Computational Approaches to Drug Repurposing: Methods, Challenges, and Opportunities.

Drug repurposing refers to the inference of therapeutic relationships between a clinical indication and existing compounds. As an emerging paradigm in drug development, drug repurposing enables more efficient treatment of rare diseases, stratified patient populations, and urgent threats to public health. However, prioritizing well-suited drug candidates from among a nearly infinite number of repurposing options continues to represent a significant challenge in drug development.

Genetic Correlations Among Corneal Biophysical Parameters and Anthropometric Traits.

Purpose: The genetic architecture of corneal dysfunction remains poorly understood. Epidemiological and clinical evidence suggests a relationship between corneal structural features and anthropometric measures. We used global and local genetic similarity analysis to identify genomic features that may underlie structural corneal dysfunction.

Integrative analysis of functional genomic screening and clinical data identifies a protective role for spironolactone in severe COVID-19.

We demonstrate that integrative analysis of CRISPR screening datasets enables network-based prioritization of prescription drugs modulating viral entry in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by developing a network-based approach called Rapid proXimity Guidance for Repurposing Investigational Drugs (RxGRID). We use our results to guide a propensity-score-matched, retrospective cohort study of 64,349 COVID-19 patients, showing that a top candidate drug, spironolactone, is associated with improved clinical prognosis, measured by intensive care unit (ICU) admission and mechanical ventilation rates. Finally, we show that spironolactone exerts a dose-dependent inhibitory effect on viral entry in human lung epithelial cells.

Assessment of Team Dynamics and Operative Efficiency in Hip and Knee Arthroplasty.

Importance: Surgical team communication is a critical component of operative efficiency. The factors underlying optimal communication, including team turnover, role composition, and mutual familiarity, remain underinvestigated in the operating room.

Objective: To assess staff turnover, trainee involvement, and surgeon staff preferences in terms of intraoperative efficiency.

Association between spironolactone use and COVID-19 outcomes in population-scale claims data: a retrospective cohort study.

Background: Spironolactone has been proposed as a potential modulator of SARS-CoV-2 cellular entry. We aimed to measure the effect of spironolactone use on the risk of adverse outcomes following COVID-19 hospitalization.

Methods: We performed a retrospective cohort study of COVID-19 outcomes for patients with or without exposure to spironolactone, using population-scale claims data from the Komodo Healthcare Map.

Influence of team composition on turnover and efficiency of total hip and knee arthroplasty.

Aims: Surgical costs are a major component of healthcare expenditures in the USA. Intraoperative communication is a key factor contributing to patient outcomes. However, the effectiveness of communication is only partially determined by the surgeon, and understanding how non-surgeon personnel affect intraoperative communication is critical for the development of safe and cost-effective staffing guidelines.

Regional Infoveillance of COVID-19 Case Rates: Analysis of Search-Engine Query Patterns.

Background: Timely allocation of medical resources for coronavirus disease (COVID-19) requires early detection of regional outbreaks. Internet browsing data may predict case outbreaks in local populations that are yet to be confirmed.

Objective: We investigated whether search-engine query patterns can help to predict COVID-19 case rates at the state and metropolitan area levels in the United States.

Nailfold Capillary Morphology in Alzheimer's Disease Dementia.

Background: Cerebrovascular disease (CVD) is highly comorbid with Alzheimer's disease (AD), yet its role is not entirely understood. Nailfold video capillaroscopy (NVC) is a noninvasive method of live imaging the capillaries near the fingernail's cuticle and may help to describe further vascular contributions to AD.

Objective: To examine finger nailfold capillary morphology using NVC in subjects with AD dementia, mild cognitive impairment (MCI), and normal cognition (NC).

Toward Precision Medicine for Neurological and Neuropsychiatric Disorders.

The genetic complexity, clinical variability, and inaccessibility of affected tissue in neurodegenerative and neuropsychiatric disorders have largely prevented the development of effective disease-modifying therapeutics. A precision medicine approach that integrates genomics, deep clinical phenotyping, and patient stem cell models may facilitate identification of underlying biological drivers and targeted drug development.