Search Results (685)

Gastric-type cervical adenocarcinoma (GCA) is a rare and aggressive subtype of cervical adenocarcinoma. Despite its clinical significance, its molecular carcinogenesis and therapeutic targets remain poorly understood. This study aimed to compare the clinicopathological, immunohistochemical, and molecular profiles of GCA and usual-type cervical adenocarcinoma (UCA), exploring prognostic and therapeutic biomarkers in a Japanese population. A total of 110 cervical adenocarcinoma cases, including 16 GCA and 94 UCA cases, were retrospectively analyzed for clinicopathological features, and a panel of immunohistochemical markers was assessed. Sanger sequences were performed for the KRAS, PIK3CA, and BRAF genes, and survival and clinicopathological correlations were assessed using Kaplan–Meier and Cox regression analyses. GCA was significantly associated with more aggressive features than UCA, including lymph node involvement, advanced FIGO stages, increasing recurrence rate, and poor survival status. High ARID1B expression was observed in a subset of GCA cases and correlated with worse progression-free and overall survival. Additionally, PD-L1 expression was more frequent in GCA than UCA and was associated with unfavorable prognostic factors. Conversely, UCA cases showed strong p16 expression, supporting their HPV-driven pathogenesis. Molecular profiling revealed KRAS and PIK3CA mutations in both subtypes, while BRAF mutations were identified exclusively in GCA. These findings reveal distinct clinical and molecular profiles for both tumor types and underscore ARID1B and PD-L1 as predictive prognostic and therapeutic biomarkers in GCA, implicating the use of subtype-specific treatment strategies. Full article

Background: In recent years, comprehensive analyses using a genome-wide association study (GWAS) have been conducted to identify genetic factors related to athletic performance. In this study, we investigated the association between genetic variants and elite wrestling status across multiple ethnic groups using a genome-wide genotyping approach. Methods: This study included 168 elite wrestlers (64 Japanese, 67 Turkish, and 36 Russian), all of whom had competed in international tournaments, including the Olympic Games. Control groups consisted of 306 Japanese, 137 Turkish, and 173 Russian individuals without elite athletic backgrounds. We performed a GWAS comparing allele frequencies of single-nucleotide polymorphisms (SNPs) between elite wrestlers and controls in each ethnic cohort. Cross-population analysis comprised (1) identifying SNPs with nominal significance (p < 0.05) in all three groups, then (2) meta-analyzing overlapped SNPs to assess effect consistency and combined significance. Finally, we investigated whether the most significant SNPs were associated with gene expression in skeletal muscle in 23 physically active men. Results: The GWAS identified 328,388 (Japanese), 23,932 (Turkish), and 30,385 (Russian) SNPs reaching nominal significance. Meta-analysis revealed that the ATP2A3 rs6502758 and UNC5C rs265061 polymorphisms were associated (p < 0.0001) with elite wrestling status across all three populations. Both variants are located in intronic regions and influence the expression of their respective genes in skeletal muscle. Conclusions: This is the first study to investigate gene polymorphisms associated with elite wrestling status in a multi-ethnic cohort. ATP2A3 rs6502758 and UNC5C rs265061 polymorphisms may represent important genetic factors associated with achieving an elite status in wrestling, irrespective of ethnicity. Full article

Background: Several epidemiological studies have indicated that metabolic syndrome (MetS) after renal transplantation is caused by an accumulation of non-immunological risks of renal transplantation, and affects the prognosis of the kidney and the patient by increasing the risk of arteriosclerosis and cardiovascular complications. The incidence of MetS in Japanese renal transplant recipients is 14.9 to 23.8%, but its effects on cardiovascular events and kidney prognosis are not clear. Here, we report the results of a longitudinal study on MetS in renal transplant recipients. Methods: A retrospective cohort study was conducted in 104 stable renal transplant recipients who attended our outpatient department from January 2006 to June 2007 and were diagnosed with MetS at least 6 months after renal transplantation until 31 December 2020, or did not have MetS. The impact of MetS on composite vascular events was examined using multivariate Cox proportional hazards analysis. Results: The hazard ratios for the impact of MetS on composite vascular events diagnosed by NCEP Japan, NCEP Original, NCEP Asia, and IDF criteria on composite vascular events were 2.78 (95% CI: 1.15 to 6.75, p = 0.024), 2.65 (95% CI: 1.04 to 6.80, p = 0.042), 2.37 (95% CI: 0.93 to 6.01, p = 0.070), and 1.91 (95% CI: 0.77 to 4.75, p = 0.164), respectively. P for interaction was used to test the influence of each indicator, but was not statistically significant. Conclusions: MetS is a robust risk factor for graft loss and development of cardiovascular events in Japanese renal transplant recipients, even during long-term follow-up. This finding emphasizes the importance of monitoring and managing MetS in this population to improve long-term outcomes. Full article

Background/Objectives: Recent Japanese guidelines recommend using the average sodium-to-potassium (Na/K) ratio from casual urine samples to assess hypertension and cardiovascular risk, suggesting cutoffs of 2 (optimal) and 4 (feasible). We aimed to evaluate the proportion of Korean individuals who would be classified as having elevated Na/K ratios using these cutoffs, based on random urine Na/K measurements obtained from the nationally representative Korea National Health and Nutrition Examination Survey (KNHANES) dataset. Methods: We analyzed 50,440 participants from the KNHANES 2016–2023 with available random urine Na and K results. Annual urinary Na/K ratios were calculated, and the prevalence of ratios ≥2 and ≥4 was assessed by age and sex using sampling weights. Results: The weighted median Na/K ratios were consistently lower than the weighted means, indicating skewed distributions. From 2016 to 2023, the weighted median and mean values increased from 2.3 and 2.7 to 2.8 and 3.3, respectively. The prevalence of a Na/K ratio ≥2 increased from 60.5% to 72.0%, and that of a ratio ≥4 increased from 16.9% to 28.3%. A U-shaped trend in Na/K ≥4 prevalence was observed by age, highest among those <20 and ≥70 years. Males had a higher prevalence than females in all age groups except 20–29. Conclusions: A growing proportion of Koreans exceeded Na/K cutoffs of 2 and 4 over time. Age- and sex-specific variation suggests tailored interpretation may be necessary when applying these thresholds in population health monitoring. Full article

Background/Objectives: Non-syndromic cleft lip with or without palate (NSCL/P) is a common, multifactorial congenital anomaly. As genetic associations can be population-specific, this study aimed to investigate single-nucleotide polymorphisms (SNPs) in the VAX1, MAFB, and WNT3 genes for association with NSCL/P in a Japanese cohort. Methods: A case–control study was conducted with 310 Japanese patients with NSCL/P and 308 ethnically matched healthy controls from Aichi Gakuin Dental Hospital. We genotyped SNPs rs7078160 (VAX1), rs13041247 (MAFB), and rs3809857 (WNT3) using TaqMan assays. Associations were assessed using chi-squared tests, with results stratified by sex and corrected for multiple comparisons using the Bonferroni method. Results: The VAX1 rs7078160 A allele was significantly associated with an increased risk for NSCL/P (OR = 1.67, p < 0.00001). The association was particularly strong in females (OR = 1.93, p < 0.00001) but not significant in males after correction. The MAFB rs13041247 variant showed a nominal protective association with the NSCLO subtype that was not significant after Bonferroni correction. No significant association was found for WNT3. A notable gene–gene interaction was observed, where carrying risk alleles for both VAX1 and MAFB significantly increased overall NSCL/P risk (OR = 2.65, p = 0.00008). Conclusions: VAX1 rs7078160 is a significant risk factor for NSCL/P in the Japanese population, with a pronounced female-specific effect. A synergistic interaction between VAX1 and MAFB elevates disease risk, whereas WNT3 was not implicated in this cohort. These findings underscore the population-specific genetic architecture of NSCL/P. Full article

Background/Objectives: Obesity is associated with various skin complications, yet its impact on dermal elastic fibers—key components maintaining skin elasticity—remains unclear, particularly in cases of mild obesity prevalent in East Asian populations. The aim of this study was to investigate whether mild obesity is associated with the early structural deterioration of dermal elastic fibers and alterations in elastin-related gene expression in Japanese individuals. Methods: Abdominal skin samples from 31 Japanese women (the mean body mass index [BMI] 23.9 ± 3.2 kg/m², mean age 49.5 ± 4.8) undergoing breast reconstruction surgery were analyzed. Gene expression levels of elastin-regenerative and -degradative molecules were assessed by quantitative polymerase chain reaction in the epidermis, dermis, and subcutaneous fat. Dermal elastic fiber content was evaluated histologically using Elastica van Gieson staining. Results: No statistically significant correlations between the BMI and elastin-degrading gene expression (NE, MMP2, MMP9, and NEP) were observed. ELN expression in the dermis showed a significant positive correlation with the BMI (ρ = 0.517, p = 0.003), potentially reflecting a compensatory response. Histological analysis revealed a significant inverse correlation between dermal elastic fiber content and the BMI (r = −0.572, p = 0.001), independent of age or smoking history. Conclusions: Even mild obesity is associated with the early degradation of dermal elastic fibers despite limited transcriptional alterations. These findings underscore the need for early skin care interventions to mitigate obesity-related skin fragility, especially in populations with predominantly mild obesity. Full article

Background/Objectives: Nivolumab is a key therapy for advanced-stage melanoma; however, limited data are available from Asian populations comparing the efficacy and side effects of four dosing regimens: 3 mg/kg every 2 weeks (3mg/kgQ2W), 2 mg/kg every 3 weeks (2mg/kgQ3W), 240 mg every 2 weeks (240mgQ2W), and 480 mg every 4 weeks (480mgQ4W). This retrospective study evaluated Japanese patients with advanced melanoma treated with various nivolumab regimens to assess the impact of dosing interval and dosage on treatment efficacy and immune-related adverse events (irAEs). Methods: We reviewed the records of 153 participants with stage IV melanoma who received nivolumab monotherapy between February 2012 and December 2024 at Shizuoka Cancer Center. Patients were categorized by nivolumab regimen, dosing interval, and dose per body weight. We then compared treatment efficacy and incidence of irAEs across groups. Results: No significant differences were observed in objective response rate (ORR), progression-free survival (PFS), overall survival (OS), or irAE incidence between the 240mgQ2W and 480mgQ4W groups. Similar results were observed in the 3mg/kgQ2W and 2mg/kgQ3W groups. However, participants who received nivolumab within 3 weeks exhibited a significantly higher ORR than those who received nivolumab more than 3 weeks. No significant differences were found in PFS or OS. Conclusions: The administration of nivolumab at shorter intervals may provide short-term benefits in Japanese patients with advanced melanoma. However, long-term efficacy and side effects did not differ significantly across the studied nivolumab regimens. Full article

Background/Objectives: A healthy diet helps prevent noncommunicable diseases, and dairy is an essential part of this diet. Multiple meta-analyses have shown an inverse association between yogurt intake and type 2 diabetes (T2D). This study aimed to develop a simulation model and evaluate the medical and economic effects of increased yogurt intake on T2D. Methods: It predicted the T2D incidence rate, T2D mortality rate, and national healthcare expenditures (NHE) over 10 years using a Markov model for the Japanese population aged 40–79 years. Results: By increasing yogurt intake to 160 g/day or 80 g/day, the incidence rate of T2D decreased by 16.1% or 5.9%, the T2D-related mortality rate decreased by 1.6% or 0.6%, and the NHE was predicted to decrease by 2.4% and 0.9%, respectively. Conclusions: Increasing yogurt intake may be an effective strategy to prevent T2D and reduce NHE. Full article

This study investigated the percentage of iron deficiency anemia (IDA) and iron deficiency (ID) among 71 elite female athletes at a Japanese university and assessed their dietary habits. IDA was identified in 9.9% (n = 7) of participants, and only 22.5% (n = 16) self-reported dietary practices aimed at preventing or managing ID/IDA. Notably, 52.1% (n = 37) of the athletes exhibited IDA or ID but lacked an appropriate dietary approach. Moreover, even among those who reported an intentional dietary approach to the prevention or management of ID/IDA, the intake of iron- and vitamin C-rich foods was insufficient, limiting the effectiveness of their efforts. These findings highlight a gap between awareness and effective practice, indicating that many female athletes in Japan, despite being at elevated risk, do not follow evidence-based dietary strategies for preventing or treating ID/IDA. Targeted nutritional education and routine screening of iron status are strongly recommended for this population. Full article

Background: Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality, despite advances in treatment. Early detection of vascular aging is critical, as preclinical atherosclerosis often remains undiagnosed. AI-determined vascular age, originally developed using carotid-femoral pulse wave velocity (cf-PWV), may help to identify individuals at elevated risk. This study aimed to evaluate the clinical utility of an alternative AI-determined vascular age model based on the arterial velocity pulse index (AVI) and arterial pressure volume index (API) in a Japanese hospital-based cohort. Methods: This retrospective, exploratory study analyzed electronic health records of 408 patients from Yokohama City University Hospital. This study was approved by the Clinical Research Ethics Committee (approval numbers: B180300040, F240500007), and patient consent was obtained through an opt-out process. AI-determined vascular age was estimated using a Generalized Additive Model (GAM) with backward stepwise regression, substituting cf-PWV with AVI and API. Correlations with chronological age were assessed, and comparisons of cardiovascular and renal function markers were performed across age-stratified groups. Results: AI-determined vascular age showed a strong correlation with chronological age (p < 0.05). Significant differences were observed in cardiac diastolic function parameters, B-type natriuretic peptide (BNP), and estimated glomerular filtration rate (eGFR) between the highest and lowest quintiles of AI-determined vascular age. Conclusions: AI-determined vascular age using AVI and API appears to be a feasible surrogate for cf-PWV in clinical settings. This index may aid in stratifying vascular aging and identifying individuals who could benefit from early cardiovascular risk management. Full article

This study investigates the taxonomic status, phylogenetic relationships, and genetic diversity of Japanese chestnut (Castanea crenata Siebold & Zucc.) in Liaodong, China, and across East Asia. Additionally, it evaluates core germplasm resources through cluster and population structure analyses using simple sequence repeat (SSR) marker data from 13 Castanea henryi, 18 Castanea seguinii, and 27 Castanea mollissima, and 142 Japanese chestnut resources. The results show that the East Asian Castanea genus forms a monophyletic group with distinct interspecific boundaries. Japanese chestnut and two varieties/lines of C. seguinii (187 and 170) form a sister clade, indicating a close phylogenetic relationship. All Japanese chestnut resources are divided into two branches, with considerable admixture. The genetic diversity analysis revealed that the 142 Japanese chestnut varieties/lines collectively possessed 141 allelic loci, with genetic distances (GDs) ranging from 0.429 to 0.880 with an average of 0.740. Based on unique characteristics, seven resources with distinctive features were selected as mandatory. A total of 41 core germplasm resources were finally determined using the simulated annealing method. The comparative analysis revealed that, aside from a notable difference in polymorphic information loci, the core germplasm and original germplasm showed no significant differences in other genetic diversity parameters. This indicates that the 41 core germplasm resources effectively preserve the genetic diversity of the original germplasm and have been influenced by artificial selection. This study provides a scientific basis for conserving and using C. crenata germplasm resources. Full article

The optimal exploitation of genetic variability is essential for the success of breeding programs and for identifying quantitative trait loci (QTLs) in genetic association studies. These benefit from populations with a high number of individuals; however, they are expensive since extensive plant maintenance, characterization, and evaluation are required. Core collections offer a practical solution by reducing the number of individuals while representing the original diversity of the population. This study aimed to construct a core collection for Japanese plum to serve as pre-breeding material and enable genetic association studies for traits that are difficult to evaluate. Starting from a population of 1062 individuals genotyped by sequencing, genetic distance and allele coverage metrics were applied to construct several core collections. Genetic parameters and phenotype distribution comparisons allowed for the selection of a core collection of 108 individuals that maximized genetic variability while representative of the original population, confirmed by linkage disequilibrium and population structure analyses. Its usefulness was validated by successfully mapping flowering and maturity dates through marker–trait association. The core collection constructed here will help in the study of fruit quality traits and biotic and abiotic responses, ultimately generating molecular markers to assist the crop’s molecular breeding. Full article

This study examined the distribution characteristics of the standard scores on the Japanese version of the Cognitive Assessment System (CAS)’s Planning, Attention, Simultaneous Processing, and Successive Processing (PASS) scale by clustering the scores using the k-means method, focusing on clinical groups. In Study 1, 140 clinical cases evaluated using the CAS at University A’s educational counseling service were analyzed. The k-means clustering method was applied based on the full-scale standard scores, PASS scale scores, score discrepancies, and subtest scaled scores. Study 2 applied the same clustering method to a clinical group of 91 cases with ADHD, ASD, or comorbid ADHD–ASD, excluding those with intellectual developmental disorders or other disorders. In Study 1, a group with lower full-scale standard scores indicating general intellectual development was identified. Study 2 identified a cluster of cases with ADHD, ASD, or comorbid ADHD–ASD that showed distinct discrepancies among the four standard scores. In addition, there were no significant differences in the diagnoses across clusters. The Japanese version of the CAS provides valid cognitive profile insights in clinical settings, which can aid in planning support interventions beyond clinical diagnosis. Full article

Alcohol consumption is a known risk factor for esophageal and liver cancers. Recently, it was reported that mutation signatures characterized by T:A to C:G mutations (SBS16), which are suggested to be associated with alcohol intake, are frequently detected in esophageal, liver, and stomach cancers among the Japanese population. However, the scientific evidence linking alcohol consumption to SBS16 remains lacking. Acetaldehyde (AA), a carcinogenic metabolite of alcohol, is considered a key contributor to alcohol-related cancer development. Although the guanine adducts associated with alcohol exposure have been reported as part of its carcinogenic mechanism, an adenine adduct, N⁶-ethyl-deoxyadenosine (N⁶-ethyl-dA), a potential contributor to the SBS16 mutation pattern, was recently identified using a mass spectrometry-based DNA adductome approach. However, the mutagenicity assessment of N⁶-ethyl-dA using primer extension assays and the supF gene mutation test showed that this adenine adduct is not mutagenic. To identify another candidate as a driver adduct for SBS16, a DNA adductome approach was conducted, leading to the identification of a novel adenine adduct, 3-(2′-deoxyribos-1′-yl)-7,9-dimethyl-3,9-dihydro-7H-[1,3,5]oxadiazino[4,3-i]purine (N¹-oxydiethylidene-dA), in which two AA molecules are bound to an adenine base. Moreover, N¹-oxydiethylidene-dA was detected in mouse livers, and its levels increased following ethanol administration, suggesting that alcohol may contribute to SBS16 induction via the formation of N¹-oxydiethylidene-dA. Full article

Background: With the global population aging, the proportion of the elderly is increasing, leading to health challenges. The decline in the elderly’s physical function raises their fall risk, which affects their health and burdens the healthcare system. Traditional fall risk assessment methods like Short Physical Performance Battery (SPPB) have limitations, while computer vision technology shows potential but also has drawbacks. Objective: This study aims to use computer vision technology to quantify the elderly’s gait movement features, analyze their correlations with SPPB test scores and duration consumption, and explore a solution for long-term monitoring and more efficient fall risk assessment. Methods: Data from 19 elderly Japanese subjects, including SPPB test data and camera-captured body movement data, were analyzed. Python (Version 3.12.6) was used to obtain JSON data, calculate movement distances, and construct a comprehensive index. Correlation analysis and principal component analysis (PCA) were performed. Results: The variance mean indicator of the comprehensive index associated with movement distance had a significant negative correlation with the completion duration of Test 2 in SPPB, indicating that greater gait variability might be related to better physical vitality. PC1 (Muscle-Control Reserve) and PC2 (Learning-Fatigue Response) obtained from PCA had a positive relationship with the test duration. The comprehensive index had a positive but not highly significant correlation with test scores. Conclusions: This study analyzed the correlation between the elderly’s gait movement features and SPPB test performance. It innovated in data collection and analysis methods. Future research can be improved by expanding the sample size, adding more parameters, and applying deep-learning techniques. Full article