Genetic Studies Through the Lens of Gene Networks.

Understanding the genetic basis of complex traits is a longstanding challenge in the field of genomics. Genome-wide association studies have identified thousands of variant-trait associations, but most of these variants are located in noncoding regions, making the link to biological function elusive. While traditional approaches, such as transcriptome-wide association studies (TWAS), have advanced our understanding by linking genetic variants to gene expression, they often overlook gene-gene interactions.

GTExome: Modeling commonly expressed missense mutations in the human genome.

A web application, GTExome, is described that quickly identifies, classifies, and models missense mutations in commonly expressed human proteins. GTExome can be used to categorize genomic mutation data with tissue specific expression data from the Genotype-Tissue Expression (GTEx) project. Commonly expressed missense mutations in proteins from a wide range of tissue types can be selected and assessed for modeling suitability.

Regulation of chromatin architecture by transcription factor binding.

Transcription factors (TF) bind to chromatin and regulate the expression of genes. The pair Myc:Max binds to E-box regulatory DNA elements throughout the genome to control the transcription of a large group of specific genes. We introduce an implicit modeling protocol for Myc:Max binding to mesoscale chromatin fibers at nucleosome resolution to determine TF effect on chromatin architecture and shed light into its mechanism of gene regulation.

GTExome: Modeling commonly expressed missense mutations in the human genome.

A web application, GTExome, is described that quickly identifies, classifies, and models missense mutations in commonly expressed human proteins. GTExome can be used to categorize genomic mutation data with tissue specific expression data from the Genotype-Tissue Expression (GTEx) project. Commonly expressed missense mutations in proteins from a wide range of tissue types can be selected and assessed for modeling suitability.

Regulation of Chromatin Architecture by Transcription Factor Binding.

Transcription factors (TF) bind to chromatin and regulate the expression of genes. The pair Myc:Max binds to E-box regulatory DNA elements throughout the genome, controlling transcription of a large group of specific genes. We introduce an implicit modeling protocol for Myc:Max binding to mesoscale chromatin fibers to determine TF effect on chromatin architecture and shed light on its mechanism of gene regulation.

Distinct Patterns of Gene Expression Changes in the Colon and Striatum of Young Mice Overexpressing Alpha-Synuclein Support Parkinson's Disease as a Multi-System Process.

Background: Evidence supports a role for the gut-brain axis in Parkinson's disease (PD). Mice overexpressing human wild type α- synuclein (Thy1-haSyn) exhibit slow colonic transit prior to motor deficits, mirroring prodromal constipation in PD. Identifying molecular changes in the gut could provide both biomarkers for early diagnosis and gut-targeted therapies to prevent progression.

Loss of miR-24-3p promotes epithelial cell apoptosis and impairs the recovery from intestinal inflammation.

While apoptosis plays a significant role in intestinal homeostasis, it can also be pathogenic if overactive during recovery from inflammation. We recently reported that microRNA-24-3p (miR-24-3p) is elevated in the colonic epithelium of ulcerative colitis patients during active inflammation, and that it reduced apoptosis in vitro. However, its function during intestinal restitution following inflammation had not been examined.

Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.

Background: Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis.

Methods: This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites.

Perinatal Depression in Low-Income Women: A Literature Review and Innovative Screening Approach.

Purpose Of Review: This paper reviews literature on perinatal depression prevalence, consequences, and screening among low-income women and women of color. We introduce the Warm Connections program's innovative perinatal depression screening protocol and explore perinatal depression patterns among WIC participants.

Recent Findings: Perinatal depression negatively impacts maternal and child outcomes.

Elucidating the influence of supervisors' roles on implementation climate.

Background: Supervisors play an essential role in implementation by diffusing and synthesizing information, selling implementation, and translating top management's project plans to frontline workers. Theory and emerging evidence suggest that through these roles, supervisors shape implementation climate-i.e.

Building community in the gut: a role for mucosal serotonin.

A new study reveals that a novel serotonin sensor in the spore-forming gut bacteria, , might be important for host lipid and steroid metabolism. These findings support the emerging concept that bidirectional signalling pathways can influence bacterial community structure and exert effects on host physiology.

Mesenteric Adipose-derived Stromal Cells From Crohn's Disease Patients Induce Protective Effects in Colonic Epithelial Cells and Mice With Colitis.

Mesenteric adipose tissue hyperplasia is a hallmark of Crohn's disease (CD). Recently, we showed that mesenteric adipose-derived stromal cells (ADSCs) from CD, ulcerative colitis, and control patients synthesize and release adipokines in a disease-dependent manner. Here we examined the expression profiles of CD and control patient-derived mesenteric ADSCs and studied the effects of their extracellular mediators on colonocyte signaling in vitro and experimental colitis in vivo.

Sigmoid colon mucosal gene expression supports alterations of neuronal signaling in irritable bowel syndrome with constipation.

Peripheral factors likely play a role in at least a subset of irritable bowel syndrome (IBS) patients. Few studies have investigated mucosal gene expression using an unbiased approach. Here, we performed mucosal gene profiling in a sex-balanced sample to identify relevant signaling pathways and gene networks and compare with publicly available profiling data from additional cohorts.

Osteoarticular Infections Caused by Streptococcus pneumoniae in Children in the Post-Pneumococcal Conjugate Vaccine Era.

Background: Pneumococcal osteoarticular infections (OAIs) are an uncommon manifestation of invasive pneumococcal disease (IPD). We describe the demographic characteristics, hospitalization rate, serotype distribution and antibiotic susceptibility of children with pneumococcal OAI over a 16-year period.

Methods: We identified patients ≤18 years old with pneumococcal OAI at 8 children's hospitals in the United States (2000-2015).

Invasive Pneumococcal Disease in Infants Aged 0-60 Days in the United States in the 13-Valent Pneumococcal Conjugate Vaccine Era.

We identified 53 infants aged 0-60 days with invasive pneumococcal disease (IPD) at 8 children's hospitals in the United States (2005-2015). After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13), IPD caused by PCV13 serotypes decreased ~30% providing some evidence of indirect protection. However, approximately 60% of IPD was still caused by PCV13 serotypes.

Pneumococcal Pneumonia Requiring Hospitalization in US Children in the 13-Valent Pneumococcal Conjugate Vaccine Era.

Background.: The impact of PCV13 on a number of clinical aspects of pneumococcal pneumonia (PP) in children has not been reported. We compared the serotype distribution, antibiotic susceptibility, and outcomes of children with PP 4 years before and 4 years after the introduction of PCV13.

XIVth Little Brain Big Brain: next-generation enteric neuroscience.

Little Brain Big Brain has been a biannual meeting organized and attended exclusively by young investigators in neurogastroenterology since 1989. The XIVth meeting featured cutting-edge work advancing several novel hypotheses in the main themes of motility, inflammation and metabolism.

Invasive pneumococcal infections in children following transplantation in the pneumococcal conjugate vaccine era.

Background: Pediatric recipients of hematopoietic stem cell and solid organ transplants are at increased risk of invasive pneumococcal infections (IPI). Data on IPI in this population are scarce. To our knowledge, this is the first study describing the epidemiology of IPI among pediatric transplant recipients in the pneumococcal conjugate vaccine (PCV) era.

Emergence of Multidrug-Resistant Pneumococcal Serotype 35B among Children in the United States.

serotype 35B is a nonvaccine serotype associated with high rates of penicillin nonsusceptibility. An increase in the proportion of multidrug-resistant (MDR) 35B isolates has recently been reported. The genetic events contributing to the emergence of MDR serotype 35B are unknown.