Elsevier BV Acta Medica Okayama 0040-4039 179 2026 Visible-light-induced photocatalytic intermolecular cyclization for synthesis of 2,2-diarylchromanes 156034 EN Sakura Kodaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Momo Kondo Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science Junta Minato Laboratory of Cellular Drug Discovery and Development, Faculty of Pharmaceutical Sciences, Tokyo University of Science Shoko Itakura Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Makiya Nishikawa Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kosuke Kusamori Laboratory of Cellular Drug Discovery and Development, Faculty of Pharmaceutical Sciences, Tokyo University of Science Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University The photocatalytic cyclization of salicylaldehydes with 1,1-diarylalkenes for the synthesis of 2,2-diarylchromanes has been developed. The catalytic amount of Ir photocatalyst proceeds the cyclization to give the various 2,2-diaryl chromanes under irradiation with blue LEDs. The obtained 2,2-diarylchromanes exhibit noticeable free-radical-scavenging activities, which have been largely unexplored. Notably, the chromane can convert to 2,2-diaryl-2H-naphtho[1,2-b]pyran bearing strong electron withdrawing groups, which are found in various photochromic materials. Thus, the present reaction constitutes a promising tool for the synthesis of functional materials and biologically active compounds. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1472-6831 26 1 2026 Evaluation of contact-active antibacterial properties of cetylpyridinium chloride–graphene oxide coatings on dental restorative and titanium surfaces: an in vitro study 558 EN Keisuke Okubo Department of Periodontics and Endodontics, Field of Medical Development, Okayama University Gen Kano Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masato Komoda Research Institute for Interdisciplinary Science, Okayama University Hideyuki Kamata Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Nakamura Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Shinoda-Ito Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Shogo Takashiba Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective Biofilm formation on dental restorative materials and implant surfaces plays a central role in the development of dental caries, periodontal disease, and peri-implantitis. Durable antimicrobial surface treatments that inhibit bacterial adhesion and biofilm formation remain a significant unmet need in restorative and implant dentistry. Therefore, this study aimed to develop a composite coating combining cetylpyridinium chloride and graphene oxide, and to evaluate its durable antibacterial surface modification under in vitro conditions. Methods A composite coating consisting of cetylpyridinium chloride and graphene oxide was prepared and applied to composite resin and titanium surfaces. Antibacterial activity against Streptococcus mutans and Porphyromonas gingivalis was evaluated using adenosine triphosphate assays and fluorescence-based live/dead staining. Coating retention after washing and air-drying was assessed by optical microscopy and Raman spectroscopy. Results Cetylpyridinium chloride-graphene oxide-coated surfaces showed a significant reduction in bacterial viability compared with phosphate-buffered saline, ethanol, and cetylpyridinium chloride-only controls. Antibacterial effects were maintained after rinsing and air-drying on both composite resin and titanium surfaces. Raman spectroscopy confirmed the persistence of characteristic graphene oxide bands after washing, indicating stable retention of the coating on the material surfaces. Conclusions Cetylpyridinium chloride–graphene oxide coatings demonstrate sustained surface-associated antibacterial activity against key cariogenic and periodontal pathogens and remain stably adhered to common dental restorative and implant materials after washing. These findings suggest that cetylpyridinium chloride–graphene oxide coatings may serve as a durable contact-active surface modification strategy to reduce biofilm formation associated with dental caries and peri-implantitis. No potential conflict of interest relevant to this article was reported.

岡山大学法学会 Acta Medica Okayama 0386-3050 75 3-4 2026 迅速裁判条項に関する判例法理の展開と現状 706 657 EN K. Harada No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構教師教育開発センター Acta Medica Okayama 2186-1323 16 2026 特別支援教育への哲学的思考導入についての予備的考察持続・生成変化・回折の考え方に基づく方法的枠組みの試案 237 251 EN Yo HAMADA Okayama Prefectural Okayama Seto Special Needs School Miyuki TAKANO Hyogo University of Teacher Education Satoru SATO Faculty of Education, Okayama University 10.18926/CTED/70372 　本稿は，現代の特別支援教育の課題から，特別支援教育実践に哲学的思考を導入するための理論的・方法的検討を行うものである。まず，理論基盤として，ベルクソンの「記憶理論」，ドゥルーズ＆ガタリの「生成変化の哲学」，Baradの「回折的方法論」，Blomの「回折的エスノグラフィー」について概説した。そして，理論基盤を基に方法的枠組みとして，「物質－言説的実践」，「持続」，「生成変化」の三つの視点を教育実践を読み解くための相互補完的な分析視点として採用することを提案した。これらの視点は，ポスト質的研究として，出来事を関係的・過程的に捉えることを可能にするものである。今後の課題として，三つのレンズ間の理論的整理，回折的方法論と回折的エスノグラフィーの差異化，および複数の実践エピソードを接続して描くための分析手法の精緻化が挙げられた。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構教師教育開発センター Acta Medica Okayama 2186-1323 16 2026 ドイツ付近の夏の気候とシューベルトの歌曲《春に》異質な他者との出会いを促す大学での学際的授業の報告 75 89 EN Kuranoshin KATO Faculty of Education, Okayama University Isao NAGAOKA Faculty of Education, Okayama University Haruko KATO Faculty of Education, Gufu Shotoku Gakuen University (Former affiliation) 10.18926/CTED/70361 　「異質な他者」への出会いを促す授業例の更なる蓄積のため，ドイツ付近の「夏」の気候と季節感に注目した教科横断的な授業を大学で実践した。授業では，ドイツ付近の気候と季節サイクルの中での「夏」の特徴を把握すると共に，シューベルトの歌曲《春に》を鑑賞した。《春に》の3 番の「夏の間じゅう，ずっと」という歌詞で歌われている情景や情感が，ドイツ付近と日本付近を想定した場合にどう違い得るか，に関する受講生の記述を分析した。その結果，日本の夏の高温多湿な環境からは原詩の情感そのものが成立し難いと感じた学生もいるなど，本実践は，自分たちの「当たり前」とは異なる気候や季節感にも目を向ける機会になり得たといえる。一方，日本とはかなり違う気候背景の中でシューベルトが思い描いたであろう情景・心情に授業で深く迫るための，音楽表現自体への踏み込み方についても，今後検討する必要性が示唆された。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構教師教育開発センター Acta Medica Okayama 2186-1323 16 2026 説明的文章の指導における「内省」を促す批判的読み ―高等学校１年生を対象として― 15 29 EN Yumi SAISHO Graduate School of Education (Professional Degree Corse), Okayama University Masafumi IKEDA Faculty of Education, Okayama University 10.18926/CTED/70357 　批判的読みは，現代では欠かせない能力であり，学習指導要領にも明記されている。近年，批判的読みの指導に関する研究がなされているものの，内容的な価値の検討や社会的な文脈のなかで捉えることが希薄だとする指摘や，「反省性」という観点に着目した批判的読みを求める声もある。そこで，本稿では，文章そのものを批判的に読むだけでなく，自身の持っている考えをも批判的に捉える（内省する）ことを促す授業を開発した。その手立てとして，複数の社会認識が存在する二つの教材の読み比べたうえで，対立する立場からの意見交換を行うことや，教材に対する評価の記述，その記述（自己の読み）を学習者自身が評価するといった活動を取り入れた。学習者の記述の分析からは，意識的な内省に至らなかった学習者も見受けられたものの，約６割の学習者の記述には変容が見られ，用いた手立ては効果があったと推測できることを指摘した。 No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 75 3 2026 A real-world comparison of nivolumab plus cabozantinib and pembrolizumab plus lenvatinib focusing on safety outcomes in metastatic renal cell carcinoma: results from the JK-FOOT consortium 84 EN Takafumi Yanagisawa Department of Urology, The Jikei University School of Medicine Keiichiro Mori Department of Urology, The Jikei University School of Medicine Tatsushi Kawada Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Satoshi Katayama Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Takuya Tsujino Department of Urology, Osaka Medical and Pharmaceutical University Ryoichi Maenosono Department of Urology, Osaka Medical and Pharmaceutical University Shingo Toyoda Department of Urology, Faculty of Medicine, Kindai University Takuhisa Nukaya Department of Urology, Fujita-Health University School of Medicine Hirofumi Morinaka Department of Urology, Kawasaki Medical School Keita Tamura Department of Urology, Hamamatsu Medical University Wataru Fukuokaya Department of Urology, The Jikei University School of Medicine Fumihiko Urabe Department of Urology, The Jikei University School of Medicine Masaya Murakami Department of Urology, The Jikei University School of Medicine Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyoshi Takahara Department of Urology, Fujita-Health University School of Medicine Kazutoshi Fujita Department of Urology, Faculty of Medicine, Kindai University Haruhito Azuma Department of Urology, Osaka Medical and Pharmaceutical University Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Teruo Inamoto Department of Urology, Hamamatsu Medical University Kazumasa Komura Department of Urology, Kawasaki Medical School Takahiro Kimura Department of Urology, The Jikei University School of Medicine Purpose Immune checkpoint inhibitor (ICI)-based combination therapy is a standard first-line treatment for metastatic renal cell carcinoma (mRCC), with combinations such as nivolumab plus cabozantinib (Nivo + Cabo) and pembrolizumab plus lenvatinib (Pem + Len) demonstrating favorable oncologic outcomes. However, no direct comparisons between these two regimens have been conducted. This study aimed to compare the safety and oncologic outcomes of Nivo + Cabo and Pem + Len in patients with mRCC. Methods This retrospective study included 185 patients with mRCC treated with Nivo + Cabo (n = 81) or Pem + Len (n = 104) between January 2018 and June 2025 across multiple institutions. The primary outcome was a comparison of treatment-related adverse events (TrAEs). Oncologic outcomes, including objective response rate (ORR), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were compared using one-to-one propensity score matching. Results Any-grade TrAEs occurred in 90% of patients in the Nivo + Cabo group and 92% in the Pem + Len group (p = 0.6). Severe TrAEs (grade ≥ 3) were more frequent in the Pem + Len group (44%) than in the Nivo + Cabo group (30%, p = 0.048). Tyrosine kinase inhibitor dose reduction and treatment discontinuation rates were similar between groups. In the matched cohort (Nivo + Cabo: n = 74; Pem + Len: n = 74), ORRs were comparable (66% vs. 71%, p = 0.6). With a median follow-up of 17 months, no significant differences were observed in PFS (p = 0.4), CSS (p = 0.9), or OS (p = 0.5). Conclusions Nivo + Cabo and Pem + Len demonstrated similar oncologic efficacy as first-line treatments for mRCC. However, Pem + Len was associated with more severe TrAEs. Careful toxicity management and shared decision-making are essential when selecting ICI-based combinations. No potential conflict of interest relevant to this article was reported.

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

American Chemical Society (ACS) Acta Medica Okayama 1043-1802 37 3 2026 A Cysteine-Specific Cationization Strategy for Versatile Antibody Production against Intrinsically Disordered Proteins 580 589 EN Ryui Sakaguchi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ai Miyamoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Rikako Kutsuma Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takeru Mori Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Daichi Nakashima Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mirei Masui Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tomoko Honjo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Midori Futami Department of Bioscience, Faculty of Life Science, Okayama University of Science Mariko Morii Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toshiyuki Oshiki Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Junichiro Futami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Several autoantigens relevant to the immune system, especially those targeted by autoantibodies induced by antitumor responses, tend to be rich in disordered regions and are prone to aggregation. This inherent instability presents significant challenges for the production, purification, and analysis of autoantigens in laboratory settings. Cysteine-specific cationization can effectively solubilize and purify these challenging proteins, allowing the isolation of full-length water-soluble antigens in their denatured state. The purified antigens enable accurate multiplex autoantibody assays using a suspension Luminex bead array platform. However, well-validated positive control antibodies are essential to ensuring precise clinical diagnosis. In this study, we prepared and characterized a panel of control antibodies by immunizing rabbits with cysteine-specific S-cationized antigens. The resulting antibodies predominantly recognized linear epitopes and were highly effective as quality control reagents in autoantibody array assays. Additionally, these antibodies maintained their ability to bind to their native, unmodified intracellular counterparts, highlighting the usefulness of this approach for producing antibodies against intrinsically disordered proteins. Although a modest immune response against the S-cationized modification site was observed, it remained minimal and did not affect the usefulness of the antibodies for assay validation. We propose this versatile cysteine-specific cationization platform for managing unstable proteins rich in disordered regions, supporting antigen production for diagnostics, and antibody development for research and validation purposes. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1424-8220 25 21 2025 Integrated Authentication Server Design for Efficient Kerberos–Blockchain VANET Authentication 6651 EN Maya Rahayu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Md. Biplob Hossain Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Samsul Huda Interdisciplinary Education and Research Field, Okayama University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Vehicular Ad Hoc Network (VANET) is a fundamental component of the intelligent transportation systems (ITS), providing critical road information to users. However, the volatility of VANETs creates significant vulnerabilities from malicious actors. Thus, verifying joining entities is crucial to maintaining the VANET’s communication security. Authentication delays must stay below 100 ms to meet VANET requirements, posing a major challenge for security. Our previous research introduced a Kerberos–Blockchain (KBC) authentication system that contains two main components separately: Authentication Server (AS) and Ticket Granting Server (TGS). However, this KBC architecture required an additional server to accommodate increasing vehicle volumes in urban environments, leading to higher infrastructure costs. This paper presents an integrated authentication server that merges AS and TGS into a Combined Server (CBS) while retaining blockchain security. We evaluate it using OMNeT++ with SUMO for traffic simulation and Ganache for blockchain implementation. Results show that CBS removes the need for an extra server while keeping authentication delays under 100 ms. It also improves throughput by 104% and reduces signaling overhead by 45% compared to KBC. By optimizing authentication without compromising security, the integrated server greatly enhances the cost-effectiveness and efficiency of VANET systems. No potential conflict of interest relevant to this article was reported.

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

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

Wiley Acta Medica Okayama 0012-1592 68 3 2026 A Simple Method for RNA-Seq of Manually Isolated Chromatophores in Oryzias Fishes e70044 EN Makoto Goda Institute of Photonics Medicine, Hamamatsu University School of Medicine Asuka Miyagi Institute of Photonics Medicine, Hamamatsu University School of Medicine Keisuke Sugiwaka Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Masakatsu Watanabe Cellular and Structural Physiology Institute (CeSPI) and Graduate School of Pharmaceutical Sciences, Nagoya University Manabu Bessho‐Uehara Frontier Research Institute for Interdisciplinary Science, Tohoku University Masahiko Hibi Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Atsushi Toyoda Comparative Genomics Laboratory, National Institute of Genetics Rieko Tanaka World Medaka Aquarium, Nagoya Higashiyama Zoo and Botanical Gardens Kawilarang W. A. Masengi Faculty of Fisheries and Marine Science, Sam Ratulangi University Kazunori Yamahira Tropical Biosphere Research Center, University of the Ryukyus Satoshi Ansai Ushimado Marine Institute, Okayama University Hisashi Hashimoto Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University RNA sequencing (RNA-seq) has become an essential tool for analyzing gene expression and exploring cell type–specific transcriptomes. However, sample preparation and quality control remain challenging, as current approaches typically rely on dissecting tissues containing mixed cell populations or using flow cytometry to isolate fluorescently labeled cells. Here we present a simple and reliable method for RNA-seq of chromatophores (pigment cells) by manually isolating cells based on their natural pigmentation. We analyzed four chromatophore types—melanophores, xanthophores, iridophores, and leucophores—in medaka (Oryzias latipes). Remarkably, as few as 100 cells per type yielded reasonably high-quality transcriptomes sufficient to identify differentially expressed genes (DEGs). Furthermore, this method was successfully applied to a non-model medaka species, O. woworae, which shares the same four chromatophore types. Our approach enables efficient, low-cost, and cross-species transcriptome analysis of chromatophores without requiring transgenic markers or flow cytometry. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 1353-8020 143 2026 Biallelic CAG repeat expansion in the ATXN2 gene presenting with parkinsonism and spasticity 108168 EN Yosuke Osakada Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chika Matsuoka Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Taira Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuko Kawahara Department of Neurology, Okayama Saiseikai General Hospital Yumiko Kutoku Department of Neurology, Kawasaki Medical School Manabu Takaki Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Osamu Yokota Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Ishiura Department of Neurology, 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 2397-4648 11 1 2026 Band-selective plasmonic polaron in thermoelectric semimetal Ta2PdSe6 with ultra-high power factor 23 EN Daiki Ootsuki Research Institute for Interdisciplinary Science, Okayama University Akitoshi Nakano Present address: Department of Applied Physics, Nagoya University Urara Maruoka Present address: Department of Applied Physics, Nagoya University Takumi Hasegawa Graduate School of Advanced Science and Engineering, Hiroshima University Masashi Arita Research Institute for Synchrotron Radiation Science, Hiroshima University Miho Kitamura Present address: NanoTerasu Center, National Institutes for Quantum Science and Technology (QST) Koji Horiba Present address: NanoTerasu Center, National Institutes for Quantum Science and Technology (QST) Teppei Yoshida Graduate School of Human and Environmental Studies, Kyoto University Ichiro Terasaki Present address: Department of Applied Physics, Nagoya University We report the electronic structure of the thermoelectric semimetal Ta2PdSe6 with a large thermoelectric power factor and giant Peltier conductivity by means of angle-resolved photoemission spectroscopy (ARPES). The ARPES spectra reveal the coexistence of a sharp hole band with a light electron mass and a broad electron band with a relatively heavy electron mass, which originate from different quasi-one-dimensional (Q1D) chains in Ta2PdSe6. Moreover, the electron band around the Brillouin-zone (BZ) boundary shows a replica structure with respect to the energy originating from plasmonic polarons due to electron-plasmon interactions. The different scattering effects and interactions in each atomic chain lead to asymmetric transport lifetimes of carriers: a large Seebeck coefficient can be realized even in a semimetal. Our findings pave the way for exploring the thermoelectric materials in previously overlooked semimetals and provide a new platform for low-temperature thermoelectric physics, which has been challenging with semiconductors. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 0732-8893 115 3 2026 Investigation of the cefazolin inoculum effect in blood culture-isolated methicillin-susceptible Staphylococcus aureus strains: A Japanese multicenter study 117345 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Sakura Ogawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihito Koyanagi Department of Clinical Laboratory, Chutoen General Medical Center Yuji Ito Department of General Internal Medicine, Chutoen General Medical Center Hiroshi Koganemaru Department of Infectious Diseases, Tokyo Metropolitan Institute for Geriatrics and Gerontology Atsushi Yoshida Department of Infectious Diseases, Tokyo Metropolitan Institute for Geriatrics and Gerontology Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background: Cefazolin inoculum effect (CInE) is a microbiological phenomenon where the MIC of cefazolin against methicillin-susceptible Staphylococcus aureus (MSSA) strains increases with higher bacterial volumes. Method: We retrospectively investigated the prevalence and characteristics of the CInE among MSSA strains isolated from blood cultures at three Japanese hospitals. The collected isolates were screened for blaZ using PCR, and the cefazolin minimum inhibitory concentration (MIC) for the blaZ-positive MSSA isolates was measured at standard and high inoculum volumes. CInE-positive MSSA strains were defined as those with a cefazolin MIC ≥16 μg/mL at 107 CFU/mL and ≤8 μg/mL at 105 CFU/mL. In these blaZ-positive strains, we performed blaZ typing and tested a modified nitrocefin-based rapid examination to detect the CInE. Results: We collected 329 MSSA strains isolated from blood cultures. Of these, 96 (29.2%) were positive for the blaZ gene, with the following genotypes: type A (15, 15.6%), type B (3, 3.1%), type C (77, 80.2%), type D (0, 0.0%), and non-type (1, 1.0%). Among 96 blaZ-positive MSSA isolates, 11 exhibited the CInE, all of which harbored blaZ type A. The rapid nitrocefin test detected CInE positivity with high sensitivity (100%), specificity (94.1%), and diagnostic accuracy (94.8%). Conclusion: This study highlighted the low prevalence of CInE-presenting MSSA isolates in Japan. When the cefazolin MIC is ≥1 μg/mL or the penicillin G MIC is ≥0.25 μg/mL, the rapid nitrocefin test may be useful for considering the CInE in patients with high bacterial volume MSSA infections. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0145-305X 165 2025 Local immune response induced by intra-fin antigen injection in Japanese medaka (Oryzias latipes) is a useful model for immunological studies 105344 EN Tsukasa Ryu Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Marine Biochemistry, Kyushu University Mizuki Yoshino Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Marine Biology, Kyushu University William Ka Fai Tse Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Developmental Disorders and Toxicology, Kyushu University Satoshi Ansai Ushimado Marine Institute, Faculty of Science, Okayama University Taisen Iguchi Graduate School of Nanobioscience, Yokohama City University Anu Kumar Commonwealth Scientific and Industrial Research Organisation, CSIRO Environment Tomonori Somamoto Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Marine Biochemistry, Kyushu University Miki Nakao Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Marine Biochemistry, Kyushu University Yukiko Ogino Center for Promotion of International Education and Research, Faculty of Agriculture, Kyushu University Teleost fishes play a pivotal role in advancing our understanding of immune system evolution because they retain the ancient characteristics of vertebrate immunity, encompassing both innate and adaptive immune systems. Among these, innate immunity plays a critical role in fish as the first line of defense, coordinating rapid responses to pathogen infections. However, the lack of fish-specific immunological methodologies has limited progress in elucidating fish immune mechanisms. To better understand how the innate immune response develops and resolves in fish, detailed observation and integrative analysis of leukocytes at multiple time points is necessary. In the present study, an intra-fin injection method for observing local immune responses in Japanese medaka (Oryzias latipes) was tested and optimized to analyze the progression of zymosan-induced innate immune responses. Zymosan-injected medaka showed a rapid immune response characterized by leukocyte recruitment and phagocytosis. Using TG(FmpxP:mCherry) transgenic medaka with mCherry fluorescence driven by myeloperoxidase (mpx) promoter, granulocyte chemotaxis towards the site of zymosan entry was successfully visualized. The rapid increase in tumor necrosis factor α (tnfa), interleukin-1β (il1b), interleukin-6 (il6), and CXC motif chemokine ligand 8 (cxcl8) expressions in zymosan-injected anal fins provided a molecular basis for the visualized tissue-specific cellular response. Our study underscores the dynamic orchestration of immune components during the innate immune response in Japanese medaka and highlights their potential as a promising model for immunological research. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Comparative efficacy of immune checkpoint inhibitor combination therapies by metastatic site in metastatic renal cell carcinoma 3303 EN Shingo Toyoda Department of Urology, Faculty of Medicine, Kindai University Lan Inoki Department of Urology, Faculty of Medicine, Kindai University Mamoru Hashimoto Department of Urology, Faculty of Medicine, Kindai University Wataru Fukuokaya Department of Urology, The Jikei University School of Medicine Keiichiro Mori Department of Urology, The Jikei University School of Medicine Shingo Nishimura Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ryoichi Maenosono Department of Urology, Osaka Medical and Pharmaceutical University Takehiro Iwata Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kensuke Bekku Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takuhisa Nukaya Department of Urology, Fujita-Health University School of Medicine Takafumi Yanagisawa Department of Urology, The Jikei University School of Medicine Takuya Tsujino Department of Urology, Osaka Medical and Pharmaceutical University Kazumasa Komura Department of Urology, Kawasaki University School of Medicine Kiyoshi Takahara Department of Urology, Fujita-Health University School of Medicine Teruo Inamoto Department of Urology, Hamamatsu University School of Medicine Haruhito Azuma Department of Urology, Osaka Medical and Pharmaceutical University Kazutoshi Fujita Department of Urology, Faculty of Medicine, Kindai University JK-FOOT study group Few studies have investigated the efficacy of immuno-oncology (IO) combinations at different metastatic sites in renal cell carcinoma (RCC). We evaluated the differential efficacy of IO–IO and IO–tyrosine kinase inhibitor (TKI) combinations by metastatic site in metastatic RCC (mRCC). This retrospective multicenter study by the JK-FOOT Study Group included 579 patients with intermediate- or poor-risk mRCC (per International Metastatic RCC Database Consortium criteria) treated with first-line IO combinations between September 2018 and December 2024. Metastatic sites were lymph nodes, lungs, bones, liver, brain, and others. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoint was objective response rate. Efficacy was compared between IO–IO and IO–TKI for each site. For lymph node (n = 36), lung (n = 132), or brain (n = 16) metastases, OS or PFS was not significantly different between IO–IO and IO–TKI. In bone metastases (n = 80), OS tended to favor IO–TKI (P = 0.053). In liver metastases (n = 22), OS was significantly longer with IO–TKI (P = 0.011). IO–TKI may be a more appropriate first-line option than IO–IO for mRCC with bone or liver metastases, while efficacy is similar for other sites. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2261 25 1 2025 Prognostic value of right atrial strain in patients with chronic heart failure 908 EN Rie Nakayama Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Yoichi Takaya Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Mitsutaka Nakashima Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Takahiro Nishihara Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Norihisa Toh Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Miyoshi Toru Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Kazufumi Nakamura Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Shinsuke Yuasa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Aims Right ventricular dysfunction is a well-established prognostic marker in patients with heart failure (HF). However, the prognostic significance of right atrial (RA) function remains unclear. Given its sensitivity to systemic congestion, RA function may provide additional insights into HF disease progression and management. This study aimed to investigate whether RA reservoir function serves as an independent prognostic indicator in patients with chronic HF. Methods A total of 613 patients with chronic HF and a left ventricular (LV) ejection fraction of less than 50% who underwent echocardiographic assessment at Okayama University Hospital between January 2018 and March 2023 were included (median age: 68 (58–76) years; 69% male). RA reservoir function was quantified using two-dimensional speckle-tracking echocardiography. The primary endpoint was cardiovascular death or HF-related hospitalization. Kaplan–Meier survival analysis was performed to examine the association between RA reservoir function and clinical outcomes. Results During a median follow-up period of 41 months (range: 12–91 months), 119 patients experienced cardiac events. Compared with event-free patients, those with cardiac events exhibited a significantly larger RA maximum volume index (38 mL/m2 vs. 31 mL/m2, P < 0.001) and a significantly lower RA reservoir longitudinal strain (RASr) (17% vs. 22%, P < 0.001). Kaplan–Meier analysis demonstrated that patients with RASr ≤ 20% had significantly poorer event-free survival than those with RASr > 20%, even without RA volume enlargement (log-rank test, P < 0.001). Multivariate Cox regression analysis identified RASr as an independent predictor of cardiac events (hazard ratio: 0.95, 95% confidence interval: 0.93 to 0.97, P < 0.001). Conclusions In patients who experienced adverse cardiac events, a reduced RASr and an increased RA maximum volume were observed. Furthermore, a reduced RASr was independently associated with an increased risk of cardiovascular death and HF-related hospitalization in patients with chronic HF and LV dysfunction. These findings indicate that RASr may serve as a valuable prognostic marker for the risk stratification and management of chronic HF. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0165-5728 414 2026 Immuno-deficient features of thymoma-associated myasthenia gravis patients with hypogammaglobulinemia: A condition comparable to Good's syndrome 578885 EN Saki Nakashima Department of Neurology, Graduate School of Medicine, the University of Tokyo Kaori Sakuishi Department of Neurology, Teikyo University Chiba Medical Center Manato Hara Department of Neurology, Graduate School of Medicine, the University of Tokyo Reiko Kawasaki Department of Neurology, Graduate School of Medicine, the University of Tokyo Toshiyuki Kakumoto Department of Neurology, Graduate School of Medicine, the University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsushi Toda Department of Neurology, Graduate School of Medicine, the University of Tokyo Good's syndrome (GS) is a rare immunodeficiency disorder associated with thymoma, characterized by hypogammaglobulinemia and recurrent infections; however, its clinical significance in thymoma-associated myasthenia gravis (TAMG) remains unclear. We retrospectively reviewed 30 patients with TAMG admitted to our center between January 2010 and March 2022. We defined GS-like immunodeficiency as serum IgG below the institutional cutoff of 861 mg/dL and a history of two or more infections requiring antimicrobial treatment; 11 patients (36.7%) met this definition. Compared with the remaining patients, the GS-like group had higher incidences of malignancy (45.5% vs. 5.3%, p = 0.016) and autoimmune diseases other than MG (36.4% vs. 5.3%, p = 0.047), lower peripheral lymphocyte counts (median 1100/μL vs. 2200/μL, p = 0.0051), and more frequent airflow obstruction defined by one second to forced vital capacity ratio of less than 70% (60.0% vs. 5.3%, p = 0.0026). Five deaths occurred in the GS-like group, and none in the other; median survival from the first antimicrobial-treated infection was 5.0 years. These findings imply that TAMG patients with GS-like immunodeficiency have a worse prognosis, underscoring the need for close monitoring and timely adjustments of MG management. (189 words). No potential conflict of interest relevant to this article was reported.

American Medical Association (AMA) Acta Medica Okayama 2574-3805 8 11 2025 Trastuzumab Deruxtecan for ERBB2-Mutant Metastatic Non–Small Cell Lung Cancer With or Without Brain Metastases: A Secondary Analysis of Randomized Clinical Trials e2543107 EN Pasi A. Jänne Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute David Planchard Department of Medical Oncology, Thoracic Cancer Group, Gustave Roussy, Medical Oncology Koichi Goto Department of Thoracic Oncology, Nation Cancer Center Hospital East Egbert F. Smit Department of Pulmonary Diseases, Leiden University Medical Center Adrianus Johannes de Langen Department of Thoracic Oncology, Netherlands Cancer Institute Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Toshio Kubo Center for Clinical Oncology, Okayama University Hospital Maurice Pérol Department of Medical Oncology, Centre Léon Bérard Enriqueta Felip Department of Medical Oncology, Vall d’Hebron University and Vall d’Hebron Institute of Oncology Hidetoshi Hayashi Department of Medical Oncology, Kindai University Faculty of Medicine Kazuhiko Nakagawa Department of Medical Oncology, Kindai University Faculty of Medicine Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Misako Nagasaka Division of Hematology-Oncology, Department of Medicine, University of California Irvine Kaline Pereira Daiichi Sankyo Inc Ayumi Taguchi Daiichi Sankyo Co Ltd Ahmed Ali Daiichi Sankyo Europe GmbH Maha Karnoub Daiichi Sankyo Inc Rie Yonemochi Daiichi Sankyo Inc David Leung Daiichi Sankyo Inc Bob T. Li Thoracic Oncology and Early Drug Development Service, Global Research Program, Memorial Sloan Kettering Cancer Center Importance Brain metastases reduce overall survival rates of patients with non–small cell lung cancer (NSCLC); patients with epidermal growth factor receptor 2 (ERBB2 [formerly HER2])–mutant NSCLC are more likely to have baseline brain metastases. Trastuzumab deruxtecan (T-DXd) is an approved ERBB2-directed treatment for previously treated unresectable or metastatic ERBB2-mutant NSCLC. Objective To assess the clinical effectiveness and safety of T-DXd 5.4 mg/kg and 6.4 mg/kg doses in patients with previously treated ERBB2-mutant metastatic NSCLC with or without untreated or previously treated stable brain metastases. Design, Setting, and Participants This post hoc secondary analysis pooled patients from the DESTINY-Lung01 (data cutoff date: December 3, 2021) and DESTINY-Lung02 (data cutoff date: December 23, 2022) clinical trials by T-DXd dose (5.4 mg/kg and 6.4 mg/kg). DESTINY-Lung01 was a multicenter, open-label, 2-cohort, nonrandomized phase 2 study, while DESTINY-Lung02 was a dose-blinded, multicenter, 2-cohort, randomized phase 2 study. Participants had a previously treated ERBB2-mutant metastatic NSCLC with or without untreated or previously treated stable brain metastases at baseline. All statistical analyses were performed from April 2023 to October 2024. Intervention Patients received a T-DXd dose of either 5.4 mg/kg or 6.4 mg/kg intravenously every 3 weeks. Main Outcome and Measure Systemic and intracranial effectiveness by blinded independent central review using RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1, sites of progression, and safety. Results This analysis included 102 patients in the T-DXd 5.4-mg/kg dose group (65 females [64%]; median [range] age, 57.5 [37.0-83.0] years and 59.5 [30.0-79.0] years in patients with and without brain metastases, respectively) and 141 patients in the T-DXd 6.4-mg/kg dose group (94 females [67%]; median [range] age, 62.5 [29.0-88.0] years and 59.0 [27.0-83.0] years in patients with and without brain metastases, respectively). In each group, 31% (32 of 102) and 38% (54 of 141) of patients, respectively, had baseline brain metastases and 53% (17 of 32) and 44% (24 of 54), respectively, received prior brain metastasis treatment. In patients with and without brain metastases, systemic confirmed objective response rates (ORRs) were 47% (15 of 32; 95% CI, 29%-65%) and 50% (35 of 70; 95% CI, 38%-62%), respectively, with the T-DXd 5.4-mg/kg dose, and 50% (27 of 54; 95% CI, 36%-64%) and 59% (51 of 87; 95% CI, 48%-69%) with the T-DXd 6.4-mg/kg dose. Median progression-free survival was 7.1 (95% CI, 5.5-9.7) months in the T-DXd 5.4-mg/kg dose group and 7.1 (95% CI, 4.5-9.6) months in the T-DXd 6.4-mg/kg dose group of patients with baseline brain metastases. Among patients with measurable baseline brain metastases, intracranial confirmed ORRs were 50% (7 of 14; 95% CI, 23%-77%) with the T-DXd 5.4-mg/kg dose and 30% (9 of 30; 95% CI, 15%-49%) with the T-DXd 6.4-mg/kg dose. At both doses, the safety profile of T-DXd was generally manageable, regardless of baseline brain metastases, favoring the T-DXd 5.4 mg/kg dose. Conclusions and Relevance In this secondary analysis, T-DXd at the approved dose of 5.4 mg/kg showed antitumor activity in patients with previously treated ERBB2-mutant metastatic NSCLC with or without brain metastases. This finding supports T-DXd 5.4 mg/kg use in this population. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 1347-9032 2026 Clinical and Genetic Landscape of Glioblastoma, IDH-Wildtype With FGFR Gene Family Alterations EN Yasuhito Kegoya Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryo Mizuta Department of Neurological 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 Mako Kamiura Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Joji Ishida Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinichi Toyooka Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Glioblastoma, isocitrate dehydrogenase wildtype (GBM, IDH-wt), is a highly aggressive brain tumor with a poor prognosis. Alterations in the fibroblast growth factor receptor (FGFR) gene family—such as FGFR::TACC fusions and FGFR1 mutations—have emerged as potential therapeutic targets; however, their clinical and genetic features in GBM, IDH-wt remain unclear. We analyzed 1076 GBM, IDH-wt cases using comprehensive genomic profiling data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. FGFR alterations were detected in 8.0% of patients, including FGFR::TACC fusions (3.3%) and FGFR1 mutations (2.9%). The FGFR::TACC fusion-positive group was older at diagnosis and showed higher frequencies of TERT promoter mutation and MDM2 amplification, and lower frequencies of EGFR amplification and TP53 mutation, compared with the fusion-negative group. The FGFR1 mutation-positive group was enriched for ATRX, NF1, and PIK3CA mutations and had significantly fewer TERT promoter and PTEN mutations, compared with the mutation-negative group. No significant differences in overall survival were observed, although both groups tended to have longer median overall survival compared with their respective negative groups. This study represents the largest genomic cohort to date of FGFR alterations in GBM, IDH-wt. FGFR::TACC fusion-positive and FGFR1 mutation-positive GBMs exhibited distinct genetic profiles, highlighting the clinical relevance of molecular subclassification and providing insight for future therapeutic strategies. No potential conflict of interest relevant to this article was reported.

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

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

Japan Society of Mechanical Engineers Acta Medica Okayama 2187-9745 12 5 2025 Examining OpenFOAM-based LES analysis in terms of inviscid energy conservation and viscous turbulence decay 25-00095 EN Hiroki SUZUKI Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kento TANAKA Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Toshinori KOUCHI Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The present study examines an OpenFOAM-based LES analysis from the viewpoints of inviscid energy conservation and viscous turbulence decay. The Smagorinsky model is employed as the sub-grid scale (SGS) model, and a two-dimensional periodic analytical solution and a three-dimensional periodic Taylor-Green vortex (TGV) are employed to represent inviscid flows. The analytical relationship for the kinetic energy K, dK/dt = 0, with t as the dimensionless time, is utilized to validate the OpenFOAM results. For the viscous flow case, the TGV flow in a three-dimensional periodic cubic domain is adopted, and its turbulence kinetic energy distribution is compared with that obtained by a spectral method to examine the analysis. The OpenFOAM-based analysis exhibits energy conservation error in flows that should ideally conserve energy. For the two-dimensional flow, this error decreases with increasing grid resolution N. However, in the three-dimensional flow, the error does not improve even with higher N. In the three-dimensional TGV flow, the turbulence kinetic energy predicted by OpenFOAM exhibits a strong agreement with that from the spectral method when a standard constant value of the Smagorinsky model is employed and the mesh is sufficiently refined. Conversely, for a condition of relatively coarse mesh, the decay characteristics of turbulent kinetic energy deviate from those of the spectral method, and a higher constant value of the Smagorinsky model than the default value becomes necessary to reproduce comparable results. These results suggests that even in LES simulations where highly accurate conservation laws are not satisfied, adjusting the model constants so that the predicted values match experimental or numerical reference data can improve the apparent reliability of the turbulent kinetic energy in the decaying turbulence. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2590-1397 28 2025 Flow diverter treatment for internal carotid artery aneurysm following management of distal cerebral aneurysms: Technical note 100540 EN Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Hiramatsu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Sugiu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fukiko Baba Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Juntaro Fujita Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Sotome Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Kawakami Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryu Kimura Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Ebisudani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Haruma Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohito Hishikawa Department of Neurosurgery, Kawasaki Medical School Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: In recent years, the effectiveness of flow diverters (FDs) for the treatment of intracranial aneurysms has been reported. While FDs are effective, their deployment involves advancing a delivery wire distally, which may pose a risk if a distal aneurysm exists within the same artery. In such cases, the delivery wire could potentially perforate the distal aneurysm. Here, we present two cases of tandem aneurysms in which an internal carotid artery (ICA) aneurysm was treated with an FD following the treatment of a distal cerebral aneurysm. Case description: A 44-year-old woman and a 67-year-old woman underwent magnetic resonance imaging for headache or abducens nerve palsy. In both cases, two aneurysms were revealed: one at the ICA and the other either at the middle cerebral artery or the top of the ICA. Due to the risk of perforation by the delivery wire during FD deployment, the distal aneurysms were treated first—either with surgical neck clipping or stent-assisted coil embolization. One month after the initial treatment, FD placement for the ICA aneurysm was performed as planned without complications in either case. Discussion: This is the first report where tandem aneurysms were successfully treated with treatment for distal cerebral aneurysms, followed by FDs for proximal ICA aneurysms. We emphasize the potential risk of perforation of the distal aneurysm by the delivery wire during FD placement. Conclusion: Treatment of distal cerebral aneurysms beforehand can help ensure the safe and effective use of FDs in patients with tandem aneurysms. No potential conflict of interest relevant to this article was reported.

Japan Stroke Society Acta Medica Okayama 0912-0726 47 6 2025 頭蓋頚椎移行部動静脈瘻の開頭手術時における上腕動脈穿刺による脳血管撮影の有用性 410 412 EN Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Hiramatsu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Sasada Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Juntaro Fujita Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Sotome Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Kawakami Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryu Kimura Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Ebisudani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kyohei Kin Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Haruma Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Sugiu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 頭蓋頚椎移行部動静脈瘻の手術では，異常血管の確認のため術中血管撮影が重要であるが，体位変換時のsheathの固定や撮影血管へのカテーテルの誘導が困難である．今回，頭蓋頚椎移行部動静脈瘻の開頭手術において上腕動脈穿刺によりultra-long sheathを鎖骨下動脈に留置して椎骨動脈撮影（vertebral artery angiography: VAG）を行う方法の有用性を報告する．当院で本血管撮影を施行した症例の患者背景や合併症を評価した．企図した4例，5血管でVAGを施行でき，合併症も認めなかった．体位変換も腹臥位における穿刺部の観察も簡便であり，カテーテルの操作性にも優れ，VAGを容易に施行することができた．また，管球を頭側から移動する際の術野との干渉も最小限に抑えられた．本方法は利点が多く，有用な血管撮影方法であり，頭蓋頚椎移行部動静脈瘻の手術における一助となり得ると考える． No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Calcium ions play a critical role in calcification of Corynebacterium matruchotii 4591 EN Naoko Ohara Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Midori Ogawa Department of Microbiology, School of Medicine, University of Occupational and Environmental Health Katsuki Takebe Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ikue Tosa Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Serina Ono Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mitsumasa Saito Department of Microbiology, School of Medicine, University of Occupational and Environmental Health Naoya Ohara Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Dental calculus is a hardened deposit composed of calcium phosphate precipitated within dental plaque. While the involvement of dental calculus in the progression of periodontal disease is well established, many aspects of its formation process remain poorly understood. In this study, we focused on Corynebacterium matruchotii, a key bacterium involved in dental calculus formation, and investigated the role of calcium ions in calcification, as well as the associated internal and external changes in the bacterium through long-term observation. In the absence of calcium ions, no intracellular calcification was observed, and the lipid bilayer with the formation of holes in bacterial body was evident. In contrast, in the presence of calcium ions, lipid bilayer remained intact, and intracellular needle- and plate- like crystals were formed. Furthermore, calcified C. matruchotii showed increased flocculation compared to non-calcified C. matruchotii. These results indicate that the influx of calcium ions is essential for intracellular calcification. Calcium ions entry appears to reinforce the integrity of the lipid bilayer, providing a stable intracellular environment conductive to calcification. Moreover, calcified C. matruchotii may contribute to the nucleation of dental calculus by forming aggregates composed of both bacterial components and calcified material. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 11 2025 A Case of Psoas Abscess Diagnosed With Oral Bacteria as the Causative Pathogen e97584 EN Koki Umemori Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine Kyoichi Obata Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine Mayumi Yao Dentistry and Dental Surgery, Tsuyama Central Hospital Koji Fujita General Internal Medicine and Infectious Diseases, Tsuyama Central Hospital Soichiro Ibaragi Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine We report a rare case of a psoas abscess in an 87-year-old woman, in which oral commensal bacteria may have disseminated hematogenously from a chronic oral infection site and served as the causative pathogens. The patient presented with persistent left buttock pain, fever, and swelling, and imaging revealed a fracture of the left iliac bone with an associated psoas abscess. Bacterial cultures identified Streptococcus oralis and Pseudomonas aeruginosa. Her symptoms improved following antibiotic therapy and CT-guided drainage. Although the presence of P. aeruginosa in the oral cavity is generally considered transient, it has been isolated from the oral cavities of elderly and immunocompromised individuals. In the absence of lacerations or other direct portals of entry, and considering the identification of both pathogens, the oral cavity was regarded as the most likely source of infection. This case highlights the importance of correlating culture results with the most probable source of infection to improve the prognosis of systemic infections. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 3 2026 A Rare Association of Congenital Glaucoma and Retinitis Pigmentosa: A 22-Year Follow-Up Case e105012 EN Toshihiko Matsuo Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Primary congenital glaucoma is a rare congenital disease with a genetic background that shows high intraocular pressure due to ocular outflow anomalies. Retinitis pigmentosa is a predominant form of inherited retinal disorders. In this study, we present the case of a patient with primary congenital glaucoma in association with retinitis pigmentosa. A four-month-old female baby was brought to the emergency department due to corneal opacity in the left eye. The intraocular pressure measured by a hand-held applanation tonometer was 40 mmHg in the right eye and 36 mmHg in the left eye. She was otherwise healthy and diagnosed with primary congenital glaucoma. She immediately underwent trabeculotomy ab externo in both eyes under general anesthesia, and the intraocular pressure was lowered to 15 mmHg in the right eye and 12 mmHg in the left eye three weeks later. At the age of nine months, she was found to have retinal degeneration along the upper and lower vascular arcades of the fundus in both eyes and was diagnosed with retinitis pigmentosa. At the age of one year and 10 months, the visual acuity was measured at 0.2 in the right eye and 0.2 in the left eye for the first time by a preferential looking procedure. The intraocular pressure was 9 mmHg in both eyes under sedation, and she did not use any topical medication. At the age of three years and three months, the uncorrected visual acuity and best-corrected visual acuity with myopic astigmatism correction were 0.1 and 0.15, respectively, in the right eye and 0.6 and 0.7, respectively, in the left eye. Occlusion therapy with an eye patch over the left eye for one hour daily was started. At the age of four years and 10 months, the best-corrected visual acuity was 0.7 in both eyes. At the age of six years, occlusion therapy was discontinued, and full-correction glasses were prescribed, based on cycloplegic refraction. The visual acuity in the right eye decreased to 0.3 at the age of 11 years and further to 0.1 at the age of 12 years, while the visual acuity in the left eye remained 0.8. Afterwards, she maintained a visual acuity of 0.1 in the right eye and 0.8 in the left eye until the age of 22 years. An incidental presence of primary congenital glaucoma in this patient led to the detection of retinitis pigmentosa in earlier years and allowed long-term follow-up for 22 years. Even though genetic testing was not performed for this patient, the abnormal function of primary cilia, designated as ciliopathy, might explain the co-occurrence of primary congenital glaucoma and retinitis pigmentosa. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1999-4923 18 1 2026 Streamlined Radiosynthesis of [18F]Fluproxadine (AF78): An Unprotected Guanidine Precursor Enables Efficient One-Step, Automation-Ready Labeling for Clinical Use 123 EN Xinyu Chen Nuclear Medicine, Faculty of Medicine, University of Augsburg Kaito Ohta Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Kimura Agency for Health, Safety and Environment, Kyoto University Yusuke Yagi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Sasaki Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoko Nose Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaru Akehi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiko Yamane Department of Molecular Imaging Research, Kobe City Medical Center General Hospital Rudolf A. Werner Department of Nuclear Medicine, LMU Hospital, and German Cancer Consortium (DKTK), Partner Site Munich, Ludwig-Maximilians-University of Munich Takahiro Higuchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: [18F]Fluproxadine (formerly [18F]AF78) is a PET radiotracer targeting the norepinephrine transporter (NET) with potential applications in cardiac, neurological, and oncological imaging. Its guanidine moiety, while essential for NET binding, presents major radiosynthetic challenges due to high basicity and the harsh deprotection conditions required for protected precursors. Previous methods relied on multistep procedures, strong acids, and complex purification, limiting clinical translation. This study aimed to develop a practical one-step radiosynthesis suitable for routine and automated production. Methods: A direct SN2-type nucleophilic [18F]fluorination was performed using an unprotected guanidine precursor to eliminate deprotection steps. Reaction parameters, including the base system, solvent composition, precursor concentration, and temperature, were optimized under conventional and microwave heating. Radiochemical conversion (RCC) and operational robustness were evaluated, and purification strategies were assessed for automation compatibility. Results: Direct [18F]fluorination using the unprotected precursor reduced the total synthesis time to 60–70 min. Optimal conditions employed a tert-butanol/acetonitrile (4:1) solvent system with K2CO3/Kryptofix222, affording RCC up to 33% under conventional heating. Microwave irradiation further improved efficiency, achieving RCC of up to 64% within 1.5 min at 140 °C. The method showed broad tolerance to variations in the base molar ratio and precursor concentration and enabled isocratic HPLC purification. Conclusions: This one-step radiosynthesis overcomes longstanding challenges in [18F]fluproxadine production by eliminating harsh deprotection and enabling high-yield, automation-ready synthesis, thereby improving clinical feasibility. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 5 2026 Fgf10 Gene Dosage from a Single Allele Is Insufficient for Forming Multilayered Epithelial Cells in the Murine Lacrimal Gland 2113 EN Shiori Ikeda Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Keita Sato Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuki Tajika Department of Radiological Technology, Gumma Prefectural College of Health Sciences Hirofumi Fujita Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Bando Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsutomu Nohno Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Satoru Miyaishi Department of Legal Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hideyo Ohuchi Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mutations in the fibroblast growth factor 10 (FGF10) gene in humans cause aplasia of the lacrimal and salivary glands (ALSG). In patients with ALSG, heterozygous loss-of-function mutations are found, and FGF10 haploinsufficiency results in the absence of these secretory organs. Lacrimal glands (LGs) are formed through epithelial thickening, budding, and branching morphogenesis. To compare the variable phenotypes of the Fgf10+/− Harderian glands (HGs) previously reported, we examined the development of LGs in wild-type (WT), Fgf10+/−, and Fgf10-null mice. Pax6 immunostaining was performed to visualize the LG primordia from embryonic day 15.5 (E15.5) onwards. In situ hybridization of the genes encoding the epithelial receptor of FGF10, FGFR2b, and its other ligands was performed to determine their potential involvement in LG development. LG primordia were not observed in Fgf10+/− mice bilaterally at E16.5 or later stages. At E15.5, budding from the developing conjunctival epithelium (CE) was observed in a small fraction of the Fgf10+/− LG primordia. In contrast, the Fgf10-null CE failed to promote budding. Among Fgf1, Fgf3, Fgf7, Fgf10, and Fgf22, Fgf10 was expressed in the mesenchyme surrounding developing LG epithelial cells, whereas Fgf1 was expressed in the LG epithelium of WT mice. Fgf7 was initially expressed in the mesenchyme surrounding the nascent LG epithelium, but its expression subsequently became diffused. Thus, we conclude that among the FGFR2b ligands, initial LG formation is dependent on the mesenchymal factors FGF10 and FGF7, and FGF1 is likely to function as an epithelial factor in the LG primordia. A single allele of Fgf10 was found to be insufficient to support the budding process during LG morphogenesis. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 2169-3536 14 2026 FEM-Based Design and Characterization of a Millimeter-Scale Piezoelectric Resonance Force Sensor 17960 17970 EN Aoto Yamazaki Department of Mechanical Engineering, Toyohashi University of Technology Takuma Akiduki Department of Mechanical Engineering, Toyohashi University of Technology Atsuo Honna Riccoh Company Ltd. Michiteru Kitazaki Department of Computer Science and Engineering, Toyohashi University of Technology Tomoaki Mashimo Graduate School of Natural Science and Technology, Okayama University This paper presents a millimeter-scale piezoelectric effect-based force sensor that uses the change in its resonant frequency as the detection principle for high sensitivity and a wide measurement range. Such characteristics are suited for robot hand applications that not only detect small forces but also handle large payloads. We develop a methodology to estimate the relationship between applied force and resonant frequency shift by combining classical contact theory and finite element method (FEM) analysis. Although this relationship is non-linear, the designability of sensitivity and measurement range is demonstrated by the simulation. The simulation results based on the method are verified, showing good agreement with the experimental results. The static characteristics, including sensitivity, standard deviation, and resolution, are evaluated using prototype sensors with characteristic lengths ranging from 1 mm to 4 mm. The 4-mm model has a measurement range of 77 mN to 300 N, and the smallest model, which is one of the smallest force sensors suitable for practical implementation, has a measurement range of 9 mN to 20 N. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1757-2215 19 1 2025 Pan-cancer profiling links C1orf50 to DNA repair and immune modulation in ovarian cancer 13 EN Anna Rogachevskaya Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School Yusuke Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Akira Ohtsu Harvard Medical School Vanessa D. Chin UMass Chan Medical School, UMass Memorial Medical Center Tirso Peña Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School Seiji Arai Department of Urology, Gunma University Graduate School of Medicine Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Atsushi Fujimura Department of Molecular Physiology, Faculty of Medicine, Graduate School of Medicine, Kagawa University Atsushi Tanaka Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School Background C1orf50 encodes a small, evolutionarily conserved protein, the function of which remains unclear. Its significance across various human cancers, particularly its specific role in ovarian cancer within an immunogenomic context, is not yet fully understood. Utilizing The Cancer Genome Atlas and single-cell RNA sequencing (scRNA-seq) public datasets, we conducted a comprehensive profiling of C1orf50 across multiple cancer types, with a particular focus on ovarian cancer, to investigate its associations with copy-number status, genomic instability, tumor programs, and the immune microenvironment. Results Across cancer types, copy-number gain or amplification of C1orf50 was most frequent in ovarian cancer and closely tracked with higher messenger RNA levels. Higher C1orf50 expression was associated with a greater tumor mutational burden and homologous recombination deficiency, as indicated by gene-set patterns that suggested heightened cell-cycle and cellular stress responses accompanied by reduced oxidative phosphorylation, enrichment of regulatory T cells, and depletion of resting memory CD4 T cells. In ovarian cancer, focal events at chromosome 1p34.2 were accompanied by stepwise increases in C1orf50 expression by clinical stage and were linked to higher tumor mutational burden, homologous recombination deficiency, and greater loss of heterozygosity, together with more frequent gene alterations in BRCA1 or BRCA2. Immune composition clustered into profiles consistent with an immunosuppressive context in tumors with higher C1orf50 expression. The scRNA-seq data further revealed that cancer cells enhanced immune-suppressive interactions with various immune cell populations and diminished antigen-presentation signals. Analyses of genomic instability in ovarian cancer suggested mutational processes compatible with base-substitution patterns associated with cytidine deaminase activity and with insertion-deletion patterns characteristic of homologous recombination failure, while transcript-level patterns pointed to a broad downshift of canonical DNA repair activity with apparent compensatory adjustments in related pathways rather than a uniform change in any single pathway. Conclusions The overexpression of C1orf50 characterizes an aggressive immunogenomic phenotype in ovarian cancer, distinguished by genomic instability, impaired DNA repair mechanisms, and extensive immunosuppression. These findings indicate that C1orf50 warrants consideration as a potential biomarker and a prospective target for therapeutic investigation. Furthermore, they advocate for the progression to prospective validation and functional studies to ascertain its clinical significance. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2475-0328 9 6 2025 Surgery for Older Cancer Patients: Cross‐Organ Review and Good Practice Statement by the Japanese Geriatric Oncology Guideline Committee 1128 1136 EN Chie Tanaka Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine Takashi Ofuchi Department of Surgery, Kyushu University Beppu Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Inoue Department of Obstetrics and Gynecology, University of Fukui Ken Sugimoto Department of General Geriatric Medicine, Kawasaki Medical School Keiko Murofushi Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Toru Okuyama Department of Psychiatry/Palliative Care Center, Nagoya City University West Medical Center Shigeaki Watanuki National Center for Global Health and Medicine, National College of Nursing Chiyo Imamura Advanced Cancer Translational Research Institute, Showa University Daisuke Sakai Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine Naomi Sakurai Cancer Solutions Co. Ltd Kiyotaka Watanabe Division of Medical Oncology, Department of Medicine, School of Medicine, Teikyo University Kazuo Tamura NPO Clinical Hematology/Oncology Treatment Study Group Toshiaki Saeki Breast Oncology Service, Saitama Medical University International Medical Center Hiroshi Ishiguro Breast Oncology Service, Saitama Medical University International Medical Center Background: Although the number of older people is increasing, there is a lack of evidence and insufficient consensus regarding postoperative complications and survival in older cancer patients. In this study, we conducted a literature search and systematic review focusing on the outcomes after surgery for older cancer patients. Methods: Literature focusing on surgical treatment for older cancer patients was extracted from Japanese clinical practice guidelines for gastric cancer, lung cancer, colorectal cancer, liver cancer, and gynecological cancers (uterine body, uterine cervix, ovary, and external genitalia and vagina). Outcomes were reviewed, and committee members determined the strength of evidence on a four-point scale (A to D), with A being the highest and D being the lowest. Results: Older cancer patients tend to have a higher incidence of postoperative complications and postoperative syndromes, and their expected survival is generally shorter compared to non-older patients. When extensive surgeries such as para-aortic lymph node dissection and/or resection with other organs are performed for older cancer patients, the postoperative mortality rates tend to increase compared to non-older patients. Conclusion: Surgical treatments for older cancer patients tend to result in higher morbidity even when the patients are in good health status. Nevertheless, there is still a possibility that a certain fraction of the patients achieve treatment outcomes comparable to those of non-older patients. Therefore, surgical indication and procedure for older cancer patients should be carefully determined based on surgical invasiveness and patient tolerability. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2352-5789 59 2025 Evaluation of platinum-free interval and chemotherapeutic effect of subsequent platinum-containing chemotherapy in patients with recurrent ovarian cancer initially treated with bevacizumab: SGSG018/Intergroup study 101740 EN Tamaki Tanaka Department of Perinatology and Gynecology, Kagawa University Graduate School of Medicine Kazuhiro Takehara Department of Gynecologic Oncology, NHO Shikoku Cancer Center Tomoka Usami Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine Masako Ishikawa Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine Eiji Kondo Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine Masahiro Kagabu Department of Obstetrics and Gynecology, Iwate Medical University Kei Hirabayashi Department of Obstetrics and Gynecology, JCHO Tokuyama Central Hospital Noriomi Matsumura Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine Shinya Sato Department of Obstetrics and Gynecology, Faculty of Medicine Tottori University Masato Nishimura Department of Obstetrics and Gynecology, Tokushima Prefectural Central Hospital Atsushi Arakawa Department of Obstetrics and Gynecology, Nagoya City University West Medical Center Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Konno Department of Obstetrics and Gynecology, Hokkaido University Hospital Satoe Fujiwara Department of Obstetrics and Gynecology, Osaka Medical and Pharmaceutical University Kotaro Sueoka Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine Hiroko Nakamura Department of Obstetrics and Gynecology, NHO Kure Medical Center and Chugoku Cancer Center Iemasa Koh Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Hiroshima University Kimihiko Ito Department of Obstetrics and Gynecology, Kansai Rosai Hospital Atsushi Hongo Department of Obstetrics and Gynecology, Kansai Rosai Hospital Objective: The effect of bevacizumab on platinum sensitivity in recurrent ovarian cancer remains poorly understood. This study examined the association between platinum-free interval (PFI) and sensitivity to subsequent platinum-containing chemotherapy in patients with first relapsed ovarian cancer after bevacizumab chemotherapy. Methods: We retrospectively analyzed patients who received platinum-based chemotherapy for platinum-sensitive recurrence between November 2013, and December 2019, and who were initially treated by platinum-based chemotherapy with concurrent and maintenance bevacizumab. The primary endpoint was response rate to subsequent chemotherapy after various periods of PFI. The relevance between response rate and PFI was assessed for each PFI of 6–12, 12–24 and ≧24 months using Cochran-Armitage test. The secondary endpoint was progression-free survival (PFS) defined as time from chemotherapy for first recurrence to subsequent progression and response rate to subsequent chemotherapy for each treatment-free interval since last administration of bevacizumab (Bev-TFI). Results: A total of 77 patients were eligible. The median PFI until first recurrence was 12 months (range: 6–43). The response rates of subsequent chemotherapy for patients with PFI of 6–12, ≥12-24, and 24 months were 42 %, 65 %, and 80 %, showing a linear trend (p < 0.05). Median PFS among the three groups was 8 (95 %CI: 6.7–9.2), 11 (95 %CI: 8.4–13.5) and 13 months (95 % CI: 5.4–20.5) (p = 0.107, log-rank test), respectively. By contrast, no linear trend was observed between Bev-TFI and response rate (p = 0.225) Conclusion: In patients with first relapse of primary ovarian cancer and bevacizumab beyond progression, the prolonged PFS effect of bevacizumab does not seem to affect sensitivity to subsequent platinum-based chemotherapy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1068-9265 32 12 2025 Mesenteric Route Superior Mesenteric Artery First Approach in Robot-Assisted Pancreatoduodenectomy 8903 8905 EN Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atene Ito Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tsubasa Yanagihara 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. The superior mesenteric artery (SMA) approach is crucial for the successful implementation of robot-assisted pancreatoduodenectomy (RPD). Herein, we present a novel technique, the mesenteric route SMA-first approach, for RPD. Patients and Methods. A 20-year-old woman with a 50 mm intraductal papillary mucinous neoplasm underwent RPD. As the tumor was large and located close to the mesenteric vessels, we developed the mesenteric route SMA-first approach. Results. Following the mesenteric Kocher maneuver, the mesenteric route SMA-first approach was applied. With appropriate retraction of the pancreatic head, dissection around the mesenteric vessels was performed and their branches were divided. The uncinate process dissection (PL, ph II) was performed via the mesenteric route. This approach facilitated dorsal dissection, particularly around the large tumor. After dissection of the hepatoduodenal ligament, the remaining pancreatic nerve plexus (PL ph I) was dissected. Finally, the pancreas was divided on the superior mesenteric vein, and the specimen was resected. Operative time was 390 min with minimal blood loss. Conclusions. The mesenteric route SMA-first approach enables uncinate process dissection via the mesenteric route. This technique may be a safe and feasible option for selected patients, such as nonobese individuals with a large pancreatic head tumor near major vessels. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2210-2612 133 2025 Robotic pancreatoduodenectomy for a giant duodenal leiomyoma: A case report and literature review 111546 EN Susumu Doita Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Introduction: Duodenal leiomyomas are rare mesenchymal tumors. To date, several studies have reported on the safety and feasibility of surgical intervention for duodenal leiomyomas. However, minimally invasive surgery has rarely been performed in cases with duodenal leiomyomas. Herein, we present a case of a giant duodenal leiomyoma successfully treated with robotic pancreatoduodenectomy (RPD). Presentation of case: A 74-year-old man was referred to our hospital with a 6.5 cm duodenal tumor accompanied by gastrointestinal bleeding. The tumor was located in the second portion of the duodenum. Considering the tumor size and location, RPD was performed. Using the mesenteric Kocker maneuver, the posterior side of the duodenum was safely dissected, and the tumor was resected. The operative time was 373 min, with an estimated blood loss of 10 mL. The patient was followed up for 7 months with no recurrence. Discussion: To the best of our knowledge, this is the first to highlight the clinicopathological findings of a patient with duodenal leiomyoma undergoing RPD. To date, there have been 19 cases, including our case, reporting surgically treated duodenal leiomyoma. Treatment strategies should be decided depending on tumor characteristics, including the size, location, and histology of the tumor. Conclusion: We present a rare case of a giant duodenal leiomyoma that was successfully treated with RPD. Minimally invasive surgery can be safe and an alternative for the treatment of large duodenal tumors. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1435-2451 410 1 2025 Robotic distal pancreatectomy using two-surgeon technique (TAKUMI-4): a technical note and initial outcomes 171 EN Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Purpose With the increasing use of minimally invasive distal pancreatectomy, the use of robotic distal pancreatectomy (RDP) is also increasing worldwide. Standardized surgical protocols are essential for safe implementation of RDP. In this study, we present our surgical protocol and initial outcomes of RDP using “two-surgeon technique”. Methods Our standard RDP protocol included a two-surgeon technique for cooperation, rationality, and education. Short-term outcomes of RDP were also investigated. This retrospective study included 77 consecutive patients who underwent RDP at our institution between April 2021 and January 2025. Results The median operative time, estimated blood loss, and postoperative hospital stay were 214 min (interquartile range [IQR], 176–253), 10 mL (IQR, 0–50), and 9 days (IQR, 8–10), respectively. A textbook outcome was achieved in 84.4% of patients. Moreover, superior outcomes of RDP (n = 77) compared with those of laparoscopic distal pancreatectomy (n = 62) were confirmed in this study. Conclusion Using the two-surgeon technique, we successfully standardized and introduced the RDP program. The two-surgeon technique can contribute to the safe introduction of RDP and expansion of the program. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 30 7 2025 How to report and discuss subgroup analyses in clinical practice guidelines? Evaluation procedure of the clinical and statistical relevancy 1259 1267 EN Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Satoru Miura Department of Internal Medicine, Niigata Cancer Center Hospital Yuko Oya Department of Respiratory Medicine and Allergy, Fujita Health University Tomohiro Sakamoto Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori University Kentaro Tanaka Graduate School of Medical Sciences, Research Institute for Diseases of the Chest, Kyushu University Shunsuke Teraoka Internal Medicine III, Wakayama Medical University Masahiro Morise Department of Respiratory Medicine, Nagoya University Graduate School of Medicine Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University The results of subgroup analyses of clinical trials are important reference information when considering the generalizability of a study treatment, i.e., providing the best treatment for each individual patient. The results of subgroup analyses are often presented in publications, etc. as forest plots focusing on patient backgrounds. However, it is important to fully understand and grasp some of the issues involved in subgroup analyses and to interpret the results carefully to apply them in clinical practice. Although the literature includes some reports on how subgroup analyses should be evaluated and handled for the purpose of establishing medical practice guidelines, most of the papers have mainly evaluated the reliability of subgroup analyses from a statistical perspective; few of them have incorporated clinical importance in their evaluations. Therefore, in December 2019, we established a Subgroup Analysis Review Committee consisting of oncologists specializing in lung cancer treatment and statistical experts among the members of the Guidelines Review Committee of the Japanese Lung Cancer Association, with the aim of appropriately reflecting subgroup analysis in Japanese lung cancer practice guidelines. We developed a new evaluation strategy to incorporate clinical aspects as well as reliability assessment. Specifically, on the basis of a clinical and statistical review of the problems with subgroup analyses presented as clinical trial results, we developed criteria and procedures to ensure consistency and fairness in the citation of clinical guidelines. 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 Retreatment With EGFR-Tyrosine Kinase Inhibitor After Disease Progression Following Gefitinib Induction and Chemoradiotherapy in EGFR-Mutant Stage III Non-small Lung Cancer: An Efficacy and Safety Analysis of the LOGIK0902/OLCSG0905 Study e86575 EN Sho Saeki Department of Respiratory Medicine, Kumamoto University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Shinya Sakata Department of Respiratory Medicine, Kumamoto University Hospital Naohiro Oda Department of Respiratory Medicine, Okayama University Hospital Koji Inoue Department of Respiratory Medicine, Kitakyushu Municipal Medical Center Tomoki Tamura Department of Respiratory Medicine, Okayama University Hospital Ryo Toyozawa Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center Daijiro Harada Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center Kentaro Tanaka Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University Koji Inoue Department of Respiratory Medicine, Ehime Prefectural Central Hospital Yoshiyuki Shioyama Radiation Oncology, Ion Beam Therapy Center, SAGA HIMAT Foundation Kenichi Gemba Department of Respiratory Medicine, Chugoku Central Hospital Tomonari Sasaki Department of Radiation Oncology, Iizuka Hospital Akihiro Bessho Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Junji Kishimoto Center for Clinical and Translational Research, Kyushu University Hospital Kuniaki Katsui Department of Radiology, Division of Radiation Oncology, Kawasaki Medical School Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Kenji Sugio Thoracic and Breast Surgery, Oita University Background and objective: We had previously conducted a phase II study (LOGIK0902/OLCSG0905 study) involving the eight-week administration of gefitinib, followed by cisplatin-based chemoradiotherapy, to treat locally advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC). Despite favorable overall survival outcomes, more than half of the patients relapsed after the protocol therapy, highlighting the need to clarify the clinical significance of retreatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated the efficacy and safety of EGFR-TKI retreatment after disease progression. Materials and methods: We included 14 patients who relapsed after the protocol treatment and received any type of EGFR-TKI as post-progression treatment in this sub-analysis. We evaluated the efficacy and safety of retreatment with EGFR-TKI in these patients. Results: Among the 14 patients, 11 (78.6%) responded to the induction of gefitinib in the treatment protocol. After relapse, 9/14 patients (64.3%) received gefitinib, 3/14 (21.4%) received afatinib, and 2/14 (14.3%) received erlotinib monotherapy, respectively. The median duration of post-progression EGFR-TKI treatment was 17.9 (0.7-45.5) months. The overall response rate (ORR) and disease control rate were 64.3% [9/14 patients; 95% confidence interval (CI): 35.1%-87.2%] and 85.7% (12/14 patients; 95% CI: 57.2%-98.2%), respectively. The median progression-free survival (PFS) and median survival durations after the initiation of EGFR-TKI retreatment were 11.8 months (95% CI: 5.7-20.7 months) and 47.4 months (95% CI: 31.8 months to not estimable), respectively. Adverse events were comparable to those previously reported. Conclusions: Patients with disease progression after protocol therapy demonstrated sensitivity to retreatment with an EGFR-TKI, with acceptable safety. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 64 14 2025 Myeloid Sarcoma in the Small Intestine 2155 2159 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Kamio Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shoichiro Hirata Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsunori Matsueda Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daisuke Kametaka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Seiji Kawano 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 Myeloid sarcoma is a rare extramedullary tumor of immature myeloid cells that is often associated with acute myeloid leukemia (AML). We herein report an 81-year-old man who presented with intestinal obstruction due to myeloid sarcoma of the small intestine. Diagnostic challenges were overcome using double-balloon enteroscopy and a biopsy, which confirmed the diagnosis of myeloid sarcoma. The patient subsequently developed AML but responded well to chemotherapy. This case underscores the importance of considering myeloid sarcoma in the differential diagnosis of small-bowel tumors. Highlighting the significance of a histological analysis, even in patients presenting with small bowel obstruction, the early diagnosis and treatment are crucial for improving outcomes, particularly in patients without a history of hematologic malignancies. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 5 2025 Pseudoachalasia Due to Malignant Pleural Mesothelioma Involving the Esophagus e84161 EN Manami Honda Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences We report a rare case of pseudoachalasia secondary to malignant pleural mesothelioma involving the esophagus. A 66-year-old man presented with progressive dysphagia, weight loss, and postprandial hiccups. Endoscopic examination showed esophageal dilation with luminal narrowing at the esophagogastric junction, but no mucosal abnormalities. Computed tomography revealed an irregular-shaped mass extending from the peri-esophagogastric junction to the retroperitoneum, accompanied by pleural effusion, right-sided hydronephrosis, and multiple hepatic lesions. Endoscopic ultrasound-guided fine-needle aspiration from the mass lesion through the esophageal lumen revealed epithelioid malignant mesothelioma. This case highlights the importance of considering malignant mesothelioma in the differential diagnosis of pseudoachalasia, particularly when imaging reveals extrinsic esophageal compression without mucosal lesions. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 2950-2217 3 2 2025 Erythromelalgia presenting with posterior reversible encephalopathy syndrome: A pediatric case report 100078 EN Kengo Suzuki Department of Pediatrics, Okayama University Hospital Kazuhiro Uda Department of Pediatrics, Okayama University Hospital Mitsuru Tsuge Department of Pediatric Acute Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kyosuke Arakawa Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Shigehara Department of Pediatrics, Okayama University Hospital Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Erythromelalgia is a rare disorder characterized by erythema, warmth, and burning pain in the extremities. We report a pediatric case of erythromelalgia in a patient who developed posterior reversible encephalopathy syndrome (PRES), without any cutaneous signs. Case presentation: A previously healthy 12-year-old girl presented to our pediatric clinic with burning extremity pain that had persisted for 6 weeks. The patient was treated with analgesics; however, the pain was refractory to these agents. Seven days after the first visit, she developed afebrile seizures and was transferred to our hospital. Her initial blood pressure was 139/105 mmHg (+2.0 SD), and brain magnetic resonance imaging revealed high intensity areas in the bilateral parietal and occipital lobes, leading to a diagnosis of PRES. Her blood pressure was difficult to control with anti-hypertensive agents. Burning pain in her extremities was relieved by cooling and worsened by warming. Although erythema was not observed in her hands or legs, erythromelalgia was suspected based on the characteristic nature of her pain. Intravenous lidocaine was administered for diagnosis, which was dramatically effective. After initiating mexiletine, the burning pain in her extremities disappeared, and hypertension improved. A final diagnosis of erythromelalgia with PRES was made. Conclusion: A history of temperature-dependent pain relief and deterioration are important indicators of disease diagnosis, even if patients indicate a lack of erythema or warmth. Physicians should be aware that persistent pain due to erythromelalgia can lead to refractory hypertension and development of PRES. No potential conflict of interest relevant to this article was reported.

岡山大学農学部 Acta Medica Okayama 2186-7755 115 2026 北海道東部の森林において林冠木の細根が土壌窒素動態に与える影響 9 12 EN Masataka Nakayama Course of Environmental Ecology 　Plants release mixtures of labile organic matter from their fine roots (root exudates) into the surrounding soil (rhizosphere). Partly due to the release of root exudates, microbial community structures and their activities within the rhizosphere differ significantly from those in other soil areas (bulk soil). Consequently, nutrient cycling processes, including nitrogen mineralization, are accelerated in the rhizosphere, facilitating nutrient acquisition by plants. This phenomenon, known as the rhizosphere effect, has been repeatedly reported in studies of herbaceous plants; however, the impact of canopy tree fine roots on soil nitrogen dynamics through the effect in forest ecosystems remains largely unknown. Here, I introduce our research investigating the root exudates and rhizosphere effects of the fine roots of canopy trees, Quercus crispula, and how these fine roots affect soil nitrogen dynamics. The quantity of root exudates varied daily rather than seasonally, with solar radiation having a strong and positive effect on the amounts. However, even after leaf fall, root exudation was observed. In the rhizosphere, specific bacterial communities were present regardless of season, while ectomycorrhizal fungal populations were higher than in the bulk soil only in summer. Extracellular enzymatic activity relating to nitrogen cycling was higher in the rhizosphere than in the bulk soil across seasons. Nitrogen uptake by the tree was likely lower in winter and spring, leading to labile nitrogen accumulation in the rhizosphere during these periods. On an annual basis, however, the impact of fine roots on apparent inorganic nitrogen dynamics was minor. These results suggest that the canopy tree, Q. crispula, accelerates soil nitrogen cycling through root exudation and rhizosphere effects, regardless of season, while the acceleration of the cycle and the utilization of available nitrogen are well-balanced annually, thereby avoiding unnecessary carbon investment. No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 ピア・AI・教員の三者協働フィードバックによるライティング授業の再設計 ―AI利用の実践報告－ 174 194 EN Mariko Uzuka Institute for Promotion of Education and Campus Life 10.18926/70120 本稿は、アカデミック・ライティング授業におけるピア・AI・教員のそれぞれの役割と利用順序（自分→ピア→AI→（省察）→教員）を組み込んだ三者協働モデルを設計し、2024～2025年度に実践した内容を報告する。授業後の学生アンケートでは、AIの即時性・精緻化が評価される一方、依存や有効性の限界に関する懸念も表明された。成績分布においては、AI導入後に下位層が縮小し、学習成果の底上げが示唆された。また、AI誤用や濫用を防ぐには、教室内で建設的な利用法の具体的な指導（例：例文より診断的フィードバックを重視、AI提案の採否理由のメタ記述）が効果的であった。これらの結果から、AIの利点を活かしつつ、学生の判断を中心に据えるライティング授業設計の有効性と課題を提示する。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 From The Odyssey to The Zahir：The Evolution of Penelopeia Across Time and Tradition 120 128 EN Saida KHALMIRZAEVA Faculty of General Education and Global Studies, Okayama University 10.18926/70116 The story of a man who leaves home and strives to return has become one of the most enduring narrative patterns in world literature and folklore. Across centuries and cultures, it has been retold in myths, epics, folktales, and modern fiction—the story of the homecoming hero who, after long absence and peril, finds his way back to the place and the person he once called his own. This study explores the persistence and transformation of this universal motif through a comparative reading of Homer’s The Odyssey and Paulo Coelho’s The Zahir. It examines the evolving image of the waiting wife—from Homer’s Penelopeia, emblem of chastity and endurance, to Coelho’s Esther, a modern woman of independence and choice. Despite differences in setting, voice, and moral vision, both works embody the same human longing: to return, to be recognized, and to rediscover love that endures time and change. Beneath their differences lies the same truth—the heart to which every journey, whether physical or spiritual, must ultimately return. 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.

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

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 1 2026 Saliva as a Reliable and Non-invasive Sample for Detecting Influenza A in Severe Acute Respiratory Infection Cases e100872 EN Junko S Takeuchi Department of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health Security Nobuaki Matsunaga Antimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health Security Ai Tsukada Antimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health Security Noriko Iwamoto Disease Control and Prevention Center, Japan Institute for Health Security Noriko Fuwa Disease Control and Prevention Center, Japan Institute for Health Security Takahiro Ichikawa Department of Infectious Diseases, Sapporo City General Hospital Yasuyuki Kato Department of Infectious Diseases, International University of Health and Welfare (IUHW) Narita Hospital Yuka Tomita Department of Infectious Diseases, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital Hiroki Kitagawa Department of Infectious Diseases, Hiroshima University Hospital Masaya Yamato Department of General Internal Medicine and Infectious Diseases, Rinku General Medical Center Tetsuji Aoyagi Department of Clinical Infectious Diseases, Tohoku University Graduate School of Medicine Hideharu Hagiya Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryota Hase Department of Infectious Diseases, Japanese Red Cross Narita Hospital Shuji Hatakeyama Division of Infectious Diseases, Jichi Medical University Hospital Tohru Inaba Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine Koichi Izumikawa Yoshio Takesue Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences Moto Kimura Department of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health Security Norio Ohmagari Disease Control and Prevention Center, Japan Institute for Health Security Background Nasopharyngeal swab sampling remains the gold standard for influenza diagnosis; however, it has several limitations, including dependence on medical staff, invasiveness, potential for nosocomial transmission, and occupational exposure risk. Non-invasive alternatives, such as saliva and nasal vestibular swabs, may improve patient comfort and participation in clinical studies. In addition, diagnosis with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) is often delayed because it requires trained laboratory technicians and facilities with appropriate laboratory settings. Although rapid diagnostic devices such as the GenPad® offer potential alternatives to RT-qPCR, their performance with non-invasive samples remains insufficiently explored. This study addresses the two key questions for influenza detection in severe acute respiratory infection (SARI) cases: (i) whether saliva or nasal vestibular swab samples serve as suitable alternatives to nasopharyngeal swab samples, and (ii) whether the GenPad® provides a reliable option for detecting influenza using saliva samples. Methodology A prospective observational study was conducted with 16 inpatients classified as having SARIs and diagnosed with influenza between December 2024 and March 2025 in Japan. Paired saliva and nasal vestibular swab samples were collected 1-9 (median = 3.5) days after symptom onset. RT-qPCR testing was performed according to the National Institute of Infectious Diseases protocol. Saliva samples were also tested using the GenPad® system. Comparisons between sample types and diagnostic methods were analyzed using the exact McNemar's test. Results Among the 16 influenza-positive patients, saliva samples demonstrated higher sensitivity (87.5%) than nasal vestibular swabs (31.3%) in RT-qPCR when compared with the diagnostic results obtained from nasopharyngeal swabs. A comparison of RT-qPCR results between saliva and nasal vestibular swabs revealed a total agreement of 43.8%, with exact McNemar's test showing a significant difference (p = 0.0039). While nasal vestibular swabs showed inconsistent results, saliva samples consistently tested positive, particularly within seven days of symptom onset (100% positive agreement). The GenPad®, a rapid diagnostic device, showed promising performance (92.9%) using saliva samples compared to RT-qPCR. Conclusions Saliva is a reliable non-invasive alternative to nasopharyngeal swabs for influenza detection in SARI cases, particularly within seven days of symptom onset, whereas nasal vestibular swabs show lower sensitivity. Additionally, the GenPad® provides comparable performance to RT-qPCR using saliva samples, offering a rapid, portable diagnostic option. These approaches may mitigate discomfort, minimize infection risk for healthcare workers, and improve testing capacity. However, the absence of influenza-negative controls and the small sample size (n = 16) substantially limit the assessment of diagnostic accuracy and specificity. As a result, the broader applicability of our findings should be interpreted with caution, and further studies are required to validate these observations. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 0007-1188 2026 Induction of IL-9-producing CD8+ T cells by ascochlorin derivatives EN Natsumi Imano Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Mikako Nishida Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Miho Tokumasu Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Weiyang Zhao Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Nahoko Yamashita Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Heiichiro Udono Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background and Purpose: Ascochlorin (ASC) is an antiviral antibiotic from the fermented broth of Ascochyta viciae which exerts an inhibitory effect to cancers. Its impact on immune cells has not been examined. In this study, we obtained ASC derivatives with less cytotoxicity and determined whether they affected T cells, indicating possible immune-mediated antitumour effects. Experimental Approach: Newly synthesised ASC derivatives were screened for inhibitory effects on T-cell antigen receptor (TCR)-stimulated proliferative responses using murine CD4+ and CD8+ T cells. Two compounds were identified that exhibited >10-fold less toxicity compared with ASC. N184, the less toxic of the two, was analysed for its in vivo antitumour effects, and in vitro effects on CD8+ T-cell proliferation, survival, cytokine production and exhaustion, using microscopy, qPCR and flow cytometry. Key Results: N184 induced limited IL-9 production in CD8+ T cells following TCR stimulation, thereby improving cell survival. It also enhanced cytokine production in the late phase of proliferation and suppressed the induction of exhaustion. N184 suppressed tumour growth in mice in a CD8+ T cell-dependent manner. The effect was partially prevented by an IL-9-neutralising antibody. Conclusion and Implications: N184 induces differentiation of IL-9-producing CD8+ T cells in vitro and elicits antitumour immunity in an IL-9-dependent manner. No potential conflict of interest relevant to this article was reported.

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

MDPI AG Acta Medica Okayama 1999-4893 19 2 2026 A Slide Annotation System with Multimodal Analysis for Video Presentation Review 110 EN Amma Liesvarastranta Haz Department of Information and Communication Systems, Okayama University Komang Candra Brata Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Htoo Htoo Sandi Kyaw Department of Information and Communication Systems, Okayama University Evianita Dewi Fajrianti Human Centric Multimedia Research Laboratory, Department of Informatic and Computer Engineering, Politeknik Elektronika Negeri Surabaya Sritrusta Sukaridhoto Human Centric Multimedia Research Laboratory, Department of Informatic and Computer Engineering, Politeknik Elektronika Negeri Surabaya With the rapid growth of online presentations, there has been an increasing need for efficient review of recorded materials. In typical presentations, speakers verbally elaborate on each slide, providing details not captured in the slides themselves. Automatically extracting and embedding these verbal explanations at their corresponding slide locations can greatly enhance the review process for audiences. This paper presents a Slide Annotation System that employs a robust hybrid two-stage detector to identify slide boundaries, extracts slide text through Optical Character Recognition (OCR), transcribes narration, and employs a multimodal Large Language Model (LLM) to generate concise, context-aware annotations that are added to their corresponding slide locations. For evaluations, the technical performance was validated on five recorded presentations, while the user experience was assessed by 37 participants. The results showed that the system achieved a macro-average 𝐹1 score of 0.879 (𝑆𝐷=0.024, 95% 𝐶𝐼[0.849,0.909]) for slide segmentation and 90.0% accuracy (95% 𝐶𝐼[74.4%,96.5%]) for annotation alignment. Subjective evaluations revealed high annotation validity and usefulness as rated by presenters, and a high System Usability Scale (SUS) score of 80.5 (𝑆𝐷=6.7, 95% 𝐶𝐼[78.3,82.7]). Qualitative feedback further confirmed that the system effectively streamlined the review process, enabling users to locate key information more efficiently than standard video playback. These findings demonstrate the strong potential of the proposed system as an effective automated annotation system. 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 A Novel Nomogram that Predicts Chronic Hemodialysis Patients’ Survival Based on Their Sedentary Behavior 9 16 EN Kentaro Sugahara Department of Hygiene, Faculty of Medicine, Kagawa University Takashi Kondo Innoshima General Hospital Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Hiroyuki Nishi Innoshima General Hospital Kazuhiro Ujike Innoshima General Hospital Kiichi Koumoto Innoshima General Hospital Keiichi Namio Department of Hygiene, Faculty of Medicine, Kagawa University Shuhei Hishii Department of Hygiene, Faculty of Medicine, Kagawa University Akihiko Katayama Faculty of Social Studies, Shikokugakuin University Hiromi Suzuki Department of Hygiene, Faculty of Medicine, Kagawa University Yorimasa Yamamoto Innoshima General Hospital Original Article 10.18926/AMO/70068 Appropriate treatments for chronic hemodialysis patients are a public health challenge in Japan. Sedentary behavior appears to be closely associated with these patients’ survival. We thus sought to develop a nomogram that predicts survival based on the duration of chronic hemodialysis patients’ sedentary behavior. One hundred twenty-four patients under chronic hemodialysis (73 men, 51 women, age 71.7±11.1 years) were enrolled in this cohort study. The patients wore a triaxial accelerometer that measured both their sedentary behavior, i.e., total sedentary behavior (minutes) and their maximum sedentary bouts (min) on non-hemodialysis days. We obtained the Kaplan-Meier curve and used the log-rank test and a Cox proportional hazards model to evaluate the relationship between the patients’ sedentary behavior and their survival. We also used a Cox proportional hazards model to develop a nomogram for the patients’ 5-year survival rate. Forty-six patients died during the follow-up period. When we stratified the patients by the medians of total sedentary behavior and maximum sedentary bouts, we observed significant between-group differences. After adjustment for confounding factors in a Cox proportional hazards model, total sedentary behavior and maximum sedentary bouts were identified as critical survival factors, and we generated a nomogram using an index of sedentary behavior. Our analysis results demonstrated that sedentary behavior on non-dialysis days was closely associated with the survival of the chronic hemodialysis patients, suggesting that a decrease in sedentary behavior would prolong their survival. The nomogram developed herein based on sedentary behavior may be useful for predicting the outcomes of chronic hemodialysis patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Usefulness of D-dimer Assay to Confirm the Course of Overt Venous Thromboembolism (VTE) in Cancer Patients 1 7 EN Hidenaru Yamaoka Department of Cardiovascular Medicine, IMS Tokyo Katsushika General Hospital Masashi Yoshida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Sarashina Seisukai Kuroda Clinic Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuru Munemasa Department of Cardiovascular Medicine, Okayama Rosai Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/70067 Venous thromboembolism (VTE) is a serious complication in patients with cancer. In this population, the presence of thrombi is often assessed at cancer diagnosis by measuring D-dimer levels, which have high sensitivity but low specificity for identifying VTE at this clinical time point. However, the usefulness of D-dimer measurement during anticoagulation therapy has not been fully established, despite its widespread use. In this retrospective observational study, we investigated whether D-dimer measurement during anticoagulation therapy in cancer patients could predict overt VTE at follow-up. The study included patients who underwent D-dimer testing and contrast-enhanced computed tomography between 30 and 100 days after initiation of anticoagulation therapy. Eighty-two patients were included: 60 with cancer and 22 without. The diagnostic performance of D-dimer for overt VTE was as follows: sensitivity, 85.7%; specificity, 87.2%; positive predictive value, 78.3%; and negative predictive value, 89.2%. These findings suggest that D-dimer measurement at follow-up has high sensitivity and specificity for overt VTE in cancer patients and may aid in assessing thrombotic status. Clinically, if anticoagulation therapy is continued until D-dimer levels become negative, the absence of overt VTE could be inferred without additional invasive testing. No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 「新羅村落文書」に記された村の比定地 ―西原京所属の村（いわゆるＤ村）の検討― 40 53 EN Nana MURAKAMI Research Institute for the Dynamics of Civilizations, Okayama University 研究ノート (Research note) 10.18926/70053 The Silla Village Register is a fragmentary record from the Unified Silla period that details the economic conditions of villages under the jurisdiction of small capitals (小京) and local counties (郡 / 県). In analyzing this register, it is essential to consider the geographical conditions of the locations; however, the exact locations of the villages have long remained unidentified in previous studies. Therefore, this study builds on the readings proposed by Choi Kyŏng-sŏn ( 최 경 선 ) and examines official histories and geographical texts from the Chosŏn dynasty, as well as topographic maps from the early 20th century. As a result, this paper proposes a concrete candidate for the location of one of the four villages under the jurisdiction of Sŏwŏn-gyŏng (西原京), commonly referred to as Village D. It has been clarified that Village D can be read as " 西原京□椒子村" and it is highly likely to correspond to present-day Chojŏng-ri, Naesu-ŭp, Heungdeok-gu, Cheongju City (清州市清原区内秀邑椒井里). It was also found that Village D’s characteristic of having few rice paddies and a high proportion of upland field cultivation closely matches the actual local geographical conditions, which are characterized by limited water resources. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 5 1 2026 Cardiogenic cerebral infarction after Takotsubo cardiomyopathy in a patient with catatonia: A case report e70285 EN Masaki Fujiwara Department of Neuropsychiatry, Medical Development Field, Okayama University Yuto Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center Shinji Sakamoto Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Kodama Okayama Psychiatric Medical Center Background: Takotsubo cardiomyopathy (TTC) is a transient cardiac condition often triggered by an emotional or physical stress. TTC usually has a benign clinical course with full recovery. However, in rare cases, TTC is complicated by cardiogenic shock, left ventricular rupture, or ventricular thrombus. We report a case of a patient with catatonia who developed TTC and subsequently experienced extensive cerebral infarction. Case Presentation: A 71-year-old woman with no prior psychiatric history was admitted for catatonia following a suicide attempt. During hospitalization, she exhibited electrocardiography (ECG) abnormalities and elevated D-dimer levels. Transthoracic echocardiography revealed apical hypokinesis and basal hyperkinesis, consistent with TTC, along with an intraventricular thrombus. Cardiovascular CT angiography confirmed normal coronary arteries. She was diagnosed with TTC complicated by left ventricular thrombus and deep vein thrombosis. Anticoagulant therapy was initiated. Despite improvement in catatonia with lorazepam, she developed right hemiplegia and aphasia on Day 5 due to cardiogenic cerebral infarction from thromboembolism. Thrombolytic therapy was not indicated, and conservative treatment was provided. Although cardiac function normalized by Day 16, she was left with severe neurological deficits. Conclusion: The case highlights the diagnostic challenges of TTC in non-communicative psychiatric patients and the potential for severe complications. Psychiatrists need to be aware of the development of TTC as a serious physical complication in patients with catatonia. No potential conflict of interest relevant to this article was reported.

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

Japanese Society of Tribologists Acta Medica Okayama 1881-2198 20 4 2025 Tribological Properties of Amorphous-SiC-Based Coatings on Al2O3 Substrates in Normal Saline 212 219 EN Tadashi Shiota Faculty of Environmental, Life, Natural Science and Technology, Okayama University Daiki Taniya Graduate School of Natural Science and Technology, Okayama University Kazuma Shimazaki Graduate School of Natural Science and Technology, Okayama University Chiyu Nakano Department of Comprehensive Technical Solutions, Okayama University Yuya Omiya Faculty of Environmental, Life, Natural Science and Technology, Okayama University Masahiro Fujii Faculty of Environmental, Life, Natural Science and Technology, Okayama University Amorphous SiC (a-SiC)-based coatings containing not only Si–C bonds but also C–Si–O, C–C, and Si–O2 bonds were deposited on Al2O3 substrates via pulsed laser deposition. Sliding tests using SiC ceramic balls in normal saline revealed that the coating exhibited a low friction coefficient of 0.05-0.06 at a shorter running-in process than SiC bulk ceramic plates. The specific wear rate of the coating was also lower than that of the SiC plate. Reactive molecular dynamics simulations revealed that the C–Si–O bonds in the coating facilitated the generation of Si–O units, which contained Si–O bonds but no Si-C bonds, through tribochemical reactions with water, resulting in superior tribological properties in normal saline compared to those of SiC plates. These findings demonstrate that a-SiC-based coatings containing C–Si–O bonds are promising as low-friction and low-wear coatings for biomedical implants such as ceramic joint prostheses. No potential conflict of interest relevant to this article was reported.

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

Baishideng Publishing Group Inc. Acta Medica Okayama 1948-5190 17 12 2025 Endoscopic features of oral and pharyngolaryngeal papillomas and their role in distinguishing squamous cell carcinoma 110594 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Hospital Kenta Hamada 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 Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, 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 Oral and pharyngolaryngeal papillomas are occasionally detected during esophagogastroduodenoscopy. However, their endoscopic features have not been sufficiently investigated. AIM To distinguish oral and pharyngolaryngeal papillomas from elevated squamous carcinomas, this study examined their endoscopic features. METHODS Forty-seven patients with oral or pharyngeal papilloma participated in this study. The endoscopic characteristics of papillomas were identified by focusing on narrowband and blue laser imaging representations. RESULTS Papillomas were classified into three patterns based on their endoscopic features: Salmon roe-like polyps, polyps without capillary transparency, and pinecone-like polyps, with salmon roe-like polyps most prevalent (48.9%). We subsequently analyzed features differentiating papillomas and squamous cell carcinomas in the same region and found that squamous cell carcinomas exhibited at least one of the following three features: Uneven or absent lobulated structure, irregular morphology of capillaries, and coexistence of flat lesions. In contrast, papillomas displayed a uniform lobulated structure, homogeneous or non-visible capillaries, and an absence of flat components. When any of these characteristics were present, two endoscopic specialists evaluated the lesions for the diagnosis of squamous cell carcinoma, with sensitivities of 100% and 97.6% and specificities of 68.9% and 93.3%. CONCLUSION Understanding distinct endoscopic patterns of oropharyngeal papillomas and squamous cell carcinomas provides valuable guidance to endoscopists performing esophagogastroduodenoscopy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2025 Salivary short chain fatty acids serve as biomarkers of periodontal inflammatory burden 1786 EN Kazu Takeuchi-Hatanaka Division of Periodontics and Endodontics, Department of Dentistry, Okayama University Hospital Yasushi Shirahase Sysmex Corporation Toshiyuki Yoshida Sysmex Corporation Mari Kono Sysmex Corporation Naoki Toya Sysmex Corporation Kenji Konishi Present address: Diagnostics Division, IVD Enzyme Department, Nagase Diagnostics Kazuhiro Omori Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Periodontitis is a chronic inflammatory condition associated with systemic diseases. Early detection and intervention are crucial; however, conventional diagnostic methods require specialized dental procedures. Therefore, we aimed to develop a noninvasive saliva-based screening method that can be easily performed outside dental clinics. This cross-sectional pilot study evaluated three periodontal indices—probing depth, Periodontal Inflamed Surface Area (PISA), and periodontal epithelial surface area—in relation to short-chain fatty acids (SCFAs) and bacterial profiles in the saliva. Saliva samples collected during the day exhibited stronger correlations with periodontal indices than waking time samples, demonstrating a significant association with periodontal pathogens, protease activity, and elevated levels of butyric acid. The diagnostic thresholds for PISA were 300 mm2 and 600 mm2. Multivariate logistic regression and likelihood ratio analyses identified the combination of enzymatic SCFA markers and dipstick-based occult blood or leukocyte detection as a promising biomarker pair. Combining enzymatic SCFA markers with occult blood demonstrated a positive likelihood ratio of 3.4 and a negative likelihood ratio of 0.19 for PISA ≥ 600 mm2, with a post-test probability of 77%, sensitivity of 86%, and specificity of 75%. These findings suggest that combining salivary enzymatic and dipstick-based biomarkers provides a simple, cost-effective, and moderately informative screening strategy for periodontitis. No potential conflict of interest relevant to this article was reported.

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

Open Library of the Humanities Acta Medica Okayama 2056-6700 12 1 2026 Racialized Contagion and Defensive Biopolitics in The Last of Us EN Robert Yeates Faculty of Humanities and Social Sciences, Okayama University In the opening moments of the video game The Last of Us Part I, players are introduced to an emerging pandemic via Austin’s Texas Herald newspaper. Below a headline warning of mass hospitalizations from a 'mysterious infection', players read of a recall of imported crops 'potentially tainted with mold': 'Initial lists distributed to vendors nationwide warned against crops imported from South America. However now the scope has extended to include Central America and Mexico'. This scene immediately suggests the racialization of the franchise’s Cordyceps brain infection (CBI), with the contagion germinating in the global South, invading the US via its southern border, and spreading fastest in the nation’s diverse urban centres. By highlighting tainted crops as the vector of dispersal in the US, however, rather than infected humans, the franchise resists making this a simple invasion-scare narrative and instead suggests that the spread of the infection is in part a result of the capitalist exploitation of cheap land and labour in the global South. Despite its inconsistent record on racial representation and the near-absence of discussion of race across the franchise, the structures reflecting the racialization of contagion and the perpetuation of racialized hierarchies through defensive biopolitics remain present. Drawing connections with the discourse around immigration and the southern border and contemporary pandemics and epidemics, this article makes the case for reading the franchise in terms of racialized contagion and defensive biopolitics, a reading that highlights how the games and their television adaptation reflect urgent contemporary issues around race in America. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 1 2026 Endoscopic Topical Application (ETA) Therapy for Refractory Overactive Bladder: A First-in-Human Report e101143 EN Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Sugihara Department of Surgery, Nishi Fukuyama Hospital Yosuke Mitsui Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiko Watanabe 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 Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Refractory overactive bladder (OAB) remains a clinical challenge despite established therapies, such as anticholinergics, β3-agonists, and intradetrusor botulinum toxin (BTX). Emerging evidence suggests that sensory mechanisms within the bladder, including those involving the trigone where superficial afferent networks are present, may contribute to persistent urinary urgency and frequency in some patients. Although intradetrusor BTX injection is effective in selected patients, its impact on these superficial pathways may be limited because the injected drug predominantly distributes within the detrusor. Endoscopic topical application (ETA) therapy delivers BTX directly to the trigone under air cystoscopy, potentially providing targeted modulation of sensory hyperexcitability. We report a 72-year-old woman with long-standing refractory OAB who experienced only partial improvement with repeated intradetrusor BTX injections but achieved clinically meaningful symptom relief after ETA therapy. Nocturia, urgency, urgency urinary incontinence, and voided volume were improved, with no complications other than transient postoperative urethral pain. This case suggests that ETA therapy may represent a promising sensory-focused option for refractory OAB. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1341-321X 31 12 2025 Whole-genome sequencing and in vitro characterization of a disseminated ST398 Staphylococcus aureus infection: A case report 102845 EN Yosuke Sazumi Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinnosuke Fukushima Department of Bacteriology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Atsushi Kato Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuhito Suyama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Oguni Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Shoko Kutsuno Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Junzo Hisatsune Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Motoyuki Sugai Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Shuma Tsuji Department of Bacteriology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Staphylococcus aureus potentially causes systemic infections such as disseminated abscesses and bloodstream infections, leading to high mortality rates. We herein describe a case of disseminated muscle abscesses caused by sequence type (ST) 398 methicillin-sensitive S. aureus (MSSA), along with in vitro investigation results for potential pathogenic factors. A 67-year-old healthy woman was admitted to our hospital with complaints of systemic body pain. Blood cultures identified MSSA and contrast-enhanced computed tomography revealed multiple muscle abscesses extending from her neck to her soles. She received antibiotic treatment with intravenous cephazolin and underwent repeated surgical drainage, and was finally discharged. Notably, the MSSA strain exclusively affected her muscle tissues, prompting us to perform genetic analysis to uncover the underlying reason. Short-read genome analysis revealed the isolate to be ST398, harboring chp and scn genes known for immune evasion from human immunity. However, no other known pathogenic factors were identified despite rigorous assays for biofilm formation, surface and cell wall proteins, protease production, and hyaluronidase activity. ST398 S. aureus is commonly isolated from livestock, and her prior experience of being flooded could be related to the disease onset. The present case underscores the possibility of severe ST398 MSSA infections in humans, even in the absence of direct animal exposure. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1341-321X 31 12 2025 Clinical and molecular characteristics of urinary catheter-associated Pseudomonas aeruginosa prostatic infection: A case series of four postoperative nosocomial infections 102853 EN Shinnosuke Fukushima Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Sano Laboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University Takashige Kashimoto Laboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Pseudomonas aeruginosa is a causative pathogen of nosocomial catheter-associated urinary tract infections (CAUTI), but prostate involvement, including prostatitis and prostatic abscess, is rare. The clinical characteristics of P. aeruginosa-associated CAUTI with prostatic lesions, as well as the contribution of genetic backgrounds remain unclear. We describe four cases of urinary catheter-associated prostatic infection caused by P. aeruginosa following postoperative catheterization. All patients developed fever within 10 days after surgery, and three of the four patients developed bacteremia. Three patients were diagnosed with prostatic abscess by contrast-enhanced computed tomography or magnetic resonance imaging, while one case presented with prostatitis without abscess formation. Prostate-specific antigen levels were elevated over 20 ng/mL in all three measured cases. All patients were treated successfully with prolonged antibiotic therapy (28–39 days) without surgical drainage. Notably, all three abscess cases were successfully managed with fluoroquinolone-based combination therapy, highlighting its potential role in the management of prostatic abscesses. Three of four isolates were submitted for molecular investigations. All isolates harbored exoT and exoY, whereas exoU was absent. Biofilm-associated genes were detected in two cases, but not in the remaining case. Our findings suggested that P. aeruginosa strains carrying T3SS genes (exoT and exoY) potentially develop prostatic infections, independent of biofilm-associated genes. Host and iatrogenic factors, such as catheter manipulation, may play more critical roles in the development of prostatic pathology than strain-specific determinants. Assessment of prostate-specific antigen levels and early imaging may facilitate appropriate diagnosis and effective management when P. aeruginosa is detected as a cause of CAUTI. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1156-5233 35 2 2025 Cerebellar abscess caused by Cladophialophora bantiana involving an elderly Japanese woman 101548 EN Kenta Nakamoto Department of Infectious Diseases, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Kohei Oguni Department of Infectious Diseases, Okayama University Hospital Yukika Yokoyama Microbiology Division, Clinical Laboratory, Okayama University Hospital Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Shuichiro Hirano Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yaguchi Division of Clinical Research, Medical Mycology Research Center Sayaka Ban Division of Clinical Research, Medical Mycology Research Center Akira Watanabe Division of Clinical Research, Medical Mycology Research Center Hiroki Okunobu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuhito Suyama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Marina Kawaguchi Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yousuke Sazumi 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 Phaeohyphomycosis is a rare fungal infection that presents significant challenges in diagnosis and treatment. Herein, we document a case of a cerebellar abscess caused by Cladophialophora bantiana. A 77-year-old woman with type 2 diabetes mellitus and a previous history of diffuse large B-cell lymphoma gradually developed ataxia and was transferred to an emergency department. Head imaging investigations indicated a cerebellar mass and the patient underwent an emergent endoscopic drainage. Although bacterial cultures of the drainage specimen yielded no growth, a dematiaceous fungus was isolated and subsequently identified as C. bantiana through ITS sequencing analysis. The patient received antifungal combination therapy, initially with liposomal amphotericin B and voriconazole, and finally posaconazole and 5-fluorocytosine. Brain abscesses caused by C. bantiana are rarely documented, and an optimal treatment strategy has yet to be established. Given the high fatality rate, an early surgical intervention is crucial for both diagnosis and treatment. The present case was successfully treated with minimally invasive surgical intervention alongside the antifungal combination therapy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 11 2025 Perioperative Multidisciplinary Intervention Led to Complete Minimally Invasive Transthoracic Esophagectomy for a Patient With Severe Lung Dysfunction: A Case Report e97931 EN Makoto Matsumoto 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 Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Noma 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 Risk factors for postoperative pneumonia after esophagectomy include smoking, severe lung dysfunction, and sarcopenia. Heavy smokers often have chronic obstructive pulmonary disease (COPD), which is associated with poor physical activity and low muscle strength. Sarcopenia is also associated with decreased physical function and malnutrition. These factors lead to a close relationship between COPD and sarcopenia. This report describes the case of a 74-year-old man who presented with dysphagia and was diagnosed with advanced esophageal cancer with lymph node metastasis. Preoperative respiratory function testing showed a forced expiratory volume in one second (FEV1) of 0.76 L because of his past smoking and COPD. Multidisciplinary intervention was started, along with neoadjuvant chemotherapy. Preoperative management improved his physical function. Robot-assisted thoracoscopic subtotal esophagectomy with the patient in the prone position was performed with curative resection and no severe postoperative complications. The perioperative multidisciplinary intervention improved physical functions and enabled safe robot-assisted thoracoscopic esophagectomy for the patient with severe lung dysfunction in the prone position. This case highlights that not only respiratory status but also physical parameters should be taken into account when considering whether a patient can tolerate surgery safely. No potential conflict of interest relevant to this article was reported.

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

American Association for the Advancement of Science (AAAS) Acta Medica Okayama 2375-2548 11 44 2025 Structural insights into the divergent evolution of a photosystem I supercomplex in Euglena gracilis eaea6241 EN Koji Kato Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiki Nakajima Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Runa Sakamoto Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Minoru Kumazawa Institute of Low Temperature Science, Hokkaido University Kentaro Ifuku Graduate School of Agriculture, Kyoto University Takahiro Ishikawa Institute of Agricultural and Life Sciences, Academic Assembly, Shimane University Jian-Ren Shen Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Atsushi Takabayashi Institute of Low Temperature Science, Hokkaido University Ryo Nagao Faculty of Agriculture, Shizuoka University Photosystem I (PSI) forms supercomplexes with light-harvesting complexes (LHCs) to perform oxygenic photosynthesis. Here, we report a 2.82-angstrom cryo–electron microscopy structure of the PSI-LHCI supercomplex from Euglena gracilis, a eukaryotic alga with secondary green alga-derived plastids. The structure reveals a PSI monomer core with eight subunits and 13 asymmetrically arranged LHCI proteins. Euglena LHCIs bind diadinoxanthin, which is one of the carotenoids typically associated with red-lineage LHCs and is not present in the canonical LHCI belt found in green-lineage PSI-LHCI structures. Phylogenetic analysis shows that the Euglena LHCIs originated from LHCII-related clades rather than from the green-lineage LHCI group and that the nuclear-encoded PSI subunit PsaD likely originated from cyanobacteria via horizontal gene transfer. These observations indicate a mosaic origin of the Euglena PSI-LHCI. Our findings uncover a noncanonical light-harvesting architecture and highlight the structural and evolutionary plasticity of photosynthetic systems, illustrating how endosymbiotic acquisition and lineage-specific adaptation shape divergent light-harvesting strategies. No potential conflict of interest relevant to this article was reported.

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

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

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

Wiley Acta Medica Okayama 2050-0904 13 10 2025 Recurrent Septic Shock in Immunosuppressed Patients e71249 EN Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Koji Fujita Department of General Medicine and Infectious Diseases, Tsuyama Chuo Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Cytomegalovirus gastroenteritis presents with diarrhea and abdominal pain in immunosuppressed patients, and histopathological examination is essential by endoscopy. This case illustrates that cytomegalovirus enteritis may develop insidiously and possibly invoke shock in immunocompromised patients, warranting its inclusion in the differential diagnosis of recurrent septic shock. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 0925-5710 122 5 2025 Intravenous umbilical cord-derived mesenchymal stromal cell therapy may improve overall survival in Japanese patients with idiopathic pneumonia syndrome after hematopoietic stem cell transplantation: a multicenter, single-arm, phase II trial 733 743 EN Noriko Doki Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Shinichi Kako Division of Hematology, Jichi Medical University Saitama Medical Center Emiko Sakaida Department of Hematology, Chiba University Hospital Yoshinobu Kanda Division of Hematology, Department of Medicine, Jichi Medical University Idiopathic pneumonia syndrome (IPS) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) and has a poor prognosis. Although IPS is often treated with steroids, the disease can become resistant to or dependent on steroid treatment, and there is no effective cure for patients with refractory or steroid-dependent IPS. This multicenter, open-label, single-arm, phase II clinical trial investigated the efficacy and safety of HLC-001 (allogeneic umbilical cord-derived mesenchymal stromal cells) in patients with progressive steroid-dependent or refractory IPS after HSCT. Seven male patients (all male; mean age: 43.3 years) received HLC-001 and three completed the trial. The survival rate at day 56 (primary endpoint) was 71.4% (5/7 patients; 95% confidence interval: 29.0%–96.3%) and was sustained at day 100, suggesting that HLC-001 was more effective than previously reported treatment. Three of the five patients with ≥ 100 days of follow-up died. Five patients experienced at least one adverse drug reaction, none of which were serious. These findings indicate that HLC-001 was potentially effective and generally well tolerated in Japanese patients with steroid-dependent or refractory IPS after HSCT. Given there is no effective cure for steroid-dependent or refractory IPS, HLC-001 may be a promising treatment option and further clinical evaluation is warranted. Trial registration: Japan Registry of Clinical Trials identifier: jRCT2063220014. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2079-6374 16 1 2026 Magnetic Detection of Cancer Cells Using Tumor-Homing Peptide-Modified Magnetic Nanoparticles 45 EN Shengli Zhou Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yuji Furutani Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kei Yamashita Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Sakuya Kako Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazunori Watanabe Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toshihiko Kiwa Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Magnetic nanoparticles (MNPs) provide a platform for target detection because of their magnetic responsiveness to alternating magnetic fields (AMFs). We developed a detection method using MNPs modified with tumor-homing peptides (THPs), PL1 and PL3, which selectively bind to protein components enriched in malignant tissues. THP-MNPs were synthesized using maleimide-PEG-NHS linkers and characterized using transmission electron microscopy. Human glioblastoma cancer U87MG and normal tissue-derived HEK293 cells were incubated with THP-MNPs, and the magnetic signals were measured using a high-temperature superconducting quantum interference device (SQUID) magnetometer under an AMF (1.06 kHz). Dark-field microscopy confirmed the preferential binding of THP-MNPs to U87MG cells. In the absence of cells, THP-MNPs exhibited AMF-dependent signal enhancement, which correlated with particle size reduction due to THP release. This increase was completely suppressed in the presence of U87MG cells, indicating a strong THP-mediated interaction. PL3-MNPs exhibited superior discrimination between malignant and non-malignant cells. These results demonstrate that SQUID-based magnetic measurements using THP-MNPs enable rapid and label-free cancer cell detection. 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.

Elsevier BV Acta Medica Okayama 2405-6316 36 2025 A multi-institutional dummy run on segmentation variability and plan quality of stereotactic body radiotherapy for oligometastatic disease 100857 EN Hideaki Hirashima Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University Yukinori Matsuo Department of Radiation Oncology, Kindai University Faculty of Medicine Satoshi Ishikura Department of Radiation Oncology, St. Luke’s International Hospital, St. Luke’s International University Mitsuhiro Nakamura Department of Advanced Medical Physics, Graduate School of Medicine, Kyoto University Ikuno Nishibuchi Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University Daisuke Kawahara Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University Yoshihisa Shimada Department of Surgery, Tokyo Medical University Yoshiro Nakahara Department of Respiratory Medicine, Kitasato University Hospital Teiji Nishio Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka Naoto Shikama Department of Radiation Oncology, Juntendo University Graduate School of Medicine Shun-ichi Watanabe Department of Thoracic Surgery, National Cancer Center Hospital Isamu Okamoto Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University Toshiyuki Ishiba Department of Breast Surgery, Institute of Science Tokyo Fumikata Hara Department of Breast Oncology, Aichi Cancer Center Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Takashi Mizowaki Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University Background and purpose: Oligometastatic disease represents limited metastatic burden, and local ablative therapies such as stereotactic body radiotherapy (SBRT) may improve survival. However, inter-institutional variability in target segmentation and treatment planning can compromise treatment quality. This study aimed to evaluate the segmentation variability and dose distribution quality of SBRT in oligometastatic settings using a multi-institutional dummy run approach. Methods and materials: Sixty-nine institutions were provided with two anonymized cases of adrenal and spine metastases to delineate targets and organs at risk (OARs) and create intensity-modulated radiotherapy plans following a protocol. Variability was quantified using the Dice similarity coefficient (DSC), Hausdorff distance, and mean distance to agreement. Plan qualities were assessed using the Paddick conformity index, modified gradient index, and a new three-dimensional conformity–gradient index (3D-CGI). Knowledge-based planning (KBP) was applied to explore potential improvements in OAR sparing. Results: All submitted plans met protocol dose constraints. However, substantial segmentation variability was observed, particularly for the spine case. Among 136 plans, 79% demonstrated acceptable conformity and dose gradients, with 3D-CGI < 6 correlating with favorable distributions. Mean DSC was 0.93 for the clinical target volume and 0.76 for the cauda equina, which showed the highest variability. KBP reduced OAR doses for the adrenal case but showed limited impact for the spine case. Conclusions: Although dose constraints were achieved, segmentation variability remained substantial, particularly for the cauda equina in the spine case. These findings emphasize inter-institutional differences and the need for standardization and tools to improve SBRT consistency. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0066-4804 69 12 2025 Genomic portrayal of emerging carbapenem-resistant El Tor variant Vibrio cholerae O1 e00740-25 EN Sreeja Shaw ICMR-National Institute for Research in Bacterial Infections Agila Kumari Pragasam V. Ramalingaswami Bhawan, Indian Council of Medical Research Goutam Chowdhury ICMR-National Institute for Research in Bacterial Infections Prosenjit Samanta ICMR-National Institute for Research in Bacterial Infections Deboleena Roy ICMR-National Institute for Research in Bacterial Infections Debjani Ghosh ICMR-National Institute for Research in Bacterial Infections Thandavarayan Ramamurthy ICMR-National Institute for Research in Bacterial Infections Jigna Karia Medical College Baroda Govind Ninama Medical College Baroda Shin-ichi Miyoshi Okayama University Yukihiro Akeda National Institute of Infectious Diseases Hemanta Koley ICMR-National Institute for Research in Bacterial Infections Asish Kumar Mukhopadhyay ICMR-National Institute for Research in Bacterial Infections The escalating prevalence of carbapenem-resistant (CR) enteric pathogens elicits significant challenges to public health management and effective antimicrobial therapy. While carbapenem resistance is rare in Vibrio cholerae O1 (VC), the recent emergence of CR strains reveals a concerning shift in their antimicrobial resistance (AMR) landscape. This study aims to characterize the resistance mechanisms in newly identified El Tor CRVC isolated from cholera patients in Gujarat, India during 2019. Fifty VC isolates were screened for major virulence-associated genes along with the determination of their antibiotic resistance profiles using Kirby-Bauer disk diffusion and MIC assays. Whole-genome sequencing (WGS) was employed to investigate the underlying mechanisms of CR. All the isolates exhibited hypervirulent Haitian alleles of major virulence genes and AMR profiles of typical multidrug resistance (MDR). Strikingly, 12% (6/50) of them were resistant to carbapenems and other antibiotics. Molecular analysis revealed that these CR isolates were clonally related and harbored a 142 kbp IncA/C type conjugative mega-plasmid with several AMR encoding genes, including blaNDM-1, that can be easily transferred to other bacterial species and confer donor AMR patterns. The plasmid’s competence for horizontal gene transfer presents a significant risk of dissemination to other enteric pathogens and thereby may complicate the treatment. This finding emphasizes the urgent need for enhanced genomic surveillance and robust antimicrobial stewardship programs aimed at curbing the spread of CRVC strains and mitigating their impact on cholera treatment and containment strategies. No potential conflict of interest relevant to this article was reported.

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

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

Oxford University Press (OUP) Acta Medica Okayama 1347-6947 89 6 2025 PNGase activity and free N-glycans in phloem fluid prepared from Nerium oleander (oleander tree) 872 875 EN Fuki Otaguro Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshinobu Kimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Megumi Maeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Free N-glycans (FNGs) occur ubiquitously in growing plants. Recently, it was reported that these FNGs interact with auxin. In this study, we investigated whether PNGase activity responsible for producing the FNGs occurs in the extracellular fluid, where auxin is present during its polar transfer. Here, we report the occurrences of PNGase activity and FNGs in the phloem fluid. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 2467-981X 10 2025 Favorable outcomes of epilepsy with gait-induced seizures after resection of the unilateral supplementary motor area 489 492 EN Satoshi Kodama Department of Neurology, Graduate School of Medicine, The University of Tokyo Naoto Kunii Department of Neurosurgery, Jichi Medical University Yuichiro Shirota Department of Neurology, Graduate School of Medicine, The University of Tokyo Takusei Chou Department of Neurology, Graduate School of Medicine, The University of Tokyo Mizuho Kawai Department of Neurology, Graduate School of Medicine, The University of Tokyo Seijiro Shimada Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo Meiko Maeda Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hamada Department of Neurology, Graduate School of Medicine, The University of Tokyo Masako Ikemura Department of Pathology, Graduate School of Medicine, The University of Tokyo Yuko Saito Department of Neuropahtology (Brain Bank for Aging Research), Tokyo Metropoliran Institute for Geriatrics and Gerontology Naoki Akamatsu Department of Neurology, International University of Health and Walfare Narita Hospital Taira Uehara Department of Neurology, International University of Health and Walfare Narita Hospital Nobuhito Saito Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Background: Gait-induced seizures are a rare manifestation of reflex epilepsy. Pathophysiology of this phenomenon has not been fully understood. Case presentation: A 28-year-old woman presented with a long history of “falls” following paroxysmal bilateral leg stiffness triggered by walking. Scalp electroencephalogram (EEG) revealed low-amplitude rhythmic beta activity, maximal at the Cz electrode, during these events. Magnetoencephalography demonstrated repetitive sharp waves source-localized to the right primary motor cortex. Multiple anti-seizure medications failed to improve her symptoms; however, the clinical manifestation was consistent with epilepsy with gait-induced seizures. Intracranial subdural EEG recording was performed and confirmed ictal activity originating from the right supplementary motor area. Resection of this area resulted in complete resolution of her symptoms. Discussion: This is the first reported case of successful resective surgery for epilepsy with gait-induced seizure. Brain networks involving cortical regions responsible for the initiation or execution of walking presumably played a key role in the generation of gait-induced seizures. Careful assessment using non-invasive neurophysiological studies facilitated accurate diagnosis, successful intracranial recordings, and effective resective surgery. 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.

Elsevier BV Acta Medica Okayama 0167-5273 445 2026 Cardiac characteristics of Fabry disease from baseline enrolment data in a nationwide prospective Japanese registry 134071 EN Toru Kubo Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University Yuichiro Maekawa Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine Kenichi Hongo Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine Saori Yamamoto Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine Yasuhiro Izumiya Department of Cardiovascular Medicine, Osaka Metropolitan University, Graduate School of Medicine Hiroyuki Yamakawa Department of Cardiology, Keio University School of Medicine Toshiyuki Yano Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine Koji Higuchi Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University Yuki Kuramoto Department of Cardiovascular Medicine, The University of Osaka Graduate School of Medicine Naoki Nakagawa Division of Cardiology and Nephrology, Department of Internal Medicine, Asahikawa Medical University Masashi Amano Department of Heart Failure and Transplantation, National Cerebral and Cardiovascular Center Yu Yamada Department of Cardiology, Institute of Medicine, University of Tsukuba Masayoshi Oikawa Department of Cardiovascular Medicine, Fukushima Medical University Yuichiro Iida Department of Cardiovascular Medicine, Kitasato University School of Medicine Kenichi Tsujita Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Yuya Matsue Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine Hideo Izawa Department of Cardiology, Fujita Health University Atsushi Suzuki Department of Cardiology, Tokyo Women's Medical University Yuji Nagatomo Department of Cardiology, National Defense Medical College Toshiyuki Nagai Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Keisuke Kida Department of Pharmacology, St. Marianna University School of Medicine Kazuto Nakamura Department of Cardiovascular Medicine, University of Yamanashi, Faculty of Medicine Kazufumi Nakamura Center for Advanced Heart Failure, Okayama University Hospital Hiroki Ikenaga Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences Takahiro Kanda Department of Internal Medicine, Division of Cardiology, Hamamatsu Red Cross Hospital Yoshiharu Kinugasa Department of Cardiovascular Medicine and Endocrinology and Metabolism, Faculty of Medicine, Tottori University Hiromasa Ito Department of Cardiology, Mie University Hospital Kenji Onoue Department of Cardiovascular Medicine, Nara Medical University Hiromitsu Kanamori Department of Cardiology, Gifu University Graduate School of Medicine Hiroaki Kitaoka Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University Background: Fabry disease (FD) is an important disease in the cardiovascular field because a significant proportion of patients with FD die from cardiac lesions. Methods: A multicenter prospective registration study of patients with FD throughout Japan was designed. The baseline clinical characteristics of 175 patients are presented here. Results: The mean ages at enrolment and at diagnosis were 52 ± 16 and 43 ± 18 years, respectively, with men accounting for 38 % of the patients. In the cohort, 24 % of the patients had the classical hemizygote male type, whereas 14 % had the late-onset male type, and 62 % had the heterozygote female type. On electrocardiography data at enrolment in 92 patients with left ventricular hypertrophy (LVH) (maximum LV wall thickness > 12 mm), 12 % showed a short PQ interval (< 120 msec), and 33 % had a short PendQ interval (≤ 40 msec). The Sokolow-Lyon voltage was high (6.1 ± 13.1 mv). Regarding the distribution of LVH patterns, 77 % of the patients showed concentric diffuse LVH, 16 % of the patients had asymmetric septal hypertrophy, and 1 % of the patients had hypertrophy confined to the LV apex. With regard to implantation of cardiac devices, permanent pacemakers had been implanted in 5 % of the patients and defibrillators had been implanted in 12 patients (7 %), for primary prevention in nine patients and for secondary prevention in three patients. Conclusion: As the first large-scale prospective registry of FD patients in Japan, this study has provided valuable baseline data for the cardiac features and management of FD. No potential conflict of interest relevant to this article was reported.

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

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 63 13 2024 Activated CD4+ T Cell Proportion in the Peripheral Blood Correlates with the Duration of Cytokine Release Syndrome and Predicts Clinical Outcome after Chimeric Antigen Receptor T Cell Therapy 1863 1872 EN Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Shuntaro Ikegawa Department of Hematology and Oncology, Okayama University Hospital, Japan Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Chihiro Kamoi Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Division of Clinical Laboratory, Okayama University Hospital Nobuharu Fujii Division of Blood Transfusion, Okayama University Hospital Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Objective Chimeric antigen receptor (CAR) T cell therapy is an emerging and effective therapy for relapsed or refractory diffuse large B cell lymphoma (R/R DLBCL). The characteristic toxicities of CAR T cell therapy include cytokine release syndrome (CRS) and prolonged cytopenia. We investigated the factors associated with these complications after CAR T cell therapy by analyzing lymphocyte subsets following CAR T cell infusion. Methods We retrospectively analyzed peripheral blood samples on days 7, 14, and 28 after tisagenlecleucel (tisa-cel) infusion by flow cytometry at our institution between June 2020 and September 2022. Patients Thirty-five patients with R/R DLBCL who received tisa-cel therapy were included. Results A flow cytometry-based analysis of blood samples from these patients revealed that the proportion of CD4+CD25+CD127+ T cells (hereafter referred to as "activated CD4+ T cells" ) among the total CD4+ T cells on day 7 after tisa-cel infusion correlated with the duration of CRS (r=0.79, p<0.01). In addition, a prognostic analysis of the overall survival (OS) using time-dependent receiver operating characteristic curves indicated a significantly more favorable OS and progression-free survival of patients with a proportion of activated CD4+ T cells among the total CD4+ T cells <0.73 (p=0.01, and p<0.01, respectively). Conclusion These results suggest that the proportion of activated CD4+ T cells on day 7 after tisa-cel infusion correlates with the CRS duration and predicts clinical outcomes after CAR T cell therapy. Further studies with a larger number of patients are required to validate these observations. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0889 198 1 2025 Role of polar localization of the silicon transporter OsLsi1 in metalloid uptake by rice roots kiaf196 EN Noriyuki Konishi Institute of Plant Science and Resources, Okayama University Namiki Mitani-Ueno Institute of Plant Science and Resources, Okayama University Jian Feng Ma Institute of Plant Science and Resources, Okayama University Low silicon (Si) rice 1 (OsLsi1) is a key transporter mediating Si uptake in rice (Oryza sativa). It is polarly localized at the distal side of the root exodermis and endodermis. Although OsLsi1 is also permeable to other metalloids, such as boron (B), germanium (Ge), arsenic (As), antimony (Sb), and selenium (Se), the role of its polar localization in the uptake of these metalloids remains unclear. In this study, we investigated the role of OsLsi1 polar localization in metalloid uptake by examining transgenic rice plants expressing polarly or nonpolarly localized OsLsi1 variants. Loss of OsLsi1 polar localization resulted in decreased accumulation of Ge, B, and As in shoots but increased Sb accumulation, while Se accumulation remained unaffected under normal conditions. Experiments with varying B concentrations revealed that B uptake is significantly lower at low B concentrations (0.3 to 3 μm) but higher at high B concentrations (300 μm) in plants expressing nonpolarly localized OsLsi1, despite the similar B permeability of both OsLsi1 variants in Xenopus oocytes and their comparable protein abundance in roots. Additionally, the loss of OsLsi1 polarity did not affect the abundance, localization, or high B-induced degradation of the borate transporter 1 (OsBOR1), an efflux transporter that cooperates with OsLsi1 for B uptake. Taken together, our findings demonstrate that the polar localization of OsLsi1 plays a critical role in regulating metalloid uptake, depending on the presence or absence of efflux transporters cooperating with OsLsi1. No potential conflict of interest relevant to this article was reported.

Fuji Technology Press Ltd. Acta Medica Okayama 1883-8049 37 6 2025 Directed Poisoning Attacks on FRIT in Adaptive Cruise Control 1392 1399 EN Taichi Ikezaki Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kenji Sawada Graduate school of Mechanical Engineering, The University of Osaka Osamu Kaneko Graduate School of Informatics and Engineering, The University of Electro-Communications Recent advances in connected-vehicle technologies have enabled the large-scale collection of driving data, facilitating the deployment of data-driven control schemes. Although these methods offer advantages by eliminating the need for explicit modeling, they also introduce vulnerabilities due to their reliance on stored data. This study investigates a class of targeted data poisoning attacks on fictitious reference iterative tuning, a widely used data-driven controller tuning approach. We present a method that allows an adversary to influence closed-loop dynamics by manipulating the training data so that the resulting controller behavior matches a maliciously defined reference response. This strategy differs from conventional poisoning attacks, which aim only to the degrade control performance. Instead, it enables deliberate alteration of control characteristics such as overshoot and convergence time. The proposed attack is formulated as a constrained optimization problem under bounded tampering signals. Through a numerical study involving adaptive cruise control with stop functionality, we show that minor data modifications, indistinguishable from sensor noise, can cause significant degradation in control behavior. These findings highlight the need for robust security mechanisms in data-driven control implementation. 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 Effects of Thoron Inhalation and Cyclosporin A Treatment on Dextran Sulfate Sodium-Induced Oxidative Damage in Mice 421 429 EN Ayumi Tanaka Graduate School of Health Sciences, Okayama University Shota Naoe Graduate School of Health Sciences, Okayama University Reiju Takenaka Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/69844 Radon (222Rn; Rn) and thoron (220Rn; Tn) inhalation have been reported to enhance antioxidant activity in various organs. However, the effects of Tn on the colon have not been investigated. This study aimed to clarify the effects of Tn inhalation, alone and in combination with cyclosporin A (CsA), on dextran sulfate sodium (DSS)-induced colitis, and the accompanying oxidative stress, in mice. Male BALB/c mice were subjected to continuous 8-day Tn inhalation (c-Tn, 533±128 Bq/m3) or alternate-day Tn inhalation over the same period (f-Tn, 577±63Bq/m3), followed by treatment with 3% DSS and either CsA or vehicle for 7 days. Although the disease activity index (DAI) decreased significantly by day 2 in the c-Tn group, scores remained significantly higher than those in the f-Tn group. In the c-Tn group, superoxide dismutase and catalase activity in the colon were significantly elevated compared with those in sham controls. Thus, DSS-induced damage was effectively inhibited in the earlier stages by the c-Tn mode of inhalation than by the f-Tn mode. These findings suggest that continuous Tn inhalation more effectively attenuated early colitis symptoms than alternate-day inhalation, potentially through upregulation of antioxidant defenses. Tn and CsA showed no combined effects. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 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.

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

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

Wiley Acta Medica Okayama 2050-0904 13 12 2025 Focal Nodular Hyperplasia of the Liver Mimicking Gastric Submucosal Tumor e71666 EN Yohei Masuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Soejima 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 Focal nodular hyperplasia (FNH) is a common benign hepatic tumor, typically featuring a central scar with a spoke-wheel pattern on abdominal ultrasound. This case highlights a rare presentation of FNH causing extragastric compression that mimicked a gastric submucosal tumor on esophagogastroduodenoscopy. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1473-0502 64 4 2025 Factors affecting the development of hypokalemia during apheresis in healthy donors 104195 EN Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Hiroki Kobayashi Department of Hematology and Oncology, Okayama University Hospital Masaya Abe Department of Hematology and Oncology, Okayama University Hospital Takuya Fukumi Department of Hematology and Oncology, Okayama University Hospital Kazuhiro Ikeuchi Department of Hematology and Oncology, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Despite being generally safe, apheresis for peripheral blood stem cell collection potentially disrupts electrolyte balance owing to the use of citric acid as an anticoagulant. As prior research has primarily studied hypocalcemia, information on the kinetics of potassium levels during apheresis in healthy donors is scarce. We investigated the fluctuation in potassium levels during apheresis and the risk factors for hypokalemia. This subanalysis used data from an open-label, randomized controlled trial of “oral calcium supplementation versus placebo in mitigating citrate toxicity” conducted between January 2021 and July 2022, at Okayama University Hospital. Potassium levels were significantly reduced after 5-day granulocyte colony-stimulating factor (G-CSF) administration (p < 0.0001), with seven patients (16.7 %) given oral potassium administration before apheresis because the treating physician deemed potassium levels potentially unsafe and three (7.1 %) presenting with hypokalemia at apheresis. Potassium levels after apheresis were significantly lower than those before apheresis (baseline; p < 0.0001), and 28 of 42 donors (66.7 %) experienced biochemical, clinically unapparent hypokalemia immediately after the completion of apheresis. A > 15 % reduction in potassium levels from baseline was associated with age and the acid citrate dextrose solution A (ACD-A) volume in univariate analysis. In the multivariable analysis, both factors were associated (hazard ratio [HR], 11.60; 95 % confidence interval [CI], 1.60–83.70; p = 0.02 and HR, 17.50; 95 % CI, 1.07–136.00; p = 0.04). In conclusion, G-CSF administration and apheresis ultimately induced hypokalemia in two-thirds of the donors. Older age and higher ACD-A volume may affect potassium levels during apheresis in healthy donors. No potential conflict of interest relevant to this article was reported.

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

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

American Chemical Society (ACS) Acta Medica Okayama 2574-0962 8 6 2025 Effects of Metal-Cation Doping on Photocatalytic H2 Evolution Activity of Layered Perovskite Oxynitride K2LaTa2O6N 3541 3552 EN Hideya Tsuchikado Department of Chemistry, School of Science, Institute of Science Tokyo Shuji Anabuki Graduate School of Natural Science and Technology, Okayama University Ovidiu Cretu Electron Microscopy Group, National Institute for Materials Science (NIMS) Yuki Kinoshita Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Institute of Science Tokyo Masashi Hattori Institute of Integrated Research, Institute of Science Tokyo Yuta Shiroma Department of Chemistry, School of Science, Institute of Science Tokyo Dongxiao Fan Institute of Materials Structure Science High Energy Accelerator Research Organization Megumi Okazaki Department of Chemistry, School of Science, Institute of Science Tokyo Takuto Soma Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Institute of Science Tokyo Fumitaka Ishiwari Department of Applied Chemistry, Graduate School of Engineering, Osaka University Shunsuke Nozawa Institute of Materials Structure Science High Energy Accelerator Research Organization Toshiyuki Yokoi Institute of Integrated Research, Institute of Science Tokyo Michikazu Hara Institute of Integrated Research, Institute of Science Tokyo Koji Kimoto Electron Microscopy Group, National Institute for Materials Science (NIMS) Akira Yamakata Graduate School of Natural Science and Technology, Okayama University Akinori Saeki Department of Applied Chemistry, Graduate School of Engineering, Osaka University Kazuhiko Maeda Department of Chemistry, School of Science, Institute of Science Tokyo Aliovalent cation doping into a heterogeneous photocatalyst affects several of its physicochemical properties, including its morphological characteristics, optical absorption behavior, and charge carrier dynamics, causing a drastic change in its photocatalytic activity. In the present work, we investigated the effects of aliovalent cation doping on the visible-light H2-evolution photocatalytic activity of the Ruddlesden–Popper layered perovskite oxynitride K2LaTa2O6N. The photocatalytic activity toward H2 evolution from an aqueous NaI solution was found to be enhanced by an increase in the specific surface area of the K2LaTa2O6N photocatalyst, which could be realized upon doping with lower-valence cations (e.g., Mg2+, Al3+, and Ga3+). Among the dopants examined at 1 mol % doping, Ga resulted in the highest activity. The activity of the Ga-doped specimen was further improved with increasing Ga concentration, where the maximal activity was obtained at 10 mol %, corresponding to an apparent quantum yield of 2.7 ± 0.4% at 420 nm from aqueous methanol. This number is the highest reported for a layered oxynitride photocatalyst. In the Ga-doped K2LaTa2O6N, a trade-off was observed between the Ga concentration and the photocatalytic activity. Although doping with Ga reduced the particle size of K2LaTa2O6N and suppressed undesirable charge recombination, it led to an enlarged bandgap, unsuitable for visible-light absorption. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2468-2942 45 2025 Neoadjuvant FOLFOXIRI for locally advanced rectal cancer: A retrospective analysis focusing on long-term anal preservation 101049 EN Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Matsumi 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 Nobuhiko Kanaya 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 Yoshiko Mori Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University 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 To investigate the safety and efficacy of FOLFOXIRI as neoadjuvant chemotherapy (NAC) for locally advanced rectal cancer (LARC). The outcomes of preoperative and perioperative treatments, as well as long-term outcomes, were retrospectively compared between 26 patients who underwent FOLFOXIRI as NAC for LARC with cT3–4 and/or N+ at our institute between 2015 and 2022, and 31 patients with LARC who underwent neoadjuvant chemoradiotherapy (CAPOX-RT) at our institute between 2011 and 2022. Grade 3 or higher adverse events due to neoadjuvant treatment were significantly more common in the FOLFOXIRI group (11 cases, 42.3 %) than in the CAPOX-RT group (3 cases, 9.7 %), and most of these were neutropenia. Based on the postoperative pathological findings, the complete response rate was significantly lower in the FOLFOXIRI group (1 case, 3.8 %) than in the CAPOX-RT group (7 cases, 22.6 %), but there were no significant differences in the R0 resection rate, survival rate, or relapse-free survival rate. In the CAPOX-RT group, 17 patients (54.8 %) had anal preservation, and during the observation period, 4 patients required stoma construction due to loss of anal function in the late stage. In contrast, in the FOLFOXIRI group, there were no cases of loss of anal function among the 20 patients (76.9 %) who had anal preservation. FOLFOXIRI as NAC requires caution regarding hematological toxicity, but it can be an effective treatment option for patients with LARC who wish to preserve their anus. No potential conflict of interest relevant to this article was reported.

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

Oxford University Press (OUP) Acta Medica Okayama 1465-3621 55 5 2025 Multicenter, open-label, randomized, controlled study to test the utility of electronic patient-reported outcome monitoring in patients with unresectable advanced cancers or metastatic/recurrent solid tumors 547 555 EN Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Naomi Kiyota Department of Medical Oncology and Hematology, Cancer Center, Kobe University Hospital Yuichiro Kikawa Department of Breast Surgery, Kansai Medical University Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Kyoko Kato Department of Medical Oncology, National Hospital Organization Nagoya Medical Center Kaoru Kubota Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Ryosuke Tateishi Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo Akinobu Nakata Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukiya Narita Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Hiroji Iwata Department of Advanced Clinical Research and Development, Nagoya City University Akihiko Gemma Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Kojiro Shimozuma Department of Biomed Sciences, College of Life Sciences, Ritsumeikan University Kei Muro Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Tetsuya Iwamoto Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Yuki Takumoto Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takeru Shiroiwa Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takashi Fukuda Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takuhiro Yamaguchi Division of Biostatistics, Tohoku University Graduate School of Medicine Yasuhiro Hagiwara Department of Biostatistics, Division of Health Sciences and Nursing, The University of Tokyo Graduate School of Medicine Hironobu Minami Division of Medical Oncology and Hematology, Department of Medicine, Kobe University Graduate School of Medicine Electronic patient-reported outcome (ePRO) monitoring for patients undergoing cancer chemotherapy may provide qualified and early detection of adverse events or disease-related symptoms, leading to improved patient care. The aim of this study is to examine whether addition of ePRO monitoring to routine medical care contributes to improved overall survival and quality of life of cancer patients undergoing chemotherapy. Patients with unresectable advanced cancers or metastatic/recurrent solid tumors receiving systemic chemotherapy will be randomized to an ePRO monitoring group and a usual care group. The ePRO group will conduct weekly symptom monitoring using an electronic device after study enrollment until the end of the study. Monitoring results will be returned to medical personnel and used as information for patient care. The primary endpoints are overall survival and health related quality of life. The initial target sample size for the study was 1500 patients. However, due to delays in enrollment, the target was readjusted to 500 patients. Enrollment has been completed, and the study is now in the follow-up phase. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1479-5876 23 1 2025 Tumor marker–guided precision BNCT for CA19-9–positive cancers: a new paradigm in molecularly targeted chemoradiation therapy 1387 EN Noriyuki Kanehira 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 Tomoyuki Tajima Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tatsunori Osone Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Takuya Fujimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Sakurai Institute for Integrated Radiation and Nuclear Science, Kyoto University Natsuko Kondo Institute for Integrated Radiation and Nuclear Science, Kyoto University Narikazu Nagahisa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaoru Kamei Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taiga Fujita Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akira Morihara Graduate School of Environmental, Life Science, Okayama University Yutaka Takaguchi Faculty of Sustainable Design, Department of Material Design and Engineering, University of Toyama Mizuki Kitamatsu Department of Applied Chemistry, Kindai University Takeshi Takarada Department of Regenerative Science, 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 Minoru Suzuki Institute for Integrated Radiation and Nuclear Science, Kyoto University Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Background: Boron neutron capture therapy (BNCT) is a molecularly targeted chemoradiation modality that relies on boron delivery agents such as p-borophenylalanine (BPA), which require LAT1 (L-type amino acid transporter 1) for tumor uptake. However, the limited efficacy of BPA in LAT1-low tumors restricts its therapeutic scope. To address this limitation, we developed a tumor marker–guided BNCT strategy targeting cancers overexpressing the clinically validated glycan biomarker CA19-9. Methods: We conducted transcriptomic analyses using The Cancer Genome Atlas (TCGA) datasets to identify LAT1-low cancers with high CA19-9 expression. These analyses revealed elevated expression of fucosyltransferase 3 (FUT3), which underlies CA19-9 biosynthesis, in pancreatic, biliary, and ovarian malignancies. Based on this, we synthesized a novel boron compound, fucose-BSH, designed to selectively accumulate in CA19-9–positive tumors. We evaluated its physicochemical properties, pharmacokinetics, biodistribution, and antitumor efficacy in cell lines and xenograft models, comparing its performance to that of BPA. Results: Fucose-BSH demonstrated significantly greater boron uptake in CA19-9–positive cell lines (AsPC-1, Panc 04.03, HuCCT-1, HSKTC, OVISE) compared to CA19-9–negative PANC-1. In HuCCT-1 xenografts, boron accumulation reached 36.2 ppm with a tumor/normal tissue ratio of 2.1, outperforming BPA. Upon neutron irradiation, fucose-BSH–mediated BNCT achieved > 80% tumor growth inhibition. Notably, fucose-BSH retained therapeutic efficacy in LAT1-deficient models where BPA was ineffective, confirming LAT1-independent targeting. Conclusions: This study establishes a novel precision BNCT approach by leveraging CA19-9 as a tumor-selective glycan marker for boron delivery. Fucose-BSH offers a promising platform for expanding BNCT to previously inaccessible LAT1-low malignancies, including pancreatic, biliary, and ovarian cancers. These findings provide a clinically actionable strategy for tumor marker–driven chemoradiation and lay the foundation for translational application in BNCT. This strategy has the potential to support companion diagnostic development and precision stratification in ongoing and future BNCT clinical trials. Translational Relevance: Malignancies with elevated CA19-9 expression, such as pancreatic, biliary, and ovarian cancers, are associated with poor prognosis and limited response to current therapies. This study presents a tumor marker–guided strategy for boron neutron capture therapy (BNCT) by leveraging CA19-9 glycan biology to enable selective tumor targeting via fucose-BSH, a novel boron compound. Through transcriptomic data mining and preclinical validation, fucose-BSH demonstrated LAT1-independent boron delivery, potent BNCT-mediated cytotoxicity, and tumor-specific accumulation in CA19-9–positive models. These findings support a precision chemoradiation approach that addresses a critical gap in BNCT applicability, offering a clinically actionable pathway for patient stratification and therapeutic development in CA19-9–expressing cancers. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 0944-1174 2025 Mortality and cancer risk in patients with chronic pancreatitis in japan: insights into the importance of surveillance for pancreatic cancer EN Ryotaro Matsumoto Division of Gastroenterology, Tohoku University Graduate School of Medicine Kazuhiro Kikuta Division of Gastroenterology, Tohoku University Graduate School of Medicine Tetsuya Takikawa Division of Gastroenterology, Tohoku University Graduate School of Medicine Yousuke Nakai Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo Mamoru Takenaka Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine Kentaro Oki Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Eizaburo Ohno Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine Ken Ito Division of Gastroenterology and Hepatology, Toho University Omori Medical Center Nao Fujimori Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University Akio Katanuma Center for Gastroenterology, Teine-Keijinkai Hospital Atsuhiro Masuda Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine Yasuki Hori Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences Tsukasa Ikeura Department of Gastroenterology and Hepatology, Kansai Medical University Rei Suzuki Department of Gastroenterology, Fukushima Medical University School of Medicine Satoshi Yamamoto Department of Gastroenterology, Fujita Health University Bantane Hospital Yoshio Sogame Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Hiroki Kawashima Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine Tetsuhide Ito Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, International University of Health and Welfare Kosuke Okuwaki Department of Gastroenterology, Kitasato University School of Medicine Takao Itoi Department of Gastroenterology and Hepatology, Tokyo Medical University Yukiko Takayama Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University Akira Nakamura Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine Shuji Terai Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Masaki Kuwatani Department of Gastroenterology and Hepatology, Hokkaido University Hospital Masashi Kishiwada Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine Minoru Shigekawa Department of Gastroenterology and Hepatology, The University of Osaka Graduate School of Medicine Tomoaki Matsumori Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine Osamu Inatomi Department of Medicine, Shiga University of Medical Science Waku Hatta Division of Gastroenterology, Tohoku University Graduate School of Medicine Atsushi Irisawa Department of Gastroenterology, Dokkyo Medical University School of Medicine Michiaki Unno Department of Surgery, Tohoku University Graduate School of Medicine Yoshifumi Takeyama Department of Surgery, Kindai University Faculty of Medicine Atsushi Masamune Division of Gastroenterology, Tohoku University Graduate School of Medicine Japan Pancreatitis Study Group for Chronic Pancreatitis Background/Objective: Since the 2010s, Japan’s national health insurance system has covered key management for chronic pancreatitis (CP), including pancreatic enzyme replacement therapy. These therapies are expected to improve long-term prognosis; however, recent data are lacking. This study aimed to clarify the updated cancer risk and mortality among patients with CP in Japan. Methods: We conducted a multicenter, retrospective cohort study on 1,110 patients with CP treated at 28 institutions in 2011. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were calculated for comorbidities. Factors associated with the development of malignancy and overall survival were analyzed. Results: Patients with CP had an elevated SIR of 1.62 (95% confidence interval [CI], 1.43–1.83) for malignancy, with the highest risk observed for pancreatic cancer (SIR = 6.44 [95% CI, 4.64–8.90]). During follow-up, 143 patients (12.9%) died, most frequently from malignancy (47.5%). The SMR was elevated in all patients with CP (SMR = 1.20 [95% CI, 1.01–1.42]) and in those with alcohol-related CP (SMR = 1.49 [95% CI, 1.23–1.81]) but not in those with alcohol-unrelated CP. Pancreatic cancer was identified as the strongest factor associated with overall survival (hazard ratio, 48.92 in multivariate analysis). Overall survival of the patients with pancreatic cancer was significantly longer in those who underwent regular examinations for CP at least every three months (P = 0.011). Conclusions: Patients with alcohol-related CP have higher mortality than the general population in Japan. Pancreatic cancer remains a crucial prognostic factor in patients with CP. Regular surveillance for pancreatic cancer is important to improve their prognosis. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2210-2612 134 2025 Robotic posterior radical antegrade modular pancreatosplenectomy for left-sided pancreatic cancer using the ligament of Treitz first approach: A case report and technical note 111782 EN Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuyuki Matsumoto Department of Gastroenterology, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Introduction: Radical antegrade modular pancreatosplenectomy (RAMPS) is the standardized open surgical technique for treating left-sided pancreatic cancer. However, studies reporting the surgical approaches for robotic RAMPS are limited. Here, we present a robotic posterior RAMPS using the ligament of Treitz first approach. Presentation of case: A 46-year-old male patient with initially unresectable pancreatic body cancer underwent robotic posterior RAMPS as a conversion surgery after 1-year of chemotherapy with modified FOLFIRINOX. Discussion: Following evaluation of resectability, the ligament of Treitz first approach was applied. The transverse colon was lifted cranially, and the left renal vein was exposed after dissection around the ligament of Treitz. The left adrenal vein was divided, and the left adrenal gland was resected with special caution to avoid injury to the left renal artery. Retroperitoneal dissection was performed with lymphadenectomy around the superior mesenteric and celiac arteries using the ligament of Treitz first approach. After repositioning the transverse colon, the gastrocolic and gastrosplenic ligaments were dissected. Following the division of the pancreas and splenic vessels, the retroperitoneal dissection line was connected with those of the ligament of Treitz first approach. The operative time was 303 min, and the estimated blood loss was 150 mL. Conclusion: The ligament of Treitz first approach may be an option for robotic RAMPS for left-sided pancreatic cancer. Surgeons should select the best approach for performing robotic RAMPS. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 64 23 2025 A Prompt Diagnosis of Ascites and Dramatic Effect of Alectinib for Advanced Lung Adenocarcinoma Harboring EML4-ALK Fusion 3413 3418 EN Takahiro Baba Department of Respiratory Medicine, Okayama University Hospital Hirofumi Inoue Department of Medical Support, Okayama University Hospital Hiromi Matsuoka Department of Medical Support, Okayama University Hospital Mio Kyakuno Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine Yusuke Yoshinaga Department of Respiratory Medicine, Okayama University Hospital Tetsuya Takeguchi Department of Respiratory Medicine, Okayama University Hospital Miho Fujiwara Department of Respiratory Medicine, Okayama University Hospital Kotaro Yamada Department of Respiratory Medicine, Okayama University Hospital Eri Nakamura Department of Respiratory Medicine, Okayama University Hospital Ayako Morita Department of Respiratory Medicine, Okayama University Hospital Naofumi Hara Department of Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Hisao Higo Department of Respiratory Medicine, Okayama University Hospital Masanori Fujii Department of Geriatric Medicine, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Kammei Rai Center for Innovative Clinical Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Masahiro Tabata Center for Clinical Oncology, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Respiratory Medicine, Okayama University Hospital A 75-year-old never-smoker woman presented with dyspnea and loss of appetite. A mass was identified in the left upper lobe of the lung, and the patient was referred to our hospital. Despite the diagnosis of lung adenocarcinoma via bronchoscopy, anaplastic lymphoma kinase (ALK) immunostaining was negative. Rapid weight gain and abdominal distension caused by ascites prompted fluid testing using the AmoyDx® Pan Lung Cancer PCR Panel. EML4-ALK fusion was confirmed, and alectinib therapy was initiated immediately. The tumor size had decreased significantly, and the patient was discharged on day 34. This case highlights the necessity of multiplex genetic testing even when ALK immunostaining is negative. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 1556-0864 20 5 2025 Amivantamab Plus Lazertinib in Patients With EGFR-Mutant NSCLC After Progression on Osimertinib and Platinum-Based Chemotherapy: Results From CHRYSALIS-2 Cohort A 651 664 EN Benjamin Besse Paris-Saclay University, Institut Gustave Roussy Koichi Goto National Cancer Center Hospital East Yongsheng Wang Institute of Clinical Trial Center and Cancer Center, West China Hospital, Sichuan University Se-Hoon Lee Samsung Medical Center, Sungkyunkwan University School of Medicine Melina E. Marmarelis University of Pennsylvania, Perelman School of Medicine Yuichiro Ohe National Cancer Center Hospital Reyes Bernabe Caro Hospital Universitario Virgen Del Rocio Dong-Wan Kim Seoul National University College of Medicine and Seoul National University Hospital Jong-Seok Lee Seoul National University College of Medicine and Seoul National University Hospital Sophie Cousin Institut Bergonié Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Yongsheng Li Chongqing University Cancer Hospital Luis Paz-Ares Hospital Universitario 12 de Octubre Akira Ono Shizuoka Cancer Center Rachel E. Sanborn Earle A. Chiles Research Institute, Providence Cancer Institute Naohiro Watanabe Department of Thoracic Oncology, Aichi Cancer Center Hospital Maria Jose de Miguel START Madrid-CIOCC, Hospital HM Sanchinarro Carole Helissey Clinical Research unit, Military Hospital Begin Catherine A. Shu Columbia University Medical Center Alexander I. Spira Virginia Cancer Specialists Pascale Tomasini Aix Marseille University - CNRS, INSERM, CRCM; CEPCM - AP-HM Hopital de La Timone James Chih-Hsin Yang National Taiwan University Cancer Center Yiping Zhang Zhejiang Cancer Hospital Enriqueta Felip Medical Oncology Service, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital Campus, Universitat Autonoma de Barcelona Frank Griesinger Pius-Hospital, University Medicine of Oldenburg Saiama N. Waqar Division of Oncology, Washington University School of Medicine Antonio Calles Hospital General Universitario Gregorio Marañón Joel W. Neal Stanford University Medical Center Christina S. Baik University of Washington, Fred Hutchinson Cancer Center Pasi A. Jänne Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute S. Martin Shreeve Johnson & Johnson Joshua C. Curtin Johnson & Johnson Bharvin Patel Johnson & Johnson Michael Gormley Johnson & Johnson Xuesong Lyu Johnson & Johnson Jun Chen Johnson & Johnson Pei-Ling Chu Johnson & Johnson Janine Mahoney Johnson & Johnson Leonardo Trani Johnson & Johnson Joshua M. Bauml Johnson & Johnson Meena Thayu Johnson & Johnson Roland E. Knoblauch Johnson & Johnson Byoung Chul Cho Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine Introduction: Treatment options for patients with EGFR-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy are limited. Methods: CHRYSALIS-2 cohort A evaluated amivantamab plus lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy. Primary end point was investigator-assessed objective response rate (ORR). The patients received 1050 mg of intravenous amivantamab (1400 mg if ≥ 80 kg) plus 240 mg of oral lazertinib. Results: In cohort A (N = 162), the investigator-assessed ORR was 28% (95% confidence interval [CI]: 22–36). The blinded independent central review–assessed ORR was 35% (95% CI: 27–42), with a median duration of response of 8.3 months (95% CI: 6.7–10.9) and a clinical benefit rate of 58% (95% CI: 50–66). At a median follow-up of 12 months, 32 of 56 responders (57%) achieved a duration of response of more than or equal to 6 months. Median progression-free survival by blinded independent central review was 4.5 months (95% CI: 4.1–5.8); median overall survival was 14.8 months (95% CI: 12.2–18.0). Preliminary evidence of central nervous system antitumor activity was reported in seven patients with baseline brain lesions and no previous brain radiation or surgery. Exploratory biomarker analyses using next-generation sequencing of circulating tumor DNA revealed responses in patients with and without EGFR- or MET-dependent resistance. The most frequent adverse events were rash (grouped term; 81%), infusion-related reaction (68%), and paronychia (52%). The most common grade greater than or equal to 3 treatment-related adverse events were rash (grouped term; 10%), infusion-related reaction (9%), and hypoalbuminemia (6%). Conclusions: For patients with limited treatment options, amivantamab plus lazertinib demonstrated an antitumor activity with a safety profile characterized by EGFR- or MET-related adverse events, which were generally manageable. No potential conflict of interest relevant to this article was reported.

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

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

AME Publishing Company Acta Medica Okayama 2790-8852 3 2024 Airway management during sedation for dental treatment in people with intellectual disabilities: a review 28 EN Hitoshi Higuchi Department of Dental Anesthesiology, Okayama University Hospital Yukiko Nishioka Department of Dental Anesthesiology, Okayama University Hospital Saki Miyake Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Miyawaki Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The oral health of people with intellectual disabilities remains poor due to a complex combination of physical and social problems, and often requires invasive dental treatment. However, it can be difficult to obtain their cooperation for dental treatment because they may not fully understand the need for treatment or may experience high levels of anxiety due to lack of understanding and/or sensory aversions to stimuli present in the dental environment, and behavioral management is often necessary during such treatment. Sedation is a very useful patient management method for dental treatment for people with intellectual disabilities; however, the dental treatment-related sedation of people with intellectual disabilities has different characteristics to the dental treatment-related sedation of others or other procedure-related sedation. For example, deep sedation is required for behavioral management; drug interactions between the patient’s regular medications, such as antiepileptic and antipsychotic drugs, and anesthetics may make the depth of sedation deeper; and the prevalence rate of obesity is higher among people with intellectual disabilities. The fact that the patient is in the supine position with their mouth open also makes airway management during sedation for dental treatment more difficult. It is therefore imperative that airway management during dental treatment for people with intellectual disabilities be conducted with the utmost precision and vigilance. Various attempts have been made to improve airway management during such sedation, and new technologies, such as capnography, nasal high-flow systems, and acoustic respiration monitors, may help. The objective of this review is to enhance comprehension of the attributes of airway management in dental sedation for people with intellectual disabilities and to properly understand the usefulness of the techniques that have been attempted thus far to ensure safer and more secure airway management for this population. The ultimate goal is to provide them with safe and secure medical care and improve their health outcomes. No potential conflict of interest relevant to this article was reported.

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

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

Wiley Acta Medica Okayama 1616-301X 2025 A Biologically-Architected Wear and Damage-Resistant Nanoparticle Coating From the Radular Teeth of Cryptochiton stelleri e21664 EN Taifeng Wang Department of Materials Science and Engineering, University of California Yu Chen Lyles School of Civil and Construction Engineering, Purdue University Ezra Sarmiento Department of Materials Science and Engineering, University of California Taige Hao Materials and Manufacturing Technologies Program, University of California Atsushi Arakaki Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology Michiko Nemoto Graduate School of Environmental and Life Science, Okayama University Pablo Zavattieri Lyles School of Civil and Construction Engineering, Purdue University David Kisailus Department of Materials Science and Engineering, University of California Nature utilizes simple building blocks to construct mechanically robust materials that demonstrate superior performance under extreme conditions. These exquisite structures result from the controlled synthesis and hierarchical assembly of nanoscale organic and mineral components that have provided critical evolutionary advantages to ensure survival. One such example is the ultrahard radular teeth found in mollusks, which are used to scrape against rock to feed on algae. Here, it is reported that the leading edges of these teeth consist of a wear-resistant coating that is comprised of densely packed ≈65 nm magnetic nanoparticles integrated within an organic matrix of chitin and protein. These mesocrystalline magnetite-based structures are assembled from smaller, highly aligned nanocrystals with inter/intracrystalline organics introduced during the crystallization process. Nanomechanical testing reveals that this multi-scale, nano-architected coating has a combination of increased hardness and a slight decrease in modulus versus geologic magnetite provides the surface of the chiton tooth with superior abrasion resistance. The mesocrystalline structures fracture at primary domain interfaces, corroborated by computational models, providing significant toughening to the tooth under extreme contact stresses. The design features revealed provide insight for the design and fabrication of next-generation advanced wear- and impact-resistant coatings for tooling, machinery, wind turbines, armor, etc. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 0305-182X 2025 Is Pain Intensity Related to Psychosocial Factors in Chronic Non‐Nociceptive Orofacial Pain Patients? EN Akiko Kawase Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Higuchi Department of Dental Anesthesiology, Okayama University Hospital Fumika Hashimoto Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Saki Miyake Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukiko Nishioka Department of Dental Anesthesiology, Okayama University Hospital Midori Inoue Department of Dental Anesthesiology, Okayama University Hospital Hitomi Ujita Department of Dental Anesthesiology, Okayama University Hospital Aki Kawauchi Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Shigeru Maeda Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Takuya Miyawaki Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: In order to understand the psychological aspects of chronic pain, it is important to consider the relationships between pain and psychosocial factors in patients with chronic pain. While psychosocial factors are known to affect pain intensity in temporomandibular disorders, few studies have evaluated them in patients with other types of chronic orofacial pain. Objective: The purpose of the present study was to evaluate the relationships between pain intensity and patient characteristics, diagnostic categories and psychosocial factors in chronic non-nociceptive orofacial pain patients. Methods: In a retrospective, cross-sectional study, we collected information from the medical records of 123 patients with chronic non-nociceptive orofacial pain. Pain intensity was measured using the Brief Pain Inventory (BPI) total score. Analysis of the correlations among the variables revealed several strong correlations. Principal component analysis identified two components: the psychological distress and self-efficacy/quality of life (QOL) components. Multiple linear regression analyses of the overall study population and each ICOP pain category were also performed. Results: In the overall sample, higher BPI scores were significantly associated with a greater psychological distress component and lower self-efficacy/QOL component. The pain category was not a significant predictor of the BPI score. In the subgroup analyses, both components were significant predictors of the BPI score in myofascial orofacial pain; whereas, only the self-efficacy/QOL component was in idiopathic orofacial pain. Conclusion: The results indicated that pain intensity in chronic non-nociceptive orofacial pain is related to the self-efficacy/QOL psychosocial factor component. These findings suggest that assessing psychosocial factors may be clinically important for the diagnosis and treatment of chronic orofacial pain. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1349-0079 68 1 2026 Evaluation of Mycobacterium-derived plasmids for application in oral Actinomyces species 100718 EN Sakiko Ohara Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yijuan Sheng Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Nishiya Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikue Tosa Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuki Takebe Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Arimura Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Mese Department of Dentistry and Oral Surgery, Fukuyama City Hospital Naoko Ohara Department of Operative Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoya Ohara Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives: Genetic manipulation tools are essential for elucidating the pathogenic mechanisms of microorganisms. Several species of Actinomyces, including A. israelii, are present in the oral cavity and they are the causative agents of actinomycosis. However, efficient gene-editing tools for these species have not yet been developed. In this study, the aim was to evaluate the introduction of foreign genes into Actinomyces using plasmids derived from Mycobacterium, which belong to the same class as Actinomycetes. Methods: A truncated derivative of pYT923, pYT923S, which contains the replication origin of the M. scrofulaceum plasmid pMSC262 was constructed and introduced into A. israelii by electrotransformation. Results: pYT923S was successfully introduced into A. israelii. The transformation efficiency of A. israelii was approximately 7–66 CFU/μg of DNA, and all transformed colonies harbored pYT923S. The plasmid recovered from A. israelii replicated in Escherichia coli. Conclusions: pYT923S was introduced into and maintained within A. israelii. Therefore, the pYT923S vector represents a useful genetic tool for Actinomyces and it is expected to facilitate future studies on the biology and pathogenicity of Actinomyces. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-3921 14 12 2025 Roles of ROS and NO in Plant Responses to Individual and Combined Salt Stress and Waterlogging 1455 EN Taufika Islam Anee Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University Nasser A. Sewelam Botany Department, Faculty of Science, Tanta University Nonnatus S. Bautista Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Baños Takashi Hirayama Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University During the climate change era, plants are increasingly exposed to multiple environmental challenges occurring simultaneously or sequentially. Among these, salt stress and waterlogging are two major factors that severely constrain crop productivity worldwide and often occur together. To survive under such conditions, plants have evolved sophisticated systems to scavenge harmful levels of reactive oxygen species (ROS). Despite their cytotoxic potential, ROS also act as key signaling molecules that interact with nitric oxide (NO), Ca2+, protein kinases, ion homeostasis pathways, and plant hormones. These signaling and acclimatory mechanisms are closely associated with the functions of energy-regulating organelles—chloroplasts and mitochondria—which are major sources of ROS under both individual and combined stresses. While many of these responses are shared between salt stress, waterlogging and their combination, it is likely that specific signaling mechanisms are uniquely activated when both stresses occur together—mechanisms that cannot be inferred from responses to each stress alone. Such specificity may depend on precise coordination among organelle-derived signals and the tight regulation of their cross-communication. Within this network, ROS and NO likely serve as central hubs, fine-tuning the integration of multiple signaling pathways that enable plants to adapt to complex and fluctuating stress environments. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 10 2025 Risk Stratification for the Prediction of Skeletal-Related Events in Patients With Bone Metastases From Non-small Cell Lung Cancer e95808 EN Yoshihiro Sakamoto Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eiji Nakata Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Hamada Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshimi Katayama Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Sugihara Department of Orthopedic Surgery, Shikoku Cancer Center Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Skeletal-related events (SREs) frequently occur in patients with bone metastases from non-small cell lung cancer (NSCLC). This study aimed to identify risk factors for SREs in patients with NSCLC. Based on these factors, we also aimed to stratify patients into subgroups to facilitate the assessment of SRE risk. This retrospective analysis used medical records of 139 patients with NSCLC bone metastases who received treatment at our institution between 2011 and 2014. The incidence of SREs was assessed, and SRE-free survival was analyzed using the Kaplan-Meier method. Clinical information collected at registration was assessed to identify factors associated with the onset of SREs within six months. Univariate analysis was performed using Fisher’s exact test, and multivariate analysis was performed using Cox regression. Of the 139 patients, 36 (26%) developed SREs after registration. The SRE-free survival rates were 80% and 64% at 6 and 12 months, respectively. The univariate and multivariate analyses revealed that the absence of epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangement (hazard ratio (HR): 4.51, 95% confidence interval (CI): 1.32-15.7, p = 0.017) and a lactate dehydrogenase (LDH) level ≥400 U/L (HR: 8.08, 95% CI: 1.78-36.6, p = 0.0067) were risk factors for SRE presentation within six months. Patients were classified into the following three subgroups: with EGFR mutation or ALK rearrangement and LDH level <400 U/L; without EGFR mutation or ALK rearrangement and LDH level <400 U/L; with/without EGFR mutation or ALK rearrangement and LDH level ≥400 U/L. The corresponding six-month SRE-free survival rates were 92%, 69%, and 34%, respectively, showing significant differences (p < 0.001). Close monitoring is recommended for patients with LDH levels ≥400 U/L in daily clinical practice, particularly with the help of the proficiency of orthopedic and radiological experts, to prevent complications such as pathological fractures and paraplegia. 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 1 2025 Mid-term Clinical and Radiographic Outcomes of the Actis Total Hip System: A Retrospective Study e77632 EN Yasutaka Masada Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomonori Tetsunaga Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Yamada Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Koura Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Inoue Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichiro Okuda Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoko Tetsunaga Department of Orthopaedic Surgery, Okayama University Hospital Yusuke Yokoyama Department of Orthopaedic Surgery, Okayama University Hospital Yuki Okazaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Introduction Implant technology for total hip arthroplasty (THA) was developed to improve hip function and patient satisfaction. Actis (DePuy Synthes, Warsaw, IN, USA) is a short fit-and-fill titanium stem, with a medial-collared and triple-taper (MCTT) geometry, that is fully coated with hydroxyapatite (HA). We evaluated the radiographic and clinical outcomes of the Actis Total Hip System during a mean follow-up of five years. Patients and methods We retrospectively analyzed data from 80 patients (14 male and 66 female, mean age: 65 ± 8.4 years) who underwent primary THA using Actis stems (anterolateral approach, 60 hips; posterior approach, 20 hips). Radiographs were obtained postoperatively and at the time of the final examination. Radiographic assessments included the alignment of the femoral stem, spot welds, stress shielding, cortical hypertrophy, subsidence (>2 mm), radiolucent line, pedestal formation, Dorr type, canal fill ratio (CFR), and stem fixation. Clinical evaluation included the Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ) and Harris Hip Score (HHS). Results The mean follow-up period was 64.0 ± 6.0 months. No significant differences were observed in the alignment of the femoral components between approaches. Of the 80 hips, 53 (66.3%) showed radiographic signs of stem osseointegration, predominantly in the mid-distal region of the stem at the final follow-up. Multiple logistic regression analysis revealed that younger age and a higher CFR (20 mm proximal to the lesser trochanter) were associated with the presence of spot welds. Mild stress shielding occurred in 25 hips (31.3%), and no patient experienced severe stress shielding. All stems were fixed by bone on growth. The JHEQ and HHS significantly improved at the final assessment. Conclusion At the five-year follow-up, patients who received the Actis Total Hip System during THA had good radiographic and clinical outcomes. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Grafting Islets to a Prevascularized Subcutaneous Site to Improve Transplant Survival and Function: A Mouse Model EN Tsuyoshi OKADA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1465-3621 55 4 2025 Current management of neurotrophic receptor tyrosine kinase fusion-positive sarcoma: an updated review 313 326 EN Yuta Kubota Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Masanori Kawano Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Tatsuya Iwasaki Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Ichiro Itonaga Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Nobuhiro Kaku Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Toshifumi Ozaki Department of Orthopaedic Surgery , Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Tanaka Department of Orthopaedic Surgery, Faculty of Medicine, Oita University In recent years, pembrolizumab has demonstrated significant efficacy in treating tumors characterized by a high tumor mutational burden and high microsatellite instability. Tropomyosin receptor kinase (TRK) inhibitors have shown considerable efficacy against tumors harboring neurotrophic receptor tyrosine kinase (NTRK) fusion genes, highlighting the growing importance of personalized medicine in cancer treatment. Advanced sequencing technologies enable the rapid analysis of numerous genetic abnormalities in tumors, facilitating the identification of patients with positive biomarkers. These advances have increased the likelihood of providing effective, tailored treatments. NTRK fusion genes are present in various cancer types, including sarcomas, and the TRK inhibitors larotrectinib and entrectinib have been effectively used for these malignancies. Consequently, the treatment outcomes for NTRK fusion-positive tumors have improved significantly, reflecting a shift toward more personalized therapeutic approaches. This review focuses on NTRK fusion-positive sarcomas and comprehensively evaluates their epidemiology, clinical features, and radiological and histological characteristics. We also investigated the treatment landscape, including the latest methodologies involving TRK inhibitors, and discussed the long-term efficacy of these inhibitors, and their optimal order of use. Notably, larotrectinib has demonstrated a high response rate in infantile fibrosarcoma, and its efficacy has been confirmed even in advanced cases. However, further research is warranted to optimize treatment duration and subsequent management strategies. The accumulation of clinical cases worldwide will play a pivotal role in refining the treatment approaches for tumors associated with NTRK fusion genes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 4 2025 Subcutaneous and Periorbital Emphysema Following a Dental Procedure e83089 EN Takafumi Obara Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Kazuki Nakatsuji Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Hospital Takashi Hongo Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Tetsuya Yumoto Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Subcutaneous emphysema following dental procedures is rare. We present the case of a young, healthy woman who was transferred from a dental clinic to our emergency department due to sudden swelling of the left orbit immediately after a dental procedure involving the use of the dental air and water syringe. The diagnosis of subcutaneous facial emphysema was made based on the patient's history, physical examination, and computed tomography imaging. The patient received prophylactic amoxicillin, and the lesion resolved completely in one week. Prompt clinical suspicion and a thorough evaluation of the signs and symptoms, including a detailed clinical history, are crucial for diagnosing subcutaneous emphysema following a dental procedure. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1320-5358 30 5 2025 A Case of IgA Nephropathy With Membranoproliferative Glomerulonephritis-Like Features Miyu Kanazawa, e70057 EN Miyu Kanazawa Okayama University Medical School Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoya Aoki Okayama University Medical School Mihiro Sue Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Miyake Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences A 73-year-old man was referred due to the onset of nephrotic-range proteinuria. He had been diagnosed with rheumatoid arthritis 18 years prior and had achieved remission with treatment, including methotrexate and janus kinase (JAK) inhibitor. Although routine follow-ups had not revealed any urinary abnormalities, subsequent tests detected proteinuria and hematuria in the absence of infection or other symptoms. As the urinary abnormalities persisted, with a serum albumin decrease and proteinuria measuring 5.7 g/day, indicating nephrotic syndrome, the patient was referred to our hospital for further evaluation, and a renal biopsy was performed. Light microscopy revealed mesangial cell proliferation, endocapillary proliferation and double-contoured basement membranes. Immunofluorescence microscopy showed IgA-dominant deposits in both mesangial areas and glomerular capillary walls. Transmission electron microscopy demonstrated electron-dense deposits in the mesangium and subendothelial regions, leading to the diagnosis of membranoproliferative glomerulonephritis (MPGN)-type IgA nephropathy. Immunostaining with the Gd-IgA1 (galactose-deficient IgA1)-specific antibody (KM55) was positive, consistent with the diagnosis. Following the initiation of steroid therapy, proteinuria rapidly decreased, achieving complete remission within 5 months. IgA nephropathy with MPGN-like features often presents as nephrotic syndrome, differing from the typical pathological and clinical presentation of IgA nephropathy, making differentiation from secondary MPGN and other diseases sometimes challenging. This case suggests that KM55 staining may offer additional information in differentiating atypical IgA nephropathy with non-classical pathological features. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2040-1116 16 6 2025 Relation between obesity and health disorders as revealed by the J-ORBIT clinical information collection system directly linked to electronic medical records (J-ORBIT 1) 1100 1111 EN Seiji Nishikage Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Yushi Hirota Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Yasushi Nakagawa Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Masamichi Ishii Center for Medical Informatics Intelligence, National Center for Global Health and Medicine Mitsuru Ohsugi Diabetes and Metabolism Information Center, Research Institute, National Center for Global Health and Medicine Eiichi Maeda Division of Medical Informatics, Department of Internal Medicine, Kobe University Graduate School of Medicine Kai Yoshimura Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Akane Yamamoto Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Tomofumi Takayoshi Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Takehiro Kato Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine Daisuke Yabe Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine Munehide Matsuhisa Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University 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 Yukihiro Fujita Department of Medicine, Shiga University of Medical Science Shinji Kume Department of Medicine, Shiga University of Medical Science Hiroshi Maegawa Department of Medicine, Shiga University of Medical Science Kana Miyake Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine Nobuhiro Shojima Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine Toshimasa Yamauchi Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine Koutaro Yokote Chiba University Kohjiro Ueki Diabetes Research Center, Research Institute, National Center for Global Health and Medicine Kengo Miyo Center for Medical Informatics Intelligence, National Center for Global Health and Medicine Wataru Ogawa Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Aims/Introduction: Obesity triggers various health disorders, but information on these disorders in real-world settings remains limited. To address this knowledge gap, we developed a database directly linked to electronic medical records (EMRs). We here present the baseline data for this database, designated Japan Obesity Research Based on electronIc healTh Records (J-ORBIT). Materials and Methods: Individuals with obesity disease diagnosed according to the criteria of the Japan Society for the Study of Obesity were registered in J-ORBIT from seven medical centers in Japan. We analyzed the relationship between body mass index (BMI), clinical characteristics, and the prevalence of obesity-related health disorders in this cohort. Results: Data were obtained from 1,169 individuals, with a mean (±SD) age of 56.9 ± 15.3 years and a BMI of 31.4 ± 6.1 kg/m2. The prevalence of health disorders varied substantially across BMI categories, with a higher BMI being associated with an increased prevalence of hyperuricemia or gout, obstructive sleep apnea syndrome or obesity hypoventilation syndrome, musculoskeletal disorders, and obesity-related kidney disease, as well as with a higher frequency of both a family history of obesity and of a history of childhood obesity. Among individuals with a BMI of ≥25 kg/m2, the prevalence of hypertension and dyslipidemia did not increase with BMI, whereas that of glucose intolerance decreased with increasing BMI. Conclusions: The J-ORBIT system, which collects clinical data in real time directly from EMRs, has the potential to provide insight into obesity and its associated health conditions, thereby contributing to improved care of affected individuals. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1664-3224 16 2025 A pilot transcriptomic study of a novel multitargeted BRT regimen for anti–MDA5 antibody-positive dermatomyositis: improving survival over conventional therapy 1568338 EN Moe Tokunaga Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Nakai Division of Rheumatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital Yoshiharu Sato DNA Chip Research Inc., Medical Laboratory Mitori Hiratsuka DNA Chip Research Inc., Medical Laboratory Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Nakatsue Division of Rheumatology and Nephrology, Department of Internal Medicine, Nagaoka Red Cross Hospital Takako Saeki Division of Rheumatology and Nephrology, Department of Internal Medicine, Nagaoka Red Cross Hospital Takatsune Umayahara Division of Dermatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Koyama Division of Rheumatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital Background: Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (MDA5-DM) is associated with severe outcomes, primarily due to rapidly progressive interstitial lung disease (RP-ILD), which is often refractory to standard therapies such as calcineurin inhibitors (e.g., tacrolimus) combined with cyclophosphamide (TC-Tx). This study evaluated the efficacy of a novel multitargeted regimen combining baricitinib, rituximab, and tacrolimus (BRT-Tx) in improving survival outcomes for MDA5-DM patients with poor prognostic factors. Methods: Fourteen MDA5-DM patients with multiple adverse prognostic factors were studied. Seven received the BRT-Tx regimen, and the remaining seven, previously treated with TC-Tx, served as historical controls. Twelve-month survival was assessed. Transcriptome analysis was performed for six patients (BRT=3, TC=3), beginning with cluster analysis to evaluate whether changes in peripheral blood gene expression varied according to treatment or prognosis. Gene ontology analysis characterized expression profiles in survivors and distinguished treatment effects. Alterations in the type I, II, and III interferon signatures were also assessed. Results: In the TC-Tx group, four of seven patients succumbed to RP-ILD, whereas all seven BRT-Tx patients survived the 12-month observation period. Only one BRT-Tx patient required combined rescue therapies, including plasma exchange, and one case of unexplained limbic encephalitis (LE) occurred. Cytomegalovirus reactivation was observed in both groups (BRT: 5/7; TC: 6/7). Transcriptomic analysis revealed no treatment-specific clustering of differentially expressed genes (DEGs) before and after therapy. However, survivors and nonsurvivors formed distinct clusters, with survivors showing significant posttreatment suppression of B-cell-related gene expression. Moreover, interferon signature scores were significantly lower after treatment in survivors than in nonsurvivors. BRT-Tx effectively suppressed B-cell-mediated immune responses and maintained a low interferon signature, while TC-Tx resulted in nonspecific gene suppression, and in nonsurvivors, an elevated interferon signature was observed. Conclusion: BRT-Tx has the potential to improve survival in MDA5-DM patients by effectively targeting hyperactive immune pathways. The combination of rituximab and tacrolimus is expected to disrupt B-cell–T-cell interactions and reduce autoantibody production, whereas baricitinib may suppress both IFN and GM-CSF signaling, regulating excessive autoimmunity mediated by cells such as macrophages. Unlike TC-Tx, BRT-Tx avoids cyclophosphamide-associated risks such as infertility and secondary malignancies. Future randomized controlled trials are warranted to validate its efficacy and safety. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1328-8067 67 1 2025 Pediatric stroke risk and neurotrauma from roller coasters in amusement parks e70221 EN Tomoki Morikawa Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Tokioka 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 Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Although rare, neurotrauma has been documented as a potential risk of high-speed, high-acceleration amusement park rides such as roller coasters. These attractions generate rapid acceleration, deceleration, sharp turns, and significant gravitational forces, which may stress the central nervous system and cerebrovascular structures. This review analyzed pediatric stroke cases (children 15 years old or younger) linked to roller-coaster rides reported in PubMed and summarized the key mechanisms and clinical features associated with such neurotrauma. Documented complications include internal and vertebral carotid artery dissections, with or without stroke, subdural hemorrhage, intraparenchymal hemorrhage, and post-traumatic migraines. The aim of this review is to alert healthcare providers to the possibility of stroke induced by roller-coaster rides, emphasizing the importance of timely diagnosis and management to prevent adverse outcomes. Key considerations include the recognition of risk factors, public education on potential risks, and strategies for preventing complications in at-risk populations. Although intracranial hemorrhage from roller-coaster rides is rare, individuals with predisposing conditions, such as prior head trauma or vascular abnormalities, should be evaluated carefully when presenting with neurological symptoms after such activities. No potential conflict of interest relevant to this article was reported.

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

Ivyspring International Publisher Acta Medica Okayama 1837-9664 16 14 2025 CXCR4 Inhibition Induces Tumor Necrosis by Selectively Targeting the Proliferating Blood Vessels in Oral Squamous Cell Carcinoma 4055 4070 EN Yamin Soe Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Htoo Shwe Eain Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Saori Yoshida Preliminary Examination Room, Okayama University Hospital May Wathone Oo Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Zin Zin Min Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University The C-X-C chemokine receptor type 4 (CXCR4) is a G protein-coupled transmembrane receptor that contributes to tumor growth and angiogenesis. While prior studies have primarily focused on CXCR4 expression in cancer cells and its role in metastasis, a few have examined its involvement in tumor-associated vasculature. In this study, we reported for the first time that CXCR4 expression within the tumor vasculature is significantly associated with higher pathological grades of human oral squamous cell carcinoma (OSCC) (p<0.03). A previous study reported that inhibiting CXCR4 with AMD3100 induces tumor cell death and enhances the efficacy of the chemotherapeutic agent cisplatin. These findings suggest that CXCR4 is an important target for cancer treatment. However, the tumor vascular system is known to be heterogeneous within the tumor microenvironment (TME), which may influence the treatment outcomes. Therefore, this study aimed to explore the effect of CXCR4 antagonism on various blood vessels present within the oral squamous cell carcinoma (OSCC) tumor stroma. Although the efficiency of AMD3100 was not significant in MOC cancer cells, necrosis was induced in the TME when applied to a poorly differentiated OSCC model, highlighting the role of the TME. Notably, CXCR4 is found to be highly overlapped with CD105+ angiogenic tumor vessels among various vascular markers. Treatment with AMD3100 leads to a marked reduction in the CD105+ vessels and impairs the maturation of tumor micro-vessels, explaining the cause of observed necrosis. Thus, CXCR4 serves as a promising biomarker in OSCC, and its inhibition with AMD3100 offers the therapeutic potential, particularly in cases with advanced pathological grades. No potential conflict of interest relevant to this article was reported.

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

American Society of Hematology Acta Medica Okayama 2473-9529 9 18 2025 Refinement of day 28 treatment response criteria for acute GVHD: a collaboration study of the JSTCT and MAGIC 4640 4653 EN Yu Akahoshi Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Yoshihiro Inamoto Department of Blood and Marrow Transplantation and Cellular Therapy, Fujita Health University School of Medicine Nikolaos Spyrou Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Hideki Nakasone Division of Hematology, Jichi Medical University Saitama Medical Center Marcio A. Diniz Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Francis Ayuk Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf Hannah K. Choe Division of Hematology, Blood and Marrow Transplantation Program, The Ohio State University Comprehensive Cancer Center Noriko Doki Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Tetsuya Eto Department of Hematology, Hamanomachi Hospital Aaron M. Etra Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Elizabeth O. Hexner Department of Medicine and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania Nobuhiro Hiramoto Department of Hematology, Kobe City Medical Center General Hospital William J. Hogan Division of Hematology, Mayo Clinic Ernst Holler Department of Hematology and Oncology, Internal Medicine III, University of Regensburg Keisuke Kataoka Division of Molecular Oncology, National Cancer Center Research Institute Toshiro Kawakita Department of Hematology, National Hospital Organization Kumamoto Medical Center Masatsugu Tanaka Department of Hematology, Kanagawa Cancer Center Takashi Tanaka Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital Naoyuki Uchida Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital Ingrid Vasova Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg and University Hospital Erlangen Satoshi Yoshihara Department of Hematology, Hyogo Medical University Hospital Fumihiko Ishimaru Technical Department, Japanese Red Cross Blood Service Headquarters Takahiro Fukuda Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital Yi-Bin Chen Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital Junya Kanda Department of Hematology, Graduate School of Medicine, Kyoto University Ryotaro Nakamura Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation James L. M. Ferrara Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Yoshinobu Kanda Division of Hematology, Jichi Medical University Saitama Medical Center John E. Levine Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Takanori Teshima Department of Hematology, Hokkaido University Faculty of Medicine and Graduate School of Medicine Overall response (OR) that combines complete (CR) and partial responses (PR) is the conventional end point for acute graft-versus-host disease (GVHD) trials. Because PR includes heterogeneous clinical presentations, reclassifying PR could produce a better end point. Patients in the primary treatment cohort from the Japanese Society for Transplantation and Cellular Therapy (JSTCT) were randomly divided into training and validation sets. In the training set, a classification and regression tree algorithm generated day 28 refined response (RR) criteria based on symptoms at treatment and day 28. We then evaluated RR for primary and second-line treatments, using the area under the receiver operating characteristic curve (AUC) and negative predictive value (NPV) for 6-month nonrelapse mortality as performance measures. RR considered patients with grade 0/1 at day 28 without additional treatment as responders. RR for primary treatment produced higher AUCs than OR with small improvement of NPVs in both validation sets: JSTCT (AUC, 0.73 vs 0.69 [P < .001]; NPV, 92.0% vs 89.6% [P < .001]) and the Mount Sinai Acute GVHD International Consortium (MAGIC; AUC, 0.71 vs 0.68 [P = .032]; NPV, 90.9% vs 89.8% [P = .009]). RR for second-line treatment produced similar AUCs but much higher NPVs than OR in both validation sets of JSTCT (AUC, 0.64 vs 0.63 [P = .775]; NPV, 74.5% vs 66.0% [P < .001]) and MAGIC (AUC, 0.67 vs 0.64 [P = .105]; NPV, 86.8% vs 76.1% [P = .004]). Classifying persistent but mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses were major drivers in improving the prognostic performance of RR. Our externally validated day 28 RR would serve as a better end point than conventional criteria in future first- and second-line treatment trials. No potential conflict of interest relevant to this article was reported.

The Company of Biologists Acta Medica Okayama 0950-1991 152 22 2025 ROS produced by Dual oxidase regulate cell proliferation and haemocyte migration during leg regeneration in the cricket dev204763 EN Misa Okumura-Hirono Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Bando Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshimasa Hamada Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideyo Ohuchi Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Many animals regenerate lost body parts through several signalling pathways; however, the triggers that initiate regeneration remain unclear. In the present study, we focused on the role of reactive oxygen species (ROS) produced by the NADPH oxidase Dual oxidase (Duox) during cricket leg regeneration. The results showed that ROS levels were upregulated during leg regeneration and decreased by DuoxRNAi. In DuoxRNAi nymphs, wound closure and scab formation were incomplete 2 days after amputation, and hypertrophy occurred in the distal region of the regenerating legs at 5 days after amputation. In addition, the hypertrophic phenotype was induced by DuoxARNAi and NADPH oxidase inhibitor treatment. During hypertrophy, haemocytes, including plasmatocytes, oenocytoids and granulocytes, accumulated. Proliferation of haemocytes in regenerating legs was not increased by DuoxRNAi; however, haemocyte accumulation was regulated by the Spatzle (Spz) family molecules, which are Toll receptor ligands. As the exoskeleton of DuoxRNAi nymphs was thinner than that of the control, excessive haemocyte accumulation can cause hypertrophy in DuoxRNAi nymphs. Thus, Duox-derived ROS are involved in wound healing and haemocyte accumulation through the Spz/Toll signalling pathway during leg regeneration in crickets. No potential conflict of interest relevant to this article was reported.

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

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

岡山大学経済学会 Acta Medica Okayama 2433-4146 57 2 2025 対話型美術鑑賞における創造性の理論的考察と分析フレームワークの構築 17 30 EN Satoru Miyazaki Shizuka Teramoto 10.18926/OER/69551 　In this study, we theoretically examined the mechanism of creativity in interactive art appreciation and presented it as an analytical framework. 　In interactive art appreciation, viewers engage in collaborative dialogue with the artwork and other viewers, and are influenced by the promotion of creativity and improvement of the quality of the dialogue through the intervention of facilitation. This introduces an otherness that is different from the self, which creates a deviation from existing interpretations. This discrepancy in interpretation brings about a conceptual shift in the viewer, resulting in the creation of a new theory; this newly created theory eventually becomes the existing theory, and once again a collaborative dialogue takes place, giving birth to a new theory. 　In this cyclical process of creativity in interactive art appreciation, knowledge is created and accumulated, and existing knowledge is creatively destroyed to reconstruct new knowledge. Learning takes place through mutual learning mediated by intrinsic motivation, and eventually learning takes place to arrive at new interpretations, although sometimes learning support is handed over from the facilitator to the viewers. For viewers whose abilities to create meaning and grasp value are underdeveloped, interactive art appreciation helps to encourage this development, and it has the potential to have a ripple effect on development not only in art but also in the broader realm of everyday knowledge outside of art. 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.

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

Springer Science and Business Media LLC Acta Medica Okayama 1471-2253 24 1 2024 Efficacy of Pericapsular Nerve Group (PENG) block in preoperative rehabilitation (Prehabilitation) for patients with femoral neck fractures: study protocol for a randomized, placebo-controlled, double-blinded trial 436 EN Zhuan Jin Department of Anesthesiology and Resuscitology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Daisuke Sugiyama Department of Anesthesiology, Kameda Medical Center Fumiya Higo Department of Rehabilitation, Kameda Medical Center Takahiro Hirata Department of Rehabilitation, Kameda Medical Center Osamu Kobayashi Department of Anesthesiology, Kameda Medical Center Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kenichi Ueda Department of Anesthesiology, Kameda Medical Center Background Despite surgery intervention for femoral neck fractures is recommended within 48 h of admission, achieving timely surgery presents challenges for patients with severe comorbidities, or in resource-limited settings. Preoperative rehabilitation (prehabilitation) reduces bedridden time, enhances mobility, and improves postoperative outcomes for patients scheduled for hip arthroplasty due to femoral neck fractures. However, prehabilitation is hindered by insufficient pain control. The pericapsular nerve group (PENG) block provides effective analgesia while preserving motor function. We designed a study to assess the efficacy of PENG block in facilitating prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty. Methods This prospective randomized placebo-controlled double-blinded trial aims to enroll 100 patients with Garden 3 or 4 femoral neck fractures who are scheduled for hip arthroplasty. Participants will be randomly assigned to receive a PENG block with 0.375% ropivacaine (PENG group) or with normal saline (placebo group) before the initial prehabilitation session. The prehabilitation program comprises five items: Bed-sitting, Edge-sitting, Stand-up, Maintaining-standing, and Wheelchair-transfer, performed with the assistance of a single physical therapist. The primary outcome is the percentage of patients completing the entire prehabilitation program. Secondary outcomes during the initial prehabilitation session are the achievement of each program item and the Numerical Rating Scale (NRS) pain score. Other secondary outcomes include intraoperative bleeding amounts, thromboembolic events during postoperative day 0 to 7, postoperative 3-day cumulative Cumulated Ambulation Score (CAS), and discharge destination. The postoperative outcomes will be compared between subgroups of patients undergoing surgery within 48 h of admission and those undergoing surgery more than 48 h of admission. Discussion This is the first study aiming to assess the efficacy of PENG block in prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty. PENG block could be beneficial, especially for patients facing delayed surgery, providing a potential treatment option during the waiting period. Trial registration Japan Registry of Clinical Trials, jRCT1031220294, registered on August 26, 2022. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0300-9572 215 2025 Compression only CPR and mortality in pediatric out-of-hospital cardiac arrest during COVID-19 pandemic 110706 EN Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: The COVID-19 pandemic influenced resuscitation practices worldwide, leading to a notable decline in rescue breathing cardiopulmonary resuscitation (RB-CPR), even in pediatric out-of-hospital cardiac arrest (OHCA). Understanding the impact of this decline is important to assess the role of rescue breathing in pediatric resuscitation. This study aimed to evaluate the impact of the reduced RB-CPR during the COVID-19 pandemic on mortality and neurological outcomes among pediatric OHCA patients in Japan. Methods: This retrospective cohort study utilized data from the nationwide All-Japan Utstein Registry for pediatric OHCA patients (≤17 years) who received bystander CPR between January 2017 and December 2021. Data were compared in pre-COVID-19 (2017–2019) versus pandemic (2020–2021) periods. Bystander CPR were classified as RB-CPR or chest compression-only CPR (CO-CPR). The primary outcome was 30-day mortality, with secondary outcomes including the absence of return of spontaneous circulation and unfavorable neurological outcomes (Cerebral Performance Category scores of 3–5). Adjusted risk ratios (aRR) with 95 % confidence intervals (CI) were estimated using Poisson regression. Results: Of 7,162 pediatric OHCA cases, 3,352 (46.8 %) received bystander CPR. RB-CPR decreased from 33.0 % pre-pandemic to 21.1 % during the pandemic. CO-CPR was associated with higher 30-day mortality (aRR: 1.16; 95 % CI: 1.08–1.24) and unfavorable neurological outcomes (aRR: 1.10; 95 % CI: 1.05–1.16). These trends were consistent across age groups and arrest etiologies, particularly for non-cardiac causes. More significantly, the decrease in RB-CPR was estimated to contribute to 10.7 excess deaths annually during the pandemic. Conclusions: The findings highlight the importance of rescue breathing in pediatric OHCA. CO-CPR, while suitable for adults, may compromise outcomes in children. Emphasizing rescue breathing in pediatric resuscitation training and integrating infection control measures is essential for future public health emergencies. No potential conflict of interest relevant to this article was reported.

Microbiology Society Acta Medica Okayama 0022-1317 106 7 2025 Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Fungal and Protist Viruses Subcommittee, 2025 002115 EN Sead Sabanadzovic Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University Chantal Abergel Information Génomique & Structurale, UMR7256, CNRS & Aix-Marseille Université, Marseille, IMM, IM2B, IOM Marı́a A. Ayllón Departamento de Biotecnología-Biología Vegetal, Escuela Técnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas, Universidad Politécnica de Madrid (UPM) Leticia Botella Forest Protection and Wildlife Management Mendel University in Brno Marta Canuti Department of Veterinary and Animal Sciences, University of Copenhagen Yuto Chiba School of Agriculture, Meiji University Jean-Michel Claverie Information Génomique & Structurale, UMR7256, CNRS & Aix-Marseille Université, Marseille, IMM, IM2B, IOM Robert H.A. Coutts School of Health, Medicine and Life Sciences, University of Hertfordshire Stefania Daghino Institute for Sustainable Plant Protection, National Research Council of Italy Livia Donaire Centro de Edafología y Biología Aplicada del Segura-CSIC Marco Forgia Institute for Sustainable Plant Protection, CNR Ondřej Hejna Department of Genetics and Biotechnologies, University of South Bohemia Jichun Jia College of Plant Protection, Shanxi Agricultural University Daohong Jiang College of Plant Science and Technology, Huazhong Agricultural University Ioly Kotta-Loizou School of Health, Medicine and Life Sciences, University of Hertfordshire Mart Krupovic Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit Andrew S. Lang Department of Biology, Memorial University of Newfoundland Matthieu Legendre Information Génomique & Structurale, UMR7256, CNRS & Aix-Marseille Université, Marseille, IMM, IM2B, IOM Shin-Yi Lee Marzano United States Department of Agriculture, Agricultural Research Service, Application Technology Research Unit Luca Nerva Council for Agricultural Research and Economics - Research Centre for Viticulture and Enology Judit Pénzes Department of Entomology, Texas A&M University Anna Poimala Natural Resources Institute Finland (Luke) Sofia Rigou Information Génomique & Structurale, UMR7256, CNRS & Aix-Marseille Université, Marseille, IMM, IM2B, IOM Yukiyo Sato Department of Biology, Institute for Plant Sciences, University of Cologne Wajeeha Shamsi Department of Molecular Biology and Genetics, Aarhus University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University Massimo Turina Department of Plant Protection, School of Agriculture, The University of Jordan Syun-ichi Urayama Department of Life and Environmental Sciences, University of Tsukuba Eeva J. Vainio Natural Resources Institute Finland (Luke) Jiatao Xie College of Plant Science and Technology, Huazhong Agricultural University The Fungal and Protist Viruses Subcommittee (SC) of the International Committee on Taxonomy of Viruses (ICTV) has received a total of eight taxonomic proposals for the 2024 annual cycle. The extent of proposed changes varied, including nomenclatural updates, creation of new taxa and reorganization of established taxa. Following the ICTV procedures, all proposals were reviewed and voted upon by the members of the Executive Committee with ratification in March 2025. As a result, a total of 52 species in the families Botourmiaviridae and Marnaviridae were renamed to comply with the mandated binomial format. A new genus has been added to the dsRNA virus family Amalgaviridae, while two new families, Splipalmiviridae (Wolframvirales) and Mycoalphaviridae (Hepelivirales), were created to classify new groups of positive-sense (+) RNA mycoviruses. The class Arfiviricetes (Cressdnaviricota) was expanded by a new order Lineavirales and a new family Oomyviridae of ssDNA viruses. Additionally, a new class Orpoviricetes was created in the kingdom Orthornavirae to classify a group of bisegmented (+)RNA viruses reported from fungi and oomycetes. Finally, the order Pimascovirales was reorganized to better depict evolutionary relationships of pithoviruses and related viruses with large dsDNA genomes. The summary of updates in the taxonomy of fungal and protist viruses presented here is limited to taxa within the remit of this Subcommittee. For information on taxonomy changes on other fungal viruses closely related to animal and/or plant viruses, please see reports from sister ICTV Subcommittees (i.e. Plant Virus SC and Animal dsRNA and ssRNA(−) Viruses SC). No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2051-5960 13 1 2025 Rotenone targets midbrain astrocytes to produce glial dysfunction-mediated dopaminergic neurodegeneration 234 EN Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nami Isooka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Kikuoka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Imafuku Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaori Masai Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kana Tomimoto Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiharu Sogawa Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology Norio Sogawa Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Kitamura Department of Pharmacotherapy, School of Pharmacy, Shujitsu University Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Exposure to pesticides, such as rotenone or paraquat, is an environmental factor that plays an important role in the pathogenesis of Parkinson's disease (PD). Rotenone induces PD-like pathology and is therefore used to develop parkinsonian animal models. Dopaminergic neurotoxicity caused by rotenone has been attributed to the inhibition of mitochondrial complex I, oxidative stress and neuroinflammation; however, the mechanisms underlying selective dopaminergic neurodegeneration by rotenone remain unclear. To resolve this, we focused on glial diversity and examined whether the brain region-specific glial response to rotenone could determine the vulnerability of dopaminergic neurons using primary cultured neurons, astrocytes and microglia from the midbrain and striatum of rat embryos and rotenone-injected PD model mice. Direct neuronal treatment with low-dose rotenone failed to damage dopaminergic neurons. Conversely, rotenone exposure in the presence of midbrain astrocyte and microglia or conditioned media from rotenone-treated midbrain glial cultures containing astrocytes and microglia produced dopaminergic neurotoxicity, but striatal glia did not. Surprisingly, conditioned media from rotenone-treated midbrain astrocytes or microglia monocultures did not affect neuronal survival. We also demonstrated that rotenone targeted midbrain astrocytes prior to microglia to induce dopaminergic neurotoxicity. Rotenone-treated astrocytes produced secreted protein acidic and rich in cysteine (SPARC) extracellularly, which induced microglial proliferation, increase in IL-1β and TNF-α, and NF-κB (p65) nuclear translocation in microglia, resulting in dopaminergic neurodegeneration. In addition, rotenone exposure caused the secretion of NFAT-related inflammatory cytokines and a reduction in the level of an antioxidant metallothionein (MT)-1 from midbrain glia. Furthermore, we observed microglial proliferation and a decrease in the number of MT-positive astrocytes in the substantia nigra, but not the striatum, of low-dose rotenone-injected PD model mice. Our data highlight that rotenone targets midbrain astrocytes, leading to SPARC secretion, which promotes the neurotoxic conversion of microglia and leads to glial dysfunction-mediated dopaminergic neurodegeneration. No potential conflict of interest relevant to this article was reported.

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

Journal of Neurosurgery Publishing Group (JNSPG) Acta Medica Okayama 2694-1902 10 13 2025 Endovascular treatment for a symptomatic dissecting ophthalmic artery aneurysm occurring in the orbit: illustrative case CASE25483 EN Kohei Izumihara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Haruma Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Sugiu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fukiko Baba Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Juntaro Fujita Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Sotome Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Kawakami Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryu Kimura Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Hiramatsu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences BACKGROUND: Peripheral ophthalmic artery aneurysms (POAAs) arising from the main trunk or branches of the ophthalmic artery (OphA) are extremely rare. However, their epidemiology and optimal management remain poorly understood. The authors report a rare case of a symptomatic POAA caused by arterial dissection that was successfully treated using endovascular therapy, leading to favorable visual recovery. OBSERVATIONS: A 77-year-old woman presented with sudden-onset visual impairment in the right eye. Ophthalmological examination revealed a defect in the right visual field. CT angiography revealed a fusiform aneurysm in the right intraorbital OphA. Digital subtraction angiography revealed a pearl and string sign, consistent with a dissecting aneurysm. A balloon test occlusion (BTO) of the OphA origin confirmed collateral circulation from the external carotid artery. Internal trapping of the OphA was performed under general anesthesia. Postoperatively, the patient’s visual function gradually improved, and complete recovery was achieved within 3 months. LESSONS: Although POAAs are exceptionally rare, they may lead to significant visual dysfunction owing to optic nerve compression. When visual symptoms are present, prompt intervention may reverse the symptoms. Preoperative assessment of collateral circulation using BTO is essential for treatment planning. Internal trapping may be an effective strategy when sufficient collateral flow is confirmed. No potential conflict of interest relevant to this article was reported.

Copernicus GmbH Acta Medica Okayama 2194-9034 XLVIII-4/W9-2024 2024 3D MONITORING OF COASTAL EROSION CONTROL STRUCTURES USING UAV 313 320 EN N. Sakamoto Graduate School of Environmental and Life Science, Okayama University S. Nishiyama Graduate School of Environmental and Life Science, Okayama University Coastal erosion has increasingly become a problem in recent years due to rising sea levels caused by global warming. To prevent further coastal erosion and damage, control structures like seawalls and breakwaters have been installed along vulnerable coastlines. However, it is crucial that these structures are regularly and thoroughly inspected for any abnormalities or deformations. At present, inspections are done manually by visual surveys which are time-consuming and inefficient. There is great potential to optimize this process using drone technology equipped with 3D laser scanners. In this study, we utilized a drone with a green laser scanner to inspect and diagnose control structures along the coast. We conducted surveys to determine the basic performance of this approach and used ICP algorithms to extract any deformations in vanishing wave blocks over two time periods. Our results showed high variability in basic performance due to the influence of waves during the surveys. However, we were still able to detect strain of around 50 cm in a submerged breakwater located 3 meters below the water's surface. Furthermore, an overall settlement of approximately 34 cm was observed in the vanishing wave blocks along with some localized movements. This demonstrates that drones can be successfully implemented for efficient inspection, diagnosis and detection of abnormalities and deformations in coastal structures that are extremely difficult to identify through visual surveys alone. The use of this advanced technology will allow for quicker identification of at-risk structures, enabling timely maintenance and prevention of further coastal erosion. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0919-8172 32 11 2025 Role of Cytoreductive Nephrectomy in the Immune Checkpoint Inhibitor Era: A Multicenter Collaborative Study 1677 1685 EN Takuhisa Nukaya Department of Urology, Fujita-Health University School of Medicine Kiyoshi Takahara Department of Urology, Fujita-Health University School of Medicine Shingo Toyoda Department of Urology, Kindai University Faculty of Medicine Lan Inoki Department of Urology, Kindai University Faculty of Medicine Wataru Fukuokaya Department of Urology, The Jikei University School of Medicine Keiichiro Mori Department of Urology, The Jikei University School of Medicine Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine Ryoichi Maenosono Department of Urology, Osaka Medical and Pharmaceutical University Takuya Tsujino Department of Urology, Osaka Medical and Pharmaceutical University Yosuke Hirasawa Department of Urology, Tokyo Medical University Takafumi Yanagisawa Department of Urology, The Jikei University School of Medicine Takeshi Hashimoto Department of Urology, Tokyo Medical University Kazumasa Komura Department of Urology, Osaka Medical and Pharmaceutical University Motoo Araki Department of Urology, Okayama University Graduate School of Medicine Kazutoshi Fujita Department of Urology, Kindai University Faculty of Medicine Yoshio Ohno Department of Urology, Tokyo Medical University Ryoichi Shiroki Department of Urology, Fujita-Health University School of Medicine Objectives: We aimed to evaluate overall survival (OS) and determine the optimal timing of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitor (ICI)-based therapy. Methods: This retrospective study reviewed medical records of 447 patients with mRCC treated with ICI at multiple Japanese institutions between January 2018 and August 2023. From this cohort, 178 patients with lymph node or distant metastases received either cytoreductive nephrectomy (CN group; n = 72) or ICI therapy without cytoreductive nephrectomy (non-CN group; n = 106) as first-line treatment. Results: Median progression-free survival was 15.7 months, and median overall survival was 58.1 months. CN significantly improved OS, with the CN group's median OS not reached, compared to 29.6 months in the non-CN group (p = 0.01). Deferred CN also showed improved survival outcomes. Poor prognostic factors for immediate CN included International Metastatic Renal Cell Carcinoma Database Consortium poor risk, sarcomatoid differentiation, and a high neutrophil-to-lymphocyte ratio. Conclusions: We developed a prognostic model to guide patient selection for CN, emphasizing the need for personalized treatment strategies. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0266-352X 178 2025 End-to-end time-dependent probabilistic assessment of landslide hazards using hybrid deep learning simulator 106920 EN Menglu Huang Department of Civil and Environmental Engineering, Okayama University Shin-ichi Nishimura Department of Civil and Environmental Engineering, Okayama University Toshifumi Shibata Department of Civil and Environmental Engineering, Okayama University Ze Zhou Wang Marie Skłodowska-Curie Fellow, Department of Engineering, University of Cambridge Early warning detection of landslide hazards often requires real-time or near real-time predictions, which can be challenging due to the presence of multiple geo-uncertainties and time-variant external environmental loadings. The propagation of these uncertainties at the system level for understanding the spatiotemporal behavior of slopes often requires time-consuming numerical calculations, significantly hindering the establishment of an early warning system. This paper presents a hybrid deep learning simulator, which fuses parallel convolutional neural networks (CNNs) and long short-term memory (LSTM) networks through attention mechanisms, termed PCLA-Net, to facilitate time-dependent probabilistic assessment of landslide hazards. PCLA-Net features two novelties. First, it is capable of simultaneously handling both temporal and spatial information. CNNs specialize in interpreting spatial data, while LSTM excels in handling time-variant data. Coupled with two attention mechanisms, the two modules are combined to probabilistically predict the spatiotemporal behavior of slopes. Second, PCLA-Net realizes end-to-end predictions. In this paper, the Liangshuijing landslide in the Three Gorges Reservoir area of China is used to illustrate PCLA-Net. It is first validated followed by a comparison with existing techniques to demonstrate its improved predictive capabilities. The proposed PCLA-Net simulator can achieve the same level of accuracy with at least 50% reduction in computation resources. No potential conflict of interest relevant to this article was reported.

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

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.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 23 27 2025 Fluorescence detection of DNA with a single-base mismatch by a Tm-independent peptide nucleic acid (PNA) twin probe 6557 6563 EN Koki Ishii Department of Applied Chemistry, Kindai University Hajime Shigeto Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Shohei Yamamura Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Yoshitane Imai Department of Applied Chemistry, Kindai University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mizuki Kitamatsu Department of Applied Chemistry, Kindai University There is a need to develop efficient methods for detecting target nucleic acids to enable the rapid diagnosis and early treatment of diseases. We previously demonstrated that a peptide nucleic acid (PNA) twin probe, consisting of two PNAs each containing a fluorescent dye, with pyrene at one end, detects target DNA sequence-specifically through pyrene excimer emission. In this study, to advance the development of this probe system, we further investigated the fluorescence properties of the PNA twin probe P1 and P2, and found that the excimer fluorescence was significantly reduced when a mismatched base in the DNA sequence was present at the site of P1 closest to the pyrene. In other words, this probe was found to detect single-base mismatches without taking into account the thermal stability of the PNA/DNA hybrid. The detection limit of this PNA twin probe for the single-base-mismatched DNA was 2.7 nM. In the future, this probe should lead to a method to detect point mutations in endogenous nucleic acids within cells. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 9 2025 Incidence and Factors Influencing Locomotive Syndrome in Cancer Patients Living in the Community e91856 EN Yoshiteru Akezaki Division of Physical Therapy, Kochi Professional University of Rehabilitation Eiji Nakata Department of Orthopaedic Surgery, Okayama University Hospital Masato Kikuuchi Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Yoshimi Katayama Department of Rehabilitation Medicine, Okayama University Hospital Shinsuke Sugihara Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Background Investigating locomotive syndrome (LS) of cancer survivors in the community will help clarify the importance of rehabilitation for cancer survivors in the community and provide a basis for exploring effective interventions. The primary purpose of this study was to conduct a comparison of LS, fatigue, psychological problems, and physical activity in cancer survivors and those without cancer in the community. The secondary purpose was to analyze factors influencing LS in cancer patients. Methods The study involved 59 cancer patients undergoing chemotherapy at home and 59 people without cancer. The cancer patients were those undergoing chemotherapy as outpatients and constituted the cancer group. The non-cancer people were living in the community and constituted the non-cancer group. Cancer and non-cancer groups were surveyed and measured for LS, fatigue, psychological problems, and physical activity. The cancer group was also surveyed for the duration of chemotherapy treatment and the presence or absence of bone metastases. Results The cancer group was significantly more likely than the non-cancer group to have LS stage 2, to have fatigue, and to have psychological problems. Fatigue and psychological problems were significantly associated with LS stage 2. Conclusions Cancer patients in the community need to be assessed regularly by healthcare providers and interventions should be made according to their condition. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 10 2025 Histopathological Study of Regenerative Endodontic Therapy on an Immature Mandibular Second Premolar With Pulp Necrosis: A Case Report e95647 EN Hidefumi Sako Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazuhiro Omori Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Shinoda-Ito Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake Department of Oral Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitoshi Nagatsuka Department of Oral Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Regenerative endodontic therapy (revascularization) for immature permanent teeth with pulp necrosis and/or apical periodontitis is an effective treatment to promote root maturation. Previous histological studies have reported the formation of cementoid or osteoid tissue and periodontal ligament-like tissue within the root canals. This case report presents the histopathological findings of a human immature permanent tooth with pulp necrosis following revascularization. A 11-year-old male patient presented with tenderness on biting and the formation of a sinus tract in the mandibular right second premolar (tooth #29), diagnosed as pulp necrosis with symptomatic apical periodontitis. Revascularization was performed using calcium hydroxide as an intracanal medicament, with reference to the American Association of Endodontists (AAE) 2018 Position Paper on Regenerative Endodontics. At the 12-month follow-up, radiographs showed thickening of the canal walls, apical narrowing, root elongation, and recovery of pulp sensibility. The tooth was later extracted for orthodontic reasons at 42 months and processed for histological examination. Histological evaluation revealed cementum-like hard tissue continuous with the existing dentin in the apical region, suggesting apical closure. In contrast, the coronal portion showed less mature cementum-like tissue accompanied by loose connective tissue and neovascularization. These findings indicate that revascularization with calcium hydroxide can induce the formation of cementum-like and dentin-like tissues with vascular regeneration in immature permanent teeth with pulp necrosis. No potential conflict of interest relevant to this article was reported.

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

American Geophysical Union (AGU) Acta Medica Okayama 2169-9313 130 10 2025 Electrical Conductivity of Carbonated Hydrous Basaltic Melt: Implications for the Conductivity Anomaly Beneath the Ocean Floors e2025JB032215 EN Bin Zhao Institute for Planetary Materials, Okayama University Jintao Zhu Institute for Planetary Materials, Okayama University Jinze He Institute for Planetary Materials, Okayama University Takashi Yoshino Institute for Planetary Materials, Okayama University We measured the electrical conductivity of CO2 and H2O-bearing basaltic melts up to 1750 K at 2 GPa, corresponding to pressure around the lithosphere-asthenosphere boundary. The electrical conductivity of the dry and hydrous samples is comparable to those reported by previous studies on the Fe-free basaltic melt. The substantial CO2 can limit the water solubility in basaltic melt at 2 GPa. Both CO2 and H2O, which cannot completely dissolve in the melt, coexist as fluid phases, resulting in reduced electrical conductivity of the basaltic melt, which has a lower water content relative to the amount of volatile components in the bulk starting system. The activation enthalpy of basaltic melt is markedly higher than those of more evolved silicate melts, especially on the H2O-poor condition, due to the more enriched alkaline earth elements. The present results suggest that an overall melt fraction of 0.1–5.3 vol% is needed to account for the high electrical conductivity anomalies (10−1.3 to 10−0.3 S/m) beneath the oceanic plate near the East Pacific Rise and Cocos plate. However, for those regions where the electrical conductivity is extremely high (≥10−0.3 S/m), more than 6 wt% H2O is expected to incorporate to maintain a melt fraction that will not trigger mechanical instability. In turn, it requires a low CO2 budget or degree of carbonation within these regions. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 0022-510X 478 2025 Two Japanese families with adult-onset leukoencephalopathy caused by pathogenic variants in CST3 123708 EN Kenta Orimo Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Kazutaka Shiomi Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki Ryoji Goto Department of Neurology, Graduate School of Medicine, The University of Tokyo Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Yumiko Kuromi Department of Neurology, Fukushima Medical University Nozomu Matsuda Department of Neurology, Fukushima Medical University Kazuaki Kanai Department of Neurology, Fukushima Medical University Ryo Kurokawa Department of Radiology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Junko Nomoto Institute of Medical Genomics, International University of Health and Welfare Masaki Tanaka Institute of Medical Genomics, International University of Health and Welfare Yosuke Omae Genome Medical Science Project, National Institute of Global Health and Medicine Yosuke Kawai Genome Medical Science Project, National Institute of Global Health and Medicine Katsushi Tokunaga Genome Medical Science Project, National Institute of Global Health and Medicine Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo CST3 (NM_000099.4) encodes cystatin C, whose C-terminal truncating variants in this gene have recently been reported to cause adult-onset leukoencephalopathy, characterized by headaches, transient neurological symptoms, and distinct imaging findings. We present four patients from two Japanese families, including one with a novel variant (c.358-2_395del). Three patients from one family developed chronic headaches around the age of 20, whereas the patient from the other family remained asymptomatic until his fifties. mRNA analysis of the patient with c.358-2_395del revealed a splicing alteration leading to an in-frame deletion (p.Lys120_Gln133del), representing the first CST3 variant that does not result in a truncated protein. These findings broaden our understanding of the clinical and genetic spectra of CST3-related leukoencephalopathy (114 words). No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 8 2025 Subacute Progression of Gait Disturbance and Consciousness Impairment Due to Communicating Hydrocephalus Associated With Vestibular Schwannoma e89880 EN Satoka Yano Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Akatsuki Kubota Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Mizuho Kawai Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Daiki Yashita Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Wataru Satake Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Kaoru Yamada Department of Neuropathology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Yuki Shinya Department of Neurosurgery, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Satoru Miyawaki Department of Neurosurgery, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Takeshi Iwatsubo Department of Neuropathology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Tatsushi Toda Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Patients with vestibular schwannomas (VSs) present with vestibulocochlear nerve dysfunction such as vertigo and tinnitus. VSs occasionally develop communicating hydrocephalus as a complication, which is typically characterized by an insidious progression of symptoms. We report a case of an 84-year-old female patient with a VS who developed gait disturbance and consciousness impairment over a three-week period, ultimately resulting in an inability to walk and communicate. A thorough evaluation ruled out encephalitis and other differential diagnoses. Imaging studies demonstrated findings consistent with communicating hydrocephalus, and a tap test temporarily improved her consciousness disturbances. The patient underwent ventriculoperitoneal shunting and stereotactic radiosurgery (SRS), after which both consciousness and gait disturbances dramatically improved 10 days postoperatively. The subacute development of symptoms due to normal pressure hydrocephalus associated with VSs is rare. Furthermore, to the best of our knowledge, this is the first reported case of severe gait impairment and disturbance of consciousness progressing within a short period. This case highlights the importance of considering communicating hydrocephalus associated with VSs as a differential diagnosis, even in cases of subacute consciousness disturbance. We also discuss the pathophysiology of hydrocephalus in relation to cerebrospinal fluid (CSF) clearance into the extracranial space. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0916-7005 2025 Refinement of interval approximations for fully commutative quivers EN Yasuaki Hiraoka Kyoto University Ken Nakashima Shimane University Ippei Obayashi Okayama University Chenguang Xu Kyoto University A central challenge in the theory of multiparameter persistence modules lies in defining effective descriptors for representations of infinite or wild type. In this work, we propose a novel framework for analyzing interval approximations of fully commutative quivers, which offers a tunable trade-off between approximation resolution and computational complexity. Our approach is evaluated on commutative ladder modules of both finite and infinite type. For finite-type cases, we establish an efficient method for computing indecomposable decompositions using solely one-parameter persistent homology. For infinite-type cases, we introduce a new invariant that captures persistence in the second parameter by connecting standard persistence diagrams through interval approximations. Furthermore, we present several models for constructing commutative ladder filtrations, providing new insights into the behavior of random filtrations and demonstrating the utility of our framework in topological analysis of material structures. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0013-8703 2025 Artificial Selections for Life-History Traits Affect Effective Cumulative Temperature and Developmental Zero Point in Zeugoducus cucurbitae EN Takahisa Miyatake Graduate School of Environment, Life, Natural Science and Technology, Okayama University Kentarou Matsumura Department of General Systems Studies, Graduate School of Arts and Sciences, the University of Tokyo Effective cumulative temperature and developmental zero point are important indicators for estimating the timing of organism development and the area of distribution. These indicators are generally considered to have unique values for different species of organisms and are also important for predicting the distribution range of animals and plants, especially insect pests. These values generally are species-specific, but there is variation within populations in traits having a genetic component. However, there are no studies on what kind of selection pressure affects these indicator values. To address this issue, it would be worthwhile to compare these values using individuals of strains that have been artificially selected for life-history traits by rearing them at various temperatures and calculating these indicators from developmental days and temperatures. In the present study, eggs were taken from adults of strains with many generations of artificial selection on two life-history traits (age at reproduction and developmental period) of the melon fly, Zeugodacus cucurbitae, under constant temperature conditions. Eggs were reared at five different temperatures, and the effective cumulative temperatures and developmental zero points of the larval and developmental periods were compared. The results demonstrate that artificial selection on life-history traits in Z. cucurbitae induces evolutionary changes in both the effective cumulative temperature and the developmental zero point across successive generations. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0003-6862 2025 Comparison of flight behaviors among laboratory and field strains in Tribolium castaneum (Coleoptera: Tenebrionidae) using a simple method to measure flight ability EN Sota Sone Faculty of Environment, Life, Natural Science and Technology, Okayama University Takahisa Miyatake Faculty of Environment, Life, Natural Science and Technology, Okayama University Most insects can fly. The acquisition of flight is a factor that allows insects to prosper on Earth. On the other hand, in the same species and population, individual differences in flight ability may occur. Flight ability can vary due to geographical conditions and cumulative rearing. Investigating these changes in flight performance is important for understanding dispersal polymorphism and the evolution of flight performance. Thus, in the present study, the flight behaviors between cumulative rearing and field strains and changes in flight behaviors between strains of the red flour beetle, Tribolium castaneum Herbst (Coleoptera: Tenebrionidae), which is distributed around the world were compared. Tribolium castaneum is a worldwide pest of stored grains. Its body length is about 3–4 mm. Previous studies have investigated the influence of environmental and physiological factors on the flight of this species, but no studies have examined individual differences or polymorphism in flight behaviors within this species. In this study, we developed a simple apparatus that can quantify the flight behavior of this species. The experimental apparatus was set up as a double structure with two different size containers. This apparatus was able to assess the flight activity of insects by counting individuals in a big container because insects transfer to the big container only by flight. Moreover, upward flight ability was possible to be assessed by the apparatus adding the barrier. Then, the flight behavior was compared between strains of this species that have been bred in the laboratory for more than 45 years and several strains of this species collected in the field. The results showed no variation in flight activity between strains, but flying ability was higher in strains originating from warmer regions. Here, we discussed the variations in flight behavior of T. castaneum. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 10 2025 Primary Lacrimal Sac Diffuse Large B-cell Lymphoma Treated With Local Radiotherapy Alone: A Case With No Relapse After 21 Years of Follow-Up e95411 EN Toshihiko Matsuo Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takehiro Tanaka Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mitsuhiro Takemoto Radiotherapy, Himeji Red Cross Hospital Primary lacrimal sac lymphoma is rare and diagnosed as diffuse large B-cell lymphoma in a predominant histopathological type. Systemic chemotherapy would be the standard of care, but local radiotherapy may be a treatment option toward a localized lesion. The present patient is a 54-year-old otherwise healthy woman with a right lacrimal sac mass, which was proven by excisional biopsy to be diffuse large B-cell lymphoma. Since she did not have any other systemic lesions on gallium scintigraphy and neck-to-abdominal computed tomography scans, which were the standard procedure at that time, she underwent local radiotherapy at 40 Gy. Two years later, at the age of 56 years, she developed radiation retinopathy with macular edema in the right eye and had spotty laser photocoagulation in the nasal half of the fundus. At the age of 57 years, she developed radiation cataract and underwent cataract surgery with intraocular lens implantation in the right eye. At the age of 58 years, the macular edema in the right eye became worse and remained active, resulting in poor visual acuity of 0.1. She thus underwent 25-gauge vitrectomy in the right eye to peel off the adhering posterior vitreous surface, together with the internal limiting membrane, as the standard procedure at that time. The visual acuity in the right eye was elevated to 0.6. She maintained the visual acuity afterward and had no relapse of lymphoma in 21 years from the diagnosis of primary right lacrimal sac diffuse large B-cell lymphoma. Local radiotherapy would still be a treatment option for localized lymphoma lesions such as primary lacrimal sac lymphoma. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 20 2025 Neurofibromin Encoded by the Neurofibromatosis Type 1 (NF1) Gene Promotes the Membrane Translocation of SPRED2, Thereby Inhibiting the ERK Pathway in Breast Cancer Cells 10072 EN Nang Thee Su Pwint Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tong Gao Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuze Wang Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masakiyo Sakaguchi Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Neurofibromin (NF) inhibits the RAS/RAF/ERK pathway through its interaction with SPRED1 (Sprouty-related EVH1 domain-containing protein 1). Here, we investigated the functional relationship between NF and SPRED2 in breast cancer (BC). Human BC cell lines were transfected to downregulate or overexpress NF and SPRED2 and subsequently subjected to functional assays. Protein and mRNA levels were analyzed by Western blotting and RT-qPCR, respectively. Protein–protein interactions were examined by immunoprecipitation. Database analyses and immunohistochemistry (IHC) of BC tissues were performed to validate the in vitro findings. Downregulating NF or SPRED2 expression in BC cells enhanced cell proliferation, migration and invasion accompanied by RAF/ERK activation, whereas overexpression produced opposite effects. NF formed a protein complex with SPRED2 and facilitated its translocation to the plasma membrane. By IHC, SPRED2 membrane localization was absent in NF-negative luminal A and triple-negative BC (TNBC) but present in a subset of luminal A BC. By database analyses, both NF1 and SPRED2 mRNA levels were reduced in BC tissues, and luminal A BC patients with high expression of both NF1 and SPRED2 mRNA exhibited improved relapse-free survival. These results suggest a critical role for the NF–SPRED2 axis in BC progression and highlight it as a potential therapeutic target. No potential conflict of interest relevant to this article was reported.

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

Japanese Society of Microbial Ecology Acta Medica Okayama 1342-6311 40 3 2025 Role of Formate Chemoreceptor in Pseudomonas syringae pv. tabaci 6605 in Tobacco Infection ME25019 EN Phuoc Quy Thang Nguyen The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuta Watanabe The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiteru Noutoshi The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Chemotaxis is essential for infection by plant pathogenic bacteria. The causal agent of tobacco wildfire disease, Pseudomonas syringae pv. tabaci 6605 (Pta6605), is known to cause severe leaf disease and is highly motile. The requirement of chemotaxis for infection has been demonstrated through the inoculation of mutant strains lacking chemotaxis sensory component proteins. Pta6605 possesses 54 genes that encode chemoreceptors (known as methyl-accepting chemotaxis proteins, MCPs). Chemoreceptors are classified into several groups based on the type and localization of ligand-binding domains (LBD). Cache LBD-type chemoreceptors have been reported to recognize formate in several bacterial species. In the present study, we identified Cache_3 Cache_2 LBD-type Mcp26 encoded by Pta6605_RS00335 as a chemoreceptor for formate using a quantitative capillary assay, and named it McpF. Although the deletion mutant of mcpF (ΔmcpF) retained attraction to 1% yeast extract, its chemotactic response to formate was markedly reduced. Swimming and swarming motilities were also impaired in the mutant. To investigate the effects of McpF on bacterial virulence, we conducted inoculations on tobacco plants using several methods. The ΔmcpF mutant exhibited weaker virulence in flood and spray assays than wild-type and complemented strains, highlighting not only the involvement of McpF in formate recognition, but also its critical role in leaf entry during the early stages of infection. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1876-2018 108 2025 Introduction to the “Japanese and Western approaches to psychotrauma” symposium 104508 EN Masanori Nagamine Division of Behavioral Science, National Defense Medical College Research Institute Tomoyo Nakao Graduate School of Humanities and Social Sciences, Okayama University Leo van Bergen Freelance Medical Historian Jun Shigemura Faculty of Health Sciences, Mejiro University Taku Saito Division of Behavioral Science, National Defense Medical College Research Institute Florentine H.S. van der Does Department of Psychiatry, Leiden University Medical Center (LUMC) Masato Kitano Division of Behavioral Science, National Defense Medical College Research Institute Erik J. Giltay Department of Psychiatry, Leiden University Medical Center (LUMC) Nic J. van der Wee Department of Psychiatry, Leiden University Medical Center (LUMC) Eric Vermetten Department of Psychiatry, Leiden University Medical Center (LUMC) Understandings of psychotrauma have changed throughout medical history, shaped by cultural and social factors. Reviewing transcultural perspectives of psychotrauma helps understand its complexities and contextual impacts. This paper summarizes the Japan–Netherlands symposium on psychotrauma held on March 1, 2024. Despite experiencing psychological trauma from World War II and numerous natural disasters, Japan did not actively research post-traumatic stress disorder (PTSD) for nearly 50 years after the war. The Great Hanshin-Awaji Earthquake and the Tokyo subway Sarin gas attack (1995) popularized the term PTSD in Japan and triggered related research. The absence of psychotrauma research in Japan may reflect a form of state-level PTSD, characterized by avoidance. Japan’s collectivist culture, stigma against seeking psychological help, view of patience as a virtue, survivor guilt, and moral injury were potential related factors. Additionally, sociocultural factors (e.g., insufficient collective grieving and focusing on post-war reconstruction) were discussed as potential hinderances to discussing war experiences. From a European perspective, we examined how “Konzentrationslager” (KZ) syndrome, a trauma-related disorder, evolved independently into diverse conceptual frameworks, ultimately contributing to the acceptance of PTSD following its introduction in 1980. Beyond state compensation for concentration camp survivors, advocacy by feminist movements and veterans' groups increased awareness of psychotrauma across Europe, fostering scholarly research and public discourse. Both PTSD and KZ syndromes are diagnostic categories shaped by specific historical and cultural contexts and should not be regarded as simple, universally applicable medical conditions. They reflect how trauma is interpreted and responded to differently depending on cultural, political, and historical factors. No potential conflict of interest relevant to this article was reported.

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

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

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

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

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

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

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

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

Oxford University Press (OUP) Acta Medica Okayama 1465-3621 55 6 2025 Real-world clinical usage and efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer: a multi-institutional study in the CsJUC 643 649 EN Yoichiro Tohi Department of Urology, Faculty of Medicine, Kagawa University Keita Kobayashi Department of Urology, Graduate School of Medicine, Yamaguchi University Kei Daizumoto Department of Urology, Tokushima University Graduate School of Biomedical Sciences Yohei Sekino Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hideo Fukuhara Department of Urology, Kochi Medical School Heima Niigawa Department of Urology, Kawasaki Medical School Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryutaro Shimizu Division of Urology, Department of Surgery, Faculty of Medicine, Tottori University Atsushi Takamoto Department of Urology, Fukuyama City Hospital Kenichi Nishimura Department of Urology, Ehime University Taichi Nagami Department of Urology, Shimane University Faculty of Medicine Yushi Hayashida Department of Urology, Sakaide City Hospital Hiromi Hirama Department of Urology, KKR Takamatsu Hospital Koji Shiraishi Department of Urology, Graduate School of Medicine, Yamaguchi University Ryotaro Tomida Department of Urology, Tokushima University Graduate School of Biomedical Sciences Kohei Kobatake Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University Keiji Inoue Department of Urology, Kochi Medical School Yoshiyuki Miyaji Department of Urology, Kawasaki Medical School Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuichi Morizane Division of Urology, Department of Surgery, Faculty of Medicine, Tottori University Noriyoshi Miura Department of Urology, Ehime University Koichiro Wada Department of Urology, Shimane University Faculty of Medicine Mikio Sugimoto Department of Urology, Faculty of Medicine, Kagawa University Chu-shikoku Japan Urological Consortium Objective: To evaluate the real-world clinical usage and effectiveness of apalutamide in men with nonmetastatic castration-resistant prostate cancer (nmCRPC). Methods: We retrospectively reviewed the data of 186 men who received apalutamide across 17 institutions. The primary outcomes were the clinical usage of apalutamide for nmCRPC: prior usage of other androgen receptor signaling inhibitors (ARSIs), prior radical treatment, and the distribution of the prostate-specific antigen (PSA) doubling time (PSA-DT) at the initial administration of apalutamide. The secondary outcomes were the efficacy of apalutamide: PSA response (50% or 90% decline), progression-free survival, and skin-adverse events (AEs). Results: We identified 75 patients with nmCRPC. A total of 31 (41.3%) patients received prior treatment with other ARSIs. A total of 42 men (56%) did not receive any prior radical treatment. The PSA-DT was <3.0, 3.0–5.9, 6.0–10, and > 10 months in 34.7%, 40%, 14.7%, and 10.6% of the patients, respectively. Patients receiving prior treatment with other ARSIs showed a significantly lower PSA response (PSA 50% decline, 88.4% vs. 18.8%; PSA 90% decline, 60.5% vs. 6.2%, P < .001, respectively) and significantly shorter progression-free survival (median: 37 months vs. 4 months; log-rank P < .001) than those without prior ARSI treatment, although cancer status did not differ between the groups. Skin-AEs were observed in 42.7%. Conclusions: This real-world study revealed that apalutamide was used for the treatment after other ARSIs in >40% of patients with nmCRPC and showed limited efficacy in this context, although the effectiveness of apalutamide without prior other ARSI treatment was comparable with that reported in clinical trial results. No potential conflict of interest relevant to this article was reported.

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