Transpulmonary generation of cell-free hemoglobin contributes to vascular dysfunction in pulmonary arterial hypertension via dysregulated clearance mechanisms.

Circulating cell-free hemoglobin (CFH) is elevated in pulmonary arterial hypertension (PAH) and associated with poor outcomes but the mechanisms are unknown. We hypothesized that CFH is generated from the pulmonary circulation and inadequately cleared in PAH. Transpulmonary CFH (difference between wedge and pulmonary artery positions) and lung hemoglobin α were analyzed in patients with PAH and healthy controls.

Scanning the medical phenome to identify new diagnoses after recovery from COVID-19 in a US cohort.

Objective: COVID-19 survivors are at risk for long-term health effects, but assessing the sequelae of COVID-19 at large scales is challenging. High-throughput methods to efficiently identify new medical problems arising after acute medical events using the electronic health record (EHR) could improve surveillance for long-term consequences of acute medical problems like COVID-19.

Materials And Methods: We augmented an existing high-throughput phenotyping method (PheWAS) to identify new diagnoses occurring after an acute temporal event in the EHR.

An Iron Refractory Phenotype in Obese Adipose Tissue Macrophages Leads to Adipocyte Iron Overload.

Adipocyte iron overload is a maladaptation associated with obesity and insulin resistance. The objective of the current study was to determine whether and how adipose tissue macrophages (ATMs) regulate adipocyte iron concentrations and whether this is impacted by obesity. Using bone marrow-derived macrophages (BMDMs) polarized to M0, M1, M2, or metabolically activated (MMe) phenotypes, we showed that MMe BMDMs and ATMs from obese mice have reduced expression of several iron-related proteins.

Integrating gene expression and clinical data to identify drug repurposing candidates for hyperlipidemia and hypertension.

Discovering novel uses for existing drugs, through drug repurposing, can reduce the time, costs, and risk of failure associated with new drug development. However, prioritizing drug repurposing candidates for downstream studies remains challenging. Here, we present a high-throughput approach to identify and validate drug repurposing candidates.

ConceptWAS: A high-throughput method for early identification of COVID-19 presenting symptoms and characteristics from clinical notes.

Objective: Identifying symptoms and characteristics highly specific to coronavirus disease 2019 (COVID-19) would improve the clinical and public health response to this pandemic challenge. Here, we describe a high-throughput approach - Concept-Wide Association Study (ConceptWAS) - that systematically scans a disease's clinical manifestations from clinical notes. We used this method to identify symptoms specific to COVID-19 early in the course of the pandemic.

ConceptWAS: a high-throughput method for early identification of COVID-19 presenting symptoms.

Objective: Identifying symptoms highly specific to COVID-19 would improve the clinical and public health response to infectious outbreaks. Here, we describe a high-throughput approach - Concept-Wide Association Study (ConceptWAS) that systematically scans a disease's clinical manifestations from clinical notes. We used this method to identify symptoms specific to COVID-19 early in the course of the pandemic.

Detecting time-evolving phenotypic topics via tensor factorization on electronic health records: Cardiovascular disease case study.

Objective: Discovering subphenotypes of complex diseases can help characterize disease cohorts for investigative studies aimed at developing better diagnoses and treatments. Recent advances in unsupervised machine learning on electronic health record (EHR) data have enabled researchers to discover phenotypes without input from domain experts. However, most existing studies have ignored time and modeled diseases as discrete events.