MDPI AG Acta Medica Okayama 1422-0067 27 5 2026 Aerobic Exercise Attenuates Epidermal Hyperplasia in an Obesity-Associated Psoriasiform Dermatitis Model 2308 EN Yoshihiro Matsuda Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daiki Takezaki Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuma Sakamoto Department of Immunology and Molecular Genetics, Kawasaki Medical School Nobuyasu Baba Department of Immunology and Molecular Genetics, Kawasaki Medical School Masanori Iseki Department of Immunology and Molecular Genetics, Kawasaki Medical School Yoshio Kawakami Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsushi Shiomi Department of Pathology, Kawasaki Medical School Tomoyuki Mukai Department of Immunology and Molecular Genetics, Kawasaki Medical School Obesity is an important risk factor for psoriasis, and clinical studies indicate that exercise interventions can improve disease severity. However, the mechanisms by which exercise influences psoriatic pathogenesis remain insufficiently understood. To investigate the effects of aerobic exercise on obesity-associated psoriasis, wild-type mice were fed a high-fat diet (HFD) for 7 weeks to induce obesity and subsequently underwent moderate-intensity treadmill running for 3 weeks. Psoriasiform dermatitis was induced by daily topical application of imiquimod (IMQ) to the skin for five consecutive days. HFD increased body weight, epididymal fat mass, and serum cholesterol. HFD-fed mice developed more severe IMQ-induced psoriatic skin changes compared with normal diet-fed mice. Treadmill exercise modestly reduced body weight gain and attenuated epidermal hyperplasia in HFD-fed mice. In contrast, inflammatory cytokine expression, including Tnfa, Il17a, and Il23a, showed modest increases in the skin of HFD-fed exercised mice, which did not parallel the improvement in epidermal hyperplasia. Overall, these findings indicate that while obesity exacerbates psoriasiform dermatitis, aerobic exercise ameliorates epidermal hyperplasia in obese mice without corresponding changes in inflammatory cytokine expression in the skin, suggesting that exercise may influence psoriatic skin changes through multiple metabolic and immunological pathways. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 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.<br> 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.<br> 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.<br> 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.

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

Springer Science and Business Media LLC Acta Medica Okayama 2662-4435 7 1 2026 Stability and distribution of dense hydrous magnesium silicates in the mantle transition zone under low water activity conditions 265 EN Yunke Song Key Laboratory of High-temperature and High-pressure Study of the Earth’s Interior, Institute of Geochemistry, Chinese Academy of Sciences Xinzhuan Guo State Key Laboratory of Critical Mineral Research and Exploration, Institute of Geochemistry, Chinese Academy of Sciences Kuan Zhai Key Laboratory of High-temperature and High-pressure Study of the Earth’s Interior, Institute of Geochemistry, Chinese Academy of Sciences Wei Guo State Key Laboratory of Geomicrobiology and Environmental Changes, School of Earth Sciences, China University of Geosciences (Wuhan) Takashi Yoshino Institute for Planetary Materials, Okayama University Water plays a central role in controlling the physical and chemical properties of Earth’s deep interior. It remains uncertain how water is stored in subducting slabs within the mantle transition zone, between depths of about 410 and 660 kilometers, and whether dense hydrous magnesium silicates act as major water carriers to greater depths. Here we report high-pressure and high-temperature laboratory experiments on the Mg-Si-H system at pressures of 16 and 21.5 GPa and a temperature of 1400 K to evaluate hydrous phase stability under transition zone conditions. We find that when bulk water content is below 1.22 wt%, H2O is predominantly incorporated into wadsleyite and ringwoodite rather than forming dense hydrous magnesium silicates. Because estimated water contents in subducted oceanic slabs are typically lower than one weight percent, formation of these silicates is unlikely, suggesting that the mantle transition zone may restrict large scale water transport into the lower mantle. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2238-7854 42 2026 An electric field temporarily strengthens zirconia ceramics 1806 1810 EN Akira Kishimoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takahiro Shimizu Faculty of Environmental, Life, Natural Science and Technology, Okayama University Mitsuru Nishiyama Faculty of Environmental, Life, Natural Science and Technology, Okayama University Shinya Kondo Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takashi Teranishi Faculty of Environmental, Life, Natural Science and Technology, Okayama University By applying an electric field to yttria-stabilized zirconia (8YSZ) equipped with an inert electrode, oxide ions are localized near the positive electrode, causing it to expand. When polarization was performed under different conditions, it was possible to strengthen the material to 1.5 times that of an untreated sample. The lattice constant of the positive electrode surface after polarization was larger than before polarization. When the Vickers hardness of the positive electrode surface was measured by changing the test load, the smaller the load, the higher the hardness value. Polarization caused oxide ions to move near the positive electrode, filling in the defects and generating an expanded layer with a large lattice constant. It is believed that this was subjected to compressive stress from the bulk layer, which had not changed in volume, resulting in an increase in strength. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2662-4443 6 1 2025 From localized 4f electrons to anisotropic exchange interactions in ferromagnetic CeRh6Ge4 269 EN Shoichiro Itokazu Department of Physics, Okayama University Akimitsu Kirikoshi Research Institute for Interdisciplinary Science, Okayama University Harald O. Jeschke Research Institute for Interdisciplinary Science, Okayama University Junya Otsuki Research Institute for Interdisciplinary Science, Okayama University CeRh6Ge4 is a cerium-based ferromagnetic material exhibiting a quantum critical behavior under pressure. We derive effective exchange interactions, using the framework of density functional theory combined with dynamical mean-field theory. Our results reveal that the nearest-neighbor ferromagnetic interaction along the c axis is isotropic in spin space, leading to a formation of spin chains. On the other hand, the inter-chain coupling is highly anisotropic: The in-plane moment weakly interacts ferromagnetically in the a–b plane to stabilize the ferromagnetic state, whereas the z-component couples antiferromagnetically, contributing to its destabilization. The magnetic anisotropy of the interchain interactions as well as of the local 4f wavefunctions characterizes the magnetic properties underlying the ferromagnetic transition and the quantum critical behavior in CeRh6Ge4. 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 大学院共通科目『リーダーシップとSDGs』の教育モデル構築と成果分析 理論学習・ピアレビュー・省察活動によるリーダーシップ教育の新展開 221 235 EN Mamoru ISHIDA Faculty of General Education and Global Studies, Okayama University Shinichi OTSUNE Graduate student, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takuya NAKAZAWA Graduate student, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University 10.18926/CTED/70371 　岡山大学大学院では、博士課程人材のリーダーシップ育成に向け、共通科目『リーダーシップとSDGs』を設計・実践している。本科目はSDGsに貢献するリーダー育成に主眼を置き、理論学習・ピアレビュー・省察・グループディスカッション等の手法を組み合わせ、学生同士の学び合い・自己成長の促進を目的としている。本稿では、学部・研究科ごとに学習成果を分析し、理論に基づく省察的学びと協働的な批評活動がリーダーシップ理解や成長に有用であることを明らかにした。本研究は、学術的理論と実践的活動を織り交ぜたモデル構築と、その継続的改善の意義を示している。 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 立憲主義に対する認識の改善を目指した高等学校公民科の授業開発研究 ―米国公民教育センター開発『我ら合衆国人民』を手がかりにして― 167 180 EN Toshinori KUWABARA Faculty of Education, Okayama University Ayuha MIYAMOTO Graduate School of Humanities and Social Sciences, Okayama University 10.18926/CTED/70367 　本研究は、憲法理解の基本としての立憲主義に対する認識形成を目標とする、高等学校公民科で実践可能な授業の開発を目指したものである。従来の日本の社会科教育においては、憲法理解は日本国憲法の基本原則である国民主権、基本的人権の尊重、平和主義の理解を基本としていたが、近年、そもそも憲法とは何かを理解させるために、立憲主義の概念が注目されるようになり、教科書にも記述されている。本研究は、そのような立憲主義という概念について生徒に適切に理解させることを目指した授業の提案をしようとするものである。授業計画作成にあたっては、米国の公民教育センターが開発し、長年活用されている『我ら合衆国人民（原題 We the People）』を参照し、その一部を活用し、米国の歴史的背景に基づいて作られた教材を、日本の文脈にそって改変した。 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 刑法の意義を捉えさせる社会科における法教育実践の方法 ―模擬裁判を取り入れた中学校社会科の授業開発を通して― 153 165 EN Ayuha MIYAMOTO Graduate School of Human ities and So cial Sciences, Okayama University Toshinori KUWABARA Faculty of Education, Okayama University 10.18926/CTED/70366 　本研究は、刑法の理解に焦点をあて、模擬裁判を取り入れた中学校社会科の授業開発を行なおうとするものである。日本の社会科における法教育は、従来から憲法学習が中心となっており、その他の法律について学ぶ機会は非常に少ない。そのような現状を踏まえて、近年、民法や刑法などを取り上げた法教育の授業開発が行われるようになった。その一方で、裁判員制度導入以降、模擬裁判を取り入れた社会科授業の開発・実践がよく見られるようになっており、刑事事件が社会科授業で取り上げられることも珍しくはなくなった。しかし、そのような授業を担当する教員に、刑法等に関する知識が十分ではなく、模擬裁判の内容と実際の裁判が乖離しているという課題もある。本研究では、従来の模擬裁判を取り入れた授業の特質と課題を検討したうえで、刑法の意義を捉えさせる中学校社会科の授業開発を目指す。 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 日韓の音楽文化交流を通した中学校音楽科におけるグローバル・シティズンシップ教育の構想 ―APCEIUでのインターンシップにおける調査の成果に基づいて― 107 121 EN Hikari KONISHI Graduate School of Education Toshinori KUWABARA Faculty of Education Yumi KONISHI Graduate School of Education 10.18926/CTED/70363 　本論文は、中学校音楽科において、日本と韓国の音楽文化を取り上げて、互いの文化の違いや共通性を捉えさせたうえで相互理解を促進する、グルーバル・シティズンシップ教育（以下、GCED と表記）プログラムを構想しようとするものである。プログラムの構想の際には、筆者である小西が、韓国のソウルのAPCEIU（アジア太平洋国際理解教育センター）で行なった約一か月間のインターンシップの間の実地調査で把握した、韓国で展開されているGCED の方法を参考にした。開発プログラムでは、日韓両国の打楽器を取り上げて、その比較から互いの文化の違いを捉えさせたうえで、違いを受け入れながら、それぞれの国の音楽文化の根底にある歴史的背景に気づかせたうえで、文化の多様性や両国の文化の固有の価値に対する理解を深めることを目指した。 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 地域社会とグローバルをつなぐ和楽器音楽次世代育成の実践研究（３） 小中学生の質問紙調査に見る「異文化間能力」育成の可能性 91 105 EN Rinko HAYAKAWA Okayama University Yuko BEPPU Kurashiki City College Miho YAMAJI Part-time Lecturer at Okayama University Yoko HANAKUSA Research Student at the Joint Graduate School in Science of School Education Hyogo University of Teacher Education Noriko TAKESHITA Biwako-Gakuin University Hiromi TAKASU Okayama University Keiko MIYOSHI Research Student at the Joint Graduate School in Science of School Education Hyogo University of Teacher Education Naoko SHIMIZU Doctoral Student at the Joint Graduate School in Science of School Education Hyogo University of Teacher Education Chihiro TOSA Yamaha Corporation Ai NAKAMURA Doctoral Student at the Joint Graduate School in Science of School Education Hyogo University of Teacher Education Aki HIGUCHI Okayama Prefectural School for the Deaf 10.18926/CTED/70362 　本研究は，「おかやま国際和楽器学生フェスティバル」の実践における，異文化間能力育成の可能性について，参加した小中学生の質問紙調査結果から検討した。<br> 　その結果，１）体験を通して形成された新たな認識により，和楽器音楽文化と自己との関係性を再認識・再構築し，和楽器音楽文化への積極的な関与を示す価値づけ・意味づけが行われ，内在化が促されたこと，２）越境文化としての和楽器音楽文化に対して，開放的・尊重的態度を示していたが，自己の文化的アイデンティティを意識する契機となったこと，３）和楽器音楽の共有を通して生じた共感の上に，相互理解や協働関係が構築されていたこと，４）「文化の共有の可能性についての認識」が形成されるなど，フェスティバルでの経験が，文化観の形成に影響を与える契機となっていたこと，が明らかになった。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 教師教育開発センター Acta Medica Okayama 2186-1323 16 2026 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.

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

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.

Wiley Acta Medica Okayama 2688-4046 6 3 2026 PPy‐Coated Wire Actuators for the Micromechanostimulation of Cells: Fabrication and Characterization e202500639 EN Amaia B. Ortega‐Santos Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Linköping University Satoru Hayano Department of Orthodontics, Okayama University Hospital Emilio Satoshi Hara Advanced Research Center for Oral and Craniofacial Sciences Dental School, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jose G. Martínez Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Linköping University Hiroshi Kamioka Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Edwin W. H. Jager Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Linköping University Cellular mechanotransduction signals play a crucial role in physiological and pathological conditions, including skeletal disorders. Although various systems exist to mechanically stimulate cultured cells, most are constrained by incubator incompatibility, limited physiological relevance, nonuniform stimulation, or complexity. The objective of this article is to develop and validate a compact, incubator-compatible tool capable of delivering localized and physiologically relevant mechanical stimulation to small cell populations. Here, we introduce a polypyrrole-based wire-shaped microactuator designed to induce localized mechanical stress to adjacent cells. These wire-shaped microactuators are biocompatible, easy-to-use, and compact for use within standard in vitro cell culture systems. Using a noncontact optical method, we characterize the actuation of polypyrrole-coated wires in an aqueous NaDBS electrolyte, showing radial expansion of 1.5–8 µm depending on the deposited polypyrrole film thickness, comparable to cellular dimensions. Next, the actuation is confirmed to be robust and stable to use in cell culture media at physiological temperature. To evaluate biological relevance, osteoblastic KUSA-A1 cells are mechanically stimulated inside the incubator and transcriptomic changes are assessed. Mechanical stimulation resulted in upregulation of genes previously associated with mechanotransduction, including Fos and Fosb. Additionally, several uncharacterized long noncoding RNAs are differentially expressed, suggesting potential novel players in the mechanotransduction pathway. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1467-5463 27 1 2026 SGCRNA: spectral clustering-guided co-expression network analysis without scale-free constraints for multi-omic data bbag021 EN Tatsunori Osone Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoka Takao Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shigeo Otake Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Takarada Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Weighted gene co-expression network analysis (WGCNA) is among the most widely employed methods in bioinformatics. WGCNA enables the identification of gene clusters (modules) exhibiting correlated expression patterns, the association of these modules with traits, and the exploration of candidate biomarker genes by focusing on hub genes within the modules. WGCNA has been successfully applied in diverse biological contexts. However, conventional algorithms manifest three principal limitations: the assumption of scale-free topology, the requirement for parameter tuning, and the neglect of regression line slopes. These limitations are addressed by SGCRNA. SGCRNA provides Julia functions for the analysis of co-expression networks derived from various types of biological data, such as gene expression data. The Julia packages and their source code are freely available at https://github.com/C37H41N2O6/SGCRNAs.jl. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2410-387X 9 4 2025 Role-Based Efficient Proactive Secret Sharing with User Revocation 80 EN Yixuan He Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuta Kodera Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Samsul Huda Interdisciplinary Education and Research Field, Okayama University Proactive secret sharing (PSS), an extension of secret-sharing schemes, safeguards sensitive data in dynamic distributed networks by periodically refreshing shares to counter adversarial attacks. In our previous work, we constructed a non-interactive proactive secret scheme by integrating threshold homomorphic encryption (ThHE) while reducing the communication complexity to 𝑂(𝑛). Not only is refreshing shares important but revoking the shares of users who have left the system is also essential in practical dynamic membership scenarios. However, the previous work was insufficient for supporting explicit user revocation. This study strengthens the description of roles for authorized users and proposes a scheme to achieve non-interactive share refresh and dynamic user management. In each epoch, authorized users are classified into three roles: retain, newly join, and rejoin, and they receive a broadcast of the compact ciphertext encoding both the refresh information and the revocation instructions from the trusted center (dealer). Authorized users independently derive new shares through homomorphic computations, whereas revoked users are unable to generate new shares. Hash functions are used to bind revocation parameters to the cryptographic hashes of valid users in order to guarantee integrity during revocation, allowing for effective verification without compromising non-interactivity. Our new scheme not only extends the revocation structure but also preserves the 𝑂(𝑛) communication complexity. 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.

BON VIEW PUBLISHING PTE Acta Medica Okayama 2810-9503 5 1 2025 A Study on Zeek IDS Effectiveness for Cybersecurity in Agricultural IoT Networks 133 142 EN Samsul Huda Interdisciplinary Education and Research Field, Okayama University Muhammad Bisri Musthafa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University S. M. Shamim Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University As agriculture moves toward Agriculture 4.0, which uses Internet of Things (IoT) devices to collect data in real time and monitor things from a distance, these networks are becoming increasingly vulnerable to cyberattacks. A common method used to protect against these kinds of threats is the use of intrusion detection systems (IDS). However, the agricultural environment is often changing and has limited resources, which makes cybersecurity challenging. Several available IDS tools are not designed to work properly in places with few resources, intermittent access, and unpredictable network conditions. This paper investigates the performance of Zeek, an open-source IDS, in identifying potential threats in agricultural IoT networks. We performed both offline and real-time experiments: offline analysis used pcap files from the Stratosphere Laboratory dataset, and real-time evaluation involved simulated live attack scenarios, focusing on unauthorized access attempts and distributed denial-of-service (DDoS) attacks. Zeek's performance was assessed based on CPU and memory utilization, as well as quality of service (QoS) metrics. From the experimental results, we found that Zeek was quite effective in protecting agricultural IoT networks against typical threats. Memory usage remained stable around 5% during offline analysis and under 20% during active attacks. However, CPU usage was more volatile, peaking at 120% during DDoS events. In terms of QoS, the system maintained a good throughput (1,375 kbits/s) with minimal packet loss (0.000186%). Among the attack types that we tested, brute force attacks, which represent attempts at unauthorized access, had the strongest effect on network performance, increasing delay to 2.159 ms and jitter to 0.793 ms. It seems clear that a heavier traffic load during such attacks can interfere with QoS. On the basis of our observation, we recommend practical deployment strategies for agricultural IoT systems that take these limitations into consideration, aiming to keep networks both secure and efficient under pressure. No potential conflict of interest relevant to this article was reported.

岡山大学大学院ヘルスシステム統合科学研究科 Acta Medica Okayama 2436-3227 6 2026 2025 年度次世代医療機器開発人材育成プログラム BIZEN デバイスデザインコースの取り組み 59 68 EN Tsuneaki TSUZUKI Center for Innovative Clinical Medicine, Okayama University Hospital Daisuke UCHIDA Center for Innovative Clinical Medicine, Okayama University Hospital Toshio KISHIMOTO Organization for Research and Innovation Strategy, Okayama University Yoshinari SENGOKU Center for Innovative Clinical Medicine, Okayama University Hospital Toshio KORENAGA Organization for Research and Innovation Strategy, Okayama University Yu HITOBE Center for Innovative Clinical Medicine, Okayama University Hospital Yasuyuki YOSHIBA Academic Field of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jun SAKURAI Center for Innovative Clinical Medicine, Okayama University Hospital 10.18926/interdisciplinary/70331 No potential conflict of interest relevant to this article was reported.

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

John Wiley & Sons Ltd. Acta Medica Okayama 2314-6133 2025 2025 Comparing the Activity of Peripheral Blood Mononuclear Cells Frozen Under Electromagnetic Field Freezing and Standard Slow-Freezing 9884345 EN Takehiro Matsubara Okayama University Hospital Biobank Mina Takagi Faculty of Health Sciences, Okayama University Medical School Takahiro Uwabo Department of Biorepository Research and Networking, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junichi Soh Department of Thoracic Surgery, Osaka Metropolitan University Graduate School of Medicine Shinichi Toyooka Okayama University Hospital Biobank Mizuki Morita Okayama University Hospital Biobank Peripheral blood mononuclear cells (PBMCs) are cells obtained from the blood that are used not only in clinical tests but also in various research applications. The slow-freezing (SLF) method, currently the standard for PBMC cryopreservation, involves extended storage at −80°C before transfer to liquid nitrogen. Delays in this transfer, such as overnight or weekend holds, risk a gradual decline in cell viability. Additionally, variability in freezing duration can lead to inconsistent cell quality, emphasizing the need for an alternative freezing method that allows for more timely transfer to liquid nitrogen. This study is aimed at clarifying whether the method of using a freezer with an applied electromagnetic field (EMF) is superior to the currently used standard SLF method for PBMC cryopreservation. A comparison of the number of viable cells, cell viability, and cell activity showed that the EMF method was equivalent to the SLF method. However, the shortest time required for freezing was significantly shorter with the EMF method than the SLF method (0.25 vs. 3 h), allowing for earlier transfer of PBMC to liquid nitrogen. This demonstrates that the EMF method offers an advantage in operational efficiency, particularly for facilities that routinely process and store PBMCs, such as biobanks and other storage-focused departments. 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 Tribolium castaneum with longer duration of tonic immobility have more variations corresponding to the human Parkinson’s disease genomic region 8840 EN Keisuke Tanaka NODAI Genome Research Center, Tokyo University of Agriculture Ken Sasaki Graduate School of Agriculture, Tamagawa University Shunsuke Yajima NODAI Genome Research Center, Tokyo University of Agriculture Takahisa Miyatake Faculty of Environmental, Life, Natural Science and Technology, Okayama University Parkinson’s disease (PD) is a common neurodegenerative syndrome characterized by the loss of dopaminergic neurons and is also a progressive neurodegenerative disorder that is characterized by dopamine deficiency. We established strains artificially selected for longer and shorter durations of tonic immobility, an antipredator behavior that has received much attention recently, in the red flour beetle, Tribolium castaneum, a model insect species for molecular analyses different from Drosophila melanogaster. Previous studies have shown that the long strains (L-strain) have significantly lower levels of dopamine expression in the brain than the short strains (S-strain) and that they have an abnormal pattern of locomotor activity. Furthermore, previous studies have shown that administering dopamine to L-strain beetles reduces the duration of tonic immobility. Transcriptome analysis of brain and thorax of the L- and S-strains also showed differences in mRNA expression of genes involved in dopamine synthesis and tyrosine metabolism. These results indicate that the phenotype and molecular basis of the L-strain are similar to those of Parkinson’s syndrome symptoms. In order to establish a link between T. castaneum and PD, we compared the DNA sequences of the L- and S-strains to human genes affecting dopaminergic pathways. The DNA comparison revealed many mutated regions in these genes in the L-strain. We discuss the relationship between dopaminergic pathway genes and PD-like phenotypes across humans, Drosophila, and the red flour beetle. No potential conflict of interest relevant to this article was reported.

Asian Agricultural and Biological Engineering Association Acta Medica Okayama 1881-8366 19 1 2026 Biosensing method of growth diagnosis in the forced culture of strawberries ―Development of crop-identification algorithms― 42 50 EN Shogo TSUBOTA Institute of Agricultural Machinery, National Agriculture and Food Research Organization Kazuhiko NAMBA Faculty of Environmental, Life, Natural Science and Technology, Okayama University Shota KASEI Institute of Agricultural Machinery, National Agriculture and Food Research Organization Tokihiro FUKATSU Institute of Agricultural Machinery, National Agriculture and Food Research Organization An image-processing algorithm for identifying individual crops is developed for labor-savings and time-series biological information collection. Information including the leaf development frequency are diagnostic indicators of strawberry growth. The algorithm is designed for drones in greenhouses that cannot acquire location information using the global navigation satellite system (GNSS). Drones fly over crop rows and sequentially assign identification numbers (IDs) to crops. Object-detection artificial intelligence (AI) is used to estimate the crop zone, and the ID is based on the crops number difference between frames. The previous misdetection rate was 1.06 %, failing to identify crops, which decreases to 0.31 % using the proposed algorithm. Furthermore, because there are no failures in consecutive frames, IDs are assigned to all crops correctly. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0923-1811 119 1 2025 Big data-driven target identification by machine learning: DRD2 as a therapeutic target for psoriasis 9 17 EN Takashi Sakai Department of Dermatology, Faculty of Medicine, Oita University Ryusuke Sawada Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Otoha Ichinose Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology Takeshi Terabayashi Department of Pharmacology, Faculty of Medicine, Oita University Yutaka Hatano Department of Dermatology, Faculty of Medicine, Oita University Yoshihiro Yamanishi Department of Complex Systems Science, Graduate School of Informatics, Nagoya University Toshimasa Ishizaki Department of Pharmacology, Faculty of Medicine, Oita University Background: The development of medical treatments has traditionally relied on researchers leveraging scientific knowledge to hypothesize disease mechanisms and identify therapeutic agents. However, the depletion of novel therapeutic targets has become a significant challenge, resulting in stagnation within pharmaceutical research.<br> Objective: To address the scarcity of therapeutic targets, we developed a machine learning (ML)-based system capable of predicting therapeutic target molecules for diseases. To validate its utility, we applied this system to psoriasis, aiming to identify novel treatment strategies.<br> Methods: Our approach utilized a large clinical database to calculate reporting odds ratios for all drugs associated with the prevention of diseases of interest. We identified target proteins by analyzing large chemical structure databases to discover proteins commonly associated with preventive drug candidates. Experimental validation was conducted by administering a predicted therapeutic candidate in an imiquimod-induced psoriasis mouse model.<br> Results: The ML-based predictions identified drugs for Parkinson’s disease as potential preventive candidates for psoriasis. Further analysis highlighted dopamine receptor D2 (DRD2) as a therapeutic target. Administration of a DRD2 agonist alleviated psoriasis symptoms in mice, evidenced by the downregulation of mRNA expression in the IL-17 pathway and reduced serum tumor necrosis factor-α levels.<br> Conclusion: This study demonstrates the utility of a novel ML-based system for identifying therapeutic targets, as shown by its successful application in uncovering the role of DRD2 in psoriasis. Beyond psoriasis, this system offers significant potential for exploring pathological mechanisms and discovering therapeutic targets across various diseases. No potential conflict of interest relevant to this article was reported.

Japan Society of Mechanical Engineers Acta Medica Okayama 1880-5558 20 1 2025 Numerical analysis validating the standard k-epsilon model for the kinetic energy of turbulence subjected to weak but long-lasting wind tunnel blockage acceleration JFST0004 EN Akira ONO Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroki SUZUKI Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Toshinori KOUCHI Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kento TANAKA Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The aim of this study is to investigate the effect of weak but prolonged mean flow accelerations, such as those observed in wind tunnel blockage acceleration, on free-stream turbulence. Specifically, this research aims to validate a model previously developed based on the k-epsilon model. To test this model, the study focuses on scenarios where the turbulence under acceleration is steady and isotropic, since the model suggests that this type of acceleration has no effect on the turbulent kinetic energy. To examine this suggestion, the turbulence within a periodic box was analyzed using large-eddy simulation (LES) based on the conventional Smagorinsky model framework. The numerical analysis is based on a method that conserves velocity fluctuation intensities. The results show that while high rate of acceleration deviates turbulent kinetic energy, low rate acceleration has hardly any effect on turbulent kinetic energy, enstrophy, pressure fluctuation, relative pressure fluctuation intensity, and higher-order statistics of a velocity fluctuation. These results validate the accuracy of the model proposed in the previous studies. These results were obtained by focusing on differences in Reynolds numbers and the spatial scale of the forcing. No potential conflict of interest relevant to this article was reported.

Universitas Islam Negeri Alauddin Makassar Acta Medica Okayama 2548-5334 17 2 2025 Trend of adjusted antenatal care visits on pregnant women and neonatal during the COVID-19 pandemic: Findings from a three districts survey in 2021 110 118 EN Juliani Ibrahim Departement of Public Health, Faculty of Medicine and Health Science, Universitas Muhammadiyah Makassar Yoko Takahata Nursing of Department, Graduate School of Health Science, Okayama University Sukaeni Ibrahim Faculty of Medicine, Bosowa University Sustainable health development efforts amid infectious disease outbreaks such as Coronavirus disease 2019 (COVID-19) require a resilient maternal health system. With cases rising globally and across Asia, Indonesia faces significant disruptions in essential services. A critical research gap exist in utilizing adjusted time-series analysis to isolated pandemic impact from seasonal variation in urban Indonesia. This study evaluates trends in antenatal care (ANC) visits (January 2019–December 2020) at three Community Health Centres in Makassar: Bara-Baraya, Jongaya and Batua using Interrupted Time Series (ITS) analysis. Findings reveal a significant decline in visits during the second and third quarters of 2020, primarily due to transmission fears. We suggest integration of telemedicine and home visits to maintain continuity of care. Although focused on urban Makassar, these results are an important reference for health and offer applicable solutions for other developing countries facing resource constraints. This study emphasizes the need for inclusive prevention strategies to protect maternal health in urban and rural areas in low- to middle-income countries during systemic health crises. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2470-1343 11 9 2026 Water-Resistant Antibacterial Coatings Using Cetylpyridinium Chloride - Graphene Oxide Composites 14570 14577 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 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 Hospital-acquired infections remain a persistent threat in healthcare settings, especially with the increasing number of elderly and immunocompromised patients. In situations where the use of disposable materials is difficult, durable antibacterial surface coatings are essential. In this study, we report the structural characterization of cetylpyridinium chloride-graphene oxide (CPC–GO) hybrid materials and the sustainability of their antibacterial effects, aiming at washable antibacterial coatings for medical applications. Graphene oxide (GO) has a large surface area and numerous functional groups, while cetylpyridinium chloride (CPC) is a quaternary ammonium compound with well-documented antibacterial activity. We hypothesized that the stable incorporation of CPC through the functional groups of GO could improve surface retention and provide long-term antibacterial performance. The structural properties of the CPC–GO composites were characterized by UV–vis spectroscopy, X-ray diffraction, thermogravimetric analysis, scanning electron microscopy, and atomic force microscopy. These analyses confirmed the formation of a complex through ionic bonds and the maintenance of a planar composite structure. The antibacterial performance of the CPC–GO coatings was examined using representative bacteria. Notably, the CPC–GO coatings maintained their antibacterial activity significantly better than the negative controls even after multiple washings. The excellent surface retention of the CPC–GO composite suggests its potential as a next-generation antibacterial coating for areas where disinfection and sterilization are impossible, such as the interior of complex medical devices. This study suggests a strategy to extend the efficacy of existing antibacterial agents through the application of nanomaterials. Future studies will focus on the controlled release, long-term stability, and biocompatibility of CPC to realize clinical applications. 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.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 61 2026 環境支出は企業リスクを軽減するのか？日本企業の実証分析 155 174 EN YUSRA NAZIR 10.18926/70283 　This study examines how environmental conservation costs (ECC) affects firm risk, using changes in leverage ratios and earnings volatility as stand-ins for risk. This study evaluates the direct impact of ECC and its relationship to profitability (ROA) using panel data of Japanese companies from 2010 to 2022 and Pooled OLS regression models. The results demonstrate the risk-mitigating function of sustainability investments by showing that, although independent ECC have little direct significance, their interaction with firm profitability dramatically lowers earnings volatility and leverage instability. These findings underscore the economic value of environmental strategies, suggesting that incorporating profitability considerations into sustainability practices enhances operational stability and reduces risk exposure. To help policymakers, investors, and corporate managers strike a balance between sustainability and financial performance, this study contributes to the growing body of research on the relationship between the environment and finance. No potential conflict of interest relevant to this article was reported.

岡山大学考古学研究室 Acta Medica Okayama 2026 岡山市向場・黒住丘陵の遺跡測量調査概要報告 EN 10.18926/70272 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 Environmental Conservation Costs and Operational Efficiency: Evidence from Japanese Manufacturing Firms 93 109 EN Yusra Nazir Doctoral student at Graduate school of humanities and social sciences, Okayama University Tatsumasa Tennojiya Faculty of humanities and social sciences, Okayama University 10.18926/OER/70264 　This study investigates whether environmental conservation costs (ECC) support the operational effectiveness and financial stability of Japanese manufacturing firms. Using a balanced panel of 128 non-financial companies listed on the Tokyo Stock Exchange from 2010 to 2022, we manually collected firm-level ECC data based on the Ministry of the Environment, Japan's guidelines from sustainability reports and matched them with financial data from Compustat Global/S&P Capital IQ. Applying pooled ordinary least squares regression with firm-level clustered standard errors and winsorized variables, we examine two aspects of performance as measures of operating efficiency and profitability: asset turnover and profit margin. The results show that ECC is positively associated with asset turnover and profit margin, and that the effect is stronger in more profitable companies, substantiating the Resource-Based View that green practices generate competitiveness. These findings contribute to sustainability finance research by going beyond perceptual measures of environmental, social, and governance ratings, and measuring actual firm-level spending on environmental activities, thereby providing more nuanced insights into how environmental practices translate into actual financial performance. This study offers clear managerial and policy implications by showing that transparent environmental conservation costs improve disclosure quality and serve as a measure of improved efficiency and profitability. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-6065 67 2026 Alcohol consumption, smoking, and the implications of their cessations for field carcinogenesis in the esophagus: a 10-year prospective cohort study 101798 EN Chikatoshi Katada Department of Medical Oncology, Kyoto University Graduate School of Medicine Tetsuji Yokoyama Department of Health Promotion, National Institute of Public Health Tomonori Yano Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East Yasuaki Furue Department of Endoscopy, Saitama Cancer Center Haruhisa Suzuki Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine Kenji Ishido Department of Gastroenterology, Kitasato University School of Medicine Keiko Yamamoto Division of Endoscopy, Hokkaido University Hospital Hiroyoshi Nakanishi Department of Gastroenterology, Ishikawa Prefectural Central Hospital Tomoyuki Koike Division of Gastroenterology, Tohoku University Graduate School of Medicine Masashi Tamaoki Department of Medical Oncology, Kyoto University Graduate School of Medicine Noboru Kawata Division of Endoscopy, Shizuoka Cancer Center Motohiro Hirao Department of Surgery, NHO Osaka National Hospital Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Ogata Department of Gastrointestinal Surgery, Kanagawa Cancer Center Atsushi Katagiri Division of Gastroenterology, Department of Medicine, Showa Medical University Hospital Takenori Yamanouchi Department of Gastroenterology, Kumamoto Regional Medical Center Hirofumi Kiyokawa Department of Gastroenterology, St. Marianna University School of Medicine Hirofumi Kawakubo Maki Konno Department of Gastroenterology, Tochigi Cancer Center Akira Yokoyama Department of Medical Oncology, Kyoto University Graduate School of Medicine Shinya Ohashi Department of Medical Oncology, Kyoto University Graduate School of Medicine Tai Omori Department of Surgery, Kawasaki Municipal Kawasaki Hospital Tadakazu Shimoda Department of Diagnostic Pathology, Shizuoka Cancer Center Atsushi Ochiai Exploratory Oncology Research and Clinicai Trial Center, National Cancer Center Hideki Ishikawa Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine Akira Yokoyama Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center Manabu Muto Department of Medical Oncology, Kyoto University Graduate School of Medicine Background Alcohol and tobacco are established carcinogens, which promote field carcinogenesis for esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the long-term effects of alcohol and tobacco cessations, and background mucosal status, on risk for metachronous ESCC (mESCC) after endoscopic resection (ER).<br> Methods This was a multicentre prospective cohort study of patients with intramucosal ESCC treated by ER. All participants received structured education on cessation, and underwent regular endoscopic surveillance. Patients were stratified by Lugol-voiding lesion (LVL) grade (A: none, B: 1–9, C: ≥10). The impacts of alcohol and smoking cessation on field carcinogenesis were assessed.<br> Findings Among 331 enrolled patients, the median follow-up was 120 months (range: 1.3–176.9). The cumulative incidences of mESCC were 10.4%, 27.2%, and 61.8% in grades A, B, and C, respectively. An increment of 1 unit (22 g ethanol) of alcohol consumption and higher LVL grade independently increased the risk for mESCC. Alcohol or smoking cessation reduced this risk (hazard ratio [HR] 0.52, 95% confidence interval [CI]: 0.31–0.88; HR 0.44, 95% CI: 0.25–0.78, respectively), and combined cessation had the greatest impact (HR 0.21, 95% CI: 0.07–0.65). Complete cessation, rather than partial reduction, was necessary to achieve meaningful risk reduction.<br> Interpretation Alcohol and tobacco exposure, and a large number of LVL, are major determinants of mESCC. Complete cessation markedly reduces risk, underscoring the importance of behavioural interventions for secondary prevention of field carcinogenesis after ER. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1478-811X 24 1 2026 MMP-3 cleavage of Lamin A induces pro-migratory nuclear deformity, nucleophagy, and their autophagic secretion with extracellular vesicles in metastatic cancer 146 EN Takanori Eguchi Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eman A. Taha Department of Biochemistry, Faculty of Science, Ain Shams University Keisuke Nakano Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Vikas Tiwari Council of Scientific & Industrial Research-Indian Institute of Toxicological Research Katsuki Takebe Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Inoue Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Lizi Xing Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chiharu Sogawa Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology Kuniaki Okamoto Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Stuart K. Calderwood Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that cleave a plethora of substrates, including components of the extracellular matrix and cell-surface-associated proteins, as well as intracellular targets. MMPs have also been found in extracellular vesicles (EVs), such as exosomes. MMP-3 promotes tumor growth, epithelial-to-mesenchymal transition, genome instability, migration, invasion, and metastasis of cancer cells, and nuclear MMP-3 controls gene transcription. Intranuclear proteolysis by MMPs may significantly alter cancer progression. However, the nuclear substrates of MMP-3 have not been well investigated. In this study, we performed proteomic analyses to identify the nuclear substrates and EV proteins regulated by MMP-3. While rabidly metastatic colon cancer (LuM1) three-dimensionally cultured tumoroids secreted EVs containing 30 protein types, including Lamin A (LMNA), MMP-3, fibronectin (FN1), HSPA8 (Hsc70), β-actin (ACTB), and vimentin (VIM), CRISPR/Cas9-based knockout of MMP-3 reduced the secretion of these proteins in EVs. Notably, EV-bound cleaved Lamin secretion was confirmed by immunoelectron microscopy. Also, MMP-3 formed proteolytic dimers via its hemopexin-like repeat domains in nuclei. Many nuclear MMP-3-binding proteins, including Lamin A/C, histones, topoisomerases, and hnRNPs, were screened by co-immunoprecipitation followed by proteomics. Proteolytic MMP-3 overexpression generated a C-terminal 30-kDa fragment of Lamin A, whose cleavage site was defined via structural analysis. MMP-3 digestion of Lamin A induced nuclear deformity (atypia) required for cell migration in confined space. The cleaved Lamin A and MMP-3 were transported with autophagosomes (LC3B+), nucleophagosomes, and amphisomes (CD63 + LC3B+) and co-secreted with EVs. Proteolytic MMP-3 also induced nuclear speckles of Lamin A, suggesting their roles in transcription and splicing. Clinical analysis revealed that high expressions of MMP3 and LMNA were significantly seen in head and neck squamous cell carcinoma (HNSC) than in the other 16 cancer types, and predicted poor prognosis of patients suffering from HNSC, pancreatic, rectum and lung adenocarcinomas at specific stages. Immunohistochemistry revealed that nuclear MMP-3 and cleaved Lamin were significantly higher expressed in stage IV metastatic HNSC cases than in stage I non-metastatic cases. Taken together, MMP3-cleavage of Lamin A induces nuclear deformity, nucleophagy, and their autophagic co-secretion with EVs in metastatic cancer. Also, high expression of MMP-3 and secretion of Lamin A can predict poor prognosis in multiple cancer types at specific stages. No potential conflict of interest relevant to this article was reported.

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

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

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

American Chemical Society (ACS) Acta Medica Okayama 0022-2623 69 5 2026 Discovery of Thermal Sensitizers That Inhibit Heat-Induced SAFB Granule Formation 5944 5955 EN Yuji Furutani Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Natsuki Shimasaki Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Riko Yamada Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Ohtsuki Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazunori Watanabe Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hyperthermia is a minimally invasive cancer treatment based on heat stress-induced apoptosis. Its therapeutic efficacy, however, is often limited by tumor heterogeneity and acquired thermotolerance. Therefore, combination strategies involving hyperthermia and chemotherapy have been developed to enhance the therapeutic efficacy. Previously, we showed that SB366791 enhanced heat-induced apoptosis by inhibiting heat stress-induced scaffold attachment factor B (SAFB) granule formation, although its proapoptotic activity was insufficient. Therefore, we screened to identify novel compounds that enhance heat-induced apoptosis by suppressing SAFB granule formation. We identified four hit compounds that inhibited SAFB granule formation, all exhibiting thermal enhancement ratios > 1.0─that significantly enhanced heat-induced apoptosis efficiency. Additionally, the tumor volume in mice treated with a combination of Z19024498 and hyperthermia was significantly smaller than that in mice treated with hyperthermia or Z19024498. These results indicate that the identified compounds, specifically Z19024498, have potential as thermal sensitizers for hyperthermia therapy. 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.

American Society for Clinical Investigation Acta Medica Okayama 2379-3708 11 3 2025 Collagen-binding C-type natriuretic peptide enhances chondrogenesis and osteogenesis e198959 EN Kenta Hirai Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenta Sawamura Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Ryusaku Esaki Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Ryusuke Sawada Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuka Okusha Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eriko Aoyama Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Hiroki Saito Department of Orthopaedic Surgery, Kitasato University School of Medicine Kentaro Uchida Department of Orthopaedic Surgery, Kitasato University School of Medicine Takehiko Mima Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences Satoshi Kubota Department of Biochemistry and Molecular DentistryBacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Masaki Matsushita Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Osamu Matsushita Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuyuki Hosono Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences C-type natriuretic peptide (CNP) is known to promote chondrocyte proliferation and bone formation; however, CNP’s extremely short half-life necessitates continuous intravascular administration to achieve bone-lengthening effects. Vosoritide, a CNP analog designed for resistance to neutral endopeptidase, allows for once-daily administration. Nonetheless, it distributes systemically rather than localizing to target tissues, which may result in adverse effects such as hypotension. To enhance local drug delivery and therapeutic efficacy, we developed a potentially novel synthetic protein by fusing a collagen-binding domain (CBD) to CNP, termed CBD-CNP. This fusion protein exhibited stability under heat conditions and retained the collagen-binding ability and bioactivity as CNP. CBD-CNP localized to articular cartilage in fetal murine tibiae and promoted bone elongation. Spatial transcriptomic analysis revealed that the upregulation of chondromodulin expression may contribute to its therapeutic effects. Treatment of CBD-CNP mixed with collagen powder to a fracture site of a mouse model increased bone mineral content and bone volume compared with CNP-22. Intraarticular injection of CBD-CNP to a mouse model of knee osteoarthritis suppressed subchondral bone thickening. By addressing the limitations of CNP’s rapid degeneration, CBD-CNP leverages its collagen-binding capacity to achieve targeted, sustained delivery in collagen-rich tissues, offering a promising strategy for enhancing chondrogenesis and osteogenesis. No potential conflict of interest relevant to this article was reported.

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

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

Wiley Acta Medica Okayama 0385-5600 2026 Overexpression of Escherichia coli yaiX Confers Multidrug Resistance and Enhances Virulence in the Silkworm Infection Model EN Kinuka Hongu Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuya Ishikawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoki Kosaki Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin‐Ichi Miyoshi Research Center for Intestinal Health Science, Okayama University Kazuyuki Furuta Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikara Kaito Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The emergence of bacteria with both antimicrobial resistance and high virulence has become a global health concern, underscoring the urgent need to elucidate the molecular basis underlying these traits. Here, we employed the silkworm (Bombyx mori) infection model, which is suitable for high-throughput screening, together with an Escherichia coli library containing plasmid clones of all genes from strain W3110, to identify genes whose overexpression enhances virulence. We found that overexpression of the uncharacterized protein YaiX promoted bacterial proliferation in silkworms and increased host lethality. Compared with the empty-vector control, the YaiX-overexpressing strain exhibited resistance to multiple antimicrobial agents with diverse mechanisms of action, including β-lactams, tetracyclines, fluoroquinolones, aminoglycosides, cationic surfactants, and hydrogen peroxide. Sequence analysis revealed that amino acids 18–52 of YaiX contain a transferase hexapeptide domain predicted to form a left-handed parallel β-helix. Overexpression of YaiX mutants lacking regions outside this domain conferred ampicillin resistance, whereas deletion of the hexapeptide domain abolished this phenotype. RNA sequencing and GO enrichment analyses further indicated that YaiX overexpression altered the expression of genes encoding RNA-binding proteins and porins. These findings suggest that YaiX overexpression, through its hexapeptide domain, modulates gene expression and contributes to both multidrug resistance and enhanced virulence in E. coli. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0964-2633 70 3 2025 Prevalence and Modifiable Risk Factors of Dementia in People With Down Syndrome: Cross‐Sectional Study of Japan in Collaboration With the Intellectual Diversity for Goodness Research Consortium (INDIGO‐2019) 329 336 EN Shintaro Takenoshita Department of Neuropsychiatry, Okayama University Hospital Seishi Terada Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomokazu Inoue Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Taku Kurozumi Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Manabu Takaki Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryozo Kuwano Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Shigeru Suemitsu Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Background: People with Down syndrome (DS) have a strong genetic predisposition to Alzheimer's disease (AD). However, the clinical burden and associated risk factors in diverse, non-Western populations remain less understood. This study aimed to investigate the prevalence of dementia in Japanese adults with DS and to identify modifiable clinical factors associated with dementia.<br> Methods: This cross-sectional multicentre study surveyed 133 adults with DS (mean age 50.1 years) residing in 45 welfare facilities across Japan in 2019. Dementia was diagnosed by a consensus panel of physicians using established criteria (DSM-5, ICD-10, DC-LD) after comprehensive assessments, including the Japanese version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID-J). Logistic regression analysis was performed to identify factors independently associated with dementia.<br> Results: Forty-six participants (34.6%) were diagnosed with dementia. The prevalence rose sharply with age: 0% in their 30s, 30.8% in their 40s, 31.6% in their 50s and 65.5% in their 60s. After adjusting for covariates, older age, female sex, dyslipidaemia and visual impairment were independently associated with dementia.<br> Conclusions: This study, the largest of its kind in Asia, confirms a high prevalence of dementia in institutionalized Japanese adults with DS. Crucially, this study is the first to identify dyslipidaemia and visual impairment as independent and potentially modifiable risk factors in this population. These findings highlight tangible targets for clinical interventions aimed at mitigating dementia risk in people with DS. No potential conflict of interest relevant to this article was reported.

eLife Sciences Publications, Ltd Acta Medica Okayama 2050-084X 13 2025 Stimulatory and inhibitory G-protein signaling relays drive cAMP accumulation for timely metamorphosis in the chordate Ciona RP99825 EN Akiko Hozumi Shimoda Marine Research Center, University of Tsukuba Nozomu M Totsuka Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University Arata Onodera Shimoda Marine Research Center, University of Tsukuba Yanbin Wang Shimoda Marine Research Center, University of Tsukuba Mayuko Hamada Ushimado Marine Institute, Okayama University Akira Shiraishi Bioorganic Research Institute, Suntory Foundation for Life Sciences Honoo Satake Bioorganic Research Institute, Suntory Foundation for Life Sciences Takeo Horie Laboratory for Single-cell Neurobiology, Graduate School of Frontier Biosciences, Osaka University Kohji Hotta Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University Yasunori Sasakura Shimoda Marine Research Center, University of Tsukuba Larvae of the ascidian Ciona initiate metamorphosis tens of minutes after adhesion to a substratum via their adhesive organ. The gap between adhesion and metamorphosis initiation is suggested to ensure the rigidity of adhesion, allowing Ciona to maintain settlement after losing locomotive activity through metamorphosis. The mechanism producing the gap is unknown. Here, by combining gene functional analyses, pharmacological analyses, and live imaging, we propose that the gap represents the time required for sufficient cyclic adenosine monophosphate (cAMP) accumulation to trigger metamorphosis. Not only the Gs pathway but also the Gi and Gq pathways are involved in the initiation of metamorphosis in the downstream signaling cascade of the neurotransmitter GABA, the known initiator of Ciona metamorphosis. The mutual crosstalk of stimulatory and inhibitory G-proteins functions as the accelerator and brake for cAMP production, ensuring the faithful initiation of metamorphosis at an appropriate time and in the right situation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1364-6753 27 1 2026 Compound heterozygosity of a novel missense variant and exonic deletion in hypomyelinating leukodystrophy 15 16 EN Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology Kenta Orimo Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology Kunihiro Ueda Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology Tomonari Seki Department of Neurology, Tokyo Teishin Hospital Yasushi Shiio Department of Neurology, Tokyo Teishin Hospital Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Harushi Mori Department of Radiology, School of Medicine, Jichi Medical University, 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, Tokyo, Japan Department of Neurology Hypomyelinating leukodystrophy 15 (HLD15) results from biallelic pathogenic variants in EPRS1, but exonic deletions have not been reported. We describe a 40-year-old woman with mild intellectual disability, ataxia, dystonia, and MRI showing hypomyelination. Whole-exome sequencing identified a heterozygous missense variant in the prolyl-tRNA synthetase domain of EPRS1 (c.3430 C > G; p.Leu1144Val, NM_004446.3), without second variant. Whole-genome sequencing revealed a heterozygous 220-bp deletion spanning exon 15 (c.1743-30_1932del), and segregation analysis confirmed compound heterozygosity. RT-PCR from lymphoblastoid cells demonstrated exon-15 skipping leading to a frameshift (p.Asn582Serfs*10) and nonsense-mediated decay, leaving predominant expression of the paternally inherited missense allele. These findings support loss-of-function for the deletion and classify c.3430 C > G as likely pathogenic under ACMG/AMP criteria (PM1, PM2, PM3, PP3). This case represents the first exonic deletion reported in EPRS1. The relatively mild, adult-onset phenotype broadens both mutational and clinical spectra of HLD15 and highlights the importance of structural-variant anal No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1546-0096 23 1 2025 Comparison of clinical practices during the transitional and young adult phases between patients with oligoarticular/polyarticular juvenile idiopathic arthritis and those with rheumatoid arthritis in Japan 120 EN Sho Mori Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine Kosuke Shabana Department of Pediatrics, Osaka Medical and Pharmaceutical University Toshihiro Matsui Department of Rheumatology Research, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital Tomo Nozawa Department of Pediatrics, Graduate School of Medicine, Yokohama City University Yuko Sugita Department of Pediatrics, Osaka Medical and Pharmaceutical University Minako Tomiita Department of Allergy and Rheumatology, Chiba Children’s Hospital Yasuo Nakagishi Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children’s Hospital Yuichi Yamasaki Department of Pediatrics, Kagoshima University Hospital Hiroaki Umebayashi Department of General Pediatrics, Miyagi Children’s Hospital Masato Yashiro Department of Pediatrics, Okayama University Hospital Naomi Iwata Department of Infection and Immunology, Allergy and Immunology Center, Aichi Children’s Health and Medical Center Junko Yasumura Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences Hiroyuki Wakiguchi Department of Pediatrics, Yamaguchi University Graduate School of Medicine Takeshi Yamamoto Department of Pediatrics, Chiba University Graduate School of Medicine Shunichiro Takezaki Department of Pediatrics, Faculty of Medicinea and Graduate School of Medicine, Hokkaido University Yuka Okura Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center Tadafumi Yokoyama Department of Pediatrics, Kanazawa University Masaki Shimizu Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Masahiro Hirayama Department of Pediatrics, Mie University Graduate School of Medicine Shigeto Tohma Department of Rheumatology, National Hospital Organization Tokyo National Hospital Nami Okamoto Department of Pediatrics, Osaka Medical and Pharmaceutical University Masaaki Mori Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine Background Juvenile idiopathic arthritis (JIA) is a chronic inflammatory condition that frequently persists into adulthood, posing long-term challenges in disease control and quality of life. However, clinical management during the transitional and young adult phases remains insufficiently characterized, especially in comparison with adult-onset rheumatoid arthritis (RA). This study aimed to compare disease activity, medication use, and treatment practices between patients with oligoarticular/polyarticular JIA and those with RA, focusing on individuals aged 16–30 years.<br> Methods Data were derived from two nationwide multicenter databases in Japan—NinJa (National Database of Rheumatic Diseases in Japan) for RA and CoNinJa (a pediatric counterpart of NinJa) for JIA. A total of 176 JIA and 152 RA patients, all aged 16–30 years, were analyzed. Clinical parameters, disease activity indices, and medication profiles were compared using the Mann–Whitney U test and Fisher’s exact test.<br> Results Compared to RA patients, JIA patients demonstrated significantly lower disease activity (median SDAI 0.6 vs. 2.4) and higher remission rates, particularly Boolean remission (70% vs. 44%) (p < 0.001). MTX usage was less frequent in JIA (49% vs. 68%, p < 0.001), whereas biologic use was notably more common (69% vs. 38%, p < 0.001), with 31% involving off-label prescriptions. Among patients in CDAI remission, biologic monotherapy was observed more frequently in JIA (29% vs. 7%, p < 0.001). Discontinuation of MTX was most commonly attributed to disease improvement (58%) or gastrointestinal intolerance (nausea, 29%). Subcutaneous tocilizumab, though unapproved for JIA in Japan, had the lowest discontinuation rate (4%), suggesting favorable tolerability.<br> Conclusions Despite an overlap in age, patients with JIA and RA exhibit distinct disease characteristics and therapeutic patterns. These differences underscore the need to expand approved treatment options for JIA, promote equitable access to biologics, and strengthen transitional care frameworks. Further research is warranted to explore long-term outcomes, reproductive health considerations, and socioeconomic barriers that influence treatment continuity in young adults with childhood-onset arthritis. 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.<br> 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.<br> 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.<br> Intervention Patients received a T-DXd dose of either 5.4 mg/kg or 6.4 mg/kg intravenously every 3 weeks.<br> 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.<br> 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.<br> 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.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 191 2026 高校特別支援教育コーディネーターにおける小児がん患児支援に関する教育施策への理解と役割意識 177 185 EN Yiwen CHEN The Joint Graduate School (Ph.D. Program) in Science of School Education Hyogo University of Teacher Education Munehisa YOSHITOSHI Faculty of Education, Okayama University 10.18926/bgeou/70206 　本研究の目的は，小児がんを経験した高校生に対する特別支援教育コーディネーターの支援意識を明らかにすることである。自治体の研修講座に参加した59名を対象に質問紙調査を実施し，23名から回答を得た。量的データは単純集計，自由記述は質的記述的分析により分析した。結果として，小児がん患児に関連する新たな教育施策，特に同時双方向型授業に関する認知度が低く，制度が十分に周知されていない実態が明らかになった。医療関係者との連携については，高い役割意識が示された一方で，病院訪問はあまり重視されていなかった。また，学級通信や教材準備などは必ずしも特別支援教育コーディネーターの役割とは認識されていなかった。自由記述からは，ICT を活用した支援への積極的な姿勢が示されたものの，中学校との連携における情報共有や業務負担に関する課題がみられた。今後，連携に関するガイドラインの整備や情報共有の強化が求められることを指摘した。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 191 2026 デジタルメディア・デジタルデバイスの自律的な使用に向けて（１） ― 自己制御能力とインターネット依存傾向に関する研究の概観から ― 169 175 EN Motoko MIYAKE Faculty of Education, Okayama University 10.18926/bgeou/70205 　デジタルメディア・デジタルデバイスの使用において，使用開始年齢の低年齢化・長時間利用の実態が指摘され，低年齢の子どもについても依存等の問題が注目されつつある。本報告では，子ども自身に，デジタルメディア・デジタルデバイスと適切に付き合う力を育てることの必要性を重視する立場から，インターネット依存傾向の抑制要因の１つに挙げられる自己制御能力に着目し，両者の関連についての本邦における研究を概観する。そして，子どもの自己制御の発達過程，自己制御の発達における促進要因・抑制要因を整理した上で，インターネット依存の予防のために子どもの自己制御の発達の観点から得られる示唆について検討した。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 191 2026 制作者と造形物の対話を捉える視点の研究 ― バフチンに基づく質的な考察のための文献の検討 ― 93 100 EN Shuya OHIRA Faculty of Education, Okayama University 10.18926/bgeou/70198 　本研究では，制作者が造形行為の過程で実践する造形物との対話に着目し，造形行為において制作者に経験される学びを捉え質的に考察するための視点を，バフチン(Михаил Михайлович Бахти́н)の対話の概念に立ち検討した。まず，対話の過程でつくられる自己と他者の「相互作用，相互関係」について検討し，対話の過程において個々の「世界」が確立されると共に，確立された個々の「世界」が自己と他者の間で共有されることを検討した。次に，造形行為の過程で，制作者が素材を変化させていくにつれて，その造形物ないし作品のもつ形や色が，想像の世界，モチーフ，何らかの規則性などを纏っていく，制作者と造形物ないし作品との対話が実践されることを検討した。研究の成果として，造形物との対話の過程で制作者に経験される学びを捉え質的に考察するための視点である芸術的行為を提示した。 No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 0916-9636 2026 Distinct associations of blood pressure phenotypes with subclinical cerebrovascular disease and coronary artery calcification in Japanese men EN Nomin Bayaraa NCD Epidemiology Research Center, Shiga University of Medical Science Yuichiro Yano NCD Epidemiology Research Center, Shiga University of Medical Science Aya Kadota NCD Epidemiology Research Center, Shiga University of Medical Science Nazar Mohd Azahar Tran Ngoc Hoang Phap National Institutes of Biomedical Innovation, Health and Nutrition Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiko Kondo NCD Epidemiology Research Center, Shiga University of Medical Science Sayuki Torii NCD Epidemiology Research Center, Shiga University of Medical Science Akira Fujiyoshi Department of Hygiene, School of Medicine, Wakayama Medical University Takayoshi Ohkubo Department of Hygiene and Public Health, Teikyo University School of Medicine Akihiko Shiino Molecular Neuroscience Research Center, Shiga University of Medical Science Kazuhiko Nozaki Department of Neurosurgery, Shiga University of Medical Science Katsuyuki Miura NCD Epidemiology Research Center, Shiga University of Medical Science Hypertension, encompassing white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH), is an established risk factor for cardiovascular diseases (CVDs), including atherosclerosis. However, among the general population, findings on which target organ is affected by the different phenotypes of hypertension remain unclear. In this community-based observational study of Shiga Epidemiological Study of Subclinical Atherosclerosis, 740 Japanese men underwent brain magnetic resonance imaging to assess the presence of lacunar infarction, white-matter hyperintensities, microbleeds, and intracranial artery stenosis (ICAS) between 2012 and 2015. They also underwent office blood pressure (BP) measurements, home BP monitoring for at least five consecutive days, and coronary artery calcification (CAC) assessments between 2010 and 2014. The final analysis included 686 participants without a history of CVDs. Of the 686 participants, the mean age ( ± SD) was 68.0 ( ± 8.3) years, and 39.3% were taking antihypertensive medication. In multivariable-adjusted models, each of WCH, MH, and SH was significantly associated with a higher risk of microbleeds compared to normotension. However, the association of WCH with microbleeds was evident only among those on antihypertensive medication (adjusted odds ratio [OR] 6.75 [95% CI 1.83–24.86]) and absent in those not on such medication (adjusted OR 1.20 [95% CI 0.31–4.73]). SH was associated with lacunar infarction, ICAS, and CAC. Among Japanese men, WCH, MH, SH were associated with subclinical cerebrovascular diseases, whereas only SH was associated with CAC. Moreover, any elevated BP phenotype increased the risk of microbleeds. Our findings suggest that different hypertension phenotypes distinctly affect target organs, particularly the brain and heart. No potential conflict of interest relevant to this article was reported.

The Carbon Society of Japan Acta Medica Okayama 2436-5831 4 3 2025 Synthesis and applications of porous carbonaceous materials with inherited molecular structural features from the precursor molecules 179 187 EN Koki Chida Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Takeharu Yoshi Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Kazuhide Kamiya Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Ryota Sakamoto Department of Chemistry, Graduate School of Science, Tohoku University Fumito Tani Institute for Materials Chemistry and Engineering, Kyushu University Tomoki Ogoshi Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University Hirotomo Nishihara Institute of Multidisciplinary Research for Advanced Materials, Tohoku University The carbonization of organic crystalline materials, such as metal organic frameworks and covalent organic frameworks, has emerged as a promising approach for producing functional porous carbonaceous materials. However, both the chemically defined long-term ordered structures and the local chemical structures derived from these precursor materials are generally lost, resulting in amorphous carbons. As a result, controlling the molecular-level structure of nanoporous carbons remains a significant challenge. We report a new bottom-up synthesis approach for porous carbons with a molecular-level design, involving the carbonization of well-designed precursor molecules by thermal polymerization. Among the resulting carbons, ordered carbonaceous frameworks, which contain a high-density of regularly aligned single-atomic metal species, have been identified as promising platforms for single-atom catalysts. This approach also enables the synthesis of various three-dimensional porous carbons that reflect the structural features of their precursor molecules. Recent progress in the synthesis and applications of porous carbons derived from molecular precursors is summarized, highlighting their potential for the development of functional materials. No potential conflict of interest relevant to this article was reported.

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

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

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

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.

Frontiers Media SA Acta Medica Okayama 1664-462X 16 2025 Structural analysis of PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte alga Rhodomonas sp. NIES-2332 1716939 EN Wenyue Zhang Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nozomi Yonehara Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mizuki Ishii Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haowei Jiang Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Romain La Rocca Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pi-Cheng Tsai Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hongjie Li Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koji Kato Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Fusamichi Akita Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jian-Ren Shen Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Light energy is converted to chemical energy by two photosystems (PSI and PSII) in complex with their light-harvesting complex proteins (LHCI and LHCII) in photosynthesis. Rhodomonas is a member of cryptophyte alga whose LHCs contain unique chlorophyll a/c proteins (ACPs) and phycobiliproteins. We purified PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte Rhodomonas sp. NIES-2332 and analyzed their structures at high resolutions of 2.08 Å and 2.17 Å, respectively, using cryo-electron microscopy. These structures are largely similar to those reported previously from two other species of cryptophytes, but exhibited some differences in both the pigment locations and subunit structures. A part of the antenna subunits of both photosystems is shifted compared with the previously reported structures from other species of cryptophytes, suggesting some differences in the energy transfer rates from the antenna to the PSI and PSII cores. Newly identified lipids are found to occupy the interfaces between the antennae and cores, which may be important for assembly and stabilization of the supercomplexes. Water molecules surrounding three iron-sulfur clusters of the PSI core are found in our high-resolution structure, some of which are conserved from cyanobacteria to higher plants but some are different. In addition, our structure of PSII-ACPII lacks the subunits of oxygen-evolving complex as well as the Mn4CaO5 cluster, suggesting that the cells are in the S-growth phase, yet the PSI-ACPI structure showed the binding of PsaQ, suggesting that it is in an L-phase. These results suggest that the S-phase and L-phase can co-exist in the cryptophytic cells. The high-resolution structures of both PSI-ACPIs and PSII-ACPIIs solved in this study provide a more solid structural basis for elucidating the energy transfer and quenching mechanisms in this group of the organisms. No potential conflict of interest relevant to this article was reported.

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.<br> 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.<br> 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.

Springer Science and Business Media LLC Acta Medica Okayama 1546-0096 24 1 2026 TeMPRA: advancing continuing professional development in pediatric rheumatology in Japan EN Hiroyuki Wakiguchi Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine Kunio Hashimoto Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences Masato Yashiro Department of Pediatrics, Okayama University Hospital Kenichi Nishimura Department of Pediatrics, Yokohama City University Graduate School of Medicine Takasuke Ebato Department of Pediatrics, Kitasato University Keiji Akamine Department of Nephrology and Rheumatology, Tokyo Metropolitan Children’s Medical Center Yoji Uejima Division of Infectious Diseases and Immunology, Saitama Children’s Medical Center Tomomi Sato Clinical Education Center for Physicians, Shiga University of Medical Science Yuichi Yamasaki Department of Pediatrics, Kagoshima University Hospital Junko Yasumura Department of Pediatrics, Hiroshima Prefectural Hospital Organization Futabanosato Prefectural Hospital Fumiko Okazaki Department of Pediatrics, Yamaguchi University Graduate School of Medicine Toshitaka Kizawa Department of Pediatrics, Japan Community Health Care Organization Sapporo Hokushin Hospital Ryuhei Yasuoka Department of Pediatrics, Hamamatsu University School of Medicine Tomoaki Ishikawa Department of Pediatrics, Nara Medical University Takeshi Yamamoto Department of Pediatrics, Chiba University Graduate School of Medicine Yuji Fujita Department of Pediatrics, Dokkyo Medical University Naohiro Itoh Department of Pediatrics, Faculty of Medical Sciences, University of Fukui Asami Takasaki Department of Pediatrics, School of Medicine, University of Toyama Nodoka Sakurai Department of Pediatrics, NTT East Medical Center Sapporo Kazuo Suzuki Suzuki Kids Clinic Tasuku Tamai Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine Naoki Hirano Department of Public Health and Epidemiology, Faculty of Medicine, Oita University Nami Okamoto Department of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and Safety Masaki Shimizu Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Background In the context of the global shortage of pediatric rheumatologists, mid-career specialists who can play key roles in regional education, research, and clinical practice have become increasingly important. In Japan, the Team of Mid-career Pediatric Rheumatologists Alliance (TeMPRA) was founded in 2014 to support continuing professional development (CPD) and foster collaboration among mid-career pediatric rheumatologists. The aim of this study was to characterize the current status and future perspectives of the TeMPRA members.<br> Methods In 2024, a cross-sectional, web-based survey was conducted among all 37 active members of the TeMPRA across Japan. Data were collected on career trajectories, educational roles, research activities, clinical practices, and international engagement. Categorical variables were compared using appropriate statistical tests, with a significance level of 0.05.<br> Results Responses were obtained from 35 members (response rate: 95%). Most respondents (71%) were affiliated with university hospitals, and 60% had > 10 years of experience in pediatric rheumatology. Compared with those working in community hospitals, respondents affiliated with university hospitals were significantly more likely to be involved in research activities (50% vs. 0%, P = 0.0261) and global professional contributions (88% vs. 0%, P < 0.0001). Overall, 54% of respondents were engaged in teaching students or early-career pediatric rheumatologists, while 43% were involved in clinical or basic research, most commonly focusing on juvenile idiopathic arthritis and systemic lupus erythematosus. Collectively, respondents were responsible for the care of 1,677 children with pediatric rheumatic diseases. While all respondents reported willingness to contribute to pediatric rheumatology at the regional level, 94% and 71% reported willingness to contribute at the national and global levels, respectively.<br> Conclusions This nationwide survey highlights the substantial educational roles, research activities, and clinical practices of mid-career pediatric rheumatologists in Japan and suggests that the TeMPRA framework can serve as a valuable model for supporting CPD and workforce sustainability. Similar alliance-based approaches may be applicable in other countries facing comparable challenges in pediatric rheumatology. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1880-6546 76 1 2026 Effects of systemic ventricular assist combined with fenestration in failing Fontan: A theoretical analysis 100065 EN Shuji Shimizu Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Yasuhiro Kotani Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Naohiro Horio Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Eiri Kisamori Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Yoshinori Miyahara Pediatric Heart Disease and Adult Congenital Heart Disease Center, Showa Medical University Hospital Koji Uemura Department of Research Promotion and Management, National Cerebral and Cardiovascular Center Toshiaki Shishido Department of Research Promotion and Management, National Cerebral and Cardiovascular Center Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Biventricular assist for failing Fontan circulation remains challenging. Because fenestration effectively reduces stressed blood volume and central venous pressure in Fontan patients with increased pulmonary vascular resistance (PVR), systemic ventricular assist device (VAD) combined with fenestration may improve hemodynamics in failing Fontan patients with increased PVR who would require biventricular assist. To validate this hypothesis, we performed a computational hemodynamic simulation of the failing Fontan circulation using a lumped parameter model. We compared hemodynamic variables between the models with and without fenestration while the PVR index was increased sequentially from 3.01 to 6.81 Wood Units m2. Following VAD initiation and stressed blood volume reduction, central venous pressure was maintained at a lower level in the fenestration models. This positive effect was greater in the model with larger fenestration diameter. However, excessive fenestration caused significant desaturation. In failing Fontan circulation with elevated PVR, systemic VAD combined with fenestration significantly improved hemodynamics. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 2041-6520 17 9 2026 Gaseous CO2 electrolysis: latest advances in electrode and electrolyzer technologies toward abating CO2 emissions 4363 EN Kazuhide Kamiya Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Sora Nakasone Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Ryo Kurihara Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Asato Inoue Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Hazuki Irie Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Shoko Nakahata Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Satoshi Taniguchi Research Institute for Chemical Process Technology, National Institute of Advanced Industrial Science and Technology (AIST), Central 5 Thuy T. H. Nguyen Research Institute for Chemical Process Technology, National Institute of Advanced Industrial Science and Technology (AIST), Central 5 Sho Kataoka Research Institute for Chemical Process Technology, National Institute of Advanced Industrial Science and Technology (AIST), Central 5 The conversion of CO2 into multicarbon (C2+) products via electrochemical reduction is considered a key technology for the sustainable production of fuels and chemicals. The performance of high-rate gaseous CO2 electrolysis is governed by interrelated factors such as the electrocatalysts, electrodes, electrolytes, and cell architectures. Despite the intensive focus on catalyst research, systematic studies addressing the other components remain scarce, leaving critical gaps in our understanding toward achieving higher performance in CO2 electrolysis systems. The nanoscale design of catalyst surface electronic structures and the macroscale design of electrodes and electrolyzer architectures both influence the overall activity of the electrochemical system. In designing macroscale components, it is necessary to establish benchmarks based on a comprehensive evaluation of CO2 emissions for the entire electrolysis process, because these parameters are directly linked to output metrics such as current density and cell voltage under practical operating conditions. This review summarizes recent advances in electrodes and electrolyzers, and through life-cycle assessment (LCA), evaluates key performance indicators (KPIs) for achieving negative emissions and assesses the current technology readiness of CO2 electrolysis. 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.<br> 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.<br> 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.<br> 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 2589-0042 28 9 2025 Extensive urine production in euryhaline red stingray for adaptation to hypoosmotic environments 113274 EN Naotaka Aburatani Atmosphere and Ocean Research Institute, The University of Tokyo Wataru Takagi Atmosphere and Ocean Research Institute, The University of Tokyo Marty Kwok-Shing Wong Atmosphere and Ocean Research Institute, The University of Tokyo Nobuhiro Ogawa Atmosphere and Ocean Research Institute, The University of Tokyo Shigehiro Kuraku Department of Genomics and Evolutionary Biology, National Institute of Genetics Mana Sato Department of Genomics and Evolutionary Biology, National Institute of Genetics Kazuhiro Saito Ushimado Marine Institute, Faculty of Science, Okayama University Waichiro Godo Ushimado Marine Institute, Faculty of Science, Okayama University Tatsuya Sakamoto Ushimado Marine Institute, Faculty of Science, Okayama University Susumu Hyodo Atmosphere and Ocean Research Institute, The University of Tokyo Maintaining water balance is a prerequisite for all organisms. Euryhaline elasmobranchs face the severest water-influx potential in fresh water (FW), as they retain high concentrations of urea even in hypotonic environments. To elucidate how they overcome this osmotic challenge, we assessed urine output in conscious euryhaline red stingrays (Hemitrygon akajei). Following acclimation to 5% diluted seawater, the stingrays increased urinary output by 87-fold—the greatest change observed in vertebrates—partly due to 6.8-fold increase in glomerular filtration rate (GFR). In the nephron, expressions of Aquaporin-1 (Aqp1), Aqp3, and Aqp15 were strongly downregulated in FW, indicating that tubular diuresis bridges the gap between GFR and final urine volume. Meanwhile, FW-acclimation upregulated Aqp1 and Aqp4 in the distinct bundle structure, which promotes urea reabsorption. Euryhaline elasmobranchs resolve the huge osmotic challenge of FW by excreting massive amounts of water and retaining osmolytes including urea through coordinated regulation of GFR and Aqp expressions. No potential conflict of interest relevant to this article was reported.

岡山大学大学院法務研究科 Acta Medica Okayama 1881-1485 27 2026 岡山行政法実務研究会　研究会記録（第39回～41回） 65 67 EN No potential conflict of interest relevant to this article was reported.

岡山大学大学院法務研究科 Acta Medica Okayama 1881-1485 27 2026 瀬戸内市長としての16年間のあゆみ ― 市長の意思決定 ― 53 64 EN Akinari TAKEHISA 10.18926/OLR/70155 No potential conflict of interest relevant to this article was reported.

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

Informa UK Limited Acta Medica Okayama 1350-4622 2026 Towards place-responsive climate change education: Mongolian primary teachers’ pedagogical judgement across urban and rural contexts EN Shinetsetseg Gerelkhuu Graduate School of Humanities and Social Sciences, Okayama University Khalifatulloh Fiel’ardh Graduate School of Education, Okayama University Hiroki Fujii Graduate School of Education, Okayama University Batchuluun Yembuu Geography Department, Mongolian National University of Education Uuriintuya Dembereldorj Lifelong Learning and Distance Education Department, Mongolian National University of Education Climate change education (CCE) in primary schools is increasingly recognised as essential, yet how teachers interpret and enact CCE across diverse local contexts remains underexplored. This study examines how Mongolian primary school teachers working with students aged 6–11 in urban and rural contexts interpret and teach climate change, with particular attention to the role of place. Drawing on semi-structured interviews with 20 teachers across contrasting contexts, the study explores how environmental, cultural, and institutional conditions shape teachers’ pedagogical interpretations and classroom practices. Data were analysed using reflexive thematic analysis, informed by conceptual frameworks that position place as an active mediator of teaching and learning. Findings show that rural teachers frequently integrated traditional ecological knowledge and lived environmental experience to connect global climate processes with locally observable ecological change, emphasising livelihood impacts and intergenerational ecological memory. Urban teachers, by contrast, framed climate change through anthropogenic pressures such as air pollution, waste, and infrastructure constraints, foregrounding feasible individual actions within everyday school contexts. Across both settings, teachers exercised place-responsive pedagogical judgement by selectively adapting climate content to local realities while navigating curriculum constraints and workload pressures. The study contributes a place-responsive account of teachers’ pedagogical judgement in CCE, demonstrating how place functions not only as context but as a condition shaping pedagogical feasibility. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 0094-8276 53 5 2026 Electrical Conductivity of Amorphous and Molten CaCO3 at High Pressures and Its Implications for Mantle Conductivity Anomalies e2025GL119568 EN Bin Zhao Institute for Planetary Materials, Okayama University Takashi Yoshino Institute for Planetary Materials, Okayama University Qi Chen Center for Advanced Radiation Sources, The University of Chicago Tony Yu Center for Advanced Radiation Sources, The University of Chicago Dongzhou Zhang Center for Advanced Radiation Sources, The University of Chicago Bin Chen School of Ocean and Earth Science and Technology, University of Hawaii at Manoa Yanbin Wang Center for Advanced Radiation Sources, The University of Chicago Impedance spectrometry experiments have been conducted on CaCO3 up to 15 GPa and 2,100 K to identify its state under high pressure. The melting temperature of CaCO3 was also determined by the falling of a Re sphere observed via X-ray radiography. The phase transition from aragonite to the amorphous phase does not cause a leap in the Electrical conductivity (EC), while a drastic increase in the EC, by 1.5–2.0 log units, only occurs with the onset of melting. The EC of amorphous CaCO3 is comparable to other hydrous mantle minerals at similar pressure and temperature conditions. The required fraction of amorphous CaCO3 implies that it can be excluded from the potential origins responsible for the observed high EC anomalies in the upper mantle. If the conductivity anomalies are induced by the presence of carbonate, a low-degree melting of carbonate-bearing peridotite is anticipated. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 2644-1349 6 2026 Ultrafast Time-Compressive CMOS Image Sensors Based on Multitap Charge Modulators for Filming Light-In Flight 47 60 EN Keiichiro Kagawa Research Institute of Electronics, Shizuoka University Daisuke Hayashi Graduate School of Integrated Science and Technology, Shizuoka University Arashi Takakura Faculty of Engineering, Shizuoka University Yuto Umeki Graduate School of Integrated Science and Technology, Shizuoka University Michitaka Yoshida Faculty of Environmental, Life, Natural Science and Technology, Okayama University Keita Yasutomi Research Institute of Electronics, Shizuoka University Shoji Kawahito Research Institute of Electronics, Shizuoka University Youngcheol Chae Department of Electrical and Electronic Engineering, Yonsei University Hajime Nagahara D3 Center, The University of Osaka Ultrafast time-compressive CMOS image sensors based on multitap charge modulators can capture light-in flight using coded exposure masks on the focal plane. Transient images can then be reconstructed using iterative methods or deep learning models. Although the image sensor is based on indirect time-of-flight (ToF) image sensors, the reconstructed images are equivalent to those captured by direct ToF (D-ToF) image sensors. Important design parameters of the image sensor include the pixel block size and the number of taps of the charge modulator. Several constraints regarding the charge transfer of the multitap charge modulator, the hamming distance between exposure codes at adjacent timings, and the minimal time window duration must be considered when designing exposure codes. The influence of these factors on the fidelity of the reconstructed images is analyzed numerically. The results show that a pixel block size of 4×4 is optimal and that four or more taps are required for light detection and ranging (LiDAR) applications when 32 transient images of light-in flight are reconstructed. To demonstrate LiDAR in a scene with multipath interference, two objects were observed through a weakly diffusive sheet. The temporal resolution, as defined by the clock period of the exposure codes, was 1.65 ns. Multiple reflections were reconstructed using an iterative method (TVAL3) and a deep learning model (ADMM-Net). Although the waveforms of optical pulses reconstructed by TVAL3 are distorted, the amplitudes are more accurate. Conversely, although ADMM-Net reconstructs sharper optical pulses, the amplitudes are inaccurate. To achieve the shorter temporal resolution required for time-resolved diffuse optical tomography (DOT) and fluorescence lifetime imaging (FLIm), the feasibility of heterodyne compression was demonstrated through simulation. 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).<br> 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).<br> 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).<br> 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.<br> 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.<br> 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.<br> 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.<br> 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.

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.

岡山大学農学部 Acta Medica Okayama 2186-7755 115 2026 Evaluation of Branching Characteristics and Their Contribution to Yield in Everbearing Strawberry Cultivars under Forced Cultivation 1 8 EN Minori Hikawa-Endo Kyushu Okinawa Region Agricultural Research Center, NARO Kazuyoshi Sone Kyushu Okinawa Region Agricultural Research Center, NARO Masami Morishita Kyushu Okinawa Region Agricultural Research Center, NARO 　Enhancing continuous flowering in cultivated strawberries may result in insufficient photosynthetic products due to the lower limit of leaf number on each lateral shoot, leading to reduced yield and fruit quality. If strawberries could differentiate an appropriate number of tillers and allow each tiller to grow autonomously with sufficient leaf number on each lateral shoot, rather than flowering continuously on the main bud alone, plants could achieve high yields while preventing plant weakening and fruit quality deterioration. Therefore, this study evaluated branching characteristics of everbearing strawberry cultivars under forcing cultivation to identify cultivars with moderate tillering and moderately low continuous flowering. Pot experiments revealed that the number of tillers was high in ‘Summer Princess’ and ‘Miyazaki-natsuharuka’ but low in ‘Summer Berry’ and ‘Suzuakane’. This trend was independent of total number of lateral shoots, nodal position of first inflorescence, and the number of leaves on each lateral shoot, which serve as indicators of continuous flowering ability. Among seven tested cultivars, ‘DT17’ and ‘Miyazaki-natsuharuka’ showed intermediate values with 2.1 - 2.5 tillers per plant and 6.7 - 7.7 leaves on each lateral shoots. These cultivars showed yields of 747.0 - 1,028.5 g per plant under forcing cultivation, which were higher than other cultivars, along with consistent fruit quality. These results suggest that improving branching characteristics is a practical approach to enhancing fruit productivity in strawberries. 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.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 Developing a Short-form Scale to Assess Learner Beliefs Regarding English Learning Strategies 100 119 EN Hiroshi MORITANI Institute for Promotion of Education and Campus Life, Okayama University Alexis PUSINA Institute for Promotion of Education and Campus Life, Okayama University 10.18926/70115 Questionnaire surveys are a prevalent method in applied linguistics for investigating complex constructs, such as learner beliefs. However, their complex nature often creates overly lengthy instruments, making them impractical for classroom use or for obtaining timely educational insights. This study aimed to develop a simplified, yet robust version of an existing learner belief scale to address these challenges. The authors carefully selected 24 belief-specific items from an initial pool of 78 items from a previous study for use in an online survey, which was completed by 246 participants. The data were subject to exploratory factor analysis. This process resulted in a concise 12-item scale, could offer a more practical tool for language educators. 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 発達障害を有する高校生の保護者による障害学生支援の認知度 91 99 EN Shin HARADA General Education and Global Studies Field, Okayama University Kosuke Iketani General Education and Global Studies Field, Okayama University Megumi MATSUI General Education and Global Studies Field, Okayama University Naoto MOCHIZUKI Health and Counseling Center, The University of Osaka 10.18926/70114 　本研究では，発達障害を有する高校生の保護者が，「大学等における障害学生支援や学生相談をどの程度知っているか」，「大学等における障害学生支援や学生相談の情報をどのように入手したか」，「大学等における障害学生支援や学生相談の情報収集をする上で，大学等にどのような情報発信を期待するか」について調査を行った。その結果，まだ保護者に対し，十分に大学の学生支援の情報が行き届いていないこと，学生支援に関する情報発信を行う説明会や相談会を行うことが保護者から期待されていること，発達障害を有する高校生の高大移行を促進するために，高校の先生方に対する情報発信も精力的に行ったり，高大連携の取り組みをより行う必要があること等が見出された。 No potential conflict of interest relevant to this article was reported.

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

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 留学生受け入れにおける教員の判断基準 ―多くの留学生を受け入れている教員の視点から― 57 73 EN Takao INAMORI Faculty of General and Global Studies, Okayama University 10.18926/70112 　少子化は国内大学の定員充足率に深刻な影響を与えることから、留学生の受入増に期待が寄せられている。しかし、大学院教育において留学生受入に前向きな教員と、消極的な教員が見受けられる。本研究では、より多くの留学生を受け入れている教員が、どのような判断基準で受け入れを決定しているのかを、半構造化インタビューを通じて明らかにすることを試みた。その結果、判断基準に関しては、教員により表現は異なるが「人物」と「能力」を確認していることが分かった。また、受け入れを前向きに考える教員は、留学・在外研究員経験や、初めて受け入れた留学生指導を通じて良い経験をしたこと等が、留学生に対するプラスの印象をつくり、積極的な受け入れにつながっていることが明らかになった。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 自閉スペクトラム症特性と精神的健康の関連：自己理解による媒介効果の検討 41 56 EN Hiroki NISHIMURA Institute for Promotion of Education and Campus Life, Okayama University Akihiro UCHIDA Okayama Psychiatric Medical Center 10.18926/70111 本研究は、自閉スペクトラム症特性と精神的健康の関連において、自己理解がどのような役割を果たすかを明らかにすることを目的とした。日本の成人604名のデータを利用した二次分析の結果、自閉スペクトラム症特性の高さと精神的健康の悪化との間には関連が認められた。この関連は、自己理解の肯定的側面によって部分的に媒介されることが示された。特にこの自己理解の保護的な効果は、男性よりも女性においてより強い可能性が示唆された。一方で、自己理解の否定的側面は媒介効果を示さなかった。これらの結果から、自閉スペクトラム症特性を持つ人々への支援において、肯定的な自己理解を促進することが重要であり、性差を考慮したアプローチの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 Acta Medica Okayama 1881-5952 3 2026 オンラインによるボランティア日本語教室における参加者間のインターアクションの分析 ―地域型日本語教育の実現に向けて― 31 40 EN Miwa SUESHIGE Institute for Promotion of Education and Campus Life, Okayama University 10.18926/70110 本研究では，地域型日本語教育のモデル構築に向け，地域型の特徴を有する教室内での支援者および参加者の発話や教授行動の傾向を明らかにすべく，外国語相互作用分析システムを用い，オンラインによるボランティア教室におけるインターアクションの分析を行った。分析の結果，（1）支援者の平均発話数が学習者より多いこと，（2）支援者の発話における間接的行動の割合が直接的行動よりもやや高いことが示された。「おしゃべり型の教育」では，学習者が伝えたいことを言語化していくプロセスの中で，間接的行動の下位分類の「質問」「学習者の意図の利用」「学習者の回答の繰り返し」等を支援者が積極的に使用し支援していることが分かった。 No potential conflict of interest relevant to this article was reported.

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

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

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

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

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2026 Turning pancreatic cancer from cold to hot: the promise of a p53-expressing oncolytic adenovirus (OBP-702) EN Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Center for Innovative Clinical Medicine, Okayama University Hospital Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma Inc Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pancreatic cancer remains one of the most lethal malignancies, with limited therapeutic options and poor responsiveness to immune checkpoint inhibitors (ICIs). This resistance is largely attributed to its profoundly immunosuppressive and desmoplastic tumor microenvironment (TME), characterized by low tumor mutational burden, dense stroma, and abundant immunosuppressive cell populations. Therefore, strategies capable of enhancing tumor immunogenicity and overcoming immune evasion are urgently needed. Oncolytic virotherapy is a promising approach, offering not only tumor-selective cytotoxicity, but also potent immunomodulatory effects. Of these agents, Telomelysin (OBP-301, Suratadenoturev), a telomerase-specific oncolytic adenovirus, demonstrated clinical safety but limited efficacy in refractory tumors. To address this challenge, we developed OBP-702, a next-generation, p53-armed, oncolytic adenovirus designed to augment antitumor activity. Preclinical studies have shown that OBP-702 exerts robust cytotoxicity through multiple mechanisms, including p53-mediated apoptosis and autophagy, E1A–E2F1-mediated p21 suppression, and inhibition of oncogenic KRAS pathways. Importantly, OBP-702 induces strong immunogenic cell death, activates dendritic cells, and promotes tumor-specific T-cell responses, effectively converting immunologically “cold” pancreatic tumors into “hot” tumors. OBP-702 also remodels the immunosuppressive TME by reducing granulocyte–macrophage colony-stimulating factor (GM-CSF) secretion, suppressing myeloid-derived suppressor cells (MDSCs), and targeting stromal components, such as cancer-associated fibroblasts (CAFs). These effects contribute to enhanced responses to ICIs and standard chemotherapies. Given its multifaceted antitumor functions and ability to overcome key barriers in pancreatic cancer, OBP-702 represents a highly promising therapeutic candidate. A first-in-human clinical trial evaluating endoscopic ultrasonography-guided intratumoral injection of OBP-702 is currently in preparation, expected to advance clinical translation of this novel virotherapeutic strategy. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1201-9712 164 2026 Global trends in Clostridioides difficile infection–related mortality, 2001-2023: An observational study 108315 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Yoshito Nishimura Division of Hematology/Oncology, Mayo Clinic Ko Harada Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai Maki Yamamoto Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuaki Takeda Quynh Thi Vu Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keith Pardillada Belangoy Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hanane Ouddoud Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: Clostridioides difficile infection (CDI) is a major public health concern, particularly in aging populations. The aim of this study was to evaluate global trends in CDI-related mortality to inform sustainable and cost-effective management strategies.<br> Methods: We conducted an observational study using mortality data from the World Health Organization (WHO) database spanning 2001 to 2023. Sixty-three countries with satisfactory data quality and at least 12 years of data between 2001 and 2023 were included. Crude and age-standardized CDI-related mortality rates per 1,000,000 individuals were calculated after stratification by age, sex, WHO region, and sociodemographic index (SDI). Global trends were analyzed using locally weighted regression.<br> Results: The global age-standardized CDI-related mortality rate was 0.76 per 1,000,000 individuals in 2001, peaked at 4.08 in 2010, and declined to 2.44 in 2023. The most notable downward trends were observed in the Americas and high-SDI countries. These improvements may reflect the impact of multidisciplinary efforts in CDI prevention and management.<br> Conclusions: Although CDI-related mortality has declined globally over the past decade, the disease remains a significant threat, especially in older populations. Ongoing global efforts are essential to further reduce CDI-related deaths. 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 Changes in Prescribing Patterns of Antiviral Drugs before and after Public Coverage Termination among Hospitalized COVID-19 Patients in Regional Hospitals in Japan: A Retrospective, Multicenter Study 55 62 EN Hidemasa Akazawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Shohei Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Original Article 10.18926/AMO/70073 In Japan, antiviral agents for COVID-19 were freely available until September 2023 as part of national policy. This study evaluated changes in these agents’ prescribing patterns and the patient outcomes following the policy shift. We conducted a multicenter retrospective study at four hospitals in Japan’s Okayama and Kagawa prefectures from January 2022 to March 2024. The study period was divided into the public-expenditure phase (January 2022 to September 2023) and the post-expenditure phase (October 2023 to March 2024). We extracted the hospitalized patients’ clinical data from the electronic database. The study’s primary outcome was the antiviral prescription rate; the secondary outcome was in-hospital mortality. Among the 302 hospitalized patients (median age 85 years), 52.0% were classified as having a mild condition. Of the patients with mild conditions, 37.7% were diagnosed in outpatient settings prior to hospitalization. During the public-expenditure phase, 47.4% of the patients received antivirals as outpatients, mainly molnupiravir (80.9%). In the post-expenditure period, 80.0% of the patients were prescribed antivirals, mostly molnupiravir (91.7%). The antiviral prescription rate was significantly higher after the policy change. The overall in-hospital mortality was 15.8%, with no significant difference between the two periods (17.0% vs. 10.5%). Despite the termination of government funding, antiviral prescriptions remained frequent at community hospitals located in highly aging regions of western Japan such as Okayama and Kagawa prefectures. Mortality remains high among the elderly, highlighting the need for continued antiviral therapy and booster vaccinations. No potential conflict of interest relevant to this article was reported.

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

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

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 “God” is Coming to My Home : Catholic Images and the Sacred in the Case of a Rural Village in Western Mexico 115 133 EN Naomi KAWAMOTO Research Institute for the Dynamics of Civilizations, OKAYAMA UNIVERSITY 特集：Sacred Objects in Religions (Special Issue: Sacred Objects in Religions) 10.18926/70058 This paper aims to clarify the dynamic aspect of the sacred that the religious image is imbued with, focusing on a Catholic practice in a current rural village of western Mexico. In classical studies of the sacred, it has generally been considered disconnected from the profane and ambivalent. Other research has revealed the multi-layered nature of the sacred and its constructive aspect. In contrast, this paper will discuss a sacredness that arises from the interaction between human beings and objects, a sacredness that is both performative and intimate. Thus, this article will analyze practitioners’ everyday, contingent acts, free from formality. In conclusion, “the sacred” contains a part of the profane caused by the Catholic image going back and forth between the realms of “the sacred” and “the profane”. 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 From Festivals to the Everyday: The Circulation of Kumade at the Tori no Ichi at Hanazono Shrine 101 114 EN Mia TILLONEN Department of English Language and Culture, FUJI WOMEN’S UNIVERSITY 特集：Sacred Objects in Religions (Special Issue: Sacred Objects in Religions) 10.18926/70057 Every year in November, the Tori no Ichi festival draws huge crowds to the grounds of Hanazono Shrine in Shinjuku, Tokyo. The festival is centered around the buying and selling of kumade, or good luck rakes. These bold and colorful objects function as engimono, or good luck charms, purchased for business prosperity or home safety. This study explores the circulation and itinerary of kumade at the Tori no Ichi festival by analyzing the performances surrounding them. While previous scholarship on engimono has focused on their roles in domestic settings or disposal rituals, this research approaches them in situ at the festival. The study shows that these objects bridge the festival and the everyday, connecting people to the event and the sacred site through a dynamic network of social, spatial, and ritual practices. The research draws on fieldwork and in-depth interviews conducted at Hanazono Shrine between 2020 and 2024. 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 Area Studies のなかの「地域史」研究 ー歴史研究者、J・W・ホールから見るミシガン大岡山分室と瀬戸内海総合研究会ー 54 73 EN Shizue OSA Kobe University 研究ノート (Research note) 10.18926/70054 During the late Allied occupation and the 1950s, the University of Michigan’s Center for Japanese Studies established a field station in Okayama, where American scholars conducted rural research. This article examines the challenges of academic research under occupation and analyzes how such research was organized through specific actors and institutional arrangements, with particular attention to its intersection with the academic knowledge of the host institution, Okayama University. Focusing on the historian John W. Hall, it traces the activities of the Michigan field station and explores its interactions with Okayama University and the Seto Inland Sea Cultural Research Group. The article argues that while archival research—understood as a form of fieldwork—facilitated collaborative research, differing conceptions of rural society constituted a critical point of divergence in the production of scholarly knowledge. 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.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 島根県猪目洞窟遺跡出土人骨の年代・食性・遺伝的特徴 20 39 EN Hideaki KANZAWA-KIRIYAMA Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture Mai TAKIGAMI Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture Tsuneo KAKUDA Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi Leo SPEIDEL Center for Interdisciplinary Theoretical and Mathematical Sciences, RIKEN Garrett HELLENTHAL Department of Genetics, Evolution and Environment, University College London Genetics Institute (UGI), University College London Nancy BIRD Department of Genetics, Evolution and Environment, University College London Genetics Institute (UGI), University College London Yousuke KAWAI Genome Medical Science Project, National Institute of Global Health and Medicine, National Institute for Health Security NCBN Controls WGS Consortium Minoru SAKAMOTO National Museum of Japanese History Yuichi KAMEDA Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture Noboru ADACHI Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi Ken-ichi SHINODA National Museum of Nature and Science Naruya SAITOU National Institute of Genetics Tatsuhiko HAMADA Research Institute for the Dynamics of Civilizations, Okayama University 論文 (Research article) 10.18926/70052 This paper reports on the integrative research findings of the human bones excavated from the Inome Cave Site in Shimane Prefecture, based on dietary estimation using carbon and nitrogen isotope analysis, radiocarbon dating, and whole genome analysis. The dates of the analyzed human bones span a wide range, from the Middle to Late Kofun period, the Nara period to the Early Heian period, and the Middle to Late Heian period, indicating that the Inome Cave Site was continuously used as a burial place. Dietary habits were a mixture of C3 resources (C3 plants and terrestrial animals that consumed C3 plants) and marine resources, with individual variations in the intake of marine and terrestrial resources. A correlation was observed between differences in dietary habits and individual variations in the Jomon ratio in the nuclear genome, with individuals who consumed higher amounts of marine resources tending to have a higher Jomon ratio. This suggests that individuals with different backgrounds were buried in the same site due to interactions with surrounding settlements. 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 日本における「ロシアかぜ」流行の社会史的分析 ―1889 -1891 年パンデミックと日本社会― 1 19 EN Atsushi KAWAUCHI Uehiro Disaster Risk Reduction Research Division, International Research Institute of Disaster Science (IRIDeS), TOHOKU UNIVERSITY 論文 (Research article) 10.18926/70051 This study offers a social-historical analysis of the “Russian flu” pandemic in Japan (1889–1891). Due to scarce statistical data, the study relies primarily on contemporary newspapers and magazines. It identifies two distinct epidemic waves: the first in spring-summer 1890, and the second from late 1890 to spring 1891. The first wave, though widespread, was overshadowed by a concurrent cholera epidemic and caused relatively few deaths, whereas the second wave was far more lethal and generated widespread fear. At the time, influenza remained an “unknown disease”, with unclear etiology and no established treatments. People responded with diverse measures, from purchasing patent medicines and using folk remedies to symbolic practices such as "disease naming" (osome-kaze). The crisis also renewed attention to historical records of earlier influenza-like epidemics in Japan. In contrast, by the time of the later “Spanish flu” pandemic, advances in bacteriology had already rendered influenza a medically defined disease. This comparison highlights how shifting medical knowledge shaped societal responses. The findings not only corroborate previous excess-mortality analyses but also provide new historical insights into how societies have historically confronted pandemics. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0001-690X 153 3 2026 Impact of Schizophrenia Spectrum Disorders on the Receipt of Invasive and Systemic Therapy for Colorectal Cancer: A Nationwide Multicenter Retrospective Cohort Study in Japan 191 199 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 Taisuke Ishii Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center Tomone Watanabe Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center Maiko Fujimori Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center Naoki Nakaya Tohoku Medical Megabank Organization, Tohoku University Toshihiko Kawamura Department of Medical Informatics, Shimane University Hospital Koji Otsuki Department of Psychiatry, Faculty of Medicine, Shimane University Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Medical Development Field, Okayama University Taichi Shimazu Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center Shiro Hinotsu Department of Biostatistics and Data Management, Sapporo Medical University Yosuke Uchitomi Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine Masatoshi Inagaki Department of Psychiatry, Faculty of Medicine, Shimane University Introduction: This study examined treatment disparities for colorectal cancer among patients diagnosed with schizophrenia spectrum disorders (SSD), focusing on invasive treatments and stage-appropriate systemic therapy within a universal healthcare system.<br> Method: In this nationwide retrospective cohort study (2018–2021), we identified 248,966 colorectal cancer patients, including 2337 diagnosed with SSD, using linked cancer registry and insurance claims data in Japan. The presence of SSD was classified according to ICD-10 codes F20–29. We used multivariable logistic regression to compare the odds of receiving stage-appropriate adjuvant chemotherapy and systemic therapy, as well as the odds of receiving surgical or endoscopic treatments, between the two groups. The analysis adjusted for age, sex, clinical stage, and scores on the Charlson Comorbidity Index and Barthel Index.<br> Results: The clinical stage distribution at diagnosis for colorectal cancer differed significantly between patients with SSD and those without psychiatric disorders (p < 0.001). After adjusting for clinical stage and other covariates, patients with SSD demonstrated significantly lower odds of receiving surgical or endoscopic treatment (adjusted odds ratio [aOR], 0.83; 95% CI, 0.73–0.94). The disparities were more pronounced for systemic therapy; patients with SSD had substantially lower odds of receiving adjuvant chemotherapy for stage III disease (aOR, 0.33; 95% CI, 0.26–0.41) and systemic therapy for stage IV disease (aOR, 0.23; 95% CI, 0.17–0.31).<br> Conclusion: Patients with SSD encounter substantial disparities in accessing standard colorectal cancer care, particularly systemic therapies. These findings highlight the urgent need for interventions to ensure equitable cancer treatment for this vulnerable population. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 2950-3299 33 4 2025 Collagen depletion by pirfenidone enhances antitumor effect of oncolytic adenovirus against peritoneal metastases of gastric cancer 201045 EN Tomohiro Okura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Mikane Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ema Mitsui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Une Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Ohtsuka Laboratory of Fundamental Oncology, National Cancer Center Research Institute Rieko Ohki Laboratory of Fundamental Oncology, National Cancer Center Research Institute Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Cancer-associated fibroblasts (CAFs) play a crucial role in collagen accumulation, which develops and promotes peritoneal metastasis (PM) in gastric cancer (GC). In addition, the abundant stromal collagens in the tumor microenvironment function as a physical barrier against penetration of antitumor drugs and oncolytic viruses. This study investigated whether collagen depletion by pirfenidone (PFD), an antifibrotic drug, enhances the antitumor effects of oncolytic adenoviruses. Analysis of the clinical samples revealed a significant association of high expression of collagen 1 and α-smooth muscle actin (α-SMA) with PM development and poor prognosis of advanced GC. Human and murine GC cells enhanced collagen production by fibroblasts, which was suppressed by PFD. Abundant fibroblasts and collagen inhibited the penetration of OBP-702, which reduced the antitumor effects of OBP-702 in the spheroid model. Intraperitoneal co-injection of GC cells and fibroblasts promoted the development of collagen-rich PM and reduced the antitumor effects of OBP-702 in vivo model. PFD suppressed collagen production in PM and improved viral penetration into the tumors, which enhanced the antitumor effects of OBP-702 against PM of GC. Collagen depletion by PFD enhances the penetration of OBP-702 into PM of GC, in turn enhancing the antitumor effects of OBP-702 against PM of GC. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 1757-4749 18 1 2026 Sodium butyrate augments the antibacterial activity of tetracycline against clinical isolates of multidrug-resistant Vibrio cholerae 9 EN Sushmita Kundu Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Sourin Alu Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Abhishek Singh Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Animesh Gope Division of General Medicine, ICMR- National Institute for Research in Bacterial Infections Ranjan Kumar Nandy Division of Bacteriology, ICMR- National Institute for Research in Bacterial Infections Asish K. Mukhopadhyay Division of Bacteriology, 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 Nabendu Sekhar Chatterjee Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Sushmita Bhattacharya Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Background Antibiotic resistance poses a major challenge in treating Vibrio cholerae infections. One promising method to counter resistance is the co-administration of antibiotics with non-antibiotic adjuvants to enhance their efficacy. This study investigated the combined action of sodium butyrate (SB) and tetracycline on tetracycline-resistant V. cholerae strains.<br> Results The combined activity of SB and antibiotics was assessed on eight V. cholerae clinical isolates using the Fractional Inhibitory Concentration Index (FICI), with SB-Tetracycline showing strong synergy (FICI: 0.09–0.5). Functional and mechanistic studies, including time-kill kinetics, live/dead staining, SEM-based morphological analysis, and fluorometric assays, demonstrated a synergistic antibacterial effect of SB and Tetracycline. This effect was associated with increased membrane permeability, disruption of membrane integrity, dissipation of the proton motive force, and suppression of efflux activity. These changes collectively led to membrane damage, enhanced intracellular accumulation of Tetracycline, decreased intracellular ATP levels, and ultimately, bacterial cell death. Moreover, GM1-CT ELISA and fluorescence microscopy revealed the synergistic anti-virulence activity of the SB- Tetracycline combination. Finally, the combination of SB and Tetracycline showed enhanced efficacy in animal models compared with monotherapy.<br> Conclusion: The observed SB-Tetracycline synergy provides a promising therapeutic approach to overcome tetracycline resistance in V. cholerae, offering a potential adjunct strategy for the management of antibiotic-resistant cholera infections. No potential conflict of interest relevant to this article was reported.

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

eLife Sciences Publications, Ltd Acta Medica Okayama 2050-084X 14 2026 Dorsoventral-mediated Shh induction is required for axolotl limb regeneration RP106917 EN Sakiya Yamamoto Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Saya Furukawa Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Ayaka Ohashi Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Mayuko Hamada Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Akira Satoh Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Axolotls (Ambystoma mexicanum) exhibit a remarkable ability to regenerate limbs. Classical experiments have suggested that contact between cells derived from distinct orientations—dorsal, ventral, anterior, and posterior—within the regenerating blastema is necessary for accurate limb pattern formation. However, the molecular basis for this requirement has remained largely unknown. Here, we demonstrate that both dorsal and ventral tissues are required for limb formation via induction of Shh expression, which plays a crucial role in limb patterning. Using the accessory limb model, we induced position-specific blastemas lacking cells derived from a single orientation (anterior, posterior, dorsal, or ventral). Limb patterning occurred only in blastemas containing both dorsal- and ventral-derived cells. We further observed that Shh expression requires dorsoventral contact within a blastema, highlighting the necessity of dorsoventral contact for inducing Shh expression. Additionally, we identified WNT10B and FGF2 as dorsal- and ventral-mediated signals, respectively, that create the inductive environment for Shh expression. Our findings clarify the role of dorsal and ventral cells in inducing Shh, a mechanism that has rarely been studied in the context of limb regeneration and pattern formation. This model provides new insights into how cells with different positional identities drive the regeneration process. No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 日本の一地方の中小企業の貿易・投資相談事例分析― アクションリサーチ及びショーン（1983）の「省察的実践論」を活用した直近三年間の相談事例の現況分析の試み ― 205 224 EN Masaaki NAGAMITSU 10.18926/70029 No potential conflict of interest relevant to this article was reported.

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

SAGE Publications Acta Medica Okayama 1756-2848 19 2026 Clinical efficacy and safety of endoscopic ultrasound-guided ablation therapies for pancreatic neuroendocrine tumors: a systematic review and meta-analysis EN Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Hospital Yasuto Takeuchi Department of Gastroenterology and Hepatology, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Background: Pancreatic neuroendocrine tumors (pNETs) are rare; however, they are increasingly being detected. Although surgical resection remains the standard treatment, its invasiveness has prompted interest in less invasive alternatives, particularly for small non-functional pNETs (NF-pNETs) and insulinomas.<br> Objectives: To evaluate the clinical efficacy and safety of endoscopic ultrasound-guided ethanol injection (EUS-EI) and radiofrequency ablation (EUS-RFA) for pNETs.<br> Design: A systematic review and meta-analysis.<br> Data sources and methods: A literature search of PubMed, MEDLINE, and Google Scholar was conducted (April 2005–April 2025). Studies were eligible if they reported clinical outcomes of EUS-EI or EUS-RFA in adult patients with insulinomas or NF-pNETs. The primary endpoints were clinical success (short-term symptom resolution or radiological response) and adverse event (AE) rates. Data were pooled using a random-effects model.<br> Results: Twenty-six studies were included in the meta-analysis. For insulinomas, the pooled clinical success rate was 77% (95% confidence interval (CI), 59–88) for EUS-EI and 95% (95% CI, 89–97) for EUS-RFA. The pooled incidence of total AEs was 32% (95% CI, 17–51) for EUS-EI and 25% (95% CI, 15–39) for EUS-RFA. For NF-pNETs, the pooled clinical success rates were 76% (95% CI, 54–90) for EUS-EI and 85% (95% CI, 74–92) for EUS-RFA, and the pooled incidence of total AEs was 27% (95% CI, 20–35) and 26% (95% CI, 17–38), respectively. The most common moderate or severe AEs were pancreatitis in 12 patients (7.6%) after EUS-EI, and pancreatic fluid collection in 4 patients (1.9%) and pancreatic duct stricture in 3 patients (1.4%) after EUS-RFA. One fatal case occurred in a 97-year-old patient following EUS-RFA.<br> Conclusion: Both EUS-EI and EUS-RFA are effective, relatively safe, and minimally invasive treatment options for pNETs. However, severe AE can occur, and careful patient selection and treatment indication are essential.<br> Trial registration: Not registered. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0008-6215 558 2025 First total synthesis of cyanopterin, a pterin glycoside isolated from a cyanobacterium 109710 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Yuta Maeda Department of Chemistry, Faculty of Science, Okayama University Kazumasa Ejiri Department of Chemistry, Faculty of Science, Okayama University The first total synthesis and structural identification of cyanopterin, a pterin glycoside isolated from the cyanobacterium Synechocystis sp. PCC 6803, has been accomplished. The synthesis was achieved by convergent coupling of three key derivatives: d-glucuronate, d-galactose, and 6-hydroxymethylpterin. An α-selective glycosylation enabled efficient construction of the glucuronate–galactose disaccharide, while subsequent β-exclusive glycosylation with the 6-hydroxymethylpterin derivative furnished the desired pterin–disaccharide glycoside. Final deprotection provided cyanopterin in its natural form, allowing confirmation of its precise structure. No potential conflict of interest relevant to this article was reported.

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

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

Elsevier BV Acta Medica Okayama 2352-409X 70 2026 A semi-quantitative archaeothermometer based on feldspar and volcanic glass compositions in ancient ceramics from the Kibi region, Japan 105566 EN Toshio Nozaka Department of Earth Sciences, Okayama University Naoya Ohbayashi Department of Earth Sciences, Okayama University Yuki Toda Department of Earth Sciences, Okayama University Taiji Anami Department of Earth Sciences, Okayama University Kanako Sugiura Department of Archaeology, Okayama University Takahiro Nozaki Research Institute for the Dynamics of Civilizations, Okayama University Osamu Kimura Research Institute for the Dynamics of Civilizations, Okayama University Naoko Matsumoto Research Institute for the Dynamics of Civilizations, Okayama University Akira Seike Department of Archaeology, Okayama University In this study, we analyzed the chemical compositions of feldspar and volcanic glass clasts in haniwa from kofuns and Sue ware from the Sabukaze kiln site, both in the Kibi region, southwestern Japan, to estimate the thermal conditions of ceramic firing in the 5th–8th centuries CE. Based on the coexistence of molten and unmolten feldspar rims, the solidus temperatures were estimated at ∼ 1050°C–1150°C for haniwa and ∼ 1150°C–1200°C for Sue ware. Volcanic glass compositions changed systematically during firing, showing increases in K2O and decreases in Na2O. From these observations, we propose a semi-quantitative archaeothermometer using variations in the K/Na molar ratio of volcanic glass within a ceramic matrix. This approach can be applied to investigate the development of kiln-firing in the Kibi region, the existence of haniwa potters employing different firing methods, variation in heat input for producing Sue vessels of differing sizes or functions, and temperature-controlled practices in Sue ware production. No potential conflict of interest relevant to this article was reported.

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

BMJ Acta Medica Okayama 2044-6055 15 12 2025 Effectiveness of education programme to increase competency of health cadres in Indonesia: a cluster non-randomised controlled trial e095428 EN Dewie Sulistyorini Graduate School of Biomedical and Health Sciences, Hiroshima University K A T M Ehsanul Huq Graduate School of Biomedical and Health Sciences, Hiroshima University Abdulfatai Olamilekan Babaita Graduate School of Biomedical and Health Sciences, Hiroshima University Sadia A Aivey Graduate School of Biomedical and Health Sciences, Hiroshima University Gao Huiying Graduate School of Biomedical and Health Sciences, Hiroshima University Kana Kazawa Faculty of Health Sciences, Okayama University Yasuko Fukushima Graduate School of Biomedical and Health Sciences, Hiroshima University Mayumi Kako Graduate School of Biomedical and Health Sciences, Hiroshima University Michiko Moriyama Graduate School of Biomedical and Health Sciences, Hiroshima University Objectives Health cadres, who assist midwives in supporting pregnant women in community settings, need to enhance their competencies in identifying risk factors and referring high-risk pregnant women to midwives for further care. Since the capabilities of these health cadres are influenced by maternal complications, an educational programme was implemented to strengthen their skills. Therefore, this study aimed to evaluate the competency of health cadres by providing a researcher-developed educational programme.<br> Design An open-label, cluster non-randomised controlled trial.<br> Setting and participants Health cadres with at least 1 year of work experience were recruited at six public health centres (PHCs) in Banjarnegara Regency, Indonesia.<br> Interventions Six PHCs were selected and allocated into intervention group (IG=3 PHCs) and control group (CG=3 PHCs) groups. A total of 133 female health cadres were enrolled across the selected PHCs. At each PHC, a systematic random sampling method was used to select the participants. The researchers and health professionals provided a 3-week period of theoretical and scenario-based simulations to the IG, while the CG received no education.<br> Outcome measures Researcher-developed questionnaires and checklists were used to assess the knowledge, skills (health assessment, communication, attitude) and confidence. The primary endpoint was competency, a total score of knowledge and skills. The outcome domains were compared between the two groups, and a linear mixed-effect model was used to account for cluster-level variation.<br> Results A total of 130 (97.7%) completed the study (IG:64, CG:66). The competency score showed significant improvement at endline (CG=49.5 and IG=52.5; p=0.002). The median scores for health assessment skills (CG=12 vs IG=14; p<0.001) and communication skills (CG=7 vs IG=8; p<0.001) were increased in the IG compared with the CG. Mixed-effect model indicated that groups (β (95% CI) 2.49 (0.57 to 4.41), p=0.012), baseline knowledge (β(95% CI) 0.73 (0.54 to 0.92), p<0.001) and midline health assessment skills (β (95% CI) 0.54 (0.25 to 0.82), p<0.001) were significant positive predictors, while age was negatively associated with competency (β (95% CI) −0.20 (−0.30 to −0.10), p<0.001)).<br> Conclusion Education effectively increased the competency of health cadres. A well-structured education programme is necessary for health cadres to improve and maintain their competencies in monitoring high-risk pregnant women.<br> Trial registration number NCT06134518. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2211-1247 45 1 2026 Immunopeptidomics combined with full-length transcriptomics uncovers diverse neoantigens 116781 EN Takamasa Ishino Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Tomofumi Watanabe Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Serina Tokita Division of Cancer Immunology, Graduate School of Medical and Dental Sciences, Niigata University Youki Ueda Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Katsushige Kawase Division of Cell Therapy, Chiba Cancer Center Research Institute Yuka Takano Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Yin Min Thu Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Yuta Suzuki Department of Computational Biology and Medical Sciences, The University of Tokyo Chie Owa Department of Computational Biology and Medical Sciences, The University of Tokyo Takashi Inozume Department of Dermatology, Chiba University Graduate School of Medicine Wenhao Zhou Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Joji Nagasaki Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Vitaly Kochin Department of Immunology, Nagoya University Graduate School of Medicine Toshihide Ueno Division of Cellular Signaling, National Cancer Center Research Institute Shinya Kojima Division of Cellular Signaling, National Cancer Center Research Institute Akiko Honobe-Tabuchi Department of Dermatology, University of Yamanashi Tatsuyoshi Kawamura Department of Dermatology, University of Yamanashi Takehiro Ohnuma Department of Dermatology, Kumamoto Kenhoku Hospital Takamitsu Matsuzawa Department of Dermatology, Chiba University Graduate School of Medicine Yu Kawahara Department of Dermatology, Chiba University Graduate School of Medicine Kazuo Yamashita KOTAI Biotechnologies, Inc Jason Lin Division of Cell Therapy, Chiba Cancer Center Research Institute Jun Koseki Division of Systems Biology, Nagoya University Graduate School of Medicine Hiroyoshi Nishikawa Department of Immunology, Nagoya University Graduate School of Medicine Motoo Araki Department of Urology, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Naoya Kato Department of Gastroenterology, Graduate School of Medicine, Chiba University Teppei Shimamura Division of Systems Biology, Nagoya University Graduate School of Medicine Shinichi Morishita Department of Computational Biology and Medical Sciences, The University of Tokyo Yutaka Suzuki Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo Hiroyuki Mano Division of Cellular Signaling, National Cancer Center Research Institute Toshihiko Torigoe Takayuki Kanaseki Division of Cancer Immunology, Graduate School of Medical and Dental Sciences, Niigata University Masahito Kawazu Division of Cell Therapy, Chiba Cancer Center Research Institute Yosuke Togashi Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Neoantigens are crucial for antitumor immunity and immune checkpoint inhibitor (ICI) efficacy by triggering strong immune responses. However, conventional methods for identifying neoantigens, such as whole-exon sequencing and short-read RNA sequencing (RNA-seq), appear to be insufficient, and the tumor mutational burden cannot sufficiently predict ICI efficacy. In this study, we employed a proteogenomic approach using long-read RNA-seq with Pacific Biosciences Single-Molecule Real-Time Sequencing technology to analyze full-length transcripts in combination with the human leukocyte antigen ligandome. As a result, many neoantigen candidates were identified, which were unregistered in a comprehensive database, including those from non-coding regions. Additionally, we validated the responses of specific T cell receptors (TCRs) to these candidates and identified several pairs of TCRs and neoantigens. These findings highlight the presence of more diverse neoantigens than expected that cannot be identified by conventional methods. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 2169-9313 131 1 2026 Electrical Conductivity of Carbonatite Melts to 20 GPa: Constraints on Partial Melting Atop the 410‐km Discontinuity and in the Lower Mantle Transition Zone e2025JB033390 EN Bin Zhao Institute for Planetary Materials, Okayama University Jintao Zhu Institute for Planetary Materials, Okayama University Qi Chen Center for Advanced Radiation Sources, University of Chicago Takashi Yoshino Institute for Planetary Materials, Okayama University Deep-origin carbonatite melts are considered to be the products of partial-melting of the oceanic crust in the subduction zones. In this study, we conducted electrical conductivity (EC) measurements on two samples, the composition of which resemble the partial-melting products atop the 410-km discontinuity and in the lower part of the transition zone. The EC of carbonatite melts was investigated using impedance spectroscopy combined with a multi-anvil press up to 20 GPa. Pressure has a great effect on the EC of the carbonatite melts. While the EC dropped overall by 0.6 log unit from 3 to 20 GPa for varying compositions, the pressure effect becomes weaker above 10 GPa. The Hashin-Shtrikman mixing model indicates that melt fraction of 0–0.3 vol% is necessary to account for the EC atop the 410-km discontinuity beneath NE China, north Philippine Sea, north Pacific, and Australian craton. However, this value soars to 1–4.5 vol% for the lower part of the transition zone in the same regions, and further increases to 3.7–7.3 vol% for cold subduction regions if the slab surface temperature is 300 K lower. The difference in the needed melt fraction at different depths implies that the magnitude of partial melting is much larger in the lower part of the mantle transition zone, and it is thus likely to be the main barrier to the recycled carbonates towards the deep interior. No potential conflict of interest relevant to this article was reported.

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

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

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

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

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 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.

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

International Union of Crystallography (IUCr) Acta Medica Okayama 2056-9890 82 2 2026 Crystal structure of tris[4-(3,4-dimethoxythiophen-2-yl)phenyl]amine E82 EN Masafumi Yano Kansai University Yukiyasu Kashiwagi Osaka Research Institute of Industrial Science and Technology Koki Oishi Kansai University Minori Yano Kansai University Koichi Mitsudo Okayama University In the title compound tris­[4-(3,4-di­meth­oxy­thio­phen-2-yl)phen­yl]amine (DMOT-TPA), C36H33NO6S3, the central nitro­gen atom shows no pyramidalization, with the three para-phenyl­ene rings arranged in a propeller-like geometry. Each thio­phene ring is twisted by about 25–29° relative to the adjacent phenyl­ene ring, giving a distorted π-conjugated framework. In the crystal, mol­ecules are linked through multiple C—H⋯π inter­actions into two-dimensional sheets, which extend into a three-dimensional network. A Cambridge Structural Database survey revealed no prior examples of tri­phenyl­amines bearing 3,4-di­meth­oxy­thio­phen units at the para positions. This unique structure provides new insights into the design of redox-active organic materials. 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.

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

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

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.

Elsevier BV Acta Medica Okayama 0753-3322 193 2025 Deciphering the structural impact of norepinephrine analog radiopharmaceuticals on organic cation transporter affinity 118724 EN Saskia Mühlig Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital Würzburg Xinyu Chen Nuclear Medicine, Faculty of Medicine, University of Augsburg Anna Tutov Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of Würzburg Naoko Nose Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Constantin Lapa Nuclear Medicine, Faculty of Medicine, University of Augsburg Rudolf A. Werner Department of Nuclear Medicine, LMU Hospital, Ludwig-Maximilians-University of Munich Michael Decker Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of Würzburg Takahiro Higuchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose: Previous studies have investigated the kinetics and affinities of norepinephrine transporter (NET)-targeting radiotracers, including [123I]MIBG, but the role of organic cation transporters (OCTs) remains unclear. This study aimed to evaluate how the structural design of selective NET-targeting tracers affects OCT-mediated non-specific uptake, identifying factors influencing both NET and OCT affinity.<br> Methods: Cellular uptake assays were conducted using SK-N-SH cells expressing human NET, and human OCT1-, OCT2-, and OCT3-expressing cells with [3H]norepinephrine, [3H]MPP+, and [131I]MIBG. Competitive uptake assays used non-radioactive reference compounds for several NET-targeting radiopharmaceuticals (MIBG, HED, EPI, PHEN, LMI1195, and PHPG), along with a new PET radiotracer [18F]AF78, and its two analogs with meta-iodide [18F]AF78(I) or hydroxyl group [18F]AF78(OH). Dynamic PET imaging in non-human primates assessed the in vivo uptake of [18F]AF78 after NET inhibition with desipramine.<br> Results: Monoamine-based tracers (EPI, PHEN, HED) exhibited high NET selectivity with minimal OCTs interaction, while guanidine-containing tracers (e.g., MIBG, LMI1195) displayed substantial OCTs affinity. Lower lipophilicity in guanidine-containing compounds, influenced by substitutions on the benzene ring (e.g., PHPG, AF78), correlated with weaker OCT interactions. PET imaging confirmed that cardiac uptake of [18F]AF78 is sensitive to desipramine pretreatment (***P < 0.0005), indicating its NET-specificity, while persistent hepatic retention suggests an OCT-mediated transport mechanism.<br> Conclusion: This study highlights the critical influence of the compounds’ chemical structure on NET and OCT affinities. Structural modifications that reduce OCT-mediated uptake while maintaining high NET affinity could improve the specificity and theranostic potential of NET-targeting ligands. These findings provide insights for designing next-generation radiotracers with enhanced selectivity and clinical utility. No potential conflict of interest relevant to this article was reported.

European Respiratory Society (ERS) Acta Medica Okayama 2312-0541 11 6 2025 Global trends in idiopathic pulmonary fibrosis mortality rates during 2001–2022 00362-2025 EN Ko Harada Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai Yoshito Nishimura Division of Hematology/Oncology, Mayo Clinic Quynh Thi Vu Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Maki Yamamoto Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and ultimately fatal lung disease. Updated global mortality data, especially from underexplored countries, are limited. This study aimed to understand the current global trends in IPF-associated mortality rates.<br> Methods This observational study used the World Health Organization Mortality Database to analyse data stratified by sex, age and geographic region, encompassing 64 countries between 2001 and 2022. IPF was defined according to the International Code for Diseases-10 code J84.1. Crude and age-standardised mortality rates per 100 000 individuals were calculated to estimate long-term mortality trends. Mortality rates were calculated by dividing IPF-associated deaths by the corresponding population, with age-specific rates determined for each 5-year age group. Trends in the 2001–2022 period were analysed using a locally weighted regression model, and the average annual percentage change in mortality rates between 2010 and 2022 was estimated using joinpoint regression analysis.<br> Results Overall, 874 998 deaths associated with IPF were analysed. The LOESS-smoothed crude mortality rate increased from 2.10 (95% confidence interval (CI) 1.77–2.43) per 100 000 in 2001 to 3.14 (95% CI 2.71–3.57) per 100 000 by 2022. The LOESS-smoothed age-standardised mortality rates increased overall, peaking at 1.59 (95% CI 1.51–1.67) per 100 000 in 2018 and declining slightly to 1.57 (95% CI 1.35–1.79) per 100 000 in 2022. Mortality was higher among males than females; furthermore, 87.5% of deaths occurred in individuals aged ≥65 years. Mortality rates were highest among the American population, with a notable increase in Latin American countries.<br> Conclusion IPF-associated mortality rates have increased globally, particularly in males. Significant geographical, age and sex disparities were observed, emphasising the need for targeted public health measures and improved disease management. No potential conflict of interest relevant to this article was reported.

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

Japanese Association of Rehabilitation Medicine Acta Medica Okayama 2432-1354 10 2025 Reliability and Validity of the Japanese Perme ICU Mobility Score: An Initial Psychometric Evaluation 20250037 EN Sho Katayama Department of Rehabilitation Medicine, Okayama University Hospital Tomohiro Ikeda Department of Rehabilitation Medicine, Okayama University Hospital Nobuto Nakanishi Department of Disaster and Emergency Medicine, Graduate School of Medicine, Kobe University Hajime Katsukawa Department of Scientific Research, Japanese Society for Early Mobilization Ricardo Kenji Nawa Department of Critical Care Medicine, Hospital Israelita Albert Einstein Christiane Perme Department of Rehabilitation Services, Houston Methodist Hospital Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masanori Hamada Department of Rehabilitation Medicine, Okayama University Hospital Ikumi Sato Academic Field of Health Science, Okayama University Satoshi Hirohata Academic Field of Health Science, Okayama University Objectives : The Perme ICU Mobility Score is widely used to assess functional status, but no version of this assessment tool has been validated for use in Japan. This study aimed to translate the Perme Score into Japanese and evaluate its reliability and validity.<br> Methods : Following forward–backward translation, the Japanese Perme Score was tested at ICU discharge. Inter-rater reliability was examined using weighted kappa coefficient. Construct validity was assessed through correlations with the Medical Research Council Sum Score (MRC-SS), Functional Status Score for the ICU (FSS-ICU), and ICU Mobility Scale (IMS). Predictive validity for activities of daily living (ADL) independence (Barthel Index ≥ 85) and discharge destination was evaluated using Receiver operating characteristic (ROC) analysis. Floor and ceiling effects were also analyzed.<br> Results : In 69 patients, the Japanese Perme Score showed high inter-rater reliability (κ=0.83). It showed moderate correlation with FSS-ICU (rho=0.61) and IMS (rho=0.73), and it showed weak correlation with MRC-SS (rho=0.36). Predictive validity for ADL independence and home discharge yielded AUCs of 0.76 and 0.73, respectively. A ceiling effect was noted in 10% of cases, with no floor effect.<br> Conclusions: The Japanese Perme Score is a reliable, valid instrument for evaluating physical function at ICU discharge. No potential conflict of interest relevant to this article was reported.

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

Japan Radioisotope Association Acta Medica Okayama 0033-8303 75 1 2026 自然起源放射性物質（NORM）を用いた232Th/212Pbジェネレーターによる短寿命放射性核種の作製—非密封放射性同位元素の安全取扱実習への応用— 13 19 EN Yui Imada Advanced Science Research Center, Okayama University Midori Isobe Advanced Science Research Center, Okayama University Hiroaki Terato Advanced Science Research Center, Okayama University Tadashi Hanafusa Advanced Science Research Center, Okayama University 我々は自然起源放射性物質（NORM）を放射線源とする232Th/212Pbジェネレーターを作製した。ジェネレーターから室温で約500 Bqの高純度の212Pbをミルキングできた。これを用いて32Pを用いた非密封放射性同位元素の安全取扱実習を置き換えることができることを示した。ジェネレーターの作製の容易さ，ミルキング操作の簡便性，212Pb及びその子孫核種の放射性同位元素としての特性から，今回作製した232Th/212Pbジェネレーターは放射線教育に有効に活用できると結論した。 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.

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

Elsevier BV Acta Medica Okayama 0040-8166 93 2025 Detection of the nuclear translocation of androgen receptor using quantitative and automatic cell imaging analysis 102631 EN Lanlan Bai Graduate School of Science and Engineering, Iwate University Tao Wu Graduate School of Science and Engineering, Iwate University Mizuki Fukasawa Neuro-AI Integration Science Laboratory, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Sayo Kashiwagi Rohto Pharmaceutical Co., Ltd., Basic Research Development Division Haruka Tate Graduate School of Science and Engineering, Iwate University Taku Ozaki Graduate School of Science and Engineering, Iwate University Eriko Sugano Graduate School of Science and Engineering, Iwate University Hiroshi Tomita Graduate School of Science and Engineering, Iwate University Tsuyoshi Ishii Rohto Pharmaceutical Co., Ltd., Basic Research Development Division Takuya Akashi Neuro-AI Integration Science Laboratory, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tomokazu Fukuda Graduate School of Science and Engineering, Iwate University Testosterone signaling mediates diseases such as androgenetic alopecia and prostate cancer and is controlled by the activation of the androgen receptor (AR) and nuclear translocation of the ligand-receptor complex. This study established an immortalized dermal papilla cell line that stably expresses the AR labeled with a monomeric green fluorescence marker. The cells expressed the histone H2B protein as visualized using a red fluorescence marker, enabling the Detection of nuclear translocation under live cell conditions using image analysis. The AR was observed to be translocated from the cytoplasm to the nucleus of cells after stimulation with dihydrotestosterone (DHT). The signal intensity of the nuclear/cytoplasm ratio was analyzed using automatic image analysis and a newly developed algorithm. The quantitation method to detect nuclear translocation revealed that the AR nuclear signal plateaued approximately 20 min after DHT exposure. Our developed method has the potential to save human labor by the automatic process of the image. No potential conflict of interest relevant to this article was reported.

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

岡山医学会 Acta Medica Okayama 0030-1558 137 3 2025 岡山大学小児医科学教室における最近の研究成果 108 117 EN Hirokazu Tsukahara Department of Pediatrics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 3 2025 令和６年度岡山医学会賞　胸部・循環研究奨励賞（砂田賞） 95 97 EN Shinichi Kawana Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 3 2025 令和６年度岡山医学会賞　がん研究奨励賞（林原賞・山田賞） 89 91 EN Shota Takihira Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 0312-5963 64 12 2025 Evaluation of Fentanyl-Emerged Adverse Events and Pharmacokinetics in Neonates: A Physiologically Based Pharmacokinetic Modeling Approach 1811 1825 EN Walaa Yousef Bassyouni Mahdy Department of Pharmacy, Kobe University Hospital Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Risa Joji Department of Pharmacy, Kobe University Hospital Mari Hashimoto Department of Pharmacy, Kobe University Hospital Ruka Nakasone Department of Pediatrics, Graduate School of Medicine, Kobe University Kazumichi Fujioka Department of Pediatrics, Graduate School of Medicine, Kobe University Kotaro Itohara Department of Pharmacy, Kobe University Hospital Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Tomohiro Omura Department of Pharmacy, Kobe University Hospital Ikuko Yano Department of Pharmacy, Kobe University Hospital Background Despite its common use for analgesia in neonatal intensive care units, the optimal dosing and safety profile of fentanyl, particularly regarding suspected fentanyl-emerged adverse events (FEAEs), such as hypotension, desaturation, and oliguria, are not well-defined.<br> Objective This study aimed to develop an optimal therapeutic monitoring and dosing strategy for fentanyl for neonates. A physiologically based pharmacokinetic (PBPK) model for predicting fentanyl pharmacokinetics across various populations, including preterm and term neonates, was developed, and the relationship between predicted fentanyl exposure and FEAE incidence in neonates was assessed.<br> Methods A PBPK model was developed and validated against the observed values in the literature. The model’s predictive accuracy for fentanyl pharmacokinetics and association with FEAE incidence in an external retrospective cohort of Japanese neonates was evaluated using the predicted concentrations and pharmacokinetic parameters estimated by PBPK simulation.<br> Results The PBPK model exhibited reasonable predictive performance for serum fentanyl concentrations in actual neonatal patients (mean error: 9.27% [standard error: 5.06%], root mean squared error: 54.7%). The incidence of any FEAE, particularly oxygen desaturation, was associated with the fentanyl concentration-to-dose ratio, but not with some exposure parameters, such as the area under the curve and maximum concentration. The recommended reduced infusion rate allowed serum fentanyl concentrations to fall within the ranges established by the reported values and our data.<br> Conclusions Our PBPK model and proposed dosing strategy may contribute to safer and more effective fentanyl use in neonates. No potential conflict of interest relevant to this article was reported.

Ceramic Society of Japan Acta Medica Okayama 1348-6535 134 1 2026 Preparation of brookite-type titanium dioxide particle layer on titanium surfaces via hydrothermal treatment and evaluation of in vitro apatite-forming ability 24 30 EN Satoshi Hayakawa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yushi Nakamoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Seiya Kojima Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Takuya Kataoka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tomohiko Yoshioka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University In this study, we prepared a brookite-type titanium dioxide particle layer on the surface of titanium substrates via hydrothermal treatment in aqueous urea solutions containing sodium chloride (NaCl) and examined its in vitro apatite-forming ability. Increasing the urea concentration suppressed the formation of anatase-type titanium dioxide on the titanium substrate, forming a particle layer composed of pure brookite-type titanium dioxide. The size and packing density of brookite-type titanium dioxide particles formed on the titanium substrate increased with the NaCl concentration in a 7.0 mol·dm−3 urea solution. When titanium substrates hydrothermally treated in aqueous solutions of 7.0 mol·dm−3 urea and 2.0 mol·dm−3 NaCl were soaked in a simulated body fluid for various periods up to 7 d, the substrate surface was densely covered with hemispherical apatite particles (5.3 µm in diameter) within 3 d, indicating that the brookite-type titanium dioxide particle layer had an excellent apatite-forming ability comparable to that of the anatase-type titanium dioxide particle layer. 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.<br> 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.<br> 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.<br> 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.

International Institute of Anticancer Research Acta Medica Okayama 0250-7005 46 1 2025 Near-infrared Photoimmunotherapy Targeting High-risk Human Neuroblastoma Cells Expressing GD2 25 38 EN HIROSHI NOUSO Department of Pediatric 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 TERUTAKA TANIMOTO Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences MORIMICHI TANI Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HINAKO WATANABE Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TAKANORI OYAMA Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KAZUHIRO NOMA Department of Pediatric 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 HISATAKA KOBAYASHI Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health TAKUO NODA Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SHINJI KURODA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOSHIYOSHI FUJIWARA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aim: Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system in infancy. Despite advances in treatment, the prognosis remains poor for high-risk NB patients. Although immunotherapy using anti-GD2 antibodies is available for high-risk NB, the therapeutic efficacy is insufficient. Near-infrared photoimmunotherapy (NIR-PIT) is an antitumor strategy that induces tumor-specific cytotoxicity by combining an antibody-photoabsorber conjugate (APC) with NIR light irradiation. In this study, we investigated the therapeutic efficacy of GD2-targeted NIR-PIT against human NB cells.<br> Materials and Methods: GD2 expression was analyzed on the surface of high-risk human NB cells (CHP-134, LA-N-5, IMR-32) and non-high-risk human NB cells (SK-N-SH) by flow cytometry. The APC was synthesized by incubating anti-GD2 antibody and IR700. The cytotoxic effect of GD2-targeted NIR-PIT was evaluated using the XTT assay. The distribution of dead cells within tumor spheres was evaluated using a live/dead assay. The in vivo antitumor effect of GD2-targeted NIR-PIT was assessed using a subcutaneous human NB xenograft tumor model.<br> Results: GD2 protein was expressed on the surface of CHP-134, LA-N-5, and IMR-32 cells but not SK-N-SH cells. GD2-targeted NIR-PIT significantly suppressed the viability of GD2-positive NB cells but not GD2-negative NB cells, compared to the control and monotherapy groups. GD2-targeted NIR-PIT significantly reduced the volume of GD2-positive CHP-134 tumor spheres by inducing the accumulation of dead cells. Subcutaneous CHP-134 xenograft tumor models demonstrated that GD2-targeted NIR-PIT significantly inhibited tumor growth compared with the control and monotherapy groups.<br> Conclusion: GD2-targeted NIR-PIT is a promising antitumor strategy for treating high-risk NB tumors expressing GD2. No potential conflict of interest relevant to this article was reported.

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

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

Wiley Acta Medica Okayama 1347-9032 2025 Genomic Profiling of Pediatric Solid Tumors With a Dual DNA/RNA Panel: JCCG-TOP2 Study EN Kayoko Tao Department of Pediatrics, National Cancer Center Hospital Takako Yoshioka Department of Pathology, National Center for Child Health and Development Miho Kato Department of Childhood Cancer Data Management, National Center for Child Health and Development Kazuyuki Komatsu Department of Pediatrics, Hamamatsu University School of Medicine Shinichi Tsujimoto Department of Pediatrics, Yokohama City University Kenichi Sakamoto Department of Pediatrics, Shinshu University School of Medicine Kazuki Tanimura Department of Pediatrics, National Cancer Center Hospital Minako Sugiyama Department of Pediatrics, National Cancer Center Hospital Masahiro Sekiguchi Department of Pediatrics, The University of Tokyo Yoshiko Nakano Department of Pediatrics, The University of Tokyo Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushi Yatabe Department of Diagnostic Pathology, National Cancer Center Hospital Akihiko Yoshida Department of Diagnostic Pathology, National Cancer Center Hospital Hajime Okita Department of Pathology, Keio University School of Medicine Junko Hirato Department of Pathology, Public Tomioka General Hospital Kenichi Kohashi Department of Pathology, Graduate School of Medicine, Osaka Metropolitan University Yukichi Tanaka Department of Pathology, Kanagawa Children's Medical Center Shinji Kohsaka Division of Cellular Signaling, National Cancer Center Research Institute Takashi Kubo Department of Clinical Genomics, National Cancer Center Research Institute Kuniko Sunami Department of Laboratory Medicine, National Cancer Center Hospital Makoto Hirata Department of Genetic Medicine and Services, National Cancer Center Hospital Shuichi Tsutsumi Genome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of Tokyo Hiroyuki Aburatani Genome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of Tokyo Katsuyoshi Koh Department of Hematology and Oncology, Saitama Children's Medical Center Masahiro Hirayama Department of Pediatrics, Mie University Graduate School of Medicine Shuhei Karakawa Department of Pediatrics, Hiroshima University Hospital Yukayo Terashita Department of Pediatrics, Hokkaido University Hospital Hiroyuki Fujisaki Department of Pediatric Hematology and Oncology, Osaka City General Hospital Takeshi Yagi Okinawa Prefectural Nanbu Medical Center & Children's Medical Center Akihiro Yoneda Department of Pediatric Surgery, National Center for Child Health and Development Shinji Mochizuki Department of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health Security Hiroyuki Shichino Department of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health Security Tatsuya Suzuki Department of Hematology, National Cancer Center Hospital Tetsuya Takimoto Department of Childhood Cancer Data Management, National Center for Child Health and Development Koichi Ichimura Department of Pathology, Kyorin University Faculty of Medicine Chitose Ogawa Department of Pediatrics, National Cancer Center Hospital Kimikazu Matsumoto Children's Cancer Center National Center for Child Health and Development Hitoshi Ichikawa Department of Clinical Genomics, National Cancer Center Research Institute Motohiro Kato Department of Pediatrics, The University of Tokyo To develop an optimized genomic medicine platform for pediatric cancers, a nationwide cancer genome profiling project was conducted from January 2022 to February 2023 in collaboration with the Japan Children's Cancer Group. This prospective observational study analyzed matched blood and FFPE tumor samples from patients aged 0–29 years with solid tumors. Genomic analysis used the TOP2 hybrid capture–enrichment system, targeting 737 and 455 genes in the DNA and RNA panels, along with allele-specific genome copy number alterations. A total of 210 patients from 50 institutions were enrolled across Japan (median age, 8 years; range, 0–25). Of these, 154 (77%) were enrolled at diagnosis or during/after initial treatment and 56 (27%) at disease progression or relapse. The TOP2 findings had great benefits in clarifying the diagnosis of pediatric solid tumors. Among the 204 patients with genomic results, 147 (72%) had potentially actionable findings, including diagnostic, prognostic, and therapeutic findings in 111 (54%), 61 (30%), and 64 (31%), respectively. Oncogenic fusions were noted in 45 (23%) patients. A copy number alteration was identified in at least one genomic region in 170 (83%) patients. Two patients exhibited a high tumor mutation burden. Seventeen (8%) patients harbored a germline pathogenic/likely pathogenic variant in cancer-predisposing genes. This study highlighted the feasibility of implementing a nationwide precision medicine platform and the clinical utility of the TOP2 system for pediatric cancers. The results support the integration of genomic data into the standard clinical care of pediatric patients with cancer, both at diagnosis and at relapse. No potential conflict of interest relevant to this article was reported.

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

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

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 2399-3642 8 1 2025 A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS 1720 EN Ryoichi Nakamura Department of Neurology, Aichi Medical University School of Medicine Genki Tohnai Division of ALS Research, Aichi Medical University School of Medicine Naoki Atsuta Department of Neurology, Aichi Medical University School of Medicine Yumi Matsuda Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine Satoru Morimoto Keio University Regenerative Medicine Research Center, Kawasaki Daisuke Ito Department of Neurology, Nagoya University Graduate School of Medicine Masahisa Katsuno Department of Neurology, Nagoya University Graduate School of Medicine Yuishin Izumi Department of Neurology, Tokushima University Graduate School of Biomedical Sciences Mitsuya Morita Division of Neurology, Department of Internal Medicine, Jichi Medical University Ikuko Iwata Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Ichiro Yabe Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Tomoko Nakazato Department of Neurology, Juntendo University School of Medicine Nobutaka Hattori Department of Neurology, Juntendo University School of Medicine Takehisa Hirayama Department of Neurology, Toho University Faculty of Medicine Osamu Kano Department of Neurology, Toho University Faculty of Medicine Asako Tamura Department of Neurology, Mie University Graduate School of Medicine Naoki Suzuki Department of Neurology, Tohoku University Graduate School of Medicine Masashi Aoki Department of Neurology, Tohoku University Graduate School of Medicine Kazumoto Shibuya Department of Neurology, Graduate School of Medicine, Chiba University Satoshi Kuwabara Department of Neurology, Graduate School of Medicine, Chiba University Masaya Oda Department of Neurology, Vihara Hananosato Hospital Rina Hashimoto Department of Neurology, NHO Higashinagoya National Hospital Ikuko Aiba Department of Neurology, NHO Higashinagoya National Hospital Tomohiko Ishihara Department of Neurology, Brain Research Institute, Niigata University Osamu Onodera Department of Neurology, Brain Research Institute, Niigata University Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Bokuda Department of Neurology, Tokyo Metropolitan Neurological Hospital Toshio Shimizu Department of Neurology, Tokyo Metropolitan Neurological Hospital Yoshio Ikeda Department of Neurology, Gunma University Graduate School of Medicine Kazuko Hasegawa Division of Neurology, NHO Sagamihara National Hospital Fumiaki Tanaka Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine Takanori Yokota Department of Neurology and Neurological Science, NucleoTIDE and PepTIDE Drug Discovery Center (TIDE), Institute of Science Tokyo Kazuaki Kanai Department of Neurology, Fukushima Medical University School of Medicine Yu-ichi Noto Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Ryuji Kaji Department of Neurology, Tokushima University Graduate School of Biomedical Sciences Hirohisa Watanabe Department of Neurology, Fujita Health University Tomoko Konishi Division of ALS Research, Aichi Medical University School of Medicine Mikiko Hasegawa Division of ALS Research, Aichi Medical University School of Medicine Hozuki Fukaya Division of ALS Research, Aichi Medical University School of Medicine Jun-ichi Niwa Department of Neurology, Aichi Medical University School of Medicine Manabu Doyu Department of Neurology, Aichi Medical University School of Medicine Yohei Okada Department of Neurology, Aichi Medical University School of Medicine Shiho Nakamura Keio University Regenerative Medicine Research Center, Kawasaki Fumiko Ozawa Keio University Regenerative Medicine Research Center, Kawasaki Hideyuki Okano Keio University Regenerative Medicine Research Center, Kawasaki Masahiro Nakatochi Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine Gen Sobue Division of ALS Research, Aichi Medical University School of Medicine Amyotrophic lateral sclerosis (ALS) exhibits considerable clinical variability, such as differences in age at onset (AAO). Multiple factors, including genetic factors, may underlie this variability; however, the specific determinants remain unclear. To identify genes affecting AAO, we have conducted a genome-wide association study in Japanese patients with ALS (discovery cohort: n = 1808; replication cohort: n = 207). Here, we show that the minor A allele of rs113161727 at the ADAM29-GPM6A locus is associated with a younger AAO in the discovery cohort (effect, -4.27 years; p = 4.60 × 10-8); this finding has been confirmed in the replication cohort (p = 0.0068) and meta-analysis (p = 1.08 × 10−9). Among 65 ALS patients with a SOD1 mutation, the AAO has been found to be 10.2 years younger in those with the A allele than in those without it (p = 0.002). This variant correlates with GPM6A upregulation in iPSC-derived motor neurons, suggesting GPM6A as a candidate AAO modifier. Overall, our study highlights the impact of genetic modifiers on ALS heterogeneity and provides a potential target for delaying disease onset. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2949-7744 3 2025 Efficient variant phasing utilizing a replication cycle reaction system 103457 EN Akihiko Mitsutake 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 Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Purpose: When 2 heterozygous variants are detected in autosomal recessive disease genes, determining whether they are in cis or in trans is essential. Subcloning polymerase chain reaction products or complementary DNA is limited by variant distance (up to 10 kb) and complementary DNA availability. Droplet digital polymerase chain reaction, effective up to 100 kb, faces probe design challenges. We used replication cycle reaction (RCR), which replicates large DNA fragments based on E. coli chromosome replication, to phase widely spaced heterozygous variants.<br> Methods: Circular DNA molecules were formed by ligating CRISPR/Cas9-cleaved genomic fragments with an oriC-AmpR cassette, then amplified by RCR. Using a genomic DNA (gDNA) sample that is previously analyzed by long-read sequencing, we optimized reaction conditions (including gDNA to oriC-AmpR cassette ratios) and validated phasing accuracy via electrophoresis and Sanger sequencing. Finally, we applied this method to 7 patients harboring 2 heterozygous pathogenic variants (4.3-152 kb apart).<br> Results: RCR amplified genomic regions up to 104 kb. Lower gDNA-to-cassette ratios favored monoallelic amplification, enabling straightforward phasing, whereas higher ratios yielded biallelic products requiring transformation-based allele separation. For variants 152 kb apart, an intervening single-nucleotide variant enabled phased reconstruction. Ultimately, RCR confirmed compound heterozygosity in all 7 patients.<br> Conclusion: This method effectively phases multiple heterozygous variants across large genomic distances. 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.<br> 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.<br> 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.

Informa UK Limited Acta Medica Okayama 2167-8421 2025 Novel in-frame duplication variant of SOD1 in a Japanese family with familial amyotrophic lateral sclerosis EN Masanori Nakajima Department of Neurology, Kyorin University School of Medicine Hiroya Naruse Department of Neurology, Graduate School of Medicine, The University of Tokyo Yuichi Riku Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Kunihiro Ueda Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Mitsui Department of Neurology, Graduate School of Medicine, The University of Tokyo Yoshitsugu Nakamura Division of Neurology, Department of Internal Medicine IV, Osaka Medical and Pharmaceutical University Shimon Ishida Division of Neurology, Department of Internal Medicine IV, Osaka Medical and Pharmaceutical University Takashi Yamada Department of Pathology, Osaka Medical and Pharmaceutical University Naoki Moro Department of Neurology, Kyorin University School of Medicine Naoki Kotsuki Department of Neurology, Kyorin University School of Medicine Kentaro Nagai Department of Neurology, Kyorin University School of Medicine Shin-ichi Tokushige Department of Neurology, Kyorin University School of Medicine Ayumi Uchibori Department of Neurology, Kyorin University School of Medicine Chizuko Oishi Department of Neurology, Kyorin University School of Medicine Hiroyuki Yabata Department of Neurology, Shiga University of Medical Science Makoto Urushitani Department of Neurology, Shiga University of Medical Science Yasushi Iwasaki Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;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 Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Yaeko Ichikawa Department of Neurology, Kyorin University School of Medicine Objectives: To analyze the cases of a family with a novel in-frame duplication variant (NM_000454.5:c.357_357 + 2dup, p.Val120dup) of SOD1 and a structural model of the mutated SOD1 protein. Methods: The clinical profiles of three patients in the family were analyzed, including the neuropathological findings of the proband’s mother. Genetic analyses were conducted for three patients. cDNA and in silico structural analyses were performed to evaluate the effects of duplication variants on the structure of SOD1. Results: The clinical features of the patients included predominant involvement of the lower motor neurons, asymmetric onset of motor symptoms in the lower limbs, and a relatively rapid progression of muscular weakness and respiratory insufficiency. Neuropathological findings revealed severe loss of spinal cord motor neurons, and immunohistochemistry using an anti-misfolded SOD1 antibody revealed aggregates in the spinal cord. Genetic analyses revealed a c.357_357 + 2dup at the exon 4–intron 4 boundary of SOD1 in three patients. cDNA analysis of the proband suggested the presence of a valine (p.Val120dup) duplication in the heterozygous state, and the SOD1 transcript level showed no significant differences from those of healthy controls. In silico structural analyses predicted that p.Val120dup could affect the structure of the β-barrels and copper ion binding site of SOD1, suggesting an abnormal conformation of SOD1 that is predicted to interfere with the binding of copper ions. Conclusion: We identified a novel in-frame duplication variant in the C-terminus of β7 of SOD1. This genotype–structure–phenotype study of SOD1 provides valuable insights into disease-causing mechanisms. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0969-806X 237 2025 Impact of different X-ray tube positions on actual dose measurements during CT examinations -An effect of patient physique- 113001 EN Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Tatsuya Maeda Graduate School of Medical Sciences, Kanazawa University Kazuki Takegami Department of Radiological Technology, Yamaguchi University Hospital 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 Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Yuki Kanazawa Faculty of Life Science, Kumamoto University Kazuta Yamashita Department of Orthopedics, School of Medicine, Tokushima University Takeshi Konishi MEDITEC JAPAN Co., Ltd. Motochika Maki MEDITEC JAPAN Co., Ltd. Dose management of patients is very important during X-ray Computed Tomography (CT) examinations, but because the patient's surface dose is inhomogeneous, it is difficult to measure the most probable value using a small passive-type dosimeter, lent to the patient. To solve this problem, our research group developed a precise dose analysis procedure in which a systematic uncertainty related to the X-ray incident direction (θin) is reduced. θin information was analyzed from CT images. However, the applicability of our procedure to actual patients with various physiques has not been examined. This study aims to propose a dose analysis procedure that can be applied to patients with various physiques, and to show its impact on dose measurement. Clinical data of 198 patients with Body Mass Index (BMI) values between 15 and 40 kg/m2 (mean value: 23.1 ± 3.8 kg/m2) who underwent chest CT scans were analyzed after dividing them into three groups based on BMI values. The absorbed dose was measured with a small-type Optically Stimulated Luminescence (OSL) dosimeter. To derive correction factors related to θin, the dependence of the actually-measured dose values of various patients on θin was analyzed. The correction coefficients were determined independently for the three groups classified by BMI values. By correcting the effect of θin, the systematic uncertainty element could be reduced, resulting in 30 % reduction of the uncertainty. Furthermore, it was found that our analysis procedure makes it possible to visualize outliers. In comparison with the expected dose values based on Computed Tomography Dose Index (CTDI) values, most of the data fell within the range of ±1.34 mGy (=1σ). However, 7 % of the data showed large deviations larger than 2σ. In conclusion, our research group has developed a procedure for measuring patient surface doses that can be applied to patients having various physiques, in which the effects of X-ray incident direction were accurately corrected. The procedure could be one solution to the problems with actual dose measurements during CT examinations, and will be useful for dose management based on the small-type dosimeter. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0169-555X 493 2026 Coast uplifted by nearby shore-parallel active submarine faults during the 2024 Mw 7.5 Noto Peninsula earthquake 110069 EN Hideaki Goto Hiroshima University Tomoru Yamanaka Natural History Museum and Institute Chiba Tomohiro Makita Hiroshima University Yoshiya Iwasa University of Teacher Education Fukuoka Takuro Ogura Hyogo University of Teacher Education Kyoko Kagohara Yamaguchi University Yasuhiro Kumahara Hiroshima University Yasuhiro Suzuki Nagoya University Nobuhisa Matta Okayama University Tatsuto Aoki Kanazawa University Wataru Mori Hiroshima University Kenta Haranishi Hiroshima University Takashi Nakata Hiroshima University An Mw 7.5 earthquake occurred at 16:10 JST on January 1, 2024 at a depth of 16 km on the Noto Peninsula, central Japan. This earthquake was the second-largest intraplate earthquake recorded in Japan during 120 years of seismic observation, and it caused approximately 100 km of coastal seafloor emergence along the peninsula's northern coast. Herein, we mapped the emergence of this coastal seafloor and measured the uplift along the coast. The movement of the coastline led to the emergence of approximately 4.4 km2 of seafloor, which is continuous and probably the longest in the world. We determined the uplift distribution along the coast using the white remains of a reddish seaweed called Corallina pilulifera. Its upper limit exhibited a distinct horizontal line, effectively representing the uplift amount throughout the peninsula. Two large, uplifted regions were identified, around Cape Saruyama (5.21 m) in the west and Cape Kurasaki (2.70 m) in the north. Although active offshore submarine faults have been extensively researched, the fault traces remain poorly defined because they are primarily interpreted from seismic reflection profiles. We identified the distribution of active submarine faults using anaglyph-type stereoscopic images, confirming the subsurface deformation structure seen through the seismic reflection profiles. The main fault trace is primarily straight and contiguous with the nearby north coast. The uplift amount is greater near the active fault traces on the north side and diminishes sharply with increasing distance from these faults, indicating a southward tilt of surface uplift related to the active submarine faults. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0169-555X 468 2025 Surface exposure ages of middle–late Pleistocene marine and fluvial terraces along the northern and southern Sanriku coasts, Northeast Japan 109497 EN Sachi Wakasa Institute of Regional Innovation, Hirosaki University Tatsuya Ishiyama Earthquake Research Institute, University of Tokyo Daisuke Hirouchi Faculty of Education, Shinshu University Nobuhisa Matta Faculty of Education, Okayama University Natsuko Fujita Tono Geoscience center, Japan Atomic Energy Agency Tomoo Echigo Kankyo Chisitsu, Co. To estimate long-term rates of coastal uplift along the northern Pacific coast of Northeast Japan, we determined the surface exposure ages of marine and fluvial terraces based on terrestrial in situ cosmogenic radionuclide dating of exposed bedrock surfaces. Based on reinterpretation of marine and fluvial terraces, we collected samples from the northern and southern Sanriku coast. The surface exposure ages from 10Be concentrations in quartz calculated from the measured 10Be/9Be ratios commonly suggest MIS 5 and MIS 7 for the marine and fluvial terraces and averaged coastal uplift rates of ca. 0.25 ± 0.15 and 0.4 mm/yr along the northern and southern Sanriku coast at intermediate timescales. The results may demonstrate different styles of crustal strain accommodation in the northern Northeast Japan arc above the subducting Pacific plate. No potential conflict of interest relevant to this article was reported.

Microbiology Society Acta Medica Okayama 0022-1317 106 12 2025 Thorough characterization of a new curvulavirid from a Japanese strain of Cryphonectria nitschkei 002177 EN Sabitree Shahi ​Institute of Plant Science and Resources, Okayama University Sakae Hisano ​Institute of Plant Science and Resources, Okayama University Wasiatus Sa'diyah ​Institute of Plant Science and Resources, Okayama University Yoshihiro Takaki ​Institute for Extra-cutting-edge Science and Technology Avant-garde Research (X-star), Japan Agency for Marine-Earth Science and Technology (JAMSTEC) Hideki Kondo ​Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki ​Institute of Plant Science and Resources, Okayama University A new curvulavirid was isolated from a Japanese strain of the filamentous ascomycete Cryphonectria nitschkei and thoroughly characterized. The virus termed Cryphonectria nitschkei curvulavirus 1 (CnCvV1) has a bi-segmented dsRNA genome. CnCvV1 dsRNA1 encodes an RNA-dependent RNA polymerase (592 amino acids), while dsRNA2 possesses two ORFs, one that encodes a protein associated with the genomic dsRNA and the other that encodes a hypothetical protein of unknown function. CnCvV1 could be experimentally introduced into another virus-free strain of C. nitschkei and two strains of different fungal species within the genus Cryphonectria (Cryphonectria parasitica and Cryphonectria carpinicola). Based on phenotypic comparison, the virus caused asymptomatic infection in the three newly established fungal strains. However, there was a reduced colony growth rate and increased CnCvV1 accumulation in an RNA silencing-deficient mutant (Δdcl2), relative to the wt strain EP155 of a model virus host fungus (C. parasitica). These findings suggest that CnCvV1 is targeted by RNA silencing in C. parasitica. This study provides a foundation for further exploration of curvulavirids that have been biologically understudied. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 1085-9489 30 4 2025 A Case of Retinopathy–Sensory Neuropathy Syndrome With a Novel Compound Heterozygous FLVCR1 Variant e70082 EN Yumiko Nakano Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Fukui Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Deguchi Department of Neurology, Okayama City General Medical Center Chika Matsuoka Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohito Kawano Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Taira Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayaka Matsuo Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Osakada Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taijun Yunoki Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Emi Nomura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Takemoto Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuta Morihara 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 Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background and Aims: Retinopathy–sensory neuropathy syndrome (RETSNS), also known as posterior column ataxia with retinitis pigmentosa (PCARP), is a rare neurodegenerative disorder that is caused by biallelic pathogenic variants in FLVCR1. Here, we report a case of a Japanese patient with RETSNS.<br> Methods: Clinical, neuroradiological, and electrophysiological findings were documented. Whole-genome sequencing was performed. Subcloning was carried out to confirm compound heterozygosity. A functional assay was performed to assess the pathogenicity of the variants.<br> Results: The patient showed retinitis pigmentosa and sensory ataxia. Over the course of the disease, autonomic dysfunction has become increasingly evident. Despite consanguinity in the family, whole-genome sequencing identified two heterozygous variants in FLVCR1 (c.369T>G, p.Phe123Leu and c.733A>G, p.Asn245Asp). Cloning of the PCR product followed by Sanger sequencing indicated compound heterozygosity of the variants. Immunocytochemistry of HEK293FT cells transfected with plasmids containing wild-type or variant FLVCR1 cDNA demonstrated altered subcellular localization of the variant FLVCR1 proteins, characterized by reduced membrane localization.<br> Interpretation: We report a novel variant in FLVCR1 causing RETSNS. The functional assay supports the pathogenicity of the variants. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 13 4 2025 Identification of New Repeat Expansion Diseases 244 249 EN Hiroyuki Ishiura Department of Neurology, Okayama UniversityGraduate School of Medicine, Dentistry and Pharmaceutical Sciences Through a genetic study of benign adult familial myoclonus epilepsy (BAFME) type 1, TTTCA and TTTTA repeat expansions have been identified in intron 4 of SAMD12. Lengths of expanded repeats inversely correlated with age at onset of epilepsy. Gain-of-toxic function mechanisms are suggested by the presence of UUUCA-repeat-containing RNA foci. From families with BAFME who did not have repeat expansions in SAMD12, we identified expanded TTTCA and TTTTA repeats in TNRC6A and RAPGEF2. These findings indicated a strong correlation between the repeat motif and the phenotype, leading to the identification of other types of BAFME. We then conducted genetic analysis of neuronal intranuclear inclusion disease (NIID), oculopharyngeal myopathy with leukoencephalopathy (OPML), and oculopharyngodistal myopathy (OPDM). From the observation that NIID, OPML, and OPDM, in addition to fragile X-associated tremor/ataxia syndrome, have shared clinical features, a direct search for CGG repeat expansions successfully led to the identification of the causative genes. Here, I review recent studies on repeat expansions. No potential conflict of interest relevant to this article was reported.

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

American Astronomical Society Acta Medica Okayama 0004-637X 992 1 2025 Observing Supernova Neutrino Light Curves with Super-Kamiokande. VI. A Practical Data Analysis Technique Considering Realistic Experimental Backgrounds 27 EN Fumi Nakanishi Department of Physics, Okayama University Ken’ichiro Nakazato Faculty of Arts and Science, Kyushu University Masayuki Harada Kamioka Observatory, Institute for Cosmic Ray Research, The University of Tokyo Yusuke Koshio Department of Physics, Okayama University Ryuichiro Akaho Faculty of Science and Engineering, Waseda University Yosuke Ashida Department of Physics, Tohoku University Akira Harada National Institute of Technology, Ibaraki College Masamitsu Mori Division of Science, National Astronomical Observatory of Japan Kohsuke Sumiyoshi National Institute of Technology, Numazu College Yudai Suwa Department of Earth Science and Astronomy, The University of Tokyo Roger A. Wendell Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU, WPI), Todai Institutes for Advanced Study, The University of Tokyo Masamichi Zaizen Department of Earth Science and Astronomy, The University of Tokyo Neutrinos from supernovae, especially those emitted during the late phase of core collapse, are essential for understanding the final stages of massive star evolution. We have been dedicated to developing methods for the analysis of neutrinos emitted during the late phase and observed at Super-Kamiokande (SK). Our previous studies have successfully demonstrated the potential of various analysis methods in extracting essential physical properties; however, the lack of background consideration has limited their practical application. In this study, we address this issue by incorporating a realistic treatment of the experimental signal and background events with the on-going SK experiment. We therefore optimize our analysis framework to reflect realistic observational conditions, including both signal and background events. Using this framework we study several long-time supernova models, simulating the late phase neutrino observation in SK and focusing in particular on the identification of the last observed event. We discuss the possibility of model discrimination methods using timing information from this last observed event. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2772-3755 11 2025 Robustness of the RGB image-based estimation for rice above-ground biomass by utilizing the dataset collected across multiple locations 100998 EN Kota Nakajima Graduate School of Agriculture, Kyoto University Kazuki Saito International Rice Research Institute (IRRI) Yasuhiro Tsujimoto Japan International Research Center for Agricultural Sciences Toshiyuki Takai Japan International Research Center for Agricultural Sciences Atsushi Mochizuki CHIBA Prefectural Agriculture and Forestry Research Center Tomoaki Yamaguchi Faculty of Applied Biological Sciences, Gifu University Ali Ibrahim Africa Rice Center (AfricaRice), Regional Station for the Sahel Salifou Goube Mairoua Africa Rice Center (AfricaRice) Bruce Haja Andrianary Laboratoire des Radioisotopes, Université d′Antananarivo Keisuke Katsura Graduate School of Agriculture, Kyoto University Yu Tanaka Graduate School of Environment, Life, Natural Science and Technology, Okayama University Above-ground biomass (AGB) is a critical phenotype representing crop growth. Non-invasive evaluations of AGB, including deep-learning-based red-green-blue (RGB) image analyses, are often specific to the training data. The robustness of the estimation model across untrained conditions is essential to monitor crop productivity globally, but it has yet to be fully assessed. This study aims to assess the robustness of a convolutional neural network (CNN) model for rice AGB estimation across five locations in three countries, and to demonstrate the feasibility of robust model via a practical approach. From transplanting to heading, 1957 RGB images were captured vertically downward over the rice canopy, covering approximately 1 m2. First, a base model was established using data collected from a single location. Then, its robustness was assessed using test datasets taken from the other four locations. The CNN model showed a significant variation in estimation accuracy across the untrained four locations, indicating insufficient robustness of the base model. Subsequently, we quantitatively tested the impact of improving training data diversity on model robustness by adding data from each of the four locations to the base model's training data. Adding at most 48 data points from a location achieved practical accuracy for the added location, with R2Ad above 0.8. Interestingly, adding data from one location sometimes improved the accuracy for other untrained locations as well. These findings suggest that collecting diverse training data for RGB-based estimation, combined with evaluation of robustness paves the way for on-site and instant AGB monitoring of rice. 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 Recurrence of FVIII Inhibitor during Surgery in a Patient with Severe Hemophilia A Receiving Emicizumab Prophylaxis 451 455 EN Moe Hagihara Department of Hematology and Oncology, Okayama University Hospital Keisuke Seike Department of Hematology and Oncology, Okayama University Hospital Kenta Hayashino Department of Hematology and Oncology, Okayama University Hospital Takao Yasuhara Department of Neurological Surgery, Okayama University Hospital Kyohei Kin Department of Neurological Surgery, Okayama University Hospital Yuichi Hirata Department of Neurological Surgery, Okayama University Hospital Hiroki Kobayashi Department of Hematology and Oncology, Okayama University Hospital Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Division of Transfusion and Cell Therapy, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Case Report 10.18926/AMO/69848 Emicizumab, a bispecific monoclonal antibody, benefits patients with severe hemophilia A. It alters laboratory assessments of coagulation activity, requiring anti-idiotype monoclonal antibodies for accurate monitoring. A 64-year-old man, receiving emicizumab regularly, was admitted for laminoplasty. We planned to use FVIII replacement during the perioperative period after confirming the disappearance of inhibitors, monitoring coagulation activity with anti-idiotype monoclonal antibodies. Activated partial thromboplastin time was prolonged on postoperative day 2, prompting an immediate switch to eptacog alfa. The patient recovered without bleeding. This case underscores the necessity of anti-idiotype monoclonal antibodies for accurate monitoring. No potential conflict of interest relevant to this article was reported.

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

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

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

Elsevier BV Acta Medica Okayama 2772-5022 5 2 2025 Amelioration of Cd-induced bone deterioration by orally administered calcium phosphate 101482 EN Ping-chin Sung Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ahmad Bikharudin Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Okada Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Randa Musa Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenta Uchida Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihisa Otaka Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadaaki Matsusaka Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University Aira Matsugaki Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University Takayoshi Nakano Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University Takuya Matsumoto Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Cadmium (Cd) is a heavy metal that accumulates in the body, primarily through daily grain intake, and has a high affinity for bone, leading to skeletal diseases such as osteomalacia and fractures. Hydroxyapatite (HAp), a major bone mineral component, is highly pH-sensitive and is known to incorporate Cd, as observed in studies of Itai-itai disease. Based on these findings, we hypothesized that HAp could serve as an effective oral detoxification material for heavy metals. This study investigated the efficacy of orally administered HAp in inhibiting Cd-induced changes in bone physical and chemical properties, comparing its effects to those of activated charcoal (AC), a common detoxifying agent. Six-week-old male ICR mice were exposed to cadmium via drinking water containing CdCl2 and subsequently given diets containing either HAp or AC for four weeks. Three-point bending tests, micro-CT analysis, and histological observations of the femurs demonstrated that mice receiving HAp exhibited improved mechanical strength and enhanced bone quality protection compared to the control and other Cd-treated groups. Activated charcoal also contributed to bone quality improvement at low concentrations, but its effect diminished at high concentrations. These results suggest that the oral administration of HAp may be a promising therapeutic strategy for suppressing cadmium-induced osteomalacia. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0021-9606 163 22 2025 Fourier-transform infrared spectroscopy of hydrogen fluoride dimers in solid parahydrogen 224312 EN Yuki Miyamoto Research Institute for Interdisciplinary Science, Okayama University Hiroki Ooe Graduate School of Natural Science and Technology, Okayama University Susumu Kuma Department of Physics, Rikkyo University We investigate the Fourier-transform infrared spectra of hydrogen fluoride dimers in solid parahydrogen, the detailed analysis of which has remained unexplored. We propose a plausible analysis based on concentration dependence, light polarization, annealing, and time evolution. The absorption lines exhibited multiple peaks, with intensity ratios significantly altered by annealing and by time evolution at a constant temperature. The spectral patterns and isotopic effects suggest that the dimers do not rotate freely in solid parahydrogen, while multiple peaks arise from different stable structures, including single and double substitution sites. Unlike in the gas phase and helium droplets, no tunneling splitting was observed. The broad ν1 band suggests that some dimer structures may exhibit axial rotation. Spectral changes due to annealing likely result from site conversion, while observed IR-induced changes indicate preferential dissociation of dimers in double substitution sites. These findings still remain tentative, necessitating further experimental and theoretical studies. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-3921 14 9 2025 Clinical Evaluation of Oxidative Stress Markers in Patients with Long COVID During the Omicron Phase in Japan 1068 EN Osamu Mese 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 Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Morita Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Eguchi Biobank Center, Mie University Hospital Sanae Fukuda Department of Health Welfare Sciences, Kansai University of Welfare Sciences Junzo Nojima Department of Laboratory Medicine, Yamaguchi University Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences To characterize changes in markers of oxidative stress for the clinical evaluation of patients with long COVID, we assessed oxidative stress and antioxidant activity based on serum samples from patients who visited our clinic between May and November 2024. Seventy-seven patients with long COVID (41 [53%] females and 36 [47%] males; median age, 44 years) were included. Median [interquartile range] serum levels of diacron-reactive oxygen metabolites (d-ROM; CARR Unit), biological antioxidant potential (BAP; μmol/L), and oxidative stress index (OSI) were 533.8 [454.9–627.6], 2385.8 [2169.2–2558.1] and 2.0 [1.7–2.5], respectively. Levels of d-ROMs (579.8 vs. 462.2) and OSI (2.3 vs. 1.8), but not BAP (2403.4 vs. 2352.6), were significantly higher in females than in males. OSI levels positively correlated with age and body mass index, whereas BAP levels negatively correlated with these parameters. d-ROM and OSI levels were significantly associated with inflammatory markers, including C-reactive protein (CRP) and fibrinogen, whereas BAP levels were inversely correlated with CRP and ferritin levels. Notably, serum free thyroxine levels were negatively correlated with d-ROMs and OSI, whereas cortisol levels were positively correlated with d-ROMs. Among long COVID symptoms, patients reporting brain fog exhibited significantly higher OSI levels (2.2 vs. 1.8), particularly among females (d-ROMs: 625.6 vs. 513.0; OSI: 2.4 vs. 2.0). The optimal OSI cut-off values were determined to be 1.32 for distinguishing long COVID from healthy controls and 1.92 for identifying brain fog among patients with long COVID. These findings suggest that oxidative stress markers may serve as indicators for the presence or prediction of psycho-neurological symptoms associated with long COVID in a gender-dependent manner. 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.

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

Wiley Acta Medica Okayama 0031-9317 177 4 2025 Comparative Transcriptome Reveals ART1-Dependent Regulatory Pathways for Fe Toxicity Response in Rice Roots e70398 EN Yoshiaki Ueda Crop, Livestock and Environment Division, Japan International Research Center for Agricultural Sciences Naoki Yamaji Institute of Plant Science and Resources, Okayama University Matthias Wissuwa Crop, Livestock and Environment Division, Japan International Research Center for Agricultural Sciences Iron (Fe) is an essential element for plants, but an excess supply can have detrimental effects. Fe toxicity induces complex physiological and genetic responses, and due to this complexity, the knowledge of transcriptional regulatory mechanisms under Fe toxicity is very limited. Previous studies suggested that plant responses to excess Fe involve oxidative stress caused by reactive oxygen species (ROS), which itself causes transcriptional changes. We hypothesized that dissecting these complex responses could lead to the identification of a novel factor and conducted a comparative transcriptome analysis using roots of rice plants exposed to nutrient solutions containing 1 or 5 mM of hydrogen peroxide (a major form of ROS) or 300 mg L−1 of Fe (as FeSO4). Genes induced by hydrogen peroxide overlapped with 62%, 49%, and 30% of Fe toxicity-upregulated genes at 3 h, 1 day, and 3 days following treatment initiation. Subsequent gene co-expression analyses classified genes into 21 groups with varying responsiveness to ROS and Fe toxicity. Genes in group 15 were specifically upregulated by Fe toxicity and overlapped significantly with aluminum (Al)-inducible genes and target genes of the Zn-finger transcription factor, ART1, which regulates Al response in rice roots. Additional experiments using the art1 knock-out mutant demonstrated that ART1 is crucial for upregulating genes such as STAR2 and FRDL4 in response to Fe toxicity. This study reveals the contribution of ART1-dependent regulatory pathways in rice roots under Fe toxicity. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2155-5435 15 14 2025 Mesoporous Oxyhalide Aggregates Exhibiting Improved Photocatalytic Activity for Visible-Light H2 Evolution and CO2 Reduction 12551 12562 EN Hiroto Ueki Department of Chemistry, School of Science, Institute of Science Tokyo Toshiya Tanaka Department of Chemistry, School of Science, Institute of Science Tokyo Shuji Anabuki Graduate School of Natural Science and Technology, Okayama University Ryuichi Nakada Department of Chemistry, School of Science, Institute of Science Tokyo Megumi Okazaki Department of Chemistry, School of Science, Institute of Science Tokyo Kenta Aihara Department of Chemistry, School of Science, Institute of Science Tokyo Masashi Hattori Materials and Structures Laboratory, Institute of Integrated Research, Institute of Science Tokyo Fumitaka Ishiwari Department of Applied Chemistry, Graduate School of Engineering, Osaka University Rie Haruki Institute of Materials Structure Science, High Energy Accelerator Research Organization Shunsuke Nozawa Institute of Materials Structure Science, High Energy Accelerator Research Organization Toshiyuki Yokoi Nanospace Catalysis Unit, Institute of Integrated Research, Institute of Science Tokyo Michikazu Hara Materials and Structures Laboratory, Institute of Integrated Research, Institute of Science Tokyo Osamu Ishitani Department of Chemistry, Graduate School of Advanced Science and Engineering, Hiroshima University Akinori Saeki Department of Applied Chemistry, Graduate School of Engineering, Osaka University Akira Yamakata Graduate School of Natural Science and Technology, Okayama University Kazuhiko Maeda Department of Chemistry, School of Science, Institute of Science Tokyo Oxyhalides are promising visible-light photocatalysts for water splitting and CO2 conversion; however, those exhibiting high activity for these reactions have rarely been reported. Here, we show that using water-soluble Ti complexes as precursors in the microwave-assisted hydrothermal synthesis of the oxyhalide photocatalyst Pb2Ti2O5.4F1.2 (PTOF) resulted in the production of nanoparticulate PTOF. The primary particle size of the synthesized PTOF ranged from several tens of nanometers to several hundreds of nanometers. Using Ti-citric acid or Ti-tartaric acid complexes as precursors, the PTOF was formed as mesoporous aggregates, compared with a bulky analogue (0.5–1 μm) prepared using a TiCl4 precursor. The PTOF prepared from Ti-citric acid complex had a particle size of 50–100 nm and showed a one-order-of-magnitude greater activity for H2 evolution from an aqueous ethylenediaminetetraacetic acid solution with the aid of a Rh cocatalyst. An apparent quantum yield (AQY) of 15.4 ± 1.0% at 420 nm, which is the highest among the reported oxyhalide photocatalysts, was achieved under optimal conditions. Although excess particle size reduction of PTOF lowered the H2 evolution activity, the PTOF with the smallest possible primary particle size of 15–30 nm, prepared from Ti-tartaric acid complex, showed the highest activity toward the selective reduction of CO2 into formate in a nonaqueous environment when combined with a binuclear Ru(II) complex. The CO2 reduction AQY was 10.4 ± 1.8% at 420 nm, a record-high value among metal-complex/semiconductor binary hybrid photocatalysts. This study highlights the importance of morphological control of oxyhalides for realizing their full potential as photocatalysts for artificial photosynthesis. 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.

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

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

MDPI AG Acta Medica Okayama 2504-3129 6 4 2025 Drip Fertigation in Greenhouse Eggplant Cultivation: Reducing N2O Emissions and Nitrate Leaching 116 EN Wataru Shiraishi Kochi Prefectural Agricultural Research Center Shion Nishimura Department of Bioresource Production Science, United Graduate School of Agriculture, Ehime University Morihiro Maeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hideto Ueno Department of Bioresource Production Science, United Graduate School of Agriculture, Ehime University Drip fertigation (DF) is a sustainable agricultural management technique that optimizes water and nutrient usage, enhances crop productivity, and reduces environmental impact. Herein, we compared the effects of DF and conventional fertilization (CF) with a basal fertilizer on yield, soil inorganic nitrogen dynamics, N2O emissions, and nitrogen leaching during facility-grown eggplant cultivation. The experiment was conducted in a greenhouse from September 2023 to May 2024, with treatments arranged in three rows and three replicates. Soil, gas, and water samples were collected and analyzed throughout the growing season. The results revealed that the DF treatment produced yields comparable to those obtained with the CF treatment while significantly reducing nitrogen and phosphorus inputs. DF effectively prevented excessive nitrogen accumulation in the soil and reduced nitrogen loss through leaching and gas emissions. N2O emissions were significantly lower by more than 60% under DF than under CF. Precise nutrient management in DF suppressed nitrification and denitrification processes, mitigating N2O emissions. DF also significantly reduced nitrogen leaching by more than 70% compared with that in CF. These findings demonstrate that DF effectively enhances agricultural sustainability by improving nutrient use efficiency, reducing greenhouse gas emissions, and minimizing nitrogen leaching during the cultivation of facility-grown eggplant. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2771-9316 2025 Photochemical Macrolactonization of Hydroxyaldehydes via C–H Bromination EN Sakura Kodaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haru Ando Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 16 1 2025 Efficient and stable n-type sulfide overall water splitting with separated hydrogen production 8786 EN Haolin Luo Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University Zhixi Liu Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University Haifeng Lv State Key Laboratory of Precision and Intelligent Chemistry, School of Chemistry and Material Sciences, and Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), University of Science and Technology of China Junie Jhon M. Vequizo Institute of Aqua Regeneration, Shinshu University Mengting Zheng College of Chemical and Biological Engineering, Zhejiang University Feng Han Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University Zhen Ye Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University Akira Yamakata Faculty of Natural Science and Technology, Okayama University Wenfeng Shangguan Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University Adam F. Lee Centre for Catalysis and Clean Energy, School of Environment and Science, Griffith University Xiaojun Wu State Key Laboratory of Precision and Intelligent Chemistry, School of Chemistry and Material Sciences, and Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), University of Science and Technology of China Domen Kazunari Institute of Aqua Regeneration, Shinshu University Jun Lu College of Chemical and Biological Engineering, Zhejiang University Zhi Jiang Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University N-type sulfide semiconductors are promising photocatalysts due to their broad visible-light absorption, facile synthesis and chemical diversity. However, photocorrosion and limited electron transport in one-step excitation and solid-state Z-scheme systems hinder efficient overall water splitting. Liquid-phase Z-schemes offer a viable alternative, but sluggish mediator kinetics and interfacial side reactions impede their construction. Here we report a stable Z-scheme system integrating n-type CdS and BiVO₄ with a [Fe(CN)₆]³⁻/[Fe(CN)₆]⁴⁻ mediator, achieving 10.2% apparent quantum yield at 450 nm with stoichiometric H₂/O₂ evolution. High activity reflects synergies between Pt@CrOx and Co3O4 cocatalysts on CdS, and cobalt-directed facet asymmetry in BiVO₄, resulting in matched kinetics for hydrogen and oxygen evolution in a reversible mediator solution. Stability is dramatically improved through coating CdS and BiVO4 with different oxides to inhibit Fe4[Fe(CN)6]3 precipitation and deactivation by a hitherto unrecognized mechanism. Separate hydrogen and oxygen production is also demonstrated in a two-compartment reactor under visible light and ambient conditions. This work unlocks the long-sought potential of n-type sulfides for efficient, durable and safe solar-driven hydrogen production. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1340-2838 32 6 2025 MedakaBase as a unified genomic resource platform for medaka fish biology dsaf030 EN Kenji Morikami Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems Yasuhiro Tanizawa Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems Masaru Yagura Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems Mika Sakamoto Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems Shoko Kawamoto Department of Genetics, Sokendai (Graduate University for Advanced Studies) Yasukazu Nakamura Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems Katsushi Yamaguchi Trans-Omics Facility, National Institute for Basic Biology Shuji Shigenobu Trans-Omics Facility, National Institute for Basic Biology Kiyoshi Naruse Laboratory of Bioresources, National Institute for Basic Biology, National Institutes of Natural Sciences Satoshi Ansai Ushimado Marine Institute, Okayama University Shigehiro Kuraku Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems Medaka, a group of small, mostly freshwater fishes in the teleost order Beloniformes, includes the rice fish Oryzias latipes, a useful model organism studied in diverse biological fields. Chromosome-scale genome sequences of the Hd-rR strain of this species were obtained in 2007, and its improved version has facilitated various genome-wide studies. However, despite its widespread utility, omics data for O. latipes are dispersed across various public databases and lack a unified platform. To address this, the medaka section of the National Bioresource Project (NBRP) of Japan established a genome informatics team in 2022 tasked with providing various in silico solutions for bench biologists. This initiative led to the launch of MedakaBase (https://medakabase.nbrp.jp), a web server that enables gene-oriented analysis including exhaustive sequence similarity searches. MedakaBase also provides on-demand browsing of diverse genome-wide datasets, including tissue-specific transcriptomes and intraspecific genomic variations, integrated with gene models from different sources. Additionally, the platform offers gene models optimized for single-cell transcriptome analysis, which often requires coverage of the 3′ untranslated region (UTR) of transcripts. Currently, MedakaBase provides genome-wide data for seven Oryzias species, including original data for O. mekongensis and O. luzonensis produced by the NBRP team. This article outlines technical details behind the data provided by MedakaBase. 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.

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