Resolving chromatin-remodeling-linked gene expression changes at cell-type resolution is important for understanding disease states. Here we describe MAGICAL (Multiome Accessibility Gene Integration Calling and Looping), a hierarchical Bayesian approach that leverages paired single-cell RNA sequencing and single-cell transposase-accessible chromatin sequencing from different conditions to map disease-associated transcription factors, chromatin sites, and genes as regulatory circuits. By simultaneously modeling signal variation across cells and conditions in both omics data types, MAGICAL achieved high accuracy on circuit inference.
View Article and Find Full Text PDFBackground: Outcomes from Gram-negative bacteremia (GNB) in solid organ transplant (SOT) recipients are poorly understood.
Methods: This is a single center prospective cohort study comparing the clinical characteristics and outcomes of SOT recipients with GNB to immunocompetent non-SOT patients with GNB between 1/1/2002 through 12/31/2018. Outcomes of interest included incidence of septic shock, respiratory failure, and time to death.
Background: Staphylococcus aureus bacteremia (SAB) disproportionately affects Black patients. The reasons for this disparity are unclear.
Methods: We evaluated a prospectively ascertained cohort of patients with SAB from 1995 to 2020.
Importance: Obtaining follow-up blood cultures (FUBCs) in patients with Staphylococcus aureus bloodstream infection (BSI) is standard practice, although its utility in patients with gram-negative bacterial BSI (GN-BSI) is unclear.
Objective: To examine whether obtaining FUBCs is associated with decreased mortality (key question [KQ] 1) and whether positive vs negative FUBCs are associated with increased mortality (KQ2).
Data Sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and gray literature were searched from inception to March 11, 2022.
Introduction: Outcomes from Staphylococcus aureus bacteremia (SAB) in solid organ transplant (SOT) recipients are poorly understood.
Methods: This is a prospective cohort study comparing the bacterial genotype and clinical outcomes of SAB among SOT and non-transplant (non-SOT) recipients from 2005 to 2019. Each subject's initial S.
Rationale & Objective: Staphylococcus aureus (Saureus) bacteremia (SAB) is associated with morbidity and mortality in patients receiving maintenance hemodialysis (HD). We evaluated changes in clinical and bacterial characteristics, and their associations with clinical outcomes with SAB in this population over a 21-year period.
Study Design: Prospective cohort study.
Background: The epidemiology, and outcome of infective endocarditis (IE) among solid organ transplant (SOT) recipients is unknown.
Methods: We used data from the 2013-2018 Nationwide Readmissions Database (NRD). IE- and SOT-associated hospitalizations were identified using diagnosis and procedure codes.
Background: Infective endocarditis (IE) is a rare but serious infection that complicates pregnancy. Little is known about IE management and outcomes in this population.
Methods: The National Readmissions Database was used to obtain data between October 2015 and October 2018.
We undertook a prospective, matched cohort study of patients with Staphylococcus aureus bacteremia (SAB) and gram-negative bacteremia (GNB) to compare the characteristics, outcomes, and chemokine and cytokine response in transplant recipients to immunocompetent, nontransplant recipients. Fifty-five transplant recipients (GNB n = 29; SAB n = 26) and 225 nontransplant recipients (GNB n = 114; SAB n = 111) were included for clinical analysis. Transplant GNB had a significantly lower incidence of septic shock than nontransplant GNB (10.
View Article and Find Full Text PDFEur J Clin Microbiol Infect Dis
November 2020
The complement system is a vital component of the innate immune system, though its role in bacteremia is poorly understood. We present complement levels in Staphylococcus aureus bacteremia (SAB) and Gram-negative bacteremia (GNB) and describe observed associations of complement levels with clinical outcomes. Complement and cytokine levels were measured in serum samples from 20 hospitalized patients with SAB, 20 hospitalized patients with GNB, 10 non-infected hospitalized patients, and 10 community controls.
View Article and Find Full Text PDFBackground: To understand the clinical, bacterial, and host characteristics associated with recurrent Staphylococcus aureus bacteremia (R-SAB), patients with R-SAB were compared to contemporaneous patients with a single episode of SAB (S-SAB).
Methods: All SAB isolates underwent spa genotyping. All isolates from R-SAB patients underwent pulsed-field gel electrophoresis (PFGE).
Historically, intravenous (IV) antibiotics have been the cornerstone of treatment for uncomplicated bacteremia (SAB). However, IV antibiotics are expensive, increase the rates of hospital readmission, and can be associated with catheter-related complications. As a result, the potential role of oral antibiotics in the treatment of uncomplicated SAB has become a subject of interest.
View Article and Find Full Text PDFCefiderocol is a novel catechol siderophore cephalosporin antibiotic developed to treat resistant gram-negative infections. We describe its successful use as rescue therapy, combined with surgical debridement, to treat a patient with osteomyelitis due to extensively drug-resistant Bacterial whole-genome sequencing identified the strain and antibiotic resistance determinants.
View Article and Find Full Text PDFBackground: Currently, only indirect evidence suggests that preoperative pneumonia is a significant risk factor for poor postsurgical outcomes. Although this relationship is clinically intuitive, this is the first study that aims to quantify the extent to which pneumonia impacts morbidity and mortality. The objective of this study was to determine the impact of preoperative pneumonia on 30-day mortality and morbidity among both elective and emergency surgical patients.
View Article and Find Full Text PDFPublic Health Genomics
April 2018
Purpose: As precision medicine continues its expansion into clinical practice and research settings, it is time to investigate genetic and genomic research in the Middle East and North Africa (MENA) region to identify the strengths and deficits and to provide suggestions for future development.
Methods: We performed a literature review of any genetic or genomic publications on breast cancer and type 2 diabetes for the years 2000-2015 and evaluated the translational value of the research using multiple evaluation metrics, including the "continuum of translation" and the Health Impact Pyramid.
Results: A total of 138 type 2 diabetes and 231 breast cancer publications were included.
Background: Most educational institutions lack a structured system that provides undergraduate students with research exposure in the medical field. The objective of this paper is to describe the structure of the Medical Research Volunteer Program (MRVP) which was established at the American University of Beirut, Lebanon, as well as to assess the success of the program.
Methods: The MRVP is a program that targets undergraduate students interested in becoming involved in the medical research field early on in their academic career.