ABSTRACT
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replication transcription complex (RTC) is a multi-domain protein responsible for replicating and transcribing the viral mRNA inside a human cell. Attacking RTC function with pharmaceutical compounds is a pathway to treating COVID-19. Conventional tools, e.g., cryo-electron microscopy and all-atom molecular dynamics (AAMD), do not provide sufficiently high resolution or timescale to capture important dynamics of this molecular machine. Consequently, we develop an innovative workflow that bridges the gap between these resolutions, using mesoscale fluctuating finite element analysis (FFEA) continuum simulations and a hierarchy of AI-methods that continually learn and infer features for maintaining consistency between AAMD and FFEA simulations. We leverage a multi-site distributed workflow manager to orchestrate AI, FFEA, and AAMD jobs, providing optimal resource utilization across HPC centers. Our study provides unprecedented access to study the SARS-CoV-2 RTC machinery, while providing general capability for AI-enabled multi-resolution simulations at scale.
ABSTRACT
Hyperthyroidism is associated with an elevated risk of cardiovascular events and worse hospital outcomes. The Nationwide Readmissions Database (NRD) 2018 was used to determine the characteristics of 30-day readmission in patients with hyperthyroidism. The 30-day all-cause readmission rate for hyperthyroidism was 10.3%. About 21.7% had hyperthyroidism as the principal diagnosis on readmission. Readmissions were associated with an increased odds of inpatient mortality (odds ratio, 7.04; 95% confidence interval [CI], 3.97 to 12.49), length of stay (5.2 days vs. 4.0 days; 95% CI, 0.7 to 1.8), total hospital charges, and cost of hospitalizations. Independent predictors of 30-day all-cause readmissions included Charlson Comorbidity Index ≥3 (adjusted hazard ratio [aHR], 1.76; 95% CI, 1.15 to 2.71), discharge against medical advice (aHR, 2.30; 95% CI, 1.50 to 3.53), protein-energy malnutrition (aHR, 1.54; 95% CI, 1.15 to 2.07), and atrial fibrillation (aHR, 1.41; 95% CI, 1.11 to 1.79). Aggressive but appropriate monitoring is warranted in patients with hyperthyroidism to prevent readmissions.