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Exposomics: a review of methodologies, applications, and future directions in molecular medicine.
EMBO Mol Med
January 2025
Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.
The exposome is the measure of all the exposures of an individual in a lifetime and how those exposures relate to health. Exposomics is the emerging field of research to measure and study the totality of the exposome. Exposomics can assist with molecular medicine by furthering our understanding of how the exposome influences cellular and molecular processes such as gene expression, epigenetic modifications, metabolic pathways, and immune responses.
View Article and Find Full Text PDFGenetic coupling of enhancer activity and connectivity in gene expression control.
Nat Commun
January 2025
MRC Laboratory of Medical Sciences, London, UK.
Gene enhancers often form long-range contacts with promoters, but it remains unclear if the activity of enhancers and their chromosomal contacts are mediated by the same DNA sequences and recruited factors. Here, we study the effects of expression quantitative trait loci (eQTLs) on enhancer activity and promoter contacts in primary monocytes isolated from 34 male individuals. Using eQTL-Capture Hi-C and a Bayesian approach considering both intra- and inter-individual variation, we initially detect 19 eQTLs associated with enhancer-eGene promoter contacts, most of which also associate with enhancer accessibility and activity.
View Article and Find Full Text PDFPrediction of Radiation Therapy Induced Cardiovascular Toxicity from Pretreatment CT Images in Patients with Thoracic Malignancy via an Optimal Biomarker Approach.
Acad Radiol
January 2025
Medical Image Processing Group, 602 Goddard building, 3710 Hamilton Walk, Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (M.L., M.A., J.K.U., Y.T., C.W., N.P., S.M., D.A.T.). Electronic address:
Rationale And Objectives: Cardiovascular toxicity is a well-known complication of thoracic radiation therapy (RT), leading to increased morbidity and mortality, but existing techniques to predict cardiovascular toxicity have limitations. Predictive biomarkers of cardiovascular toxicity may help to maximize patient outcomes.
Methods: The machine learning optimal biomarker (OBM) method was employed to predict development of cardiotoxicity (based on serial echocardiographic measurements of left ventricular ejection fraction and longitudinal strain) from computed tomography (CT) images in patients with thoracic malignancy undergoing RT.
Lerodalcibep and evolocumab for the treatment of homozygous familial hypercholesterolaemia with PCSK9 inhibition (LIBerate-HoFH): a phase 3, randomised, open-label, crossover, non-inferiority trial.
Lancet Diabetes Endocrinol
January 2025
LIB Therapeutics, Cincinnati, OH, USA. Electronic address:
Background: Lerodalcibep, a small binding anti-PCSK9 protein (adnectin), showed effective LDL cholesterol reduction in heterozygous familial hypercholesterolaemia. We aimed to assess the safety and efficacy of lerodalcibep and evolocumab in a globally diverse homozygous familial hypercholesterolaemia population.
Methods: This phase 3, randomised, open-label, crossover, non-inferiority study consisted of two 24-week treatment periods separated by an 8-week washout.
Termination of Resuscitation Rules for In-Hospital Cardiac Arrest.
JAMA Intern Med
January 2025
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Importance: There are no validated decision rules for terminating resuscitation during in-hospital cardiac arrest. Decision rules may guide termination and prevent inappropriate early termination of resuscitation.
Objective: To develop and validate termination of resuscitation rules for in-hospital cardiac arrest.
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