Consortium profile: the methylation, imaging and NeuroDevelopment (MIND) consortium.

Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults.

Genome-Wide Pleiotropy Analysis Identifies Shared and Opposing Pathways Influencing Coronary Artery Disease and Cancer.

Background: Coronary artery disease (CAD) and cancer are 2 leading global causes of mortality, with shared modifiable risk factors, yet the genetic and molecular mechanisms underlying their comorbidity remain poorly understood.

Methods: We performed a genome-wide pleiotropy analysis to identify shared genetic mechanisms across CAD and 4 common cancers that share modifiable risk factors with CAD (breast, colorectal, lung, prostate).

Results: Using genome-wide pleiotropy and colocalization analysis, we identified 60 colocalized susceptibility loci shared by CAD and site-specific cancer, of which 43 are novel, including loci at , , and .

Characteristics of Children Aged 0 to 23 Months Hospitalized With Respiratory Syncytial Virus.

Background And Objectives: Respiratory syncytial virus (RSV) is a leading cause of hospitalization among young children. Nirsevimab is recommended for all infants younger than 8 months and children aged 8 to 19 months who are at increased risk of severe RSV entering their second RSV season. Additional data are necessary to identify children aged 8 to 19 months at increased risk for severe disease.

Extreme exercise in males is linked to mTOR signalling and onset of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is thought to be caused by interaction between genetic and environmental factors leading to motor neuron (MN) degeneration. Physical exercise has been linked to ALS but controversy remains. A key question is to determine which individuals might be at risk of exercise-associated ALS, because unnecessary avoidance of exercise could be harmful.

Proteogenomic and observational evidence implicate ANGPTL4 as a potential therapeutic target for colorectal cancer prevention.

Background: The role of lipid-perturbing medications in cancer risk is unclear.

Methods: We employed cis-Mendelian randomization and colocalisation to evaluate the role of 5 lipid-perturbing drug targets (ANGPTL3, ANGPTL4, APOC3, CETP, PCSK9) in risk of 5 cancers (breast, colorectal, head and neck, ovarian, prostate). We triangulated findings using pre-diagnostic protein measures in prospective analyses in EPIC (977 colorectal cancer cases, 4,080 sub-cohort members) and the UK Biobank (860 colorectal cancer cases, 50,177 controls).

Clustering Patients with Pulmonary Hypertension Using the Plasma Proteome.

Patients with pulmonary hypertension are classified according to clinical criteria to inform treatment decisions. Knowledge of the molecular drivers of pulmonary hypertension might better inform treatment choice. To investigate plasma protein clusters in patients with a diagnosis of pulmonary hypertension.

Longitudinal prediction of DNA methylation to forecast epigenetic outcomes.

Background: Epigenetic changes in early life play an important role in the development of health conditions in children. Longitudinally measuring and forecasting changes in DNA methylation can reveal patterns of ageing and disease progression, but biosamples may not always be available.

Methods: We introduce a probabilistic machine learning framework based on multi-mean Gaussian processes, accounting for individual and gene correlations across time to forecast the methylation status of an individual into the future.

Diagnostic MicroRNA Signatures to Support Classification of Pulmonary Hypertension.

Background: Patients with pulmonary hypertension (PH) are classified based on disease pathogenesis and hemodynamic drivers. Classification informs treatment. The heart failure biomarker NT-proBNP (N-terminal pro-B-type natriuretic peptide) is used to help inform risk but is not specific to PH or sub-classification groups.

Atrial fibrillation is associated with higher oxygen extraction in the human heart.

Introduction: Atrial fibrillation (AF) is a prevalent cardiac arrhythmia characterized by irregular atrial contractions that compromise ventricular function and cardiac output. In this study we investigated the impact of AF on myocardial oxygen utilization, hypothesizing that myocardial oxygen extraction is more pronounced in AF due to less efficient ventricular function and reduced myocardial blood flow.

Methods: We conducted a prospective, observational study involving 45 patients undergoing AF catheter ablation at the University of Washington Medical Center between 2022 and 2024, categorizing them based on their presenting rhythm, i.

Short-term diet intervention comprising of olive oil, vitamin D, and omega-3 fatty acids alters the small non-coding RNA (sncRNA) landscape of human sperm.

Offspring health outcomes are often linked with epigenetic alterations triggered by maternal nutrition and intrauterine environment. Strong experimental data also link paternal preconception nutrition with pathophysiology in the offspring, but the mechanism(s) routing effects of paternal exposures remain elusive. Animal experimental models have highlighted small non-coding RNAs (sncRNAs) as potential regulators of paternal effects.

PSC-specific prognostic scores associated with graft loss and overall mortality in recurrent PSC after liver transplantation.

Background: Primary sclerosing cholangitis (PSC) is a progressive liver disease with no treatment apart from liver transplantation (LT). After LT, patients can develop recurrent PSC (rPSC). The United-Kingdom (UK-PSC) and Amsterdam-Oxford (AOPSC) scores are used as prognostic models for PSC outcomes.

Linking obesity-associated genotype to child language development: the role of early-life neurology-related proteomics and brain myelination.

Background: The association between childhood obesity and language development may be confounded by socio-environmental factors and attributed to comorbid pathways.

Methods: In a longitudinal Singaporean mother-offspring cohort, we leveraged trans-ancestry polygenic predictions of body mass index (BMI) to interrogate the causal effects of early-life BMI on child language development and its effects on molecular and neuroimaging measures. Leveraging large genome-wide association studies, we examined whether the link between obesity and language development is causal or due to a shared genetic basis.

Impact of age-related changes in buccal epithelial cells on pediatric epigenetic biomarker research.

Cheek swabs, heterogeneous samples consisting primarily of buccal epithelial cells, are widely used in pediatric DNA methylation studies and biomarker creation. However, the decrease in buccal proportion with age in adults remains unexamined in childhood. We analyzed cheek swabs from 4626 typically developing children 2-months to 20-years-old.

Perceptions and Barriers to Outpatient Antiviral Therapy for COVID-19 and Influenza as Observed by Infectious Disease Specialists in North America: Results of an Emerging Infections Network (EIN) Survey, February 2024.

Antiviral therapy is underutilized for outpatients at increased risk for severe COVID-19 or influenza. Results from this survey offer insights into treatment barriers from the infectious disease specialist perspective. Further education is needed about the benefits of early antiviral therapy.

Prospective prediction of childhood body mass index trajectories using multi-task Gaussian processes.

Background: Body mass index (BMI) trajectories have been used to assess the growth of children with respect to their peers, and to anticipate future obesity and disease risk. While retrospective BMI trajectories have been actively studied, models to prospectively predict continuous BMI trajectories have not been investigated.

Materials And Methods: Using longitudinal BMI measurements between birth and age 10 y from a mother-offspring cohort, we leveraged a multi-task Gaussian process approach to develop and evaluate a unified framework for modeling, clustering, and prospective prediction of BMI trajectories.

Multi-trait association analysis reveals shared genetic loci between Alzheimer's disease and cardiovascular traits.

Several cardiovascular traits and diseases co-occur with Alzheimer's disease. We mapped their shared genetic architecture using multi-trait genome-wide association studies. Subsequent fine-mapping and colocalisation highlighted 16 genetic loci associated with both Alzheimer's and cardiovascular diseases.

Multi-output prediction of dose-response curves enables drug repositioning and biomarker discovery.

Drug response prediction is hampered by uncertainty in the measures of response and selection of doses. In this study, we propose a probabilistic multi-output model to simultaneously predict all dose-responses and uncover their biomarkers. By describing the relationship between genomic features and chemical properties to every response at every dose, our multi-output Gaussian Process (MOGP) models enable assessment of drug efficacy using any dose-response metric.

Discovery of Hypoxanthine and Inosine as Robust Biomarkers for Predicting the Preanalytical Quality of Human Plasma and Serum for Metabolomics.

In cold human blood, the anomalous dynamics of adenosine triphosphate (ATP) result in the progressive accumulation of adenosine diphosphate (ADP), adenosine monophosphate (AMP), inosine monophosphate (IMP), inosine, and hypoxanthine. While the ATP, ADP, AMP, and IMP are confined to red blood cells (RBCs), inosine and hypoxanthine are excreted into plasma/serum. The plasma/serum levels of inosine and hypoxanthine depend on the temperature of blood and the plasma/serum contact time with the RBCs, and hence they represent robust biomarkers for evaluating the preanalytical quality of plasma/serum.

Cluster of Influenza A(H5) Cases Associated with Poultry Exposure at Two Facilities - Colorado, July 2024.

Persons who work in close contact with dairy cattle and poultry that are infected with highly pathogenic avian influenza (HPAI) A(H5N1) virus are at increased risk for infection. In July 2024, the Colorado Department of Public Health & Environment responded to two poultry facilities with HPAI A(H5N1) virus detections in poultry. Across the two facilities, 663 workers assisting with poultry depopulation (i.

Omada: robust clustering of transcriptomes through multiple testing.

Background: Cohort studies increasingly collect biosamples for molecular profiling and are observing molecular heterogeneity. High-throughput RNA sequencing is providing large datasets capable of reflecting disease mechanisms. Clustering approaches have produced a number of tools to help dissect complex heterogeneous datasets, but selecting the appropriate method and parameters to perform exploratory clustering analysis of transcriptomic data requires deep understanding of machine learning and extensive computational experimentation.

Dapagliflozin reduces systemic inflammation in patients with type 2 diabetes without known heart failure.

Objective: Sodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac outcomes via beneficial effects on systemic and cardiac inflammation and cardiac fibrosis.

Research And Design Methods: This randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type 2 diabetes (T2D) without known heart failure.

Measles Outbreak Associated with a Migrant Shelter - Chicago, Illinois, February-May 2024.

Measles, a highly contagious respiratory virus with the potential to cause severe complications, hospitalization, and death, was declared eliminated from the United States in 2000; however, with ongoing global transmission, infections in the United States still occur. On March 7, 2024, the Chicago Department of Public Health (CDPH) confirmed a case of measles in a male aged 1 year residing in a temporary shelter for migrants in Chicago. Given the congregate nature of the setting, high transmissibility of measles, and low measles vaccination coverage among shelter residents, measles virus had the potential to spread rapidly among approximately 2,100 presumed exposed shelter residents.