岡山大学環境管理センターActa Medica Okayama0917-1533482026岡山大学環境管理センター報 第48号ENNo potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0012-369217042026Impact of Preexisting Schizophrenia Spectrum Disorders on the Receipt of Surgery and Other Treatments for Non-Small Cell Lung Cancer: A Multicenter Nationwide Cohort Study in JapanENYutoYamadaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasakiFujiwaraDepartment of Neuropsychiatry, Medical Development Field, Okayama UniversityTaisukeIshiiDivision 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 CenterMaikoFujimoriDivision 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 UniversityEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalTaichiShimazuDivision 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 (SSDs) experience higher cancer mortality than the general population. Disparities in treatments for non-small cell lung cancer (NSCLC) among this population remain underexamined.<br>
Research Question: Are patients with SSDs less likely to receive surgery, adjuvant chemotherapy for stage II/IIIA, concurrent chemoradiotherapy for stage III, and systemic therapy for stage IV NSCLC compared with those without psychiatric disorders?<br>
Study Design and Methods: This retrospective cohort study used national Hospital-Based Cancer Registry data linked to hospital-based administrative data in Japan. It included patients who received initial treatment for NSCLC between 2018 and 2021. Presence of SSDs was defined as a diagnosis using F20 to F29 codes from International Classification of Diseases, 10th Revision. The primary outcome was receipt of surgery for NSCLC. Secondary outcomes were receipt of the following: (1) adjuvant chemotherapy within 180 days in patients with pathologic stage II/IIIA NSCLC; (2) concurrent chemoradiotherapy in clinical stage III NSCLC; and (3) systemic therapy in stage IV NSCLC. Multivariable logistic regression adjusted for age, sex, clinical stage, comorbidities, and functional status was performed.<br>
Results: The final cohort comprised 166,663 patients, 1,346 of whom had SSDs. Patients with SSDs were more likely to be diagnosed at stage IV NSCLC (45.0% vs 31.4%) and less likely to undergo surgery (31.5% vs 49.9%; adjusted OR [aOR], 0.70; 95% CI, 0.57-0.85), receive adjuvant chemotherapy (aOR, 0.31; 95% CI, 0.17-0.57), or receive systemic therapy (aOR, 0.54; 95% CI, 0.45-0.65). No significant difference was observed in concurrent chemoradiotherapy for stage III NSCLC (aOR, 0.99; 95% CI, 0.73-1.34).<br>
Interpretation: Patients with SSDs were less likely to receive surgery and other stage-appropriate treatments for NSCLC, highlighting the need for targeted interventions to promote equitable cancer care for these individuals.No potential conflict of interest relevant to this article was reported.Informa UK LimitedActa Medica Okayama2578-58264812024Comparison of different ANCA detection methods in a predominantly MPO-ANCA-associated vasculitis cohort4757ENYasuhiroKatsumataDivision of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of MedicineKen-eiSadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesTomohiroKamedaDepartment of Rheumatology, Takamatsu Red Cross HospitalHiroakiDobashiDivision of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa UniversityShinyaKanameDepartment of Nephrology and Rheumatology, Kyorin University School of MedicineNaotakeTsuboiDepartment of Nephrology, Fujita Health University School of MedicineYoshinoriMatsumotoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKoichiAmanoDepartment of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical UniversityNaotoTamuraDepartment of Internal Medicine and Rheumatology, Juntendo University School of MedicineMasayoshiHarigaiDivision of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of MedicineResearch Committee of Intractable Vasculitis Syndrome and the Research Committee of Intractable Renal Disease of the Ministry of Health, Labour and Welfare of JapanWe compared different antineutrophil cytoplasmic antibody (ANCA) detection methods using a predominantly myeloperoxidase (MPO)-ANCA-associated vasculitis cohort. Stored sera from 147 patients with untreated ANCA-associated vasculitis (AAV), including microscopic polyangiitis and granulomatosis with polyangiitis (n = 115 and 32, respectively), and 124 disease controls were tested for P-ANCA and C-ANCA with immunofluorescence (IIF), and for MPO-ANCA and proteinase 3 (PR3)-ANCA with different antigen-specific immunoassays: direct enzyme-linked immunosorbent assay (ELISA), chemiluminescent enzyme immunoassay (CLEIA), third-generation fluorescent enzyme immunoassay (FEIA), and latex turbidimetrical immunoassay (LTIA). In addition, MPO-ANCA and PR3-ANCA titers were calibrated using certified reference materials (CRMs). The sensitivities and specificities for AAV diagnoses were 95% and 94% (IIF), 86% and 98% (ELISA), 93% and 94% (CLEIA), 92% and 96% (FEIA), and 68% and 88% (LTIA). Dual IIF/antigen-specific immunoassay testing reduced diagnostic accuracies from 94% to 93%. The quantitative agreement between ANCA levels measured using CLEIA and FEIA and calibrated using CRMs was not good. In conclusion, this study demonstrated the high performance of antigen-specific immunoassays for AAV diagnosis in a predominantly MPO-ANCA-associated vasculitis cohort and suggested that the benefit of dual IIF/antigen-specific immunoassay testing is limited. Standardizing ANCA measurements using different immunoassays was difficult, even when using CRMs.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0912-38144152026Direct and Element‐Mediated Edaphic Effects Shape Resource‐Conservative Leaf Trait Variation Across Serpentine and Limestone Soilse70124ENShogoUeyamaDepartment of Biology, Okayama UniversityEmiKusatakeDepartment of Biology, Okayama UniversityMakikoMimuraDepartment of Biology, Okayama UniversityEdaphically extreme substrates, such as serpentine and limestone, impose strong physiological constraints on plants and are frequently associated with resource-conservative leaf traits and narrow plant endemism. However, it remains unclear how edaphic selection shapes leaf traits and whether these shifts are driven primarily by direct soil-imposed constraints or indirectly by changes in leaf elemental composition. Here, we examined soil–leaf elemental relationships, leaf functional traits, and CSR strategies (Competitive, Stress-tolerant, and Ruderal strategy) using piecewise structural equation modeling across 16 populations of five closely related Epimedium taxa distributed on serpentine, limestone, and other substrates in western Japan. Despite marked differences in soil and leaf elemental composition between serpentine and limestone sites, populations on both substrates converged toward resource-conservative leaf traits, including lower specific leaf area (SLA) and a shift toward thicker leaves and higher leaf dry matter content (LDMC), even after accounting for species identity. Piecewise structural equation modeling revealed two pathways consistent with the proposed hypotheses: A strong direct association between soil elemental composition and leaf trait variation and a weaker indirect association involving leaf elemental composition. Together, our results suggest that edaphic mosaics are linked to convergent resource-conservative phenotypes through two partly overlapping pathways across serpentine and limestone soils: strong direct associations with leaf functional traits and weaker associations involving leaf elemental composition.No potential conflict of interest relevant to this article was reported.Informa UK LimitedActa Medica Okayama2150-55941712026Rotavirus-NSP5 interacts with and hijacks host ATP citrate lyase to viroplasms, enhancing lipid biosynthesis for facilitating rotavirus infection2709258ENRanjanaSharmaRegional VRDL, ICMR- National Institute for Research in Bacterial Infections (formerly ICMR-NICED)ShreyaBanerjeeRegional VRDL, ICMR- National Institute for Research in Bacterial Infections (formerly ICMR-NICED)Ratul DattaChaudhuriRegional VRDL, ICMR- National Institute for Research in Bacterial Infections (formerly ICMR-NICED)Kaushik KumarDeyDivision of Applied Biosciences, ICMR- National Institute for Research in Bacterial Infections (Formerly ICMR-NICED)AnimeshGopeDepartment of Central Instrumental Facility, ICMR- National Institute for Research in Bacterial Infections (Formerly ICMR-NICED)Shin-ichiMiyoshiICMR- National Institute for Research in Bacterial Infections (Formerly ICMR-NICED), Collaborative Research Center of Okayama University for Infectious Diseases in IndiaDaisukeImamuraICMR- National Institute for Research in Bacterial Infections (Formerly ICMR-NICED), Collaborative Research Center of Okayama University for Infectious Diseases in IndiaMamtaChawla-SarkarRegional VRDL, ICMR- National Institute for Research in Bacterial Infections (formerly ICMR-NICED)Rotavirus (RV) replication occurs within viroplasms (VMs) and is initiated by two RV non-structural proteins NSP2 and NSP5. Viruses exploit host cellular components for their replication and assembly; however, information on the roles of host proteins in VM dynamics and RV replication is limited. Thus, in the current study, we used proteomics to identify host proteins that interact with NSP5 during RV infection to delineate their role in virus replication. A large number of host proteins (n = 128) were found to interact with NSP5, and Gene Ontology enrichment analysis revealed the enrichment of various metabolic processes during RV infection. One of the essential host proteins, ATP citrate lyase (ACLY), which is involved in the de novo lipid synthesis pathway, was found to interact with C-terminal region of RV-NSP5 and colocalize within VMs. Following RV infection, the serine 455 phosphorylation of ACLY was induced, suggesting increased enzymatic activation. This correlates with enhanced lipid droplet production via increased acetyl-coenzyme A expression levels, which in turn supports VM formation. The ACLY inhibitors SB204990 or hydroxycitric acid tripotassium hydrate significantly reduced RV-infection in vitro. This anti-rotaviral effect of drug was further validated in BALB/c suckling mice by measuring viral protein expression and viral titers. In the presence of ACLY inhibitor, reduced viral titers, reduced viral protein expression, and improved small intestinal histopathology were observed. These findings suggest a protective effect of drugs against RV infection in vivo and highlight ACLY as a potential anti-rotaviral target for the development of new therapeutics.No potential conflict of interest relevant to this article was reported.公益社団法人日本都市計画学会Acta Medica Okayama0916-06476132026CIDパイロットプロジェクトとSpecial Rate型BIDおよび寄付金型BIDの比較分析 -オーストラリア・ニューサウスウェールズ州を対象として-895902ENHirofumiHoriOkayama UniversityTatsuyaKitanoOkayama University日本のエリアマネジメント負担金制度は、合意形成に要する高い同意要件が原因で停滞している。本研究は、オーストラリア・ニューサウスウェールズ州における三類型のBID（Business Improvement District）を調査し、日本のエリアマネジメント活動の改善に資する提案を行うことを目的とする。調査の結果、制度は都市規模に応じて活用されていることが明らかとなった。地方都市では行政が主な権限を要する「Special Rate型BID」が展開されている一方、都市部では民間側が主な権限を要する「CIDパイロットプロジェクト」や「寄付金型BID」が展開されている。これらの知見に基づき、本論文は、地域の組織能力の成熟度に合わせて行政主導から民間主体へと体制を移行させる「段階的移行モデル」を提案する。柔軟かつ都市規模に適した制度選択を可能にすることは、導入障壁を下げ、日本の都市におけるエリアマネジメント活動を活性化させる上で不可欠である。No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8052026Dynamics of Serum Amyloid A Levels in the Blood, Brain and Liver in a Mouse Model of Focal Cerebral Ischemia309316ENSakiEgashiraDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityTakafumiNakanoDepartment of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka UniversityKeiichiIrieDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversitySoichiroUshioDepartment of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka UniversityAkikoManabeDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityAyukoMasakiDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityRieMukaiDepartment of Microbiology Laboratory, Faculty of Pharmaceutical Sciences, Fukuoka UniversityYoshihikoNakamuraDepartment of Emergency and Critical Care Medicine, Fukuoka University HospitalMasatoHosokawaDepartment of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityTomomitsuSathoDepartment of Microbiology Laboratory, Faculty of Pharmaceutical Sciences, Fukuoka UniversityKazunoriSanoDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityKenichiMishimaDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka UniversityOriginal Article10.18926/AMO/71340This study examined the dynamics of serum amyloid A (SAA) levels in the blood, brain, and liver over time using a mouse model of focal cerebral ischemia induced by occlusion of the middle cerebral artery (MCA) for 4 h followed by reperfusion. Blood SAA concentrations increased transiently after cerebral infarction, coinciding with changes in brain and liver SAA gene expression and protein levels. SAA concentrations in the brain, liver, and blood increased at similar time points after cerebral infarction, suggesting that SAA may serve as an important indicator of the associated pathological condition.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8052026Prognostic Value of Combined Preoperative CALLY and SII Assessment in Patients Undergoing Resection for Esophageal Squamous Cell Carcinoma299308ENTaoXuDepartment of Oncology, The General Hospital of Western Theater CommandYingZhengDepartment of Oncology, The General Hospital of Western Theater CommandXuemeiHuangDepartment of Oncology, The General Hospital of Western Theater CommandHongLuoDepartment of Oncology, The General Hospital of Western Theater CommandOriginal Article/10.18926/AMO/71339This study evaluated the prognostic significance of the C-reactive protein–albumin–lymphocyte (CALLY) index and systemic immune-inflammation (SII) index in predicting postoperative outcomes in patients with esophageal squamous cell carcinoma (ESCC). A retrospective analysis was performed on clinical data from 102 patients with ESCC who underwent surgical resection at Western Theater General Hospital of China between January 2020 and July 2023. The associations between preoperative CALLY and SII indices and relapse-free survival (RFS) and overall survival (OS) were examined. Survival curves were generated using the Kaplan–Meier method, and prognostic factors were identified using Cox proportional hazards regression analysis. Patients with a high CALLY index had significantly longer RFS (HR=0.30, 95% CI: 0.13-0.71), and those with a low SII index also had significantly longer RFS (HR=2.23, 95% CI: 1.12-4.41). Similarly, patients with a high CALLY index had significantly longer OS (HR=0.27, 95% CI: 0.13-0.55), and those with a low SII index had significantly longer OS (HR=2.27, 95% CI: 1.09-4.71). When patients were stratified into four groups, the low-CALLY–high-SII group showed significantly shorter RFS than the high-CALLY–low-SII group (HR=0.26, 95% CI: 0.11-0.61; p=0.013), and OS was also significantly worse in the low-CALLY–high-SII group (HR=0.22, 95% CI: 0.09-0.54; p=0.016). Univariate Cox regression analysis identified both CALLY and SII as significant prognostic factors. In multivariate analysis, the CALLY index and N stage were independently associated with RFS, whereas only tumor size remained independently associated with OS. The combined assessment of preoperative CALLY and SII indices may be useful for prognostic stratification in patients with ESCC undergoing upfront surgical resection. It may help identify high-risk patient subgroups with distinct survival outcomes, thereby providing a potential rationale for stratifying postoperative surveillance and tailoring individualized adjuvant strategies, although validation in larger prospective cohorts is warranted.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2662-2963762026A simple proof for the existence of V-form fronts in reaction–diffusion equations48ENSatomuNagashimaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMasaharuTaniguchiResearch Institute for Interdisciplinary Science, Advanced Research Field, Okayama UniversityGeorgeTaylorGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThis paper studies V-form traveling fronts to a bistable reaction–diffusion equation. V-form traveling fronts have been studied so far for many reaction–diffusion equations. The proof of its existence is often based on the multi-scale method. In this paper we present a new simple proof for the existence of V-form traveling fronts based on estimates by inscribed balls.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0008-621534012005Synthesis and structural analysis of 6-deoxy-6-hydroxyphosphinyl-d-fructopyranose derivatives3137ENTadashiHanayaDepartment of Chemistry, Faculty of Science, Okayama UniversityKumikoImaiDepartment of Chemistry, Faculty of Science, Okayama UniversityYurij V.Prikhod’koDepartment of Chemistry, Faculty of Science, Okayama UniversityHiroshiYamamotoDepartment of Chemistry, Faculty of Science, Okayama University3,4-Di-O-benzyl-6-deoxy-6-diethoxyphosphinyl-1,2-O-isopropylidene-β-d-fructofuranose (13) was prepared from the known 1,2-O-isopropylidene-6-O-tosyl-β-d-fructofuranose in five steps. Reduction of 13 with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by the action of hydrochloric acid and then hydrogen peroxide, afforded the 6-deoxy-6-hydroxyphosphinyl-d-fructopyranose derivative. This was converted into the 1,2,3,4,5-penta-O-acetyl-6-deoxy-6-methoxyphosphinyl-d-fructopyranoses, whose structure and conformation were established by 1H NMR spectroscopy.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Cinnamyl alcohol dehydrogenase (CAD) underlies the orange lemma trait and lignin reduction in barley30805ENKazuhiroSatoInstitute of Plant Science and Resources, Okayama UniversityMahoMoritaInstitute of Plant Science and Resources, Okayama UniversityNamiYamajiInstitute of Plant Science and Resources, Okayama UniversityRinkaKakoGraduate School of Agricultural Science, Setsunan UniversityTomokazuUshijimaGraduate School of Agricultural Science, Setsunan UniversityHiroshiHisanoInstitute of Plant Science and Resources, Okayama UniversityBarley (Hordeum vulgare L.) is one of the world’s major cereal crops and is widely used for feed, brewing, and food. Reducing lignin content in barley grain and straw is beneficial for improving forage digestibility and enhancing the efficiency of bioethanol production. The orange lemma mutation―characterized by orange pigmentation of husks and nodes―has long been associated with altered lignin metabolism; however, its genetic basis has remained unclear. We show that Cinnamyl Alcohol Dehydrogenase (CAD) is the causal gene underlying the orange lemma phenotype in barley. Genetic mapping using a ‘Haruna Nijo’ × ‘L053’ F₂ population and the Barley 50 K SNP array defined a candidate region on chromosome 6H containing the CAD gene. Sequence analysis revealed that all orange lemma mutants, including both naturally occurring and EMS-induced lines, carried nucleotide changes in the CAD gene, resulting in amino acid substitutions or premature stop codons. Furthermore, CRISPR/Cas9-mediated knockout of CAD in the cultivar ‘Golden Promise’ reproduced the orange lemma phenotype, providing functional validation. The knockout plants also showed significantly lower lignin content than wild-type plants. These findings resolve a long-standing question regarding the genetic basis of the orange lemma trait and demonstrate that disruption of CAD alters lignin accumulation in barley. This work provides a valuable genetic resource for breeding barley cultivars with improved biomass utilization for feed and bioenergy applications.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-00672732026Bioinformatic Prediction of Activation States in Molecular Network Pathways of Eukaryotic Initiation Factor 2 (EIF2) Signaling and Coronavirus Pathogenesis1525ENShihoriTanabeDivision of Risk Assessment, Center for Biological Safety and Research, National Institute of Health SciencesSabinaQuaderInnovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial PromotionRyuichiOnoDivision of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health SciencesHiroyoshi Y.TanakaDepartment of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHoracioCabralDepartment of Bioengineering, Graduate School of Engineering, The University of TokyoEukaryotic initiation factor 2 (EIF2) signaling plays a crucial role in regulating mRNA translation and initiating eukaryotic protein synthesis. Computational molecular network pathway analysis of the canonical pathways of the coronaviral infection revealed that EIF2 signaling is inactivated when the coronavirus pathogenesis pathway is activated and vice versa. Our computational analyses indicated that the coronavirus pathogenesis pathway and EIF2 signaling had inverse activation states. Computational investigation of upstream or downstream microRNA (miRNA) revealed that EIF2 signaling directly interacted with miRNAs, including let-7, miR-1292-3p (miRNAs with the seed CGCGCCC), miR-15, miR-34, miR-378, miR-493, miR-497, miR-7, miR-8, and MIRLET7. A total of 36 nodes, including 8 molecules (ATF4, BCL2, CCND1, DDIT3, EIF2A, EIF2AK3, EIF4E, and ERK1/2), 1 complex (the ribosomal 40s subunit), and 1 function (apoptosis) in the coronavirus pathogenesis pathway, overlapped with EIF2 signaling. Alterations in EIF2 signaling may play a role in the pathogenesis of coronavirus.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2076-260714102026Single-Cell Genomics Uncovers an Unexpectedly Abundant, Phylogenetically Hyperdiverse Patescibacteria (Candidate Phyla Radiation) Community in Agricultural Paddy Soil2213ENArslanAliInstitute of Plant Science and Resources, Okayama UniversityDaisukeSaishoInstitute of Plant Science and Resources, Okayama UniversityKeiichiMochidaRIKEN Center for Sustainable Resource ScienceAkioTaniInstitute of Plant Science and Resources, Okayama UniversityPatescibacteria, also known as the Candidate Phyla Radiation (CPR), are among the most diverse yet functionally reduced bacterial lineages whose diversity in agricultural soils remains poorly characterized. We applied single-cell genomics to bulk soil from an unfertilized paddy field after rice harvest and drainage. From 384 randomly sorted single cells, 126 medium-to-high-quality SAGs (Single-Amplified Genomes) were recovered, spanning 24 bacterial and archaeal phyla. Unexpectedly, 108 of the 384 SAGs (28.1%) were assigned to Patescibacteria―the most frequently recovered phylum―including 42 of the 126 reliable SAGs. These genomes were notably small (mean 973 kb vs. 1.4–3.2 Mb for other phyla). Because CheckM underestimates completeness in reduced CPR genomes, CheckM2 was applied, raising mean completeness from 59.9% to 83.3% and reclassifying 15 genomes as near-complete (>90%). Phylogenomic analysis using 16 ribosomal protein markers revealed extensive diversity and low average amino acid identity to reference genomes (mean 44.6%), indicating substantial taxonomic novelty. Despite this diversity, functional annotation and OrthoFinder analysis showed a conserved, reduced gene repertoire dominated by translation and DNA repair genes and depleted in amino acid, cofactor, and nucleotide biosynthesis. These results show that modest soil sampling can recover outsized Patescibacteria diversity, underscoring the need for CPR-appropriate completeness assessment.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2662-4435712026Rapid fluvial response to meter-scale coseismic coastal uplift during the 2024 Noto Peninsula earthquake742ENTakayukiTakahashiInternational Research Institute of Disaster Science, Tohoku UniversityTakuroOguraGraduate School of Social Sciences, Hitotsubashi UniversityKotaroIizukaCenter for Spatial Information Science, The University of TokyoYoshiyaIwasaFaculty of Education, University of Teacher Education FukuokaYuichi S.HayakawaCenter for Spatial Information Science, The University of TokyoTatsutoAokiInstitute of Human and Social Sciences, Kanazawa UniversityNobuhisaMattaGraduate School of Education, Okayama UniversityThe response of river profiles to relative base-level change is a key topic in earth surface processes, but observations capturing these changes on unconsolidated deposits at a 1–10 years timescales are scarce. We monitored geomorphic changes at the Hakka River mouth after the 3.5-meter base-level fall caused by coseismic uplift of the 2024 Noto Peninsula earthquake, Japan. Utilizing uncrewed aerial vehicle surveys, we documented a maximum vertical riverbed lowering of 2 m and knickpoint upstream migration of 770-m within the first-year post-earthquake, primarily triggered by erosion during major floods that followed the earthquake. Our findings demonstrate that fluvial terraces can develop within a year or less, following co-seismic coastal uplift. However, the river has not yet reached a renewed graded stage because riverbed armoring resulting from sediment sorting during incision currently inhibits further incision. We suggest that the abandonment of alluvial plains and lowering and widening of the riverbed in the lower 10-km segment will continue over the next decade.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama3059-3700212026Delta morphology reveals timings of early ocean regression and hydrologic shift on ancient Mars37ENRenKitoInstitute for Planetary Materials, Okayama UniversityHitoshiHasegawaFaculty of Science and Technology, Kochi UniversityTrishitRujInstitute for Planetary Materials, Okayama UniversityTetsujiMutoDepartment of Environmental Science, Nagasaki UniversityGian GabrieleOriInternational Research School of Planetary Sciences, Università d’AnnunzioGoroKomatsuInternational Research School of Planetary Sciences, Università d’AnnunzioMars’ ancient hydrologic history remains a subject of debate, with competing interpretations suggesting either a large ocean or scattered lacustrine environments. Here, we show that delta morphology on Mars records a shift between these hydrologic regimes. Through controlled tank experiments, we identify two distinct delta types: “lobe-extruding deltas” formed during water-level falls and “stepped fan-deltas” formed during rising water levels. The lobe-extruding deltas occur near proposed paleo-coastlines and are dated to ~3.8–3.2 Ga, consistent with the existence of a Late Noachian–Hesperian ocean and its subsequent regression in the Late Hesperian. In contrast, stepped fan-deltas are found at a wider range of elevations and exhibit significantly younger ages (~2.1–0.1 Ga), suggesting episodic, localized lake formation during the Amazonian. Our findings constrain the timing of the planetary-scale transition from a global hydrosphere to localized aqueous environments and refine the understanding of Mars’ paleoclimate evolution and potential habitability.No potential conflict of interest relevant to this article was reported.American Association for Cancer Research (AACR)Acta Medica Okayama1078-043232172026Sequential Immune Activation of Effector T Cells as Biomarkers of Response to Durvalumab in Patients with Locally Advanced NSCLC38803890ENAtsutoMouriDepartment of Respiratory Medicine, International Medical Center, Saitama Medical UniversityHirotsuguKenmotsuDivision of Thoracic Oncology, Shizuoka Cancer CenterHiroshiKagamuDepartment of Respiratory Medicine, International Medical Center, Saitama Medical UniversityKoichiAzumaDivision of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of MedicineRyotaSaitoDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineHiroakiAkamatsuInternal Medicine III, Wakayama Medical UniversityKimioYonesakaDepartment of Medical Oncology, Kindai University Faculty of MedicineMikikoKakegawaDepartment of Respiratory Medicine, Kitasato University School of MedicineHiromiNagashimaDepartment of Respiratory Medicine, Iwate Medical University School of MedicineSatoshiTakahashiDepartment of Thoracic Surgery, Tokyo Medical University HospitalMasakiFujitaDepartment of Respiratory Medicine, Fukuoka University HospitalNorikoYanagitaniDepartment of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer ResearchKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalYasuhikoNishiokaDepartment of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima UniversityKeitaMoriDepartment of Biostatistics, Clinical Research Support Center, Shizuoka Cancer CenterShigehisaKitanoDepartment of Advanced Medical Development, The Cancer Institute Hospital of Japanese Foundation for Cancer ResearchKojiTamadaDepartment of Immunology, Yamaguchi University Graduate School of MedicineNobuyukiYamamotoInternal Medicine III, Wakayama Medical UniversityAkihikoGemmaDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical SchoolTetsuyaMitsudomiDivision of Thoracic Surgery, Izumi City General HospitalPurpose: Durvalumab therapy following concurrent chemoradiotherapy (cCRT) improves progression-free survival (PFS) in patients with unresectable locally advanced non–small cell lung cancer. In this prospective observational study, we evaluated the changes in peripheral blood immune cell counts to elucidate the immunologic mechanisms underlying cCRT and durvalumab therapy.<br>
Experimental Design: Peripheral blood mononuclear cell (PBMC) samples were collected at four time points: before cCRT, after cCRT, at the start of durvalumab, and 8 weeks after the start of durvalumab, and analyzed by multicolor flow cytometry.<br>
Results: Of the 149 enrolled patients, 115 received durvalumab consolidation therapy after cCRT. The median PFS in the overall population was 24.2 months, and the 3-year PFS rate was 38.9%. PBMC analysis showed an increased effector fraction of CD4+ T cells before and after cCRT but no change in CD8+ T cells. Following durvalumab therapy, the effector fraction ratio of CD8+ T cells (CD62Llow CD8+ T cells) increased and positively correlated with increased CD62Llow CD4+ T cells during cCRT. Patients whose proportion of CD62Llow CD4+ T cells exceeded the threshold for cCRT had better PFS than those below the threshold. Patients whose CD62Llow CD8+ T-cell proportion exceeded the threshold after durvalumab therapy showed prolonged PFS compared with those below the threshold.<br>
Conclusions: cCRT promotes an increase in effector CD4+ T cells, and the subsequent increase in CD8+ T cells following durvalumab therapy prolongs PFS. Peripheral blood effector–type CD4+ and CD8+ T cells are potential biomarkers for evaluating the immune status of patients and predicting treatment efficacy.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1718-77293362026Limited Immune-Mediated Efficacy of Anti-PD-L1/VEGF in EGFR-TKI-Naïve Egfr-Mutant Lung Cancer with Non-Inflamed Tumor Microenvironment315ENAtsukoHirabaeDepartment of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTadahiroKuribayashiDepartment of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalSachiOkawaDepartment of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakamasaNakasukaDepartment of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuyaNishiiDepartment of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunNishimuraDepartment of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityGoMakimotoDepartment of Respiratory Medicine, Okayama University HospitalKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalHisaoHigoDepartment of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKammeiRaiCenter for Innovative Clinical Medicine, Okayama University HospitalEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalMasamichiSugimotoProduct Research Department, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd.YosukeTogashiDepartment of Respiratory Medicine, Okayama University HospitalYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKatsuyukiKiuraDepartment of Respiratory Medicine, Okayama University HospitalKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalImmune checkpoint inhibitors (ICIs) show limited efficacy in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma due to its non-inflamed tumor microenvironment (TME). While quadruple therapy combining chemotherapy, anti-programmed death-ligand 1 (PD-L1), and anti-vascular endothelial growth factor (VEGF) antibodies has shown inconsistent results in EGFR-tyrosine kinase inhibitor (TKI)-pretreated patients, whether anti-VEGF therapy can modulate the intrinsic non-inflamed TME remains unknown. We employed an EGFR-TKI-naïve syngeneic Egfr-mutant mouse model and evaluated effects of anti-VEGF, anti-PD-L1, carboplatin, and paclitaxel as monotherapies and combinations, with TME analysis via immunohistochemistry (IHC), flow cytometry, and RNA sequencing. Anti-PD-L1 showed no antitumor effect, and adding anti-VEGF failed to convert the TME to an inflamed status. Although paclitaxel―but not carboplatin―combined with low-dose anti-VEGF inhibited tumor growth, adding anti-PD-L1 provided no benefit, indicating the anti-VEGF-A antibody evaluated here has a limited role in sensitizing tumors to anti-PD-L1 regardless of chemotherapy. CD8+ T-cell depletion did not attenuate the effect of paclitaxel plus low-dose anti-VEGF, and IHC and RNA sequencing revealed increased natural killer cell infiltration, suggesting a CD8+ T-cell-independent, innate immune mechanism. These findings provide preclinical evidence that the evaluated anti-VEGF has limited immunomodulatory activity in EGFR-TKI-naïve Egfr-mutant tumors with a non-inflamed TME, and suggest immunotherapeutic strategies beyond CD8+ T-cell-mediated immunity warrant investigation.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1759-770617102026Interstitial Lung Disease in Patients With Unresectable Stage III NSCLC Treated With Chemoradiotherapy Followed by Durvalumab in Japan: Analysis From the Multicenter Prospective AYAME Studye70299ENNobuyukiYamamotoInternal Medicine III, Wakayama Medical UniversityHirotsuguKenmotsuDivision of Thoracic Oncology, Shizuoka Cancer CenterKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalBurakAkdemirOncology Medical, AstraZeneca K.KShinyaUematsuOncology Medical, AstraZeneca K.KAyakoFukuiEvidence and Observational Research, Medical, AstraZeneca K.KRyoKotoEvidence and Observational Research, Medical, AstraZeneca K.KMasakazuFujiwaraEvidence and Observational Research, Medical, AstraZeneca K.KChikakoIwaoOncology Medical, AstraZeneca K.KHiroshiKitagawaOncology Medical, AstraZeneca K.KIchiroYoshinoDepartment of Thoracic Surgery, International University of Health and Welfare Narita HospitalAkihikoGemmaDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical SchoolTetsuyaMitsudomiDivision of Thoracic Surgery, Department of Surgery, Kindai University Faculty of MedicineYoshinobuSaitoDepartment of Pulmonary Medicine, Nippon Medical School Musashi Kosugi HospitalIntroduction: Interstitial lung disease (ILD) is a concerning adverse event associated with immune checkpoint inhibitors, including durvalumab. This analysis of the multicenter AYAME study assessed the longterm safety of durvalumab, focusing on ILD.<br>
Methods: AYAME enrolled patients prescribed durvalumab for unresectable stage III non-small cell lung cancer (NSCLC) after chemoradiotherapy (CRT) from July 2019 to December 2020 in Japan. Patients received durvalumab for ≤ 12 months and were prospectively followed for 3 years. Incidence, severity, and management of ILD were examined. Multivariable logistic regression analysis was conducted to investigate the association of patient characteristics with grade ≥ 2 ILD occurrence.<br>
Results: Of 511 patients in the safety analysis population, ILD occurred in 383 patients (75.0%) from durvalumab initiation to subsequent treatment start; median time to occurrence was 44.0 days. ILD led to permanent durvalumab discontinuation in 121/383 patients (31.6%), dose interruption in 111/383 (29.0%), and corticosteroid intervention in 168/383 (43.9%). Grade ≥ 2 ILD occurrence was higher in patients with volume of lung parenchyma that received 20 Gy (V20) ≥ 25% versus < 25% (60.3% vs. 29.4%; adjusted odds ratio 2.20, 95% confidence interval 1.08–4.48), 5 Gy (V5) ≥ median (37.85%) versus < median (51.5% vs. 27.2%; 1.79, 1.07–3.00), and grade 1 ILD before durvalumab administration versus no ILD (50.0% vs. 37.6%; 2.11, 1.07–4.17).<br>
Conclusions: This study of durvalumab for NSCLC after CRT in a real-world setting indicated factors associated with grade ≥ 2 ILD and provided valuable insights into ILD management strategies. These findings may contribute to establishing effective approaches to minimize ILD risk in practice.<br>
Trial Registration: UMIN000037090/NCT03995875No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1556-08642112026Long-Term Safety and Effectiveness of Durvalumab in Unresectable Stage III NSCLC in Japan: A Multicenter Prospective Study (AYAME)160173ENHirotsuguKenmotsuDivision of Thoracic Oncology, Shizuoka Cancer CenterYoshinobuSaitoDepartment of Respiratory Medicine, Nippon Medical School, Musashi Kosugi HospitalKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalShinyaUematsuOncology Medical, AstraZeneca K.K.BurakAkdemirOncology Medical, AstraZeneca K.K.AyakoFukuiEvidence and Observational Research, Medical, AstraZeneca K.K.RyoKotoEvidence and Observational Research, Medical, AstraZeneca K.K.MasakazuFujiwaraEvidence and Observational Research, Medical, AstraZeneca K.K.ChikakoIwaoOncology Medical, AstraZeneca K.K.HiroshiKitagawaOncology Medical, AstraZeneca K.K.IchiroYoshinoDepartment of Thoracic Surgery, International University of Health and Welfare Narita HospitalAkihikoGemmaDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical SchoolTetsuyaMitsudomiDivision of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine and Faculty of Medicine & HospitalNobuyukiYamamotoInternal Medicine III, Wakayama Medical UniversityIntroduction: Based on the PACIFIC trial results, durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III NSCLC. However, few large-scale studies have prospectively evaluated its long-term effectiveness and safety, including subsequent treatment.<br>
Methods: This multicenter, noninterventional study (AYAME) enrolled patients who were prescribed durvalumab for unresectable stage III NSCLC after CRT (July 2019–December 2020; 52 sites; Japan). Patients received durvalumab for a maximum of 12 months and were prospectively followed up for 3 years, including the post-durvalumab treatment period. Primary end points were real-world progression-free survival (rwPFS), the incidence of interstitial lung disease (ILD), and adverse events of special interest (AESIs).<br>
Results: Of the 529 enrolled patients, 512 received durvalumab and 511 comprised the safety analysis population. The median time to onset of the first presentation or occurrence of ILD was 45.0 days. ILD of any grade occurred in 387 patients (75.7%) over the 3-year study period: grade 3, 57 (11.2%); grade 4, none (0.0%); and grade 5, 9 (1.8%). The most common AESIs of any grade during durvalumab treatment were thyroid dysfunction (12.5%), hepatic dysfunction (7.2%), and colitis (2.0%). No durvalumab treatment-related ILD or AESIs occurred during the post-treatment period. The median [95% confidence interval] rwPFS was 23.2 [18.2, 27.2] months in the effectiveness analysis population (n = 495). rwPFS rates were 62.5%, 54.6%, 49.4%, and 40.4% at 12, 18, 24, and 36 months, respectively.<br>
Conclusions: This first and largest prospective, observational study demonstrated the long-term safety and effectiveness of durvalumab for unresectable stage III NSCLC after CRT in a real-world clinical setting.<br>
Clinical Trial Registration: UMIN000037090 and NCT03995875No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841752025Phase II Study of Platinum Re-administration in Non-small Cell Lung Cancer Following Chemoimmunotherapy Resistancee84709ENKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalShinobuHosokawaRespiratory Medicine, Japanese Red Cross Okayama HospitalToshihideYokoyamaRespiratory Medicine, Kurashiki Central HospitalMasaakiInoueChest Surgery, Shimonoseki City HospitalKeisukeSugimotoRespiratory Medicine, Japanese Red Cross Kobe HospitalKenichiroKudoRespiratory Medicine, National Hospital Organization Okayama Medical CenterToshiakiOkadaRespiratory Medicine, National Hospital Organization Fukuyama Medical CenterTadashiMaedaRespiratory Medicine, National Hospital Organization Yamaguchi Ube Medical CenterHaruyukiKawaiInternal Medicine, Okayama Saiseikai General HospitalMasayukiYasugiRespiratory Medicine, Chugoku Central HospitalKojiInoueRespiratory Medicine, Ehime Prefectural Central HospitalShoichiKuyamaRespiratory Medicine, Iwakuni Medical CenterTakashiNinomiyaRespiratory Medicine, National Hospital Organization Shikoku Cancer CenterIsaoOzeDivision of Molecular Medicine, Aichi Cancer Center Research InstituteYoshinobuMaedaHematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalPlatinum compounds represent standard treatments for various cancers. However, the efficacy of re-administrating platinum compounds has been demonstrated only in ovarian cancer and small cell lung cancer (SCLC), with its utility in non-small cell lung cancer (NSCLC) remaining unclear. Given that the prognosis of NSCLC has improved with effective treatments such as immune checkpoint inhibitors (ICIs), we propose a multicenter, single-arm, prospective phase II trial of re-administrating platinum-based combination therapy for NSCLC. Patients with NSCLC who have progressed after chemoimmunotherapy and exhibit a platinum-free interval of 85 days or more will receive carboplatin combination therapy. The drugs combined with carboplatin - pemetrexed, nab-paclitaxel, or gemcitabine - must not have been administered previously. The primary endpoint is progression-free survival (PFS), assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Assuming a threshold PFS of 4.2 months and an expected hazard ratio of 0.60, the required sample size is calculated as 40 patients to achieve 70% power with a 5% alpha error. Secondary endpoints included objective response rate, toxicity, and overall survival. This study will clarify the efficacy of re-administrating platinum compounds to patients with NSCLC who have developed resistance to chemoimmunotherapy.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-90322026Clinical Significance of a Cell-Of-Origin-Based Classification in Pancreatic Ductal AdenocarcinomaENTatsuyaKikuchiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSoichiroAkoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHironariKatoDepartment of Gastroenterology, Okayama City HospitalHideakiKinugasaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasakiUchidaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiOdaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyosukeHiraiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkihiroMatsumiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiTerasawaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiFujiiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeUchidaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoichiroTsutsumiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShigeruHoriguchiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokazuFujiDepartment 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 SciencesHirokazuKatoBioinformatics Analysis Center, Kagawa UniversityTomoyukiHondaDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited therapeutic options and poor clinical outcomes. Although PDAC has traditionally been thought to arise from ductal epithelial cells, recent studies using genetically engineered mouse models have demonstrated that acinar cells can also serve as a cell of origin, giving rise to tumors with distinct biological properties. Here, we investigated whether such lineage-specific differences are preserved in human PDAC. RNA sequencing was performed on resected specimens from 40 treatment-naïve patients with PDAC, and tumors were classified into Acinar- and Ductal-subtypes using lineage-specific gene expression signatures derived from mouse models. This classification strategy was further applied to human PDAC cell lines, followed by in vitro drug sensitivity assays. Patients with Acinar-subtype tumors had significantly longer overall survival than those with Ductal-subtype tumors (median, 54.0 vs. 26.5 months; p < 0.01), and multivariate analysis identified the ductal cell-derived tumor signature as an independent predictor of poor prognosis (HR, 3.74 [95% CI, 1.41–9.97]; p = 0.01). Among patients who developed postoperative recurrence, Acinar-subtype tumors were associated with more durable disease control (≥ 10 months) following gemcitabine-based chemotherapy than Ductal-subtype tumors (63.6% vs. 16.7%; p = 0.02). Consistently, pancreatic cancer cell lines classified as Acinar-subtype showed greater sensitivity to gemcitabine (p < 0.01) and paclitaxel (p < 0.05). These findings extend the clinical relevance of cell-of-origin signatures beyond prognostic stratification, highlighting the potential of cell-of-origin-based classification for treatment stratification and precision medicine in PDAC.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama0366-70225592026Size-dependent reflection behavior of graphene oxide-based photonic crystalsupag176ENDaisukeOgawaDepartment of Chemistry and Materials, Faculty of Textile Science and Technology, Shinshu UniversityYutaNishinaResearch Institute for Interdisciplinary Science, Okayama UniversityKokiSanoDepartment of Chemistry and Materials, Faculty of Textile Science and Technology, Shinshu UniversityGraphene oxide (GO) nanosheets can spontaneously self-assemble into photonic crystals in water, exhibiting structural colors based on Bragg reflection. In this study, we systematically investigated the effect of GO lateral size on the reflection behavior of GO-based photonic crystals. Reflection spectroscopy revealed that both the reflection peak intensity and its time-dependent evolution strongly depended on the GO lateral size, suggesting the existence of an optimal size range for maximizing their reflection intensity.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0008-62153061-21998Effect of a phosphorus atom upon vicinal – coupling constants in pyranose derivatives having a C–P bond: Additivity rule for the effect of phosphorus substituents157162ENTadashiHanayaDepartment of Chemistry, Faculty of Science, Okayama UniversityHiroshiYamamotoDepartment of Chemistry, Faculty of Science, Okayama UniversityAdditivity constants for phosphorus were estimated for the prediction of vicinal 1H–1H coupling constants by means of an additivity rule in a series of pyranose analogs having phosphorus as the ring heteroatom. The experimental J values were well reproduced by employing the proposed additivity constants with a small overall root-mean-square difference of 0.32 Hz. The prediction of coupling constants was employed for the investigation of conformational equilibria of pyranose analogs having a phosphinyl group in the ring or on the ring-carbon.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-006727192026Impaired Myostatin Function Alters Body Composition Without Detectable Attenuation of Imiquimod-Induced Psoriasiform Dermatitis8518ENYoshihiroMatsudaDepartment of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinMorizaneDepartment of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYumaSakamotoDepartment of Immunology and Molecular Genetics, Kawasaki Medical SchoolNobuyasuBabaDepartment of Immunology and Molecular Genetics, Kawasaki Medical SchoolMasanoriIsekiDepartment of Immunology and Molecular Genetics, Kawasaki Medical SchoolDaikiTakezakiDepartment of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshioKawakamiDepartment of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShin-IchiroNishimatsuDepartment of Natural Sciences, Kawasaki Medical SchoolYutakaOhsawaDepartment of Neurology, Kawasaki Medical SchoolYoshihideSunadaDepartment of Neurology, Kawasaki Medical SchoolTomoyukiMukaiDepartment of Immunology and Molecular Genetics, Kawasaki Medical SchoolPsoriasis is a chronic inflammatory skin disease closely associated with obesity and metabolic dysfunction. While excess adiposity is considered a key risk factor, the independent contribution of body composition to psoriatic inflammation remains unclear. Myostatin negatively regulates skeletal muscle growth, and its inhibition leads to muscle hypertrophy and reduced adiposity. In this study, we investigated whether altered body composition due to impaired myostatin function affects imiquimod (IMQ)-induced psoriasiform dermatitis. Wild-type (WT) and dominant-negative myostatin transgenic mice were fed either a normal diet or a high-fat diet (HFD) for 10 weeks, followed by topical IMQ treatment to induce dermatitis. Mutant mice exhibited increased skeletal muscle mass and reduced visceral fat compared with WT controls, indicating marked changes in body composition. In WT mice, HFD feeding increased fat mass and tended to aggravate IMQ-induced ear swelling. In contrast, no significant effect of impaired myostatin function on ear thickness, epidermal hyperplasia, or the expression of psoriasis-associated genes was detected, despite reduced visceral fat. Under the present experimental conditions, these changes in body composition were not associated with a detectable attenuation of psoriasiform skin inflammation. Our results suggest that obesity-related psoriasis is influenced by metabolic and immunological factors beyond body composition.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0021-88202026Amino acid mapping–guided scaffold selection and hit identification of histidine kinase inhibitors from a virtual library of over 12 million compoundsENTeruhikoIshikawaGraduate School of Education, Okayama UniversityYokoEguchiDepartment of Science and Technology on Food Safety, Faculty of Biology-Oriented Science and Technology, Kindai UniversityToshihideOkajimaSANKEN, The University of OsakaMasayukiIgarashiInstitute of Microbial Chemistry (BIKAKEN)ShinoOhiraAnalysis Technology Center, FUJIFILM CorporationKyosukeTsumuraAnalysis Technology Center, FUJIFILM CorporationKazumasaSakuraiHigh Pressure Protein Research Center, Institute of Advanced Technology, Kindai UniversityYoshimasaIshizakiInstitute of Microbial Chemistry (BIKAKEN)ChigusaHayashiInstitute of Microbial Chemistry (BIKAKEN)ShammiAkterLaboratory of Microbial Technology, Division of Systems Bioengineering, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu UniversityJiroNakayamaLaboratory of Microbial Technology, Division of Systems Bioengineering, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu UniversityChieKohayakawaDepartment of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, The University of OsakaAkiyoshiTaniDepartment of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, The University of OsakaNaokiSawaGraduate School of Education, Okayama UniversityTakaomiKatsumotoGraduate School of Education, Okayama UniversityFumiyaMatsumotoGraduate School of Education, Okayama UniversityJun-IchiHarutaDepartment of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, The University of OsakaRyutaroUtsumiSANKEN, The University of OsakaWaldiomycin is a natural product originally isolated from actinomycete extracts. It inhibits histidine kinases (HKs), which are essential components of bacterial two-component signal transduction systems, by targeting the conserved H-box region and suppressing autophosphorylation. Here, we identified novel HK inhibitors using amino acid mapping (AAM)-based virtual screening. We compared the AAM descriptor of the naphthoquinone moiety of waldiomycin, which directly interacts with the H-box region, with those of approximately 12 million commercially available compounds and identified 714 candidates with similar descriptor values. From these candidates, we selected 9-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one as a promising and structurally distinct scaffold and synthesized 15 derivatives. The inhibitory activities of these derivatives were evaluated against the HKs WalK, VicK, and EnvZ. Three 4H-pyrido[1,2-a]pyrimidin-4-one derivatives (FF-054, FF-055, and FF-060) exhibited potent inhibitory activity, with IC50 values ranging from 4.39 to 259 µM. Notably, the IC50 values of these compounds increased three- to six-fold against the EnvZ S242A mutant, in which the conserved H-box residue is substituted. Furthermore, nuclear magnetic resonance (NMR) analysis using the EnvZ DHp domain (residues 223–289, encompassing the H-box region) confirmed direct interaction with this domain. Taken together, these results demonstrate that pyrido[1,2-a]pyrimidin-4-one derivatives FF-054, FF-055, and FF-060 are novel HK inhibitors that target the H-box region. This study represents the first successful application of AAM-based screening to identify HK inhibitors targeting this highly conserved region.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0140-77912026Natural Variation in Brachypodium distachyon Primarily Links Lignin Reinforcement to Rhizoctonia solani ResistanceENRoziFernandaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNiranjanMahadevanTea Research Institute of Sri LankaMegumiWatanabeGraduate 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 UniversityYoshiteruNoutoshiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2210-60141512025Relationship Between Heated Tobacco Products and Placental Abruption: A Prospective Cohort Study Using Online Questionnaire30ENHikaruOobaCenter for Innovative Clinical Medicine, Okayama University HospitalJotaMakiDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroTabuchiDivision of Epidemiology, School of Public Health, Tohoku University Graduate School of MedicineHisashiMasuyamaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Placental abruption (PA) is a critical obstetric complication, with maternal smoking recognized as a key risk factor. Despite the increased use of heated tobacco products (HTPs), the impact of HTPs remains unclear. This study investigated whether pregnant women using HTPs are at a higher risk of PA than non-users.<br>
Methods: We analyzed data from “the Japan COVID-19 and Society Internet Survey,” a prospective, self-reported online survey cohort. Questionnaires were randomly distributed between July 28, 2021, and August 30, 2021. Pregnant respondents in 2021 were invited to complete an additional survey from February 14, 2022, to February 28, 2022. We set the outcome as the absolute risk difference (aRD) and relative risk ratio (rRR) of PA incidence due to smoking HTPs in the first trimester of pregnancy. The sample size included 12 836 participants. We calculated outcomes using a generalized linear model (GLM) and inverse probability of treatment weighting (IPTW). We also performed a Bayesian approach and multiple-bias analysis for sensitivity analysis.<br>
Results: We found the robust aRD of 0.07 (95% confidence interval (CI): 0.06, 0.09) and the rRR of 11.3 (95% CI: 7.5, 17.0). Multiple bias analyses showed that unmeasurable confounders would need to have at least an rRR = 14 relationship with both exposure and outcome to disprove the observed association. There has not been post hoc analysis or secondary use of data.<br>
Conclusion: Early pregnancy use of HTPs is associated with an increased risk of PA.No potential conflict of interest relevant to this article was reported.Japanese Society of Preventive MedicineActa Medica Okayama2758-7916232024Relationship between food security and dietary habits and subjective sense of health and subjective sense of well-being among residents of large-scale housing complexes in Japan4556ENKeikoWakimotoSchool of Food Sciences and Nutrition, Mukogawa Women’s UniversityMiyukiYokoro-HisanariFaculty of Education, Okayama UniversityAkiraOhtsuboCommunity Liaison Division for Education and Research, Mukogawa Women’s UniversityTatsuyaFujiiSchool of Education, Mukogawa Women’s UniversityJotaroKatoSchool of Letters, Mukogawa Women’s UniversityHitoshiOgasawaraSchool of Nursing, Mukogawa Women’s UniversityDaisukeKudoSchool of Nursing Science, Meiji University of Integrative MedicineMinaeFukuiIchikan Nursing Development center for Diversity, Kobe City College of NursingYuichiFujitaSchool of Nursing, Mukogawa Women’s UniversityBackground: This study aimed to determine the relationship between food security and dietary habits and subjective health and subjective well-being among residents of a large-scale housing complex in Japan. Methods: This study used a cross-sectional design through a self-administered questionnaire survey. The study subjects were residents of Mukogawa Danchi in Nishinomiya City, Hyogo Prefecture, Japan, and data from 515 households out of 6,857 total dwelling units were used for the analysis. Food security status (HFSSM), dietary diversity score (HDDS), diet, eating behavior, subjective sense of health, and subjective sense of well-being were examined using logistic regression analysis. Results: Food insecurity was negatively associated with household dietary diversity scores (OR [95%CI]:0.49 [0.24–0.98] p = 0.044). Similarly, food insecurity was negatively associated with having a nutritionally balanced diet and having a satisfactory amount of food. There was also a negative association with family meals. There was a negative association between food insecurity and a subjective sense of health and a negative association (0.35 [0.15–0.78] p = 0.011) with a subjective sense of well-being among those aged 65 and older. Conclusions: In a large-scale housing complex in Japan, inadequate dietary intake was observed in food-insecure households; they ate meals less frequently with their families. Additionally, residents experiencing food insecurity tended to have lower subjective health and subjective well-being, depending on their age.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2079-63821432025Influence of Educational Films on Antiviral Prescription for COVID-19: Insights from Web-Based Survey in Japan276ENKosakuKomiyaRespiratory Medicine and Infectious Diseases, Oita University Faculty of MedicineAkihikoHagiwaraRespiratory 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 Health, JapanHiroshiKakeyaDepartment 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 University School of MedicineYukaSasakiCenter for Pulmonary Disease, National Hospital Organization Tokyo 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 CenterBackground: Prescribing antiviral agents for severe acute respiratory syndrome coronavirus 2 requires careful consideration based on the patient’s risk factors for severe disease progression and their vaccination status. However, effective interventions ensuring the appropriate use of antiviral agents by physicians have yet to be fully established. Thus, this study evaluated the impact of an educational film on antiviral prescription rates for coronavirus disease 2019 (COVID-19). Methods: This prospective, nationwide, web-based survey enrolled 1500 physicians. They were instructed to view a short educational film and assess the necessity of prescribing antiviral agents in 16 fictitious scenarios featuring adult patients with COVID-19 with varying risk factors for severe disease and vaccination statuses. We compared the antiviral prescription rates before and after viewing the educational film. Results: There was a significant increase in the antiviral prescription rates after viewing the educational film, particularly nirmatrelvir/ritonavir prescribed in cases involving immunocompromised patients (from 31.3% to 49.4%) and those with obesity (from 15.1% to 33.7%) who were unvaccinated and had no risk of drug interactions. However, viewing the educational film made little to no impact on the prescription rates for the patients with hypertension and hyperlipidemia or those with no underlying conditions. Conclusions: Short educational films may promote the appropriate use of antiviral agents for COVID-19. However, their impact on altering prescription behavior appears limited and varies according to the clinical context.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0961-836835102026Conformational stability and domain‐specific structural features of tumor autoantigens regulate autoantibody epitope propensitye70808ENAiMiyamotoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityRikaYamamotoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityRyuiSakaguchiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityRikakoKutsumaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakeruMoriGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMireiMasuiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTomokoHonjoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMidoriFutamiDepartment of Bioscience, Faculty of Life Science, Okayama University of ScienceMarikoMoriiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHiromiWatanabeDepartment of Respiratory Medicine, Okayama University HospitalTadahiroKuribayashiDepartment of Respiratory Medicine, Okayama University HospitalKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalKatsuyukiKiuraDepartment of Respiratory Medicine, Okayama University HospitalJunichiroFutamiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAutoantibodies against tumor-associated autoantigens are clinically valuable biomarkers for cancer diagnosis; however, the structural determinants governing epitope selectivity remain unknown. Here, we investigated whether the intrinsic conformational stability of target autoantigens regulates the epitope propensity of tumor-associated autoantibodies in non-small cell lung cancer. Using a dual-antigen Luminex bead-based assay that presents each autoantigen in both native and S-cationized denatured forms, we directly compared IgG autoantibody reactivity toward conformational and linear epitopes across 11 autoantigens. Intrinsically disordered aggregation-prone autoantigens, including cancer/testis antigens, NY-ESO-1, and XAGE-1b, predominantly elicit linear epitope-directed responses, whereas thermodynamically stable soluble autoantigens generally drive conformational epitope recognition. Intriguingly, for autoantigens harboring both ordered and disordered segments, the immune response is strictly guided by domain-specific biophysics: while p53-specific antibodies preferentially target their flanking disordered regions, the Wilms' tumor protein 1 exceptionally drives conformational recognition directed toward its structured zinc-finger domains. Recombinant solubility in Escherichia coli broadly correlated with epitope class across all 11 autoantigens, confirming that prokaryotic folding efficiency generally reflects intrinsic conformational stability in vivo for autonomously folding monomeric cytosolic proteins. Independent computational validation was provided by the concordance between the experimental solubility ratios and AlphaFold3-derived Rosetta energy unit/solvent-accessible surface area values, demonstrating the convergence of thermodynamic estimates and patient-derived immune data within a unifying biophysical framework. These findings establish that the autoantibody epitope propensity is closely associated with the thermodynamic stability of the target autoantigen and provide a rational basis for tailoring antigen preparation strategies for autoantibody-based cancer diagnosis.No potential conflict of interest relevant to this article was reported.American Geophysical Union (AGU)Acta Medica Okayama0094-827653182026Hydrogen-Bond Symmetrization in Hydrous Aluminous Silica Enhances Deep-Mantle Water Cyclee2026GL123823ENChaoshuaiZhaoState Key Laboratory of Precision Geodesy, University of Science and Technology of ChinaZhuMaoState Key Laboratory of Precision Geodesy, University of Science and Technology of ChinaYingxinYuDepartment of Earth Sciences, University of OxfordNingyuSunState Key Laboratory of Precision Geodesy, University of Science and Technology of ChinaYunhuaFuSKLab‐DeepMinE, MOEKLab‐OBCE, School of Earth and Space Sciences, Peking UniversityJianboZhangCenter for High‐Pressure Science and Technology Advance ResearchHanns‐PeterLiermannDeutsches Elektronen‐Synchrotron DESYRenbiaoTaoCenter for High‐Pressure Science and Technology Advance ResearchTakayukiIshiiInstitute for Planetary Materials, Okayama University(Al, H)-bearing CaCl2-type SiO2 serves as a key water carrier in Earth's deep-water cycle. Evolution of hydrogen-bond symmetrization in this phase was measured up to 62 GPa and 800 K by synchrotron infrared and Raman spectroscopy, and X-ray diffraction. It undergoes symmetrization at ∼30 GPa and 300 K, while elevated temperature to 800 K lowers the onset pressure to ∼12 GPa. This implies that the symmetrized phase will form directly near the base of the transition zone in (Al, H)-rich subducted slabs, and deeper in (Al, H)-poor slabs via transformation from stishovite. More importantly, this symmetrization state stiffens the crystal lattice and immobilizes hydrogen within the structure, enhancing water retention and preventing hydrogen loss during subduction to the lower mantle. Our findings suggest that this phase acts as an important deep-water reservoir capable of transporting water to the lower mantle, thereby linking the deep-water cycle from Earth's surface to core-mantle boundary.No potential conflict of interest relevant to this article was reported.Microbiology SocietyActa Medica Okayama0022-26157532026Investigation of carbapenem-hydrolysing Klebsiella oxytoca strains lacking detectable carbapenemase genes002139ENHiroshiTeraguchiDepartment of Clinical Laboratory, Kindai University Nara HospitalAyakaOdaDental School, Okayama UniversitySatoyoWakaiAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health SecuritySayokoKawakamiAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health SecurityKokiYoshidaDepartment of Clinical Laboratory, Kindai University Nara HospitalWataruHayashiAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health SecurityNorikazuKitamuraAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health SecurityYoSugawaraAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health SecurityNaoyaOharaDental School, Okayama UniversityMotoyukiSugaiAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health SecurityKojiYaharaAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health SecurityAkiHirabayashiAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health SecurityIntroduction. Carbapenemase-producing Enterobacterales (CPE) pose a clinical concern due to limited treatment options and plasmid-mediated spread of carbapenemase genes. The modified carbapenem inactivation method (mCIM) is increasingly used in clinical settings to detect CPE.<br>
Gap Statement. Interpretation of mCIM results for isolates with reduced carbapenem susceptibility remains challenging.<br>
Aim. To assess the interpretation of positive mCIM results in Klebsiella oxytoca isolates lacking detectable carbapenemase genes and exhibiting reduced carbapenem susceptibility and to propose a phenotypic testing strategy for accurate evaluation.<br>
Methodology. Antimicrobial susceptibility testing with clavulanic or dipicolinic acid supplementation, phenotypic carbapenemase assays, carbapenem hydrolysis assays and whole-genome sequencing (WGS) were conducted on K. oxytoca strains.<br>
Results. K. oxytoca strains were isolated from both blood and urine samples of a patient in a Japanese hospital. Although classified as susceptible by clinical breakpoints, these isolates exhibited reduced susceptibility to carbapenems. Although these strains were mCIM-positive, the zinc-supplemented carbapenem inactivation method did not support the presence of metallo-β-lactamase (MBL) activity. MIC reductions in the presence of CVA were consistent with inhibition of a class A β-lactamase. In contrast, dipicolinic acid supplementation did not reduce the meropenem MIC, ruling out MBL production. Furthermore, WGS revealed that both K. oxytoca strains lacked known carbapenemase genes, with blaOXY-2-4 being the only identifiable β-lactamase gene encoding a class A enzyme. No novel β-lactamase genes were identified; however, an enhanced blaOXY-2-4 expression-associated point mutation was found in the promoter region. Both K. oxytoca strains exhibited carbapenem-hydrolysing activity, although to a lesser extent than that of the MBL-producing strain.<br>
Conclusion. We identified K. oxytoca strains that lacked known carbapenemase genes but that yielded positive mCIM results, possibly due to OXY-2 overproduction. Our study findings emphasize the need for cautious mCIM result interpretation for K. oxytoca and highlight the diagnostic value of combined susceptibility testing with clavulanic and dipicolinic acids to distinguish the underlying resistance mechanisms. Combining complementary clinical laboratory tests will enable clarification of the factors underlying mCIM positivity and guide clinical decision-making.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2751-1219592026Proton‐Radiation‐Tolerant Silicon Photonic Charge Sensor for Spacecraft Applicationse70208ENWataruTakahamaDepartment of Physics and Electronics, Osaka Metropolitan UniversityKoseiOtsukaDepartment of Physics and Electronics, Osaka Metropolitan UniversityAyumiIshiharaDepartment of Physics and Electronics, Osaka Metropolitan UniversityRikutoHojoDepartment of Space Systems Engineering, Kyushu Institute of TechnologyTomofumiMogamiElectrostaticEngineering DEPT, Kasuga Denki INCKazuhiroToyodaDepartment of Space Systems Engineering, Kyushu Institute of TechnologyKohtakuSuzukiResearch and Development, The Wakasa Wan Energy Research CenterYasushiTakahashiFaculty of Environmental, Life, Natural Science and Technology,Okayama UniversitySilicon waveguides are promising platforms for spacecraft potential sensing owing to their compactness and immunity to electromagnetic interference. However, proton-induced optical absorption in operating silicon waveguides has not been quantitatively clarified, despite their direct exposure to the space radiation environment during spacecraft operation. Here, we present a systematic elucidation of proton-radiation effects on a photonic charge sensor based on silicon photonic crystal waveguides. During proton irradiation at 20 keV, we quantitatively evaluate the increase in optical absorption under device operation and find that a fluence of 1.0 ×1014 cm− 2 induces an additional absorption coefficient of approximately 0.41 cm− 1 . We further demonstrate that the sensor retains its ability to measure spacecraft potential even after exposure to a high proton fluence of 1.0 ×1015 cm− 2 , confirming its intrinsic radiation tolerance. These results establish the radiation robustness of silicon-waveguide- based sensing mechanisms and provide the first quantitative basis for implementing photonic charge sensors in radiation-rich spacecraft environments.
No potential conflict of interest relevant to this article was reported.American Physical Society (APS)Acta Medica Okayama0031-900713792026Strain-Tuned Nodal Superconductivity in the Charge-Ordered Kagome Metal CsV3Sb5096003ENYusukeTakeuchiDepartment of Physics, Okayama UniversityAkitoKobayashiDepartment of Physics, Okayama UniversitySakiUchidaDepartment of Physics, Okayama UniversityTakumiNagaoDepartment of Physics, Okayama UniversitySeigoOgawaDepartment of Physics, Okayama UniversityRuiZhouInstitute of Physics, Chinese Academy of Sciences, and Beijing National Laboratory for Condensed Matter PhysicsShinjiKawasakiDepartment of Physics, Okayama UniversityFeiSongFujian Provincial Collaborative Innovation Center for Advanced High-Field Superconducting Materials and Engineering, College of Physics and Energy, Fujian Normal UniversityHaoNiFujian Provincial Collaborative Innovation Center for Advanced High-Field Superconducting Materials and Engineering, College of Physics and Energy, Fujian Normal UniversityYongZhaoFujian Provincial Collaborative Innovation Center for Advanced High-Field Superconducting Materials and Engineering, College of Physics and Energy, Fujian Normal UniversityGuo-qingZhengDepartment of Physics, Okayama UniversityThe nature of the superconducting pairing symmetry in the kagome metal CsV3Sb5 and its relationship with the charge density wave (CDW) order are central unresolved issues. Here, we investigate the evolution of superconductivity in CsV3Sb5 under in situ uniaxial pressure using 121Sb nuclear quadrupole resonance (NQR). We find that tensile strain significantly enhances the superconducting transition temperature, 𝑇c, while the CDW remains unchanged, demonstrating that superconductivity can be tuned independently of the bulk charge order. At a tensile strain of 𝜖 =+0.90%, the nuclear spin-lattice relaxation rate reveals a remarkable double transition: an upper transition at 𝑇c1=3.6 K to a nodal gap state, and a lower one at 𝑇c2=3.0 K characterized by a nodeless gap. These results evidence degenerate superconducting states with different gap symmetry in the kagome metal at ambient pressure which split under strain. Our Letter demonstrates a high tunability of superconductivity by uniaxial pressure.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0008-6215338162003Stereoselectivity in deoxygenation of 5-hydroxy-5-phosphinyl-hexofuranoses (α-hydroxyphosphonates)16411650ENTadashiHanayaDepartment of Chemistry, Faculty of Science, Okayama UniversityKen-ichiSugiyamaDepartment of Chemistry, Faculty of Science, Okayama UniversityHeizanKawamotoDepartment of Chemistry, Faculty of Science, Okayama UniversityHiroshiYamamotoDepartment of Chemistry, Faculty of Science, Okayama UniversityThe addition of dimethyl phosphonate to six different hexofuranos-5-uloses in the presence of DBU, followed by esterification with methoxalyl chloride and then radical reduction, afforded 5-deoxy-5-dimethoxyphosphinyl-d- and l-hexofuranoses. The stereoselectivity of the deoxygenation and possible transition-state models are discussed.No potential conflict of interest relevant to this article was reported.Japan Medical AssociationActa Medica Okayama2433-3298822025Unraveling Causality: Innovations in Epidemiologic Methods323337ENEtsujiSuzukiDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityFor several decades, the counterfactual model and the sufficient cause model have shaped our understanding of causation in biomedical science and, more recently, the link between these two models has enabled us to obtain a deeper understanding of causality. In this article, I provide a brief overview of these fundamental causal models using a simple example. The counterfactual model focuses on one particular cause or intervention and gives an account of the various effects of that cause. By contrast, the sufficient cause model considers sets of actions, events, or states of nature which together inevitably bring about the outcome under consideration. In other words, the counterfactual framework addresses the question “what if?” while the sufficient cause framework addresses the question “why does it happen?” Although these two models are distinct and address different causal questions, they are closely related and used to elucidate the same cause-effect relationships. Importantly, the sufficient cause model makes clear that causation is a multifactorial phenomenon, and it is a “finer” model than the counterfactual model; an individual is of one and only one response type in the counterfactual framework, whereas an individual may be at risk of none, one, or several sufficient causes. Understanding the link between the two causal models can provide greater insight into causality and can facilitate the use of each model in appropriate contexts, highlighting their respective strengths. I will briefly present three topics of interest from our research: the relationship between the concepts of confounding and of covariate balance; distinctions between attributable fractions and etiologic fractions; and the identification of operating mediation and mechanism. It is important to scrutinize observed associations in a complementary manner, using both the counterfactual model and the sufficient cause model, employing both inductive and deductive reasoning. This holistic approach will better help us to unravel causality.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0929-19033252025Tob negatively regulates NF-κB activation in breast cancer through its association with the TNF receptor complex573583ENMihoTokumasuDepartment of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAtsukoSatoCell Signal Unit, Okinawa Institute of Science and Technology Graduate UniversityTakuIto-KurehaCell Signal Unit, Okinawa Institute of Science and Technology Graduate UniversityMizukiYamamotoResearch Center for Asian Infectious Diseases, The Institute of Medical Science, The University of TokyoNaoOhmineCell Signal Unit, Okinawa Institute of Science and Technology Graduate UniversityKentaroSembaDepartment of Life Science and Medical Bioscience, Waseda UniversityJun-ichiroInoueThe University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA)TadashiYamamotoCell Signal Unit, Okinawa Institute of Science and Technology Graduate UniversityNF-κB mediates transcriptional regulation crucial to many biological functions, and elevated NF-κB activity leads to autoimmune and inflammatory diseases, as well as cancer. Since highly aggressive breast cancers have few therapeutic molecular targets, clarification of key molecular mechanisms of NF-κB signaling would facilitate the development of more effective therapy. In this report, we show that Tob, a member of the Tob/BTG family of antiproliferative proteins, acts as a negative regulator of the NF-κB signal in breast cancer. Studies with 35 human breast cancer cell lines reveal that Tob expression is negatively correlated with NF-κB activity. Analysis of The Cancer Genome Atlas (TCGA) database of clinical samples reveals an inverse correlation between Tob expression and NF-κB activity. Tob knockdown in human breast cancer cells promoted overactivation of NF-κB upon TNF-α treatment, whereas overexpression of Tob inhibited TNF-α stimulation-dependent NF-κB activation. Mechanistically, Tob associates with the TNF receptor complex I and consequently inhibits RIPK1 polyubiquitylation, leading to possible prevention of overwhelming activation of NF-κB.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1362-10173162026Bridging the Awareness–Action Gap in Disaster Preparedness: A Qualitative Study of Immersive Virtual Reality Learning Among Nursing Studentse70681ENKeikoMoriGraduate School of Health Sciences, Okayama UniversityMiinaYamazakiKobe University HospitalYoshiyukiHarunaSnowlion. Inc.Background: Disasters increasingly challenge healthcare systems, highlighting the need to strengthen preparedness among future healthcare professionals. Although disaster risk awareness is important, it does not consistently translate into preparedness behaviours, reflecting the awareness–action gap. Immersive virtual reality (VR) may enhance experiential disaster learning, but how it influences preparedness processes remains insufficiently understood, particularly in healthcare and critical care education.<br>
Aims: To explore how immersive VR-based disaster simulations influence disaster risk perception and preparedness among nursing students, with particular attention to the awareness–action gap and implications for future healthcare and critical care practice.<br>
Study Design: A qualitative descriptive study using immersive VR-based disaster simulations followed by semi-structured interviews. Twelve undergraduate and graduate nursing students in Japan experienced immersive VR simulations depicting floods and landslides. Individual semi-structured interviews explored emotional responses, disaster risk perception, preparedness awareness and anticipated behavioural responses. Data were analysed using Krippendorff's content analysis with researcher triangulation.<br>
Results: Five categories were identified: (1) heightened vulnerability and psychological burden through immersion; (2) persistence of the awareness–action gap despite increased risk perception; (3) enhanced risk recognition and preparedness intentions; (4) recognition of the need for social and structural support systems; and (5) emerging responsibility accompanied by perceived limitations. VR transformed abstract disaster risk into emotionally salient experiences, strengthening threat appraisal and preparedness awareness; however, awareness did not consistently translate into preparedness behaviours, reflecting insufficient coping appraisal and self-efficacy.<br>
Conclusions: Immersive VR may strengthen disaster risk perception and preparedness awareness, but immersive experiences alone may be insufficient to bridge the awareness–action gap. Combining VR with reflective learning, skills-based training and collaborative simulation may strengthen coping appraisal and preparedness action.<br>
Relevance to Clinical Practice: Immersive VR combined with reflective and skills-based learning may support psychological readiness, situational awareness and disaster preparedness competencies among future nurses, including those preparing for critical care practice.No potential conflict of interest relevant to this article was reported.Walter de Gruyter GmbHActa Medica Okayama2294-19322026Direct evidence for water-filled yet hydraulically isolated xylem vessels in two temperate tree species114ENMayumi Y.OgasaKansai Research Center, Forestry and Forest Products Research InstituteYasuhiroUtsumiAshoro Research Forest, Kyushu UniversityKenichiYazakiHokkaido Research Center, Forestry and Forest Products Research InstituteNaoko H.MikiFaculty of Environmental, Life, Natural Science and TechnologyKenjiFukudaGraduate School of Agricultural and Life Sciences, The University of TokyoXylem vessels in sapwood are typically interpreted as either conductive or non-functional following embolism or occlusion, implicitly assuming that the presence of water within the lumen reflects participation in the transpiration stream. However, the relationship between lumen water content and hydraulic connectivity has rarely been examined directly at the cellular level. In this study, we combined cryo-scanning electron microscopy and fluorescence microscopy to compare lumen water status with hydraulic connectivity on the same xylem surface in current-year xylem of Carpinus tschonoskii and Aria alnifolia, using tension-driven dye uptake to identify conductive vessels. Most vessels were stained and water-filled, consistent with functional conduits, whereas unstained gas-filled vessels corresponded to embolized conduits. Notably, certain vessels retained water despite lacking dye signals, indicating hydraulic isolation from the conductive xylem network. Although these vessels represented a minor fraction of the conduit population, their occurrence suggests that the traditionally binary classification should be expanded to incorporate an additional conduit function. These vessels were observed in both species, suggesting that hydraulically disconnected vessels represent a common phenomenon across species. These findings reveal previously underrecognized heterogeneity in xylem hydraulic organisation and demonstrate that conduit status cannot always be inferred from the presence of water alone. Recognising this intermediate condition refines current interpretations of xylem function and highlights the value of integrating high-resolution imaging with hydraulic measurements.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1058-83882026MIT/TFE family transcription factors, Mitf and Tfec, redundantly promote pigment cell differentiation and retinal epithelium pigmentation in teleosts115ENJamesListerDepartment of Human and Molecular Genetics and Massey Cancer Center, Virginia Commonwealth University School of MedicineKeisukeSugiwakaDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityTetsuakiKimuraDepartment of Basic Biology, School of Life Science, Graduate University of Advanced Studies (SOKENDAI) & Laboratory of Bioresources, National Institute for Basic BiologyRiekoTanakaWorld Medaka Aquarium, Nagoya Higashiyama Zoo and Botanical GardensMakotoGodaInstitute of Photonics Medicine, Hamamatsu University School of MedicineHikaruKobayashiDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityChikakoInoueR&D Fish Breeding Group, Regional Fish Institute, Ltd.Kawilarang W. A.MasengiFaculty of Fisheries and Marine Science, Sam Ratulangi UniversityKazunoriYamahiraTropical Biosphere Research Center, University of the RyukyusKiyoshiNaruseDepartment of Basic Biology, School of Life Science, Graduate University of Advanced Studies (SOKENDAI) & Laboratory of Bioresources, National Institute for Basic BiologySatoshiAnsaiUshimado Marine Institute, Graduate School of Natural Science and Technology, Okayama UniversityRobert N.KelshDepartment of Life Sciences, University of BathMasahikoHibiDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityHisashiHashimotoDepartment of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya UniversityBackground: Transcription factors of the MIT/TFE family―mitfa, mitfb, and tfec―play essential roles in specifying pigment cells derived from neural crest cells in vertebrates. In teleosts, which possess multiple pigment cell types, these factors exhibit partially redundant but largely distinct functions across different pigment lineages. We previously reported that the combined loss of mitfa and mitfb leads to a complete absence of melanophores, xanthophores, and leucophores in medaka.<br>
Results: Here, we describe newly generated hypomorphic alleles of mitfa and mitfb, which result in delayed melanophore development. Using these hypomorphic mutants in combination with a newly generated null allele of tfec, we show that Tfec can partially compensate for the loss of Mitfa and Mitfb in melanophore, xanthophore, and leucophore differentiation. Consistent with previous findings in zebrafish, loss of tfec alone results in the complete absence of iridophores. Importantly, simultaneous null mutations in all three genes cause a complete loss of all four chromatophore types and lead to defective pigmentation of the retinal pigmented epithelium (RPE), which is not derived from the neural crest in both Oryzias species and in zebrafish. Using an RPE-specific marker, we further show that the RPE is specified and structurally intact but fails to melanize.<br>
Conclusions: These findings indicate that the redundant functions of Mitfa, Mitfb, and Tfec are not only essential for the specification of diverse pigment cell types but also critical for RPE pigmentation.No potential conflict of interest relevant to this article was reported.BMJActa Medica Okayama2044-60551682026Study protocol for a phase II clinical trial evaluating the safety and efficacy of favipiravir injection combined with oseltamivir in influenza treatmente106715ENSayakaHikidaDisease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health SecurityHidetoshiNomotoDisease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health SecurityYukariUemuraLaboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health SecurityTadakiSuzukiDepartment of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health SecurityKoichiIzumikawaDepartment of Infectious Diseases, Nagasaki University Graduate School of Biomedical SciencesHirokiOhgeProject Research Center for Nosocomial Infectious Diseases, Hiroshima UniversityMasayaYamatoInfectious Diseases Center, Rinku General Medical CenterYasuyukiKatoDepartment of Infectious Diseases, International University of Health and Welfare Narita HospitalRyotaHaseDepartment of Infectious Diseases, Japanese Red Cross Narita HospitalTetsujiAoyagiDepartment of Clinical Microbiology and Infection, Tohoku University Graduate School of MedicineHideharuHagiyaDepartment of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYokoNukuiDepartment of Infection Control & Laboratory Medicine, Kyoto Prefectural University of MedicineKazukoYamamotoFirst Department of Internal Medicine, Division of Infectious, Respiratory, and Digestive Medicine, University of the Ryukyus Graduate School of MedicineYoshioTakesueChita Peninsula General Medical Organization, Rinku HospitalKotaSawadaLaboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health SecurityYosukeShimizuLaboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health SecurityShoMiyamotoDepartment of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health SecurityNamikoTamuraDisease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health SecurityKozueTakahashiDisease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health SecurityShoSaitoDisease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health SecurityKazukiMiyazakiCenter for Clinical Sciences, Japan Institute for Health SecurityErikoMorinoCenter for Clinical Sciences, Japan Institute for Health SecurityDaisukeTokitaCenter for Clinical Sciences, Japan Institute for Health SecurityNorioOhmagariDisease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health SecurityIntroduction Older adults are at an increased risk of influenza-related hospitalisation and mortality due to a combination of risk factors. Severe influenza and excess mortality in this population remain major public health concerns, underscoring the need for novel treatment strategies.<br>
Methods and analysis This multicentre, investigator-initiated, randomised, double-blind clinical trial evaluated the efficacy and safety of the investigational drug favipiravir injection (T-705IV) in combination with oseltamivir phosphate, compared with oseltamivir monotherapy in hospitalised patients with influenza aged ≥65 years. Both T-705IV and oseltamivir phosphate will be administered for 5 days. The primary endpoint is time from randomisation to recovery within 15 days. Recovery is defined as either actual hospital discharge or sustained clinical status permitting discharge for 3 consecutive days. Clinical status will be assessed using a 7-point ordinal scale based on hospitalisation status and oxygen requirement. The primary analysis employs a Bayesian Cox proportional hazards model with a non-informative prior to estimate the posterior probability that the HR exceeds 1.0. The secondary endpoints include the distribution of 7-point scale scores over a 29-day period; rates of clinical worsening at days 15 and 29; duration of fever; all-cause mortality; intensive care unit admission within 29 days; pneumonia complication rate at 15 days; and changes in viral titre and viral RNA load on days 1, 2, 3 and 7. Safety will be assessed through the collection of adverse events (AEs) up to day 29. Pharmacokinetic evaluation will include measurement of plasma favipiravir concentrations on day 3. The planned sample size is 80 patients (40 per group).<br>
Ethics and dissemination Written informed consent will be obtained from all participants. This study was approved by the Center Hospital of the National Center for Global Health and Medicine Institutional Review Board (approval number: NCGM-I-022-24a) and registered in the Japan Registry of Clinical Trials. Study findings will be disseminated through peer-reviewed publications and/or presentations at academic conferences.<br>
Trial registration number jRCT2031240586,No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2041-17231712026RNase-mediated defence and its association with SCCmec in Staphylococcus aureus9986ENKoheiKondoAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health SecurityAa HaerumanAzamDepartment of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health SecurityJunzoHisatsuneAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health SecurityShinjiroOjimaDepartment of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health SecurityKotaroChiharaDepartment of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health SecurityTomohiroNakamuraDepartment of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health SecurityAzumiTamuraDepartment of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health SecurityWakanaYamashitaDepartment of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health SecuritySatoshiNakanoAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health SecurityShokoKutsunoAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health SecurityYoSugawaraAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health SecurityJumpeiUchiyamaDepartment of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayukiAmagaiDepartment of Dermatology, Keio University School of MedicineTetsuoYamaguchiDepartment of Microbiology and Infectious Diseases, Toho University School of MedicineYoshikazuIshiiDepartment of Microbiology and Infectious Diseases, Toho University School of MedicineKoichiWatashiDepartment of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health SecurityYoshimasaTakahashiResearch Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health SecurityKotaroKigaDepartment of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health SecurityMotoyukiSugaiAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health SecurityThe rise of antibiotic resistance in Staphylococcus aureus is a major threat to global health. Resistance often emerges when bacteria acquire foreign DNA elements, such as the SCCmec cassette that makes strains resistant to nearly all β-lactam antibiotics. Yet, not all S. aureus lineages take up these elements equally, raising the question of what prevents some strains from becoming drug-resistant. Here we identify a previously unknown defence factor that explains this mystery in a common skin lineage (ST188), frequently isolated from patients with atopic dermatitis. Such defence factor is encoded by a gene, which we name sadR, that is present in methicillin-susceptible ST188 strains but absent from resistant counterparts. SadR exhibits RNase activity that provides anti-bacteriophage and anti-plasmid defence, thus acting as a barrier to the uptake of mobile genetic elements. Gene sadR is found in methicillin-susceptible strains in S. aureus lineages other than ST188, and is consistently located adjacent to rlmH, the canonical SCCmec integration site. Moreover, SadR homologues are widespread across staphylococci and other bacteria suggesting a previously unrecognised family of RNase-based defence systems.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0031-39982026Long-term association between the COVID-19 pandemic and language development at 3 years of ageENRumiMatsuoDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaomiMatsumotoDepartment of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazueNakamuraDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalTakashiYorifujiDepartment of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: Few studies have examined the long-term association between the COVID-19 pandemic and language development in preschoolers or its effect modifiers. We therefore examined this association during health checkups of 3-year-olds in Japan.<br>
Methods: This repeated cross-sectional study included 40,898 3-year-olds who underwent checkups in Okayama City, Japan. We compared children examined before (2017–2019) and during the pandemic (2020–2023). The primary outcome was physician-determined risk of language difficulties. The secondary outcome was children’s infrequent questions using words such as “what,” “who,” and “where.” Modified Poisson regression estimated RRs adjusted for confounders. Subgroup analyses examined effect modification by sex, childcare setting, and family size.<br>
Results: The COVID-19 pandemic was associated with increased risk of language difficulties (RR 1.52, 95% CI 1.35–1.72). The association peaked in fiscal year 2021 and remained elevated throughout the pandemic. Secondary outcome showed elevated risk (RR 1.16, 95% CI 1.05–1.29). Girls and home-care children showed higher RRs than boys and preschool attendees.<br>
Conclusions: The COVID-19 pandemic was associated with risk of language difficulties among 3-year-old children, with associations varying by sex and childcare setting. These findings suggest the importance of maintaining social interaction opportunities for young children during public health crises.No potential conflict of interest relevant to this article was reported.The Korean Geriatrics SocietyActa Medica Okayama2508-47983022026Variation in the Association between Frailty and Disability over 10 Years: A Cohort Study143150ENAkikazuHagiyamaDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalSoshiTakaoDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiYorifujiDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: Although frailty is associated with disability, its long-term persistence and changes over time remain unclear. This study aimed to investigate the long-term association between frailty and the incidence of disability over a 10-year follow-up period, evaluating how this association changed over time. Methods: This cohort study was conducted in Okayama City, Japan. Community-dwelling older adults aged ≥65 years were included. Frailty was assessed using the Kihon Checklist, and disability was defined as a new certification for long-term care insurance. The association between frailty and disability was examined across five time periods (years 1–2, 3–4, 5–6, 7–8, and 9–10) using a marginal structural model with inverse probability of treatment weighting and inverse probability of censoring weighting. Results: The final analysis included 45,291 participants, with 17.3% classified as frail. The adjusted odds ratios (ORs) for the association between frailty and the incidence of disability gradually decreased over time but remained throughout the 10-year follow-up period. The adjusted ORs and 95% confidence intervals were 2.90 (2.55–3.29) for years 1–2, 2.40 (2.09–2.75) for years 3–4, 2.03 (1.76–2.34) for years 5–6, 1.75 (1.52–2.01) for years 7–8, and 1.58 (1.38–1.82) for years 9–10. Conclusion: Frailty was consistently associated with the incidence of disability over a 10-year follow-up period, with a stronger association in the earlier years and a gradual decline over time.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama2328-89571232025Effects of Amikacin Liposome Inhalation Suspension and Amikacin Resistance Development in Patients With Refractory Mycobacterium avium Complex Pulmonary Diseaseofaf118ENYuKuraharaDepartment of Internal Medicine, NHO Kinki Chuo Chest Medical CenterShiomiYoshidaClinical Research Center, NHO Kinki Chuo Chest Medical Center , Osaka ,AsamiOsugiDepartment of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis AssociationYuyaTanakaDepartment of Internal Medicine, NHO Kinki Chuo Chest Medical CenterTakehikoKobayashiClinical Research Center, NHO Kinki Chuo Chest Medical CenterToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalYoheiKawasakiDepartment of Biostatistics, Graduate School of Medicine, Saitama Medical UniversitySatoshiMitaraiDepartment of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis AssociationKazunariTsuyuguchiDepartment of Internal Medicine, NHO Kinki Chuo Chest Medical CenterBackground. Amikacin liposome inhalation suspension (ALIS) is key for treating refractory Mycobacterium avium complex pulmonary disease (MAC-PD). However, microbiological efficacy by subtype remains unknown. The frequency and mechanism of amikacin (AMK) resistance during ALIS administration are also unclear.<br>
Methods. We retrospectively analyzed data from refractory MAC-PD patients who received ALIS for at least 6 months as an adjunct to guideline-based therapy at the NHO Kinki Chuo Chest Medical Center. We investigated the efficacy of ALIS and analyzed gene expression and the frequency of AMK resistance.<br>
Results. We enrolled 44 patients (median age, 72.0 years): 19 (43.2%) with the noncavitary nodular bronchiectatic (NC-NB) subtype and 25 (56.8%) with the cavitary subtype. Overall, sputum culture conversion was 56.8% (25/44): 84.2% (16/19) in the NC-NB subtype and 36.0% (9/25) in the cavitary subtype (P = .001). During intermittent dosing, conversion occurred in 50.0% (9/18). In patients with C-reactive protein (CRP) ≥1 mg/dL, cavitary subtype, and clarithromycin (CLM) resistance, the risk ratio for persistently positive cultures was 10.81 (95% CI, 1.66–70.40) compared with those with CRP <1 mg/dL, NC-NB subtype, and CLM susceptibility. Of all participants, 15.9% (7/44) had isolates with AMK resistance (minimum inhibitory concentration ≥128 µg/mL), and of these 71.4% (5/7) had rrs mutations.<br>
Conclusions. Regimens that included ALIS achieved higher culture conversion in NC-NB than cavitary MAC-PD cases. High CRP levels, cavitary disease, and CLM resistance predicted persistent culture positivity. AMK resistance acquired during ALIS administration may limit treatment options for refractory MAC-PD.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841862026Routine Generative AI Use and Acceptance of Medical AI: A Cross-Sectional Survey of Healthcare Workers and the Public in Japane110118ENToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Medical Development Field, Okayama UniversityBackground<br>
Acceptance of medical artificial intelligence (AI) is critical for successful implementation, yet its acceptance may vary by clinical application and stakeholder group. Whether routine use of generative AI (GAI) is associated with acceptance of medical AI remains unclear.<br>
Methods<br>
A cross-sectional web survey was conducted in Japan in November 2025 using web-panel convenience sampling from an online research panel. The small analytic sample comprised 200 participants aged 20-69 years, including 100 healthcare workers and 100 non-healthcare workers. GAI use was assessed using two five-point items (GAI use at work and in daily life) and dichotomized as at least monthly use in either daily life or work versus less than monthly use in both settings, based on prespecified criteria. Acceptance of medical AI was measured for five scenario-based applications - AI-assisted imaging interpretation, AI-based health risk prediction, AI-based treatment recommendations, AI-enabled triage guidance, and AI-assisted robotic surgery - using a four-point acceptability scale; responses were dichotomized as acceptable versus not acceptable. Calibration weights were constructed to approximate Japanese internet users by raking on sex-by-age group and household income, normalized to the analytic sample size, and truncated at prespecified bounds. Adjusted prevalence ratios (aPRs) were estimated using modified Poisson regression with robust standard errors, stratified by occupation; covariates were selected a priori using a modified disjunctive cause criterion. This study was exploratory; therefore, adjustments for multiple comparisons were not performed.<br>
Results<br>
Among healthcare workers, the lower-use group had a higher prevalence of non-acceptance of AI-based health risk prediction (aPR 6.980, 95% CI 1.412-34.506) and AI-based treatment recommendations (aPR 4.364, 95% CI 1.331-14.305), whereas estimates for imaging interpretation, triage guidance, and robotic surgery remained statistically uncertain. Among non-healthcare workers, the lower-use group had a higher prevalence of non-acceptance of AI-assisted imaging interpretation (aPR 13.906, 95% CI 1.624-119.052), AI-based health risk prediction (aPR 4.861, 95% CI 1.133-20.862), AI-based treatment recommendations (aPR 6.288, 95% CI 1.386-28.530), and AI-assisted robotic surgery (aPR 6.173, 95% CI 1.435-26.561); the adjusted estimate for AI-enabled triage guidance was not statistically supported (aPR 1.840, 95% CI 0.521-6.505). Several estimates had wide confidence intervals, indicating substantial imprecision.<br>
Conclusions<br>
In this small exploratory web-panel convenience sample, lower-frequency GAI use was associated with higher non-acceptance of several medical AI applications. Associations were observed across more applications among non-healthcare workers than among healthcare workers. Because the study was cross-sectional, used convenience sampling, and included imprecise estimates with wide confidence intervals, the findings should not be interpreted causally. Larger studies using longitudinal or interventional designs are needed to clarify temporality and mechanisms.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0969-806X2512027A rule-based calculation approach to derive bone-suppressed chest X-ray images using photon-counting techniques114493ENNatsumiKimotoDepartment of Radiological Science, Faculty of Health Sciences, Junshin Gakuen UniversityRinaNishigamiGraduate School of Medical Sciences, Kanazawa UniversityTakashiAsaharaDepartment of Radiological Technology, Faculty of Health Sciences, Okayama UniversityManaMitaniDivision of Radiology, Medical Support Department, Okayama University HospitalDaikiKobayashiGraduate School of Medical Sciences, Kanazawa UniversityNoriakiAkagiDivision of Radiology, Medical Support Department, Okayama University HospitalToshihiroIguchiDepartment of Radiological Technology, Faculty of Health Sciences, Okayama UniversityTakaoHirakiDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroakiHayashiCollege of Transdisciplinary Sciences for Innovation, Kanazawa UniversityImproving the visibility of lung nodules, which are often hidden by bone shadows and difficult to identify, remains a challenge in chest radiography. This study aims to develop an algorithm for generating novel bone-suppressed images using photon-counting techniques. The core idea of our algorithm is to fit photon interaction cross-sections to X-ray attenuation data measured with photon-counting detectors. Based on further calculations using the derived fitting coefficients, both density (ρ) and amount-of-substance concentration (mol) were determined. The product of these values produced a ρ×mol image exhibiting a clear bone-suppression effect. We conducted a virtual chest imaging simulation using 10 patient datasets acquired via clinical photon-counting computed tomography (PC-CT). The CT images were converted into ρ×mol images following the proposed processing procedure, and two-dimensional chest images were generated through projection. Quantitative evaluations confirmed that the proposed images achieved sufficient bone suppression. Furthermore, commercial software provided by a vendor was used to generate bone-suppressed images from conventional images projected from CT data. A comparable bone-suppression effect on the ribs was observed between the vendor-generated images and our proposed images, while lesion visibility (e.g., lung nodules) was preserved. Additionally, bone-suppression effects in our images were observed in the vertebrae and clavicles located outside the lung fields. Our research demonstrates the value of constructing general X-ray imaging systems using photon-counting detectors.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2197-42841312026Carbon solubility and liquid–liquid immiscibility in Fe–C–S ternary system up to 6 GPa: implications for the core of small planetary bodies60ENBinZhaoInstitute for Planetary Materials, Okayama UniversityGuillaumeMorardUMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne UniversitéGeethManthilakeLaboratoire Magmas et Volcans, Université Clermont-AuvergneParaskevasParisiadesUMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne UniversitéJingYangEarth and Planets Laboratory, Carnegie Institution for ScienceYingweiFeiEarth and Planets Laboratory, Carnegie Institution for ScienceYannLe GodecUMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne UniversitéNozomiKondoInstitute for Planetary Materials, Okayama UniversityTakashiYoshinoInstitute for Planetary Materials, Okayama UniversityDanieleAntonangeliUMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne UniversitéHigh-pressure, high-temperature experiments were conducted in a multi-anvil press using seven different starting compositions to investigate the phase relations of Fe–C–S liquids at pressures up to 6 GPa and temperatures up to 2000 K. Quenched samples revealed immiscible C-rich and S-rich metallic liquids at 2 and 4 GPa, manifesting as either large immiscible zones or emulsified smaller droplets. On the contrary, no immiscibility was observed at 5 or 6 GPa. At these higher pressures, the carbon solubility limit, significantly reduced by increasing sulfur content in the ternary liquid, prevents the formation of a liquid phase rich in both C and S. Our findings thus indicate that super-liquidus immiscibility in Fe-rich compositions does not occur at pressures above 5 GPa, due to the differential pressure dependence of C solubility and miscibility. The limited C solubility in S-rich liquids at higher pressures effectively suppresses immiscibility. Based on these results, terrestrial planetary bodies with fluid cores at pressures exceeding 5 GPa are unlikely to experience liquid–liquid immiscibility, even when both carbon and sulfur are abundant, as sulfur limits carbon solubility and promotes its exsolution. For the Moon, immiscibility-induced core stratification is not expected, though local emulsification could occur near the core–mantle boundary (CMB). In smaller bodies, a two-liquid Fe–C–S core may form at high temperatures, but progressive cooling may lead to graphite crystallization and the potential development of a graphitic crust.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1010-60304782026Deep-blue solid-state emission from Ternaphthalene: Photophysical tuning via multi-chromophore architectures117156ENMinoruYamajiDivision of Molecular Science, Graduate School of Science and Engineering, Gunma UniversityKengoSuzukiHamamatsu Photonics K.K.HidekiOkamotoDepartment of Chemistry, Faculty of Environment, Life, Natural Sciences and Technology, Okayama UniversityWe report the synthesis and photophysical characterization of a series of “all-naphthalene” multi-chromophore systems, ternaphthalenes (TNps), designed for efficient deep-blue solid-state emission. Unlike planar polycyclic aromatic hydrocarbons that suffer from aggregation-caused quenching (ACQ), the twisted molecular architecture of TNps effectively inhibits π-π stacking interactions. Consequently, several TNps exhibit crystallization-induced emission enhancement (CIEE) or retain high quantum yields (up to 0.94) in the solid state. Kinetic analysis revealed that this efficiency stems from the significant suppression of non-radiative rates (knr) due to the restricted intramolecular rotation in the rigid crystal lattice. Furthermore, a decisive topological effect on the radiative rate (kf) was demonstrated. The 1,4-, 1,5- and 2,6-linked isomers display allowed transitions with large oscillator strengths (f) and fast radiative rate (kf = ca. 5 × 108 s−1), whereas the 2,7-linked isomers exhibit forbidden-like character with prolonged lifetimes. A distinct linear correlation between the experimental and calculated values empirically supports the applicability of the Strickler-Berg relationship in both solution and solid states. These findings demonstrate that controlling the chromophore connectivity is a powerful strategy to tune excited-state dynamics for developing high-performance deep-blue organic emitters.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2367-09321032026Substitution‐Dependent Modulation of Photophysical Properties of 2,7‐ and 3,6‐Dinaphthyl‐9‐phenylcarbazoles in Solution and Solid Statee202500335ENMinoruYamajiDivision of Molecular Science, Graduate School of Science and Engineering, Gunma UniversityTadashiMoriResearch Center for Environmental Preservation and Graduate School of Engineering, The University of OsakaHidekiOkamotoDepartment of Chemistry, Faculty of Environment, Life, Natural Sciences and Technology, Okayama UniversityThe photophysical properties of two positional isomers of dinaphthyl-9-phenylcarbazoles (2,7-DNpPCz and 3,6-DNpPCz) were systematically investigated in solution and solid states. Experimental measurements revealed a pronounced positional dependence, although both compounds exhibit fluorescence in solution and the solid state. On average, the 2,7-isomers exhibit larger fluorescence rate values than the 3,6-isomers, although the magnitude of this difference varies among individual compounds. To gain mechanistic insight, density function theory (DFT) and time-dependence DFT calculations were performed at the (TD)-B3LYP/6-31+G(d) level. The results show that 2,7-DNpPCz derivatives possess delocalized frontier orbitals and large oscillator strengths for the S1 ← S0 transition, whereas 3,6-DNpPCz derivatives exhibit smaller oscillator strengths with mixed orbital contributions, leading to weaker transition probabilities. These combined findings demonstrate that substitution geometry critically governs radiative decay dynamics in carbazole-based luminophores and provide valuable guidelines for the molecular design of efficient solid-state organic emitters.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2238-7854452026Enhancement of mechanical properties in a cast hypereutectic Al–Si alloy via rapid cooling in heated mold continuous casting485494ENShuheiTakeuchiGraduate School of Environment, Life, Natural Science and Technology, Okayama UniversityShotaNakagawaUACJ CorporationYoshifumiShinzatoUACJ CorporationTadashiMinodaUACJ CorporationNaotakaOhtsukaUACJ CorporationMitsuhiroOkayasuDepartment of Mechanical and Systems Engineering, Okayama UniversityTo enhance mechanical properties in cast hypereutectic Al–Si alloys, Al–14.5Si samples were produced by the heated mold continuous casting (HMC). The HMC process was conducted under unidirectional solidification at cooling rates (CRs) ranging from 4.6 × 10−1 to 1.3 × 103 K/s, which were obtained by controlling the casting speed (CS). The microstructure basically consisted of α-Al dendrite, Al–Si eutectic and primary Si, while their area fractions (fα-Al, fe, and fp-Si) varied depending on the CR. At the low CR of 4.6 × 10−1 K/s, their area fractions were as follows: fα-Al = 0.2%, fe = 97.3%, and fp-Si = 2.5%, which is the typical microstructural morphology of a hypereutectic Al-Si alloy. In contrast, at the high CR of 1.3 × 103 K/s, those area fractions were altered to fα-Al = 32.3% and fe = 67.7%, while primary Si was strongly suppressed (fp-Si ≈ 0%) despite the hypereutectic Al–14.5Si alloy. Moreover, at the high CR, the aluminum matrix appears to exhibit a nearly uniform crystal orientation along <101>. These microstructural changes may be related not only to high CR but also the difference in growth kinetics between primary Si and α-Al dendrites. Accordingly, an apparent eutectic composition shifted from 12.6 to 19.7 wt% Si. The atypical microstructural formation led to a significant improvement in the tensile properties: the ultimate tensile strength of 400 MPa and fracture strain of 17%. These tensile properties are more than twice those of the conventional cast hypereutectic Al–14.5Si alloy.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama3050-5976212026Older patients with LBCL show comparable outcomes to younger patients and product-specific profiles in CAR-T therapy100037ENShoShibataDepartment of Hematology, Kyoto University HospitalYasuyukiAraiDepartment of Hematology, Kyoto University HospitalJunyaKandaDepartment of Hematology, Kyoto University HospitalDaisukeKajiDepartment of Hematology, Toranomon HospitalDaisukeMinakataDivision of Hematology, Department of Medicine, Jichi Medical UniversityToshioKitawakiDepartment of Hematology, Kyoto University HospitalKazuyukiShimadaDepartment of Hematology and Oncology, Nagoya University Graduate School of MedicineTatsuShimoyamaDepartment of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalSatoshiYoshiharaDepartment of Hematology, Hyogo Medical University HospitalShinichiMakitaDepartment of Hematology, National Cancer Center Hospital, TokyoNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalGoYamamotoDepartment of Hematology, Toranomon HospitalEmikoSakaidaDepartment of Hematology, Chiba University HospitalYasuhiroNakashimaDepartment of Hematology, Osaka Metropolitan University HospitalAkiyoYoshidaDivision of Transfusion Medicine, Kanazawa University HospitalYoshihiroUmezawaDepartment of Hematology, Institute of Science Tokyo HospitalJunKatoDivision of Hematology, Department of Medicine, Keio University School of MedicineHaryoonKimDivision of Hematology, Department of Medicine, Keio University School of MedicineKeisukeKataokaDivision of Hematology, Department of Medicine, Keio University School of MedicineHidekiGotoDivision of Laboratory and Transfusion Medicine, Hokkaido University HospitalYoshikoAtsutaJapanese Data Center for Hematopoietic Cell TransplantationKojiKatoDepartment of Hematology, Oncology and Cardiovascular Medicine, Kyushu University HospitalAnti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a key treatment option for patients with relapsed or refractory large B-cell lymphoma (LBCL). However, data on its effectiveness and safety in older populations remain limited, particularly in real-world clinical practice. Moreover, comparative outcomes among different CAR-T products across age groups have not yet been fully characterized. We conducted a nationwide retrospective cohort study using data from the Japanese Society for Transplantation and Cellular Therapy. A total of 908 patients who received CAR-T therapy between January 2019 and September 2024 were included. Patients were categorized as younger (aged <65 years) or older (aged ≥65 years). Subgroup analyses were performed by CAR-T product (tisagenlecleucel [tisa-cel], lisocabtagene maraleucel [liso-cel], and axicabtagene ciloleucel [axi-cel]). In univariate analysis, 1-year overall survival (OS) and progression-free survival (PFS) were comparable between younger and older patients (OS, 69.4% vs 65.7% [P = .40]; PFS, 47.9% vs 54.1% [P = .17]). In multivariate analysis, age ≥65 years showed no significant association with OS (hazard ratio, 0.88; 95% confidence interval, 0.65-1.21; P = .44). The incidence of immune effector cell–associated neurotoxicity syndrome was significantly higher in older patients (12.7% vs 7.0%; P = .005). Compared with tisa-cel, axi-cel and liso-cel were associated with superior PFS, predominantly in younger patients. Among older patients, axi-cel was associated with higher nonrelapse mortality rate than tisa-cel. CAR-T therapy is feasible and effective for older patients with LBCL. These findings support age-adapted treatment strategies that consider both the efficacy and toxicity of each product.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1866-629985132026Intensity of chemical weathering and its implications for soil erosion across lithological and climatic gradients in the Chemoga watershed, Upper Blue Nile Basin317ENAlebachew TarekeKehaliThe United Graduate School of Agricultural Sciences, Tottori UniversityHiroshiKitagawaInstitute for Planetary Materials, Okayama UniversityNigussieHaregeweynInternational Platform for Dryland Research and Education, Tottori UniversityMitsuruTsuboInternational Platform for Dryland Research and Education, Tottori UniversityZelalem LeyewAntenehDepartment of Geology, School of Earth Sciences, Bahir Dar UniversityBelay TesfaAyalewDepartment of Geology, School of Earth Sciences, Bahir Dar UniversityZena TessemaTerefeThe United Graduate School of Agricultural Sciences, Tottori UniversityAshebir SewaleBelayDepartment of Geology, School of Earth Sciences, Bahir Dar UniversityAyele AlmawFentaInstitute for Planetary Materials, Okayama UniversityAtsushiTsunekawaInstitute for Planetary Materials, Okayama UniversityThe geochemistry of rocks, regolith/soil, surficial and core sediments, and clay mineral assemblages from these sediments was analyzed to elucidate the transition from fresh to chemically altered materials. These data were used to evaluate the intensity of chemical weathering and its implications for erosion across contrasting lithological and climatic gradients in the Chemoga watershed of the Upper Blue Nile Basin, Ethiopia. Our findings show depletion of Na+, Ca2+, Mg2+, and K+, and enrichment of Al3+, Fe3+, Ti4+, and Mn2+ in the regolith/soil, upper part of surficial sediment, and upper layer of the core sediment (10 m). Chemical Index of Alteration (CIA) values are rocks 35–47, regolith/soil 75–96, surficial river sediments 45–96, and core sediments 50–90. River sediments in the highland area are dominated by kaolinite (39%), illite (34%), and chlorite (27%), while the lower study area has illite (76%), chlorite (11%), and kaolinite (12%). Geochemistry, ternary plots, and clay mineralogy show that the highland region underwent intensive chemical weathering, while the midland experienced intermediate to high weathering, and the lowland had weak weathering. The highlands experience severe weathering due to a humid, bimodal precipitation climate; despite having younger, weathering-resistant rocks (basalt, andesite, trachyte), the lower regions consist of older, more mafic rocks (basalt and trachybasalt). Like the surficial river sediment, core sediment showed intense chemical weathering and kaolinite dominance in the upper layers (0–10 m depth, CIA > 80). Weathering intensity decreased with depth, suggesting changes in weathering and in clay mineral formation that reflect past climate. The high weathering gradient from highland to lowland correlates with erosion, indicating that weathering strongly influences soil erosion variability in the watershed. This work provides a reasonable basis for improving our understanding of the degree of weathering across contrasting environments and its implications for soil erosion by connecting the relationship between parent materials and chemically altered samples with the degree of soil erosion.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0005-2728186812027Structural and functional analysis of a photosystem II mutant PsbA3-S264V149607ENSongboFanAdvanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYoshikiNakajimaAdvanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKojiKatoAdvanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHaoweiJiangAdvanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityPi-ChengTsaiAdvanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAnqiJiaAdvanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMiwaSugiuraProteo-Science Research Center, Ehime UniversityJian-RenShenAdvanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityPhotosystem II (PSII) catalyzes water oxidation and oxygen evolution by a light-induced electron transfer chain, leading to the generation of electrons, protons and dioxygen. D1-S264 is a residue located close to the QB-binding site, and mutation of this residue has been shown to bring significant effects on the electron transfer and oxygen-evolving activities. Here we analyzed the structure of a Thermosynechococcus elongatus mutant PsbA3-S264V by cryo-electron microscopy at 1.96 Å resolution, which showed significant changes in the structure surrounding the bicarbonate and QB-binding region. Due to change of Ser to Val, the hydrogen-bond between the QB carbonyl oxygen and S264 is altered, which changed the protonation pathway of QB from the original route of D1-H252 through D1-S264 to QB, to a new, longer and less efficient route of D1-H252 through D1-F265 to QB. Two residues, D1-E244 and D2-E242, changed their side chain orientations significantly. Among them, D2-E242 adopted two conformations, and both are largely deviated from the original structure. All these changes led to alterations in hydrogen-bonding networks of two channels, channel A and channel B, that connect the stromal surface to QB and may function to transport protons to protonate QB. Furthermore, isothermal titration calorimetry experiments showed a diminished 3-(3,4-dichlorophenyl)-1, 1-dimethylurea (DCMU) binding affinity of the mutated PSII, which may be explained by a structural rotation of D1-F255 in the mutant based on structural analysis of DCMU-bound PSII. These findings offer valuable insights into the functions of D1-S264 in QB protonation and function, as well as in the DCMU-binding.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1520-541X2832026Sexual Dimorphism in Vertebral Number: Developmental Implications Inferred From Vertebral and Body Proportionse70062ENKazunoriYamahiraTropical Biosphere Research Center, University of the RyukyusV. K.AnoopTropical Biosphere Research Center, University of the RyukyusRajeevRaghavanDepartment of Fisheries Resource Management, Kerala University of Fisheries and Ocean StudiesYoshitakaTanakaUshimado Marine Institute, Okayama UniversitySatoshiAnsaiUshimado Marine Institute, Okayama UniversitySegmentation is a fundamental feature of vertebrate body plans, and variation in vertebral number contributes substantially to morphological diversity. Although sexual dimorphism in vertebral number has been documented in several vertebrate lineages, its developmental basis remains poorly understood. Here, we report pronounced sexual dimorphism in vertebral number in the western Indian endemic ricefish Oryzias setnai, distributed across ~1800 km. Radiographic analyses of individuals collected throughout its range revealed that vertebral number increased with latitude in both sexes, while males consistently possessed more vertebrae than females irrespective of geographic origin. Size-adjusted analyses showed that this dimorphism is associated with sex differences in head size and position-dependent variation in vertebral length. However, positional allometric analyses demonstrated that both the magnitude and direction of these sex differences vary markedly during growth. In particular, among smaller individuals, posterior vertebrae were relatively shorter in males than in females, suggesting reduced somite length in the posterior body axis of male embryos and potentially reflecting sex-specific differences in the dynamics of somitogenesis. Given that this variation arises between males and females within a single species sharing an essentially identical genetic background, O. setnai provides a rare empirical system not only for linking early developmental processes to intraspecific sexual variation in vertebrate body plans but also as a powerful model to investigate the developmental basis of body plan variation across species.No potential conflict of interest relevant to this article was reported.SAGE PublicationsActa Medica Okayama2045-1253162026Seizures associated with clozapine augmentation by other antipsychotics: a pharmacovigilance–pharmacodynamic analysis using VigiBaseENMasakazuHatanoDepartment of Pharmacotherapeutics and Informatics, Fujita Health University School of MedicineHirofumiHamanoDepartment of Pharmacy, Okayama University HospitalMasayaKandaDepartment of Pharmacy, Asahikawa Medical University HospitalTakenaoKosekiDepartment of Pharmacotherapeutics and Informatics, Fujita Health University School of MedicineTsuyoshiNakaiDepartment of Pharmacotherapeutics and Informatics, Fujita Health University School of MedicineRinaHoriiDepartment of Pharmacotherapeutics and Informatics, Fujita Health University School of MedicineNozomiYoshiharaDepartment of Pharmacotherapeutics and Informatics, Fujita Health University School of MedicineTakeoSaitoDepartment of Psychiatry, Fujita Health University School of MedicineKenshiTakechiDepartment of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama UniversitySatoruEsumiThe Faculty of Pharmaceutical Sciences, Kobe Gakuin UniversityYoshitoZamamiDepartment of Pharmacy, Okayama University HospitalShigekiYamadaDepartment of Pharmacotherapeutics and Informatics, Fujita Health University School of MedicineBackground: Clozapine is associated with a high risk of central nervous system abnormalities. However, seizure risk related to interactions between clozapine and other antipsychotics remains poorly characterized, and the pharmacological mechanisms underlying these seizures are unclear.
Objectives: We aimed to evaluate safety signals for seizures associated with clozapine augmentation by other antipsychotics and analyze the relationship between these signals and neurotransmitter receptor occupancy profiles.<br>
Design: A pharmacovigilance–pharmacodynamic analysis using a spontaneous reporting system.<br>
Methods: This pharmacovigilance study used VigiBase, an adverse drug reaction database maintained by the World Health Organization. Drug–drug interactions (DDIs) between clozapine and other antipsychotics were assessed using the Ω shrinkage measure model. The association between DDI signals and neurotransmitter receptor occupancy was evaluated using linear regression. Robustness was tested using four frequency statistical models: additive, multiplicative, combination risk ratio, and chi-square statistic models.
Results: Of 38,758,077 reports in VigiBase between 1990 and 2024, 230,371 involved clozapine. Among antipsychotics classified under ATC code N05A, DDIs with clozapine were detected for amisulpride, chlorpromazine, haloperidol, lurasidone, olanzapine, penfluridol, risperidone, sulpiride, zotepine, and zuclopenthixol. A significant association between dopamine D4 receptor occupancy and the point estimates of signal values was observed in the Ω shrinkage measure model (β = 0.295, 95% confidence interval: 0.119–0.471, p = 0.002) and replicated across all frequency statistical models.<br>
Conclusions: These findings suggest a potential role of dopamine D4 receptor occupancy in seizures associated with clozapine augmentation by other antipsychotics. Further large-scale epidemiological studies are needed to validate these findings.No potential conflict of interest relevant to this article was reported.American Society for MicrobiologyActa Medica Okayama2165-04971482026High-throughput screening system for antimycobacterial compounds using in vitro infected cells: construction and application to compounds in the Ōmura Natural Compound Librarye00484-26ENTakemasaTakiiDepartment of Mycobacterium Reference and Research, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis AssociationAoiKimishimaŌmura Satoshi Memorial Institute, Kitasato UniversityMasatoIwatsukiŌmura Satoshi Memorial Institute, Kitasato UniversityYoshihiroWatanabeŌmura Satoshi Memorial Institute, Kitasato UniversityNaoyaOharaDepartment of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama UniversityYukihiroAsamiŌmura Satoshi Memorial Institute, Kitasato UniversityThe global increase in multidrug-resistant tuberculosis strains poses a major threat; consequently, there is an urgent need to identify and develop novel drugs. We have previously presented a simple fibroblast assay (SFA) screening method that enables the simultaneous assessment of antibacterial activity and cytotoxicity toward host cells. This method was developed based on our finding that live (but not dead) Mycobacterium tuberculosis bacilli exhibit cytotoxic activity against human lung fibroblasts, and that this cytotoxicity, which is proportional to the number of viable bacterial cells, is inhibited by known antimycobacterial drugs. While conventional methods to measure M. tuberculosis growth require 2–4 weeks to detect antibacterial activity; the SFA method enables detection within 2–3 days and can detect compounds that are active within host cells. Here, we applied high-throughput screening, based on assessment of cytotoxicity, to identify candidate antimycobacterial agents. In parallel, by comparing the direct antibacterial activity of compounds in liquid medium (using the broth dilution test) with that observed via SFA, we developed a new SFA-based screening system to select compounds with low cytotoxicity that are active outside or inside the host cells. Using this dual system, we screened 742 compounds from the Ōmura Natural Compound Library (Kitasato University, Japan), with 62 hits. Of these, 19 were excluded owing to their toxicity, and six exhibited antibacterial activity only via SFA screening. Four promising antimycobacterial candidates with no cytotoxicity at the 10 μg/mL threshold―aridicin A, lankamycin, streptovaricin, and lariatin A―were identified. identified.This novel system supports the rapid identification of low-cytotoxicity antimycobacterial compounds that are active inside or outside the host cells.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0376-73887572026Multi-criteria evaluation of graphene oxide nanofiltration membranes for decaffeination125992ENYihanTianSchool of Materials Science and Engineering, University of New South WalesTongxiLinSchool of Materials Science and Engineering, University of New South WalesYutaNishinaResearch Institute for Interdisciplinary Science, Okayama UniversityXiaojunRenSchool of Materials Science and Engineering, University of New South WalesRakeshJoshiSchool of Materials Science and Engineering, University of New South WalesNanofiltration (NF) offers a promising low-energy approach for producing decaffeinated instant coffee, while requires membranes that balance caffeine removal, water permeance, and retention of key coffee matrix compounds. Here, graphene oxide membranes (GOMs) were modified by sodium alginate (SA) intercalation, Ca2+ crosslinking, and their combined strategy to tune nanochannel structure and separation performance. The results show that membrane modification does not follow a simple monotonic trend; instead, small structural and chemical changes generate competing effects on permeance and selectivity through coupled transport, adsorption, and confinement mechanisms. To identify the most suitable membrane, a multi-criteria evaluation framework (MCEF) combining entropy weighting and TOPSIS was established using five key performance indicators: caffeine removal, flavour-related marker retention index, choline retention, water permeance, and concentration increase. This framework identified CGSM-1 as the best-performing flat membrane, which also showed promising performance in hollow-fibre form. In coffee filtration tests, CGSM-1 reduced caffeine concentration from 24.64 to 12.95 μg/mg, corresponding to a 47.4% reduction, while retaining measurable levels of HMF, trigonelline, NMP, and choline. These findings demonstrate the potential of engineered GOMs for selective caffeine reduction in coffee liquor and provide a practical evaluation strategy for membrane-based decaffeination.No potential conflict of interest relevant to this article was reported.American Geophysical Union (AGU)Acta Medica Okayama0094-827653132026Limits of Water Storage in Stishovite at Deep Mantle Conditionse2025GL120078ENFeiWangBayerisches Geoinstitut, University of BayreuthArtemChanyshevBayerisches Geoinstitut, University of BayreuthLianjieManBayerisches Geoinstitut, University of BayreuthYunkeSongBayerisches Geoinstitut, University of BayreuthLinWangBayerisches Geoinstitut, University of BayreuthTakayukiIshiiInstitute for Planetary Materials, Okayama UniversityNoriyoshiTsujinoJapan Synchrotron Radiation Research InstituteShrikantBhatDeutsches Elektronen‐Synchrotron DESYRobertFarlaDeutsches Elektronen‐Synchrotron DESYTomooKatsuraBayerisches Geoinstitut, University of BayreuthThe deep Earth water cycle is a key process in Earth's evolution. Stishovite has been proposed as a major carrier of water from the surface into the lower mantle. However, its role remains unclear because its water solubility is controversial. We investigated the water solubility of Al-free stishovite at pressures of 33–38 GPa and temperatures of 700–1200 K using in situ X-ray diffraction in an advanced multianvil apparatus. Water solubility is high, around 3 wt%, at 700 K but decreases rapidly with increasing temperature and becomes negligible (<1,000 ppm), at temperatures above 1000 K. These results suggest that pure stishovite is unlikely to transport significant amounts of water into Earth's lower mantle under comparable pressure-temperature conditions. Previously reported high water contents in pure stishovite under deep Earth conditions likely reflect the solubility of post-stishovite or experimental artifacts.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Cold SiO2-rich slabs reaching the CMB revealed by the seifertite phase boundary26394ENRyosukeSinmyoDepartment of Physics, School of Science and Technology, Meiji UniversitySaoriKawaguchi-ImadaJapan Synchrotron Radiation Research InstituteReiSatoDepartment of Earth and Planetary Science, School of Science, The University of TokyoKeisukeOtsuruJapan Synchrotron Radiation Research InstituteKenjiKawaiJapan Synchrotron Radiation Research InstituteHiroshiSakumaEnvironmental Circulation Composite Materials Group, National Institute for Materials ScienceShigeruSueharaEnvironmental Circulation Composite Materials Group, National Institute for Materials ScienceTakayukiIshiiInstitute for Planetary Materials, Okayama UniversityShuhouMaitaniDepartment of Physics, School of Science and Technology, Meiji UniversityA cold silica (SiO2)-rich subducted slab creates notable heterogeneity above the core-mantle boundary (CMB), influencing the evolution of the Earth’s mantle. This slab may exhibit characteristic anomalies in the longitudinal and shear wave seismic velocity above the CMB, attributed to the SiO2 phase transition into its dense polymorph, seifertite. However, the transition depth remains unclear due to the often-observed metastable phases in experiments. To address this long-standing challenge, we conducted laser-heated diamond anvil cell experiments with synchronised rapid X-ray diffraction measurements alongside theoretical calculations. The slope of the seifertite phase boundary was less steep than previously estimated, and consequently, the temperature profile of the slab crosses the boundary twice, like the post-perovskite transition. We observed a decrease in shear wave velocity beneath Hawaii and Central America, and we found anti-correlation in seismic wave velocities matching the depth range of the seifertite transition in a cold slab beneath Central America. This may provide evidence that a cold SiO2-rich slab descends towards the CMB.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0009-25417132026Tungsten(VI) speciation in aqueous fluids at high pressures and high temperatures: in-situ Raman spectroscopy supported by DFT calculations123411ENNaokoTakahashiDepartment of Earth Science, Graduate School of Science, Tohoku UniversityMichihikoNakamuraDepartment of Earth Science, Graduate School of Science, Tohoku UniversityShigeruYamashitaInstitute for Planetary Materials, Okayama UniversityHiroyukiKagiGeochemical Research Center, Graduate School of Science, The University of TokyoTungsten (W) is mobile in magmatic–hydrothermal and deep subduction zone fluids, and its stable isotopes offer potential as tracers of fluid-rock interactions. We investigated W behavior in aqueous fluids using in-situ Raman spectroscopy on slightly acidic to alkaline Na2WO4 solutions (10−3–10−1 M W) and WO3–H2O/D2O ± NaCl systems up to 1.4 GPa and ∼800 °C, with the band assignments supported by density functional theory (DFT) calculations. Raman spectra showed that the ν1 mode of WO42− persisted to the highest P–T conditions in alkaline fluids, while additional high-frequency bands near 950 or 973 cm−1 appeared at elevated T in the studied fluids. Their relative intensities depended on T, pH, and NaCl content; the 973 cm−1 band was only observed above 650 °C in Na-free fluids. Substitution of H2O with D2O did not significantly affect the band frequencies. Based on analogous molybdenum experiments, previous in-situ studies, and thermodynamic models, these high-T bands are assigned to mononuclear species rather than polynuclear species, consistent with the stepwise formation of hydrogentungstate anion, HWO4−, and then neutral tungstic acid, H2WO4, as T increases. DFT vibrational frequency calculations for HWO4−, H2WO4, and their D-substituted species support this interpretation, suggesting tetrahedral HWO4− and higher-coordinated H2WO4 as plausible species. The present study clarifies Raman band assignments for HWO4− and paratungstate A (W7O246−) to address previous ambiguities in the literature, and confirms that polynuclear species play a negligible role in high-T ore-forming fluids. The tetrahedral HWO4− appears to be a predominant transport species in NaCl-bearing metamorphic fluids and may govern stable W isotope fractionation during deep fluid-rock interactions.No potential conflict of interest relevant to this article was reported.American Geophysical Union (AGU)Acta Medica Okayama0094-827652172025Phase Relations in the MgSiO3 System Associated With Hot Mantle Upwelling Across the 660 km Depthe2025GL115385ENArtemChanyshevBayerisches Geoinstitut, University of BayreuthNarangooPurevjavBayerisches Geoinstitut, University of BayreuthDmitryBondarBayerisches Geoinstitut, University of BayreuthHuTangBayerisches Geoinstitut, University of BayreuthHongzhanFeiBayerisches Geoinstitut, University of BayreuthLinWangBayerisches Geoinstitut, University of BayreuthFeiWangBayerisches Geoinstitut, University of BayreuthEun JeongKimBayerisches Geoinstitut, University of BayreuthDanLiuBayerisches Geoinstitut, University of BayreuthTakayukiIshiiInstitute for Planetary Materials, Okayama UniversityShrikantBhatDeutsches Elektronen‐Synchrotron DESYRobertFarlaDeutsches Elektronen‐Synchrotron DESYTomooKatsuraBayerisches Geoinstitut, University of BayreuthThe phase transformations of MgSiO3 bridgmanite control the structure, dynamics and chemistry of the Earth's mantle. Formation of bridgmanite occurs at a depth of about 660 km causing the strong and abrupt seismic discontinuity. Previous experimental studies have revealed that this discontinuity is caused by ringwoodite dissociation in the average mantle. However, the cause of the 660-km seismic discontinuity beneath hotspots remains unclear. Here we determine the phase relations in the MgSiO3 system near the 660-km seismic discontinuity conditions. At 2,200–2,350 K with decreasing pressure, MgSiO3 bridgmanite first transforms to akimotoite and then to garnet. The akimotoite-bridgmanite boundary has almost no temperature dependence, whereas the garnet–akimotoite transition has a very steep positive boundary slope. Based on these slopes, we calculated the garnet–bridgmanite boundary slope. Depending on the temperature regime, the akimotoite-bridgmanite or the garnet–bridgmanite transition may occur in ascending plume beneath hotspots near the 660 km depth.No potential conflict of interest relevant to this article was reported.International Institute of Anticancer ResearchActa Medica Okayama0250-70054692026Antiproteinuric Effect of SGLT2 Inhibitors in Patients With Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab51415154ENTOMOKIHORIDepartment of Pharmacy, Nara Prefecture General Medical CenterKAZUHIROYAMAMOTODepartment of Integrated Clinical and Basic Pharmaceutical Science, Okayama UniversityHIROSHIAOIDepartment of Pharmacy, Nara Medical University HospitalYUSUKEKOIZUMIDepartment of Pharmacy, Nara Medical University HospitalMAKOTOKUROMATSUDepartment of Pharmacy, Tenri HospitalAIKOFUKUIDepartment of Pharmacy, Kindai University Nara HospitalHIROYOOKAMOTODepartment of Pharmacy, Kindai University Nara HospitalATSUSHIHIRATADepartment of Pharmacy, Kindai University Nara HospitalKENTAROSHINMORIDepartment of Pharmacy, Yamatotakada Municipal HospitalYUKIIMANAKADepartment of Pharmacy, Yamatotakada Municipal HospitalMIYUNAMBADepartment of Pharmacy, Nara Prefecture General Medical CenterSYUNSUKEKITAMURADepartment of Nephrology, Nara Medical University HospitalKEISUKENAKANISHIDepartment of Gastroenterology, Nara Prefecture General Medical CenterHIDEOTSUSHIMADepartment of Nephrology, Nara Prefecture General Medical CenterIKUKOYANODepartment of Pharmacy, Kobe University HospitalKEIMORIYADepartment of Gastroenterology, Nara Prefecture General Medical CenterMASARUMATSUIDepartment of Nephrology, Nara Medical University HospitalSHIGEKIIKUSHIMADepartment of Pharmacy, Nara Prefecture General Medical CenterBackground/Aim: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce proteinuria in patients with diabetes mellitus and chronic kidney disease. However, their effect on vascular endothelial growth factor inhibitor-induced proteinuria remains unclear. This study evaluated the prophylactic effect of SGLT2i on bevacizumab-induced proteinuria in patients with hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab.<br>
Patients and Methods: This multicenter retrospective study included patients with HCC who started therapy with atezolizumab plus bevacizumab between September 2020 and December 2023. The primary outcome was the time to exacerbation of proteinuria from baseline within 6 months after treatment initiation according to SGLT2i use. Secondary outcomes included the development of grade ≥2 proteinuria.<br>
Results: A total of 188 patients were included, of whom 29 received SGLT2i. No significant difference in the time to exacerbation of proteinuria was observed between the SGLT2i and non-SGLT2i groups considering the overall population (median: 157 vs. 116 days, p=0.95). Multivariate analysis identified diabetes with systolic blood pressure ≥130 mmHg as an independent risk factor for proteinuria exacerbation (hazard ratio=2.19, 95% confidence interval=1.18-4.06, p=0.013), whereas SGLT2i use was not significantly associated with proteinuria exacerbation. In patients with both diabetes and systolic blood pressure ≥130 mmHg, SGLT2i significantly prolonged the time to proteinuria exacerbation.<br>
Conclusion: SGLT2i may suppress proteinuria progression only in high-risk patients with HCC complicated by diabetes and hypertension.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2041-17231712026Water exchange process and bulk composition regulate slab dynamics and deep earthquakes8291ENJintaoZhuInstitute for Planetary Materials, Okayama UniversityRenbiaoTaoCenter for High Pressure Science and Technology Advanced Research (HPSTAR)LifeiZhangSKLab-DeepMinE, MOEKLab-OBCE, School of Earth and Space Sciences, Peking UniversityTakayukiIshiiInstitute for Planetary Materials, Okayama UniversityWater strongly influences deep mantle processes, including geochemical cycles, slab dynamics, and deep-focus earthquakes. Yet the stability and interactions of hydrous minerals with nominally anhydrous minerals (NAMs) under the water-undersaturated conditions of subducting slabs remain unclear. Here we show, using high-pressure and high-temperature experiments on MgO–SiO2–H2O systems (~2 wt% H2O), that hydrous minerals progressively dehydrate in the mantle transition zone, transferring water to NAMs such as wadsleyite and ringwoodite, while the cold slab core stays nearly dry. Rapid dehydration near the top of the lower mantle may generate fluids linked to the deepest earthquakes. Our results indicate that dry olivine transformations, rather than dehydration embrittlement, likely trigger most deep-focus earthquakes, and that hydration variations in NAMs influence slab deformation and stagnation above 660 km. The bulk Mg/Si ratio controls hydrous mineral stability, suggesting harzburgite transports water more efficiently than peridotite.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2212-87781122026Adaptive oligodendrogenesis regulates blood-hypothalamus barrier permeability, hypothalamic glucose sensing and systemic glucose homeostasis in male mice102428ENSophieBullerInstitute of Metabolic Science Metabolic Research Laboratories, University of CambridgeEmily O.StaricoffInstitute of Metabolic Science Metabolic Research Laboratories, University of CambridgeChristineRichesInstitute of Metabolic Science Metabolic Research Laboratories, University of CambridgeAnthonyTsangInstitute of Metabolic Science Metabolic Research Laboratories, University of CambridgeGiadaGiavaraInstitute of Metabolic Science Metabolic Research Laboratories, University of CambridgeMasaJosipovicInstitute of Metabolic Science Metabolic Research Laboratories, University of CambridgeKentaroIkemuraDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityGabrielOpokuDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityIkumiSatoDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversitySatoshiHirohataDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversitySaskiaStenzelInstitute of Metabolic Science Metabolic Research Laboratories, University of CambridgeStuart G.NayarWolfson Institute for Biomedical Research, University College LondonMartaRamos VegaGUBRAJacobHecksher-SørensenGUBRASebastianTimmlerCambridge Stem Cell Institute, University of CambridgeGeorgina K.C.DowsettInstitute of Metabolic Science Metabolic Research Laboratories, University of CambridgeBrian Y.H.LamInstitute of Metabolic Science Metabolic Research Laboratories, University of CambridgeGiles S.H.YeoInstitute of Metabolic Science Metabolic Research Laboratories, University of CambridgeKimberly M.AlongeDiabetes Institute, University of WashingtonHuiliangLiWolfson Institute for Biomedical Research, University College LondonWilliam D.RichardsonWolfson Institute for Biomedical Research, University College LondonMark L.EvansInstitute of Metabolic Science Metabolic Research Laboratories, University of CambridgeClemenceBlouetInstitute of Metabolic Science Metabolic Research Laboratories, University of CambridgeObjective: Brain glucose sensing is critical for survival during hypoglycaemia, yet how glucose-sensing neurons access circulating glucose concentrations to maintain glucose homeostasis remains poorly understood. Here we tested the hypothesis that adult oligodendrogenesis in the median eminence (ME) is responsive to changes in blood glucose levels and contributes to hypothalamic glucose sensing through regulation of the blood-hypothalamus barrier.<br>
Methods: We used glycemic challenges and hypoinsulinaemic clamp studies to identify the effect of systemic changes in glycaemia on hypothalamic oligodendrocyte lineage cells. We used conditional knockout mouse models to dissect the respective contributions of adult oligodendrogenesis and new myelin formation to glucose homeostasis in adult male mice. Analyses combined immunofluorescence, serial electron microscopy, whole-brain tissue clearing, and transcriptomic analyses.<br>
Results: We found that adult oligodendrogenesis in the median eminence (ME) is modulated by changes in circulating glucose levels and rapidly upregulated by hypoglycaemia. Genetic blockade of new oligodendrocyte production in adult male mice impairs the regulation of glucose homeostasis, the integrity of the ME blood-hypothalamus barrier, and hypothalamic glucose sensing. Unexpectedly, functional integrity of adult-formed myelin is not required for the maintenance of glucose homeostasis. Instead, we show that blockade of adult oligodendrogenesis disrupts hypothalamic expression of A disintegrin and metallopeptidase with thrombospondin motifs 4 (ADAMTS4), a metallopeptidase whose brain expression is restricted to the oligodendrocyte lineage and whose ME expression requires ongoing adult oligodendrogenesis. We show that ADAMTS4 regulates hypothalamic perineuronal net deposition, vascular permeability and glucose sensing. Finally, we show that ME ADAMTS4 expression is regulated by changes in peripheral glycaemia and is dysregulated in diabetes, providing a mechanism by which ME oligodendrocytes contribute to the regulation of glucose homeostasis.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1474-97182552026UNC45B Reduction With Aging: A Myofiber-Intrinsic Promoting Factor for Sarcopeniae70502ENTaigaMishimaCellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)TaigaNagamuneDepartment of Life Science and Applied Chemistry, Nagoya Institute of TechnologySaoriTadaCellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)DaikiWatanabeGraduate School of Sport and Health Sciences, Osaka University of Health and Sport SciencesNaoTokudaGraduate School of Health Sciences, Sapporo Medical UniversityTakashiYamadaGraduate School of Health Sciences, Sapporo Medical UniversityAkikoHashimoto‐HachiyaCellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)SayakaHigo‐YamamotoCellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)KoheiKidoHealth and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)NoriyukiNagaokaAdvanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama UniversityAoiIkedoDivision of Integrative Pathophysiology, Proteo‐Science Center, PIAS, Ehime UniversityYuukiImaiDivision of Integrative Pathophysiology, Proteo‐Science Center, PIAS, Ehime UniversityRyoFujitaDivision of Regenerative Medicine, Transborder Medical Research Center, Institute of Medicine, University of TsukubaSeiyaMizunoLaboratory Animal Resource Center in Transborder Medical Research Center, Institute of Medicine, University of TsukubaSatoruTakahashiLaboratory Animal Resource Center in Transborder Medical Research Center, Institute of Medicine, University of TsukubaKatsutakaOishiCellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)SatoruAtoFaculty of Medical Science, Nippon Sport Science UniversityRikiOgasawaraCellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)Skeletal muscle mass and force decline with age, and the loss of muscle force precedes muscle atrophy. However, the underlying mechanisms remain unclear. Here, we investigated the role of the myosin co-chaperone, uncoordinated mutant number-45 myosin chaperone B (UNC45B), in regulating muscle mass and force. UNC45B expression decreased in mouse gastrocnemius muscle with age, particularly at 24 months old, and adeno-associated virus vector-mediated knockdown of Unc45b in 3-month-old mouse triceps surae muscle first reduced plantar flexor torque and then decreased gastrocnemius muscle mass. In addition, Unc45b knockdown in the triceps surae muscle resulted in lower bone mineral density. While maximum Ca2+-activated force in mechanically skinned fibers was not affected by Unc45b knockdown, Unc45b knockdown decreased the ratio of depolarization-induced force to the maximum Ca2+-activated force. We established tamoxifen-inducible skeletal muscle-specific Unc45b knockout (Unc45b imKO) mice to investigate whether the muscle atrophy and weakness due to the loss of Unc45b impacts metabolism and behavior. We found that Unc45b imKO reduced muscle mass and force at a whole-body level, but did not influence systemic glucose tolerance, insulin sensitivity, or the respiratory exchange ratio. However, Unc45b imKO mice reduced the amount of deeper non-rapid eye movement sleep, locomotor activity, and body temperature during the sleep phase. We conclude that UNC45B is essential for maintaining fast-twitch muscle mass and muscle force. In addition, Unc45b deficiency-mediated muscle loss is also associated with bone fragility, decreased body temperature, and impaired sleep quality.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1873-96012032026Critical role of cellular communication network factor 1 in early osteogenesis of mesenchymal stem cells primed by low‐intensity pulsed ultrasound and bone morphogenetic protein 2e70101ENHsu MyatPaingDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesSatoshiKubotaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesMasaharuTakigawaAdvanced Research Center for Oral and Craniofacial Sciences, Okayama University Faculty of Medicine Dentistry and Pharmaceutical SciencesTakuoKubokiDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTakashiNishidaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesThere is a known reciprocal inhibitory relationship between adipogenesis and osteogenesis in mesenchymal stem cells (MSCs). Our previous study showed that low-intensity pulsed ultrasound (LIPUS) did not promote osteogenesis of a murine MSC line C3H10T1/2, although LIPUS treatment suppressed adipogenesis. Therefore, we investigated the effect of a combination of an osteoinductive factor such as bone morphogenic protein-2 (BMP-2) and LIPUS treatment on osteogenesis. This combination significantly upregulated the gene expressions of BMP receptors and RUNX2, which is a key early osteogenic transcription factor. Interestingly, cellular communication network factor 1 (CCN1) was significantly increased at the mRNA and protein levels. Additionally, Runx2 expression was increased by a recombinant CCN1 protein and decreased in CRISPR-Cas9-generated Ccn1 knockout (KO) cells treated with the combination of LIPUS treatment and BMP-2. Moreover, Runx2 expression was recovered through the transfection of a Ccn1 expression plasmid into Ccn1 KO cells. These findings indicate that treatment with the combination of LIPUS treatment and BMP-2 promoted CCN1 production, and the CCN1 regulates the Runx2 expression in C3H10T1/2 cells, thus suggesting that CCN1 induced by mechanical stimulation and an osteoinductive factor plays a pivotal role in osteogenesis of MSCs.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1873-96012022026Species‐specific roles of cellular communication network proteins in cartilage development: A comparative study using in vitro chondrogenic modelse70089ENZhangzhengWangDepartment of Anatomy, Histology and Embryology Faculty of Medicine, University of DebrecenJuditVágóDepartment of Anatomy, Histology and Embryology Faculty of Medicine, University of DebrecenRolandTakácsDepartment of Anatomy, Histology and Embryology Faculty of Medicine, University of DebrecenSzilárdPóliskaGenomic Medicine and Bioinformatics Core Facility Department of Biochemistry and Molecular Biology Faculty of Medicine, University of DebrecenEe HyunKimDepartment of Biomedical Materials Science Graduate School of JABA, Wonkwang UniversityEun‐JungJinDepartment of Biomedical Materials Science Graduate School of JABA, Wonkwang UniversitySatoshiKubotaDepartment of Biochemistry and Molecular Dentistry, Okayama University, Faculty of Medicine, Dentistry and Pharmaceutical ScienceCelina GKleerDepartment of Pathology, University of Michigan Medical SchoolBernardPerbalInternational CCN SocietyCsabaMattaDepartment of Anatomy, Histology and Embryology Faculty of Medicine, University of DebrecenCellular communication network (CCN) proteins are key matricellular regulators of cartilage development, yet their species-specific roles and network-level context remain unclear. This study integrated bulk RNA sequencing from chicken and mouse embryonic limb bud micromass cultures and human mesenchymal stem cell chondrogenesis with co-expression, protein–protein interaction, and ortholog analyses to construct CCN-centered regulatory networks across models. CCN1 and CCN2 emerged as dominant, conserved hubs enriched in collagen-containing extracellular matrix, cartilage development, and growth factor signaling modules, whereas CCN3–CCN6 showed lower context-dependent expression and connectivity. Functional and ortholog analyses revealed moderate pathway conservation, with high conservation of IGF, EGFR, and HIF-1 signaling, but reduced overlap in hypoxia and mechanosensing/Hippo categories, indicating species-specific tuning of environmental sensing. A focused ortholog screen identified multifunctional conserved hubs, including COL2A1, TGFBR1, SMAD3, RUNX2, HIF1A, IGF1, SPP1, and CD44. Single-cell RNA-seq meta-analysis of human iPSC-derived chondrogenesis and embryonic limb datasets showed CCN1/2 expression and homologous network activity peaking in mesenchymal and early chondrocyte populations, consistent with model-dependent persistence into hypertrophic and ossification stages in vivo. Overall, this work defines a conserved CCN1/2-centered axis integrating extracellular matrix formation with growth factor and mechanical cues, providing a framework for model selection and CCN-targeted cartilage regeneration strategies.No potential conflict of interest relevant to this article was reported.The Society for Free Radical Research JapanActa Medica Okayama0912-00097922026Organ-specific modulation of antioxidant functions by combined voluntary exercise and radon inhalation in mice141149ENReijuTakenakaGraduate School of Health Sciences, Okayama UniversityAyumiTanakaGraduate School of Health Sciences, Okayama UniversityShogoMiyanagaGraduate School of Health Sciences, Okayama UniversityShotaNaoeNingyo-toge Environmental Engineering Center, Japan Atomic Energy AgencyShunaGotoGraduate School of Health Sciences, Okayama UniversityMitsukiNaganoGraduate School of Health Sciences, Okayama UniversityKotaroTanoGraduate School of Health Sciences, Okayama UniversityNorieKanzakiNingyo-toge Environmental Engineering Center, Japan Atomic Energy AgencyAkihiroSakodaNingyo-toge Environmental Engineering Center, Japan Atomic Energy AgencyKiyonoriYamaokaFaculty of Health Sciences, Okayama UniversityTakahiroKataokaFaculty of Health Sciences, Okayama UniversityRadon inhalation as well as voluntary exercise increase antioxidant function in experimental animals. However, the combined effects of radon inhalation and exercise on antioxidant functions have not yet been investigated. In this study, we examined the effects of combined voluntary wheel running (VWR) and radon inhalation on antioxidant functions in various organs of mice. Mice were individually housed in cages equipped with running wheels, and allowed voluntary exercise for 5, 15, or 25 days, followed by radon inhalation at 2,000 Bq/m3 for 24 h. Antioxidant function was enhanced by the combined treatment in the kidneys, pancreas, spleen, and stomach, with responses varying according to exercise duration. In contrast, antioxidant function was reduced in the lungs and heart. No clear interaction effects of the combined treatment were observed in the liver, small intestine, colon, and brain. These findings suggest that the combined effects of voluntary exercise and radon inhalation on antioxidant functions are organ-specific and can be categorized into distinct response patterns across tissues.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1078-81743272026Patient-centred communication in radiographer education: A five-country comparative document analysis of curriculum and competency standards103553ENY.KomatsuDivision of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityY.ChikamotoIndependent ResearcherK.TsukanoDepartment of Psychosomatic Medicine, Yokohama Rosai HospitalS.AbeDepartment of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care SciencesS.TsudouDepartment of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care SciencesY.YamamotoDivision of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityY.TanabeDivision of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityIntroduction: Patient-centred communication is fundamental to radiographic practice, particularly when patients experience anxiety or uncertainty during imaging or treatment. However, it remains unclear whether broad communication expectations in radiography education and professional standards are translated into explicit, observable behaviours and integrated into education and assessment. This comparative document analysis examined the representation of patient-centred communication in selected national-level documents from five countries, using listening-related behaviours as an illustrative example.<br>
Methods: Selected national-level curriculum, accreditation, registration, capability, and competency documents from the United States, the United Kingdom, Australia, Canada, and Japan were analysed deductively using a predefined extraction framework. The framework assessed communication competence, listening-related behaviours, patient-centred care, patient/family relationships, interprofessional collaboration, education, and assessment.<br>
Results: Communication was addressed in all five selected national-level document sets, although institutional framing differed. It was framed as a professional competency or capability in the United Kingdom and Australia, a role-based competency framework in Canada, clinical competency and accreditation requirements in the United States, and primarily as curriculum content in Japan. Explicit observable behavioural expectations, such as listening-related behaviours, were uncommon. Listening was explicitly defined only in the Australian capability standards; elsewhere, it was represented indirectly through broader concepts, such as patient interaction, information gathering, and interpersonal communication.<br>
Conclusion: The selected documents differed in the explicitness, structure, and educational integration of communication-related standards, without implying differences in education quality or clinical outcomes. Defining patient-centred communication through observable behaviours may strengthen alignment among professional expectations, learning outcomes, feedback, and assessment.<br>
Implications for practice: Operationalising patient-centred communication as observable behaviours may enhance curriculum mapping, feedback, and assessment in radiographer education.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1939-84251912026GWAS and Candidate Gene Prediction of Elemental Accumulation Traits in Rice Using a Multiparental Population44ENQianZhangInstitute of Plant Science and Resources, Okayama UniversityTomoyukiFurutaInstitute of Plant Science and Resources, Okayama UniversityKazunariKashiharaInstitute of Plant Science and Resources, Okayama UniversityDaisukeOgawaInstitute of Crop Science, National Agriculture and Food Research OrganizationJunichiYonemaruResearch Center for Agricultural Information Technology, National Agriculture and Food Research OrganizationJian FengMaInstitute of Plant Science and Resources, Okayama UniversityToshioYamamotoInstitute of Plant Science and Resources, Okayama UniversityRice plants accumulate essential elements to sustain physiological processes during growth and development and to ensure the nutritional quality of the grain as a food source. However, the genetic basis of elemental accumulation and the interrelationships among elemental concentrations across different tissues remain poorly understood. To conduct breeding aimed at improving the absorption characteristics of multiple interrelated elements, genetic analysis using experimental populations that retain diversity while sharing the genetic background of cultivated varieties is effective. Here we show genetic variations in the concentrations of 13 elements (P, K, Ca, Mg, As, Cd, Cr, Cu, Fe, Mo, Mn, Ni, and Zn) in rice straw at the flowering stage and grain at the mature stage using a multi-parent advanced generation inter-cross (MAGIC) population that derived from eight cultivars including both Japonica and Indica. Comprehensive evaluation of the correlation coefficients revealed divergences in the association between grain and straw for several combinations of elements. Haplotype-based genome-wide association studies (GWAS) identified 51 and 53 quantitative trait loci (QTLs) in straw and grain, respectively. In total, the 104 QTLs were grouped into 19 clusters and 60 independent QTLs. By leveraging the haplotype information from the MAGIC population, 52 candidate genes associated with the accumulation of Ca, Mg, Cd, Cu, Fe, and Mo were efficiently predicted from these QTLs, including both previously reported and novel genes. Among them, OsMOT1;1 encoding a molybdenum transporter, was predicted to be within a QTL associated with Mo accumulation in grain on chromosome 8. OsACA9, a homolog of autoinhibited Ca²⁺-ATPases, was predicted within a QTL related to Ca accumulation in straw on chromosome 2. In addition, an unidentified gene, OsCML6, which is presumed to be involved in calcium signaling, was predicted to be a candidate for a Ca-accumulation QTL on chromosome 11. These findings offer insights into haplotypes and putative genes associated with element accumulation and trait interrelationships, providing valuable information for optimizing plant growth and enhancing grain nutritional quality in rice breeding programs.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1759-87531712026Report on the seventh Japanese meeting on biological function and evolution through interactions between hosts and transposable elements6ENKenjiIchiyanagiLaboratory of Genome and Epigenome Dynamics, Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya UniversityYokoIkedaInstitute of Plant Science and Resources, Okayama UniversityKuniakiSaitoInvertebrate Genetics Laboratory, National Institute of GeneticsThe seventh Japanese meeting on host–transposon interactions, titled “Biological Function and Evolution through Interactions between Hosts and Transposable Elements,” was held on September 1st and 2nd, 2025, at the National Institute of Genetics, as well as online. This meeting was supported by the National Institute of Genetics and aimed to bring together researchers studying the diverse roles of transposable elements (TEs) in genome function and evolution, as well as host defense systems against TE mobility, TE bursts during evolution, and intron mobility in mammals, insects, land plants, fungi, and protozoa. Here, we present the highlights of these discussions.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0918-944013922026Knockout of a single aquaporin, OsPIP2;4, decreases root water permeability in rice255265ENAyaOnishiInstitute of Plant Science and Resources, Okayama UniversityTomoakiHorieDivision of Applied Biology, Faculty of Textile Science and Technology, Shinshu UniversityRyoIshitsukaInstitute of Plant Science and Resources, Okayama UniversityShizukaSasanoInstitute of Plant Science and Resources, Okayama UniversityRieHorieDivision of Applied Biology, Faculty of Textile Science and Technology, Shinshu UniversityYunosukeMitoDivision of Applied Biology, Faculty of Textile Science and Technology, Shinshu UniversityShigekoUtsugiInstitute of Plant Science and Resources, Okayama UniversityJunkoIshikawaInstitute of Crop Science, NAROMajidMahdiehInstitute of Plant Science and Resources, Okayama UniversityMakiKatsuharaInstitute of Plant Science and Resources, Okayama UniversityAquaporins (AQPs) are membrane proteins that facilitate water transport and are present in nearly all bacterial, animal, and plant cells. In plants, AQPs are classified into four or more subfamilies, with plasma membrane intrinsic proteins (PIPs) playing a key role in root water uptake and cellular water regulation. Previous studies have demonstrated that PIPs contribute to root hydraulic conductivity (Lpr) in various plant species. In this study, we examined the specific role of OsPIP2;4, one of the PIP-type aquaporins among 11 rice (Oryza sativa) PIP2s, in regulating Lpr. Transgenic rice plants, including OsPIP2;4-knockout (KO) and overexpressing (Ox) lines, were used for this investigation. Two independent KO lines, generated via the CRISPR-Cas9 system and T-DNA insertion mutagenesis, respectively, showed significantly lower Lpr compared to wild-type rice plants. The decrease in Lpr in the T-DNA KO line was associated with reduced OsPIP2;4 transcript levels, measured by real-time PCR, and lower OsPIP2;4 protein levels, as shown by immunohistochemical analysis. Conversely, no notable increase in Lpr was observed in the Ox lines. These results suggest that OsPIP2;4 is expressed in appropriate tissues in rice roots and is a key factor influencing Lpr. This research represents a significant step toward further understanding the physiological functions of OsPIP2;4 in rice.No potential conflict of interest relevant to this article was reported.岡山大学大学院教育学研究科Acta Medica Okayama1883-24231922026「創造性が社会と出会う美術教育」による教員の学びに関する基礎研究V ― 中学校美術科教員の授業記録と追跡インタビューに基づく事例研究―125135ENAiMATSUURAFaculty of Education, Okayama UniversityYusukeSENOOOkayama Prefectural Tamashima High SchoolHitoshiKIMURAShiga University Faculty of Education Elementary SchoolSoichiroTAKEDAOkayama University Junior High SchoolChandeSONOsaka Kyoiku University Tennoji Junior High SchoolTetsuoKIYOTAFaculty of Education, Okayama University10.18926/bgeou/71149 本論は，学校外の他者との対話経験が，中学校美術科教員の授業実践においてどのように意味づけられていたのかを明らかにすることを目的とする。市井プロジェクトに参加した教諭Bを対象に，市井インタビュー後に実施された表現活動の授業記録と，授業実践後の追跡インタビューを照合した。その結果，教諭Bは，学校外の他者との対話経験を，授業方法の直接的な変更としてではなく，授業中の判断，生徒理解，題材・表現理解，生活実践との関係において意味づけていたことが確認された。特に，生徒の行動や表現を統制する見方から，その背景や生成過程を見取る見方への移行があった可能性が高い。以上のことから，本論により教師の学びを学校内の研修や同僚性に限定せず学校外の生活世界との関係から捉える意義が示唆された。No potential conflict of interest relevant to this article was reported.岡山大学大学院教育学研究科Acta Medica Okayama1883-24231922026子どもの自己が立ち上がる造形行為についての文献研究 ― 木村敏の文献に基づいた子どもの学びを捉える視点 ―6977ENShuyaOHIRAFaculty of Education, Okayama University10.18926/bgeou/71145 本研究では，造形行為において，子どもの「自己」が立ち上がることをその子ども自身の学びとして捉える視点について，木村の文献を手掛かりに検討した。まず，「自我」，「無意識」，「自己」の概念を整理し，造形行為において個々の子どもに経験される学びを考察した。次に，個々の子どもに経験される学びが，活動場所や造形行為を共有する他の子どもへと知られ受容されていく関係が，造形行為の過程で形成されることを考察した。最後に，造形行為において形成される子ども同士の関係へと参与し，同じ経験を共有していくあり方が，子どもの「自己」が立ち上がる学びを捉える視点そのものであることを示した。今後は，芸術教育や芸術実践を対象とした研究により，本研究の知見を深めていく。No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2666-5174112026Interbacterial antagonism mediates plant growth modulation by rhizosphere synthetic communities in barley100639ENMd AsifMahamudInstitute of Plant Science and Resources, Okayama UniversityRungnapaPichaikarnSchool of Science, Walailak UniversityMuhammad AmmarLatifInstitute of Plant Science and Resources, Okayama UniversityTakakazuMatsuuraInstitute of Plant Science and Resources, Okayama UniversityIzumi CMoriInstitute of Plant Science and Resources, Okayama UniversityDaisukeSaishoInstitute of Plant Science and Resources, Okayama UniversityPakpimolUngcharoenwiwatSchool of Science, Walailak UniversityAkioTaniInstitute of Plant Science and Resources, Okayama UniversityMicrobial communities in plant roots are shaped by complex interbacterial interactions, yet how these interactions translate into plant fitness remains poorly understood. In this study, 127 bacterial isolates were obtained from barley (Hordeum vulgare L.) roots of two cultivars grown in a non-fertilized field, representing 45 genera and 72 species. Screening identified isolates with growth-promoting, growth-reducing, and neutral phenotypes. Co-inoculation experiments using synthetic communities (SynComs) demonstrated that growth-promoting isolates effectively cancelled the inhibitory effects of growth-reducing isolates on barley seedling growth. Mechanistic investigation revealed that growth-promoting isolates Variovorax sp. 14F-2.1 and Pseudomonas sp. 37A kill growth-reducing isolates Flavobacterium sp. 2D-1 through direct cell-to-cell contact. Deletion of the Type VI secretion system (T6SS) gene tssA in Variovorax sp. 14F-2.1 substantially reduced this activity, implicating T6SS as a key antagonistic mechanism. Phytohormone profiling revealed that growth-promoting and neutral isolates, but not growth-reducing isolates, produce cytokinins, and only Variovorax sp. 14F-2.1 could degrade IAA, suggesting a potential hormonal basis for differential growth effects. A two-year field microbiome study showed that fertilization regimen and seasonal sampling times were dominant drivers of rhizosphere community composition, while bacterial inoculation had limited and inconsistent effects on microbial diversity and plant growth under field conditions. These results demonstrate that interbacterial antagonism is a key determinant of community-level plant growth outcomes and highlight the complexity of translating laboratory inoculant effects to field settings.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0934-97232026Streptococcal toxic shock syndrome caused by ST525 Streptococcus dysgalactiae subsp. equisimilis with genomic characterization of virulence and antimicrobial resistanceENShumaTsujiDepartment of Medical Laboratory Science, Okayama University Graduate School of Health SciencesShinnosukeFukushimaDepartment of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyoshiGotohDepartment of Medical Laboratory Science, Okayama University Graduate School of Health SciencesKojiIioMicrobiology Division, Clinical Laboratory, Okayama University HospitalMakiTaniokaClinical Oncology Center, Okayama University HospitalHideharuHagiyaResearch Center for Intestinal Health Science, Okayama UniversityStreptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of severe invasive infections. We describe the clinical course of an immunocompromised patient with advanced breast cancer who developed streptococcal toxic shock syndrome, necrotizing fasciitis, and disseminated intramuscular abscesses caused by a multidrug-resistant Lancefield group G SDSE isolate, alongside a comprehensive genomic characterization of its virulence and antimicrobial resistance profiles. Genomic analysis identified the isolate as emm subtype stG840.0 and sequence type 525 (ST525), harboring genes encoding several virulence-associated factors, including an emm-like gene encoding an M-like surface protein, streptokinase, streptolysin O, streptolysin S, and SpeG. Through comprehensive genomic analysis of the highly virulent SDSE isolate, we provided insights into its underlying genetic background. Further accumulation of genomic data is expected to fully elucidate the mechanisms of virulence and antimicrobial resistance in SDSE.No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama1523-70602812025Optimization of the External Directing Group Depending on the Substrates for the Regioselective C–H Alkenylation of Phenyl Ethers9499ENKokiYanoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDaisukeSawadaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityUsing an external directing group (externalDG), we have succeeded in ortho-selective C–H alkenylation of various DG-free phenyl ethers, including bulky silyl ethers. Also, we demonstrated a strategy to develop regioselective C–H activation by optimizing externalDG depending on the substrate. The means for optimizing externalDG include the selection of the precursor, the addition of a Lewis acid, and changing the ratio of the precursor/Pd, to control the reactivity and regioselectivity.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-006727172026Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer’s Disease in a Mouse Model7542ENMomokoNakaharaDepartment of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKotaKataokaDepartment of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama UniversityTakayukiMaruyamaDepartment of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMohammadNurhamimDepartment of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityYixuanZhangDepartment of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityDaikiFukuharaDepartment of Preventive Dentistry, Dental School, Okayama UniversityYokoUchida-FukuharaLaboratory of Biological Anthropology, Research Center for Integrative Evolutionary Science, The Graduate University for Advanced Studies, SOKENDAIMd MonirulIslamCentre for Policy Studies, University College CorkManabuMoritaDepartment of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health CareTakashiSaitoDepartment of Neuropathology, Graduate School of Medicine, The University of TokyoDaisukeEkuniDepartment of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThe purpose of the present study was to investigate how periodontitis and diabetes mellitus (DM) are associated with Alzheimer’s disease (AD) through microRNA (miRNA) using AD model mice. The experimental period was 8 weeks. Twenty-four male knock-in mice (B6-AppNL-G-F/NL-G-F/J) were divided into four groups: control group fed a normal diet (C), DM group fed a high-fat/sucrose diet (DM), periodontitis (P) group, and DM + periodontitis (DM+P) group. Memory performance was compared using the Y-maze test. Next-generation sequencing was performed on brain samples, and fold changes in miRNA expression were calculated by comparing the DM+P and C groups. Integrated miRNA–mRNA analysis identified putative miRNA-targeted mRNAs, and protein expression of the top candidate gene was assessed. Memory function in the DM+P group was significantly lower than in the C group. Among the seven mRNAs identified by the integrated analysis, Neurod1 showed the greatest decrease in expression, and it was predicted to be regulated by miR-693-3p. Neurod1 protein expression in the hippocampus was significantly lower in the DM+P group than the C group. Our results suggest that the combined exposure to periodontitis and DM was associated with AD-like pathological changes and identified the miR-693-3p/Neurod1 pair as a candidate regulatory axis.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0005-2728186742026Cryo-EM structure of photosystem II D1-V185T mutant from Thermosynechococcus vestitus149598ENHaoweiJiangResearch Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYoshikiNakajimaResearch Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityFusamichiAkitaResearch Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHongjieLiCenter for Transformative Science, School of Life Science and Technology and Shanghai Clinical Research and Trial Center, ShanghaiTech UniversityKojiKatoResearch Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMiwaSugiuraProteo-Science Research Center, Ehime UniversityJian-RenShenResearch Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityPhotosystem II (PSII) catalyzes water oxidation into electrons, protons and dioxygen at its catalytic center, a Mn4CaO5 cluster, utilizing light energy. An amino acid residue D1-V185 in the D1 protein is located close to the Mn4CaO5 cluster, and plays a critical role in its catalytic function. In this research we purified PSII dimers from a D1-V185T mutant of Thermosynechococcus vestitus and analyzed its structure using low-damage cryo-electron microscopy (cryo-EM) at a resolution of 1.88 Å. The results revealed the presence of multi-conformations at the mutation site. Unlike the wild-type valine, which does not allow water molecules to be able to form hydrogen-bonds with it, both conformations of the mutant formed hydrogen bonds with nearby water molecules, which leads to rearrangement of the hydrogen bond networks in the O1 and Cl-1 channels. In conformation-A, the mutated Thr residue forms a hydrogen bond with a water molecule W6, which creates a new channel that bypasses the original O1 channel. Due to the hydrophilic OH group of Thr, the side-chain of D1-Glu189 was attracted and shifted toward the mutant Thr residue. In conformation-B, it forms a hydrogen bond with a water molecule W9 in the Cl-1 channel, bringing W9 closer and thereby disrupting the hydrogen bond network of the Cl-1 channel. In addition, multi-conformations of D2-K317, which is a ligand of Cl-1, were found in the mutant. These changes alter the environment surrounding the Cl-1 ion and Mn4CaO5, thereby affecting the PSII water-oxidation activity.No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama2643-6728742026Graphene Oxide: Designing a Functional Smarter Material for Advanced Biomedicine399409ENCéciliaMénard-MoyonCNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISISYutaNishinaResearch Institute for Interdisciplinary Science, Okayama UniversityAlbertoBiancoResearch Institute for Interdisciplinary Science, Okayama UniversityGraphene oxide (GO) has emerged as one of the most extensively studied two-dimensional (2D) materials, thanks to its large surface area and abundance of functional groups, which enable applications across energy, catalysis, electronics, construction, and mobility. Its exceptional dispersibility in water further expands its use in the biomedical field. However, researchers have consistently expressed concerns about the limited control over GO chemical composition and structural heterogeneity. These factors are often overlooked, strongly affecting the reproducibility in both synthesis and applications. Because GO is considered a promising platform for advanced drug delivery, achieving reproducible preparation and precise structural control is essential to make it a reliable alternative to the many nanomaterials currently being explored for nanomedicine.<br>
Motivated by these challenges, we have focused our work on identifying and controlling the key parameters that govern GO structure and surface chemistry. Over the past decade, we have developed methods to produce GO with controlled and tunable chemical structures, clarified the reactivity of its major functional groups, and developed robust strategies for postfunctionalizing GO with therapeutic agents, targeting ligands, and imaging dyes. In parallel, we have established systematic approaches to evaluate GO biocompatibility and biodegradability, revealing how specific physicochemical features influence biological responses and clearance pathways.<br>
Together, these findings provide a unified framework linking GO synthesis, chemical modification, and biological behavior. By integrating chemical control, functional performance, and safety assessment, our work outlines a coherent strategy for the rational design of GO-based biomedical materials. We believe that this Account offers a solid foundation for the targeted exploitation of GO in nanomedicine and will help facilitate its eventual clinical translation.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813822026感染症学分野創設マニフェスト―日本屈指の感染症研究拠点を目指して―4549ENHideharuHagiyaDepartment of Infectious Diseases, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813822026令和７年度岡山医学会賞 がん研究奨励賞（林原賞・山田賞）3839ENHibikiUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813822026令和７年度岡山医学会賞 胸部・循環研究奨励賞（砂田賞）3537ENYoshihikoItohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1616-301X2026Biomineral-Inspired Organic/Inorganic Colloidal Liquid-Crystalline Hybrids for Photoresponsive Adhesione77420ENJunyaUchidaResearch Institute for Interdisciplinary Science, Okayama UniversityRyutaKiguchiDepartment of Chemistry and Biotechnology School of Engineering, The University of TokyoRikiKatoResearch Institute for Interdisciplinary Science, Okayama UniversityYutaNishinaResearch Institute for Interdisciplinary Science, Okayama UniversityTakashiKatoResearch Institute for Interdisciplinary Science, Okayama UniversityBioinspired hybrid nanostructures offer a promising strategy for developing dynamic functional materials. Herein, we report a new class of photoresponsive liquid-crystalline (LC) adhesives based on organic/inorganic nanostructured colloidal hybrids. These LC materials are composed of a biomineral-inspired hydroxyapatite (HAp) nanorod and azobenzene-based forklike molecules. The organic/inorganic LC hybrids exhibit unusual photo-enhanced adhesion upon photoinduced order–disorder phase transitions of these LC materials. The photoresponsive adhesion functions of the colloidal LC hybrids are tuned by spacer moieties of the forklike molecules as well as mixing of the hybrids with the forklike molecules. The reversible photo-enhanced adhesion of the LC hybrids is achieved when the forklike molecule having oligooxyethylene spacers is hybridized with the HAp nanorod. The flexible oligooxyethylene spacers of the forklike molecule are effective for the formation of less ordered packing of the azobenzene units in the LC hybrids, which enables the dynamic photoresponsive functions. We propose an approach to the development of bioinspired photoresponsive LC materials through self-assembly of functional organic molecules and biomineral-based colloidal hybrids.No potential conflict of interest relevant to this article was reported.Royal Society of Chemistry (RSC)Acta Medica Okayama1759-995417292026Effect of graphene oxide sheet size on pickering miniemulsion polymerization of styrene32263236ENYueZhangCluster for Advanced Macromolecular Design, School of Chemical Engineering, The University of New South WalesYaseminFadilCluster for Advanced Macromolecular Design, School of Chemical Engineering, The University of New South WalesYutaNishinaResearch Core for Interdisciplinary Sciences, Okayama UniversityVipulAgarwalCluster for Advanced Macromolecular Design, School of Chemical Engineering, The University of New South WalesPer B.ZetterlundCluster for Advanced Macromolecular Design, School of Chemical Engineering, The University of New South WalesThe effect of graphene oxide (GO) sheet size on the progression of Pickering miniemulsion polymerization of styrene was systematically investigated using two GO samples with lateral dimensions (∼500 nm and 5–10 µm). Key parameters, including the presence of the conventional surfactant sodium dodecyl sulfate (SDS), GO loading, and initiator concentration, were investigated individually. Miniemulsion polymerization with GO was successfully conducted both in the absence and presence of SDS, with the addition of SDS leading to a significant rate enhancement attributed to SDS-induced secondary nucleation. In the presence of SDS, GO sheet size influenced polymerization behavior, and its effect on polymerization rate and monomer conversion exhibited opposite trends at different GO loadings. Small GO (∼500 nm) led to higher conversion and faster rates at high GO loading (5 wt%), whereas large GO (5–10 µm) resulted in higher conversion and faster rates at low GO loading (0.5 wt%). This size-dependent effect became more pronounced at lower initiator concentration. Overall, while GO sheet size exhibited a measurable influence on polymerization behavior, the overall kinetics were primarily governed by SDS-induced secondary nucleation. These findings provide new insights into the role of GO lateral dimensions in miniemulsion polymerization and offer guidance for the design and synthesis of polymer/graphene (oxide) nanocomposites with tunable properties.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2072-669418102026Racial/Ethnic Disparities in Neoplasm-Related Mortality and the Social Determinants of Health1572ENYoshitoNishimuraDivision of Hematology, Mayo ClinicMarikoFujiiDepartment 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 UniversityKoHaradaBrookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount SinaiHideharuHagiyaDepartment of Infectious Diseases, Okayama University Hospital,UrshilaDuraniDivision of Hematology, Mayo ClinicStephen M.AnsellDivision of Hematology, Mayo ClinicJames R.CerhanDepartment of Quantitative Health Sciences, Mayo ClinicToshihiroKoyamaDepartment of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground/Objectives: Racial/ethnic and regional disparities in neoplasm-related mortality remain a significant public health challenge. In this study, we aimed to evaluate long-term trends in county-level neoplasm-related mortality rates by race/ethnicity in the United States and examine associations with social determinants of health. Methods: We conducted a cross-sectional ecological study using population-based data from the Global Burden of Disease Study, including individuals residing in 50 states of the United States and the District of Columbia from 2000 to 2019. We analyzed age-standardized neoplasm-related mortality rates by ethnicity/race. Joinpoint regression analysis was used to identify significant changes in mortality trends, summarized as average annual percentage change. County-level correlations between mortality and key social determinants of health were also assessed. Results: Neoplasm-related mortality rates declined across all racial/ethnic groups from 2000 to 2019; however, disparities persisted. The age-standardized neoplasm-related mortality rates per 100,000 population decreased in all racial/ethnic subgroups. The average annual percentage change ranged from −0.94% (Hispanic and non-Hispanic American Indian or Alaska Native) to −1.90% (Black). Sex-specific analyses revealed similar trends. Southeastern states experienced slower declines than Northeastern states did. County-level smoking and poverty rates were positively correlated, whereas the primary care physician-to-population ratio, excessive alcohol consumption rate, mammography screening rate, and median household income were inversely correlated with neoplasm-related mortality rate, varying by race/ethnicity. Conclusions: Targeted, community-specific interventions are required to reduce inequities in cancer outcomes.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1356-95973152026Transforming Life Science Through Chromosome‐Level Genome Assembliese70145ENTetsuoKonDepartment of Neurosciences and Developmental Biology, University of ViennaKosukeKataokaGraduate School of Engineering, Tokyo University of Agriculture and TechnologyYi‐JyunLuoBiodiversity Research Center, Academia SinicaJohannes NicolausWibisanaGenomics and Regulatory Systems Unit, Okinawa Institute of Science and Technology Graduate UniversityKouheiTogaLaboratory of BioDX, PtBio Co‐Creation Research Center, Genome Editing Innovation Center, Hiroshima UniversityNarumiUnoLaboratory of Bioengineering, School of Life Sciences, Tokyo University of Pharmacy and Life SciencesYukiMondenGraduate School of Environmental, Life, Natural Science, and Technology, Okayama UniversityMayukoHamadaUshimado Marine Institute, Okayama UniversityAdvances in long-read sequencing and Hi–C scaffolding have made chromosome-level genome assembly increasingly accessible to individual laboratories, shifting genome research from large consortium-led projects toward investigator-driven studies across diverse taxa. This transition allows researchers to select organisms based on biological questions rather than the prior availability of genomic resources. In this review, we summarize the core experimental and computational steps for generating, evaluating, and annotating chromosome-level assemblies, and examine how they have advanced research in non-model organisms and genetically complex systems. Representative case studies illustrate four major contributions: resolving structural variation and lineage-specific genome architecture, linking genome organization to phenotypic innovation and plasticity, reconstructing deep chromosome evolution and macrosynteny, and distinguishing homologous and homoeologous chromosomes in polyploid genomes. These examples show that chromosome-level assemblies provide more than complete reference sequences. They establish a continuous genomic coordinate system through which genes, regulatory elements, transposable element insertions, sequence variants, and cellular states can be interpreted within broader chromosomal, population, and evolutionary contexts. We describe this integrative perspective as “glocal biology.” Future progress will require pangenomic, population-scale, and haplotype-resolved resources integrated with multi-omics and functional analyses. Collectively, chromosome-level genomics is reshaping life science by embedding molecular functions within chromosomal and evolutionary contexts.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2699-9307662026NUAK2 Inhibition Enhances Macromolecular Drug Delivery in a 3D Fibrotic Model of the Pancreatic Tumor Microenvironmente202500237ENMisakiNakamuraDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroyoshi Y.TanakaDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityMayuOhiraDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityHarukoOhta‐OkanoDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityReikaNakamuraDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityYuSenoDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversitySaayaYaraDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversitySakuraFujitaDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityDaichiShibataDepartment of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayaYamamotoDepartment of Materials Processing Graduate School of Engineering, Tohoku UniversityShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityKensukeOsadaDepartment of Molecular Imaging and Theranostics Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST) HoracioCabralDepartment of Bioengineering Graduate School of Engineering, The University of TokyoAtsushiMasamuneDivision of Gastroenterology Graduate School of Medicine, Tohoku UniversityMitsunobu R.KanoDepartment of Pharmaceutical Biomedicine Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityPancreatic ductal adenocarcinoma (PDAC) features a fibrotic tumor microenvironment that impedes drug delivery and significantly limits the successful clinical application of nanomedicines. Targeting signaling in pancreatic stellate cells (PSCs), which drive fibrosis via excessive secretion of extracellular matrix proteins such as collagen I, may be useful in overcoming this fibrotic barrier. The AMPK-related kinases NUAK1/2 have recently gained interest as promoters of fibrosis, but whether they play a profibrotic role in PSCs remains unknown. Here, patient PSCs are used to assess NUAK1/2 involvement in the PDAC fibrotic barrier. Leveraging a 3D cell culture model of PDAC fibrosis, the effect of targeting NUAK1/2 on the permeability of macromolecular dextrans of various sizes, as well as physiologically relevant macromolecules, albumin and IgG, and clinical nanomedicines, Doxil and Abraxane, is investigated. NUAK1/2 inhibition is shown to diminish collagen I to enhance macromolecular permeability, via a mechanism independent of established pathways involving transforming growth factor-β (TGFβ) and yes-associated protein (YAP). Through isoform-specific knockdown, predominant NUAK2 involvement is demonstrated. Mechanistically, actin stress fiber regulation by NUAK2 is shown to be important. Altogether, these results show in vitro that NUAK2 promotes fibrotic signaling in PSCs and may be targeted to enhance macromolecular drug delivery in PDAC.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2589-00422962026Posterior shift of Shh-Fgf signaling in axolotl limb regeneration drives sequential digit formation116256ENSayaFurukawaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySakiyaYamamotoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHarukiNakayamaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAyakaOhashiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAkiraSatohGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityDo conserved morphogen modules generate a given form only via a single spatiotemporal deployment, or can alternative deployments yield the same morphology? Axolotl limb regeneration provides a tractable test bed. SHH and FGF8, universally used in limb formation across vertebrates, also operate in axolotl, although the spatial domain of Fgf8 differs markedly from that in amniotes. A mutual Shh/Fgf feedback loop is likewise conserved. Here, we show that, in axolotl, the active domain of this loop shifts progressively posterior as digit formation proceeds. In step with this anterior-to-posterior displacement, digit-forming regions are sequentially induced posteriorly, explaining the axolotl’s reversed order relative to the amniote posterior-to-anterior sequence. These findings indicate that conserved molecular toolkits can overcome differences in spatial deployment to produce equivalent final limb architectures, demonstrating that there is not a single route to a target morphology.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2056-306X1212026Knockout analysis of period and timeless and EGFP-based visualization of per-expressing clock cells in the cricket circadian clock12ENKenjiTomiokaGraduate School of Natural Science and Technology, Okayama UniversityShintaroInoueBio-Innovation Research Center, Tokushima UniversityTaroMitoBio-Innovation Research Center, Tokushima UniversityYoshiyukiMoriyamaDepartment of Natural Sciences, Kawasaki Medical SchoolTaishiYoshiiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityIn the present study, we generated crickets with knockout of either period (per) or timeless (tim) gene by CRISPR/Cas9-based genome editing. We also identified a naturally occurring per- mutant lacking a large coding region including PAS domains. To examine possible synergistic effects, a per- and timKO double mutant was generated by applying genome editing to the per- crickets. Under constant darkness (DD), timKO crickets exhibited a locomotor rhythm with a free-running period of 23.06 ± 0.20 h (mean ± SD), which was significantly shorter than that of the parental strain (23.78 ± 0.12 h). By contrast, perKO and per- crickets showed basically similar phenotype of locomotor rhythm: they exhibited an arrhythmic pattern during the first two to three weeks after transfer to DD but subsequently showed a complex rhythmic pattern with one or multiple components with significantly longer free-running periods (33.35 ± 10.72 h). In the per-;timKO double mutants, approximately 60% of individuals became arrhythmic, while the remaining 40% exhibited complex rhythms with extremely longer free-running periods (37.0 ± 9.17 h) under DD. These results suggest the existence of an underlying oscillatory mechanism that is responsible for regulating locomotor rhythms independently of the canonical per/tim feedback loop. Furthermore, we generated a reporter line on a per− background by knocking egfp into exon 1 of the per gene, allowing egfp expression to report per transcription. EGFP expression was detected in three distinct clusters of cells within the optic lobe: two located along the dorsal and ventral boundaries between the lamina and medulla neuropils, and one situated near the accessory medulla. These findings raise the possibility that these form part of the circadian clock network that governs circadian locomotor rhythms.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0960-741212732026AHG1–AFP interaction as a regulatory node in the ABA response during seed germinatione71081ENNoriyukiNishimuraInstitute of Agrobiological Sciences, National Agriculture and Food Research OrganizationShoUshiyamaInstitute of Plant Science and Resources, Okayama UniversityMasatoOtagiriInstitute of Plant Science and Resources, Okayama UniversityKoujiSatohInstitute of Agrobiological Sciences, National Agriculture and Food Research OrganizationNahomiSuzukiInstitute of Agrobiological Sciences, National Agriculture and Food Research OrganizationTomokoIrisaInstitute of Agrobiological Sciences, National Agriculture and Food Research OrganizationNobutakaMitsudaBiomanufacturing Process Research Center, National Institute of Advanced Industrial Science and TechnologyTaishiUmezawaGraduate School of Advanced Interdisciplinary Science, Tokyo University of Agriculture and TechnologyHidekiNishimuraInstitute of Plant Science and Resources, Okayama UniversityKeiichirouNemotoProteo-Science Center, PIAS, Ehime UniversityWataruTsuchiyaResearch Center for Advanced Analysis, National Agriculture and Food Research OrganizationRyoichiYanoResearch Center for Advanced Analysis, National Agriculture and Food Research OrganizationTatsuyaSawasakiProteo-Science Center, PIAS, Ehime UniversityToshimasaYamazakiResearch Center for Advanced Analysis National Agriculture and Food Research Organization Tsukuba Ibaraki 305‐8518 JapanTakashiHirayamaResearch Center for Advanced Analysis, National Agriculture and Food Research OrganizationSeed dormancy and germination are tightly regulated by complex signaling networks that integrate internal and external cues, including the endogenous phytohormone abscisic acid (ABA). ABA HYPERSENSITIVE GERMINATION 1 (AHG1), a group A type 2C protein phosphatase (PP2C), is thought to modulate the activity of transcription factors such as ABA INSENSITIVE 5 (ABI5) in seeds and during germination. AHG1 is regulated by DELAY OF GERMINATION 1 (DOG1), a key regulator of seed dormancy, through physical interaction. We previously reported that AHG1 also interacts with ABI FIVE BINDING PROTEIN 2 (AFP2), a member of the AFP family; however, the molecular basis of AHG1–AFP coordination has remained unclear. In this study, we show that AHG1 interacts with all AFP family members and that AFP3 binds AHG1 and ABI5 through adjacent but distinct amino acid residues within its C-domain, allowing simultaneous association with both proteins. In addition, AHG1 modulates the phosphorylation status of AFP3 at Ser60 in a DOG1-dependent manner, suggesting that DOG1–AHG1 regulates AFP3 post-translationally. Transcriptomic analyses of AHG1- or AFP3-overexpressing lines revealed that these factors are associated with the regulation of a shared set of ABA-responsive genes, including AFPs, and that AFP3 overexpression is predominantly associated with altered expression of genes involved in transcriptional regulation. Large-scale protein interaction analyses showed that AFPs interact with multiple classes of transcription factors, suggesting their involvement in diverse regulatory pathways, including ABA signaling. Together, these findings demonstrate that DOG1 regulates ABI5 function and modulates ABA responses, at least in part, by controlling AHG1-mediated dephosphorylation of AFPs.No potential conflict of interest relevant to this article was reported.AIP PublishingActa Medica Okayama0021-960616572026High-resolution analysis of the S1–S0 transition of magnesium phthalocyanine: Rotational structure and electronic angular momentum074308ENYukiMiyamotoResearch Institute for Interdisciplinary Science, Okayama UniversityKatsunariEnomotoDepartment of Physics, University of ToyamaKanaIwakuniInstitute for Laser Science, University of Electro-CommunicationsSusumuKumaDepartment of Physics, Rikkyo UniversityKoichi M. T.YamadaInstitute for Laser Science, University of Electro-CommunicationsWe report a high-resolution spectroscopic analysis of the S1–S0 transition of magnesium phthalocyanine (MgPc), obtained by probing buffer-gas-cooled molecules with a narrow-linewidth laser. The observed spectrum exhibits a characteristic three-peak pattern, which is well reproduced by modeling MgPc as an oblate symmetric top with D4h symmetry. A key result of this work is that the spectrum is strongly influenced by electronic Coriolis coupling, which is associated with electronic angular momentum. The electronic Coriolis constant is determined to be ∼2, indicating an effective orbital angular momentum of about 2 in the excited S1 state, originating from the π-conjugated ring excitation. This provides a direct spectroscopic signature of electronic angular momentum in a large polyatomic molecule. The presence of nonzero electronic orbital angular momentum is qualitatively consistent with the perimeter model of phthalocyanines. The value lies within the range inferred from previous magnetic circular dichroism (MCD) studies. Compared with the previous MCD estimate, the present analysis provides a more state-specific and narrower constraint, demonstrating that high-resolution spectroscopy enables direct access to electronic and magnetic properties beyond conventional structural characterization.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2077-038315132026Changing Trends in Cardiovascular Disease Burden in North Africa and the Middle East, 1990–2023: A Joinpoint Analysis of GBD 2023 Data4866ENHananeOuddoudDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityJudah Israel OngLescanoDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKeith PardilladaBelangoyDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYoshitoNishimuraDivision of Hematology and Oncology, Mayo ClinicKoHaradaDivision of Hematology and Oncology, Mayo ClinicHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalQuynh ThiVuDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityNaohiroIwataDepartment of Pharmacy, Okayama University HospitalTatsuakiTakedaDepartment of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama UniversityYoshitoZamamiDepartment of Pharmacy, Okayama University HospitalToshihiroKoyamaDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityBackground/Objectives: Cardiovascular disease (CVD) burden decreased in the North Africa and Middle East (NAME) region between 1990 and 2019. This study used Global Burden of Disease (GBD) 2023 data to examine whether trends in mortality, disability-adjusted life years (DALYs), incidence, and prevalence continued through 2023 across all 21 NAME countries. Methods: We analysed age-standardised CVD mortality, incidence, prevalence, and DALY rates from 1990 to 2023. Joinpoint regression identified changes in temporal trends and calculated the annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals (CIs). Results: Age-standardised CVD mortality decreased from 579.6 per 100,000 in 1990 to 358.2 in 2023 (AAPC: −1.42%; 95% CI: −1.48 to −1.35). However, no significant reduction occurred between 2019 and 2023 (APC: −0.33%; 95% CI: −1.37 to 1.75). DALY, incidence, and prevalence rates followed similar patterns, with no significant decline in the final years of this study. Egypt was the only country with a long-term increase in CVD mortality, which accelerated after 2020 (APC: +5.20%; 95% CI: 1.20 to 12.87). High systolic blood pressure, dietary risks, lead exposure, and air pollution were the leading modifiable risk factors. Conclusions: The earlier decline in CVD burden in the NAME region did not clearly continue after 2019. The region is currently off track to meet Sustainable Development Goal 3.4 by 2030. Future progress may depend on improved blood pressure control, lipid management, dietary habits, and environmental risk reduction.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2399-3642812025Structural insights into tRNA recognition of the human FTSJ1-THADA complex893ENKensukeIshiguroLaboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics ResearchAtsushiFujimuraDepartment of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMikakoShirouzuLaboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics ResearchtRNA undergoes various post-transcriptional modifications in the anticodon loop. FTSJ1, a protein conserved among most eukaryotes, mediates 2’-O-methylations at position 32 (Nm32) or position 34 (Nm34), complexed with THADA or WDR6, respectively. These methylations are crucial for accurate translation and cellular growth. FTSJ1 mutations are associated with non-syndromic X-linked intellectual disability. Although the structure of the FTSJ1-WDR6 complex in yeast has been solved, the structural details of the FTSJ1-THADA complex formation and substrate recognition remain unclear. Herein, using cryo-electron microscopy, we solve the high-resolution structure of FTSJ1-THADA with or without a tRNA substrate. FTSJ1 binds to THADA via its C-terminal region, with a unique interaction mode distinct from the FTSJ1-WDR6 complex. The tRNA substrate is anchored inside THADA, and key THADA residues for THADA-tRNA interaction are identified via structural and biochemical analyses. These findings demonstrate how FTSJ1 and THADA form a complex to mediate Nm32 modification in various tRNAs.No potential conflict of interest relevant to this article was reported.American Society of Clinical Oncology (ASCO)Acta Medica Okayama0732-183X43112025Trastuzumab-Pertuzumab Plus Eribulin or Taxane as First-Line Chemotherapy for Human Epidermal Growth Factor 2–Positive Locally Advanced/Metastatic Breast Cancer: The Randomized Noninferiority Phase III EMERALD Trial13021313ENToshinariYamashitaDepartment of Breast Surgery and Oncology, Kanagawa Cancer CenterShigehiraSajiDepartment of Medical Oncology, Fukushima Medical UniversityToshimiTakanoDepartment of Breast Medical Oncology, The Cancer Institute Hospital of JFCRYoichiNaitoDepartment of General Internal Medicine, National Cancer Center Hospital EastMichikoTsuneizumiDepartment of Breast Surgery, Shizuoka General HospitalAkiyoYoshimuraDepartment of Breast Oncology, Aichi Cancer Center HospitalMasatoTakahashiDepartment of Breast Surgery, Hokkaido University HospitalJunjiTsurutaniAdvanced Cancer Translational Research Institute, Showa UniversityTsuguoIwataniBreast and Endocrine Surgery, Okayama University HospitalMasahiroKitadaDepartment of Breast Disease Center, Asahikawa Medical University HospitalHiroshiTadaDepartment of Surgery, Division of Breast and Endocrine Surgery, Tohoku University HospitalNatsukoMoriDepartment of Breast Surgery, Seirei Hamamatsu General HospitalToruHiguchiDepartment of Breast Unit, Japanese Red Cross Saitama HospitalTsutomuIwasaDepartment of Medical Oncology, Kindai University HospitalKazuhiroArakiDepartment of Breast Medical Oncology, Gunma Prefectural Cancer CenterKeiKoizumiDepartment of Surgery 1, Division of Breast Surgery, Hamamatsu University School of MedicineHirokiHasegawaMedical HQs, Eisai Co, LtdYoheiUchidaMedical HQs, Eisai Co, LtdSatoshiMoritaDepartment of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto UniversityNorikazuMasudaDepartment of Breast Surgery, Graduate School of Medicine, Kyoto UniversityPurpose Trastuzumab-pertuzumab (HP) plus taxane is a current standard first-line therapy for recurrent or metastatic human epidermal growth factor 2 (HER2)+ breast cancer (BC). We investigated noninferiority of eribulin to a taxane when combined with dual HER2 blockade as first-line systemic treatment for locally advanced/metastatic HER2+ BC.<br>
Methods In the phase III EMERALD trial (target sample size, 480; ClinicalTrials.gov identifier: NCT03264547/UMIN000027938), patients were randomly assigned (1:1) to receive eribulin 1.4 mg/m2 once daily on days 1 and 8 (eribulin group) or a taxane (docetaxel 75 mg/m2 once on day 1 or paclitaxel 80 mg/m2 once daily on days 1, 8, and 15; taxane group) intravenously in a 21-day cycle, each with HP on day 1. The primary end point was progression-free survival (PFS; intention-to-treat population). Secondary end points included objective response rate, overall survival (OS), patient-reported quality of life (QoL), and safety. Noninferiority was tested using the stratified Cox proportional hazards model to estimate hazard ratios (HRs) for PFS events, with a noninferiority HR margin of 1.33.<br>
Results Between August 2017 and June 2021, 446 patients (median age, 56.0 years) were enrolled. The median PFS was 14.0 and 12.9 months in the eribulin group (n = 224) and taxane group (n = 222 [docetaxel/paclitaxel, n = 186/36]), respectively (HR, 0.95 [95% CI, 0.76 to 1.19]), which confirmed the noninferiority of the study regimen. The median OS was 65.3 months in the taxane group but has not been reached in the eribulin group. Median time to QoL deterioration was numerically longer with eribulin than with taxane. Adverse event (AE) rates were similar, despite the longer duration of eribulin use. Infusion reaction, skin-related AEs, diarrhea, and edema were more common with taxane, whereas neutropenia was more common with eribulin.<br>
Conclusion The results suggested that eribulin + HP is an option for first-line treatment of locally advanced/metastatic HER2+ BC.No potential conflict of interest relevant to this article was reported.AME Publishing CompanyActa Medica Okayama2304-38651352024Primary angiosarcoma of the breast: a literature review68ENYidanZhuDepartment of Breast Surgery, Liaoning Cancer Hospital & InstituteShogoNakamotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityTakahiroTsukiokiDepartment of Breast and Endocrine Surgery, Okayama University HospitalYukoTakahashiDepartment of Breast and Endocrine Surgery, Okayama University HospitalYokoIwataniDepartment of Breast and Endocrine Surgery, Okayama University HospitalTsuguoIwataniDepartment of Breast and Endocrine Surgery, Okayama University HospitalXinfengZhangDepartment of Breast Surgery, Liaoning Cancer Hospital & InstituteMakiTaniokaDepartment of Clinical AI Human Resources Development Program, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityTadahikoShienDepartment of Breast and Endocrine Surgery, Okayama University HospitalBackground and Objective: Primary angiosarcoma of the breast (PBA) is an extremely rare and heterogeneous disease. PBA is difficult to diagnose and has a poor prognosis. In order to better understand the disease and provide evidence-based treatment for PBA patients, a review of the published literature in the English language was conducted.<br>
Methods: A literature review in agreement with the PRISMA protocol was conducted. Medline and Cochrane databases were searched for English articles on PBA patients in September 2023 with a predetermined strategy. The articles were categorized and assessed based on hierarchical levels of scientific evidence.<br>
Key Content and Findings: A total of 255 articles were identified, among these 137 publications which included 1,888 patients met the criteria for inclusion in the final analysis. No prospective, randomized trials exclusive to PBA have been recognized. This article provides an overview of the most current and comprehensive evidence concerning the epidemiology, etiology, genomic features, clinical presentations, diagnosis, treatment, and prognosis of PBA.<br>
Conclusions: Despite the fact that current evidence is largely derived from retrospective studies, database analyses, and case reports, we utilized this information to tackle important clinical questions concerning optimal patient management practices for PBA. Complete surgical excision continues to be the mainstay treatment for PBA. However, the effectiveness of adjuvant therapies is still unclear. This narrative review highlights the urgent need for more rigorously designed research to enhance the management and treatment strategies for PBA.No potential conflict of interest relevant to this article was reported.Ovid Technologies (Wolters Kluwer Health)Acta Medica Okayama2226-71901332024Hormonal changes revealed by selective arterial calcium injection tests in patients with insulinoma treated with EUS–guided ethanol injection193195ENKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalMotoshiKomatsubaraDepartment of Endocrinology, Okayama City HospitalKenichiInagakiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHironariKatoDepartment of Gastroenterology and Hepatology, Okayama University HospitalMotoyukiOtukaDepartment of Gastroenterology and Hepatology, Okayama University HospitalNo potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1648-91446272026Diabetes Burden in the Middle East and North Africa Region, 1990–2023: An Ecological Time-Trend Analysis of GBD Estimates1352ENHananeOuddoudDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityJudah Israel OngLescanoDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKeith PardilladaBelangoyDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYoshitoNishimuraDivision of Hematology and Oncology, Mayo ClinicKoHaradaBrookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount SinaiHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalQuynh ThiVuFaculty of Pharmacy, Haiphong University of Medicine and PharmacyNaohiroIwataDepartment of Pharmacy, Okayama University HospitalTsukasaHigashionnaDepartment of Pharmacy, Okayama University HospitalTatsuakiTakedaDepartment of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama UniversityYoshitoZamamiDepartment of Pharmacy, Okayama University HospitalToshihiroKoyamaDepartment of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityBackground and Objectives: The Middle East and North Africa (MENA) region has one of the highest age-standardized diabetes prevalence rates globally, yet all-age, diabetes-specific evidence incorporating GBD 2023 estimates through 2023 remains limited. Materials and Methods: Using Global Burden of Disease (GBD) 2023 estimates for 21 MENA countries from 1990 to 2023, this ecological time-trend analysis quantified 33-year trends in incidence, prevalence, mortality, and disability-adjusted life-years (DALYs); compared pre-2019 and post-2019 trajectories using joinpoint regression; characterized age- and sex-specific burden patterns; and quantified contributions of modifiable risk factors. Results: Age-standardized incidence increased 92%, from 251.7 (95% uncertainty interval [UI]: 231.5 to 272.4) to 482.5 (95% UI: 451.5 to 516.4) per 100,000, and prevalence more than doubled, from 5564 (95% UI: 5088 to 6024) to 11,247 (95% UI: 10,382 to 12,132) per 100,000. In 2023, males exhibited higher DALY rates than females in most adult age groups from age 15 years onward, shifting away from the female-predominant pattern seen in 1990; female rates remained higher at several of the oldest age groups. Children aged 0 to 14 years were the only group with declining DALY rates (−52% to −57%). Post-2019 incidence was higher in 15 of 21 countries, and six countries had higher DALY trends with non-overlapping confidence intervals. Because we only have four to five years of data, these short trends are preliminary and require care when evaluating. High body-mass index was the leading modifiable risk factor. Conclusions: These data support country-specific prevention and chronic-care strategies across the MENA region.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2452-302X10102025Inhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-Induced Heart Failure Progression101308ENToshiomiKatsukiDepartment of Cardiology, Keio University School of MedicineDaiKusumotoDepartment of Cardiology, Keio University School of MedicineYoheiAkibaDepartment of Cardiology, Keio University School of MedicineMaiKimuraDepartment of Cardiology, Keio University School of MedicineJinKomuroDepartment of Cardiology, Keio University School of MedicineTakahiroNakamuraDepartment of Cardiology, Keio University School of MedicineHisayukiHashimotoDepartment of Cardiology, Keio University School of MedicineThukaaKoukaDepartment of Cardiology, Keio University School of MedicineKazuhisaSugaiInstitute for Integrated Sports Medicine, School of Medicine, Keio UniversityYoshinoriKatsumataDepartment of Cardiology, Keio University School of MedicineMasakiMiyasakaDepartment of Computational Biology and Medical Sciences, the University of TokyoYutakaSuzukiDepartment of Computational Biology and Medical Sciences, the University of TokyoJunkoKuramotoDepartment of Pathology, Keio University School of MedicineYoshiakiKubotaDepartment of Anatomy, Keio University School of MedicineKeiichiFukudaDepartment of Cardiology, Keio University School of MedicineShinsukeYuasaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasakiIedaDepartment of Cardiology, Keio University School of MedicineInappropriate endothelial cell (EC) interactions contribute to heart failure; however, their precise mechanisms remain poorly understood. This study investigated EC-fibroblast interactions mediated by Scarb1 using single-cell RNA-sequencing analysis in a mouse heart failure model. ECs exhibited inflammatory and fibrotic gene expression, with Scarb1-mediated fibroblast-EC interactions driving disease progression. EC-specific Scarb1 knockout and systemic SCARB1 inhibition attenuated heart failure progression. In vitro and spatial omics analyses confirmed the role of SCARB1 in ECs and cell-cell interaction during heart failure progression. These findings highlight SCARB1 as a promising therapeutic target for EC-focused interventions.No potential conflict of interest relevant to this article was reported.Copernicus GmbHActa Medica Okayama1816-34593522026An interdisciplinary approach to sampling hard rock cores of the oceanic crust for microbiological and biogeochemical research159169ENWilliam J.BrazeltonSchool of Biological Sciences, University of UtahOscarCavazosInternational Ocean Discovery Program, Texas A&M UniversityJordyn A.RobareSchool of Molecular Sciences, Arizona State UniversityGordonSouthamSchool of the Environment and Sustainable Minerals Institute, University of QueenslandJohannaSuhonenInternational Ocean Discovery Program, Texas A&M UniversityFengpingWangSchool of Oceanography, Shanghai Jiao Tong UniversitySusan Q.LangDept. of Geol. and Geophys., Woods Hole Oceanographic InstitutionAndrewMcCaigSchool of Earth and Environment, University of LeedsPeterBlumInternational Ocean Discovery Program, Texas A&M UniversityNatsueAbeJapan Agency for Marine-Earth Science and TechnologyRémiColtatISTO, UMR 7327, Univ. Orleans, CNRS, BRGM, OSUCJeremy R.DeansSchool of Biological, Environmental, and Earth Sciences, University of Southern MississippiKristin L.DickersonDept. of Earth and Planetary Sciences, University of CaliforniaMargueriteGodardGeosciences Montpellier, CNRS, University of MontpellierBarbara E.JohnDept. of Geology and Geophysics, University of Wyoming, LaramieFriederKleinDept. of Geol. and Geophys., Woods Hole Oceanographic Institution,RebeccaKuehnInstitute of Geosciences and Geography, Martin Luther University Halle-WittenbergKuan-YuLinElectron Microscopy Core Facility, Purdue UniversityC. JohanLissenbergSchool of Earth and Environmental Sciences, Cardiff UniversityHaiyangLiuCenter of Deep Sea Research, Institute of Oceanology, Chinese Academy of SciencesEthan L.LopesDept. of Geophysics, Stanford UniversityToshioNozakaDept. Earth Sciences, Okayama UniversityAndrew J.ParsonsSchool of Geography, Earth and Environmental Sciences, University of PlymouthVamdevPathakDept. Geology, Central University of PunjabMark K.ReaganDept. of Earth and Environmental Sciences, University of IowaC. GeoffreyWheatGlobal Undersea Research Unit, University of Alaska FairbanksStudying life in the deep, rocky subseafloor involves many layers of technological and methodological challenges, and each drilling project or expedition must make a series of choices to address these challenges. We report on the workflow for sampling hard rock cores for microbiological and biogeochemical research that was developed and optimized during International Ocean Discovery Program (IODP) Expedition 399. All steps of the workflow, including selection of the sample and its shipboard homogenization and subsampling for specific analyses, were designed to maximize the potential for interdisciplinary collaborations and syntheses of results. Furthermore, multiple strategies to minimize and detect potential microbial and organic chemical contamination of the core samples were employed, including the shipboard detection of a fluorescent chemical tracer pumped into the drill fluid. Contamination tracer levels were detectable on the exterior surfaces of the core but absent in the homogenized interiors of most core samples. Based on the experiences and preliminary results of this expedition, recommendations for processing samples on future expeditions are presented.No potential conflict of interest relevant to this article was reported.American Geophysical Union (AGU)Acta Medica Okayama2169-931313182026Effect of Fluorine on the Stability of Dense Hydrous Mg Silicates With Implications for the Deep Water Cyclee2025JB033593ENTakashiYoshinoInstitute for Planetary Materials, Okayama UniversityYunfanMiaoInstitute for Planetary Materials, Okayama UniversitySatheesh T.SajiInstitute for Planetary Materials, Okayama UniversityDaijoIkutaInstitute for Planetary Materials, Okayama UniversityNozomiKondoInstitute for Planetary Materials, Okayama UniversityTakayukiIshiiInstitute for Planetary Materials, Okayama UniversityXuejingHeGeochemical Research Center Graduate School of Science, The University of TokyoTsutomuOtaInstitute for Planetary Materials, Okayama UniversityTakuyaKunihiroInstitute for Planetary Materials, Okayama UniversityWater is believed to be transported, at least locally, into the Earth's deep mantle via hydrous minerals. Fluorine not only tends to interact with water but also influences the stability of hydrous minerals. Thus, knowledge of its stability could be important in understanding the deep-water cycle. In this study, we conducted high-pressure experiments to investigate the stability of dense hydrous Mg silicates in the presence of fluorine at pressures ranging from 9 to 23 GPa. In the presence of even small amounts of fluorine, clinohumite or phase E survives up to approximately 17 GPa, allowing it to exist without dehydration at temperatures by about 200°C higher than a fluorine-free system. At pressures above 18 GPa, superhydrous phase B stabilizes as a major fluorine host. Fluorine partitions very little into phase D, leaving its stability field unchanged, but the stability field of superhydrous phase B extends to temperatures above 1400°C, thereby enabling the hydrous phase in the dragged wedge mantle just above the slab to have transport potential into the lower mantle.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8042026Spinous Process Plate Fixation Alone for an AO Spine Osteoporotic Fracture (OF) 5 Diffuse Idiopathic Skeletal Hyperostosis (DISH)-Associated Thoracolumbar Fracture in a Nonagenarian259264ENSatoruYabunoDepartment of Neurosurgery, Kagawa Rosai HospitalMasatoshiYunokiDepartment of Neurosurgery, Kagawa Rosai HospitalSaoriTakeuchiDepartment of Neurosurgery, Kagawa Rosai HospitalKojiHirashitaDepartment of Neurosurgery, Kagawa Rosai HospitalCase Report10.18926/AMO/71070Diffuse idiopathic skeletal hyperostosis (DISH) predisposes the spine to highly unstable fractures because of long lever-arm biomechanics. Unstable injuries, including AO Spine Osteoporotic Fracture (OF) type 5, are typically treated with long-segment posterior instrumentation; however, pedicle-screw fixation may be infeasible in very elderly patients with severe osteoporosis, critically narrow pedicles, and/or significant comorbidities. A 93-year-old Japanese woman presented with severe back pain without apparent trauma. Computed tomography (CT) revealed a T12 fracture with DISH, classified as OF5. The pedicles were critically narrow (3.7-4.1 mm), and dual-energy X-ray absorptiometry confirmed severe osteoporosis. Because conventional pedicle-screw fixation was considered technically unsafe and excessively invasive, limited posterior stabilization was performed using a single spinous process plate spanning T10-L1. The operative time was 48 min and the estimated blood loss was 10 ml. Immediate postoperative CT confirmed appropriate implant positioning and maintained alignment. At the 1-year follow-up, CT demonstrated solid bony union with preserved alignment and no implant failure; the patient had remained pain-free and ambulatory. This case demonstrates that spinous process-plate fixation can be a minimally invasive salvage option for carefully selected very-elderly patients with DISH when pedicle-screw instrumentation is not feasible.No potential conflict of interest relevant to this article was reported.American Geophysical Union (AGU)Acta Medica Okayama2169-931313182026Spin Transition of Ferric Iron in Silicate Glasses Inferred by High‐Pressure Electrical Conductivity Measurementse2026JB034225ENIzumiMashinoInstitute for Planetary Materials, Okayama UniversityTakashiYoshinoInstitute for Planetary Materials, Okayama UniversityShinjiKitaoInstitute for Integrated Radiation and Nuclear Science, Kyoto UniversityTakayaMitsuiSynchrotron Radiation Research Center, Kansai Photon Science Institute, Quantum Beam Science Research Directorate, National Institutes for Quantum Science and TechnologyRyoMasudaGraduate School of Science and Technology, Hirosaki UniversityMakotoSetoInstitute for Integrated Radiation and Nuclear Science, Kyoto UniversitySilicate melt has been proposed to exist near the base of the mantle and has been invoked to explain seismic and electrical conductivity anomalies observed near the core-mantle boundary; however, its presence and stability under lowermost-mantle conditions remain uncertain. Here we report high-pressure electrical conductivity measurements of Fe2+- and Fe3+-bearing pyroxene glasses (Fe3+/ΣFe ≈ 0.5), used as analogs of silicate melts, up to megabar pressures at room temperature. At lower pressures, conductivity increases with pressure and iron content, consistent with electron-hole hopping between Fe2+ and Fe3+. Above 77–85 GPa, all samples show a marked conductivity decrease, suggesting a pressure-induced spin transition of Fe3+. Previous studies have suggested that lower-mantle silicate melts may be enriched in Fe3+, and iron spin-state changes may modify iron partitioning between silicate melts and coexisting crystalline phases. Therefore, the Fe3+ spin transition inferred here may affect the evolution of deep-mantle melts through pressure-dependent changes in iron partitioning behavior.No potential conflict of interest relevant to this article was reported.BMJActa Medica Okayama0022-25932026Updated ENIGMA recommendations for reporting germline variants in cancer susceptibility genes and their translation into twenty languagesENArcangelaDe NicoloDepartment of Experimental Oncology, Unit of Predictive Medicine: Molecular Bases of Genetic Risk, Fondazione IRCCS Istituto Nazionale dei TumoriDiana MEcclesFaculty of Medicine, University of SouthamptonKirsimariAaltonenDuodecim Medical Publications LtdPiaAlhopuroHUS Diagnostic Center, Laboratory of Genetics, Helsinki University Hospital and University of HelsinkiSarah LouiseAriansenDepartment of Medical Genetics, Oslo University HospitalMichelaBiancolellaDepartment of Biology, University of Rome Tor VergataSandrine MCaputoDepartment of Genetics, Institut CurieOlivierCaronDépartement de Médecine Oncologique, Gustave RoussyPietroCavalliMedical Genetics, IRCCS Humanitas Research HospitalJianbangChiangDivision of Medical Oncology, Cancer Genetics Service, National Cancer Centre SingaporeKathleen B MClaesCenter for Medical Genetics, Ghent University HospitalEdgar Christian SCuaresmaSt. Luke’s Medical CenterMiguelde la HoyaHospital Clínico San Carlos, Molecular Oncology Laboratory, Instituto de Investigación Sanitaria del Hospital Clínico San CarlosAntoineDe PauwDepartment of Genetics, Institut CurieOrlandDíezVall d’Hebron Hospital Universitari, Area of Clinical and Molecular Genetics, Vall d’Hebron Barcelona Hospital CampusMevDomínguez-ValentinInstitute of Cancer Research, Department of Tumor Biology, The Norwegian Radium HospitalHansEhrencronaDepartment of Clinical Genetics, Pathology and Molecular Diagnostics, Skåne University HospitalMagnhild KFjeldværDepartment of Medical Genetics, Oslo University HospitalFlorentiaFostiraINRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-DemokritosMarie Belle DFranciaSt. Luke’s Medical CenterJavierGalego-CarroFundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de CompostelaEncarna BGómez GarcíaDepartment of Clinical Genetics, Maastricht University Medical CentreNur TiaraHassanCancer Research MalaysiaJanHaukeFaculty of Medicine and Center for Familial Breast and Ovarian Cancer, University of Cologne, University Hospital CologneAkiraHirasawaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of Clinical Genomic Medicine, Okayama UniversityXinHuangDepartment of Breast Surgery, Peking Union Medical College HospitalElaine Marisse HIlagan-CargulloSt. Luke’s Medical CenterIsseiImotoAichi Cancer Center Research InstituteSowmyaJonnagadlaDivision of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore, SiManasadeviKarthikeyanDivision of Medical Oncology, Cancer Genetics Service, National Cancer Centre SingaporePetraKleiblovaInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in PragueIreneKonstantopoulouINRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-DemokritosArturKowalikDepartment of Molecular Diagnostics, Holy Cross Cancer CentreAndersKvistDepartment of Clinical Sciences Lund, Division of Oncology, Lund UniversityFabienneLesueurPSL Research UniversityShao-TzuLiDivision of Medical Oncology, Cancer Genetics Service, National Cancer Centre SingaporeAdriàLópez-FernándezHereditary Cancer Genetics Group, Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebron Institute of Oncology (VHIO)EvaMachackovaCenter for Medical Genetics, Masaryk Memorial Cancer InstituteAlexandraMartinsUniv Rouen Normandie, Inserm U1245Arjen RMensenkampDepartment of Human Genetics, Radboud University Medical CenterYukihideMomozawaLaboratory for Genotyping Development, RIKEN Center for Integrative Medical SciencesGemmaMontalbanDepartment of Oncogenetics, MRC HollandAlvaro N AMonteiroDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research InstituteHeliNevanlinnaHUS Diagnostic Center, Laboratory of Genetics, Helsinki University Hospital and University of HelsinkiJoanneNgeowDivision of Medical Oncology, Cancer Genetics Service, National Cancer Centre SingaporeEdenir InezPalmeroMolecular Oncology Research Center, Barretos Cancer HospitalInge SokildePedersenMolecular Diagnostics and Clinical Cancer Research Centre, Aalborg University HospitalFrances Victoria FQueSt. Luke’s Medical CenterMartaSantamariñaFundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de CompostelaElizabethSantana dos SantosDepartment of Medical Oncology, A.C. Camargo Cancer CenterChristian FSingerComprehensive Cancer Center, Department of Obstetrics and Gynecology, Medical University of ViennaMonikaSiołekGenetic Clinic, Holy Cross Cancer CentreAngela RSolanoDepartmento de Analisis Clinicos, Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" (CEMIC)JanaSoukupovaInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in PraguePriyadharshini d/oSureshDivision of Medical Oncology, Cancer Genetics Service, National Cancer Centre SingaporeMagdalenaSzczepaniakDepartment of Molecular Diagnostics, Holy Cross Cancer CentreYen YTanComprehensive Cancer Center, Department of Obstetrics and Gynecology, Medical University of ViennaSoo HwangTeoCancer Research MalaysiaEmmaThamDepartment of Clinical Genetics and Genomics, Karolinska University HospitalMadsThomassenDepartment of Clinical Genetics, Odense University HospitalGeorgiosTsaousisGenekor Medical S.AThomas van OvereemHansenDepartment of Clinical Genetics, Copenhagen University Hospital RigshospitaletAnaVegaFundación Pública Galega de Medicina Xenómica and Instituto de Investigación Sanitaria de Santiago de CompostelaEladio AVelasco-SampedroInstituto de Biología y Genética Molecular, Splicing and Genetic Susceptibility to Cancer, Consejo Superior de Investigaciones Científicas - Universidad de Valladolid (CSIC-UVa)TeresiaWangensteenDepartment of Medical Genetics, Oslo University HospitalBarbaraWappenschmidtFaculty of Medicine and Center for Familial Breast and Ovarian Cancer, University of Cologne, University Hospital CologneDrakoulisYannoukakosINRASTES, Human Molecular Genetics Laboratory, National Centre for Scientific Research-DemokritosSook-YeeYoonCancer Research MalaysiaAmanda BSpurdlePopulation Health Program, QIMR Berghofer Medical Research InstitutePaoloRadiceDepartment of Experimental Oncology, Unit of Predictive Medicine: Molecular Bases of Genetic Risk, Fondazione IRCCS Istituto Nazionale dei TumoriGenetic testing for cancer susceptibility underpins precision cancer prevention and care. Gaps in the healthcare providers’ genetic literacy and an ambiguous lexicon for variant description may hinder proper delivery and clinical application of consistently trustworthy test results. The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) international consortium supports controlled terminology and recommends a framework for reporting germline variants in cancer susceptibility genes, using breast cancer as an exemplar. Moving forward towards terminological coherence across disciplines and borders, the ENIGMA Clinical Working Group launched a multinational effort to release consortium-approved translations of the published recommendations. The herein reported Vocabulary Translation Project offered an opportunity to reappraise and align the reference text to the recent BRCA1 and BRCA2 specifications to the American College of Medical Genetics and Genomics/Association for Molecular Pathology rules by the ENIGMA Variant Curation Expert Panel and to highlight country-specific differences in breast cancer risk assessment and management. The updated recommendations and their 20 translations are now provided as easy to handle documents, covering 11 of the most widely spoken languages in the world. They will contribute to minimised erroneous inferences, more informed decision-making, improved health outcomes and equity in the use of genetic testing for cancer predisposition and in translational oncology.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2662-9984712026Diversity of hymenopteran assemblages prevailed during reproductive stage of cotton―implications for natural control1039ENMd MizanurRahmanInsect Biotechnology and Biopesticide Laboratory, Department of Entomology, Bangladesh Agricultural UniversityTohruHayakawaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMohammad Tofazzal HossainHowladerInsect Biotechnology and Biopesticide Laboratory, Department of Entomology, Bangladesh Agricultural UniversityHymenoptera is one of the most important insect orders contributes to pollination, biocontrol and natural control largely unexplored from Bangladesh. We, therefore, assess the diversity and relative abundance of hymenopteran insects in cotton fields from five locations of Bangladesh using five types of traps (Malaise, Yellow Pan, Fluorescent Yellow Pan, Pitfall, and Sweep Net). Analysis of samples revealed presence of diverse type of hymenopteran insects from the studied locations, with a total of 1642 insects collected, representing 28 morphospecies and 16 families of the Hymenoptera. Formicidae, Braconidae, Diapridae, Figitidae, Ichneumonidae, Scelionidae constitutes the major families comprises of 36.37, 25.09, 5.36, 5.24, 5.18 and 4.93% of the populations respectively. Among the locations, cotton fields of Rangpur showed the highest species richness, diversity indices (Simpson, and Shannon values), while cotton fields located at Jashore had the lowest. Yellow and fluorescent pan traps captured insects from nearly all families, indicating broad sampling effectiveness. Malaise traps also sampled a wide range of families except for low captures of Formicidae. Pitfall traps primarily targeted Formicidae, consistent with their ground-dwelling hymenopterans. Sweep nets captured fewer families, reflecting a more selective sampling role. Among functional guilds, parasitoids were the most abundant, followed by predators, pollinators, and herbivores of hymenopteran insects. Overall, the hymenopteran community in cotton agroecosystems from Bangladesh was dominated by parasitoid families, indicating strong potential for natural biological control. Leveraging this natural enemy dominance could significantly reduce dependence on chemical insecticides. These findings support the integration of parasitoid conservation strategies into national Integrated Pest Management (IPM) programs and landscape-level pest management policies.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0275-5319912026Does ESG performance enhance investment efficiency and firm performance? Evidence from Japan103582ENYusraNazirGraduate School of Humanities and Social Sciences, Okayama UniversityXiaojingCaiGraduate School of Humanities and Social Sciences, Okayama UniversityTatsumasaTennojiyaGraduate School of Humanities and Social Sciences, Okayama UniversityThis study examines the association between investment sensitivity to growth opportunities, firm performance, and environmental, social, and governance (ESG) performance in Japanese listed firms. To determine whether ESG performance is associated with a firm’s investment sensitivity to growth opportunities rather than directly increasing investment levels, panel data covering the period from 2002 to 2023 and an investment-Q sensitivity framework are employed. To evaluate robustness and reduce endogeneity issues, high-dimensional fixed effects (HDFE), the System Generalized Method of Moments (GMM), and a difference-in-differences (DID) design based on Japan’s post-2015 governance and disclosure environment are added to the baseline fixed-effects estimations. The findings show a positive association between investment-Q sensitivity and ESG performance, indicating a conditional association wherein firms with higher ESG performance are more receptive to expansion prospects. The findings, however, contradict the hypothesis that ESG performance and investment intensity are consistently associated. Stricter identification techniques diminish positive baseline associations, demonstrating sensitivity to model specification and cross-sectional firm variations. As a result, firm performance results are mixed. Governance-related factors are comparatively more consistently associated with investment outcomes across all ESG components. By focusing on ESG performance and capital allocation behavior under various economic scenarios rather than on whether ESG generally enhances firm outcomes, this study expands the ESG literature. The results imply that ESG serves more as a governance and information mechanism associated with investment sensitivity than as a reliable indicator of firm performance or investment efficiency.No potential conflict of interest relevant to this article was reported.American Society for Horticultural ScienceActa Medica Okayama0018-53456192026Stomatal Traits in Strawberry Cultivars: Variation among Plant Parts and Associations with Growth and Yield19881991ENMinoriHikawa-EndoOkayama University, Graduate School of Environmental, Life, Natural Science and TechnologyRyosukeYamanakaWestern Region Agricultural Research Center, NAROTakayoshiYanoWestern Region Agricultural Research Center, NAROStomatal traits are important determinants of photosynthesis and water use; however, their variation among plant parts and cultivars and their relationships with growth and yield in strawberry remain unclear. This study characterized stomatal density and guard cell length among plant parts and across 34 cultivars and examined their associations with growth and yield. Stomata were found not only on the abaxial leaf surface but also on petioles and calyces and occasionally on the adaxial surface of leaves. Both traits varied widely among cultivars and decreased between November and May. Stomatal density was significantly negatively correlated with plant height, estimated leaf area, and total yield in both seasons, whereas guard cell length showed no significant association with these traits. These results suggest that stomatal density may be a more relevant indicator of growth and yield in strawberries and that characterizing stomatal traits across plant parts and cultivars may support breeding and cultivation research.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama0449-30606742026Enhancement of antioxidant function in various organs in mice using combined thermal and radon inhalation treatment538549ENShogoMiyanagaGraduate School of Health Sciences, Okayama UniversityAyumiTanakaGraduate School of Health Sciences, Okayama UniversityReijuTakenakaGraduate School of Health Sciences, Okayama UniversityShotaNaoeNingyo-toge Environmental Engineering Center, Japan Atomic Energy AgencyShunaGotoGraduate School of Health Sciences, Okayama UniversityMitsukiNaganoGraduate School of Health Sciences, Okayama UniversityKotaroTanoGraduate School of Health Sciences, Okayama UniversityNorieKanzakiNingyo-toge Environmental Engineering Center, Japan Atomic Energy AgencyAkihiroSakodaNingyo-toge Environmental Engineering Center, Japan Atomic Energy AgencyKiyonoriYamaokaFaculty of Health Sciences, Okayama UniversityTakahiroKataokaFaculty of Health Sciences, Okayama UniversityEnhancing antioxidant function is a key strategy for preventing and treating oxidative stress-related diseases. Radon inhalation and thermal treatment (TT) increase the levels of antioxidant enzymes, such as superoxide dismutase (SOD). The positive effects of this combination on pain-related diseases have been reported; however, few studies have elucidated the underlying mechanisms. In this study, we examined the enhancement of antioxidant function in various organs of mice subjected to combined TT and radon inhalation. The mice were placed in an incubator once daily for 40 min at 38.5 ± 0.5°C and treated for 1, 3 and 7 days. The mice then inhaled radon at a concentration of 2000 Bq/m3 for 24 h. The characteristic changes in antioxidant function following combined TT and radon inhalation could be categorized into four groups: (i) increased antioxidant function in the brain and colon; (ii) increased or decreased antioxidant function, as observed in the kidney; (iii) decreased antioxidant function, such as in the lungs and (iv) no changes, such as in the small intestine, spleen, pancreas, heart, liver and stomach. Additionally, SOD may be the antioxidant enzyme most sensitive to combined TT and radon treatment. Collectively, the combined treatment may be the most effective in activating antioxidative functions in the brain and colon. This study provides new insights into the effects of combined TT and radon inhalation.No potential conflict of interest relevant to this article was reported.Japanese Society for Lymphoreticular Tissue ResearchActa Medica Okayama1346-42806622026RHOA G17V mutation analysis redirecting diagnosis: nodal T-follicular helper cell lymphoma with classic Hodgkin lymphoma feature122129ENRioYamadaDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesMidori FilizNishimuraDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesAsamiNishikoriDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesTakuyaFukumiDepartment of Hematology, Okayama City HospitalKumikoOhsawaDepartment of Pathology, Saitama Medical Center, Saitama Medical UniversityShujiMomoseDepartment of Pathology, Saitama Medical Center, Saitama Medical UniversityYasuharuSatoDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesNodal T-follicular helper cell lymphoma (nTFHL) may present with Hodgkin/Reed–Sternberg (HRS)-like cells and can morphologically mimic classic Hodgkin lymphoma (CHL), although these entities are usually distinguishable. We report an unusual case showing marked morphologic and molecular overlap with CHL, creating a diagnostic challenge but ultimately considered biologically consistent with nTFHL.<br>
An 81-year-old woman presented with stage IV disease involving the bone marrow and markedly elevated serum soluble interleukin-2 receptor levels. Excisional lymph node biopsy revealed scattered HRS cells in a T-cell–rich background, with strong CD30 and PD-L1 expression and weak PAX5 positivity, findings consistent with CHL. Fluorescence in situ hybridization demonstrated copy-number alterations at the 9p24.1 locus in HRS cells, further supporting molecular features characteristic of CHL.<br>
However, the presence of two T-follicular helper markers, detection of the RHOA p.Gly17Val (G17V) mutation, and oligoclonal T-cell receptor rearrangements with shared peaks in lymph node and bone marrow indicated an underlying nTFHL. The differential therapeutic response also supported a diagnosis of nTFHL, which could not have been established on morphology alone.<br>
In this case, although the HRS cells displayed morphological, immunophenotypic, and molecular features highly suggestive of CHL, the biological nature of the lesion was consistent with nTFHL. Compared with previously reported cases of nTFHL with HRS-like cells, this case more closely resembled CHL and may represent a distinct subset best described as “nTFHL with CHL features,” a concept warranting greater recognition among pathologists and clinicians.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841732025Cholecystectomy Is Linked to Worse Clinical Outcomes in Primary Sclerosing Cholangitise80184ENNozomiMiyakeDepartment of Gastroenterology and Hepatology, Okayama UniversityKengoYasugiDepartment of Gastroenterology and Hepatology, Okayama UniversityAkinobuTakakiDepartment of Gastroenterology and Hepatology, Okayama UniversityKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama UniversityRecent findings have suggested that gallbladder-derived retinoic acid signaling plays a crucial role in the regeneration of damaged intrahepatic biliary ducts. This retrospective cohort study analyzed the clinical records of 20 patients with primary sclerosing cholangitis (PSC) treated at our hospital between 2013 and 2024. We investigated the clinical implications of gallbladder removal in patients with PSC, a progressive cholangiopathy with limited therapeutic options. We retrospectively analyzed the data of patients with PSC and compared patients with and without prior cholecystectomy to assess the impact on disease progression using the Mayo risk score, Fibrosis-4 (FIB4) index, and other clinical parameters. Our findings indicated that cholecystectomy was associated with worse Mayo risk scores (p = 0.0004) and an elevated FIB4 index (p = 0.021), suggesting a potential link between gallbladder removal and accelerated disease progression. Furthermore, mortality and transplant-free survival analysis revealed significantly worse outcomes in the cholecystectomy group (odds ratio = 21.0, p = 0.032). However, given the retrospective nature and small sample size of this study, selection bias cannot be excluded, and further research is needed to confirm these findings. These findings support the hypothesis that gallbladder-derived factors, such as retinoic acid, may influence PSC progression and highlight the need for further research into therapeutic interventions targeting this pathway.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1526-99142772026Potential of quantitative X‐ray imaging from photon‐counting CT: A novel analysis based on effective atomic number and physical densitye70673ENTakashiAsaharaDepartment of Radiological Technology, Faculty of Health Sciences, Okayama UniversityRinaNishigamiGraduate School of Medical Sciences, Kanazawa UniversityNatsumiKimotoDepartment of Radiological Science, Faculty of Health Sciences, Junshin Gakuen UniversityManaMitaniDivision of Radiological Technology, Medical Support Department, Okayama University HospitalYusukeMorimitsuDivision of Radiological Technology, Medical Support Department, Okayama University HospitalNoriakiAkagiDivision of Radiological Technology, Medical Support Department, Okayama University HospitalFumiyoHigakiDepartment of Radiology, Medical Development Field, Okayama UniversityToshihiroIguchiDepartment of Radiological Technology, Faculty of Health Sciences, Okayama UniversityTakaoHirakiDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroakiHayashiCollege of Transdisciplinary Sciences for Innovation Kanazawa University Kanazawa Ishikawa JapanBackground: Conventional CT assessment of lung lesions is based mainly on morphological features. CT values represent relative X-ray attenuation that does not directly reflect tissue composition and/or physical density. Quantitative imaging using photon-counting CT (PC-CT) has the potential to provide quantitative parameters, such as effective atomic number (Zeff) and effective physical density (ρeff).<br>
Purpose: The purpose is to develop and demonstrate the potential of an algorithm that generates both the Zeff and ρeff images, derived directly from virtual monoenergetic images (VMIs) acquired with a clinical PC-CT system.<br>
Methods: The ρeff image was generated by fitting a database of mass attenuation coefficients (μ/ρ) to the measured linear attenuation coefficients (μ), which were obtained from two VMIs at 70 and 100 keV. As an effective material, Zeff information was also determined and fed back into the ρeff calculation. An in-house low-density phantom was scanned for quantitative evaluation of ρeff. In addition, to demonstrate the applicability of our procedure to actual clinical imaging, representative chest PC-CT images from patients were analyzed.<br>
Results: In experiments using low-density phantoms, the CT values did not necessarily correlate with Zeff values, but they showed a very good correlation with the ρeff values. The ρeff values calculated using our procedure correlated well with the correct values of ρ. A relative root mean square error of ρeff calculation was 5.5%. Furthermore, we found that in pulmonary diagnosis, image contrast information from ρeff makes it easier to identify and distinguish lesions compared to that from Zeff.<br>
Conclusions: The proposed procedure directly generated Zeff and ρeff images from PC-CT data and enabled quantitative interpretation of CT value in terms of elemental composition and physical density. In this study, the feasibility of generating Zeff and ρeff images was demonstrated.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0021-925830282026Proton pump rhodopsins for optogenetic manipulation of biological activities and beyond113318ENKeiichiKojimaFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMiyuInokuchiGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiSudoFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityWater (H2O), the principal component of living organisms including humans, dissociates into H+ and OH- in aqueous environments, and the resulting H+ concentration determines both cellular pH and the proton motive force (PMF) across cellular membranes. These physicochemical parameters are fundamental regulators of a wide range of biological processes. Optogenetics enables the manipulation of biological and cellular functions using light, typically through the ectopic expression of microbial rhodopsins as photoreceptive proteins in target cells or organs. This review provides a comprehensive overview of optogenetic studies employing H+ pump rhodopsins in diverse biological systems and highlights their growing relevance to neuroscience, cell biology, bioengineering, and therapeutic research. Notably, optical control of H+ concentration allows the precise modulation of neural and non-neural activities in animals and bacteria, highlighting the broad applicability and significant potential of H+ pump rhodopsins for optogenetics. Based on previous and current studies, we discuss how further expansion of the molecular toolkit of H+ pump rhodopsins could enable increasingly fine-tuned manipulation of intracellular pH dynamics and PMF for probing cellular physiology and designing next-generation therapeutic strategies and consider emerging directions that extend beyond classical optogenetics toward the optical control of bioenergetic and chemical processes.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0305-18465242026Frontotemporal Lobar Degeneration‐TDP Type C With Striatal Glial Cytoplasmic Inclusions and Motor Neuron Degeneratione70090ENAkikoUchinoDepartment of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of GerontologyKazutomiKanemaruDepartment of Neurology, Tokyo Metropolitan Geriatric Hospital and Institute of GerontologyAiriTarutaniDepartment of Clinical Medical Sciences, Tokyo Metropolitan Institute of Medical ScienceMasatoHasegawaDepartment of Clinical Medical Sciences, Tokyo Metropolitan Institute of Medical ScienceHiroyaNaruseDepartment of Neurology, Graduate School of Medicine, The University of TokyoHiroyukiIshiuraDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShigeoMurayamaDepartment of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of GerontologyYukoSaitoDepartment of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of GerontologyNo potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0168-01022292026Enhanced calcium activity and transcriptomic alterations in iPSC-derived neurons from BAFME patients with repeat expansions105080ENYukiNagasakoDepartment of Neurology, Graduate School of Medicine, The University of TokyoMitsuruIshikawaDepartment of Physiology, Keio University School of MedicineHiroyukiIshiuraDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSopakSupakulDepartment of Physiology, Keio University School of MedicineSumihiroMaedaDepartment of Physiology, Keio University School of MedicineTatsushiTodaDepartment of Neurology, Graduate School of Medicine, The University of TokyoShojiTsujiDepartment of Neurology, Graduate School of Medicine, The University of TokyoHideyukiOkanoDepartment of Physiology, Keio University School of MedicineBenign adult familial myoclonus epilepsy (BAFME) is caused by intronic TTTCA and TTTTA repeat expansions in SAMD12 and other genes; the neuronal basis of cortical hyperexcitability, however, remains unclear. We generated induced pluripotent stem cell (iPSC)-derived glutamatergic and GABAergic neurons from three BAFME1 patients and examined functional and transcriptomic phenotypes. Patient-derived neurons retained the pathogenic repeat expansions and showed a tendency toward upstream intronic RNA accumulation. Calcium imaging revealed increased spontaneous Ca2 + transient frequency in both neuronal subtypes, indicating heightened activity. Pharmacological profiling demonstrated attenuated responses to calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor (CP-AMPAR) blockade and GABAA receptor antagonism in GABAergic neurons, suggesting altered inhibitory signaling. RNA sequencing revealed transcriptomic alterations without differential expression of ion channels and neurotransmitter receptors. In glutamatergic neurons, ATF4-regulated genes, including SLC7A5 encoding LAT1, a Kv1.2 channel modulator, were downregulated. Reduced SLC7A5 expression was validated at both mRNA and protein levels. In GABAergic neurons, synapse-associated genes PTPRD and GPC6 were upregulated. TCERG1L and NLRP2 were suppressed across both neuronal subtypes. These findings suggest subtype-specific alterations may contribute to neuronal hyperexcitability in BAFME and provide a platform for mechanistic studies of repeat expansion-associated epilepsies.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2076-26071472026Upregulation of the Outer Membrane Protein OmpV and Its Role in Polymyxin B Stress Adaptation in Vibrio mimicus1527ENShin-ichiMiyoshiGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYutaOnoderaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShunkiAnnoiGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBasilua AndreMuzemboResearch Center for Intestinal Health Science, Okayama UniversityDaisukeImamuraResearch Institute of Nursing Care for People and Community, University of HyogoOmpV is an outer membrane protein found in a variety of Gram-negative bacteria. In this study, we demonstrated that V. mimicus strain CS-66, isolated from a patient with diarrhea, was resistant to polymyxin B (PL-B) and colistin (CL) but susceptible to chloramphenicol and ciprofloxacin. When strain CS-66 was cultured in Luria–Bertani broth containing a sub-minimal inhibitory concentration of each antibiotic used for the susceptibility tests, ompV expression as assayed by reverse transcription-qPCR, significantly increased regardless of the antibiotic tested. In contrast, cell aggregation during the early log phase was observed only when the strain was grown in the broth supplemented with PL-B or CL. A space-filling model of V. mimicus OmpV was generated. The model showed that, although OmpV adopted a β-barrel conformation, it had closed top and bottom ends and possessed a lateral cavity. Structural analysis further indicated that the interior of this lateral cavity was negatively charged and sufficiently large to accommodate PL-B. These results suggest that V. mimicus may adapt to PL-B stress through physical sequestration within the negatively charged cavity of OmpV.No potential conflict of interest relevant to this article was reported.American Society for Horticultural ScienceActa Medica Okayama1063-01983652026Effects of Transplanting Date and Photoperiod on Flowering of Everbearing Strawberries789797ENMinoriHikawa-EndoOkayama University, Graduate School of Environmental, Life, Natural Science and TechnologyRyosukeYamanakaWestern Region Agricultural Research Center, NAROTakayoshiYanoWestern Region Agricultural Research Center, NAROEverbearing strawberries have the potential to produce fruit year-round if transplanted early. However, temperature and plant physiological status limit the continuous flowering. Herein, we aimed to investigate whether promoting flowering through long-day phototreatment enables earlier transplanting. The interaction between transplanting date and photoperiod in two everbearing strawberry cultivars was examined. In the 04 cultivar, which exhibited strong everbearing characteristics, rapid and continuous flowering occurred largely independent of long-day treatment, and early transplanting alone increased inflorescence number and early yield. However, excessive flowering was associated with reduced average fruit weight, soluble solid concentration, and firmness. Conversely, in Yotsuboshi, a cultivar with weak everbearing characteristics, earlier transplanting combined with extended photoperiods advanced the emergence of the first and second inflorescences. However, gains in total early yield were small, and the average fruit weight decreased compared with that in the control, indicating physiological stress. Across the cultivars, earlier inflorescence emergence was negatively correlated with days to flowering and positively associated with cumulative yield. For practical applications, cultivars with strong everbearing characteristics can be managed with early transplanting and minimal long-day supplementation to ensure early production. In contrast, cultivars with weak everbearing characteristics require extended photoperiods following early transplanting along with stress-mitigation strategies to maintain fruit size and quality.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0022-17595412025Development of a novel histidine-rich glycoprotein measurement system as a biomarker for sepsis113868ENTakaokiUchiumiDiagnostic Drug Office, Shionogi & Co., Ltd.MasahiroNishiboriDepartment of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMorimatsuDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYokoInoueDiagnostic Drug Office, Shionogi & Co., Ltd.HiroshiNishiDiagnostic Drug Office, Shionogi & Co., Ltd.NorioOtaDiagnostic Drug Office, Shionogi & Co., Ltd.The plasma histidine-rich glycoprotein concentration is a marker of sepsis severity. In this study, we generated selective and specific monoclonal antibodies against histidine-rich glycoprotein for use in a prototype enzyme-linked immunosorbent assay-based in vitro diagnostic system. First, we investigated the properties of monoclonal antibodies produced by 21 hybridomas that we developed using immunized mice, and we identified monoclonal antibodies 69-1A and 75-2D to be the most suitable combination for use in the sandwich enzyme-linked immunosorbent assay. Wild-type histidine-rich glycoprotein (Form-1, 75 kDa) with a proline residue at amino acid position 204 is the most common isoform of the protein in humans, followed by its variant (Form-2, 77 kDa), which has a serine residue at position 204.<br>
The epitope mapping was examined for the HRG amino acid sequence with 69-1A and 75-2D mAbs to achieve the identification of respective specific binding domains, though the other kinds of mAbs showed considerably complex domains. The identified epitopes recognized by 69-1A and 75-2D monoclonal antibodies did not span position 204. Furthermore, immunoprecipitation-immunoblotting analysis showed that the 69-1A and 75-2D monoclonal antibodies could bind to both Form-1 and Form-2 in human plasma samples. Thus, these two new antibodies can be used to clearly detect both forms of histidine-rich glycoproteins in human plasma samples. In our analysis of clinical samples by enzyme-linked immunosorbent assays using various combinations of our newly synthesized antibodies, we found that the histidine-rich glycoprotein concentration was significantly lower in plasma samples from septic patients than in those from healthy volunteers (p < 0.01). Thus, our novel analysis system using the new antibodies is expected to be a useful tool for sepsis research, and it may be adapted as an in vitro diagnostic tool for many other kinds of diseases in the future.No potential conflict of interest relevant to this article was reported.American Society for MicrobiologyActa Medica Okayama2165-04972026Escalation of CTX-M-producing extensively drug-resistant Shigella spp. in Kolkata, India, following the COVID-19 pandemice02824-25ENPujaBoseDivision of Bacteriology, ICMR-National Institute for Research in Bacterial InfectionsGourabHalderDivision of Bacteriology, ICMR-National Institute for Research in Bacterial InfectionsPratanuKayetDivision of Bioinformatics, ICMR-National Institute for Research in Bacterial InfectionsGoutamChowdhuryDivision of Bacteriology, ICMR-National Institute for Research in Bacterial InfectionsSurajitBasakDivision of Bioinformatics, ICMR-National Institute for Research in Bacterial InfectionsDeboleenaRoyDivision of Bacteriology, ICMR-National Institute for Research in Bacterial InfectionsDaisukeImamuraResearch Center for Intestinal Health Science, Okayama UniversityShin-ichiMiyoshiResearch Center for Intestinal Health Science, Okayama UniversityMasatomoMoritaDepartment of Bacteriology I, National Institute of Infectious DiseasesThandavarayanRamamurthyDivision of Bacteriology, ICMR-National Institute for Research in Bacterial InfectionsHemantaKoleyDivision of Bacteriology, ICMR-National Institute for Research in Bacterial InfectionsSantasabujDasDivision of Clinical Medicine, ICMR-National Institute for Research in Bacterial InfectionsAsish KumarMukhopadhyayDivision of Bacteriology, ICMR-National Institute for Research in Bacterial InfectionsShigella spp. is recognized by the World Health Organization as a high-priority pathogen due to its global prevalence, unique pathogenic mechanisms, and growing antimicrobial resistance (AMR). Nearly half of all Shigella strains worldwide are now multidrug-resistant (MDR), and the emergence of extensively drug-resistant (XDR) variants―resistant to ciprofloxacin, ceftriaxone, and azithromycin―has severely limited effective treatment options. The present study is based on prospective laboratory surveillance involving 323 Shigella isolates collected during 2021–2023, with pre-COVID-19 pandemic data included from a previously published study solely for historical comparison. The presence of antibiotic resistance genes (ARGs) was investigated, and whole-genome sequencing (WGS) was performed on representative isolates to assess phylogenetic relatedness with global isolates. Approximately 10% of isolates exhibited resistance to third-generation cephalosporins. While only 3% of Shigella isolates carried the blaCTX-M-15 gene from 2013 to 2019, its prevalence increased to 26% by 2022–2023. Among 38 ceftriaxone-resistant S. sonnei isolates, 33 were also resistant to azithromycin, categorizing them as XDR. These isolates showed 48% clonal similarity and high phylogenetic resemblance to the isolates reported from England. Hybrid genome assembly revealed a plasmid harboring both the blaCTX-M-15 and mphA ARGs. Conjugation experiments and plasmid profiling confirmed the plasmid’s transferability. We report a rising trend in third-generation cephalosporin resistance among Shigella spp., primarily driven by the spread of extended-spectrum β-lactamase-producing S. flexneri and the emergence of XDR S. sonnei. These findings underscore the urgent need for strengthened national AMR containment strategies and enhanced international surveillance of cephalosporin-resistant Shigella to mitigate this growing public health threat.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0916-96364972026Effect of population-approach programs promoting salt reduction and potassium intake in Japan: the Population-based Sodium/Potassium Improvement Program (PoSPIP)19922003ENTakashiHisamatsuDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMinakoKinutaDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakayoshiOhkuboDepartment of Hygiene and Public Health, Teikyo University School of MedicineTakuyaTsuchihashiCardiovascular Center, Steel Memorial Yawata HospitalKatsushiYoshitaDepartment of Public Health, Nutrition, School of Human Life and Ecology, Osaka Metropolitan UniversityYukariTakemiFaculty of Nutrition, Kagawa Nutrition UniversityHitomiHayabuchiGraduate School of Health and Environmental Sciences, Fukuoka Women’s UniversityYukikoOkamiGunma University Center for Food Science and WellnessKaoriKitaokaNCD Epidemiology Research Center, Shiga University of Medical ScienceKeikoSakaguchiFaculty of Nursing and Nutrition, Shukutoku UniversityAtsushiHozawaDivision of Epidemiology, School of Public Health, Tohoku University Graduate School of MedicineTomonoriOkamuraDepartment of Preventive Medicine and Public Health, Keio University School of MedicineHiroshiItohJapanese Society of HypertensionHiromiRakugiJapanese Society of HypertensionKoichiNodeJapanese Society of HypertensionKatsuyukiMiuraNCD Epidemiology Research Center, Shiga University of Medical ScienceReducing sodium intake in populations is essential, but insufficient for preventing and managing high blood pressure, while the importance of increasing potassium intake is overlooked. We investigated the effects of 1-year population-approach programs (2021–2022) promoting salt reduction and potassium intake using urinalysis feedback and food environment improvement. This retrospective observational study included 7649 participants (mean age, 54.0 years; 45.3% women) from 11 municipalities and 4 workplaces. Outcomes in intensive support programs―including urinary sodium, potassium, and sodium-to-potassium (Na/K) ratio measurements with feedback, dietary promotion, and food environment improvement―were compared with standard support programs providing usual health guidance. In linear regression adjusted for demographics, lifestyle factors, and medical history, the reduction in urinary Na/K ratio was greater in the intensive support group (n = 4064) than in the standard support group (n = 3585) (mean difference −0.14 [95% confidence interval, −0.27 to −0.01]). Although estimated potassium intake decreased in both groups, the decline was smaller in the intensive support group (mean difference 31 [12 to 51] mg/day). Estimated salt intake did not differ between the groups. The intensive support group showed greater increases in diastolic blood pressure and high-density lipoprotein cholesterol and smaller increases in blood glucose, as well as greater reductions in hemoglobin A1c and Salt Check Sheet scores. Mean differences between the groups for endpoints were not heterogeneous across intensive support program types. Our findings support the development of hypertension prevention and management strategies that promote healthier dietary behaviors and can be implemented in community and workplace settings, with broad public health applicability.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama2296-4185142026High horizontal force and lateral force transmission induced by the twist of the Achilles tendon1874501ENShotaEnomotoGraduate School of Education, Okayama UniversityKohtaItoArtificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST)The Achilles tendon―the largest and strongest of the many tendons in the human body―consists of subtendons arising from each head of the triceps surae. These subtendons run helically and intertwine to form a twisted three-dimensional structure. More than a century has passed since the twisted structure of the Achilles tendon was first described, and numerous studies have investigated its functional morphology. However, it remains unclear how the presence or degree of twist affects the mechanical function of the lower limbs. Here, using finite element models of the Achilles tendon with and without twist, we show that the presence and degree of twist can modulate the forces transmitted from muscle to skeleton in a complex manner. In contrast to the model without twist, the twisted models clearly exhibit anterolaterally directed horizontal forces at the distal end under a simple proximal tensile load. The lateral and anterior components reach approximately 101 N and 63 N, respectively. Furthermore, the twisted structure induces inter-subtendon force transmission, and the magnitude of the transmitted force increases with increasing degree of twist. These results indicate that the uniaxial contractile force generated by the triceps surae is transformed into triaxial forces by the twisted Achilles tendon and is redistributed in a complex three-dimensional manner through inter-subtendon interactions.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1344-6223842026Factors that delay discovery in cases of death at home in Japan102895ENYukieYamasakiDepartment of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNanakoTamiyaDepartment of Health Services Research, Faculty of Medicine, University of TsukubaHidekiYamamotoDepartment of Environmental Health, Faculty of Pharma-Science, Teikyo UniversityMasanobuMiuraDepartment of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKaoriTaniguchiDepartment of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChieKobayashiDepartment of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasafumiMotomuraFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAyakoHimemiya-HakuchoDepartment of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruMiyaishiDepartment of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIn Japan, solitary deaths have become a social issue, with an increasing number of cases in which the body is discovered long after death. This study aimed to clarify the factors underlying such delays. Cases of death at home were extracted from forensic autopsies. In each case, we collected information about the deceased and their living conditions. The postmortem interval until finding (PMI-f) was calculated by measuring the time between death and discovery. We classified the cases into long PMI-f (LPMI-f; having PMI-f of ≥3 days) and short PMI-f (SPMI-f; having PMI-f of <3 days), and examined the factors that lead to LPMI-f. The characteristics of the group living alone with a PMI-f of <24 h and living with family or acquaintances with an LPMI-f were also analyzed. Among the 420 cases included, 244 (58.1%) were in the LPMI-f group. The LPMI-f group had higher number of males; older individuals; those living alone; those found inside their homes; single, retired, or non-employed individuals; those without long-term care certification; and those with drinking habits. Forty-seven individuals lived alone and had PMI-f of <24 h. Regular visits from relatives living separately led to early detection after death. In the LPMI-f group, 56 individuals lived with family or acquaintances. The absence of regular visits can result in delayed discovery after death; however, the time between death and discovery could be shortened by implementing systems such as allowing neighbors to check the person's safety by noticing uncollected mail.No potential conflict of interest relevant to this article was reported.American Geophysical Union (AGU)Acta Medica Okayama0094-827653142026Electrical Conductivity of Hydrous Ultramafic Melts With Implications for Origin of Low Velocity Layer Atop of the 410 km Seismic Discontinuitye2026GL122472ENTakashiYoshinoInstitute for Planetary Materials, Okayama UniversityLongjianXieCenter for High Pressure Science & Technology Advanced ResearchLow-velocity layers (LVLs) above the 410-km discontinuity are commonly attributed to partial melt generated by dehydration melting when hydrous mantle transition-zone material rises into the upper mantle, where water solubility in nominally anhydrous minerals decreases. Interpreting coexisting high-conductivity anomalies requires constraints on the intrinsic conductivity of the melt phase at pressures just above the transition zone. We measured electrical conductivity of hydrous ultramafic melts representative of incipient melts, ranging from 6.3 to 18.6 wt% H2O at 13 GPa using impedance spectroscopy in a Kawai-type multi-anvil apparatus. Hydrous ultramafic melts are extremely conductive, and conductivity increases systematically with H2O content to values comparable to alkali-carbonate melts. The high conductivity implies that even small fractions of interconnected hydrous melt can dominate bulk mantle conductivity. Combining our measurements with geophysical conductance estimates indicates that <1 vol% melt can produce conductive layers thicker than 10 km, consistent with seismological constraints on LVL structure.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1639-44882026Triple Oxygen Isotope Compositions of Isotopic Reference Waters: Implications for VSMOW-Scale and VSMOW–SLAP-Scale Δ′17O CalibrationENRyojiTanakaThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityAndreasPackGeorg-August-Universität Göttingen, Geowissenschaftliches ZentrumTyler B.CoplenUS Geological SurveyTriple oxygen isotope ratios of waters are commonly reported on the VSMOW–SLAP scale, whereas comparison with theoretical calculations and assessment of instrumental scale distortion require accurate constraints on the measured isotopic compositions of the primary isotopic reference materials (iRMs) themselves. In particular, the measured δ17OVSMOW and Δ′17OVSMOW values for SLAP and its substitute, SLAP2, remain insufficiently constrained and reported values differ among laboratories. Here, we measured triple oxygen isotope ratios for two primary iRMs (VSMOW and SLAP) and twelve secondary iRMs (VSMOW2, SLAP2, GISP, GRESP, USGS45, USGS46, USGS46a, USGS47, USGS48, USGS49, USGS50 and USGS53) using BrF5 fluorination and dual-inlet isotope-ratio mass spectrometry. For SLAP, we obtained δ18OVSMOW = -55.50 ± 0.15‰ and δ17OVSMOW = -29.66 ± 0.08‰, giving Δ′17OVSMOW = 34 ± 6 per meg (all expanded uncertainties, k = 2). The corresponding values for SLAP2 agree within uncertainty. When expressed on the conventional VSMOW–SLAP scale, our Δ′17OVSMOW–SLAP values for all secondary iRMs with available literature values agree with previously published values within uncertainty, confirming interlaboratory comparability on that scale. In contrast, waters with low δ18O values, Δ′17OVSMOW values are systematically higher than the corresponding Δ′17OVSMOW–SLAP values. These results further suggest that accurate determination of the VSMOW-scale isotopic composition of SLAP and/or SLAP2 across laboratories is essential, particularly for low-δ18O samples, for which the difference between VSMOW-scale and VSMOW–SLAP-scale Δ′17O values becomes large, and for meaningful comparison between measured data and theoretical calculations.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.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 Okayama1756-05001912025Plasma expression levels of microRNA-101 are downregulated in patients with Parkinson’s disease19ENTomohiroOmuraDepartment of Pharmacy, Kobe University HospitalHirokiNishiguchiDepartment of Pharmacy, Kobe University HospitalHarukaKanedaDepartment of Pharmacy, Kobe University HospitalYumiKitahiroDepartment 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 UniversityToshiyasuSakaneDepartment of Pharmaceutical Technology, Kobe Pharmaceutical UniversityIkukoYanoDepartment of Pharmacy, Kobe University HospitalObjective Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons. Endoplasmic reticulum (ER) stress contributes to PD pathogenesis, with the ER-associated degradation (ERAD) system playing a protective role. HRD1, an ER-resident ubiquitin ligase, and its stabilizer SEL1L are involved in ERAD and neuronal survival. This study investigated alterations in the plasma levels of microRNA-101 (miR-101), which targets SEL1L, in patients with PD, and its potential role as a biomarker.<br>
Results Plasma miR-101 levels in patients with PD significantly decreased compared with those in healthy controls. Receiver operating characteristic curve analysis demonstrated that miR-101 could moderately discriminate patients with PD from healthy individuals (area under the curve = 0.781, 95% confidence interval = 0.547–1.00). The optimal cutoff, as determined by the Youden index, was 0.737 (expression ratio relative to that in the healthy control group), yielding a sensitivity of 50% and specificity of 100%. These results suggested that reduced plasma miR-101 expression may reflect the pathophysiological state of PD, and miR-101 has potential as minimally invasive biomarker for PD.No potential conflict of interest relevant to this article was reported.American Geophysical Union (AGU)Acta Medica Okayama0094-827653142026Calcium Solubility of Bridgmanite in Subducted Basalt in Earth's Lower Mantlee2026GL121981ENChengweiZhangDepartment of Earth and Planetary Sciences, Jackson School of Geosciences The University of Texas at AustinTakashiYoshinoInstitute for Planetary Materials, Okayama UniversityEliasEl GhazaouiSchool of Earth and Environmental Sciences, Seoul National UniversityStellaCharitonCenter for Advanced Radiation Sources, The University of ChicagoVitali B.PrakapenkaCenter for Advanced Radiation Sources, The University of ChicagoLuoLiDepartment of Earth and Planetary Sciences, Jackson School of Geosciences The University of Texas at AustinYanyaoZhangEarth and Planetary Sciences, Stanford UniversityJung‐FuLinDepartment of Earth and Planetary Sciences, Jackson School of Geosciences The University of Texas at AustinThe calcium solubility in bridgmanite and the resulting abundance of davemaoite under lower-mantle pressure-temperature conditions have been under debate following a recent report of extensive calcium dissolution in bridgmanite. We experimentally investigated the calcium solubility in bridgmanite in a basaltic composition at pressures up to 125 GPa and temperatures up to 3,520 K. Our experimental data are modeled thermodynamically along the bridgmanite-davemaoite solvus to quantify the calcium solubility in bridgmanite and the davemaoite proportion in basaltic and pyrolitic assemblages along lower mantle geotherms. Our results indicate that bridgmanite hosts only 0.001–0.03 Ca cations per formula unit in the lower mantle, while davemaoite remains as an abundant mineral, accounting for 8 and 25 vol% of pyrolitic and basaltic mineralogical models, respectively, along representative lower-mantle geotherms. Our thermoelastic modeling further indicates that the effect of calcium dissolution on the density and bulk sound velocity of lower-mantle assemblages is negligible.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―119ENKensukeKobayashiSatoruMiyazaki/10.18926/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.Fuji Technology Press Ltd.Acta Medica Okayama1883-80302112026Developing and Implementing a Disaster Prevention Game to Enhance Local Understanding128135ENMiriShirokaneOkayama UniversityAiriYamadaOkayama UniversityRyoMisawaOkayama UniversityNobuhisaMattaOkayama UniversityThis study developed and implemented a local disaster prevention sugoroku-style game to address challenges in preserving and transmitting regional knowledge in areas with high population mobility. Many Japanese communities face both natural and social vulnerabilities, and effective disaster education requires linking hazard knowledge with local characteristics. Conducted at Sonan Junior High School in Okayama, the project combined lectures, workshops, and a community engagement event. Students learned about regional topography, land use, and disaster history and used this knowledge to design quizzes, rules, and disaster scenarios for the game. The final sugoroku set included a map-based board, thematic quiz areas, and preparedness item cards, enabling players to predict damage and consider appropriate actions. After creating the game, students shifted from identifying familiar landmarks to describing concrete disaster impacts such as liquefaction or infrastructure collapse. Interaction with local residents further enriched learning through shared experiences. The model proved feasible in terms of time and cost, and its structure is easily adaptable to other regions by incorporating local information. The findings suggest that this participatory, place-based approach enhances imagination, self-efficacy, and intergenerational knowledge transfer, contributing to community-wide disaster preparedness. Future studies will examine long-term educational impacts and broader regional applications.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.Elsevier BVActa Medica Okayama1877-056811232026Relationship between the Hounsfield Unit value of the greater trochanter and the risk of greater trochanteric fractures in anterolateral muscle-sparing minimally invasive total hip arthroplasty104642ENRyuichiroOkudaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama UniversityTomonoriTetsunagaDepartment of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazukiYamadaDepartment of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama UniversityTomokoTetsunagaDepartment of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomohiroInoueDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama UniversityYasutakaMasadaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama UniversityTetsuyaYamamotoDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama UniversityShinMatsumotoDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama UniversityYukiOkazakiDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama UniversityToshifumiOzakiDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama UniversityBackground: No previous studies have investigated the association between the risk of greater trochanteric fractures and the Hounsfield Unit (HU) of the greater trochanter in muscle-sparing minimally invasive total hip arthroplasty (MIS-THA). This study aimed to investigate the risk factors for greater trochanteric fractures in anterolateral MIS-THA.<br>
Hypothesis: Lower HU values of the greater trochanter are associated with a higher risk of intraoperative and early postoperative greater trochanteric fractures.<br>
Patients and methods: This single-center retrospective observational study included 223 patients (257 hips) who underwent primary THA for osteoarthritis or osteonecrosis between January 2010 and August 2024 using a minimally invasive anterolateral approach in the lateral position. All surgeries were performed by four surgeons. Preoperative CT was used to reconstruct coronal sections including the femoral head center and proximal femoral axis, and cancellous HU values of the greater trochanter were measured. Postoperative CT (1 week) with metal artifact reduction was routinely performed; fractures were defined as cortical fracture lines on 3D-reconstructed CT and assessed by two independent orthopedic surgeons. Patients were divided into two groups according to the presence or absence of fractures.<br>
Results: The incidence of greater trochanteric fractures was 6.6% (17/257 hips). Twelve of these fractures (70.6%) were recognized intraoperatively or immediately postoperatively. Full hydroxyapatite (HA)-coated stems were associated with an increased fracture risk compared with other designs (relative risk [RR], 2.68; 95% CI, 1.07–6.68). Age, sex, BMI, ASA physical status, and diagnosis were not significantly associated with fractures. Multivariate analysis identified lower HU values (odds ratio [OR], 0.973; p < 0.0001) and full HA-coated stems (OR, 13.3; p = 0.04) as independent predictors. Receiver operating characteristic (ROC) analysis determined an optimal cut-off of 72.0 HU (sensitivity, 0.941; specificity, 0.742), with a value ≤72.0 HU demonstrating high predictive power (RR, 36.7; p < 0.0001).<br>
Conclusion: Preoperative measurement of HU values in the greater trochanter is a useful screening tool for identifying patients at increased risk of fractures in anterolateral MIS-THA. While an HU value of ≤ 72.0 necessitates careful intraoperative management and increased vigilance, it should be interpreted as an indicator of risk rather than a definitive predictor of fracture due to its moderate specificity.<br>
Level of evidence: IV; retrospective study.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 Okayama2041-17231712026Atomic imaging for hydrogen and boron aggregates in boron-doped diamond by spectro-photoelectron holography3482ENHirotoTomitaGraduate School of Science and Technology, Nara Institute of Science and TechnologyWataruHosodaResearch Institute for Interdisciplinary Science, Okayama UniversityTakumiTaniguchiResearch Institute for Interdisciplinary Science, Okayama UniversityHirokazuFujiwaraDepartment of Advanced Materials Science, Graduate School of Frontier Sciences, The University of TokyoNoriyukiKataokaResearch Institute for Interdisciplinary Science, Okayama UniversityTaisukeKageuraSensing Technology Research Institute, National Institute of Advanced Industrial Science and TechnologyYoshihikoTakanoResearch Center for Materials Nanoarchitectonics, National Institute for Materials ScienceHiroshiKawaradaFaculty of Science and Engineering, Waseda UniversityTamioOguchiCenter for Spintronics Research Network, The University of OsakaTakayoshiYokoyaResearch Institute for Interdisciplinary Science, Okayama UniversityTomohiroMatsushitaGraduate School of Science and Technology, Nara Institute of Science and TechnologyThe electrical properties of diamond are modulated by impurity doping. Isolated substitutional boron atoms introduce holes; however, the fraction of electrically inactive boron atoms increases at higher doping concentrations. This has been attributed to boron aggregation and hydrogen passivation, although their structural identification based on atomic arrangement has yet to be experimentally verified. Here we show the origin of multiple chemical states in homoepitaxially grown boron-doped diamond thin films by analyzing the atomic environment of boron using spectro-photoelectron holography. Our analysis identifies boron dimers and boron-hydrogen complexes, with hydrogen occupying different atomic sites that give rise to distinct chemical shifts. These results suggest that hydrogen incorporation during growth leads to passivation of boron acceptors. We demonstrate that photoelectron holography serves as a promising tool for imaging hydrogen as well as determining the atomic sites of dopants.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1472-68312612026Differences in understanding of explanations and risk perception between dental staff and patients: a questionnaire study at a university hospital1050ENShihoOtomoSchool of Environment and Society, Institute of Science TokyoMaokoFujisakiSchool of Environment and Society, Institute of Science TokyoRisakoYanagaseSchool of Environment and Society, Institute of Science TokyoKanakoNoritakeInstitute of Science Tokyo Hospital, Institute of Science TokyoYoshinobuYanagiFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTaroSugiharaSchool of Environment and Society, Institute of Science TokyoBackground and purpose: Proper self-care necessitates behavioral changes, underpinned by correct knowledge. Oral health literacy (OHL) research constitutes a fundamental foundation for fostering effective self-care practices. However, the extent of the awareness gap between patients and dental staff regarding explanations provided during treatment remains unknown. This descriptive study was conducted to serve as an initial step in bridging this gap.<br>
Methods: Questionnaires were distributed to 92 dental staff members and 205 patients at university hospitals, with responses from 72 staff members and 157 patients.<br>
Results: In the category assessing understanding of explanations (patient vs. dental staff), patients’ self-assessed understanding exceeded the dental staff’s estimates in three aspects: disease name (p = 0.03, r = 0.17), treatment period (p = 0.01, r = 0.21), and pain relief (p = 0.01, r = 0.19). Regarding health self-awareness, the high-scoring group significantly outperformed the low-scoring group in explaining treatment risks (p = 0.03, r = 0.21) and understanding (p = 0.01, r = 0.23). Nevertheless, patients’ risk recognition was higher than that of dental staff in three aspects: root canal treatment (p < 0.01, r = 0.23), holes in the teeth (p < 0.01, r = 0.24), and bleeding during toothbrushing (p = 0.02, r = 0.17). Questions on “crack” (p = 0.02, r = 0.21) by sex, holes in one’s own teeth (p = 0.05, r = 0.03), and feeling one’s own teeth wobble (p < 0.01, r = 0.07) in the intergenerational comparison showed significant differences.<br>
Conclusion: Dental staff should not be satisfied merely with having "explained" something to the patient; they must engage in a confirmation process to verify the patient's correct understanding of the information or to identify excessive anxiety.No potential conflict of interest relevant to this article was reported.Ovid Technologies (Wolters Kluwer Health)Acta Medica Okayama2047-99801592026Insomnia and the Risk of Atrial Fibrillation: A Nationwide, Real‐World Cohort Studye045149ENTakuroMasudaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidehiroKanekoDepartment of Cardiovascular Medicine, The University of TokyoYutaSuzukiDepartment of Advanced Cardiology, The University of TokyoToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiTayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeiichiroIwasakiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiNakagawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuhiroNishiiDepartment of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMoritaDepartment of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkiraOkadaDepartment of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of TokyoKatsuhitoFujiuDepartment of Cardiovascular Medicine, The University of TokyoNorifumiTakedaDepartment of Cardiovascular Medicine, The University of TokyoHiroyukiMoritaDepartment of Cardiovascular Medicine, The University of TokyoHideoYasunagaDepartment of Clinical Epidemiology and Health Economics, School of Public Health, The University of TokyoNorihikoTakedaDepartment of Cardiovascular Medicine, The University of TokyoShinsukeYuasaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Insomnia is one of the most prevalent diseases observed in clinical practice, contributing to increased death and a range of chronic diseases. While numerous studies have explored the relationship between insomnia and cardiovascular disease, research on its association with atrial fibrillation (AF) remains limited. This study aimed to investigate the association between insomnia and incident AF in the general population by comprehensive, nationwide, real‐world data in Japan.<br>
Methods: A total of 1 780 764 individuals without prior cardiovascular disease including AF from the DeSC database were included between April 2014 and August 2023. Insomnia was defined by International Classification of Diseases, Tenth Revision (ICD‐10) codes (F510, G470) before the baseline health checkup. The primary outcome was incident AF (I480–I482 and I489). Cox proportional hazards models were used to estimate hazard ratios of AF according to present insomnia (versus absent).<br>
Results: Insomnia was observed in 216 919 individuals (12.2%), showing a significant association with incident AF after adjusting for potential confounding factors (adjusted hazard ratio, 1.14 [95% CI, 1.10–1.18]). Among subgroups, a similar pattern in the association between insomnia and incident AF was seen, while the association was stronger in younger individuals aged <65 years (versus ≥65 years) and women (versus men) (P for interaction=0.01 and 0.03, respectively).<br>
Conclusions: Insomnia was significantly associated with the risk of AF. It highlighted the importance of recognizing insomnia as a risk factor for AF, given its high prevalence in the general population and the substantial impact of AF on quality of life and prognosis.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 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.Springer Science and Business Media LLCActa Medica Okayama2041-17231712026Bacterial collagenase harnesses collagen geometry for processive cleavage5485ENHiroyaOkiDepartment of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, The University of OsakaKatsukiTakebeDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAdjoaBonsuDepartment of Chemistry and Biochemistry, University of ArkansasKazunoriFujiiDepartment of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda UniversityRyoMasudaWaseda Research Institute for Science and Engineering, Waseda UniversityNicholasHendersonDepartment of Chemistry and Biochemistry, University of ArkansasTakehikoMimaDepartment of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health SciencesTakakiKoideDepartment of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda UniversityMahmoudMoradiDepartment of Chemistry and Biochemistry, University of ArkansasOsamuMatsushitaDepartment of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJoshuaSakonDepartment of Chemistry and Biochemistry, University of ArkansasKazukiKawaharaGraduate School of Pharmaceutical Sciences, The University of OsakaCollagen, the major structural protein in the animal extracellular matrix, forms a triple helix that resists proteolysis and requires specialised enzymes for degradation. Flesh-eating bacteria secrete collagenases that unwind the collagen triple helix and processively trim Gly–X–Y triplet repeats, yet the molecular basis of this process has remained obscure. Here, cryo-electron microscopy reveals how Hathewaya histolytica collagenase ColH engages its substrate and exploits the helix’s architecture for catalysis. ColH encircles a single collagen triple helix in a closed-ring conformation and, through dynamic domain motions, dehydrates and destabilises it. The enzyme undergoes substrate-assisted twisting to adopt a rigid ratcheted conformation, in which one chain is bent into a tripeptide-long ‘bight’ and threaded into the active site for cleavage, while two uncut strands are partitioned to non-catalytic sites. Release of the bight appears to reset the enzyme, with the uncut strands serving as guiding tracks. Repeated cycling between dynamic and rigid states likely enables triplet-by-triplet translocation, allowing ColH to harness collagen’s geometry for processive degradation. These findings reveal a bacterial strategy for collagen unwinding and cleavage distinct from that of mammalian collagenases, highlighting divergent evolutionary solutions for degrading one of nature’s most intractable substrates.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama2977-0548232026Truncation by death in the sufficient-cause frameworkuuag021ENBronner PGonçalvesFaculty of Health and Medical Sciences, University of SurreyEijiYamamotoOkayama University of ScienceEtsujiSuzukiDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThe sufficient-cause framework has been used for decades to improve our understanding of both basic and complex causal concepts in epidemiology, such as mediation and interaction. Here, we make use of this framework to provide a description of truncation by death, in which the outcome of interest is undefined for individuals who die before the assessment time at the end of follow-up. We explain the noncausal nature of the crude estimand that compares outcomes by treatment levels conditional on observed survival by showing that it corresponds to a comparison of distinct risk-status types, which are defined based on their susceptibility to sufficient causes. Further, expressions for the crude estimand and for the survivor average causal effect (SACE)―a causal estimand defined under the principal stratification approach―are provided in terms of population-level joint frequencies of the background factors of sufficient causes. Finally, we also describe conditions, based on background factors of sufficient causes, under which the SACE is null. Our description of this problem, which studies truncation by death from a new perspective, might encourage further analyses of principal stratification-based estimands using sufficient causes.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 Physical Society (APS)Acta Medica Okayama2470-001011352026Analytical study of birefringent cavities for axionlike dark matter search055009ENTadashiKuramotoResearch Institute for Interdisciplinary Science, Okayama UniversityYasutakaImaiResearch Institute for Interdisciplinary Science, Okayama UniversityTakahikoMasudaResearch Institute for Interdisciplinary Science, Okayama UniversityYutakaShikanoInstitute of Systems and Information Engineering, University of TsukubaSayuriTakatoriResearch Institute for Interdisciplinary Science, Okayama UniversitySatoshiUetakeResearch Institute for Interdisciplinary Science, Okayama UniversityLight polarization plays a crucial role in optical-cavity experiments; however, mirror birefringence presents a significant challenge that must be addressed carefully. In this study, a rigorous, nonperturbative framework is developed to quantify birefringence effects by incorporating variations in reflectance and polarization misalignment. We analyze the impact of this framework on the sensitivity of axionlike particle (ALP) dark matter searches. The results show that both birefringence and misalignment contribute to sensitivity degradation in the low-mass regime; however, the adverse effects of misalignment can be mitigated by selecting a postselection angle greater than the misalignment angle. Furthermore, birefringence produces an additional resonance peak in the high-mass region, which remains largely unaffected by misalignment and postselection variations. This rigorous framework underscores the importance of considering birefringence in high-precision optical-cavity experiments for ALP detection.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.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.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.Georg Thieme Verlag KGActa Medica Okayama0013-726X57042024Efficacy and safety of endoscopic ultrasonography-guided ethanol injections of small pancreatic neuroendocrine neoplasms: a prospective multicenter study321329ENKazuyukiMatsumotoGastroenterology and Hepatology, Okayama University HospitalHironariKatoGastroenterology and Hepatology, Okayama University HospitalTakaoItoiGastroenterology and Hepatology, Tokyo Medical UniversityMasayukiKitanoSecond Department of Internal Medicine, Wakayama Medical UniversityKazuoHaraGastroenterology, Aichi Cancer Center HospitalMasakiKuwataniGastroenterology and Hepatology, Hokkaido University HospitalMamoruTakenakaGastroenterology and Hepatology, Kindai University Faculty of Medicine Graduate School of Medical SciencesReikoAshidaSecond Department of Internal Medicine, Wakayama Medical UniversityShuntaroMukaiGastroenterology and Hepatology, Tokyo Medical UniversityNozomiOkunoGastroenterology, Aichi Cancer Center HospitalKazumichiKawakuboGastroenterology and Hepatology, Hokkaido University HospitalTatsuhiroYamazakiGastroenterology and Hepatology, Okayama University HospitalJunSakuraiCenter for Innovative Clinical Medicine, Okayama University HospitalYukiNakatsukaCenter for Innovative Clinical Medicine, Okayama University HospitalMichihiroYoshidaCenter for Innovative Clinical Medicine, Okayama University HospitalMotoyukiOtsukaGastroenterology and Hepatology, Okayama University HospitalBackground Endoscopic ultrasonography (EUS)-guided ethanol injection (EI) has recently been introduced as one of the management strategies for pancreatic neuroendocrine neoplasms (PNENs); however, its role as a surgical alternative is unclear. We evaluated the efficacy and safety of EUS-EI in treating small PNENs through a prospective multicenter study.<bR>
Methods Patients with grade 1 tumors of ≤15 mm confirmed by pathology were included. The primary end point assessed efficacy and safety, measuring complete ablation using computed tomography at 1 and 6 months, prevention of adverse events (AEs) within 1 month, severe pancreatic fistula at 1 month, and incidence/worsening of diabetes mellitus (DM) at 6 months. The composite end point of EUS-EI was compared with that of historical results of a study based on surgical treatment.<br>
Results 25 patients with PNENs, with a median tumor size of 10.1 mm, were treated using EUS-EI. The composite primary end point was achieved by 76.0% of patients (19/25; 95%CI 54.9%–90.6%), a proportion significantly higher than that of surgical treatment (P = 0.008). Regarding efficacy, 88.0% (22/25) of patients achieved complete ablation at 1 and 6 months (95%CI 68.8%–97.5%). Regarding safety, 96.0% (24/25) of patients had no severe AEs within 1 month (95%CI 79.7%–99.9%). No patients had severe pancreatic fistulas at 1 month, and 84.0% (21/25) had no incidence or exacerbation, or both, of DM at 6 months (95%CI 63.9%–95.5%).<br>
Conclusion EUS-EI is safe and could be a potent treatment option for patients with small PNENs.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.Elsevier BVActa Medica Okayama0022-05312262025Costly subjective learning105997ENYouichiroHigashiFaculty of Economics, Okayama UniversityKazuyaHyogoFaculty of Economics, Ryukoku UniversityNorioTakeokaDepartment of Economics, Hitotsubashi UniversityWe examine the behavioral foundation of rational inattention within a menu-choice framework. Unlike previous studies, our approach enables the unique identification of nonadditive information costs. The nonadditivity of information costs makes the effective cost inherently dependent on benefits of information. In contrast to additive cost models, this feature may lead to a violation of the preference for early resolution of menu uncertainty. Early resolution is typically preferable as it allows the agent to fine-tune information for relevant menus. However, if the effective cost function is convex in benefits of information, late resolution may reduce the effective information costs. The violation occurs when this cost-reduction effect outweighs the benefits of early resolution.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0025-583139212025Global well-posedness and scattering in weighted space for nonlinear Schrödinger equations below the Strauss exponent without gauge-invariance10511097ENMasakiKawamotoResearch Institute for Interdisciplinary Science, Okayama UniversitySatoshiMasakiDepartment of Mathematics, Hokkaido UniversityHayatoMiyazakiTeacher Training Courses, Faculty of Education, Kagawa UniversityIn this paper, we consider the nonlinear Schrödinger equation (NLS) with a general homogeneous nonlinearity in dimensions up to three. We assume that the degree (i.e., power) of the nonlinearity is such that the equation is mass-subcritical and short-range. We establish global well-posedness (GWP) and scattering for small data in the standard weighted space for a class of homogeneous nonlinearities, including non-gauge-invariant ones. Additionally, we include the case where the degree is less than or equal to the Strauss exponent. When the nonlinearity is not gauge-invariant, the standard Duhamel formulation fails to work effectively in the weighted Sobolev space; for instance, the Duhamel term may not be well-defined as a Bochner integral. To address this issue, we introduce an alternative formulation that allows us to establish GWP and scattering, even in the presence of poor time continuity of the Duhamel term.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1279-851746102024Radiological assessment of the dissection area in supraomohyoid neck dissection16431652ENYoheiTakeshitaDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJoeIwanagaClinical Anatomy Research Association in Oral and Maxillofacial SurgeryYoshioOhyamaClinical Anatomy Research Association in Oral and Maxillofacial SurgerySoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiMatsushitaClinical Anatomy Research Association in Oral and Maxillofacial SurgeryR. ShaneTubbsClinical Anatomy Research Association in Oral and Maxillofacial SurgeryNorioKitagawaClinical Anatomy Research Association in Oral and Maxillofacial SurgeryToshiyukiKawazuMikiHisatomiDepartment of Oral and Maxillofacial Radiology, Okayama University HospitalShunsukeOkadaDepartment of Oral and Maxillofacial Radiology, Okayama University HospitalMamikoFujikuraDepartment of Oral and Maxillofacial Radiology, Okayama University HospitalJunichiAsaumiDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPurpose The current supraomohyoid neck dissection (SOHND) is performed above the omohyoid muscle to dissect levels I, II, and III in the levels of cervical lymph nodes. However, the anatomical boundary between levels III and IV is the inferior border of the cricoid cartilage. We investigated the anatomical relationship between the omohyoid muscle and cricoid cartilage using contrast-enhanced CT (CE-CT) images to assess the validity of the current SOHND.<br>
Methods CE-CT images of the head and neck regions in patients were reviewed. The patients were divided into two groups: “malignant tumors” and “others”. The vertebral levels corresponding to the positions of anatomical structures such as the intersection of the omohyoid muscle and internal jugular vein (OM-IJ), and the inferior border of the cricoid cartilage (CC), were recorded.<br>
Results The OM-IJ was located around the seventh cervical to the first thoracic vertebra. There was a significant difference between the malignant tumor and others groups in females (p = 0.036). The CC was located around the sixth to seventh cervical vertebrae. There was a significant sex difference in each group (malignant tumor: p < 0.0001; others: p = 0.008). Both sexes tended to have lower OM-IJ than CC, and females had significantly lower OM-IJ than males.<br>
Conclusion This study provides clear anatomical evidence showing the difference between the SOHND dissection area and levels I, II, and III. It could be considered that in most cases SOHND invades level IV, not just levels I, II, and III, especially in female patients.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama0366-70225452025Highly emissive and robust diarylethene fluorophore incorporating imide-fused phenanthryl moietiesupaf091ENKeitoNoseDepartment of Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMinoruYamajiProgram of Applied Chemistry, Cluster of Materials and Environment, Gunma UniversityTadashiMoriResearch Center for Environmental Preservation and Graduate School of Engineering, The University of OsakaFumitoTaniInstitute for Materials Chemistry and Engineering, Kyushu UniversityKentaGotoInstitute for Materials Chemistry and Engineering, Kyushu UniversityHidekiOkamotoDepartment of Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThe fluorescence properties and photostabilities of (E)-diarylethenes (DPEs), featuring two 3-phenanthryl moieties, were investigated. Pristine (E)-di-1,2-(3-phenanthryl)ethene and its ester derivative, respectively referred to as DPE-H and DPE-E, exhibited blue fluorescence. However, they underwent a two-step photoreaction sequence that yielded [7]helicenes, resulting in a gradual reduction of the fluorescence intensity. In contrast, the imide-fused derivative DPE-I displayed intense green fluorescence and it was unexpectedly photostable in solution, maintaining its highly efficient fluorescent nature even after prolonged light exposure. DPE-I, thus, provides a new type of highly efficient and robust diarylethene fluorophore.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.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.Geological Society of AmericaActa Medica Okayama0091-761353112025Long-term and multi-stage ice accumulation in the martian mid-latitudes during the Amazonian945950ENTrishitRujInstitute for Planetary Materials, Okayama UniversityHanayaOkudaKochi Institute for Core Sample Research (X-star), JAMSTECGoroKomatsuInternational Research School of Planetary Sciences, Università d’AnnunzioHitoshiHasegawaDepartment of Global Environment and Disaster Prevention, Faculty of Science and Technology, Kochi UniversityJames W.HeadDepartment of Earth, Environmental and Planetary Sciences, Brown UniversityTomohiroUsuiInstitute of Space and Astronautical Science, Japan Aerospace Exploration AgencyShunMihiraInstitute of Space and Astronautical Science, Japan Aerospace Exploration AgencyMakitoKobayashiDepartment of Systems Innovation, School of Engineering, University of TokyoSubsurface ice in the mid-latitudes of Mars represents one of the largest present-day water ice reservoirs. While atmospheric models predict Late Amazonian (during the past hundreds of millions of years) obliquity-driven ice accumulation, its long-term variations, and the factors influencing accumulation remain unclear. Using geomorphological evidence and numerical modeling, we reveal a southwestern depositional trend within northern mid-latitudinal crater walls and floors. Detailed crater-fill deposit analyses indicate multiple glaciation stages, including an earlier, high-intensity stage followed by a later, lower-intensity stage, both exhibiting this southwestern trend (ca. 640–98 Ma). We conclude that persistent multiple-stage Amazonian glaciations were governed by atmospheric water availability and obliquity-driven climate cycles.No 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.Elsevier BVActa Medica Okayama0960-98223652026Compound starch granule formation in grass seeds is associated with distinct temporal patterns of gene expression11421155.e6ENAlexanderWatson-LazowskiJohn Innes Centre, Norwich Research ParkDoreenFeikeJohn Innes Centre, Norwich Research ParkQi YangNgaiJohn Innes Centre, Norwich Research ParkLaraEschJohn Innes Centre, Norwich Research ParkNaokoFujitaDepartment of Biological Production, Akita Prefectural UniversityRyoMatsushimaInstitute of Plant Science and Resources, Okayama UniversityAlison M.SmithJohn Innes Centre, Norwich Research ParkDavidSeungJohn Innes Centre, Norwich Research ParkThere is extensive interspecies variation in starch granule morphology in the endosperm of grass species, but the factors underpinning this variation are poorly understood. The two major granule morphology types among species are simple and compound granules, where simple granules arise from a single initiation per amyloplast, and compound granules form from multiple granule initiations. Here, we carried out an extensive survey of seed starch morphology, examining specimens from 105 species within the Pooideae using electron microscopy. This not only expanded our current knowledge of the diversity of starch granule types but also confirmed the homoplasy of simple and compound starch granules. We then selected species representing independent origins of simple (Brachyelytrum japonicum, Phaenosperma globosa, and Brachypodium distachyon) and compound granules (Nardus stricta, Melica altissima, and Calamagrostis brachytricha) for analysis of starch structure and gene expression. There were no clear patterns in starch content, amylopectin structure, or amylose content that could distinguish the two granule types. However, comparative transcriptomics over seed development revealed gene expression patterns associated with granule type, most notably increasing expression of STARCH SYNTHASE 3a (SS3a), STARCH BRANCHING ENZYME 1 (SBE1), and limit dextrinases (LDAs) between 3 and 9 days post anthesis in species with compound granules. Mutation of these genes in rice, which natively produces compound granules, resulted in altered granule shape and/or size. Our work highlights differences in gene expression that could contribute to natural variation in granule morphology within the Pooideae while providing important new starch phenotype and gene expression datasets that can be widely used to study endosperm development.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2075-47011522025A Review on the Magnetovolume Effect of the Full Heusler Alloys Ni2MnZ (Z = In, Sn, Sb)215ENTakeshiKanomataResearch Institute for Engineering and Technology, Tohoku Gakuin UniversityXiaoXuDepartment of Materials Science, Graduate School of Engineering, Tohoku UniversityTakuoSakonFaculty of Advanced Science and Technology, Ryukoku UniversityYukiNagataFaculty of Advanced Science and Technology, Ryukoku UniversityShinImadaCollege of Science and Engineering, Ritsumeikan UniversityToshihiroOmoriDepartment of Materials Science, Graduate School of Engineering, Tohoku UniversityRyosukeKainumaDepartment of Materials Science, Graduate School of Engineering, Tohoku UniversityTetsujiroEtoKurume Institute of TechnologyYoshiyaAdachiGraduate School of Science and Technology, Yamagata UniversityTakumiKiharaResearch Institute for Interdisciplinary Science, Okayama UniversityYasushiAmakoFaculty of Science, Shinshu UniversityMasaakiDoiResearch Institute for Engineering and Technology, Tohoku Gakuin UniversityYoshiyaUwatokoInstitute for Solid State Physics, The University of TokyoThe full Heusler alloys Ni2MnZ (Z = In, Sn, Sb) exhibit ferromagnetic properties with a Curie temperature (TC) above room temperature. The magnetic properties of Ni2MnZ (Z = In, Sn, Sb) were studied through a combination of experiments and band calculations under ambient and elevated pressures. The main results of this study open up further prospects for controlling the magnetic properties of the multifunctional Heusler alloys Ni2Mn1+xZ1−x (Z = In, Sn, Sb) and their practical application.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.Springer Science and Business Media LLCActa Medica Okayama2041-17231612025Low melt viscosity enables melt doublets above the 410-km discontinuity3239ENLongjianXieCenter for High Pressure Science & Technology Advanced ResearchDenisAndraultUniversité Clermont Auvergne, CNRS, IRD, OPGC, Laboratoire Magmas et VolcansTakashiYoshinoInstitute for Planetary Materials, Okayama UniversityCunruiHanSchool of Natural Sciences, Birkbeck, University of LondonJames O. S.HammondSchool of Natural Sciences, Birkbeck, University of LondonFangXuSchool of Earth Sciences, Zhejiang UniversityBinZhaoInstitute for Planetary Materials, Okayama UniversityOliver T.LordSchool of Earth Sciences, University of BristolYingweiFeiEarth & Planets Laboratory, Carnegie Institution for ScienceSimonFalvardUniversité Clermont Auvergne, CNRS, IRD, OPGC, Laboratoire Magmas et VolcansShoKakizawaJapan Synchrotron Radiation Research InstituteNoriyoshiTsujinoJapan Synchrotron Radiation Research InstituteYujiHigoJapan Synchrotron Radiation Research InstituteLauraHenrySynchrotron SOLEILNicolasGuignotSynchrotron SOLEILDavid P.DobsonDepartment of Earth Sciences, University College LondonSeismic and magnetotelluric studies suggest hydrous silicate melts atop the 410 km discontinuity form 30–100 km thick layers. Importantly, in some regions, two layers are observed. These stagnant layers are related to their comparable density to the surrounding mantle, but their formation mechanisms and detailed structures remain unclear. Here we report a large decrease of silicate melt viscosity at ~14 GPa, from 96(5) to 11.7(6) mPa⋅s, as water content increases from 15.5 to 31.8 mol% H₂O. Such low viscosities facilitate rapid segregation of melt, which would typically prevent thick layer accumulation. Our 1D finite element simulations show that continuous dehydration melting of upwelling mantle material produces a primary melt layer above 410 km and a secondary layer at the depth of equal mantle-melt densities. These layers can merge into a single thick layer under low density contrasts or high upwelling rates, explaining both melt doublets and thick single layers.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.Microbiology SocietyActa Medica Okayama2057-58581142025Whole-genome-based characterization of Escherichia albertii strains isolated from paediatric diarrhoeal cases in Kolkata, India001363ENGoutamChowdhuryCollaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute of Cholera and Enteric DiseasesYukiHoshikoDivision of Microbiology, Department of Infectious Medicine, School of Medicine, Kurume UniversityMikiOkunoDivision of Microbiology, Department of Infectious Medicine, School of Medicine, Kurume UniversityKeiKitaharaCollaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute of Cholera and Enteric DiseasesM JohnAlbertDepartment of Microbiology, College of Medicine, Kuwait UniversityShin-ichiMiyoshiGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshitoshiOguraDivision of Microbiology, Department of Infectious Medicine, School of Medicine, Kurume UniversityShantaDuttaDivision of Bacteriology, ICMR-National Institute of Cholera and Enteric DiseasesThandavarayanRamamurthyDivision of Bacteriology, ICMR-National Institute of Cholera and Enteric DiseasesAsish K.MukhopadhyayDivision of Bacteriology, ICMR-National Institute of Cholera and Enteric DiseasesEscherichia albertii is a Gram-negative facultative anaerobic bacterium that causes diarrhoea in humans. This study shows the isolation of E. albertii from hospitalized paediatric diarrhoeal cases and genome-based characteristics with putative virulence factors and antimicrobial resistance. E. albertii isolates were identified by species-specific PCR, targeting the gene encoding cytolethal distending toxin (Ea-cdt). The genome of E. albertii was sequenced to identify (i) genes encoding virulence factors (ii) antibiotic resistance-encoding genes, including the mobile genetic elements and (iii) core gene-based phylogenetic relationships and pan-genome features. A total of 10 (1.2%) E. albertii isolates were isolated from 854 faecal samples, of which 6 (60%) were found as the sole pathogen and the remaining 4 (40%) were identified along with other pathogens, such as enteroaggregative Escherichia coli, rotavirus and adenovirus. Patients from whom E. albertii was isolated presented cholera-like diarrhoea, i.e. with watery stool (60%) with moderate dehydration (100%), fever (20%) and abdominal pain (20%). The antimicrobial susceptibility testing of E. albertii showed that most of the isolates were susceptible or reduced susceptible to most of the antibiotics except resistance to erythromycin (80%), tetracycline (50%), nalidixic acid (40%), ampicillin (40%), doxycycline (30%) and ceftriaxone (20%). In the whole-genome sequence, E. albertii isolates revealed several virulence-encoding genes, namely the intimin (eae, E. coli attaching and effacing), the cytolethal distending toxin type II subunit A (cdt-IIA), adhesion (paa, porcine attaching- and effacing-associated), non-LEE (locus of enterocyte effacement) encoded effector A (nleA) and antimicrobial resistance genes (ARGs) conferring resistance to tetracycline (tetA, tetR), sulphonamides (sul2), fluoroquinolones (qnrS) and beta-lactamases (blaCTX-M, blaTEM). The SNP-based phylogenetic analysis of 647 whole genomes of E. albertii isolates from the National Center for Biotechnology Information databases did not reveal any comparable clustering pattern based on the biological source and place of isolation. The genome of some of the E. albertii was closely related to those of the isolates from China and the United Kingdom. The PFGE patterns revealed that most of the E. albertii isolates were distinct clones. This study reports on the extensive genome analysis of diarrhoea-associated E. albertii harbouring multiple virulence and ARGs.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.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 Okayama0969-80432362026An algorithm to calculate physical density of biomedical objects having 3 ≤ Zeff ≤ 20: an application study using clinical photon-counting computed tomography equipment112768ENHiroakiHayashiCollege of Transdisciplinary Sciences for Innovation, Kanazawa UniversityRinaNishigamiGraduate School of Medical Sciences, Kanazawa UniversityTakashiAsaharaDepartment of Radiological Technology, Faculty of Health Sciences, Okayama UniversityNatsumiKimotoDepartment of Radiological Science, Faculty of Health Sciences, Junshin Gakuen UniversityDaikiKobayashiGraduate School of Medical Sciences, Kanazawa UniversityManaMitaniDivision of Radiological Technology, Medical Support Department, Okayama University HospitalNoriakiAkagiDivision of Radiological Technology, Medical Support Department, Okayama University HospitalFumiyoHigakiDepartment of Radiology, Medical Development Field, Okayama UniversityToshihiroIguchiDepartment of Radiological Technology, Faculty of Health Sciences, Okayama UniversityRecently, photon-counting computed tomography (PC-CT) devices have become clinically available for X-ray diagnosis, and developments of analysis algorithms to generate various quantitative images have focused attention. This study proposes an algorithm to calculate the effective physical density (ρeff) of biological objects having an effective atomic number (Zeff) of 3–20. In our procedure, ρeff was determined when fitting the interaction cross sections (σs) to the measured linear attenuation coefficients (μs), which were determined from virtual monochromatic images (VMIs). In this process, the Zeff was analyzed in advance, and this information was fed back to the ρeff analysis. A key feature of our procedure is that it does not require calibration processes based on specific substances, which allow us to analyze any substance without making assumptions.<br>
To validate the availability of the proposed algorithm, we conducted an experiment using a clinical PC-CT scanner. A multi-energy CT phantom, a water phantom, an in-house low-density phantom, food samples, and a chest phantom were scanned. The results showed that our procedure can calculate ρeff of water with an uncertainty of 4.5%. The academic significance of the present research results lies in demonstrating that the factors contributing to contrast, previously obtained from CT values, can be physically interpreted using information from Zeff and ρeff. This analysis cannot be performed with conventional single-energy CT scanners and is possible with PC-CT and dual-energy CT scanners. Our novel procedure is expected to provide useful additional information in X-ray diagnosis.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.Okayama University Medical SchoolActa Medica Okayama0386-300X8032026Common Bile Duct Stone Formed Around an Ingested Fish Bone219223ENKaitaroHigashiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterMotoyasuTabuchiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterShinyaSakamotoDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterShutaTamuraDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterSunaoUemuraDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterTeppeiTokumaruDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterTakehiroOkabayashiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterCase Report/10.18926/AMO/70858An 86-year-old man presented with epigastric pain. He had previously undergone distal gastrectomy with Roux-en-Y reconstruction. Computed tomography (CT) revealed a 32×17 mm common bile duct (CBD) stone with an internal 20 mm linear hyperdense component. Endoscopic removal was unsuccessful due to the size and impaction of the stone. Open choledochotomy retrieved multiple stones and a calcified fish bone, which was confirmed by infrared spectroscopy using the potassium bromide (KBr) wafer method. Although fish bone ingestion is relatively common, this case highlights that such foreign bodies can occasionally serve as a nidus for CBD stone formation, leading to unexpected and clinically significant pathologies. When CT demonstrates a linear high-attenuation intraductal structure, clinicians should suspect a bone fragment and follow a stepwise approach, considering early surgical intervention when endoscopic extraction is unsuccessful or likely to be challenging.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.Springer Science and Business Media LLCActa Medica Okayama2041-17231712026Structural insights into YheS-mediated release of SecM-arrested ribosome4963ENKaishiIsoDepartment of Biological Sciences, Graduate School of Science, The University of TokyoTomaIkedaSchool of Life Science and Technology, Institute of Science TokyoKoheiYamasakiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYushinAndoDepartment of Biological Sciences, Graduate School of Science, The University of TokyoFumiya K.SanoDepartment of Biological Sciences, Graduate School of Science, The University of TokyoTadaomiFurutaSchool of Life Science and Technology, Institute of Science TokyoHidekiTaguchiSchool of Life Science and Technology, Institute of Science TokyoOsamuNurekiDepartment of Biological Sciences, Graduate School of Science, The University of TokyoYuheiChadaniFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityYuzuruItohDepartment of Biological Sciences, Graduate School of Science, The University of TokyoATP-binding cassette subfamily F (ABCF) proteins interact with the ribosome to resolve translation defects near the peptidyl transferase center (PTC). In Escherichia coli, four ABCF proteins (EttA, Uup, YbiT, and YheS) selectively promote translation of distinct problematic nascent peptide sequences, but their molecular mechanisms remain unclear. Here, we present a 2.8 Å cryo-EM structure of the ribosome in complex with an ATPase-deficient mutant of YheS and investigate how it releases ribosomes arrested by the SecM nascent chain. YheS binds to the ribosomal E-site via the L1 stalk, and its P-site tRNA-interaction motif (PtIM) extends toward the PTC, displacing the CCA end of the P-site tRNA. Notably, the cryo-EM density corresponding to the SecM nascent chain within the exit tunnel is largely lost upon YheS binding. These observations suggest that YheS relieves peptide sequence-dependent stalling by perturbing nascent chain-tunnel interactions through P-site tRNA relocation. Steered molecular dynamics simulations provide qualitative support for this model. Together, our findings provide mechanistic insight into a mode of arrest release distinct from the translocon-mediated release mechanism.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.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.International Institute of Anticancer ResearchActa Medica Okayama0258-851X4012026Modified Subtraction Technique for the Middle Hepatic Vein Tributary and Glissonean Pedicle in Right Lobe Graft Procurement349354ENKOSEITAKAGIDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTOMOKAZUFUJIDepartment 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 SciencesTAKEYOSHINISHIYAMADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYASUONAGAIDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSHOHEIYOKOYAMADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYUZOUMEDADepartment of Hepatobiliary Pancreatic Surgery, Ehime University Graduate School of MedicineTOSHIYOSHIFUJIWARADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground/Aim: The procurement of right lobe grafts while preserving the middle hepatic vein (MHV) tributaries (V5 and V8) just before graft retrieval is technically challenging. Moreover, the safe isolation of the hepatic duct from the Glissonean pedicle is essential in living donor hepatectomy. To date, few studies have reported surgical techniques for preserving the MHV tributaries during right lobe graft procurement.<br>
Patients and Methods: This report presents our modified subtraction technique for managing the MHV tributaries and Glissonean pedicle during right lobe graft procurement. First, a subtraction technique for the MHV tributaries was initiated by isolating the right Glissonean pedicle. The lower tip of the tape was placed behind the caudate lobe and passed behind the right hepatic vein. Each end of the tape was then passed behind V5 and V8, followed by dissection of the remaining liver parenchyma between them. Subsequently, a subtraction technique for the Glissonean pedicle was applied to safely isolate the right hepatic duct and hilar plate.<br>
Results: Between September 2011 and May 2025, seven donors underwent right lobe graft procurement using the subtraction technique for the middle hepatic vein tributaries. The mean operative time was 381 min with an estimated blood loss of 217 ml. Using the subtraction technique, all middle hepatic vein tributaries were preserved just before graft retrieval.<br>
Conclusion: This study presents subtraction techniques used during living donor hepatectomy. The technique may facilitate liver parenchyma dissection while preserving MHV tributaries just before graft retrieval and isolating the Glissonean pedicle.No potential conflict of interest relevant to this article was reported.International Institute of Anticancer ResearchActa Medica Okayama0258-851X4032026Impact of Donor Cirrhosis Outcome Risk Estimator (CORE) Score on Recipient Outcomes Following Living-donor Liver Transplantation15701576ENKOSEITAKAGIDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTOMOKAZUFUJIDepartment 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 SciencesTAKEYOSHINISHIYAMADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYASUONAGAIDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNAOHIROOKADADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSHOHEIYOKOYAMADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTOSHIYOSHIFUJIWARADepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground/Aim: Several studies have investigated predictive factors for outcomes of living-donor liver transplantation (LDLT). However, few have examined the clinical significance of the Cirrhosis Outcome Risk Estimator (CORE) score on prognosis following LDLT. This study aimed to investigate the impact of donor CORE scores in predicting the outcomes of patients undergoing LDLT.<br>
Patients and Methods: This single-center retrospective study included 362 adult LDLT recipients at our Institution between January 1998 and December 2024. Patient and graft survival rates were compared between the groups with low (≤0.05) and high (>0.05) CORE scores. Subsequently, multivariate analyses were performed to investigate prognostic factors for survival, including the CORE score.<br>
Results: Patients in the group with a low CORE score had significantly better survival (p=0.001; 5-year, 85.3% vs. 76.2%) and graft survival (p=0.001; 5-year, 84.1% vs. 74.6%) than those with a high CORE score. Multivariate analyses identified the CORE score (>0.05) as an independent predictor of patient survival (hazard ratio=1.70, 95% confidence interval=1.01-2.62, p=0.018) and graft survival (hazard ratio=1.66, 95% confidence interval=1.07-2.57, p=0.024).<br>
Conclusion: This study demonstrated the clinical significance of donor CORE scores in recipient outcomes after LDLT. Assessment of the donor CORE score may be useful for evaluating the quality of liver grafts and estimating recipient outcomes.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.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 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 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.Springer Science and Business Media LLCActa Medica Okayama1341-96253132026Clinical complete response and predictive factors in HER2-positive early breast cancer treated with neoadjuvant chemotherapy aimed at omission of surgery: an exploratory analysis of the JCOG1806 trial528536ENHideoShigematsuDepartment of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University HospitalTomomiFujisawaGunma Prefectural Cancer CenterFumikataHaraAichi Cancer CenterHirojiIwataGraduate School of Medical Sciences, Nagoya City UniversityToshiyukiIshibaInstitute of Science Tokyo HospitalYukinoriOzakiCancer Institute Hospital of the Japanese Foundation for Cancer ResearchTakehikoSakaiCancer Institute Hospital of the Japanese Foundation for Cancer ResearchYasuakiSagaraHakuaikai Sagara HospitalAkihikoShimomuraNational Center for Global Health and MedicineKazukiSudoNational Cancer Center HospitalKaoriTerataAkita University HospitalYoichiNaitoNational Cancer Center Hospital EastKazukiNozawaGraduate School of Medical Sciences, Nagoya City UniversityKeitaSasakiJapan Clinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalNorikoMitomeJapan Clinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalRyoSadachiJapan Clinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalTaroShibataJapan Clinical Oncology Group Data Center/Operations Office, National Cancer Center HospitalTadahikoShienOkayama University HospitalPurpose The JCOG1806 trial (jRCTs031190129) is underway to evaluate the omission of surgery in patients with human epidermal growth factor receptor (HER2)-positive early breast cancer who have a clinical complete response (cCR) after primary systemic therapy (PST). We aimed to assess the cCR rate in this trial and identify predictive factors.<br>
Methods HER2-positivity was defined as an immunohistochemistry (IHC) score of 3 + or in situ hybridization-positivity. A cCR was defined as the absence of detectable lesions upon palpation, contrast-enhanced magnetic resonance imaging, and ultrasonography; biopsy-based confirmation was optional in hormone receptor (HR)-negative cases and mandatory in HR-positive cases. Multivariate logistic regression analyses were used to identify predictors of a cCR.<br>
Results The cCR rate was 57.6% (196/340 patients; 95% confidence interval [CI]: 52.2–63.0%). Strongly estrogen-receptor (ER)-positive tumors (≥ 10%) were significantly less likely to have a cCR than ER-negative tumors (odds ratio [OR], 0.41; 95% CI: 0.20–0.81). IHC 3 + tumors had higher cCR rates than IHC 1 + or 2 + tumors (OR, 2.19; 95% CI: 1.01–4.74). Compared with histological grade I tumors, cCR odds were higher in grade II (OR: 2.92; 95% CI: 1.07–7.93) and III (OR: 4.90; 95% CI: 1.76–13.7) tumors. Among patients without a cCR patients undergoing surgery, 22.2% were diagnosed with ypT0 tumors upon analysis of surgical specimens.<br>
Conclusion ER-negativity, an IHC score of 3 + , and a higher histological grade were independent predictors of a cCR. Identifying these features may improve the feasibility and safety of surgery omission for patients with HER2-positive early breast cancer.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Post-weaning maternal presence exerts a protective effect against social isolation-induced behavioural alterations in mice44248ENHiroshiUenoDepartment of Medical Technology, Kawasaki University of Medical WelfareErikoKitanoDepartment of Psychiatry, Kawasaki Medical SchoolYuTakahashiDepartment of Psychiatry, Kawasaki Medical SchoolSachikoMoriDepartment of Psychiatry, Kawasaki Medical SchoolShinjiMurakamiDepartment of Psychiatry, Kawasaki Medical SchoolKentaWaniDepartment of Psychiatry, Kawasaki Medical SchoolYosukeMatsumotoDepartment of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMotoiOkamotoDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityTakeshiIshiharaDepartment of Psychiatry, Kawasaki Medical SchoolParental “watchful presence” is considered an important factor influencing behavioural and emotional development in offspring across mammalian species, including humans. However, the effects of such parental presence remain insufficiently understood, even in human studies. In laboratory mice, offspring are typically weaned at approximately three weeks of age, leaving the impact of post-weaning maternal presence on behavioural development largely unexplored. This study aimed to investigate whether maternal presence in an adjacent cage after weaning can attenuate behavioural effects of social isolation stress in mice. Furthermore, we sought to assess whether this experimental paradigm could serve as a novel animal model for studying the effects of parental watchful presence, with potential relevance to human parent–child relationship research. Mouse pups were weaned at postnatal day 21 and housed either adjacent to their mother (maternal presence group) or without maternal presence (control group). The pups were subsequently housed either in groups with littermates or individually until eight weeks of age. After maturation, behavioural tests were conducted to assess locomotor activity, anxiety-like behaviour, social behaviour, and depression-like behaviour. In group-housed mice, maternal presence did not influence behavioural outcomes. However, in individually housed mice, maternal presence partially attenuated social isolation-induced behavioural alterations, suggesting a subtle protective effect, including hyperlocomotion, reduced anxiety-like behaviour, and abnormal social interactions. Our findings demonstrate that maternal presence during the post-weaning period can offer a protective effect against certain behavioural abnormalities induced by social isolation stress in mice. This simple adjacent-cage paradigm provides a novel and practical model for elucidating the impact of parental watchful presence on behavioural and emotional development, offering insights relevant to the understanding of parent–child relationships in humans.No potential conflict of interest relevant to this article was reported.