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

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

MDPI AG Acta Medica Okayama 2072-6694 18 4 2026 Antigen Remodeling in Colorectal Cancer: How Radiotherapy and Chemotherapy Enhance Immunotherapy Responsiveness 715 EN 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 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Colorectal cancer (CRC) is traditionally considered a “cold tumor” characterized by low immunogenicity and limited responsiveness to immune checkpoint inhibitors (ICIs). However, recent findings reveal that cytotoxic modalities can reprogram this immunologically inert landscape. This review integrates these evolving concepts to guide the optimization of future treatments. Radiotherapy induces extensive DNA double-strand breaks, which may generate de novo mutations through error-prone repair while simultaneously exposing cryptic antigens via increased transcriptional instability, alternative splicing, and enhanced proteasomal processing. Chemoradiation also amplifies epigenetic and epitranscriptomic sources of neoepitope diversity, including RNA editing and stress-induced splicing alterations, expanding the immunopeptidome beyond canonical mutation-driven neoantigens. These changes collectively enhance antigen presentation and facilitate T-cell priming. Chemotherapy further reduces immunosuppressive cell populations and promotes dendritic cell activation, creating a permissive milieu for subsequent immune engagement. Clinically, the VOLTAGE studies demonstrated that long-course chemoradiotherapy can sensitize even mismatch repair–proficient rectal cancers to PD-1 blockade, yielding clinically meaningful pathological responses. In contrast, mismatch repair–deficient rectal tumors may respond completely to ICIs alone. Short-course radiotherapy combined with chemotherapy and ICIs has also shown encouraging activity in the setting of total neoadjuvant therapy. Collectively, these findings support a paradigm in which radiotherapy, chemotherapy, and epigenetic/epitranscriptomic alterations—including RNA editing—act as potent modulators of tumor antigenicity. By expanding the neoantigen repertoire and reshaping the tumor microenvironment, these strategies can transform CRC from a cold tumor into one that is increasingly responsive to immunotherapy. 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 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.

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.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 3 2025 Prospective Evaluation of the Safety and Compression Performance of Novel Compression Denim Jeans in Healthy Volunteers and Patients With Lymphedema e80971 EN Daiki Ousaka Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyoshi Yamada Departments of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriko Sakano Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoe Kirino Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazumasa Miyake Department of Rehabilitation, Lymphedema Treatment Center, Kousei Hospital Takumi Takahashi Division of Business Management, Matsuoka Corporation Akihiro Matsuoka Division of Production Engineering, Matsuoka Corporation Shintaro Yamada Division of Sales, Kaihara Corporation Akira Shinaoka Department of Lymphatics and Edematology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Oozawa Department of Clinical Safety, Okayama University Hospital Objectives: The treatment of lower-extremity lymphedema, whether congenital or acquired, remains challenging. Long-term management aimed at reducing complications and maximizing quality of life is essential. Compression stockings are crucial in this management; however, their application is limited by patient experience (ease of wear, texture, breathability, and appearance). This highlights the need to evaluate alternative compression garments that maintain therapeutic efficacy while improving patient adherence.<br> Methods: We developed a novel compression denim product (Flow plus Jeans®) using advanced sewing technology. Its baseline performance (compression ability) was evaluated by measuring pressure gradients at three points (ankle, calf, and thigh) using a mannequin-based compression testing system and compared with those of existing stockings. Thereafter, a safety assessment was conducted on healthy volunteers to evaluate potential adverse effects, including changes in lower limb circumference, signs of deep vein thrombosis (DVT) via ultrasound, and skin complications. A clinical trial in patients with lymphedema was then performed to compare its efficacy with that of conventional compression stockings.<br> Results: Baseline performance testing with a mannequin revealed that Flow plus Jeans demonstrated compression levels and pressure gradients at three calf points comparable to those of standard compression stockings. A safety study involving nine healthy volunteers confirmed that Flow plus Jeans caused no significant changes in lower-limb circumferences after three days of wear, with no cases of DVT or skin complications. In a subsequent clinical trial involving nine female patients with lymphedema, the jeans showed non-inferiority to existing stockings concerning lower-limb circumference measurements at six points (pre-use vs. six months post-use), with patient-reported experiences assessed via questionnaires. Notably, patients reported enhanced satisfaction regarding the jeans' fashionability, which could serve as an incentive for long-term adherence.<br> Conclusion: Our findings suggest that Flow plus Jeans represent a promising novel option for the long-term management of lymphedema, offering an alternative that balances medical efficiency with improved patient satisfaction and demonstrates safety in healthy individuals. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1873-149X 33 1 2026 Bridging the Gap Between Static Histology and Dynamic Organ-on-a-Chip Models 10 EN Zheyi Wang Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Takahashi Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University For more than a century, pathology has served as a cornerstone of modern medicine, relying primarily on static microscopic assessment of tissue morphology—such as H&E staining—which remains the “gold standard” for disease diagnosis. However, this conventional paradigm provides only a snapshot of disease states and often fails to capture their dynamic evolution and complex functional mechanisms. Moreover, animal models are constrained by marked interspecies differences, creating a persistent gap in translational research. To overcome these limitations, we propose the concept of New Pathophysiology, a research framework that transcends purely morphological descriptions and aims to resolve functional dynamics in real time. This approach integrates Organ-on-a-Chip (OOC) technology, multi-omics analyses, and artificial intelligence to reconstruct the entire course of disease initiation and to enable personalized medicine. In this review, we first outline the foundations and limitations of traditional pathology and animal models. We then systematically summarize more than one hundred existing OOC disease models across multiple organs—including the kidney, liver, and brain. Finally, we elaborate on how OOC technologies are reshaping the study of key pathological processes such as inflammation, metabolic dysregulation, and fibrosis by converting them into dynamic, mechanistic disease models, and we propose future perspectives in the field. This review adopts a relatively uncommon classification strategy based on pathological mechanisms (mechanism-based), rather than organ-based categorization, allowing readers to recognize shared principles underlying different diseases. Moreover, the focus of this work is not on emphasizing iteration or replacement of existing approaches, but on preserving past achievements from a historical perspective, with an emphasis on overcoming current limitations and enabling new advances. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1759-9954 16 47 2025 Synthesis of sterically unhindered Lewis acidic boron-doped π-conjugated polymers 5035 5039 EN Naoki Takahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University We report the synthesis of sterically unhindered boron-doped π-conjugated polymers via polymerization of organo-dilithium reagents with boron trichloride. The resulting polymer exhibits Lewis acidity and catalyzes the transesterification of methyl benzoate. This performance is attributed to the electron-accepting ability, and thermally labile Lewis acid–base interactions, facilitating catalytic turnover. No potential conflict of interest relevant to this article was reported.

American Society of Clinical Oncology (ASCO) Acta Medica Okayama 2473-4276 9 2025 Development and Validation of an Ipsilateral Breast Tumor Recurrence Risk Estimation Tool Incorporating Real-World Data and Evidence From Meta-Analyses: A Retrospective Multicenter Cohort Study e2500182 EN Yasuaki Sagara Department of Breast and Thyroid Surgical Oncology, Hakuaikai Sagara Hospital Atsushi Yoshida Department of Breast Surgical Oncology, St Luke's International Hospital Yuri Kimura Department of Breast Surgical Oncology, The Cancer Institute Hospital of JFCR Makoto Ishitobi Department of Breast Surgery, Osaka Habikino Medical Center Yuka Ono Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Koji Takada Department of Breast Surgical Oncology, Osaka Metropolitan University Graduate School of Medicine Yuri Ito Department of Medical Statistics, Osaka Medical and Pharmaceutical University Tomo Osako Division of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research Takehiko Sakai Department of Breast Surgical Oncology, The Cancer Institute Hospital of JFCR Purpose Ipsilateral breast tumor recurrence (IBTR) remains a critical concern for patients undergoing breast-conserving surgery (BCS). Reliable risk estimation tools for IBTR risk can support personalized surgical and adjuvant treatment decisions, especially in the era of evolving systemic therapies. We aimed to develop and validate models to estimate IBTR risk.<br> Patients and Methods This multicenter retrospective cohort study included 8,938 women who underwent partial mastectomy for invasive breast cancer between 2008 and 2017. Prediction models were developed using Cox proportional hazards regression and validated via bootstrap resampling. Model performance was assessed using Harrell's C-index, Brier scores, calibration plots, and goodness-of-fit tests.<br> Results During a median follow-up of 9.0 years (IQR, 6.6-10.9), IBTR occurred in 320 patients (3.6%). The initial model, based on variables from Sanghani et al, achieved a Harrell's C-index of 0.74. Incorporating hormonal receptor status, human epidermal growth factor receptor 2 status, radiotherapy, and targeted therapy as predictors reduced the C-index to 0.65, despite their clinical relevance. Importantly, the inclusion of these factors improved calibration, demonstrating better alignment between predicted and observed IBTR probabilities. Although the hazard ratios (HRs) for radiotherapy aligned with the Early Breast Cancer Trialists’ Collaborative Group meta-analyses (MA), those for chemotherapy and endocrine therapy showed slight differences. Therefore, HRs from the MA were used to represent treatment effects in our model.<br> Conclusion We have developed and internally validated a new risk estimation model for IBTR using Cox regression and bootstrap methods. A Web-based risk estimation tool is now available to facilitate individualized risk assessment and treatment planning. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2772-5723 5 2 2026 Feasibility and Diagnostic Utility of Mucosal T-Cell Flow Cytometry for Intestinal Graft-Versus-Host Disease 100820 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takumi Kondo Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daisuke Ennishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuharu Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mai Hiramatsu Division of Medical Support, Okayama University Hospital Araki Hirabata Division of Medical Support, Okayama University Hospital Takahide Takahashi Division of Medical Support, Okayama University Hospital Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background and Aims: Timely diagnosis of intestinal complications after hematopoietic stem cell transplantation (HSCT), including graft-versus-host disease (GVHD), transplant-associated thrombotic microangiopathy, and cytomegalovirus infection, is essential for appropriate management. This study evaluated whether mucosal T-cell profiling from endoscopic biopsies could support the diagnosis of these post-transplant conditions.<br> Methods: We prospectively analyzed 58 intestinal biopsy specimens from 21 post-HSCT patients. Paired samples were obtained from the stomach and duodenum during upper endoscopy and from the ileum and large intestine during colonoscopy. Lymphocytes were isolated from each specimen and analyzed using flow cytometry. These data were integrated with those of a previously collected cohort (35 patients, 51 samples) for comparative immunophenotypic analysis across histologically defined groups.<br> Results: Duodenal biopsies yielded more lymphocytes than did gastric biopsies (mean ± standard deviation: 532 ± 823 vs 233 ± 392 cells; P = .070), with comparable yields between the ileum and colon. Among 41 evaluable cases, the CD56+:CD3+ ratio was significantly lower in patients with GVHD (5.5 ± 2.2%) than in those with nonspecific or no inflammation (28.4 ± 16.3%; P = .006). A cutoff value of <11% provided 85.7% sensitivity and 83.3% specificity for diagnosing GVHD (area under the curve = 0.91).<br> Conclusion: Mucosal T-cell profiling using endoscopic biopsies is feasible and may aid in the diagnosis of GVHD after HSCT. A decreased CD56+:CD3+ ratio is a promising marker for distinguishing GVHD from other post-transplant intestinal conditions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 32 6 2025 Clinical significance on switching CDK4/6 inhibitors among 13,284 patients with metastatic breast cancer 1405 1416 EN Takuya Nishina Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Maki Tanioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kenji Takada Medical AI Project, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takahiro Tsukioki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuko Takahashi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tadahiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Recent clinical trials have shown that switching to a combination therapy of a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) prolongs progression-free survival (PFS) compared with ET monotherapy. Reports indicate that abemaciclib provides benefits regardless of the PIK3CA mutation status; however, its clinical benefits remain insufficient. This study aimed to evaluate the clinical significance of switching CDK4/6i + ET in a large real-world cohort. Using a medical database, we identified 13,284 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer who received CDK4/6i + ET between 2008 and 2022. Patients were categorized into five groups based on their first- and second-line therapy patterns. We compared the median time to discontinuation (TTD) among the groups. In patients who switched from one CDK4/6i + ET to another CDK4/6i + ET, the second-line TTD and total TTD of first- and second-line therapies (n = 542) were significantly longer than those in patients who switched from CDK4/6i + ET to ET monotherapy (n = 490) (the second-line TTD: 11.2 vs. 4.9 months, p < 0.01; total TTD: 25.1 vs. 20.5 months, p < 0.01). The order of palbociclib and abemaciclib administration did not significantly affect the second-line or total TTD in patients who switched from one CDK4/6i + ET to another CDK4/6i + ET. Switching from one CDK4/6i + ET to another CDK4/6i + ET resulted in a significantly longer TTD than switching to ET monotherapy. Considering the phase III clinical trial results of capivasertib, switching to CDK4/6i + ET is a viable therapeutic option regardless of the PIK3CA mutation status. No potential conflict of interest relevant to this article was reported.

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

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

American Society for Clinical Investigation Acta Medica Okayama 2379-3708 10 24 2025 Enhancement of drug delivery through fibroblast activation protein–targeted near-infrared photoimmunotherapy e195776 EN Seitaro Nishimura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Tasuku Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Yasushige Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Tatsuya Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hijiri Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hotaka Kawai Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Masaaki Akai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Teruki Kobayashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Noriyuki Nishiwaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hajime Kashima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Takuya Kato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Toshiaki Ohara Department of Gastroenterological Surgery, 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 Science Yasuhiro Shirakawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Peter L. Choyke Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH Hisataka Kobayashi Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science The tumor microenvironment plays a key role in cancer progression and therapy resistance, with cancer-associated fibroblasts (CAFs) contributing to desmoplasia, extracellular matrix (ECM) remodeling, and elevated interstitial fluid pressure, all of which hinder drug delivery. We investigated fibroblast activation protein–targeted (FAP-targeted) near-infrared photoimmunotherapy (NIR-PIT) as a strategy to improve drug penetration in CAF-rich tumors. In clinical esophageal cancer samples, FAP expression strongly correlated with increased collagen I, hyaluronic acid, and microvascular collapse. CAF-rich 3D spheroids demonstrated elevated ECM deposition and significantly impaired drug uptake compared with CAF-poor models. FAP-targeted NIR-PIT selectively reduced CAFs, reduced ECM components, and restored drug permeability. In vivo, FAP-targeted NIR-PIT enhanced the accumulation of panitumumab and Abraxane in CAF-rich tumors and improved antitumor efficacy when combined with chemotherapy. These findings highlight FAP-targeted NIR-PIT as a promising therapeutic approach to remodel the tumor stroma and overcome drug resistance in desmoplastic solid tumors. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0305-1048 53 22 2025 eIF2D promotes 40S ribosomal subunit recycling during intrinsic ribosome destabilization gkaf1322 EN Kazuya Ichihara Division of Biological Science, Graduate School of Science, Nagoya University Taichi Shiraishi Division of Biological Science, Graduate School of Science, Nagoya University Yuhei Chadani Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yuki Kito Division of Cell Biology, Medical Institute of Bioregulation, Kyushu University Chisa Shiraishi Division of Biological Science, Graduate School of Science, Nagoya University Mina Hirata Division of Biological Science, Graduate School of Science, Nagoya University Yuta Takahashi Division of Biological Science, Graduate School of Science, Nagoya University Akinao Kobo School of Life Science and Technology, Institute of Science Tokyo Atsushi Hatano Department of Omics and Systems Biology, Graduate School of Medical and Dental Sciences, Niigata University Masaki Matsumoto Department of Omics and Systems Biology, Graduate School of Medical and Dental Sciences, Niigata University Kodai Machida Graduate School of Engineering, University of Hyogo Hiroaki Imataka Graduate School of Engineering, University of Hyogo Atsushi Toyoda Advanced Genomics Center, National Institute of Genetics Emi Mishiro-Sato Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University Takayuki Nojima Medical Institute of Bioregulation, Kyushu University Takuhiro Ito Laboratory for Translation Structural Biology, RIKEN Center for Integrative Medical Sciences Hideki Taguchi School of Life Science and Technology, Institute of Science Tokyo Keiichi I Nakayama Division of Cell Biology, Medical Institute of Bioregulation, Kyushu University Akinobu Matsumoto Division of Biological Science, Graduate School of Science, Nagoya University Although eukaryotic initiation factor 2D (eIF2D) is implicated in translation initiation, reinitiation, and ribosome recycling, its precise role remains unclear. Here, we show that eIF2D promotes 40S ribosome recycling during intrinsic ribosome destabilization (IRD), a process in which ribosomes stochastically destabilize while translating proteins with consecutive acidic amino acids at their NH2-terminus. Unrecycled 40S ribosomes accumulate in eIF2D-deficient cells, leading to 80S ribosome stalling. Selective translation complex profiling (TCP-seq) reveals that eIF2D preferentially associates with IRD-prone regions. The winged helix domain, unique to eIF2D but absent in MCTS1–DENR, enhances its binding to 40S subunits, but likely clashes with ABCE1 during stop-codon-associated recycling. Loss of eIF2D reduces the expression of IRD-inducing proteins, including splicing factors. Together, these findings define a previously unappreciated role for eIF2D in 40S recycling and clarify its mechanistic divergence from the MCTS1–DENR complex. No potential conflict of interest relevant to this article was reported.

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

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 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.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1463-9262 27 18 2025 Deoxygenative dual CO2 conversions: methylenation and switchable N-formylation/N-methylation of tryptamines 5359 5365 EN Kazuto Takaishi Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hajime Morishita Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kosuke Iwaki Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tadashi Ema Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The unprecedented one-pot synthesis of N-formyl/N-methyltryptolines from tryptamines was achieved via phenylsilane-assisted deoxygenative dual CO2 conversions. Two CO2 molecules acted as different synthons and were converted into methylene and N-formyl/N-methyl groups. The CO2 reduction step was catalyzed by a pentanuclear zinc complex at atmospheric pressure under solvent-free conditions. The N-formyl/N-methyl products could be switched by changing the amount of phenylsilane, and the amounts of in situ generated bis(silyl)acetals and silyl formates were key to the chemoselectivity. Methylenation, N-formylation, and N-methylation proceeded via the Pictet–Spengler reaction, amine–acid condensation, and the Eschweiler–Clarke reaction, respectively. The CO2 reduction with phenylsilane could also be applied to the one-pot three-step synthesis of spiro[oxindole-pyrrolidine]s. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1613-6810 2025 Atomic-Level Insights into Thermal Carbonization of Ethynyl-Containing Boron Compounds e13537 EN Kentaro Ohkura Research Institute for Interdisciplinary Science, Okayama University Satoshi Hayakawa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Naoki Takahashi Graduate School of Environment Life Natural Science and Technology, Okayama University Ken Yamazaki Graduate School of Environment Life Natural Science and Technology, Okayama University Jun Kano Graduate School of Environment Life Natural Science and Technology, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University This study reports the design, synthesis, and characterization of boron-doped carbon (BDC) derived from a triethynylborane-pyridine complex. Triethynylborane is stabilized by coordination with pyridine, facilitating its synthesis and handling in ambient conditions. The complex is subjected to thermal treatment at various temperatures to form BDC. Powder XRD and single-crystal XRD analyses reveal that BDC prepared at 200 °C retains an ordered structure, while higher temperatures induce alkyne structural changes without significant weight or surface area alterations. Coin cells are assembled using BDC as the anode, demonstrating unique Li-ion and Na-ion storage properties distinct from graphite. These results suggest that the BDC reflects the precursor's crystal structure, enabling novel electrochemical behavior. These findings offer insight into the development of advanced BDC materials for energy storage applications. 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 Conversion to Hip Arthroplasty After Internal Fixation Failure in an Intertrochanteric Femoral Fracture: A Case Report e90112 EN Shiro Fukuoka Department of Orthopedics, Kagawa Prefectural Central Hospital Tomoo Inoue Department of Orthopedics, Kagawa Prefectural Central Hospital Motoki Takahashi Department of Orthopedics, Kagawa Prefectural Central Hospital Keisuke Kawasaki Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Intertrochanteric femoral fractures are mainly managed by internal fixation. However, failures such as over-telescoping, cut-out, nonunion, or implant failure can occur, especially in osteoporotic elderly patients. We report the case of a patient in whom we performed artificial hip replacement surgery after fixation failure following internal fixation of an intertrochanteric femoral fracture. We report the case of an 85-year-old woman who sustained a left intertrochanteric femoral fracture treated with a dynamic hip screw (DHS). One week postoperatively, radiographs revealed over-telescoping of the lag screw. The patient did not complain of pain, but she underwent conversion to cemented bipolar hemiarthroplasty under general anesthesia. One possible cause of over-telescoping of the lag screw after surgery was that the longitudinal fracture line in the calcar of the proximal bone fragment, as seen in the initial CT image, may have extended horizontally at the neck level. During surgery, a fracture at the same site caused the anterior medial fragment to fail, resulting in a coronal shear fracture and fixation failure. When a longitudinal fracture line is observed in the calcar of the proximal fragment, it is necessary to keep in mind that it may extend horizontally at the neck level. 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 Clinical Outcomes and Biomechanical Evaluation of the Cement-Catching Screw Technique for Osteoporotic Vertebral Fractures e85955 EN Hisakazu Shitozawa Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruo Misawa Department of Orthopaedic Surgery, Ryusou Orthopaedic Hospital Yoshiaki Oda Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryoji Joko Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Masaya Takahashi Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Yasuyuki Shiozaki Department of Orthopaedic surgery, Mitoyo General Hospital Tomoko Tetsunaga Department of Orthopaedic Surgery, Okayama University Hospital Kensuke Shinohara Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Nakamichi Department of Orthopaedic Surgery, Okayama University Hospital Masataka Ueda Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Takatori Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazutaka Yamashita Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: We developed a cement-catching screw (CCS) technique for pedicle screw insertion into hardened cement, connecting anterior and posterior vertebral elements during balloon kyphoplasty (BKP) for osteoporotic vertebral fractures (OVFs). This study reports the CCS technique, clinical outcomes, and biomechanical properties.<br> Methods: This retrospective study included 59 patients (20 men, 39 women; mean age, 77.4 ± 8.7 years) who underwent BKP with one-above-one-below posterior fixation for OVFs between 2020 and 2023. Patients were divided into CCS (−) (without intermediate screws, n = 28) and CCS (+) (with intermediate CCSs, n = 31) groups. Clinical and radiographic outcomes, including activities of daily living, vertebral wedge angle (VWA), surgical level Cobb angle (CA), anterior vertebral body height (AVBH), screw loosening, pullout, and adjacent vertebral fractures, were evaluated preoperatively, postoperatively, and at the final follow-up (≥6 months). Biomechanical pullout strength was assessed at different insertion depths (5, 10, and 15 mm) using polymethylmethacrylate cement.<br> Results: No significant differences were observed between groups in age, sex, follow-up duration, or blood loss; however, the operation time was significantly longer in the CCS (+) group than in the CCS (−) group (P < 0.0001). Radiographic outcomes showed no significant differences in the VWA, CA, AVBH, adjacent vertebral fracture rates, and reoperation rates. However, the incidence of adjacent pedicle screws loosening and pullout was significantly higher in the CCS (−) group than in the CCS (+) group (P = 0.046 and 0.0084, respectively). The correction loss of the CA was significantly lower in the CCS (+) group (CCS (−), 5.6° ± 4.8°; CCS (+), 3.5° ± 4.8°, P = 0.023). The biomechanical test revealed pullout strengths of 683 ± 164, 2231 ± 208, and 3477 ± 393 N for insertion depths of 5, 10, and 15 mm, respectively, with significant increases by depth (P = 0.003 and 0.009).<br> Conclusions: The CCS technique improves anterior-posterior vertebral body stability, enhances fixation strength, and contributes to better surgical outcomes in OVFs treatment. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 ADAR1-high tumor-associated macrophages induce drug resistance and are therapeutic targets in colorectal cancer EN Hibiki OTSUKI (UMEDA) Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 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.

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

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.

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

Wiley Acta Medica Okayama 1532-0626 37 27-28 2025 Algebraic Connectivity Maximizing Regular Graphs: Special Case Analysis and Depth‐First Search e70357 EN Masashi Kurahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Najd Salaani Polytech Sorbonne, Sorbonne University Tsuyoshi Migita Faculty of Environmental, Life, Natural Science and Technology, Okayama University Norikazu Takahashi Faculty of Environmental, Life, Natural Science and Technology, Okayama University The algebraic connectivity is an indicator of how well connected a graph is. It also characterizes the convergence speed of some dynamic processes over networks. In this paper, taking into account that homogeneous networks are modeled as regular graphs, we tackle the following problem: given a pair (𝑛, 𝑘) of positive integers such that 𝑘 is less than 𝑛 and kn is an even number, find a 𝑘-regular graph with 𝑛 vertices that have the maximum algebraic connectivity. We first consider some special cases and derive solutions through theoretical analysis. We next present depth-first search algorithms for solving the problem, which reduce the search space by making use of some known properties of the regular graph and the algebraic connectivity.We also show the results of execution of the proposed algorithms for the values of 𝑛 up to 12. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 The significance of adding posterior decompression to spine stabilization in metastatic spinal surgery: a multicenter prospective study 27684 EN Hiroyuki Tominaga Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Ichiro Kawamura Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Hirofumi Shimada Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Hiromi Sasaki Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Noboru Taniguchi Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Yuki Shiratani Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University Akinobu Suzuki Department of Orthopaedic Surgery, Osaka Metropolitan University Hidetomi Terai Department of Orthopaedic Surgery, Osaka Metropolitan University Takaki Shimizu Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Kenichiro Kakutani Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Yutaro Kanda Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Masayuki Ishihara Department of Orthopaedic Surgery, Kansai Medical University Hospital Masaaki Paku Department of Orthopaedic Surgery, Kansai Medical University Hospital Yohei Takahashi Department of Orthopaedic Surgery, Keio University Toru Funayama Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba Kousei Miura Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba Eiki Shirasawa Department of Orthopaedic Surgery, Kitasato University School of Medicine Hirokazu Inoue Rehabilitation Center, Jichi Medical University Hospital Atsushi Kimura Department of Orthopaedics, Jichi Medical University Takuya Iimura Department of Orthopaedic Surgery, Dokkyo Medical University Hiroshi Moridaira Department of Orthopaedic Surgery, Dokkyo Medical University Hideaki Nakajima Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui Shuji Watanabe Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui Koji Akeda Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Norihiko Takegami Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Kazuo Nakanishi Department of Orthopaedic Surgery, Kawasaki Medical School Hirokatsu Sawada Department of Orthopaedic Surgery, Nihon University School of Medicine Koji Matsumoto Department of Orthopaedic Surgery, Nihon University School of Medicine Masahiro Funaba Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Hidenori Suzuki Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Haruki Funao Department of Orthopaedic Surgery, International University of Health and Welfare Narita Hospital Tsutomu Oshigiri Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine Takashi Hirai Department of Orthopedic Surgery, Institute of Science Tokyo Bungo Otsuki Department of Orthopaedic Surgery, Kyoto University Hospital Kazu Kobayakawa Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Hiroaki Manabe Department of Orthopedics, Tokushima University Shinji Tanishima Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University Ko Hashimoto Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine Chizuo Iwai Department of Orthopaedic Surgery, Gifu University Hospital Daisuke Yamabe Department of Orthopaedic Surgery, Iwate Medical University Akihiko Hiyama Department of Orthopaedic Surgery, Tokai University School of Medicine Shoji Seki Department of Orthopaedic Surgery, University of Toyama Yuta Goto Department of Orthopaedic Surgery, Nagoya City University Masashi Miyazaki Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Kazuyuki Watanabe Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine Toshio Nakamae Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Takashi Kaito Department of Orthopedic Surgery, Osaka University Graduate School of Medicine Hiroaki Nakashima Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Narihito Nagoshi Department of Orthopaedic Surgery, Keio University Satoshi Kato Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Kota Watanabe Department of Orthopaedic Surgery, Keio University Gen Inoue Department of Orthopaedic Surgery, Kitasato University School of Medicine Takeo Furuya Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University The usefulness of spine stabilization for treating metastatic spinal tumors with tumor-induced instability has been reported. However, no reports have prospectively evaluated the effectiveness of adding posterior decompression to stabilization surgery for improving symptoms. This multicenter prospective study aimed to determine whether adding posterior decompression to spine stabilization surgery for metastatic spinal tumors affects postoperative outcomes and complications. A total of 263 patients who underwent spine stabilization with (n = 189) or without (n = 74) decompression were analyzed. Patient demographics, the Spinal Instability Neoplastic Score (SINS), and the Epidural Spinal Cord Compression (ESCC) score were recorded. The outcomes were assessed preoperatively and at 1 and 6 months postoperatively in terms of neurological status, the Barthel Index, the EQ-5D-5 L, and the visual analog scale (VAS). Decompression was primarily performed in patients with severe neurological deficits and high-grade ESCC. Both groups showed postoperative improvement. Propensity score matching was applied to adjust for baseline differences. After matching, there were no significant differences in functional improvement between the decompression and nondecompression groups, and the complication rates were comparable. In matched patients presenting primarily with spinal instability and pain, the addition of decompression did not appear to confer a significant functional benefit within 6 months postoperatively. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 20 2025 Tertiary Lymphoid Structures Are Associated with Favorable Clinical Outcomes and Negatively Correlated with Cancer-Associated Fibroblasts in Esophageal Cancer 3351 EN Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Noma Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Noriyuki Nishiwaki Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seitaro Nishimura Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasushige Takeda Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hijiri Matsumoto Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuya Takahashi Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kento Kawasaki Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaaki Akai Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoaki Maeda Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoru Kikuchi Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunsuke Tanabe Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Tazawa Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Shirakawa Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Esophageal cancer remains a highly aggressive malignant tumor with poor prognosis, despite advances in combination therapies and novel immunotherapies. Tertiary lymphoid structures (TLSs), characterized by densely packed CD20+ B cells in a germinal-center-like structure, have recently been recognized as immune-stimulating components within the tumor microenvironment. In contrast, cancer-associated fibroblasts (CAFs) are stromal cells expressing fibroblast-activating protein (FAP) involved in immunosuppression. Methods: In this retrospective study, 124 clinical samples from patients who underwent radical surgery for esophageal cancer at our institute were analyzed. We investigated whether TLSs could serve as a prognostic factor and examined their association with tumor microenvironment factors. Results: The presence of TLSs was an independent prognostic factor for overall and progression-free survival in multivariate analyses. A high level of TLS formation correlated with better nutritional status, fewer M2 macrophages, and greater plasma cell infiltration. Additionally, little TLS formation was observed in areas with abundant CAFs, and quantitative analyses revealed a significant negative correlation between TLSs and CAFs. Conclusions: TLSs enhance antitumor immunity via macrophages and plasma cells and can be a valuable prognostic indicator in patients undergoing surgery for esophageal cancer. Targeting CAFs may prove to be a promising therapeutic strategy to enhance tumor-immunity-related TLSs. 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 Immunoglobulin G4-related Disease Mimicking Portal Vein Tumor Thrombus 381 385 EN Atsunobu Sakurai Department of Radiology, NHO Iwakuni Clinical Center Takayuki Yabuki Department of Radiology, NHO Iwakuni Clinical Center Hideki Aoki Department of Gastroenterological Surgery, NHO Iwakuni Clinical Center Akiko Iseki Department of Pathology, NHO Iwakuni Clinical Center Case Report 10.18926/AMO/69439 We report the case of a 72-year-old Japanese man with an incidental portal vein mass that was surgically resected and diagnosed as immunoglobulin G4 (IgG4)-related disease. The mass was discovered during an atrial fibrillation examination. The patient had a history of gastric cancer and was also diagnosed with rectal cancer, raising concerns about metastasis. Due to technical challenges, a biopsy was not feasible. Imaging findings suggested portal vein tumor thrombosis, complicating the diagnosis. This case highlights a rare presentation of IgG4-related disease mimicking portal vein tumor thrombus. 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 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.

Oxford University Press (OUP) Acta Medica Okayama 0305-7364 135 7 2025 Molecular polymorphisms of the nuclear and chloroplast genomes among African melon germplasms reveal abundant and unique genetic diversity, especially in Sudan 1329 1343 EN Odirichi Nnennaya Imoh Graduate School of Environmental and Life Science, Okayama University Gentaro Shigita Graduate School of Environmental and Life Science, Okayama University Mitsuhiro Sugiyama Institute of Vegetable and Floriculture Science, National Agriculture and Food Research Organization (NARO) Tran Phuong Dung Graduate School of Environmental and Life Science, Okayama University Katsunori Tanaka Faculty of Agriculture and Life Science, Hirosaki University Mami Takahashi Graduate School of Environmental and Life Science, Okayama University Kazusa Nishimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Monden Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidetaka Nishida Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mashaer Goda Plant Genetic Resources Conservation and Research Center, Agricultural Research Corporation Michel Pitrat INRAE, UR1052, Génétique et amélioration des fruits et légumes Kenji Kato Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Background and Aims Africa is rich in wild species of Cucumis and is considered one of the places of origin of melon. However, our knowledge of African melon is limited, and genetic studies using melon germplasms with wide geographical coverage are required. Here, we analysed the genetic structure of African melons, with emphasis on Sudan.<br> Methods Ninety-seven accessions of African melon were examined along with 77 reference accessions representing Asian melon and major horticultural groups. Molecular polymorphisms in the nuclear and chloroplast genomes were investigated using 12 RAPD, 7 SSR and 3 SNP markers. Horticultural traits, including seed size, were measured for 46 accessions, mainly from Sudan.<br> Key Results African melons were divided into large and small seed-types based on seed length: large seed-type from Northern Africa and small seed-type from Western and Southern Africa. Both seed types are common in Sudan. Molecular genetic diversity in these geographical populations was as high as in India, the Asian centre of melon domestication. Large seed-types from Northern Africa were assigned to Pop4 by structure analysis and had Ib cytoplasm in common with Cantalupensis, Inodorus and Flexuosus. Small seed-types were highly diversified and geographically differentiated; specifically, Pop1 with Ia cytoplasm in Southern Africa and South Asia, Pop2 with Ia in East Asia, including Conomon and Makuwa, and Pop3 with Ia or Ic in Africa. Sudanese small seed-types were grouped in Pop3, while their cytoplasm type was a mixture of Ia and Ic. Sudanese Tibish had Ic cytoplasm, which was unique in Africa, common in Western Africa and Sudan, and also found in wild or feral types.<br> Conclusions Melon of Ic lineage, including Tibish, originated from wild melon in the ‘western Sudan region’, and independently of melon with Ia or Ib cytoplasm, which originated in Asia. This clearly indicates the polyphyletic origin of melon. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1664-462X 16 2025 The response to thermospermine is fine-tuned by the balance between SAC51 and LHW family proteins in Arabidopsis thaliana EN Yao Xu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mitsuru Saraumi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tomohiko Toyoshima Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyasu Motose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taku Takahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Thermospermine negatively regulates xylem formation. In Arabidopsis, SAC51 and SACL3, members of the SAC51 gene family encoding basic loop-helix-loop (bHLH) proteins play a key role in this regulation. These mRNAs contain an upstream open-reading-frame (uORF) that is highly conserved across species, and its inhibitory effect on the main ORF translation is alleviated by thermospermine. A double knockout of SAC51 and SACL3 results in thermospermine insensitivity at high concentrations that normally inhibit xylem formation and shoot growth in the wild type. Conversely, uORF mutants of SAC51, SACL3, and SACL1 suppress the excessive xylem formation and dwarf phenotype of acl5, a mutant defective in thermospermine biosynthesis. In this study, we generated genome-edited uORF mutants of SACL2 and confirmed that they partially recover the acl5 phenotype. All uORF mutants exhibited increased sensitivity to thermospermine. SACL3 represses the function of LHW, a key bHLH transcription factor required for xylem proliferation, through direct interaction. We found that the lhw mutant is also hypersensitive to thermospermine, while this sensitivity was suppressed by the sac51 sacl3 double knockout. Yeast two-hybrid assays demonstrated that all four SAC51 family members interact with LHW and its family members. These findings suggest that overaccumulation of SAC51 family proteins leads to thermospermine hypersensitivity by repressing the function of LHW family proteins, whose activity must be fine-tuned to ensure proper xylem development. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0960-7412 123 5 2025 RNA processing/modifying enzymes play key roles in the response to thermospermine in Arabidopsis thaliana e70476 EN Mitsuru Saraumi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takahiro Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Daiki Koyama Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshitaka Nishi Graduate School of Engineering, Kyushu Sangyo University Yoshihiro Takahashi Department of Life Science, Faculty of Life Science, Kyushu Sangyo University Hiroyasu Motose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taku Takahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Thermospermine is involved in negative regulation of xylem differentiation by enhancing the translation of mRNAs of the SAC51 gene family in Arabidopsis (Arabidopsis thaliana). These mRNAs contain conserved upstream open reading frames (uORFs) that interfere with the translation of the main ORF. To investigate the mechanism by which thermospermine acts in this process, we isolated mutants insensitive to thermospermine, named ‘its’. We show that the four genes responsible for these mutants, its1 to its4, encode: (i) a homolog of SPOUT RNA methyltransferase, (ii) an rRNA pseudouridine synthase CBF5/NAP57, (iii) a putative spliceosome disassembly factor STIPL1/NTR1, and (iv) a plant-specific RNA-binding protein PHIP1. These four mutants were found to have much higher levels of thermospermine than the wild-type. While all these mutants except its1 appear almost normal, they enhance the dwarf phenotype of a mutant of ACL5, which encodes thermospermine synthase, resulting in tiny plants resembling a double knockout of ACL5 and SACL3, a member of the SAC51 family. Reporter assays revealed that GUS activity from the CaMV 35S promoter-SAC51 5′-GUS fusion construct was significantly reduced in its1 and its4 or not affected in its2 and its3, while it was slightly increased in its1, its3, and its4, or not changed in its2 by thermospermine. These findings underscore the critical role of RNA processing and modification in the thermospermine-dependent translational regulation of uORF-containing transcripts. No potential conflict of interest relevant to this article was reported.

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

Springer Nature Switzerland Acta Medica Okayama 0303-4216 2025 Low-Threshold Raman Silicon Lasers Using Photonic Crystal High-Q Nanocavities 95 143 EN Yasushi Takahashi Okayama University Takashi Asano Kyoto University Susumu Noda Kyoto University By utilizing stimulated Raman scattering, it is possible to generate continuous-wave laser light in silicon, an indirect bandgap semiconductor. The first part of this chapter explains the mechanism of the Raman laser using a silicon resonator with a high-quality factor (Q). In the second part, the mechanism of the ultra-low threshold Raman silicon laser using a photonic crystal high-Q nanocavity is summarized, and recent advancements are explained. 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.<br> 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.<br> 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.<br> 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.

American Institute of Mathematical Sciences (AIMS) Acta Medica Okayama 2377-9098 12 3 2025 Biophysical regulation of extracellular matrix in systemic lupus erythematosus 412 437 EN Qiwei Li Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Qiang Li Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Zhaoyang Xiao Department of Anesthesiology, The Second Affiliated Hospital of Dalian Medical University Keiji NARUSE Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Takahashi Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by immune dysregulation and multi-organ damage. Recent advances have underscored the critical involvement of extracellular matrix (ECM) biophysical properties in shaping immune cell behavior and metabolic states that contribute to disease progression. This review systematically delineates the pathological remodeling of ECM biophysics in SLE, with a focus on their roles in mechanotransduction, immune-metabolic interplay, and organ-specific tissue injury. By integrating current evidence, we highlight how ECM-derived mechanical cues orchestrate aberrant immune responses and propose new perspectives for targeting ECM-immune crosstalk in the development of organ-specific, mechanism-based therapies for SLE. No potential conflict of interest relevant to this article was reported.

Fuji Technology Press Ltd. Acta Medica Okayama 1883-8030 20 4 2025 High-Definition Topographic Archiving and Educational Applications in Regions Affected by the 2024 Noto Peninsula Earthquake 401 409 EN Takuro Ogura Graduate School of Education, Hyogo University of Teacher Education Hiroyuki Yamauchi Art Research Center, Ritsumeikan University Tatsuto Aoki Faculty of Regional Development Studies, Kanazawa University Nobuhisa Matta Graduate School of Education, Okayama University Kotaro Iizuka Center for Spatial Information Science, The University of Tokyo Yoshiya Iwasa Faculty of Education, University of Teacher Education Fukuoka Takayuki Takahashi International Research Institute of Disaster Science, Tohoku University Kiyomi Hayashi Faculty of Regional Development Studies, Kanazawa University Tsuyoshi Hattanji Institute of Life and Environmental Sciences, University of Tsukuba Takashi Oguchi Center for Spatial Information Science, The University of Tokyo The 2024 Noto Peninsula earthquake (Mw 7.5) caused extensive damage in Ishikawa Prefecture, Japan, and surrounding areas, with considerable coastal uplift and tsunami flooding. Past 100 years’ records show no earthquake above Mw 7.0 in the Noto Peninsula, so for everyone alive today, this event is truly without precedent. Therefore, we aimed to support disaster prevention education by developing teaching materials using unmanned aerial vehicles (UAVs) based on digitally archived topographic changes. High-definition topographic data collected from multiple UAV surveys were processed into digital and analog formats, including 3D models, spherical panorama images, and 3D printings. These materials were designed to provide detailed and intuitive representations of post-disaster landforms and were used as educational tools in schools. The learning materials were introduced during a workshop for disaster-affected teachers, featuring hands-on activities to help participants familiarize themselves with the materials, and explore their integration into geography and science classes. Feedback from participants indicated that these tools were highly effective in enhancing classroom learning. The results of this study are expected to contribute to preserving disaster records while enhancing disaster awareness in educational settings and local communities. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 2667-2421 18 2025 Postnatal expression of Cat-315-positive perineuronal nets in the SAMP10 mouse primary somatosensory cortex 244 256 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Eriko Kitano Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Perineuronal nets (PNNs) form at the end of the critical period of plasticity in the mouse primary somatosensory cortex. PNNs are said to have functions that control neuroplasticity and provide neuroprotection. However, it is not clear which molecules in PNNs have these functions. We have previously reported that Cat-315-positive molecules were not expressed in the PNNs of the senescence-accelerated model (SAM)P10 strain model mice at 12 months of age. To confirm whether the loss of Cat-315-positive molecules occurred early in life in SAMP10 mice, we examined Cat-315-positive PNNs in the primary somatosensory cortex during postnatal development. This research helps to elucidate the function of PNNs and the mechanism of cognitive decline associated with ageing. To confirm whether Cat-315-positive PNNs changed in an age-dependent manner in SAMP10 mice, we examined the primary somatosensory cortex at 21, 28, and 56 days after birth. We compared these results with those of senescence-accelerated mouse-resistant (SAMR) mice. In SAMP10 mice, Cat-315-positive PNNs were expressed in the primary somatosensory cortex early after birth, but their expression was significantly lower than that in SAMR1 mice. Many other molecules that calibrated the PNN were unchanged between SAMP10 and SAMR1 mice. This study revealed that the expression of the Cat-315 epitope was decreased in the primary somatosensory cortex of SAMP10 mice during postnatal development. SAMP10 mice have had histological abnormalities in their brains since early life. Furthermore, using SAMP10 will be useful in elucidating the mechanism of age-related abnormalities in brain function as well as in elucidating the function and structure of PNNs. No potential conflict of interest relevant to this article was reported.

Walter de Gruyter GmbH Acta Medica Okayama 2081-6936 16 1 2025 Age-related behavioural abnormalities in C57BL/6.KOR–Apoe shl mice EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Eriko Kitano Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Tetsuji Miyazaki Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Spontaneously hyperlipidaemic (Apoeshl) mice were discovered in 1999 as mice lacking apolipoprotein E (ApoE) owing to a mutation in the Apoe gene. However, age-related behavioural changes in commercially available Apoeshl mice have not yet been clarified. The behavioural abnormalities of ApoE-deficient mice, which are genetically modified mice artificially deficient in ApoE, have been investigated in detail, and it has been reported that they can serve as a model of Alzheimer’s disease (AD). To understand whether Apoeshl mice can also serve as a murine model of AD, it is necessary to investigate age-related behavioural abnormalities in Apoeshl mice. In this study, we conducted a series of behavioural experiments on 7- and 11-month-old Apoeshl mice to investigate the behavioural abnormalities associated with ageing in Apoeshl mice. In this study, 7-month-old Apoeshl mice showed decreased body weight and grip strength compared to age-matched wild-type mice. In the open field test, 7-month-old Apoeshl mice showed increased anxiety-like behaviour compared to wild-type mice, whereas 11-month-old Apoeshl mice showed decreased anxiety-like behaviour. Moreover, Apoeshl mice aged 7 and 11 months had increased serum cholesterol levels. These results indicate that the behaviour of Apoeshl mice changes with age. However, 11-month-old Apoeshl mice did not show a decline in cognitive function or memory ability similar to murine models of AD. Our findings indicate that Apoeshl mice can be used to investigate the function of ApoE in the central nervous system. No potential conflict of interest relevant to this article was reported.

Walter de Gruyter GmbH Acta Medica Okayama 2081-6936 16 1 2025 Rearing in an envy-like environment increases anxiety-like behaviour in mice EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Eriko Kitano Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Interest in the societal and psychological harm caused by widespread envy and social comparison is increasing. Envy is associated with anxiety and depression, though the mechanism by which envy affects neuropsychiatric disorders, such as depression, remains unclear. Clarifying the neurobiological basis of envy’s effects on behaviour and emotion regulation in experimental mice is essential for developing disease-prevention and treatment strategies. As mice recognize other mice in neighbouring cages, this study investigated whether they recognize neighbouring cages housed in environmentally enriched cages and suffer psychological stress due to envy. After being raised in an envy-like environment for 3 weeks, we revealed changes in the behaviour of the mice through a series of behavioural experiments. Mice raised in an envious environment showed increased body weight and anxiety-like behaviour but decreased social behaviour and serum corticosterone levels compared to control mice. Thus, mice recognize their neighbouring cages and experience psychological stress due to envy. This study revealed a part of the scientific basis for why envy increased anxiety. Using this novel experimental breeding environment, it may be possible to create an experimental animal model of anxiety disorders. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0953-4180 2024 2024 Mice Recognise Mice in Neighbouring Rearing Cages and Change Their Social Behaviour 9215607 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Mice are social animals that change their behaviour primarily in response to visual, olfactory, and auditory information from conspecifics. Rearing conditions such as cage size and colour are important factors influencing mouse behaviour. In recent years, transparent plastic cages have become standard breeding cages. The advantage of using a transparent cage is that the experimenter can observe the mouse from outside the cage without touching the cage. However, mice may recognise the environment outside the cage and change their behaviour. We speculated that mice housed in transparent cages might recognise mice in neighbouring cages. We used only male mice in this experiment. C57BL/6 mice were kept in transparent rearing cages with open lids, and the cage positions were maintained for 3 weeks. Subsequently, we examined how mice behaved toward cagemate mice, mice from neighbouring cages, and mice from distant cages. We compared the level of interest in mice using a social preference test. Similar to previous reports, subject mice showed a high degree of interest in unfamiliar mice from distant cages. By contrast, subject mice reacted to mice from neighbouring cages as familiar mice, similar to cagemate mice. This suggests that mice housed in transparent cages with open lids perceive the external environment and identify mice in neighbouring cages. Researchers should pay attention to the environment outside the mouse cage, especially for the social preference test. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1663-9812 16 2025 Histidine-rich glycoprotein inhibits TNF-α–induced tube formation in human vascular endothelial cells 1561628 EN Omer Faruk Hatipoglu Department of Pharmacology, Kindai University Faculty of Medicine Takashi Nishinaka Department of Pharmacology, Kindai University Faculty of Medicine Kursat Oguz Yaykasli Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen Shuji Mori Department of Pharmacology, School of Pharmacy, Shujitsu University Masahiro Watanabe Department of Pharmacology, School of Pharmacy, Shujitsu University Takao Toyomura Department of Pharmacology, School of Pharmacy, Shujitsu University Masahiro Nishibori Department of Translational Research and Dug Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Hidenori Wake Department of Pharmacology, Kindai University Faculty of Medicine Hideo Takahashi Department of Pharmacology, Kindai University Faculty of Medicine Introduction: Tumor necrosis factor-α (TNF-α)-induced angiogenesis plays a critical role in tumor progression and metastasis, making it an important therapeutic target in cancer treatment. Suppressing angiogenesis can effectively limit tumor growth and metastasis. However, despite advancements in understanding angiogenic pathways, effective strategies to inhibit TNF-α-mediated angiogenesis remain limited.<br> Methods: This study investigates the antiangiogenic effects of histidine-rich glycoprotein (HRG), a multifunctional plasma protein with potent antiangiogenic properties, on TNF-α-stimulated human endothelial cells (EA.hy926). Tube formation assays were performed to assess angiogenesis, and gene/protein expression analyses were conducted to evaluate HRG’s effects on integrins αV and β8. The role of nuclear factor erythroid 2-related factor 2 (NRF2) in HRG-mediated antiangiogenic activity was also examined through nuclear translocation assays and NRF2 activation studies.<br> Results: At physiological concentrations, HRG effectively suppressed TNF-α-induced tube formation in vitro and downregulated TNF-α-induced expression of integrins αV and β8 at both the mRNA and protein levels. HRG treatment promoted NRF2 nuclear translocation in a time-dependent manner. Furthermore, activation of NRF2 significantly reduced TNF-α-induced tube formation and integrin expression, suggesting that NRF2 plays a key role in HRG-mediated antiangiogenic effects.<br> Discussion and Conclusion: Our findings indicate that HRG suppresses TNF-α-induced angiogenesis by promoting NRF2 nuclear translocation and transcriptional activation, which in turn inhibits integrin αV and β8 expression. Given the essential role of angiogenesis in tumor progression, HRG’s ability to regulate this process presents a promising therapeutic strategy for cancer treatment. 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 Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts 30648 EN Mengxue Wang Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Harumi Idei Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chen Wang Department of Nursing, School of Life and Health Sciences, HuZhou College Yin Liang Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yun Liu Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Matsuda Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Takahashi Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University In the realm of regenerative medicine, despite the various techniques available for inducing the differentiation of induced pluripotent stem (iPS) cells into cardiomyocytes, there remains a need to enhance the maturation of the cardiomyocytes. This study aimed to improve the differentiation and subsequent maturation of iPS-derived cardiomyocytes (iPS-CMs) by incorporating mechanical stretching. Human iPS cells were co-cultured with human gingival fibroblasts (HGF) on a polydimethylsiloxane (PDMS) stretch chamber, where mechanical stretching stimulation was applied during the induction of cardiomyocyte differentiation. The maturation of iPS-CMs was assessed using qRT-PCR, immunocytochemistry, transmission electron microscopy, calcium imaging and contractility comparisons. Results indicated significantly elevated gene expression levels of cardiomyocyte markers (cTnT) and the mesodermal marker (Nkx2.5) in the stretch group compared to the control group. Fluorescent immunocytochemical staining revealed the presence of cardiac marker proteins (cTnT and MYL2) in both groups, with higher protein expression in the stretch group. Additionally, structural maturation of iPS-CMs in the stretch group was notably better than in the control group. A significant increase in the contractility and calcium cycle of iPS-CMs was observed in the stretch group. These findings demonstrate that mechanical stretching stimulation enhances the maturation of iPS-CMs co-cultured with HGF. 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.

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

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 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 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 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 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.<br> 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.<br> 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.<br> 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 2045-2322 15 1 2025 Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts 30648 EN Mengxue Wang Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Harumi Idei Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chen Wang Department of Nursing, School of Life and Health Sciences, HuZhou College Yin Liang Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yun Liu Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Matsuda Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Takahashi Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University In the realm of regenerative medicine, despite the various techniques available for inducing the differentiation of induced pluripotent stem (iPS) cells into cardiomyocytes, there remains a need to enhance the maturation of the cardiomyocytes. This study aimed to improve the differentiation and subsequent maturation of iPS-derived cardiomyocytes (iPS-CMs) by incorporating mechanical stretching. Human iPS cells were co-cultured with human gingival fibroblasts (HGF) on a polydimethylsiloxane (PDMS) stretch chamber, where mechanical stretching stimulation was applied during the induction of cardiomyocyte differentiation. The maturation of iPS-CMs was assessed using qRT-PCR, immunocytochemistry, transmission electron microscopy, calcium imaging and contractility comparisons. Results indicated significantly elevated gene expression levels of cardiomyocyte markers (cTnT) and the mesodermal marker (Nkx2.5) in the stretch group compared to the control group. Fluorescent immunocytochemical staining revealed the presence of cardiac marker proteins (cTnT and MYL2) in both groups, with higher protein expression in the stretch group. Additionally, structural maturation of iPS-CMs in the stretch group was notably better than in the control group. A significant increase in the contractility and calcium cycle of iPS-CMs was observed in the stretch group. These findings demonstrate that mechanical stretching stimulation enhances the maturation of iPS-CMs co-cultured with HGF. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 12 5 2024 The Japan MSA registry: A multicenter cohort study of multiple system atrophy 271 277 EN Ayaka Chikada Department of Neurology, Graduate School of Medicine, The University of Tokyo Kenta Orimo Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Mitsui Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine and Dentistry Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Hidehiro Mizusawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Yuji Takahashi Department of Neurology, Graduate School of Medicine, The University of Tokyo Masahisa Katsuno Department of Neurology, Nagoya University Graduate School of Medicine Kazuhiro Hara Department of Neurology, Nagoya University Graduate School of Medicine Osamu Onodera Department of Neurology, Brain Research Institute, Niigata University Tomohiko Ishihara Department of Neurology, Brain Research Institute, Niigata University Masayoshi Tada Department of Neurology, Brain Research Institute, Niigata University Satoshi Kuwabara Department of Neurology, Graduate School of Medicine, Chiba University Atsuhiko Sugiyama Department of Neurology, Graduate School of Medicine, Chiba University Yoshitaka Yamanaka Department of Neurology, Graduate School of Medicine, Chiba University Ryosuke Takahashi Department of Neurology, Kyoto University Graduate School of Medicine Nobukatsu Sawamoto Department of Human Health Sciences, Kyoto University Graduate School of Medicine Yusuke Sakato Department of Neurology, Kyoto University Graduate School of Medicine Tomoyuki Ishimoto Department of Neurology, Kyoto University Graduate School of Medicine Ritsuko Hanajima Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University Yasuhiro Watanabe Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University Hiroshi Takigawa Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University Tadashi Adachi Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University Koji Abe Department of Neurology, Okayama University Graduate School of Medicine and Dentistry Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine and Dentistry Hiroshi Takashima Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University Keiko Higashi Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University Junichi Kira Department of Neurology, Graduate School of Medical Sciences, Kyushu University Ichiro Yabe Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Masaaki Matsushima Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Katsuhisa Ogata Department of Neurology, Higashi-Saitama National Hospital Kinya Ishikawa Department of Neurology and Neurological Science, Tokyo Medical and Dental University Yoichiro Nishida Department of Neurology and Neurological Science, Tokyo Medical and Dental University Taro Ishiguro Department of Neurology and Neurological Science, Tokyo Medical and Dental University Kokoro Ozaki Department of Neurology and Neurological Science, Tokyo Medical and Dental University Tetsuya Nagata Department of Neurology and Neurological Science, Tokyo Medical and Dental University Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Background: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and various motor symptoms. While MSA-C (cerebellar type) predominates in East Asia, MSA-P (parkinsonian type) predominates in Europe and North America. This nationwide patient registry aimed to (1) conduct a prospective natural history study of MSA in Japan, (2) facilitate patient recruitment for clinical trials, and (3) deposit bioresources and clinical information in a biobank.<br> Methods: Thirteen institutions participated in this study. Clinical information was obtained by neurologists from the patients visiting the hospital every 12 months to assess the UMSARS Part 2 scores and by telephone interviews by nurses every 6 months to assess UMSARS Part 1 scores and to determine whether clinical events had occurred.<br> Results: Demographic data from 329 MSA patients (216 MSA-C and 113 MSA-P) were analyzed. The mean age at symptom onset was 58.2 years (standard deviation, 8.9); the mean duration of symptoms at enrollment was 3.5 years (standard deviation, 2.2). The mean 12-month changes in the UMSARS Part 1 and Part 2 scores were 7.9 (standard deviation, 5.6) and 6.4 (standard deviation, 5.9), respectively. The patient registry proved useful in recruiting participants for clinical trials, including those with gene variants. Clinical information and biospecimens were deposited in a biobank.<br> Discussion: The study highlighted the importance of telephone interviews in minimizing drop-out rates in natural history studies and demonstrated similar MSA progression rates across populations. The deposited bioresources are available to researchers upon request, aiming to contribute to future MSA researches. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 2049-9450 23 3 2025 Association of the expression of 5‑FU biomarkers with aging and prognosis in elderly patients with lung cancer treated with S‑1 adjuvant chemotherapy: Follow‑up results of the Setouchi Lung Cancer Group Study 1201 79 EN Junichi Soh Department of Thoracic Surgery, Okayama University Hospital Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Norihito Okumura Department of Thoracic Surgery, Kurashiki Central Hospital Hiroyuki Suzuki Department of Chest Surgery, Fukushima Medical University Hospital Masao Nakata Department of General Thoracic Surgery, Kawasaki Medical School Hospital Toshiya Fujiwara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Kenicehi Gemba Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima 720‑0001, Japan; 8Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital Isao Sano Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital Takuji Fujinaga Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center Masafumi Kataoka Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital Yasuhiro Terasaki Department of Respiratory Surgery, Saga Medical Center Koseikan Nobukazu Fujimoto Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital Kazuhiko Kataoka Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Shinji Kosaka Department of Thoracic Surgery, Shimane Prefectural Central Hospital Motohiro Yamashita Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center Hidetoshi Inokawa Department of Thoracic Surgery, National Hospital Organization Yamaguchi‑Ube Medical Center Masaaki Inoue Department of Thoracic Surgery, Shimonoseki City Hospital Hiroshige Nakamura Division of General Thoracic Surgery, Tottori University Hospital Yoshinori Yamashita Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center Yuta Takahashi Department of Thoracic Surgery, Okayama University Hospital Hidejiro Torigoe Department of Thoracic Surgery, Okayama University Hospital Hiroki Sato Department of Thoracic Surgery, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Hospital Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine Keitaro Matsuo Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute Junichi Sakamoto Tokai Central Hospital Hiroshi Date Department of Thoracic Surgery, Kyoto University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Managing elderly patients presents several challenges because of age‑related declines; however, age should not be the sole determinant for adjuvant treatment decisions in patients with non‑small cell lung cancer (NSCLC). Moreover, age may affect the expression of 5‑fluorouracil (5‑FU) biomarkers. The present study assessed: i) The effect of age on the expression levels of 5‑FU biomarkers by analyzing a public database; and ii) the ability of these biomarkers to predict clinical outcomes in elderly patients with NSCLC who underwent complete resection in the Setouchi Lung Cancer Group Study 1201 (SCLG1201) followed by S‑1 adjuvant chemotherapy. Changes in gene expression levels across age groups were assessed by analyzing The Cancer Genome Atlas (TCGA) database. The expression of 5‑FU biomarkers, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, epidermal growth factor receptor (EGFR) and excision repair cross‑complementation group 1 (ERCC1), were assessed via quantitative reverse‑transcription PCR assays in 89 elderly patients (≥75 years) with NSCLC who received adjuvant chemotherapy with oral fluoropyrimidine prodrug S‑1 in the SLCG1201 trial. TCGA database analysis (n=955) showed that TS expression decreased significantly with aging, especially in the age group ≥75. In the SCLG1201 trial, univariate analysis revealed that EGFR upregulation and TS downregulation were correlated with favorable recurrence‑free survival (RFS) and overall survival (OS), respectively. Multivariate analysis demonstrated that pathological stage was an independent prognostic factor for both RFS and OS. EGFR mutations were associated with upregulation of DPD and EGFR, and downregulation of TS and ERCC1. In conclusion, although pathological stage is an independent prognostic factor for survival, EGFR upregulation and TS downregulation may be a greater predictor of clinical outcomes in elderly patients with NSCLC treated with S‑1 adjuvant chemotherapy. The age‑related decrease in TS expression supports the potential benefit of 5‑FU therapies in elderly patients. Nonetheless, further research is warranted to validate these results. 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 2045-2322 15 1 2025 ADAR1 as a prognostic marker for patients with colorectal cancer and synchronous liver metastasis and a predictor of chemotherapy efficacy 26752 EN Kaori Nitta 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 Hibiki Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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 Kazuhiro Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sho Takeda 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 Hiroyuki Kishimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi 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 Shunsuke Nakamura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Hideki Yamamoto Department of Clinical Genomic Medicine, 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 Yuhei Kondo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiki Miyake 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 Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences RNA editing by adenosine deaminase acting on RNA (ADAR) enzymes plays a role in cancer progression. However, its clinical significance in metastatic colorectal cancer (CRC) remains unclear. This study aimed to evaluate whether ADAR1 expression predicts prognosis and treatment response in colorectal cancer (CRC) with synchronous liver metastasis. This study included 40 patients with stage IV CRC and synchronous liver metastases. ADAR1 expression in tumor tissues was evaluated using immunohistochemistry. Expression levels were quantified using the immunoreactive score, and associations with clinicopathological features, overall survival (OS), and chemotherapy response were examined. High ADAR1 expression was significantly associated with multiple liver metastases (P = 0.0206), lymph node metastasis (P = 0.0241), and reduced response to chemotherapy (P = 0.0224). Significantly shorter OS was observed in patients with high ADAR1 expression in the nucleus (P = 0.0458). ADAR1 expression was an independent prognostic factor comparable to the presence of extrahepatic metastases. Low ADAR1 expression was correlated with a higher likelihood of achieving a response to chemotherapy. ADAR1 expression can reflect tumor aggressiveness and chemotherapy resistance in patients with CRC and synchronous liver metastasis. ADAR1 has considerable potential as a dual-purpose biomarker for stratifying patients based on prognosis and optimizing treatment intensity. 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 Survival days of patients with metastatic spinal tumors of lung cancer requiring surgery: a prospective multicenter study 24117 EN Takuya Takahashi Department of Orthopedic Surgery, Institute of Science Tokyo Takashi Hirai Department of Orthopedic Surgery, Institute of Science Tokyo Yuki Shiratani Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University Akinobu Suzuki Department of Orthopaedic Surgery, Osaka Metropolitan University Kenichiro Kakutani Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Satoshi Kato Department of Orthopaedic Surgery Graduate School of Medical Sciences, Kanazawa University Hiroyuki Tominaga Department of Orthopedic Surgery Graduate School of Medical and Dental Sciences, Kagoshima University Hirokazu Inoue Rehabilitation Center, Jichi Medical University Hospital Hirokatsu Sawada Department of Orthopaedic Surgery, Nihon University School of Medicine Norihiko Takegami Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Kazuo Nakanishi Department of Orthopaedic Surgery, Kawasaki Medical School Hideaki Nakajima Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui Masayuki Ishihara Department of Orthopaedic surgery, Kansai Medical University Hospital Tsutomu Oshigiri Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine Toru Funayama Department of Orthopaedic Surgery Institute of Medicine, University of Tsukuba Takuya Iimura Department of Orthopaedic Surgery, Dokkyo Medical University Shinji Tanishima Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University Hiroaki Nakashima Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Daisuke Yamabe Department of Orthopaedic Surgery, Iwate Medical University Ko Hashimoto Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Masahiro Funaba Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Narihito Nagoshi Department of Orthopaedic Surgery, Keio University Kazu Kobayakawa Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University Toshitaka Yoshii Department of Orthopedic Surgery, Institute of Science Tokyo Kazuyuki Watanabe Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine Toshio Nakamae Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Takashi Kaito Department of Orthopedic Surgery, Osaka University Graduate School of Medicine Gen Inoue Department of Orthopaedic Surgery, Kitasato University School of Medicine Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Kota Watanabe Department of Orthopaedic Surgery, Keio University Takeo Furuya Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University Surgery for metastatic spinal tumors has improved postoperative activities of daily living. A few studies reported on prognostic factors assessed in large multicenter prospective studies for metastatic spinal tumors of lung cancer origin. This study aimed to determine preoperative prognostic factors in patients undergoing surgery for metastatic spinal tumors associated with lung cancer. This prospective registry study included 74 patients diagnosed and operated with metastatic spine tumors derived from lung cancer in 39 high-volume cancer centers. We examined the postoperative survival period and the preoperative factors related to postoperative survival time. We conducted univariate and multivariate Cox regression analyses to determine preoperative prognostic factors. The mean postoperative survival period was 343 days. Multivariate Cox regression analysis revealed a higher feeding score of vitality index, indications for molecularly targeted therapy, and a higher mobility score of Barthel index as independent factors associated with postoperative survival time in metastatic spinal tumors derived from lung cancer. Patients with indications for molecular-targeted therapy and good vitality exhibited longer survival. These results may help in surgical selection for patients with metastatic spinal tumors derived from lung cancer. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 2192-5682 15 4 2024 Effects of Palliative Surgical Treatment for Spinal Metastases on the Patient’s Quality of Life With a Focus on the Segment of the Metastasis: A Prospective Multicenter Study 2286 2299 EN Naoki Segi Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Hiroaki Nakashima Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Sadayuki Ito Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Jun Ouchida Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Yuki Shiratani Department of Orthopaedic Surgery, Chiba University Hospital Takaki Shimizu Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Akinobu Suzuki Department of Orthopaedic Surgery, Osaka Metropolitan University Hidetomi Terai Department of Orthopaedic Surgery, Osaka Metropolitan University Kenichiro Kakutani Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Yutaro Kanda Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Hiroyuki Tominaga Department of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Ichiro Kawamura Department of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Masayuki Ishihara Department of Orthopaedic Surgery, Kansai Medial University Hospital Masaaki Paku Department of Orthopaedic Surgery, Kansai Medial University Hospital Yohei Takahashi Department of Orthopaedic Surgery, Keio University Masahiro Funaba Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Toru Funayama Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba Hideaki Nakajima Department of Orthopaedics and Rehabilitation Medicine, University of Fukui Faculty of Medical Sciences Koji Akeda Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Takashi Hirai Department of Orthopedic Surgery, Tokyo Medical and Dental University Hirokazu Inoue Rehabilitation Center, Jichi Medical University Hospital Kazuo Nakanishi Department of Orthopaedic Surgery, Kawasaki Medical School Haruki Funao Department of Orthopaedic Surgery, International University of Health and Welfare Narita Hospital Tsutomu Oshigiri Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine Bungo Otsuki Department of Orthopaedic Surgery, Kyoto University Hospital Kazu Kobayakawa Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University Shinji Tanishima Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University Ko Hashimoto Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine Takuya Iimura Department of Orthopaedic Surgery, Dokkyo Medical University Hirokatsu Sawada Department of Orthopaedic Surgery, Nihon University School of Medicine Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Hiroaki Manabe Department of Orthopedics, Tokushima University Chizuo Iwai Department of Orthopaedic Surgery, Gifu University Hospital Daisuke Yamabe Department of Orthopaedic Surgery, Iwate Medical University Akihiko Hiyama Department of Orthopaedic Surgery, Tokai University School of Medicine Shoji Seki Department of Orthopaedic Surgery, University of Toyama Yuta Goto Department of Orthopaedic Surgery, Nagoya City University Masashi Miyazaki Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Kazuyuki Watanabe Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine Toshio Nakamae Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Takashi Kaito Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine Narihito Nagoshi Department of Orthopaedic Surgery, Keio University Satoshi Kato Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Kota Watanabe Department of Orthopaedic Surgery, Keio University Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Gen Inoue Department of Orthopaedic Surgery, Kitasato University School of Medicine Takeo Furuya Department of Orthopaedic Surgery, Chiba University Hospital Study Design: Prospective multicenter study.<br> Objectives: Palliative surgery is crucial for maintaining the quality of life (QOL) in patients with spinal metastases. This study aimed to compare the short-term outcomes of QOL after palliative surgery between patients with metastatic spinal tumors at different segments.<br> Methods: We prospectively compared the data of 203 patients with spinal metastases at 2-3 consecutive segments who were divided into the following three groups: cervical, patients with cervical spine lesions; thoracic, patients with upper–middle thoracic spine lesions; and TL/L/S, patients with lesions at the thoracolumbar junction and lumbar and sacral regions. Preoperative and postoperative EuroQol 5-dimension (EQ5D) 5-level were compared.<br> Results: All groups exhibited improvement in the Frankel grade, performance status, pain, Barthel index, EQ5D health state utility value (HSUV), and EQ5D visual analog scale (VAS) postoperatively. Although preoperative EQ5D HSUVs did not significantly differ between the groups (cervical, 0.461 ± 0.291; thoracic, 0.321 ± 0.292; and TL/L/S, 0.376 ± 0.272), the thoracic group exhibited significantly lower postoperative EQ5D HSUVs than the other two groups (cervical, 0.653 ± 0.233; thoracic, 0.513 ± 0.252; and TL/L/S, 0.624 ± 0.232). However, postoperative EQ5D VAS was not significantly different between the groups (cervical, 63.4 ± 25.8; thoracic, 54.7 ± 24.5; and TL/L/S, 61.7 ± 21.9).<br> Conclusions: Palliative surgery for metastatic spinal tumors provided comparable QOL improvement, irrespective of the spinal segment involved. Patients with upper and middle thoracic spinal metastases had poorer QOL outcomes than those with metastases in other segments; however, sufficient QOL improvement was achieved. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1099-5129 27 2 2025 SCN5A variant type-dependent risk prediction in Brugada syndrome euaf024 EN Takanori Aizawa Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Takeru Makiyama Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Hai Huang Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine , 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 , Tomohiko Imamura Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Megumi Fukuyama Department of Cardiovascular Medicine, Shiga University of Medical Science Keiko Sonoda Medical Genome Center, National Cerebral and Cardiovascular Center Koichi Kato Department of Cardiovascular Medicine, Shiga University of Medical Science Takashi Hisamatsu Department of Public Health, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Yuko Nakamura Department of Pediatrics, Tsuchiura Kyodo General Hospital Kenji Hoshino Department of Cardiology, Saitama Children’s Medical Center Junichi Ozawa Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences Hiroshi Suzuki Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital Kazushi Yasuda Department of Pediatric Cardiology, Aichi Children’s Health and Medical Center Hisaaki Aoki Department of Pediatric Cardiology, Osaka Women’s and Children’s Hospital Takashi Kurita Division of Cardiovascular Center, Kindai University School of Medicine Yoko Yoshida Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital Tsugutoshi Suzuki Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital Yoshihide Nakamura Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital Yoshiharu Ogawa Division of Cardiology, Hyogo Prefectural Kobe Children’s Hospital Shintaro Yamagami Department of Cardiology, Tenri Hospital Hiroshi Morita Department of Cardiovascular Therapeutics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinsuke Yuasa Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Masakazu Fukuda Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine Makoto Ono Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine Hidekazu Kondo Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University Naohiko Takahashi Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University Seiko Ohno Medical Genome Center, National Cerebral and Cardiovascular Center Yoshihisa Nakagawa Department of Cardiovascular Medicine, Shiga University of Medical Science Koh Ono Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Minoru Horie Department of Cardiovascular Medicine, Shiga University of Medical Science Aims The variant in SCN5A with the loss of function (LOF) effect in the cardiac Na+ channel (Nav1.5) is the definitive cause for Brugada syndrome (BrS), and the functional analysis data revealed that LOF variants are associated with poor prognosis. However, which variant types (e.g. missense or non-missense) affect the prognoses of those variant carriers remain unelucidated.<br> Methods and results We defined SCN5A LOF variants as all non-missense and missense variants that produce peak INa < 65% of wild-type previously confirmed by patch-clamp studies. The study population consisted of 76 Japanese BrS patients (74% patients were male and the median age [IQR] at diagnosis was 28 [14–45] years) with LOF type of SCN5A variants: 40 with missense and 36 with non-missense variants. Non-missense variant carriers presented significantly more severe cardiac conduction disorder compared to the missense variant carriers. During follow-up periods of 9.0 [5.0–14.0] years, compared to missense variants, non-missense variants were significant risk factors of lifetime lethal arrhythmia events (LAEs) (P = 0.023). When focusing only on the missense variants that produce no peak INa, these missense variant carriers exhibited the same clinical outcomes as those with non-missense (log-rank P = 0.325). After diagnosis, however, both variant types were comparable in risk of LAEs (P = 0.155).<br> Conclusion We identified, for the first time, that SCN5A non-missense variants were associated with higher probability of LAE than missense variants in BrS patients though it did not change significantly after diagnosis. 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 1868-4300 2025 Efficacy of transcatheter patent foramen ovale closure for drug-resistant migraine: initial experience in Japan and long-term outcome EN Teiji Akagi Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoichi Takaya Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Miki Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rie Nakayama Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Nakagawa Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mitsuki Nakashima Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Takahashi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinsuke Yuasa Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study evaluates the efficacy and safety of transcatheter patent foramen ovale (PFO) closure for the treatment of drug-resistant migraine in Japan. Previous studies have suggested a potential benefit for migraine with aura, although large-scale trials in the United States and Europe have failed to confirm efficacy as a primary endpoint. The study included 27 patients (mean age 36.4 years, 15 female, 21 with aura) who had more than two migraine attacks per month despite medication. All had PFO confirmed by transesophageal echocardiography and underwent transcatheter closure with the Amplatzer PFO Occluder. Patients were followed up to 12 months with migraine severity monitored by headache specialist. The procedure was successful and without complications in all cases. One patient required a larger occluder (35 mm) due to the size of PFO. At 12 months, 22 of 27 (81%) patients reported either complete resolution or improvement of migraine. Specifically, 10 of 21 (48%) patients with aura experienced complete resolution of migraine at one year. Patients without aura had a lower response rate, with only one case of complete resolution. Despite limitations such as the lack of a control group and potential patient selection bias, the study demonstrated that PFO closure may provide significant relief for patients with drug-resistant migraine, particularly those with aura. These findings support further investigation to better define its clinical indications and potential benefits. 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.<br> 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.<br> 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.<br> 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.

Elsevier BV Acta Medica Okayama 0021-9258 301 7 2025 A repertoire of visible light–sensitive opsins in the deep-sea hydrothermal vent shrimp Rimicaris hybisae 110291 EN Yuya Nagata Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Norio Miyamoto Institute for Extra-Cutting-Edge Science and Technology Avant-Garde Research (X-Star), Japan Agency for Marine-Earth Science and Technology (JAMSTEC) Keita Sato Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Nishimura Research Center for Bioscience and Nanoscience (CeBN), Research Institute for Marine Resources Utilization, Japan Agency for Marine-Earth Science and Technology (JAMSTEC) Yuki Tanioka School of Pharmaceutical Sciences, Okayama University Yuji Yamanaka School of Pharmaceutical Sciences, Okayama University Susumu Yoshizawa Atmosphere and Ocean Research Institute, The University of Tokyo Kuto Takahashi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Obayashi Department of Biology, Graduate School of Science, Kobe University Hisao Tsukamoto Department of Biology, Graduate School of Science, Kobe University Ken Takai Institute for Extra-Cutting-Edge Science and Technology Avant-Garde Research (X-Star), Japan Agency for Marine-Earth Science and Technology (JAMSTEC) Hideyo Ohuchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Yamashita Department of Biophysics, Graduate School of Science, Kyoto University Yuki Sudo Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichi Kojima Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Unlike terrestrial environments, where humans reside, there is no sunlight in the deep sea. Instead, dim visible light from black-body radiation and bioluminescence illuminates hydrothermal vent areas in the deep sea. A deep-sea hydrothermal vent shrimp, Rimicaris hybisae, is thought to detect this dim light using its enlarged dorsal eye; however, the molecular basis of its photoreception remains unexplored. Here, we characterized the molecular properties of opsins, universal photoreceptive proteins in animals, found in R. hybisae. Transcriptomic analysis identified six opsins: three Gq-coupled opsins, one Opn3, one Opn5, and one peropsin. Functional analysis revealed that five of these opsins exhibited light-dependent G protein activity, whereas peropsin exhibited the ability to convert all-trans-retinal to 11-cis-retinal like photoisomerases. Notably, all the R. hybisae opsins, including Opn5, convergently show visible light sensitivity (around 457–517 nm), whereas most opsins categorized as Opn5 have been demonstrated to be UV sensitive. Mutational analysis revealed that the unique visible light sensitivity of R. hybisae Opn5 is achieved through the stabilization of a protonated Schiff base by a counterion residue at position 83 (Asp83), which differs from the position identified in other opsins. These findings suggest that the vent shrimp R. hybisae has adapted its photoreceptive devices to dim deep-sea hydrothermal light by selectively maintaining a repertoire of visible light–sensitive opsins, including the uniquely tuned Opn5. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Spatial and temporal evaluations of fulvic acid iron in Takahashi and Asahi Rivers in Okayama Prefecture, Japan EN ROHDOF LACTEM YENGEH Graduate School of Environmental and Life Science, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Rates and risk factors of bleeding after gastric endoscopic submucosal dissection with continuous warfarin or 1-day withdrawal of direct oral anticoagulants EN Shoichiro HIRATA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Non-woven masks and SARS-CoV-2 infection in a cluster setting in Japan EN Yukari TAKAHASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 Emotional Changes among Young Patients with Breast Cancer to Foster Relationship-Building with Their Partners: A Qualitative Study 185 195 EN Ayumi Yoshikawa Faculty of Nursing, Osaka Dental University Naruto Taira Kawasaki Medical School, Department of Breast and Thyroid Surgery Mayumi Okanaga Gifu College of Nursing, Nursing of Children and Child-Rearing Families Shinya Saito Graduate School of Health Sciences, Okayama University Original Article 10.18926/AMO/68726 We investigated the emotional changes that young patients with breast cancer need to undergo in order to foster relationship-building with their partners by conducting a qualitative descriptive study (March 1 to Nov. 26, 2021) and semi-structured interviews with eight postoperative patients (age 20-40 years) with breast cancer. The data were analyzed using the modified grounded theory approach (M-GTA), yielding five categories: (i) Awareness of being a breast cancer patient, (ii) Being at a loss, (iii) Support from significant others, (iv) The struggle to transition from being a patient with cancer to becoming “the person I want to be”, and (v) Reaching the “me” I want to be who can face building a relationship with a partner. These findings suggest that young breast cancer patients must feel that they can lead a normal life through activities such as work or acquiring qualifications before building relationships with their partners, and that getting closer to their desired selves is important. Nurses can provide information to young patients with breast cancer to assist them in building a solid relationship with their partners. We believe that this support may enhance the patients’ quality of life and help them achieve stronger relationships with their partners. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 Promising Effectiveness of Combined Chemotherapy and Immunotherapy in Patients with Advanced Non-small Cell Lung Cancer: A Real-World Prospective Observational Study (CS-Lung-003) 167 176 EN Nobuhiro Kanaji Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University Kazuya Nishii Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center Yukari Tsubata Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Mika Nakao Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Takae Okuno Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Sachi Okawa Department of Allergy and Respiratory Medicine, Okayama University Hospital Kenji Takata Department of Allergy and Respiratory Medicine, Okayama University Hospital Masahiro Kodani Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University Masahiro Yamasaki Department of Respiratory Disease, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital Kazunori Fujitaka Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Tetsuya Kubota Department of Respiratory Medicine and Allergology, Kochi University Masaaki Inoue Department of Chest Surgery, Shimonoseki City Hospital Naoki Watanabe Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital CS-Lung-003 Investigator Original Article 10.18926/AMO/68724 This prospective observational study investigated the clinical status of patients with advanced non-small cell lung cancer (NSCLC) treated with cytotoxic chemotherapy+an immune checkpoint inhibitor (chemo + IO) as first-line treatment in a real-world setting. The cases of 98 patients treated with chemo + IO were prospectively collected and analyzed for effectiveness and safety. The response rate to chemo + IO was 46.9%, and the disease control rate was 76.5%. The median progression-free survival and overall survival (OS) in the total population were 5.2 and 22.3 months, respectively. The patients positive for PD-L1 (≥ 1%) showed significantly longer OS than the negative group (<1%) (median 26.7 vs. 18.7 months, p=0.04). Pre-existing interstitial lung disease (ILD) was associated with shorter OS than the absence of ILD (median 9.0 vs. 22.6 months, p<0.01). Immunerelated adverse events (irAEs) were observed in 28 patients (28.6%). The most frequent irAE was ILD (n=11); Grade 1 (n=1 patient), G2 (n=5), G3 (n=4), and only a single patient with a G5 irAE. In this CS-Lung-003 study, first-line chemo + IO in a real-world setting showed good effectiveness, comparable to that observed in international clinical trials. In real-world practice, chemo + IO is a promising and steadfast strategy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 Continuous Stimulation with Glycolaldehyde-derived Advanced Glycation End Product Reduces Aggrecan and COL2A1 Production via RAGE in Human OUMS-27 Chondrosarcoma Cells 157 166 EN Omer Faruk Hatipoglu Department of Pharmacology, Faculty of Medicine, Kindai University Takashi Nishinaka Department of Pharmacology, Faculty of Medicine, Kindai University Kursat Oguz Yaykasli Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen Shuji Mori Department of Pharmacology, School of Pharmacy, Shujitsu University Masahiro Watanabe Department of Pharmacology, School of Pharmacy, Shujitsu University Takao Toyomura Department of Pharmacology, School of Pharmacy, Shujitsu University Masahiro Nishibori Department of Translational Research & Dug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Hideo Takahashi Department of Pharmacology, Faculty of Medicine, Kindai University Hidenori Wake Department of Pharmacology, Faculty of Medicine, Kindai University Original Article 10.18926/AMO/68723 Chondrocytes are responsible for the production of extracellular matrix (ECM) components such as collagen type II alpha-1 (COL2A1) and aggrecan, which are loosely distributed in articular cartilage. Chondrocyte dysfunction has been implicated in the pathogenesis of rheumatic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). With age, advanced glycation end products (AGEs) accumulate in all tissues and body fluids, including cartilage and synovial fluid, causing and accelerating pathological changes associated with chronic diseases such as OA. Glycolaldehyde-derived AGE (AGE3), which is toxic to a variety of cell types, have a stronger effect on cartilage compared with other AGEs. To understand the long-term effects of AGE3 on cartilage, we stimulated a human chondrosarcoma cell line (OUMS-27), which exhibits a chondrocytic phenotype, with 10 μg/ml AGE3 for 4 weeks. As a result, the expressions of COL2A1 and aggrecan were significantly downregulated in the OUMS-27 cells without inducing cell death, but the expressions of proteases that play an important role in cartilage destruction were not affected. Inhibition of the receptor for advanced glycation end products (RAGE) suppressed the AGE3-induced reduction in cartilage component production, suggesting the involvement of RAGE in the action of AGE3. No potential conflict of interest relevant to this article was reported.

IOP Publishing Acta Medica Okayama 1367-2630 27 4 2025 Characterization of the thorium-229 defect structure in CaF2 crystals 043024 EN S. Takatori Research Institute for Interdisciplinary Science (RIIS), Okayama University M. Pimon Faculty of Physics, TU Wien S. Pollitt Faculty of Physics, TU Wien M. Bartokos Faculty of Physics, TU Wien K. Beeks Faculty of Physics, TU Wien A. Grueneis Faculty of Physics, TU Wien T. Hiraki Research Institute for Interdisciplinary Science (RIIS), Okayama University T. Honma Japan Synchrotron Radiation Research Institute N. Hosseini Faculty of Physics, TU Wien A. Leitner Faculty of Physics, TU Wien T. Masuda Research Institute for Interdisciplinary Science (RIIS), Okayama University I Morawetz Faculty of Physics, TU Wien K. Nitta Japan Synchrotron Radiation Research Institute K. Okai Research Institute for Interdisciplinary Science (RIIS), Okayama University T. Riebner Faculty of Physics, TU Wien F. Schaden Faculty of Physics, TU Wien T. Schumm Faculty of Physics, TU Wien O. Sekizawa Japan Synchrotron Radiation Research Institute T. Sikorsky Faculty of Physics, TU Wien Y. Takahashi Department of Earth and Planetary Science, The University of Tokyo Col, L. Toscani De Col Faculty of Physics, TU Wien R. Yamamoto Research Institute for Interdisciplinary Science (RIIS), Okayama University T. Yomogida Department of Earth and Planetary Science, The University of Tokyo A. Yoshimi Research Institute for Interdisciplinary Science (RIIS), Okayama University K. Yoshimura Research Institute for Interdisciplinary Science (RIIS), Okayama University Recent advancements in laser excitation of the low-energy thorium-229 (229Th) nuclear isomeric state in calcium fluoride (CaF2) single crystals render this system a promising candidate for a solid-state nuclear clock. Nonetheless, the precise experimental determination of the microscopic ion configuration surrounding the doped 229Th and its electronic charge state remains a critical challenge. Such characterization is essential for precisely controlling the clock transition and evaluating the performance of this solid-state nuclear clock system. In this study, we use x-ray absorption fine structure spectroscopy of 229Th:CaF2 to investigate the charge state and coordination environment of doped 229Th. The results indicate that 229Th displays a 4+ oxidation state at the substitutional site of a Ca2+ ion, with charge compensated provided by two F− ions positioned at interstitial sites adjacent to 229Th. No potential conflict of interest relevant to this article was reported.

Optica Publishing Group Acta Medica Okayama 1094-4087 33 8 2025 Demonstration of enhanced Raman scattering in high-Q silicon nanocavities operating below the silicon band-gap wavelength 18515 18529 EN Yu Shimomura Department of Physics and Electronics, Osaka Metropolitan University Takashi Asano Department of Electronic Science and Engineering, Kyoto University Ayumi Ishihara Department of Physics and Electronics, Osaka Metropolitan University Susumu Noda Department of Electronic Science and Engineering, Kyoto University Yasushi Takahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University We experimentally determined the quality factor (Q) and the intensity of the Raman scattered light for different silicon photonic-crystal nanocavities operating at wavelengths shorter than the silicon band-gap wavelength. Despite the relatively large absorption of silicon in this wavelength region, we observed Q values greater than 10,000 for cavities with a resonance wavelength of 1.05 mu m, and Q values greater than 30,000 for cavities with a resonance wavelength of 1.10 mu m. Additionally, we measured the Raman scattering spectra of cavities with resonance wavelengths of 1.10 mu m and 1.21 mu m. On average, the generation efficiency of the Raman scattered light in a 1.10-mu m nanocavity is 6.5 times higher than that in a 1.21-mu m nanocavity. These findings suggest that silicon nanocavities operating below the silicon band-gap wavelength could be useful in the development of silicon-based light sources. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1476-4598 24 1 2025 ADAR1-high tumor-associated macrophages induce drug resistance and are therapeutic targets in colorectal cancer 116 EN Hibiki Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiaki 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 Yoshitaka Kondo 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 Sho Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shuya Yano 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 Hiroyuki Kishimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hideki Yamamoto Department of Clinical Genomic Medicine, 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 Masashi Kayano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Gradu�ate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshiko Mori Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuzo Umeda 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 Ajay Goel Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute, City of Hope Comprehensive Cancer Center Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background Colorectal cancer (CRC) is considered the third most common type of cancer worldwide. Tumor-associated macrophages (TAMs) have been shown to promote drug resistance. Adenosine-to-inosine RNA-editing, as regulated by adenosine deaminase acting on RNA (ADAR), is a process that induces the posttranscriptional modification of critical oncogenes. The aim of this study is to determine whether the signals from cancer cells would induce RNA-editing in macrophages.<br> Methods The effects of RNA-editing on phenotypes in macrophages were analyzed using clinical samples and in vitro and in vivo models.<br> Results The intensity of the RNA-editing enzyme ADAR1 (Adenosine deaminase acting on RNA 1) in cancer and mononuclear cells indicated a strong positive correlation between the nucleus and cytoplasm. The ADAR1-positive mononuclear cells were positive for CD68 and CD163, a marker for M2 macrophages. Cancer cells transport pro-inflammatory cytokines or ADAR1 protein directly to macrophages via the exosomes, promoting RNA-editing in AZIN1 (Antizyme Inhibitor 1) and GLI1 (Glioma-Associated Oncogene Homolog 1) and resulting in M2 macrophage polarization. GLI1 RNA-editing in the macrophages induced by cancer cells promotes the secretion of SPP1, which is supplied to the cancer cells. This activates the NF kappa B pathway in cancer cells, promoting oxaliplatin resistance. When the JAK inhibitors were administered, oncogenic RNA-editing in the macrophages was suppressed. This altered the macrophage polarization from M2 to M1 and decreased oxaliplatin resistance in cancer cells.<br> Conclusions This study revealed that ADAR1-high TAMs are crucial in regulating drug resistance in CRC and that targeting ADAR1 in TAMs could be a promising treatment approach for overcoming drug resistance in CRC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 A Case of Retinitis Pigmentosa Diagnosed with Severe Anterior Capsule Contraction after Cataract Surgery 129 134 EN Akihiro Tsuji 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 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 Tetsuro Morita Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosuke Takahashi Fukuyama City Hospital, Fukuyama City Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/68652 A 66-year-old woman presented with significant anterior capsule contraction and intraocular lens dislocation in both eyes 4 months after cataract surgery. Postoperative examinations such as fluorescein angiography, Goldmann perimetry, and electroretinography revealed retinitis pigmentosa (RP). Patients with significant anterior capsule contraction after cataract surgery should be closely examined because RP may be a contributing factor. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Macular Hole Formation Six Months after Hemorrhage Displacement for Submacular and Henle Fiber Layer Hemorrhage due to Retinal Arterial Macroaneurysm Rupture 123 127 EN Riku Akatsuka 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 Ryo Matoba 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 Yusuke Shiode 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 Shinichiro Doi 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 Case Report 10.18926/AMO/68651 A 78-year-old woman presented with sudden vision loss and central scotoma. Visual acuity in the right eye was 20/222, with submacular hemorrhage (SMH) and Henle fiber layer hemorrhage (HFLh) due to retinal arterial macroaneurysm (RAM) rupture. She underwent SMH displacement, including cataract surgery, vitrectomy, intravitreal injection of tissue-plasminogen activator, and air tamponade. Three months postoperatively the SMH and HFLh had disappeared and visual acuity had improved to 20/200. Six months postoperatively, a macular hole had developed. We performed an inverted internal limiting membrane flap and gas tamponade. Ten months later, the hole had closed and visual acuity had improved to 20/100. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Lower Work Engagement Is Associated with Insomnia, Psychological Distress, and Neck Pain among Junior and Senior High School Teachers in Japan 93 100 EN Rina Tsuchie 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 Hideki Tsumura Department of Psychology, Graduate School of Technology, Industrial and Social Sciences, Tokushima University Minako Kinuta Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/68647 School teachers are subject to both physical and mental health problems. We examined cross-sectional relationships between work engagement and major health outcomes among junior and senior high school teachers in Japan via a nationwide survey in 2019-2020. A total of 3,160 respondents were included in the analyses (19.9% response rate). Work engagement was assessed with the Utrecht Work Engagement Scale-9 (UWES-9), and we thus divided the teachers into quartiles according to their UWES-9 scores. Based on validated questionnaires, we assessed insomnia, psychological distress, and neck pain as health outcomes. A binomial logistic regression adjusted for age, gender, school type, teacher’s roles, involvement in club activities, division of duties, employment status, and whether they lived with family demonstrated that the teachers with lower UWES-9 scores had higher burdens of insomnia, psychological distress, and neck pain (odds ratios [95% confidence intervals] in 4th vs. 1st quartile, 2.92 (2.34-3.65), 3.70 (2.81-4.88), and 2.12 (1.68-2.68), respectively; all trend p<0.001). There were no significant differences in these associations between full-time and part-time teachers. Our findings indicate that low work engagement may contribute to physical and mental health issues among junior and senior high school teachers, thus providing insights for preventing health problems in this profession. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Association between the Pretreatment Body Mass Index and Anamorelin’s Efficacy in Patients with Cancer Cachexia: A Retrospective Cohort Study 65 73 EN Masatoshi Maki Department of Hospital Pharmacy, NHO Fukuyama Medical Center Ryo Takada Department of Hospital Pharmacy, NHO Fukuyama Medical Center Tomoyuki Ishigo Department of Pharmacy, Sapporo Medical University Hospital Miki Fujiwara Department of Hospital Pharmacy, NHO Fukuyama Medical Center Yoko Takahashi Department of Hospital Pharmacy, NHO Fukuyama Medical Center Shinya Otsuka Department of Surgery, NHO Fukuyama Medical Center Koji Tamura Department of Hospital Pharmacy, NHO Fukuyama Medical Center Terutaka Hamaoka Department of Hospital Pharmacy, NHO Fukuyama Medical Center Original Article 10.18926/AMO/68644 Anamorelin (ANAM) is used to treat cancer-associated cachexia, a syndrome involving muscle loss and anorexia. The timing of the initiation of ANAM treatment is crucial to its efficacy. Although the body mass index (BMI) is a diagnostic criterion for cancer cachexia, no studies have explored its association with ANAM efficacy. We conducted a single-center, retrospective cohort study to investigate the association between the pre-treatment BMI and ANAM efficacy in patients with cancer-associated cachexia (n=47). The ANAM treatment was considered effective if the patient’s appetite improved within 30 days of treatment initiation. We calculated a BMI cutoff value (19.5 kg/m2) and used it to divide the patients into high- and low-BMI groups. Their background, clinical laboratory values, cancer types, and treatment lines were investigated. Twenty (42.6%) had a high BMI (≥ 19.5 kg/m2) and 27 (57.4%) had a low BMI (< 19.5 kg/m2). High BMI was significantly associated with ANAM effectiveness (odds ratio 7.86, 95% confidence interval 1.99-31.00, p=0.003). Together these results indicate that it is beneficial to initiate ANAM treatment before a patient’s BMI drops below 19.5 kg/m2. Our findings will help advance cancer cachexia treatment and serve as a reference for clinicians to predict ANAM’s efficacy. No potential conflict of interest relevant to this article was reported.

岡山大学大学院ヘルスシステム統合科学研究科 Acta Medica Okayama 2436-3227 5 2025 イノベーションループの実践：2024年度先進病院実習報告と未来課題 39 45 EN Nahoko HARADA Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Satoshi TAKAHASHI Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Tomoaki MORI Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Haruka HIKASA Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Keisuke SHISHIDO Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Masaki MAGARI Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Toyohiko WATANABE Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Jin Wang Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Mizuki MORITA Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university 10.18926/interdisciplinary/68625 No potential conflict of interest relevant to this article was reported.

岡山大学教育学部 Acta Medica Okayama 0471-4008 108 1998 高梁市についての研究ノート 141 152 EN Masao NOBE Department of Social Studies Education, Faculty of Education, Okayama University 10.18926/bgeou/68561 No potential conflict of interest relevant to this article was reported.

岡山大学教育学部 Acta Medica Okayama 0471-4008 112 1999 「高梁市高齢女性のパーソナル・ネットワークと 主観的幸福感調査」の基礎分析 57 78 EN Masao NOBE Department of Social Studies Education, Faculty of Education, Okayama University 10.18926/bgeou/68557 　筆者は，平成9年から平成10年にかけて高齢女性を対象に岡山県高梁市において集団加入やパーソナル・ネットワークに関する調査を実施した。本稿では，この調査の概要を説明し，単純集計表を提示した。そして，このデータを用いて，高梁市への流入過程，身体的健康，身体的活動能力，モラール，生活満足度，各種の集団への加入，町内会などがおこなう活動への参加，パーソナル・ネットワークについて検討をおこなった。さて，高梁市は都市部（＝市街地）と農村部からなりたっているが，都市部と農村部で暮らす高齢女性の違いについても考察した。 No potential conflict of interest relevant to this article was reported.

岡山大学教育学部 Acta Medica Okayama 0471-4008 113 2000 高梁市の高原部に住む高齢女性の暮らし 69 85 EN Masao NOBE Department of Social Studies Education, Faculty of Education, Okayama University 10.18926/bgeou/68556 　本稿では，まず，過疎化と高齢化が岡山県高梁市を構成する各地区でどのくらい進行しているかを国勢調査のデータによって明らかにした。次に，箪者が1999年4月から5月にかけて高梁市で聞き取り調査をおこなったが，この調査によって収集した事例のうちから4つの事例を提示した。これを検討することによって，同市の高原部に住む高齢女性がどのような暮らしをしているかを明らかにした。 No potential conflict of interest relevant to this article was reported.

岡山大学教育学部 Acta Medica Okayama 0471-4008 114 2000 高梁市の高原部に住む一人暮らしの高齢女性の生活 47 57 EN Masao NOBE Department of Social Studies Education, Faculty of Education, Okayama University 10.18926/bgeou/68555 　筆者は2000年2月に高梁市の高原部に住む一人暮らしの高齢女性に聞き取り調査をおこなった。本稿では，収集した事例のうちから3つの事例を提示し，これを検討することによって，一人暮らしの高齢女性がどのような暮らしをしているかを明らかにした。 No potential conflict of interest relevant to this article was reported.

岡山大学教育学部 Acta Medica Okayama 0471-4008 116 2001 高梁市の市街地に住む高齢女性の暮らし（その１) 43 53 EN Masao NOBE Department of Social Studies Education, Faculty of Education, Okayama University 10.18926/bgeou/68553 　筆者は2000年10月から11月にかけて高梁市の市街地に住む高齢女性に聞き取り調査をおこなった。本稿では，収集した事例のうちから６つの事例を提示し，これを検討することによって，地方小都市の市街地に住む高齢女性がどのような暮らしをしているかを明らかにした。 No potential conflict of interest relevant to this article was reported.

岡山大学教育学部 Acta Medica Okayama 0471-4008 117 2001 高梁市の市街地に住む高齢女性の暮らし（その２） 35 41 EN Masao NOBE Department of Social Studies Education, Faculty of Education, Okayama University 10.18926/bgeou/68552 　筆者は2000年10月から11月にかけて高梁市の市街地に住む高齢女性に聞き取り調査をおこなった。本稿では，収集した事例のうちから６つの事例を提示し，これを検討することによって，地方小都市の市街地に住む高齢女性がどのような暮らしをしているかを明らかにした。 No potential conflict of interest relevant to this article was reported.

岡山大学教師教育開発センター Acta Medica Okayama 2186-1323 15 2025 保育者志望学生の地震防災に対する意識の傾向 75 89 EN Daisuke SATOH Faculty of Health and Welfare, Kawasaki University of Medical Welfare Kei TAKAHASHI Faculty of Childhood Education, Kurashiki Sakuyo University Noriko BABA Faculty of Education, Okayama University 10.18926/CTED/68483 　近年，南海トラフ巨大地震や都市直下型地震に対する危機感が高まる中，地震防災に対する高い意識を持ち，普段から防災に関する取り組みに努めることが求められている。本研究では，子どもの命を守る保育者を目指す志望学生が，地震災害に対する意識をどのように持ち，地震防災に関する知識や理解をどの程度保持しているのかについて，その実態を明らかにすることを目的とした。保育者養成校４大学の学生に対する質問紙調査を行った結果，地震への危機意識が学年によって異なる傾向にあることや，地震防災に関する意識の高低によって，地震に対する知識や認識の違いがあることが判明した。今後，幼児教育・保育施設における避難訓練の実施や，保育者養成課程において防災教育に関する指導を検討していくことが求められる。 No potential conflict of interest relevant to this article was reported.

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

Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 64 2 2024 Atypical lymphoplasmacytic and immunoblastic proliferation: A Systematic Review 97 106 EN Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Toshiaki Takahashi Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Kensuke Takaoka Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Sharina Macapagal Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Chalothorn Wannaphut Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Hiroko Toda Department of Pathology, Chugoku Central Hospital Yoshito Nishimura Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) was first reported in 1984 as characteristic histological findings in lymph nodes associated with autoimmune diseases, but it has not been clearly defined to date. To summarize the histological characteristics and clinical diagnoses associated with ALPIBP, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including “atypical lymphoplasmacytic and immunoblastic lymphadenopathy” from their inception to December 27, 2023. We also summarized the courses of three cases with a pathological diagnosis of ALPIBP. Nine articles with 52 cases were included. Among the total of 55 cases, including the three from our institution, the median age of the cases was 63.5 years with a female predominance (69.5%). Lymphadenopathy was generalized in 65.6% and regional in 34.4% of cases. RA (24.4%), SLE (24.4%), and autoimmune hemolytic anemia (20.0%), were common clinical diagnoses. A combination of cytotoxic chemotherapy was used in 15.6% of cases due to the suspicion of malignancy. Nodal T-follicular helper cell lymphoma, angioimmunoblastic type, methotrexate-associated lymphoproliferative disorders, and IgG4-related diseases were listed as important diseases that need to be pathologically differentiated from ALPIBP. This review summarizes the current understanding of the characteristics of ALPIBP. Given that underrecognition of ALPIBP could lead to overdiagnosis of hematological malignancy and unnecessary treatment, increased awareness of the condition in pathologists and clinicians is crucial. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 1 2025 A Rare Case of Compression Neuritis due to Intraorbital Arteriovenous Fistula (IOAVF) Mimicking Retrobulbar Optic Neuritis 59 64 EN Shun Minakawa Department of Ophthalmology, Japanese Red Cross Society Himeji Hospital Masayuki Hirano Department of Ophthalmology, Japanese Red Cross Society Himeji Hospital Kazuya Takahashi Department of Neurosurgery, Japanese Red Cross Society Himeji Hospital Yuta Imamura Department of Ophthalmology, Japanese Red Cross Society Himeji Hospital Takashi Watanabe Department of Ophthalmology, Japanese Red Cross Society Himeji Hospital Case Report 10.18926/AMO/68363 Intraorbital arteriovenous fistulas (IOAVFs) are rare vascular abnormalities. We describe a case of an IOAVF featuring a direct shunt between the accessory meningeal artery and the superior ophthalmic artery. A 55-year-old woman presented with a 1-month history of visual impairment in her right eye, and magnetic resonance imaging (MRI) revealed optic neuritis-like findings. Steroid pulse therapy temporarily resolved visual impairment. However, 1 month later, she experienced decreased visual acuity, ocular conjunctival hyperemia, edema, and a pulsatile murmur. Contrast-enhanced MRI and digital subtraction angiography revealed compression optic neuropathy due to an IOAVF. Following successful treatment with transarterial embolization, her symptoms disappeared. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 1 2025 Gastrectomy Causes an Imbalance in the Trunk Muscles 9 19 EN Nanami Ikeya Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Okita Department of Surgery, Okayama City Hospital Shinsuke Hashida Department of Surgery, Okayama City Hospital Sumiharu Yamamoto Department of Surgery, Okayama City Hospital Hirokuni Ikeda Department of Surgery, Okayama City Hospital Kazunori Tsukuda Department of Surgery, Okayama City Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/68354 Muscle loss negatively affects gastrectomy prognosis. However, muscle loss is recognized as a systemic change, and individual muscle function is often overlooked. We investigated changes in the muscle volume of individual muscles after gastrectomy to identify clues for prognostic factors and optimal rehabilitation programs. Patients who underwent R0 gastrectomy for Stage I gastric cancer at our hospital from 2015 to 2021 were retrospectively selected to minimize the effects of malignancy and chemotherapy. Trunk muscle volume was measured by computed tomography to analyze body composition changes. Statistical analysis was performed to identify risk factors related to body composition changes. We compared the preoperative and 6-month postoperative conditions of 59 patients after gastrectomy. There was no difference in the psoas major muscle, a conventional surrogate marker of sarcopenia. There were significant decreases in the erector spinae (p=0.01) and lateral abdominal (p=0.01) muscles, and a significant increase in the rectus abdominis muscle (p=0.02). No significant correlation was found between these muscle changes and nutritional status. Body composition imbalance may serve as a new indicator of the general condition of patients after gastrectomy. Rehabilitation to correct this imbalance may improve prognosis after gastrectomy. No potential conflict of interest relevant to this article was reported.

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

BMC Acta Medica Okayama 1471-2407 25 1 2025 Predictive marker for response to trifluridine/tipiracil plus bevacizumab in metastatic colorectal cancer patients 1 EN Toshiaki Takahashi 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 Sho Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hibiki Umeda 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 Yuya Sakurai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunsuke Nakamura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masafumi Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kaori Nitta 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 Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Kishimoto 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 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 Hajime Kashima 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 Shinji Kuroda 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 Objective Trifluridine/tipiracil (FTD/TPI) is one of the options for late-line treatment of colorectal cancer (CRC). However, the specific patient populations that would particularly benefit from it remain unclear. This study attempted to identify predictive markers of chemotherapy efficacy with trifluridine/tipiracil (FTD/TPI), focusing on the RNA-editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) expression and neutrophil-lymphocyte ratio (NLR).<br> Methods To assess the effectiveness of FTD/TPI in CRC patients, we retrospectively analyzed 72 CRC patients at Okayama University Hospital from 2014 to 2022.<br> Results Adding bevacizumab to FTD/TPI resulted in a more prolonged progression-free survival (PFS), consistent with the SUNLIGHT study findings (p = 0.0028). Among the participants, those with a high NLR had a shorter PFS (p = 0.0395). Moreover, high ADAR1 expression was associated with longer PFS (p = 0.0151). In multivariate analysis, low ADAR1 (HR = 3.43, p = 0.01) and absence of bevacizumab (HR = 4.25, p = 0.01) were identified as factors shortening PFS. The high ADAR1 group demonstrated fewer cases of progressive disease and a higher proportion of stable disease than the low ADAR1 group (p = 0.0288). Low NLR and high ADAR1 were predictive markers of prolonged PFS in the bevacizumab-treated group (p = 0.0036).<br> ConclusionLow NLR and high ADAR1 were predictive markers for a positive response to the FTD/TPI plus bevacizumab regimen associated with prolonged PFS. The FTD/TPI plus bevacizumab regimen should be proactively implemented in the low NLR and high ADAR1 subgroups. No potential conflict of interest relevant to this article was reported.

Lippincott, Williams & Wilkins Acta Medica Okayama 0025-7974 103 50 2024 Relevance of oxidative stress for small intestinal injuries induced by nonsteroidal anti-inflammatory drugs: A multicenter prospective study e40849 EN Yuki Baba Department of Internal Medicine, Japanese Red Cross Himeji Hospital Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akinobu Takaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiyasu Kono Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joichiro Horii Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center Sakuma Takahashi Department of Gastroenterology, Kagawa Prefectural Central Hospital Daisuke Kawai Department of Internal Medicine, Okayama Saiseikai General Hospital Sayo Kobayashi Department of Internal Medicine, Fukuyama City Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Several reports revealed that oxidative stress was involved in the mouse model of nonsteroidal anti-inflammatory drug (NSAIDs)-induced small intestinal mucosal injuries. Thus, we aimed to investigate in the prospective clinical study, that the relevance of oxidative stress balance in small intestinal mucosal injury in NSAIDs users. We prospectively included 60 patients who had been taking NSAIDs continuously for more than 3 months and exhibited obscure gastrointestinal bleeding (number UMIN 000011775). Small intestinal mucosal injuries were assessed by capsule endoscopy (CE), and reactive oxygen metabolites (d-ROMs) levels and oxidant capacity (OXY) adsorbent test were performed to investigate the relevance of oxidative stress balance. More than half of the patients (N = 32, 53%) had small intestinal mucosal injuries by CE, and 14 patients (24%) had ulcers. The incidence of ulcers was relatively higher in nonaspirin users. Serum OXY levels were significantly lower in the mucosal injury group (P = .02), and d-ROM levels were significantly higher in the ulcer group (P < .01). In aspirin users, d-ROM and OXY levels did not differ significantly with respect to mucosal injuries or ulcers. However, in nonaspirin users, OXY level was significantly lower in the mucosal injury group (P = .04), and d-ROM levels were significantly higher in the ulcer group (P = .02). Nonaspirin NSAIDs-induced intestinal mucosal injury is associated with antioxidant systems, resulting in increased oxidative stress. No potential conflict of interest relevant to this article was reported.

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

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 187 2024 保育者志望学生に見る保育時の地震発生対応に関する課題 23 33 EN Noriko BABA Faculty of Education, Okayama University Daisuke SATOH Kawasaki University of Medical Welfare Kei TAKAHASHI Kurashiki Sakuyo University 10.18926/bgeou/67891 　保育者養成校での地震防災に関する授業や指導内容の再検討に示唆を得るため，保育者志望学生に見る保育現場で地震が発生した際の対応に関する不安と，保育職に就く前に学んでおきたい内容について検証した。その結果，保育時に地震が発生した際の対応に関して，①子どもを落ち着かせるための対応，②自分の冷静な行動や判断，③安全な避難や誘導，に不安を感じていることが確認できた。また，保育職に就く前に，①安全な避難の仕方や子どもを守るための方法，②子どもを落ち着かせるための方法や対応，③地震や地震防災の知識，を学びたいと考えていることが分かった。学びたい内容と学ばせたい内容をすり合わせ，確かな防災力の習得と実践力を培う授業内容の検討が今後の課題である。 No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 6 2024 Traumatic Neuroma Arising from Surgical Trauma during Conversion from Laparoscopic to Open Cholecystectomy 459 464 EN Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Rika Yoshimatsu Department of Radiology, Kochi Health Sciences Center Manabu Matsumoto Department of Diagnostic Pathology, Kochi Health Sciences Center Jun Iwata Department of Diagnostic Pathology, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Case Report 10.18926/AMO/67872 Traumatic neuroma is an abnormal proliferation of injured nerves resulting from trauma or surgery. We present a case of traumatic neuroma arising in the cystic duct after cholecystectomy. A 66-year-old man was referred to our department due to a biliary tumor. He had undergone cholecystectomy 20 years prior. Cholangioscopy showed an elevated lesion covered with smooth mucosa. Histological examination revealed normal bile duct mucosa. Although benign disease was suspected, the possibilities of malignant disease could not be excluded. Extrahepatic bile duct resection was planned to include intraoperative rapid-freezing of a biopsy specimen followed by histopathological examination. These intraoperative histology results showed proliferation of nerve and fibrous tissue only, resulting in the diagnosis of traumatic neuroma, so no lymph nodes were removed. To avoid excessive surgical intervention, histopathological examination of an intraoperative rapid-frozen biopsy specimen may be important for diagnosing traumatic neuroma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 6 2024 Closure of Ventricular Septal Rupture through a Left Thoracotomy in a Patient with a History of Esophageal Reconstruction 449 452 EN Gentaro Kato Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Tatsuya Ogawa Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Tomohiro Hayashida Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Shuji Shimizu Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Shu Yamamoto Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Takeshi Shichijo Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Case Report 10.18926/AMO/67870 A 73-year-old man who had undergone esophagectomy and retrosternal gastric tube reconstruction for esophageal cancer 8 years prior was transferred to our hospital for the treatment of an acute myocardial infarction. Emergent percutaneous coronary intervention for the left anterior descending artery (#7) was successfully performed. However, echocardiography revealed a ventricular septal rupture (25×27 mm). Seventeen days after admission, the rupture was successfully treated with a double-patch closure via a left anterolateral thoracotomy to avoid a surgical injury to his retrosternal gastric tube. Determining the best surgical approach to the heart is important for safe cardiac surgery in patients after esophageal reconstruction. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 6 2024 Partial versus Radical Nephrectomy for Small Renal Cancer: Comparative Propensity Score-Matching Analysis of Cardiovascular Event Risk 429 437 EN Risa Kubota 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 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 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 Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/67868 Although partial nephrectomy (PN) is preferred over radical nephrectomy (RN) for preserving renal function in patients with cT1 renal cancer, its impact on cardiovascular events (CVe) remains controversial. This study aimed to compare PN and RN in regard to the occurrence of CVe, including cerebrovascular events and exacerbation of hypertension (HT). We retrospectively analyzed 418 consecutive patients who underwent PN or RN for cT1 renal cancer. Propensity score-matching analysis was used to adjust for imbalances between patients who underwent PN and RN, leaving 102 patients in each group. The 5-year probability of cumulative CVe incidence was 6% in the PN group and 12% in the RN group (p=0.03), with a median follow-up of 73.5 months. The statistical significance was retained after propensity score matching for patients without preoperative proteinuria (p=0.03). For all CVe including cerebrovascular events and exacerbation of HT analyzed, PN provided a lower probability of occurrence than RN in patients with small renal cancers. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 The association between problematic internet use and neck pain among Japanese schoolteachers EN Rina TANABE Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Lysyl oxidase-like 4 promotes the invasiveness of triple-negative breast cancer cells by orchestrating the invasive machinery formed by annexin A2 and S100A11 on the cell surface EN Tetta TAKAHASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 19 10 2024 The protective effect of carbamazepine on acute lung injury induced by hemorrhagic shock and resuscitation in rats e0309622 EN Yaqiang Li Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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 Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Risa Sakamoto Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Emiko Omori Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Takahashi Okayama Saidaiji Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hemorrhagic shock and resuscitation (HSR) enhances the risk of acute lung injury (ALI). This study investigated the protective effect of carbamazepine (CBZ) on HSR-induced ALI in rats. Male Sprague-Dawley rats were allocated into five distinct groups through randomization: control (SHAM), saline + HSR (HSR), CBZ + HSR (CBZ/HSR), dimethyl sulfoxide (DMSO) + HSR (DMSO/HSR), and CBZ + chloroquine (CQ) + HSR (CBZ/CQ/HSR). Subsequently, HSR models were established. To detect tissue damage, we measured lung histological changes, lung injury scores, and wet/dry weight ratios. We measured neutrophil counts as well as assessed the expression of inflammatory factors using RT-PCR to determine the inflammatory response. We detected autophagy-related proteins LC3II/LC3I, P62, Beclin-1, and Atg12-Atg5 using western blotting. Pretreatment with CBZ improved histopathological changes in the lungs and reduced lung injury scores. The CBZ pretreatment group exhibited significantly reduced lung wet/dry weight ratio, neutrophil aggregation and number, and inflammation factor (TNF-alpha and iNOS) expression. CBZ changed the expression levels of autophagy-related proteins (LC3II/LC3I, beclin-1, Atg12-Atg5, and P62), suggesting autophagy activation. However, after injecting CQ, an autophagy inhibitor, the beneficial effects of CBZ were reversed. Taken together, CBZ pretreatment improved HSR-induced ALI by suppressing inflammation, at least in part, through activating autophagy. Thus, our study offers a novel perspective for treating HSR-induced ALI. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0085-2538 106 5 2024 A randomized, open-label, clinical trial examined the effects of canagliflozin on albuminuria and eGFR decline using an individual pre-intervention eGFR slope 972 984 EN Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Hiddo J.L. Heerspink Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Dick de Zeeuw Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Kota Sakamoto Center for Innovative Clinical Medicine, Okayama University Hospital Michihiro Yoshida Center for Innovative Clinical Medicine, Okayama University Hospital Masao Toyoda Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine Daisuke Suzuki Suzuki Diadetes Clinic Takashi Hatanaka Department of Diabetes and Endocrinology, National Hospital Organization Fukuyama Medical Center Tohru Nakamura Diabetes Internal Medicine, Sumitomo Besshi Hospital Shinji Kamei Department of Diabetic Medicine, Kurashiki Central Hospital Satoshi Murao Department of Diabetes and Endocrinology, Takamatsu Hospital Kazuyuki Hida Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Shinichiro Ando Department of Internal Medicine Diabetic Center, Okayama City Hospital Hiroaki Akai Division of Diabetes and Metabolism, Faculty of Medicine, Tohoku Medical and Pharmaceutical University Yasushi Takahashi Department of Diabetes, Ochiai General Hospital Munehiro Kitada Department of Diabetology and Endocrinology, Kanazawa Medical University Hisashi Sugano Department of Diabetes and Endocrinology, Kochi Health Sciences Center Tomokazu Nunoue Nunoue Clinic Akihiko Nakamura Internal Medicine, Osafune Clinic Motofumi Sasaki Department of Diabetes and Endocrinology, Matsue City Hospital Tatsuaki Nakatou Diabetes Center, Okayama Saiseikai General Hospital Kei Fujimoto Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, The Jikei University Kashiwa Hospital Daiji Kawanami Department of Endocrinology and Diabetes, Fukuoka University School of Medicine Takashi Wada Department of Nephrology and Laboratory Medicine, Graduate School of Medical Sciences, Kanazawa University Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Hiromi Kuramoto Center for Innovative Clinical Medicine, Okayama University Hospital Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Demonstrating drug efficacy in slowing kidney disease progression requires large clinical trials when targeting participants with an early stage of chronic kidney disease (CKD). In this randomized, parallel-group, open-labeled trial (CANPIONE study), we assessed the effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin using the individual’s change in estimated glomerular filtration rate (eGFR) slope before (pre-intervention slope) and during treatment (chronic slope). We randomly assigned (1:1) participants with type 2 diabetes, urinary albumin-to-creatinine ratio (UACR) of 50 to under 300 mg/g, and an eGFR of at least 45 ml/min/1.73m2 to receive canagliflozin or guideline-recommended treatment except for SGLT2 inhibitors (control). The first and second primary outcomes were the geometric mean percentage change from baseline in UACR and the change in eGFR slope, respectively. Of 98 randomized participants, 96 received at least one study treatment. The least-squares mean change from baseline in log-transformed geometric mean UACR was significantly greater in the canagliflozin group than the control group (between group-difference, −30.8% (95% confidence interval −42.6 to −16.8). The between-group difference (canagliflozin group – control group) of change in eGFR slope (chronic – pre-intervention) was 4.4 (1.6 to 7.3) ml/min/1.73 m2 per year, which was more pronounced in participants with faster eGFR decline. In summary, canagliflozin reduced albuminuria and the participant-specific natural course of eGFR decline in participants with type 2 diabetes and microalbuminuria. Thus, the CANPIONE study suggests that the within-individual change in eGFR slope may be a novel approach to determine the kidney protective potential of new therapies in early stages of CKD. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1173-8804 39 1 2024 Real-World Comparative Analysis of Trastuzumab Originator and Biosimilars: Safety, Efficacy, and Cost Effectiveness 131 142 EN Tomoka Mamori Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Maki Tanioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kenji Takada Medical AI Project, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Takahiro Tsukioki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuko Takahashi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuguo Iwatani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tadahiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background Despite the global use of trastuzumab biosimilars, concerns remain regarding their efficacy and safety. In particular, when used concurrently with pertuzumab, trastuzumab biosimilars lack extensive real-world data and safety information. Additionally, as cancer drug expenditures continue to rise worldwide, cost savings from biosimilars have become increasingly important.<br> Objective This study aims to assess the safety, efficacy, and cost effectiveness of trastuzumab originators and their biosimilars in real-world clinical settings, focusing on a large patient population.<br> Methods The analysis included 31,661 patients with HER2-positive breast cancer from the Medical Data Vision Co., Ltd. database in Japan. Additionally, adverse event reports for the trastuzumab originator and its biosimilars were obtained for 58,799 patients from the World Health Organization’s VigiBase, the global adverse event reporting database.<br> Results No significant differences were observed in heart failure hospitalizations, liver dysfunction, or infusion reaction rates in both the Medical Data Vision Co., Ltd. database and the World Health Organization’s VigiBase. In the Medical Data Vision Co., Ltd. database, the addition of pertuzumab did not significantly influence the incidence of adverse events, and the use of biosimilars significantly reduced medical costs, with no significant difference in breast cancer recurrence rates.<br> Conclusions By analyzing two large and diverse datasets from multiple perspectives, we obtained reliable results that the trastuzumab originator and its biosimilars have similar safety profiles. The concurrent use of pertuzumab was also found to be safe. The use of biosimilars can lead to cost savings. These findings provide crucial insights for the evaluation and adoption of biosimilars in clinical practice. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Small-for-Gestational-Age Status and the Risk of Kawasaki Disease: A Nationwide Birth Cohort in Japan 363 370 EN Satoe Takanaga Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoka Kadowaki Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soshi Takao Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Original Article 10.18926/AMO/67656 Kawasaki disease (KD) is a pediatric disease of unknown etiology that commonly affects infants in East Asia. Infants born small for gestational age (SGA) have weaker immune systems and are more susceptible to infection. Using data from a nationwide Japanese birth cohort study conducted in 2010 (n=34,579), we investigated whether SGA increases the risk of KD. SGA was defined as birth weight below the 10th percentile for gestational age. The outcome was hospitalization for KD between 6 and 30 months of age. The association between SGA and hospitalization for KD, adjusted for child and maternal factors, was examined using logistic regression. Of the 231 children hospitalized for KD, 9.5% were SGA. Further statistical analysis showed that SGA did not increase the odds ratio (OR) of hospitalization for KD (adjusted OR 1.12, 95% confidence interval 0.71-1.75). This result was not changed with stratification by early daycare attendance and preterm status. Reasons for the lack of association may include the multifactorial pathogenesis of KD; in addition, the types of infections to which SGA infants are predisposed may differ from those triggering KD. Overall, our large nationwide study found no association between SGA and KD. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0815-9319 39 12 2024 Rates and risk factors of bleeding after gastric endoscopic submucosal dissection with continuous warfarin or 1‐day withdrawal of direct oral anticoagulants 2760 2766 EN Shoichiro Hirata Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenta Hamada Department of Practical Gastrointestinal Endoscopy, Okayama University Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Mouri Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Koji Miyahara Department of Internal Medicine, Hiroshima City Hospital Takao Tsuzuki Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital Kenji Yamauchi Department of Gastroenterology, Mitoyo General Hospital Sayo Kobayashi Department of Internal Medicine, Fukuyama City Hospital Sakuma Takahashi Department of Gastroenterology, Kagawa Prefectural Central Hospital Ryuta Takenaka Department of Internal Medicine, Tsuyama Chuo Hospital Shinichiro Hori Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital Masafumi Inoue Department of Gastroenterology, Japanese Red Cross Okayama Hospital Tatsuya Toyokawa Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center Mamoru Nishimura Department of Internal Medicine, Okayama City Hospital Shuhei Ishiyama Department of Internal Medicine, Okayama Saiseikai General Hospital Jiro Miyaike Department of Internal Medicine, Saiseikai Imabari Hospital Ryo Kato Department of Gastroenterology, National Hospital Organization Iwakuni Clinical Center Minoru Matsubara Department of Internal Medicine, Sumitomo Besshi Hospital Naoko Yunoki Department of Internal Medicine, Akaiwa Medical Association Hospital Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Okayama University Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Ishikawa Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Gut Study Group Background and Aim: The 2017 Japanese guidelines recommend continuing warfarin therapy during the perioperative period or discontinuing direct oral anticoagulants (DOACs) only on the day of endoscopic submucosal dissection for early gastric cancer. However, their safety has not been sufficiently explored. This study aimed to validate this management method.<br> Methods: This retrospective, multicenter study analyzed the characteristics and outcomes of patients who underwent gastric endoscopic submucosal dissection between July 2017 and June 2019. The patients were categorized according to the use of warfarin or DOACs.<br> Results: Among the 62 eligible patients, 53 (85%) were male (median age, 76 years). Warfarin was used in 10 patients (16%) and DOACs in 52 patients (84%). Fourteen patients taking DOACs (27%) used concomitant antiplatelet agents, with seven patients (13%) continuing treatment at the time of the endoscopic procedure. No postprocedural bleeding occurred in patients receiving warfarin (0%), whereas 10 cases (19%) of bleeding occurred in patients receiving DOACs: rivaroxaban, 0% (0/22); dabigatran, 0% (0/2); edoxaban, 43% (6/14); and apixaban, 29% (4/14). The type of anticoagulant (P < 0.01) and continuation of antiplatelet therapy (P = 0.02) were risk factors for postprocedural bleeding in patients receiving DOACs. Intraprocedural bleeding requiring transfusion or symptomatic thromboembolic events were not reported.<br> Conclusions: Continuous warfarin therapy is preferred. DOAC withdrawal 1 day before a procedure is associated with a high bleeding rate, which may differ for different types of anticoagulants. The continuation of antiplatelet medications in patients receiving DOACs carries a high risk of bleeding and is a future challenge. No potential conflict of interest relevant to this article was reported.

Elmer Press, Inc. Acta Medica Okayama 1923-4155 15 11 2024 Intravitreal Fluconazole Injection for Fungal Endophthalmitis as Treatment Option in a Patient With End-Stage Liver and Kidney Diseases 359 366 EN Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yasuyuki Kobayashi Department of Urology, Okayama University Hospital Shingo Nishimura Department of Urology, Okayama University Hospital Naoko Yoshioka Department of Gastroenterology and Hepatology, Kawasaki Medical School Yasushi Takahashi Department of Internal Medicine, Ochiai Hospital Yasutaka Iguchi Department of Internal Medicine, Ochiai Hospital Endogenous endophthalmitis is an infectious disease of the intraocular tissue that is a consequence of bloodstream infection. The efficacy of intravitreal fluconazole injection to assist low-dose oral fluconazole in fungal endophthalmitis remains unknown in older adults with advanced liver and renal disease. In this case report, a 78-year-old man with hepatitis C virus-related liver cirrhosis and hepatocellular carcinoma who also had end-stage renal disease with temporary nephrostomy noticed blurred vision and showed a large retinal infiltrate with vitreous opacity in the right eye. In the clinical diagnosis of endogenous fungal endophthalmitis, he had an intravitreal injection of 0.1% fluconazole in 0.2 - 0.3 mL every 2 weeks four times in total, in addition to a minimum dose of oral fluconazole. One month before the ophthalmic presentation, he developed a fever and computed tomography scan showed ureterolithiasis with hydronephrosis on the right side, indicating that the renal pelvic stone fell into the ureter. He underwent nephrostomy tube insertion on the right side in the diagnosis of obstructive urinary tract infection. In the course, a potassium hydroxide (KOH) preparation of the urine sediments which were obtained from the nephrostomy tube showed yeast-like fungi, suggestive of Candida, 1 week before the development of eye symptoms. One week after the ophthalmic presentation, the nephrostomy tube at 14 Fr (French gauge) which had been inserted 1 month previously was replaced with a new tube with a larger size at 16 Fr because urine excretion from the tube was reduced. Immediately after the exchange of the nephrostomy tube, a large volume of urine was excreted from the tube. In a week, he had no systemic symptoms and serum C-reactive protein became low. In the meantime, the retinal infiltrate became inactive and vitreous opacity resolved. Intravitreal fluconazole injection is a treatment option for fungal endophthalmitis in the case that a patient cannot undergo vitrectomy and cannot take a maximum dose of fluconazole because of poor renal function. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1022-1336 46 1 2024 Elastomer Particle Monolayers Formed by the Compression of Poly(methyl acrylate) Microparticles at an Air/Water Interface 2400604 EN Yuma Sasaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuichiro Nishizawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Natsuki Watanabe Department of Physics, Nagoya University Takayuki Uchihashi Department of Physics, Nagoya University Daisuke Suzuki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University In the previous study (Green Chem., 2023, 25, 3418), highly stretchable and mechanically tough poly(methyl acrylate) (pMA) microparticle-based elastomers can be formed by drying a microparticle-containing aqueous dispersion. This discovery has the potential to overcome the mechanical weakness of industrially produced aqueous latex films. However, in 3D-arranged particle films, structural complexity, such as the existence of defects, makes it difficult to clearly understand the relationship between the particle film structure and its mechanical properties. In this study, 2D-ordered pMA particle monolayers at the air/water interface of a Langmuir trough are prepared. Under high compression at the air/water interface, the microparticles contact their neighboring particles, and the resulting monolayers can be successfully transferred onto a solid substrate. The compression of the monolayer films is linked to an increase in the elastic modulus of the monolayer film on the solid substrate as evident from the local Young's modulus mapping using atomic force microscopy. Thus, pMA particle films with different mechanical properties can be created using a Langmuir trough. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4409 13 16 2024 Direct Binding of Synaptopodin 2-Like Protein to Alpha-Actinin Contributes to Actin Bundle Formation in Cardiomyocytes 1373 EN Hiroshi Yamada Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirona Osaka Graduate School of Science, Nagoya University Nanami Tatsumi Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miu Araki Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Abe Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiko Kaihara Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Takahashi Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eizo Takashima Division of Malaria Research, Proteo-Science Center, Ehime University Takayuki Uchihashi Graduate School of Science, Nagoya University Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohji Takei Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric alpha-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with alpha-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused a bundling of the actin filaments in the absence of alpha-actinin and enhanced the alpha-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to alpha-actinin via its globular ends. The interaction between alpha-actinin and SYNPO2La fixed the movements of the two proteins on the actin filaments. These results strongly suggest that SYNPO2L cooperates with alpha-actinin during actin bundle formation to facilitate sarcomere formation and maintenance. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 14 1 2024 Human heart-on-a-chip microphysiological system comprising endothelial cells, fibroblasts, and iPSC-derived cardiomyocytes 18063 EN Yun Liu Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rumaisa Kamran Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xiaoxia Han Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mengxue Wang Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Qiang Li Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daoyue Lai Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Takahashi Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University In recent years, research on organ-on-a-chip technology has been flourishing, particularly for drug screening and disease model development. Fibroblasts and vascular endothelial cells engage in crosstalk through paracrine signaling and direct cell-cell contact, which is essential for the normal development and function of the heart. Therefore, to faithfully recapitulate cardiac function, it is imperative to incorporate fibroblasts and vascular endothelial cells into a heart-on-a-chip model. Here, we report the development of a human heart-on-a-chip composed of induced pluripotent stem cell (iPSC)-derived cardiomyocytes, fibroblasts, and vascular endothelial cells. Vascular endothelial cells cultured on microfluidic channels responded to the flow of culture medium mimicking blood flow by orienting themselves parallel to the flow direction, akin to in vivo vascular alignment in response to blood flow. Furthermore, the flow of culture medium promoted integrity among vascular endothelial cells, as evidenced by CD31 staining and lower apparent permeability. The tri-culture condition of iPSC-derived cardiomyocytes, fibroblasts, and vascular endothelial cells resulted in higher expression of the ventricular cardiomyocyte marker IRX4 and increased contractility compared to the bi-culture condition with iPSC-derived cardiomyocytes and fibroblasts alone. Such tri-culture-derived cardiac tissues exhibited cardiac responses similar to in vivo hearts, including an increase in heart rate upon noradrenaline administration. In summary, we have achieved the development of a heart-on-a-chip composed of cardiomyocytes, fibroblasts, and vascular endothelial cells that mimics in vivo cardiac behavior. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 136 2 2024 薬物相互作用（60―慢性疼痛治療薬の薬物相互作用） 80 82 EN Tetta Takahashi Department of Pharmacy, Okayama University Hospital Tsukasa Higashionna Department of Pharmacy, Okayama University Hospital Hirohumi Hamano Department of Pharmacy, Okayama University Hospital Yoshito Zamami Department of Pharmacy, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 4 2024 Pneumocephalus with Inverted Papilloma in the Frontoethmoidal Sinus: Case Report and Literature Review 337 343 EN Seiichiro Makihara Department of Otolaryngology-Head & Neck 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 Kensuke Uraguchi Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sawako Ono Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aiko Shimizu Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Ikemachi Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Okazaki Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Ota Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Matsumoto Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shotaro Miyamoto Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Munechika Tsumura Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Seiya Hayashi Department of Neurosurgery, Kagawa Rosai Hospital Michiari Umakoshi Department of Neurosurgery, Kagawa Rosai Hospital Koji Hirashita Department of Neurosurgery, Kagawa Rosai Hospital Mizuo Ando Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/67550 Here, we describe the unique case of a pneumocephalus originating from an inverted papilloma (IP) in the frontoethmoidal sinus. A 71-year-old man with diabetes presented with headaches and altered consciousness. Imaging revealed the pneumocephalus together with bone destruction in the left frontal sinus. He underwent simultaneous endoscopic endonasal and transcranial surgery using an ORBEYE exoscope. Pathological diagnosis of the tumor confirmed IP. Post-surgery, the pneumocephalus was significantly resolved and the squamous cell carcinoma antigen level, which had been elevated, decreased. This case underscores the importance of a multidisciplinary approach and innovative surgical methods in treating complex sinonasal pathologies. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0958-3947 49 4 2024 Evaluation of the trend of set-up errors during the treatment period using set-up margin in prostate radiotherapy 291 297 EN Hinako Sasaki Department of Radiological Technology, Faculty of Health Sciences, Okayama University Medical School Takumi Morishita Department of Radiological Technology, Faculty of Health Sciences, Okayama University Medical School Naho Irie Department of Radiological Technology, Faculty of Health Sciences, Okayama University Medical School Rena Kojima Department of Radiological Technology, Faculty of Health Sciences, Okayama University Medical School Tetsukazu Kiriyama Department of Radiology, Uwajima City Hospital Akira Nakamoto Department of Radiology, Tokuyama Central Hospital Kunio Nishioka Department of Radiology, Tokuyama Central Hospital Shotaro Takahashi Department of Radiology, Tokuyama Central Hospital Yoshinori Tanabe Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Accurate information on set-up error during radiotherapy is essential for determining the optimal number of treatments in hypofractionated radiotherapy for prostate cancer. This necessitates careful control by the radiotherapy staff to assess the patient's condition. This study aimed to develop an evaluation method of the temporal trends in a patient's specific prostate movement during treatment using image matching and margin values. This study included 65 patients who underwent prostate volumetric modulated arc therapy (mean treatment time, 87.2 s). Set-up errors were assessed using bone, inter-, and intra-fraction marker matching across 39 fractions. The set-up margin was determined by dividing the four periods into 39 fractions using Stroom's formula and correlation coefficient. The intra-fraction set-up error was biased in the anterior-superior (AS) direction during treatment. The temporal trend of set-up errors during radiotherapy slightly increased based on bone matching and inter-fraction marker matching, with a 1.6-mm difference in the set-up margin fractions 11 to 20. The correlation coefficient of the mean prostate movement during treatment significantly decreased in the superior-inferior direction, while remaining high in the left-right and anterior-posterior directions. Image matching contributed significantly to the improvement of set-up errors; however, careful attention is needed for prostate movement in the AS direction, particularly during short treatment times. Understanding the trend of set-up errors during the treatment period is essential in numerical information sharing on patient condition and evaluating the margins for tailored hypo-fractionated radiotherapy, considering the facility's image-guided radiation therapy technology. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0167-6806 208 2024 Comparison of proportions and prognostic impact of pathological complete response between evaluations of representative specimen and total specimen in primary breast cancer after neoadjuvant chemoradiotherapy: an ancillary study of JCOG0306 145- 154 EN Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hitoshi Tsuda Department of Basic Pathology, National Defense Medical College Keita Sasaki JCOG Data Center/Operations Office, National Cancer Center Hospital Junki Mizusawa JCOG Data Center/Operations Office, National Cancer Center Hospital Futoshi Akiyama Department of Pathology, Cancer Institute Hospital Masafumi Kurosumi Department of Diagnostic Pathology, Kameda Kyobashi Clinic Masataka Sawaki Department of Breast Oncology, Aichi Cancer Center Hospital Nobuko Tamura Department of Breast Surgery, Toranomon Hospital Kiyo Tanaka Department of Breast Surgery, Toranomon Hospital Takahiro Kogawa Department of Breast Medical Oncology, Cancer Institute Hospital Mina Takahashi Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center Naoki Hayashi Department of Breast Surgery Oncology, St Lukes International Hospital Hirofumi Mukai Department of Breast and Medical Oncology, National Cancer Center Hospital East Norikazu Masuda Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital Fumikata Hara Department of Breast Medical Oncology, Cancer Institute Hospital Hiroji Iwata Department of Breast Oncology, Aichi Cancer Center Hospital Background In JCOG0306 trial, a phase II study to examine the efficacy of neoadjuvant chemotherapy followed by radiation therapy (NAC-RT) to primary breast cancer, pathological complete response (pCR) was evaluated from specimens of the representative cross-section including the tumor center that had been accurately marked [representative specimen (RS) method]. In this ancillary study, we examined if the RS method was comparable to the conventional total specimen (TS) method, which is widely employed in Japan, to identify the pCR group showing excellent prognosis.<br> Methods We obtained long-term follow-up data of 103 patients enrolled in JCOG0306 trial. As histological therapeutic effect, pCR (ypT0 and ypT0/is) and quasi-pCR [QpCR, ypT0/is plus Grade 2b (only a few remaining invasive cancer cells)] were evaluated with RS and TS methods. Concordance of pCR between these two methods and associations of the pCR with prognosis were examined.<br> Results ypT0, ypT0/is, and QpCR were observed in 28 (27.2%), 39 (37.9%), and 45 (43.7%) patients with RS method, whereas these were 20 (19.4%), 25 (24.3%) and 40 (38.9%) with TS method, respectively. Between RS and TS methods, concordance proportions of ypT0 and ypTis were 92.2% and 86.4%, respectively. Risk of recurrence of ypT0/is group was lower than that of non-ypT0/is group (HR 0.408, 95% CI [0.175–0.946], P = 0.037) and risk of death of ypT0/is group was lower than that of non-ypT0/is group (HR 0.251, 95% CI [0.073–0.857], P = 0.027). The ypT0 and ypT0/is groups with RS method showed excellent prognosis similarly with those with TS method, and RS method was able to differentiate the OS and RFS between pCR and non-pCR than TS method significantly even if pCR was classified ypT0 or ypT0/is. With TS method, QpCR criteria stratified patients into the better and worse prognosis groupsmore clearly than pCR criteria of ypT0 or ypT0/is.<br> Conclusions RS method was comparable to TS method for the evaluation of pCR in the patients who received NAC-RT to primary breast cancer provided the tumor center was accurately marked. As pCR criteria with RS method, ypT0/is appeared more appropriate than ypT0. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 11 2024 Anti-HMGB1 mAb Therapy Reduces Epidural Hematoma Injury 5889 EN Shangze Gao Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Dengli Wang Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keyue Liu Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuko Tomono Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Li Fu Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuan Gao Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yohei Takahashi Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Yata Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Nishibori Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Epidural and subdural hematomas are commonly associated with traumatic brain injury. While surgical removal is the primary intervention for these hematomas, it is also critical to prevent and reduce complications such as post-traumatic epilepsy, which may result from inflammatory responses in the injured brain areas. In the present study, we observed that high mobility group box-1 (HMGB1) decreased in the injured brain area beneath the epidural hematoma (EDH) in rats, concurrent with elevated plasma levels of HMGB1. Anti-HMGB1 monoclonal antibody therapy strongly inhibited both HMGB1 release and the subsequent increase in plasma levels. Moreover, this treatment suppressed the up-regulation of inflammatory cytokines and related molecules such as interleukin-1-beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in the injured areas. Our in vitro experiments using SH-SY5Y demonstrated that hematoma components—thrombin, heme, and ferrous ion— prompted HMGB1 translocation from the nuclei to the cytoplasm, a process inhibited by the addition of the anti-HMGB1 mAb. These findings suggest that anti-HMGB1 mAb treatment not only inhibits HMGB1 translocation but also curtails inflammation in injured areas, thereby protecting the neural tissue. Thus, anti-HMGB1 mAb therapy could serve as a complementary therapy for an EDH before/after surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 Calcification of a Hydrophilic Acrylic Intraocular Lens after Glaucoma Surgery 295 300 EN Sara Okamoto 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 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 Hiroya Kindo 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 Akihiro Tsuji Fukuyama City Hospital Kosuke Takahashi Fukuyama City Hospital Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/67206 A Japanese woman in her 70s was referred to our hospital for the evaluation and treatment of high intraocular pressure (IOP) in her right eye. She had undergone bilateral cataract surgeries and the insertion of hydrophilic acrylic intraocular lenses (IOLs). We performed trabeculotomy and trabeculectomy to lower her right IOP; thereafter, a circular opacity was observed on the right eye’s IOL surface. We removed the right IOL because that eye’s vision had decreased due to IOL opacification. The analysis of the removed IOL revealed that the main opacity component was calcium phosphate. This is the first post-glaucoma-surgery IOL calcification case report. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 A Case of Gallbladder Metastasis of Malignant Melanoma 291 294 EN Hitoshi Minagi Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Hideki Aoki Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Susumu Doita Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Eiki Miyake Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Toshihiro Ogawa Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Fumitaka Taniguchi Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Megumi Watanabe Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Takashi Arata Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Koh Katsuda Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Kohji Tanakaya Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Case Report 10.18926/AMO/67205 In the clinical course of malignant melanoma, which can metastasize to multiple organs, gallbladder metastases are rarely detected. A 69-year-old man who underwent resection of a primary malignant melanoma was subsequently treated with nivolumab for lung metastases and achieved complete response. Seven years after surgery, multiple nodules were found in the gallbladder, and he underwent laparoscopic cholecystectomy. The postoperative diagnosis was metastases of malignant melanoma. He has been recurrence-free 8 months after surgery. If radical resection is possible, such surgery should be performed for gallbladder metastases found in patients with other controlled lesions of malignant melanoma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 Organized Chronic Subdural Hematoma (OCSDH) Mimicking Meningioma 285 290 EN Shuichiro Hirano 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 Kentaro Fujii Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/67204 Organized chronic subdural hematoma (OCSDH) is a relatively rare condition that forms over a longer period of time compared to chronic subdural hematoma and is sometimes difficult to diagnose with preoperative imaging. We resected an intracranial lesion in a 37-year-old Japanese man; the lesion had been increasing in size for >17 years. The preoperative diagnosis based on imaging findings was meningioma; however, pathological findings revealed OCSDH. Clinicians should be aware that OCSDH mimics other tumors and consider surgical strategies for this disease. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 The Impact of Reduced Skeletal Muscle Mass on Patients with Knee Osteoarthritis 245 250 EN Manabu Akagawa Department of Orthopedic Surgery, Omagari Kousei Medical Center Hidetomo Saito Department of Orthopedic Surgery, Akita University Graduate School of Medicine Yasuhiro Takahashi Department of Orthopedic Surgery, Omagari Kousei Medical Center Yosuke Iwamoto Department of Orthopedic Surgery, Omagari Kousei Medical Center Junpei Iida Department of Orthopedic Surgery, Omagari Kousei Medical Center Takayuki Yoshikawa Department of Orthopedic Surgery, Omagari Kousei Medical Center Toshiki Abe Department of Orthopedic Surgery, Omagari Kousei Medical Center Kimio Saito Department of Orthopedic Surgery, Akita University Graduate School of Medicine Hiroaki Kijima Department of Orthopedic Surgery, Akita University Graduate School of Medicine Yuji Kasukawa Department of Orthopedic Surgery, Akita University Graduate School of Medicine Michio Hongo Department of Orthopedic Surgery, Akita University Graduate School of Medicine Naohisa Miyakoshi Department of Orthopedic Surgery, Akita University Graduate School of Medicine Original Article 10.18926/AMO/67199 Although several studies have suggested a possible association between sarcopenia and knee osteoarthritis (OA) in the elderly, there remains no definitive evidence. Recently, however, the serum creatinine/cystatin C ratio (sarcopenia index: SI) was reported to correlate with skeletal muscle mass. The present retrospective study therefore investigated the impact of reduced skeletal muscle mass on advanced knee OA using SI. In 55 individuals scheduled for knee osteotomy or knee arthroplasty, correlations between SI and patient-reported outcomes such as the Knee Society Score (KSS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Oxford Knee Score (OKS) were explored. Significant associations were found between SI and the KSS functional activity score (β=0.37; p=0.022), KOOS subscale for activities of daily living (β=0.42; p=0.0096), and OKS (β=0.42; p=0.0095). This study underscores the role of reduced muscle mass in functional outcomes and introduces SI as a valuable marker for assessing muscle loss in knee OA patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 Thoughts on and Proposal for the Education, Training, and Recruitment of Infectious Disease Specialists 205 213 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Review 10.18926/AMO/67195 The global pandemic of COVID-19 has underscored the significance of establishing and sustaining a practical and efficient infection control system for the benefit and welfare of society. Infectious disease (ID) specialists are expected to take on leadership roles in enhancing organizational infrastructures for infection prevention and control (IPC) at the hospital, community, and national levels. However, due to an absolute shortage and an uneven distribution, many core hospitals currently lack the ID specialists. Given the escalating global risk of emerging and re-emerging infectious diseases as well as antimicrobial resistance pathogens, the education and training of ID specialists constitutes an imperative concern. As demonstrated by historical changes in the healthcare reimbursement system, the establishment and enhancement of IPC measures is pivotal to ensuring medical safety. The existing structure of academic society-driven certification and training initiatives for ID specialists, contingent upon the discretionary decisions of individual physicians, possesses both quantitative and qualitative shortcomings. In this article, I first address the present situations and challenges related to ID specialists and then introduce my idea of securing ID specialists based on the new concepts and platforms; (i) ID Specialists as National Credentials, (ii) Establishment of the Department of Infectious Diseases in Medical and Graduate Schools, (iii) Endowed ID Educative Courses Funded by Local Government and Pharmaceutical Companies, and (iv) Recruitment of Young Physicians Engaged in Healthcare Services in Remote Areas. As clarified by the COVID-19 pandemic, ID specialists play a crucial role in safeguarding public health. Hopefully, this article will advance the discussion and organizational reform for the education and training of ID specialists. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2210-2612 118 2024 The effectiveness of palliative middle meningeal artery embolization prior to craniotomy for large acute epidural hematoma: A case report 109704 EN Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Takahashi Department of Neurological Surgery, Kagawa Prefectural Central Hospital Satoshi Kuramoto Department of Neurological Surgery, Kagawa Prefectural Central Hospital Shingo Nishihiro Department of Neurological Surgery, Kagawa Prefectural Central Hospital Yasuhiro Ono Department of Neurological Surgery, Kagawa Prefectural Central Hospital Tomotsugu Ichikawa Department of Neurological Surgery, Kagawa Prefectural Central Hospital Introduction and importance: Acute epidural hematoma is typically managed with craniotomy. However, there are a few reports on transcatheter arterial embolization (TAE) as an adjunctive therapy. <br> Case presentation: A 70-year-old female with no obvious history of trauma was transported to our hospital. Computed tomography scan revealed an epidural hematoma of approximately 80 ml with a midline shift of 5 mm. We decided to perform an emergency craniotomy. However, the operating room (OR) was already occupied by a scheduled surgery and it would take 30 min to an hour to prepare it. We opted to wait for our OR, considering that, even if the patient was transferred to another hospital, it would take time for the craniotomy to commence. <br> Clinical discussion: We performed TAE for the middle meningeal artery (MMA) as a palliative measure to prevent hematoma enlargement. The MMA was selectively embolized with 20 % n-butyl-2-cyanoacrylate (NBCA), resulting in no hematoma enlargement or observed complications. The criteria for endovascular treatment of acute epidural hematoma are not yet well-established. This case demonstrates the potential role of endovascular treatment for large acute epidural hematomas in carefully selected patients. <br> Conclusion: If there is a time gap before craniotomy, TAE could be considered a viable option for large acute epidural hematomas as a palliative intervention before craniotomy. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 歯の移動初期における歯根膜組織の大規模三次元イメージング EN Haruka TAKAHASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Antimicrobial prescription practices for outpatients with uncomplicated cystitis in Japan EN Misa TAKAHASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Reduced Immunogenicity of COVID-19 Vaccine in Obese Patients with Type 2 Diabetes: A Cross-Sectional Study EN Hiroko TAKAHASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Mouse embryonic stem cells embody organismal-level cold resistance EN Koukyou SUITA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2210-2612 117 2024 Surgical repair for a parahiatal hernia with an esophageal hiatal hernia: A case report and literature review 109565 EN Yosuke Takahashi 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 Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Introduction and importance: A parahiatal hernia (PH) is a rare diaphragmatic hernia (DH) adjacent to but separated from the esophageal hiatus. The surgical repair for PH needs primary suture closure or complicated hernioplasty and the addition of an anti-reflux procedure. This report describes a case of PH with a symptomatic esophageal hiatal hernia managed using three-dimensional (3D) laparoscopy. <br> Case presentation: A 65-year-old woman with back pain and breathlessness was referred to our hospital for a DH. Computed tomography showed a diaphragmatic defect on the left side of the esophageal hiatus. Upper gastrointestinal endoscopy and 24-hour esophageal impedance-pH monitoring showed a symptomatic esophageal hiatal hernia. Laparoscopic repair for both hernias was performed using 3D laparoscopy. The DH orifice was located in the left crus of the diaphragm, and it was separated from the esophageal hiatus. These findings showed that this DH was a PH. The PH was repaired with primary suturing, and a hiatoplasty was performed. Toupet fundoplication was performed with a 270 degrees posterior wrap of the gastric fornix. The patient has remained asymptomatic a year after surgery without any complications. <br> Clinical discussion: 3D laparoscopy provides significant advantages in surgeries requiring precise suturing. PH repairs require complex procedures, including mesh repair or suturing. Approximately 44 % of PH cases also necessitate fundoplication. 3D laparoscopy was useful for the present case. <br> Conclusions: A rare PH and a symptomatic type 1 hiatal hernia were repaired with 3D laparoscopy, which is helpful for PH treatment in cases requiring complicated procedures. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0167-6806 202 3 2023 Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer 473 483 EN Shinsuke Sasada Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University Naoto Kondo Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences Hiroya Hashimoto Core Laboratory, Nagoya City University Graduate School of Medical Sciences Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Kaori Terata Department of Breast and Endocrine Surgery, Akita University Hospital Kumiko Kida Department of Breast Surgical Oncology, St. Luke’s International Hospital Yasuaki Sagara Department of Breast and Thyroid Surgical Oncology, Social medical corporation Hakuaikai, Sagara Hospital Takayuki Ueno Breast Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Keisei Anan Department of Surgery, Kitakyushu Municipal Medical Center Akihiko Suto Department of Breast Surgery, National Cancer Center Hospital Chizuko Kanbayashi Department of Breast Oncology, Niigata Cancer Center Hospital Mina Takahashi Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center Rikiya Nakamura Department of Breast Surgery, Chiba Cancer Center Toshiyuki Ishiba Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Michiko Tsuneizumi Department of Breast Surgery, Shizuoka General Hospital Seiichiro Nishimura Department of Breast Surgery, Shizuoka Cancer Center Hospital Yoichi Naito Department of General Internal Medicine, National Cancer Center Hospital East Fumikata Hara Breast Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroji Iwata Department of Breast Oncology, Aichi Cancer Center Hospital Purpose Mammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain.<br> Methods We evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided.<br> Results Adjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32–0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39–0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33).<br> Conclusions The prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0040-5752 136 4 2023 FLOURY ENDOSPERM 6 mutations enhance the sugary phenotype caused by the loss of ISOAMYLASE1 in barley 94 EN Ryo Matsushima Institute of Plant Science and Resources, Okayama University Hiroshi Hisano Institute of Plant Science and Resources, Okayama University Ivan Galis Institute of Plant Science and Resources, Okayama University Satoko Miura Department of Biological Production, Akita Prefectural University Naoko Crofts Department of Biological Production, Akita Prefectural University Yuto Takenaka College of Life Sciences, Ritsumeikan University Naoko F. Oitome Department of Biological Production, Akita Prefectural University Takeshi Ishimizu College of Life Sciences, Ritsumeikan University Naoko Fujita Department of Biological Production, Akita Prefectural University Kazuhiro Sato Institute of Plant Science and Resources, Okayama University Starch is a biologically and commercially important glucose polymer synthesized by plants as semicrystalline starch granules (SGs). Because SG morphology affects starch properties, mutants with altered SG morphology may be useful in breeding crops with desirable starch properties, including potentially novel properties. In this study, we employed a simple screen for mutants with altered SG morphology in barley (Hordeum vulgare). We isolated mutants that formed compound SGs together with the normal simple SGs in the endosperm and found that they were allelic mutants of the starch biosynthesis genes ISOAMYLASE1 (HvISA1) and FLOURY ENDOSPERM 6 (HvFLO6), encoding starch debranching enzyme and CARBOHYDRATE-BINDING MODULE 48-containing protein, respectively. We generated the hvflo6 hvisa1 double mutant and showed that it had significantly reduced starch biosynthesis and developed shrunken grains. In contrast to starch, soluble α-glucan, phytoglycogen, and sugars accumulated to higher levels in the double mutant than in the single mutants. In addition, the double mutants showed defects in SG morphology in the endosperm and in the pollen. This novel genetic interaction suggests that hvflo6 acts as an enhancer of the sugary phenotype caused by hvisa1 mutation. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1759-9954 14 37 2023 Catalytic synthesis and physical properties of CO2-based cross-linked poly(cyclohexene carbonate)s 4338 4343 EN Chihiro Maeda Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Kenta Kawabata Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Kaito Niki Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Yuma Sako Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Takumi Okihara Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tadashi Ema Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Bifunctional aluminum porphyrins (0.001 mol%) catalyzed the terpolymerization of cyclohexene oxide (CHO), bis(CHO), and CO2 to give cross-linked polycarbonates (CLPs) under solvent-free conditions. A small amount of bis(CHO) acted as a cross-linking agent, and the use of only 0.1 mol% bis(CHO) to CHO produced polymers of quite large sizes. The thermal and mechanical properties of CLPs could be altered by changing the structure and amount of bis(CHO), and the CLPs showed improved thermal stability and tensile strength as compared to linear poly(cyclohexene carbonate)s (PCHCs). The degradation of the CLPs was also investigated, and the selective cleavage of the cross-links was achieved by UV light irradiation to give linear PCHCs. The present study disclosed the potentials of cross-linking terpolymerization for the preparation of various CLPs with a constant CO2 content (31 wt%). No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 A Case of Gallbladder Cancer with Trousseau Syndrome Successfully Treated Using Radical Resection 201 204 EN Akari Masunaga Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Rika Yoshimatsu Department of Radiology, Kochi Health Sciences Center Manabu Matsumoto Department of Radiology, 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/66931 Trousseau syndrome is characterized by cancer-associated systemic thrombosis. We describe the first case of a successfully treated gallbladder adenocarcinoma accompanied by Trousseau syndrome. A 66-year-old woman presented with right hemiplegia. Magnetic resonance imaging identified multiple cerebral infarctions. Her serum carbohydrate antigen 19-9 and D-dimer levels were markedly elevated, and a gallbladder tumor was detected via abdominal computed tomography. Venous ultrasonography of the lower limbs revealed a deep venous thrombus in the right peroneal vein. These findings suggested that the brain infarctions were likely caused by Trousseau syndrome associated with her gallbladder cancer. Radical resection of the gallbladder tumor was performed. The resected gallbladder was filled with mucus and was pathologically diagnosed as an adenocarcinoma. Her postoperative course was uneventful, and she received a one-year course of adjuvant therapy with oral S-1. No cancer recurrence or thrombosis was noted 26 months postoperatively. Despite concurrent Trousseau syndrome, a radical cure of the primary tumor and thrombosis could be achieved with the appropriate treatment. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 0163-5581 76 6 2024 Perioperative and Postoperative Continuous Nutritional Counseling Improves Quality of Life of Gastric Cancer Patient Undergoing Gastrectomy 476 485 EN Shunya Hanzawa 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 Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hajime Kashima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayako Takahashi Clinical Nutrition, Okayama University Hospital Yoshihiko Kakiuchi 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 Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenichi Shikata Clinical Nutrition, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Post-gastrectomy syndrome (PGS) and body weight loss (BWL) decrease quality of life (QOL) and survival of the patient undergoing gastrectomy. We have introduced perioperative and post-discharge continuous nutritional counseling (CNC) to prevent BWL and improve QOL after gastrectomy. In the present study, we evaluated the effect of CNC on QOL using the Post-gastrectomy Syndrome Assessment Scale-45 (PGSAS-45). Eighty-three patients with gastric cancer (GC) who underwent curative gastrectomy between March 2018 and July 2019 were retrospectively analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n = 45) or CNC (CNC group, n = 38) after gastrectomy. QOL at 12 months after gastrectomy was compared between the two groups. In QOL assessment, change in body weight (−7.98% vs. −12.77%, p = 0.0057), ingested amount of food per meal (7.00 vs. 6.07, p = 0.042) and ability for working (1.89 vs. 2.36, p = 0.049) were significantly better in CNC group than control group. Multiple regression analysis showed that CNC was a significantly beneficial factor for abdominal pain subscale (p = 0.028), diarrhea subscale (p = 0.047), ingested amount of food per meal (p = 0.012), Ability for working (p = 0.031) and dissatisfaction at the meal (p = 0.047). Perioperative and postoperative CNC could improve QOL in the patient undergoing gastrectomy in addition to preventing postoperative BWL. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 Reduced Immunogenicity of COVID-19 Vaccine in Obese Patients with Type 2 Diabetes: A Cross-Sectional Study 185 191 EN Hiroko Takahashi Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayu Watanabe Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Nakayama Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66927 The global pandemic of coronavirus infection 2019 (COVID-19) was an unprecedented public health emergency. Several clinical studies reported that heart disease, lung disease, diabetes, hypertension, dyslipidemia, and obesity are critical risk factors for increased severity of and hospitalization for COVID-19. This is largely because patients with these underlying medical conditions can show poor immune responses to the COVID-19 vaccinations. Diabetes is one of the underlying conditions most highly associated with COVID-19 susceptibility and is considered a predictor of poor prognosis of COVID-19. We therefore investigated factors that influence the anti-SARS-CoV-2 spike IgG antibody titer after three doses of vaccination in patients with type 2 diabetes. We found that obesity was associated with low anti-SARS-CoV-2 spike IgG antibody titers following three-dose vaccination in type 2 diabetics. Obese patients with type 2 diabetes may have attenuated vaccine efficacy and require additional vaccination; continuous infection control should be considered in such patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression 151 161 EN Tadashi Komatsubara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joe Hasei Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshinori Omori Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhisa Sugiu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Mochizuki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Demiya Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aki Yoshida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66924 Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors’ growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 The Roles of Neuropeptide Y in Respiratory Disease Pathogenesis via the Airway Immune Response 95 106 EN Junko Itano Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital Review 10.18926/AMO/66912 The lungs are very complex organs, and the respiratory system performs the dual roles of repairing tissue while protecting against infection from various environmental stimuli. Persistent external irritation disrupts the immune responses of tissues and cells in the respiratory system, ultimately leading to respiratory disease. Neuropeptide Y (NPY) is a 36-amino-acid polypeptide and a neurotransmitter that regulates homeostasis. The NPY receptor is a seven-transmembrane-domain G-protein-coupled receptor with six subtypes (Y1, Y2, Y3, Y4, Y5, and Y6). Of these receptors, Y1, Y2, Y4, and Y5 are functional in humans, and Y1 plays important roles in the immune responses of many organs, including the respiratory system. NPY and the Y1 receptor have critical roles in the pathogenesis of asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. The effects of NPY on the airway immune response and pathogenesis differ among respiratory diseases. This review focuses on the involvement of NPY in the airway immune response and pathogenesis of various respiratory diseases. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1867-1071 42 2 2023 Evaluation of the ear ossicles with photon-counting detector CT 158 164 EN Yuka Takahashi Department of Radiology, Okayama University Hospital Fumiyo Higaki Department of Radiology, Okayama University Hospital Akiko Sugaya Department of Otolaryngology‑Head and Neck Surgery, Okayama University Hospital Yudai Asano Department of Radiology, Okayama University Hospital Katsuhide Kojima Department of Radiology, Okayama University Hospital Yusuke Morimitsu Department of Radiological Technology, Okayama University Hospital Noriaki Akagi Department of Radiological Technology, Okayama University Hospital Toshihide Itoh Department of CT‑Research and Collaboration, Siemens Healthineers Yusuke Matsui Department of Radiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Takao Hiraki Department of Radiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Recently, computed tomography with photon-counting detector (PCD-CT) has been developed to enable high-resolution imaging at a lower radiation dose. PCD-CT employs a photon-counting detector that can measure the number of incident X-ray photons and their energy. The newly released PCD-CT (NAEOTOM Alpha, Siemens Healthineers, Forchheim, Germany) has been in clinical use at our institution since December 2022. The PCD-CT offers several advantages over current state-of-the-art energy-integrating detector CT (EID-CT). The PCD-CT does not require septa to create a detector channel, while EID-CT does. Therefore, downsizing the anode to achieve higher resolution does not affect the dose efficiency of the PCD-CT. CT is an indispensable modality for evaluating ear ossicles. The ear ossicles and joints are clearly depicted by PCD-CT. In particular, the anterior and posterior legs of the stapes, which are sometimes unclear on conventional CT scans, can be clearly visualized. We present cases of congenital anomalies of the ossicular chain, ossicular chain dislocation, tympanosclerosis, and cholesteatoma in which PCD-CT was useful. This short article reports the usefulness of PCD-CT in the 3D visualization of the ear ossicles. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 2234-943X 14 2024 Lysyl oxidase-like 4 promotes the invasiveness of triple-negative breast cancer cells by orchestrating the invasive machinery formed by annexin A2 and S100A11 on the cell surface 1371342 EN Tetta Takahashi 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 Rie Kinoshita 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 Hitoshi Murata Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Fan Jiang Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuma Gohara 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 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 Yoshihiko Sakaguchi Department of Microbiology, Tokushima Bunri University Akira Yamauchi Department of Biochemistry, Kawasaki Medical School Futoshi Kuribayashi Department of Biochemistry, Kawasaki Medical School 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 Junichiro Futami Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshito Zamami Department of Pharmacy, Okayama University Hospital Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Our earlier research revealed that the secreted lysyl oxidase-like 4 (LOXL4) that is highly elevated in triple-negative breast cancer (TNBC) acts as a catalyst to lock annexin A2 on the cell membrane surface, which accelerates invasive outgrowth of the cancer through the binding of integrin-β1 on the cell surface. However, whether this machinery is subject to the LOXL4-mediated intrusive regulation remains uncertain.<br> <br> Methods: Cell invasion was assessed using a transwell-based assay, protein–protein interactions by an immunoprecipitation–Western blotting technique and immunocytochemistry, and plasmin activity in the cell membrane by gelatin zymography.<br> <br> Results: We revealed that cell surface annexin A2 acts as a receptor of plasminogen via interaction with S100A10, a key cell surface annexin A2-binding factor, and S100A11. We found that the cell surface annexin A2/S100A11 complex leads to mature active plasmin from bound plasminogen, which actively stimulates gelatin digestion, followed by increased invasion.<br> <br> Conclusion: We have refined our understanding of the role of LOXL4 in TNBC cell invasion: namely, LOXL4 mediates the upregulation of annexin A2 at the cell surface, the upregulated annexin 2 binds S100A11 and S100A10, and the resulting annexin A2/S100A11 complex acts as a receptor of plasminogen, readily converting it into active-form plasmin and thereby enhancing invasion. No potential conflict of interest relevant to this article was reported.

岡山大学教師教育開発センター Acta Medica Okayama 2186-1323 14 2024 日本におけるレッジョ・エミリア教育の展開と可能性 ―受容・導入期の様相と実践期の課題― 325 339 EN Toshiyuki TAKAHASHI Faculty of Education, Okayama University Kei TAKAHASHI Faculty of Childhood Education, Kurashiki Sakuyo University Kumiko ODA Faculty of Human Life Sciences, Notre Dame Seishin University 10.18926/CTED/66790 　本論は，日本への受容・導入期から実践期に移行しつつあるレッジョ・エミリア教育に関して正しく理解を深めるためには，何が問題や課題になるかについて考察する。第１に，レッジョ・エミリア市の子どもの造形芸術の背景にある造形原理や教育原理を正しく把握する必要がある。第２に，幼児教育を基礎から学び，子どもの造形表現を研究し，美術制作と鑑賞に従事できる「アトリエリスタ」養成の仕組み作りが要請される。第３に，日本の保育理念である「遊び＝学び」の上位概念として「プロジェクト」を位置付け，根本的な保育理念の転換が求められる。第４に，子どもの主体性を大切にした保育実践のために，年間行事を精選しなければならない。第５に，これまでの日本の保育記録の仕方を「ドキュメンテーション」に代替できるかどうかの検討が不可欠である。 No potential conflict of interest relevant to this article was reported.

岡山大学教師教育開発センター Acta Medica Okayama 2186-1323 14 2024 レッジョ・エミリア教育の研究動向と課題 309 323 EN Kei TAKAHASHI Faculty of Childhood Education, Kurashiki Sakuyo University Mari OKAYAMA Faculty of Human Sciences, Chikushi Jogakuen University Toshiyuki TAKAHASHI Faculty of Education, Okayama University 10.18926/CTED/66789 　本論は，レッジョ・エミリア教育に関する研究動向を整理し，実践及び研究上の課題を明らかにするものである。研究の第一段階として日本国内の研究を中心に先行研究を概観した結果，「プロジェクト」「プロジェクト型保育」「創造性と表現活動」にかかわる研究成果が充実していることが判明した。それと同時に，日本の保育理念や保育方法との一致点や相違点も明らかになった。今後は，レッジョ・エミリア教育の根幹と言われる「芸術性」「創造性」「協同性（共同性）」とその理解を学術研究の主題にして，芸術教育や子どもの造形表現を考察した研究成果が待ち望まれる。 No potential conflict of interest relevant to this article was reported.

岡山大学教師教育開発センター Acta Medica Okayama 2186-1323 14 2024 幼稚園４歳児学級における草花を使った遊びの展開に見る教師の役割 33 46 EN Saki YOKOTA Minan Certified Child Center Kana NISHIMURA (NAKAGAWA) Former The Kindergarten Attached to the Faculty of Education, Okayama University Mika KATAYAMA Faculty of Education，Okayama University Toshiyuki TAKAHASHI Faculty of Education，Okayama University 10.18926/CTED/66770 　本論は，幼稚園４歳児学級における草花を使った遊びにおいて，教師の役割を整理し，考察するものである。幼児教育では，遊びの展開に伴って，調和的で多様な学びが深化・発展し，遊びや学びは，幼児主体で偶発的に生じているように見える。しかし，遊びの展開や学びの背景には，「幼児の姿を予想した環境構成」「遊び方の変化に合わせた物的環境の整備」「遊びの発展への架け橋」といった教師の役割が見出された。 No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 12 3 2024 Vogt-Koyanagi-Harada disease in pregnancy: Case report and review of 32 patients in the literature e8643 EN Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kasumi Takahashi Division of Obstetrics and Gynecology, Ochiai Hospital Tsunemasa Kondo Division of Obstetrics and Gynecology, Ochiai Hospital A 30-year-old woman in 31 weeks of pregnancy with metamorphopsia and headache was diagnosed Vogt-Koyanagi-Harada disease. She underwent steroid pulse therapy and oral prednisolone 20 mg daily for 3 weeks until complete resolution of serous retinal detachment monitored by optical coherence tomography. Oral prednisolone was tapered and discontinued until uneventful delivery. No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 185 2024 保育者志望学生の地震防災意識と地震防災教育への課題 83 91 EN Noriko BABA Faculty of Education, Okayama University Daisuke SATOH Kawasaki University of Medical Welfare Kei TAKAHASHI Kurashiki Sakuyo University 10.18926/bgeou/66709 　保育者志望学生を対象に，保育における地震防災に関する意識や子どもへの地震防災教育の実践に関する課題等について質問紙調査を行った。その結果，実習経験の有無に関わらず，保育職に就く前に地震防災について理解しておく必要性について強く認識している傾向があることが分かった。また，実習経験の有無で差異が生じる意識もあることが確認できた。地震防災教育を実践する上での教育内容や自身の課題については，実習経験のない学生は，一般論的な内容で具体性に欠け，幅広い視点で防災教育を捉えていることが分かった。一方，実習経験のある学生は，保育現場の状況や子どもの発達過程を考慮した保育者としての視点や願いの表れた課題を持っている傾向があることが示唆された。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 185 2024 愛媛県と東京都における法令と手工科加設校の変遷との関連性（後編）― 愛媛県手工教育史（第五報） ― 53 71 EN Toshiyuki TAKAHASHI Faculty of Education, Okayama University 10.18926/bgeou/66707 　本論では，阿部七五三吉（1936）による「手工教育基礎建設の曙光時代」［1907（明治40）年頃～ 1926（大正15）年頃まで］の20 年間を調査対象期間として，小学校手工科関係の法令条文等を分析し，法令改正に則して『日本帝国文部省年報』を基に愛媛県の手工科加設校の数量的な変遷を東京都と比較検討することによって，愛媛県の尋常小学校と高等小学校における手工科の展開過程を探った。その結果，（1）法令条文等における尋常小学校と高等小学校の加設科目の取り扱い及び設置の条件と手工科加設校の増減には，強い関連性が見られ，特に「土地ノ情況」に影響を受けることが判明した。（2）高等小学校の加設科目に関する法令改正は，改正のない尋常小学校にも波及することが示唆された。（3）改善を期待して法令改正し文部大臣が訓令を発しても，必ずしも法令が目的とするようには，教育現場や教育界が反応しない場合もあることが明らかになった。 No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Ectopic Breast Cancer Arising within an Axillary Lymph Node 89 93 EN Kei Toshima Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Midori Filiz Nishimura Department of Molecular Hematopathology, Graduate School of Health Sciences, Okayama University Yoko Suzuki Department of Breast and Endocrine Surgery, Okayama University Hospital Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Maya Uno Department of Breast and Endocrine Surgery, Okayama University Hospital Ryo Yoshioka 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 Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Tsuguo Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyuki Yanai Department of Diagnostic Pathology, Okayama University Hospital Case Report 10.18926/AMO/66676 We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Significance of Continuous Low-Dose Lenvatinib for the Treating of the Patients with Unresectable Thyroid Carcinoma 63 70 EN Daizo Murakami Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine Kohei Nishimoto Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Miyamaru Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine Tomoka Kadowaki Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruki Saito Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine Hiroki Takeda Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine Momoko Ise Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine Koichi Suyama Department of Medical Oncology, Toranomon Hospital Yorihisa Orita Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine Original Article 10.18926/AMO/66672 The tyrosine kinase inhibitor lenvatinib has been confirmed as an effective treatment option for patients with unresectable thyroid carcinoma. We conducted a retrospective analysis of the significance of the effect of continued lenvatinib treatment for the longest duration possible at a reasonable daily dose and with a minimum discontinuation period in 42 patients with unresectable thyroid carcinoma treated with lenvatinib between 2015 and 2020. A Cox proportional hazard model-based analysis revealed that the overall survival of the patients treated with a <8 mg/day mean dose of lenvatinib was significantly better than that of the patients treated with 8-24 mg/day (hazard ratio [HR] 0.38 for 1.14-4.54 mg/day, and HR 0.01 for 4.56-7.97 mg/day) adjusted for various factors (e.g., sex, age, drug interruption period). The cumulative dose of lenvatinib administered tended to be higher in the patients treated with low doses (< 8 mg/day) than in the patients treated with relatively high doses (8-24 mg/day). Considering its adverse events, the continuation of lenvatinib treatment with an adequate daily dose and drug interruption may help prolong the survival of patients with unresectable thyroid carcinoma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Long-Term Follow-up Data of a Multi-Institutional Phase-2 Study of S-1/oxaliplatin and Bevacizumab Therapy in Patients with Advanced Colorectal Cancer: The HiSCO-02 Study 47 52 EN Manabu Shimomura Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Katsunori Shinozaki Division of Clinical Oncology, Hiroshima Prefectural Hospital Takuya Yano Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Shintaro Akabane Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Hideki Ohdan Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Hiroshima Surgical study group of Clinical Oncology (HiSCO) Original Article 10.18926/AMO/66670 Oral fluoropyrimidines (FUs) have certain advantages over intravenous FUs, such as longer intervals between outpatient visits, no requirement for central venous port (CVP) implantation, and lower incidence of neutropenia. We previously reported the efficacy of S-1/oxaliplatin (SOX) with bevacizumab therapy as a first-line treatment for advanced colorectal cancer (CRC) in a prospective phase-II multi-institutional clinical trial (HiSCO-02 study). However, our prognostic data at the time lacked a sufficient observation period. Herein, we analyze the longer-term follow-up data, focusing on the status of eventual CVP implantation via an open-label, non-randomized, multicenter study. This study enrolled 55 patients (mean age, 64 years), of whom 43 died (41 of primary cancer). The median overall survival was 22.7 months (95% CI: 20.1-34.7 months). Post-treatment regimens after failure of first-line treatment were initiated in 43 patients; CPT11-based regimens were selected in most cases, and other oral FU combinations in nine. CVP was implanted in 35 patients prior to first-line treatment; eleven of the remaining 20 patients did not require CVP implantation. In conclusion, we report here the final prognostic update of the Phase II clinical trial examining the efficacy of SOX plus bevacizumab therapy, the results of which confirm the clinical efficacy of this regimen. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Lung Oligometastasis of Breast Cancer: Prospective Cohort Study of Treatment Strategies (SBP-06) 15 20 EN Reina Maeda Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Mina Takahashi Department of Breast Oncology, NHO Shikoku Cancer Center Kengo Kawada Department of Breast and Endocrine Surgery, Kagawa Prefectural Central Hospital Yukiko Kajiwara Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital Shinichiro Kubo Department of Breast and Thyroid Surgery, Fukuyama City Hospital Daisuke Takabatake Department of Breast Surgery, Kochi Health Sciences Center Shoichiro Ohtani Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital Kinya Matsuoka Department of Breast and Thyroid Surgery, Ehime Prefectural Central Hospital Hajime Hikino Department of Breast Surgery, Matsue Red Cross Hospital Yutaka Ogasawara Department of Breast and Endocrine Surgery, Kagawa Prefectural Central Hospital Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Shozo Osumi Department of Breast Oncology, NHO Shikoku Cancer Center Masahiko Ikeda Department of Breast and Thyroid Surgery, Fukuyama City Hospital Hiroyoshi Doihara Department of Breast and Endocrine Surgery, Okayama University Hospital Original Article 10.18926/AMO/66666 While local treatment of metastases is considered to be unrelated to prognosis, previous studies have suggested that local treatment of isolated lung metastases may have positive prognostic impact. We designed this prospective cohort study to investigate the clinical situation and its outcomes. We enrolled patients with fewer than 3 lung nodules suspected of being oligometastases after curative breast cancer surgery. Treatments, including local and systemic therapy, were selected by the physician and patient in consultation. The primary outcome was overall survival (OS); secondary outcomes were the efficacy and the safety of the surgery for lung oligometastases. Between May 2015 and May 2019, 14 patients were enrolled. Resection of lung nodules (metastasectomy) was performed in 11 (78.6%) of 14 patients, and one of these cases was diagnosed as primary lung cancer. Metastasectomies were all performed employing video-assisted thoracic surgery (VATS) without perioperative complications. Systemic therapies were administered to all patients except one. The respective 3-year and 5-year OS rates of patients with lung oligometastases were 91.6% and 81.5%, respectively. Progression occurred in 6 patients: 3 of the 10 with metastasectomy and all 3 without this surgical procedure. Lung metastasectomy was worthwhile as a diagnostic evaluation and may provide long-term benefit in some patients. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 22 9 2024 Synthetic strategies for the construction of C3–N1′ bisindoles 1756 1764 EN Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University C3–N1′ bisindoles are unique structures, and the construction of these structures has drawn much attention. However, their synthesis still presents significant challenges that limit the functional group compatibility. This minireview summarizes the recent progress in the methodology for constructing C3–N1′ bisindoles. There are two approaches for access to C3–N1′ bisindoles: (1) direct approaches including reverse polarity techniques. (2) Stepwise approaches using designed and prefunctionalized substrates enable further functionalization by additional reactions to facilitate access to the target products. I believe that this review will allow its readers to develop novel approaches for the synthesis of C3–N1′ bisindoles. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0343-8651 81 3 2024 Mutational analysis of the transmembrane α4-helix of Bacillus thuringiensis mosquito-larvicidal Cry4Aa toxin 80 EN Hirokazu Takahashi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mami Asakura Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toru Ide Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tohru Hayakawa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Cry4Aa, produced by Bacillus thuringiensis subsp. israelensis, exhibits specific toxicity to larvae of medically important mosquito genera. Cry4Aa functions as a pore-forming toxin, and a helical hairpin (α4-loop-α5) of domain I is believed to be the transmembrane domain that forms toxin pores. Pore formation is considered to be a central mode of Cry4Aa action, but the relationship between pore formation and toxicity is poorly understood. In the present study, we constructed Cry4Aa mutants in which each polar amino acid residues within the transmembrane α4 helix was replaced with glutamic acid. Bioassays using Culex pipiens mosquito larvae and subsequent ion permeability measurements using symmetric KCl solution revealed an apparent correlation between toxicity and toxin pore conductance for most of the Cry4Aa mutants. In contrast, the Cry4Aa mutant H178E was a clear exception, almost losing its toxicity but still exhibiting a moderately high conductivity of about 60% of the wild-type. Furthermore, the conductance of the pore formed by the N190E mutant (about 50% of the wild-type) was close to that of H178E, but the toxicity was significantly higher than that of H178E. Ion selectivity measurements using asymmetric KCl solution revealed a significant decrease in cation selectivity of toxin pores formed by H178E compared to N190E. Our data suggest that the toxicity of Cry4Aa is primarily pore related. The formation of toxin pores that are highly ion-permeable and also highly cation-selective may enhance the influx of cations and water into the target cell, thereby facilitating the eventual death of mosquito larvae. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 13 1 2023 Bundling of collagen fibrils influences osteocyte network formation during bone modeling 22028 EN Mana Hashimoto Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruka Takahashi Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaori Tabata-Okubo Department of Orthodontics, Okayama University Hospital Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Kazuaki Tokunaga Nikon Corporation Haruka Matsumori Nikon Corporation Yoshihito Ishihara Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaru Kaku Division of Bio‑prosthodontics, Faculty of Dentistry and Graduate School of Medical and Dental Sciences, Niigata University Tadahiro Iimura Department of Pharmacology, Faculty and Graduate School of Dental Medicine, Hokkaido University Toru Hara Research Center for Structural Materials, National Institute for Materials Science Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Osteocytes form a cellular network by gap junctions between their cell processes. This network is important since intercellular communication via the network is essential for bone metabolism. However, the factors that influence the formation of this osteocyte network remain unknown. As the early stage of osteocyte network formation occurs on the bone surface, we observed a newly formed trabecular bone surface by orthogonal focused ion beam-scanning electron microscopy. The embedding late osteoblast processes tended to avoid bundled collagen fibrils and elongate into sparse collagen fibrils. Then, we examined whether the inhibition of bundling of collagen fibrils using a potent lysyl oxidase inhibitor, beta-aminopropionitrile (BAPN) changed the cellular network of the chick calvaria. The osteocyte shape of the control group was spindle-shape, while that of the BAPN group was sphere-shaped. In addition, the osteocyte processes of the control group were elongated vertically to the long axis of the cell body, whereas the osteocyte processes of the BAPN group were elongated radially. Therefore, it was suggested that the bundling of collagen fibrils influences normal osteocyte network formation during bone modeling. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0014-2336 220 2 2024 Tamyb10-D1 restores red grain color and increases grain dormancy via suppressing expression of TaLTP2.128, non-specific lipid transfer protein in wheat 16 EN Eiko Himi Kibi International University Shiho Kurihara-Yonemoto Hokkaido Agricultural Research Center, National Agriculture and Food Research Organization Fumitaka Abe Institute of Crop Science, National Agriculture and Food Research Organization Hidekazu Takahashi Fukushima University Keisuke Tanaka NODAI Genome Research Center, Tokyo University of Agriculture Takakazu Matsuura Institute of Plant Science and Resources, Okayama University Masahiko Maekawa Institute of Plant Science and Resources, Okayama University Takuji Sasaki NODAI Research Institute, Tokyo University of Agriculture Kazuhide Rikiishi Institute of Plant Science and Resources, Okayama University Grain dormancy of wheat is closely associated with grain color: red-grained lines show higher dormancy than white-grained lines. The production of red pigments is regulated by R-1, Tamyb10 gene. However, the relation between grain color and dormancy remains unknown. For this study, we generated transgenic lines which were introduced a DNA fragment containing Tamyb10-D1 gene and its a 2 kb promoter including the 5′ untranslated region into white-grained wheat. Transgenic lines showed red-grained and higher dormant traits. Contents of plant hormones and gene expression of embryos at 30 days after pollination were examined in a wild type and a transgenic line. No differences were observed in the contents of plant hormones, but several genes are differentially expressed between these lines. One differentially expressed gene, TaLTP2.128, is a member of non-specific lipid transfer proteins. It was expressed higher in white grains than in red grains. A putative amino acid sequence showed similarity to that of OsHyPRP5, which is identified as QTL controlling low-temperature germinability in rice. Expression of TaLTP2.128 was increased by grain imbibition. The increasing levels were higher not only in other white-grained lines, but also in non-dormant red-grained lines. TaLTP2.128 was expressed at a quite early stage of germination. These study findings indicate that Tamyb10 regulates dormancy release by the modification of TaLTP2.128 acting as trigger of germination. No potential conflict of interest relevant to this article was reported.

eLife Sciences Publications Acta Medica Okayama 2050-084X 12 2023 Characterization of tryptophan oxidation affecting D1 degradation by FtsH in the photosystem II quality control of chloroplasts RP88822 EN Yusuke Kato Institute of Plant Science and Resources (IPSR), Okayama University Hiroshi Kuroda Research Institute for Interdisciplinary Science, Okayama University Shin-Ichiro Ozawa Institute of Plant Science and Resources (IPSR), Okayama University Keisuke Saito Research Center for Advanced Science and Technology, The University of Tokyo Vivek Dogra Shanghai Center for Plant Stress Biology, Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences Martin Scholz Institute of Plant Biology and Biotechnology, University of Münster Guoxian Zhang Institute of Plant Science and Resources (IPSR), Okayama University Catherine de Vitry Institut de Biologie Physico-Chimique, Unité Mixte de Recherche 7141, Centre National de la Recherche Scientifique and Sorbonne Université Pierre et Marie Curie Hiroshi Ishikita Research Center for Advanced Science and Technology, The University of Tokyo Chanhong Kim Shanghai Center for Plant Stress Biology, Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences Michael Hippler Institute of Plant Science and Resources (IPSR), Okayama University Yuichiro Takahashi Research Institute for Interdisciplinary Science, Okayama University Wataru Sakamoto Institute of Plant Science and Resources (IPSR), Okayama University Photosynthesis is one of the most important reactions for sustaining our environment. Photosystem II (PSII) is the initial site of photosynthetic electron transfer by water oxidation. Light in excess, however, causes the simultaneous production of reactive oxygen species (ROS), leading to photo-oxidative damage in PSII. To maintain photosynthetic activity, the PSII reaction center protein D1, which is the primary target of unavoidable photo-oxidative damage, is efficiently degraded by FtsH protease. In PSII subunits, photo-oxidative modifications of several amino acids such as Trp have been indeed documented, whereas the linkage between such modifications and D1 degradation remains elusive. Here, we show that an oxidative post-translational modification of Trp residue at the N-terminal tail of D1 is correlated with D1 degradation by FtsH during high-light stress. We revealed that Arabidopsis mutant lacking FtsH2 had increased levels of oxidative Trp residues in D1, among which an N-terminal Trp-14 was distinctively localized in the stromal side. Further characterization of Trp-14 using chloroplast transformation in Chlamydomonas indicated that substitution of D1 Trp-14 to Phe, mimicking Trp oxidation enhanced FtsH-mediated D1 degradation under high light, although the substitution did not affect protein stability and PSII activity. Molecular dynamics simulation of PSII implies that both Trp-14 oxidation and Phe substitution cause fluctuation of D1 N-terminal tail. Furthermore, Trp-14 to Phe modification appeared to have an additive effect in the interaction between FtsH and PSII core in vivo. Together, our results suggest that the Trp oxidation at its N-terminus of D1 may be one of the key oxidations in the PSII repair, leading to processive degradation by FtsH. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2590-0595 5 12 2023 Kidney Veno-Muscular Characteristics and Kidney Disease Progression: A Native Kidney-Biopsy Study 100733 EN Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kensaku Takahashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takafumi Morita Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yizhen Sang Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Fukushima 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 Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kitamura 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 Rationale & Objective: Assessment of kidney biopsies provides crucial information for diagnosis and disease activity, as well as prognostic value. Kidney-biopsy specimens occasionally contain veno-muscular complex (VMC), which consists of muscle tissues around the kidney venous system in the corticomedullary region. However, the role of VMC and the clinical significance of VMC variants are poorly understood. In the present study, we investigated kidney prognostic values of VMC variants.<br> Study Design: Retrospective cohort study.<br> Setting & Participants: Among 808 patients who underwent a kidney biopsy from 2011 to 2019, 246 patients whose kidney biopsy specimens contained VMC were enrolled.<br> Predictors: VMC variants; inflammatory-VMC (an infiltration of ≥80 inflammatory cells/mm2-VMC area) and VMC hypertrophy (hyper-VMC, a VMC average width ≥850 μm), and the interstitial fibrosis/tubular atrophy (IFTA) score.<br> Outcomes: A decline in estimated glomerular filtration rate (eGFR) ≥40% from the baseline or commencement of kidney replacement therapy.<br> Analytical Approach: Cox proportional hazards model.<br> Results: Among 246 patients with data on VMC, mean baseline eGFR was 56.0±25.6 ml/min per 1.73 m2; 80 had high inflammatory-VMC, and 62 had VMC hypertrophy. There were 51 kidney events over median follow-up of 2.5 years. We analyzed 2 VMC variants. Multivariable logistic regression analysis revealed that eGFR negatively correlated with the presence of both inflammatory-VMC and hyper-VMC. A Cox proportional hazards analysis revealed that inflammatory-VMC (but not hyper-VMC) was independently associated with the primary outcome after adjustments for known risk factors of progression, including proteinuria, eGFR, and the interstitial fibrosis/tubular atrophy (IFTA) score (hazard ratio, 1.97; 95% confidence interval, 1.00-3.91).<br> Limitations: Single-center study and small sample size.<br> Conclusions: Assessment of inflammatory-VMC provides additional kidney prognostic information to known indicators of kidney disease progression in patients who undergo kidney biopsy. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 135 3 2023 COVID-19に対する感染管理活動を通して得られた官民学連携の協働体制― 岡山県クラスター対策班（OCIT）の取り組み― 158 166 EN Kazutaka Takahashi Risk Management Office for COVID-19, Department of Health and Medical Care, Okayama Prefectural Government Yukari Takahashi Department of Intractable Diseases, Health Service Bureau, Ministry of Health, Labour and Welfare Yasunori Ichimura Bureau of International Health Cooperation, National Center for Global Health and Medicine Kenya Uno Risk Management Office for COVID-19, Department of Health and Medical Care, Okayama Prefectural Government Sato Imajo Risk Management Office for COVID-19, Department of Health and Medical Care, Okayama Prefectural Government Satoshi Mitsui Okayama Prefecture Mimasaka Public Health Center Toshiaki Noriyasu Department of Health and Medical Care, Okayama Prefectura Government Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 A Case of Migration of a Hydrogel Spacer for Radiotherapy into the Pulmonary Artery 647 650 EN Katsuhide Kojima Department of Radiology, Okayama University Hospital Yuka Takahashi Department of Radiology, Okayama University Hospital Soichi Sugiyama Department of Proton Beam Therapy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yudai Asano 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 Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Case Report 10.18926/AMO/66157 A 67-year-old man was referred to our hospital for the diagnosis and treatment of prostate cancer. Multidisciplinary discussion led to intensity-modulated radiotherapy preceded by hormone therapy. Before radiotherapy, a biodegradable hydrogel spacer (HS) was placed between the prostate and rectum to reduce radiation injury risk. Three weeks postplacement, pelvic magnetic resonance imaging revealed HS migration into the pelvic vein. Subsequent whole-body contrast-enhanced computed tomography (CECT) revealed HS migration into the pulmonary artery. The patient showed no symptoms or clinical signs. Radiotherapy was completed uneventfully. Complete absorption of the migrated HS was confirmed using CECT images 5 months postplacement. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Effects of Nutritional Support Combined with Neuromuscular Electrical Stimulation on Muscle Strength and Thickness: A Randomized Controlled Trial in Healthy Young Adult Males 635 645 EN Tomohiro Ikeda Department of Rehabilitation Medicine, Okayama University Hospital Kazunori Okamura Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Masaki Hasegawa Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Satoshi Tanaka Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Shusaku Kanai Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Original Article 10.18926/AMO/66156 In the management of post-injury patients with activity limitations, methods to prevent musculoskeletal disorders and hasten recovery are important. This randomized controlled, single-blinded study was a preliminary investigation of the combined effect of nutritional support with neuromuscular electrical stimulation (NMES) on muscle strength and thickness. Healthy young adult males (median age, 21 years) were enrolled; each of their hands was randomly assigned to one of the following four groups: Placebo, Nutrition, NMES, and Nutrition + NMES. All participants received whey protein or placebo (3x/week for 6 weeks) and NMES training (3x/week for 6 weeks) on the abductor digiti minimi (ADM) muscle of either the left or right hand. ADM muscle strength and thickness were analyzed at baseline and at week 7. We analyzed 38 hands (9 Placebo, 10 Nutrition, 9 NMES, 10 Nutrition + NMES). There was significantly greater muscle strengthening in the Nutrition + NMES group compared to the Placebo group or the NMES group, but no significant difference in gain of muscle thickness. The combined intervention may be effective in improving muscle strength. Future clinical trials targeting various muscles after sports-related injuries are warranted. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Abnormal Vaginal Cytology after Total Laparoscopic Hysterectomy in Patients with Cervical Intraepithelial Neoplasia 627 634 EN Yumi Hibino Department of Gynecologic Oncology, NHO Shikoku Cancer Center Mika Okazawa-Sakai Department of Gynecologic Oncology, NHO Shikoku Cancer Center Takanori Yokoyama Department of Gynecologic Oncology, NHO Shikoku Cancer Center Etsuko Fujimoto Department of Gynecologic Oncology, NHO Shikoku Cancer Center Shinichi Okame Department of Gynecologic Oncology, NHO Shikoku Cancer Center Norihiro Teramoto Department of Pathology, NHO Shikoku Cancer Center Kazuhiro Takehara Department of Gynecologic Oncology, NHO Shikoku Cancer Center Original Article 10.18926/AMO/66155 To explore the incidence of abnormal vaginal cytology after total laparoscopic hysterectomy for the treatment of cervical intraepithelial neoplasia 3, we retrospectively analyzed the medical records of patients treated at NHO Shikoku Cancer Center (Japan) in 2014-2019. The cases of 99 patients who underwent a laparoscopic (n=36) or open (n=63) hysterectomy and postoperative follow-up were examined. Abnormal vaginal cytology was detected in 13.9% (5/36) of the laparoscopic-surgery (LS) group and 14.3% (9/63) of the open-surgery (OS) group. A vaginal biopsy was performed at the physicians’ discretion; one LS patient and six OS patients were diagnosed with vaginal intraepithelial neoplasia. The cumulative incidence of abnormal vaginal cytology at 3 years post-hysterectomy was 21.4% (LS group) and 20.5% (OS group), a nonsignificant difference. A multivariate analysis showed that age > 50 years was the only independent risk factor for abnormal vaginal cytology among the covariates examined including age; body mass index; histories of vaginal delivery, abdominal surgery, and smoking; and surgical approach (hazard ratio 8.11; 95% confidence interval 1.73-37.98; p=0.01). These results suggest that the occurrence of abnormal vaginal cytology after a hysterectomy may not be influenced by the laparoscopic procedure but is associated with older age. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Concomitant Use of Multiple Nephrotoxins including Renal Hypoperfusion Medications Causes Vancomycin-Associated Nephrotoxicity: Combined Retrospective Analyses of Two Real-World Databases 595 605 EN Takashi Bando Department of Pharmacy, Tokushima University Hospital Masayuki Chuma Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Hirofumi Hamano Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Takahiro Niimura Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Naoto Okada Department of Pharmacy, Tokushima University Hospital Masateru Kondo Department of Pharmacy, Tokushima University Hospital Yuki Izumi Department of Pharmacy, Tokushima University Hospital Shunsuke Ishida Department of Pharmacy, Tokushima University Hospital Toshihiko Yoshioka Department of Pharmacy, Tokushima University Hospital Mizuho Asada Department of Medical Molecular Informatics, Meiji Pharmaceutical University Yoshito Zamami Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Kenshi Takechi Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University Mitsuhiro Goda Department of Pharmacy, Tokushima University Hospital Koji Miyata Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Kenta Yagi Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Yuki Izawa-Ishizawa Department of Pharmacology, Tokushima University Graduate School of Biomedical Sciences Momoyo Azuma Department of Infection Control and Prevention, Tokushima University Hospital Hiroaki Yanagawa Department of Nursing, Faculty of Health and Welfare, Tokushima Bunri University Yoshikazu Tasaki Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical University Keisuke Ishizawa Department of Pharmacy, Tokushima University Hospital Original Article 10.18926/AMO/66151 There is a growing concern about the relationship between vancomycin-associated nephrotoxicity (VAN) and concomitant use of nephrotoxins. We examined this relationship by combined retrospective analyses of two real-world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was analyzed for the effects of concomitant use of one or more nephrotoxins on VAN and the types of combinations of nephrotoxins that exacerbate VAN. Next, electronic medical records (EMRs) of patients who received vancomycin (VCM) at Tokushima University Hospital between January 2006 and March 2019 were examined to confirm the FAERS analysis. An elevated reporting odds ratio (ROR) was observed with increases in the number of nephrotoxins administered (VCM + one nephrotoxin, adjusted ROR (95% confidence interval [CI]) 1.67 [1.51-1.85]; VCM + ≥2 nephrotoxins, adjusted ROR [95% CI] 1.54 [1.37-1.73]) in FAERS. EMRs analysis showed that the number of nephrotoxins was associated with higher incidences of VAN [odds ratio: 1.99; 95% CI: 1.42-2.78]. Overall, concomitant use of nephrotoxins was associated with an increased incidence of VAN, especially when at least one of those nephrotoxins was a renal hypoperfusion medication (furosemide, non-steroidal anti-inflammatory drugs, and vasopressors). The concomitant use of multiple nephrotoxins, especially including renal hypoperfusion medication, should be avoided to prevent VAN. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Cochlear Implantation in the Poorer-Hearing Ear Is a Reasonable Choice 589 593 EN Ryotaro Omichi Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Kariya Department of Otolaryngology-Head and Neck Surgery, Kawasaki Medial University Yukihide Maeda Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunihiro Fukushima Hayashima Clinic of Otolaryngology and Dermatology Yuko Kataoka Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Sugaya Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazunori Nishizaki 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 Original Article 10.18926/AMO/66150 Choosing the optimal side for cochlear implantation (CI) remains a major challenge because of the lack of evidence. We investigated the choice of the surgery side for CI (i.e., the better- or poorer-hearing ear) in patients with asymmetric hearing. Audiological records of 74 adults with a unilateral hearing aid who had undergone surgery at Okayama University Hospital were reviewed. The definition of ‘better-hearing ear’ was the aided ear, and the unaided ear was considered the poorer-hearing ear. We performed a multiple regression analysis to identify potential predictors of speech recognition performance after unilateral CI in the patients. Fifty-two patients underwent CI in the poorer-hearing ear. The post-Ci bimodal hearing rate was far higher in the poorer-ear group (77.8% vs. 22.2%). A multivariate analysis revealed that prelingual hearing loss and the patient’s age at CI significantly affected the speech recognition outcome (beta coefficients: 24.6 and −0.33, 95% confidence intervals [11.75-37.45] and [−0.58 to −0.09], respectively), but the CI surgery side did not (−6.76, [−14.92-1.39]). Unilateral CI in the poorer-hearing ear may therefore be a reasonable choice for adult patients with postlingual severe hearing loss, providing a greater opportunity for postoperative bimodal hearing. No potential conflict of interest relevant to this article was reported.

American Physiological Society Acta Medica Okayama 0022-3077 127 5 2022 Tactile angle discriminability improvement: contributions of working memory training and continuous attended sensory input 1398 1406 EN Wu Wang School of Psychological and Cognitive Sciences, Peking University Jiajia Yang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yinghua Yu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Huazhi Li Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yulong Liu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yiyang Yu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jiabin Yu College of Information Engineering, China Jiliang University Xiaoyu Tang School of Psychology, Liaoning Collaborative Innovation Center of Children and Adolescents Healthy Personality Assessment and Cultivation, Liaoning Normal University Jingjing Yang School of Computer Science and Technology, Changchun University of Science and Technology Satoshi Takahashi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yoshimichi Ejima Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jinglong Wu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Perceptual learning is commonly assumed to enhance perception through continuous attended sensory input. However, learning is generalizable to performance in untrained stimuli and tasks. Although previous studies have observed a possible generalization effect across tasks as a result of working memory (WM) training, comparisons of the contributions of WM training and continuous attended sensory input to perceptual learning generalization are still rare. Therefore, we compared which factors contributed most to perceptual generalization and investigated which skills acquired during WM training led to tactile generalization across tasks. Here, a Braille-like dot pattern matching n-back WM task was used as the WM training task, with four workload levels (0, 1, 2, and 3-back levels). A tactile angle discrimination (TAD) task was used as a pre- and posttest to assess improvements in tactile perception. Between tests, four subject groups were randomly assigned to four different workload n-back tasks to consecutively complete three sessions of training. The results showed that tactile n-back WM training could enhance TAD performance, with the 3-back training group having the highest TAD threshold improvement rate. Furthermore, the rate of WM capacity improvement on the 3-back level across training sessions was correlated with the rate of TAD threshold improvement. These findings suggest that continuous attended sensory input and enhanced WM capacity can lead to improvements in TAD ability, and that greater improvements in WM capacity can predict greater improvements in TAD performance.<br> NEW & NOTEWORTHY Perceptual learning is not always specific to the trained task and stimuli. We demonstrate that both continuous attended sensory input and improved WM capacity can be used to enhance tactile angle discrimination (TAD) ability. Moreover, WM capacity improvement is important in generalizing the training effect to the TAD ability. These findings contribute to understanding the mechanism of perceptual learning generalization across tasks. No potential conflict of interest relevant to this article was reported.

Japanese Society of Breeding Acta Medica Okayama 1344-7610 73 5 2023 Genomic traces of Japanese malting barley breeding in two modern high-quality cultivars, ‘Sukai Golden’ and ‘Sachiho Golden’ 435 444 EN Shin Taketa Institute of Plant Science and Resources, Okayama University June-Sik Kim Institute of Plant Science and Resources, Okayama University Hidekazu Takahashi Faculty of Food and Agricultural Sciences, Fukushima University Shunsuke Yajima NODAI Genome Research Center, Tokyo University of Agriculture Yuichi Koshiishi NODAI Genome Research Center, Tokyo University of Agriculture Toshinori Sotome Tochigi Prefectural Agricultural Experiment Station Tsuneo Kato Tochigi Prefectural Agricultural Experiment Station Keiichi Mochida Bioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource Science Two modern high-quality Japanese malting barley cultivars, ‘Sukai Golden’ and ‘Sachiho Golden’, were subjected to RNA-sequencing of transcripts extracted from 20-day-old immature seeds. Despite their close relation, 2,419 Sukai Golden-specific and 3,058 Sachiho Golden-specific SNPs were detected in comparison to the genome sequences of two reference cultivars: ‘Morex’ and ‘Haruna Nijo’. Two single nucleotide polymorphism (SNP) clusters respectively showing the incorporation of (1) the barley yellow mosaic virus (BaYMV) resistance gene rym5 from six-row non-malting Chinese landrace Mokusekko 3 on the long arm of 3H, and (2) the anthocyanin-less ant2 gene from a two-row Dutch cultivar on the long arm of 2H were detected specifically in ‘Sukai Golden’. Using 221 recombinant inbred lines of a cross between ‘Ishukushirazu’ and ‘Nishinochikara’, another BaYMV resistance rym3 gene derived from six-row non-malting Japanese cultivar ‘Haganemugi’ was mapped to a 0.4-cM interval on the proximal region of 5H. Haplotype analysis of progenitor accessions of the two modern malting cultivars revealed that rym3 of ‘Haganemugi’ was independently introduced into ‘Sukai Golden’ and ‘Sachiho Golden’. Residual chromosome 5H segments of ‘Haganemugi’ surrounding rym3 were larger in ‘Sukai Golden’. Available results suggest possibilities for malting quality improvement by minimizing residual segments surrounding rym3. No potential conflict of interest relevant to this article was reported.

Taylor and Francis Acta Medica Okayama 1559-2316 18 1 2023 Microtubule-associated proteins WDL5 and WDL6 play a critical role in pollen tube growth in Arabidopsis thaliana 2281159 EN Takashi Okamoto Department of Biological Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyasu Motose Department of Biological Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taku Takahashi Department of Biological Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Morphological response of cells to environment involves concerted rearrangements of microtubules and actin microfilaments. A mutant of WAVE-DAMPENED2-LIKE5 (WDL5), which encodes an ethylene-regulated microtubule-associated protein belonging to the WVD2/WDL family in Arabidopsis thaliana, shows attenuation in the temporal root growth reduction in response to mechanical stress. We found that a T-DNA knockout of WDL6, the closest homolog of WDL5, oppositely shows an enhancement of the response. To know the functional relationship between WDL5 and WDL6, we attempted to generate the double mutant by crosses but failed in isolation. Close examination of gametophytes in plants that are homozygous for one and heterozygous for the other revealed that these plants produce pollen grains with a reduced rate of germination and tube growth. Reciprocal cross experiments of these plants with the wild type confirmed that the double mutation is not inherited paternally. These results suggest a critical and cooperative function of WDL5 and WDL6 in pollen tube growth. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 RNA Editing is a Valuable Biomarker for Predicting Carcinogenesis in Ulcerative Colitis EN Kazutaka TAKAHASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0014-4819 240 3 2022 Global surface features contribute to human haptic roughness estimations 773 789 EN Huazhi Li Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jiajia Yang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yinghua Yu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Wu Wang School of Psychological and Cognitive Sciences, Peking University Yulong Liu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mengni Zhou Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Qingqing Li Department of Teacher Education, Wenzhou University Jingjing Yang School of Computer Science and Technology, Changchun University of Science and Technology Shiping Shao School of Social Welfare, Yonsei University Satoshi Takahashi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yoshimichi Ejima Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jinglong Wu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Previous studies have paid special attention to the relationship between local features (e.g., raised dots) and human roughness perception. However, the relationship between global features (e.g., curved surface) and haptic roughness perception is still unclear. In the present study, a series of roughness estimation experiments was performed to investigate how global features affect human roughness perception. In each experiment, participants were asked to estimate the roughness of a series of haptic stimuli that combined local features (raised dots) and global features (sinusoidal-like curves). Experiments were designed to reveal whether global features changed their haptic roughness estimation. Furthermore, the present study tested whether the exploration method (direct, indirect, and static) changed haptic roughness estimations and examined the contribution of global features to roughness estimations. The results showed that sinusoidal-like curved surfaces with small periods were perceived to be rougher than those with large periods, while the direction of finger movement and indirect exploration did not change this phenomenon. Furthermore, the influence of global features on roughness was modulated by local features, regardless of whether raised-dot surfaces or smooth surfaces were used. Taken together, these findings suggested that an object’s global features contribute to haptic roughness perceptions, while local features change the weight of the contribution that global features make to haptic roughness perceptions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0721-832X 259 9 2021 Assessment of epiretinal membrane formation using en face optical coherence tomography after rhegmatogenous retinal detachment repair 2503 2512 EN 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 Shinichiro Doi Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sayumi Kanzaki 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 Morizane Hosokawa 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 Kosuke Takahashi Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose　To investigate epiretinal membrane (ERM) formation using en face optical coherence tomography (OCT) after vitrectomy for rhegmatogenous retinal detachment (RRD).<br> Methods　We retrospectively reviewed the medical records of 64 consecutive eyes (64 patients) with RRD treated by vitrectomy without ERM and internal limiting membrane peeling. ERMs and retinal folds were detected by B-scan and en face imaging. The maximum depth of retinal folds (MDRF) was quantified using en face imaging. ERM severity was staged using B-scan imaging. Main outcome measures were ERM detection rate with B-scan and en face imaging, MDRF, ERM staging, postoperative best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution), and risk factors for ERM formation.<br> Results　The detection rate for ERM formation was significantly higher with en face imaging (70.3%) than with B-scan imaging (46.9%; P = 0.007). There was no significant difference in postoperative BCVA between eyes with ERM formation (0.06 ± 0.26) and those without ERM formation (0.01 ± 0.14; P = 0.298). Forty of 45 (88.9%) eyes with ERM formation were classified as stage 1. Twenty-seven of 45 (60.0%) eyes with ERM formation developed parafoveal retinal folds. The mean MDRF was 27.4 ± 32.2 μm. Multiple retinal breaks and a maximum retinal break size of ≥ 2 disc diameters were significantly associated with ERM formation (P = 0.033 and P = 0.031, respectively).<br> Conclusion　Although ERM formation was observed in 70.3% patients after RRD repair, the formed ERM was not severe and had minimal impact on the postoperative visual acuity. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0925-5001 84 3 2022 A novel update rule of HALS algorithm for nonnegative matrix factorization and Zangwill’s global convergence 755 781 EN Takehiro Sano Graduate School of Natural Science and Technology, Okayama University Tsuyoshi Migita Graduate School of Natural Science and Technology, Okayama University Norikazu Takahashi Graduate School of Natural Science and Technology, Okayama University Nonnegative Matrix Factorization (NMF) has attracted a great deal of attention as an effective technique for dimensionality reduction of large-scale nonnegative data. Given a nonnegative matrix, NMF aims to obtain two low-rank nonnegative factor matrices by solving a constrained optimization problem. The Hierarchical Alternating Least Squares (HALS) algorithm is a well-known and widely-used iterative method for solving such optimization problems. However, the original update rule used in the HALS algorithm is not well defined. In this paper, we propose a novel well-defined update rule of the HALS algorithm, and prove its global convergence in the sense of Zangwill. Unlike conventional globally-convergent update rules, the proposed one allows variables to take the value of zero and hence can obtain sparse factor matrices. We also present two stopping conditions that guarantee the finite termination of the HALS algorithm. The practical usefulness of the proposed update rule is shown through experiments using real-world datasets. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Effective Epilepsy Surgery for Post-Traumatic West Syndrome Following Abusive Head Trauma 561 566 EN Hiroki Tsuchiya Department of Pediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Takashi Shibata Department of Pediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Tatsuya Sasaki Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Takushi Inoue Department of Pediatrics, National Hospital Organization Okayama Medical Center Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Tomoyuki Akiyama Department of Pediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Katsuhiro Kobayashi Department of Pediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Case Report 10.18926/AMO/65980 West syndrome, an infantile developmental and epileptic encephalopathy with a deleterious impact on long-term development, requires early treatment to minimize developmental abnormality; in such cases, epilepsy surgery should be considered a powerful therapeutic option. We describe a 10-month-old female admitted with West syndrome associated with a hemispheric lesion following abusive head trauma. Her seizures were suppressed by hemispherotomy at 12 months of age, leading to developmental improvement. Surgical treatment of West syndrome following traumatic brain injury has not been reported previously but is worth considering as a treatment option, depending on patient age and brain plasticity. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Favorable Outcome of Repeated Salvage Surgeries for Rare Metastasis to the Ligamentum Teres Hepatis and the Upper Abdominal Wall in a Stage IV Gastric Cancer Patient 553 559 EN Takahiro Murokawa Department of Gastroenterological Surgery, Kochi Health Sciences Center Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Kenta Sui Department of Gastroenterological Surgery, Kochi Health Sciences Center Kazuhide Ozaki Department of Gastroenterological Surgery, 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 Hiroshi Yoshida Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School Case Report 10.18926/AMO/65979 Gastric cancer with peritoneal metastases is typically a devastating diagnosis. Ligamentum teres hepatis (LTH) metastasis is an extremely rare presentation with only four known cases. Herein, we report salvage surgery of successive metastases to the abdominal wall and LTH in a patient originally presenting with advanced gastric cancer with peritoneal metastasis, leading to long-term survival. A 72-year-old man with advanced gastric cancer underwent curative-intent distal gastrectomy with D2 lymph node dissection for gastric outlet obstruction. During this procedure, three small peritoneal metastases were detected in the lesser omentum, the small mesentery, and the mesocolon; however, intraoperative abdominal lavage cytology was negative. We added cytoreductive surgery for peritoneal metastasis. The pathological diagnosis of the gastric cancer was tubular adenocarcinoma with pT4aN1pM1(PER/P1b)CY0 stage IV (Japanese classification of gastric carcinoma/JCGC 15th), or T4N1M1b stage IV (UICC 7th). Post-operative adjuvant chemotherapy with S-1 (TS-1)+cisplatin (CDDP) was administered for 8 months followed by S-1 monotherapy for 4 months. At 28 months after the initial surgery, a follow-up computed tomography (CT) detected a small mass beneath the upper abdominal wall. The ass showed mild avidity on 18F-fluorodeoxyglucose positron-emission (FDG-PET) CT. Salvage resection was performed for diagnosis and treatment, and pathological findings were consistent with primary gastric cancer metastasis. At 49 months after the initial gastrectomy, a new lesion was detected in the LTH with a similar level of avidity on FDG-PET CT as the abdominal wall metastatic lesion. We performed a second salvage surgery for the LTH tumor, which also showed pathology of gastric cancer metastasis. There has been no recurrence up to 1 year after the LTH surgery. With multidisciplinary treatment the patient has survived almost 5 years after the initial gastrectomy. Curative-intent gastrectomy with cytoreductive surgery followed by adjuvant chemotherapy for advanced gastric cancer with localized peritoneal metastasis might have had a survival benefit in our patient. Successive salvage surgeries for oligometastatic lesions in the abdominal wall and the LTH also yielded favorable outcomes. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Endoscopic Manifestations and Clinical Characteristics of Localized Gastric Light-Chain Amyloidosis 545 552 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shouichi Tanaka Department of Gastroenterology, National Hospital Organization Iwakuni Clinical Center Tatsuya Toyokawa Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center Mamoru Nishimura Department of Internal Medicine, Okayama City Hospital Takao Tsuzuki Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital Koji Miyahara Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital Shin Negishi Department of Gastroenterology, Kagawa Prefectural Central Hospital Shogen Ohya Kawaguchi Medical Clinic Takehiro Tanaka Department of Pathology, 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 Original Article 10.18926/AMO/65978 To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine patients (eight men and one woman) encountered by the hospitals in our network. Lesions were predominantly flat and depressed with surface vascular dilatation (n=5); others were characterized by subepithelial lesions (n=2), mucosal color change (n=1), and a mass-like morphology with swollen mucosal folds (n=1). Colonoscopy (n=7), video capsule enteroscopy (n=2), serum (n=5) and urine immunoelectrophoresis (n=4), and bone marrow examination (n=3) were performed to exclude involvement of organs other than the stomach. As treatment for gastric lesions of AL amyloidosis, one patient each underwent endoscopic submucosal dissection (n=1) and argon plasma coagulation (n=1), while the remaining seven patients underwent no specific treatment. During a mean follow-up of 4.2 years, one patient died 3.2 years after diagnosis, but the cause of death, which occurred in another hospital, was unknown. The remaining eight patients were alive at the last visit. In conclusion, although localized gastric AL amyloidosis can show various macroscopic features on esophagogastroduodenoscopy, flat, depressed lesions with vascular dilatation on the surface are predominant. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Clinical Characteristics of Retroperitoneal Fibrosis Patients at a Tertiary Hospital in Japan 527 536 EN Miho Ando Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Hanayama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya 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/65975 Retroperitoneal fibrosis (RPF) is a rare cause of hydronephrosis and progressive renal dysfunction with unidentified origin. RPF is categorized into idiopathic RPF with/without immunoglobulin G4 (IgG4)-related disease (IgG4-RD), and secondary RPF. Identifying the underlying cause is challenging and often associated with delayed diagnosis or therapeutic interventions. We investigated RPF’s clinical characteristics based on different etiologies and factors that may help distinguish the underlying causes. We analyzed the cases of 49 patients with RPF that was radiographically diagnosed at our institution (2008-2022). The cohort was 77.6% males; 75.5% had idiopathic RPF and 24.5% had secondary RPF. Among the idiopathic patients, 54.1% had IgG4-RD. The patients were likely to have abdominal pain, lower back pain/lumbago, and constitutional symptoms including generalized fatigue and fever. The idiopathic patients were likely to have higher serum IgG4 and IgG levels and lower serum C3 levels compared to secondary RPF. The IgG4-RPF patients were likely to have higher serum IgG4 levels and lower serum C-reactive protein, ferritin, and C3 levels compared to the idiopathic RPF patients without IgG4-RD. These findings might reflect underlying systemic inflammatory responses. Comprehensive laboratory testing, including serum inflammatory markers and immunological panels, is recommended for radiologically diagnosed RPF patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Associations among Preoperative Malnutrition, Muscle Loss, and Postoperative Walking Ability in Intertrochanteric Fractures: A Retrospective Study 511 516 EN Kohei Sato Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironori Tsuji Department of Orthopedic Surgery, Japanese Red Cross Okayama Hospital Masanori Yorimitsu Department of Orthopedic Surgery, Okayama University Hospital Takenori Uehara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Okazaki Department of Orthopedic Surgery, Tsuyama Chuo Hospital Shinichiro Takao Department of Orthopedic Surgery, Okayama Medical Center Toshiaki Hata Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shiro Fukuoka Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Noda Department of Orthopedic Surgery, Kawasaki Medical School, General Medical Center Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65973 Sarcopenia and malnutrition are increasing in older adults and are reported risk factors for functional impairment after hip fracture surgery. This study aimed to investigate the associations between skeletal muscle mass loss, malnutrition, and postoperative walking ability in patients with hip fracture. We retrospectively reviewed patients who underwent intertrochanteric fracture surgery at our institute. The psoas muscle index, controlling nutritional status score, and functional ambulation category (FAC) were used to evaluate skeletal muscle mass, nutritional status, and walking ability, respectively. Six months after surgery, walking ability was assessed as either “gait disturbance” or “independent gait”. Multivariate binomial logistic regression analysis, with skeletal muscle mass, nutritional status, and other factors, was used to predict the risk of being assigned to the gait disturbance group. This study included 95 patients (mean age, 85.2 years; 70 women). Sixty-six patients had low skeletal muscle mass, 35 suffered from malnutrition, and 28 had both. Malnutrition and low skeletal muscle mass were significantly associated with postoperative gait disturbance (FAC < 3). Preoperative low skeletal muscle mass and malnutrition were risk factors for postoperative poor walking ability. Further preventive interventions focusing on skeletal muscle mass and nutritional status are required. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Neurological Analysis Based on the Terminal End of the Spinal Cord and the Narrowest Level of Injured Spine in Thoracolumbar Spinal Injuries 499 509 EN Yuji Hatakeyama Department of Orthopaedic Surgery, Akita Red Cross Hospital Michio Hongo Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Tadato Kido Department of Orthopaedic Surgery, Akita Rosai Hospital Masakazu Urayama Department of Orthopaedic Surgery, Ogachi Central Hospital Yuji Kasukawa Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Hiroshi Sasaki Department of Orthopaedic Surgery, Noshiro Kousei Medical Center Toshiaki Aizawa Department of Orthopaedic Surgery, Kitaakita Municipal Hospital Daisuke Kudo Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Ryota Kimura Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Yuichi Ono Department of Orthopaedic Surgery, Akita Red Cross Hospital Fumihito Kasama Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Naohisa Miyakoshi Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Original Article 10.18926/AMO/65972 This study aimed to clarify neurological differences among the epiconus, conus medullaris, and cauda equina syndromes. Eighty-seven patients who underwent surgery for acute thoracolumbar spinal injuries were assessed. We defined the epiconus as the region from the terminal end of the spinal cord to the proximal 1.0 to 2.25 vertebral bodies, the conus medullaris as the region proximal to < 1.0 vertebral bodies, and the cauda equina as the distal part of the nerve roots originating from the spinal cord. On the basis of the distance from the terminal end of the spinal cord to the narrowest level of the spinal canal, the narrowest levels were ordered as follows: the epiconus followed by the conus medullaris and cauda equina. The narrowest levels were the epiconus in 22 patients, conus medullaris in 37 patients, and cauda equina in 25 patients. On admission, significantly more patients had a narrowed epiconus of Frankel grades A-C than a narrowed cauda equina. At the final follow-up, there were no significant differences in neurological recovery among those with epiconus, conus medullaris, or cauda equina syndrome. Anatomically classifying the narrowest lesion is useful for clarifying the differences and similarities among these three syndromes. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Participation in the Setouchi Triennale and the Health of Residents in Naoshima: A Cross-Sectional Study 491 497 EN Hiroshi Habu Department of Epidemiology, 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 Chikara Miyaji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naomi Matsumoto Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Aoo Graduate School of Humanities and Social Sciences, Okayama University Yosuke Nishita Graduate School of Humanities and Social Sciences, Okayama University Masao Tsuri Faculty of Economics, Musashi University Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65971 Arts festivals have become increasingly popular in various parts of Japan in recent years. The purpose of this study was to investigate the relationships between arts festival activities participation at the Setouchi Triennale and the health of residents in the town of Naoshima. This was a cross-sectional study. Questionnaires were distributed to all residents of Naoshima who were 20 years old or older (n=2,588). We analyzed responses from 708 people. The associations between arts festival activities participation and health (measured by self-rated health) were analyzed using logistic regression analysis as the primary outcome. Kessler’s psychological distress scale scores were also analyzed in the same manner as the primary outcome. The participating group had an adjusted odds ratio of 1.86 (95% confidence interval: 1.03-3.33) for higher self-rated health compared with those who did not participate. Kessler’s psychological distress scale results showed that the participating group had an adjusted odds ratio of 3.23 (95% confidence interval: 1.19-8.81) for lower psychological distress compared with those who did not participate. In conclusion, arts festival activities participation was associated with higher self-rated health and lower psychological distress. However, caution must be taken in regard to generalizability and causality when interpreting these results. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Childcare and Child Development in Japan 479 490 EN Akiko Murata Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naomi Matsumoto Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikara Miyaji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soshi Takao Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Original Article 10.18926/AMO/65970 For decades, the notion has persisted in developed countries that exclusive care by the mothers is best for the development of children up to 3 years of age. To examine the veracity of this “myth of the first three years” in Japan, we examined the effects of childcare facility use for children younger than 3 years on their development using the cohorts of the Longitudinal Survey of Newborns in the 21st Century conducted in Japan. Of the 47,015 respondents to the survey, we studied the children of 5,508 mothers with university/professional education to evaluate the relationships between primary early (< 2.5 years) childcare providers during weekday daytime hours and specific development indices for the ages of 2.5, 5.5, and 8 years. At the age of 2.5 and 5.5 years, children attending childcare facilities were judged as having more advanced developmental behaviors by their parents, such as being able to compose a two-word sentence (adjusted odds ratio [aOR]: 0.22) or to express emotions (aOR: 0.81), compared with those cared for by mothers. However, at the age of 8 years, children who attended childcare facilities as infants < 2.5 years showed more aggressive behavior in interrupting people (aOR: 1.20) and causing disturbances in public (aOR: 1.26) than those cared for by mothers (after adjustment for numerous child and parental factors). Although these results are generally consistent with previous studies, issues potentially involved with problem behavior such as quality of childcare require further investigation, as does the case of children of mothers with more modest educational attainment. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Low Patient Weight and Long Intubation Time Are Key Factors for Pain during Colonoscopy 471 478 EN Shohei Oka Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keita Harada Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shumpei Yamamoto Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eriko Yasutomi Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoko Igawa Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masayasu Ohmori Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Hirai Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushi Yamasaki Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Inokuchi Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Kinugasa Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Takahara Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakiko Hiraoka Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65969 Although the clinical usefulness of colonoscopy has been established, the procedure remains painful for many patients. This study was designed to clarify the factors predicting colonoscopy-related pain. We evaluated 283 consecutive patients who completed a first-ever, total colonoscopy without sedatives or analgesics. The severity of pain symptoms was evaluated by a numeric rating scale (NRS) in a questionnaire immediately after the colonoscopy. Patient backgrounds and endoscopic findings were analyzed to evaluate their association with pain. Out of 283 patients, 53 scored their pain 0-1 on the NRS while 48 scored it 6-10. We defined the colonoscopies of the former and latter patients as painless and painful, respectively, and compared the two. Multivariate analyses revealed that low body weight (OR 4.95, 95%CI 1.89-12.99) and longer intubation time (OR 3.63, 95%CI 1.46-9.03) were significant risk factors for painful colonoscopy. To identify factors contributing to the increased intubation time, we divided subjects into short- and long-intubation-time groups based on a median insertion time of 7 min. Older age (OR 2.28, 95%CI 1.31-3.98), previous abdominal surgery (OR 1.93, 95%CI 1.13-3.32) and findings of invasive cancer (OR 10.90, 95%CI 1.34-88.90) were significant factors for longer intubation time. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1068-9265 30 13 2023 Prognostic Impact of Tumor-Infiltrating Lymphocytes, Tertiary Lymphoid Structures, and Neutrophil-to-Lymphocyte Ratio in Pulmonary Metastases from Uterine Leiomyosarcoma 8727 8734 EN Naoki Matsuda Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Habu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuma Iwata Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Matsubara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Hashimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Toji Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuhito Takahashi Department of Sarcoma Medicine, Center for Sarcoma Multidisciplinary Treatment, Kameda Medical Center Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background　The presence of tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) in tumor tissue has been related to the prognosis in various malignancies. Meanwhile, neutrophil-to-lymphocyte ratio (NLR) as a systemic inflammation marker also has been associated with the prognosis in them. However, few reports have investigated the relationship between pulmonary metastases from sarcoma and these biomarkers.<br> Methods　We retrospectively recruited 102 patients undergoing metastasectomy for pulmonary metastases from uterine leiomyosarcoma at Okayama University Hospital from January 2006 to December 2019. TILs and TLSs were evaluated by immunohistochemical staining of surgically resected specimens of pulmonary metastases using anti-CD3/CD8/CD103/Foxp3/CD20 antibodies. NLR was calculated from the blood examination immediately before the most recent pulmonary metastasectomy. We elucidated the relationship between the prognosis and these factors. Because we considered that the status of tumor tissue and systemic inflammation were equally valuable, we also assessed the impact of the combination of TILs or TLSs and NLR on the prognosis.<br> Results　As for TILs, CD3-positive cells and CD8-positive cells were correlated with the prognosis. The prognosis was significantly better in patients with CD3-high group, CD8-high group, TLSs-high group, and NLR-low group, respectively. The prognosis of CD8-high/NLR-low group and TLSs-high/NLR-low group was significantly better than that of CD8-low/NLR-high group and TLSs-low/NLR-high group, respectively.<br> Conclusions　CD3-positive TILs, CD8-positive TILs, TLSs, and NLR are correlated with the prognosis, respectively. The combination of CD8-positive TILs or TLSs and NLR may be the indicators to predict the prognosis of patients with pulmonary metastases from uterine leiomyosarcoma. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0009-2363 71 2 2023 Identification of a Functionally Efficient and Thermally Stable Outward Sodium-Pumping Rhodopsin (BeNaR) from a Thermophilic Bacterium 154 164 EN Marie Kurihara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Vera Thiel Department of Biological Sciences, Tokyo Metropolitan University Hirona Takahashi Department of Chemistry, Graduate School of Science, Okayama University of Science Keiichi Kojima Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University David M. Ward Department of Land Resources and Environmental Sciences, Montana State University Donald A. Bryant Department of Biochemistry and Molecular Biology, The Pennsylvania State University Makoto Sakai Department of Chemistry, Graduate School of Science, Okayama University of Science Susumu Yoshizawa Atmosphere and Ocean Research Institute, The University of Tokyo Yuki Sudo Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rhodopsins are transmembrane proteins with retinal chromophores that are involved in photo-energy conversion and photo-signal transduction in diverse organisms. In this study, we newly identified and characterized a rhodopsin from a thermophilic bacterium, Bellilinea sp. Recombinant Escherichia coli cells expressing the rhodopsin showed light-induced alkalization of the medium only in the presence of sodium ions (Na+), and the alkalization signal was enhanced by addition of a protonophore, indicating an outward Na+ pump function across the cellular membrane. Thus, we named the protein Bellilinea Na+-pumping rhodopsin, BeNaR. Of note, its Na+-pumping activity is significantly greater than that of the known Na+-pumping rhodopsin, KR2. We further characterized its photochemical properties as follows: (i) Visible spectroscopy and HPLC revealed that BeNaR has an absorption maximum at 524 nm with predominantly (>96%) the all-trans retinal conformer. (ii) Time-dependent thermal denaturation experiments revealed that BeNaR showed high thermal stability. (iii) The time-resolved flash-photolysis in the nanosecond to millisecond time domains revealed the presence of four kinetically distinctive photointermediates, K, L, M and O. (iv) Mutational analysis revealed that Asp101, which acts as a counterion, and Asp230 around the retinal were essential for the Na+-pumping activity. From the results, we propose a model for the outward Na+-pumping mechanism of BeNaR. The efficient Na+-pumping activity of BeNaR and its high stability make it a useful model both for ion transporters and optogenetics tools. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2694-2453 3 5 2023 Highly Stretchable Stress-Strain Sensor from Elastomer Nanocomposites with Movable Cross-links and Ketjenblack 394 405 EN Ryohei Ikura Department of Macromolecular Science, Graduate School of Science and Forefront Research Center for Fundamental Sciences, Osaka University Kota Kajimoto Department of Macromolecular Science, Graduate School of Science, Osaka University Junsu Park Department of Macromolecular Science, Graduate School of Science and Forefront Research Center for Fundamental Sciences, Osaka University Shunsuke Murayama Graduate School of Organic Materials Engineering, Yamagata University Yusei Fujiwara Department of Mechanical Engineering, Osaka Institute of Technology Motofumi Osaki Department of Macromolecular Science, Graduate School of Science and Forefront Research Center for Fundamental Sciences, Osaka University Tomohiro Suzuki Kanagawa Technical Center, Yushiro Chemical Industry Co., Ltd. Hidenori Shirakawa Kanagawa Technical Center, Yushiro Chemical Industry Co., Ltd. Yujiro Kitamura Kanagawa Technical Center, Yushiro Chemical Industry Co., Ltd. Hiroaki Takahashi Kanagawa Technical Center, Yushiro Chemical Industry Co., Ltd. Yasumasa Ohashi Kanagawa Technical Center, Yushiro Chemical Industry Co., Ltd. Seiji Obata Research Core for Interdisciplinary Sciences, Okayama University Akira Harada SANKEN (The Institute of Scientific and Industrial Research), Osaka University Yuka Ikemoto Japan Synchrotron Radiation Research Institute Yuta Nishina Research Core for Interdisciplinary Sciences, Okayama University Yasutomo Uetsuji Department of Mechanical Engineering, Osaka Institute of Technology Go Matsuba Graduate School of Organic Materials Engineering, Yamagata University Yoshinori Takashima Department of Macromolecular Science, Graduate School of Science and Forefront Research Center for Fundamental Sciences, Osaka University Practical applications like very thin stress-strain sensors require high strength, stretchability, and conductivity, simultaneously. One of the approaches is improving the toughness of the stress-strain sensing materials. Polymeric materials with movable cross-links in which the polymer chain penetrates the cavity of cyclodextrin (CD) demonstrate enhanced strength and stretchability, simultaneously. We designed two approaches that utilize elastomer nanocomposites with movable cross-links and carbon filler (ketjenblack, KB). One approach is mixing SC (a single movable cross-network material), a linear polymer (poly(ethyl acrylate), PEA), and KB to obtain their composite. The electrical resistance increases proportionally with tensile strain, leading to the application of this composite as a stress- strain sensor. The responses of this material are stable for over 100 loading and unloading cycles. The other approach is a composite made with KB and a movable cross-network elastomer for knitting dissimilar polymers (KP), where movable cross-links connect the CD-modified polystyrene (PSCD) and PEA. The obtained composite acts as a highly sensitive stress-strain sensor that exhibits an exponential increase in resistance with increasing tensile strain due to the polymer dethreading from the CD rings. The designed preparations of highly repeatable or highly responsive stress-strain sensors with good mechanical properties can help broaden their application in electrical devices. No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 183 2023 手工教育基礎建設の曙光時代における愛媛教育協会機関誌に 見られる手工教育の実態（後編） ― 愛媛県手工教育史（第四報） ― 15 27 EN Toshiyuki TAKAHASHI Faculty of Education, Okayama University 10.18926/bgeou/65922 　本論は，阿部七五三吉（1936）による「手工教育基礎建設の曙光時代」［1907（明治40 年）頃～ 1926（大正15）年頃まで］における，1911（明治44）年の「改正小学校令」から1926（大正15）年の「改正小学校令」までの14 年９か月間を調査対象期間として，愛媛教育協会機関誌に見られる手工教育関係史料を調査し，愛媛県の尋常小学校及び高等小学校における手工科の成立及び展開過程を探った。その結果，1911（明治44）年の「改正小学校令」によって手工科は，高等小学校実業科目の選択必修科目の一つとなったが，実業科目としての性格が強くなると同時に，授業時数の増加が小学校にとって負担になり，手工科加設校は結果的に減少し，愛媛県の小学校における手工教育は混迷した。 No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1462-8902 24 8 2022 Rationale, design and baseline characteristics of the effect of canagliflozin in patients with type 2 diabetes and microalbuminuria in the Japanese population: The CANPIONE study 1429 1438 EN Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Hiddo J. L. Heerspink Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Dick de Zeeuw Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Masao Toyoda Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine Daisuke Suzuki Suzuki Diadetes Clinic Takashi Hatanaka Department of Diabetes and Endocrinology, National Hospital Organization Fukuyama Medical Center Tohru Nakamura Diabetes Internal Medicine, Sumitomo Besshi Hospital Shinji Kamei Department of Diabetic Medicine, Kurashiki Central Hospital Satoshi Murao Department of Diabetes and Endocrinology, Takamatsu Hospital Kazuyuki Hida Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Shinichiro Ando Department of Internal Medicine Diabetic Center, Okayama City Hospital Hiroaki Akai Division of Diabetes and Metabolism, Faculty of Medicine, Tohoku Medical and Pharmaceutical University Yasushi Takahashi Department of Diabetes, Ochiai General Hospital Daisuke Koya Department of Diabetology and Endocrinology, Kanazawa Medical University Munehiro Kitada Department of Diabetology and Endocrinology, Kanazawa Medical University Hisashi Sugano Department of Diabetes and Endocrinology, Kochi Health Sciences Center Tomokazu Nunoue Nunoue Clinic Akihiko Nakamura Internal Medicine, Osafune Clinic, Setouchi Motofumi Sasaki Department of Diabetes and Endocrinology, Matsue City Hospital Tatsuaki Nakatou Diabetes Center, Okayama Saiseikai General Hospital Kei Fujimoto Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, The Jikei University Kashiwa Hospital Daiji Kawanami Department of Endocrinology and Diabetes Mellitus, Fukuoka University School of Medicine Takashi Wada Department of Nephrology and Laboratory Medicine, Graduate School of Medical Sciences, Kanazawa University Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Michihiro Yoshida Center for Innovative Clinical Medicine, Okayama University Hospital Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital the CANPIONE study Investigators Aim: To evaluate the effect of canagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, on albuminuria and the decline of estimated glomerular filtration rate (eGFR) in participants with type 2 diabetes and microalbuminuria.<br> Methods: The CANPIONE study is a multicentre, randomized, parallel-group and open-labelled study consisting of a unique 24-week preintervention period, during which the rate of eGFR decline before intervention is estimated, followed by a 52-week intervention and a 4-week washout period. Participants with a geometric mean urinary albumin-to-creatinine ratio (UACR) of 50 and higher and less than 300 mg/g in two consecutive first-morning voids at two different time points, and an eGFR of 45 ml/min/1.73m2 or higher, are randomly assigned to receive canagliflozin 100 mg daily or to continue guideline-recommended treatment, except for SGLT2 inhibitors. The first primary outcome is the change in UACR, and the second primary outcome is the change in eGFR slope.<br> Results: A total of 258 participants were screened and 98 were randomized at 21 sites in Japan from August 2018 to May 2021. The mean baseline age was 61.4 years and 25.8% were female. The mean HbA1c was 7.9%, mean eGFR was 74.1 ml/min/1.73m2 and median UACR was 104.2 mg/g.<br> Conclusions: The CANPIONE study will determine whether the SGLT2 inhibitor canagliflozin can reduce albuminuria and slow eGFR decline in participants with type 2 diabetes and microalbuminuria. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 A Case of Acute Zonal Occult Outer Retinopathy in which Oct en Face Imaging Was Useful for Diagnosis and Follow-up 433 437 EN Ryuki Ono 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 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 Hiroya Kindo 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 Case Report 10.18926/AMO/65756 A 23-year-old woman presented with a 1-month history of visual abnormalities in her right eye. A visual field test revealed temporal abnormalities in the right eye. Optical coherence tomography revealed an indistinct ellipsoid zone (EZ) on the B-scan image and hyporeflective areas in the EZ layer on the en face image in the right eye. We diagnosed the patient with acute zonal occult outer retinopathy. Visual field tests and B-scan images improved to almost normal at 6 months, but hyporeflective areas remained on the en face images. Thus, en face images may be more sensitive at detecting abnormalities in the outer retina than other modalities. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Feasibility of Flow Cytometry Analysis of Gastrointestinal Tract-Residing Lymphocytes in Hematopoietic Stem Cell Transplant Recipients 347 357 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takumi Kondo Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Ennishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuharu Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahide Takahashi Division of Medical Support, Okayama University Hospital Araki Hirabata Division of Medical Support, Okayama University Hospital Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65740 The feasibility of lymphocyte isolation and flow cytometry using a single endoscopic biopsy specimen from the gastrointestinal tract of patients who have undergone hematopoietic stem cell transplantation has not been investigated. We acquired 51 endoscopic biopsy specimens from the gastrointestinal tract of 35 patients. We divided the flow cytometry samples into two groups: group A, successful lymphocyte isolation (n=24), and group B, incomplete isolation (n=27). We compared the backgrounds of the samples between the groups to reveal crucial elements in the successful isolation of lymphocytes residing in the gastrointestinal tract. Comparison between the groups revealed lymphocyte isolation success rates differed between biopsy sites. Isolation was most successful in samples from the duodenum (8/9, 88.9%), followed by the ileum (4/8, 50.0%), large intestine (4/11, 36.4%), and stomach (8/23, 34.8%). Tacrolimus was used more frequently in group B (92.6%) than in group A (62.5%) (p=0.015). Logistic regression analysis revealed that isolation from the duodenum or ileum was a significant factor for successful isolation, while tacrolimus use was not statistically significant. In conclusion, the duodenum and ileum are more suitable sites than the stomach and colorectum for acquiring samples for flow cytometry. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0022-3263 88 14 2023 Oxytrofalcatin Puzzle: Total Synthesis and Structural Revision of Oxytrofalcatins B and C 9920 9926 EN Kazuma Sugitate Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiki Yamashiro Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ibuki Takahashi Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-tobetsu, Hokkaido 0610293, Japan Koji Yamada Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The previously reported structures of oxytrofalcatins B and C possess a benzoyl indole core. However, following synthesis and NMR comparison of both the proposed structure and the synthesized oxazole, we have revised the structure of oxytrofalcatins B and C as oxazoles. The synthetic route developed herein can further our understanding of the biosynthetic pathways that govern the production of natural 2,5-diaryloxazoles. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 13 1 2023 ADAR1 is a promising risk stratification biomarker of remnant liver recurrence after hepatic metastasectomy for colorectal cancer 2078 EN Nanako Hata 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 Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shuya Yano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sho Takeda 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 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 Hibiki Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiaki Takahashi 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 Hiroyuki Kishimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshiko Mori 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 Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Adenosine-to-inosine RNA editing is a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family. It has been discovered recently as an epigenetic modification dysregulated in human cancers. However, the clinical significance of RNA editing in patients with liver metastasis from colorectal cancer (CRC) remains unclear. The current study aimed to systematically and comprehensively investigate the significance of adenosine deaminase acting on RNA 1 (ADAR1) expression status in 83 liver metastatic tissue samples collected from 36 patients with CRC. The ADAR1 expression level was significantly elevated in liver metastatic tissue samples obtained from patients with right-sided, synchronous, or RAS mutant-type CRC. ADAR1-high liver metastasis was significantly correlated with remnant liver recurrence after hepatic metastasectomy. A high ADAR1 expression was a predictive factor of remnant liver recurrence (area under the curve = 0.72). Results showed that the ADAR1 expression level could be a clinically relevant predictive indicator of remnant liver recurrence. Patients with liver metastases who have a high ADAR1 expression requires adjuvant chemotherapy after hepatic metastasectomy. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0893-6080 164 2023 Design of continuous-time recurrent neural networks with piecewise-linear activation function for generation of prescribed sequences of bipolar vectors 588 605 EN Norikazu Takahashi Okayama University Tsuyoshi Yamakawa Kyushu University Yasuhiro Minetoma Kyushu University Tetsuo Nishi Kyushu University Tsuyoshi Migita Okayama University A recurrent neural network (RNN) can generate a sequence of patterns as the temporal evolution of the output vector. This paper focuses on a continuous-time RNN model with a piecewise-linear activation function that has neither external inputs nor hidden neurons, and studies the problem of finding the parameters of the model so that it generates a given sequence of bipolar vectors. First, a sufficient condition for the model to generate the desired sequence is derived, which is expressed as a system of linear inequalities in the parameters. Next, three approaches to finding solutions of the system of linear inequalities are proposed: One is formulated as a convex quadratic programming problem and others are linear programming problems. Then, two types of sequences of bipolar vectors that can be generated by the model are presented. Finally, the case where the model generates a periodic sequence of bipolar vectors is considered, and a sufficient condition for the trajectory of the state vector to converge to a limit cycle is provided. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Endobronchial Metastasis with Bloody Sputum 20 Years after Complete Resection of type A Non-Invasive Thymoma 331 334 EN Mototsugu Watanabe Department of Thoracic Surgery, Okayama University Hospital Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Kentaroh Miyoshi Department of Thoracic Surgery, Okayama University Hospital Seiichiro Sugimoto Department of Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Case Report 10.18926/AMO/65503 Masaoka stage I type A thymomas rarely recur. We report the case of an 82-year-old man who developed endobronchial metastasis after thymothymectomy for Masaoka stage I type A thymoma. Twenty years after surgery, the patient developed bloody sputum, and chest computed tomography revealed a neoplasm obstructing the right upper lobe bronchus of the lung with enlarged mediastinal lymph nodes. He underwent right upper lobectomy and mediastinal lymph node dissection. Although preoperative pathological diagnosis was squamous cell carcinoma of the lung, postoperative histopathology revealed endobronchial metastasis of the thymoma. Nine years later, at age 89, the patient is alive and well. No potential conflict of interest relevant to this article was reported.

nature portfolio Acta Medica Okayama 2399-3642 6 1 2023 NFYA promotes malignant behavior of triple-negative breast cancer in mice through the regulation of lipid metabolism 596 EN Nobuhiro Okada Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Chihiro Ueki Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Masahiro Shimazaki Laboratory for Malignancy Control Research, Medical Innovation Center, Kyoto University Goki Tsujimoto Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Susumu Kohno Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University Hayato Muranaka Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University Kiyotsugu Yoshikawa Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts Chiaki Takahashi Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University Two splicing variants exist in NFYA that exhibit high expression in many human tumour types. The balance in their expression correlates with prognosis in breast cancer, but functional differences remain unclear. Here, we demonstrate that NFYAv1, a long-form variant, upregulates the transcription of essential lipogenic enzymes ACACA and FASN to enhance the malignant behavior of triple-negative breast cancer (TNBC). Loss of the NFYAv1-lipogenesis axis strongly suppresses malignant behavior in vitro and in vivo, indicating that the NFYAv1-lipogenesis axis is essential for TNBC malignant behavior and that the axis might be a potential therapeutic target for TNBC. Furthermore, mice deficient in lipogenic enzymes, such as Acly, Acaca, and Fasn, exhibit embryonic lethality; however, Nfyav1-deficient mice exhibited no apparent developmental abnormalities. Our results indicate that the NFYAv1-lipogenesis axis has tumour-promoting effects and that NFYAv1 may be a safe therapeutic target for TNBC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Associations between Comorbidities and Acute Exacerbation of Interstitial Lung Disease after Primary Lung Cancer Surgery 301 309 EN Takahide Kato Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Seigo Miyoshi Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Chizuru Hamada Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Yoshifumi Sano Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Naoyuki Nogami Department of Community Medicine, Pulmonology and Cardiology, Ehime University Graduate School of Medicine Osamu Yamaguchi Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Naohiko Hamaguchi Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Original Article 10.18926/AMO/65495 Acute exacerbation (AE) of interstitial lung disease (ILD) is a severe complication of lung resection in lung cancer patients with ILD (LC-ILD). This study aimed to assess the predictive value of comorbidities other than ILD for postoperative AE in patients with LC-ILD. We retrospectively evaluated 68 patients with LC-ILD who had undergone lung resection. We classified them into two groups: those who had developed postoperative AE within 30 days after resection and those who had not. We analyzed patient characteristics, high-resolution computed tomography findings, clinical data, pulmonary function, and intraoperative data. The incidence of postoperative AEs was 11.8%. In univariate analysis, performance status (PS), honeycombing, forced vital capacity (FVC), and high hemoglobin A1c (HbA1c) levels without comorbidities were significantly associated with postoperative AE. Patients were divided into two groups according to cutoff levels of those four variables as determined by receiver operating characteristic curves, revealing that the rates of patients without postoperative AE differed significantly between groups. The present results suggested that preoperative comorbidities other than ILD were not risk factors for postoperative AE in patients with LC-ILD. However, a high preoperative HbA1c level, poor PS, low FVC, and honeycombing may be associated with postoperative AE of LC-ILD. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Brown Adipose Tissue PPARγ Is Required for the Insulin-Sensitizing Action of Thiazolidinediones 243 254 EN Yusuke Shibata Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65489 Brown adipose tissue (BAT) plays a critical role in metabolic homeostasis. BAT dysfunction is associated with the development of obesity through an imbalance between energy expenditure and energy intake. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is the master regulator of adipogenesis. However, the roles of PPARγ and thiazolidinediones (TZDs) in the regulation of BAT metabolism remain unclear. TZDs, which are selective PPARγ activators, improve systemic insulin resistance in animals and humans. In the present study, we generated brown adipocyte-specific PPARγ-deficient mice (BATγKO) to examine the in vivo roles of PPARγ and TZDs in BAT metabolism. In electron microscopic examinations, brown adipocyte-specific PPARγ deletion promoted severe whitening of brown fat and morphological alteration of mitochondria. Brown adipocyte-specific PPARγ deletion also reduced mRNA expression of BAT-selective genes. Although there was no difference in energy expenditure between control and BATγKO mice in calorimetry, norepinephrine-induced thermogenesis was impaired in BATγKO mice. Moreover, pioglitazone treatment improved diet-induced insulin resistance in the control mice but not in the BATγKO mice. These findings suggest that BAT PPARγ is necessary for the maintenance of brown adipocyte function and for the insulin-sensitizing action of TZDs. No potential conflict of interest relevant to this article was reported.

Nature Research Acta Medica Okayama 2045-2322 13 1 2023 Dexmedetomidine improves acute lung injury by activating autophagy in a rat hemorrhagic shock and resuscitation model EN Yifu Lu Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Hiroko Shimizu Department of Anesthesiology and Resuscitology, Okayama University Medical School Ryu Nakamura Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Yaqiang Li Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Risa Sakamoto Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Emiko Omori Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Toru Takahashi Okayama Saidaiji Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Dexmedetomidine (DEX) can reduce lung injury in a hemorrhagic shock (HS) resuscitation (HSR) model in rats by inhibiting inflammation. Here, we aimed to investigate if these effects of DEX are due to autophagy activation. Therefore, we established HSR rat models and divided them into four groups. HS was induced using a blood draw. The rats were then resuscitated by reinjecting the drawn blood and saline. The rats were sacrificed 24 h after resuscitation. Lung tissues were harvested for histopathological examination, determination of wet/dry lung weight ratio, and detection of the levels of autophagy-related marker proteins LC3, P62, Beclin-1, and the ATG12-ATG5 conjugate. The morphological findings of hematoxylin and eosin staining in lung tissues and the pulmonary wet/dry weight ratio showed that lung injury improved in HSR + DEX rats. However, chloroquine (CQ), an autophagy inhibitor, abolished this effect. Detecting the concentration of autophagy-related proteins showed that DEX administration increased LC3, ATG12-ATG5, and Beclin-1 expression and decreased P62 expression. The expression levels of these proteins were similar to those in the HSR group after CQ + DEX administration. In summary, DEX induced autophagic activation in an HSR model. These findings suggest that DEX administration partially ameliorates HSR-induced lung injury via autophagic activation. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Study on the effect of facial feature and expression in visual cuteness perception EN Lichang YAO Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University No potential conflict of interest relevant to this article was reported.