Protocol to establish an accelerated murine model for Helicobacter-induced gastric cancer.

Helicobacter-induced gastric cancer progresses very slowly, even in animal models, making it difficult to study. Here, we present a protocol to establish an accelerated murine model for Helicobacter-induced gastric cancer. We describe steps for infecting mice with Helicobacter felis, harvesting gastric tissue, assessing disease severity by histopathologic scoring, and performing gene expression studies with RT-qPCR and RNA sequencing.

Position-dependent function of human sequence-specific transcription factors.

Patterns of transcriptional activity are encoded in our genome through regulatory elements such as promoters or enhancers that, paradoxically, contain similar assortments of sequence-specific transcription factor (TF) binding sites. Knowledge of how these sequence motifs encode multiple, often overlapping, gene expression programs is central to understanding gene regulation and how mutations in non-coding DNA manifest in disease. Here, by studying gene regulation from the perspective of individual transcription start sites (TSSs), using natural genetic variation, perturbation of endogenous TF protein levels and massively parallel analysis of natural and synthetic regulatory elements, we show that the effect of TF binding on transcription initiation is position dependent.

Quality Improvement Project Reducing Sputum Cultures for Pediatric Patients With a Tracheostomy.

Background And Objectives: Current research implies overuse of diagnostic testing and overtreatment in children with tracheostomies. There are no guidelines for obtaining sputum cultures for these patients, yet they are commonly obtained without significantly affecting management or outcomes. The aim of our quality improvement project was to decrease rate of sputum cultures in this population by 50%, from 64% to 32%.

Triclosan administration to humanized UDP-glucuronosyltransferase 1 neonatal mice induces UGT1A1 through a dependence on PPARα and ATF4.

Triclosan (TCS) is an antimicrobial toxicant found in a myriad of consumer products and has been detected in human tissues, including breastmilk. We have evaluated the impact of lactational TCS on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) neonatal mice. In hUGT1 mice, expression of the hepatic UGT1A1 gene is developmentally delayed resulting in elevated total serum bilirubin (TSB) levels.

TRIF-IFN-I pathway in -induced gastric cancer in an accelerated murine disease model and patient biopsies.

( infection is a known cause of many digestive diseases, including gastritis, peptic ulcers, and gastric cancer. However, the underlying mechanisms by which infection triggers these disorders are still not clearly understood. Gastric cancer is a slow progressing disease, which makes it difficult to study.

Drug target prediction through deep learning functional representation of gene signatures.

Many machine learning applications in bioinformatics currently rely on matching gene identities when analyzing input gene signatures and fail to take advantage of preexisting knowledge about gene functions. To further enable comparative analysis of OMICS datasets, including target deconvolution and mechanism of action studies, we develop an approach that represents gene signatures projected onto their biological functions, instead of their identities, similar to how the word2vec technique works in natural language processing. We develop the Functional Representation of Gene Signatures (FRoGS) approach by training a deep learning model and demonstrate that its application to the Broad Institute's L1000 datasets results in more effective compound-target predictions than models based on gene identities alone.

Breakthrough infections by SARS-CoV-2 variants boost cross-reactive hybrid immune responses in mRNA-vaccinated Golden Syrian hamsters.

Hybrid immunity (vaccination + natural infection) to SARS-CoV-2 provides superior protection to re-infection. We performed immune profiling studies during breakthrough infections in mRNA-vaccinated hamsters to evaluate hybrid immunity induction. The mRNA vaccine, BNT162b2, was dosed to induce binding antibody titers against ancestral spike, but inefficient serum virus neutralization of ancestral SARS-CoV-2 or variants of concern (VoCs).

Clinical Predictors of Major Intrathoracic Injury in Pediatric Blunt Trauma.

Objectives: Blunt trauma in pediatric patients accounts for a significant proportion of pediatric death from traumatic injury. Currently, there are no clinical decision-making tools available to guide imaging choice in the evaluation of pediatric patients with blunt thoracic trauma (BTT). This study aimed to analyze the rates of missed major intrathoracic injuries on chest x-ray (CXR) and identify clinical risk factors associated with major intrathoracic injuries to formulate a clinical decision-making tool for computed tomography (CT) use in pediatric patients with BTT.

Effects of Early Life Oral Arsenic Exposure on Intestinal Tract Development and Lipid Homeostasis in Neonatal Mice: Implications for NAFLD Development.

Background: Newborns can be exposed to inorganic arsenic (iAs) through contaminated drinking water, formula, and other infant foods. Epidemiological studies have demonstrated a positive association between urinary iAs levels and the risk of developing nonalcoholic fatty liver disease (NAFLD) among U.S.

Breakthrough infections by SARS-CoV-2 variants boost cross-reactive hybrid immune responses in mRNA-vaccinated Golden Syrian Hamsters.

Hybrid immunity to SARS-CoV-2 provides superior protection to re-infection. We performed immune profiling studies during breakthrough infections in mRNA-vaccinated hamsters to evaluate hybrid immunity induction. mRNA vaccine, BNT162b2, was dosed to induce binding antibody titers against ancestral spike, but inefficient serum virus neutralization of ancestral SARS-CoV-2 or variants of concern (VoCs).

Combining TSS-MPRA and sensitive TSS profile dissimilarity scoring to study the sequence determinants of transcription initiation.

Cis-regulatory elements (CREs) can be classified by the shapes of their transcription start site (TSS) profiles, which are indicative of distinct regulatory mechanisms. Massively parallel reporter assays (MPRAs) are increasingly being used to study CRE regulatory mechanisms, yet the degree to which MPRAs replicate individual endogenous TSS profiles has not been determined. Here, we present a new low-input MPRA protocol (TSS-MPRA) that enables measuring TSS profiles of episomal reporters as well as after lentiviral reporter chromatinization.

Activation of the TRIF pathway and downstream targets results in the development of precancerous lesions during infection with .

( infection is an established cause of many digestive diseases, including gastritis, peptic ulcers, and gastric cancer. However, the mechanism by which infection with causes these disorders is still not clearly understood. This is due to insufficient knowledge of pathways that promote -induced disease progression.

Strain and sex-related behavioral variability of oxycodone dependence in rats.

Over the past two decades, the escalating prescription of opioid medications for pain management has culminated in a widespread opioid epidemic, significantly impacting public health, social dynamics, and economic stability. The urgent need for improved treatments for opioid addiction necessitates a deeper understanding of its biological underpinnings, with genetic variations playing a crucial role in individual susceptibility to opioid use disorder (OUD) and influencing clinical practices. In this study, we leverage the genetic diversity of four rat strains (ACI/N, BN/NHsd, WKY/N, and F344/N) to examine the contribution of genetic factors to oxycodone metabolism and addiction-like behaviors.

Bottle mix-up: Ethanol intoxication in an infant.

Alcohol intoxication is a common ingestion in pediatrics with close to 10,000 reports to poison control centers annually. Hypoglycemia, neurological depression (ataxia, coma, nystagmus, etc.) and unstable vitals (hypothermia, hypotension, bradycardia, and respiratory depression) are common presentations.

Oral arsenic administration to humanizedUDP-glucuronosyltransferase1 neonatal mice induces UGT1A1 through a dependence on Nrf2 and PXR.

Inorganic arsenic (iAs) is an environmental toxicant that can lead to severe health consequences, which can be exacerbated if exposure occurs early in development. Here, we evaluated the impact of oral iAs treatment on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) mice. We found that oral administration of iAs to neonatal hUGT1 mice that display severe neonatal hyperbilirubinemia leads to induction of intestinal UGT1A1 and a reduction in total serum bilirubin values.

Yeast derlin Dfm1 employs a chaperone-like function to resolve misfolded membrane protein stress.

Protein aggregates are a common feature of diseased and aged cells. Membrane proteins comprise a quarter of the proteome, and yet, it is not well understood how aggregation of membrane proteins is regulated and what effects these aggregates can have on cellular health. We have determined in yeast that the derlin Dfm1 has a chaperone-like activity that influences misfolded membrane protein aggregation.

Ovarian Torsion and Its Remediation in a Three-Year-Old Girl.

Ovarian torsion is a rare, emergent occurrence seen in the premenarchal population. If detected promptly, ovarian torsion can be treated via detorsion. We present a case of a three-year-old girl whose ovary spontaneously torsed and was corrected via ovarian detorsion.

An epidural brain abscess and thrombus in the superior sagittal sinus in a 12 year-old with sinusitis.

Background: Upper respiratory infections can be complicated by acute bacterial sinusitis in pediatric patients, and usually resolve with antibiotic therapy (DeMuri and Wald, 2011). However, intracranial complications such as: epidural abscess, meningitis and more rarely cerebral sinus venous thrombosis (CSVT) can occur (Germiller et al., 2006).

Classic Presentation of Catecholaminergic Polymorphic Ventricular Tachycardia: A Case Report.

Syncope is a common reason for children and adolescents to seek care in the emergency department. Often syncopal episodes are benign and most commonly due to a vasovagal event. Occasionally an underlying cardiac arrhythmia is responsible.

MEPP: more transparent motif enrichment by profiling positional correlations.

Score-based motif enrichment analysis (MEA) is typically applied to regulatory DNA to infer transcription factors (TFs) that may modulate transcription and chromatin state in different conditions. Most MEA methods determine motif enrichment independent of motif position within a sequence, even when those sequences harbor anchor points that motifs and their bound TFs may functionally interact with in a distance-dependent fashion, such as other TF binding motifs, transcription start sites (TSS), sequencing assay cleavage sites, or other biologically meaningful features. We developed motif enrichment positional profiling (MEPP), a novel MEA method that outputs a positional enrichment profile of a given TF's binding motif relative to key anchor points (e.

SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus.

The emergence of Zika virus (ZIKV) as a global health threat has highlighted the unmet need for ZIKV-specific vaccines and antiviral treatments. ZIKV infects dendritic cells (DC), which have pivotal functions in activating innate and adaptive antiviral responses; however, the mechanisms by which DC function is subverted to establish ZIKV infection are unclear. Here we develop a genomics profiling method that enables discrete analysis of ZIKV-infected versus neighboring, uninfected primary human DCs to increase the sensitivity and specificity with which ZIKV-modulated pathways can be identified.