WileyActa Medica Okayama0140-77912026Tripartite Interaction Between Penicillium pinophilum-Host Plants and CMV-Y: A Model for Endophyte-Mediated Viral BiocontrolENSarah R.IbiangGroup of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama UniversityIvanGalisGroup of Plant-Insect Interactions, Institute of Plant Science and Resources, Okayama UniversityHidekiKondoGroup of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama UniversityNobuhiroSuzukiGroup of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama UniversityPlant-fungus-virus tripartite interactions represent complex ecological systems in which mutualistic endophytes can influence host physiology, yet the molecular basis of endophyte-mediated defence remains poorly understood. Here, we demonstrate that the endophytic fungus Penicillium pinophilum EU0013 suppresses the yellow strain of cucumber mosaic virus (CMV-Y) in Solanum lycopersicum and Nicotiana benthamiana. CMV-Y infection induced pronounced oxidative and hormonal perturbations, which were mitigated by P. pinophilum colonisation. Endophyte-associated plants exhibited early accumulation of jasmonate intermediates, consistent with the activation of jasmonate signalling. This response promoted the degradation of jasmonate-ZIM-domain proteins and release of core JA-responsive transcription factors. Virus-induced gene silencing identified MYC2 as a key regulator required for endophyte-mediated antiviral protection, with WRKY17 contributing to defence modulation. In parallel, transcriptome analysis revealed the upregulation of a Dicer-like gene, indicating enhanced engagement of RNA silencing, a primary antiviral mechanism targeting viral RNA. This coordinated activation occurred alongside significant induction of pathogenesis-related proteins, particularly PR9, and improved control of reactive oxygen species. Salicylic acid-responsive defences showed a host-modulated pattern, with PR1 induced by CMV and PR2/PR5 preferentially enhanced in endophyte-associated plants. Collectively, these findings demonstrate that P. pinophilum enhances antiviral immunity through coordinated defence integration pathways, providing a framework for endophyte-based viral disease management.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2050-09041472026Custom‐Made Mouthpiece‐Assisted Oral Cryotherapy During Hematopoietic Stem Cell Transplantation in a Patient With Hemimaxillectomy‐Related Oroantral Communication: A Case Reporte73156ENKumikoMatsuzakiDivision of Hospital Dentistry, Okayama University HospitalFuminobuMiyazakiDental Laboratory Division, Okayama University HospitalYasujiMotoyamaDental Laboratory Division, Okayama University HospitalSeikoTakedaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University HospitalTakuoKubokiDental Laboratory Division, Okayama University HospitalYoshihikoSogaDivision of Hospital Dentistry, Okayama University HospitalA custom-made mouthpiece enabled safe oral cryotherapy in a patient with extensive oroantral communication after hemimaxillectomy and may also be applicable to other patients with communication between the oral cavity and the maxillary sinus or nasal cavity.No potential conflict of interest relevant to this article was reported.Ceramic Society of JapanActa Medica Okayama1348-653513472026Dielectric response modulation in relaxor (Sr,Ba)Nb2O6 via engineered defect455460ENRyuseiShiotaGraduate School of Natural Science and Technology, Okayama UniversityTakashiTeranishiGraduate School of Natural Science and Technology, Okayama UniversityShinyaKondoDepartment of Energy Engineering, Nagoya UniversityAkiraKishimotoGraduate School of Natural Science and Technology, Okayama UniversityDefect engineering provides an effective pathway to tune the dielectric response of relaxor ferroelectrics, yet the roles of individual defect species in tungsten bronze (TTB) systems remain unclear. Here, we investigated how engineered Ti–VO•• defect dipoles and native oxygen vacancies introduced through reduction annealing modify the dielectric properties of relaxor (Sr0.5,Ba0.5)Nb2O6 (0.5-SBN). Ti loading forms stable defect dipoles that generate smaller polar nanoregions (PNRs), suppress their overgrowth, and increase the number of dynamically active PNRs at room temperature, leading to enhanced permittivity ε′ while preserving DC-bias stability and breakdown strength (EB). Reduction annealing generates Nb4+-related local polarizations aligned with the external electric field, which strengthen dipole fluctuations and slightly increase ε′. Electron localization further relaxes the TTB-A2 site disorder–induced random fields, yielding a sharper dielectric peak and promoting more uniform PNR growth. Microwave dielectric spectroscopy combined with electromagnetic simulations revealed that the increases in ε′ for both Ti-loaded and reduced samples (0.5-SBNT and Reduced 0.5-SBN, respectively) originate predominantly from enhanced dipole polarization. Despite grain coarsening in 0.5-SBNT, the EB remained unchanged, indicating that defect dipoles act as pinning centers that inhibit field-induced PNR aggregation. In reduced 0.5-SBN, EB increased up to pO0 = 4.3 × 10−3 atm owing to relaxed random fields, whereas excessive reduction reduced EB through carrier-driven space-charge effects. These results demonstrate that precise control of defect species enables simultaneous optimization of ε′, DC-bias stability, and EB in TTB-type relaxor ferroelectrics.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2045-89401622026Recurrence of Pulmonary Hypertension After Unilateral Lung Transplantation: Histological Evidence of Vasoconstrictive Mechanisme70289ENSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMegumiKondoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoichiIchimuraDepartment of Pathology, Hiroshima City Hiroshima Citizens HospitalTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraCenter for Advanced Heart Failure, Okayama University HospitalShinsukeYuasaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPulmonary hypertension (PH) is widely recognized as a disease driven by both vasoconstriction and vascular remodeling. Vasoconstriction is thought to play a predominant role in the early stages of PH, whereas the contribution of vascular remodeling increases as the disease progresses. However, clinical or histological evidence of this pathological progression has not been reported. We describe a case of recurrent PH after unilateral right lung transplantation, ultimately requiring bilateral transplantation 9 years later, and discuss the pathogenesis of PH based on histological findings in the transplanted normal lungs and changes in pulmonary blood flow observed by lung perfusion scintigraphy. Serial lung perfusion scintigraphy revealed a dynamic shift in pulmonary blood flow, initially favoring the transplanted lung, followed by a gradual decline. Histological examination demonstrated that the right lung of the second transplantation showed minimal vascular remodeling. These findings provide compelling evidence that vasoconstriction was the predominant contributor to PH after the first transplantation, offering unique insight into early PH pathobiology.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama1664-462X172026Quantitative resistance to Rhizoctonia solani AG-4 develops independently in leaves and roots of Brachypodium distachyon1875734ENRoziFernandaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNiranjanMahadevanGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNatsukaKohnoSchool of Agriculture, Okayama UniversityReikoNagaoSchool of Agriculture, Okayama UniversityMegumiWatanabeGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNanamiSakataGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHidenoriMatsuiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKazuhiroToyodaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYukiIchinoseGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYusukeKouzaiCrop Stress Management Group, Division of Plant Molecular Regulation Research, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO)KeiichiMochidaRIKEN Center for Sustainable Resource ScienceYoshiteruNoutoshiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityRhizoctonia solani is a soil-borne phytopathogen with a broad host range, classified into multiple anastomosis groups (AGs). While the rice sheath blight pathogen AG-1 IA is well-studied, defense mechanisms against AG-4, which infects diverse monocots and dicots, remain unclear. Here, we screened 153 Brachypodium distachyon accessions for resistance to AG-4 HG-I+II using both leaf and soil inoculation assays. The accessions exhibited a quantitative resistance spectrum in both assays. Some accessions were resistant to both methods, while others showed resistance in only one, indicating that leaf and root defenses operate independently. Unlike the salicylic acid (SA)-dependent resistance observed in several accessions against AG-1 IA, AG-4 leaf resistance appears to be largely SA-independent. Among 22 resistant accessions, only eight induced the SA marker BdWRKY38, whereas twelve induced the jasmonic acid (JA) marker BdAOS. Additionally, resistance in Bd3–1 was unaffected by expression of the SA hydroxylase NahG. These results are consistent with previous findings that exogenous application of SA, JA, or ethylene fails to confer AG-4 resistance. Instead, most AG-4-resistant accessions showed common upregulation of cell wall biosynthesis-related genes following leaf infection, suggesting that cell wall fortification may contribute to defense against AG-4. These findings establish B. distachyon as a valuable model for dissecting resistance mechanisms against R. solani AG-4.No potential conflict of interest relevant to this article was reported.Japan Atherosclerosis SocietyActa Medica Okayama1340-34783322026A Case of Acquired LCAT Deficiency with the Discrepancy between Spontaneous Resolution of Proteinuria and Continually Low HDL Cholesterol Levels228236ENMikiMatsuoDepartment of Nephrology and Hypertension, National Cerebral and Cardiovascular CenterMasatsuneOguraDepartment of Clinical Laboratory Technology, Faculty of Medical Science, Juntendo UniversityMasayukiKurodaCenter for Advanced Medicine, Chiba University Hospital, Chiba UniversityTetsuyaArisatoDepartment of Nephrology and Hypertension, National Cerebral and Cardiovascular CenterMasatsuguKishidaDepartment of Nephrology and Hypertension, National Cerebral and Cardiovascular CenterMarikoHarada-ShibaCardiovascular Center, Osaka Medical and Pharmaceutical UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoutaroYokoteDepartment of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of MedicineFumikiYoshiharaDepartment of Nephrology and Hypertension, National Cerebral and Cardiovascular CenterA 79-year-old Chinese man was referred for nephrotic syndrome (proteinuria 4.4 g/day). In blood tests, serum high-density lipoprotein (HDL) cholesterol was undetectable, and the esterified cholesterol to total cholesterol ratio was very low. Lecithin: cholesterol acyltransferase (LCAT) activity was also undetectable. Since he had neither corneal opacity nor pathological mutations in the LCAT gene and anti-LCAT antibodies were detected in serum, a diagnosis of acquired LCAT deficiency was made. Renal biopsy revealed glomerulopathy associated with LCAT deficiency and membranous nephropathy (MN). Since the patient’s proteinuria did not improve despite prescribing an angiotensin II receptor blocker (ARB), we suggested the prescription of prednisolone, but he returned to China due to the expiration of his residence visa for Japan. One year after the initial visit, his proteinuria had improved to 0.9 g/day without immunosuppressive therapy. However, his HDL cholesterol level was still low at around 3 mg/dL, indicating a discrepancy between remission of nephrotic syndrome and lack of improvement in lipid levels.<br>
Of the 11 patients with acquired LCAT deficiency reported to date, 4 with undetectable LCAT activity and MN on renal biopsy required immunosuppressive therapy to alleviate proteinuria. The present patient was prescribed only an ARB according to his preference, which happened to be consistent with the MN treatment guideline that states, “Wait 6 months for spontaneous remission while using maximal antiproteinuric therapy.” The clinical course of acquired LCAT deficiency varies, and further case reports are needed to determine the necessity of immunosuppressive therapy.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1323-89307532026Outcomes following the discontinuation of biologic therapy in patients with severe asthma400408ENTadaoNagasakiDepartment of Respiratory Medicine and Allergology, Kindai University Nara HospitalHisakoMatsumotoDepartment of Respiratory Medicine and Allergology, Kindai University Faculty of MedicineTakashiIwanagaDepartment of Respiratory Medicine and Allergology, Kindai University Faculty of MedicineKazutoMatsunagaDepartment of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi UniversityKiyoshiSekiyaClinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National HospitalTomoyaHaradaDepartment of Multidisciplinary Internal Medicine, Division of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori UniversityShogoSakuraiDepartment of Respiratory Medicine, Shizuoka General HospitalNorihiroHaradaDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of MedicineToshiyukiKoyaDepartment of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental SciencesKoichiFukunagaDivision of Pulmonary Medicine, Department of Medicine, Keio University, School of MedicineTakeshiKanekoDepartment of Pulmonology, Yokohama City University Graduate School of MedicineKazuhisaAsaiDepartment of Respiratory Medicine, Graduate School of Medicine, Osaka Metropolitan UniversityYukoKomaseDepartment of Respiratory Medicine, St.Marianna University School of Medicine, Yokohama Seibu HospitalYasuhiroGonDivision of Respiratory Medicine, Department of Internal Medicine, Nihon University School of MedicineAkihikoTanakaDepartment of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of MedicineHironoriSagaraDepartment of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University, School of MedicineHironobuSunadomeDepartment of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto UniversityTatsuyaNaganoDivision of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineYoichiNakamuraMedical Center for Allergic and Immune Diseases, Yokohama City Minato Red Cross HospitalAkioNiimiDepartment of Respiratory Medicine, Allergy, and Clinical Immunology, Nagoya City University Graduate School of Medical SciencesNoboruHattoriDepartment of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima UniversityTakashiHajiroDepartment of Respiratory Medicine, Tenri HospitalHajimeFujimotoDepartment of Pulmonary and Critical Care Medicine, Mie University Graduate School of MedicineMasayukiHojoDivision of Respiratory Medicine, National Center for Global Health and MedicineNobuakiMiyaharaDepartment of Medical Technology, Okayama University Graduate School of Health SciencesMasafumiYamaguchiDivision of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical ScienceKimikoTsujiDepartment of Respiratory Medicine and Allergology, Kochi Medical School, Kochi UniversityAkikoSanoDepartment of Respiratory Medicine and Allergology, Kindai University Faculty of MedicineRyutaHaraguchiDepartment of Respiratory Medicine and Allergology, Kindai University Faculty of MedicineHiroyukiSanoDepartment of Respiratory Medicine and Allergology, Kindai University Faculty of MedicineMasatoMurakiDepartment of Respiratory Medicine and Allergology, Kindai University Nara HospitalYujiTohdaDepartment of Respiratory Medicine and Allergology, Kindai University Faculty of MedicineBackground: Biologic therapies are pivotal in managing severe asthma. Despite their efficacy, some patients discontinue biologics, with varying outcomes. Predictors of successful versus unsuccessful discontinuation remain poorly defined. This study aimed to identify clinical factors associated with post-discontinuation outcomes in a real-world practice.<br>
Methods: This retrospective cohort included adults with severe asthma who had received biologics for at least 12 months and subsequently discontinued therapy for a minimum of three consecutive months. We assessed the effects of baseline blood eosinophilia (≥300 cells/μL), residual sputum symptoms during biologic therapy, treatment responsiveness, biologic class, and discontinuation reasons on post-discontinuation asthma exacerbation rates using multivariable Cox models.<br>
Results: A total of 118 patients were analyzed. The Kaplan–Meier analysis estimated a 65 % exacerbation-free probability at 12 months after discontinuation. Factors associated with successful discontinuation included a robust clinical response and absence of exacerbations before cessation. Conversely, baseline eosinophilia, residual sputum symptoms during biologics, and discontinuation due to inadequate therapeutic response or financial burden were associated with post-discontinuation exacerbations. In class-stratified restricted models, persistent sputum remained significantly associated with post-discontinuation exacerbations after stopping anti-IL-5 therapies, while baseline eosinophilia was associated with post-discontinuation exacerbations after stopping anti-IgE or anti-IL-4Rα. Among patients with sputum symptoms or poor-response discontinuation, the overall frequency of exacerbations declined after discontinuation.<br>
Conclusions: Baseline eosinophilia, persistent sputum during therapy, and discontinuation prompted by poor response or cost may serve as risk factors for post-discontinuation exacerbations; however, risk is phenotype- and class-dependent. Careful patient selection and monitoring are essential when considering the discontinuation of biologic treatment.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1745-62152712025Oral health care during pregnancy to prevent preterm birth and low birth weight: study protocol for a randomized controlled trial35ENJunkoYasuokaDivision of Global Health Sciences, Graduate School of Public Health, St. Luke’s International UniversityYoheiTakeshitaDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShunsukeOkadaDepartment of Oral and Maxillofacial Radiology, Medical Development Field, Okayama UniversityProdhan MD RubayetAlamDepartment of Orthodontics, Dental Unit, TMSS Medical College & Rafatullah Community HospitalAkiraShibanumaDepartment of Community and Global Health, Graduate School of Medicine, The University of TokyoKeikoNanishiOffice of International Academic Affairs, Graduate School of Medicine, The University of TokyoYokoSatoDepartment of Health Sciences, Graduate School of Medical Sciences, Kyushu UniversityMd. ZahidHossainDepartment of Periodontology and Oral Pathology, Holy Family Red Crescent Medical College HospitalMusfiqaAmanDepartment of Periodontology, Dental Unit, TMSS Medical College & Rafatullah Community HospitalFahmidaKarimDepartment of Obstetrics & Gynecology, Holy Family Red Crescent Medical College HospitalSultanaRaziaDepartment of Obstetrics & Gynecology, TMSS Medical College & Rafatullah Community HospitalRifatRezwanaDepartment of Molecular and Cellular Biochemistry, Division of Oral Health, Brain Health and Total Health, Faculty of Dental Science, Kyushu UniversityMd MahmudurRahmanGlobal Communication Center, Grameen CommunicationsNusratJahan KhanGlobal Communication Center, Grameen CommunicationsNaokiNakashimaDepartment of Medical Informatics, Graduate School of Medical Sciences, Kyushu UniversityRafiqulIslamDivision of Healthcare Digital Transformation, Kyushu UniversityKimiyoKikuchiDepartment of Research Promotion, Institute for Asian and Oceanian Studies, Kyushu UniversityBackground Periodontal disease during pregnancy has been associated with an increased risk of preterm birth (PTB) and low birth weight (LBW). However, most previous interventional studies have reported that scaling and root planing (SRP), a form of basic periodontal treatment, is insufficient to effectively prevent PTB and LBW. Recent systematic reviews and meta-analyses suggest that combining SRP with routine use of chlorhexidine gluconate (CHG) mouthwash may reduce the risk of these adverse birth outcomes by approximately half. This study will be among the first randomized controlled trials (RCTs) to evaluate the potential synergistic effects of this combined approach on improving birth outcomes.<br>
Methods This multi-center, three-arm RCT will be conducted at two hospitals in Dhaka and Bogura, Bangladesh, between April 2025 and September 2026. A total of 480 pregnant women less than 20 weeks’ gestation attending antenatal checkups will be recruited. Participants diagnosed with periodontal disease will be randomly assigned to either an intervention group or a positive control group. Participants without periodontal disease will be assigned to a negative control group. The intervention consists of SRP combined with continued use of CHG mouthwash throughout pregnancy. The primary outcome will be the rate of PTB. Secondary outcomes include the birth weight of the newborn baby, maternal periodontal status, and oral health-related quality of life (OHRQoL). Effectiveness will be assessed by comparing outcomes across the study groups.<br>
Discussion The oral health intervention is expected to improve both birth outcomes and maternal oral health. Demonstrating its effectiveness in a real-world setting may support the integration of oral health care into broader maternal, neonatal, and child health strategies, particularly in resource-limited settings.<br>
Trial registration UMIN Clinical Trials Registry. UMIN000057519. Registered on April 4, 2025. https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000065719.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0289-07712026Sex differences and contest experience shape walking patterns in the broad-horned flour beetleENKentarouMatsumuraGraduate School of Arts and Sciences, The University of TokyoSoraHashiokaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNaohisaNagayaFaculty of Information Science and Engineering, Kyoto Sangyo UniversityRyusukeFujisawaFaculty of Environmental Engineering, University of Kitakyushu,TakahisaMiyatakeGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAnimal movement patterns vary widely across species, and sex differences are often expected because males typically need to encounter multiple females and acquire resources. In species where males engage in male–male combat using exaggerated weapons, variation in weapon size and contest outcomes is known to influence male reproductive strategies, and may therefore also affect movement behavior. However, sex-specific and male-specific differences in locomotor behavior, particularly in relation to weapon size and social interactions, remain poorly understood. Here, we investigated walking trajectories in the broad-horned flour beetle (Gnatocerus cornutus) to test for (1) sex differences, (2) associations between male weapon size and movement behavior, and (3) the effects of male–male combat. Males exhibited more tortuous and localized movement, whereas females showed straighter and more spatially extensive trajectories. Following contests, all males showed a reduction in activity regardless of contest outcome; however, winners and losers exhibited divergent changes in movement patterns, with winners showing straighter and more spatially extensive trajectories and losers showing more tortuous and localized trajectories. In contrast, body-size-corrected weapon size was not associated with any aspect of walking behavior. These results indicate that locomotor behavior in G. cornutus varies with sex and contest experience, and that variation in walking behavior is more closely associated with social experience than with weapon morphology.No potential conflict of interest relevant to this article was reported.岡山大学経済学会Acta Medica Okayama2433-41465812026ライブラリ・スキーマによる大学図書館構造の可視化と知識創造 ―共有認知の形成に基づく研究枠組みの構築―119ENKensukeKobayashiSatoruMiyazaki10.18926/OER/70973 This study proposes a theoretical framework for understanding the relationship between the structural representation of university libraries and knowledge creation. In recent years, university libraries have experienced significant transformations due to the digitization of scholarly information, the expansion of research data management, and the increasing importance of learning support services. As their functions diversify, it has become increasingly difficult to comprehensively understand the structure and roles of university libraries.<br>
To address this issue, this study focuses on the concept of a library schema, which represents the structural relationships among the elements that constitute a library, including people, resources, services, and activities. While previous research has discussed methods for organizing library components, little attention has been paid to how structural understanding of libraries contributes to knowledge creation and service value.<br>
Drawing on schema theory, shared cognition in organizational studies, and the knowledge creation theory of Nonaka and Takeuchi, this study constructs a conceptual framework linking library schema visualization, shared cognition, interaction, knowledge creation processes, and library service value. The framework proposes that visualization of library structure through a library schema promotes shared cognition among librarians and users, which in turn facilitates interactions that activate knowledge creation processes. These processes ultimately contribute to the creation of library service value that supports learning and research activities.<br>
Furthermore, the framework introduces two moderating factors: schema representation methods and operational constraints of library management. Based on this framework, six research propositions are presented.<br>
By integrating concepts from library and information science with knowledge management theory, this study contributes to the theoretical understanding of university libraries as knowledge infrastructures and provides a foundation for future empirical research on knowledge creation in library environments.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2666-63673242026Spatial Transcriptomics Analysis of Macrophage-to-Myofibroblast Transition in Bronchiolitis Obliterans Following Hematopoietic Stem Cell Transplantation454465ENAkiraYamamotoDepartment of Hematology and Oncology, Okayama University HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalKeisukeSeikeDepartment of Hematology and Oncology, Okayama University HospitalSeiichiroSugimotoDepartment of General Thoracic Surgery and Organ Transplant Center, Okayama University HospitalYusukeNaoiCenter for Comprehensive Genomic Medicine, Okayama University HospitalTomohiroNaganoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSayaKubotaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuiKambaraDan L Duncan Comprehensive Cancer Center, Baylor College of MedicineKanakoFujiwaraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshikiTeraoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTadashiOyamaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMariKunihiroDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirokiKobayashiDepartment of Hematology and Oncology, Okayama University HospitalTakumiKondoDepartment of Hematology and Oncology, Okayama University HospitalHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University HospitalKeikoFujiiDepartment of Hematology and Oncology, Okayama University HospitalShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalBronchiolitis obliterans (BO) is a severe, fibrotic manifestation of chronic graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Macrophage-derived TGF-β is linked to GVHD-related fibrosis; however, its role in BO remains unclear. Given emerging evidence of macrophage-to-myofibroblast transition (MMT) in fibrosis, this study aimed to investigate whether MMT contributes to BO development. We analyzed lung samples from 3 HSCT recipients with BO who underwent lung transplantation, with tissues from 2 patients with lung cancer as controls. Immunofluorescent staining for CD68, CD206, and α-SMA was used to identify cells undergoing MMT. Spatial transcriptomics was performed to profile gene expression in foamy macrophages across anatomical regions and histological stages, compared to control peribronchiolar regions. Immunostaining showed strong co-expression of CD68, CD206, and α-SMA in foamy macrophages within and surrounding bronchioles in BO samples, with minimal expression in controls, suggesting MMT involvement. In BO, spatial transcriptomics revealed upregulation of macrophage- and TGF-β signaling genes, with distinct stage- and region-specific gene expression patterns. Unsupervised clustering revealed a shift from inflammation to fibrosis. These findings indicate that MMT contributes to fibrosis in BO. Gene expression shifts from inflammation to fibrosis as the disease advances, underscoring the importance of early intervention.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama2329-69332352026Global trends in sarcoidosis-associated mortality, 2001–2023: insights from the World Health Organization mortality database823827ENKoHaradaBrookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount SinaiMarikoFujiiDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityNanamiSakoDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityQuynh ThiVuDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYoshitoNishimuraDivision of Hematology and Oncology, Mayo ClinicKeith PardilladaBelangoyDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHananeOuddoudDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTatsuakiTakedaDepartment of Education and Research Centre for Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYoshitoZamamiDepartment of Pharmacy, Okayama University HospitalHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalToshihiroKoyamaDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.American Society of Tropical Medicine and HygieneActa Medica Okayama0002-963711432026A Case of Heavy Paragonimiasis Involving a Multi-Organ Presentation with Hypereosinophilia and Hepatic Migration486489ENHidemasaAkazawaDepartment of Infectious Diseases, Okayama University HospitalHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalShinnosukeFukushimaDepartment of Infectious Diseases, Okayama University HospitalKentaNakamotoDepartment of Infectious Diseases, Okayama University HospitalKoheiOguniDepartment of Infectious Diseases, Okayama University HospitalYoheiManabeDepartment of Pharmacy, Okayama University HospitalMioKokubo-TanakaDivision of Parasitology, Department of Infectious Diseases, Faculty of Medicine, University of MiyazakiHaruhikoMaruyamaDivision of Parasitology, Department of Infectious Diseases, Faculty of Medicine, University of MiyazakiFumioOtsukaDepartment of General Medicine, Okayama University HospitalParagonimiasis is a parasitic disease caused by the genus Paragonimus, typically transmitted through the ingestion of raw or undercooked freshwater crabs. Although pulmonary involvement is typical, ectopic migration to subcutaneous or hepatic sites is rare and poses diagnostic challenges. A case of paragonimiasis in a 29-year-old Cambodian woman residing in Japan who presented with painless subcutaneous nodules on the chest and abdomen is reported in the current study. She had consumed raw crab 4 months before presentation. Laboratory findings revealed marked eosinophilia (21,000/µL) and elevated immunoglobulin E (5,049 IU/mL). Computed tomography scans revealed pleural effusion, club-shaped pulmonary consolidation, funicular hypodense lesions in the liver, and subcutaneous lesions. Stool and sputum test results were negative for parasite eggs; however, a microplate ELISA indicated a Paragonimus westermani infection. The patient responded well to 3 consecutive days of praziquantel (75 mg/kg/day) and was discharged a week later. This case highlights the importance of considering paragonimiasis in patients with unexplained subcutaneous nodules and eosinophilia, especially when supported by dietary risk factors.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-291865112026Endotracheal and Endobronchial Metastases in Epidermal Growth Factor Receptor Exon 19 Deletion Lung Adenocarcinoma: A Case Successfully Managed with Bronchoscopic Therapy and Sequential Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors15201523ENMihoFujiwaraDepartment of Respiratory Medicine, Okayama University HospitalTakahiroBabaDepartment of Respiratory Medicine, Okayama University HospitalKotaroYamadaDepartment of Respiratory Medicine, Okayama University HospitalEriNakamuraDepartment of Respiratory Medicine, Okayama University HospitalTetsuyaTakeguchiDepartment of Respiratory Medicine, Okayama University HospitalYukiTakigawaDepartment of Respiratory Medicine, NHO Okayama Medical CenterAyakoMoritaCenter for Clinical Oncology, Okayama University HospitalNaofumiHaraDepartment of Respiratory Medicine, Okayama University HospitalHiromiWatanabeDepartment of Respiratory Medicine, NHO Okayama Medical CenterKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalKammeiRaiCenter for Innovative Clinical Medicine, Okayama University HospitalEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalKenSatoDepartment of Respiratory Medicine, NHO Okayama Medical CenterYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYosukeTogashiDepartment of Respiratory Medicine, Okayama University HospitalGoMakimotoDepartment of Respiratory Medicine, Okayama University HospitalEndotracheal and endobronchial metastases from peripheral lung adenocarcinoma are rare, and optimal clinical management remains unclear. We herein report a 60-year-old woman with epidermal growth factor receptor (EGFR) exon 19 deletion-positive early-stage lung adenocarcinoma who underwent surgical resection followed by osimertinib treatment for recurrence. She later developed oligoprogressive disease with airway metastases. Bronchoscopic tumor removal was performed, and next-generation sequencing of the resected specimen revealed an acquired EGFR C797S mutation, along with exon 19 deletion. Gefitinib treatment was initiated, which led to a partial response. This case underscores the utility of repeated molecular profiling and local intervention in managing acquired resistance in EGFR-mutant non-small-cell lung cancer.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1572-1000582026Pathological features of residual head and neck cancer after near-infrared photoimmunotherapy: implications of an unfavorable tumor immune microenvironment105422ENTakumaMakinoDepartment of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuharuSatoDepartment of Hematopathology, Okayama University Graduate School of Health SciencesAsamiNishikoriDepartment of Hematopathology, Okayama University Graduate School of Health SciencesYutoNaoiDepartment of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMizuoAndoDepartment of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPurpose: Near-infrared photoimmunotherapy has been approved in Japan for unresectable locally advanced or recurrent head and neck cancer. While this therapy theoretically induces selective necrosis of epidermal growth factor receptor-expressing tumor cells following administration of cetuximab sarotalocan sodium and irradiation with 690-nm light, residual disease is not uncommon in clinical practice. The mechanisms underlying such persistence remain poorly understood.<br>
Methods: We examined two patients with head and neck squamous cell carcinoma who underwent salvage resection due to residual disease after four cycles of near-infrared photoimmunotherapy. Resected specimens were subjected to histopathological evaluation, including immunohistochemistry for epidermal growth factor receptor, cluster of differentiation 8, programmed cell death protein 1, and forkhead box P3 proteins.<br>
Results: In both cases, residual tumor cells were predominantly localized in the superficial mucosal layers, while deeper layers were replaced by fibrosis. All residual tumors retained expression of epidermal growth factor receptor. Lymphocytic infiltration was sparse, with scattered cluster of differentiation 8-positive cells but few programmed cell death protein 1-positive or forkhead box P3-positive lymphocytes. These findings suggest that the tumor microenvironment surrounding residual tumors may have been unfavorable for the induction of robust antitumor immune responses.<br>
Conclusion: Residual tumors after near-infrared photoimmunotherapy can occur despite adequate laser irradiation and epidermal growth factor receptor expression. Our observations imply that insufficient immune activation within the tumor microenvironment may contribute to treatment resistance. Further characterization of the post-photoimmunotherapy tumor microenvironment will be essential to better understand treatment mechanisms and to optimize therapeutic efficacy.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0168-95254242026Medaka: a novel model for analyzing genome–environment interactions350361ENKiyoshiNaruseLaboratory of Bioresources, National Institute for Basic BiologyFelixLoosliInstitute of Biological and Chemical Systems, Biological Information Processing (IBCS-BIP), Karlsruhe Institute of TechnologySatoshiAnsaiUshimado Marine Institute, Okayama UniversityEwanBirneyEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI)JoachimWittbrodtCentre for Organismal Studies (COS), Heidelberg UniversityMedaka is an established vertebrate model system for biological and biomedical research. It possesses unique features that make it particularly suitable for studying genome–environment interactions. Endemic to habitats spanning from 4 to 40°C and varying salinities, it combines broad ecological adaptability with experimental tractability. Its exceptional tolerance to inbreeding enabled the creation of the Medaka Inbred Kiyosu-Karlsruhe panel—80 near-isogenic, fully sequenced lines derived from a single wild population. More than 100 wild-derived, fully sequenced strains, collected throughout East Asia for more than 40 years, show relatively low intra-strain variation (inbreeding coefficient of >0.75) but high inter-strain variability (SNP rates >4%). Advanced quantification methods facilitate genome-wide association studies and quantitative trait locus mapping. The system’s amenability to clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 editing and emerging epigenomic profiling enables causal validation and regulatory-mechanism discovery. Collectively, medaka offers an unparalleled vertebrate framework for integrating genetics, environment, and epigenetics—bridging evolutionary, biomedical, and population-level perspectives.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Asthma-like bronchodilator responsiveness in patients with neuronal intranuclear inclusion disease16760ENDaisukeTaharaDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityNaoTaharaDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityChisatoTamaiDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityAkioAkagiDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityYuichiRikuDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityHiroakiMiyaharaDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityReiKobayashiDepartment of Neurology, NHO Nagoya Medical CenterHisashiOkadaDepartment of Neurology, NHO Nagoya Medical CenterMichiKawamotoDepartment of Neurology, Kobe City Medical Center General HospitalJunkoIshiiDepartment of Neurology, Kobe City Medical Center General HospitalHirokiYamazakiDepartment of Neurology, Tokushima University Graduate School of Biomedical ScienceTakashiKurashigeDepartment of Neurology, NHO Kure Medical Center and Chugoku Cancer CenterAtsuhikoSugiyamaDepartment of Neurology, Chiba UniversityAkikoNagaishiDepartment of Neurology, NHO Nagasaki Kawatana Medical CenterKatsuyaNishidaDepartment of Neurology, NHO Hyogo Chuo National HospitalKazumaSugieDepartment of Neurology, Nara Medical University HospitalTakayasuFukudomeDepartment of Neurology, NHO Nagasaki Kawatana Medical CenterKazukoHasegawaDepartment of Neurology, NHO Sagamihara National HospitalHiroyukiIshiuraDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHarukiKoikeDepartment of Neurology, Saga UniversityTakashiKasaiDepartment of Neurology, Kyoto Prefectural University of MedicineToshikiMizunoDepartment of Neurology, Kyoto Prefectural University of MedicineMasahiroAndoDepartment of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental SciencesYujiroHiguchiDepartment of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental SciencesFumiakiTanakaDepartment of Neurology and Stroke Medicine, Yokohama City University Graduate School of MedicineYuishinIzumiDepartment of Neurology, Tokushima University Graduate School of Biomedical ScienceGenSobueAichi Medical UniversityYasushiIwasakiDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversitySatoruItoDivision of Respiratory Medicine and Allergology, Department of Internal Medicine, School of Medicine, Aichi Medical UniversityJunSoneDepartment of Neuropathology, Institute for Medical Science of Aging, Aichi Medical UniversityNeuronal intranuclear inclusion disease (NIID) is a neurodegenerative condition characterized by the presence of intranuclear inclusions in neuronal and visceral cells. Patients with NIID can present respiratory symptoms; however, data on pulmonary functions in NIID are lacking. This study investigated the respiratory conditions in NIID patients diagnosed with histopathological and genetic studies. We conducted two spirometries before and after administrating the bronchodilator in NIID patients with asthmatic histories or symptoms. We statistically compared pre- and post-measured values including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF). Before two spirometries, we also measured fractional concentration of exhaled nitric oxide (FeNO), if possible. Of the 51finally enrolled patients, 17 (33.3%, 95% CI 20.8% to 47.9%) patients had asthmatic histories or symptoms, and 14 patients received two spirometries. After administrating the bronchodilator, FEV1 and PEF significantly increased by 150 mL (6.01%, p = 0.002) and 260 mL/s (6.72%, p = 0.017), respectively. The median (interquartile range) of FeNO measured in nine patients was 15 (10–21) ppb. Patients with NIID have airflow reversibility like asthma. This condition appears to be less associated with airway inflammation and may be related to autonomic dysfunction.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama0032-07812026NIMA-related kinases redundantly regulate vegetative and reproductive development in <i>Arabidopsis thaliana</i>pcag056ENShogoTakataniGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMaiKanazawaDepartment of Biology, Faculty of Science, Okayama UniversityKotaroSakamotoDepartment of Biology, Faculty of Science, Okayama UniversityYukiTomitaGraduate School of Biostudies, Division of Integrated Life Science, Kyoto UniversityNozomiKawamotoGraduate School of Biostudies, Division of Integrated Life Science, Kyoto UniversityTatsuyaSakaiGraduate School of Science and Technology, Niigata UniversityTakashiArakiGraduate School of Biostudies, Division of Integrated Life Science, Kyoto UniversityHiroyasuMotoseGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNever-in-mitosis A-related kinases (NEKs) are conserved protein kinases in eukaryotes that regulate cell division and elongation. In Arabidopsis thaliana, NEK6 has been shown to control anisotropic growth through cortical microtubule depolymerization, but the functions of other NEK family members remain largely unknown. Here, we show that Arabidopsis NEKs redundantly regulate organ growth and flowering through phosphorylation-dependent mechanisms. Expression analyses revealed overlapping promoter activities of NEK genes in meristems, vascular tissues, and floral organs. While most single mutants showed no obvious phenotype, multiple mutants exhibited defects in root growth direction, leaf elongation, vascular formation, and floral transition. Biochemical analysis showed that NEK3 and NEK6 phosphorylate both β-tubulin and γ-tubulin, indicating a conserved role in microtubule regulation. In addition, several NEKs interacted with the florigen FLOWERING LOCUS T (FT), and NEK3 phosphorylated FT in vitro and inhibited the FT–FD interaction in transient assays, suggesting a role in flowering regulation. These findings show that Arabidopsis NEKs redundantly coordinate vegetative and reproductive development through phosphorylation-dependent regulation of microtubules and the flowering pathway.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2072-664318112026GLP-1 Receptor Agonists in the Rehabilitation of Patients with Heart Failure: Mechanisms, Clinical Evidence, and Future Perspectives1688ENLuh Oliva SaraswatiSuastikaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuko K.BandoDepartment of Molecular Physiology and Cardiovascular Biology, Mie University Graduate School of MedicineKeijiHoshinoDivision of Cardiology, Gunma Prefectural Cardiovascular CenterNorimichiKoitabashiDivision of Cardiology, Gunma Prefectural Cardiovascular CenterYukihiroSaitoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinsukeYuasaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHeart failure (HF) remains associated with high morbidity and mortality, with heart failure with preserved ejection fraction (HFpEF) becoming increasingly prevalent and therapeutically challenging despite advances in pharmacological and rehabilitative care. Beyond their glucose-lowering effects, glucagon-like peptide-1 receptor agonists (GLP-1RAs) confer cardiometabolic benefits and may serve as effective adjuncts to cardiac rehabilitation (CR), particularly in obese patients with HFpEF. Obesity plays a central role in the pathophysiology of HFpEF, and GLP-1RAs promote weight loss, reduce insulin resistance and leptin signaling, and improve hemodynamic and metabolic abnormalities associated with HFpEF. Accumulating evidence suggests that the benefits of GLP-1RAs are phenotype-specific and more pronounced in patients with HFpEF than in patients with HF with reduced ejection fraction. Current clinical guidelines recommend GLP-1RAs for patients who have type 2 diabetes mellitus and established cardiovascular (CV) disease or are at high CV risk, with recent updates recognizing their potential benefits in patients with HFpEF and obesity. Cardiac rehabilitation, delivered through multidisciplinary programs, remains a cornerstone of HF management. Although caloric restriction and aerobic exercise can be beneficial in patients with HFpEF and obesity, these interventions alone are often insufficient. Sarcopenia is common in older patients with HFpEF and contributes to adverse outcomes, underscoring the importance of incorporating resistance training into CR programs. The most frequent adverse effects of GLP-1RAs are gastrointestinal events, which are generally mild to moderate but may lead to treatment discontinuation in some patients. Future studies should investigate the potential synergistic effects of GLP-1RAs and CR, clarify their long-term safety and efficacy in HF populations, and define their role beyond obese HFpEF phenotypes.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1432-058410572026WT1 mRNA in peripheral blood enables early prognostic stratification in AML patients receiving venetoclax and azacitidine therapy105ENHiroyukiSugiuraDivision of Internal Medicine, Fukuyama City HospitalNoboruAsadaDepartment of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakeruAsanoDepartment of Hematology and Oncology, Japanese Red Cross Society Himeji HospitalYasushiHiramatsuDepartment of Hematology and Oncology, Japanese Red Cross Society Himeji HospitalTomohiroUrataDepartment of Hematology and Blood Transfusion, Kochi Health Sciences CenterToshiImaiDepartment of Hematology and Blood Transfusion, Kochi Health Sciences CenterMakotoNakamuraDepartment of Hematology, Okayama City HospitalKazuhikoYamamotoDepartment of Hematology, Okayama City HospitalTatsunoriIshikawaDepartment of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School TeachersMasanoriMakitaDepartment of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School TeachersTakanoriYoshiokaDepartment of Hematology, NHO Okayama Medical CenterKazutakaSunamiDepartment of Hematology, NHO Okayama Medical CenterKyosukeSaekiDivision of Hematology, Ehime Prefectural Central HospitalYuichiroNawaDivision of Hematology, Ehime Prefectural Central HospitalMaikoKimuraDepartment of Hematology, Japanese Red Cross Okayama HospitalMakotoTakeuchiDepartment of Hematology, Japanese Red Cross Okayama HospitalMasayaAbeDepartment of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShojiAsakuraDepartment of Internal Medicine, Okayama Rosai HospitalTomofumiYanoDepartment of Internal Medicine, Okayama Rosai HospitalYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineVenetoclax and azacitidine (VEN/AZA), which target BCL-2 and DNA methylation, have demonstrated substantial efficacy, particularly in older or unfit patients with acute myeloid leukemia (AML). Wilms’ Tumor-1 (WT1) mRNA, measurable in peripheral blood (PB), is an established biomarker for monitoring treatment response and predicting AML prognosis. We conducted a retrospective analysis of patients with AML treated with VEN/AZA within the Okayama Hematology Study Group (OHSG). Patients who showed a marked reduction in PB WT1 mRNA levels from baseline after the first or second treatment cycle had significantly improved overall survival (OS) and progression-free survival (PFS). Moreover, achieving PB WT1 mRNA negativity-regardless of whether this occurred early or later in the therapy།was consistently associated with superior OS and PFS. These findings suggest that PB WT1 mRNA is a sensitive and reliable biomarker for predicting treatment response and long-term outcomes in patients with AML receiving VEN/AZA.No potential conflict of interest relevant to this article was reported.SAGE PublicationsActa Medica Okayama1022-55363412026Similar functional outcomes but different remodeling patterns: A minimum 5-years radiographic comparison of short fit-and-fill stem and quadrangular taper stem110ENYasutakaMasadaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomonoriTetsunagaDepartment of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuoFujiwaraDepartment of Orthopaedic Surgery, Okayama City General Medical Center, Okayama City HospitalKazukiYamadaDepartment of Orthopaedic Surgery, Okayama University HospitalTomohiroInoueDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyuichiroOkudaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomokoTetsunagaDepartment of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiOkazakiCenter for Education in Medicine and Health Sciences, Okayama UniversityToshifumiOzakiDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPurpose: ACTIS and CORAIL are cementless titanium femoral stems with hydroxyapatite (HA) coating but differing macro-geometries: ACTIS features a variable triple-taper with a medial collar, whereas CORAIL is a straight double-tapered design available with or without a collar. We compared mid-term clinical and radiographic outcomes of these stems with a minimum 5-years follow-up.<br>
Methods: We retrospectively reviewed 114 primary total hip arthroplasties using ACTIS (63 hips) or CORAIL (51 hips). Clinical outcomes and standardized radiographic parameters were assessed and compared between groups.<br>
Results: The canal-fill ratio (CFR) was significantly greater at the proximal, middle, and distal levels in the ACTIS group. Spot-weld formation was more frequent with ACTIS than with CORAIL (58.7% vs 35.3%). In logistic regression, proximal CFR significantly predicted spot-weld formation for ACTIS, with an optimal cutoff of 66.2% (sensitivity 91.9%, specificity 72.0%). Rates of subsidence, radiolucent lines, and pedestal formation did not differ significantly between groups. No severe stress shielding was observed with ACTIS, whereas three CORAIL hips demonstrated severe stress shielding (0% vs 5.9%). Clinical scores improved significantly in both groups, with no significant between-group differences at final follow-up.<br>
Conclusions: Both stems yielded favorable radiographic and clinical mid-term outcomes. In ACTIS, greater proximal canal fill was associated with radiographic osseointegration, suggesting proximal CFR as a probabilistic radiographic marker of stem ingrowth.No potential conflict of interest relevant to this article was reported.American Society of HematologyActa Medica Okayama2473-952910132026Drivers of temporal improvement in CAR T-cell therapy for large B-cell lymphoma: a Japanese nationwide registry analysis44274438ENYuYagiDepartment of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome HospitalYusukeKanemasaDepartment of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome HospitalToshikiTerao2Department of Hematology, Okayama University Hospital, Okayama, JapanMotohiroKatoDepartment of Pediatrics, The University of TokyoTomoyasuJoDepartment of Hematology, Kyoto University HospitalTatsuShimoyamaDepartment of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome HospitalToshioKitawakiDepartment of Hematology, Kyoto University HospitalRyoHanajiriDepartment of Hematology and Oncology, Nagoya University Graduate School of MedicineNorikoDokiHematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome HospitalSatoshiYoshiharaDepartment of Hematology, Hyogo Medical University HospitalNobuharuFujiiDepartment of Hematology, Okayama University HospitalNorikoIwakiDepartment of Hematology, National Cancer Center HospitalGoYamamotoDepartment of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon HospitalMasatoshiSakuraiDivision of Hematology, Department of Medicine, Keio University School of MedicineToshihiroMatsukawaDepartment of Hematology, Hokkaido University HospitalEmikoSakaidaDepartment of Hematology, Chiba University HospitalYasuhiroNakashimaHematology and Hematopoietic Cell Transplantation, Osaka Metropolitan University HospitalAkiyoYoshidaDivision of Transfusion Medicine, Kanazawa University HospitalYoshihiroUmezawaDepartment of Hematology, Institute of Science Tokyo HospitalHaryoonKimDivision of Hematology, Department of Medicine, Keio University School of MedicineKeisukeKataokaDivision of Hematology, Department of Medicine, Keio University School of MedicineHidekiGoto11Department of Hematology, Hokkaido University Hospital, Sapporo, JapanYoshikoAtsutaJapanese Data Center for Hematopoietic Cell TransplantationKojiKatoDepartment of Hematology, Oncology, and Cardiovascular Medicine, Kyushu University HospitalReal-world CD19 chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL) is characterized by expanded eligibility and evolving management practices. However, the prognostic impact of these changes remains inconsistent, and the specific drivers of outcomes remain unclear. This study analyzed 913 patients with relapsed/refractory (R/R) LBCL from a Japanese registry and compared the outcomes between 2 calendar periods (2019-2021 vs 2022-2024). The 2022-2024 cohort was older, had more adverse baseline features, and was less pretreated. Treatment patterns have shifted toward higher utilization of second-line therapy, a growing preference for axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel), and improved disease control before infusion. Accordingly, the 2022-2024 cohort achieved a longer progression-free survival (PFS; 6-month PFS, 63.2% vs 55.2%; P = .005), which persisted after adjusting for baseline characteristics using propensity score matching. Multivariable analysis identified second-line therapy, improved preinfusion disease control, and a shift in product selection from tisagenlecleucel to axi-cel or liso-cel as the primary drivers of this improvement. This benefit was pronounced in high-risk populations, including patients with stable or progressive disease at infusion (6-month PFS, 54.6% vs 43.8%; P = .012) and those who were refractory to first-line therapy (6-month PFS, 51.7% vs 40.3%; P = .013). Despite broader use in higher-risk populations and greater axi-cel exposure, 6-month nonrelapse mortality remained low (2.1% vs 1.5%). Real-world outcomes of CD19 CAR T-cell therapy for R/R LBCL have improved, predominantly driven by second-line therapy, enhanced preinfusion disease control, and increased use of more potent CAR T products.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2041-17231712026The role of Pth1r in posterior cranium cartilage regulation and craniosynostosis5862ENKatsuhikoAmanoDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeOkuzakiLaboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of OsakaYujiFujimotoLaboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of OsakaYu-ChenLiuLaboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, University of OsakaMikihikoKogoThe First Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of DentistrySeijiIidaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCraniosynostosis is a major craniofacial congenital disorder that causes developmental complications. During normal cranial development, intramembranous ossification forms the flat bones and sutures, while cartilage appears transiently in the posterior calvarial region. However, in craniosynostosis, premature suture fusion disturbs normal calvarial morphogenesis. To clarify the role of transient cartilage in this morphogenetic disruption, we investigated its molecular regulation and pathology in mice, focusing on parathyroid hormone 1 receptor (Pth1r) signaling. Conditional deletion of Pth1r in the cranial mesenchyme unexpectedly caused acrocephalic dysmorphology and craniosynostosis, with altered cartilage differentiation. Occipito–interparietal synostosis consistently occurred in Pth1r-ablated Gli1+ and Acan+ lineages, but not after adult Gli1-CreERT2 deletion, indicating a developmental role. Bulk and single-cell RNA-seq analysis revealed nine mesenchymal subsets, with mutant cells showing abnormal chondrocyte differentiation and upregulated Indian hedgehog (Ihh) signaling. These findings indicate that Pth1r maintains proper chondrogenic regulation during calvarial development, and its loss induces craniosynostosis through Ihh overactivation.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama0278-03724632026Estimating the distributional expansion of the invasive crayfish Procambarus clarkii (Girard, 1852) (Decapoda: Astacidea: Cambaridae) in South Korea using environmental DNA analysisruag033ENSeong-NamHamGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKaitoMoriuchiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMayukoHamadaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKazuyoshiNakataGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThe red swamp crayfish Procambarus clarkii (Girard, 1852) is a globally invasive species that poses serious threats to native biodiversity and ecosystem functioning. In South Korea, established populations of P. clarkii have been documented from the Jiseokcheon River in the Yeongsangang River basin since 2018; however, information on its current nationwide distribution remains limited. We conducted environmental DNA (eDNA) surveys at 19 sites across 11 river systems in South Korea, including sites with no prior distributional records, to evaluate the current distribution and potential range expansion of P. clarkii. Water samples collected during July-August 2024 were analyzed using quantitative real-time PCR (qPCR) with two species-specific primer-probe sets targeting the mitochondrial COI gene. Procambarus clarkii eDNA was detected at three sites in the Yeongsangang River basin, whereas no eDNA was detected in the other surveyed river systems. Notably, P. clarkii eDNA was not detected at a site in the Mangyeonggang River system despite previous reports of individuals and eDNA data sampled there, indicating a possible local population decline or very low abundance. By contrast, detections within the Yeongsangang River basin, together with elevated eDNA concentrations at some sites, are consistent with localized upstream expansion and increased local abundance. The concordant results from the two primer-probe sets, together with Sterivex-based on-site filtration, support the reliability of the applied eDNA framework. These findings identify the Yeongsangang River basin as the current primary focus of the P. clarkii invasion in South Korea, with evidence consistent with localized upstream expansion and increasing abundance, and provide baseline data for early detection and long-term monitoring, as well as for developing management strategies.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1465-36212026Impact of pre-existing schizophrenia spectrum disorder on the receipt of invasive and systemic therapy for gastric cancer: a multicenter nationwide cohort study in Japanhyag102ENMyo MinKhantDepartment of Psychiatry, Faculty of Medicine, Shimane UniversityMasakiFujiwaraDepartment of Neuropsychiatry, Medical Development Field, Okayama UniversityYutoYamadaDivision of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer CenterTaisukeIshiiDivision of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer CenterTomoneWatanabeDivision of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer CenterTakashiFukaoDepartment of Neuropsychiatry, Medical Development Field, Okayama UniversityMaikoFujimoriDivision of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer CenterNaokiNakayaTohoku Medical Megabank Organization, Tohoku UniversityToshihikoKawamuraDepartment of Medical Informatics, Shimane University HospitalKojiOtsukiDepartment of Psychiatry, Faculty of Medicine, Shimane UniversityYoshihikoKakiuchiDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTaichiShimazuDivision of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer CenterShiroHinotsuDepartment of Biostatistics and Data Management, Sapporo Medical UniversityYosukeUchitomiDepartment of Cancer Survivorship and Digital Medicine, The Jikei University School of MedicineMasatoshiInagakiDepartment of Psychiatry, Faculty of Medicine, Shimane UniversityBackground: Patients with schizophrenia spectrum disorders (SSD) experience higher cancer mortality, partly because of later-stage diagnosis and lower rates of recommended treatments. While treatment disparities have been reported across several cancer types, no study has specifically examined stage-appropriate treatment for gastric cancer among patients with SSD.<br>
Methods: We conducted a retrospective cohort study using a nationwide Hospital-Based Cancer Registry linked to administrative data in Japan. Patients who received initial treatment for gastric cancer between 2018 and 2021 were included. Multivariable logistic regression models examined the association between SSD and the receipt of stage-appropriate cancer treatments, adjusting for age, sex, clinical stage, Charlson Comorbidity Index, and Barthel Index.<br>
Results: Among 189 447 patients from 709 hospitals, 1312 had SSD. Patients with SSD were more likely to be diagnosed at advanced stages. In crude analysis, SSD was associated with lower rates of surgical or endoscopic treatment; however, this association was not statistically significant after adjustment (adjusted odds ratio [aOR], 0.90; 95% confidence interval [CI], 0.75–1.08). In contrast, SSD was independently associated with lower rates of postoperative adjuvant chemotherapy for pathological stage II/III disease (aOR, 0.64; 95% CI, 0.45–0.91) and systemic therapy for stage IV disease (aOR, 0.36; 95% CI, 0.28–0.47).<br>
Conclusions: Among patients with gastric cancer, SSD was associated with reduced receipt of systemic therapy but not surgical or endoscopic treatment. Efforts to improve early detection among patients with SSD may be important for reducing treatment disparities, alongside strengthened support for systemic therapy to ensure equitable access to guideline-recommended gastric cancer care.No potential conflict of interest relevant to this article was reported.American Geophysical Union (AGU)Acta Medica Okayama2169-909713172026Surface Geology and Evolution of Asteroid Ryugu: Insights From Hayabusa2 Global Mappinge2025JE009578ENLisa M.VincentDepartment of Earth Sciences, Utrecht UniversityTrishitRujInstitute for Planetary Materials, Okayama UniversityGoroKomatsuInternational Research School of Planetary Sciences, Università G. d'AnnunzioAdityaRayDepartment of Geology, Presidency UniversityHiroshiKikuchiGakushuin UniversityRyodoHemmiInstitute of Space and Astronautical Science, Japan Aerospace Exploration AgencyHideakiMiyamotoDepartment of Systems Innovation School of Engineering, The University of TokyoSeijiSugitaPlanetary Exploration Research Center, Chiba Institute of Technologythe Hayabusa2 ONC science teamRubble-pile asteroids, characterized by loose aggregates of debris held together by gravity, represent both a significant planetary hazard and a key to understanding planetesimal formation. Geologic mapping of these bodies provides essential insights into their origins, evolution, and surface processes. This knowledge is crucial for advancing space mission capabilities, from precise navigation and safe sampling to assessing the feasibility of future asteroid mining. Here, we present the most comprehensive geologic map of Ryugu in comparison to previous early-stage and single-feature maps, integrating Optical Navigation Camera (ONC) mosaics, LIDAR-derived topography, Mobile Asteroid Surface Scout (MASCOT) descent images, and spectral slope data. The analysis includes reclassification of previously identified features and newly identified features from global to local scales. The geologic mapping technique followed United States Geological Survey (USGS) planetary cartography standards using the ArcGIS Pro platform. This global framework provides an essential geologic context for interpreting returned samples and constraining rubble-pile evolution. We identified geomorphological, structural, and surface texture units on Ryugu's unconsolidated rubble-pile surface using 0.2–0.7 m/pixel image mosaics. Elongated troughs at the poles and mirrored, oblique lineaments near the equatorial ridge are consistent with rotational strain. Compared with another rubble-pile asteroid Bennu, Ryugu shows a more uniform boulder distribution, and its immensely prominent equatorial ridge indicates a more intense period of rotational deformation. However, the western bulge deviates from this trend; its fewer boulders, underdeveloped ridges, and older degraded craters suggest selective resurfacing. These features show evidence of catastrophic disruption, rotational reshaping, and ongoing surface movement.No potential conflict of interest relevant to this article was reported.Institute of Electrical and Electronics Engineers (IEEE)Acta Medica Okayama2187-01361412025Study of Signal Separation and Demodulation Techniques Considering IQ Imbalance by Stored Data Batch Signal Processing3033ENYudaiMitaGraduate School of Natural Science and Technology, Okayama UniversityYutaHiraokaGraduate School of Natural Science and Technology, Okayama UniversityTomofumiHikasaGraduate School of Natural Science and Technology, Okayama UniversityShigeruTomisatoGraduate School of Natural Science and Technology, Okayama UniversitySatoshiDennoGraduate School of Natural Science and Technology, Okayama UniversityKazuhiroUeharaGraduate School of Natural Science and Technology, Okayama UniversityWith the arrival of the IoT era, the problem of interference has become even more serious, and the challenge is to establish techniques for separating and demodulating collide signals. To achieve this, we are conducting research on stored data batch signal processing technology using short-time Fourier transform (STFT). In this paper, we used a feature quantity demodulation method proposed as a method for stored data batch signal processing to evaluate the effect of IQ imbalance, which is a factor in signal degradation in the transmitter, on signal separation and demodulation performance. Furthermore, we proposed a receiver configuration that estimates the amount of degradation due to IQ imbalance from the extracted feature quantities and compensates for the signal degradation. Computer simulation results confirmed that the proposed compensation method can improve signal separation and demodulation performance when degraded by IQ imbalance.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1478-63622712025Performance of the modified 2022 ACR/EULAR giant cell arteritis classification criteria without age restriction for discriminating from Takayasu arteritis19ENTakahikoSugiharaDepartment of Rheumatology, Graduate School of Medical and Dental Sciences, Institute of Science TokyoMasayoshiHarigaiDivision of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of MedicineHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHajimeYoshifujiDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityYasuhiroMaejimaDepartment of Cardiovascular Medicine, Graduate School of Medical and Dental Sciences, Institute of Science TokyoJunIshizakiDepartment of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of MedicineYoshikoWatanabeDepartment of General Medicine, Kawasaki Medical SchoolHiroakiDobashiDivision of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa UniversityYoshinoriKomagataDepartment of Nephrology and Rheumatology, Kyorin University School of MedicineNaotoTamuraDepartment of Internal Medicine and Rheumatology, Juntendo University School of MedicineYoshikazuNakaokaDepartment of Vascular Physiology, National Cerebral and Cardiovascular Center Research InstituteJapan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS)Objective To evaluate the ability to discriminate giant cell arteritis (GCA) from Takayasu arteritis (TAK) according to the modified 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) GCA classification criteria.<br>
Methods Patients enrolled in the Japanese nationwide retrospective registry were evaluated using the criteria with partial modification; wall thickening of descending thoracic-abdominal aorta were mainly diagnosed by contrast-enhanced computed tomography (CT) or magnetic resonance imaging instead of evaluating with positron emission tomography (PET)-CT. The discriminability of the criteria was evaluated using C-statistic (> 0.7: good ability).<br>
Results Newly diagnosed patients with GCA (n = 139) and TAK (n = 129) were assessed, and 23.3% of TAK were aged 50 years or older at onset. The sensitivity of the modified 2022 ACR/EULAR GCA classification criteria with a score ≥ 6 was 82.0%, 68.5%, and 32.1% in all GCA, GCA with large-vessel involvement, and GCA without cranial arteritis, respectively. The specificity of the modified criteria was 96.1% for the 129 TAK as controls. Five patients with late-onset TAK met the modified criteria, and four had cranial signs and symptoms, two had bilateral axillary artery involvement, and four had descending thoracic-abdominal aorta involvement. The discriminability of the criteria was good (C-statistic: 0.986, 95% confidence interval [CI]: 0.976–0.996) and remained good after excluding age (C-statistic: 0.927, 95% CI: 0.894–0.961). The discriminability of a set of large-vessel lesions (bilateral axillary artery and descending thoracic-abdominal aorta) and inflammatory markers was markedly decreased with poor C-statistic value (C-statistic: 0.598, 95% CI: 0.530–0.667). Discriminability was improved after adding polymyalgia rheumatica (PMR) (C-statistic: 0.757, 95% CI: 0.700–0.813) or age (C-statistic: 0.913, 95%CI: 0.874–0.951) to the set of large-vessel lesions. In GCA patients with a score ≤ 5, 52% had bilateral subclavian and/or axillary artery involvement.<br>
Conclusion The modified 2022 ACR/EULAR GCA classification criteria well performed in classifying GCA and TAK without PET-CT in routine clinical practice. A set of items included in the modified GCA classification criteria had good discriminative ability for GCA and TAK, even when age was excluded. However, age restriction or PMR was required to distinguish GCA without cranial lesions from TAK.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Nitric oxide induces p53-mediated cell death in human nasal epithelial cells10055ENShizukiKamiuezonoDepartment of Medicinal Pharmacology, Faculty of Pharmaceutical Sciences, Okayama UniversityShoKubotaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTomokiTsuchidaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityNobumasaTakasugiDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakashiUeharaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityNitric oxide (NO) is a key signaling molecule that plays a vital role in maintaining homeostasis of physiological processes such as immune responses and neurotransmission. However, excessive NO production during inflammatory responses to infection can lead to cytotoxicity and tissue damage. The nasal epithelial barrier is a crucial first line of immunological defense against viral infections, and it is likely exposed to excessive NO levels during chronic inflammation. Therefore, clarifying the effects of NO on this barrier is thus critical. In this study, we investigated the biological effects of sustained NO exposure on RPMI2650 human nasal epithelial cells. Post-NO exposure transcriptomic analyses revealed significant upregulation of genes involved in the p53 signaling pathway. RT-qPCR analyses confirmed the temporal upregulation of p53 target genes associated with apoptosis and cell cycle regulation. These gene expression changes downregulated cell proliferation and induced cell death. Our findings suggest that excessive NO exposure induces nasal epithelial cell death via the p53 pathway, which over the long term can result in tissue damage and dysfunction under inflammatory conditions. These results provide new insights into how prolonged NO exposure affects the nasal epithelial cells and may contribute to the progression of chronic infectious diseases.No potential conflict of interest relevant to this article was reported.American Society for Clinical InvestigationActa Medica Okayama1558-8238136102026Spatial single-cell proteotyping reveals immunotherapy-resistant features within the complex tumor microenvironment of metastatic NSCLCe195021ENKohsukeIsomotoDepartment of Medical Oncology, Kindai University Faculty of MedicineKojiHarataniDepartment of Medical Oncology, Kindai University Faculty of MedicineTakahiroTsujikawaDepartment of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of MedicineShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalYusukeMakutaniDepartment of Surgery, Kindai University Faculty of MedicineMasayukiTakedaDepartment of Medical Oncology, Kindai University Faculty of MedicineKimioYonesakaDepartment of Medical Oncology, Kindai University Faculty of MedicineKaoruTanakaDepartment of Medical Oncology, Kindai University Faculty of MedicineTsutomuIwasaDepartment of Medical Oncology, Kindai University Faculty of MedicineKazukoSakaiDepartment of Genome Biology, Kindai University Faculty of MedicineKazutoNishioDepartment of Genome Biology, Kindai University Faculty of MedicineAkihikoItoDepartment of Pathology, Kindai University Faculty of MedicineKazuhikoNakagawaDepartment of Medical Oncology, Kindai University Faculty of MedicineHidetoshiHayashiDepartment of Medical Oncology, Kindai University Faculty of MedicineBACKGROUND. Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1 axis have revolutionized metastatic non–small cell lung cancer (mNSCLC) treatment. However, disease progression remains a concern, and the role of the complex tumor microenvironment (TME) in treatment failure is not fully understood.<br>
METHODS. In this biomarker study involving 103 patients with mNSCLC, including 81 patients who received ICI treatment, we evaluated the association between heterogeneous immune cell subsets and ICI efficacy through single-cell spatial profiling of pretreatment tumor tissue, using a 29-marker multiplex IHC platform built for in-depth dissection of the TME.<br>
RESULTS. Among various types of intratumoral lymphocytes, including Th1, Treg, and NK cells, only CD8+ T cells (tumor-infiltrating lymphocytes [TILs]) were associated with ICI efficacy. Computational tissue segmentation underscored the importance of direct physical interactions between CD8+ TILs and cancer cells for ICI efficacy. TIL phenotyping identified CD39/CD103/Ki-67 positivity as a hallmark of exhausted yet functional tumor-reactive CD8+ TILs. Immunosuppressive tumor-associated macrophages (TAMs) and cancer-associated fibroblasts were independent unfavorable adversaries. High CD73 expression on cancer cells was suggested to confer tolerance to ICI in EGFR/ALK-oncogene+ NSCLC, potentially through M2-TAM accumulation and aberrant angiogenesis.<br>
CONCLUSION. Our study delineates the clinical relevance of heterogeneous immune cell subsets in ICI-treated mNSCLC, aiding the development of targeted therapeutic strategies.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Dual-calibration RT-qPCR reveals distinct dnaK1/2/3 and groEL1/2 expression dynamics under heat and acid stress in the sinefungin producer Streptomyces incarnatus19282ENZhaoXiao-HuiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMaoKuboGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHarukaYamagataGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYurikoNakashimaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTomohisaHasunumaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTadayoshiKanaoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTakashiTamuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityStreptomyces incarnatus NRRL8089 produces sinefungin, a nucleoside antibiotic whose yield is enhanced under defined environmental stresses. Here, dual-calibration RT-qPCR was used to resolve paralogue-specific expression dynamics of the dnaK and groE chaperone systems under heat and acid stress conditions that increase sinefungin titres. The canonical dnaK1–dnaJ1 and groES–groEL1 operons exhibited moderate induction, whereas monocistronic paralogues (dnaK2, dnaK3 and groEL2) showed markedly higher inducibility, with up to ~ 125-fold increases relative to baseline expression. Promoter analyses revealed conserved inverted repeats and differences in predicted secondary-structure stability, suggesting that promoter architecture contributes to paralogue-specific responsiveness. Structural modelling indicated divergence among DnaK paralogues in regions associated with substrate interaction, whereas GroEL paralogues retained a conserved overall scaffold, consistent with kinetic rather than structural differentiation. Together, these findings indicate that duplicated paralogues are not functionally redundant but are differentially regulated to partition proteostasis capacity under stress. This paralogue-specific regulation may provide a framework linking environmental perturbation to secondary-metabolite production in actinomycetes.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Metastatic promoting role of mesenchymal stem cells in oral squamous cell carcinoma revealed by an improved bone marrow chimeric model20445ENHtoo ShweEainDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityHotakaKawaiDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityShoSanouDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityYaminSoeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityMay WathoneOoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityTianyanPiaoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityZin ZinMinDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityKeisukeNakanoDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversitySoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama UniversityMesenchymal stem cells (MSCs) are essential stromal regulators that coordinate tissue repair, angiogenesis, and immune balance. Within tumours, MSCs remodel the microenvironment and influence disease progression, yet their systemic contribution remains unclear due to the limited recovery of functional MSCs in conventional bone marrow transplantation models. Here, we developed an improved bone marrow collection (iBMC) method using enzymatic digestion, which markedly increases MSC yield while preserving their native phenotype. GFP bone marrow chimeric mice generated by iBMC and conventional transplantation displayed comparable hematopoietic reconstitution but differed in MSC abundance, enabling direct analysis of MSC-specific effects under physiological conditions. In mouse models of oral squamous cell carcinoma (OSCC), MSCs profoundly affected tumour development. MSC-deficient tumours exhibited necrosis and infiltration of immature myeloid-derived suppressor cells (MDSCs), whereas MSC-rich tumours showed enhanced vascularisation, adaptive immune infiltration, and stromal remodelling. Notably, lung metastasis occurred only in MSC-rich mice, accompanied by bone marrow–derived endothelial activation and TNF-α–driven inflammation. Pharmacological inhibition of LepR signalling using SHU9119 unexpectedly increased metastasis, underscoring the dual, context-dependent functions of MSCs. These findings establish iBMC as a reproducible and physiologically relevant model to study MSC-mediated regulation of tumour immunity, angiogenesis, and metastasis.No potential conflict of interest relevant to this article was reported.American Society for MicrobiologyActa Medica Okayama0066-48046912025Genomic epidemiology and genetic characteristics of clinical Campylobacter species cocirculating in West Bengal, India, 2019, using whole genome analysise01108-24ENDaichiMoritaDepartment of Microbiology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityAsish KumarMukhopadhyayDivision of Bacteriology, ICMR - National Institute of Cholera and Enteric DiseasesGoutamChowdhuryDivision of Bacteriology, ICMR - National Institute of Cholera and Enteric DiseasesFumitoMaruyamaSection of Microbial Genomics and Ecology, The IDEC Institute, Hiroshima UniversityMiyukiKandaDepartment of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityYukiYamamotoDepartment of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityHidetoshiTaharaDepartment of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityPiyaliMukherjeeDivision of Bacteriology, ICMR - National Institute of Cholera and Enteric DiseasesMainakBardhanDivision of Bacteriology, ICMR - National Institute of Cholera and Enteric DiseasesTakanoriKumagaiDepartment of Microbiology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityKeiKitaharaCollaborative Research Centre of Okayama University for Infectious Diseases at ICMR-NICEDShin-IchiMiyoshiCollaborative Research Centre of Okayama University for Infectious Diseases at ICMR-NICEDShantaDuttaDivision of Bacteriology, ICMR - National Institute of Cholera and Enteric DiseasesTeruoKurodaDepartment of Microbiology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityCampylobacter species are the most common pathogens responsible for foodborne gastroenteritis worldwide. India is a region with frequent diarrheal infections and a high level of Campylobacter infection incidence, but the detailed genomic information is limited. This study aimed to characterize 112 isolates of Campylobacter from diarrhea patients at two hospitals in Kolkata, West Bengal, by whole genome analysis. The Campylobacter isolates consisted of 90 C. jejuni, 20 C. coli, and 2 C. lari isolates. Multilocus sequence typing analysis revealed that the largest sequence type (ST) populations were ST-2131 in C. jejuni and ST-830 in C. coli and seven novel STs were found in C. jejuni and one in C. coli. Notably, ST-2131, which is rarely seen elsewhere, was positive for a sialylated LOS-related gene (wlaN +neuA + cstIII) associated with Guillain-Barré syndrome. Antibiotic resistance factors predicted from the genome sequence included blaOXA variants (58.9%), tet(O) (54.5%), tet(W) (0.9%), ant(6)-Ia (0.9%), mutation in GyrA (T86I, T86I+D90N, T86I+P104S, T86I+D90N+P104S) (79.5%), and mutation in 23S rRNA (A2075G) (12.5%). In addition to the high drug resistance of Campylobacter in Kolkata, Campylobacter pathogens were circulating that may be associated with Guillain-Barré syndrome. This study indicates the importance of genomic analysis in the surveillance of pathogens, which provides genomic information on genetic diversity, virulence mechanisms, and determinants of antimicrobial resistance.No potential conflict of interest relevant to this article was reported.American Society for MicrobiologyActa Medica Okayama0019-95679312025A newly developed oral infection mouse model of shigellosis for immunogenicity and protective efficacy studies of a candidate vaccinee00346-2ENRishaHaldarDivision of Clinical Medicine, ICMR-National Institute of Cholera and Enteric DiseasesProlayHalderDivision of Bacteriology, ICMR-National Institute of Cholera and Enteric DiseasesHemantaKoleyDivision of Bacteriology, ICMR-National Institute of Cholera and Enteric DiseasesShin-ichiMiyoshiDivision of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySantasabujDasDivision of Clinical Medicine, ICMR-National Institute of Cholera and Enteric DiseasesShigella infection poses a significant public health challenge in the developing world. However, lack of a widely available mouse model that replicates human shigellosis creates a major bottleneck to better understanding of disease pathogenesis and development of newer drugs and vaccines. BALB/c mice pre-treated with streptomycin and iron (FeCl3) plus desferrioxamine intraperitoneally followed by oral infection with virulent Shigella flexneri 2a resulted in diarrhea, loss of body weight, bacterial colonization and progressive colitis characterized by disruption of epithelial lining, loss of crypt architecture with goblet cell depletion, increased polymorphonuclear infiltration into the mucosa, submucosal swelling (edema), and raised proinflammatory cytokines and chemokines in the large intestine. To evaluate the usefulness of the model for vaccine efficacy studies, mice were immunized intranasally with a recombinant protein vaccine containing Shigella invasion protein invasion plasmid antigen B (IpaB). Vaccinated mice conferred protection against Shigella, indicating that the model is suitable for testing of vaccine candidates. To protect both Shigella and Salmonella, a chimeric recombinant vaccine (rIpaB–T2544) was developed by fusing IpaB with Salmonella outer membrane protein T2544. Vaccinated mice developed antigen-specific serum IgG and IgA antibodies and a balanced Th1/Th2 response and were protected against oral challenge with Shigella (S. flexneri 2a, Shigella dysenteriae, and Shigella sonnei) using our present mouse model and Salmonella (Salmonella Typhi and Paratyphi) using an iron overload mouse model. We describe here the development of an oral Shigella infection model in wild-type mouse. This model was successfully used to demonstrate the immunogenicity and protective efficacy of a candidate protein subunit vaccine against Shigella.No potential conflict of interest relevant to this article was reported.Japanese Society of Veterinary ScienceActa Medica Okayama0916-72508762025Effects of heat stress on gene expression associated with antioxidant capacity of bovine early antral follicles680684ENKoheiKAWANOLaboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama UniversityKenichiroSAKAGUCHILaboratory of Veterinary Theriogenology, Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu UniversityEriFURUKAWANational Institute of Animal Health, National Agriculture and Food Research OrganizationNattapongNINPETCHDepartment of Animal Science, Faculty of Agriculture at Kamphaeng Saen, Kasetsart UniversityYojiroYANAGAWALaboratory of Theriogenology, Department of Clinical Sciences, Division of Veterinary Medicine, Faculty of Veterinary Medicine, Hokkaido UniversitySeijiKATAGIRILaboratory of Theriogenology, Department of Clinical Sciences, Division of Veterinary Medicine, Faculty of Veterinary Medicine, Hokkaido UniversityHeat exposure at the physiological level of oocyte-cumulus-granulosa cell complexes (OCGCs) during in vitro growth (IVG) culture decreases the reduced glutathione (GSH) level of oocytes, an antioxidant, but its mechanism has been unclear. We subjected OCGCs to IVG for 4, 8, or 12 days and investigated the effects of heat exposure on the gene expression of cumulus-granulosa cells associated with antioxidant capacity. Heat exposure did not alter the expression of genes related to GSH synthesis or reuse. Conversely, heat exposure increased mRNA expression of superoxide dismutase 2 and decreased that of glutathione peroxidase 1, which are antioxidant enzymes. Ultimately, heat exposure alters the gene expression of antioxidant enzymes in growing follicles, which may indirectly decrease the GSH level of oocytes.No potential conflict of interest relevant to this article was reported.Pharmaceutical Society of JapanActa Medica Okayama0918-615847122024Staphylococcus aureus δ-Toxin Induces Ca2+ Influx-Independent Degranulation of Murine Cultured Mast Cells20582064ENKangLiuLaboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical UniversityTomoakiKatayamaDivision of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHitomiSatoDivision of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYuhoHamaoka-TamuraLaboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical UniversityMichikoSaitoBioscience Research Center, Kyoto Pharmaceutical UniversityKazuyukiFurutaDivision of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSatoshiTanakaLaboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical UniversityCutaneous colonization with Staphylococcus aureus (SA) is frequently observed in patients with atopic dermatitis. SA produces a wide variety of bacterial toxins, among which δ-toxin was found to induce degranulation of mast cells. Degranulation of mast cells could enhance bacterial clearance and protection from future SA infection but lead to exacerbation of atopic dermatitis. Because it remains to be determined how δ-toxin triggers degranulation, we investigated δ-toxin-induced changes in murine bone marrow-derived cultured mast cells in this study. We found that δ-toxin-induced degranulation could be classified into two phases, an early Ca2+-independent and a late Ca2+-dependent phase. Recent studies suggest that NOD-like receptor family, pyrin domain containing 3 is involved in the degranulation of mast cells, raising a possibility that leakage of K+ induced by δ-toxin is involved in the Ca2+-independent phase. However, Ca2+-independent degranulation remains unchanged although Ca2+-influx and degranulation induced by δ-toxin were significantly suppressed in the presence of high concentrations of K+. Because actin depolymerization was reported to induce degranulation in the absence of Ca2+ in the permeabilized rat peritoneal mast cells, a slow but steady decrease in the amount of filamentous actin observed here may be involved in Ca2+-independent degranulation induced by δ-toxin. Although Mas-related G protein-coupled receptor (MRGPR) X2 in humans and Mrgprb2 in mice are regarded as the receptors responsible for immunoglobulin E-independent degranulation, δ-toxin-induced degranulation remained unchanged in Mrgprb2−/− mast cells. Our findings pave the way for identification of the target receptors of δ-toxin.No potential conflict of interest relevant to this article was reported.American Society for MicrobiologyActa Medica Okayama0021-9193206102024Overexpression of diglucosyldiacylglycerol synthase leads to daptomycin resistance in Bacillus subtilise00307-24ENRyogoYamamotoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuyaIshikawaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusukeMiyoshiGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuyukiFurutaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShin-IchiMiyoshiGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChikaraKaitoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThe lipopeptide antibiotic daptomycin exhibits bactericidal activity against Gram-positive bacteria by forming a complex with phosphatidylglycerol (PG) and lipid II in the cell membrane, causing membrane perforation. With the emergence of daptomycin-resistant bacteria, understanding the mechanisms of bacterial resistance to daptomycin has gained great importance. In this study, we aimed to identify the genetic factors contributing to daptomycin resistance in Bacillus subtilis, a model Gram-positive bacterium. Our findings demonstrated that overexpression of ugtP, which encodes diglucosyldiacylglycerol synthase, induces daptomycin resistance in B. subtilis. Specifically, overexpression of ugtP resulted in increased levels of diglucosyldiacylglycerol (Glc2DAG) and decreased levels of acidic phospholipids cardiolipin and PG, as well as the basic phospholipid lysylphosphatidylglycerol. However, ugtP overexpression did not alter the cell surface charge and the susceptibility to the cationic antimicrobial peptide nisin or the cationic surfactant hexadecyltrimethylammonium bromide. Furthermore, by serial passaging in the presence of daptomycin, we obtained daptomycin-resistant mutants carrying ugtP mutations. These mutants showed increased levels of Glc2DAG and a >4-fold increase in the minimum inhibitory concentration of daptomycin. These results suggest that increased Glc2DAG levels, driven by ugtP overexpression, modify the phospholipid composition and confer daptomycin resistance in B. subtilis without altering the cell surface charge of the bacteria.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0304-860817112025Novel Escherichia coli phages representing a distinct genus within the subfamily Stephanstirmvirinae: genome and host range characteristics18ENTomoyoshiKanekoDepartment of Life Science and Medical Bioscience, Waseda UniversityJumpeiUchiyamaDepartment of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityToshifumiOsakaDepartment of Microbiology and Immunology, Tokyo Women’s Medical UniversitySatoshiTsunedaDepartment of Life Science and Medical Bioscience, Waseda UniversityBacteriophages play crucial roles in microbial ecosystems and have potential for biotechnological applications. However, our understanding of culturable phages remains limited. In this study, we characterized six novel Escherichia coli phages isolated from pig farm wastewater and urban sewage, using comprehensive genomic, morphological, and host-range analysis. Using multiple comparative approaches, including gene-sharing network analysis, average nucleotide identity (ANI), and nucleotide intergenomic similarity (NIS), we demonstrated that five of these phages form a distinct group within the subfamily Stephanstirmvirinae, potentially representing a novel genus, for which we propose the name "Wecvirus”. We further propose that these phages, each of which exhibits a unique host range pattern, should be classified in two distinct species within the proposed genus. This host specificity is reflected in differences in the amino acid sequences of tail fibers, which are crucial for infection. The remaining phage, which was not classified as a wecvirus, exhibited characteristics that challenged the current classification criteria, highlighting the need for more-flexible taxonomic approaches. These findings expand our understanding of phage diversity within the subfamily Stephanstirmvirinae and contribute to the evolving phage taxonomy framework.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0012-16065202025Tunicate-specific protein Epi-1 is essential for conferring hydrophilicity to the larval tunic in the ascidian Ciona4152ENKazuKuroiwaShimoda Marine Research Center, University of TsukubaKaoruMita-YoshidaShimoda Marine Research Center, University of TsukubaMayukoHamadaUshimado Marine Institute, Okayama UniversityAkikoHozumiShimoda Marine Research Center, University of TsukubaAtsuo S.NishinoDepartment of Biology, Faculty of Agriculture and Life Science, Hirosaki UniversityYasunoriSasakuraShimoda Marine Research Center, University of TsukubaAnimals must avoid adhesion to objects in the environment to maintain their mobility and independence. The marine invertebrate chordate ascidians are characterized by an acellular matrix tunic enveloping their entire body for protection and swimming. The tunic of ascidian larvae consists of a surface cuticle layer and inner matrix layer. Hydrophilic substances coat the cuticle; this modification is thought to be for preventing adhesion. However, the molecule responsible for regulating this modification has not been clarified. We here found that the tunicate-specific protein Epi-1 is responsible for preventing adhesiveness of the tunic in the ascidian Ciona intestinalis Type A. Ciona mutants with homozygous knockouts of Epi-1 exhibited adhesion to plastic plates and to other individuals. The cuticle of the Epi-1 mutants was fragile, and it lost the glycosaminoglycans supplied by test cells, the accessory cells that normally attach to the tunic surface. Although it has an apparent signal peptide for membrane trafficking, we showed that the Epi-1 protein is localized to the cytosol of the epidermal cells. Our study suggests that the emergence of the tunicate-specific protein Epi-1 made the tunic less adhesive, providing a selective advantage for the last common tunicate ancestor.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1347-694788102024Evaluation of quercetin as a potential cytoprotector against acetaldehyde using the cultured hepatocyte model with aldehyde dehydrogenase isozyme deficiency11991202ENYuhangXuGraduate School of Environmental and Life Science, Okayama UniversityTakeshiSawamotoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityRuitongSunGraduate School of Environmental and Life Science, Okayama UniversityAkiIshikuraGraduate School of Environmental and Life Science, Okayama UniversityShintaroMunemasaGraduate School of Environmental and Life Science, Okayama UniversityYoshiyukiMurataGraduate School of Environmental and Life Science, Okayama UniversityAyanoSatohGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAkikoMatsumotoDepartment of Social and Environmental Medicine, Saga UniversityToshiyukiNakamuraGraduate School of Environmental and Life Science, Okayama UniversityYoshimasaNakamuraGraduate School of Environmental and Life Science, Okayama UniversityProtective effect of quercetin against acetaldehyde was evaluated using the cultured hepatocyte models with aldehyde dehydrogenase (ALDH) isozyme deficiency (aldh2-kd and aldh1a1-kd). The quercetin-induced cytoprotection against acetaldehyde in the ALDH1A1-deficient mutant (aldh1a1-kd) was weaker than that in the wild type. Furthermore, quercetin did not enhance the ALDH activity in aldh1a1-kd cells, suggesting that ALDH1A1 is involved in quercetin-induced cytoprotection.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1347-69478882024Negative regulation of chitosan-induced stomatal closure by glutathione in Arabidopsis thaliana918922ENIsratJahanGraduate School of Environmental and Life Science, Okayama UniversityShintaroMunemasaGraduate School of Environmental and Life Science, Okayama UniversityToshiyukiNakamuraGraduate School of Environmental and Life Science, Okayama UniversityYoshimasaNakamuraGraduate School of Environmental and Life Science, Okayama UniversityYoshiyukiMurataGraduate School of Environmental and Life Science, Okayama UniversityChitosan (CHT) is a deacylated derivative of chitin and improves growth and yield performance, activates defensive genes, and also induces stomatal closure in plants. Glutathione (GSH) has significant functions in the growth, development, defense systems, signaling, and gene expression. GSH negatively regulates abscisic acid-, methyl jasmonate-, and salicylic acid-induced stomatal closure. However, the negative regulation by GSH of CHT-induced stomatal closure is still unknown. Regulation of CHT-induced stomatal closure by GSH in guard cells was investigated using two GSH-deficient mutants, cad2-1 and chlorina 1-1 (ch1-1), and a GSH-decreasing chemical, 1-chloro-2,4-dinitrobenzene (CDNB). The cad2-1 and ch1-1 mutations and CDNB treatment enhanced CHT-induced stomatal closure. Treatment with glutathione monoethyl ester restored the GSH level in the guard cells of cad2-1 and ch1-1 and complemented the stomatal phenotype of the mutants. These results indicate that GSH negatively regulates CHT-induced stomatal closure in Arabidopsis thaliana.No potential conflict of interest relevant to this article was reported.Royal Society of Chemistry (RSC)Acta Medica Okayama2050-748813112025Enhanced capacity of aluminum-ion batteries by adjusting the average pore size of the porous carbon cathode80528058ENYifengChenGraduate School of Environmental, Life, Natural Science, and Technology, Okayama UniversityHirooSuzukiGraduate School of Environmental, Life, Natural Science, and Technology, Okayama UniversityShuFukumotoGraduate School of Environmental, Life, Natural Science, and Technology, Okayama UniversityChiyuNakanoDepartment of Comprehensive Technical Solutions, Okayama UniversityTakeshiNishikawaGraduate School of Environmental, Life, Natural Science, and Technology, Okayama UniversityShigeyukiUmezawaSeiwa Electric Mfg. Co., LtdYasuhikoHayashiGraduate School of Environmental, Life, Natural Science, and Technology, Okayama UniversityLithium-ion batteries (LIBs) are widely used but with the increasing scarcity and uneven distribution of global lithium resources, there is a need to explore alternative battery technologies. Due to its abundance, low cost, and high theoretical capacity, aluminum is a strong candidate for metal anodes, making aluminum-ion batteries (AIBs) an area of considerable interest. Current mainstream research focuses on ionic liquid electrolytes, which offer a wide electrochemical window and high ionic conductivity. Carbon materials are ideal cathode candidates due to their low cost, abundance, and high voltage platform. AIBs using carbon materials typically exhibit low discharge capacity. This study addressed the challenge of improving the discharge capacity of carbon-based cathodes in AIBs. By using porous carbon (PC) materials with varying specific surface areas, average pore sizes, and total pore volumes as cathodes, average pore size was found to impact capacity. This contradicts the contention that larger specific surface areas result in higher capacities. There is a key difference in ion behavior: whereas aluminum chloride ions intercalate into layered graphite structures, they do not intercalate into PC materials but are adsorbed to the surface. By adjusting the average pore size, it is possible to increase the discharge capacity of AIBs, challenging the traditional emphasis on specific surface area. This research does not fully solve the problem of low discharge capacity in carbon-based cathodes, but provides a new perspective on the role of pore size in enhancing battery performance, offering valuable insights for future electrode design.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1433-785164112025Stereoselective Preparation and Palladium-Catalyzed Suzuki–Miyaura Cross-Coupling of Alkenyl Sulfoximinese202420949ENKosukeYasuiDepartment of Applied Chemistry Graduate School of Engineering, Osaka UniversityYuichiroTomishimaDepartment of Applied Chemistry Graduate School of Engineering, Osaka UniversityTomoyaMiuraDivision of Applied Chemistry, Okayama UniversityKenYamazakiDivision of Applied Chemistry, Okayama UniversityKojiHiranoDepartment of Applied Chemistry Graduate School of Engineering, Osaka UniversityAlthough numerous transition-metal catalyzed cross-coupling reactions of alkenyl electrophiles with a sulfur(VI) leaving group, mainly alkenyl sulfones, have been developed, most rely heavily on highly nucleophilic Grignard reagents, and the use of organoboron reagents remains challenging. We report herein facile preparation and the following Pd-catalyzed Suzuki–Miyaura cross-coupling reaction of alkenyl sulfoximine, a monoaza analog of sulfone. The condensation of alkyl sulfoximine with aldehydes, developed in this study, makes alkenyl sulfoximines more readily available. The resulting alkenes undergo an unprecedented oxidative addition of the C−S bond to the Pd center. This cross-coupling proceeds with retention of its original stereochemistry and provided alkenes bearing three different functionalities in a stereoselective fashion. DFT calculations highlight the critical role of boronic acid and in situ-generated boroxines in facilitating this transformation.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841872026Reappraisal of the Entity of Pediatric Uveitis: Bilateral Iridocyclitis With Retinal Capillaritis (BIRC) in Juveniles in 18 Additional Casese112232ENToshihikoMatsuoOphthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityObjectives: Bilateral iridocyclitis with retinal capillaritis (BIRC) in juveniles is a newly recognized entity of juvenile chronic uveitis with no systemic involvement. In this study, 18 additional consecutive patients with BIRC were reported to show that the entity would be useful in the differential diagnosis.<br>
Methods: Clinical features were retrospectively reviewed in 18 consecutive patients diagnosed with BIRC in juveniles at Okayama University Hospital, Okayama, Japan, between 1996 and 2025.<br>
Results: The 18 patients comprised 6 males and 12 females, with an age at onset ranging from 9 to 16 years (median, 13 years). All patients presented with aqueous cells and mutton-fat keratic precipitates in both eyes, and fluorescein angiography revealed varying degrees of optic disc leakage and retinal capillary leakage in the midperipheral to peripheral fundus of both eyes. None had systemic symptoms, including skin rashes, joint pain, or fever, and no abnormalities were detected on blood examinations, urinalysis, or plain chest x-rays. Oral prednisolone, tapered from 30 mg daily, together with topical 0.1% betamethasone four times daily, was administered to five patients: two with optic disc edema and three with macular edema in both eyes or the unilateral eye. The remaining 13 patients were treated with topical 0.1% betamethasone eye drops alone. In patients who developed elevated intraocular pressure, often due to a steroid response, the instillation of topical 0.1% betamethasone was reduced to twice daily, or intraocular pressure-lowering eye drops were used in combination. In two patients who showed relapse of unilateral macular edema after oral prednisolone was tapered or discontinued, oral colchicine (1 mg daily) was introduced, resulting in the subsidence of macular edema. Bilateral uveitis in all 18 patients subsided within 6 months to a few years until 19 years of age, and all topical medications were discontinued, with relapse occurring in only one patient.<br>
Conclusions: BIRC in juveniles should be included in the differential diagnosis for school-age children and young adolescents. BIRC follows a chronic course of a few years and subsides completely with a good prognosis. In cases of macular edema or optic disc edema that affects vision, oral corticosteroid treatment is recommended, whereas patients with no sight-threatening signs can be treated with topical corticosteroid eye drops alone. The entity of BIRC may be distinct from juvenile chronic iridocyclitis in young girls with onset at preschool age, which shares common features with juvenile idiopathic arthritis-associated uveitis.No potential conflict of interest relevant to this article was reported.American Society of Clinical Oncology (ASCO)Acta Medica Okayama0732-183X43162025Methotrexate, Doxorubicin, and Cisplatin Versus Methotrexate, Doxorubicin, and Cisplatin + Ifosfamide in Poor Responders to Preoperative Chemotherapy for Newly Diagnosed High-Grade Osteosarcoma (JCOG0905): A Multicenter, Open-Label, Randomized Trial18861897ENHiroakiHiragaMusculoskeletal Oncology, NHO Hokkaido Cancer CenterRyunosukeMachidaJapan Clinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalAkiraKawaiMusculoskeletal Oncology, National Cancer Center HospitalToshiyukiKunisadaOrthopaedic Surgery, Faculty of Medicine, Okayama UniversityTsukasaYonemotoOrthopaedic Surgery, Chiba Cancer CenterMakotoEndoOrthopaedic Surgery, Graduate School of Medical Sciences, Kyushu UniversityYoshihiroNishidaDepartment of Rehabilitation Medicine, Nagoya University HospitalAkihitoNaganoOrthopaedic Surgery, Gifu University School of MedicineKeisukeAeOrthopaedic Surgery, Cancer Institute HospitalShinichirouYoshidaOrthopaedic Surgery, Tohoku University Graduate School of MedicineKunihiroAsanumaOrthopaedic Surgery, Mie UniversityJunyaToguchidaDepartment of Tissue Regeneration, Center for Induced Pluripotent Stem Cell Research and Application, Institute for Frontier Medical Sciences, Kyoto UniversityTaisukeFurutaOrthopaedic Surgery, Hiroshima UniversityRobertNakayamaDepartment of Orthopaedic Surgery, Keio University School of MedicineToshihiroAkisueOrthopaedic Surgery, Kobe UniversityToruHirumaBone and Soft Tissue Tumour Surgery, Kanagawa Cancer CenterTakeshiMoriiOrthopaedic Surgery, Kyorin UniversityHidekiNishimuraOrthopaedic Surgery, Kagawa University HospitalKojiHiraokaOrthopaedic Surgery, Kurume University HospitalMasanobuTakeyamaOrthopaedic Surgery, Yokohama City University HospitalMakotoEmoriOrthopaedic Surgery, Sapporo Medical University HospitalSatoshiTsukushiOrthopaedic Surgery, Aichi Cancer CenterHiroshiHatanoMusculoskeletal Oncology, Niigata Cancer Center HospitalHiroyukiKawashimaOrthopaedic Surgery, Niigata University Medical & Dental HospitalKazuoIsuOrthopaedic Surgery, Higashi Sapporo HospitalKazuhiroTanakaAdvanced Medical Sciences, Oita University Faculty of MedicineTomokoKataokaJapan Clinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalHaruhikoFukudaJapan Clinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalYukihideIwamotoOrthopaedic Surgery, Kyushu Rosai HospitalToshifumiOzakiOrthopaedic Surgery, Faculty of Medicine, Okayama UniversityPurpose Our previous NECO phase II studies on high-grade osteosarcoma suggested that administering ifosfamide (IF; 16 g/m2 [4g/m2 once on day 1, then 2g/m2 once on days 2-7] × six) to patients showing a poor response (PrRsp) to preoperative chemotherapy with methotrexate, doxorubicin, and cisplatin (MAP) improves their prognoses. In this Japan Clinical Oncology Group (JCOG) study, JCOG0905, we aimed to investigate the efficacy and safety of IF in patients with PrRsp.<br>
Methods JCOG0905 is a multicenter, open-label, multi-institutional, randomized trial. Eligible patients (50 years and younger) had resectable, high-grade osteosarcoma (stage II or III, Union for International Cancer Control TNM) of the extremities, limb girdles, and thoracic wall. After two MAP cycles and tumor resection, patients with PrRsp were randomly assigned to either the MAP or MAP plus 15 g/m2 (3g/m2 once daily on days 1-5) × six IF (MAP + IF [MAPIF]) group. The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The planned sample size was 100 patients with a one-sided α of .1 and a power of 0.7, assuming a 3-year DFS of 50% and 65% for MAP and MAPIF, respectively. This trial is registered with the Japan Registry of Clinical Trials (jRCT; jRCTs031180126).<br>
Results Of the 287 patients registered between February 2010 and August 2020, 51 and 52 patients with PrRsp were assigned to the MAP and MAPIF groups, respectively. As of March 2022, DFS did not differ between groups (hazard ratio [HR], 1.05 [95% CI, 0.55 to 1.98]) and OS was numerically inferior in the MAPIF group (HR, 1.48 [95% CI, 0.68 to 3.22]). Nine and zero patients in the MAPIF and MAP groups discontinued treatment because of adverse events, respectively.<br>
Conclusion Evidence from JCOG0905 does not support the addition of IF for patients with PrRsp.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0911-60284042024Central dentinogenic ghost cell tumor of the maxilla: a case report with new imaging findings and review of the literature561568ENSuzukaYoshidaDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoheiTakeshitaDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiyukiKawazuDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMikiHisatomiDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShunsukeOkadaDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMamikoFujikuraDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKyoichiObataDepartment of Oral and Maxillofacial Surgery, Okayama University HospitalKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySaoriYoshidaPreliminary Examination Room, Okayama University HospitalJunichiAsaumiDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesA dentinogenic ghost cell tumor (DGCT) is a rare benign odontogenic tumor that commonly shows characteristics of solid proliferation and has a relatively high risk of recurrence after surgical treatment. We herein report a case of a central DGCT that occurred in the maxilla and resulted in bone expansion. This study highlights new imaging findings (particularly magnetic resonance imaging) along with histopathological observations. In addition, we conducted a review of the existing literature on this rare tumor. A 37-year-old man developed swelling around the right cheek. A benign odontogenic tumor such as ameloblastoma was suspected based on the imaging examination findings (including bone expansion and the internal characteristics of the tumor) on panoramic imaging, computed tomography, and magnetic resonance imaging. The lesion was surgically excised from the right maxilla. Postoperative histopathological examination led to a definitive diagnosis of central DGCT. The tumor comprised epithelial neoplastic islands, resembling ameloblastoma, inside tight fibroconnective tissue; masses of ghost cells and formation of dentin were also observed. We had suspected that the minute high-density region around the molars on the imaging examinations represented alveolar bone change; however, it represented dentin formation. This led to difficulty diagnosing the lesion. Although DGCT may present characteristic findings on imaging examinations, its occurrence is infrequent, and in some cases, the findings may include the presence or absence of an impacted tooth without obvious calcification. The present case suggests that we should consider the possibility of an odontogenic tumor with calcification when high-density structures are observed inside the lesion.No potential conflict of interest relevant to this article was reported.Royal Society of Chemistry (RSC)Acta Medica Okayama1477-052022462024A direct oxidative esterification of aldehydes with alcohols mediated by photochemical C–H bromination90329035ENHaruAndoDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversitySakuraKodakiDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityHiroyoshiTakamuraDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityIsaoKadotaDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityKentaTanakaResearch Institute for Interdisciplinary Science, Okayama UniversityThe photochemical direct esterification of aldehydes with alcohols via in situ-generated acyl-bromides presented in this report is an attractive complementary addition to hitherto reported methods, as these are usually carried out in a two-step, one-pot procedure in order to avoid side reactions such as the oxidation of alcohols by halogen sources.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0361-860910012024Different impacts of granulocyte colony‐stimulating factor administration on allogeneic hematopoietic cell transplant outcomes for adult acute myeloid leukemia according to graft type6677ENTakaakiKonumaDepartment of Hematology/Oncology, The Institute of Medical Science, The University of TokyoKazuakiKamedaDivision of Hematology, Jichi Medical University Saitama Medical CenterKaoruMoritaDivision of Hematology, Jichi Medical UniversityTadakazuKondoDepartment of Hematology, Kobe City Medical Center General HospitalFumihikoKimuraDivision of Hematology, Department of Internal Medicine, National Defense Medical CollegeHidekiNakasoneDivision of Hematology, Jichi Medical University Saitama Medical CenterFumihikoOuchiHematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome HospitalNaoyukiUchidaDepartment of Hematology, Toranomon HospitalMasatsuguTanakaDepartment of Hematology, Kanagawa Cancer CenterTetsuyaNishidaDepartment of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi HospitalTakahiroFukudaDepartment of Hematopoietic Stem Cell Transplantation, National Cancer Center HospitalYutaHasegawaDepartment of Hematology, Hokkaido University HospitalMamikoSakata‐YanagimotoDepartment of Hematology, University of Tsukuba HospitalMakotoOnizukaDepartment of Hematology and Oncology, Tokai University School of MedicineMasashiSawaDepartment of Hematology and Oncology, Anjo Kosei HospitalShuichiOtaDepartment of Hematology, Sapporo Hokuyu HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalShin‐IchiroFujiwaraDivision of Hematology, Jichi Medical UniversitySatoshiYoshiharaDepartment of Hematology, Hyogo Medical University HospitalFumihikoIshimaruTechnical Department, Japanese Red Cross Society Blood Service HeadquartersMakotoYoshimitsuDepartment of Hematology and Rheumatology, Kagoshima University HospitalYoshinobuKandaDivision of Hematology, Jichi Medical UniversityMarieOhbikiJapanese Data Center for Hematopoietic Cell TransplantationYoshikoAtsutaJapanese Data Center for Hematopoietic Cell TransplantationMasamitsuYanadaDepartment of Hematology and Oncology, Nagoya City University East Medical CenterWe retrospectively evaluated the impacts of using granulocyte colony-stimulating factor (G-CSF) and its timing on posttransplant outcomes for 9766 adults with acute myeloid leukemia (AML) between 2013 and 2022 using a Japanese database. We separately evaluated three distinct cohorts based on graft type: 3248 received bone marrow transplantation (BMT), 3066 received peripheral blood stem cell transplantation (PBSCT), and 3452 received single-unit cord blood transplantation (CBT). Multivariate analysis showed that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT. However, it was associated with a higher risk of grades II–IV acute graft-versus-host disease (GVHD) across all graft types. Moreover, an increased incidence of overall chronic GVHD was observed with G-CSF administration in BMT and CBT patients, but not in PBSCT patients. G-CSF administration significantly improved overall survival (OS) and leukemia-free survival (LFS) only following CBT. Regarding the timing of G-CSF, in comparison with late initiation of G-CSF (Days 5–10), early initiation (Days 0–4) did not provide benefits for hematopoietic recovery regardless of graft type. In contrast, late initiation was significantly associated with a lower risk of grades II–IV acute GVHD and better OS and LFS in CBT patients. These data demonstrated that G-CSF administration accelerated neutrophil recovery and increased the risk of grades II–IV acute GVHD across all graft types, but significantly improved survival outcomes but only following CBT. Therefore, routine use of G-CSF should be considered for CBT in adult patients with AML.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0031-92013612025Effect of chemistry on the compressibility and high-pressure structural evolution of the CaFe2O4-type aluminous silicate phase107331ENGiacomoCrinitiBayerisches Geoinstitut, University of BayreuthTizianaBoffa BallaranBayerisches Geoinstitut, University of BayreuthAlexanderKurnosovBayerisches Geoinstitut, University of BayreuthTakayukiIshiiInstitute for Planetary Materials, Okayama UniversityElena-MarieRogmannBayerisches Geoinstitut, University of BayreuthKonstantinGlazyrinDeutsches Elektronen-Synchrotron DESYTimofeyFedotenkoDeutsches Elektronen-Synchrotron DESYDaniel J.FrostBayerisches Geoinstitut, University of BayreuthApproximately 22–26 vol% of a basaltic phase assemblage at lower mantle conditions is comprised of a (Na,Mg,Fe2+)(Al,Si,Fe3+)2O4 phase with CaFe2O4-type (CF-type) structure. Previous experimental studies attempted to determine the equation of state of the CF-type phase but reported contrasting compressibility values, even for samples with the same composition. Therefore, the elastic properties of the CF-type phase remain, to date, largely unconstrained. Here, we conducted single-crystal X-ray diffraction (SCXRD) measurements in the diamond anvil cell (DAC) at high pressure and room temperature on three samples of CF-type phase with compositions Na0.90(1)Al1.03(2)Si1.00(2)O4 (NaCF), Na0.66(4)Mg0.28(4)Al1.22(3)Si0.78(3)O4 (MgCF) and Na0.62(2)Mg0.19(1)Fe2+0.17(1)Fe3+0.080(4)Al1.20(3)Si0.70(1)O4 (FeCF). A multi-sample loading approach was employed for most DAC runs, where two samples were loaded in the same sample chamber to reduce possible systematic deviations between datasets, thus enhancing internal consistency and corroborating data reproducibility. Experiments on the NaCF and MgCF samples were conducted up to ∼50 GPa, while the FeCF sample was compressed to ∼72 GPa to better characterize the effect of the spin crossover of octahedrally coordinated Fe3+. We found the isothermal bulk modulus (KT0) to increase with decreasing NaAlSiO4 content, accompanied by only a slight decrease in its pressure derivative (K'T0). Analysis of the crystal structures of the three samples at high pressure allowed compositional trends to be determined also for the interatomic bonds and polyhedral compressibility, as well as the distortion indices. These suggest an overall stiffening of the A site with increasing Mg2+ and Fe2+ content, as well of the two B sites with increasing Al3+ and Fe3+ content. Enhanced compressibility of the unit cell and octahedral B sites was observed between ∼26–42 GPa in the FeCF sample, suggesting a pressure-induced spin crossover of Fe3+, in agreement with some previous observations. Finally, trends in the elastic properties from experimental studies conducted along the NaAlSiO4-MgAl2O4 join are discussed and used as a proxy to evaluate the reliability of end-member properties for the CF-type phase employed in most recent mineral physical and thermodynamic databases. Our analysis suggests current mineral physical models might underestimate densities and overestimate bulk sound velocities of NaAlSiO4-rich CF-type phases with basaltic composition.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1086-937959122024Radial transport and nebular thermal processing of millimeter‐sized solids in the Solar protoplanetary disk inferred from Cr‐Ti‐O isotope systematics of chondrules32823304ENKoheiFukudaWiscSIMS, Department of Geoscience, University of Wisconsin-MadisonYukiHibiyaResearch Center for Advanced Science and Technology, Graduate School of Science, The University of TokyoCraig R.KastelleNational Oceanic and Atmospheric AdministrationKatsuhikoSuzukiSubmarine Resources Research Center, Japan Agency for Marine-Earth Science TechnologyTsuyoshiIizukaDepartment of Earth and Planetary Science, Graduate School of Science, The University of TokyoKatsuyukiYamashitaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThomas E.HelserNational Oceanic and Atmospheric AdministrationNoriko T.KitaWiscSIMS, Department of Geoscience, University of Wisconsin-MadisonUnderstanding the material transport and mixing processes in the Solar protoplanetary disk provides important constraints on the origin of chemical and isotopic diversities of our planets. The limited extent of radial transport and mixing between the inner and outer Solar System has been suggested based on a fundamental isotopic dichotomy between non-carbonaceous (NC) and carbonaceous (CC) meteorite groups. The limited transport and mixing could be further tested by tracing the formation regions of individual meteoritic components, such as Ca-Al-rich inclusions (CAIs) and chondrules. Here, we show further evidence for the outward transport of CAIs and chondrules from the inner and subsequent thermal processing in the outer region of the protoplanetary disk based on the petrography and combined Cr-Ti-O isotope systematics of chondrules from the Vigarano-like (CV) carbonaceous chondrite Allende. One chondrule studied consists of an olivine core that exhibits NC-like Ti and O, but CC-like Cr isotopic signatures, which is enclosed by a pyroxene igneous rim with CC-like O isotope ratios. These observations indicate that the olivine core formed in the inner Solar System. The olivine core then migrated into the outer Solar System and experienced nebular thermal processing that generated the pyroxene igneous rim. The nebular thermal processing would result in Cr isotope exchange between the olivine core and CC-like materials, but secondary alteration effects on the parent body are also responsible for the CC-like Cr isotope signature. By combining previously reported Cr-Ti-O isotope systematics of CV chondrules, we show that some CV chondrules larger than ~1 mm would have formed in the inner Solar System. The accretion of the millimeter-sized, inner Solar System solids onto the CV carbonaceous chondrite parent body would require their very early migration into the outer Solar System within the first 1 million years after the Solar System formation.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1341-96253032025Five-year outcomes with gefitinib induction and chemoradiotherapy in EGFR-mutant stage III non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study497503ENKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalShoSaekiDepartment of Respiratory Medicine, Kumamoto University HospitalShinyaSakataDepartment of Respiratory Medicine, Kumamoto University HospitalMasafumiYamaguchiDepartment of Thoracic Oncology, NHO Kyushu Cancer CenterDaijiroHaradaDepartment of Thoracic Oncology, National Hospital Organization Shikoku Cancer CenterAkihiroBesshoDepartment of Respiratory Medicine, Japanese Red Cross Okayama HospitalKentaroTanakaDepartment of Respiratory Medicine, Kyushu University HospitalKojiInoueDepartment of Respiratory Medicine, Kitakyushu Municipal Medical CenterKojiInoueDepartment of Respiratory Medicine, Ehime Prefectural Central HospitalKenichiGembaDepartment of Respiratory Medicine, Chugoku Central HospitalToshioKuboDepartment of Respiratory Medicine, Okayama University HospitalAkikoSatoDepartment of Respiratory Medicine, Okayama University HospitalEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalHiromiWatanabeDepartment of Respiratory Medicine, Okayama University HospitalJunjiKishimotoDepartment of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu UniversityYoshiyukiShioyamaRadiation Oncology, Ion Beam Therapy Center, SAGA HIMAT FoundationKuniakiKatsuiDepartment of Radiology, Kawasaki Medical SchoolKenjiSugioDivision of Radiation Oncology, Department of Thoracic and Breast Surgery, Oita UniversityKatsuyukiKiuraDepartment of Respiratory Medicine, Okayama University HospitalBackground We previously showed the 2-year OS rate, the primary endpoint, of 90% in a phase II trial of gefitinib induction followed by chemoradiotherapy (CRT) in unresectable, stage III, EGFR-mutant, non-small-cell lung cancer (NSCLC). However, neither long-term survival data nor late-phase adverse event profiles have been presented.<br>
Patients and methods Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy for 8 weeks. After confirming no disease progression during induction therapy, cisplatin and docetaxel on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy were subsequently administered.<br>
Results In the enrolled twenty patients, the 5-year OS rate and median survival time were 70.0% [95% confidence interval: 45.1–85.3] and 5.5 years [4.91-NE], respectively, whereas 5-year PFS rate and median PFS time were 15.0% (3.7–33.5) and 1.4 years [0.69–2.29], respectively. Efficacy did not seem influenced even if radiation field was re-planed in response to the effect of gefitinib induction. As for late adverse events, pulmonary fibrosis occurred in 7 patients (35%). The median time from completion of CRT to the occurrence of the event was 245 days. All were grade 1, and there was no evidence of cavitation of the lesions or chronic infections such as Aspergillus infection during the course of the disease. One case of small cell lung cancer occurred during the period.<br>
Conclusions With longer follow-up time, we demonstrated favorable efficacy with tolerable toxicity profiles in the EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III, NSCLC.<br>
Trial registration numbers UMIN00005086. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000006047&type=summary&language=EjRCTs071180036. https://jrct.niph.go.jp/latest-detail/jRCTs071180036No potential conflict of interest relevant to this article was reported.American Physical Society (APS)Acta Medica Okayama0031-9007134242025Acceleration of Positive Muons by a Radio-Frequency Cavity245001ENS.AritomeGraduate School of Science, University of TokyoK.FutatsukawaHigh Energy Accelerator Research OrganizationH.HaraResearch Institute for Interdisciplinary Science, Okayama UniversityK.HayasakaInstitute of Science and Technology, Niigata UniversityY.IbarakiGraduate School of Science, Nagoya UniversityT.IchikawaGraduate School of Science, Nagoya UniversityT.IijimaGraduate School of Science, Nagoya UniversityH.IinumaGraduate School of Science and Engineering, Ibaraki UniversityY.IkedoHigh Energy Accelerator Research OrganizationY.ImaiResearch Institute for Interdisciplinary Science, Okayama UniversityK.InamiGraduate School of Science, Nagoya UniversityK.IshidaHigh Energy Accelerator Research OrganizationS.KamalDepartment of Chemistry, Laboratory for Advanced Spectroscopy and Imaging Research (LASIR), University of British ColumbiaS.KamiokaHigh Energy Accelerator Research OrganizationN.KawamuraHigh Energy Accelerator Research OrganizationM.KimuraHigh Energy Accelerator Research OrganizationA.KodaHigh Energy Accelerator Research OrganizationS.KojiGraduate School of Science, Nagoya UniversityK.KojimaKobayashi-Maskawa Institute for the Origin of Particles and the Universe, Nagoya UniversityA.KondoGraduate School of Science, Nagoya UniversityY.KondoJapan Atomic Energy Agency (JAEA)M.KuzubaGraduate School of Science and Engineering, Ibaraki UniversityR.MatsushitaGraduate School of Science, University of TokyoT.MibeHigh Energy Accelerator Research OrganizationY.MiyamotoResearch Institute for Interdisciplinary Science, Okayama UniversityJ. G.NakamuraHigh Energy Accelerator Research OrganizationY.NakazawaGraduate School of Science and Engineering, Ibaraki UniversityS.OgawaResearch Center of Advanced Particle Physics, Kyushu UniversityY.OkazakiHigh Energy Accelerator Research OrganizationA.OlinDepartment of Physics and Astronomy, University of VictoriaM.OtaniHigh Energy Accelerator Research OrganizationS.OyamaGraduate School of Science, University of TokyoN.SaitoHigh Energy Accelerator Research OrganizationH.SatoGraduate School of Science and Engineering, Ibaraki UniversityT.SatoGraduate School of Science, University of TokyoY.SatoInstitute of Science and Technology, Niigata UniversityK.ShimomuraHigh Energy Accelerator Research OrganizationZ.ShioyaFaculty of Science, Kyushu UniversityP.StrasserHigh Energy Accelerator Research OrganizationS.SugiyamaGraduate School of Science, Nagoya UniversityK.SumiGraduate School of Science, Nagoya UniversityK.SuzukiKobayashi-Maskawa Institute for the Origin of Particles and the Universe, Nagoya UniversityY.TakeuchiFaculty of Science, Kyushu UniversityM.TanidaFaculty of Science, Kyushu UniversityJ.TojoFaculty of Science, Kyushu UniversityK.UedaGraduate School of Science, Nagoya University, NagoyaS.UetakeResearch Institute for Interdisciplinary Science, Okayama UniversityX. H.XieSchool of Physics, Peking UniversityM.YamadaFaculty of Science, Kyushu UniversityS.YamamotoResearch Institute for Interdisciplinary Science, Okayama UniversityT.YamazakiHigh Energy Accelerator Research OrganizationK.YamuraInstitute of Science and Technology, Niigata UniversityM.YoshidaHigh Energy Accelerator Research OrganizationT.YoshiokaResearch Center of Advanced Particle Physics, Kyushu UniversityM.YotsuzukaGraduate School of Science, Nagoya UniversityAcceleration of positive muons from thermal energy to 100 keV has been demonstrated. Thermal muons were generated by resonant multiphoton ionization of muonium atoms emitted from a sheet of laser-ablated aerogel. The thermal muons were first electrostatically accelerated to 5.7 keV, followed by further acceleration to 100 keV using a radio-frequency quadrupole with an intensity of 2×10−3 𝜇+/pulse. The transverse normalized rms emittance of the accelerated muons in the horizontal and vertical planes were 0.85±0.25(stat)+0.22−0.13(syst) 𝜋 mm mrad and 0.32±0.03(stat)+0.05−0.02(syst) 𝜋 mm mrad, respectively. The measured emittance values demonstrated phase-space reduction by a factor of 2.0 ×102 (horizontal) and 4.1 ×102 (vertical) allowing good acceleration efficiency. These results pave the way to realize the first-ever muon accelerator for a variety of applications in particle physics, material science, and other fields.No potential conflict of interest relevant to this article was reported.Department of Mathematics, Faculty of Science, Okayama UniversityActa Medica Okayama0030-15666812026Resolution theorem of the algebraic K-theory and its applications113137ENMarikoOharaCenter for Liberal Arts and Sciences Faculty of Engineering Toyama Prefectural UniversityThe main objective is showing a variant of resolution theorem of connective Waldhausen K-theory in suitable situations. We construct two sequences of subcategories, one is consisting of finitely generated symmetric module spectra which satisfy the condition of the resolution theorem and the other is consisting of the corresponding ∞-subcategories of certain finitely generated module spectra. As an application, we construct a sequence of subcategories consisting of certain DG-modules satisfying the condition of a resolution theorem.No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama2637-61058112026Solution Structure and Counterion Condensation of Carboxymethyl Cellulose in Organic Solvents81838197ENAnishGulatiInstitute of Physical Chemistry, RWTH Aachen UniversityLingziMengMaterials Science and Engineering Department, The Pennsylvania State UniversityCanHouInstitute of Physical Chemistry, RWTH Aachen UniversityTakaichiWatanabeDepartment of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityCarlos G.LopezMaterials Science and Engineering Department, The Pennsylvania State UniversityWe report scattering (SANS and SAXS) and electrical conductivity data for aqueous and organic solutions of carboxymethyl cellulose with tetrabutylammonium counterions. For SANS in deuterated solvents, the contrast is heavily dominated by the hydrogen-rich counterions, while for SAXS the polymer backbone has a more significant contribution to the scattering signal. The correlation length calculated from the SAXS measurements follows a scaling law of ξ ∝ c–1/2, while that measured by SANS displays a weaker exponent at higher concentrations for solvents of high dielectric constants. These results indicate a decoupling in the characteristic length scales of fluctuations of the polymer backbone and counterions at high polyelectrolyte concentrations. The stretching parameter calculated from the correlation length indicates a highly stretched local conformation for TBACMC in water and several high dielectric constant solvents, consistent with the semiflexible nature of the cellulose backbone. In solvents of lower dielectric permittivity, the chains display a higher degree of local coiling. Combining electrical conductivity and scattering data, we find that the fraction of monomers bearing a dissociated charge is nearly independent of concentration and approximately proportional to the reciprocal of the Bjerrum length of the solvent, as expected by the Oosawa-Manning model.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama2056-3426122025Optimizing β-TCP with E-rhBMP-2-infused fibrin for vertical bone regeneration in a mouse calvarium modelrbae144ENKunZhaoDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMitsuakiOnoDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesXindiMuDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesZiyiWangDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShichaoXieDepartment of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokoYonezawaDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroOkadaDivision of Dental Biomaterials, Tohoku University Graduate School of DentistryTakuyaMatsumotoDepartment of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuoKubokiDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshitakaOohashiDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEffective reconstruction of large bone defects, particularly in thickness, remains one of the major challenges in orthopedic and dental fields. We previously produced an Escherichia coli-based industrial-scale GMP-grade recombinant human bone morphogenetic protein-2 (E-rhBMP-2) and showed that the combination of E-rhBMP-2 with beta-tricalcium phosphate (β-TCP/E-rhBMP-2) can effectively promote bone reconstruction. However, the limited mechanical strength and poor morphology retention of β-TCP granules are key points that need optimization to obtain more effective grafts and further expand its clinical applications. Therefore, we combined β-TCP/E-rhBMP-2 with fibrin gel to enhance its mechanical properties and usability for vertical bone regeneration. We investigated the mechanical properties and vertical bone regeneration effects of the materials applied, with or without fibrin containing E-rhBMP-2, in a calvarial defect model in mice. Compression tests were conducted to assess the initial stability of the materials. Scanning electron microscopy and Fourier transform infrared spectroscopy were conducted to characterize the presence of fibrin on the scaffold. After 4 and 12 weeks of implantation, micro-computed tomography and histological and immunofluorescent analyses were performed to assess the morphology and volume of the newly formed bone. The fibrin-containing groups had significantly higher initial mechanical strength and higher ability to maintain their morphology in vivo compared to the counterparts without fibrin. However, fibrin gel alone suppressed the bone formation ability of β-TCP/E-rhBMP-2 whereas the presence of high doses of E-rhBMP-2 in fibrin gel resulted in material resorption and enhanced new bone formation. In conclusion, fibrin gel significantly improved the mechanical strength and surgical manageability of the β-TCP/E-rhBMP-2 scaffold, and the addition of E-rhBMP-2 to the fibrin gel further enhanced the vertical bone regeneration and initial structural integrity of the scaffold.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2673-8937512025The Early Response After Radiation Therapy on Three-Dimensional Oral Cancer Model Using Patient-Derived Cancer-Associated Fibroblasts12ENIzumiYamamotoNeutron Therapy Research Center, Okayama UniversityKazuyoIgawaNeutron Therapy Research Center, Okayama UniversityNatsukoKondoParticle Radiation Oncology Center, Institute for Integrated Radiation and Nuclear Science, Kyoto UniversityYoshinoriSakuraiParticle Radiation Oncology Center, Institute for Integrated Radiation and Nuclear Science, Kyoto UniversityAtsushiFujimuraDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPengHuangNeutron Therapy Research Center, Okayama UniversityHiroyukiMichiueNeutron Therapy Research Center, Okayama UniversitySoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenjiIzumiDivision of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityBackground/Objectives: Cancer-associated fibroblasts (CAFs), which are an important component of the tumor microenvironment, have been reported to have an adverse effect on conventional radiotherapy. This study aims to elucidate the effects of CAFs in boron neutron capture therapy (BNCT) using a three-dimensional (3D) oral cancer model. Methods: Three-dimensional cancer models were fabricated using patient-derived CAFs or patient-derived normal oral fibroblasts (NOFs) and a human oral squamous cell carcinoma cell line. Each 3D cancer model was performed with either a conventional X-ray treatment or BNCT and additionally analyzed histomorphologically. Results: The 3D oral cancer-CAFs model demonstrated a greater depth of cancer cell invasion than the 3D oral cancer-NOFs model. Radiation therapy for the 3D oral cancer models indicated a trend for decreasing cancer cell invasion and cell number with dose dependence in both X-ray and BNCT. In comparison with X-rays, BNCT showed a consistent increase in the number of NOFs and a significant reduction in the number of CAFs. Conclusions: BNCT for the 3D oral cancer model was shown to be effective against cancer cells and CAFs but not against NOFs, indicating its usefulness as a minimally invasive treatment for advanced cancer. Furthermore, it is indicated that the 3D oral cancer-CAFs model is a valuable tool to evaluate cancer treatment and research, particularly in high-grade malignant tumors with invasion.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1718-77293262025Global Incidence Trend of Early-Onset Obesity-Related and Non-Obesity-Related Cancers324ENMiyuTerashimaOkayama University Medical SchoolKotaNakayamaOkayama University Medical SchoolSatokoUgaiDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USAHwa-YoungLeeGraduate School of Public Health and Healthcare Management, The Catholic University of KoreaYutaTsukumoDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthEtsujiSuzukiDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokiMizunoDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthMinkyoSongLaboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of HealthNaokoSasamotoPublic Health Sciences Division, Fred Hutchinson Cancer CenterIchiroKawachiDepartment of Social and Behavioral Sciences, Harvard T.H. Chan School of Public HealthTomotakaUgaiDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthThe global rise in obesity prevalence and the incidence of early-onset cancer (diagnosed between 20 and 49 years of age) is a serious public health concern. We, therefore, evaluated the recent global trends in the incidence of early-onset obesity-related cancers and compared them to those of non-obesity-related cancers. We obtained age-standardized incidence rates of early-onset cancers diagnosed between 2000 and 2012 in 44 countries from the Cancer Incidence in Five Continents database. Using joinpoint regression models, we calculated the average annual percentage changes (AAPCs) and their corresponding 95% confidence intervals (95% CIs) for combined and individual categories of obesity-related cancers (11 and 9 cancer types in females and males, respectively) and non-obesity-related cancers (12 cancer types in both females and males). Differences in the AAPC were assessed by comparing 95% CIs, where nonoverlapping 95% CIs were considered statistically significantly different. We observed statistically significant positive AAPCs for early-onset obesity-related cancers in all available countries combined among females (global AAPC, 4.3%; 95% CI, 4.1–4.6%) and males (global AAPC, 1.4%; 95% CI, 1.2–1.7%). When analyzed by countries, we observed statistically significant positive AAPCs in 26 countries among females and 11 countries among males. AAPCs for early-onset obesity-related cancers were statistically significantly higher than those of non-obesity-related cancers in several regions, especially North America and Oceania. In conclusion, this study indicates that the incidence of early-onset obesity-related cancers exhibited a more pronounced increasing trend than non-obesity-related cancers among both sexes in many countries and regions.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0021-925830132025Taste receptor type 1 member 3 in osteoclasts regulates osteoclastogenesis via detection of glucose108273ENAnnaYoshimuraDivision of Molecular Signaling and Biochemistry, Kyushu Dental UniversityTakumaMatsubaraDivision of Molecular Signaling and Biochemistry, Kyushu Dental UniversityNaoKodamaDivision of Molecular Signaling and Biochemistry, Kyushu Dental UniversityYoshimitsuKakutaLaboratory of Structural Biology, Graduate School of Systems Life Sciences, Kyushu UniversityKazumaYasudaDivision of Molecular Signaling and Biochemistry, Kyushu Dental UniversityRyusukeYoshidaDepartment of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityOsamuKaminumaDepartment of Disease Model, Research Institute of Radiation Biology and Medicine, Hiroshima UniversityShuheiHosomiDepartment of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan UniversityHirojiShinkawaDepartment of Hepatobiliary-Pancreatic Surgery, Graduate School of Medicine, Osaka Metropolitan UniversityQuanYuanState Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan UniversityTatsuoKawamotoDivision of Orofacial Functions and Orthodontics, Kyushu Dental UniversityShoichiroKokabuDivision of Molecular Signaling and Biochemistry, Kyushu Dental UniversityThe taste system extends beyond the oral cavity, with various taste receptors found in extraoral organs. Mice deficient in the taste receptor type 1 (TAS1R) family member, TAS1R3, and fed a high-fat, high-sugar diet showed high bone mass without altering food consumption. However, the underlying mechanisms, including the cell types responsible for TAS1R3 expression, remain unclear. Here, we demonstrate the expression and function of TAS1R3 in osteoclasts, which are responsible for bone resorption. The expression of Tas1r3, but not Tas1r1 or Tas1r2, is evoked during osteoclast differentiation. Osteoclastogenesis-related genes were downregulated in TAS1R3-deficient mice, whereas the opposite phenotypes were elicited by TAS1R3 overexpression. Contrary to the common heterodimerization with TAS1R1 or TAS1R2, TAS1R3 formed a homodimer that functioned to detect glucose, enhance p38 phosphorylation, and induce osteoclastogenesis. These results provide novel insights into the role of TAS1R3 in bone metabolism and suggest that TAS1R3 may be a viable target for therapeutic agents in bone metabolic diseases.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1756-46461262025Proteome analysis reveals the molecular mechanisms of fucoxanthin-induced apoptosis in glial cells PC12 after nanoencapsulation106710ENChunyanWangSchool of Food Science, Henan Institute of Science and TechnologyXinxinMaSchool of Food Science, Henan Institute of Science and TechnologyYoshimasaNakamuraGraduate School of Environmental and Life Science, Okayama UniversityHangQiSKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, School of Food Science and Technology, Dalian Polytechnic UniversityFucoxanthin (FX) is a natural pigment belonging to the xanthophyll carotenoid, which has been proven to have inhibitory effects on glioblastoma. In our previous study, nano-FX was fabricated through whey protein and flaxseed gum co-encapsulated for improved stability and glial cell (PC12) inhibitory activity of FX. To investigate the molecular mechanisms of FX-induced apoptosis in PC12 after nanoencapsulation, proteomics analysis based on TMT technology was performed. Protein profiles in PC12 were determined after 0 (Control), 8 (L_Treat), and 24 (H_Treat) μg/mL nano-FX intervention. Results indicated 78 differential abundant proteins (DAPs) linked to the cytotoxicity of nano-FX could be potential biomarkers. GO and KEGG analysis revealed altered proteasome and NF-kappa B/MAPK/TNF. Proteins involved in cell proliferation were downregulated, while proteins response to autophagy and apoptosis were upregulated. The multiple mechanisms involved in the anti-tumor activity of nano-FX will provide a reference for the development of FX high value-added functional foods.No potential conflict of interest relevant to this article was reported.Ferrata Storti Foundation (Haematologica)Acta Medica Okayama1592-872111152025Distinct interleukin-6 production in IPL and TAFRO subtypes of idiopathic multicentric Castleman disease17051715ENAsamiNishikoriDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesMidori FilizNishimuraDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesYoshitoNishimuraDivision of Hematology/Oncology, Mayo ClinicRioYamadaDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesTomokaHaratakeDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan; Department of Hematology and Oncology, Okayama University HospitalRyotaChijimatsuCenter for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan; Department of Hematology and Oncology, Okayama University HospitalToshihiroItoDepartment of Immunology, Nara Medical UniversityTomohiroKogaDepartment of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical SciencesSayakaOchiDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesYuriKawaharaDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesHimawariUetaDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesYudaiTakedaDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesMichael V.GonzalezCenter for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of PennsylvaniaDavid C.FajgenbaumCenter for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of PennsylvaniaFritsVan RheeUniversity of Arkansas for Medical SciencesShujiMomoseDepartment of Pathology, Saitama Medical Center, Saitama Medical UniversityYasuharuSatoDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesIdiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder characterized by systemic inflammation and lymphadenopathy. Two major clinical subtypes, idiopathic plasmacytic lymphadenopathy (iMCD-IPL) and iMCD with thrombocytopenia, anasarca, fever, renal dysfunction/reticulin fibrosis, and organomegaly (iMCD-TAFRO), have distinct pathophysiological mechanisms. While interleukin-6 (IL-6) is known to be elevated in iMCD, differences in the sources of IL-6 production between subtypes remain unclear. We examined the source of IL-6 production and its transcriptional regulation across iMCD subtypes using immunohistochemistry, in situ hybridization, and gene expression profiling. Immunohistochemistry and in situ hybridization revealed that plasma cells were the predominant IL-6-expressing cells in iMCD-IPL, whereas vascular endothelial cells expressed IL-6 in iMCD-TAFRO. Plasma cells exhibited stronger IL-6 protein expression in iMCD-IPL than in iMCD-TAFRO. Gene expression analysis revealed upregulation of XBP1, MZB1, DERL3, SSR4, FKBP11, FKBP2, PIM2, RABAC1, and SDF2L1 in iMCD-IPL, implicating endoplasmic reticulum stress and plasma cell differentiation in IL-6 dysregulation. Our findings suggest that XBP1-mediated IL-6 production may contribute to the pathogenesis of iMCD-IPL, potentially explaining its favorable responses to IL-6 blockade therapy. In contrast, IL-6 production in iMCD-TAFRO may be predominantly from vascular endothelial cells, suggesting that elevated serum IL-6 is a secondary phenomenon of the cytokine storm in this subtype. Future studies should clarify how proteomics and gene expression profiling could inform subtype-specific therapeutic strategies in iMCD.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Boulder populations and orientation trends on asteroid Ryugu: implications for rubble-pile surface processes14404ENAdityaRayInstitute for Planetary Materials, Okayama UniversityTrishitRujInstitute for Planetary Materials, Okayama UniversityGoroKomatsuInternational Research School of Planetary Sciences, Università G. d‘AnnunzioLisa M.VincentDepartment of Earth Sciences, Utrecht UniversityHiroshiKikuchiGakushuin UniversityRyodoHemmiInstitute of Space and Astronautical Science, Japan Aerospace Exploration AgencyJensOrmöCentro de Astrobiología (CAB), CSIC-INTAAsteroid (162173) Ryugu is a spinning-top shaped, rubble-pile C-type asteroid with a surface dominated by boulders spanning a broad size-range. Using Hayabusa2 ONC-T mosaics for mapping, we present the most extensive global boulder dataset to date, representing an eleven-fold increase over the earliest survey and greater completeness than later AI-based estimates. Crucially, this work provides the first global boulder orientation dataset. The cumulative size-frequency distribution follows a power-law slope of − 2.665 ± 0.066 (boulders ≥ 3 m), indicating its fragmented nature. Boulder density is lower along the equatorial ridge, consistent with regolith accumulation during earlier YORP-driven spin-up and poleward migration of blocks during the present spin-down phase. Orientation analyses reveal systematic hemispheric trends in what we define as slope-breaker zones (i.e., regions of high slope differentials), with NW–SE alignment in the northern hemisphere and NE–SW in the southern hemisphere, but absent at the equatorial ridge and poles. We interpret these as reorientations that developed during downslope boulder migration, as despite ongoing spin-down, the current spin rate remains high enough to drive such motion. In addition, fresh craters exhibit locally heightened boulder densities, recording ongoing resurfacing by impact events that exhume buried subsurface boulders and segregate them from finer regolith via seismic shaking induced granular convection. Together, these results yield new insights into rubble-pile surface evolution, rotational dynamics, and impact-driven resurfacing, with boulder orientations providing critical evidence of spin-related downslope transport and establish a framework for comparative asteroid studies.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1931-52442952026A novel spontaneous rat model of chronic kidney disease with mitochondrial dysfunction driven by thioredoxin insufficiency5164ENIori K.OhmoriSection of Developmental Physiology and Pathology, Faculty of Education, Okayama UniversityMamoruOuchidaDepartment of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshikoHadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinyaToyokuniDepartment of Pathology and Biological Responses, Nagoya University Graduate School of MedicineTomojiMashimoDivision of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of TokyoBackground: Chronic kidney disease (CKD) is a global health burden with high prevalence and poor prognosis. Although oxidative stress and mitochondrial dysfunction have been implicated in its pathogenesis, in vivo causal evidence remains limited. Thioredoxin (Trx), encoded by Txn1, is a redox-active protein that plays a central role in controlling oxidative stress and maintaining intracellular redox homeostasis.<br>
Methods: To address this gap, we investigated the lifelong phenotypes of Txn1-F54L mutant rats harboring approximately one-third of the normal Trx activity. These rats were generated via N-ethyl-N-nitrosourea mutagenesis and validated by clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 genome editing. Comprehensive analyses included biochemical testing, histopathology, immunohistochemistry, transmission electron microscopy, RNA-sequencing, western blotting, and cytokine profiling.<br>
Results: Txn1-F54L mutant rats spontaneously developed progressive CKD, with median survival times of 110–119 days for homozygotes and 303–346 days for heterozygotes. Their clinical features—elevated blood urea nitrogen, hypoalbuminemia, hypercholesterolemia, hypertension, and arterial medial sclerosis—closely resembled those of human CKD. Histopathological evaluation revealed extensive tubular injury, interstitial fibrosis, and glomerulosclerosis. Transcriptomic profiling identified 3,418 differentially expressed genes significantly enriched in immune activation and fibrosis pathways. Mitochondrial dysfunction was prominent in proximal tubules, accompanied by oxidative stress accumulation and concurrent activation of regulated cell death pathways (apoptosis, necroptosis, and pyroptosis). Elevated serum levels of interleukin-1β, interleukin-6, and interferon-γ indicated systemic inflammation.<br>
Conclusions: Our findings demonstrate that lifelong Trx deficiency induces oxidative stress–mediated mitochondrial dysfunction and regulated cell death, leading to inflammation and progressive CKD. This study establishes the Txn1 mutant rat as a valuable spontaneous CKD model, providing translational insights and a platform for developing therapeutic strategies targeting oxidative stress–induced pathways.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama3042-6081222026Interfacial Bond Strength of Resin Cement to Polyetheretherketone (PEEK) Using Experimental Primers Doping Multifunctional Methacrylate and Acrylate Monomers12ENYukinoriMaruoDepartment of Prosthodontics, Okayama UniversityKumikoYoshiharaHealth Research Institute, National Institute of Advanced Industrial Science and TechnologyMasaoIrieOkayama University Dental SchoolNoriyukiNagaokaAdvanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental SchoolNaokiKodamaDepartment of Prosthodontics, Okayama UniversityYukiTanakaDepartment of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMihoKuwaharaDepartment of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroAkiyamaDepartment of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPolyetheretherketone (PEEK) is a high-performance thermoplastic polymer with low surface energy, chemical inertness, and a highly crystalline structure, which limit durable adhesion to resin-based materials and require improved bonding strategies. This in vitro study evaluated the effect of incorporating multifunctional methacrylate (TMPTMA) and acrylate monomers (A-TMPT and A-DPH) into an experimental primer on the 24 h shear bond strength (SBS) of resin cement to PEEK (n = 6 per group). Experimental primers were prepared by adding varying amounts (100–500 µL) of each multifunctional monomer to a UDMA/MMA-based primer, and SBS was measured after cementation with a dual-cure resin cement. TMPTMA-containing primers produced median SBS values of approximately 10–12 MPa, while acrylate-based primers showed slightly higher values, particularly at higher concentrations, reaching up to ~15.8 MPa; however, no statistically significant improvement over the control group was observed (p > 0.05). Failure modes were predominantly mixed across all conditions. These findings indicate that multifunctional monomers, despite their potential to enhance cross-link density and wetting, do not substantially overcome the intrinsic adhesion-resistant nature of polished PEEK. The results underscore that monomer modification alone is insufficient and that effective adhesion to PEEK likely requires integrated strategies combining chemical activation with mechanical surface conditioning.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2075-17291662026Disease-Suppressive Activity of Lecithin Against Foliar Infection by Rhizoctonia solani Isolates in Cabbage, Rice, and Brachypodium distachyon998ENTran XuanCuongGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMisakiAsanoSchool of Agriculture, Okayama UniversityDaikiHonmaSchool of Agriculture, Okayama UniversityMoekoSoedaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMegumiWatanabeGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNanamiSakataGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHidenoriMatsuiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKazuhiroToyodaGraduate School of Environmental, Life, Natural Science and Technology, Okayama University, Okayama 700-8530, JapanYukiIchinoseGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKentaroIkedaFaculty of Bioscience and Applied Chemistry, Hosei UniversityYoshiteruNoutoshiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityRhizoctonia solani is a necrotrophic phytopathogenic fungus that causes disease in various crops. In agriculture, many crops suffer from root or seedling rot caused by this soil-borne pathogen, whereas cabbage and rice develop lesion-like symptoms on aboveground tissues. Diseases caused by R. solani are generally controlled using chemical fungicides; however, environmentally friendly alternatives are needed for sustainable agriculture. In this study, we evaluated the efficacy of lecithin, a mixture of phospholipids previously registered in Japan as an agrochemical for controlling cucumber powdery mildew, against Rhizoctonia diseases. In cabbage, foliar spraying of 0.2–1.0% soybean lecithin effectively suppressed leaf symptoms caused by R. solani isolate RhiCa-2, which was identified as AG-1 IB. In rice and Brachypodium distachyon, 0.2–1.0% lecithin significantly suppressed leaf symptoms induced by R. solani AG-1 IA. Hyphal staining of inoculated leaves revealed reduced hyphal density on lecithin-treated leaves. Consistently, hyphal growth of R. solani on cellophane placed on water agar was retarded by lecithin treatment. However, 5.0% lecithin induced phytotoxicity in B. distachyon. Egg yolk-derived lecithin also exhibited disease-suppressive activity in cabbage and B. distachyon, with efficacy comparable to that of soybean lecithin under the conditions tested. These results suggest that lecithin suppresses foliar infection by R. solani, at least in part, through direct inhibitory effects on fungal hyphae, and may serve as a potential alternative material for disease control in sustainable crop production.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Variations in the perceived value of anti-SARS-CoV-2 therapeutics based on physicians’ clinical backgrounds5705ENAkihikoHagiwaraRespiratory Medicine and Infectious Diseases, Oita University Faculty of MedicineKosakuKomiyaRespiratory Medicine and Infectious Diseases, Oita University Faculty of MedicineYuichiroShindoDepartment of Respiratory Medicine, Nagoya University Graduate School of MedicineKazufumiTakamatsuDepartment of Respiratory Medicine and Allergology, Kochi Medical School, Kochi UniversityNaokiNishimuraDepartment of Respiratory Medicine, National Center for Global Health and MedicineYukakoTakechiIki-iki ClinicEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalTakahiroTakazonoDepartment of Respiratory Medicine, Nagasaki University Graduate School of Biomedical SciencesShinyuIzumiDepartment of Respiratory Medicine, National Center for Global Health and MedicineShimpeiGotohDepartment of Clinical Application, Center for iPS Cell, Research and Application, Kyoto UniversitySeiichiroSakaoDepartment of Pulmonary Medicine, School of Medicine, International University of Health and WelfareTakehiroIzumoDepartment of Respiratory Medicine, Japanese Red Cross Medical CenterKazukoYamamotoDivision of Infectious, Respiratory, and Digestive Medicine, First Department of Internal Medicine, University of the Ryukyus Graduate School of MedicineKazuhiroYateraDepartment of Respiratory Medicine, School of Medicine, University of Occupational and Environmental HealthHiroshiKakeyaDepartment of Infection Control Science, Osaka Metropolitan University Graduate School of MedicineYokoShibataDepartment of Pulmonary Medicine, Fukushima Medical University School of MedicineKeisukeTomiiDepartment of Respiratory Medicine, Kobe City Medical Center General HospitalHironoriSagaraDepartment of Medicine, Division of Respiratory Medicine and Allergology, Showa Medical University School of MedicineYukaSasakiCenter for Pulmonary Disease, National Hospital Organization Tokyo National HospitalToyohiroHiraiDepartment of Respiratory Medicine, Graduate School of Medicine, Kyoto UniversityAkihitoYokoyamaDepartment of Respiratory Medicine and Allergology, Kochi Medical School, Kochi UniversityHiroshiMukaeDepartment of Respiratory Medicine, Nagasaki University Graduate School of Biomedical SciencesTakashiOguraDepartment of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory CenterAlthough the global emergency phase of the coronavirus disease 2019 (COVID-19) pandemic has ended, antiviral therapy remains crucial for patients at high risk of severe illness. In Japan, the out-of-pocket costs for antiviral drugs shifted from full public coverage to partial patient payment in April 2024. However, the impact of physicians’ background characteristics on antiviral cost perceptions and prescribing behavior remains underexplored. This study involved a secondary analysis of a nationwide, web-based interventional survey of 1,500 physicians treating COVID-19. Participants reported whether they avoided prescribing antivirals owing to drug costs and identified what they considered an appropriate cost per treatment course. Associations between physicians’ characteristics and their cost perceptions were analyzed. Among 1,500 physicians surveyed, 1,193 (79.5%) reported avoiding antiviral prescriptions owing to drug costs. The most commonly selected appropriate cost was ≤ 33 USD (65.0%). Generalists, pulmonologists, ear, nose, and throat specialists, and clinic-based physicians were more likely to refrain from prescribing antivirals and favor lower treatment costs compared with physicians in other specialties or hospital settings. A multivariate analysis revealed workplace setting as the only factor independently associated with cost-related prescribing behavior. High antiviral drug costs in Japan may contribute to underprescription, particularly among clinic-based physicians, and this underprescription could hypothetically lead to delays in treatment, which might increase the risk of severe outcomes in high-risk patients. As high-risk patients with mild COVID-19 often first seek care in clinics, promoting appropriate antiviral use in these settings is essential. Strengthening communication and sharing clinical experiences between hospitals and clinics may help reduce prescribing disparities driven by drug costs.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1999-59031862026A Batch-Based VNF Deployment Mechanism for Privacy-Preserving Multi-Domain SFC Deployment Using Deep Reinforcement Learning312ENArif IndraIrawanGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYukinobuFukushimaFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityFuture 6G networks require higher performance and wider service coverage. Multi-domain Service Function Chain (SFC) deployment enables service provisioning across multiple network domains to meet these demands. However, when collaboration occurs among different network operators, privacy-preserving mechanisms are required to protect sensitive information such as internal topology and resource availability. Existing SIRM-based mechanisms, such as the Privacy-Preserving Deployment Mechanism (PPDM), address this challenge but suffer from structural limitations: PPDM performs whole-chain feasibility evaluation with extensive virtual occupation. This paper proposes a ℬ-Batch Sequential Deployment mechanism for privacy-preserving multi-domain SFC deployment. Instead of evaluating whole-chain feasibility at once, the proposed ℬ-Batch mechanism partitions each incoming SFC into fixed-size VNF batches and constructs a batch-level SIRM. This design confines virtual occupation to the current batch and reduces both its magnitude and duration while remaining fully compatible with the SIRM privacy model and the hierarchical multi-domain control architecture. A Deep Q-Network (DQN) is employed to learn substrate node selection policies based solely on SIRM-based state information, without exposing domain-internal topology or resource details. Simulation results on a three-domain AARNET substrate topology demonstrate that the proposed mechanism consistently improves deployment robustness under varying traffic intensities and SFC lengths, including short (3–6 VNFs), medium (6–9 VNFs), and long (9–12 VNFs) service chains. Compared with PPDM, the proposed ℬ-Batch mechanism achieves higher acceptance ratios under moderate-to-heavy traffic while reducing end-to-end delay and improving average substrate resource utilization. Node selection analysis further shows that smaller batch sizes preserve feasibility through compact node reuse, whereas larger batch sizes encourage broader substrate exploration. Overall, the proposed ℬ-Batch mechanism enhances feasibility preservation and deployment robustness in privacy-preserving multi-domain SFC orchestration.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8032026Determination of the Side Responsible for Bilateral Pneumothorax due to Pleural Communication225228ENKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruchikaYamamotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKumiNakajimaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidejiroTorigoeDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/70859Simultaneous bilateral spontaneous pneumothorax associated with pleuro-pleural communication is a rare but potentially life-threatening condition, most commonly occurring after major thoracic surgery. We report the case of an 81-year-old man with severe emphysema and a history of esophagectomy who presented with sudden-onset dyspnea. Chest computed tomography revealed bilateral pneumothorax with pleuro-pleural communication. Although bilateral chest tube drainage was performed, the primary side of air leakage could not be identified preoperatively. After induction of general anesthesia, a double-lumen endotracheal tube clamping test identified the right pleural cavity as the source of air leakage, thereby enabling appropriate thoracoscopic surgery.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8032026A Novel Flap Design to Reduce Urethral Complications in Anterolateral Thigh Phalloplasty: The Pipe Flap Technique213217ENToshiroImaiDepartment of Plastic and Reconstructive Surgery, Tohoku University Graduate School of MedicineToshiyukiWatanabeDepartment of Plastic and Reconstructive Surgery, Okayama University HospitalShihoWatanabeDepartment of Plastic and Reconstructive Surgery, National Hospital Organization Tokyo Medical CenterMasanobuHayashiDepartment of Plastic and Reconstructive Surgery, Tohoku University Graduate School of MedicineYusukeTominagaDepartment of Urology, Okayama University HospitalYuzaburoNambaGender Center, Okayama University HospitalCase Report10.18926/AMO/70857Phalloplasty is one of the most challenging procedures in gender-affirming surgery, and urethral complications remain common despite numerous preventive efforts. No definitive solution has been established, and many patients still require subsequent corrective procedures. We designed a novel anterolateral thigh flap that creates a planned external fistula at the penile base to mitigate urethral complications. The fistula was closed in a second-stage procedure one year later, and the postoperative course was uneventful. We report a case of a transgender man treated with this two-stage “pipe flap” technique, resulting in satisfactory urinary function. This approach may offer a safe and less invasive option for mitigating urethral complications in phalloplasty.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8032026HIP COMPASS®: A Mechanical Intraoperative Navigation Guide Associated with Improved Revision-Free Implant Survivorship after Ceramic-on-Ceramic Total Hip Arthroplasty at Minimum 10-Year Follow-up195202ENYoshiakiTeiDivision of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental SciencesNorioImaiDivision of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental SciencesKeishiKimuraDivision of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental SciencesYukiHiranoDivision of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental SciencesYojiHorigomeDivision of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental SciencesKenSudaDivision of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental SciencesHiroyukiKawashimaDivision of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental SciencesOriginal Article10.18926/AMO/70855HIP COMPASS® has demonstrated improved accuracy in intraoperative support for the acetabular component insertion angle. We assessed long-term revision-free implant survivorship following total hip arthroplasty (THA) using HIP COMPASS, with ≥10 years of follow-up. We retrospectively analyzed 210 hips of 186 patients who underwent cementless THA with ceramic-on-ceramic bearing couples, with or without HIP COMPASS. The mean follow-up duration was 10.8 years in the HIp COMPASS group and 12.7 years in the control group. Overall, 86.0% and 78.2% of cups were placed within Lewinnek’s safe zone with and without HIP COMPASS, respectively. Variability in radiographic inclination and anteversion was greater in the control group than in the HIP COMPASS group. Dislocation rates were 3.2% in the control group and 1.2% in the HIP COMPASS group, with no significant difference between groups. The control group had a significantly higher revision rate than the HIP COMPASS group (7.3% vs. 1.2%). Use of HIP COMPASS was associated with improved long-term revision-free implant survivorship over ≥ 10 years and more consistent acetabular component positioning at an appropriate insertion angle, which may contribute to stable initial fixation.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8032026Reducing Hesitation in Resuscitation: Educational Effects of a Female-Appearing Simulator in Basic Life Support Training185193ENTakuyaKuboDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKoheiTsukaharaDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiHongoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakafumiObaraDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshinoriKosakiDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTsuyoshiNojimaDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTetsuyaYumotoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiromichiNaitoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAtsunoriNakaoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityOriginal Article10.18926/AMO/70854Women are less likely than men to receive timely defibrillation during out-of-hospital cardiac arrest. We investigated whether using a simulator that is visually modified to resemble a female affects learners’ attitudes, knowledge, and performance in basic life support (BLS) training. In a BLS simulation training, first-year medical students (n=220) used a standard gender-neutral simulator (control group) or a modified simulator with a female-like appearance (intervention group). Pre- and post-training questionnaires concerning attitudes and knowledge plus a post-training skills evaluation assessed the students’ training outcomes. The intervention group initiated chest compressions significantly faster than the control group (33.1 vs. 39.8 sec, p<0.01) and achieved a significantly higher rate of correct AED pad placement (64.2% vs. 38.5%, p<0.01). While performing the resuscitation on the female-appearing manikin, the intervention group showed significantly greater increases in self-efficacy (p<0.01) and larger decreases in discomfort about removing the patient’s clothes (p<0.01). They were also significantly more likely to recognize that chest compressions can be performed (p=0.016) and AED pads can be applied (p=0.015) without removing the patient’s underwear. Using a female-appearing simulator in BLS training was thus associated with faster chest compression initiation, more accurate AED pad placement, and improved gender-sensitive attitudes and knowledge.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8032026Oral Eicosapentaenoic Acid and Paclitaxel-Associated Peripheral Neuropathy: A Retrospective Study at Okayama University Hospital179184ENAyakoMoritaCenter for Clinical Oncology, Okayama University HospitalHidekiKatayamaCenter for Clinical Oncology, Okayama University HospitalEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalOriginal Article10.18926/AMO/70853This retrospective study investigated whether eicosapentaenoic acid (EPA) reduces paclitaxel-associated chemotherapy-induced peripheral neuropathy (CIPN) and acute neuropathic pain in dyslipidemic cancer patients. The medical records of cancer patients treated with paclitaxel or nab-paclitaxel at Okayama University Hospital between January 2018 and December 2022 were reviewed. Patients receiving concomitant therapy for dyslipidemia were categorized as EPA users or non-EPA users. Numbness and pain severity were extracted from medical records. The primary endpoint was the change from baseline in Common Terminology Criteria for Adverse Events (CTCAE) grade for peripheral neuropathy and pain; groups were analyzed using the Mann–Whitney U test. Of 184 eligible patients, 18 received EPA. Bleeding events were more frequent in the EPA group; however, changes in numbness and pain did not differ significantly between groups at any time point. Overall, EPA did not show a preventive effect on paclitaxel-associated CIPN or acute neuropathic pain. Future studies should evaluate EPA in combination with other neuroprotective agents to better define its potential role in CIPN prevention.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8032026Peripheral Blood T-Cell Receptor Repertoire and Host Immune Background in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy169178ENYukiNakamuraDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalTakayukiIwamotoDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalYukikoKajiwaraDepartment of Breast Surgery, Hiroshima City Hiroshima Citizens HospitalAkiraHidaDepartment of Pathology, Matsuyama Shimin HospitalShogoNakamotoDepartment of Breast and Endocrine Surgery, Okayama University HospitalYuichiroMiyoshiDepartment of Breast Endocrine Surgery, Kagawa Prefectural Center HospitalTadahikoShienDepartment of Breast and Endocrine Surgery, Okayama University HospitalMasahikoIkedaDepartment of Breast and Thyroid Surgery, Fukuyama City HospitalHiroyoshiDoiharaDepartment of General Surgery, Kawasaki Medical School General Medical CenterRyoheiOgataDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalYoshikazuKoikeDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalTsunehisaNomuraDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalKatsuhiroTanakaDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalKazutakaNakashimaDepartment of General Surgery, Kawasaki Medical School General Medical CenterTomokiYamatsujiDepartment of General Surgery, Kawasaki Medical School General Medical CenterNarutoTairaDepartment of Breast and Thyroid Surgery, Kawasaki Medical School HospitalOriginal Article10.18926/AMO/70852The association between peripheral blood T-cell receptor (TCR) repertoire and chemotherapy response remains unclear. We evaluated peripheral blood TCR repertoire and gut microbiota in 21 breast cancer patients receiving neoadjuvant chemotherapy (NAC) who were enrolled in the SBP-14 prospective cohort study between October 2019 and March 2022. We analyzed stool samples obtained pre-NAC and peripheral blood samples obtained pre- and post-NAC. The primary endpoint was the association between baseline peripheral blood TCR repertoire and treatment response. Eleven patients (52%) had hormone receptor-positive breast cancer. All patients received anthracyclines and taxanes, with anti-HER2 therapy for HER2-positive disease. TCR diversity (TCR alpha chain [TRA], p=0.095; TCR beta chain [TRB], p=0.051) and clonality (TRA, p=0.271; TRB, p=0.500) were not significantly associated with treatment response. Gut microbiota diversity was not correlated with TCR diversity (TRA: ρ=0.046, p=0.845; TRB: ρ=0.021, p=0.929); however, three bacterial orders (Erysipelotrichales, Bacillales, and Pasteurellales) were significantly associated with TCR repertoire. Baseline TCR repertoire was not associated with treatment response in this cohort of breast cancer patients.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8032026Self-Reported Adolescent Menstrual Symptoms and Delayed Gynecologic Consultation among Japanese Women with Endometriosis159168ENTomokoIkedaFaculty of Health Sciences, Okayama UniversityMikiyaNakatsukaFaculty of Health Sciences, Okayama UniversityOriginal Article10.18926/AMO/70851Endometriosis symptoms often first appear during adolescence, yet delays in seeking gynecologic consultation remain a persistent challenge worldwide. Despite growing international evidence, the specific patterns of symptom recognition and consultation delay among Japanese women — particularly in relation to self-monitoring behaviors and cultural barriers — remain poorly understood. This study aimed to provide foundational data to guide menstrual education and preconception care strategies by conducting a cross-sectional online survey with retrospective recall among women with endometriosis to assess menstrual characteristics and symptom patterns from adolescence to initial care seeking. The survey was conducted in Japan in January 2024 and enrolled 166 women with endometriosis and 200 controls. Participants reported current and adolescent menstrual characteristics, symptom recognition, analgesic and low-dose estrogen–progestin use, school/work impact, and age at first gynecologic consultation for menstrual problems. Women with endometriosis reported heavier bleeding, stronger pain, and greater school/work absence than controls, both currently and retrospectively. The median age at first recognition of heavy bleeding or school/work absence was 16 years, whereas consultation occurred at approximately 21-23 years, indicating a consultation delay of 5-6 years. Notably, while self-monitoring of symptoms was more frequent among women with endometriosis, it only modestly shortened consultation delays. This study provides evidence from Japan that consultation delay persists despite active self-monitoring of symptoms, highlighting the influence of educational and cultural barriers on health-seeking behavior. These findings underscore the importance of integrating menstrual education with clinical guidance to promote timely gynecologic consultation.No potential conflict of interest relevant to this article was reported.American Physiological SocietyActa Medica Okayama0022-307713542026Characteristics of cross-modal negative BOLD responses in the human sensory subcortex and cortex747759ENToshikazuMiyataDivision of Sensory and Cognitive Brain Mapping, Department of System Neuroscience, National Institute for Physiological SciencesMasakiFukunagaSection of Brain Function Information, National Institute for Physiological SciencesJunxiangLuoDivision of Sensory and Cognitive Brain Mapping, Department of System Neuroscience, National Institute for Physiological SciencesIsaoYokoiNational Institute for Physiological SciencesTetsuyaYamamotoSection of Brain Function Information, National Institute for Physiological SciencesAyumiYoshiokaSection of Brain Function Information, National Institute for Physiological SciencesJiajiaYangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTomoyoMoritaCenter for Information and Neural Networks (CiNet), Advanced ICT Research Institute, National Institute of Information and Communications Technology (NICT)HiromasaTakemuraDivision of Sensory and Cognitive Brain Mapping, Department of System Neuroscience, National Institute for Physiological SciencesFunctional magnetic resonance imaging (fMRI) is a noninvasive method for measuring human brain activity based on blood oxygenation level-dependent (BOLD) responses. Although many studies have reported positive BOLD responses evoked by sensory stimuli, others have reported negative BOLD responses (NBRs) in the sensory cortex when stimuli from different sensory modalities are presented (i.e., cross-modal NBRs). We conducted an fMRI experiment to better understand the characteristics of cross-modal NBRs in subcortical and cortical regions. Auditory and visual stimuli were presented unilaterally to one ear and to either the left or right visual field, respectively. The lateral geniculate nucleus and medial geniculate nucleus did not show a significant cross-modal NBR. In contrast, the primary auditory cortex showed a significant cross-modal NBR when visual stimuli were presented in either the contralateral or ipsilateral visual fields. Finally, we found that the cross-modal NBR in the early visual cortex was highly variable across subjects and did not exhibit consistent trends. However, each subject’s data exhibited considerable split-half reliability. Our results suggest that cross-modal NBR in the auditory cortex likely reflects mechanisms such as interhemispheric suppression, rather than those coordinated within the same hemisphere.<br>
NEW & NOTEWORTHY This study demonstrated that the human primary auditory cortex showed a significant cross-modal negative BOLD response bilaterally, regardless of the visual field in which the visual stimuli were presented. This result suggests that the cross-modal negative BOLD response is not an epiphenomenon of visual cortex activation predominantly observed in the contralateral hemisphere, but is more likely to reflect interhemispheric suppression mechanisms.No potential conflict of interest relevant to this article was reported.American Physiological SocietyActa Medica Okayama1040-060533052026The role of S100A8/A9 in the pathogenesis of acute exacerbations of pulmonary fibrosisL593L609ENNaokiNakamuraDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHisaoHigoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalSatoruSenooDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAkihikoTaniguchiDepartment of Respiratory Medicine, National Hospital Organization Fukuyama Medical CenterTaichiOzekiDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyotaSunamiDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYumiInukaiDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShuseiYamamotoDepartment of Medical Laboratory Science, Okayama University Faculty of Health SciencesJunkoItanoDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAyakaTanakaDepartment of Respiratory Medicine, Kurashiki Central HospitalNahokoTomonobuDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRieKinoshitaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshinobuMaedaDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNobuakiMiyaharaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalAcute exacerbation of idiopathic pulmonary fibrosis is a life-threatening condition characterized by neutrophilic inflammation. S100A8/A9, an alarmin released by activated neutrophils and monocytes/macrophages, plays a pivotal role in regulating inflammatory responses. However, its specific involvement in acute exacerbations of pulmonary fibrosis remains unclear. This study evaluated the role of S100A8/A9 in the pathogenesis of acute exacerbations of pulmonary fibrosis. S100A8/A9 levels were measured in bronchoalveolar lavage fluid and serum from patients with idiopathic interstitial pneumonia, with and without acute exacerbations. To model acute exacerbations of pulmonary fibrosis, mice were intratracheally administered bleomycin followed by lipopolysaccharide. Subsequently, inflammatory cell infiltration, cytokine levels, morphological changes, and fibrosis marker levels in lung tissue and airways were analyzed. S100A8/A9 levels were significantly higher in the bronchoalveolar lavage fluid and serum of patients with idiopathic interstitial pneumonia experiencing acute exacerbations relative to those without; these levels were correlated with patient prognosis. In an experimental mouse model, intratracheal administration of bleomycin followed by lipopolysaccharide resulted in a significant increase in airway S100A8/A9 levels compared with bleomycin alone and control mice. Anti-S100A8/A9 neutralizing antibody Ab45 mitigated airway inflammation and lung fibrosis in mice with acute exacerbations of pulmonary fibrosis, reducing S100A8/A9 levels and neutrophil extracellular traps. In vitro, recombinant S100A8/A9 or lipopolysaccharide and neutrophils activated and differentiated fibroblasts; these effects were inhibited by anti-S100A8/A9 neutralizing antibody Ab45 and the humanized form of Ab45 (HuAb45). These findings highlight S100A8/A9 as a potential prognostic biomarker and therapeutic target for acute exacerbations of pulmonary fibrosis.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1574-78912026Stimulator of interferon genes agonist augmented antitumor immunity of osimertinib in <i>Egfr</i> ‐mutated lung cancerENJunNishimuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTadahiroKuribayashiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJohannesBrägelmannDepartment of Translational Genomics Faculty of Medicine and University Hospital Cologne, University of Cologne GermanySachiOkawaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatakaTaokaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuntaMoriDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokaNishimuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaakiTanakaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesGoMakimotoDepartment of Respiratory Medicine, Okayama University HospitalKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalKammeiRaiCenter for Innovative Clinical Medicine, Okayama University HospitalEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalRyoheiKatayamaDivision of Experimental Chemotherapy, Cancer Chemotherapy Centre, Japanese Foundation for Cancer ResearchKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalMasahiroTabataCenter for Clinical Oncology, Okayama University HospitalYosukeTogashiDepartment of Respiratory Medicine, Okayama University HospitalYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMartin L.SosDepartment of Translational Genomics Faculty of Medicine and University Hospital Cologne, University of Cologne GermanyKatsuyukiKiuraDepartment of Respiratory Medicine, Okayama University HospitalKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalEpidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers (NSCLCs) lack effective immunotherapy due to a noninflamed tumor microenvironment (TME). We previously reported that EGFR tyrosine-kinase-inhibitor (TKI) induced CD8+ T-cell immunity, which was insufficient for tumor eradication. We evaluated the potential of combining EGFR-TKI with stimulator of interferon genes (STING) agonists in activating a systemic antitumor response. Using a syngeneic mouse model of genetically engineered Egfr-mutant NSCLC, we evaluated the antitumor effects of STING agonist ADU-S100, alone and combined with osimertinib. Immunohistochemistry and flow cytometry were used to assess the TME. Osimertinib alone enhanced CD8+ T-cell infiltration but not Natural Killer (NK) cell infiltration. ADU-S100 injection alone modestly suppressed tumor growth with increasing CD8+/NK cell infiltration in the TME, but lacked an abscopal effect. Combining ADU-S100 with osimertinib significantly enhanced the antitumor effects and CD8+/NK cell infiltration. Depletion of either CD8+ or NK cells reduced the combination effect. Crucially, the combination induced an abscopal effect accompanied by PD-1+/CD8+ cell infiltration. Combining osimertinib with a STING agonist augmented innate and adaptive immunity, inducing systemic antitumor responses in EGFR-mutant NSCLC.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0950-923245182026Trisomy 8 alters chromatin conformations and activates Y chromosome genes in stem cells to drive a pre-leukemic state16751687ENJieBaiLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversityKimiArakiInstitute of Resource Development and Analysis, Kumamoto UniversityDaisukeKurotakiLaboratory of Chromatin Organization in Immune Cell Development, International Research Center for Medical Sciences, Kumamoto UniversityEerdundulengLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversitySupannikaSorinLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversityKeiHiramatsuDepartment of Chromosome Biomedical Engineering, Integrated Medical Sciences, Graduate School of Medical Sciences, Tottori UniversityNarumiUnoLaboratory of Bioengineering, School of Life Sciences, Tokyo University of Pharmacy and Life SciencesAiHamashimaLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversityMihokoIimoriLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversityKentaKikuchiLaboratory of Chromatin Organization in Immune Cell Development, International Research Center for Medical Sciences, Kumamoto UniversityMinoruTerashimaLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversityShoKubotaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKensakuKohrogiDepartment of Pediatrics, Graduate School of Medical Sciences, Kumamoto UniversityGangHuangDepartment of Cell Systems & Anatomy, Department of Pathology & Laboratory Medicine, UT Health San Antonio, Joe R. and Teresa Lozano Long School of Medicine, Mays Cancer Center at UT Health San AntonioMinetaroOgawaDepartment of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto UniversityMitsuoOshimuraChromosome Engineering Research Center, Tottori UniversityYasuhiroKazukiDepartment of Chromosome Biomedical Engineering, Integrated Medical Sciences, Graduate School of Medical Sciences, Tottori UniversityGoroSashidaLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversityThe mechanistic role of trisomy 8 in the development of myelodysplastic syndrome (MDS) remains poorly defined. Here, we generated a trisomy 8 mouse model by transferring a human chromosome 8 into murine embryonic stem cells and prospectively examined the effects on hematopoietic stem cells (HSC) by trisomy 8. The expression of inflammatory genes was enhanced, and hematopoietic programs mediated by transcription factors and polycomb repressive complex 2 (PRC2) were dysregulated in trisomy 8 HSC, which impaired their self-renewal and balanced differentiation. Trisomy 8 HSC altered the chromatin accessibility and conformations and activated Y chromosome genes, such as Uty/Kdm6c epigenetic modifier, which is known to demethylate histone H3K27me3 modification. The Uty gene facilitated the activation of PRC2-target and Runx1-target genes in leukemogenesis and drove the proliferation of human trisomy 8 leukemic cells. Since the RUNX1 gene is frequently mutated in patients with trisomy 8 MDS, its deletion attenuated the enhanced expression of inflammatory genes and mitigated the impaired self-renewal of trisomy 8 HSC in mice. Our findings reveal that trisomy 8 altered the transcriptional programs and chromatin conformations in HSC and drove a pre-malignant state through activating the expression of Uty, suggesting a route for the development of trisomy 8 MDS.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0951-64335232026VGLL3 Regulates DAPK2-Mediated Autophagy During Osteoblast Differentiatione70104ENYuhanHeDepartment of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityZiyiWangDepartment of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYaoWengDepartment of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHeriatiSitosariDepartment of Oral Biology, Faculty of Dentistry, Universitas Gadjah MadaYilinZhengDepartment of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYaxinQuDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMikaIkegameDepartment of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirohikoOkamuraDepartment of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityVestigial-like family member 3 (VGLL3), a transcriptional cofactor of the TEA domain family, has been previously identified as a regulator of osteoblast differentiation. Building upon our previous findings, we investigated VGLL3 function in MC3T3-E1 osteoblasts using an integrated approach combining transcriptomic analysis and functional assays to identify its downstream effectors and explore associated autophagy mechanisms. RNA-seq analysis of Vgll3-knockdown (shVgll3) cells identified death-associated protein kinase 2 (DAPK2), a regulator of autophagy, as a downstream effector. Autophagic activity was examined using transmission electron microscopy and western blot analysis of LC3-II and p62 proteins. The effects of Dapk2 knockdown (shDapk2) on osteoblast differentiation were evaluated using qPCR, western blotting, alkaline phosphatase staining, and Alizarin Red staining. Rapamycin treatment was used to determine whether pharmacologic activation of autophagy could restore osteoblast function. Vgll3 knockdown significantly suppressed autophagic flux, as evidenced by fewer autophagic vacuoles, decreased LC3-II accumulation, and increased p62 expression. A comparable reduction in autophagic activity was observed in shDapk2 cells and was accompanied by impaired osteoblast differentiation. Rapamycin treatment partially restored autophagy and osteogenic differentiation in Vgll3-deficient cells. Finally, overexpression of DAPK2 partially rescued autophagic activity and osteogenic differentiation in shVgll3 cells, supporting its role as a key downstream functional effector. FOXM1 was further implicated as a potential transcriptional regulator contributing to DAPK2 expression. Collectively, our findings suggest that VGLL3 may influence osteogenic differentiation in osteoblasts, potentially involving DAPK2-associated autophagy.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2197-11531312026Association between discoid lateral meniscus and medial meniscus posterior root tear: A retrospective cohort studye70666ENRyosukeYamashitaDepartment of Orthopaedic Surgery, Okayama University HospitalYukiOkazakiDepartment of Orthopaedic Surgery, Okayama University HospitalKeisukeKintakaDepartment of Orthopaedic Surgery, Kochi Health Sciences CenterKokiKawadaDepartment of Orthopaedic Surgery, Okayama University HospitalToshikiKoharaDepartment of Orthopaedic Surgery, Okayama University HospitalTakayukiFurumatsuDepartment of Orthopaedic Surgery, Japanese Red Cross Okayama HospitalPurpose: Medial meniscus (MM) posterior root tear (PRT) has gained increasing attention because of its biomechanical impact and rapid progression to osteoarthritis. Identifying the risk factors for MMPRT is essential for early diagnosis. Although the discoid lateral meniscus (DLM) is a common congenital variant, no studies have reported on the relationship between MMPRT and DLM. This study aimed to examine the relationship between MMPRT and DLM.<br>
Methods: This retrospective cohort study included 94 matched knees that underwent arthroscopic surgery between 2015 and 2021 (58 with MMPRT and 36 with other MM injuries). The matching was performed according to age and sex. Morphological analysis of the lateral meniscus (LM) was performed using coronal magnetic resonance imaging (MRI). DLM was defined as an LM ratio (LM width/tibial width) > 0.20. LM width, LM ratio and DLM prevalence were compared between the two groups. In the MMPRT group, subgroup analysis compared the preoperative and 1-year postoperative clinical outcomes between patients with and without DLM.<br>
Results: The PRT group showed significantly greater LM width (12.6 ± 3.1 mm vs. 11.1 ± 2.2 mm; p = 0.03) and LM ratio (0.18 ± 0.04 vs. 0.16 ± 0.03; p = 0.01) compared with the other group. The incidence of DLM was also significantly higher in the PRT group (29.3% vs. 8.3%; p = 0.02). No significant differences in clinical scores were observed between the two subgroups either preoperatively or 1 year postoperatively. However, both groups demonstrated significant improvement in all clinical outcomes 1 year postoperatively (p < 0.01).<br>
Conclusions: DLM was significantly more prevalent in patients with MMPRT than in those with other MM injuries. Favourable clinical outcomes were achieved following pullout repair in MMPRT knees regardless of the presence of DLM.<br>
Level of Evidence: Level III, retrospective cohort study.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1755-43301862026Two-dimensional metal–organic frameworks offer all-in-one cocatalysts for photocatalytic overall water splitting10531061ENJingyanGuanDepartment of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto UniversityHajimeSuzukiDepartment of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto UniversityKazuhideKamiyaResearch Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of OsakaTakashiHaradaResearch Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of OsakaRintaroAdachiGraduate School of Natural Science and Technology, Okayama UniversityOsamuTomitaDepartment of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto UniversityHirofumiKurokawaInstitute of Multidisciplinary Research for Advanced Materials, Tohoku UniversityDaisukeUnabaraInstitute of Multidisciplinary Research for Advanced Materials, Tohoku UniversityKojiYonekuraInstitute of Multidisciplinary Research for Advanced Materials, Tohoku UniversityNaoyaFukuiResearch Institute for Science and Technology, Tokyo University of ScienceHiroakiMaedaResearch Institute for Science and Technology, Tokyo University of ScienceKunihisaSugimotoDepartment of Chemistry, Kindai UniversityYuichiYamaguchiDepartment of Applied Chemistry, Faculty of Science, Tokyo University of ScienceAkinoriSaekiInnovative Catalysis Science Division, Institute for Open and Transdisciplinary Research Initiatives, The University of OsakaAkiraYamakataGraduate School of Natural Science and Technology, Okayama UniversityAkihikoKudoDepartment of Applied Chemistry, Faculty of Science, Tokyo University of ScienceRyuAbeDepartment of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto UniversityRyotaSakamotoDepartment of Chemistry, Graduate School of Science, Tohoku UniversityPhotocatalytic overall water splitting holds great promise for sustainable hydrogen production. For overall water splitting performed by one-step excitation, both the hydrogen evolution and oxygen evolution reactions are hindered kinetically; hence, it is necessary to employ site-selective modification of photocatalysts with hydrogen-evolving and oxygen-evolving cocatalysts. However, critical challenges remain, including the need for cumbersome, multi-step photodeposition processes and durable blocking layers to inhibit the reverse reactions. Here we find a conductive, two-dimensional metal–organic framework to serve as a simple, multifunctional cocatalyst. We loaded this framework on SrTiO3:Al, an overall water-splitting photocatalyst, using a one-step self-assembly method. The framework cocatalyst promoted steady photocatalysis with an apparent quantum efficiency of 31.5% at 350 nm, free from the reverse reaction even without blocking layers. We proposed the operational principles for the cocatalyst activity using spectroscopic, electrochemical and theoretical analyses. This two-dimensional metal–organic framework offers an all-in-one approach for designing efficient and practical one-step excitation overall water-splitting systems.No potential conflict of interest relevant to this article was reported.International Institute of Anticancer ResearchActa Medica Okayama2732-7787632026Predictors for Recurrences Within One Year Following Radical Nephrectomy for Non-metastatic Renal Cell Carcinomas419427ENKENSUKEBEKKUDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTOMOAKIYAMANOIDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTATSUSHIKAWADADepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYUSUKETOMINAGADepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTAKUYASADAHIRADepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSATOSHIKATAYAMADepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTAKEHIROIWATADepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSHINGONISHIMURADepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMOTOOARAKIDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground/Aim: This study aimed to identify predictors of rapid recurrence following radical nephrectomy for non-metastatic renal cell carcinomas.<br>
Patients and Methods: Patients with non-metastatic renal cell carcinoma who underwent radical nephrectomy between 2014 and 2024 at Okayama University Hospital were included. Rapid recurrence was defined as local or distant metastasis occurring within one year after radical nephrectomy, whereas recurrences occurring beyond one year were classified as non-rapid.<br>
Results: Among a total of 194 patients, 37 (19%) experienced recurrence during a median follow-up of 37 months, with 16 (43%) being classified as experiencing rapid recurrence. The multivariate Cox hazard model revealed that microscopic venous invasion and a size of 60 mm or larger were predictors of rapid recurrence (hazard ratio=4.1, 95% confidence interval=1.5-11.4, p=0.006, and hazard ratio=8.0, 95% confidence interval=2.6-25.0, p<0.001, respectively). Dividing the entire cohort into four groups based on the presence of the two risk factors (0, 1: venous invasion, 1: tumor size, and 2), the median PFS was not estimable, 87, 67, and 7 months, respectively (p<0.001).<br>
Conclusion: Microscopic venous invasion and tumor size of 60 mm or larger were identified as independent predictors of rapid recurrence following radical nephrectomy for non-metastatic renal cell carcinoma.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-90322026Afatinib Overcomes Osimertinib Resistance via Egfr V804F Mutation in a Syngeneic Egfr-Mutant Lung Cancer Mouse Model117ENTakaakiTanakaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatoFujitaniDivision of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer ResearchMasatakaTaokaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIwaoShimomuraDivision of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer ResearchSachiOkawaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuntaMoriDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTadahiroKuribayashiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunNishimuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokaNishimuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAyakoMoritaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityNaofumiHaraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalGoMakimotoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityHisaoHigoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityKammeiRaiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityEikiIchiharaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalYosukeTogashiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityRyoheiKatayamaDivision of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer ResearchKadoakiOhashiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama UniversityOsimertinib is the standard first-line treatment for advanced EGFR-mutant non-small cell lung cancer. However, acquired resistance invariably develops, and identifying novel resistance pathways is clinically important as a substantial portion remains undefined. We used an immunocompetent syngeneic lung cancer mouse model harboring an Egfr exon 19 deletion (mDEL tumors) to establish acquired resistance. Osimertinib-resistant tumors were generated in vivo using a drug-holiday/re-challenge protocol. The resistance mechanism was identified using Sanger sequencing, receptor tyrosine kinase arrays, and western blotting. Egfr V804F knock-in cells were generated using CRISPR/Cas9, and their sensitivity to osimertinib and afatinib was assessed in vitro and in vivo. We established two distinct osimertinib-resistant tumor lines in a syngeneic lung cancer mouse model (mDEL OsiR #1/#3). The analysis revealed an on-target secondary Egfr V804F mutation (corresponding to human EGFR V802F) in both tumor lines. Importantly, Egfr V804F knock-in cells demonstrated significant osimertinib resistance, with a 5.7–10.5-fold increase in in vitro IC50 (mean, 8.2-fold), but remained highly sensitive to afatinib. Furthermore, afatinib effectively overcame osimertinib resistance in the V804F knock-in cell-derived mouse model. Consistently, afatinib treatment resulted in marked tumor shrinkage and suppression of EGFR signaling in the established mDEL OsiR #1/#3 in vivo. These findings establish secondary Egfr V804F/EGFR V802F as an on-target osimertinib resistance mechanism, providing a preclinical rationale for evaluating afatinib in biomarker-selected patients harboring this alteration.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama2753-670X4152026Lung Segmental Perfusion Defect Is Associated With Airway Complications After Living-Donor Lobar Lung Transplantationivag139ENKentaroImanishiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTsuyoshiRyukoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuakiTomiokaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPURPOSE: Airway complications (ACs) are potentially fatal after lung transplantation (LT). Although bronchial blood flow to the graft is supplied mainly from the pulmonary circulation after LT, lung segmental perfusion defects (LSPDs) are occasionally identified on lung perfusion scintigraphy (Q-scinti) after living-donor lobar LT (LDLLT). Lung segmental perfusion defects may impair bronchial healing and contribute to the development of ACs. This study aimed to evaluate the relationship between LSPD and AC after LDLLT.<br>
METHODS: We retrospectively reviewed 86 recipients who underwent LDLLT and 163 living donors at our institution from October 1998 to December 2023. Transplanted lungs that developed AC were classified as the AC group, whereas those without AC were classified as the non-AC group. Blood flow in the transplanted lungs was evaluated using Q-scinti after LDLLT.<br>
RESULTS: AC developed in 8 (4.9%) of 163 transplanted lungs after LDLLT. Although there were no significant differences in recipient-related variables between the 2 groups, LSPD was detected significantly more frequently in the AC group (n = 8) than in the non-AC group (n = 155) (50.0% vs 6.5%, P = .002). Furthermore, transplanted lungs showing LSPD were associated with significantly higher grades of the pulmonary interlobar fissures at the time of living-donor lobectomy (P = .025). Overall survival did not differ between patients with and without AC after LDLLT.<br>
CONCLUSIONS: LSPD on Q-scinti, which may develop in grafts with incomplete interlobar fissures during living-donor lobectomy, is associated with the development of AC after LDLLT.<br>
CLINICAL REGISTRATION NUMBER: This study was approved by the Institutional Review Board of Okayama University Hospital (approval date: August 23, 2024; 2409-027).No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-006727112026Rice Genotype-Dependent Phyllosphere Microbiome Assembly and Isolation of Antagonistic Burkholderia for Sheath Blight Biocontrol4879ENAndrewsDanso OforiState Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural UniversityZohrehNasimiState Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural UniversityMuhammad IrfanAhmedState Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural UniversityYaotingYanState Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural UniversityWangLiState Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural UniversityAbdul GhaniKandroState Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural UniversityKazunoriOkadaAgro-Biotechnology Research Center, The University of TokyoKeiichiMochidaBioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource ScienceYoshiteruNoutoshiGraduate School of Environmental and Life Science, Okayama UniversityAipingZhengState Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural UniversityRice sheath blight (RSB), caused by Rhizoctonia solani, causes 10–50% yield losses globally. Using 16S rRNA sequencing of 100 rice cultivars, we found that resistant varieties harbor significantly more diverse bacterial communities (3230 OTUs; 2064 unique) than susceptible cultivars (599 OTUs; 36 unique). Resistant varieties were enriched in beneficial Burkholderiaceae, Bacillaceae, and Pseudomonadaceae, while Sphingobacteriaceae and Enterobacteriaceae were predominant in the susceptible rice varieties. From the 260 bacterial isolates, Burkholderia vietnamiensis J14EPLEAF2 presented potent antifungal activity (77% inhibition), suppressed lesion development, and abolished sclerotia formation. This strain displayed multiple plant growth-promoting traits, enhanced seed germination, and primed defense responses by upregulating PR5 and PR10. Hypersensitive response assays confirmed B. vietnamiensis as non-pathogenic, unlike B. gladioli and B. cepacia. This study identifies B. vietnamiensis J14EPLEAF2 as a promising, safe biocontrol agent for sustainable rice disease management.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-006727112026Genomic Basis of Lifestyle Divergence in Rice-Associated Burkholderia: From Pathogenesis to Plant Growth Promotion4730ENAndrews DansoOforiState Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural UniversityZohrehNasimiState Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural UniversityFrank KwekucherAckahDepartment of Crop Science, School of Agriculture and Natural Sciences, University of Cape CoastMuhammad IrfanAhmedState Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural UniversityYaotingYanState Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural UniversityWangLiState Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural UniversityAbdul GhaniKandroState Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural UniversityKazunoriOkadaAgro-Biotechnology Research Center, The University of TokyoKeiichiMochidaBioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource ScienceYoshiteruNoutoshiGraduate School of Environmental and Life Science, Okayama UniversityAipingZhengState Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural UniversityThe genus Burkholderia encompasses both plant pathogenic and beneficial species, yet the genomic determinants underlying this lifestyle divergence remain poorly understood. Using 16S rRNA sequencing of 100 rice cultivars, our companion study demonstrated that resistant varieties are enriched in beneficial Burkholderiaceae, leading to the isolation of three phenotypically contrasting strains. Here, we present comparative genomic analyses of non-pathogenic biocontrol strain Burkholderia vietnamiensis J14EpLeaf2 and pathogenic strains Burkholderia gladioli A1EpSeed5 and Burkholderia cepacia J14Eple. Pathogenic strains possess significantly larger genomes (8.36–8.46 Mb) enriched in mobile genetic elements compared to the streamlined 6.95 Mb genome of B. vietnamiensis. CAZyme analysis revealed broader repertoires of glycoside hydrolases and polysaccharide lyases in pathogens, consistent with enhanced plant cell wall degradation. B. gladioli possesses a complete T3SS and expanded T6SS with 301 predicted effectors, while B. cepacia lacks structural T3SS genes but harbors 271 candidate effectors predicted to be secreted via alternative secretion pathways, compared to 180 in B. vietnamiensis. Notably, B. cepacia harbors cystic fibrosis-associated markers (cable pili, ZmpA/ZmpB), raising significant biosafety concerns that preclude its agricultural application. LC-MS validated IAA, ornibactin, and AHL production in B. vietnamiensis, supporting its plant growth-promoting and biocontrol functions. Computational PPI networks predicted distinct interaction landscapes requiring experimental validation. This study provides a genomic framework for distinguishing pathogenic from beneficial Burkholderia and supports B. vietnamiensis as a safe biocontrol agent while cautioning against B. cepacia J14Eple.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama1664-2392172026Behavior of serum thyroglobulin in relation to thyroid function under low-thyrotropin conditions in general practice17568631756863ENYosukeSazumiDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshiakiSoejimaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroNakanoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoichiroYamamotoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsuhitoSuyamaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyosukeTakaseDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiOguniDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMihoYasudaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasanoriFurukawaDepartment of Laboratory Medicine, Okayama University HospitalFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction: Serum thyroglobulin (Tg) and thyroid hormones are essential biomarkers in the diagnosis and management of thyroid diseases. Although Tg is routinely measured as a marker for thyroid neoplasia and an adjunct in the diagnosis of thyrotoxicosis due to destructive thyroiditis, its clinical significance under conditions of abnormal thyroid function remains unclear.<br>Methods: We investigated the association between serum Tg levels and thyroid function in 292 patients who underwent simultaneous evaluation of serum Tg, free thyroxine (FT4), and free triiodothyronine (FT3) levels in routine clinical practice. Based on thyroid-stimulating hormone (TSH) levels, participants were classified into three groups: high-TSH (> 4.23 μIU/mL; n = 38), normal-TSH (0.61–4.23 μIU/mL; n = 191), and low-TSH (< 0.61 μIU/mL; n = 63).<br>Results: The low-TSH group exhibited significantly higher serum Tg levels (118.66 ± 32.13 ng/mL) than the normal-TSH (70.20 ± 23.48 ng/mL) and high-TSH (34.70 ± 13.62 ng/mL) groups. Among patients positive for TSH-receptor antibodies (TRAb) or thyroid-stimulating antibodies (TSAb), elevated Tg levels were observed exclusively in the low-TSH group. Correlation analyses revealed that Tg levels were positively correlated with the FT3/FT4 ratio in the low-TSH group (rho = 0.62, p < 0.01), and this association was more evident in patients positive for both TRAb and TSAb (rho = 0.71, p < 0.01). These associations remained significant after multivariable adjustment and were supported by correlations between Tg and SPINA-GD, a model-based index of thyroid function reflecting deiodinase activity, with similar findings observed in patients with autoimmune hyperthyroidism.<br>Conclusion: These findings suggest that serum Tg levels may reflect biochemical features consistent with T3 predominance in autoimmune hyperthyroidism and have potential clinical utility in characterizing disease pathophysiology.
No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1877-959X1732026Epidemiological and molecular characteristics of human-biting ticks in areas endemic to Japanese spotted fever: a prospective study102635ENShinnosukeFukushimaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiSunamiSumiyoshi Fujii HospitalYasuhiroNakanoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaNakamotoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidemasaAkazawaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshimiHidaniNumakuma HospitalKoujiKidaOkayama Prefectural Institute for Environmental Science and Public HealthGoTsurumiOkayama Prefectural Institute for Environmental Science and Public HealthHideharuHagiyaTick-borne diseases (TBDs) have become a great health concern worldwide. This study aimed to clarify the pathogenic and potentially pathogenic microorganisms carried by ticks that bite humans and to assess the risk of acquiring tick-borne infections in regions endemic for Japanese spotted fever. Tick specimens were prospectively collected from patients who presented with tick bites at 10 medical institutions in the Hiroshima, Okayama, and Kagawa prefectures, Japan between May 2023 and December 2024. The evaluated parameters included the estimated bite location, date of bite, patient age, tick species identification, and presence of TBD-associated pathogens in the collected ticks. Overall, 191 ticks were collected from 181 patients. Among patients with known sex, females were slightly more prevalent than males, and 45.9% of the patients were aged ≥ 70 years. Seasonal distribution demonstrated a peak incidence from April to July, with the highest number of cases observed in June (29.3%). Amblyomma testudinarium was the predominant species, accounting for 152 (79.6%) ticks, followed by Haemaphysalis hystricis (7.3%) and Haemaphysalis longicornis (6.8%). Nymphs represented the majority (83.8%), whereas adults and larvae accounted for 14.6% and 1.0%, respectively. A total of 27 ticks (14.1%) carried Rickettsia species, including two identified species (Rickettsia tamurae and Rickettsia monacensis) and one unclassified Rickettsia species. However, molecular analysis did not detect any known human pathogenic organisms, including Ehrlichia and Anaplasma species, Francisella tularensis, or Rickettsia japonica. Further epidemiological data regarding the abundance of tick-borne pathogens will provide valuable surveillance information with significant clinical utility for disease diagnosis and management.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1432-12624112026Navigating long-term patient-reported outcomes after colorectal cancer surgery in older adults: ostomy, nutritional status, and living conditions as determinants in a prospective cohort study97ENFuminoriTeraishiDepartment of Gastroenterological Surgery, Okayama University HospitalShioriItagakiPerioperative Management Center, Okayama University HospitalToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Medical Development Field, Okayama UniversityRieTamuraPerioperative Management Center, Okayama University HospitalYoshikazuMatsuokaPerioperative Management Center, Okayama University HospitalRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University HospitalNobuhikoKanayaDepartment of Gastroenterological Surgery, Okayama University HospitalYukiMatsumiDepartment of Gastroenterological Surgery, Okayama University HospitalYoshitakaKondoDepartment of Gastroenterological Surgery, Okayama University HospitalKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Okayama University HospitalToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University HospitalPurpose To elucidate determinants of long-term patient-reported outcomes (PROs) following colorectal cancer (CRC) surgery in older adults, focusing on the impact of ostomy creation, nutritional status, and living conditions on functional independence and quality of life (QoL).<br>
Methods This single-center, prospective observational study included patients aged ≥ 75 years who underwent elective CRC resection between July 2020 and December 2023. Comprehensive geriatric assessments were performed preoperatively, and PROs—including Instrumental Activities of Daily Living (IADL), EQ-5D, and EQ-VAS—were reassessed more than one year postoperatively. The primary outcomes were postoperative changes in IADL and QoL. Modified Poisson regression identified independent determinants of long-term decline in each PRO domain.<br>
Results Sixty patients (median age 79 years; 60% female) completed one-year follow-up. IADL declined in 35.6% of patients, EQ-5D in 26.6%, and EQ-VAS in 43.3%. Multivariate analysis revealed that stoma formation was independently associated with IADL decline (adjusted RR = 3.37, 95% CI 1.50–7.54, p = 0.003), whereas living alone postoperatively correlated with preserved IADL (adjusted RR = 0.14, 95% CI 0.02–0.87, p = 0.035). Low preoperative BMI (< 20 kg/m2) was significantly associated with EQ-5D deterioration (adjusted RR = 5.25, 95% CI 1.20–22.94, p = 0.027). No significant predictors were identified for EQ-VAS decline.<br>
Conclusion Among older CRC patients, stoma creation predicts long-term functional decline, while low BMI predicts QoL deterioration. Conversely, independent living appears protective for functional maintenance. Integrating PROs into perioperative assessment and tailoring surgical, nutritional, and social interventions may enhance survivorship outcomes in this aging population.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2072-66941872026Predictive Nomogram for Recurrence After Upfront Surgery for Resectable Pancreatic Ductal Adenocarcinoma: A Multicenter Study (OS-HBP-2)1181ENRyuichiYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasayoshiHiokiDepartment of Surgery, Fukuyama City HospitalTakehiroOkabayashiDepartment of Surgery, Kochi Health Sciences CenterToruKojimaDepartment of Surgery, Okayama Saiseikai General HospitalYoshikatsuEndoDepartment of Surgery, Himeji Red Cross HospitalDaisukeNobuokaDepartment of Surgery, Fukuyama City HospitalKentaSuiDepartment of Surgery, Kagawa Prefectural HospitalMasaruInagakiDepartment of Surgery, National Hospital Organization Fukuyama Medical CenterSusumuShinouraDepartment of Surgery, Tsuyama Chuo HospitalMasashiKimuraDepartment of Surgery, Matsuyama Shimin HospitalTatsuoMatsudaDepartment of Surgery, Tenwakai Matsuda HospitalHidekiAokiDepartment of Surgery, National Hospital Organization Iwakuni Clinical CenterToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground/Objectives: Postoperative recurrence is a critical issue in the treatment of resectable pancreatic ductal adenocarcinoma (rPDAC). Moreover, the prognosis after early recurrence is extremely poor. This study aimed to develop a recurrence prediction model and to define early recurrence after upfront surgery (UFS) for rPDAC. Methods: This multicenter retrospective study included patients who underwent UFS for anatomically rPDAC between January 2013 and December 2017. Multivariate analyses were conducted to identify the risk factors for recurrence-free survival and to construct a recurrence prediction model. Subsequently, a minimum p value approach was used to determine the optimal cutoff values for early and late recurrence. Results: The cohort included 603 patients (325 men and 278 women). During the median follow-up period of 25 months (interquartile range, 15–38 months), 381 patients (63.2%) experienced a recurrence. Multivariate analyses revealed carbohydrate antigen 19-9 ≥37 U/mL (hazard ratio [HR], 1.58; p < 0.001), tumor size ≥ 2.2 cm (HR, 1.59; p < 0.001), lymph node metastasis (HR, 1.86; p < 0.001), R1 resection (HR, 1.56; p = 0.002), and no adjuvant chemotherapy (HR, 1.54; p < 0.001) as independent predictors. The recurrence prediction model demonstrated an area under the curve of 0.72–0.75. The optimal threshold for early and late recurrences was a recurrence-free interval of five months. Carbohydrate antigen 19-9 ≥ 156 U/mL was a significant predictor of early recurrence (OR, 3.28; p < 0.001). Conclusions: This study identified the prognostic risk factors for recurrence and developed a recurrence prediction model for patients undergoing UFS for rPDAC. Moreover, a recurrence-free interval of five months was identified as the optimal threshold for distinguishing between early and late recurrences.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2072-669417222025Prognosis Prediction Model After Upfront Surgery for Resectable Pancreatic Ductal Adenocarcinoma: A Multicenter Study (OS-HBP-2)3694ENKoseiTakagiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityRyuichiYoshidaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKazuyaYasuiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMasayoshiHiokiDepartment of Surgery, Fukuyama City HospitalTakehiroOkabayashiDepartment of Surgery, Kochi Health Sciences CenterToruKojimaDepartment of Surgery, Okayama Saiseikai General HospitalYoshikatsuEndoDepartment of Surgery, Himeji Red Cross HospitalDaisukeNobuokaDepartment of Surgery, Fukuyama City HospitalKentaSuiDepartment of Surgery, Kagawa Prefectural HospitalMasaruInagakiDepartment of Surgery, National Hospital Organization Fukuyama Medical CenterSusumuShinouraDepartment of Surgery, Tsuyama Chuo HospitalMasashiKimuraDepartment of Surgery, Matsuyama Shimin HospitalTatsuoMatsudaDepartment of Surgery, Tenwakai Matsuda HospitalHidekiAokiDepartment of Surgery, National Hospital Organization Iwakuni Clinical CenterToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityBackground/Objectives: Upfront surgery (UFS) remains the standard treatment for patients with resectable pancreatic ductal adenocarcinoma (PDAC). We aimed to investigate the prognostic factors for survival after UFS in patients with resectable PDAC and to develop a prognostic prediction model. Methods: This multicenter, retrospective study included 603 patients who underwent UFS for resectable PDAC between January 2013 and December 2017. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival (OS). We constructed a prognostic prediction model for OS after UFS. An internal validation was performed to evaluate the discriminative performance of the model. Results: The 1-, 3-, and 5-year OS rates were 83.7%, 48.2%, and 37.5%, respectively. The Cox proportional hazards model showed that tumor size > 2 cm (hazard ratio [HR] 1.50, p = 0.001); tumor contact with the portal and superior mesenteric veins of ≤180° (HR 1.47, p = 0.003); carbohydrate antigen 19-9 levels of 40 to 500 U/mL (HR 1.59, p = 0.002) and ≥500 U/mL (HR 2.16, p < 0.001); and a modified Glasgow Prognostic Score of two (HR 1.56, p = 0.038) were predictors associated with OS. The prognostic prediction model for 5-year OS demonstrated an area under the curve of 0.68. The calibration plots indicate a concordance index of 0.63. Conclusions: We identified the preoperative prognostic factors for OS and developed a prognostic prediction model to estimate OS in patients undergoing UFS for resectable PDAC. Our model may be useful and internally validated for predicting OS.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2072-669417182025Outcomes of Robotic Pancreatectomy in the Octogenarian: A Multicenter Retrospective Cohort Study3038ENKoseiTakagi Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYuichiroUchida Department of Surgery, Fujita Health UniversityTomokazuFuji Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakeshiTakahara Department of Surgery, Fujita Health UniversityKazuyaYasui Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakeyoshiNishiyama Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityIchiroUyama Department of Advanced Laparoscopic and Robotic Surgery, Fujita Health UniversityKoichiSuda Department of Surgery, Fujita Health UniversityToshiyoshiFujiwara Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityBackground/Objectives: Due to the increasing incidence of pancreatic and periampullary cancers with advancing age, coupled with the growing evidence supporting minimally invasive pancreatectomy, the demand for such procedures is rising. However, data on the feasibility of robotic pancreatectomy in octogenarian patients remain scant. This study aimed to investigate overall outcomes of robotic pancreatectomy and evaluate its safety and feasibility in octogenarian patients. Methods: A multicenter, retrospective study was conducted, including 380 patients who underwent robotic pancreatectomy at two high-volume centers in Japan from April 2020 to December 2024. Using prospectively collected data, we compared outcomes between younger patients (<80 years) and octogenarian patients (≥80 years). Multivariable logistic regression analyses were performed to assess the impact of age on postoperative outcomes. Results: Among the 380 patients, with a median age of 72 (interquartile range: 61–77) years, 213 underwent robotic pancreatoduodenectomy (RPD), and 167 underwent robotic distal pancreatectomy (RDP). Octogenarian patients were found to have more comorbidities and a higher incidence of malignant diseases. Octogenarians experienced significantly longer hospital stays post-RPD (22 [octogenarian; n = 36] vs. 14 [younger; n = 177] days, p < 0.001) and post-RDP (14 [n = 23] vs. 10.5 [n = 144] days, p = 0.02), yet their perioperative outcomes were comparable. Multivariable analyses indicated that age (≥80 years) was not a significant risk factor for major complications following robotic pancreatectomy (odds ratio, 1.33; 95% confidence interval, 0.59–2.84; p = 0.479). Conclusions: This multicenter study conducted at high-volume centers suggests that robotic pancreatectomy can be safely performed in carefully selected octogenarian patients.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-90322026Atezolizumab + Chemotherapy in Older Patients With Lung Cancer in Japan113ENJunichiShimizuDepartment of Thoracic Oncology, Aichi Cancer Center HospitalMakotoNishioDepartment of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer ResearchKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalAtsushiOsoegawaDepartment of Thoracic and Breast Surgery, Oita University Faculty of MedicineEikiKikuchiDepartment of Respiratory Medicine, Faculty of Medicine, Hokkaido UniversityHideharuKimuraDepartment of Respiratory Medicine, Kanazawa University HospitalYasushiGotoDepartment of Thoracic Oncology, National Cancer Center HospitalEisakuMiyauchiDepartment of Respiratory Medicine, Tohoku University HospitalHiroshigeYoshiokaDepartment of Thoracic Oncology, Kansai Medical UniversityIchiroYoshinoInternational University of Health and Welfare Narita HospitalToshihiroMisumiDepartment of Data Science, National Cancer Center Hospital EastKozoYoshimoriDepartment of Clinical Oncology, Japan Anti‐Tuberculosis Association, Fukujuji HospitalKazuhikoShibataDepartment of Medical Oncology, Kouseiren Takaoka HospitalTakeshiTsudaDivision of Respiratory Medicine, Toyama Prefectural Central HospitalMasahiroSeikeDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical SchoolTakahiroOtaDepartment of Respiratory Medicine, Kyoto City HospitalKoichiSamataChugai Pharmaceutical Co., Ltd. YukiKobayashiChugai Pharmaceutical Co., Ltd.MisaTanakaChugai Pharmaceutical Co., Ltd. AkihikoGemmaNippon Medical SchoolPivotal phase 3 trials leading to the approvals of atezolizumab─chemotherapy combinations for non-small cell and extensive-stage small cell lung cancer (NSCLC and ES-SCLC) had strict eligibility criteria. J-TAIL-2 was a prospective, observational study in Japan that evaluated atezolizumab regimens for advanced NSCLC/ES-SCLC, including patients ineligible for global trials. The primary endpoint was 12-month overall survival (OS); safety and efficacy in subgroups defined by age, ECOG PS and/or G8 score, and creatinine clearance were key secondary endpoints. As of February 3, 2023, 1217 patients were treated in clinical practice based on Japanese labeling/treatment guidelines. Patients received atezolizumab with either carboplatin and nab-paclitaxel (atezo + CnP), carboplatin/cisplatin and pemetrexed (atezo + PP), or bevacizumab and carboplatin and paclitaxel (atezo + bev + CP) in the NSCLC cohort (n = 814) or with carboplatin and etoposide (atezo + CE) in the ES-SCLC cohort (n = 403). Overall, 53.5% were ≥ 70 years old, and 11.8% had ECOG PS ≥ 2; median G8 scores were 13 (NSCLC cohort) and 12 (ES-SCLC). Patients < 70 and ≥ 70 years had similar median (m)OS and progression-free survival (mPFS) across treatment regimens. Patients with ECOG PS < 2 and G8 score ≥ median had the highest mOS/PFS vs. patients with ECOG PS ≥ 2 and G8 score<median. Patients ≥ 70 years had higher incidence of Grade ≥ 3 adverse events with atezo + CnP and atezo + PP than patients < 70 years; incidences were similar between groups for other regimens. Older vs. younger patients also had higher incidence of interstitial lung disease. Overall, these results suggest that atezolizumab-containing regimens remain effective in older patients, with no new safety signals.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-90322026Plasma Protein Analysis for Biomarker Discovery in Lung Cancer Treated With Atezolizumab Combination Therapy in J-TAIL-2113ENYasushiGotoDepartment of Thoracic Oncology, National Cancer Center HospitalMakotoNishioDepartment of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer ResearchKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalAtsushiOsoegawaDepartment of Thoracic and Breast Surgery, Oita University Faculty of MedicineEikiKikuchiDepartment of Respiratory Medicine, Faculty of Medicine, Hokkaido UniversityHideharuKimuraDepartment of Respiratory Medicine, Kanazawa University HospitalJunichiShimizuDepartment of Thoracic Oncology, Aichi Cancer Center HospitalEisakuMiyauchiDepartment of Respiratory Medicine, Tohoku University HospitalHiroshigeYoshiokaDepartment of Thoracic Oncology, Kansai Medical UniversityIchiroYoshinoDepartment of Thoracic Surgery, International University of Health and Welfare Narita HospitalToshihiroMisumiDepartment of Data Science, National Cancer Center Hospital EastYasutakaWatanabeDepartment of Thoracic Oncology, Saitama Cancer CenterNobuyukiKatakamiDepartment of Pulmonary Medicine and Medical Oncology Takarazuka City Hospital Takarazuka JapanAkiraKisoharaDepartment of Respiratory Medicine, Kasukabe Medical CenterMasafumiYamaguchiDepartment of Thoracic Oncology, NHO Kyushu Cancer CenterHirotakaKurokiChugai Pharmaceutical Co., Ltd.MasamichiSugimotoChugai Pharmaceutical Co., Ltd.HisaoAshimuraChugai Pharmaceutical Co., Ltd.MisaTanakaChugai Pharmaceutical Co., Ltd.AkihikoGemmaNippon Medical SchoolJ-TAIL-2 evaluated the efficacy and safety of atezolizumab, an anti–programmed death-ligand 1 (PD-L1), plus chemotherapy in patients with non-small cell lung cancer (NSCLC) and extensive-stage small cell lung cancer (ES-SCLC) in Japanese clinical practice, demonstrating comparable outcomes to those in the corresponding Phase 3 trials. Although PD-L1 expression is predictive of atezolizumab efficacy in some settings, additional minimally invasive, blood-based biomarkers are needed. This exploratory biomarker study included 359 J-TAIL-2 patients. The NSCLC cohort received atezolizumab combined with carboplatin and nab-paclitaxel (CnP, n = 42), cisplatin/carboplatin and pemetrexed (n = 72), or bevacizumab plus carboplatin and paclitaxel (bev + CP, n = 135). The ES-SCLC cohort received atezolizumab plus carboplatin and etoposide (n = 100). Approximately 560 cancer- or immune-related proteins were evaluated using the Proximity Extension Assay from blood plasma collected at three timepoints: baseline, before the second atezolizumab dose, and at the onset of immune-related adverse events (irAEs). Protein-wise comparisons were made to evaluate significant changes (P < 0.05 and > 0.5 log2 fold change) and linked to clinical outcomes reported in J-TAIL-2. IL-6, MUC-16, and KRT-19 were associated with shorter progression-free survival across multiple regimens. Granzyme A and B, immune activation markers, were elevated in responders who received atezolizumab + CnP and atezolizumab + bev + CP. High levels of baseline immune stimulation proteins were associated with irAEs across regimens. Protein expression changes were varied and regimen-dependent in subgroup analyses including older patients and those with EGFR-mutant tumors. These data warrant further investigation across different cancer types and atezolizumab-containing regimens to determine their relevance to efficacy and irAE occurrence of atezolizumab combination therapy.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0012-1592684-52026Computer‐Aided Sperm Analysis Protocol for Evaluating Sperm Motility in Japanese Medakae70061ENMiwaKuroyanagiDepartment of Advanced Aquaculture Science, Faculty of Marine Bioscience and Technology, Fukui Prefectural UniversitySatoshiAnsaiUshimado Marine Institute, Faculty of Science, Okayama UniversityKeigoOkamotoLaboratory of Aquatic Molecular Developmental Biology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu UniversityAiKatoInteruniversity Bio-Backup Project Center, National Institute for Basic Biology (NIBB)ToukoYamazakiLaboratory of Bioresources, National Institutes of Natural SciencesYasuhiroKameiOptics and Bioimaging Facility, NIBBEijiWatanabeBasic Biology Program, Graduate University for Advanced Studies (SOKENDAI)KiyoshiNaruseLaboratory of Bioresources, National Institutes of Natural SciencesYukikoOginoLaboratory of Aquatic Molecular Developmental Biology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu UniversityChanges in sperm motility can serve as an early indicator of reproductive effects caused by environmental chemicals or genetic perturbations. However, sperm motility is highly sensitive to external factors such as osmolarity, ionic composition, and the timing of measurement after activation, making it challenging to obtain consistent and reproducible measurements. Here, we present a standardized protocol for assessing sperm motility in Japanese medaka (Oryzias latipes) using a sperm motility analysis system (SMAS), an application for computer-aided sperm motility analysis (CASA). This protocol details the procedures for sperm collection, activation, and quantitative motility assessment, with particular focus on changes in the percentage of motile sperm post activation and the effects of sperm cryopreservation. We demonstrate time-dependent declines in sperm motility and velocity, and highlight the importance of early post-activation measurements to accurately capture peak motility. Notably, cryopreservation significantly accelerated the decline in sperm motility rate without affecting the initial proportion of motile sperm. To enable reliable comparisons among experimental groups, we recommend standardizing the initiation time after sperm activation by using CASA, and show that measurements should be initiated within 1 min after activation to obtain consistent and reliable data. This standardized SMAS-based protocol provides a robust and reproducible framework for sperm motility analysis in medaka and will be valuable not only for studies in reproductive biology, toxicology, and environmental risk assessment but also for applied research, such as breeding of aquacultural fishes.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2077-038315102026Exploratory Analysis of Serum IGF-I Levels and Symptom Trajectories in Long COVID During the Omicron Period3702ENAtsuhitoSuyamaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroNakanoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazukiTokumasuDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasueSakuradaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuiMatsudaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiHondaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshiakiSoejimaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruHasegawaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyosukeTakaseDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeOmuraDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiOguniDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeigoUedaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Although several risk factors have been reported for long COVID (LC), reliable biomarkers for this illness remain lacking. Insulin-like growth factor (IGF)-I, a major mediator of growth hormones, plays an important role in metabolism, neuroprotection, and systemic homeostasis, and therefore may be useful in predicting the severity and prognosis of LC. Methods: This study included patients who visited a specialized clinic for long COVID between 2022 and 2025 during the Omicron period and had serum IGF-I measurements taken. IGF-I levels were expressed as age- and sex-adjusted standard deviation scores (IGF-I SD), and patients were classified into low (SD < −1.0), normal (−1.0 ≤ SD < 1.0), and high (SD ≥ 1.0) groups. Clinical characteristics, patient-reported outcomes, laboratory data, and follow-up duration were analyzed. Results: A total of 811 patients were included (median 42 years; 52.5% female). Compared with the normal group, the low-IGF-I group exhibited higher fatigue (FAS: 37.0 vs. 34.0; p < 0.05) and depressive (SDS: 50.0 vs. 49.0; p < 0.05) status. Multivariable linear regression analyses identified lower IGF-I SD as independently associated with higher scores of both FAS and SDS. IGF-I SD values showed negative correlations with ferritin (ρ = −0.125, p < 0.05) and TSH (ρ = −0.202, p < 0.01) and positive correlations with albumin (ρ = 0.227, p < 0.01) and FT4 (ρ = 0.165, p < 0.01). Among the 237 patients who completed follow-up, the median duration from the initial visit to recovery tended to be longer in the low-IGF-I group (221 days) compared with the normal (191 days) and high (109 days) groups, although these differences were not statistically significant overall. In patients aged < 50 years, the low-IGF-I group showed a relatively longer follow-up duration (p < 0.05). Furthermore, the low-IGF-I group had a longer time to recovery compared to the high-IGF-I group (p < 0.05), and this difference was more pronounced in patients under 50 years of age, with significant differences observed among the three IGF-I groups. Conclusions: Lower IGF-I levels in LC may be associated with greater fatigue and depressive symptoms and longer recovery time, particularly in younger patients. Further studies are needed to clarify the clinical significance of these findings.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama1663-9812172026Hochuekkito attenuates anxiety-like behavior associated with pulmonary inflammation induced by intratracheal lipopolysaccharides in mice1774957ENYasuhisaIzushiDepartment of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu UniversitySoichiroUshioDepartment of Pharmaceutical Sciences for Health Crisis Management, Faculty of Pharmaceutical Sciences, Fukuoka UniversityTeppeiUedaDepartment of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu UniversityYuichiTasakaLaboratory of Clinical Pharmacy, School of Pharmacy, Shujitsu UniversityIkukoMiyazakiDepartment of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasatoAsanumaDepartment of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshihisaKitamuraDepartment of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu UniversityIntroduction: We have previously demonstrated that intratracheal lipopolysaccharide (LPS) injection induces significant pulmonary inflammation accompanied by hippocampal microglial activation, indicative of neuroinflammation. Hochuekkito (HET) is a traditional Japanese herbal medicine used to treat various conditions, including mental disorders and physical weakness. We have previously reported that HET ameliorates anxiety-like behaviors induced by intraperitoneal LPS injections in mice. However, its anxiolytic effects on anxiety-like behaviors due to pulmonary inflammation remain poorly understood. Therefore, in the present study, we aimed to investigate the effects of HET on anxiety-like behaviors induced by intratracheal LPS injection in mice.<br>
Methods: Mice received HET (1.0 g/kg) once daily for 2 weeks through oral gavage prior to LPS treatment. The light-dark box test was conducted 24 h following LPS injection to assess anxiety-like behaviors. Diazepam, a clinically used anxiolytic, served as a positive control. The lung wet-to-dry weight ratio was determined, and the concentrations of interleukin-6 (IL-6) in the lungs and serum were assessed.<br>
Results: Repeated administration of HET prevented the development of anxiety-like behaviors and reduced serum IL-6 concentrations and hippocampal Il6 mRNA expression levels in LPS-treated mice. Diazepam failed to exert significant effects in LPS-treated mice, whereas HET remained effective under inflammatory conditions. Moreover, LPS injections significantly increased the number of Iba-1-immunoreactive microglial cells in the CA1 region of the hippocampus, whereas this effect was suppressed by treatment with HET. In the bronchoalveolar lavage fluid (BALF), the LPS-induced increase in white blood cell count was significantly reduced by treatment with HET. Furthermore, HET alleviated LPS-induced pulmonary inflammation, as evidenced by decreased lung wet-to-dry weight ratios.<br>
Conclusion: This study suggests that inflammation induced by intratracheal LPS injection contributes to anxiety-like behaviors in mice and that IL-6 may play a key role in linking peripheral inflammation to neuroinflammatory responses. The anxiolytic effects of HET appear to be associated, at least in part, with the suppression of IL-6 elevation in both the periphery and the hippocampus, along with attenuation of microglial activation. Our findings suggest that HET may serve as a potential therapeutic agent for anxiety-like behaviors associated with pulmonary inflammation.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0039-60601952026Biliverdin supplementation in perfusate and preservation solution attenuates ischemia-reperfusion injury in a rat donation-after-circulatory-death heart transplantation model110231ENKoheiTokiokaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTsuyoshiNojimaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroHirayamaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiHongoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakafumiObaraDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiAgetaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuroIgawaDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyukiAokageBiological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and GerontologyKoheiTsukaharaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Heart transplantation faces a persistent donor shortage; therefore, hearts from donation after circulatory death have become a feasible option despite unavoidable warm ischemia and subsequent ischemia-reperfusion injury. Biliverdin, an endogenous bile pigment with strong antioxidant and anti-inflammatory properties, has shown protective effects against ischemia-reperfusion injury in several organ transplantation models. Whether biliverdin attenuates warm ischemic injury in donation after circulatory death heart transplantation remains unclear. This study evaluated biliverdin supplementation in the perfusate and preservation solution in a rat donation after circulatory death model.<br>
Methods: Circulatory death was induced under deep anesthesia, and warm ischemia was maintained for 18 minutes, including the mandatory 5-minute stand-off period. Donor hearts were then flushed and subsequently cold-stored in the same biliverdin-supplemented extracellular-type trehalose–containing Kyoto solution, whereas control grafts received extracellular-type trehalose–containing Kyoto without biliverdin at both stages before heterotopic transplantation. Grafts were assessed at 3 and 24 hours after reperfusion (n = 6 per group). Evaluations included early graft recovery, myocardial injury markers, histological and ultrastructural changes, and inflammatory and stress-response gene expression.<br>
Results: Biliverdin significantly improved early graft recovery, shortening reanimation time and increasing left ventricular fractional shortening at 24 hours. Serum troponin I levels were lower in biliverdin-treated grafts. Biliverdin also reduced histological injury and inflammatory cell infiltration. Ultrastructural analysis showed preserved mitochondrial architecture and ultrastructural integrity. Early proinflammatory gene expression was suppressed.<br>
Conclusion: Biliverdin supplementation in the perfusate and preservation solution attenuates ischemia-reperfusion injury in the experimental rat donation after circulatory death heart transplantation model. These findings provide proof of concept for further mechanistic and translational evaluation of biliverdin for myocardial protection in donation after circulatory death.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0919-81723352026Comparative Efficacy of First-Line Immune Checkpoint Inhibitor-Based Combination Therapies in Patients With Sarcomatoid Renal Cell Carcinoma: A Japanese Multicenter Cohort Studye70494ENKeitaTamuraDepartment of Urology, Hamamatsu University School of MedicineYutoMatsushitaDepartment of Urology, Hamamatsu University School of MedicineHiromitsuWatanabeDepartment of Urology, Hamamatsu University School of MedicineTakafumiYanagisawaDepartment of Urology, Jikei University School of MedicineKeiichiroMoriDepartment of Urology, Jikei University School of MedicineHirofumiMorinakaDepartment of Urology, Kawasaki Medical SchoolKensukeBekkuDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShingoToyodaDepartment of Urology, Kindai University Faculty of MedicineTakuhisaNukayaDepartment of Urology, Fujita-Health University School of MedicineRyoichiMaenosonoDepartment of Urology, Osaka Medical and Pharmaceutical UniversityKazumasaKomuraDepartment of Urology, Kawasaki Medical SchoolMotooArakiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazutoshiFujitaDepartment of Urology, Kindai University Faculty of MedicineKiyoshiTakaharaDepartment of Urology, Fujita-Health University School of MedicineHaruhitoAzumaDepartment of Urology, Osaka Medical and Pharmaceutical UniversityTeruoInamotoDepartment of Urology, Hamamatsu University School of MedicineObjectives: Sarcomatoid renal cell carcinoma (sRCC) is an aggressive histological variant associated with a poor prognosis. While immune checkpoint inhibitor (ICI)-based combinations have become the standard of care, the optimal first-line regimen, specifically dual immunotherapy (IO-IO) vs. IO plus tyrosine kinase inhibitor (IO-TKI), remains controversial. We herein examined the real-world clinical outcomes of Japanese patients with sRCC.<br>
Methods: We conducted a retrospective multicenter study on 46 patients with advanced or metastatic sRCC receiving first-line ICI-based combination therapy between January 2018 and December 2024 (IO-IO: n = 18; IO-TKI: n = 28). In a comparative survival analysis, three favorable-risk patients in the IO-TKI group were excluded to align risk profiles, focusing on intermediate/poor-risk groups (n = 43). The primary endpoint was overall survival (OS).<br>
Results: In the entire cohort (n = 46), the objective response rate was numerically higher in the IO-TKI group (64.3%) than in the IO-IO group (50.0%) (p = 0.37). In the comparative analysis of intermediate/poor-risk patients (n = 43), progression-free survival (PFS) was slightly longer (p = 0.071), and OS was significantly longer (p = 0.016) in the IO-TKI group than in the IO-IO group. A multivariable analysis adjusted for IMDC risk categories showed favorable survival with the IO-TKI regimen (HR 0.37, p = 0.061).<br>
Conclusions: The present study indicates that first-line IO-TKI combination therapy represents a promising treatment option with a potential survival advantage over IO-IO therapy for Japanese patients with sRCC. However, due to the retrospective design and small sample size, reliably determining the comparative efficacy of these regimens remains challenging, and further validation is warranted.No potential conflict of interest relevant to this article was reported.Portland Press Ltd.Acta Medica Okayama0144-84634662026Tubulogenesis of bovine uterine glands by epidermal growth factor and collagen I in 3D culture systemsBSR20260010ENYosukeSuginoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityReiIchikawaGraduate School of Bioagricultural Sciences, Nagoya UniversityShuichiMatsuyamaGraduate School of Bioagricultural Sciences, Nagoya UniversityYukiYamamotoDepartment of Veterinary Medicine, Tokyo University of Agriculture and TechnologyKoheiKawanoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKojiKimuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityUterine glands are endometrial exocrine epithelia that support early embryo development. Their secretions are particularly essential for conceptus elongation in cattle. Uterine glands develop from the luminal epithelium and elongate into the stromal layer toward the myometrium. This process is regulated by growth factors, WNT proteins, and the surrounding extracellular matrix (ECM); however, the precise mechanisms that govern bovine uterine gland morphogenesis remain unclear. In this study, we determined how these signaling factors and ECM components affect the tubular formation of bovine uterine gland fragments in 3D culture systems. Uterine gland fragments were enzymatically isolated from bovine endometria and 3D-cultured in Matrigel with or without growth factors (EGF, FGF1, FGF2, FGF7, FGF10, and IGF-1) and WNT (WNT3A, WNT5A, and WNT7A) proteins. Of these, only EGF stimulated the elongation of uterine gland fragments and eventually induced the formation of uterine gland-like structures. EGF-induced tubulogenesis was accompanied by a rapid increase in cell proliferation and alterations in cell–ECM interactions. The supplementation of collagen I with Matrigel further promoted the elongation of the tubular structures. Although the addition of collagen I did not alter the gene expression profiles of the uterine gland-like structures, the integrin-ROCK pathway contributed to the collagen-induced enhancement of elongation. Our findings clarified that EGF and collagen I, but not FGFs, IGF-1, or WNTs, are key regulators for the tubular formation of 3D-cultured bovine uterine gland fragments. This 3D culture system provides a new platform to examine the cellular and molecular mechanisms underlying bovine uterine gland morphogenesis.No potential conflict of interest relevant to this article was reported.Institute of Electrical and Electronics Engineers (IEEE)Acta Medica Okayama2169-3536142026Construction of a Lightweight Simulation Environment Based on Topological Mapping73466 73478ENYukinagaKatoGraduate School of Environmental, Life, Natural Science, and Technology, Okayama UniversityYuichiroTodaFaculty of Environmental, Life, Natural Science, and Technology, Okayama UniversityTakayukiMatsunoFaculty of Environmental, Life, Natural Science, and Technology, Okayama UniversityAutonomous mobile robots require safe and efficient environmental representations for traversability-aware navigation and learning. In particular, self-learning of traversability from real-world driving experience can require robots to operate near the limits of their mobility, which introduces physical risks such as falls, malfunctions, or hardware damage. To provide a safer complementary environment for such validation and future learning, this paper proposes ATC-Mesh. This framework constructs a lightweight, simulation-ready mesh environment from the topological map produced by Adaptive Resonance Theory-based Topological Clustering with Different Topologies (ATC-DT) using high-density LiDAR point clouds. Unlike standard mesh reconstruction methods that directly process dense point clouds, ATC-Mesh generates a compact mesh from the node–edge structure of the topological map while preserving traversability attributes associated with the topological map. Experiments using two real-world LiDAR datasets show that ATC-Mesh achieves competitive mesh-construction quality compared with standard baseline methods while reducing construction time and mesh size. Gazebo experiments further show that the generated meshes can support waypoint-based navigation with a low simulation load.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0753-33221942026Elucidation of mechanisms underlying the therapeutic effects of cordycepin on pulmonary hypertension, with a focus on cell senescence and gut microbiota118923ENGaopengLiDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa UniversityZhixinZhaoInner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural UniversityMitsuhiroMachitaniDivision of Cancer Stem Cell, National Cancer Center Research InstituteRyouIshikawaDepartment of Diagnostic Pathology, Kagawa University HospitalKaoriIshikawaDepartment of General Medicine, Kagawa University HospitalNaoyaYokotaDepartment of General Thoracic Surgery, Faculty of Medicine, Kagawa UniversityReijiHabaDepartment of Diagnostic Pathology, Kagawa University HospitalKazufumiNakamuraCenter for Advanced Heart Failure, Okayama University HospitalZhihongSunInner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural UniversityLin-HaiKuraharaDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa UniversityKatsuyaHiranoDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa UniversityIntroduction: Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder characterized by excessive pulmonary vascular remodeling and aberrant proliferation of pulmonary artery smooth muscle cells (PASMCs). Emerging evidence suggests that gut microbiota dysbiosis contributes to PH development. Cordycepin, a natural adenosine analogue derived from Cordyceps militaris, has demonstrated antiproliferative and microbiota-modulating properties; however, its mechanism of action in PH remains unclear.<br>
Objective: Elucidate the mechanisms underlying the therapeutic effects of cordycepin on PH, focusing on cellular senescence and gut microbiota.<br>
Methods: The effects of cordycepin on PH pathology were investigated by transcriptome analysis of PASMCs from patients, and metagenomic analysis of rodent PH models. Cellular senescence was analyzed in lung tissue from p16Ink4a-CreERT2 reporter mice and in rat bone marrow-derived macrophages (BMDMs).<br>
Results: RNA sequencing analysis revealed activation of p53 signaling by cordycepin in PASMCs. Cordycepin suppressed CDK1 expression and TERT phosphorylation at threonine 249. It ameliorated vascular and cardiac remodeling in PH rat and mouse models. Cordycepin induced M1-like macrophage senescence in p16 Ink4a reporter mice lungs and rat BMDMs. Cordycepin significantly reshaped the gut microbiota, increasing beneficial genera (e.g. Alistipes and Acetatifactor) and reducing proinflammatory taxa (e.g., Ruminococcus), with modulating key metabolic pathways, including short-chain fatty acid, tryptophan, and vitamin K2 metabolism.<br>
Conclusion: Cordycepin exerts multi-target therapeutic effects in PH by inhibiting PASMC proliferation via the p53–CDK1/pTERT axis, modulating gut microbiota-linked immunometabolism and induces proinflammatory macrophage senescence. These findings support cordycepin as a promising candidate for PH therapies targeting the vascular, immune, and gut–lung axes.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0040-40391832026Photochemical oxidative synthesis of carboxylic acids from aldehydes or alcohols with water via CH bromination156163ENMohamed R.El-kholanyGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAtsuyaMiyamotoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMorganeFalconeGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHiroyoshiTakamuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityIsaoKadotaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKentaTanakaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThe photoinduced oxidation of aldehydes or alcohols with water to give the corresponding carboxylic acids is described. This photochemical carboxylation proceeds via the in-situ generation of acyl-bromide intermediates upon irradiation with purple or UV LED light; these intermediates subsequently react with water to give the desired carboxylic acids. This mild photochemical reaction affords diverse carboxylic acids without peroxide generation or the need to use transition-metal catalysts and a stoichiometric amount of base, highlighting its potential utility for the synthesis of natural products and bioactive compounds.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1349-00796812026Roles of the aryl hydrocarbon receptor and its ligands in osteoclast differentiation and temporomandibular joint osteoarthritis100726ENTakashiIzawaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIslamy RahmaHutamiDepartment of Orthodontics, Universitas Islam Sultan AgungYuriYoshikawaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityGohjiKozakiDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusakuHamadaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiNambaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMisaTaguchiDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJiaminChenDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJanvierHabumugishaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiKamiokaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays an essential role in skeletal homeostasis. Increasing evidence indicates that AhR critically regulates osteoclast differentiation and activity, thereby influencing bone mass, bone resorption, and susceptibility to skeletal diseases. Although AhR has also been implicated in osteoblast-lineage cells, its regulatory roles in osteoclasts and immune cells are less well understood but are increasingly recognized as central to bone remodeling. In particular, AhR signaling modulates immune cell subsets relevant to bone metabolism and governs the differentiation of bone marrow-derived macrophages into osteoclasts.<br>
Highlight: This review summarizes the recent findings regarding the regulation of osteoclast differentiation by AhR and its ligands under both physiological and pathological conditions. Special emphasis is placed on the interaction between AhR and the RANKL signaling axis in osteoclasts, as well as on how exogenous and endogenous ligands, including benzo[a]pyrene (B[a]P) and 6-formylindolo[3,2-b]carbazole (FICZ), modulate bone resorption and subchondral bone remodeling in temporomandibular joint osteoarthritis. Furthermore, the role of macrophages as osteoclast progenitors and immunomodulators has been highlighted, positioning AhR as a critical intermediary that links environmental exposure, inflammation, and skeletal metabolism.<br>
Conclusion: In this review, we outlined the diverse functions of AhR signaling and its ligands in oral and temporomandibular joint osteoarthritis. AhR plays a central role in bone remodeling. The harmful exogenous ligand B[a]P generally promotes bone loss, whereas the endogenous ligand FICZ exerts protective actions. These insights highlight AhR as a key regulatory switch linking the skeletal and immune systems and as a promising therapeutic target for bone-destructive disorders.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-72571932026Successful management and 10-year survival of a rectal neuroendocrine tumor with rare systemic metastases via a non-portal venous pathway491498ENShigeruHoriguchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalAkihiroMatsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalHiroyukiTerasawaDepartment of Gastroenterology and Hepatology, Okayama University HospitalYukiFujiiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKoseiTakagiDepartment of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakashiKuiseDepartment of Gastroenterological Surgery, Okayama Red Cross HospitalTakehiroTanakaDepartment of Pathology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University HospitalMetastatic neuroendocrine tumors (NETs) typically involve the liver and lymph nodes. Metastases in the orbit, heart, and ovary are rare and present unique clinical challenges. We report a woman who was 70 years old at the time of initial presentation with liver metastases from a rectal neuroendocrine tumor. Following a right hepatectomy for liver metastases, she remained free of hepatic recurrence for 10 years. Notably, four years after the right hepatectomy, she developed new metastases in the left orbit, right ventricle, and left ovary, with diplopia as the sole clinical symptom. This clinical course suggests a distinct metastatic pathway associated with the lower rectum that bypasses the portal circulation, consistent with the dual drainage system of the rectal region. Management involved a strategic multimodal approach that includes systemic therapy with everolimus and lanreotide as well as targeted surgical resectioning of the cardiac and ovarian lesions. The orbital lesion achieved a complete response through systemic therapy alone, preserving visual function. Currently, 10 years after the initial treatment, the patient maintains an excellent performance status (ECOG PS 0) while receiving peptide receptor radionuclide therapy (PRRT). This case demonstrates that recognizing atypical metastatic pathways and employing strategic multimodal therapies can achieve long-term survival and functional preservation in rectal NETs.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2090-6528202612026Selective ARID1A Loss Restricted to the Undifferentiated Component of a Mismatch Repair‐Deficient Gastric Carcinoma: A Case Report8863202ENRikaOmoteDepartment of Diagnostic Pathology, NHO Fukuyama Medical CenterRyosukeHamanoDepartment of Surgery, NHO Fukuyama Medical CenterShinyaOtsukaDepartment of Surgery, NHO Fukuyama Medical CenterTakehiroTanakaDepartment of Pathology, Okayama University HospitalHiroyukiYanaiDepartment of Pathology, Okayama University HospitalMismatch repair-deficient (dMMR) gastric carcinomas often harbor ARID1A alteration, but a sharply demarcated undifferentiated/rhabdoid component with selective ARID1A loss is uncommon and may create a diagnostic dilemma. An 80-year-old man underwent esophagogastroduodenoscopy for anemia, which revealed a circumferential Borrmann Type 3 lesion in the gastric body, and distal gastrectomy was performed. Histologically, the tumor was composed predominantly of undifferentiated carcinoma with focal rhabdoid features and a minute well-differentiated adenocarcinoma component, with an abrupt transition between the two. Immunohistochemistry showed loss of nuclear MLH1 and PMS2 in both components, whereas loss of ARID1A expression was confined to the undifferentiated component; SMARCB1 (INI1), SMARCA2 (BRM), and SMARCA4 (BRG1) were retained. EBER in situ hybridization was negative. Because gene-level testing, MSI testing, and MLH1 promoter methylation analysis were not performed, the molecular basis of the dMMR phenotype and ARID1A loss could not be determined. The restricted scope of molecular testing limits the ability to draw broad or generalizable conclusions and to fully establish clinicopathological correlations. The value of this report is, therefore, not mechanistic proof but recognition of a practical morphologic-immunophenotypic observation: When a gastric carcinoma shows a sharply demarcated shift from differentiated to undifferentiated/rhabdoid morphology, dMMR should be considered, and selective ARID1A loss in the undifferentiated component may be associated with dedifferentiation. These findings should be interpreted with caution as preliminary, hypothesis-generating observations that require validation in larger studies with more extensive molecular profiling.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1340-68683342026Differences in drug efficacy and prognosis between primary and metastatic sites for de novo stage IV breast cancer: an exploratory analysis of a phase III trial, JCOG1017829838ENKiyoTanakaDepartment of Breast Surgery, Toranomon HospitalAkihikoShimomuraDepartment of Breast and Medical Oncology, National Center for Global Health and MedicineMakotoIshitobiDepartment of Breast Surgery, Osaka Habikino Medical CenterTakashiYamanakaDepartment of Breast Surgery, Kanagawa Cancer CenterTakahiroTsukiokiDepartment of Breast and Endocrine Surgery, Okayama University HospitalHirojiIwataDepartment of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical SciencesFumikataHaraDepartment of Breast Oncology, Aichi Cancer CenterTomomiFujisawaDepartment of Breast Oncology, Gunma Prefectural Cancer CenterKeitaSasakiClinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalRyoSadachiClinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalRikuKajikawaClinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalTakehikoSakaiDepartment of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer ResearchYasuakiSagaraDepartment of Breast Surgery, Sagara HospitalHideoShigematsuDepartment of Breast Surgery, Hiroshima University HospitalYukinoriOzakiDepartment of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer ResearchKazukiNozawaDepartment of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical SciencesKazukiSudoDepartment of Medical Oncology, National Cancer Center HospitalYoichiNaitoDepartment of General Internal Medicine, National Cancer Center Hospital EastKaoriTerataDepartment of Breast and Endocrine Surgery, Akita University HospitalToshiyukiIshibaDepartment of Breast Surgery, Institute of Science Tokyo HospitalHaruhikoFukudaClinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalTadahikoShienDepartment of Breast and Endocrine Surgery, Okayama University HospitalBackground Breast cancer is a highly heterogeneous disease, with biological factors like estrogen receptor, progesterone receptor, and HER2 receptor differing between primary and metastatic sites, potentially affecting treatment response.<br>
This exploratory analysis aims to differentiate drug efficacy and long-term prognosis between these sites in stage IV breast cancer.<br>
Methods Patients from JCOG1017, a phase III trial evaluating the role of primary tumor resection, who received primary systemic therapy (PST) were evaluated at three months. In this analysis, treatment response was assessed separately in primary and metastatic sites. Patients were categorized into four groups: discordant I (primary non-PD, metastatic PD), concordant I (both PD), discordant II (primary PD, metastatic non-PD), and concordant II (both non-PD).<br>
Results Among 271 patients, overall discordance proportion of treatment response between primary and metastatic sites was 25.1%. Group distribution was 24.7% (discordant I), 9.6% (concordant I), 0.4% (discordant II), and 65.3% (concordant II). Discordance was more frequent in luminal (28.9%), triple-negative (25.0%), and luminal-HER2 (22.0%) subtypes than in HER2-enriched (11.1%). Survival analysis showed prognostic differences: concordant II, with both sites non-PD, demonstrated the most favorable outcome compared with discordant I (HR 0.556; 95% confidence interval, 0.396–0.782).<br>
Conclusions One-fourth of patients exhibited discordant responses between primary and metastatic sites in early treatment phases. These discrepancies were associated with survival differences, emphasizing the importance of evaluating both primary and metastatic lesions when assessing efficacy and determining treatment strategies in de novo stage IV breast cancer.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0007-104820862026Decreased renal function predicts severe cytokine release syndrome after CAR-T-cell therapy for large B-cell lymphoma21242133ENYasuyukiAraiDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityTomoyasuJoDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityTakayukiSatoDepartment of Hematology and Oncology, Kurashiki Central HospitalMasatoshiSakuraiDivision of Hematology, Department of Medicine, Keio University School of MedicineDaisukeKajiDepartment of Hematology, Toranomon HospitalToshioKitawakiDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityKazuyukiShimadaDepartment of Hematology and Oncology, Nagoya University Graduate School of MedicineTatsuShimoyamaDivision of Clinical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalSatoshiYoshiharaDepartment of Hematology, Hyogo Medical University HospitalShinichiMakitaDepartment of Hematology, National Cancer Center HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalGoYamamotoDepartment of Hematology, Toranomon HospitalKeisukeKataokaDivision of Hematology, Department of Medicine, Keio University School of MedicineEmikoSakaidaDepartment of Hematology, Chiba University HospitalHidekiGotoDepartment of Hematology, Hokkaido University HospitalYasuhiroNakashimaDepartment of Hematology, Osaka Metropolitan University HospitalAkiyoYoshidaDepartment of Hematology, Kanazawa University HospitalYoshihiroUmezawaDepartment of Hematology, Institute of Science Tokyo HospitalHaryoonKimDivision of Hematology, Department of Medicine, Keio University School of MedicineMotohiroKatoDepartment of Pediatrics, The University of TokyoYoshikoAtsutaJapanese Data Center for Hematopoietic Cell TransplantationKojiKatoHematology, Oncology and Cardiovascular Medicine, Kyushu University HospitalCytokine release syndrome (CRS) remains a major toxicity of chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL), and robust pre-infusion predictors are needed for risk-adapted management. We retrospectively analysed LBCL patients in the Japanese nationwide registry who underwent CD19 CAR-T-cell therapy between 2019 and 2024. Among 900 patients (median age 62 years), cumulative incidences of CRS within 30 days after infusion were 75.0% for any grade, 20.8% for grade ≥ 2 and 14.0% for grade ≥ 3. In multivariable analysis, lower estimated glomerular filtration rate (eGFR) (adjusted hazard ratio [aHR] 1.108 per 10 mL/min per 1.73 m2 decrease; 95% confidence interval [CI] 1.015–1.209; p = 0.022), higher ferritin (aHR 1.006 per 100 ng/mL; 95% CI 1.001–1.010; p = 0.016), C-reactive protein (CRP) (aHR 1.142 per mg/dL; 95% CI 1.091–1.195; p < 0.001) and lactate dehydrogenase (LDH) (aHR 1.073 per 100 U/L; 95% CI 1.008–1.142; p = 0.028) independently predicted grade ≥ 2 CRS. We then built a four-factor CRS pre-infusion risk evaluation model, cytokine release syndrome-pre-infusion risk evaluation (CRS-PRE), that stratified grade ≥ 2 CRS risk into low, intermediate and high groups with incidences of 2.8%, 26.0% and 50.0% respectively. Decreased eGFR, a surrogate of host renal reserve, with elevated ferritin, CRP and LDH emerged as predictors of high-grade CRS. The CRS-PRE may facilitate risk-adapted monitoring and intervention in clinical practice.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0006-291X8272026Staphylococcus aureus activates dendrite elongation in dendritic cells154001ENKaiKobataGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKazuyukiFurutaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYukiIkeyaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYoheiChishakiGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKazuyaIshikawaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityChikaraKaitoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityDendritic cells (DCs) are thought to extend dendrites to enhance the efficiency of antigen uptake and presentation. We previously reported that short-chain fatty acids (SCFAs), such as butyrate and valerate, promote dendrite extension in DCs. In this study, we found that the human pathogen Staphylococcus aureus also induces dendrite extension in DCs and investigated the underlying mechanisms. Dendrite extension in DC2.4 cells was induced not only by live S. aureus but also by heat-killed bacteria and purified peptidoglycan (PGN). DC2.4 cells lacking TLR2 or its adaptor protein MyD88 extend dendrites in response to SCFAs, but failed to extend dendrites in response to S. aureus. Furthermore, inhibitors of ERK, PI3K, and Cdc42 suppressed dendrite extension triggered by S. aureus. Co-stimulation with S. aureus and butyrate enhanced dendrite extension beyond either stimulus alone. DC2.4 cells co-stimulated with S. aureus and butyrate also showed increased uptake of insoluble beads and, upon co-culture with T cells, induced elevated production of IL-17 and IL-10 by T cells. Collectively, these findings suggest that S. aureus activates ERK/PI3K/Cdc42 signaling through TLR2 recognition of PGN to drive dendrite extension in DCs. In addition, S. aureus promotes dendrite extension in DCs via a pathway distinct from that of SCFAs, thereby acting cooperatively with SCFAs to enhance immune responses.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama0032-07812026Cytokinin receptor AHK3 influences leaf size by modulating trans-zeatin-type cytokinin levels in xylempcag052ENKotaMondenInstitute of Plant Science and Resources, Okayama UniversityTakamasaSuzukiCollege of Bioscience and Biotechnology, Chubu UniversityMikikoKojimaRIKEN Center for Sustainable Resource ScienceYumikoTakebayashiRIKEN Center for Sustainable Resource ScienceTakehiroKamiyaGraduate School of Agricultural and Life Sciences, Tokyo UniversityTakatoshiKibaInstitute of Plant Science and Resources, Okayama UniversityHitoshiSakakibaraRIKEN Center for Sustainable Resource ScienceTsuyoshiNakagawaDepartment of Molecular and Functional Genomics, Interdisciplinary Centerfor Science Research, Shimane UniversityTakushiHachiyaDepartment of Molecular and Functional Genomics, Interdisciplinary Centerfor Science Research, Shimane UniversityTrans-zeatin (tZ)-type cytokinins (CKs) are predominantly synthesized in roots, transported to the shoot via the xylem, and coordinate diverse physiological processes in aerial organs. Within this process, the regulation of CK biosynthesis by nitrate signaling via nodule inception-like protein 7, as well as the loading of tZ-type CKs into the xylem by ATP-binding cassette transporter G14, have been well studied. However, the roles of other components remain unclear. Here, we show that CK perception and degradation in roots, as mediated by Arabidopsis histidine kinase 3 (AHK3) and CK oxidase/dehydrogenase 4 (CKX4), modulate root-to-shoot tZ-type cytokinin transport in response to nitrate. Grafting experiments demonstrate that root-specific AHK3 deficiency systemically increases the leaf blade area through long-distance signals of root-derived tZ-type CKs, perceived by shoot-expressed AHK3. Transcriptome and hormonome analyses reveal that root-specific AHK3 deficiency reduces CKX4 expression in roots, elevating tZ-type CK levels in roots and xylem sap and thereby enhancing the leaf CK response. Transfer experiments manipulating root nitrate levels show that root-specific AHK3 deficiency promotes the leaf blade area in a manner dependent on both nitrate and root-derived tZ-type CK signaling. Moreover, both nitrate signals and root-expressed AHK3 are required for maximal CKX4 induction in roots, and root-specific CKX4 deficiency enhances the leaf blade area in a nitrate-dependent manner. These findings reveal a novel mechanism in which an AHK3–CKX4 module governs xylem transport of tZ-type CKs, fine-tuning leaf size according to root nitrate status.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2072-669418102026Activation of TAS2R Signaling by Diphenidol Suppresses Tumor Growth and Remodels the Tumor Immune Microenvironment in Oral Squamous Cell Carcinoma1527ENNisrina EkayaniNasrunDivision of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of HokkaidoAkihikoTanimuraDivision of Pharmacology, Department of Oral Biology, School of Dentistry, Health Sciences University of HokkaidoKokiYoshidaDivision of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of HokkaidoOsamuUeharaDivision of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of HokkaidoYukiKunisadaDepartment of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKiyofumiTakabatakeDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkihiroHosoyaDivision of Craniofacial Development and Tissue Biology, Tohoku University Graduate School of DentistryHiroakiTakebeDivision of Histology, Department of Oral Biology, School of Dentistry, Health Sciences University of HokkaidoHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihiroAbikoDivision of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of HokkaidoMuhammadRuslinDepartment of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hasanuddin UniversityTsuyoshiShimoDivision of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of HokkaidoBackground: Oral squamous cell carcinoma (OSCC) remains a clinically challenging malignancy characterized by aggressive behavior and limited therapeutic options. Bitter taste receptors (TAS2Rs), expressed across multiple tissues and cancer types, have recently emerged as regulators of tumor biology and immune responses; however, their functional significance in OSCC remains poorly understood. Methods: Immunohistochemical analysis was performed using surgically resected human tongue OSCC specimens and a tissue microarray (TMA) cohort. In parallel, four TAS2R agonists were evaluated in SCC7 cells to assess intracellular calcium responses. RNA sequencing was conducted to analyze transcriptional changes following diphenidol treatment, and functional assays, including proliferation, migration, and apoptosis analyses, were performed in vitro. Antitumor effects were further evaluated in a syngeneic SCC7 mouse model, followed by TUNEL staining and flow cytometry to assess apoptosis and immune cell infiltration. Results: TAS2R38 expression was markedly upregulated in dysplastic and invasive OSCC lesions with predominant nuclear localization and was associated with histological grade and clinical stage, indicating an early and sustained alteration during tumor progression. Among the agonists tested, diphenidol most strongly induced IP3-dependent intracellular Ca2+ elevation. RNA sequencing revealed upregulation of Il1rl1 and Lzts2. Functionally, diphenidol significantly suppressed SCC7 cell proliferation and migration and induced apoptosis in vitro. In vivo, diphenidol reduced tumor volume and weight and increased apoptotic activity. Flow cytometry demonstrated a marked reduction in tumor-infiltrating CD4+CD25+Foxp3+ regulatory T cells, indicating modulation of the tumor immune microenvironment. Conclusions: TAS2R activation by diphenidol suppresses tumor growth through both tumor-intrinsic mechanisms and modulation of the tumor immune microenvironment in OSCC. These findings define TAS2R-mediated calcium signaling as a novel axis linking tumor progression and immunoregulation. Given that diphenidol is a clinically approved drug with an established safety profile, our results provide a strong rationale for TAS2R-targeted drug repurposing strategies in cancer therapy.No potential conflict of interest relevant to this article was reported.Ovid Technologies (Wolters Kluwer Health)Acta Medica Okayama0090-34935462026Institutional Variability in Brain-Dead Organ Donation Processes and Practices: A Multicenter Cohort Study13191328ENTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMinejiHayakawaDepartment of Emergency Medicine, Hokkaido University HospitalShojiYokoboriDepartment of Emergency and Critical Care Medicine, Nippon Medical SchoolKeiNishiyamaDivision of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental ScienceTakahiroAtsumiDepartment of Emergency and Disaster Medicine, Hamamatsu University School of MedicineOsamuTasakiAcute and Critical Care Center, Nagasaki University HospitalJunyaTsurukiriEmergency and Critical Care Medicine, Tokyo Medical University Hachioji Medical CenterMarikoHayamizuDepartment of Emergency Medicine, Hokkaido University HospitalShimonMurahashiAcute and Critical Care Center, Nagasaki University HospitalMunehiroHayashiDepartment of Emergency and Critical Care Medicine, Japanese Red Cross Medical CenterTakeshiNishimuraDepartment of Emergency and Critical Care Medicine, Hyogo Emergency Medical CenterYukariGotoDepartment of Emergency Medicine, Nagoya Ekisaikai HospitalHiromichiNarumiyaDepartment of Emergency and Critical Care Medicine, Japanese Red Cross Kyoto Daini HospitalAtsushiMizutaniDepartment of Emergency Medicine, Hamamatsu Medical CenterMamoruMiyajimaEmergency and Critical Care Center, Nagaoka Red Cross HospitalJunyaShimazakiDepartment of Emergency and Critical Care Medicine, Kansai Medical University Medical CenterTakeshiMiuraDepartment of Emergency and Critical Care Medicine, Institute of Medicine, University of Tsukuba HospitalNozomuShimaDepartment of Emergency and Critical Care Medicine, Wakayama Medical UniversityKazukiDeuchiDivision of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental ScienceHitomiNakayasuEmergency and Critical Care Medicine, Seirei Hamamatsu General HospitalHitoshiKanoDepartment of Emergency and Critical Care Medicine, Nippon Medical SchoolTakashiYorifujiDepartment of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityJapan Comprehensive Process for End-of-Life Care and Organ Donation after Brain Death (J-RESPECT) study groupOBJECTIVES: To determine whether key institutional and clinical differences exist between highly and moderately active hospitals in Japan with respect to brain-dead organ donation practices.<br>
DESIGN: Retrospective multicenter cohort study.<br>
SETTING: Sixteen tertiary emergency and critical care centers across Japan.<br>
PATIENTS: All brain-dead organ donors from participating institutions who had at least one organ procured and transplanted between July 17, 2010, and December 31, 2023. Hospitals were categorized as highly active (≥ 14 donations) or moderately active (≤ 13 donations) during the study period.<br>
INTERVENTIONS: None.<br>
MEASUREMENTS AND MAIN RESULTS: Institutional donation practices were compared, including donor management strategies, use of vasopressors and corticosteroids, time intervals in the donation process, and frequency of multidisciplinary team meetings. A total of 204 donors were included; the median age was 47 years (interquartile range, 37–56), and 92 (45.1%) were female. Donor characteristics were similar between groups. Vasopressin was used in nearly all donors, though dosing protocols varied. Corticosteroid use was significantly higher in highly active hospitals compared with moderately active ones (58.3% vs. 38.0%; p = 0.004). Time from admission to coordinator notification was similar; however, time to family consent (median, 8 vs. 5 d; p < 0.001) and time to organ procurement (median, 12 vs. 9 d; p = 0.006) were longer in highly active hospitals. These hospitals also conducted more multidisciplinary meetings during donor management (median, 2 vs. 0; p < 0.001).<br>
CONCLUSIONS: Highly active hospitals demonstrated more intensive donor management practices, longer timeframes for key donation steps, and greater multidisciplinary engagement. Standardization of donation practices may enhance efficiency and support broader dissemination of effective institutional strategies to improve brain-dead organ donation rates in Japan.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2590-0285302026Extracellular matrix remodeling in calcific aortic valve disease: Localized enrichment of type III collagen and LTBP-4100194ENReikoKemmochiDepartment of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHarukoMiyazakiDepartment of Molecular Biology and Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiTagaNippi Research Institute of BiomatrixNaokiTakahashiLaboratory of Veterinary Anatomy, School of Veterinary Medicine, Rakuno Gakuen UniversityTakafumiWatanabeLaboratory of Veterinary Anatomy, School of Veterinary Medicine, Rakuno Gakuen UniversityKentaroIkemuraDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityTakakoSasakiDepartment of Pharmacology, Faculty of Medicine, Oita UniversityKazunoriMizunoNippi Research Institute of BiomatrixSatoshiHirohataDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityMitsuakiMatsumotoDepartment of Cardiovascular Surgery, Tsuyama Chuo HospitalToshitakaOohashiDepartment of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityCalcific aortic valve disease (CAVD) is characterized by progressive extracellular matrix (ECM) remodeling that promotes valve fibrosis and calcification. However, its molecular and structural basis remains unclear. In this study, we comprehensively analyzed ECM remodeling in human CAVD valves, focusing on collagen dynamics and key ECM-associated regulatory components. Histopathological analysis revealed fibrous layer thickening, collagen disorganization, and focal loss of the spongiosa in the CAVD group. Polarized picrosirius red staining demonstrated increased yellow-orange birefringence in the fibrotic and calcified regions, indicating altered collagen organization. Quantitative liquid chromatography–mass spectrometry analysis showed region-specific shifts toward an increased type III collagen proportion in fibrotic and calcific regions despite the reduced total collagen content in calcified areas. Collagen with improper triple-helical structure primarily accumulated around the calcified nodules, suggesting abnormal collagen turnover. Transmission electron microscopy revealed thinner and more heterogeneous collagen fibrils in lesioned regions than that in pre-lesional region. In normal valves, immunohistochemistry suggested that the hyaluronan-versican-fibrillin complex contributes to local regulation of Transforming growth factor-beta 1 (TGF-β1) activity via latent TGF-β binding proteins (LTBP); however, this regulatory structure was disrupted in CAVD. Notably, LTBP-4 showed strong, regionally restricted localization in the fibrotic and calcific regions and was positively correlated with collagen yellow-orange birefringence. Collectively, these findings indicate that CAVD is associated with a localized shift toward a structurally heterogeneous, type III collagen-enriched matrix, accompanied by collagen denaturation and abnormal accumulation of LTBP-4, highlighting ECM dysregulation as a key feature of disease progression.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama0009-26739962026Synthesis of boranils by iodide-mediated demethylative borylation and their propertiesuoag070ENKoichiMitsudoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityRyoMagataGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityEisukeSatoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTomoyaNakamuraInstitute for Chemical Research, Kyoto UniversityAtsushiWakamiyaInstitute for Chemical Research, Kyoto UniversitySeijiSugaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityBoranils, difluoroboron complexes with imine and phenoxy moieties, were synthesized by iodide-promoted demethylative borylation. The use of appropriate amounts of BF3•OEt2, Bu4NI, and Et3N enabled the highly efficient synthesis of boranils. Boranils containing heteroaromatics and highly π-extended boranils were also readily obtained by this method. Their physical properties were studied, and the properties were consistent with those calculated by DFT calculations.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2730-71822612026Revised taxonomy reveals sustained introgression and secondary contact in ancient lake ricefishes46ENYukiYashimaTropical Biosphere Research Center, University of the RyukyusAndy B.NofriantoTropical Biosphere Research Center, University of the RyukyusHandungNuryadiTropical Biosphere Research Center, University of the RyukyusRyoKakiokaDepartment of Applied Aquabiology, National Fisheries UniversityHirozumiKobayashiThe Natural History Museum and InstituteSatoshiAnsaiUshimado Marine Institute, Okayama UniversityIxchel F.MandagiFaculty of Fisheries and Marine Science, Sam Ratulangi UniversityKawilarang W. A.MasengiFaculty of Fisheries and Marine Science, Sam Ratulangi UniversitySjamsu A.LawelleFaculty of Fisheries and Marine Science, Halu Oleo UniversityAtsushi J.NaganoBioscience and Biotechnology Center, Nagoya UniversityJunkoKusumiFaculty of Social and Cultural Studies, Kyushu UniversityKazunoriYamahiraTropical Biosphere Research Center, University of the RyukyusBackground Biotic diversification in ancient lakes is shaped by complex geological histories and genetic exchange among populations. The Malili Lake system on Sulawesi Island represents a classic natural laboratory for studying freshwater fish evolution and harbors multiple endemic Oryzias species that diversified under repeated hydrological reorganizations. Previous genomic analyses inferred that two sympatric species in Lake Towuti (O. profundicola and O. loxolepis) experienced a single ancient introgression event from a “ghost lineage” derived from O. marmoratus inhabiting another lake. However, recent taxonomic re-evaluation has revealed the presence of an extant O. marmoratus population within Lake Towuti itself. This finding suggests that the putative ghost lineage may in fact represent a living population co-occurring in the lake, calling for a re-examination of the introgression history and speciation mode in Lake Towuti.<br>
Results By incorporating newly generated ddRAD-seq data from the true O. marmoratus in Lake Towuti, we reanalyzed phylogenetic relationships and population genetic structure among Malili Lake Oryzias. Previously reported major phylogenetic relationships and inter-lake introgression patterns were largely reproduced. In contrast, TreeMix and f4-statistic analyses revealed that introgression signals previously attributed to a “ghost lineage” into O. profundicola and O. loxolepis instead originated from the extant O. marmoratus population coexisting within Lake Towuti. Demographic model comparisons explicitly incorporating within-lake gene flow further supported a scenario in which O. profundicola and O. loxolepis diverged in allopatry, subsequently came into secondary contact within Lake Towuti, and later experienced additional gene flow following secondary contact with O. marmoratus that entered the lake.<br>
Conclusion Our results demonstrate that introgression from the O. marmoratus lineage into O. profundicola and O. loxolepis was not a single ancient event, but rather a more sustained process. This finding highlights the critical importance of taxonomic resolution for accurately inferring introgression and divergence history. Comparative studies across other ancient lakes on Sulawesi will be valuable for understanding how the timing and nature of gene flow from third lineages influence patterns of population divergence and the strength of reproductive isolation.No potential conflict of interest relevant to this article was reported.Institute of Electrical and Electronics Engineers (IEEE)Acta Medica Okayama2169-3536142026Programmable Clock Distribution Using Switching Matrices for Field Programmable Gate Arrays5264152653ENAyumuOguraOkayama UniversityMinoruWatanabeOkayama UniversityNobuyaWatanabeOkayama UniversityEvery digital systems using very large scale integration require clock distributions, for which a dedicated clock tree or a mesh clock is frequently used. Field programmable gate arrays have numerous general-purpose programmable wires based on switching matrices to connect the outputs and inputs of look-up tables and input–output ports. However, field programmable gate arrays never use numerous general-purpose programmable wires for their clock distributions to satisfy the clock skew margin similarly to very large scale integrations. Field programmable gate arrays also use dedicated clock trees, although their programmability is not high. Currently, field programmable gate arrays can support multiple dedicated clock routing or multiple clock trees. Unfortunately, the number of clock trees is fixed. They remain limited to a small number. Even if an application requires many clock distributions, such a clock distribution cannot be supported in current field programmable gate arrays. This paper therefore presents a proposal of a more flexible clock distribution method based on wiring channels and switching matrices. The method uses general-purpose programmable wires. In addition, to resolve clock skew increase difficulties, we have introduced a new flip-flop with a two-phase clock signal. This paper presents simulation results obtained using the proposed clock distribution method on an originally designed field programmable gate array. In addition, experimentally obtained results indicate that the proposed clock distribution method can function correctly on a Cyclone V field programmable gate array.No potential conflict of interest relevant to this article was reported.Pharmaceutical Society of JapanActa Medica Okayama0918-61584932026Bortezomib Induces Apoptosis via Upregulation of Abhd4 in Peripheral Nerve Cells496 502ENYusukeKonishiDepartment of Pharmacy, Kobe University HospitalTomohiroOmuraDepartment of Pharmacy, Kobe University HospitalTakeshiIjichiDepartment of Pharmacy, Kobe University HospitalHirokiNishiguchiDepartment of Pharmacy, Kobe University HospitalRyunosukeHayakawaEducation and Research Center for Clinical Pharmacy, Kobe Pharmaceutical UniversityYumiKitahiroDepartment of Pharmacy, Kobe University HospitalKotaroItoharaDepartment of Pharmacy, Kobe University HospitalKazuhiroYamamotoDepartment of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIkukoYanoDepartment of Pharmacy, Kobe University HospitalBortezomib, a first-in-class proteasome inhibitor, is widely used to treat multiple myeloma and other hematological malignancies. Despite its therapeutic efficacy, bortezomib causes peripheral neuropathy (PN) in approximately 20–30% of patients, often leading to dose reduction or discontinuation. Preventive or therapeutic approaches to bortezomib-induced PN are currently unavailable, as its precise mechanism remains unclear. In this study, we compared the effects of bortezomib and the second-generation proteasome inhibitor carfilzomib on peripheral nerve cells to identify candidate molecules involved in PN development. Transcriptome profiling of differentiated F11 cells, a hybridoma of a rat embryonic dorsal root ganglion and mouse neuroblastoma cell line N18TG2, revealed that bortezomib selectively upregulated α/β-hydrolase containing domain 4 (Abhd4), whereas carfilzomib did not. This finding was confirmed by quantitative RT-PCR and immunoblotting, which demonstrated consistent increases in Abhd4 mRNA and protein levels following bortezomib treatment. Functional analysis further revealed that Abhd4 overexpression promoted early apoptosis, suggesting a mechanistic link between bortezomib-induced Abhd4 elevation and neuronal vulnerability. Therefore, these results suggest that Abhd4 represents a candidate molecular signature associated with bortezomib-induced PN. Although further in vivo validation is needed, these findings warrant further investigation of Abhd4 as a potential contributor to bortezomib-induced PN.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-903211742026Roles of TIF1β in Leukemic Stem Cell Through SETDB1-Dependent and Independent Mechanisms896903ENMarikoMoriiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityShoKubotaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityGoroSashidaLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto UniversityTIF1β/TRIM28/KAP1 has been recognized as a scaffold protein that partners with KRAB-ZFPs and heterochromatin complexes to enforce gene silencing. In embryonic and pluripotent stem cells, it maintains self-renewal by silencing endogenous retroelements through the establishment of heterochromatin. While these canonical functions have been extensively examined in embryonic stem (ES) cells, accumulating evidence also highlights its diverse contributions to cancer biology. We herein focused on the oncogenic role of TIF1β in leukemic progression, contrasting this with its physiological roles in hematopoietic stem cell maintenance, differentiation, and immune regulation, thereby providing a comparative perspective on H3K9 methyltransferase SETDB1-dependent and -independent mechanisms. TIF1β-mediated epigenetic plasticity was recently shown to establish a leukemic chromatin environment for promoting oncogenic transcriptional programs while repressing lineage-differentiation regulators, which drives leukemic progression in a context-dependent manner. This review summarizes the dual role of TIF1β as a chromatin modulator, functioning both as a canonical transcriptional co-repressor and as a context-dependent co-activator, and also discusses how these modalities cooperate to sustain leukemic stem cell programs.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0915-56353832026Effectiveness and Safety of Enteroscopy-Assisted ERP-Guided Versus EUS-Guided Pancreatic Duct Drainage for Pancreaticojejunostomy Strictures: A Multicenter Observational Studye70128ENShogoOtaDivision of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical UniversityHideyukiShiomiDivision of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical UniversityYukiFujiiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalMasatakaKanoDivision of Gastroenterology and Hepatology, Kansai Medical University Medical CenterMasaakiShimataniDivision of Gastroenterology and Hepatology, Kansai Medical University Medical CenterNaokiFujitaDepartment of Gastroenterology and Neurology, Kagawa UniversityHidekiKamadaDepartment of Gastroenterology and Neurology, Kagawa UniversitySaoriUenoSecond Department of Internal Medicine, Osaka Medical and Pharmaceutical UniversityTakeshiOguraSecond Department of Internal Medicine, Osaka Medical and Pharmaceutical UniversityMamoruTakenakaDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Kindai UniversityKaeNagaoDivision of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of MedicineArataSakaiDivision of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of MedicineShuheiShintaniDepartment of Gastroenterology, Shiga University of Medical ScienceOsamuInatomiDepartment of Gastroenterology, Shiga University of Medical ScienceKohKitagawaDepartment of Gastroenterology, Nara Medical UniversityRyotaNakanoDivision of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical UniversityMitsuhitoKoizumiDepartment of Gastroenterology and Metabology, Ehime University Graduate School of MedicineYoshikiImamuraDepartment of Gastroenterology and Metabology, Ehime University Graduate School of MedicineAkihisaOhnoDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu UniversityNaoFujimoriDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu UniversityTakaakiTamuraSecond Department of Internal Medicine, Wakayama Medical UniversityTsukasaMiyagaharaDepartment of Gastroenterology, National Hospital Organization Beppu Medical CenterMikioNakajimaEmergency and Critical Care Center, Tokyo Metropolitan Hiroo HospitalMasayukiKitanoSecond Department of Internal Medicine, Wakayama Medical UniversityObjectives: Enteroscopy-assisted endoscopic retrograde pancreatography-guided pancreatic duct drainage (eERP-PDD) and endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD) are minimally invasive alternatives to surgery for pancreaticojejunostomy stricture (PJS); however, comparative data remain limited. We compared the effectiveness and safety of these approaches and identified factors associated with technical failure.<br>
Methods: This multicenter retrospective study included 88 patients (111 procedures) who underwent endoscopic intervention for PJS at 13 Japanese tertiary centers. We compared clinical outcomes between eERP-PDD and EUS-PDD. The primary outcome was technical success; secondary outcomes included clinical success, procedure time, and adverse events (AEs). Propensity-score overlap weighting was used to adjust for baseline differences.<br>
Results: As initial treatment, 77 patients underwent eERP-PDD and 11 underwent EUS-PDD. After adjustment, EUS-PDD achieved higher technical success (eERP-PDD, 28% vs. EUS-PDD, 71%; p = 0.012) and clinical success (22% vs. 71%; p = 0.003), with shorter procedure time (76 min vs. 41 min; p = 0.001). AE incidence was higher with EUS-PDD before adjustment (5% vs. 27%; p = 0.039) but comparable after adjustment (7% vs. 29%; p = 0.15); all AEs resolved with conservative management. Age < 75 years, male sex, and main pancreatic duct (MPD) diameter ≥ 5 mm were independently associated with eERP-PDD failure.<br>
Conclusions: EUS-PDD demonstrated higher technical and clinical success than eERP-PDD for PJS, with comparable safety after adjustment. An MPD diameter ≥ 5 mm was associated with eERP-PDD failure. An MPD-based algorithm is proposed: eERP-PDD for MPD < 5 mm with EUS-PDD as salvage, and EUS-PDD for MPD ≥ 5 mm. This algorithm is hypothesis-generating and requires prospective validation.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1432-08517542026Immunological effects of amivantamab in EGFR or MET-expressing non-small cell lung cancer121ENRyoYoshichikaDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityFumiakiMukoharaDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKotaroYamadaDepartment of Respiratory Medicine, Okayama University HospitalJojiNagasakiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokoWatanabeDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoukiUedaDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama UniversityKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama UniversityShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama UniversityTakamasaIshinoDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYosukeTogashiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground Epidermal growth factor receptor (EGFR) mutations represent one of the most frequent oncogenic driver in non-small cell lung cancer (NSCLC). Amivantamab, a bispecific antibody targeting EGFR and MET proto-oncogene, receptor tyrosine kinase (MET), has demonstrated clinical benefit in EGFR-mutant NSCLC through dual blockade, but its immunological role in human clinical specimens, especially tumor-infiltrating lymphocytes (TILs), has not been directly evaluated.<br>
Methods We analyzed surgically resected tumor samples from 40 patients with NSCLC to investigate immune responses and their associations with EGFR and MET expression. TILs were characterized by flow cytometry (FCM) and immunohistochemistry (IHC). To assess the immunomodulatory potential of amivantamab, fresh tumor digests containing live tumor cells and TILs were cultured ex vivo with CD3 and CD28 stimulation in the absence or presence of amivantamab, followed by FCM. EGFR and MET expression were also evaluated by IHC.<br>
Results EGFR mutations and high EGFR protein expression were associated with a trend toward reduced CD8⁺ T-cell and dendritic cell (DC) infiltration. In ex vivo TIL assays, exposure to amivantamab significantly activated CD8⁺ T cells, such as programmed cell death-1 expression and cytokine production, and promoted DC maturation. These effects were most pronounced in tumors with high EGFR or MET protein expression rather than EGFR mutations.<br>
Conclusions This study provides the first direct evidence from ex vivo fresh TIL assays using human NSCLC clinical specimens that amivantamab can activate immune responses. EGFR and MET expression may serve as potential biomarkers for amivantamab-induced immune responses.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2666-3643732026Potential Immune Microenvironment Biomarkers in SCLC: J-TAIL-2 Observational Study100926ENMasayukiShirasawaDepartment of Thoracic Oncology, National Cancer Center HospitalMakotoNishioDepartment of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer ResearchKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalAtsushiOsoegawaDepartment of Thoracic and Breast Surgery, Oita University Faculty of MedicineEikiKikuchiDepartment of Respiratory Medicine, Faculty of Medicine, Hokkaido UniversityHideharuKimuraDepartment of Respiratory Medicine, Kanazawa University HospitalYasushiGotoDepartment of Thoracic Oncology, National Cancer Center HospitalJunichiShimizuDepartment of Thoracic Oncology, Aichi Cancer Center HospitalEisakuMiyauchiDepartment of Respiratory Medicine, Tohoku University HospitalHiroshigeYoshiokaDepartment of Thoracic Oncology, Kansai Medical UniversityIchiroYoshinoInternational University of Health and Welfare Narita HospitalToshihiroMisumiDepartment of Data Science, National Cancer Center Hospital EastYasushiYatabeDepartment of Diagnostic Pathology, National Cancer Center HospitalTatsuyaYoshidaDepartment of Thoracic Oncology, National Cancer Center HospitalJumpeiKashimaDepartment of Diagnostic Pathology, National Cancer Center HospitalMasahideOkiDepartment of Respiratory Medicine, NHO Nagoya Medical CenterHisaoAshimuraChugai Pharmaceutical Co., Ltd.YukiKobayashiChugai Pharmaceutical Co., Ltd.MisaTanakaChugai Pharmaceutical Co., Ltd.AkihikoGemmaNippon Medical SchoolIntroduction: Effective predictors of response to atezolizumab plus carboplatin/etoposide (CE) therapy in extensive-stage SCLC (ES-SCLC) remain limited. This exploratory analysis from J-TAIL-2 aimed to identify markers of survival benefit with atezolizumab plus CE therapy in ES-SCLC.<br>
Methods: J-TAIL-2 (ClinicalTrials.gov ID, NCT04501497) was a multicenter observational study that enrolled patients receiving atezolizumab plus CE (ES-SCLC cohort) in clinical practice in Japan per local label and treatment guidelines. In this exploratory analysis, the association of CD8+ tumor-infiltrating lymphocyte (TIL) density and SCLC subtypes (SCLC-A [ASCL1 dominant], SCLC-N [NEUROD1 dominant], SCLC-P [ASCL1/NEUROD1 double-negative with POU2F3 expression], and SCLC-O [ASCL1/NEUROD1 double-negative not otherwise specified]) with overall survival (OS) and progression-free survival (PFS) was evaluated. SCLC subtyping was performed by immunohistochemistry.<br>
Results: SCLC samples (n = 100; data cutoff, February 3, 2023) were categorized as SCLC-A (73%), SCLC-N (16%), SCLC-P (8%), and SCLC-O (3%). Among 96 patients who received first-line atezolizumab plus CE, median age was 72 (range, 39–87) years and 81% were male. Furthermore, 56 patients were classified into the CD8+ TIL-high subgroup and 40 into the TIL-low subgroup. Median (m)PFS with atezolizumab plus CE was 6.1 months (95% confidence interval [CI]: 4.5–7.5) in the TIL-high versus 4.4 months (95% CI: 4.0–5.1) in the TIL-low subgroup (p = 0.01); mOS was 18.4 (95% CI: 11.8–not estimable) versus 10.8 months (95% CI: 7.7–16.2; p = 0.04). mOS and mPFS were not significantly different between SCLC subtypes but were numerically shorter in the SCLC-N group.<br>
Conclusions: CD8+ TIL density is a potential biomarker of clinical benefit in ES-SCLC and may facilitate patient selection for atezolizumab combination therapy.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-903211752026TGF-β Inhibitor Potentiates Osimertinib-Induced Anti-Tumor Immunity in Egfr-Mutant Lung Cancer12601272ENTadahiroKuribayashiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunNishimuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSachiOkawaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatakaTaokaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuntaMoriDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaakiTanakaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokaNishimuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAyakoMoritaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaofumiHaraDepartment of Respiratory Medicine, Okayama University HospitalKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalGoMakimotoDepartment of Respiratory Medicine, Okayama University HospitalKammeiRaiCenter for Innovative Clinical Medicine, Okayama University HospitalEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalYosukeTogashiDepartment of Respiratory Medicine, Okayama University HospitalYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Respiratory Medicine, Okayama University HospitalKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalImmunotherapy for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) remains challenging. We previously found that EGFR-tyrosine kinase inhibitors induced antitumor immunity but also triggered immunosuppressive cytokines, including transforming growth factor-β (TGF-β), in Egfr-mutant lung cancer. Here, we investigate whether TGF-β inhibition potentiates osimertinib-induced antitumor immunity using a syngeneic mouse model of Egfr-mutated lung cancer, with cancer cells subcutaneously transplanted into wild-type C57BL/6J mice. We evaluated the antitumor effect of the combination therapy with osimertinib and either nintedanib (an indirect TGF-β inhibitor) or vactosertib (a specific TGF-β type I receptor kinase inhibitor). Changes in the tumor microenvironment during treatment were assessed using immunohistochemical staining, western blot analysis, and flow cytometry. We found that TGF-β expression was upregulated in the tumor treated with osimertinib. Nintedanib monotherapy showed no significant antitumor effect, whereas osimertinib combined with nintedanib significantly potentiates the antitumor effect compared with osimertinib monotherapy in vivo. Crucially, no additive effect of nintedanib on osimertinib monotherapy was observed in vitro. Combination therapy with osimertinib and nintedanib significantly increased effector T cells (CD8+CD44+CD62L−) and Granzyme B+ areas and decreased CD206+ cells, while significantly decreasing TGF-β and SMAD2/3 expression. Similar effects were observed with vactosertib but not with a vascular endothelial growth factor receptor 2 inhibitor. In conclusion, combination therapy with osimertinib and TGF-β inhibitors potentiates osimertinib-induced antitumor immunity. These findings highlight a novel therapeutic strategy for EGFR-mutated NSCLC and warrant further clinical investigation.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1471-24072612026High-risk soft-tissue sarcomas in elderly patients: does perioperative radiotherapy improve local control and prognosis?329ENTomohiroFujiwaraDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiharuMitsuhashiCentre for Innovative Clinical Medicine, Medical Development Field, Okayama UniversityYutakaNezuDepartment of Orthopaedic Surgery, Yokohama City UniversityTakashiTajimaDepartment of Orthopaedic Surgery, Kyorin University Faculty of MedicineShinjiMiwaDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa UniversityToshioKojimaDepartment of Orthopaedic Surgery, Nihon University School of MedicineShuichiFujiwaraDepartment of Orthopaedic Surgery, Kobe University Graduate School of MedicineAkiraKawaiDepartment of Musculoskeletal Oncology, National Cancer Centre HospitalKazuhiroTanakaDepartment of Advanced Medical Sciences, Oita University Faculty of MedicineToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAims Accumulating evidence suggests that advanced age is associated with poor local control and prognosis in patients with soft-tissue sarcomas (STSs), highlighting the need to optimise treatment for this age group. However, real-world data on treatment details and outcomes in elderly patients are limited. This study aimed to clarify the role of perioperative radiotherapy (RT) for treating high-risk STSs in elderly patients.<br>
Methods Patients aged ≥ 70 years who underwent surgery for localised, high-grade, deep-seated non-small round cell STSs measuring ≥ 5 cm were included in the Bone and Soft Tissue Tumour Registry in Japan. Patients with small-round cell STSs or myxoid liposarcomas, or those who received perioperative chemotherapy or intraoperative RT, were excluded.<br>
Results Among the 1,214 patients who met the criteria, 47 (4%), 219 (18%), and 2 (0.2%) received neoadjuvant, adjuvant, and both neoadjuvant and adjuvant RT, respectively. The 5- and 10-year disease-specific survival (DSS) rates were 72.7% and 64.7%, respectively. Tumour size ≥ 10 cm, intralesional margin, and local recurrence were associated with poorer DSS; however, perioperative RT did not affect DSS. The 5- and 10-year cumulative probabilities of local recurrence (LR) were 14.6% and 19.5%, respectively. Trunk wall tumours, dedifferentiated liposarcomas, marginal margins, and intralesional margins were associated with a higher probability of LR. Adjuvant RT was associated with a reduced LR probability in patients with intralesional (p = 0.005) or marginal margins (p = 0.044); however, no such benefit was observed in patients with wide margins, who constituted the majority of the cohort, resulting in no significant association between perioperative RT and LR in overall analyses. In the propensity score-matched cohort, no significant differences in DSS or cumulative probability of LR were observed between patients with and without perioperative RT.<br>
Conclusion Adjuvant RT was associated with reduced LR rates in elderly patients with high-risk STSs who had intralesional or marginal margins. However, because most patients achieved wide margins and no benefit of perioperative RT was observed in this group, RT was not associated with reduced LR or improved survival in the overall or propensity score–matched analyses. Prospective trials are warranted to define the role of perioperative RT in elderly patients with high-risk STSs.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-00672722026Possible Involvement of Hypothalamic Dysfunction in Long COVID Patients Characterized by Delayed Response to Gonadotropin-Releasing Hormone832ENYukiOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshiakiSoejimaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroNakanoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsuhitoSuyamaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyosukeTakaseDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiOguniDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoheiMasudaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeOmuraDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasueSakuradaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuiMatsudaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruHasegawaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiHondaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazukiTokumasuDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeigoUedaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesLong COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic–pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. Between February 2021 and November 2025, 1251 patients with long COVID were evaluated, of whom 207 (19%) had relatively low random ACTH or cortisol levels. Ultimately, 16 underwent anterior pituitary stimulation tests and were included. All tests were performed in an inpatient setting without exogenous steroids. Fifteen patients (six women, mean age 35.6 years) underwent corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH) tests. All patients had mild acute COVID-19, eight had ≥2 vaccinations, and the mean interval from infection was 343 days. Frequent symptoms included fatigue (100%), insomnia (66.7%), headache (60.0%), anorexia/nausea (40.0%), and brain fog (40.0%). Mean early-morning cortisol and 24 h urinary free cortisol were 7.5 μg/dL and 41.0 μg/day, respectively. MRI showed an empty sella in one case. Peak hormonal responses were preserved (ΔACTH 247%, ΔTSH 918%, ΔPRL 820%, ΔFSH 187%, ΔLH 1150%); however, peaks were delayed beyond 60 min in ACTH (13%), LH (33%), and FSH (87%). Notably, significantly delayed elevations remained at 120 min in the responses of TSH (4.1-fold), PRL (1.8-fold), LH (9.3-fold), and FSH (2.8-fold), suggesting possible hypothalamic involvement, particularly in the gonadotropin responses. Additionally, serum IGF-I was lowered (−0.70 SD), while GH response (mean peak 35.5 ng/mL) was preserved by growth hormone-releasing peptide (GHRP)-2 stimulation. Low-dose hydrocortisone and testosterone were initiated for three patients. Although direct viral effects and secondary suppression have been proposed, our findings may suggest that, at least in part, the observed response characteristics are consistent with functional secondary hypothalamic dysfunction rather than irreversible primary injury. These findings highlight the need for objective endocrine evaluation before initiating hormone replacements.No potential conflict of interest relevant to this article was reported.American Association for Cancer Research (AACR)Acta Medica Okayama2767-9764642026Constitutive EGFR Activation Induced by PTPRR Downregulation Confers Resistance to KRAS Inhibitors728 741ENHiroakiKanemuraDepartment of Medical Oncology, Kindai University Faculty of MedicineToshiyukiTakeharaDivision of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of MedicineOsamuMaenishiDepartment of Pathology, Kindai University Faculty of MedicineShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalNatsumiIwawakiDivision of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of MedicineKeiKunimasaDepartment of Thoracic Oncology, Osaka International Cancer InstituteTomohiroNakayamaDepartment of Medical Oncology, Kishiwada City HospitalSatomiWatanabeDepartment of Medical Oncology, Kishiwada City HospitalShinichiroSuzukiDepartment of Medical Oncology, Kindai University Faculty of MedicineKazukoSakaiDepartment of Genome Biology, Kindai University Faculty of MedicineKoichiAzumaDivision of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of MedicineKeitaKudoDepartment of Medical Oncology, National Hospital Organization Osaka Minami Medical CenterKazutoNishioDepartment of Genome Biology, Kindai University Faculty of MedicineKazuhikoNakagawaDepartment of Medical Oncology, Kindai University Faculty of MedicineHidetoshiHayashiDepartment of Medical Oncology, Kindai University Faculty of MedicineTakeshiTeramuraDivision of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of MedicineKimioYonesakaDepartment of Medical Oncology, Kindai University Faculty of MedicineKRASG12C inhibitors, such as sotorasib, show clinical efficacy for non–small cell lung cancer (NSCLC) positive for the G12C mutations of KRAS, but primary and acquired resistance to these drugs remains a clinical problem. In this study, we show that the development of resistance to sotorasib in KRASG12C-positive NSCLC cells was mediated by constitutive activation of EGFR resulting from downregulation of the protein tyrosine phosphatase receptor type R (PTPRR). PTPRR has been identified as a physiologic regulator of ERK signaling in several cancer types. In our study, PTPRR was demonstrated to bind directly to EGFR, facilitating its dephosphorylation on tyrosine residues. Resumption of PTPRR expression in the resistant cells attenuated EGFR phosphorylation and restored sotorasib sensitivity. PTPRR downregulation was associated with gene promoter hypermethylation in the sotorasib-resistant cells and NSCLC tissue samples. Furthermore, low PTPRR expression in tumor specimens was associated with shorter progression-free and overall survival for patients with NSCLC treated with sotorasib. In contrast to sotorasib, high PTPRR expression was associated with a poor response to EGFR tyrosine kinase inhibitors in EGFR-mutated NSCLC, suggesting that PTPRR may broadly regulate EGFR dependence in NSCLC. Finally, dual blockade of KRASG12C and EGFR showed a substantial antitumor effect in a xenograft model of sotorasib-resistant NSCLC. This approach is therefore a rational therapeutic strategy for KRASG12C-positive NSCLC, especially for tumors showing PTPRR downregulation.<br>
Significance: The current study shows that downregulation of PTPRR induces EGFR activation and resistance to KRASG12C inhibitors in NSCLC, suggesting dual KRAS-EGFR blockade as a rational therapy. PTPRR may help identify patient subgroups that would benefit from the addition of EGFR inhibitors to KRASG12C-targeted therapies.No potential conflict of interest relevant to this article was reported.The Japan Society of Applied PhysicsActa Medica Okayama2758-2450122026Quest for the non-perturbative magnetic field effects in the 1000-Tesla magnetic field region011001ENYasuhiro H.MatsudaISSP, Univ. of TokyoKentoYamamuraISSP, Univ. of TokyoYutoIshiiISSP, Univ. of TokyoAkihikoIkedaISSP, Univ. of TokyoHironobuSawabeISSP, Univ. of TokyoHayatoNakaharaGNST, Okayama UniversityYujiMuraokaRIIS, Okayama UniversityThe low-temperature insulator phase is found to be completely suppressed by ultrahigh magnetic fields of 500 T and transformed to the metallic phase in a V1-xWxO2 (x = 0.06) thin film, which has a slightly lower metal-insulator transition temperature (TMI) than that of the film reported in the previous ultrahigh magnetic field experiment [1,2]. It is also found that the insulator phase is more robust against a magnetic field for a highly W-doped film (x = 0.12), suggesting a different origin of the insulator phases between x = 0.06 and 0.12.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2214-1804512026Highly sensitive detection of cancer cells using a voltage-tuned terahertz chemical microscope100972ENXueDingGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYutoOhmiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJinWangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHirofumiInoueDepartment of Medical Support, Okayama University HospitalToshihikoKiwaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTerahertz chemical microscopy (TCM) is a promising label-free technique for detecting biochemical interactions by monitoring changes in terahertz (THz) wave emission from semiconductor sensing plates. However, quantitative biological detection has been hindered by large plate-to-plate variations originating from uncontrolled depletion-layer electric fields formed during fabrication. These variations shift the response curve of THz amplitude and reduce reproducibility and sensitivity. Here, we introduce a voltage-tuned sensing plate that allows direct control of the depletion-layer electric field by applying a bias voltage to the Si layer of the sensing plate. This enables deliberate adjustment of surface potential and alignment of the THz response curve to the region of highest gain. Using lung adenocarcinoma cells (PC9) captured via AE1/AE3 antibodies targeting specific cell-surface antigens, we demonstrate that voltage tuning enhances detection sensitivity by up to 50-fold and restores linearity between THz amplitude and the logarithm of cell concentration, even in plates with negligible response at 0 V. These findings establish voltage control as a simple, universally applicable strategy to stabilize TCM performance, reduce fabrication-induced variability, and improve analytical sensitivity for biosensing and materials-analysis applications.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1880-65467622026Pharmaceutical agents targeting KATP channel modulate sweet taste sensitivity in mice100082ENChikaSawaiDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKuanyuWangDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKengoHorieDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshihiroMitohDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirotakaUedaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiKamiokaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyusukeYoshidaDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySweet detection involves at least two mechanisms: a G-protein coupled sweet taste receptor (Tas1r2/Tas1r3) and glucose transporters. As in pancreatic β-cells, glucose transport may lead to closure of ATP-sensitive potassium (KATP) channels. Since expression of KATP channels in sweet taste cells has been reported, modulation of KATP channel activity would affect sweet taste sensitivity. Here, we examined the effect of glibenclamide (a KATP channel closer) and diazoxide (an opener) on mouse taste behavior. Glibenclamide selectively reduced taste sensitivity to glucose without affecting responses to sucrose or sucralose compared to insulin, suggesting selective impairment of the transporter-dependent pathway. In contrast, diazoxide broadly suppressed responses to all tested sweeteners, indicating a generalized effect on sweet detection. Neither drug altered responses to non-sweet taste. These findings suggest that pharmacological modulation of KATP channel differently influences sweet taste; closers reduce glucose sensitivity whereas openers attenuate response to multiple sweeteners.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0168-17023702026Toward in planta studies of persistent fungal viruses in a model plant199761ENPaulTelengechAgrivirology Laboratory, Institute of Plant Science and Resources, Okayama UniversitySakaeHisanoAgrivirology Laboratory, Institute of Plant Science and Resources, Okayama UniversityFrancescoFavarettoAgrivirology Laboratory, Institute of Plant Science and Resources, Okayama UniversityHiroakiIchikawaAgrivirology Laboratory, Institute of Plant Science and Resources, Okayama UniversityKazuyukiMaruyamaAgrivirology Laboratory, Institute of Plant Science and Resources, Okayama UniversityKiwamuHyodoAgrivirology Laboratory, Institute of Plant Science and Resources, Okayama UniversityHidekiKondoAgrivirology Laboratory, Institute of Plant Science and Resources, Okayama UniversityNobuhiroSuzukiAgrivirology Laboratory, Institute of Plant Science and Resources, Okayama UniversityA model plant, Nicotiana benthamiana, was examined as a host for persistent fungal viruses capable of crossing organismal kingdoms. Protoplasts of N. benthamiana were transfected with a mixture of virions of a betapartitivirus, Rosellinia necatrix partitivirus 18 (RnPV18), and an alphapartitivirus, RnPV19, and were then subjected to plantlet regeneration. Primary RT-PCR-based screening showed that nearly 100% of the resulting calli tested positive for RnPV18, whereas approximately 90% were positive for RnPV19. However, secondary screening performed at a later stage of tissue culture revealed that only 6% of the calli retained RnPV19, whereas approximately 33% retained RnPV18. These results suggest that the calli were chimeric, consisting of virus-infected and virus-free sectors, and that the partitiviruses were progressively lost during callus maintenance. It is also possible that these fungal partitiviruses were unable to fully adapt to, or counteract, host defense responses sufficiently to establish stable infection. We succeeded in obtaining RnPV18-positive calli and suspension cultures that maintained the virus at detectable levels, as shown by northern blotting, after prolonged subculture for at least 9 months. High-throughput small RNA analyses revealed both similarities and differences in virus-derived small RNA profiles among protoplasts, calli, and suspension cultures. Viral genome analyses further revealed developmental stage-specific and stage-independent substitutions compared with the RnPV18 genomic sequence maintained in the original fungal host. Interestingly, a C-to-U mutation in the RNA-dependent RNA polymerase-encoding region of RnPV18 was detected much more frequently in a particular line, designated B21, than in another stably RnPV18-infected line, P8, irrespective of whether the virus was maintained in suspension cultures or calli. This may explain why virus accumulation in B21 calli and suspension cultures was much lower than that in P8 cell cultures, as RNA-seq analyses showed 159 K counts per million for P8 versus 44 K counts per million for B21. Taken together, this study provides a platform for investigating partitiviruses and other ubiquitous persistent viruses, which are generally difficult to inoculate experimentally.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0010-799918172026Electrical conductivity of geikielite (MgTiO3) at lunar mantle conditions: the role of metastable defect states and thermal history55 ENTakashiYoshinoInstitute for Planetary Materials, Okayama UniversityDaisukeYamazakiInstitute for Planetary Materials, Okayama UniversityThe electrical conductivity of geikielite (MgTiO3), the Mg endmember of the ilmenite group, was investigated at mantle pressures of 2 and 4.3 GPa and temperatures up to 1850 K using a Kawai-type multi-anvil apparatus. Electrical conductivity increases by more than seven orders of magnitude between 800 and 1700 K and exhibits two distinct conduction regimes separated by a transition at ~ 1500–1700 K. The high-temperature regime is characterized by large activation enthalpies (ΔH ≈ 1.8–2.3 eV), whereas the low-temperature regime shows much lower values (ΔH ≈ 0.19–0.31 eV). Stepwise annealing experiments reveal a pronounced thermal-history dependence: repeated heating to progressively higher maximum temperatures (Tmax) produces metastable conductivity states, enhancing low-temperature conductivity by up to six orders of magnitude and systematically reducing activation enthalpy. This behavior indicates activation and freezing-in of defect-related charge carriers. Negative activation volumes further support a hopping-type conduction mechanism. Although Ti³⁺ was not directly detected, the combination of reducing experimental conditions, Al³⁺ impurities (~ 0.35 wt% Al₂O₃), low activation energies, and strong thermal memory is most consistent with small-polaron hopping involving Ti³⁺–Ti⁴⁺ pairs. At lunar core–mantle boundary temperatures, geikielite reaches conductivities of 10¹–10² S/m, exceeding those of olivine and overlapping estimates for the lunar low-velocity zone. Our results demonstrate that solid-state Ti-rich oxides can produce high electrical conductivity without partial melting, providing new constraints on the thermochemical evolution and electromagnetic structure of the lunar interior.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama0032-07812026Involvement of tRNA thiolation in uORF-mediated translational regulation during Xylogenesis in Arabidopsis thaliana pcag055ENYuichiNishiiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityDaichiArakiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMitsuruSaraumiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTakuTakahashiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityPost-transcriptional modification of tRNAs is an important mechanism for regulating translation efficiency and cellular homeostasis, yet its contribution to upstream open reading frame (uORF)-mediated translational control remains largely unexplored. In this study, we investigated the role of tRNA thiolation in thermospermine-dependent regulation of xylem development in Arabidopsis thaliana. Using a suppressor screen of the thermospermine-deficient mutant acaulis5 (acl5), which exhibits dwarfism and excessive xylem differentiation, we identified suppressor-of-acl502 (sac502) as a recessive loss-of-function allele of CTU2, a gene encoding a key enzyme in the biosynthesis of the wobble uridine modification 5-methoxycarbonylmethyl-2-thiouridine. Mutations in other components of the same modification pathway, including ROL5 and TRM9, similarly suppressed the acl5 phenotype. Translational analyses using 5′ leader-GUS reporter constructs revealed that the ctu2 mutation did not enhance translation of the mRNA containing a thermospermine-responsive uORF of SAC51, but instead significantly reduced translation of that of SACL3, a member of the SAC51 family, and that of LONESOME HIGHWAY (LHW), which contains another conserved uORF in the 5′ leader region. Polysome profiling further demonstrated decreased association of SACL3 and LHW mRNAs with actively translating ribosomes in ctu2. Genetic interaction analyses supported the conclusion that the suppression of excessive xylem formation in acl5 by ctu2 is attributable to reduced LHW activity. In addition, ctu2 mutants displayed increased sensitivity to exogenous thermospermine, resembling the response of lhw mutants. Together, our results reveal that tRNA thiolation contributes to uORF-mediated translational regulation of key developmental regulators and identify tRNA modification as an important regulatory layer controlling vascular development.No potential conflict of interest relevant to this article was reported.Castledown PublishersActa Medica Okayama2982-3749212026AI-assisted writing feedback in EFL: Tracking student performance and reflections103382ENJunkoOtoshiOkayama UniversityNaomiFujishimaKawasaki Medical SchoolThis study explores how AI-assisted writing feedback supports English as a Foreign Language (EFL) learners' writing development and feedback literacy in a Japanese university. Twenty-one first-year students completed nine Write & Improve (W&I) tasks, progressing from descriptive to argumentative essays. Each task was revised following W&I feedback, and students were asked to write a short reflective log. An explanatory mixed-methods approach was adopted, combining quantitative analyses of writing performance and linguistic features with qualitative coding of students' reflections. Findings showed measurable gains in both higher- and lower-level groups, with particularly notable improvement among lower-level students in complexity, fluency, and sophistication. While the higher group consistently outperformed the lower group in Term 1, this gap narrowed in Term 2. Reflection logs provided important insights into feedback literacy: students initially valued W&I for surface-level corrections but later expressed frustration as tasks became more complex and scores plateaued. This tendency was especially evident among lower-level students, reflecting both the affordances and limitations of automated feedback. The study concludes that AI-assisted tools can foster writing development and emerging feedback literacy, but sustained progress requires teacher mediation. Integrating Automated Writing Evaluation (AWE) into ecological feedback environments - combining AI, teacher, and student reflection - offers a promising approach for sustainable L2 writing instruction.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841862026Pathway Enrichment Analysis of Whole-Exome Sequencing Data from Formalin-Fixed, Paraffin-Embedded Enucleated Eyes with Retinoblastoma and Choroidal Malignant Melanomae110548ENToshihikoMatsuoOphthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakehiroTanakaPathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityDaisukeEnnishiMedical Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityAkiraSaitoGenomic Statistics, Stagen Co. Ltd.MitsuhiroAmemiyaGenomic Statistics, Stagen Co. Ltd.ShigeoKamitsujiGenomic Statistics, Stagen Co. Ltd.Objectives: Intraocular tumors are extremely rare, small in size, and difficult to approach by biopsy. In the era of cancer genome analysis, we designed a pilot study to perform whole-exome sequencing of formalin-fixed paraffin-embedded enucleated eyes of retinoblastoma and choroidal malignant melanoma as two major intraocular malignancies.<br>
Methodology: Genomic DNA was isolated from intraocular tumor areas of 105 paraffin sections with a 5 μm thickness of seven enucleated eyes with retinoblastoma and seven eyes with choroidal malignant melanoma. One of 7 samples of retinoblastoma and another of seven samples of choroidal malignant melanoma were excluded from the study since the sequencing output and depth of reads were lower compared with the other samples. The sequencing data after quality control were aligned to the reference genome sequence (hg38, GRCh38 Assembly, Genome Reference Consortium Human Build 38), and the mapped reads were processed to improve data quality. Somatic mutations (single nucleotide variants, insertions and deletions, and multiple nucleotide variants) in each sample were extracted after excluding variants reported in a Panel of Normals (PON) from the 1000 Genomes Project. Additional selection criteria included a mutation depth of ≥5 reads and either no registration in or an allele frequency of less than 5% in the Tohoku Medical Megabank of Japan (ToMMo 60KJPN-SNV/INDEL Allele Frequency Panel).<br>
Results: Candidate genes with somatic mutations were selected by three criteria: genes with the same mutation shared by two samples or more, recurrently mutated genes three times or over, and genes of driver candidates identified in combining several different driver mutation-detecting programs by Integrative OncoGenomics (IntOGen). Using candidate genes detected by any of the three criteria as input, enrichment analyses identified 28 pathways in Gene Ontology (GO) and 2 pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) for retinoblastoma, while 385 pathways in GO, 12 in KEGG, 2 in the Hallmark gene set of the Molecular Signatures Database (MSigDB), and 47 in Reactome were identified for choroidal malignant melanoma. The enrichment maps showed three major pathways differently in retinoblastoma and choroidal malignant melanoma: one with dynein in retinoblastoma and another with MET in choroidal malignant melanoma.<br>
Conclusions: Although there were limitations related to the small amounts of DNA available from formalin-fixed, paraffin-embedded small-sized tissues and the absence of matched normal control tissue, whole-exome sequencing provided clues to somatic mutations that were enriched in specific pathways and differed between retinoblastoma and choroidal malignant melanoma.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1055-79032232026Reticulate evolution, introgression, and recent diversification in Epimedium sect. Macroceras108646ENEmiKusatakeDepartment of Biology, Okayama UniversityMomokaKonishiDepartment of Biology, Okayama UniversityShutoTomokuniDepartment of Biology, Okayama UniversityYosukeYanagiDepartment of Biology, Okayama UniversityShungoKariyamaSociety of Kurashiki Museum of Natural HistoryTakehitoItohSchool of Life Science and Technology, Institute of Science TokyoAtsushiToyodaDepartment of Genomics and Evolutionary Biology, National Institute of GeneticsSeung-ChulKimDepartment of Biological Sciences, Sungkyunkwan UniversityMakikoMimuraDepartment of Biology, Okayama UniversityHybridization can hinder or promote diversification, and growing genomic evidence suggests that it can facilitate adaptation and speciation. Despite recent progress, however, the quantitative contribution and temporal scope of hybridization to diversification remain poorly understood. The genus Epimedium is a recently diverged lineage, and sect. Macroceras largely consists of endemic species in Japan that are distributed across diverse environments, including limestone, serpentine, coastal habitats, heavy-snow regions, and regions with mild winters. Although natural hybridization and hybrid species have been reported in this section, molecular evidence demonstrating the contribution of hybridization to lineage diversification is limited. We reconstructed phylogenetic relationships using genome-wide single-nucleotide polymorphism (SNP) data from Epimedium sect. Macroceras and tested for genomic signatures consistent with hybridization. Phylogenetic analyses suggest that E. koreanum from Korea is sister to Japanese Epimedium lineages, consistent with an initial colonization of Japan from the Korean Peninsula. The analyses also revealed complex relationships among Japanese species and frequent signals of historical interspecific introgression. Our results are consistent with a history of recent diversification in sect. Macroceras accompanied by introgressive hybridization, which may have contributed to diversification across heterogeneous environments in Japan. This study provides the first genome-wide insights into the evolutionary history of Epimedium sect. Macroceras and reveals complex reticulate relationships among the lineages.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0924-42474082026Tip position estimation of a 3-DOF soft mechanism using artificial muscles with optical fibers117938ENRikimaruOkadaGraduate School of Environment, Life, Natural Science and Technology, Okayama UniversityShuichiWakimotoGraduate School of Environment, Life, Natural Science and Technology, Okayama UniversityYuichiroTodaGraduate School of Environment, Life, Natural Science and Technology, Okayama UniversityShunMiuraGraduate School of Environment, Life, Natural Science and Technology, Okayama UniversityDaisukeYamaguchiGraduate School of Environment, Life, Natural Science and Technology, Okayama UniversityTakefumiKandaGraduate School of Environment, Life, Natural Science and Technology, Okayama UniversityMcKibben-type pneumatic artificial muscles (PAMs) are lightweight and flexible soft actuators with a high power-to-weight ratio, and have been widely applied to rehabilitation devices, power-assist systems, and soft robotic mechanisms. By integrating sensing functions into PAMs, their usability and controllability can be enhanced, enabling the development of more practical and advanced soft mechanisms. We previously proposed a smart artificial muscle (SAM) by integrating an optical fiber into the braided sleeve of a McKibben-type PAM, which enables displacement estimation by measuring optical bending loss. The SAM is compatible with conventional PAM fabrication processes; however, the sensor output exhibits strong nonlinearity and time dependency. In this study, an LSTM-based state estimation framework is extended from a single SAM to a three-degree-of-freedom soft mechanism composed of multiple SAMs, where strong nonlinear coupling and mutual interference arise among actuators. In the proposed framework, the LSTM model jointly processes time-series data of multi-channel optical sensor outputs and applied pressures of the three SAMs, along with past estimated states as inputs. This structure enables the model to capture nonlinear coupling, hysteresis, and time-dependent behavior, allowing estimation of the tip position of the soft mechanism. Experimental results demonstrate that the proposed method accurately captures complex nonlinear dynamics and mutual mechanical interference among multiple SAMs, achieving accurate tip position estimation. These results indicate that SAMs with integrated sensing and actuation capabilities, combined with machine-learning-based estimation, provide an effective approach for state estimation of multi-DOF soft robotic mechanisms.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1432-058410552026HLA-matched versus haploidentical donor transplantation with post-transplant cyclophosphamide: a study on behalf of the donor/source working group of the Japanese society for transplantation and cellular therapy255ENYosukeNakayaDepartment of Hematology, Osaka Metropolitan University Graduate School of MedicineHirohisaNakamaeDepartment of Hematology, Osaka Metropolitan University Graduate School of MedicineJunichiSugitaDepartment of Hematology, Sapporo Hokuyu HospitalJunyaKandaDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityYutaHasegawaDepartment of Hematology, Hokkaido University HospitalTetsuyaEtoDepartment of Hematology, Hamanomachi HospitalTakahiroFukudaDepartment of Hematopoietic Stem Cell Transplantation, National Cancer Center HospitalNaokiKuritaDepartment of Hematology, University of Tsukuba HospitalNobuhiroHiramotoDepartment of Hematology, Kobe City Medical Center General HospitalKojiNagafujiDivision of Hematology and Oncology, Department of Medicine, Kurume University HospitalDepartment of Hematology, Sapporo Hokuyu HospitalShuichiOtaDepartment of Hematology, Sapporo Hokuyu HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalToshihikoAndoDivision of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga UniversityToshiroKawakitaDepartment of Hematology, NHO Kumamoto Medical CenterTakashiAkasakaDepartment of Hematology, Tenri HospitalYasuoMoriHematology, Oncology & Cardiovascular medicine, Kyushu University HospitalTomohikoKamimuraDepartment of Hematology, Harasanshin HospitalMakotoOnizukaDepartment of Hematology/Oncology, Tokai University School of MedicineYoshikoAtsutaJapanese Data Center for Hematopoietic Cell TransplantationHidekiNakasoneDivision of Hematology, Jichi Medical University Saitama Medical CenterPost-transplant cyclophosphamide (PTCy) is now being increasingly applied to HLA-matched donor (MD) transplantation. Prior studies in Western countries have demonstrated that allogeneic hematopoietic cell transplantation (allo-HCT) employing PTCy yields better outcomes with HLA-matched donors (MDs) than with haploidentical donors (HIDs). However, the effect of HLA mismatch may differ among racial groups. We retrospectively analyzed adult patients with hematological malignancies who underwent their first allo-HCT with PTCy from MDs or HIDs registered to the Japanese registry database between 2013 and 2021. Among 63 (related, n = 33; unrelated, n = 30) and 1261 patients who received MD and HID allo-HCT with PTCy, 50 (related, n = 30; unrelated, n = 20) and 100 patients were assigned to MD and HID groups by 1:2 propensity score matching (PSM). The results showed that MD recipients had better neutrophil recovery (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.04–2.10; P = 0.031) and lower risk of non-relapse mortality (NRM) (HR, 0.19; 95% CI, 0.05–0.81; P = 0.024) than HID recipients. Multivariable analyses in the entire cohort before PSM confirmed these findings. Fatal infection was the primary cause of NRM in the HID group. This study is the first to demonstrate that, within a homogeneous Asian cohort, MD may have an advantage over HID in PTCy-based allo-HCT in facilitating neutrophil engraftment and reducing the risk of NRM.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1432-058410552026Donor selection for patients with HLA-homozygous haplotypes in allogeneic hematopoietic stem cell transplantation244ENNoriyoshiYoshinagaDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityMakotoIwasakiDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityKojiKatoDepartment of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical SciencesFumihikoKimuraDivision of Hematology, Department of Internal Medicine, National Defense Medical CollegeMasahiroHirayamaDepartment of Pediatrics, Mie University Graduate School of MedicineMinoruKanayaBlood Disorders Center, Aiiku HospitalSatokoMorishimaCentral Japan Cord Blood BankNaoyukiUchidaDepartment of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon HospitalNorikoDokiHematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome HospitalTakahiroFukudaDepartment of Hematopoietic Stem Cell Transplantation, National Cancer Center HospitalYoshinobuKandaDivision of Hematology, Jichi Medical UniversityTetsuyaNishidaDepartment of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi HospitalYutaHasegawaDepartment of Hematology, Hokkaido University HospitalShinichiKakoDivision of Hematology, Jichi Medical University Saitama Medical CenterMasatsuguTanakaDepartment of Hematology, Kanagawa Cancer CenterMineoKurokawaDepartment of Cell Therapy and Transplantation Medicine, The University of Tokyo HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalToshiroKawakitaDepartment of Hematology, NHO Kumamoto Medical CenterKeisukeKataokaDivision of Hematology, Department of Medicine, Keio University School of MedicineYukioKondoDepartment of Hematology, Toyama Prefectural Central HospitalKazunoriImadaDepartment of Hematology, Japanese Red Cross Osaka HospitalTatsuoIchinoheDepartment of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima UniversityMakotoOnizukaDepartment of Hematology/Oncology, Tokai University School of MedicineYoshikoAtsutaJapanese Data Center for Hematopoietic Cell TransplantationJunyaKandaDepartment of Hematology, Graduate School of Medicine, Kyoto UniversityHLA homozygous haplotypes occur worldwide, but outcomes after allogeneic hematopoietic stem cell transplantation using alternative donor sources remain uncertain. We retrospectively analyzed the Japanese national transplantation registry to compare outcomes after first allogeneic hematopoietic stem cell transplantation in patients with HLA homozygous haplotypes. Donors were classified as homo-to-homo, defined as HLA-matched, or hetero-to-homo, defined as allele-level mismatches at HLA-A, -B, -C, and/or -DRB1 restricted to the host-versus-graft direction. The unrelated donor homo-to-homo group served as the reference. We included 691 patients: related donor homo-to-homo (n = 121), related donor hetero-to-homo (n = 76), unrelated donor homo-to-homo (n = 374), unrelated donor hetero-to-homo (n = 22), cord blood homo-to-homo (n = 40), and cord blood hetero-to-homo (n = 58). Compared with the unrelated donor homo-to-homo group, overall survival was inferior in the cord blood homo-to-homo group (adjusted hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.11–2.64; P = 0.015), whereas the unrelated donor hetero-to-homo group showed a nonsignificant trend toward inferior overall survival (adjusted HR, 1.77; 95% CI, 0.97–3.22; P = 0.061). In this Japanese cohort, cord blood homo-to-homo transplantation was associated with inferior overall survival, whereas related donor hetero-to-homo and cord blood hetero-to-homo transplantation were not. These findings should be interpreted cautiously given the retrospective design and long study period, and require validation in contemporary, ethnically diverse cohorts.No potential conflict of interest relevant to this article was reported.Royal Society of Chemistry (RSC)Acta Medica Okayama2052-412913112026Photoinduced sulfanyloximation of styrenes using N-nitrosamines and thiols33673375ENKenYamazakiDivision of Applied Chemistry, Okayama UniversityToshikiTamuraDivision of Applied Chemistry, Okayama UniversityShutaAkimotoDivision of Applied Chemistry, Okayama UniversityTomoyaMiuraDivision of Applied Chemistry, Okayama UniversityMolecules featuring both sulfur and nitrogen atoms are privileged scaffolds in medicinal chemistry and biological systems. However, methods for the direct and regioselective installation of these heteroatoms onto alkenes remain limited. Herein, we report a visible-light-induced, three-component sulfanyloximation of styrenes utilizing thiols and N-nitrosamine as a bench-stable nitrogen oxide (NO) surrogate. This regioselective protocol operates under mild conditions with remarkable functional group tolerance. The synthetic utility of this methodology is further demonstrated by its extension to the synthesis of 2,3-disubstituted indoles and the divergent downstream derivatization of α-sulfanyl ketoxime products via imidoyl fluoride intermediates. An extensive mechanistic investigation supports a pathway initiated by thiyl radical addition to alkenes followed by radical coupling with in situ generated NO.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2090-6447202612026A Case of Peripheral Odontogenic Myxofibroma Arising in the Palatal Gingiva of the Maxillary Second Premolar Region: A Case ReportENMasanoriMasuiDepartment of Oral and Maxillofacial Surgery , Faculty of Medicine , Dentistry and Pharmaceutical Sciences Okayama UniversityHirokazuYutoriDepartment of Oral and Maxillofacial Surgery , Kagawa Prefectural Central HospitalAiFujimuraDepartment of Oral and Maxillofacial Surgery , Kagawa Prefectural Central HospitalSoichiroIbaragiDepartment of Oral and Maxillofacial Surgery , Faculty of Medicine , Dentistry and Pharmaceutical Sciences Okayama UniversityOdontogenic myxofibroma (OMF) is a rare benign mesenchymal odontogenic tumor characterized by myxoid stroma with a prominent fibrous component. Although it usually arises intraosseously within the jaws, the peripheral variant, peripheral odontogenic myxofibroma (POMF), which occurs in extraosseous soft tissues, is uncommon and may be clinically misdiagnosed as a reactive gingival lesion. We report a case of POMF in a 68-year-old man who was referred for evaluation of a painless, slowly enlarging swelling of the palatal gingiva in the left maxillary second premolar region, which had initially been diagnosed as chronic periodontitis at a local clinic. An intraoral examination revealed an elastic, firm mass with partial erythema on the palatal marginal gingiva. Panoramic radiography showed mild generalized horizontal bone loss without lesion-specific changes, and computed tomography revealed no bone resorption associated with the lesion. Exfoliative cytology was negative for intraepithelial lesions or malignancy. The lesion was excised with a 5-mm clinical margin, including periosteum, and superficial peripheral ostectomy of the adjacent cortical bone was performed. Histopathological examination revealed a myxoid stroma rich in mucinous matrix and collagen fibers, containing sparsely distributed spindle-shaped cells and scattered nests of odontogenic epithelium. Alcian blue staining revealed diffuse positivity, supporting the diagnosis of POMF. No recurrence was observed during a 2-year follow-up period. This case highlights a diagnostic pitfall in the tooth-bearing gingiva and underscores the importance of histopathological confirmation of persistent gingival masses. When imaging shows no apparent bone involvement, and clinical suspicion of malignancy is low, complete excision with an adequate soft-tissue margin and selective, limited bone removal may achieve local control while preserving the adjacent teeth; long-term follow-up remains advisable.No potential conflict of interest relevant to this article was reported.Public Library of Science (PLoS)Acta Medica Okayama1932-62032162026A multicenter, randomized, parallel-group confirmatory study protocol to evaluate the efficacy of Soft Protector CPC, a novel oral mucosal protectant, in preventing oral mucositis and alleviating pain in patients with breast cancere0350803ENKazuhiroOmoriDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKoheiFurukawaDepartment of Dentistry and Oral Surgery, Shikoku Cancer CenterMasatoshiUsubuchiDepartment of Dentistry, Miyagi Cancer CenterTomofumiHamadaDepartment of Dentistry and Oral Surgery, Sagara HospitalTadahikoShienDepartment of Breast and Endocrine Surgery, Okayama University HospitalMichihiroYoshidaCenter for Innovative Clinical Medicine, Okayama University HospitalYukiNakatsukaCenter for Innovative Clinical Medicine, Okayama University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalSoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShogoTakashibaDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityOral mucositis is a frequent and debilitating adverse event observed in patients undergoing chemotherapy or radiotherapy. Current management strategies are limited in duration, require frequent application, and fail to address the mechanical irritation from teeth. A novel device, Soft Protector CPC, was developed to overcome these limitations. This multicenter, randomized, two-arm, open-label, confirmatory trial aims to evaluate the efficacy and safety of Soft Protector CPC in patients with breast cancer undergoing chemotherapy. A total of 154 participants will be randomly assigned in a 1:1 ratio to receive either oral care with Soft Protector CPC or oral care alone. The primary endpoint will be oral mucositis as assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 during the comparative treatment period. The secondary endpoints will include CTCAE v3.0 during the continuous treatment period, oral mucositis, pain (CTCAE v5.0), quality of life (Patient Reported Outcomes-CTCAE version 1.0 [PRO-CTCAE v1.0], the 15-item oral health questionnaire of the European Organization For Research And Treatment Of Cancer [EORTC QLQ-OH15], and the pain Numeric Rating Scale), onset and site of mucositis, completion of chemotherapy, use of rescue medications, technical feasibility, and patient preference. The safety endpoints will include adverse events, device malfunction, and laboratory tests. This trial is expected to establish the clinical utility of the Soft Protector CPC for the prevention and management of oral mucositis, with the potential to improve the patients’ quality of life and adherence to cancer therapy. This study was approved by the Clinical Research Review Board and registered with the Japan Registry of Clinical Trials, jRCTs062250005, on April 18, 2025.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1860-18712026Effects of Juniperus sabina coverage on plant community structure in semiarid areas of ChinaENLongQinGraduate School of Environmental and Life Science, Okayama UniversityAyakaYamabayashiGraduate School of Environmental and Life Science, Okayama UniversityTetsuya K.MatsumotoFaculty of Environmental and Life Science, Okayama UniversityGuoshengZhangCollege of Ecology and Environment, Inner Mongolia Agricultural UniversityNorikazuYamanakaArid Land Research Center, Tottori UniversityMunetoHirobeFaculty of Environmental and Life Science, Okayama UniversityNaoko H.MikiFaculty of Environmental and Life Science, Okayama UniversityPlant interactions are one of the fundamental processes shaping the structure and function of plant communities and help create species diversity. Species diversity affects the current functioning of ecosystems and their resistance and resilience to future climate change. In harsh environments such as drylands, positive plant–plant interactions are important in promoting species diversity. Juniperus sabina is an evergreen shrub that is native to the semiarid areas of northern China. Because J. sabina can modify some harsh environmental conditions in its role as a nurse plant, it is expected to facilitate species diversity, although it may exhibit allelopathic inhibition. Previous research has only examined effects of J. sabina coverage onα-diversity in a single-year, and its effects on the β-diversity of the plant community structure in the local ecosystem are still unclear. We compared environmental conditions and plant species composition inside and outside of 11 J. sabina patches to evaluate the effects of its coverage on the species diversity of the understory community structure through modifying microhabitat conditions. Water and nutrient conditions were higher inside the patches, whereas light conditions were higher outside. More perennial herbs and C3 plants were found inside and more annual herbs and C4 plants were found outside. There were different trends in α-diversity each year, while β-diversity was consistently greater inside the patches. This research suggests that the coverage of J. sabina can drive different community structures by providing heterogeneous environmental conditions, and would increase plant species diversity in the local ecosystem.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1999-49071752026Photosynthetic Response of Larix gmelinii var. japonica Saplings After Exogenous Glutathione Foliar Application530ENResa SriRahayuGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityWataruIshizuka Forestry Research Institute, Hokkaido Research OrganizationAyuNarita Forestry Research Institute, Hokkaido Research OrganizationRieMiyata Forestry Research Institute, Hokkaido Research OrganizationNaoko H.Miki Faculty of Environmental, Life, Natural Science and Technology, Okayama UniversityHirokazuKon Forestry Research Institute, Hokkaido Research OrganizationYukoMiyazaki Faculty of Environmental, Life, Natural Science and Technology, Okayama UniversitySapling survival and growth depend on photosynthetic assimilates. Therefore, improving physiological performance during early stages may enhance subsequent performance and nursery production. This study evaluated whether exogenous oxidized glutathione (GSSG), reported to enhance photosynthesis, improves the photosynthetic, physiological, and growth-related traits of Larix gmelinii var. japonica saplings. Sixteen saplings were assigned to four treatments: GSSG, 5-aminolevulinic acid, Hyponex, and a water control. Photosynthetic, nitrogen-related, and growth traits were measured before treatment and at 3, 6, 13, and 31 days after treatment, and biomass was assessed after three months. The GSSG treatment showed no difference in the net CO2 assimilation rate (Amax) compared with the control, but exhibited a significantly earlier peak at 6 days than the other treatments. This response was supported by the stability of GSSG-treated saplings against photoinhibition (Fv/Fm) and a tendency toward greater resilience to midday light stress (ΦPSII). Enhanced photosynthetic performance was associated with reduced carbon and nitrogen fluctuations and was accompanied by numerically greater root and stem biomass in the 2024 terminal shoots. Although fertilization effects were generally weak and transient, GSSG elicited notable responses, suggesting that the immediate enhancement of photosynthesis underlies its impact. However, its antioxidant properties under stressful conditions warrant further investigation.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1471-24312612026Hypernatremia during the first week of life in very preterm infants and neurodevelopmental outcomes at 3 to 4 years of age: a cohort study181ENMichikoMurakamiDivision of Neonatology, NHO Okayama Medical CenterKeiTamaiDepartment of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaomiMatsumotoDepartment of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAkihitoTakeuchiDivision of Neonatology, NHO Okayama Medical CenterMakotoNakamuraDivision of Neonatology, NHO Okayama Medical CenterTakashiYorifujiDepartment of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMisaoKageyamaDivision of Neonatology, NHO Okayama Medical CenterBackground Hypernatremia is a common electrolyte disorder in both term and preterm infants. Previous studies have suggested a correlation between hypernatremia and short-term complications in preterm infants, such as intraventricular hemorrhage and chronic lung disease. However, the relationship between hypernatremia and neurodevelopmental outcomes is less well understood. This study aimed to assess the association between hypernatremia during the first week of life and neurodevelopmental outcomes at 3–4 years of age in very preterm infants.<br>
Methods This single-center, retrospective cohort study analyzed data from preterm infants born at less than 32 weeks of gestation between 2010 and 2020. Infants with peak whole blood sodium levels > 145 mEq/L during the first week of life were included in the hypernatremia group and those with ≤ 145 mEq/L in the non-hypernatremia group. The primary outcome was neurodevelopmental impairment (NDI) at 3–4 years of age, defined as developmental impairment (developmental quotient < 70), cerebral palsy, hearing impairment, or visual impairment. Secondary outcomes were the components of the primary outcome. We conducted Poisson regression analyses with robust variance, adjusting for perinatal confounders.<br>
Results Of 272 infants with neurodevelopmental data, 82 and 190 infants were in the hypernatremia and non-hypernatremia groups, respectively. The median (interquartile range) gestational age and birth weight were 26.4 (25.1–28.0) and 28.7 (26.6–30.3) weeks and 860 (670–1062) and 997 (778–1264) g for infants in the hypernatremia and non-hypernatremia groups, respectively. Infants in the hypernatremia group had a greater incidence of NDI (29.3% vs. 14.7%, adjusted risk ratio [RR] 1.75, 95% CI 1.08–2.84) and cerebral palsy (8.5% vs. 1.6%, adjusted RR 5.5, 95% CI 1.72–17.63) than those in the non-hypernatremia group.<br>
Conclusions Hypernatremia during the first week of life was associated with an increased risk of NDI at 3–4 years of age in very preterm infants.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0902-00634062026Risk Factors for Waiting List Mortality in Lung Transplant Candidates With Post‐Hematopoietic Stem Cell Transplantation Non‐Infectious Pulmonary Complicationse70582ENHisaoHigoDepartment of Respiratory Medicine, Okayama University HospitalSatoruSenooDepartment of Respiratory Medicine, Okayama University HospitalSatokoMakimotoDepartment of Radiology, Okayama University HospitalTomohiroNaganoDepartment of Hematology, Okayama University HospitalTakumiKondoDepartment of Hematology, Okayama University HospitalHaruchikaYamamotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinobuMaedaDepartment of Respiratory Medicine, Okayama University HospitalYosukeTogashiDepartment of Respiratory Medicine, Okayama University HospitalNobuakiMiyaharaDepartment of Respiratory Medicine, Okayama University HospitalBackground: Late-onset non-infectious pulmonary complications (LONIPCs) following hematopoietic stem cell transplantation (HSCT) are a known indication for need of lung transplantation. This study aimed to clarify the clinical characteristics of patients with LONIPCs after HSCT who were registered for lung transplantation and reveal the risk factors for waiting list mortality.<br>
Methods: We retrospectively reviewed the clinical data of patients with LONIPCs after allogeneic HSCT who were referred to Okayama University Hospital and registered in the Japan Organ Transplant Network for deceased-donor lung transplantation between 2005 and 2023. Pediatric patients aged <18 years at the time of registration were excluded.<br>
Results: Thirty-four patients were included in this study. Notably, two distinct phenotypic groups were identified: One with a bronchiolitis obliterans pattern on high-resolution computed tomography and a mixed ventilatory defect, and the other with a pleuroparenchymal fibroelastosis pattern and a restrictive ventilatory defect. The median waiting duration for a deceased-donor lung transplant was 662 days, and 16 patients died during the waiting period. The cumulative incidence of waiting list mortality was 20.6% (95% confidence interval [CI], 8.9%–35.6%) at 1 year and 46.1% (95% CI, 27.8%–62.7%) at 3 years. A history of pneumothorax, greater dyspnea on exertion, and higher serum Krebs von den Lungen-6 levels were associated with an increased risk of waiting list mortality.<br>
Conclusion: In patients with LONIPCs after HSCT, a history of pneumothorax may be a marker of a poor prognosis and could serve as a criterion for referral of lung transplantation.No potential conflict of interest relevant to this article was reported.AIP PublishingActa Medica Okayama2468-20471112025Pressure calibrations of high-pressure large-volume presses at HPSTAR017803ENYongjiangXuCenter for High Pressure Science and Technology Advanced ResearchPeiyanWuCenter for High Pressure Science and Technology Advanced ResearchShengShangCenter for High Pressure Science and Technology Advanced ResearchXueWangCenter for High Pressure Science and Technology Advanced ResearchTaihangLiCenter for High Pressure Science and Technology Advanced ResearchShuchangGaoCenter for High Pressure Science and Technology Advanced ResearchShijieLvCenter for High Pressure Science and Technology Advanced ResearchHangChengCenter for High Pressure Science and Technology Advanced ResearchQianzhiXuCenter for High Pressure Science and Technology Advanced ResearchShangLeiCenter for High Pressure Science and Technology Advanced ResearchJiajiaFengCenter for High Pressure Science and Technology Advanced ResearchLeiZhaoCenter for High Pressure Science and Technology Advanced ResearchWimvan WestrenenCenter for High Pressure Science and Technology Advanced ResearchTakayukiIshiiInstitute for Planetary Materials, Okayama UniversityBinChenCenter for High Pressure Science and Technology Advanced ResearchLeiSuCenter for High Pressure Science and Technology Advanced ResearchYangDingCenter for High Pressure Science and Technology Advanced ResearchWengeYangCenter for High Pressure Science and Technology Advanced ResearchHo-KwangMaoCenter for High Pressure Science and Technology Advanced ResearchYanhaoLinCenter for High Pressure Science and Technology Advanced ResearchLarge-volume presses (LVPs) are widely utilized in diverse research fields—including high-pressure physics, chemistry, materials science, and Earth and planetary sciences—to investigate the physical and chemical properties of materials under extreme high-pressure and high-temperature conditions. A prerequisite for achieving reproducible property measurements is the determination and control of pressure within experimental setups. However, the lack of precise pressure calibration in LVPs hinders the broader application of such devices in ultrahigh-pressure studies. This study employs a suite of standard phase transition-based pressure markers—comprising metallic conductors, semiconductors, and minerals—through both in situ and ex situ identification approaches, to establish pressure calibration curves ranging from 0.4 to >30 GPa for various types of LVP installed at the Center for High Pressure Science and Technology Advanced Research (HPSTAR), Beijing, including piston–cylinder, cubic, and multi-anvil presses. The results provide a unified and traceable pressure reference for high-pressure experiments conducted at HPSTAR, while also offering technical guidance and calibration standards for other researchers utilizing similar LVP systems, thereby enabling more consistent comparison between different laboratories. This work facilitates the advancement of LVP research toward broader applications in higher-pressure regimes.No potential conflict of interest relevant to this article was reported.American Geophysical Union (AGU)Acta Medica Okayama0094-827653102026Spin Transition of Fe3+ in δ-(Al,Fe)OOH and Implication for Mid-Lower Mantle Seismic Heterogeneitiese2025GL121007ENChaoshuaiZhaoState Key Laboratory of Precision Geodesy, University of Science and Technology of ChinaZhuMaoState Key Laboratory of Precision Geodesy, University of Science and Technology of ChinaXinyueZhangState Key Laboratory of Precision Geodesy, University of Science and Technology of ChinaYingxinYuState Key Laboratory of Precision Geodesy, University of Science and Technology of ChinaNingyuSunState Key Laboratory of Precision Geodesy, University of Science and Technology of ChinaJianboZhangCenter for High Pressure Science and Technology Advanced ResearchYuzhuWangShanghai Advanced Research Institute, Chinese Academy of SciencesTakayukiIshiiInstitute for Planetary Materials, Okayama Universityδ-(Al,Fe)OOH is an important water carrier and plays a critical role on Earth's deep water cycle. Lattice parameters of δ-(Al0.89Fe0.11)OOH were measured by synchrotron single-crystal X-ray diffraction at simultaneously high temperature and pressure up to 65 GPa and 800 K in diamond anvil cells. The results reveal that the spin crossover increases from 30 to 37 GPa at 300 K to 36–48 GPa at 700 K. Moreover, at the spin crossover, the KT and VΦ of δ-(Al0.89Fe0.11)OOH occur significant elastic softening, with maximum reductions of 50% on KT and 29% on VΦ at 33 GPa and 300 K to 37% on KT and 23% on VΦ at 41 GPa and 700 K. The anomalous elastic properties of δ-(Al,Fe)OOH at the spin crossover enhance our understanding of local seismic observations anomalies and help identify potential water-rich regions in the mid-lower mantle.No potential conflict of interest relevant to this article was reported.American Geophysical Union (AGU)Acta Medica Okayama0094-82765332026Sound Velocities of FeO‐Bearing Ringwoodite and Majorite: Implication for Martian Mantle Seismic Profilese2025GL118991ENLuoLiDepartment of Earth and Planetary Sciences, Jackson School of Geosciences, The University of Texas at AustinTakayukiIshiiInstitute for Planetary Materials, Okayama UniversityYoung JayRyuGeoSoilEnviroCARS, University of ChicagoDongzhouZhangGeoSoilEnviroCARS, University of ChicagoStellaCharitonGeoSoilEnviroCARS, University of ChicagoVitali B.PrakapenkaGeoSoilEnviroCARS, University of ChicagoJung‐FuLinDepartment of Earth and Planetary Sciences, Jackson School of Geosciences, The University of Texas at AustinCompressional and shear wave velocities (Vp, Vs) of candidate Martian deep-mantle minerals, FeO-rich ringwoodite ((Mg0.66Fe0.34)2SiO4) and majorite (Mg0.75Fe0.10Al0.26Ca0.07Si0.84O3), were measured up to 25 GPa and 700 K using Brillouin light scattering coupled with externally-heated diamond anvil cells. Thermoelastic modeling of our results and literature data along a representative areotherm showed that Vp and Vs of FeO-bearing ringwoodite are approximately 7.5% and 11.0% higher than that of the majorite. Our results reveal that velocity profiles of these Martian deep-mantle minerals are more sensitive to variations in the ringwoodite/majorite (Mg/Si) ratio than to thermal and FeO chemical perturbations. Our best-fit velocity model to a recent seismic model by Samuel et al. (2023, https://doi.org/10.1038/s41586-023-06601-8) indicates the Martian mantle contains approximately 67 vol.% ringwoodite and 33 vol.% majorite, suggesting a ringwoodite-rich aggregate in the Martian lowermost solid mantle. The ringwoodite-majorite mantle likely co-evolved with the FeO and other incompatible elements in the molten silicate layer above the Martian core-mantle boundary.No potential conflict of interest relevant to this article was reported.American Geophysical Union (AGU)Acta Medica Okayama0094-82765322026Davemaoite Elasticity Reveals Slab‐Induced Heterogeneity in the Mantle Transition Zonee2025GL118147ENYingxinYuState Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of ChinaXinyueZhangState Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of ChinaDongzhouZhangGeoSoilEnviroCARS, University of ChicagoLuoLiState Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of ChinaZhuMaoState Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of ChinaNingyuSunState Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of ChinaDengleiWangState Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of ChinaJingLiState Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of ChinaChaoshuaiZhaoState Key Laboratory of Precision Geodesy, School of Earth and Space Sciences, University of Science and Technology of ChinaChengQianState Key Laboratory of Geological Processes and Mineral Resources, China University of GeosciencesYingzhanWeiState Key Laboratory of High Pressure and Superhard Materials, College of Physics, Jilin UniversityXinyangLiState Key Laboratory of High Pressure and Superhard Materials, College of Physics, Jilin UniversityYuzhuWangShanghai Advanced Research Institute, Chinese Academy of SciencesTakayukiIshiiInstitute for Planetary Materials, Okayama UniversityThe observed 2%–7% low-shear velocity (VS) anomalies near the subducted slab at the bottom mantle transition zone (MTZ) indicate strong lateral heterogeneity, which is commonly attributed to subducted oceanic crust. However, davemaoite, a major constituent of the subducted oceanic crust, has been poorly constrained in its elasticity, hindering accurate velocity modeling and obscuring the origin of these low-velocity features. Here we report single-crystal elasticity of Ti-bearing davemaoite with the composition of Ca(Si0.57Ti0.43)O3 under high pressure-temperature and found that Ti incorporation significantly reduces velocities and alters the pressure dependence of the shear modulus. Further velocity modeling demonstrated that subducted crusts with varying Ti content have seismic signatures of 1.7(2)–6.8(5)% low-VS at the bottom MTZ, consistent with the observed low-VS structure in the region. These findings highlight the role of slab-derived chemical heterogeneity in generating mantle seismic anomalies and provide new experimental constraints on the structure and dynamics of the deep Earth.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0892-03621152026Long-term neurological and neurocognitive deficits in adults prenatally exposed to methylmercury: Minamata disease107590ENTakashiYorifujiDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukaYamamuraDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityItsukaNaganoNon-Profit Organization HamachidoriMarikoYasudaClinical Psychology Center, Kawasaki Medical School HospitalTerukoMorookaDivision of Medical Support, Okayama University HospitalYokoKadoDepartment of Psychology, Faculty of Letters, Kansai UniversityMinamata disease, officially recognized in 1956, is a well-known food poisoning event that was caused by the consumption of fish and seafood contaminated with methylmercury. Although patients with congenital Minamata disease (CMD) with severe neurological impairments after birth are widely recognized, few studies have examined the effects of prenatal methylmercury exposure among residents, which is likely at lower levels than in CMD patients. We aimed to investigate the relationship between prenatal methylmercury exposure and subsequent neurological and neurocognitive outcomes. We conducted a cross-sectional study during 2024–2025 among 51 individuals aged approximately 70 years, 27 residents from an existing cohort established in 1970 in Minamata and 24 age-matched individuals who had lived in less-exposed regions. We performed a battery of neurological and neurocognitive tests in both groups and compared the results using multiple linear regression analyses. We also examined the association between intelligence scores obtained in 1970, and intelligence scores obtained in the present investigation, only among exposed participants. We found that exposed individuals had unfavorable neurological and neurocognitive test scores, in comparison with less-exposed controls. Scores on the Montreal Cognitive Assessment, Japanese Edition were 5.91 points lower (95% confidence interval: 3.09 to 8.73) for exposed residents than for the less-exposed group. Moreover, intelligence scores evaluated during exposed participants' adolescence were correlated with their neurocognitive scores in adulthood. Our findings showed that prenatal methylmercury exposure affected subsequent neurological and neurocognitive functions, including among individuals with lower exposure than in CMD patients, and even approximately 70 years after the initial exposure.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0342-17915322026High-pressure spectroscopic investigation of ε-FeOOH: toward a better understanding of pressure-induced hydrogen-bond symmetrization18ENIzumiMashinoInstitute for Planetary Materials, Okayama UniversityShigeruYamashitaInstitute for Planetary Materials, Okayama UniversityTakashiYoshinoInstitute for Planetary Materials, Okayama UniversityHigh-pressure spectroscopic measurements of ε-FeOOH were conducted up to ~ 65 GPa at room temperature in diamond anvil cells. The pressure evolution of the Raman vibrational modes confirms that a hydrogen-bond-symmetrization-induced phase transition from P21nm to Pnnm occurs at ~ 18 GPa. Infrared (IR) spectroscopic measurements suggest that the Pnnm phase has a disordered hydrogen state, and no spectroscopic evidence for fully centered hydrogen bonds is observed within the investigated pressure range. Above ~ 45 GPa, Fe3+ in ε-FeOOH undergoes a high-spin to low-spin transition as indicated by a reduction of the unit cell volume, together with reductions in IR transmitted and Raman signals. These results demonstrate that ε‑FeOOH preserves a disordered hydrogen‑bond configuration up to at least 45 GPa, whereas δ-AlOOH transforms to a centered hydrogen-bond configuration at ~ 18 GPa. This compositional contrast suggests that Fe‑bearing oxyhydroxides follow a distinct evolution of hydrogen bonding under compression, providing insight into hydrogen behavior in deep Earth materials.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Involvement of ADAM12 in TGF-β1-induced cell proliferation of rheumatoid arthritis synovial fibroblastsENDETINGLINGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Single-cell and spatial transcriptomic characterization of pulmonary pleomorphic carcinomaENAtsushiMATSUOKAGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Induction of IL-9-producing CD8+ T cells by ascochlorin derivatives ENNatsumiIMANOGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Neurofibromin Encoded by the Neurofibromatosis Type 1 (NF1) Gene Promotes the Membrane Translocation of SPRED2, Thereby Inhibiting the ERK Pathway in Breast Cancer Cells ENNANG THEE SU PWINTGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Bone marrow microenvironment disruption and sustained inflammation with prolonged haematologic toxicity after CAR T-cell therapyENWataruKITAMURAGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026TRPV2 in muscle satellite cells is crucial for skeletal muscle remodelling ENYANZHUCHENGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Dual molecular therapy targeting tumor cell heterogeneity improves therapeutic efficacy in glioblastomaENShuichiroHIRANOGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Repetitive Fasting-Refeeding Enhances Metformin-Induced CXCR6⁺ CD8⁺T Cell Tumor Infiltration via VCAM-1 Upregulation on Normalized Vasculature During RefeedingENWEIYANGZHAOGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026ROS produced by Dual oxidase regulate cell proliferation and haemocyte migration during leg regeneration in the cricketENMisaOKUMURAGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026p53-armed oncolytic adenovirus induces apoptosis in pancreatic cancer-associated stellate cells via macropinocytosisENTakeyoshiNISHIYAMAGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Risk Stratification for the Prediction of Skeletal-Related Events in Patients With Bone Metastases From Non-small Cell Lung CancerENYoshihiroSAKAMOTOGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Near-infrared Photoimmunotherapy Targeting High-risk Human Neuroblastoma Cells Expressing GD2ENHiroshiNOSOGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Inhibitory Effects of Vandetanib on Catecholamine Synthesis in Rat Pheochromocytoma PC12 Cells ENYoshihikoITOGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblastsENMENGXUEWANGGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Oncolytic virus-mediated p53 activation boosts the antitumor immunity of a p53-transduced dendritic cell vaccineENMotohikoYAMADAGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Precise stratification of prognosis in pancreatic ductal adenocarcinoma patients based on pre- and postoperative genomic informationENKokichiMIYAMOTOGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026The diagnostic utility and frequency of CD56 expression in plasma cell myelomaENMidoriIMAIGraduate School of Health Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026The role of TFAM-mediated mitochondrial DNA replication in mouse oocytesENDO QUANG SONGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Electroreductive Organic Transformations with a Catalytic Amount of ElectricityENMayuFUJIIGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Long-term trends in disease burden at global, regional, and national levels: findings from the Global Burden of Disease Study 2019 and the World Health Organization Mortality DatabaseENVU THI QUYNHGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Dynamin 2 is involved in osteoblast migration by regulating the organization of F-actinENTakumiMORIYAGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026Effect of Oral Peritumoral Tissue on Infiltration and Differentiation of Tumor-Associated Macrophages in Oral Squamous Cell CarcinomaENTIANYANPIAOGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2026CXCR4 Inhibition Induces Tumor Necrosis by Selectively Targeting the Proliferating Blood Vessels in Oral Squamous Cell CarcinomaENYAMINSOEGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1445-5781252026TFAM-Mediated mtDNA Replication is Essential for Developmental Competence of In Vitro Grown Oocytese70031ENSon QuangDoDepartment of Animal Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHidetakaTasakiDepartment of Animal Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHiroakiFunahashiDepartment of Animal Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTakuyaWakaiDepartment of Animal Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityPurpose<br>
Mitochondria are essential for oocyte maturation and early embryonic development, supplying ATP and maintaining mitochondrial DNA (mtDNA) integrity. During oogenesis, mtDNA undergoes dramatic amplification, but the mechanisms and functional significance of this process remain unclear. The purpose of this study was to elucidate the role of mitochondrial transcription factor A (TFAM) in mouse oocytes using an in vitro growth (IVG) system.<br>
Methods<br>
Oocytes at different growth stages were analyzed for mtDNA copy number and expression of mitochondrial biogenesis genes. To assess TFAM function, siRNA targeting Tfam was microinjected into secondary follicles, which were then cultured for 12 days under IVG conditions. Following culture, oocyte growth, mtDNA content, mitochondrial membrane potential, and developmental competence after in vitro fertilization (IVF) were evaluated.<br>
Results<br>
mtDNA copy number increased nonlinearly during oocyte growth, with a pronounced rise at the secondary follicle stage accompanied by TFAM upregulation. TFAM knockdown reduced mtDNA copy number and mitochondrial function without affecting oocyte size or meiotic maturation, but significantly decreased blastocyst formation and total cell numbers per blastocyst.<br>
Conclusions<br>
TFAM-mediated mtDNA replication is crucial for mitochondrial function and developmental competence of IVG-derived oocytes, underscoring its importance in early embryonic development.No potential conflict of interest relevant to this article was reported.Japan Surgical SocietyActa Medica Okayama2198-77931212026Tailored Management of Anomalous Systemic Arterial Supply to the Basal Segment of the Lung: A Case Report and Literature Reviewcr.26-0288ENShunsukeMoriDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiTomitaDepartment of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruchikaYamamotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKumiNakajimaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidejiroTorigoeDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaoHirakiDepartment of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesINTRODUCTION: Parenchyma-preserving strategies for anomalous systemic arterial supply to the basal segment of the lung have gained increasing attention. However, pulmonary infarction of the preserved lung has been reported, and clear criteria for selecting the optimal treatment have yet to be established. We report 2 cases in which detailed preoperative imaging informed tailored management—right posterior basal segmentectomy in 1 patient and endovascular embolization of the aberrant artery in the other—both without postoperative complications. A review of the relevant literature is also provided, with an emphasis on potential selection criteria.<br>
CASE PRESENTATION: Case 1: A 20-year-old asymptomatic woman was referred after an abnormal screening chest radiograph. CT demonstrated an aberrant artery arising from the abdominal aorta supplying the right posterior basal segment (S10) with a large intravascular thrombus. The pulmonary artery showed hypoplasia limited to A10, while the other branches were normal, and no parenchymal congestion was identified. Following resection of the aberrant artery, robot-assisted right S10 segmentectomy was performed. The postoperative course was uneventful, and the patient was discharged on POD 6. Case 2: A 27-year-old woman was incidentally diagnosed on CT for an unrelated indication. An aberrant artery arising from the descending thoracic aorta supplied the left basal segment. Pulmonary arterial branches were preserved, with only minimal congestion in S9-10. Angiography revealed no evidence of an arteriovenous fistula. As surgical lung resection was considered unnecessary, coil embolization of the aberrant artery was performed. No complications occurred, and the patient was discharged on day 3 after the procedure.<br>
CONCLUSIONS: In patients with anomalous systemic arterial supply to the basal segment of the lung, when pulmonary arterial branches are preserved and background parenchymal congestion is minimal, parenchyma-sparing approaches should be considered.No potential conflict of interest relevant to this article was reported.Royal Society of Chemistry (RSC)Acta Medica Okayama2633-0679712026Programmable synthesis of alkaloidal frameworks integrating Michael acceptor generates covalent probes for targeting POLE3 in HBV replication105119ENNobutoKanekoDepartment of Chemistry, Graduate School of Science, The University of TokyoMisaoHimenoDepartment of Developmental Medical Sciences, Graduate School of Medicine, The University of TokyoYuhiKobayashiDepartment of Chemistry, Graduate School of Science, The University of TokyoRyoTanifujiDepartment of Chemistry, Graduate School of Science, The University of TokyoHirokiKubotaDepartment of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and TechnologyHarukiMizoguchiGraduate School of Natural Science and Technology, Okayama UniversityMakotoMuroiCentre for Sustainable Resource Science, RIKENTakehiroSuzukiCentre for Sustainable Resource Science, RIKENMasayaSugiyamaDepartment of Viral Pathogenesis and Control, National Institute of Global Health and Medicine, Japan Institute for Health SecurityNaoshiDohmaeCentre for Sustainable Resource Science, RIKENHiroyukiOsadaCentre for Sustainable Resource Science, RIKENTaketomoKidoLaboratory of Cell Growth and Differentiation, Institute for Quantitative Biosciences, The University of TokyoAtsushiMiyajimaLaboratory of Cell Growth and Differentiation, Institute for Quantitative Biosciences, The University of TokyoHirokiOguriDepartment of Chemistry, Graduate School of Science, The University of TokyoThe growing need for effective HBV treatments and lead compounds with novel mechanisms prompted us to explore synthetic strategies for generating skeletally diverse alkaloidal Michael acceptors. Our approach uniquely embeds Michael acceptors directly within multicyclic alkaloid-inspired frameworks, exploiting the azepinoindole scaffold—a privileged structure in indole alkaloids. A single-step assembly between the versatile intermediate 13 with methyl propiolate 14 or its derivatives enabled the rapid and divergent synthesis of six alkaloidal Michael acceptors (15–20). This strategy facilitated systematic diversification of three-dimensional functional group arrangements and precise tuning of the electronic and steric properties of the embedded α,β-unsaturated carbonyl moieties. The optimal hit 15 inhibited hepatitis B surface antigen (HBsAg) production with an IC50 of 2.48 μM and significantly reduced levels of covalently closed circular DNA (cccDNA), the master template of HBV. Unlike existing nucleoside/nucleotide-based anti-HBV drugs that primarily inhibit reverse transcription, the alkaloidal Michael acceptor 15 suppressed both cccDNA and relaxed circular DNA (rcDNA) levels, suggesting a potential pathway toward a functional HBV cure. Our study also streamlined the target identification by leveraging the covalent binding properties of the Michael acceptors and the operational simplicity of biotin- or fluorescent-tag attachment via a pre-installed alkyne moiety. Competitive pull-down experiments identified several potential target proteins, involving DNA polymerase epsilon subunit 3 (POLE3). Notably, the alkaloidal Michael acceptor 15 was demonstrated to covalently modify Cys51 in POLE3, providing new insights into virus–host interactions and opening novel avenues for targeted anti-HBV therapies. This approach represents a significant advance beyond traditional screening methods and underscores the potential of skeletally diverse alkaloidal Michael acceptors in antiviral drug development.No potential conflict of interest relevant to this article was reported.American Geophysical Union (AGU)Acta Medica Okayama0094-8276532026Discovery of Repeating Shallow Moonquakes in the Apollo Lunar Seismic Datae2026GL122541ENKeisukeOnoderaInstitute for Planetary Materials, Okayama UniversityShallow moonquakes have been considered unique due to their large magnitudes and affinities with intraplate earthquakes. However, the small number of detections (<80 events) has prevented detailed characterization. In this study, I identified a pair of repeating shallow moonquakes by analyzing a recently updated moonquake data set. Relative-phase assessment revealed that these events exhibit a consistent fault-slip direction despite their occurrence at opposite tidal phases. This differs from what was observed for repeating deep moonquakes, which are closely related to tides, implying that tidal stress does not dominantly control fault-slip initiation of the repeating shallow moonquakes. Also, the identified repeating shallow moonquakes exhibit a similar relationship between seismic moment and the spatial scale of the slip area to earthquakes. This may indicate that earthquake-like fault physics operates on the Moon, albeit with a different driving mechanism than on Earth.No potential conflict of interest relevant to this article was reported.SAGE PublicationsActa Medica Okayama1756-2848192026Second-look endoscopy does not reduce delayed bleeding after endoscopic papillectomy: a multicenter propensity score-matched analysisENYukiFujiiDepartment of Endoscopy, Okayama University HospitalKazuyukiMatsumotoDepartment of Endoscopy, Okayama University HospitalToruUekiDepartment of Gastroenterology, Fukuyama City HospitalHitomiHimeiDepartment of Gastroenterology, Hiroshima City Hiroshima Citizens HospitalIchiroSakakiharaDepartment of Gastroenterology, Kagawa Prefectural Central HospitalEijiroUetaDepartment of Gastroenterology, National Hospital Organization Iwakuni Clinical CenterTatsuyaToyokawaDepartment of Gastroenterology, NHO Fukuyama Medical CenterRyoHaradaDepartment of Gastroenterology, Japanese Red Cross Okayama HospitalTaijiOgawaDepartment of Gastroenterology, Tsuyama Chuo HospitalTakeshiTomodaDepartment of Gastroenterology, Okayama City HospitalHironariKatoDepartment of Gastroenterology, Okayama City HospitalToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Medical Development Field, Okayama UniversityRyosukeSatoDepartment of Gastroenterology and Hepatology, Okayama University HospitalAkihiroMatsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalDaisukeUchidaDepartment of Gastroenterology and Hepatology, Okayama University HospitalShigeruHoriguchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKoichiroTsutsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University HospitalBackground: Delayed bleeding is a frequent and serious complication after endoscopic papillectomy (EP). Second-look endoscopy (SLE) is often scheduled on the following day for wound assessment and prophylactic hemostasis, but its clinical value remains unclear.<br>
Objectives: This study evaluated the effectiveness of SLE in preventing delayed bleeding after EP.<br>
Design: This study was a multicenter, retrospective cohort study.<br>
Methods: We retrospectively reviewed 132 consecutive patients who underwent EP at nine high-volume centers between 2003 and 2024 (SLE group, n = 73; non-SLE group, n = 59). Propensity score matching was performed to balance baseline characteristics. The primary outcome was delayed bleeding, and secondary outcomes were risk factors, the impact of prophylactic hemostasis during SLE, and hospital stay.<br>
Results: After matching, 43 patients were included in each group. The incidence of delayed bleeding did not differ between the SLE and non-SLE groups (14% vs 9%, p = 0.50). Multivariate analysis identified a lack of preventive clipping closure as the only independent risk factor (odds ratio 15, 95% confidence interval 1.3–177, p = 0.030). Prophylactic hemostasis during SLE did not reduce bleeding but was associated with prolonged hospitalization (13 vs 9 days, p = 0.012).<br>
Conclusion: Routine SLE after EP does not reduce delayed bleeding. Moreover, prophylactic hemostasis in asymptomatic patients may unnecessarily prolong hospitalization. Hemostasis should be reserved for patients who develop clinical signs of bleeding.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama1574-69683732026Intercellular signal transduction within the mother cell compartment during Bacillus subtilis sporulation fnag055ENNobukiKuwabaraDepartment of Frontier Bioscience, Hosei UniversityMasatoAnzueDepartment of Frontier Bioscience, Hosei UniversityShin-ichiMiyoshiResearch Center for Intestinal Health Science, Okayama UniversityTsutomuSatoDepartment of Frontier Bioscience, Hosei UniversityDaisukeImamuraResearch Center for Intestinal Health Science, Okayama UniversityIntercellular signaling contributes to the spatiotemporal regulation of gene expression during sporulation in Bacillus subtilis. The mother cell transcription factor σE is initially produced as an inactive precursor protein pro-σE and activated by the processing enzyme SpoIIGA in response to the forespore-produced putative signaling molecule SpoIIR. However, the mechanism underlying the SpoIIR-mediated signal transduction remains poorly understood. In this study, we showed that the spoIIR-positive, spoIIGA-deleted strain was able to induce SpoIIGA-dependent pro-σE processing in co-cultured spoIIR-deleted, spoIIGA-positive strains. This signaling was dependent on SpoIIR expression and did not involve DNA transfer. Extracellular materials including secreted proteins and membrane vesicles were unlikely to be involved in this signaling pathway. Interestingly, cessation of co-incubation shaking enhanced the signaling, while the addition of membrane-solubilizing detergent abolished it. In addition, SpoIIR signaling did not necessitate release from the forespore membrane or extracellular translocation. A SpoIIR variant lacking the putative signal peptide-like hydrophobic domain produced solely in the mother cell compartment was still able to activate pro-σE. Overall, the study findings suggested that the forespore-produced SpoIIR is neither secreted nor externally translocated. Instead, SpoIIR appeared to be transferred into the mother cell compartment and interacts with the SpoIIGA cytoplasmic domain to trigger pro-σE processing.No potential conflict of interest relevant to this article was reported.American Association for Cancer Research (AACR)Acta Medica Okayama1078-04322026Incidence of B-cell Malignancies in Patients with Lung Cancer Receiving PD-1 Blockade TherapyENToshifumiNinomiyaDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityCaiyangFangDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirofumiHamanoDepartment of Pharmacy, Okayama University Hospital, Okayama UniversityTeruyaMorinagaDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityWenhaoZhouDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshihiroKoyamaDepartment of Pharmaceutical Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversitySakuraMikiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityLiZhuDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusukeNaoiDepartment of Hematology, Oncology and Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDaisukeEnnishiDepartment of Hematology, Oncology and Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomoyaKatsutaDepartment of Respiratory Medicine, Ehime Prefectural Central HospitalKadoakiOhashiDepartment of Respiratory Medicine, Okayama University Hospital, Okayama UniversityShinMorizaneDepartment of Dermatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomokaOhki-IkedaDepartment of Pathology, Okayama University Hospital, Okayama UniversityTatsuyaNishiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoukiUedaDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakamasaIshinoDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIsamuOkamotoDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityYoshitoZamamiDepartment of Pharmacy, Okayama University Hospital, Okayama UniversityJojiNagasakiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYosukeTogashiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPurpose: Many patients with various cancer types have received immune checkpoint inhibitors (ICI) worldwide since their approval, and novel unexpected complications from their long-term use are apparent. We identified some cases of B-cell lymphoma occurring during PD-1 blockade therapy as such unexpected complications. In this study, we aimed to evaluate the incidence of hematologic malignancies in patients with lung cancer receiving PD-1 blockade therapy and to elucidate the mechanisms underlying the progression of these malignancies.<br>
Experimental Design: We performed IHC staining on the clinical samples from patients with B-cell lymphoma that developed during PD-1 blockade therapy and analyzed large-scale real-world datasets. We further investigated the underlying mechanisms through in vitro and in vivo experiments.<br>
Results: A higher incidence of B-cell malignancies has been observed in patients with lung cancer treated with PD-1 blockade therapies based on large-scale real-world data analyses (n = 15,670). The identified lymphomas had a large amount of CD4+ T follicular helper (TFH) cell infiltration. In addition, PD-1 blockade activated PD-1+ TFH cells, which promoted lymphoma proliferation via the IL4/IL4R, IL21/IL21R, and CD40L/CD40 axes. Notably, the lymphomas exhibited high expression of IL4R, IL21R, and CD40.<br>
Conclusions: Our findings highlight the need for careful monitoring and consideration of the potential B-cell malignancy complications in clinical settings in which ICIs are used.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2055-02941212026Adverse events of romidepsin versus tucidinostat for peripheral T-cell lymphoma: a pharmacovigilance study using the Japanese adverse drug event report database48ENNaoTakatsuDepartment of Pharmacy, Okayama University HospitalJunMatsumotoDepartment of Pharmacy, Okayama University HospitalYurieOkaDepartment of Pharmacy, Okayama University HospitalTomonoriSakaiDepartment of Pharmacy, Okayama University HospitalNaohiroIwataDepartment of Pharmacy, Okayama University HospitalTsukasaHigashionnaDepartment of Pharmacy, Okayama University HospitalTatsuakiTakedaDepartment of Pharmacy, Okayama University HospitalHirofumiHamanoDepartment of Clinical Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshitoZamamiDepartment of Clinical Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of lymphomas with poor prognosis, particularly in patients with relapsed or refractory (R/R) disease. Romidepsin and tucidinostat are histone deacetylase inhibitors used to treat R/R PTCL. No head-to-head post-marketing surveillance studies have compared adverse events (AEs) between the two agents. In this brief report, the AE profiles of romidepsin and tucidinostat were compared using the Japanese Adverse Drug Event Report (JADER) database to facilitate their differentiation and promote the management of AEs.<br>
Methods We conducted a descriptive analysis using data from the JADER database from April 2018 to July 2025. The reported AEs for romidepsin and tucidinostat were extracted and classified according to preferred terms (PTs) and system organ classes (SOCs). Reporting odds ratios with 95% confidence intervals were calculated to compare the AE profiles between the groups.<br>
Results In total, 998,397 reports were analysed for all drugs, including 323 for romidepsin and 753 for tucidinostat. Compared with all drugs, both agents showed significant disproportionality signals in four SOCs: Blood and lymphatic system disorders; General disorders and administration site conditions; Investigations; and Neoplasms benign, malignant and unspecified. Romidepsin exhibited additional significant signals in six SOCs: Cardiac disorders, Eye disorders, Gastrointestinal disorders, Immune system disorders, Infections and infestations, and Metabolism and nutrition disorders. Direct comparison between the two agents revealed broader AE profiles for romidepsin, with AEs more frequently reported in eight SOCs, whereas tucidinostat showed AEs in only two SOCs. Romidepsin was associated with AEs more frequently reported in several PTs, including atrial fibrillation and gastrointestinal toxicities, such as constipation, tumour lysis syndrome, hepatotoxicity, and peripheral neuropathy, which was consistent with the results at the SOC level. In contrast, several significant PTs for tucidinostat were observed in General disorders and administration site conditions and Investigations.<br>
Conclusions The Japanese real-world pharmacovigilance analysis showed differences in the AE profiles between romidepsin and tucidinostat. These differences in safety profiles may be useful for treatment selection and AE management in routine clinical practice among patients with R/R PTCL. Further studies are warranted to confirm these findings and better characterise the safety profiles of these agents.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2673-3943722026Relationship Between Numbers of Patients Registered and Procedures Performed at Lung Transplantation Centers in Japan9ENTakashiInoueDepartment of General Thoracic Surgery, School of Medicine, Dokkyo Medical UniversityMasayukiChidaDepartment of General Thoracic Surgery, School of Medicine, Dokkyo Medical UniversityYoshinoriOkadaDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityMasaakiSatoDepartment of Thoracic Surgery, University of TokyoHidemiSuzukiDepartment of General Thoracic Surgery, Chiba University Graduate School of MedicineYasushiHoshikawaDepartment of Thoracic Surgery, Fujita Health University School of MedicineToyofumiChen-YoshikawaDepartment of Thoracic Surgery, Nagoya University Graduate School of MedicineDaisukeNakajimaDepartment of Thoracic Surgery, Kyoto University Graduate School of MedicineYasushiSintaniDepartment of General Thoracic Surgery, The Osaka University Graduate School of MedicineShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama ToshihikoSatoDepartment of General Thoracic, Breast and Pediatric Surgery, Fukuoka University School of MedicineTakeshiShiraishiDepartment of General Thoracic, Breast and Pediatric Surgery, Fukuoka University School of MedicineKeitaroMatsumotoDepartment of Surgical Oncology, Nagasaki University Graduate School of Biomedical SciencesTakahiroNakajimaDepartment of General Thoracic Surgery, School of Medicine, Dokkyo Medical UniversitySumikoMaedaDepartment of General Thoracic Surgery, School of Medicine, Dokkyo Medical UniversityBackground: Recently, there has been a dramatic increase in deceased lung transplantation (DLT) procedures performed in Japan. However, there is concern that the number of transplantations may reach the limit of capacity in some centers. The present study was conducted to analyze the relationship between the numbers of individuals registered for DLT by the Japan Organ Transplantation Network (JOT) and procedures subsequently performed at lung transplantation centers. Methods: Using a database and registry reports provided by the Japanese Society of Lung and Heart-lung Transplantation, the numbers of individuals registered in the JOT and DLT procedures performed from January 2014 to December 2023 were analyzed. Results: The number of registrations was found to be correlated with the number of DLTs, with the coefficient of determination (R2) 0.962 and slope of the regression line (X coefficient) 0.407. The facility with the greatest number of registrations, with a registration-to-transplantation ratio of 0.353, was identified as an outlier (p < 0.05) and excluded from analysis. This exclusion increased both the correlation coefficient value to 0.986 and X coefficient value to 0.461. Conclusions: The present analysis showed that the number of DLTs was well correlated with number of registrations at each of the transplantation facilities. Both registration and transplantation numbers have increased in the recent decade. The facility with the highest number of registrations showed a lower registration-to-transplantation ratio, because the increase in registrations outpaced the number of transplantations.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2575-6265722026Exogenous Glutathione and Nitric Oxide Improve Waterlogging Stress Tolerance in Maizee70136ENProdipto BishnuAngonApplied Plant Biology and Bioinformatics Lab, Department of Biochemistry and Molecular Biology, Bangladesh Agricultural UniversityMd.Tahjib‐Ul‐ArifApplied Plant Biology and Bioinformatics Lab, Department of Biochemistry and Molecular Biology, Bangladesh Agricultural UniversityMd. SarwarJahanApplied Plant Biology and Bioinformatics Lab, Department of Biochemistry and Molecular Biology, Bangladesh Agricultural UniversityMd. MahadiHasanBasic and Applied Scientific Research Centre, Imam Abdulrahman Bin Faisal UniversityYoshiyukiMurataGraduate School of Environmental and Life Science, Okayama UniversityMaize (Zea mays L.) is one of the major grain crops worldwide that is particularly vulnerable to waterlogging (WL) stress. Glutathione (GSH) and nitric oxide (NO) are known to protect plants from a variety of abiotic stresses; however, their potential for improving WL tolerance in maize remains unexplored. The present study examined the impact of exogenously applied GSH and NO on maize plants exposed to WL-stress. Our findings revealed that GSH + NO-treated waterlogged maize plants grew better and produced more biomass than only WL-stressed plants. The improved performance of GSH + NO-sprayed WL-stressed maize seedlings was supported by the increased root dry and fresh weight, shoot length, shoot dry and fresh weight, chlorophyll a, chlorophyll b, and carotenoid content. Exogenous GSH and NO treatments significantly enhanced the amounts of leaf proline, leaf soluble sugars, and total protein in maize seedlings, suggesting adaptive metabolic reprogramming under stress. The increased malondialdehyde (MDA) levels and accumulation of hydrogen peroxide (H2O2) in maize leaves and roots revealed that WL caused significant oxidative damage. Exogenous GSH, NO individually, and combinedly significantly decreased total H2O2 and MDA contents in both leaves and roots. Exogenous GSH and NO reduced oxidative stress by increasing peroxidase activity, ascorbic acid, and anthocyanin content in maize leaf and root tissues. Our findings emphasize the possible relevance of GSH and NO, simultaneously and individually, in enhancing adaptive mechanisms in maize seedlings for reducing WL-induced damage. Although the GSH + NO-mediated approach shows promise for mitigating WL-stress in maize under controlled conditions, further field-based investigations are required to validate its practical applicability.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1557-1963212026Surface Plasmon Resonances in Silver Nanodendrites : Trunk Length and Branch Connectivity Dependence22472258ENQingyuanMaGraduate School of Informatics and Engineering, The University of Electro-communicationsYukiKishidaGraduate School of Informatics and Engineering, The University of Electro-communicationsNobuyukiTakeyasuGraduate School of Natural Science and Technology, Okayama UniversitySatoruShojiGraduate School of Informatics and Engineering, The University of Electro-communicationsThis study systematically investigates how trunk length and branch connectivity govern surface plasmon resonances in silver nanodendrites in the infrared (IR) region using a computational modeling strategy. We show that a continuous conductive trunk is essential for exciting long-wavelength collective plasmon modes. In a simulated bottom-up construction scheme, the trunk length is gradually increased to conductively connect additional branches to the backbone. Our results reveal that the fundamental δ mode resonance can be deterministically tuned across the mid-infrared spectrum (from 3840 nm to 4360 nm) primarily by controlling the trunk connectivity. As the number of connected branches grows, the lowest-order collective resonance peak exhibits a systematic redshift, and its resonance wavelength scales linearly with the effective dipole length Leff of the electron oscillation path. Concurrently, new higher-order modes emerge as local resonances of the connected substructures. These observations indicate that interrupting the conductive pathway causes a global collective mode to decompose into multiple resonances associated with more weakly coupled subsystems. The established linear scaling relationship provides a highly predictable design rule for this “programmable” connectivity, offering a robust platform for advanced applications such as multi-spectral infrared imaging, selective chemical sensing, and surface-enhanced infrared absorption (SEIRA) spectroscopy, where precise, a priori control over narrow-band infrared resonances is essential.
No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama8756-32822092026PPy-coated wire actuators for micromechanostimulation of cells – identification of immediate-early responsive mechanoregulatory genes in osteoblasts117914ENJiaminChenDepartment of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAmaia B.Ortega-SantosDepartment of Physics, Chemistry and Biology (IFM), Linköping UniversitySatoruHayanoDepartment of Orthodontics, Okayama University HospitalZiyiWangDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJose G.MartinezDepartment of Physics, Chemistry and Biology (IFM), Linköping UniversityEmilio SatoshiHaraDepartment of Advanced International and Information Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEdwin W.H.JagerDepartment of Physics, Chemistry and Biology (IFM), Linköping UniversityHiroshiKamiokaDepartment of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMechanotransduction, i.e., the conversion of mechanical cues into biochemical signals, is essential for bone development, remodeling, and adaptation. Although mechanical loading is known to regulate osteoblast function and bone homeostasis, dissecting the early and sustained mechanotransductive responses at the microscale remains challenging due to limitations of existing in vitro models. Here, we report the development and application of a mechanostimulation system comprising a polypyrrole (PPy)-based wire actuator that expands and contracts (4 μm in radius) upon electrical actuation and enables precise, localized micromechanical stimulation of a small number of cells within standard culture formats. Using this system, we applied short-term (30 min) cyclic (Cyc30) or static (Stat30), as well as prolonged (120 min) cyclic (Cyc120) stimulations to two osteoblast-like cells (MC3T3-E1 or KUSA-A1). Subsequent transcriptomic profiling and computational network analyses revealed that Cyc30 was not capable of inducing significant changes in mRNA expression, suggesting cellular adaptation to short-term cyclic loading. In contrast, Stat30 induced the upregulation of Fos, Btg2, Egr1, and Fosl1, all known genes associated with mechanotransduction, supporting the validity and reproducibility of our experimental mechanostimulation system. Notably, two long non-coding RNAs (B930036N10Rik and 5430431A17Rik) were identified for the first time as being upregulated in response to Stat30 stimuli. Among the differentially expressed genes (DEGs) upregulated by Cyc120 stimuli, Hmox1, a stress-inducible enzyme known for its roles in maintaining cellular homeostasis and promoting survival, was the only DEG repeatedly observed across the Cyc30/Cyc120 and Stat30/Cyc120 comparisons in both cell types, potentially emerging as a key stress-response gene under prolonged mechanical loading. Collectively, these results establish the PPy-based microactuator as a powerful tool for microscale mechanobiology, and provide molecular insight into immediate-early responsive transcriptional programs underlying osteoblastic mechanoadaptation conserved across different cell types.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0003-68622026Effect of caffeine on life-history traits on the red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae)ENShine ShaneNaingOkayama University (Graduate School of Environmental, Life, Natural Science and Technology)TeruhisaMatsuuraOkayama University (Graduate School of Environmental, Life, Natural Science and Technology)TakahisaMiyatakeOkayama University (Graduate School of Environmental, Life, Natural Science and Technology)Nowadays, addressing insect pest infestation effectively requires environmentally sound and sustainable pest control methods that minimize environmental pollution. Caffeine (1, 3, 7-trimethylxanthine), a plant-derived secondary metabolite, has insecticidal, hormonal and antifeedant properties, making it a promising and more sustainable alternative for pest management. In this study, the red flour beetle Tribolium castaneum Herbst (Coleoptera: Tenebrionidae), a serious stored pest, was used to investigate the effects of different caffeine concentrations on life-history traits. We applied two delivery methods: 1) oral exposure through a caffeine–sucrose solution for adults, and 2) dietary incorporation of caffeine powder mixed with wheat flour and brewer’s yeast for adults and their larvae. To evaluate the effect of caffeine on life-history traits, adult longevity, pupation rate, larval period, pupal weight, adult body size and food consumption were examined. Results revealed higher caffeine concentrations (> 1%) significantly reduced longevity, delayed pupation, decreased pupal number, pupal weight and adult body size in both males and females. Lower caffeine concentration (0.01%) increased pupal number but resulted in lower offspring quality, such as smaller pupal weight and adult size. The results show that caffeine has negative effects on life-history traits of T. castaneum, suggesting its potential use as a natural pesticide in caffeine-based sustainable pest-management programs and integrated pest management (IPM).No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2077-038315102026Long-Term Outcomes of Endoscopic Ultrasound-Guided Gallbladder Drainage for Acute Cholecystitis in Non-Surgical Candidates: A Multicenter Retrospective Study3621ENKeiHaradaDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyukiMatsumotoDepartment of Endoscopy, Okayama University HospitalKosakuMorimotoDepartment of Internal Medicine, Tsuyama Chuo HospitalEijiroUetaDepartment of Gastroenterology, National Organization Iwakuni Clinical CenterYutakaAkimotoDepartment of Gastroenterology, Japanese Red Cross Okayama HospitalNaoHattoriDepartment of Gastroenterology and Hepatology, Okayama University HospitalTaisukeObataDepartment of Gastroenterology and Hepatology, Okayama University HospitalRyosukeSatoDepartment of Gastroenterology and Hepatology, Okayama University HospitalAkihiroMatsumiDepartment of Endoscopy, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama 700-8558, JapanHiroyukiTerasawaDepartment of Gastroenterology and Hepatology, Okayama University HospitalYukiFujiiDepartment of Endoscopy, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama 700-8558, JapanDaisukeUchidaDepartment of Gastroenterology and Hepatology, Okayama University HospitalShigeruHoriguchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKoichiroTsutsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University HospitalBackground/Objectives: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is a minimally invasive alternative for managing acute cholecystitis in patients who are unsuitable for surgery. Although its short-term efficacy is well-established, its long-term outcomes, especially in patients with malignancy-associated cholecystitis, remain unclear. Methods: This multicenter, retrospective study included 139 patients who underwent EUS-GBD with a plastic stent for inoperable acute cholecystitis between January 2010 and October 2023. Patients were divided into two groups: a malignant group (n = 60) with cystic duct obstruction caused by cancer invasion or self-expandable metal stents, and a benign group (n = 79) with calculous or acalculous cholecystitis. The outcomes assessed included cholecystitis recurrence, time to recurrence, adverse events, and risk factors for recurrence. Results: Technical success was achieved in all patients, with an overall clinical success rate of 94.6%. Cholecystitis recurred significantly more frequently in the malignant group than in the benign group (13.3% vs. 2.5%; p = 0.015). Univariate analysis identified malignancy as a significant risk factor of recurrence (odds ratio, 5.92; p = 0.028). Conclusions: EUS-GBD is a safe and effective long-term treatment for cholecystitis in non-surgical candidates. However, malignancy-associated cholecystitis carries a high risk of recurrence, warranting careful follow-up and individualized management.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1432-107618562026Drug-induced sarcoidosis-like reaction following IL-4/IL-13 receptor blockade by dupilumab391ENKozoYasuiDepartment of Pediatrics, Dentistry and Pharmaceutical Science, Okayama University Graduate School of MedicineMasatoYashiroOkayama University Hospital Center for Innovative Clinical MedicineThe purpose of the study is to review reported cases of dupilumab-associated drug-induced sarcoidosis-like reaction (DISR) and consider possible immunologic mechanisms. This short review aims to raise awareness of dupilumab-associated DISR and discuss safety considerations in pediatric patients.<br>
Conclusion: Dupilumab is a human monoclonal antibody that reduces inflammation driven by T helper 2 (Th2) cells and is used to treat type 2 inflammatory disorders, including atopic dermatitis. The most common adverse reactions during the first year of treatment are local reactions at the injection site, conjunctivitis, and headache. Although DISR is rare, it has been documented in dupilumab-treated patients. We hypothesized that dupilumab shifts the Th1/Th2 equilibrium toward Th1 and granulomatous inflammation, which may present as DISR. We identified and reviewed 10 recently reported DISR cases and observed that reported features of DISR—including uveitis, optic neuritis and meningoencephalitis, bilateral hilar lymphadenopathy, and histopathologically noncaseating granulomas—can mimic systemic sarcoidosis. Discontinuation of dupilumab resulted in favorable outcomes in most reported DISR cases; however, symptoms worsened in some cases and sequelae became a concern. Case reports of DISR have so far been limited to adults or adolescents, but awareness of potential adverse effects of dupilumab remains important in pediatric patients.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2731-58942026Comparative study of Ni–CeO2 catalysts prepared by impregnation and coprecipitation for CO2 methanationENNobukoFukudaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityShuichiImanoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNozomiNakaharaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThis study explores how synthesis methods affect the structure and CO2 methanation performance of Ni–CeO2 catalysts prepared by coprecipitation and impregnation under identical conditions. Coprecipitation generated particles below 100 nm with uniform elemental distribution, together with large bulk-like particles exhibiting locally concentrated Ni species, attributed to differences in hydroxide solubility. Impregnation, by contrast, produced very large particles (> 500 nm) with smaller particles attached, while maintaining relatively homogeneous elemental distribution. Coprecipitated catalysts showed slightly higher surface area and oxygen vacancy concentration, resulting in higher apparent turnover frequencies (TOFapp) below 300 °C due to enhanced CO2 adsorption and high Ni site density. However, at temperatures above 350 °C, impregnated catalysts displayed higher CH4 selectivity and TOFapp, indicating reduced kinetic limitations and more efficient active-site utilization. These results provide insights for rational design of efficient CO2 methanation catalysts.No potential conflict of interest relevant to this article was reported.American Geophysical Union (AGU)Acta Medica Okayama0094-82765392026Apollo 17 Lunar Surface Gravimeter as a Seismometer: Relocating Shallow‐Moonquake Sources and Implications for Source Mechanisme2025GL121619ENKeisukeOnoderaInstitute for Planetary Materials, Okayama UniversityTaichiKawamuraInstitut de Physique du Globe de Paris, Université Paris CitéAmong the reported seismic events on the Moon, shallow moonquakes are known for their unique features, such as high-frequency energy excitation, similarity to intraplate earthquakes, and the largest energy release of all reported moonquakes. Despite these interesting features, a small number of samples (<80 events) and sparse seismic network observations prevented us from gaining an in-depth understanding of shallow moonquakes. In this study, by using the Apollo 17 gravimeter as a pseudo-seismometer, we extend the Apollo lunar seismic network and located a few shallow moonquakes more accurately. In addition, comparing the located shallow-moonquake epicenters with surface/subsurface geological features indicates that at least one event may be better explained by deep-seated faults within the crust. Along with a previous demonstration of low-frequency moonquakes, our analysis of high-frequency events shows that the Apollo 17 gravimeter can serve as a seismometer over a broader frequency range than previously considered.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0935-96482026Turning Unpredictable Biomolecule Adsorption to Controlled Corona Formation: Focus on Carbon Nanomaterialse23328ENYajuanZouResearch Institute for Interdisciplinary Science, Okayama UniversityYaleiHuCNRS, Immunology Immunopathology and Therapeutic Chemistry University of Strasbourg ISISJieYuGraduate School of Human and Environmental Studies, Kyoto UniversityNaokiKomatsuGraduate School of Human and Environmental Studies, Kyoto UniversityYutaNishinaResearch Institute for Interdisciplinary Science, Okayama UniversityAlbertoBiancoResearch Institute for Interdisciplinary Science, Okayama UniversityWith unique optical and physicochemical properties, carbon nanomaterials (CNMs), including carbon nanotubes, graphene-related materials, nanodiamonds, and carbon dots, are extensively explored as platforms for cancer diagnosis and treatment. However, in biofluids, CNMs spontaneously adsorb biomolecules to form an unpredictable corona, obstructing the implementation of their designed functions. In this review, we summarize how the intrinsic and acquired properties of CNMs affect protein corona formation, and the consequent biological and toxicological outcomes, as well as strategies to reshape the composition and structural organization of adsorbed proteins. This comprehensive knowledge will provide insights into developing CNMs with tailored corona and requested functions in cancer nanomedicine, advancing their translations into clinics.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0953-81943842026Type III CD38 is present in the membrane of neurosecretory vesicles and has a cytosol-facing catalytic domain in primate oxytocin neuronse70187ENTatsukiMiyamotoDepartment of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama UniversityAkariMatsushimaDepartment of Biology, Faculty of Science, Okayama UniversityAkitoOtuboDepartment of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama UniversityChihongSongExploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural SciencesKazuyoshiMurataExploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural SciencesTakumiOtiDepartment of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama UniversityHirotakaSakamotoDepartment of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama UniversityCD38, an ADP-ribosyl cyclase that generates cyclic ADP-ribose (cADPR), is essential for Ca2+-dependent oxytocin release. However, its subcellular localisation and membrane topology within oxytocin neurones have remained unclear. We investigated the distribution and orientation of CD38 in oxytocin-producing neurones of Japanese macaques (Macaca fuscata) using immunoelectron microscopy combined with biochemical isolation of neurosecretory vesicles (NSVs). CD38 immunoreactivity was selectively detected on oxytocin-containing NSVs in axon terminals in the posterior pituitary and dendrites of the supraoptic nucleus, whereas vasopressin vesicles and the plasma membrane lacked detectable labelling. Cryo-electron microscopy confirmed the structural integrity of purified NSV fractions, and Western blotting verified the presence of CD38 protein within these fractions. Permeabilisation-dependent immunogold labelling further demonstrated that the NSV membrane localisation of CD38 and that the N-terminal region of CD38 is oriented toward the vesicle lumen, consistent with a type III membrane topology in which the catalytic domain faces the cytosol. This arrangement positions the active site near cytosolic NAD+, enabling localised cADPR production adjacent to Ca2+-mobilising channels that support regulated exocytosis. These findings identify, in primate oxytocin neurones, a previously unrecognised, vesicle-associated pool of CD38 with a cytosol-facing catalytic domain and provide a structural framework for understanding how intracellular type III CD38 contributes to neuropeptide release.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2051-33801432026An Atypical Surgical Case of Lung Cancer With Unilateral Absence of the Pulmonary Artery, With Only the Superior Branch Remaininge70554ENKazuhiroOkadaDepartment of Thoracic Surgery, Okayama University HospitalShinTanakaDepartment of Thoracic Surgery, Okayama University HospitalTsuyoshiRyukoDepartment of Thoracic Surgery, Okayama University HospitalYasuakiTomiokaDepartment of Thoracic Surgery, Okayama University HospitalKazuhikoShienDepartment of Thoracic Surgery, Okayama University HospitalKenSuzawaDepartment of Thoracic Surgery, Okayama University HospitalKentarohMiyoshiDepartment of Thoracic Surgery, Okayama University HospitalMikioOkazakiDepartment of Thoracic Surgery, Okayama University HospitalSeiichiroSugimotoDepartment of Thoracic Surgery, Okayama University HospitalShinichiToyookaDepartment of Thoracic Surgery, Okayama University HospitalA 69-year-old woman was referred to our department for an abnormal shadow on chest radiography. Contrast-enhanced computed tomography (CT) revealed a solid nodule in the right lower lobe and defects in the branches of the middle and lower lobes of the pulmonary artery (PA). Furthermore, collateral circulation had developed via the right internal thoracic, bronchial, intercostal, inferior phrenic, and subdiaphragmatic arteries. The solid nodule was diagnosed as adenocarcinoma by CT-guided biopsy. The day before surgery, embolization was performed using interventional radiology (IVR) to mitigate the risk of bleeding during thoracotomy, resulting in minimal intraoperative bleeding during the subsequent right middle and lower lobectomies with lymph node dissection (ND2a-1). UAPA is a rare congenital abnormality characterized by unilateral pulmonary artery agenesis. The presence of recurrent infections, extensive intrathoracic adhesions, and developed collateral circulation may pose challenges during surgical procedures.No potential conflict of interest relevant to this article was reported.American Physical Society (APS)Acta Medica Okayama3070-224012026Cryogenic buffer gas beam source with in situ ablation target replacement000016ENZhenHanDepartment of Physics, University of ChicagoZackLasnerDepartment of Physics, Harvard UniversityCollinDiverCenter for Fundamental Physics, Northwestern UniversityPeiranHuDepartment of Physics, University of ChicagoTakahikoMasudaResearch Institute for Interdisciplinary Science, Okayama UniversityXingWuFacility for Rare Isotope Beams, Michigan State UniversityAyamiHiramotoResearch Institute for Interdisciplinary Science, Okayama UniversityMayaWattsCenter for Fundamental Physics, Northwestern UniversitySatoshiUetakeResearch Institute for Interdisciplinary Science, Okayama UniversityKojiYoshimuraResearch Institute for Interdisciplinary Science, Okayama UniversityXingFanDepartment of Physics, Harvard UniversityGeraldGabrielseCenter for Fundamental Physics, Northwestern UniversityJohn M.DoyleDepartment of Physics, Harvard UniversityDavidDeMilleDepartment of Physics, University of ChicagoThe design and performance of a cryogenic buffer gas beam source with a load-lock system is presented. The third generation of advanced cold molecule electric dipole moment search (ACME III) uses this source to produce a beam of cold, slow thorium monoxide (ThO) molecules. A feature of the apparatus is the capability of replacing the ablation targets without interrupting the vacuum or cryogenic conditions, thus increasing the average signal in the eEDM search. The beam source produces 1.3×1011 ground-state ThO molecules per pulse on average, with rotational temperature of 4.8K, molecular beam solid angle of 0.31sr, and forward velocity of 200ms−1, parameters that are consistent with the performance of a traditional source (without a load lock) requiring time-consuming thermal cycles for target replacement. Long-term yield improvement of ∼40% is achieved when the load-lock system is employed to replace targets every two weeks.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0969-02392026Counterion condensation, ion pairing and scattering properties of carboxymethyl cellulose with mono- and di-valent ionsENElmira AbbasiGharehTapehMaterials Science and Engineering Department, The Pennsylvania State UniversityTakaichiWatanabeDepartment of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama UniversityFerencHorkaySection on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthCanHouInstitute of Physical Chemistry, RWTH Aachen UniversityCarlos G.LopezMaterials Science and Engineering Department, The Pennsylvania State UniversityMaxHohenschutzInstitute of Physical Chemistry, RWTH Aachen UniversityWe study the scattering and conductometric properties of a semiflexible polyelectrolyte, carboxymethyl cellulose (CMC), with monovalent and divalent counterions in aqueous media without added salts. The scattering patterns for the magnesium salts of CMC display a broad shoulder instead of the scattering peak observed for the monovalent salts. This suggests weaker electrostatic repulsion between chains and a consequent loss of local order. The result is consistent with conductivity measurements, which reveal that the effective charge of the backbone for MgCMC is approximately half that of NaCMC. The decrease in charge density agrees with Oosawa–Manning condensation, which expects the charge density to be inversely proportional to the counterion valence. Alkali metal counterions show large differences in ion-pair formation but only a weak effect in counterion condensation. We suggest that paired ions are a subset of condensed ions. A review of different methods to evaluate counterion condensation, including potentiometry, osmometry and viscosity-based methods is presented. Qualitative agreement between these methods is found and possible reasons for the discrepancies are discussed.No potential conflict of interest relevant to this article was reported.SpringerActa Medica Okayama0918-94402026CDPKs as Ca2+ signaling decoders in guard cell signalingENIzumi C.MoriInstitute of Plant Science and Resources, Okayama UniversityStomatal movements are essential for balancing photosynthetic carbon dioxide uptake with water conservation and defense against pathogens. These processes are controlled by complex signaling networks in guard cells, in which calcium ions (Ca2+) act as a ubiquitous second messenger. Although stimulus-specific Ca2+ signatures have been well documented, how these signals are decoded into distinct physiological responses remains a central question in plant biology. Increasing evidence highlights calcium-dependent protein kinases (CDPKs) as key signal decoders in guard cell signaling. This mini-review summarizes recent advances in our understanding of how CDPKs perceive and translate Ca2+ fluctuations into stomatal responses. We focus on the roles of CDPKs in signaling pathways triggered by diverse stimuli, including phytohormones such as abscisic acid ABA, jasmonates, and salicylic acid, as well as biotic cues such as microbe- or pathogen-associated molecular patterns (MAMPs/PAMPs) and pathogen infection. We also discuss how gaseous signals and metabolic cues are integrated into CDPK-mediated pathways. In addition to their established role as downstream decoders of Ca2+ signals, emerging studies suggest that CDPKs can act upstream of Ca2+ oscillations and may also function through Ca2+-independent mechanisms. Together, these findings highlight the context-dependent and integrative roles of CDPKs in regulating stomatal behavior, contributing to plant fitness under fluctuating environmental conditions.No potential conflict of interest relevant to this article was reported.John Wiley & Sons LtdActa Medica Okayama1362-10173132026Early sedation intensity and psychological outcomes in critically ill adultse70500ENMikikoIwataniOkayama University Hospital; Graduate School of Health Sciences, Doctoral Program, Okayama UniversityMichikoMorimotoFaculty of Health Sciences, Okayama UniversityBackground: Long-term psychological impairment is a major concern for intensive care unit (ICU) survivors. Early deep sedation during mechanical ventilation has been associated with poor short-term outcomes and mortality after ICU discharge; however, its relationship with psychological outcomes remains unclear.<br>
Aim: To investigate sedation intensity during the first 24 h of mechanical ventilation and its association with psychological impairment 3 months after ICU discharge.<br>
Study Design: This retrospective ancillary analysis of a single-centre cohort study was conducted in two general ICUs at a university hospital in Japan. Eligible patients stayed in the ICU for more than 48 h and received mechanical ventilation for more than 8 h. Sedation intensity was quantified using the Sedation Index (SI) and Agitation Index (AI) derived from Richmond Agitation-Sedation Scale scores during the first 24 h. Psychological impairment 3 months post-ICU discharge was assessed based on symptoms of post-traumatic stress, anxiety and depression. Associations were examined using hierarchical logistic regression.<br>
Results: Among 130 participants, the median age was 64 years, and the median ventilation duration was 14 h. The median SI was 3.0; 47% had SI > 3, and 8.5% had AI > 0. Sedation intensity showed no significant association with psychological impairment (SI: adjusted odds ratio [OR] 0.87, 90% confidence interval [CI] 0.57–1.33, p = 0.59; AI: adjusted OR 0.21, 90% CI 0.01–3.08, p = 0.34). However, any agitation during the ICU stay was associated with psychological outcomes (adjusted OR 2.61, 90% CI 1.16–5.88, p = 0.05).<br>
Conclusions: This study did not identify a statistically significant association between early sedation intensity and psychological impairment 3 months after ICU discharge.<br>
Relevance to Clinical Practice: Critical care nurses should carefully titrate sedation from the initiation of mechanical ventilation to avoid unnecessary deep sedation, considering sedation intensity over time, while actively assessing agitation and its underlying causes.No potential conflict of interest relevant to this article was reported.Japan Poultry Science AssociationActa Medica Okayama1346-7395632026Supplementation of 5-Aminolevulinic Acid Suppressed Body Weight Loss and Reduced Disease Severity During Eimeria tenella Infection in Broiler Chickens2026010ENTaqi AhmadHanifLaboratory of Animal Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMakotoMatsubayashiDepartment of Veterinary Science, Graduate School of Veterinary Sciences, Osaka Metropolitan UniversityToshimitsuHatabuLaboratory of Animal Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThis study aimed to evaluate the effects of 5-aminolevulinic acid (5-ALA) supplementation in broiler chickens infected with Eimeria tenella. To assess these effects, chickens supplemented with 20 ppm 5-ALA (5-ALA group) were compared with non-supplemented controls (control group). Sporulated E. tenella oocysts (2.0 × 103 oocysts per animal) were administered orally to 2-week-old broiler chickens. Body weight was measured weekly, and fecal samples were collected daily from 4 to 15 days post-infection (dpi). Fecal oocyst shedding was quantified using the sucrose flotation method. Cecal tissues were collected at 5 dpi for histopathological analysis and lesion scoring. The animals in the 5-ALA group exhibited significantly greater weight gain and milder clinical signs than those in the control group. Fecal oocyst shedding was highest at 7 dpi in both groups; however, the 5-ALA group exhibited significantly lower oocyst output than the control group. The total number of fecal oocysts shed during the acute infection period was significantly lower in the 5-ALA group than in the control group. Histopathological analysis revealed that although both groups exhibited epithelial hyperplasia and E. tenella schizonts in the cecal submucosa, inflammatory cell infiltration, cecal tissue damage, and histological lesion scores were significantly lower in the 5-ALA group than in the control group. These results suggest that 5-ALA supplementation may mitigate the clinical, parasitological, and histological effects of E. tenella infection in broiler chickens.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2045-76341552026Multi-Transcriptomic Analysis Reveals That EREG-Driven TME Crosstalk Defines Anti-EGFR Response in Colorectal Cancere71853ENAtsukiTaniguchiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShunsukeKagawaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShoheiNogiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomohikoYagiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNobuhikoKanayaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinjiKurodaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatoruKikuchiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshihikoKakiuchiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiTazawaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySidedness influences colorectal cancer (CRC) prognosis and treatment response, yet the mechanism dictating differential EGFR inhibitor (EGFRI) sensitivity is unclear. This study investigated the tumor microenvironment (TME) in relation to EGFRI eligibility―clinically defined by factors such as tumor sidedness (e.g., left-sided), RAS/BRAF wild-type status, and microsatellite stability (MSS)―using integrated single-cell RNA sequencing (scRNA-seq), with bulk RNA-seq and spatial transcriptomics validation. We found cancer cell features reflected EGFRI eligibility more strongly than sidedness. EGFRI eligible tumors exhibited high Epiregulin (EREG) expression by cancer cells. Cell interaction analysis revealed a specific “EREG/EGFR/CSF axis” in EGFRI eligible CRC: EREG derived from cancer cell stimulates EGFR-expressing non-myCAF subtypes of cancer-associated fibroblasts (CAFs), which signal via CSF to M1/M2-like Tumor-Associated Macrophages/Monocytes (TAM/TAMo), potentially promoting M2 polarization. Spatial analysis confirmed the proximity of these interacting cell populations and localized EGFR pathway activation near cancer cells specifically in eligible tumors. This study provides a TME-centric view of EGFRI eligibility, identifying a key intercellular communication network driving differential responses. These findings suggest TME features could offer more precise patient stratification than sidedness alone, potentially improving CRC therapeutic strategies.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-2322162026Sex-related differences in blood concentrations and emergence profiles following total intravenous anesthesia with remimazolam and remifentanil13650ENRikoSatoDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiHiguchiDepartment of Dental Anesthesiology, Okayama University HospitalYukikoNishiokaDepartment of Dental Anesthesiology, Okayama University HospitalSakiMiyakeDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaMiyawakiDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRemimazolam is a novel, short-acting benzodiazepine, which is characterized by rapid onset and quick recovery. The clinical efficacy and metabolism of many intravenous anesthetics are known to be influenced by sex; however, the effects of sex on the anesthetic efficacy and metabolism of remimazolam remain unclear. This prospective observational study examined sex-related differences in pharmacokinetics and emergence profiles after total intravenous anesthesia was induced with remimazolam and remifentanil in patients undergoing oral and maxillofacial surgery. Thirty-five American Society of Anesthesiologists Physical Status 1 adults (19 females, 16 males), aged 18–49 years, received standardized dosing based on their actual body weights. Serum remimazolam concentrations were measured at the end of administration and immediately before extubation using high-performance liquid chromatography. Although the emergence time did not differ significantly between the sexes, the mean emergence time of the females was approximately 80 s shorter. Serum remimazolam concentrations were significantly lower in females at both measurement time points (p < 0.001). This may suggest that remimazolam is metabolized more rapidly in women. Although these sex-related pharmacokinetic differences did not affect the time to awakening under combined remimazolam and remifentanil anesthesia, clinicians should be aware of potential sex differences in the pharmacokinetics of remimazolam.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2589-00422952026Wnt3-mediated fibrosis and carcinogenesis of lung squamous cell carcinoma in idiopathic pulmonary fibrosis115667ENAtsushiMatsuokaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalMasayoshiOhkiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidejiroTorigoeDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyaHisamatsuDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyotaFujiwaraDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiIshimuraDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeMoriDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyunosukeFujiiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAsukaMimataDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOkadaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoYoshichikaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMaoYoshikawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYumaFukumotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruchikaYamamotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKumiNakajimaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirofumiInoueCenter for Comprehensive Genomic Medicine, Okayama University HospitalDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University HospitalShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIdiopathic pulmonary fibrosis (IPF) increases the risk of lung squamous cell carcinoma (LUSC), yet its molecular pathogenesis remains unclear. We conducted multi-omics analysis, including single-cell RNA sequencing and digital spatial profiling, on LUSC specimens from seven patients with usual interstitial pneumonia (UIP). In UIP lung tissue, metaplastic basal cells arising from the transdifferentiation of alveolar type 2 (AT2) cells were increased. LUSC tumors arising within UIP exhibited molecular profiles and trajectory dynamics suggesting derivation from these metaplastic basal cells. Both UIP-affected tissue and associated tumors showed activation of Wnt signaling, particularly WNT3 expression. Additionally, enrichment of the nuclear factor erythroid 2-related factor 2 (NRF2)-linked antioxidant response was observed in LUSC within UIP. Targeting Wnt/β-catenin signaling restored the sensitivity of these stress-adapted cancer cell lines to oxidative damage. These findings suggest that LUSC within UIP originates from AT2-derived metaplastic basal cells and involves aberrant Wnt3 activation, linking fibrosis to carcinogenesis and highlighting a potential therapeutic strategy.No potential conflict of interest relevant to this article was reported.