Gene Expression Profiling in Pediatric Appendicitis.

Importance: Appendicitis is the most common indication for urgent surgery in the pediatric population, presenting across a range of severity and with variable complications. Differentiating simple appendicitis (SA) and perforated appendicitis (PA) on presentation may help direct further diagnostic workup and appropriate therapy selection, including antibiotic choice and timing of surgery.

Objective: To provide a mechanistic understanding of the differences in disease severity of appendicitis with the objective of developing improved diagnostics and treatments, specifically for the pediatric population.

Persistence is key: unresolved immune dysfunction is lethal in both COVID-19 and non-COVID-19 sepsis.

Introduction: Severe COVID-19 and non-COVID-19 pulmonary sepsis share pathophysiological, immunological, and clinical features, suggesting that severe COVID-19 is a form of viral sepsis. Our objective was to identify shared gene expression trajectories strongly associated with eventual mortality between severe COVID-19 patients and contemporaneous non-COVID-19 sepsis patients in the intensive care unit (ICU) for potential therapeutic implications.

Methods: Whole blood was drawn from 20 COVID-19 patients and 22 non-COVID-19 adult sepsis patients at two timepoints: ICU admission and approximately a week later.

Post-COVID symptoms are associated with endotypes reflecting poor inflammatory and hemostatic modulation.

Introduction: Persistent symptoms after COVID-19 infection ("long COVID") negatively affects almost half of COVID-19 survivors. Despite its prevalence, its pathophysiology is poorly understood, with multiple host systems likely affected. Here, we followed patients from hospital to discharge and used a systems-biology approach to identify mechanisms of long COVID.

Facilitating systems-level analyses of all-cause and Covid-mediated sepsis through SeptiSearch, a manually-curated compendium of dysregulated gene sets.

Background: Sepsis is a dysfunctional host response to infection. The syndrome leads to millions of deaths annually (19.7% of all deaths in 2017) and is the cause of most deaths from severe Covid infections.

Severe COVID-19 and non-COVID-19 severe sepsis converge transcriptionally after a week in the intensive care unit, indicating common disease mechanisms.

Introduction: Severe COVID-19 and non-COVID-19 pulmonary sepsis share pathophysiological, immunological, and clinical features. To what extent they share mechanistically-based gene expression trajectories throughout hospitalization was unknown. Our objective was to compare gene expression trajectories between severe COVID-19 patients and contemporaneous non-COVID-19 severe sepsis patients in the intensive care unit (ICU).

Predicting severity in COVID-19 disease using sepsis blood gene expression signatures.

Severely-afflicted COVID-19 patients can exhibit disease manifestations representative of sepsis, including acute respiratory distress syndrome and multiple organ failure. We hypothesized that diagnostic tools used in managing all-cause sepsis, such as clinical criteria, biomarkers, and gene expression signatures, should extend to COVID-19 patients. Here we analyzed the whole blood transcriptome of 124 early (1-5 days post-hospital admission) and late (6-20 days post-admission) sampled patients with confirmed COVID-19 infections from hospitals in Quebec, Canada.

Gene Expression Profiling: Identification of Novel Pathways and Potential Biomarkers in Severe Acute Pancreatitis.

Background: Determining the risk of developing severe acute pancreatitis (AP) on presentation to hospital is difficult but vital to enable early management decisions that reduce morbidity and mortality. The objective of this study was to determine global gene expression profiles of patients with different acute pancreatitis severity to identify genes and molecular mechanisms involved in the pathogenesis of severe AP.

Study Design: AP patients (n = 87) were recruited within 24 hours of admission to the Emergency Department and were confirmed to exhibit at least 2 of the following features: (1) abdominal pain characteristic of AP, (2) serum amylase and/or lipase more than 3-fold the upper laboratory limit considered normal, and/or (3) radiographically demonstrated AP on CT scan.

Predicting sepsis severity at first clinical presentation: The role of endotypes and mechanistic signatures.

Background: Inter-individual variability during sepsis limits appropriate triage of patients. Identifying, at first clinical presentation, gene expression signatures that predict subsequent severity will allow clinicians to identify the most at-risk groups of patients and enable appropriate antibiotic use.

Methods: Blood RNA-Seq and clinical data were collected from 348 patients in four emergency rooms (ER) and one intensive-care-unit (ICU), and 44 healthy controls.

An Overview of Biological and Computational Methods for Designing Mechanism-Informed Anti-biofilm Agents.

Bacterial biofilms are complex and highly antibiotic-resistant aggregates of microbes that form on surfaces in the environment and body including medical devices. They are key contributors to the growing antibiotic resistance crisis and account for two-thirds of all infections. Thus, there is a critical need to develop anti-biofilm specific therapeutics.

Systems Biology Approaches to Understanding the Human Immune System.

Systems biology is an approach to interrogate complex biological systems through large-scale quantification of numerous biomolecules. The immune system involves >1,500 genes/proteins in many interconnected pathways and processes, and a systems-level approach is critical in broadening our understanding of the immune response to vaccination. Changes in molecular pathways can be detected using high-throughput omics datasets (e.

The Stringent Stress Response Controls Proteases and Global Regulators under Optimal Growth Conditions in Pseudomonas aeruginosa.

The bacterial stringent stress response, mediated by the signaling molecule guanosine tetraphosphate, ppGpp, has recently gained attention as being important during normal cellular growth and as a potential new therapeutic target, which warrants detailed mechanistic understanding. Here, we used intracellular protein tracking in PAO1, which indicated that RelA was bound to the ribosome, while SpoT localized at the cell poles. Transcriptome sequencing (RNA-Seq) was used to investigate the transcriptome of a ppGpp-deficient strain under nonstressful, nutrient-rich broth conditions where the mutant grew at the same rate as the parent strain.

NtrBC Regulates Invasiveness and Virulence of During High-Density Infection.

is an opportunistic pathogen that is a major cause of nosocomial and chronic infections contributing to morbidity and mortality in cystic fibrosis patients. One of the reasons for its success as a pathogen is its ability to adapt to a broad range of circumstances. Here, we show the involvement of the general nitrogen regulator NtrBC, which is structurally conserved but functionally diverse across species, in pathogenic and adaptive states of .