For several decades, protein drugs (biologics) made in cell cultures have been delivered as sterile injections, decreasing their affordability and patient preference. Angiotensin Converting Enzyme 2 (ACE2) gum is the first engineered human blood protein expressed in plant cells approved by the FDA without the need for purification and is a cold-chain and noninvasive drug delivery. This biologic is currently being evaluated in human clinical studies to debulk SARS-CoV-2 in the oral cavity to reduce coronavirus infection/transmission (NCT00543318).
View Article and Find Full Text PDFBackground: Accurate assessment of cardiovascular disease (CVD) risk is crucial for effective prevention and resource allocation. However, few CVD risk estimation tools consider social determinants of health (SDoH), despite their known impact on CVD risk. We aimed to estimate 10-year CVD risk in the Eastern Caribbean Health Outcomes Research Network Cohort Study (ECS) across multiple risk estimation instruments and assess the association between SDoH and CVD risk.
View Article and Find Full Text PDFBackground: Verbal autopsy (VA) has been a crucial tool in ascertaining population-level cause of death (COD) estimates, specifically in countries where medical certification of COD is relatively limited. The World Health Organization has released an updated instrument (Verbal Autopsy Instrument 2022) that supports electronic data collection methods along with analytical software for assigning COD. This questionnaire encompasses the primary signs and symptoms associated with prevalent diseases across all age groups.
View Article and Find Full Text PDFThe hypertension patient population has doubled since 1990, affecting 1.3 billion globally and >75% live in low-and middle-income countries. Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB) are the most prescribed drugs (>160 million times in the US), but mortality increased >30% since 1990s globally.
View Article and Find Full Text PDFDespite extensive mapping of cis-regulatory elements (cREs) across cellular contexts with chromatin accessibility assays, the sequence syntax and genetic variants that regulate transcription factor (TF) binding and chromatin accessibility at context-specific cREs remain elusive. We introduce ChromBPNet, a deep learning DNA sequence model of base-resolution accessibility profiles that detects, learns and deconvolves assay-specific enzyme biases from regulatory sequence determinants of accessibility, enabling robust discovery of compact TF motif lexicons, cooperative motif syntax and precision footprints across assays and sequencing depths. Extensive benchmarks show that ChromBPNet, despite its lightweight design, is competitive with much larger contemporary models at predicting variant effects on chromatin accessibility, pioneer TF binding and reporter activity across assays, cell contexts and ancestry, while providing interpretation of disrupted regulatory syntax.
View Article and Find Full Text PDF