Grape cluster compactness is a key trait that influences fruit quality, yield, and disease susceptibility. Understanding the genetic basis of this trait is essential for optimizing vineyard management and improving grapevine cultivars. In this study, we performed quantitative trait locus (QTL) mapping to identify genomic regions associated with cluster architecture and yield components in a bi-parental population derived from Vitis vinifera cv. Riesling × Cabernet Sauvignon. A total of 138 full-sibling progeny were evaluated over two growing seasons at Oakville, Napa Valley, California. Traditional yield-related traits were measured, including cluster number, total cluster weight, and average cluster weight. Additionally, an image-based phenotyping pipeline leveraging the foundation model Segment Anything Model (SAM) was employed to segment individual berries, measure their size and shape, and compute cluster compactness with minimal manual intervention. Trait correlations revealed that compact clusters tended to have a higher berry count but smaller berry size, highlighting the role of compactness in modulating cluster structure. Heritability estimates varied across traits, with berry dimensions and compactness displaying moderate to high heritability, indicating strong genetic control. Two parental linkage maps were constructed using a pseudo-test cross strategy. QTL mapping identified multiple loci associated with cluster architecture and yield components, with several stable QTLs detected across both years, with marker effects ranging from 7.6% to 22.1%. Notably, a QTL for cluster compactness was found in both seasons on chromosome 1 in Cabernet Sauvignon. Other stable QTLs were associated with berry size (chromosomes 6 and 17) and berry count (chromosome 5 in Cabernet Sauvignon and chromosome 7 in Riesling). Additional QTLs were detected in a single year, reflecting the influence of environmental variation. Our findings provide valuable insights into the application of foundation models requiring no prior training and minimal intervention for high-quality segmentation and enhance our understanding of the genetic architecture of cluster compactness and yield traits. The genomic regions identified in this study offer promising targets for breeding programs aimed at improving grape quality and disease resistance.

AXIN1 (axis inhibition protein1), as a rate-limiting component of canonical Wingless-type mouse mammary tumor virus integration site (Wnt)/β-catenin signaling pathway, may influence midbrain dopaminergic neurons. A recent genome-wide association study identified AXIN1 as a candidate gene for Parkinson's disease (PD). Our study aimed to investigate the potential relevance of AXIN1 single nucleotide polymorphisms (rs13337493 and rs9921222) in the risk, clinical characteristics, and pathology of PD. Data were collected from the Northern Han Chinese and Parkinson's Progression Markers Initiative (PPMI) cohorts. Associations between AXIN1 variants, PD-related biomarkers, and clinical manifestations were analyzed. Both loci were identified as risk factors in the Northern Han Chinese population, and the Aallele of rs13337493 [odds ratio (OR) 1.320, 95% confidence interval (CI) 1.052, 1.653, Pc = 0.036] and the Tallele of rs9921222 (OR 1.351, 95%CI 1.045, 1.747, Pc = 0.042) showed increased susceptibility to PD. The risk effect of rs9921222 was predominant in the male cohort (OR 1.504, 95%CI 1.058, 2.139, Pc = 0.044). Rs13337493 was related to worse motor function in white individuals, which was represented by the Hoehn & Yahr stage (OR 2.775, 95%CI 1.195, 6.447, Pc = 0.036). It also correlated with compensatory elevation of cerebrospinal fluid (CSF) 3,4-dihydroxyphenylalanine (DOPA, β = 0.040, 95%CI 0.007, 0.073, Pc = 0.038). Our findings support a gatekeeper role for AXIN1; its polymorphisms contribute to increased PDsusceptibility and accelerated motor progression, yet may also trigger a compensatory presynaptic response, as evidenced by elevated CSF DOPA levels, to counteract neurodegeneration. Future studies should include larger sample sizes, more diverse ethnic populations, and protein-level investigations.

Metabolic syndrome (MetS) comprises several interrelated conditions, including central obesity, insulin resistance, hypertension, and dyslipidemia-all substantially raise the risk of cardiovascular disease and type 2 diabetes mellitus. National Family Health Survey-5 survey findings indicate that the Andaman and Nicobar Islands has a high risk of MetS due to the high prevalence of obesity, hypertension, and diabetes. Ayurveda highlights that an individual's psychosomatic constitution (Prakriti) plays a key role in determining disease susceptibility, prognosis, and treatment outcomes. Few studies have demonstrated the association and specific Prakriti types with diabetes, hypertension, dyslipidemia, insulin resistance, Parkinson disease, and rheumatoid arthritis. However, the association between MetS and Prakriti remains uninvestigated. Moreover, data on the prevalence of MetS in these islands are limited, and the variations reported in prevalence studies on MetS from mainland India point to challenges in generalizing those findings. Additionally, the unique geography, ethnicity, lifestyle, and health care infrastructure of the Andaman and Nicobar Islands further stress the need for this study. This study examines the prevalence of MetS and noncommunicable disease (NCD) risk factors in the South Andaman district and their association with Prakriti and socioeconomic status (SES). A cross-sectional study will be conducted with 1000 randomly sampled adult participants from the South Andaman district, Andaman and Nicobar Islands, India. In this study, participants aged 18 years and older who are willing to provide written consent will be included. The exclusion criteria include pregnant women, nonambulant individuals, and those who are unable to undergo Prakriti assessment. MetS will be assessed using the International Diabetes Federation criteria, and NCD risk factors will be recorded via the WHO STEPS (World Health Organization STEPwise approach to noncommunicable disease risk factor surveillance) instrument. Prakriti will be assessed using the Central Council for Research in Ayurvedic Sciences Prakriti Assessment Scale, and SES will be determined using the Modified Kuppuswamy Scale. Data analyses will include descriptive statistics to estimate MetS and NCD risk factor prevalence. Bivariate analyses (chi-square) will explore associations between the variables, quantifying strength with crude and adjusted odds ratios. A multivariable logistic regression will be used to adjust for confounders. Propensity score matching will serve as a sensitivity analysis. Significance is set at an α of .05, using STATA (version 16.1; Stata Corp LLC) software. The study started in August 2024; as of June 2025, the survey covered 619 participants. This study will provide crucial data on the prevalence of MetS and NCD risk factors in the South Andaman population and investigate associations between constitutional Prakriti types and SES with MetS and NCD risk factors. Despite the constraints inherent to its cross-sectional design, the research offers essential baseline information to support future studies on both Prakriti and MetS in this unique population. DERR1-10.2196/81329.

Adipocytes play essential roles in lipid metabolism and energy homeostasis, with regional differences affecting their functions and disease susceptibility. However, the mechanisms underlying this regional heterogeneity remain unclear. Here we demonstrate that the Bithorax Complex (BX-C) genes, specifically abdominal A (abd-A) and Abdominal B (Abd-B), define regional differences in Drosophila larval adipocytes. Abdominal adipocytes, expressing abd-A and Abd-B exhibit unique characteristics compared to thoracic adipocytes, with active Wnt/Wingless signaling further amplifying these regional differences. Depleting abd-A and Abd-B in adipocytes delays larval-pupal transition, causes pupal lethality, and attenuates the expression of Wnt/Wg target genes, thereby dampening Wnt signaling-induced lipid mobilization. Additionally, Wnt signaling enhances the transcription of abd-A and Abd-B, establishing a feedforward loop that reinforces the interplay between Wnt signaling and BX-C genes. These findings reveal how the cell-autonomous expression of BX-C genes defines adipocyte heterogeneity, a process further modulated by Wnt signaling in Drosophila larvae.

To examine pregnant women's willingness to get the COVID-19 vaccine and the factors influencing this decision. A questionnaire to collect sociodemographic and health status data, knowledge of COVID-19 and vaccines was administered to pregnant women who had visited the hospital for a prenatal check-up. Additionally, specific questions to explore perceptions of disease susceptibility, severity, barriers, benefits, cues for action based on the Health Belief Model, and beliefs in conspiracy theories, as well as trust in the healthcare system and vaccine production, were included. A high level of knowledge about COVID-19 disease and vaccines (odds ratio [OR] 4.16, 95% confidence interval [CI] 1.46-11.85) and multiparity (OR 3.39, 95% CI 1.42-8.07) are linked to acceptance of the COVID-19 immunization, according to the multivariable regression model. Vaccination is positively correlated with trust in the ability of the Italian health system to provide adequate care (OR 22.04, 95% CI 2.53-191.98) and with the level of recommendation of the COVID-19 vaccine during pregnancy by family doctors, gynecologists, and family members (OR 2.19, 95% CI 1.59-3.00). Targeted communication strategies, information campaigns, and addressing any concerns could improve vaccine acceptance and increase vaccination coverage, improving protection for both mothers and their children.

Association of FOXP3 (rs3761548) polymorphism and serum FOXP3 level with graves' disease susceptibility and treatment response in Iraqi patients

Pursuing healthy aging and longevity through natural product and stem cell-driven rejuvenation.

Analysis of immune cell remodeling and functional alterations induced by aging and obesity in mice.

Derivation of pluripotent stem cell lines (RFSCi005-A, RFSCi006-A) from siblings harboring identical high-risk complement variants with discordant age-related macular degeneration.

Gender and Sex Conscious Medicine and the future direction of health care: An invited scientific review by the European Board and College of Obstetrics and Gynaecology (EBCOG).

Dementia and stroke are major global causes of disability, with modifiable lifestyle factors playing a significant role in their development. The updated LIfestyle for BRAin health (LIBRA2) score integrates 15 modifiable risk and protective factors to quantify lifestyle-based dementia risk, but its relationship with stroke and dementia subtypes remains unexplored. We investigated LIBRA2's association with stroke and dementia subtypes while also assessing potential interactions with genetic susceptibility. Prospective data were used from the French multicenter Three-City (3C) Study, with participants aged 65 years and older followed for up to 17 years. Weighted LIBRA2 scores at baseline were constructed based on the presence of 15 modifiable risk and protective factors, with higher scores representing higher lifestyle-based dementia risk. Cox proportional hazards models were used to study the association of LIBRA2 with incident dementia (and subtypes) and stroke, adjudicated by expert neurologist panels. Genetic susceptibility to dementia and stroke was assessed using APOE ε4 carriership and disease-specific genetic risk scores. Analyses included 4,731 participants for stroke (mean age 73.8 years, 60.1% female) and 4,737 participants for dementia (mean age 73.8 years, 59.9% female). One-point increases in LIBRA2 scores (theoretical range -6.1 to +25.7) were associated with increased dementia risk (hazard ratio [HR] 1.08; 1.06-1.11), with a stronger association for vascular and mixed dementia (HR 1.13; 1.08-1.18) compared with Alzheimer disease (AD) dementia (HR 1.06; 1.03-1.09). LIBRA2 was not significantly associated with incident stroke risk (HR 1.03; 0.99-1.07). No significant interaction was found between LIBRA2 and APOE ε4 carriership or disease-specific genetic risk scores in relation to dementia subtypes or stroke. LIBRA2 serves as a valuable tool for assessing lifestyle-related dementia risk and its subtypes but showed no association with stroke, highlighting the potential for a stroke-specific risk reduction model. These associations were independent of genetic disease susceptibility, reinforcing the universal benefits of lifestyle modifications on dementia risk reduction. The stronger association between LIBRA2 (and some individual components) and vascular or mixed dementia, compared with AD dementia, highlights the pivotal role of vascular mechanisms in the relationship between lifestyle and brain health.

Sarcoidosis is a complex, immune-mediated disease characterized by a broad spectrum of clinical and molecular phenotypes-often referred to as endophenotypes-some of which progress to chronic outcomes such as pulmonary fibrosis. Despite decades of research, the pathogenesis of sarcoidosis remains incompletely understood, primarily due to its clinical heterogeneity and the absence of robust preclinical models. Established risk factors include age, sex, ethnicity, geographic origin, and environmental exposures, all of which contribute to granuloma formation and the activation of profibrotic pathways. These inflammatory cascades promote fibroblast proliferation and aberrant tissue remodeling, ultimately leading to interstitial lung pathology and fibrosis. A central feature of sarcoidosis is the dysregulation of immune regulatory mechanisms, likely driven by genetic susceptibility and immune dysfunction. Understanding the genetic architecture of sarcoidosis is crucial for identifying the molecular drivers of the disease, discovering biomarkers for early diagnosis and prognosis, and developing targeted therapies. This review synthesizes current knowledge on the genetic and genomic landscape of sarcoidosis, highlighting key loci and biological pathways implicated in disease susceptibility and progression.

Ficolins, encoded by FCN genes, are key pattern recognition molecules of the lectin complement pathway involved in immune complex clearance, a process often impaired in systemic lupus erythematosus (SLE). Genetic polymorphisms in FCN genes may influence disease susceptibility. However, their functional significance in SLE remains unclear. The present study aimed to investigate the association of selected FCN gene single-nucleotide polymorphisms (SNPs) with SLE, lupus nephritis (LN), and serum ficolin levels in a Western Indian cohort. Seven SNPs in FCN1 (rs2989727, rs1071583), FCN2 (rs7851696, rs17549193, rs7865453, rs17514136), and FCN3 (rs3813800) were genotyped in 200 SLE patients and 200 healthy controls using polymerase chain reaction (PCR) sequence-specific primer and PCR restriction fragment length polymorphism. Serum ficolin-1, -2, and -3 levels were measured using ELISA. Statistical analysis included χ2 test, Kruskal–Wallis test, and logistic regression to assess associations and calculate odds ratios with 95% confidence intervals. The analysis identified significant associations of FCN2 rs7851696, rs7865453, and rs17514136, as well as FCN3 rs3813800, with SLE susceptibility. Among LN patients, FCN1 rs2989727 and rs1071583, FCN2 rs17514136, and FCN3 rs3813800 showed significant associations. FCN3 rs3813800 was significantly associated with ficolin-3 levels, while FCN2 rs7865453 was associated with complement component 1q–circulation immune complex levels. These findings provide novel insight into associations of FCN gene polymorphisms with SLE and LN susceptibility, with genotype–phenotype correlations suggesting their biological relevance. Future longitudinal and mechanistic studies are warranted to validate these associations and explore their therapeutic potential.

Cardiovascular disease (CVD) and Alzheimer's disease (AD) are leading causes of death and disability worldwide, and recent research has increasingly illuminated a complex, bidirectional relationship between the two. This review synthesizes epidemiological, mechanistic, imaging, and genetic evidence linking CVD and AD through the heart-brain axis—a network of interrelated physiological and demographic pathways. We detail how cerebral hypoperfusion, inflammation, blood-brain barrier dysfunction, imbalance of the autonomic nervous system, and systemic amyloidosis contribute to shared neurodegenerative and cardiovascular outcomes. Multi-organ imaging studies, including MRI and PET, reveal that dysfunction of the cardiovascular system correlates with brain atrophy, white matter lesions, glymphatic impairment, and accumulation of AD-related proteinopathies. Genetic analyses further support overlapping risk architectures, particularly involving APOE and loci associated with lipid metabolism, vascular integrity, and inflammation. Age and sex are critical modifiers, with midlife CVD exerting the strongest influence on later cognitive decline, and sex-specific physiological responses shaping disease susceptibility. Finally, we explore how modifiable lifestyle factors, pharmacologic interventions, and precision medicine approaches targeting inflammatory and vascular pathways can jointly reduce the burden of both CVD and AD. Multidisciplinary collaboration to understand the interconnected biology of the heart and brain is essential for advancing integrated prevention and treatment strategies in aging populations.

Frailty is increasingly recognized as a critical factor in neurology, influencing disease susceptibility, progression, and outcomes. Emerging evidence highlights the pivotal role of sex and gender in shaping frailty trajectories across major neurological disorders, including stroke, Parkinson's disease (PD), dementia, and multiple sclerosis. This systematic review synthesizes current knowledge on the interplay between frailty and neurological disease, with a focus on sex-specific patterns. Recognizing sex- and gender-related differences in frailty expression is critical to advancing a more personalized and equitable model of neurological care, and reducing disparities in a growing population affected by age-related neurological conditions. ANN NEUROL 2025.

Developmental reprogramming of cytochrome P450 enzymes in offspring by adverse maternal factors exposure: Implications for long-term metabolic disease susceptibility.

GBA1 variants cause Gaucher's disease (GD) in biallelic forms and increase Parkinson's disease (PD) risk in heterozygous carriers. Carriers of mild or severe variants (causing GD type 1 or types 2-3) can enroll in clinical trials, whereas those with GBA1 variants classified as unknown are typically excluded. We assessed the contribution of unknown variants to PD risk and their relevance for trial stratification. We meta-analyzed 34 case-control studies (24,060 PD cases, 14,465 controls). Odds ratios (ORs) were estimated using random-effects models and stratified by the American College of Medical Genetics and Genomics (ACMG) criteria. Unknown variants also classified as variants of uncertain significance (VUSs) per ACMG criteria were associated with PD (OR = 1.59, 95% confidence interval [CI]: 1.25-2.02; I2 = 0%). VUSs + likely pathogenic + pathogenic also showed an association (OR = 1.63, 95% CI: 1.28-2.06; I2 = 0%). Unknown GBA1 variants may be considered provisionally in clinical trials if also classified as VUS, likely pathogenic, or pathogenic per ACMG criteria. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Enteric glia and purinergic signaling in health and disease.

Background:Community-Based Surveillance (CBS) refers to involving community members in the detection and reporting of diseases within their communities for timely and effective response. Hence, it is necessary to study the factors that influence community participation in CBS.Objective:This study aims to utilize the Health Belief Model (HBM) to identify predictors of community engagement in CBS activities in Kelantan state, Malaysia.Design and methods:Perceived Benefit (BEN), Perceived Barriers (BARR), Perceived Susceptibility (SUS), and Behavioral Likelihood (BL) were assessed using a validated questionnaire (KAP-CBS-ID). A Covariance-based Structural Equation Modeling (SEM) approach was used to understand the relationships between the study variables.Results:The model demonstrated a good fit (RMSEA = 0.048, 90% CI [0.042, 0.054]; CFI = 0.935; TLI = 0.925; SRMR = 0.078) and explained 40.5% of the variance in the behavioral likelihood of engaging in CBS. Self-efficacy (SE) emerged as a strong direct predictor of participation. SUS showed both direct and indirect (mediated) effects on behavioral likelihood to participate in CBS, with the indirect effect occurring through SE. Similarly, BEN influenced BL indirectly through SE. The perceived barriers, on the other hand, had a significant negative direct effect on participation (BL). The effects of SE, BARR, and SUS on participation in CBS were substantial.Conclusion:Public health interventions should focus on improving community self-efficacy to participate in CBS initiatives, as well as raising awareness of disease susceptibility, highlighting the benefits of CBS, and addressing participation barriers to increase community engagement in surveillance systems.

Genetically predicted KIR2DS4 mediate the association between gut microbe K10 and osteoporosis fractures: A mediation Mendelian randomization study.