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BackgroundVisual vertigo (VV) refers to dizziness or discomfort provoked by dynamic visual environments and is common after vestibular disorders. The Visual Vertigo Analogue Scale (VVAS) is a nine-item questionnaire developed to assess VV. However, no validated Japanese version has been available. This study aimed to translate the VVAS into Japanese (VVAS-J) and evaluate its reliability and validity.MethodsThe VVAS-J was translated and cross-culturally adapted according to standardized guidelines. The study included 168 patients with vestibular disorders and 73 healthy controls. Reliability was assessed by internal consistency and test-retest reliability using Cronbach's &#x3b1;, intraclass correlation coefficient [ICC(3,1)], and Cohen's &#x3ba;. Validity was examined in terms of content, criterion-related, and construct validity. For criterion-related validity, VV Severity and VVAS Positive were calculated and analyzed in relation to the Dizziness Handicap Inventory (DHI), Hospital Anxiety and Depression Scale (HADS), and stabilometry. For construct validity, VV Severity and VVAS Positive were compared between patients and controls and across diagnostic subgroups.ResultsThe VVAS-J showed excellent internal consistency (Cronbach's &#x3b1; = 0.911) and good test-retest reliability (ICC = 0.87). VV Severity correlated strongly with the DHI (r = 0.62, p < 0.001) but weakly with the HADS and stabilometry. VV Severity and all items were significantly higher in patients with vestibular disorders than in controls, and highest in PPPD among diagnostic subgroups (p < 0.001).ConclusionThe VVAS-J demonstrated good reliability and validity, providing a simple, standardized tool to quantify VV in Japanese patients.

The European Moral Case Deliberation Outcomes Instrument (Euro-MCD 2.0) is a widely used instrument for evaluating moral case deliberation (MCD); however, its psychometric properties have not been fully validated in Japan. Our goal is to assess the validity, reliability, and score patterns of the Japanese version of the Euro-MCD 2.0 among healthcare providers in six national hospitals. A cross-sectional web-based survey was conducted at six national centers for advanced and specialized medicine in Japan. Construct validity was assessed through exploratory and confirmatory factor analysis. Convergent and discriminant validity were examined using composite reliability and average variance extracted. Internal consistency was evaluated with Cronbach's alpha and McDonald's omega. The sample included 359 doctors, nurses, pharmacists, and other healthcare providers involved in clinical practice. Participants who were not in an employment relationship (e.g., trainees) or directly involved with patients and their families in clinical practice were excluded. Items in the moral action domain had elevated 'I don't know' response rates, whereas Moral Competence items showed higher agreement. The three-factor model demonstrated acceptable fit, although discriminant validity between moral teamwork and moral action was limited. Healthcare providers with more years of experience scored higher across all subscales. The Japanese Euro-MCD 2.0 demonstrated acceptable validity and reliability, supporting its use in future evaluations in Japan.

Early-stage diagnosis of paroxysmal atrial fibrillation (PAF) is challenging owing to its asymptomatic nature. However, the genetic factors underlying PAF and predictive utility of polygenic risk scores (PRSs) for PAF in Asian populations remain elusive. We aimed to explore the PAF-associated genetic variants in a Japanese cohort and evaluate the predictive performance of PAF-specific PRSs. This study included 2,604 participants. Following exclusion, quality control, and genotype imputation, a genome-wide association study (GWAS) was conducted. The predictive performance of 30 sets of PRS models constructed across various thresholds was evaluated using three machine learning methods. Model performance was assessed using area under the curve (AUC) and SHapley Additive exPlanations (SHAP). The GWAS using 1,038 PAF cases and 744 controls identified 82 genome-wide significant variants (P&#x2009;<&#x2009;5&#x2009;&#xd7;&#x2009;10-8), all on chromosome 4q25. Of these, 80 variants clustered upstream of PITX2, and two were located in LINC01438. Fine mapping identified two independent intergenic signals, with rs2200732 as the lead single-nucleotide polymorphism. The best PRS-only model achieved an AUC of >0.70, which was improved up to 0.737 in additive models incorporating both PRS and clinical variables. SHAP analysis consistently ranked PRS as the most influential predictor among the clinical variables included in this study. These results suggest that genetic risk, particularly at the established 4q25/PITX2 locus, contributes substantially to PAF susceptibility in this Japanese cohort and that PRS may improve early risk stratification when integrated with clinical risk factors.

[Purpose] Although non-cognitive skills have been linked to academic performance, their relevance to physical therapy students remains unclear. This study examined associations between non-cognitive skills and academic performance among Japanese physical therapy students, focusing on metacognition, motivation, professional identity, self-control, and grit. [Participants and Methods] Thirty first-year students enrolled in a four-year physical therapy program completed self-reported questionnaires. Cumulative grade point average (GPA) and GPA for required specialized courses were obtained for the first and second academic years. Correlation analyses examined associations between non-cognitive skills and academic performance. [Results] Metacognitive knowledge and professional identity were positively correlated with GPA in required specialized courses in both academic years. In the second academic year, consistency of interest (grit), self-efficacy, and study skills as measured by the Motivated Strategies for Learning Questionnaire were significantly associated with GPA in required specialized courses. [Conclusion] Metacognitive knowledge and professional identity were associated with academic performance among Japanese physical therapy students. These findings suggest that non-cognitive skills may be relevant when examining academic outcomes in physical therapy education.

Japanese encephalitis (JE), caused by mosquito-borne Japanese encephalitis virus (JEV), presents significant public health challenges. To facilitate effective prevention and control, this study conducted an epidemiological and genomic characterization of JEV in mosquitoes across China during the period from 2021 to 2022, utilizing the national surveillance system for mosquito-borne pathogens. In total, 832&#x2009;734 female mosquitoes were collected at 130 surveillance sites spanning 29 provinces. with a minimum infection rate (MIR) of 0.20&#x2030;. JEV was detected in 12 provinces and five different mosquito species. The highest MIR was observed in Culex tritaeniorhynchus, reaching 0.73&#x2030;. The highest detection rate of JEV was found in the pigsty habitat (MIR: 0.95&#x2030;). Notably, peak JEV infections in mosquitoes occurred in July, preceding the peak incidence of human cases observed in August. Eight JEV sequences were obtained from six provinces, seven of which were near full-length. Phylogenetic analysis of the whole genome showed that eight JEV strains obtained from provinces in northern and southern China belonged to the emerging variant of GIb-clade 2. In comparison to vaccine strains, current strains displayed between 12 and 14 amino acid variations within the E protein, and there was an additional glycosylation site at N108 resulting from a G110S mutation. These findings underscore active transmission of JEV across multiple mosquito species within China, highlight critical vector and habitat risks, and advocate for enhanced mosquito surveillance as an early warning system. The nationwide dissemination of GIb-clade 2 strains provides a scientific foundation for targeted control measures against JE.

The objective of this study is to comprehensively investigate associations between cognitive function and lifestyle factors. We analyzed data from a cross-sectional study of Japanese adults that included approximately 1,800 variables (e.g., physical characteristics, body composition, and lifestyle habits) and cognitive function assessed using CNS Vital Signs. For participants aged 40 years or older (n&#x2009;=&#x2009;710), we performed partial correlation analysis and analysis of covariance adjusted for sex, age, and years of education. Given the large number of variables, we controlled the false discovery rate within predefined data types (real, positive, ordered categorical, categorical) using the Benjamini-Hochberg procedure. We adjusted p-values to q-values and identified variables with q&#x2009;<&#x2009;0.1 for exploratory purposes. In total, 28 variables met this criterion, with particularly prominent associations for gait characteristics, vascular function, grip strength, and oral conditions, whereas blood components and other general biomarkers did not meet the threshold. These exploratory findings identify candidate correlates of cognitive function in this relatively healthy, primarily urban Japanese cohort and require confirmation in independent longitudinal studies.

Glucagon is a key hormone regulating gluconeogenesis and glucose homeostasis in mammals, yet its regulatory mechanisms in glucose metabolism in carnivorous fish remain incompletely understood. To systematically investigate glucagon-mediated glucose metabolism in Japanese flounder (Paralichthys olivaceus), liver samples were collected before glucagon injection (0&#xa0;h) and at 1&#xa0;h and 6&#xa0;h post-injection for transcriptome sequencing (RNA-seq). Transcriptome analysis identified numerous differentially expressed genes involved in glucose and energy metabolism. In total, 507, 1458, and 709 differentially expressed genes were detected in the comparisons of 0&#xa0;h vs 1&#xa0;h, 1&#xa0;h vs 6&#xa0;h, and 0&#xa0;h vs 6&#xa0;h, respectively. KEGG enrichment analysis showed that glucagon activated pathways related to glucagon signaling, insulin resistance, FoxO signaling, and energy metabolism, including AMPK and PPAR pathways, suggesting that glucagon rapidly stimulates gluconeogenesis. At 6&#xa0;h post-injection, genes involved in glycolysis and glucose transport were upregulated, whereas key gluconeogenic genes were downregulated, indicating attenuation of glucagon-induced metabolic responses. Further analysis showed that glucagon suppressed the insulin-mediated PI3K/AKT signaling pathway. Among the candidate genes, SOCS3 and TRIB3 were upregulated and may serve as key regulators linking glucagon and insulin signaling. Functional experiments further showed that knockdown of TRIB3 reduced glucose levels in hepatocyte culture medium and increased the expression of insulin signaling-related genes. Overall, glucagon regulates glucose metabolism in Japanese flounder by promoting gluconeogenesis while suppressing insulin signaling, providing transcriptomic insights into endocrine regulation in carnivorous fish.

Peripheral intravenous catheters (PIVCs) are used in neonatal intensive care units (NICUs) and growing care units (GCUs). However, neonates/infants in these units frequently experience catheter failure (CF) because of complications, such as extravasation and phlebitis. Nonetheless, data on PIVCs from Japan remain limited. Therefore, this study aimed to investigate the use of infusion catheters and the incidence, characteristics, and risk factors of PIVC-related catheter failure in Japanese NICUs and GCUs. This study was conducted between August 2024 and February 2025 using cross-sectional and prospective surveys. Data from 600 hospitalized neonates/infants and 259 PIVC cases were analyzed. CF was defined as unplanned catheter removal before the completion of therapy owing to loss of function or an inability to administer fluids. Overall, 48.0% of neonates/infants had infusion catheters. The incidence proportion of CF was 47.1%, with an incidence density of 173.1/1,000 catheter-days. Extravasation was the most frequently identified cause of CF (95.9%), and swelling and leaking were primary symptoms. Multivariate Cox regression showed that gestational age (hazard ratio=0.96, p=.03) and infusion flow volume at the time of PIVC removal (hazard ratio=1.28/1 mL/h, p<.01) were significant risk factors. Long PIVCs had significantly longer dwell times than PIVCs (log-rank p=.01). CF is highly prevalent in Japanese infants in NICUs/GCUs, with a rate similar to that reported internationally. Long PIVCs may help extend the catheter dwell times. These findings highlight the need for standardized prevention strategies and improved catheter management protocols.

Background/Purpose: Rectal neuroendocrine tumors (NETs) with distant metastases are uncommon, and evidence supporting the effectiveness of peptide receptor radionuclide therapy (PRRT) in this population remains limited, particularly in Asian cohorts. This study aimed to evaluate the clinical role and real-world outcomes of PRRT in Japanese patients with somatostatin receptor-positive metastatic rectal NETs. Methods: We retrospectively analyzed 20 patients with metastatic rectal NETs who underwent PRRT at the University Hospital Basel (Switzerland) and Yokohama City University Hospital (Japan) between April 2015 and May 2023. The primary endpoint was progression-free survival (PFS), and secondary endpoints included disease control rate (DCR), overall response rate (ORR), overall survival (OS), and adverse events (AEs). Exploratory subgroup analyses were performed according to clinical characteristics, including changes in serum neuron-specific enolase (NSE). Results: The median PFS was 18.9 months (95% CI, 13.5-24.3), and the median OS was 30.3 months (95% CI, 18.9-41.7). The DCR was 80.0%, and the ORR was 15.0%. Treatment responses included partial response in 3 patients, stable disease in 13, progressive disease in 3, and not evaluable in 1. The most common AEs were lymphopenia and anemia, and no secondary malignancies were observed. No clinical factors were significantly associated with PFS; however, higher baseline NSE levels showed a trend toward shorter PFS. Patients with post-treatment declines in NSE showed more favorable treatment responses. Conclusions: PRRT may provide durable disease control with a favorable safety profile in Japanese patients with metastatic rectal NETs. However, these findings should be interpreted with caution given the small sample size and heterogeneous patient population. Baseline NSE elevation and early post-treatment declines may serve as potential prognostic indicators. These results are hypothesis-generating and warrant validation in larger, multicenter studies.

Rotavirus A infects many animal species, including humans, and causes severe diarrhea and acute gastrointestinal diseases. This virus also infects various bird species including pigeons; however, information on avian rotavirus A (ARVA) infection in pigeon populations in Japan is limited. Here, we retrospectively report the genetic characterization based on whole-genome sequences of two Japanese ARVA isolates from pigeons in 2012. The isolates were obtained by inoculation into primary chicken kidney cell cultures and subsequently subjected to near-complete genome sequencing using an NGS system. The genotype constellation of the two ARVA isolates was G18-P[17]-I4-R4-C4-M4-A4-N4-T4-E19-H4, which were identical to those derived from several pigeons. Genetic analysis based on each segment revealed that the genomic sequences of all 11 genes from these ARVAs are closely related to those of ARVAs from foreign countries such as Germany, Italy, or China rather than those of the Japanese ARVAs in previous reports. These data suggest an ancestor common to the ARVA analyzed in this study might be distributed and maintained worldwide. This information will help researchers better understand the evolution and epidemiology of ARVA in feral birds.

Zika virus (ZIKV) is a key member of the Flavivirus genus that has emerged as a major global public health concern. The fusion loop region (residues 98-110), located within domain II of the envelope protein, is highly conserved among flaviviruses, including ZIKV and Japanese encephalitis virus (JEV). However, the functional consequences of such conservation for cross-reactive immunity remains unclear. Here, we integrated bioinformatic analyses, functional assays in vitro and mouse models in vivo to systematically determine the effects of antibodies directed against the JEV fusion loop (FL) region on ZIKV infection. Sequence alignment and structural analysis revealed complete amino acid identity and almost identical three-dimensional conformations between the FL regions of the two viruses, providing a molecular basis for cross-reactivity. Antisera generated against the JEV FL region recognized ZIKV particles and displayed concentration-dependent bidirectional effects. Increased and decreased antibody levels respectively neutralized viral entry and replication, and facilitated infection via antibody-dependent enhancement (ADE). These effects were confirmed in vivo, in which high and low antibody doses reduced tissue pathology and improved survival, and increased viremia and exacerbated inflammatory responses, respectively. These findings highlight the importance of antibody concentration in determining whether cross-reactive responses to conserved structural elements engender neutralization or enhancement response. Our findings provide experimental evidence for assessing ZIKV susceptibility in JEV-vaccinated populations and offer structural insights for designing flavivirus vaccines that maximize protection while minimizing ADE risk. These findings further highlight potential pathogenic and clinical considerations for optimizing vaccine formulations to reduce cross-reactive enhancement risks.

Japanese encephalitis (JE) remains a significant threat to the human, horse, and pig industries throughout the Asia-Pacific region. Emerging genotype V and IV JE virus (JEV) can evade vaccine-induced immunity and exacerbate the disease burden after spreading into JE-na&#xef;ve or epidemic areas through the movement of mosquitoes, pigs, and birds. This study aimed to assess the risk of viral importation into Taiwan by conducting mosquito-based surveillance. Our phylogenetic results revealed that at least six JEV importation events occurred in Taiwan between 1958 and 2024. Over the past 16&#xa0;years of mosquito-based surveillance, three imported events of two genotype I (GI) subclusters (Sub I and Sub II) were detected and sustained local transmission in Taiwan from the first identification in 2008 and 2009 to 2024, without evidence of repeated importations. We further identified three distinct evolutionary stages of local GI JEVs: (1) an initial decade (2009-2018) characterized by co-circulation of Sub I and Sub II; (2) a reduction in viral population size, a decline in genetic heterogeneity, and the extinction of Sub II after 2018; and (3) emergence of a novel, dominant Sub I-I cluster bearing the E-V441I substitution in the stem region of envelope (E) protein. Our findings suggest that Taiwan has faced a low risk of JEV importation over the past 67&#xa0;years. However, when the virus was introduced, it could subsequently establish a long-term circulation and overwinter in Taiwan. These findings underscore the importance of ongoing surveillance of potential JEV overwintering hosts to guide future control strategies.

Men living with HIV face elevated risks for alcohol use disorder (AUD), yet few studies have examined sociodemographic and psychosocial correlates of AUD risk in Asian populations. Sense of coherence (SOC), reflecting the ability to cope with stress, may serve as a protective factor against AUD. This study investigated factors associated with AUD risk among men living with HIV in Japan. This cross-sectional study analyzed data from the third HIV Futures Japan nationwide survey (November 2019-July 2020). Of 908 respondents, 883 biologically male participants who completed alcohol use disorder screening were analyzed. AUD status was classified as low-risk drinking, at-risk drinker, or suspected AUD. Multinomial logistic regression examined sociodemographic and psychosocial predictors. Among participants, 46.8% were classified as low-risk drinking, 44.7% as at-risk drinkers, and 8.5% as suspected AUD. Compared with the low-risk drinking group, heterosexual orientation (OR: 0.38, 95% CI: 0.17-0.86), higher education (OR: 0.63, 95% CI: 0.43-0.90), and older age (OR: 0.98, 95% CI: 0.96-1.00) were associated with lower odds of at-risk drinking. No sociodemographic factors associated with suspected AUD. In the fully adjusted psychosocial model, higher SOC was associated with lower odds of both at-risk drinking (OR: 0.98, 95% CI: 0.96-0.99) and suspected AUD (OR: 0.96, 95% CI: 0.93-0.98). The prevalence of suspected AUD among men living with HIV in Japan (8.5%) was substantially higher than in the general Japanese population (0.5%). SOC emerges as a robust protective factor, suggesting that interventions strengthening SOC may help mitigate AUD risk in this vulnerable population.

Host lipid metabolism is a critical determinant of viral pathogenesis. Although the interferon-inducible cholesterol 25-hydroxylase (CH25H) typically acts as a broad-spectrum antiviral protein, its expression and regulatory patterns during Japanese Encephalitis Virus (JEV) infection display unique features. Here, we demonstrate that 25-hydroxycholesterol (25HC), the product of CH25H, potently inhibits JEV proliferation by suppressing SREBP2 activation. Distinct from the majority of viral infections that induce CH25H upregulation, JEV infection elicits a transient reduction in CH25H abundance immediately after infection, coupled with a persistent elevation in SREBP2 expression. This inverse correlation suggests that JEV actively suppresses the CH25H-mediated metabolic checkpoint to maintain a cholesterol-synthetic environment favorable for replication. By pharmacologically simulating the activity of 25HC, we further verify that targeting the SREBP2 signaling axis can efficiently counteract this virally induced metabolic reprogramming. Our study identifies CH25H downregulation and concomitant SREBP2 activation as a key metabolic signature of JEV pathogenesis.

Advances in medical management have markedly improved early and late outcomes after pediatric heart transplantation. Although survival data are well established in Western countries, evidence from Asia remains limited. We retrospectively reviewed the records of 75 patients who underwent heart transplantation younger than 18 years and received posttransplant care at The University of Osaka Hospital, Japan, between 2000 and 2024. The cohort included 35 male patients, with a median age of 6 years at transplantation. Forty-six patients (61%) underwent transplantation in Japan and 29 (39%) underwent transplantation in other countries. Underlying diagnoses were dilated cardiomyopathy in 42 patients (56%), restrictive cardiomyopathy in 23 (31%), and congenital heart disease in 4 (5%). Overall survival was 96% at 5 and 10 years, 86% at 15 years. Major posttransplant complications included posttransplant lymphoproliferative disease (n = 9), rejection requiring intensified immunosuppression (n = 14), cardiac allograft vasculopathy (n = 5), and renal failure requiring kidney transplantation or dialysis (n = 9). Among the 38 patients who reached adulthood, 15 (39%) were employed, 14 (37%) were pursuing higher education, and 9 (24%) were neither employed nor in education. Pediatric heart transplantation at our institution yielded long-term survival rates comparable with international registry data. Most patients achieved stable school attendance and successful adult social reintegration.

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While the FLOW trial established the renoprotective effects of subcutaneous semaglutide, real-world evidence regarding the long-term renal effects of therapeutic switching from injectable glucagon-like peptide-1 receptor agonists (GLP-1RAs) to oral semaglutide remains limited. We evaluated long-term changes in renal function following this therapeutic switch. This retrospective cohort study included 36 patients with type 2 diabetes (T2D) who were switched from liraglutide or dulaglutide to oral semaglutide (7&#xa0;mg/day). Changes in the urinary albumin-to-creatinine ratio (UACR) and annual estimated glomerular filtration rate (eGFR) slope were compared between the 3-year periods immediately before and after the switch. Three years after switching, the median UACR significantly decreased from 54.3 to 35.8&#xa0;mg/g creatinine (p&#x2009;<&#x2009;0.05). The annual eGFR slope improved from&#x2009;-&#x2009;1.92 (95% CI&#x2009;-&#x2009;2.66 to&#x2009;-&#x2009;1.18) before switching to&#x2009;-&#x2009;0.26 (95% CI&#x2009;-&#x2009;1.01 to 0.50) mL/min/1.73 m2/year after switching (difference: 1.67; p&#x2009;<&#x2009;0.01). Subgroup analysis showed a significant improvement in eGFR slope among patients with baseline eGFR&#x2009;&#x2265;&#x2009;60&#xa0;mL/min/1.73 m2 (difference: 1.85; p&#x2009;<&#x2009;0.01). Reductions in glycated hemoglobin (-&#x2009;0.33%, p&#x2009;<&#x2009;0.05) and body weight (-&#x2009;3.50&#xa0;kg, p&#x2009;<&#x2009;0.01) were sustained at 3&#xa0;years. Improvement in eGFR slope was significantly associated with the magnitude of weight loss (p&#x2009;<&#x2009;0.05) and lower baseline HbA1c (p&#x2009;<&#x2009;0.01). Therapeutic switching from injectable GLP-1RAs to oral semaglutide was associated with attenuation of renal function decline and reduction in albuminuria over 3&#xa0;years. These findings suggest potential long-term renal benefits of oral semaglutide in routine clinical practice.

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