, Graduate School of Science, The University of Tokyo Sayaka Suzuki Center for Ecological Research, Kyoto University Shogo Harada Department of Biology, Graduate School of Science, Osaka City University Yurie Otake Center for Ecological Research, Kyoto University Naoto Shinohara Center for Ecological Research, Kyoto University Koki R. Katsuhara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Recognizing and maintaining locally rooted human–nature interactions is essential for utilizing ecosystem services. Although the general public's awareness of biodiversity and ecosystem services has been examined using various proxies, it remains unclear how local governments―key sectors in creating conservation policies―appreciate them within a solid local context. Here, we focused on the “city flower,” an official symbolic species of Japanese cities, as a new proxy for measuring governmental attitudes toward biota and its services. We aimed to capture temporal changes in the awareness of species with locally relevant value at the city government level by examining the changes in city flowers over more than half a century. Data from the official websites of municipalities, including the names, the adoption years, and the reasons for adoption, revealed two major periods of adoption, with a notable increase in species diversity in and after 1993. This increase could be attributed to a recent reduction in bias toward popular flowers and growing interest in alternative, less popular flowers. Analysis of the reasons for adoption suggested that the temporal change in adopted flower species was related to the increasing emphasis on species with an explicit local context, especially those with instrumental value to the city. Our findings indicate the tendency for local governments to increasingly recognize their biocultural backgrounds and the ecosystem services of plants within their regions. The growing awareness of the local governments regarding their biocultural background is a positive sign for the conservation of biodiversity and ecosystem services. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1344-3941 96 1 2025 Presence of a Deletion Mutation of Myostatin (MSTN) Gene Associated With Double-Muscling Phenotype in Japanese Black Cattle Population e70055 EN Nu Anh Thu Le Faculty of Veterinary Medicine Okayama University of Science Imabari Rena Kubo Faculty of Veterinary Medicine Okayama University of Science Imabari Liushiqi Borjigin Faculty of Veterinary Medicine Okayama University of Science Imabari Takayuki Ibi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shinji Sasaki Faculty of Agriculture Ryukyu University Nishihara Tetsuo Kunieda Faculty of Veterinary Medicine Okayama University of Science Imabari Mutations in the bovine myostatin (MSTN) gene have been identified as the causative factor for the double-muscling phenotype in several European cattle breeds, including Belgian Blue, Piedmontese, and Shorthorn. In Japan, following the Meiji Restoration, several European breeds, including Shorthorn, Brown Swiss, Devon, Simmental, and Ayrshire, were introduced and crossbred with native cattle to develop modern Japanese beef cattle breeds, such as Japanese Black cattle. Historical records regarding the breeding of Japanese Black cattle indicate that the double-muscling phenotype, referred to as “Butajiri,” occasionally appeared in Japanese Black cattle population. These historical observations suggest the potential presence of MSTN gene mutation in the Japanese Black cattle population. The aim of this study was, therefore, to investigate the presence of MSTN gene mutation in the current Japanese Black cattle population. Through screening 400 reproductive females, we identified one cow carrying an 11-bp deletion in the MSTN gene. While further investigation of the animals in the pedigree of this cow could not reveal any living animals with this mutation, this is the first report demonstrating the presence of the MSTN mutation in the Japanese Black cattle population. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1936-5209 19 3 2025 Oregon Wolfe barley genetic stocks – Research and teaching tools for next generation scientists e70004 EN Margaret R. Krause Department of Crop and Soil Science, Oregon State University Juan David Arbelaez Department of Crop Sciences, University of Illinois at Urbana-Champaign Åsmund Asdal Nordic Genetic Resource Centre Ramzi Belkodja CIHEAM-Zaragoza Nancy Boury Department of Plant Pathology, Entomology, and Microbiology, Iowa State University Victoria C. Blake Department of Plant Sciences and Plant Pathology, Montana State University Patrick J. Brown Department of Plant Sciences, University of California-Davis Ana Casas Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC Luis Cistué Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC Alba Farré‐Martínez AGROTECNIO-CERCA Center, Universidad de Lleida Scott Fisk Department of Crop and Soil Science, Oregon State University Gregory S. Fuerst U.S. Department of Agriculture-Agricultural Research Service, Corn Insects and Crop Genetics Research Unit, Iowa State University Estela Giménez Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid Carla Guijarro‐Real Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid Katy Guthrie Department of Agronomy and Plant Genetics, University of Minnesota Margaret Halstead Aardevo North America Laura Helgerson Department of Crop and Soil Science, Oregon State University Hiroshi Hisano Institute of Plant Science and Resources, Okayama University Ernesto Igartua Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC Morten Lillemo Department of Plant Sciences, Norwegian University of Life Sciences Marina Martínez‐García Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid Mariona Martínez‐Subirà AGROTECNIO-CERCA Center, Universidad de Lleida Susan McCouch Plant Breeding and Genetics Section, School of Integrative Plant Science, Cornell University Laurie McGhee Colfax-Mingo Community High School Travis Nickols Department of Crop and Soil Science, Oregon State University Nick Peters Department of Plant Pathology, Entomology, and Microbiology, Iowa State University Raymond Porter Haupert Institute for Agricultural Studies, Huntington University Ignacio Romagosa AGROTECNIO-CERCA Center, Universidad de Lleida Anja Karine Ruud Department of Plant Sciences, Norwegian University of Life Sciences Kazuhiro Sato Institute of Plant Science and Resources, Okayama University Silvio Salvi Department of Agricultural and Food Sciences, University of Bologna Giuseppe Sangiorgi Department of Agricultural and Food Sciences, University of Bologna Rebekka Schüller Department of Crop Sciences, University of Illinois at Urbana-Champaign Taner Z. Sen Crop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service José Miguel Soriano AGROTECNIO-CERCA Center, Universidad de Lleida Robert M. Stupar Department of Agronomy and Plant Genetics, University of Minnesota To‐Chia Ting Agronomy Department, Purdue University Kelly Vining Department of Crop and Soil Science, Oregon State University Maria von Korff Institute of Plant Genetics, Heinrich-Heine-Universität Düsseldorf Agatha Walla Institute of Plant Genetics, Heinrich-Heine-Universität Düsseldorf Diane R. Wang Agronomy Department, Purdue University Robbie Waugh Division of Plant Sciences, School of Life Sciences, University of Dundee Roger P. Wise Department of Plant Pathology, Entomology, and Microbiology, Iowa State University Robert Wolfe Agriculture and Agri-Food Canada Eric Yao Crop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service Patrick M. Hayes Department of Crop and Soil Science, Oregon State University The Oregon Wolfe Barley (OWB) mapping population (Reg. no. MP-4, NSL 554937 MAP) is a resource for genetics research and instruction. The OWBs are a set of doubled haploid barley (Hordeum vulgare L.) lines developed at Oregon State University from the F1 of a cross between Dr. Robert Wolfe's dominant and recessive marker stocks. Exhibiting a high level of genetic and phenotypic diversity, the OWBs are used throughout the world as a research tool for barley genetics. To date, these endeavors have led to 56 peer-reviewed publications, as well as three reports in the Barley Genetics Newsletter. At the same time, the OWBs are widely used as an instructor resource at the K–12, undergraduate, graduate, and professional levels. They are currently used at universities and/or institutes in German, Italy, Norway, Spain, and the United States and are currently being developed further for educational use in other countries. Genotype and phenotype data, lesson plans, and seed availability information are available herein and online. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 14 17 2025 Photon-Counting CT Enhances Diagnostic Accuracy in Stable Coronary Artery Disease: A Comparative Study with Conventional CT 6049 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 Shohei Hara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Miyagi 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 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/Objectives: Coronary CT angiography (CCTA) is a cornerstone in evaluating stable coronary artery disease (CAD), but conventional energy-integrating detector CT (EID-CT) has limitations, including calcium blooming and limited spatial resolution. Photon-counting detector CT (PCD-CT) may overcome these drawbacks through enhanced spatial resolution and improved tissue characterization. Methods: In this retrospective, propensity score–matched study, we compared CCTA findings from 820 patients (410 per group) who underwent either EID-CT or PCD-CT for suspected stable CAD. Primary outcomes included stenosis severity, high-risk plaque features, and downstream invasive coronary angiography (ICA) referral and yield. Results: The matched cohorts were balanced in demographics and cardiovascular risk factors (mean age 67 years, 63% male). PCD-CT showed a favorable shift in stenosis severity distribution (p = 0.03). High-risk plaques were detected less frequently with PCD-CT (22.7% vs. 30.5%, p = 0.01). Median coronary calcium scores did not differ (p = 0.60). Among patients referred for ICA, those initially evaluated with PCD-CT were more likely to undergo revascularization (62.5% vs. 44.1%), and fewer underwent potentially unnecessary ICA without revascularization (3.7% vs. 8.0%, p = 0.001). The specificity in diagnosing significant stenosis requiring revascularization was 0.74 with EID-CT and 0.81 with PCD-CT (p = 0.04). Conclusions: PCD-CT improved diagnostic specificity for CAD, reducing unnecessary ICA referrals while maintaining detection of clinically significant disease. This advanced CT technology holds promise for more accurate, efficient, and patient-centered CAD evaluation. 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.

MDPI AG Acta Medica Okayama 2673-6497 5 3 2024 Synthesis and Crystal Structure of Ilmenite-Type Silicate with Pyrope Composition 394 403 EN Takayuki Ishii Institute for Planetary Materials, Okayama University Ryosuke Sinmyo Department of Physics, School of Science and Technology, Meiji University Tomoo Katsura Bavarian Research Institute of Experimental Geochemistry and Geophysics, University of Bayreuth Akimotoite, ilmenite-type MgSiO3 high-pressure polymorph can be stable in the lower-mantle transition zone along average mantle and subducting slab geotherms. Significant amounts of Al2O3 can be incorporated into the structure, having the pyrope (Mg3Al2Si3O12) composition. Previous studies have investigated the effect of Al2O3 on its crystal structure at nearly endmember compositions. In this study, we synthesized high-quality ilmenite-type Mg3Al2Si3O12 phase at 27 GPa and 1073 K by means of a Kawai-type multi-anvil press and refined the crystal structure at ambient conditions using a synchrotron X-ray diffraction data via the Rietveld method to examine the effect of Al2O3. The unit-cell lattice parameters were determined to be a = 4.7553(7) Å, c = 13.310(2) Å, and V = 260.66(6) Å3, with Z = 6 (hexagonal, R3̲ ). The volume of the present phase was placed on the akimotoite-corundum endmember join. However, the refined structure showed a strong nonlinear behavior of the a- and c-axes, which can be explained by Al incorporation into the MgO6 and SiO6 octahedral sites, which are distinctly different each other. Ilmenite-type Mg3Al2Si3O12 phase may be found in shocked meteorites and can be a good indicator for shock conditions at relatively low temperatures of 1027–1127 K. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 17 2025 Anti-HMGB1 Antibody Therapy Ameliorates Spinal Cord Ischemia–Reperfusion Injury in Rabbits 8643 EN Genya Muraoka Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Fujii Department of Translational Research, Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Keyue Liu Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Handong Qiao Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Dengli Wang Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daiki Ousaka Department of Medical Technology, Faculty of Science, Okayama University of Science Susumu Oozawa Division of Medical Safety Management, Safety Management Facility, Okayama University Hospital Shingo Kasahara Department of Cardiovascular Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Nishibori Department of Translational Research and Drug Development, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Spinal cord ischemia–reperfusion (SCI/R) injury remains a major clinical challenge with limited therapeutic options. High-mobility group box 1 (HMGB1), a proinflammatory mediator released during cellular stress, has been implicated in the pathogenesis of ischemia–reperfusion-induced neural damage. In this study, we investigated the neuroprotective potential of the anti-HMGB1 monoclonal antibody (mAb) in a rabbit model of SCI/R injury. Male New Zealand White rabbits were anesthetized and subjected to 11 min of abdominal aortic occlusion using a micro-bulldog clamp following heparinization. Anti-HMGB1 mAb or control IgG was administered intravenously immediately after reperfusion and again at 6 h post-reperfusion. Neurological function was assessed at 6, 24, and 48 h after reperfusion using the modified Tarlov scoring system. The rabbits were euthanized 48 h after reperfusion for spinal cord and blood sampling. Treatment with anti-HMGB1 mAb significantly improved neurological outcomes, reduced the extent of spinal cord infarction, preserved motor neuron viability, and decreased the presence of activated microglia and infiltrating neutrophils. Furthermore, it attenuated apoptosis, oxidative stress, and inflammatory responses in the spinal cord, and helped maintain the integrity of the blood–spinal cord barrier. These findings suggest that anti-HMGB1 mAb may serve as a promising therapeutic agent for SCI/R injury. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1078-8174 31 6 2025 Evaluation of a method to predict positioning errors in orthopantomography using cephalography 103174 EN S. Imajo Division of Radiology, Medical Support Department, Okayama University Hospital M. Honda Division of Radiology, Medical Support Department, Okayama University Hospital Y. Tanabe Faculty of Medicine, Graduate School of Health Sciences, Okayama University Introduction: Various radiographic examinations are used to diagnose diseases and determine treatment plans, and the quality of radiographic images affects diagnostic accuracy. This study assessed the relationship between orthopantomography and cephalometric analysis in predicting positioning errors before orthopantomography. Methods: This study evaluated four human head phantom types and included 300 patients aged ≥18 years who underwent orthopantomography. The correlation between the Frankfort horizontal plane and occlusal plane angles in the orthopantomogram was analyzed. The occlusal plane angle at a Frankfort horizontal plane of 0° was estimated using a linear approximation formula. Frankfort horizontal plane and occlusal plane angles were measured on the cephalograms, and their differences were analyzed for correlation with the occlusal plane angle at a Frankfort horizontal plane of 0° in the corresponding orthopantomograms. The cephalogram’s condylar plane–corpus line angle was also compared with orthopantomogram measurements. Results: Frankfort horizontal and occlusal plane angles demonstrated a strong negative correlation (r < －0.9) in phantom studies and moderate negative correlation (r < －0.4) in clinical orthopantomograms. In the phantoms, the occlusal plane at a Frankfort horizontal of 0° in the orthopantomogram strongly correlated with the difference between the Frankfort horizontal and condylar plane–corpus line angles in the cephalogram. Conclusion: Adjusting patient positioning based on individual skeletal differences and angles may reduce positioning errors and improve image quality. Cephalogram analysis could help determine an appropriate Frankfort plane angle for each patient when acquiring orthopantomograms. Implications for practice: Integrating cephalometric analysis into positioning protocols enhances radiographic accuracy, reduces retakes, and improves diagnostic reliability in clinical positioning. This research could improve image quality by identifying reference indicators for orthopantomography by incorporating data from images other than cephalograms, such as computed tomography and magnetic resonance imaging. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-7257 2025 A case of retrograde colonic intussusception by tubulovillous adenoma EN Michiko Iki 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 Ryohei Shoji 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 Yoshitaka Kondo 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 Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction Retrograde colonic intussusception is a rare condition in adults, often caused by organic lesions such as tumors. Autonomic dysfunction in disorders like multiple system atrophy (MSA) might contribute to its occurrence. Case presentation An 81-year-old bedridden woman with a history of MSA presented with severe abdominal pain and abdominal distension lasting 4 days. She had chronic severe constipation managed with laxatives and manual disimpaction. CT imaging revealed retrograde intussusception of the rectum into the sigmoid colon. Endoscopic reduction was attempted but was unsuccessful due to scope impassability. Emergency laparotomy identified a 4–5 cm tumor at the lead point, and manual reduction resulted in bowel perforation. Hartmann’s procedure with D2 lymphadenectomy was performed. The tumor was histopathologically diagnosed as a tubulovillous adenoma with no malignant features. The patient’s postoperative recovery was uneventful except for a urinary tract infection (Clavien–Dindo Grade II), and she was transferred to a rehabilitation facility on postoperative day 24. Conclusion Failure of reduction by air enema should raise suspicion for retrograde intussusception, warranting prompt surgery if an organic lead point is suspected. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1475-2867 25 1 2025 Precise stratification of prognosis in pancreatic ductal adenocarcinoma patients based on pre- and postoperative genomic information 305 EN Kokichi Miyamoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Toshiaki Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Moriwake Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masashi Kayano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mizuki Morita Department of Biomedical Informatics, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate among all cancers; hence, multidisciplinary treatment is essential for patients with PDAC. Although the resectability status, tumour marker, KRAS circulating tumour DNA (mutKRAS-ctDNA) mutations, and GATA binding 6 (GATA6) expression status are promising prognostic biomarkers, their effective integration before and after surgery remains unclear. Methods In this retrospective cohort study, patients with PDAC who had undergone radical resection were enrolled, and pre- and postoperative independent factors associated with poor prognosis were identified using Cox hazard modelling. Risk stratification systems were developed using the identified prognostic factors and investigated for the ability to predict prognosis. Results A total of 91 patients with PDAC were included (median follow-up duration, 28 months). Borderline resectable or locally advanced cancer at diagnosis, elevated carbohydrate antigen 19–9 (CA19-9) level, and mutKRAS-ctDNA-positive status were identified as independent preoperative factors associated with poor prognosis. The postoperative factors significantly associated with shorter overall survival were low GATA6 expression, elevated CA19-9 level, and mutKRAS-ctDNA-positive status. Finally, the preoperative and postoperative risk scoring systems developed using Cox modelling hazard ratio values could significantly stratify prognosis after curative resection for PDAC. Conclusion A risk stratification system based on liquid biopsy, specialised for each phase (pre- and post-surgery), has been proven to be a useful, simple, and practical prognostic prediction clinical tool to determine the optimal multidisciplinary treatment protocol for PDAC. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1758-5902 18 1 2025 Clinical Impacts of Minimally Invasive Transperineal Abdominoperineal Resection in Crohn's Disease: A Retrospective Analysis e70149 EN Yoshitaka Kondo 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 Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Inokuchi Research Center for Intestinal Health Science, Okayama University Sakiko Hiraoka Department of Gastroenterology and Hepatology, 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 Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Crohn's disease (CD) often leads to complex anorectal complications, posing significant challenges in surgical management. Transperineal abdominoperineal resection (TpAPR) has emerged as a minimally invasive alternative to APR. This study aims to evaluate the safety and efficacy of TpAPR compared to APR in patients with CD. Methods: A retrospective analysis was conducted on 19 CD patients who underwent either minimally invasive TpAPR (n = 11) or APR (n = 8) between 2008 and 2023 from a single institution. The primary outcomes were assessed: intraoperative blood loss, operative time, and surgical site infection (SSI) rates. Results: The minimally invasive TpAPR group exhibited significantly reduced intraoperative blood loss (223 mL vs. 533 mL, p = 0.04) and a lower incidence of SSI rates (36.4% vs. 75%, p = 0.07). Operative time and hospital stay were comparable between groups. Conclusion: Minimally invasive TpAPR demonstrates potential benefits over APR in reducing blood loss and SSI rates in CD patients. Further large-scale studies are warranted to confirm these findings. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1071-2690 2025 S100A8/A9-MCAM signaling promotes gastric cancer cell progression via ERK-c-Jun activation EN Youyi Chen Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine Xu Yang Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine Rie Kinoshita 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 Bo Pan The First Affiliated Hospital, Zhejiang University School of Medicine Fangping Wu School of Pharmaceutical Sciences, Zhejiang Chinese Medical University Xu Zhang Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine Kazumi Sagayama Faculties of Educational and Research Management Field, Okayama University Bei Sun Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences S100 protein family members S100A8 and S100A9 function primarily as a heterodimer complex (S100A8/A9) in vivo. This complex has been implicated in various cancers, including gastric cancer (GC). Recent studies suggest that these proteins play significant roles in tumor progression, inflammation, and metastasis. However, the exact mechanisms by which S100A8/A9 contributes to GC pathogenesis remain unclear. This study investigates the role of S100A8/A9 and its receptor in GC. Immunohistochemical analysis was performed on GC tissue samples to assess the expression of the S100A8/A9 receptor melanoma cell adhesion molecule (MCAM). In vitro transwell migration and invasion assays were used to evaluate the motility and invasiveness of GC cells. Cell proliferation was assessed using a growth assay, and Western blotting (WB) was employed to examine downstream signaling pathways, including ERK and the transcription factor c-Jun, in response to S100A8/A9–MCAM interaction. S100A8/A9 stimulation enhanced both proliferation and migration through MCAM binding in GC cell lines. These cellular events were accompanied by ERK activation and c-Jun induction. Downregulation of MCAM suppressed both ERK phosphorylation and c-Jun expression, highlighting the importance of the S100A8/A9‒MCAM‒ERK‒c-Jun axis in promoting GC progression. These findings indicate that S100A8/A9 contributes to GC progression via MCAM, which activates the ERK‒c-Jun pathway. The S100A8/A9‒signaling axis may represent a novel therapeutic target in GC. 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.

Wiley Acta Medica Okayama 0915-5635 2025 Vendor‐Agnostic Vision Transformer‐Based Artificial Intelligence for Peroral Cholangioscopy: Diagnostic Performance in Biliary Strictures Compared With Convolutional Neural Networks and Endoscopists EN Ryosuke Sato Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Masahiro Tomiya Healthcare Solutions Division, Ryobi Systems Co., Ltd Takayoshi Tanimoto Healthcare Solutions Division, Ryobi Systems Co., Ltd Akimitsu Ohto Healthcare Solutions Division, Ryobi Systems Co., Ltd Kentaro Oki Department of Gastroenterology and Hepatology, Okayama University Hospital Satoshi Kajitani Department of Gastroenterology and Hepatology, Okayama University Hospital Tatsuya Kikuchi Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Yoshiro Kawahara Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Objectives: Accurate diagnosis of biliary strictures remains challenging. This study aimed to develop an artificial intelligence (AI) system for peroral cholangioscopy (POCS) using a Vision Transformer (ViT) architecture and to evaluate its performance compared to different vendor devices, conventional convolutional neural networks (CNNs), and endoscopists. Methods: We retrospectively analyzed 125 patients with indeterminate biliary strictures who underwent POCS between 2012 and 2024. AI models including the ViT architecture and two established CNN architectures were developed using images from CHF-B260 or B290 (CHF group; Olympus Medical) and SpyScope DS or DS II (Spy group; Boston Scientific) systems via a patient-level, 3-fold cross-validation. For a direct comparison against endoscopists, a balanced 440-image test set, containing an equal number of images from each vendor, was used for a blinded evaluation. Results: The 3-fold cross-validation on the entire 2062-image dataset yielded a robust accuracy of 83.9% (95% confidence interval (CI), 80.9–86.7) for the ViT model. The model's accuracy was consistent between CHF (82.7%) and Spy (86.8%, p = 0.198) groups, and its performance was comparable to the evaluated conventional CNNs. On the 440-image test set, the ViT's accuracy of 78.4% (95% CI, 72.5–83.8) was comparable to that of expert endoscopists (82.0%, p = 0.148) and non-experts (73.0%, p = 0.066), with no statistically significant differences observed. Conclusions: The novel ViT-based AI model demonstrated high vendor-agnostic diagnostic accuracy across multiple POCS systems, achieving performance comparable to conventional CNNs and endoscopists evaluated in this study. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 0093-9994 61 5 2025 Impact of SMC Property on Axial-Flux Permanent Magnet Machine in Traction Applications 6848 6860 EN Ren Tsunata Division of Industrial Innovation Sciences Graduate School of Natural Science and Technology, Okayama University Masatsugu Takemoto Division of Industrial Innovation Sciences Graduate School of Natural Science and Technology, Okayama University Jun Imai Division of Industrial Innovation Sciences Graduate School of Natural Science and Technology, Okayama University Tatsuya Saito Sumitomo Electric Industries Ltd. Tomoyuki Ueno Sumitomo Electric Industries Ltd. This paper investigates the impact of soft magnetic composite (SMC) properties on an axial flux permanent magnet machine (AFPM) employing ferrite permanent magnet (PM) in traction applications. In general, the efficiency of an AFPM increases as the iron loss of the SMC decreases. However, the torque and output power of the AFPM also decrease at higher speed above the base speed due to the decrease in magnetic permeability because, typically, when the iron loss of an SMC decreases, the permeability also decreases. In this paper, many virtual SMC materials with different iron loss and permeability are used for finite element analysis of the proposed AFPM in order to clarify the sensitivity to SMC characteristics. First, the impact of the permeability on the torque and output power is investigated because the output power is very important in traction applications. Additionally, the total energy loss of AFPMs employing various SMCs is evaluated using the WLTC driving cycle. Furthermore, accuracy of simulation is evaluated using experiments of downscaled and actual size prototypes employing some SMC materials. Finally, this paper shows the newly developed SMC materials and discusses suitable SMC properties from the perspective of efficiency and output power in traction applications. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 2644-1284 6 2025 Time-Efficient and Practical Design Method for Skewed PMSMs: Integrating Numerical Calculations With Limited 3-D-FEA 1370 1386 EN Ren Tsunata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yu Ichimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Masatsugu Takemoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jun Imai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University This article proposes a time-efficient and practical design method for determining appropriate skew structures for permanent magnet synchronous motors (PMSMs). Various PMSMs use skew to suppress torque ripple, but 3-D finite element analysis (3-D-FEA) is required in order to accurately determine an appropriate structure for skewed PMSMs, resulting in a long analysis time. Therefore, this article constructs a hybrid analysis method that combines numerical calculations and minimal 3-D-FEA. The aim of this method is to be practical and easy to use, even for novice designers, and to accurately and quickly design skewed PMSMs. In this article, the effectiveness of the proposed method is clarified through several case studies, and then, a skewed PMSM designed using the proposed method is verified experimentally. It is also revealed that suppression of voltage harmonics contributes to improving the performance of PMSMs in experiments. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1609-0985 2025 An Alternative Approach Based on Skin Electrical Impedance to Determine Transepidermal Water Loss for Skin Barrier Function Assessments EN Osamu Uehara Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Takao Nakamura Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Purpose: The transepidermal water loss (TEWL) has long been measured as an indicator to assess the skin barrier function in dermatological research and clinical practice. However, practical limitations such as time requirement, environmental sensitivity, and measurement complexity hinder the widespread uptake of conventional TEWL measurements in clinical settings and routine monitoring. Consequently, there is a growing need for rapid, robust, and clinically applicable alternatives to conventional TEWL measurements. Here, we present a simple, non-invasive, and time-efficient method based on the skin electrical impedance for skin barrier function assessments. Methods: The skin electrical impedance, TEWL, stratum corneum (SC) thickness, and SC surface water content of 25 healthy adult participants with no history of dermatological diseases were measured at two adjacent forearm sites: intact site with a normal skin barrier and tape-stripped site with an impaired skin barrier. The measured impedance was used to calculate the SC thickness and surface water content, from which the TEWL was estimated and then compared against the TEWL measured using a Tewameter. The estimation accuracy was evaluated by determining the correlation coefficient (R) and root mean square error (RMSE) between estimated and measured TEWL. Results: A strong correlation (R = 0.891) was observed between estimated and measured TEWL, with an RMSE of 6.05 g/m²/h, indicating high accuracy of the proposed method. Conclusion: This impedance-based method provides accurate estimations of the TEWL, indicating its potential as a practical alternative to conventional TEWL measurements for skin barrier function assessments, particularly in clinical or high-throughput settings. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 17 2025 Augmentation of the Benzyl Isothiocyanate-Induced Antiproliferation by NBDHEX in the HCT-116 Human Colorectal Cancer Cell Line 8145 EN Ruitong Sun Graduate School of Environmental and Life Science, Okayama University Aina Yano Graduate School of Environmental and Life Science, Okayama University Ayano Satoh Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Increased drug metabolism and elimination are prominent mechanisms mediating multidrug resistance (MDR) to not only chemotherapy drugs but also anti-cancer natural products, such as benzyl isothiocyanate (BITC). To evaluate the possibility of combined utilization of a certain compound to overcome this resistance, we focused on glutathione S-transferase (GST)-dependent metabolism of BITC. The pharmacological treatment of a pi-class GST-selective inhibitor, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX), significantly increased BITC-induced toxicity in human colorectal cancer HCT-116 cells. However, NBDHEX unexpectedly increased the level of the BITC–glutathione (GSH) conjugate as well as BITC-modified proteins, suggesting that NBDHEX might increase BITC-modified protein accumulation by inhibiting BITC–GSH excretion instead of inhibiting GST. Furthermore, NBDHEX significantly potentiated BITC-induced apoptosis with the enhanced activation of apoptosis-related pathways, such as c-Jun N-terminal kinase and caspase-3 pathways. These results suggested that combination treatment with NBDHEX may be an effective way to overcome MDR with drug efflux and thus induce the biological activity of BITC at lower doses. 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 Prevalence of Streptococcus mutans harboring the cnm gene encoding cell surface protein Cnm in Japanese children 27047 EN Yuto Suehiro Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Makoto Okuda Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Masatoshi Otsugu Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Marin Ochiai Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Misato Takagi Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Fumikazu Tojo Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Yusuke Mikasa Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Shuhei Naka Department of Pediatric Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Michiyo Matsumoto-Nakano Department of Pediatric Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jinthana Lapirattanakul Department of Oral Microbiology, Faculty of Dentistry, Mahidol University Rena Okawa Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Ryota Nomura Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University Kazuhiko Nakano Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Dental caries is a highly prevalent infectious disease primarily caused by the pathogenic bacterium Streptococcus mutans, which has also been associated with systemic disease. A 120-kDa collagen-binding protein (Cnm) produced by S. mutans contributes to cardiovascular disease pathogenicity. Few studies have addressed the current prevalence of S. mutans and the cnm gene in Japanese children or examined caries pathology in relation to cnm presence. Here, we investigated the prevalence of S. mutans and the distribution of cnm-positive S. mutans among 490 children who visited two university hospitals in Japan. The caries experience index (dmft/DMFT) was calculated, and the collagen-binding ability of cnm-positive S. mutans strains was assessed. S. mutans was isolated from the oral cavities of 158 patients (36.8%); 10.1% (16/158) harbored cnm-positive S. mutans. When caries experience indices were compared across dentitions, patients harboring cnm-positive strains had significantly higher dmft/DMFT scores than those with cnm-negative strains (P < 0.05). Additionally, a positive correlation was observed between the collagen-binding capacity of cnm-positive S. mutans and the dmft/DMFT score (r = 0.601, P < 0.05). These findings suggest that cnm contributes to caries progression through collagen-mediated adherence to tooth surfaces. The presence of cnm-positive S. mutans may represent a risk factor for increased caries susceptibility in children. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 2 2025 令和６年度岡山医学会賞　がん研究奨励賞（林原賞・山田賞） 49 51 EN Yuto Naoi Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 2 2025 令和６年度岡山医学会賞　総合研究奨励賞（結城賞） 46 48 EN Hitoshi Urakami Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2227-9059 12 10 2024 Development and Characterization of a Three-Dimensional Organotypic In Vitro Oral Cancer Model with Four Co-Cultured Cell Types, Including Patient-Derived Cancer-Associated Fibroblasts 2373 EN Yuka Aizawa Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Kenta Haga Division of Reconstructive Surgery for Oral and Maxillofacial Region, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Nagako Yoshiba Department of Oral Health and Welfare, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Witsanu Yortchan Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Sho Takada Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Rintaro Tanaka Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Eriko Naito Division of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Tatsuya Abé Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Satoshi Maruyama Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Manabu Yamazaki Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Jun-ichi Tanuma Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Kazuyo Igawa Neutron Therapy Research Center, Okayama University Kei Tomihara Division of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Shinsaku Togo Department of Respiratory Medicine, Graduate School of Medicine, Juntendo University Kenji Izumi Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Background/Objectives: Cancer organoids have emerged as a valuable tool of three-dimensional (3D) cell cultures to investigate tumor heterogeneity and predict tumor behavior and treatment response. We developed a 3D organotypic culture model of oral squamous cell carcinoma (OSCC) to recapitulate the tumor–stromal interface by co-culturing four cell types, including patient-derived cancer-associated fibroblasts (PD-CAFs). Methods: A stainless-steel ring was used twice to create the horizontal positioning of the cancer stroma (adjoining normal oral mucosa connective tissue) and the OSCC layer (surrounding normal oral mucosa epithelial layer). Combined with a structured bi-layered model of the epithelial component and the underlying stroma, this protocol enabled us to construct four distinct portions mimicking the oral cancer tissue arising in the oral mucosa. Results: In this model, α-smooth muscle actin-positive PD-CAFs were localized in close proximity to the OSCC layer, suggesting a crosstalk between them. Furthermore, a linear laminin-γ2 expression was lacking at the interface between the OSCC layer and the underlying stromal layer, indicating the loss of the basement membrane-like structure. Conclusions: Since the specific 3D architecture and polarity mimicking oral cancer in vivo provides a more accurate milieu of the tumor microenvironment (TME), it could be crucial in elucidating oral cancer TME. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 15 2025 The Concept of “Platinum Sensitivity” in Endometrial Cancer 2557 EN Shoji Nagao Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Fujikawa Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryoko Imatani Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Tani Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirofumi Matsuoka Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoyuki Ida Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junko Haraga Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikako Ogawa Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Nakamura Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hisashi Masuyama Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The concept of “platinum sensitivity” has long guided prognostic assessment and treatment selection in recurrent ovarian cancer. However, the emergence of targeted agents, such as bevacizumab and poly (ADP-ribose) polymerase inhibitors, has complicated its clinical utility. In contrast, emerging evidence suggests that platinum sensitivity may also be applicable to recurrent endometrial cancer. As in ovarian cancer, a prolonged platinum-free interval (PFI) in recurrent endometrial cancer is associated with an improved efficacy of subsequent platinum-based chemotherapy. The PFI is linearly correlated with the response rate to platinum re-administration, progression-free survival, and overall survival. Patients are typically classified as having platinum-resistant or platinum-sensitive disease based on a PFI cutoff of 6 or 12 months. However, unlike in ovarian cancer―where the duration of response to second-line platinum-based chemotherapy rarely exceeds the prior PFI (~3%)―approximately 30% of patients with recurrent endometrial cancer exhibit a sustained response to platinum rechallenge that extends beyond their preceding PFI. Despite the incorporation of immune checkpoint inhibitors into the treatment landscape of endometrial cancer, the role of platinum sensitivity in clinical decision-making―particularly regarding treatment sequencing and drug selection―remains a critical and unresolved issue. Further research is warranted to elucidate the mechanisms underlying platinum resistance and to guide optimal therapeutic strategies. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1076-0296 31 2025 Activated Clotting Time Requires Adaptation Across Altered Measurement Devices: Determination of Appropriate Range During Atrial Fibrillation Ablation EN Haruna Sakanoue Department of Nursing, Okayama Heart Clinic Hirosuke Yamaji Heart Rhythm Center, Okayama Heart Clinic Sayaka Okamoto Department of Nursing, Okayama Heart Clinic Kumi Okano Department of Nursing, Okayama Heart Clinic Yuka Fujita Department of Nursing, Okayama Heart Clinic Shunichi Higashiya Heart Rhythm Center, Okayama Heart Clinic Takashi Murakami Heart Rhythm Center, Okayama Heart Clinic Satoshi Hirohata Department of Medical Technology, Okayama University Graduate School of Health Sciences Shozo Kusachi Department of Medical Technology, Okayama University Graduate School of Health Sciences Background: Methods for measuring activated clotting time (ACT) are not yet standardized. Objectives: To adjust and compare values between two measurement systems and to optimize ACT during atrial fibrillation (AF) ablation. Methods: Two systems were compared: electromagnetic detection using a rotating tube (EM system; Hemochron Response) and photo-optical detection using a cartridge immersed in blood (PO system; ACT CA-300TM). Results: ACT was measured simultaneously in 124 instances in 53 patients before and during AF ablations using both methods. A linear regression analysis showed ACT (EM system) = 1.19 × ACT (PO system) + 9.03 (p < .001, r = 0.90). Bland–Altman plots indicated an average difference of 50 s between the two systems. In 3364 ACT measurements from 1161 ablations, the EM system recorded a mean ACT of 320 ± 44 s (range 156-487 s). Estimating the target range as mean ± 1 SD range, the EM system's range was 275-365 s, in 5-s increments. The pre-ablation ACT measured on the EM system was 143 ± 28 s (115-170 s). Cardiac tamponade occurred in 4 out of 2085 ablations (0.19%) over 5 years, with ACT values ranging from 330 to 391 s on the EM system. Based on these findings, the estimated optimal ACT range for the PO system was adjusted to 225-300 s to align with the EM system's range of 275-365 s. Conclusions: ACT target ranges should be system-specific, and direct extrapolation between devices is not recommended. Adjustment is clinically necessary when switching systems. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0360-3199 140 2025 Advances in filler-crosslinked membranes for hydrogen fuel cells in sustainable energy generation 745 776 EN Aminul Islam Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Mamun Shahriar Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Md. Tarekul Islam Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology Siow Hwa Teo Industrial Chemistry Program, Faculty of Science and Natural Resources, Universiti Malaysia Sabah M. Azizur R. Khan Department of Chemistry, Jashore University of Science and Technology Yun Hin Taufiq-Yap Catalysis Science and Technology Research Centre, Faculty of Science, Universiti Putra Malaysia Suman C. Mohanta Department of Chemistry, Jashore University of Science and Technology Ariyan Islam Rehan Department of Chemistry, School of Science, The University of Tokyo Adiba Islam Rasee Department of Chemistry, Graduate School of Science, Osaka University Khadiza Tul Kubra Department of Chemistry, Graduate School of Science, Osaka University Md. Munjur Hasan Department of Chemistry, Graduate School of Science, Osaka University Md. Shad Salman Institute for Chemical Research, Kyoto University R.M. Waliullah Institute for Chemical Research, Kyoto University Md. Nazmul Hasan Department of Chemistry, School of Science, The University of Tokyo Md. Chanmiya Sheikh Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tetsuya Uchida Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Mrs Eti Awual Institute for Chemical Research, Kyoto University Mohammed Sohrab Hossain Department of Chemistry, Graduate School of Science, Osaka University Hussein Znad Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University Md. Rabiul Awual Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University Fuel cell membranes can be used in various ways to achieve zero-emission transport and energy systems, which offer a promising way to power production due to their higher efficiency compared to the internal combustion engine and the eco-environment. Perfluoro sulfonic acid membranes used for proton exchange membranes (PEMs) have certain drawbacks, like higher fuel permeability and expense, lower mechanical and chemical durability, and proton conductivity under low humidity and above 80 °C temperature. Researchers have drawn their attention to the production of polymer electrolyte membranes with higher proton conductivity, thermal and chemical resilience, maximum power density, lower fuel permeability, and lower expense. For sustainable clean energy generation, a review covering the most useful features of advanced material-associated membranes would be of great benefit to all interested communities. This paper endeavors to explore several types of novel inorganic fillers and crosslinking agents, which have been incorporated into membrane matrices to design the desired properties for an advanced fuel cell system. Membrane parameters such as proton conductivity, the ability of H2 transport, and the stability of the membrane are described. Research directions for developing fuel cell membranes are addressed based on several challenges suggested. The technological advancement of nanostructured materials for fuel cell applications is believed to significantly promote the future clean energy generation technology in practice. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1438-4957 2025 From sewage sludge to agriculture: governmental initiatives, technologies, and sustainable practices in Japan EN Thu Huong Nguyen Graduate School of Engineering, Kyoto University Taku Fujiwara Graduate School of Engineering, Kyoto University Hiromasa Yamashita Water Supply and Sewerage Department, National Institute for Land and Infrastructure Management Hironori Togawa Water Supply and Sewerage Department, National Institute for Land and Infrastructure Management Haruo Miyake R & D Department, Japan Sewage Works Agency Masako Goto 1St Research Department, Japan Institute of Wastewater Engineering and Technology Hideaki Nagare Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Masato Nakamura Institute for Rural Engineering, NARO Fumiko Oritate Institute for Rural Engineering, NARO Hirotaka Ihara Institute for Agro-Environmental Sciences, NARO Morihiro Maeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sewage sludge (SS), an underutilized but valuable resource for agriculture, contains essential nutrients, such as phosphorus. In Japan, where dependence on imported fertilizers is high and global price fluctuations persist, using SS as fertilizer presents a sustainable alternative aligned with circular economy goals. This review analyzes Japan’s current efforts to repurpose SS, focusing on technological developments and key policy initiatives that promote safe and effective application. Selective phosphorus recovery technologies mitigate resource depletion, while holistic approaches, such as composting and carbonization, maximize sludge utilization for agricultural applications. Government-led initiatives, including public awareness campaigns, quality assurance standards and research support, have facilitated the adoption of sludge-based fertilizers. To contextualize Japan’s position, international trends, particularly in the EU, are also examined. These comparisons reveal both common strategies and areas for policy and technological advancement, especially regarding regulation of emerging contaminants. By integrating national case studies with global perspectives, the study offers insights into the economic, environmental, and social benefits of SS reuse, contributing to Japan’s goals of resource self-sufficiency and carbon neutrality, while also informing broader sustainable agriculture transitions worldwide. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 14 2025 Definitions of, Advances in, and Treatment Strategies for Breast Cancer Oligometastasis 2406 EN Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Yuki Fujiwara Department of Breast and Endocrine Surgery, Okayama University Hospital Maya Kosaka Department of Breast and Endocrine Surgery, Okayama University Hospital Yuki Narahara Department of Breast and Endocrine Surgery, Okayama University Hospital Kento Fujii Department of Breast and Endocrine Surgery, Okayama University Hospital Reina Maeda Department of Breast and Endocrine Surgery, Okayama University Hospital Shutaro Kato Department of Breast and Endocrine Surgery, Okayama University Hospital Asuka Mimata Department of Breast and Endocrine Surgery, Okayama University Hospital Ryo Yoshioka Department of Breast and Endocrine Surgery, Okayama University Hospital Chihiro Kuwahara Department of Breast and Endocrine Surgery, Okayama University Hospital Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Tsuguo Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Maki Tanioka Department of Breast and Endocrine Surgery, Okayama University Hospital Oligometastasis represents a clinically relevant state of limited metastatic disease that could be amenable to selected local therapies in carefully chosen patients. Although initial trials such as SABR-COMET demonstrated a survival benefit with aggressive local treatment, breast cancer was underrepresented. Subsequent breast cancer-specific trials, including NRG-BR002, failed to show a clear survival benefit, highlighting uncertainties and the need for further refinement in patient selection and integration with systemic approaches. The definitions of oligometastasis continue to evolve, incorporating radiological, clinical, and biological features. Advances in imaging and molecular profiling suggest that oligometastatic breast cancer might represent a distinct biological subtype, with potential biomarkers including PIK3CA mutations and YAP/TAZ expression. Organ-specific strategies using stereotactic radiotherapy, surgery, and proton therapy have shown favorable local control in certain settings, though their impact on the overall survival remains under investigation. Emerging techniques, including circulating tumor DNA (ctDNA) analysis, are being explored to improve patient selection and disease monitoring. Ongoing trials may provide further insight into the role of local therapy, particularly in hormone receptor-positive or HER2-positive subtypes. Local and systemic strategies need to be carefully coordinated to optimize the outcomes. This review summarizes the current definitions of and evidence and therapeutic considerations for oligometastatic breast cancer and outlines potential future directions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2090-4762 56 1 2025 Evaluating a discretized data acquisition method for couch modeling to streamline the commissioning process of radiological instruments 64 EN Syouta Tomimoto Department of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama University Yusuke Saeki Department of Radiological Technology, Kawasaki Medical School Hospital Okihiro Motoda Department of Radiological Technology, Kawasaki Medical School Hospital Masato Tanaka Department of Radiological Technology, Kawasaki Medical School Hospital Syouki Tsumoto Department of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama University Hana Nishikawa Department of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama University Yuki Miyashima Department of Radiological Technology, Kawasaki Medical School Hospital Makiko Higuchi Department of Radiological Technology, Kawasaki Medical School Hospital Tadashi Tani Department of Radiological Technology, Kawasaki Medical School Hospital Kuniaki Katsui Department of Radiology, Kawasaki Medical School Yoshinori Tanabe Department of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama University Background The commissioning of radiotherapy treatment planning system (RTPS) involves many time-consuming tests to maintain consistency between actual and planned dose. As the number of new technologies and peripheral devices increases year by year, there is a need for time-efficient and accurate commissioning of radiation therapy equipment. Couch modeling is one type of commissioning, and there are no recommended values for CT due to differences in equipment calibration between facilities. This study evaluated the optimal electron density (ED) for the couch using discretized gantry angles. Results All discrete-angle groups showed a high correlation between the surface ED and dose difference between the actual and planned doses (|r|> 0.9). AcurosXB did not demonstrate a significant correlation between dose differences and each energy. For a small number of discretized gantry groups, the optimal couch modeling results revealed several combinations of surface and interior ED with the same score. Upon adding all couch thickness scores, all energy scores, and both algorithm scores, the optimal surface and interior EDs with the highest score across all couch thicknesses were 0.4 and 0.07, respectively. Conclusions The optimal couch surface ED dose difference trend was identified, and the effectiveness indicated using the dose difference score from discrete-angle couch modeling. Using this method, couch modeling can be evaluated in a highly precise and quick manner, which helps in the commissioning of complicated linear accelerator and radiological treatment plans. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0002-8177 156 2 2025 The greater palatine nerve and artery both supply the maxillary teeth 151 159.e1 EN Joe Iwanaga Division of Gross and Clinical Anatomy, Department of Anatomy, School of Medicine, Kurume University Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Muralidharan Anbalagan Department of Structural and Cellular Biology, School of Medicine, Tulane University Binghao Zou Department of Structural and Cellular Biology, School of Medicine, Tulane University Taku Toriumi Department of Anatomy, School of Life Dentistry at Niigata, The Nippon Dental University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University R. Shane Tubbs University of Queensland Background. It is generally accepted that the greater palatine nerve and artery supply the palatal mucosa, gingiva, and glands, but not the bone or tooth adjacent to those tissues. When the bony palate is observed closely, multiple small foramina are seen on the palatal surface of the alveolar process. The authors hypothesized that the greater palatine nerve and artery might supply the maxillary teeth via the foramina on the palatal surface of the alveolar process and the superior alveolar nerve and artery. The authors aimed to investigate the palatal innervation and blood supply of the maxillary teeth. Methods. Eight cadaveric maxillae containing most teeth or alveolar sockets were selected. The mean age at the time of death was 82.4 years. The samples were examined with colored water injection, latex injection, microcomputed tomography with contrast dye, gross anatomic dissection, and histologic observation. Results. Through both injection studies and microcomputed tomographic analysis, the authors found that the small foramina on and around the greater palatine groove connected to the alveolar process and tooth sockets. The small foramina in the greater palatine and incisive canal also continued inside the alveolar process and the tooth sockets. Conclusions. The alveolar branches of the greater palatine nerve and artery as well as the nasopalatine nerve and sphenopalatine artery supply maxillary teeth, alveolar bone, and periodontal tissue via the palatal alveolar foramina with superior alveolar nerves and arteries. Practical Implications. This knowledge is essential for dentists when administering local anesthetic to the maxillary teeth and performing an osteotomy. Anatomic and dental textbooks should be updated with this new knowledge for better patient care. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2692-4609 4 1 2023 Alcohol consumption, multiple Lugol‐voiding lesions, and field cancerization e261 EN Chikatoshi Katada Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Tetsuji Yokoyama Department of Health and Promotion, National Institute of Public Health Tomonori Yano Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East Haruhisa Suzuki Endoscopy Division, National Cancer Center Hospital Yasuaki Furue Department of Gastroenterology, Kitasato University School of Medicine Keiko Yamamoto Division of Endoscopy, Hokkaido University Hospital Hisashi Doyama Department of Gastroenterology, Ishikawa Prefectural Central Hospital Tomoyuki Koike Division of Gastroenterology, Tohoku University Graduate School of Medicine Masashi Tamaoki Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Noboru Kawata Division of Endoscopy, Shizuoka Cancer Center Motohiro Hirao Department of Surgery, National Hospital Organization Osaka National Hospital Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Ogata Department of Gastroenterology, Kanagawa Cancer Center Atsushi Katagiri Department of Medicine, Division of Gastroenterology, Showa University Hospital Takenori Yamanouchi Department of Gastroenterology, Kumamoto Regional Medical Center Hirofumi Kiyokawa Division of Gastroenterology, Department of Internal Medicine, St. Marianna University School of Medicine Hirofumi Kawakubo Department of Surgery, Kawasaki Municipal Kawasaki Hospital Maki Konno Department of Gastroenterology, Tochigi Cancer Center Akira Yokoyama Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Shinya Ohashi Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Yuki Kondo Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Yo Kishimoto Department of Otolaryngology-Head and Neck Surgery, Kyoto University Hospital Koichi Kano Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine Kanae Mure Department of Public Health, Wakayama Medical University School of Medicine Ryuichi Hayashi Department of Head and Neck Surgery, National Cancer Center Hospital East Hideki Ishikawa Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine Akira Yokoyama Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center Manabu Muto Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University The development of multiple squamous cell carcinomas (SCC) in the upper aerodigestive tract, which includes the oral cavity, pharynx, larynx, and esophagus, is explained by field cancerization and is associated with alcohol consumption and cigarette smoking. We reviewed the association between alcohol consumption, multiple Lugol-voiding lesions, and field cancerization, mainly based on the Japan Esophageal Cohort study. The Japan Esophageal Cohort study is a prospective cohort study that enrolled patients with esophageal SCC after endoscopic resection. Enrolled patients received surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months. The Japan Esophageal Cohort study showed that esophageal SCC and head and neck SCC that developed after endoscopic resection for esophageal SCC were associated with genetic polymorphisms related to alcohol metabolism. They were also associated with Lugol-voiding lesions grade in the background esophageal mucosa, the score of the health risk appraisal model for predicting the risk of esophageal SCC, macrocytosis, and score on alcohol use disorders identification test. The standardized incidence ratio of head and neck SCC in patients with esophageal SCC after endoscopic resection was extremely high compared to the general population. Drinking and smoking cessation is strongly recommended to reduce the risk of metachronous esophageal SCC after treatment of esophageal SCC. Risk factors for field cancerization provide opportunities for early diagnosis and minimally invasive treatment. Lifestyle guidance of alcohol consumption and cigarette smoking for esophageal precancerous conditions, which are endoscopically visualized as multiple Lugol-voiding lesions, may play a pivotal role in decreasing the incidence and mortality of esophageal SCC. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0169-5002 207 2025 Intracranial activity of sotorasib vs docetaxel in pretreated KRAS G12C-mutated advanced non-small cell lung cancer from a global, phase 3, randomized controlled trial 108683 EN Anne-Marie C. Dingemans Erasmus MC Cancer Institute, University Medical Center Konstantinos Syrigos Sotiria General Hospital Lorenzo Livi Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence Astrid Paulus Centre Hospitalier Universitaire de Liège Sang-We Kim Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine Yuanbin Chen The Cancer & Hematology Centers of Western Michigan Enriqueta Felip Medical Oncology Department, Vall d’Hebron University Hospital Frank Griesinger Pius-Hospital Oldenburg Kadoaki Ohashi Okayama University Hospital Gerard Zalcman Hospital Bichat-Claude Bernard Brett G.M. Hughes The Prince Charles Hospital, University of Queensland Jens Benn Sørensen Rigshospitalet Normand Blais Department of Medicine, Centre Hospitalier de l’Université de Montréal Carlos G.M. Ferreira Oncoclinicas Colin R. Lindsay Division of Cancer Sciences, University of Manchester and The Christie NHS Foundation Trust Rafal Dziadziuszko University Clinical Centre, Medical University of Gdansk Patrick J. Ward SCRI at OHC Cynthia Chinedu Obiozor Amgen Inc. Yang Wang Amgen Inc. Solange Peters Lausanne University Hospital Objectives: To assess the efficacy and safety of sotorasib in patients with brain metastases using data from the phase 3 CodeBreaK 200 study, which evaluated sotorasib in adults with pretreated advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC). Materials and methods: Patients with KRAS G12C-mutated NSCLC who progressed after platinum-based chemotherapy and checkpoint inhibitor therapy were randomized 1:1 to sotorasib or docetaxel. An exploratory post-hoc analysis evaluated central nervous system (CNS) progression-free survival (PFS) and time to CNS progression in patients with treated and stable brain metastases at baseline. Measures were assessed by blinded independent central review per study-modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Results: Of the patients randomly assigned to receive sotorasib (n=171) or docetaxel (n=174), baseline CNS metastases were present in 40 (23%) and 29 (17%) patients, respectively. With a median follow-up of 20.0 months for this patient subgroup, median CNS PFS was longer with sotorasib compared with docetaxel (9.6 vs 4.5 months; hazard ratio, 0.43 [95% CI, 0.20–0.92]; P=0.02). Among patients with baseline treated CNS lesions of ≥10 mm, the percentage of patients who achieved CNS tumor shrinkage of ≥30% was two-fold higher with sotorasib than docetaxel (33.3% vs 15.4%). Treatment-related adverse events among patients with CNS lesions at baseline were consistent with those of the overall study population. Conclusions: These results suggest intracranial activity with sotorasib complements the overall PFS benefit observed with sotorasib vs docetaxel, with safety outcomes similar to those in the general CodeBreaK 200 population. Clinical trials registration number: NCT04303780. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0815-9319 40 6 2025 Real-World Effectiveness and Safety of Vedolizumab in Patients ≥ 70 Versus < 70 Years With Ulcerative Colitis: Multicenter Retrospective Study 1435 1445 EN Tadakazu Hisamatsu Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Taku Kobayashi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital Satoshi Motoya Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital Toshimitsu Fujii Department of Gastroenterology and Hepatology, Institute of Science Tokyo Reiko Kunisaki Inflammatory Bowel Disease Center, Yokohama City University Medical Center Tomoyoshi Shibuya Department of Gastroenterology, Juntendo University School of Medicine Minoru Matsuura Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Sakiko Hiraoka Ken Takeuchi Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha Hiroshi Yasuda Department of Gastroenterology, St. Marianna University School of Medicine Kaoru Yokoyama Department of Gastroenterology, Kitasato University School of Medicine Noritaka Takatsu Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital Atsuo Maemoto Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital Toshiyuki Tahara Department of Gastroenterology, Saiseikai Utsunomiya Hospital Keiichi Tominaga Department of Gastroenterology, Dokkyo Medical University Masaaki Shimada Department of Gastroenterology, NHO Nagoya Medical Center Nobuaki Kuno Department of Gastroenterology and Medicine, Fukuoka University Hospital Jovelle L. Fernandez Japan Medical Office, Takeda Pharmaceutical Company Limited Lisa Hirose Japan Medical Office, Takeda Pharmaceutical Company Limited Kaori Ishiguro Japan Medical Office, Takeda Pharmaceutical Company Limited Mary Cavaliere Japan Medical Office, Takeda Pharmaceutical Company Limited Toshifumi Hibi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital Background and Aim: Vedolizumab (VDZ) is often used in older patients with ulcerative colitis (UC) in clinical practice; however, real-world evidence is still limited, including in those with late-onset UC. Methods: This post hoc analysis of a multicenter, retrospective, observational chart review, enrolling 370 patients with UC receiving VDZ between December 2018 and February 2020, compared effectiveness and safety of VDZ among patients ≥ 70 (n = 40) versus < 70 years (n = 330), and among patients ≥ 70 years with and without late-onset UC (age at disease onset: ≥ 70 [n = 13] versus < 70 years [n = 26]). Results: There were no differences between patients ≥ 70 and < 70 years in clinical remission rates (week 6: 57.5% vs. 47.6%, p = 0.9174; week 14: 62.5% vs. 54.8%, p = 0.1317; week 54: 47.5% vs. 46.4%, p = 0.8149), primary nonresponse (10.0% vs. 15.5%, p = 0.6248), loss of response (12.5% vs. 9.4%, p = 0.5675), or overall safety. Among patients ≥ 70 years, the incidence of adverse drug reactions was numerically greater in those with concomitant corticosteroids than in those without. For older patients with and without late-onset UC, week 54 remission rates were 23.1% versus 57.7% (p = 0.0544); surgery was reported in 3/13 versus 2/26 patients and hospitalization in 5/13 versus 6/26 patients. One death was reported in patients with late-onset UC. Conclusions: VDZ effectiveness and safety were similar in patients ≥ 70 and < 70 years; VDZ may be a suitable treatment option for patients ≥ 70 years with UC. Patients with late-onset UC tended to have more frequent surgery/hospitalization and lower effectiveness than those without, possibly necessitating greater caution when using VDZ. Trial Registration: Japanese Registry of Clinical Trials registration number: jRCT-1080225363 No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-1068 35 1 2024 Association between lower limb muscle strength and musculoskeletal ambulation disability symptom complex in patients with medial meniscus posterior root tears 40 EN Mikao Fukuba Department of Physical Medicine and Rehabilitation, Okayama University Hospital Koki Kawada 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 Yoshimi Katayama Department of Physical Medicine and Rehabilitation, Okayama University Hospital Masanori Hamada Department of Physical Medicine and Rehabilitation, Okayama University Hospital Toshifumi Ozaki 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 In this study, we aimed to evaluate the changes in and the relationship between lower limb muscle strength and physical function before and after medial meniscus posterior root (MMPR) repair. Methods Thirty-three patients who underwent MMPR repair were evaluated. Pain was evaluated with the numerical rating scale (NRS), and knee flexor/extensor muscle strength was assessed using a handheld dynamometer. Physical function was evaluated using a timed up and go (TUG) test. The NRS, knee flexor/extensor muscle strength, and TUG were compared preoperatively and 1 year postoperatively using the Wilcoxon signed-rank test. The correlation of patient characteristics, NRS score, knee flexor/extensor muscle strength, and preoperative TUG with the postoperative TUG was analyzed using Spearman’s correlation coefficient. Results NRS (3.5 ± 2.1 to 0.1 ± 0.5 points), knee flexor strength (111.9 ± 50.2 to 146.7 ± 51.5 Nm), knee extensor strength (181.9 ± 92.8 to 256.9 ± 107.1 Nm), and TUG (12.3 ± 5.7 to 9.2 ± 2.2 s) all improved significantly from preoperatively to 1 year postoperatively (p < 0.001). The postoperative TUG was negatively correlated with the preoperative TUG (r = 0.578, p < 0.001), preoperative knee flexor muscle strength (r = － 0.355, p = 0.042), preoperative knee extensor muscle strength (r = － 0.437, p = 0.010), and postoperative knee extensor muscle strength (r = － 0.478, p = 0.004). Conclusion In patients undergoing MMPR repair, surgery and rehabilitation significantly improve lower limb muscle strength and physical function. There was a significant correlation between lower limb muscle strength and TUG, and further strengthening of the lower limb muscles from the preoperative level is desirable to improve patients’ physical function further. Level of evidence IV. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 A Case of Surgical Treatment for a Large Pulmonary Artery Aneurysm with a Quadricuspid Pulmonary Valve 317 320 EN Kei Morioka Department of Cardiovascular Surgery, Okayama University Hospital Yosuke Kuroko Department of Cardiovascular Surgery, Okayama University Hospital Sachiko Kadowaki Department of Cardiovascular Surgery, Okayama University Hospital Junko Kobayashi Department of Cardiovascular Surgery, Okayama University Hospital Yasuhiro Kotani Department of Cardiovascular Surgery, Okayama University Hospital Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Hospital Case Report 10.18926/AMO/69160 A 65-year-old man was referred to our hospital for the annual assessment of the diameter and dilation of a pulmonary artery (PA) aneurysm. He had a small ventricular septal defect (VSD) that had closed naturally. Echocardiography revealed a dilated main PA, mild pulmonary regurgitation and no VSD. Computed tomography confirmed the dilation of the main PA (66.7×47.8 mm), right PA (37.1×32.9 mm), and left PA (36.7×34.0 mm). The patient underwent pulmonary artery replacement using a prosthetic vascular graft. A quadricuspid pulmonary valve was identified intraoperatively. Early surgical intervention could help to prevent rupture and dissection of PA aneurysms. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Mimicking Contralateral Pneumothorax during Thoracoscopic Bullectomy Associated with Intraoperative Hyperinflation of a Large Bulla in an Obese Patient 311 315 EN Kei Matsubara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Kei Matsubara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Yutaka Hirano Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Toshiya Fujiwara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Case Report 10.18926/AMO/69159 A 55-year-old obese Japanese male with left pneumothorax presented to our hospital. Bilateral pulmonary emphysema was confirmed. Persistent air leakage was observed, and a thoracoscopic bullectomy was performed. Although the thoracoscopic bullectomy was completed uneventfully, pre-extubation chest X-ray imaging indicated hyper-lucency occupying the right upper part of the thoracic cavity, suggesting right-sided pneumothorax. CT imaging indicated a right-upper-lobe expanded bulla. Extubation was performed, and the hyperinflated bulla gradually deflated. Careful management of bulla expansion and respiratory status may be necessary for patients with obesity and large bullae, especially in one-lung ventilation cases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 A Rare Presentation of Pneumonic-Type Adenocarcinoma Hidden behind Empyema 305 309 EN Satoru Senoo Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Eito Niman Department of General Thoracic Surgery, National Hospital Organization Fukuyama Medical Center Ryoko Tsuji Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Kohei Takata Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Shunsuke Matsumori Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Fumika Murano Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Yuka Sugisaki Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Hiroki Omori Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Akihiko Taniguchi Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Rika Omote Department of Diagnostic Pathology, National Hospital Organization Fukuyama Medical Center Eiki Ichihara Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Kenji Takahashi Department of General Thoracic Surgery, National Hospital Organization Fukuyama Medical Center Toshiaki Okada Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Case Report 10.18926/AMO/69158 Pneumonic-type adenocarcinoma (P-ADC) can closely mimic pneumonia. We report a P-ADC initially diagnosed as pneumonia which developed into a pulmonary abscess and empyema. A 50-year-old Japanese male diagnosed with pneumonia, pulmonary abscess, and empyema was administered antibiotics and a chest tube for drainage, which improved his symptoms and blood test results. However, chest computed tomography showed an enlarged infiltrative shadow. The patient underwent bronchoscopy and was diagnosed with an adenocarcinoma. This case highlights the importance of considering P-ADC in differential diagnoses when a pneumonia-like shadow enlarges post-empyema treatment. Diagnostic and clinical tests, e.g., bronchoscopy, should be performed in such cases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Pulmonary Calcium Phosphate Cement Embolism After Percutaneous Vertebroplasty for Thoracic Vertebrae Fractures 299 303 EN Ruibin Feng Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University Bikang Zhu Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University Danyun Wei Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University Dingjiao Zhu Department of Radiology, the Ninth Affiliated Hospital of Guangxi Medical University Cairu Chen Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University Case Report 10.18926/AMO/69157 Pulmonary cement embolism (PCE) is a rare but severe complication following percutaneous vertebroplasty (PVP). Calcium phosphate cement (CPC) has emerged as an alternative to traditional materials for vertebral augmentation. There appear to be no established guidelines for managing symptomatic PCE, and there is scarce literature on CPC embolisms. This is a first report of a case of pulmonary CPC embolism following PVP. The patient, a 63-year-old Chinese female, was administered anticoagulant treatment and achieved a satisfactory outcome. Her case highlights the severe potential morbidity associated with CPC leakage and emphasizes the efficacy of anticoagulant treatment for managing pulmonary CPC embolisms. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Effectiveness of Pallidal Stimulation for Dystonic Storm and Subsequent Ssevere Posterior Reversible Encephalopathy Syndrome in a Patient with GNAO1 Variant 293 297 EN Koji Kawai Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsuya Sasaki Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shun Tanimoto Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoya Saijo Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Sasada Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Akiyama Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Hiraide Department of Biochemistry, Hamamatsu University School of Medicine Hirotomo Saitsu Department of Biochemistry, Hamamatsu University School of Medicine Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/69156 GNAO1 variant affects primarily the brain and neurodevelopment, leading to a range of motor disorders including seizures beginning in infancy and involuntary movements such as dyskinesia and dystonia. Our patient, a 15-year-old Japanese female, began exhibiting involuntary movements at age 4. A de novo missense mutation (NM_020988.3: c.228C>G, NP_066268.1: p.(Asn76Lys)) in the GNAO1 gene was identified when the patient was 15, and during the same year she developed influenza pneumonia, accompanied by dystonic storm. She required intensive care with mechanical ventilation and underwent a tracheostomy. She also developed posterior reversible encephalopathy syndrome. Globus pallidal stimulation was administered, leading to an improvement in the dystonic storm. Early consideration of globus pallidal stimulation is recommended when treating difficult-to-manage dystonic storms. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Long-Term Survival Following Extended Cholecystectomy for Synchronous Gallbladder and Regional Lymph Node Metastasis of Lung Adenocarcinoma, with Subsequent Pulmonary Lobectomy 279 282 EN Mao Yoshikawa Department of General Thoracic Surgery, Okayama University Hospital Hiroyuki Tao Department of Thoracic Surgery, Japanese Red Cross Society Himeji Hospital Case Report 10.18926/AMO/69153 An 80-year-old male underwent an extended cholecystectomy for node-positive gallbladder adenocarcinoma. Two weeks later, hemoptysis revealed a left hilar tumor obstructing the bronchus, which was diagnosed as adenocarcinoma. Three months post-cholecystectomy, a left upper pulmonary lobectomy was performed. Histological similarity and positive thyroid transcription factor-1 (TTF-1) immunostaining in both tumors confirmed lung adenocarcinoma with gallbladder metastasis. Despite the generally poor prognosis for gallbladder metastasis from lung cancer, the patient achieved 3 years of survival. Patients with isolated synchronous gallbladder metastasis from lung cancer may benefit from oligometastasectomy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Femoral and Global Femoral Offset, but not Anteroposterior Offset, to Improve Postoperative Outcomes Following Total Hip Arthroplasty: Considerations Independent of the Contralateral Side 269 278 EN Norio Imai Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Yuki Hirano Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Daisuke Homma Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Yuki Endo Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Yoji Horigome Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Hayato Suzuki Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Hiroyuki Kawashima Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Original Article 10.18926/AMO/69152 The global femoral offset (the sum of the acetabular and femoral offsets) influences outcomes after total hip arthroplasty (THA). The optimal offset using plain radiographs has been reported, but internal and external rotations of the hip affect the offset value, producing unclear results when the nonsurgical side is not intact. We investigated the relationship between a functional hip score, i.e., the Harris Hip Score (HHS) and its effect on the post-THA anteroposterior and lateral offsets, and we sought to identify the optimal offset value. The cases of 158 patients with hemilateral hip osteoarthritis who underwent THA at a single center were retrospectively analyzed in this cross-sectional study. Three-dimensional pelvic and femoral models generated from computed tomography were used to examine several parameters, and the results revealed a significant binomial correlation among the modified HHS and femoral and global femoral offsets, with maximum values of 21.3 mm and 40 mm/100 cm body height, respectively. Pelvic and femoral parameters were measured and evaluated via alignment with a specific coordinate system. Our findings indicate that preoperative planning using these parameters may improve postoperative hip function, even when the nonoperative side is unsuitable for use as a reference, as in bilateral hip osteoarthritis cases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Outcome of Decompression Surgery Following Rapid Neurological Deterioration in Patients with Spinal Cord Injury Without Radiographic Evidence of Trauma (SCIWORET) 261 267 EN Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Sugahara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Sasada Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hayato Miyake Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Nagase Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Yasuhara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/69151 Cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL) increase the likelihood of spinal cord injury without radiographic evidence of trauma (SCIWORET). Opinions regarding the optimal timing for surgery in such cases vary, however. We retrospectively investigated the demographics and outcomes of patients with SCIWORET who underwent surgery shortly after experiencing rapid neurological deterioration, and we matched patients who underwent standby surgery for CSM or OPLL. Although the optimal timing of surgery for SCIWORET remains unclear, our findings suggest that early stage surgery for SCIWORET may yield favorable neurological improvements. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 A Study of Periprosthetic Femoral Stem Fractures in Hip Arthroplasty for Femoral Neck Fracture 253 259 EN Yoshiaki Miyake Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Toru Takagi Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Taizo Konishiike Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Original Article 10.18926/AMO/69150 This study investigated the risk factors for bone fragility and perioperative periprosthetic femoral stem fractures in patients undergoing hip arthroplasty for femoral neck fractures. The records of 215 patients (42 male, 173 female; mean age, 84.4 years) were analyzed to assess correlations among periprosthetic fracture rates and sex, age, body mass index (BMI), Dorr classification, femoral stem fixation type (cemented/cementless), and bone mineral density (BMD) of the contralateral proximal femur. The overall prevalence of perioperative periprosthetic fractures was 4.7%. All patients with periprosthetic fractures were female, and all but one were ≥ 80 years of age. Fracture rates were higher in patients with lower BMI, although this difference was not significant. The fracture rates were 0%, 4.7%, and 7.9% for Dorr types A, B, and C, respectively, and 0% and 5.3% for patients who received cemented and cementless stems, respectively. The findings indicated that female patients, those of advanced age, those with lower BMI, and those with Dorr type C had lower BMDs. Although BMD was significantly lower in patients who received cemented stems compared to those who received cementless stems, no fractures were observed in the former group, suggesting that the use of cemented stems is safe for this high-risk population. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 The Work Productivity of Cancer-survivor and Non-cancer-survivor Workers 243 251 EN Mika Kamano Department of Public Health, Faculty of Medicine, Kagawa University Kanae Kanda Department of Public Health, Faculty of Medicine, Kagawa University Nlandu Roger Ngatu Department of Public Health, Faculty of Medicine, Kagawa University Akitsu Murakami Cancer Center, Kagawa University Hospital Yusuke Yamadori Department of Anesthesiology, Faculty of Medicine, Kagawa University Tomohiro Hirao Department of Public Health, Faculty of Medicine, Kagawa University Original Article 10.18926/AMO/69149 We investigated the work productivity levels of employed cancer survivors and non-cancer-survivor workers by conducting a cross-sectional study in Japan between February and March 2019, using an online survey. A total of 561 employed individuals aged 20-64 years were analyzed. Work productivity was assessed using the Work Productivity and Activity Impairment-General Health questionnaire which evaluates absenteeism, presenteeism, and overall work productivity loss. The questionnaire responses demonstrated that the cancer survivors within 1 year of diagnosis had significantly higher absenteeism compared to the non-cancer workers (p=0.048). Although presenteeism and overall work productivity loss were also higher in the non-cancer-survivor group, the differences were not significant. Cancer survivors within 1 year of diagnosis exhibited higher absenteeism, but their work productivity appeared to recover to levels comparable to those of the non-cancer workers over time. These findings may contribute to workplace policies supporting cancer survivors’ return to work. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Bloodstream Infections Caused by Gram-Negative Bacteria in Geriatric Patients: Epidemiology, Antimicrobial Resistance and The Factors Affecting Mortality 231 242 EN M Enes Kardan Department of Infectious Diseases, Faculty of Medicine, Namik Kemal University Ilknur Erdem Department of Infectious Diseases, Faculty of Medicine, Namik Kemal University Emre Yildiz Department of Infectious Diseases, Faculty of Medicine, Namik Kemal University Nuri Kiraz Department of Medical Microbiology, Faculty of Medicine, Namik Kemal University Aliye Çelikkol Department of Biochemistry, Faculty of Medicine, Namik Kemal University Original Article 10.18926/AMO/69148 Bloodstream infections (BSIs) are an important cause of morbidity and mortality in geriatric patients. We retrospectively analyzed the cases of geriatric patients who developed BSIs due to gram-negative bacteria in order to evaluate the epidemiology, antimicrobial resistance, and the factors affecting mortality. The cases of 110 patients aged ≥ 65 years admitted to our hospital between January 1, 2017, and December 31, 2022 were assessed; 70 (63.6%) of the BSIs were healthcare-associated BSIs. The urinary system was the most common detectable source of infection at 43.6%. The most frequently isolated bacteria were Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, in that order. Carbapenem resistance was detected in 17 patients (15.5%), and extended-spectrum beta-lactamase (ESBL) production from Enterobacterales family members was detected in 37 (51.4%) patients. Multivariate analysis revealed that (i) the probability of mortality in the patients with total bilirubin was increased by approx. sixfold and (ii) the likelihood of mortality for those with a Pitt bacteremia score (PBS) ≥ 4 points was approx. 17 times higher. PBS and simplified qPitt scores can help predict mortality and manage geriatric patients. There is a significant increase in mortality among patients with procalcitonin (PCT) levels at ≥ 2 nm/ml. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Organ Donation after Extracorporeal Cardiopulmonary Resuscitation: Clinical and Ethical Perspectives 221 229 EN Tetsuya Yumoto 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 Takashi Hongo Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Kosaki Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Ageta Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Review 10.18926/AMO/69147 Extracorporeal cardiopulmonary resuscitation (ECPR) has evolved into a life-saving therapy for select cardiac arrest patients, yet a growing body of evidence suggests it also holds promise as a bridge to organ donation in non-survivors. This review explores the clinical outcomes, ethical complexities, and evolving policies surrounding organ donation after ECPR. We summarize recent international and Japanese data demonstrating favorable graft function from ECPR donors, with the exception of lung transplantation. The ethical challenges ― particularly those involving brain death determination on extracorporeal membrane oxygenation and adherence to the dead donor rule ― are discussed in the context of Japan’s recent regulatory reforms. Additionally, we highlight the importance of structured end-of-life communication through multidisciplinary team meetings in facilitating ethically sound transitions from rescue efforts to donation pathways. Moving forward, improvements in donor management, standardized legal frameworks, and public and professional education are essential to optimizing the life-saving and life-giving potential of ECPR. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2197-1153 11 4 2024 Quadriceps muscle strength of the affected limb in medial meniscus posterior root tears is negatively correlated with the progression of postoperative medial joint space narrowing e70057 EN Koki Kawada Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mikao Fukuba Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuki Okazaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masanori Tamura Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yusuke Yokoyama Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takayuki Furumatsu Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Purpose: The effect of quadriceps muscle strength on medial joint space (MJS) narrowing after repair for medial meniscus (MM) posterior root tears (MMPRTs) has not yet been determined. This study aimed to evaluate the effect of preoperative and postoperative quadriceps muscle strength on the change in MJS (ΔMJS) in MMPRTs. Methods: Thirty patients who underwent pullout repair for MMPRTs were retrospectively evaluated. The MJS width using fixed-flexion view radiographs, MM extrusion (MME) using magnetic resonance imaging, quadriceps muscle strength using the Locomo Scan-II and clinical scores were measured and compared preoperatively and 1 year postoperatively. Correlations between the ΔMJS, change in MME (ΔMME), and preoperative and postoperative quadriceps muscle strength were evaluated using Spearman's rank correlation coefficient. Results: MJS narrowing and MME progressed significantly at 1 year postoperatively (p < 0.001). Quadriceps muscle strength in MMPRT knees and all clinical scores significantly improved at 1 year postoperatively (p < 0.001). ΔMJS and ΔMME showed a significant positive correlation (0.50 ± 0.70 and 1.22 ± 0.92 mm, respectively; r = 0.516, p = 0.004). Both preoperative and postoperative quadriceps muscle strength in MMPRT knees showed significant negative correlations with ΔMJS (preoperative: r = －0.529, p = 0.003; postoperative: r = －0.477, p = 0.008) and ΔMME (preoperative: r = －0.431, p = 0.018; postoperative: r = －0.443, p = 0.014). Conclusions: In pullout repair for MMPRTs, preoperative and postoperative quadriceps muscle strength in MMPRT knees was negatively correlated with the progression of MJS narrowing and MME. Rehabilitation with a focus on quadriceps muscle strengthening, including preoperative rehabilitation, may delay knee-osteoarthritis progression after pullout repair for MMPRTs. Level of Evidence: Level IV. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1351-5101 32 1 2025 Lyme neuroborreliosis in Japan: Borrelia burgdorferi sensu lato as a cause of meningitis of previously undetermined etiology in hospitalized patients outside of the island of Hokkaido, 2010–2021 e70005 EN Masayuki Ohira Department of Clinical Laboratory and Internal Medicine, National Center of Neurology and Psychiatry Ai Takano Department of Veterinary Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University Kentaro Yoshi National Research Center for the Control and Prevention of Infectious Diseases, Nagasaki University Akira Arai Department of Neurology, Aomori Prefectural Central Hospital Yashuhiro Aso Department of Neurology, Oita Prefectural Hospital Rikiya Furutani Department of Neurology, National Hospital Organization, Shinshu Ueda General Hospital Tadanori Hamano Department of Neurology, University of Fukui Hospital Ikuko Takahashi‐Iwata Department of Neurology, Hokkaido University Hospital Chikako Kaneko Department of Neurology, Southern Tohoku General Hospital Tohru Matsuura Division of Neurology, Jichi Medical University Norihisa Maeda Department of Neurology, National Hospital Organization Beppu Medical Center Hideto Nakajima Department of Neurology, Nihon University Itabashi Hospital Katsuro Shindo Department of Neurology, Kurashiki Central Hospital Toshihiko Suenaga Department of Neurology, Tenri Hospital Kazuma Sugie Department of Neurology, Nara Medical University Hospital Yasuhiro Suzuki Department of Neurology, National Hospital Organization Asahikawa Medical Center Toru Yamashita Department of Neurology, Okayama University Hospital Frederick J. Angulo Vaccines and Antivirals Medical Affairs, Pfizer Vaccines Juanita Edwards Vaccines and Antivirals Medical Affairs, Pfizer Vaccines Cody Matthew Bender Vaccines and Antivirals Medical Affairs, Pfizer Vaccines Lisa R. Harper Vaccines and Antivirals Medical Affairs, Pfizer Vaccines Yoshikazu Nakayama Vaccines Medical Affairs, Pfizer Japan Inc Shuhei Ito Vaccines Medical Affairs, Pfizer Japan Inc Andreas Pilz Vaccines and Antivirals Medical Affairs, Pfizer Vaccines James H. Stark Vaccines and Antivirals Medical Affairs, Pfizer Vaccines Jennifer C. Moïsi Vaccines and Antivirals Medical Affairs, Pfizer Vaccines Hidehiro Mizusawa Department of Neurology, National Center of Neurology and Psychiatry Masaki Takao Department of Clinical Laboratory and Internal Medicine, National Center of Neurology and Psychiatry Background and Purpose: Clinical manifestations of Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), include erythema migrans, Lyme neuroborreliosis (LNB), carditis, and arthritis. LB is a notifiable disease in Japan with <30 surveillance-reported LB cases annually, predominately from Hokkaido Prefecture. However, LB, including LNB, may be under-diagnosed in Japan since diagnostic tests are not readily available. We sought to determine if LNB could be a cause of previously undiagnosed encephalitis or meningitis in Japan. Methods: Investigators at 15 hospitals in 10 prefectures throughout Japan retrieved serum and/or cerebrospinal fluid (CSF) samples collected in 2010–2021 from 517 patients hospitalized with encephalitis or meningitis which had an etiology that had not been determined. Samples were tested for Bbsl-specific antibodies using ELISA and Western blot tests. In alignment with the European Union LNB case definition, a confirmed LNB case had CSF pleocytosis and intrathecal production of Bbsl-specific antibodies and a probable LNB case had a CSF sample with pleocytosis and Bbsl-specific antibodies. Results: LNB was identified in three hospitalized patients with meningitis of previously undetermined etiology: a male resident of Aomori Prefecture was a confirmed LNB case, and two female residents of Oita Prefecture were probable LNB cases. None of the patients with confirmed or probable LNB had traveled in the month prior to symptom onset and none had samples previously tested for LB. Conclusion: The identification of previously undiagnosed LNB cases indicates a need for enhanced disease awareness in Japan, particularly beyond Hokkaido Island, and more readily available LB diagnostic testing. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1435-2451 409 1 2024 Subjective global assessment for nutritional screening and its impact on surgical outcomes: A prospective study in older patients with colorectal cancer 356 EN Fuminori Teraishi 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 Ryohei Shoji 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 Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshitaka Kondo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Tamura Perioperative Management Center, Okayama University Hospital Yoshikazu Matsuoka Perioperative Management Center, Okayama University Hospital Hiroshi Morimatsu Perioperative Management Center, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose Our perioperative management center provides preoperative intervention and functional and nutritional assessments for colorectal cancer patients aged over 75 years. This study evaluated the associations of preoperative nutritional status with postoperative outcomes and prognosis in colorectal cancer patients aged 75 years or older. Methods This was a prospective, observational study of 71 colorectal cancer patients aged 75 years or older who underwent surgery between July 2020 and September 2022. The Subjective Global Assessment (SGA) was evaluated as a nutritional index. The patients were classified into three groups: SGA-A (well nourished), B (moderately malnourished), and C (severely malnourished), and the correlations with postoperative outcomes and prognosis were examined. Results The median age of the 71 patients (34 males, 37 females) was 78 (75–92) years, and their median body mass index (BMI) was 22.3 (13.4–31.9) kg/m2. Forty-eight patients had colon cancer, and 23 had rectal cancer. On the SGA, 28 patients were SGA-A, 25 SGA-B, and 18 SGA-C. The SGA-B/C group had significantly higher BMI (p < 0.01) and more ICU admissions (p = 0.02). The G8 score was significantly lower (p = 0.03) in the SGA-B/C group, suggesting coexisting functional decline. In terms of postoperative outcomes, the SGA-B/C group had a significantly longer postoperative hospital stay (p = 0.04). The 3-year OS rates for all stages were 100% in the SGA-A group and 49.7% in the SGA-B/C group (p = 0.03), while the 3-year OS rates for patients excluding Stage IV were 100% in the SGA-A group and 68.5% in the SGA-B/C group, not significantly different (p = 0.14). The 3-year RFS rate was 95.5% in the SGA-A group and 65.3% in the SGA-B/C group (p = 0.15). Conclusion The SGA is a promising nutritional index associated with short-term outcomes in older patients undergoing colorectal cancer surgery. The SGA can be assessed in a few minutes during an outpatient visit, making it useful for routine clinical use. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1071-2690 60 10 2024 Enhanced design of pCMViR-TSC plasmid vector for sustainably high cargo gene expression in mammalian cells 1215 1227 EN Masakiyo Sakaguchi Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Rie Kinoshita Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Nahoko Tomonobu Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshihiko Sakaguchi Department of Microbiology, Tokushima Bunri University Junichiro Futami Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Akira Yamauchi Department of Biochemistry, Kawasaki Medical School Hitoshi Murata Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ken-ichi Yamamoto Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tetta Takahashi Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuma Gohara Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshiki Ochi Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Fan Jiang Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ni Luh Gede Yoni Komalasari Faculty of Medicine, Udayana University Youyi Chen Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine I Made Winarsa Ruma Faculty of Medicine, Udayana University I Wayan Sumardika Faculty of Medicine, Udayana University Jin Zhou Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology Tomoko Honjo Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Futoshi Kuribayashi Department of Biochemistry, Kawasaki Medical School Kazumi Sagayama Organization for Research and Innovation Strategy, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Eisaku Kondo Division of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical University Yusuke Inoue Faculty of Science and Technology, Division of Molecular Science, Gunma University The first-generation pCMViR-TSC, implemented through the promoter sandwich rule, yields 10- to 100-fold higher gene expression than the standard plasmid used with the CMV (cytomegalovirus) or CAG promoter. However, the vector’s shortcomings limit its utility to transient expression only, as it is not suitable for establishing stable transformants in mammalian cells. To overcome this weakness, we here introduce the improved plasmid vector pSAKA-4B, derived from pCMViR-TSC as a second-generation chromosome-insertable vector. This vector facilitates the linear entry of the expression unit into the TTAA site of DNA universally with transposase assistance. The vector is helpful for the indefinite expression of our target gene. The new vector system is proven here to be efficient in establishing stable transformants with a high likelihood of positive clones that exhibit significantly elevated expression levels of the delivered foreign gene. This system, alongside the first-generation vector, is therefore instrumental for diverse basic research endeavors concerning genes, proteins, cells, and animals, and potentially for clinical applications such as gene therapy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2662-4435 6 1 2025 Biogeochemical impact of nickel and urea in the great oxidation event 654 EN Dilan M. Ratnayake The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Ryoji Tanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Eizo Nakamura The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University The Great Oxidation Event marks the first substantial increase in atmospheric oxygen on Earth. Despite the oxygenic photosynthesis that emerged hundreds of million years before this event, the specific biogeochemical mechanisms responsible for maintaining low oxygen levels for an extended period remain elusive. Here, we show the critical role of urea as a nitrogen source for cyanobacteria, the cascading impact of nickel on abiotic urea production, and their combined effects on the proliferation of cyanobacteria leading to the great oxidation event. Urea formation was experimentally evaluated under simulated Archean conditions and cyanobacterial growth was monitored providing urea as the nitrogen source. Our findings demonstrate that urea can be produced in the Archean cyanobacterial habitats with UV-C irradiation, shedding light on the controversy regarding the evolution of nitrogen-fixing enzymes in primitive cyanobacteria. We propose that environmental conditions in the early Archean, characterized by elevated urea and nickel concentration, may have hindered cyanobacterial expansion, contributing to the delay between the evolution of oxygenic photosynthesis and the onset of the great oxidation event. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 2473-0114 9 3 2024 A Characteristic Magnetic Resonance Imaging Finding to Identify Morton Neuroma: The Slug Sign EN Masahiro Horita Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kenta Saiga Department of Sports Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tomohiro Fujiwara Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Eiji Nakata Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: Morton neuroma is a common cause of forefoot pain and sensory disturbances, but it is difficult to identify on magnetic resonance imaging (MRI). The aim of this study was to verify the usefulness of a characteristic MRI finding (slug sign) for identifying Morton neuroma and to clarify the relationship between excised neuroma characteristics and preoperative MRI findings. Methods: Twenty-two web spaces were retrospectively assessed from the second and third intermetatarsal spaces of 11 feet of 10 patients (7 women and 3 men, aged average 59.5 years) who underwent surgical excision of Morton neuroma between 2017 and 2022. Asymptomatic web spaces were used as control. Neuromas with 2 branches of the plantar digital nerves on axial T1-weighted MRI (MRI-T1WI) were considered the slug sign. We investigated the preoperative presence of the slug sign in Morton neuroma and asymptomatic control web spaces. We also investigated the relationship between the maximum transverse diameter of the excised specimen and that estimated on coronal MRI-T1WI. Results: A total of 15 Morton neuromas were excised and assessed. The slug signs were present in 10 intermetatarsal spaces in 15 web spaces with Morton neuroma whereas the sign was found in 1 intermetatarsal space in 7 asymptomatic web spaces. The sensitivity and specificity for the slug sign to diagnose Morton neuroma was 66.7% and 85.7%, respectively. The positive and negative predictive values were 90.9% and 54.5%, respectively. The mean maximum transverse diameter of excised neuromas was 4.7 mm. The mean maximum transverse diameter of neuromas on coronal MRI-T1WI was 3.4 mm. A significant positive correlation was found between the maximum transverse diameters of excised specimens and diameters estimated on coronal MRI-T1WI (r = 0.799, P < .001). Conclusion: The slug sign may be a useful indicator of Morton neuroma on MRI to confirm nerve involvement after bifurcation. Level of Evidence: Level IV, retrospective series. No potential conflict of interest relevant to this article was reported.

Proceedings of the National Academy of Sciences Acta Medica Okayama 0027-8424 122 32 2025 Structural insights into a citrate transporter that mediates aluminum tolerance in barley e2501933122 EN Tran Nguyen Thao Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Namiki Mitani-Ueno Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University Ryo Urano Division of Superconducting and Functional Materials, Research Institute for Interdisciplinary Science, Okayama University Yasunori Saitoh Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Peitong Wang Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University Naoki Yamaji Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University Jian-Ren Shen Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Wataru Shinoda Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Jian Feng Ma Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University Michihiro Suga Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University HvAACT1 is a major aluminum (Al)-tolerance gene in barley, encoding a citrate transporter that belongs to the multidrug and toxic compound extrusion (MATE) family. This transporter facilitates citrate secretion from the roots, thereby detoxifying external Al ions―a major constraint of crop production on acidic soils. In this study, we present the outward-facing crystal structure of HvAACT1, providing insights into a citrate transport mechanism. The putative citrate binding site consists of three basic residues―K126 in transmembrane helix 2 (TM2), R358 in TM7, and R535 in TM12―creating substantial positive charges in the C-lobe cavity. Proton coupling for substrate transport may involve two pairs of aspartate residues in the N-lobe cavity, one of which corresponds to the essential Asp pair found in prokaryotic H+-coupled MATE transporters belonging to the DinF subfamily. Structural coupling between proton uptake in the N-lobe and citrate extrusion in the C-lobe can be enabled by an extensive, unique hydrogen-bonding network at the extracellular half of the N-lobe. Mutation-based functional analysis, structural comparisons, molecular dynamics simulation, and phylogenic analysis suggest an evolutionary link between citrate MATE transporters and the DinF MATE subfamily. Our findings provide a solid structural basis for citrate transport by HvAACT1 in barley and contribute to a broader understanding of citrate transporter structures in other plant species. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0919-8172 32 1 2024 What is the identity of Gerota fascia? Histological study with cadavers 62 68 EN Yasuyuki Kobayashi Minimally Invasive Therapy Center, Okayama University Hospital Kohei Edamura Department of Urology, Okayama University Hospital Takuya Sadahira Department of Urology, Okayama University Hospital Yusuke Tominaga Department of Urology, Okayama University Hospital Satoshi Katayama Department of Urology, Okayama University Hospital Takehiro Iwata Department of Urology, Okayama University Hospital Shingo Nishimura Organ Transplant Center, Okayama University Hospital Tomoko Kobayashi Department of Urology, Okayama University Hospital Keita Sato Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaaki Komiyama Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryusuke Momota Department of Human Morphology, 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 Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives: The advancement of laparoscopic surgery has allowed surgeons to see finer anatomical structures during surgery. As a result, several issues have arisen regarding Gerota fascia that cannot be explained by previous interpretations, such as its various forms observed during surgery. To address these issues, we histologically examined the structure of Gerota fascia. Methods: Specimens for study were prepared from kidneys with Gerota fascia from four cadavers, and the structure was studied histologically. Its thickness and collagen fiber area ratios were measured using ImageJ and compared to those of the epimysium of the rectus abdominis muscle. Results: Connective tissue that appeared to be Gerota fascia was observed in 26 specimens. Histologically, the basic structure of Gerota fascia was a sandwich-like structure with a thin layer of thick, long collagen fibers in the central layer, and small granular collagen fibers scattered at the edges. However, not all areas observed had a similar structure; eight specimens were composed only of small granular collagen fibers. The average thickness of the Gerota fascia was 466 μm, and the area ratio of collagen was 27.1%. In contrast, the epimysium was much thicker than Gerota fascia, and its collagen fibers were much thicker and denser. Conclusions: Gerota fascia, unlike the epimysium, was a very thin and fragile layer of collagen fibers, and its structure was diverse. This explains why Gerota fascia was observed in various states during surgery. It is important for surgeons to understand the properties of Gerota fascia and to treat it appropriately. 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.

Wiley Acta Medica Okayama 2692-4609 6 1 2025 A Case of Gastric Atypical Lipomatous Tumor/Well‐Differentiated Liposarcoma With Endoscopic Morphological Changes e70146 EN Rika Omote Department of Diagnostic Pathology, NHO Fukuyama Medical Center Shizuma Omote Department of Internal Medicine, Fukuyama Minami Hospital Hiroshi Sonobe Department of Diagnostic Pathology, NHO Fukuyama Medical Center Ryosuke Hamano Department of Surgery, NHO Fukuyama Medical Center Tatsuya Toyokawa Department of Gastroenterology, NHO Fukuyama Medical Center Shinya Otsuka Department of Surgery, NHO Fukuyama Medical Center Takehiro Tanaka Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Yanai Department of Pathology, Okayama University Hospital Masaru Inagaki Department of Surgery, NHO Fukuyama Medical Center Hidetaka Yamamoto Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atypical lipomatous tumor/well-differentiated liposarcoma is a locally aggressive mesenchymal neoplasm composed of adipocytes and stromal cells. Gastric cases are exceedingly rare, and their malignant potential remains unclear. We report a case of a woman in her 60s who was found to have multiple submucosal tumor-like lesions of the stomach. Over time, the tumors increased in size, requiring a laparoscopic partial gastrectomy. Histological examination revealed a tumor composed of both fatty tissue and fibrous stroma with nuclear atypia. Immunohistochemistry showed positivity for CDK4 and MDM2, and fluorescence in situ hybridization confirmed MDM2 amplification, leading to a diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma. This case presented an unusual gastric manifestation, with multiple submucosal tumor-like lesions on endoscopy and exhibiting progressive morphological changes over several years. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 14 10 2025 Endoscopic Bridging Stent Placement Improves Bile Leaks After Hepatic Surgery 3381 EN Taisuke Obata Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Kei Harada Department of Gastroenterology and Hepatology, Okayama University Hospital Nao Hattori Department of Gastroenterology and Hepatology, Okayama University Hospital Ryosuke Sato Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama 700-8558, Japan Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroyuki Terasawa Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Background: Endoscopic treatment is one of the first-line treatments for bile leaks after hepatic surgery. However, detailed reports of endoscopic treatment for bile leaks after hepatic resection (HR) or liver transplantation (LT) are scarce. The outcomes of endoscopic treatment for bile leaks after hepatic surgery were examined, and factors related to successful treatment were identified. Methods: A total of 122 patients underwent endoscopic treatment for bile leaks after hepatic surgery. The diagnosis of a bile leak is based on the ISGLS criteria. The decision to perform endoscopic retrograde cholangiography (ERC) is made based on the amount of drainage output, laboratory data, clinical symptoms, and CT scan findings. In our study, the site of the bile leak was assessed using ERC. Endoscopic stents were placed to bridge across the bile leak site as much as possible. Otherwise, stents were placed near the leak site. Endoscopic stents were replaced every 2–3 months until an improvement in the bile leak was observed with or without biliary strictures. The outcomes of endoscopic treatment and the factors related to clinical success were evaluated. Results: Seventy-four patients with HR and forty-eight patients with LT were treated endoscopically. Technical and clinical success was achieved in 89% (109/122) and 82% (100/122) of patients, respectively. Three (2%) patients died from uncontrollable bile leaks. Bridging stent placement (p < 0.001), coexistent percutaneous drainage (p = 0.0025), and leak severity (p = 0.015) were identified as independent factors related to the clinical success of endoscopic treatment. During a median observation period of 1162 days after the achievement of clinical success, bile leak recurrence was observed in only three cases (3%). Conclusions: Endoscopic treatment is safe and effective for bile leaks after hepatic surgery. Bridging stent placement across the leak site is the most crucial factor for clinical success. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2772-963X 4 2 2025 Simplified Outcome Prediction in Patients Undergoing Transcatheter Tricuspid Valve Intervention by Survival Tree-Based Modelling 101575 EN Vera Fortmeier Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum Mark Lachmann First Department of Medicine, Klinikum rechts der Isar, Technical University of Munich Lukas Stolz DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance Jennifer von Stein Department of Cardiology, Heart Center, University of Cologne Karl-Philipp Rommel Department of Cardiology, Heart Center Leipzig, University of Leipzig Mohammad Kassar Department of Cardiology, Inselspital Bern, Bern University Hospital Muhammed Gerçek Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum Anne R. Schöber Department of Cardiology, Heart Center Leipzig, University of Leipzig Thomas J. Stocker DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance Hazem Omran Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum Michelle Fett Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum Jule Tervooren Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum Maria I. Körber Department of Cardiology, Heart Center, University of Cologne Amelie Hesse First Department of Medicine, Klinikum rechts der Isar, Technical University of Munich Gerhard Harmsen Department of Physics, University of Johannesburg Kai Peter Friedrichs Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Tanja K. Rudolph Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum Michael Joner DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance Roman Pfister Department of Cardiology, Heart Center, University of Cologne Stephan Baldus Department of Cardiology, Heart Center, University of Cologne Karl-Ludwig Laugwitz First Department of Medicine, Klinikum rechts der Isar, Technical University of Munich Stephan Windecker Department of Cardiology, Inselspital Bern, Bern University Hospital Fabien Praz Department of Cardiology, Inselspital Bern, Bern University Hospital Philipp Lurz Department of Cardiology, Heart Center Leipzig, University of Leipzig Jörg Hausleiter DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance Volker Rudolph Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum Background Patients with severe tricuspid regurgitation (TR) typically present with heterogeneity in the extent of cardiac dysfunction and extra-cardiac comorbidities, which play a decisive role for survival after transcatheter tricuspid valve intervention (TTVI). Objectives This aim of this study was to create a survival tree-based model to determine the cardiac and extra-cardiac features associated with 2-year survival after TTVI. Methods The study included 918 patients (derivation set, n = 631; validation set, n = 287) undergoing TTVI for severe TR. Supervised machine learning-derived survival tree-based modelling was applied to preprocedural clinical, laboratory, echocardiographic, and hemodynamic data. Results Following univariate regression analysis to pre-select candidate variables for 2-year mortality prediction, a survival tree-based model was constructed using 4 key parameters. Three distinct cluster-related risk categories were identified, which differed significantly in survival after TTVI. Patients from the low-risk category (n = 261) were defined by mean pulmonary artery pressure ≤28 mm Hg and N-terminal pro–B-type natriuretic peptide ≤2,728 pg/mL, and they exhibited a 2-year survival rate of 85.5%. Patients from the high-risk category (n = 190) were defined by mean pulmonary artery pressure >28 mm Hg, right atrial area >32.5 cm2, and estimated glomerular filtration rate ≤51 mL/min, and they showed a significantly worse 2-year survival of only 52.6% (HR for 2-year mortality: 4.3, P < 0.001). Net re-classification improvement analysis demonstrated that this model was comparable to the TRI-Score and outperformed the EuroScore II in identifying high-risk patients. The prognostic value of risk phenotypes was confirmed by external validation. Conclusions This simple survival tree-based model effectively stratifies patients with severe TR into distinct risk categories, demonstrating significant differences in 2-year survival after TTVI. No potential conflict of interest relevant to this article was reported.

Microbiology Society Acta Medica Okayama 0022-1317 106 7 2025 Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Animal dsRNA and ssRNA(－) Viruses Subcommittee, 2025 002112 EN Holly R. Hughes Centers for Disease Control and Prevention Matthew J. Ballinger Biological Sciences, Mississippi State University Yiming Bao National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences Nicolas Bejerman Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and Instituto Nacional de Tecnología Agropecuaria (INTA) Kim R. Blasdell CSIRO Health and Biosecurity Thomas Briese Center for Infection and Immunity, and Department of Epidemiology, Mailman School of Public Health, Columbia University Julia Brignone Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS Jean Paul Carrera Instituto Conmemorativo Gorgas de Estudios de la Salud Lander De Coninck Division of Clinical and Epidemiological Virology, KU Leuven William Marciel de Souza Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky Humberto Debat Instituto Nacional de Tecnología Agropecuaria (INTA) Ralf G. Dietzgen QAAFI, The University of Queensland Ralf Dürrwald Robert Koch Institut Mert Erdin Department of Virology, University of Helsinki Anthony R. Fooks Animal and Plant Health Agency (APHA) Kristian M. Forbes Department of Biological Sciences, University of Arkansas Juliana Freitas-Astúa Embrapa Cassava and Fruits Jorge B. Garcia Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS Jemma L. Geoghegan Department of Microbiology and Immunology, University of Otago Rebecca M. Grimwood Department of Microbiology and Immunology, University of Otago Masayuki Horie Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University Timothy H. Hyndman School of Veterinary Medicine, Murdoch University Reimar Johne German Federal Institute for Risk Assessment John D. Klena Viral Special Pathogens Branch, The Centers for Disease Control and Prevention Hideki Kondo Institute of Plant Science and Resources, Okayama University Eugene V. Koonin Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health Alexei Y. Kostygov University of Ostrava 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 Michael Letko Paul G. Allen School for Global Health, Washington State University Jun-Min Li Institute of Plant Virology, Ningbo University Yiyun Liu National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences Maria Laura Martin Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS Nathaniel Mull Department of Natural Sciences, Shawnee State University Yael Nazar Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS Norbert Nowotny College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health Márcio Roberto Teixeira Nunes Universidade Federal do Pará Arnfinn Lodden Økland Pharmaq Analytiq Dennis Rubbenstroth Institute of Diagnostic Virology, Friedrich-Loeffler-Institut Brandy J. Russell Centers for Disease Control and Prevention Eric Schott Institute of Marine and Environmental Technology, University of Maryland Center for Environmental Science Stephanie Seifert Paul G. Allen School for Global Health, Washington State University Carina Sen Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS Elizabeth Shedroff Viral Special Pathogens Branch, The Centers for Disease Control and Prevention Tarja Sironen Department of Virology, University of Helsinki Teemu Smura Department of Virology, University of Helsinki Camila Prestes Dos Santos Tavares Integrated Group of Aquaculture and Environmental Studies, Federal University of Paraná Robert B. Tesh Department of Pathology, The University of Texas Medical Branch Natasha L. Tilston Department of Microbiology and Immunology, Indiana University School of Medicine Noël Tordo Institut Pasteur Nikos Vasilakis Department of Pathology, The University of Texas Medical Branch Peter J. Walker University of Queensland Fei Wang Wuhan Institute of Virology, Chinese Academy of Sciences Anna E. Whitfield North Carolina State University Shannon L.M. Whitmer Viral Special Pathogens Branch, The Centers for Disease Control and Prevention Yuri I. Wolf Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health Han Xia Wuhan Institute of Virology, Chinese Academy of Sciences Gong-Yin Ye Institute of Insect Sciences, Zhejiang University Zhuangxin Ye Institute of Plant Virology, Ningbo University Vyacheslav Yurchenko University of Ostrava Mingli Zhao Department of Pathobiology and Population Sciences, Royal Veterinary College RNA viruses are ubiquitous in the environment and are important pathogens of humans, animals and plants. In 2024, the International Committee on Taxonomy of Viruses Animal dsRNA and ssRNA(－) Viruses Subcommittee submitted 18 taxonomic proposals for consideration. These proposals expanded the known virosphere by classifying 9 new genera and 88 species for newly detected virus genomes. Of note, newly established species expand the large family of Rhabdoviridae to 580 species. A new species in the family Arenaviridae includes a virus detected in Antarctic fish with a unique split nucleoprotein ORF. Additionally, four new species were established for historically isolated viruses with previously unsequenced genomes. Furthermore, three species were abolished due to incomplete genome sequence information, and one family was moved from being unassigned in the phylum Negarnaviricota into a subphylum and order. Herein, we summarize the 18 ratified taxonomic proposals and the general features of the current taxonomy, thereby supporting public and animal health responses. No potential conflict of interest relevant to this article was reported.

Microbiology Society Acta Medica Okayama 0022-1317 106 7 2025 Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses from the Plant Viruses Subcommittee, 2025 002114 EN Luisa Rubino Istituto per la Protezione Sostenibile delle Piante, CNR Peter Abrahamian USDA-ARS, BARC, National Germplasm Resources Laboratory Wenxia An Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University Miguel A. Aranda Centro de Edafología y Biología Aplicada del Segura-CSIC José T. Ascencio-Ibañez Department of Molecular and Structural Biochemistry, North Carolina State University Nicolas Bejerman Unidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICET Arnaud G. Blouin Plant Protection Department Thierry Candresse UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE Tomas Canto Margarita Salas Center for Biological Research (CIB-CSIC) Spanish Council for Scientific Research (CSIC) Mengji Cao National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University John P. Carr Department of Plant Sciences, University of Cambridge Won Kyong Cho Agriculture and Life Sciences Research Institute, Kangwon National University Fiona Constable Agriculture Victoria Research, Department of Energy, Environment and Climate Action and School of Applied Systems Biology, La Trobe University Indranil Dasgupta University of Delhi South Campu Humberto Debat Unidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICET Ralf G. Dietzgen Queensland Alliance for Agriculture and Food Innovation, The University of Queensland Michele Digiaro CIHEAM, Istituto Agronomico Mediterraneo of Bari Livia Donaire Centro de Edafología y Biología Aplicada del Segura-CSIC Toufic Elbeaino CIHEAM, Istituto Agronomico Mediterraneo of Bari Denis Fargette Virus South Data Fiona Filardo Queensland Department of Primary Industries Matthias G. Fischer Max Planck Institute for Marine Microbiology Nuria Fontdevila Plant Protection Department Adrian Fox Fera Science Ltd (Fera), York Biotech Campus Juliana Freitas-Astua Embrapa Cassava and Fruits, Brazilian Agricultural Research Corporation Marc Fuchs Plant Pathology, Cornell University Andrew D.W. Geering Queensland Alliance for Agriculture and Food Innovation, The University of Queensland Mahan Ghafari Department of Biology, University of Oxford Anders Hafrén Swedish University of Agriculture John Hammond USDA-ARS, USNA, Floral and Nursery Plants Research Unit Rosemarie Hammond USDA-ARS, BARC, Molecular Plant Pathology Laboratory Beata Hasiów-Jaroszewska Institute of Plant Protection-NRI Eugenie Hebrard PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro Carmen Hernández Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de Valencia-CSIC Jean-Michel Hily Institut Français de la Vigne et du Vin Ahmed Hosseini Vali-e-Asr University of Rafsanjan, Department of Plant Protection Roger Hull Retired from John Innes Centre Alice K. Inoue-Nagata Embrapa Hortaliças Ramon Jordan USDA-ARS, USNA, Floral and Nursery Plants Research Unit Hideki Kondo Institute of Plant Science and Resources, Okayama University Jan F. Kreuze International Potato Center (CIP) Mart Krupovic Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit Kenji Kubota Institute for Plant Protection, NARO Jens H. Kuhn Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health Scott Leisner Department of Biological Sciences, University of Toledo Jean-Michel Lett CIRAD, UMR PVBMT Chengyu Li Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University Fan Li State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University Jun Min Li Institute of Plant Virology, Ningbo University Paola M. López-Lambertini Instituto de Patología Vegetal (IPAVE), INTA, Unidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICET Juan J. Lopez-Moya Centre for Research in Agricultural Genomics, CRAG (CSIC-IRTA-UAB-UB) Francois Maclot UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE Kristiina Mäkinen Department of Agricultural Sciences, University of Helsinki Darren Martin Institute of Infectious Disease and Molecular Medicine, University of Cape Town Sebastien Massart Plant Pathology Laboratory, TERRA Gembloux Agro-Bio Tech, University of Liege W. Allen Miller Department of Plant Pathology, Entomology and Microbiology, Iowa State University Musa Mohammadi Department of Plant Protection, Gorgan University of Agricultural Sciences and Natural Resources Dimitre Mollov USDA-APHIS, Plant Protection and Quarantine Emmanuelle Muller CIRAD, AGAP Institut; AGAP Institut, University of Montpellier; CIRAD, INRAE Tatsuya Nagata Instituto de Ciências Biológicas, Universidade de Brasília Jesús Navas-Castillo Instituto de Hortofruticultura Subtropical y Mediterránea “La Mayora” (IHSM-UMA-CSIC), Consejo Superior de Investigaciones Científicas Yutaro Neriya Utsunomiya University Francisco M. Ochoa-Corona Oklahoma State University, Institute for Biosecurity & Microbial Forensics Kazusato Ohshima Saga University Vicente Pallás Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de Valencia-CSIC Hanu Pappu Department of Plant Pathology, Washington State University Karel Petrzik Institute of Plant Molecular Biology Mikhail Pooggin PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD Maria Isabella Prigigallo Istituto per la Protezione Sostenibile delle Piante, CNR Pedro L. Ramos-González Applied Molecular Biology Laboratory, Instituto Biológico de São Paulo Simone Ribeiro Embrapa Recursos Genéticos e Biotecnologia Katja R. Richert-Pöggeler Julius Kühn Institute, Federal Research Centre for Cultivated Plants, Institute for Epidemiology and Pathogen Diagnostics Philippe Roumagnac CIRAD, UMR PHIM Avijit Roy USDA-ARS, BARC, Molecular Plant Pathology Laboratory, Beltsville, MD, USA Sead Sabanadzovic Department of Agricultural Science and Plant Protection, Mississippi State University Dana Šafářová Department of Cell Biology and Genetics, Faculty of Science, Palacký University Olomouc Pasquale Saldarelli Istituto per la Protezione Sostenibile delle Piante, CNR Hélène Sanfaçon Summerland Research and Development Centre, Agriculture and Agri-Food Canada Cecilia Sarmiento Department of Chemistry and Biotechnology, Tallinn University of Technology Takahide Sasaya Strategic Planning Headquarters, NARO Kay Scheets Department of Plant Pathology, Ecology and Evolution, Oklahoma State University Willem E.W. Schravesande Molecular Plant Pathology, University of Amsterdam Susan Seal Natural Resources Institute, University of Greenwich Yoshifumi Shimomoto Kochi Agricultural Research Center Merike Sõmera Department of Chemistry and Biotechnology, Tallinn University of Technology Livia Stavolone Istituto per la Protezione Sostenibile delle Piante, CNR Lucy R. Stewart Currently unaffiliated Pierre-Yves Teycheney CIRAD, UMR PVBMT & UMR PVBMT, Université de la Réunion John E. Thomas Queensland Alliance for Agriculture and Food Innovation, The University of Queensland Jeremy R. Thompson Plant Health and Environment Laboratory Antonio Tiberini Council for Agricultural Research and Economics, Research Centre for Plant Protection and Certification Yasuhiro Tomitaka Institute for Plant Protection, NARO Ioannis Tzanetakis Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System Marie Umber INRAE, UR ASTRO Cica Urbino PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro Harrold A. van den Burg Molecular Plant Pathology, University of Amsterdam René A.A. Van der Vlugt Wageningen University and Research Arvind Varsani The Biodesign Center for Fundamental and Applied Microbiomics, Center for Evolution and Medicine, School of Life Sciences, Arizona State University Adriaan Verhage Rijk Zwaan Breeding B.V. Dan Villamor Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System Susanne von Bargen Humboldt-Universität zu Berlin, Thaer-Institute of Agricultural and Horticultural Sciences Peter J. Walker The University of Queensland Thierry Wetzel Dienstleistungszentrum Ländlicher Raum Rheinpfalz Anna E. Whitfield North Carolina State University Stephen J. Wylie Food Futures Institute, Murdoch University Caixia Yang Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University F. Murilo Zerbini Dep. de Fitopatologia/BIOAGRO, Universidade Federal de Viçosa Song Zhang National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University In March 2025, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote, newly proposed taxa were added to those under the mandate of the Plant Viruses Subcommittee. In brief, 1 new order, 3 new families, 6 new genera, 2 new subgenera and 206 new species were created. Some taxa were reorganized. Genus Cytorhabdovirus in the family Rhabdoviridae was abolished and its taxa were redistributed into three new genera Alphacytorhabdovirus, Betacytorhabdovirus and Gammacytorhabdovirus. Genus Waikavirus in the family Secoviridae was reorganized into two subgenera (Actinidivirus and Ritunrivirus). One family and four previously unaffiliated genera were moved to the newly established order Tombendovirales. Twelve species not assigned to a genus were abolished. To comply with the ICTV mandate of a binomial format for virus species, eight species were renamed. Demarcation criteria in the absence of biological information were defined in the genus Ilarvirus (family Bromoviridae). This article presents the updated taxonomy put forth by the Plant Viruses Subcommittee and ratified by the ICTV. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1536-1632 26 2 2024 Evaluating the Patterns of FAPI Uptake in the Shoulder Joint: a Preliminary Study Comparing with FDG Uptake in Oncological Studies 294 300 EN Yohji Matsusaka Department of Nuclear Medicine and Comprehensive Heart Failure Center (CHFC), Molecular Imaging of the Heart, University Hospital of Würzburg Rudolf A. Werner Department of Nuclear Medicine and Comprehensive Heart Failure Center (CHFC), Molecular Imaging of the Heart, University Hospital of Würzburg Sebastian E. Serfling Department of Nuclear Medicine and Comprehensive Heart Failure Center (CHFC), Molecular Imaging of the Heart, University Hospital of Würzburg Andreas K. Buck Department of Nuclear Medicine and Comprehensive Heart Failure Center (CHFC), Molecular Imaging of the Heart, University Hospital of Würzburg Aleksander Kosmala Department of Nuclear Medicine and Comprehensive Heart Failure Center (CHFC), Molecular Imaging of the Heart, University Hospital of Würzburg Takanori Sasaki Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Alexander Weich Department of Nuclear Medicine and Comprehensive Heart Failure Center (CHFC), Molecular Imaging of the Heart, University Hospital of Würzburg Takahiro Higuchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Fibroblast activation protein inhibitor (FAPI) targeting PET has been introduced as a novel molecular imaging modality for visualizing cancer-associated fibroblasts. There have also been reports suggesting incidental findings of localized accumulation in the shoulder joints. However, further characterization in a larger patient cohort is still lacking. Methods 77 consecutive patients (28 females; mean age, 63.1 ± 11.6) who underwent Ga-68 FAPI-04 PET/CT for diagnosis of solid tumors were included. The incidence and localization of tracer uptake in shoulder joints were investigated and compared with available F-18 FDG scans serving as reference. Results Ga-68 FAPI-04 uptake was evaluated in 77 patients (154 shoulder joints), of whom 54 subjects (108 shoulder joints) also had available F-18 FDG scans for head-to-head comparison. On FAPI-targeted imaging, 67/154 shoulders (43.5%) demonstrated increased radiotracer accumulation in target lesions, which were distributed as follows: acromioclavicular (AC) joints in 25/67 (37.3%), followed by glenohumeral and subacromial (GH + SA) joints in 23/67 (34.3%), or both (AC and GH + SA joints) in the remaining 19/67 (28.4%). Ga-68 FAPI-04 correlated with quantified F-18 FDG uptake (r = 0.69, p < 0.0001). Relative to the latter radiotracer, however, in-vivo FAP expression in the shoulders was significantly increased (Ga-68 FAPI-04, 4.7 ± 3.2 vs F-18 FDG, 3.6 ± 1.3, p < 0.001). Conclusion Our study revealed focal accumulation of Ga-68 FAPI-04 in the shoulders, particularly in the AC joints, with higher uptake compared to the inflammatory-directed PET radiotracer F-18 FDG in oncological studies. As a result, further trials are warranted to investigate the potential of FAPI-directed molecular imaging in identifying chronic remodeling in shoulder joints. This could have implications for initiating anti-FAP targeted photodynamic therapy based on PET signal strength. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1467-3045 47 6 2025 Artificial Intelligence Approach in Machine Learning-Based Modeling and Networking of the Coronavirus Pathogenesis Pathway 466 EN Shihori Tanabe Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences Sabina Quader Innovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion Ryuichi Ono Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences Hiroyoshi Y. Tanaka Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihisa Yamamoto Department of Mechanical Systems Engineering, Graduate School of Systems Design Tokyo Metropolitan University Motohiro Kojima Department of Surgical Pathology, Kyoto Prefecture University of Medicine Edward J. Perkins US Army Engineer Research and Development Center Horacio Cabral Department of Bioengineering, Graduate School of Engineering, The University of Tokyo The coronavirus pathogenesis pathway, which consists of severe acute respiratory syndrome (SARS) coronavirus infection and signaling pathways, including the interferon pathway, the transforming growth factor beta pathway, the mitogen-activated protein kinase pathway, the apoptosis pathway, and the inflammation pathway, is activated upon coronaviral infection. An artificial intelligence approach based on machine learning was utilized to develop models with images of the coronavirus pathogenesis pathway to predict the activation states. Data on coronaviral infection held in a database were analyzed with Ingenuity Pathway Analysis (IPA), a network pathway analysis tool. Data related to SARS coronavirus 2 (SARS-CoV-2) were extracted from more than 100,000 analyses and datasets in the IPA database. A total of 27 analyses, including nine analyses of SARS-CoV-2-infected human-induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes and fibroblasts, and a total of 22 analyses of SARS-CoV-2-infected lung adenocarcinoma (LUAD), were identified as being related to “human” and “SARS coronavirus 2” in the database. The coronavirus pathogenesis pathway was activated in SARS-CoV-2-infected iPSC-derived cells and LUAD cells. A prediction model was developed in Python 3.11 using images of the coronavirus pathogenesis pathway under different conditions. The prediction model of activation states of the coronavirus pathogenesis pathway may aid in treatment identification. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-3417 15 13 2025 Protective Effects of the Ethyl Acetate Fraction of Distylium racemosum Against Metabolic Dysfunction-Associated Steatohepatitis 7238 EN Young-Hyeon Lee Department of Clinical Laboratory Science, Catholic University of Pusan Min-Ho Yeo Department of Clinical Laboratory Science, Catholic University of Pusan Kyung-Soo Chang Department of Clinical Laboratory Science, Catholic University of Pusan Weon-Jong Yoon Clean Bio Business Division, Biodiversity Research Institute (JBRI), Jeju Technopark (JTP) Hye-Sook Kim Department of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jongwan Kim Department of Anatomy, College of Medicine, Dongguk University Hye-Ran Kim Department of Biomedical Laboratory Science, Dong-Eui Institute of Technology Metabolic dysfunction-associated steatohepatitis (MASH), previously referred to as non-alcoholic steatohepatitis (NASH), which is a progressive non-alcoholic fatty liver disease, is accompanied by hepatic steatosis, inflammation, and fibrosis. Despite its increasing prevalence, available treatment options for MASH are limited. Here, we investigated the protective effects of the Distylium racemosum ethyl acetate fraction (DRE) using MASH models and explored its key physiologically active components. Palmitic acid (PA)-induced AML12 hepatocytes and high-fat methionine- and choline-deficient-fed C57BL/6 mice were used as MASH models. Lipid accumulation was evaluated via triglyceride measurement, oil red O staining, and histological analysis. Lipid accumulation, inflammation, and fibrosis-associated gene expression were evaluated via real-time polymerase chain reaction. The physiologically active components of DRE were identified via high-performance liquid chromatography. Lipid accumulation and triglyceride levels were significantly reduced in PA-treated AML12 cells following DRE treatment. Additionally, DRE inhibited the expression of genes involved in lipogenesis (FAS and SREBP1c), inflammation (CD68, IL-6, and MCP-1), and fibrosis (COL1A1, COL1A2, and TIMP1). DRE reduced the liver weight, liver-to-body weight ratio, and hepatic steatosis in MASH model mice. It increased carnitine palmitoyltransferase-1 levels and decreased CD36 and transforming growth factor-β levels in the MASH mouse liver. High-performance liquid chromatography revealed that the extract contained rutin flavonoid family members. Overall, DRE was involved in lipid metabolism, inflammation, and fibrosis regulation, exerting potent hepatoprotective effects partly attributed to rutin and serving as a potential preventive candidate for MASH. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2192-2640 14 10 2024 Biocompatibility of Water-Dispersible Pristine Graphene and Graphene Oxide Using a Close-to-Human Animal Model: A Pilot Study on Swine 2401783 EN Paola Nicolussi Istituto Zooprofilattico Sperimentale della Sardegna Giovannantonio Pilo Istituto Zooprofilattico Sperimentale della Sardegna Maria Giovanna Cancedda Istituto Zooprofilattico Sperimentale della Sardegna Guotao Peng Institute of Environmental Medicine, Karolinska Institutet Ngoc Do Quyen Chau CNRS, Immunology, Immunopathology and Therapeutic Chemistry Alejandro De la Cadena Dipartimento di Fisica, Politecnico di Milano Renzo Vanna Istituto di Fotonica e Nanotecnologie – CNR Yarjan Abdul Samad Cambridge Graphene Centre, University of Cambridge Tanweer Ahmed Cambridge Graphene Centre, University of Cambridge Jeremia Marcellino Cambridge Graphene Centre, University of Cambridge Giuseppe Tedde Istituto Zooprofilattico Sperimentale della Sardegna Linda Giro ImmuneNano Laboratory, Department of Biomedical Sciences Acelya Ylmazer Department of Biomedical Engineering, Ankara University Federica Loi Istituto Zooprofilattico Sperimentale della Sardegna Gavina Carta Istituto Zooprofilattico Sperimentale della Sardegna Loredana Secchi Istituto Zooprofilattico Sperimentale della Sardegna Silvia Dei Giudici Istituto Zooprofilattico Sperimentale della Sardegna Simona Macciocu Istituto Zooprofilattico Sperimentale della Sardegna Dario Polli Dipartimento di Fisica, Politecnico di Milano Yuta Nishina Graduate School of Natural Science and Technology, Okayama University Ciriaco Ligios Istituto Zooprofilattico Sperimentale della Sardegna Giulio Cerullo Dipartimento di Fisica, Politecnico di Milano Andrea Ferrari Cambridge Graphene Centre, University of Cambridge Alberto Bianco CNRS, Immunology, Immunopathology and Therapeutic Chemistry Bengt Fadeel Institute of Environmental Medicine, Karolinska Institutet Giulia Franzoni Istituto Zooprofilattico Sperimentale della Sardegna Lucia Gemma Delogu ImmuneNano Laboratory, Department of Biomedical Sciences Graphene-based materials (GBMs) are of considerable interest for biomedical applications, and the pilot study on the toxicological and immunological impact of pristine graphene (GR) and graphene oxide (GO) using swine as a close-to-human provides valuable insights. First, ex vivo experiments are conducted on swine blood cells, then GBMs are injected intraperitoneally (i.p.) into swine. Hematological and biochemical analyses at various intervals indicate that neither GO nor GR cause systemic inflammation, pro-coagulant responses, or renal or hepatic dysfunction. Importantly, no systemic toxicity is observed. Analysis of a panel of 84 immune-related genes shows minimal impact of GO and GR. The animals are sacrificed 21 days post-injection, and transient absorption imaging and Raman mapping show the presence of GO and GR in the mesentery only. Histological evaluation reveals no signs of alterations in other organs. Thus, clusters of both materials are detected in the mesentery, and GO aggregates are surrounded only by macrophages with the formation of granulomas. In contrast, modest local reactions are observed around the GR clusters. Overall, these results reveal that i.p. injection of GBMs resulted in a modest local tissue reaction without systemic toxicity. This study, performed in swine, provides essential guidance for future biomedical applications of graphene. No potential conflict of interest relevant to this article was reported.

Springer Nature Singapore Acta Medica Okayama 0302-9743 2025 RKPM: Restricted Kernel Page Mechanism to Mitigate Privilege Escalation Attacks 213 231 EN Hiroki Kuzuno Graduate School of Engineering, Kobe University Toshihiro Yamauchi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kernel memory corruption attacks against operating systems exploit kernel vulnerabilities to overwrite kernel data. Kernel address space layout randomization makes it difficult to identify kernel data by randomizing their virtual address space. Control flow integrity (CFI) prevents unauthorized kernel code execution by verifying kernel function calls. However, these countermeasures do not prohibit writing to kernel data. If the virtual address of privileged information is specified and CFI is circumvented, the privileged information can be modified by a kernel memory corruption attack. In this paper, we propose a restricted kernel page mechanism (RKPM) to mitigate kernel memory corruption attacks by introducing restricted kernel pages to protect the kernel data specified in the kernel. The RKPM focuses on the fact that kernel memory corruption attacks attempt to read the virtual addresses around the privileged information. The RKPM adopts page table mapping handling and a memory protection key to control the read and write restrictions of the restricted kernel pages. This allows us to mitigate kernel memory corruption attacks by capturing reads to the restricted kernel page before the privileged information is overwritten. As an evaluation of the RKPM, we confirmed that it can mitigate privilege escalation attacks on the latest Linux kernel. We also measured that there was a certain overhead in the kernel performance. This study enhances kernel security by mitigating privilege escalation attacks through the use of software or hardware based restricted kernel pages. 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.

Wiley Acta Medica Okayama 1861-4728 2025 Alkoxy‐Substituted Anthrabis(Thiadiazole)‐Terthiophene Copolymers for Organic Photovoltaics: A Unique Wavy Backbone Enhances Aggregation, Molecular Order, and Device Efficiency e00678 EN Yi Yan Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroki Mori Research Institute for Interdisciplinary Science, Okayama University Tomoki Yoshino Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ryuki Inami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jiaxin Chang Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Junqing Gao Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yasushi Nishihara Research Institute for Interdisciplinary Science, Okayama University Two polymer donors, PATz3T-o6BO and PATz3T-o6HD, incorporating alkoxy-substituted anthra[1,2-c:5,6-c′]bis([1,2,5]thiadiazole), were strategically designed and synthesized. The unique wavy backbone of these polymers effectively reduced aggregation, leading to enhanced solubility and significantly improved molecular ordering. Consequently, the PATz3T-o6HD:Y12-based solar cells achieved a power conversion efficiency (PCE) of 7.94%. These findings provide valuable insights into the molecular design of high-performance polymer donors for organic photovoltaics (OPVs). 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 Automated identification of the origin of energy loss in nonoriented electrical steel by feature extended Ginzburg–Landau free energy framework 23758 EN Michiki Taniwaki Tokyo University of Science Ryunosuke Nagaoka Tokyo University of Science Ken Masuzawa Tokyo University of Science Shunsuke Sato Tokyo University of Science Alexandre Lira Foggiatto Tokyo University of Science Chiharu Mitsumata Tokyo University of Science Takahiro Yamazaki Tokyo University of Science Ippei Obayashi Okayama University Yasuaki Hiraoka Kyoto University Yasuhiko Igarashi University of Tsukuba Yuta Mizutori University of Tsukuba Sepehri Amin Hossein NIMS Tadakatsu Ohkubo NIMS Hisashi Mogi Nippon Steel Masato Kotsugi Tokyo University of Science This study presents the automated identification of the complex magnetization reversal process in nonoriented electrical steel (NOES) using the feature extended Ginzburg–Landau (eX-GL) free energy framework. eX-GL provides a robust connection between microscopic magnetic domains and macroscopic magnetic hysteresis using a data science perspective. This method employs physically meaningful features to analyze the energy landscape, providing insights into the mechanisms behind function. We obtained features representing both the microstructure and energy of the domain wall. The causes of iron loss were traced to the original domain structure, through which we could successfully distinguish and visualize the role of pinning as a promoting and resisting factor. We found that the reversal process was governed not only by general grain boundary pinning but also by segmented magnetic domains within the grain. This method revealed the complex interplay between magnetism and metallography and introduced a new means for transformative material design, bridging structures and functions. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0140-7791 2025 Amino Acid Substitutions in Loop C of Arabidopsis PIP2 Aquaporins Alters the Permeability of CO2 EN Shaila Shermin Tania Institute of Plant Science and Resources, Okayama University Shigeko Utsugi Institute of Plant Science and Resources, Okayama University Yoshiyuki Tsuchiya Institute of Plant Science and Resources, Okayama University Shizuka Sasano Institute of Plant Science and Resources, Okayama University Maki Katsuhara Institute of Plant Science and Resources, Okayama University Izumi C. Mori Institute of Plant Science and Resources, Okayama University The transport of CO2 across biomembranes in plant cells is essential for efficient photosynthesis. Some aquaporins capable of CO2 transport, referred to as ‘COOporins’, are postulated to play a crucial role in leaf CO2 diffusion. However, the structural basis of CO2 permeation through aquaporins remains largely unknown. Here, we show that amino acids in loop C are critical for the CO2 permeability of Arabidopsis thaliana PIP2 aquaporins. We found that swapping tyrosine and serine in loop C to histidine and phenylalanine, which differ between AtPIP2;1 and AtPIP2;3, altered CO2 permeability when examined in the Xenopus laevis oocyte heterologous expression system. AlphaFold2 modelling indicated that these substitution induced a conformational shift in the sidechain of arginine in the aromatic/arginine (ar/R) selectivity filter and in lysine at the extracellular mouth of the monomeric pore in PIP2 aquaporins. Our findings demonstrate that distal amino acid substitutions can trigger conformational changes of the ar/R filter in the monomeric pore, modulating CO2 permeability. Additionally, phylogenetic analysis suggested that aquaporins capable of dual water/CO2 permeability are ancestral to those that are water-selective and CO2-impermeable, and CO2-selective and water impermeable. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0033-183X 262 2 2024 Analysis of the effect of permeant solutes on the hydraulic resistance of the plasma membrane in cells of Chara corallina 385 395 EN Masashi Tazawa Yoshida Biological Laboratory Randy Wayne Laboratory of Natural Philosophy, Plant Biology Section, Cornell University Maki Katsuhara Institute of Plant Science and Resources (IPSR), Okayama University In the cells of Chara corallina, permeant monohydric alcohols including methanol, ethanol and 1-propanol increased the hydraulic resistance of the membrane (Lpm－1). We found that the relative value of the hydraulic resistance (rLpm－1) was linearly dependent on the concentration (Cs) of the alcohol. The relationship is expressed in the equation: rLpm－1 = ρmCs + 1, where ρm is the hydraulic resistance modifier coefficient of the membrane. Ye et al. (2004) showed that membrane-permeant glycol ethers also increased Lp－1. We used their data to estimate Lpm－1 and rLpm－1. The values of rLpm－1 fit the above relation we found for alcohols. When we plotted the ρm values of all the permeant alcohols and glycol ethers against their molecular weights (MW), we obtained a linear curve with a slope of 0.014 M－1/MW and with a correlation coefficient of 0.99. We analyzed the influence of the permeant solutes on the relative hydraulic resistance of the membrane (rLpm－1) as a function of the external (π0) and internal (πi) osmotic pressures. The analysis showed that the hydraulic resistance modifier coefficients (ρm) were linearly related to the MW of the permeant solutes with a slope of 0.012 M－1/MW and with a correlation coefficient of 0.84. The linear relationship between the effects of permeating solutes on the hydraulic resistance modifier coefficient (ρm) and the MW can be explained in terms of the effect of the effective osmotic pressure on the hydraulic conductivity of water channels. The result of the analysis suggests that the osmotic pressure and not the size of the permeant solute as proposed by (Ye et al., J Exp Bot 55:449–461, 2004) is the decisive factor in a solute’s influence on hydraulic conductivity. Thus, characean water channels (aquaporins) respond to permeant solutes with essentially the same mechanism as to impermeant solutes. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0031-9317 177 4 2025 CNGC2 Negatively Regulates Stomatal Closure and Is Not Required for flg22- and H2O2-Induced Guard Cell [Ca2+]cyt Elevation in Arabidopsis thaliana e70396 EN Rojina Akter Graduate School of Environmental and Life Science, Okayama University Yasuhiro Inoue Graduate School of Environmental and Life Science, Okayama University Saori Masumoto Faculty of Agriculture, Okayama University Yoshiharu Mimata Graduate School of Environmental and Life Science, Okayama University Takakazu Matsuura Institute of Plant Science and Resources, Okayama University Izumi C. Mori Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University In guard cells, cytosolic Ca2+ acts as a second messenger that mediates abscisic acid (ABA)- and pathogen-associated molecular pattern (PAMP)-induced stomatal closure. It was reported that Arabidopsis cyclic nucleotide-gated ion channel 2 (CNGC2) functions as hydrogen peroxide (H2O2)- and PAMP-activated Ca2+-permeable channels at the plasma membrane of mesophyll cells and mediates Ca2+-dependent PAMP-triggered immunity. In this study, we examined the role of CNGC2 in the regulation of stomatal movement because CNGC2 is also expressed in guard cells. We found that stomata of the CNGC2 disruption mutant cngc2-3 are constitutively closed even in the absence of ABA or the flagellar-derived PAMP, flg22. Consistently, leaf temperatures of the cngc2-3 mutant were higher than those of wild-type (WT) plants. The stomatal phenotype of the cngc2-3 mutant was restored by complementation with wild-type CNGC2 under the control of the guard cell preferential promoter, pGC1. Elevation of cytosolic free Ca2+ concentration in guard cells induced by flg22 and H2O2 remained intact in the cngc2-3 mutant. The introduction of the ost1-3 mutation into the cngc2-3 background did not alter the stomatal phenotype. However, the stomatal phenotype of the cngc2-3 mutant was successfully rescued in the double disruption mutant cngc2-3aba2-2. Taken together, these results suggest that CNGC2 negatively regulates stomatal closure response and does not function as flg22– and H2O2-activated Ca2+ channels in guard cells. Though CNGC2 is responsive for H2O2- and flg22-induced [Ca2+]cyt elevation in mesophyll cells, the involvement of CNGC2 in the response to H2O2 and flg22 in guard cells is questionable. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2198-3844 12 18 2025 Cryo-EM Analysis of a Tri-Heme Cytochrome-Associated RC-LH1 Complex from the Marine Photoheterotrophic Bacterium Dinoroseobacter Shibae 2413456 EN Weiwei Wang College of Life Sciences, Zhejiang University Yanting Liu State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University Jiayi Gu College of Life Sciences, Zhejiang University Shaoya An Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine Cheng Ma Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine Haichun Gao College of Life Sciences, Zhejiang University Nianzhi Jiao State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University Jian‐Ren Shen Research Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama University John Thomas Beatty Department of Microbiology & Immunology, University of British Columbia Michal Koblížek Laboratory of Anoxygenic Phototrophs, Institute of Microbiology, Czech Academy of Science Xing Zhang Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine Qiang Zheng State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University Jing‐Hua Chen College of Life Sciences, Zhejiang University The reaction center-light harvesting 1 (RC-LH1) complex converts solar energy into electrical energy, driving the initiation of photosynthesis. The authors present a cryo-electron microscopy structure of the RC-LH1 isolated from a marine photoheterotrophic bacterium Dinoroseobacter shibae. The RC comprises four subunits, including a three-heme cytochrome (Cyt) c protein, and is surrounded by a closed LH ring composed of 17 pairs of antenna subunits. Notably, a novel subunit with an N-terminal “helix-turn-helix” motif embedded in the gap between the RC and the LH ring is identified. The purified RC-LH1 complex exhibits high stability in solutions containing Mg2+ or Ca2+. The periplasmic Cyt c2 is predicted to bind at the junction between the Cyt subunit and the membrane plane, enabling electron transfer from Cyt c2 to the proximal heme of the tri-heme Cyt, and subsequently to the special pair of bacteriochlorophylls. These findings provide structural insights into the efficient energy and electron transfer processes within a distinct type of RC-LH1, and shed light on evolutionary adaptations of photosynthesis. 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.

Wiley Acta Medica Okayama 2378-8038 10 1 2025 Short‐process incudo‐stapedioplasty in congenital ear malformation e70055 EN Ryotaro Omichi Department of Otolaryngology-Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shin Kariya Department of Otolaryngology-Head and Neck Surgery, Kawasaki Medical School Akiko Sugaya Department of Otolaryngology-Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Mizuo Ando Department of Otolaryngology-Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Objectives: Although various stapedotomy and stapedectomy techniques exist, anchoring the piston can be challenging. We present a novel surgical approach for treating congenital stapes malformations with an atypical facial nerve trajectory. Methods: This is a case of a 7-year-old boy presenting with bilateral conductive hearing loss. Prior attempts at tympanoplasty had proven unsuccessful in improving his hearing. Presurgical imaging studies revealed an unusual anatomical configuration, with the facial nerve positioned inferior to the oval window. This anatomical variation precluded the use of conventional prosthesis-anchoring techniques typically employed in stapedotomies. Thus, we devised an innovative approach, opting to anchor the prosthesis to the short process of the incus. Results: This novel technique circumvented the atypical course of the facial nerve, allowing for successful reconstruction of the ossicular chain. The patient demonstrated an acceptable improvement (30 dB gain) in hearing 1-year post-surgery, with no reported complications. Conclusion: This case underscores the critical importance of adapting surgical techniques to address the unique anatomical challenges that may arise in the context of congenital ear malformations. It also highlights the potential of the short process of the incus as a viable alternative anchoring site for stapes prostheses, thereby improving the outcomes of such complex cases. This technique not only restored the patient's hearing but also contributed valuable insights into the management of similar cases, potentially improving the quality of life for individuals with rare and challenging anatomical variations. Level of evidence: 5. 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 Science and Business Media LLC Acta Medica Okayama 0015-749X 71 3 2025 Physiological and Biochemical Traits of Dormancy Release and Growth Resumption in Japanese Cedar in the Warm-Temperate Zone 321 343 EN Shoma Hiejima The United Graduate School of Agricultural Sciences, Kagoshima University Hiroto Seino Graduate School of Agriculture, Forestry and Fisheries, Kagoshima University Rico Hachisuka The United Graduate School of Agricultural Sciences, Kagoshima University Yuka Watanabe Graduate School of Agriculture, Forestry and Fisheries, Kagoshima University Takakazu Matsuura Institute of Plant Science and Resources, Okayama University Izumi C. Mori Institute of Plant Science and Resources, Okayama University Shin Ugawa The United Graduate School of Agricultural Sciences, Kagoshima University Global warming will disturb dormancy release and growth resumption of trees. To better understand this process, it is important to investigate physiological and biochemical traits related to these stages. We examined dormancy release and growth resumption in Japanese cedar (Cryptomeria japonica [L.] D. Don), an evergreen needle-leaved tree, in the warm-temperate zone by evaluating budbreak under growth-promoting conditions, and simultaneously examining respiration rates and contents of carbohydrates and phytohormones in shoots from November 2022 to March 2023. A long time to budbreak and the lowest budbreak rates of 75% in November indicated shallow dormancy. Budbreak rates of 98%, short time to budbreak, and first appearance of budbreak in the field in March indicated growth resumption. Continuous changes in budbreak rates and time to budbreak between dormancy and growth resumption indicated dormancy was gradually released. Surges in budbreak rates in December indicated dormancy was almost completely released by early winter. Contents of abscisic acid (ABA) and salicylic acid (SA) decreased from November, remained low in March, and were strongly associated with budbreak rates according to principal component analysis. It was suggested that the depletion of SA led to the depletion of ABA, contributing to dormancy release and growth resumption. Fructose and trans-zeatin accumulated until February, and low levels of starch, indole-3-acetic acid, jasmonic acid, and jasmonic acid-isoleucine during winter was followed by accumulation in March. Although these biochemical traits were less related to budbreak rates compared to ABA and SA, they seemed to assist either dormancy release or growth resumption. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6643 17 10 2025 Clinical Characteristics of Vitamin D Deficiency Detected in Long COVID Patients During the Omicron Phase 1692 EN Yui Matsuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuya Yokota Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Takase Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Omura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: To characterize the clinical significance of vitamin D deficiency (VDD) detected in long COVID, a retrospective observational study was performed for outpatients who visited our clinic during the period from May 2024 to November 2024. Methods: Clinical trends in long COVID patients diagnosed with VDD who showed serum concentrations of 25-hydroxyvitamin D (25-OHD) lower than 20 ng/mL were compared with those in long COVID patients in a non-deficient vitamin D (NDD) group. Results: Of 126 patients with long COVID, 97 patients (female: 50) who had been infected during the Omicron phase were included. Sixty-six patients (68%) were classified in the VDD group. The median serum concentrations of 25-OHD were 14.8 ng/mL in the VDD group and 22.9 ng/mL in the NDD group. There were no significant differences between the two groups in terms of age, gender, BMI, severity of COVID-19, period after infection and vaccination history. Although the levels of serum calcium and phosphate were not significantly different between the two groups, the percentages of patients in the VDD group who complained of dizziness, memory impairment, palpitation and appetite loss were larger than those in the NDD group. Of note, the patients who complained of palpitation showed significantly lower concentrations of serum 25-OHD than those in the patients without palpitation (median: 11.9 vs. 17.3 ng/mL). Moreover, patients in the VDD group had significantly higher scores for physical and mental fatigue as well as higher scores for depressive symptoms. Conclusions: Collectively, VDD is involved in clinical manifestations of long COVID, particularly symptoms of palpitation, fatigue and depression. No potential conflict of interest relevant to this article was reported.