Mapping rare protein-coding variants on multi-organ imaging traits DOI Creative Commons

Yijun Fan,

Jie Chen, Zirui Fan

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Abstract Human organ structure and function are important endophenotypes for clinical outcomes. Genome-wide association studies (GWAS) have identified numerous common variants associated with phenotypes derived from magnetic resonance imaging (MRI) of the brain body. However, role rare protein-coding variations affecting size is largely unknown. Here we present an exome-wide study that evaluates 596 multi-organ MRI traits across over 50,000 individuals UK Biobank. We 107 variant-level associations 224 gene-based burden (67 unique gene-trait pairs) all modalities, including PTEN total volume, TTN regional peak circumferential strain in heart left ventricle, TNFRSF13B spleen volume. The singleton model AlphaMissense annotations contributed 8 pairs between approved drug target gene KCNA5 functional activity. coding signals elucidate some shared genetic regulation organs, prioritize previously GWAS loci, enriched targets. Overall, demonstrate how enhance our understanding effects on human morphology their connections to complex diseases.

Language: Английский

Integrative Machine Learning of Glioma and Coronary Artery Disease Reveals Key Tumour Immunological Links DOI Creative Commons
Youfu He, Ganhua You, Yu Zhou

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(2)

Published: Jan. 1, 2025

ABSTRACT It is critical to appreciate the role of tumour‐associated microenvironment (TME) in developing strategies for effective therapy cancer, as it an important factor that determines evolution and treatment response tumours. This work combines machine learning single‐cell RNA sequencing (scRNA‐seq) explore glioma tumour microenvironment's TME. With help genome‐wide association studies (GWAS) Mendelian randomization (MR), we found genetic variants associated with TME elements affect cancer cardiovascular disease outcomes. Using techniques high dimensional data was analysed obtain new molecular sub‐types biomarkers are prognosis response. F3 identified a top regulator revealed potential angiogenic immunogenic characteristics within could be harnessed immunotherapy. These results demonstrate machine‐learning approaches identifying dissecting heterogeneity informing precision oncology. proposes improving immunotherapeutic through targeted modulation relevant cellular interactions.

Language: Английский

Citations

1
Cognitive Impairment and Synaptic Dysfunction in Cardiovascular Disorders: The New Frontiers of the Heart–Brain Axis DOI Creative Commons
Teresa Soda, Teresa Pasqua, Giovambattista De Sarro

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2387 - 2387

Published: Oct. 18, 2024

Within the central nervous system, synaptic plasticity, fundamental to processes like learning and memory, is largely driven by activity-dependent changes in strength. This plasticity often manifests as long-term potentiation (LTP) depression (LTD), which are bidirectional modulations of efficacy. Strong epidemiological experimental evidence show that heart-brain axis could be severely compromised both neurological cardiovascular disorders. Particularly, disorders, such heart failure, hypertension, obesity, diabetes insulin resistance, arrhythmias, may lead cognitive impairment, a condition known cardiogenic dementia. Herein, we review available knowledge on molecular mechanisms dementia arise describe how LTP and/or LTD induction maintenance CA1 region hippocampus metabolic syndrome, arrhythmias. We also discuss emerging endothelial dysfunction contribute directly altering hippocampal impairing synaptically induced activation nitric oxide synthase. A better understanding CV disorders impact proper function synapses will shed novel light underpinnings dementia, thereby providing new perspective for more specific pharmacological treatments.

Language: Английский

Citations

6
Congestive heart failure and its associations with cognition and cerebral blood flow DOI Creative Commons
Sandra Kong,

Emma Gootee,

Nicole Williams

et al.

Brain Circulation, Journal Year: 2025, Volume and Issue: 11(1), P. 30 - 38

Published: Jan. 1, 2025

Congestive heart failure (CHF) has been linked to dementia but for reasons not well understood. Our retrospective cohort study aims determine if specific measures of CHF severity are associated with cognitive performance or cerebral blood flow velocity (CBFV) among decompensated outpatients. One hundred and thirty-eight patients transthoracic echocardiogram ≤1-year preceding consent were included. Forty-nine had concurrent transcranial Doppler ultrasonography administered by a trained technician assessing anterior artery, middle internal carotid artery (ICA) CBFV. characteristics considered NYHA classification, type (heart preserved ejection fraction vs. mildly reduced/reduced fraction), left ventricular (LVEF; continuous [per 5%] categorized [≤40%, 40%-55%, ≥55%]). A psychometrist standardized battery including Rey Auditory Verbal Learning Test, Complex Figure Copy Immediate Recall test, Letter-Number Sequencing (LNS) Trail Making Tests. Adjusted multivariable linear regression models determined the association between tests as CBFV, in distinct models. On average, Class 1-2 better LNS scores than 3-4 (β: 0.47; 95% CI: 0.09, 0.84). Patients LVEF 40%-55% higher ICA CBFVs those ≤40% 13.7; 1.01, 26.39). No associations other either CBFV found. Blood may be an important mechanism behind CHF-related decline, studies larger sample sizes control group without needed.

Language: Английский

Citations

0
Trends in Mortality Related to Atrial Fibrillation and Dementia in Older Adults in the United States: A 2000–2020 Analysis DOI Creative Commons
Muhammad Umer Sohail, Riffat Batool, Muhammad Saad

et al.

Journal of Cardiovascular Electrophysiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

ABSTRACT Background Atrial fibrillation (AF) and dementia are increasingly prevalent in aging US populations. Their association raises public health concerns, emphasizing the need to understand mortality trends older adults. This study examines AF dementia‐related from 2000 2020. Methods Using CDC WONDER Multiple Cause of Death database, we analyzed death certificates for individuals aged 65 older, reporting age‐adjusted rates (AAMRs) per 100 000 persons. Trends were assessed through annual percent change (APC) analysis via Joinpoint regression, with stratifications by sex, race/ethnicity, urbanization, Census regions. Results A total 400 103 deaths recorded between The AAMR increased markedly 25.4 70.4 overall showed a steady increase 2018 (APC: +4.2%; 95% CI: 2.5–5.5), sharper rise 2020 +9.5%; 4.5–12.2; p < 0.001). Mortality comparable men (AAMR: 44.4) women 43.9). NH White exhibited highest (47.0), followed Black (26.6), Hispanic (23.1), Asian/Pacific Islander (18.0) Nonmetropolitan areas had higher AAMRs (48.1) compared metropolitan (43.5). Regionally, Western at 48.2, while state‐level disparities nearly threefold difference top 90th bottom 10th percentiles. Conclusion Rising among adults highlight targeted screening intervention, particularly high‐risk demographics underserved

Language: Английский

Citations

0
Occupational stress as a risk factor for cardiovascular accidents in medical staff of anesthesiology and intensive care units (review) DOI Creative Commons
В. Е. Ироносов, Dmitry O. Ivanov, К. В. Пшениснов

et al.

Messenger of Anesthesiology and Resuscitation, Journal Year: 2025, Volume and Issue: 22(2), P. 139 - 148

Published: April 16, 2025

Introduction. Occupational stress is one of the most common causes cardiovascular catastrophe among emergency response personnel. The objective was to analyze literature sources on assessing level and its impact health indicators in medical staff anesthesiology intensive care units. Materials methods . analysis included 70 publications from PubMed e-library abstract databases for period 2017 2023. search carried out using keywords: professional burnout syndrome, stress, personality, anesthesiologist-resuscitator, unit, heart rate variability, provider anesthesiologist, physician, rhythm variability. After a primary examination abstracts, 20 articles were excluded review as there lack access full text or they devoted organizational prevention activities Results. It has been demonstrated that long working day more than 10 years associated with an increase likelihood developing coronary disease (CHD), especially men. A linear risk recurrent CHD attacks established time 40 hours week four after myocardial infarction. revealed severe occupational decrease HRV due parasympathetic influences. In resident anesthesiologists, maximum inhibition variability noted at stage induction anesthesia eve night watch. Conclusion. long-term sympathetic activity autonomic nervous system suppression impulses indicate high probability diseases stress.

Language: Английский

Citations

0
Reply to “Gender Differences and Vascular Risk: Unveiling New Pathways for Dementia Prevention” DOI
Jing Yuan, Qiushan Tao, Rhoda Au

et al.

Annals of Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

Language: Английский

Citations

0
Cardiac biomarkers as predictors of cognitive decline in neurodegenerative conditions DOI
Ali Haider Bangash, Nasrollah Moradikor

Progress in brain research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Mapping rare protein-coding variants on multi-organ imaging traits DOI Creative Commons

Yijun Fan,

Jie Chen, Zirui Fan

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Abstract Human organ structure and function are important endophenotypes for clinical outcomes. Genome-wide association studies (GWAS) have identified numerous common variants associated with phenotypes derived from magnetic resonance imaging (MRI) of the brain body. However, role rare protein-coding variations affecting size is largely unknown. Here we present an exome-wide study that evaluates 596 multi-organ MRI traits across over 50,000 individuals UK Biobank. We 107 variant-level associations 224 gene-based burden (67 unique gene-trait pairs) all modalities, including PTEN total volume, TTN regional peak circumferential strain in heart left ventricle, TNFRSF13B spleen volume. The singleton model AlphaMissense annotations contributed 8 pairs between approved drug target gene KCNA5 functional activity. coding signals elucidate some shared genetic regulation organs, prioritize previously GWAS loci, enriched targets. Overall, demonstrate how enhance our understanding effects on human morphology their connections to complex diseases.

Language: Английский

Citations

0