Simplified methods for variance estimation in microbiome abundance count data analysis.

The complex nature of microbiome data has made the differential abundance analysis challenging. Microbiome abundance counts are often skewed to the right and heteroscedastic (also known as overdispersion), potentially leading to incorrect inferences if not properly addressed. In this paper, we propose a simple yet effective framework to tackle the challenges by integrating Poisson (log-linear) regression with standard error estimation through the Bootstrap method and Sandwich robust estimation.

The Post-transplant Lymphoproliferative Disorders-Metagenomic Shotgun Microbial Sequencing (PTLD-MSMS) Study Methods and Protocol.

Post-transplant lymphoproliferative disorders (PTLDs) remain a feared complication of transplantation, with significant morbidity and mortality. The oncogenic Epstein-Barr virus (EBV) is a key pathogenic driver in 50%-80% of cases. Numerous prognostic indices, comprising multiple clinical, epidemiological and tumor characteristics, including EBV tumor positivity, do not consistently associate with worse patient survival, suggesting a potential role for EBV genome variants in determining outcome.

Metagenomic Analysis of DNA Viruses with Targeted Sequence Capture of Canine Lobular Orbital Adenomas and Normal Conjunctiva.

Our study aims are: (1) to evaluate phenotypically normal canine conjunctival and orbital tissue and tissue from canine lobular orbital adenomas (CLOAs) for the presence of viral genomic material and (2) phylogenetically classify detected DNA viruses to determine if a DNA virus is associated with CLOAs. A total of 31 formalin fixed paraffin embedded CLOA tissue samples, 4 papillomas or sarcoid, and 10 fresh clinically normal conjunctival tissues were included in this study. Genomic DNA was isolated from all samples and sequencing libraries were prepared.

Virome Analysis and Association of Positive Coxsackievirus B Serology during Pregnancy with Congenital Heart Disease.

Background: We have previously shown coxsackievirus B (CVB) to be a potent inducer of congenital heart disease (CHD) in mice. The clinical relevance of these findings in humans and the roles of other viruses in the pathogenesis of CHD remain unknown.

Methods: We obtained plasma samples, collected at all trimesters, from 89 subjects (104 pregnancies), 73 healthy controls (88 pregnancies), and 16 with CHD-affected birth (16 pregnancies), from the Perinatal Family Tissue Bank (PFTB).

Pathogen and Antibody Identification in Children with Encephalitis in Myanmar.

Objective: Prospective studies of encephalitis are rare in regions where encephalitis is prevalent, such as low middle-income Southeast Asian countries. We compared the diagnostic yield of local and advanced tests in cases of pediatric encephalitis in Myanmar.

Methods: Children with suspected subacute or acute encephalitis at Yangon Children's Hospital, Yangon, Myanmar, were prospectively recruited from 2016-2018.

A Case of Persistent Human Pegivirus Infection in Two Separate Pregnancies of a Woman.

Human pegivirus (HPgV) is best known for persistent, presumably non-pathogenic, infection and a propensity to co-infect with human immunodeficiency virus or hepatitis C virus. However, unique attributes, such as the increased risk of malignancy or immune modulation, have been recently recognized for HPgV. We have identified a unique case of a woman with high levels HPgV infection in two pregnancies, which occurred 4 years apart and without evidence of human immunodeficiency virus or hepatitis C virus infection.

Comparison of Metagenomic Sequencing and the NanoString nCounter Analysis System for the Characterization of Bacterial and Viral Communities in Vaginal Samples.

DNA sequencing assays have been used to characterize the vaginal microbiome and to identify associations with clinical outcomes. The purpose of this study was to evaluate the utility of the NanoString nCounter platform, a more efficient assay compared to sequencing, for the characterization of vaginal microbial communities. A panel of NanoString nCounter probes was designed to detect common vaginal bacteria and viruses with relevance to reproductive health.

Longitudinal Dynamics of Skin Bacterial Communities in the Context of Staphylococcus aureus Decolonization.

Decolonization with topical antimicrobials is frequently prescribed in health care and community settings to prevent Staphylococcus aureus infection. However, effects on commensal skin microbial communities remains largely unexplored. Within a household affected by recurrent methicillin-resistant S.

Fecal microbiome and bile acid metabolome in adult short bowel syndrome.

Loss of functional small bowel surface area causes short bowel syndrome (SBS), intestinal failure, and parenteral nutrition (PN) dependence. The gut adaptive response following resection may be difficult to predict, and it may take up to 2 yr to determine which patients will wean from PN. Here, we examined features of gut microbiota and bile acid (BA) metabolism in determining adaptation and ability to wean from PN.

A national survey of pediatric emergency medicine physicians on improving education in child maltreatment recognition and reporting child abuse & neglect.

Background: Child maltreatment is an important public health problem with serious consequences. Even in the face of increased research and enhanced public awareness over the last decade, the rate of child fatalities due to reported child maltreatment has increased.

Objective: This study describes pediatric emergency medicine (PEM) physicians' knowledge, training, confidence, and barriers in recognition and reporting suspected child maltreatment.

Chronic villitis of unknown etiology: Investigations into viral pathogenesis.

Introduction: Chronic villitis of unknown etiology (VUE) is a chronic inflammatory lesion of third trimester placenta, which contributes to major adverse obstetric outcomes. However, the inciting factors and mechanisms by which VUE contributes to adverse outcomes are poorly understood. This limits our ability to develop preventions or interventions.

ViroMatch: A Computational Pipeline for the Detection of Viral Sequences from Complex Metagenomic Data.

ViroMatch is an automated pipeline that takes metagenomic sequencing reads as input and performs iterative nucleotide and translated nucleotide mapping to identify viral sequences. We provide a Docker image for ViroMatch, so that users will not have to install dependencies.

Methods and implementation of a pediatric asthma pharmacogenomic study in the emergency department setting.

Objectives: The emergency department (ED) is a challenging setting to conduct pharmacogenomic studies and integrate that data into fast-paced and potentially life-saving treatment decisions. Therefore, our objective is to present the methods and feasibility of a pilot pharmacogenomic study set in the ED that measured pediatric bronchodilator response (BDR) during acute asthma exacerbations.

Methods: This is an exploratory pilot study that collected buccal swabs for DNA and measured BDR during ED encounters for pediatric asthma exacerbations.

Using an Online Vaccination Registry to Confirm Tetanus Status in Children with Tetanus-prone Wounds.

Introduction: Tetanus vaccination status is an important consideration for emergency physicians managing patients with tetanus-prone wounds. Physicians must identify at-risk patients, but vaccination histories are often unknown and commonly lack documentation. The study objective was to determine the potential impact of an online immunization registry (Florida SHOTS - State Health Online Tracking System) on the appropriate administration of tetanus prophylaxis for pediatric patients managed in the emergency department (ED).

A virome sequencing approach to feline oral squamous cell carcinoma to evaluate viral causative factors.

Feline oral squamous cell carcinoma (FOSCC) may be the best naturally-occurring model of human head and neck squamous cell carcinoma (HNSCC). HNSCC can be broadly divided into human papillomavirus (HPV)-negative cancers and HPV-positive cancers where HPV is the causative agent. Previous studies in FOSCC have used both species-specific and species-nonspecific PCR primers that may be insensitive to the detection of PVs and other viruses that may be divergent from known sequences.

Reducing Variability in the Infant Sepsis Evaluation (REVISE): A National Quality Initiative.

Background: Substantial variability exists in the care of febrile, well-appearing infants. We aimed to assess the impact of a national quality initiative on appropriate hospitalization and length of stay (LOS) in this population.

Methods: The initiative, entitled Reducing Variability in the Infant Sepsis Evaluation (REVISE), was designed to standardize care for well-appearing infants ages 7 to 60 days evaluated for fever without an obvious source.

Impaired Chylomicron Assembly Modifies Hepatic Metabolism Through Bile Acid-Dependent and Transmissible Microbial Adaptations.

The mechanisms by which alterations in intestinal bile acid (BA) metabolism improve systemic glucose tolerance and hepatic metabolic homeostasis are incompletely understood. We examined metabolic adaptations in mice with conditional intestinal deletion of the abetalipoproteinemia (ABL) gene microsomal triglyceride transfer protein (Mttp-IKO), which blocks chylomicron assembly and impairs intestinal lipid transport. Mttp-IKO mice exhibit improved hepatic glucose metabolism and augmented insulin signaling, without weight loss.

Genome Organization of Canada Goose Coronavirus, A Novel Species Identified in a Mass Die-off of Canada Geese.

The complete genome of a novel coronavirus was sequenced directly from the cloacal swab of a Canada goose that perished in a die-off of Canada and Snow geese in Cambridge Bay, Nunavut, Canada. Comparative genomics and phylogenetic analysis indicate it is a new species of Gammacoronavirus, as it falls below the threshold of 90% amino acid similarity in the protein domains used to demarcate Coronaviridae. Additional features that distinguish the genome of Canada goose coronavirus include 6 novel ORFs, a partial duplication of the 4 gene and a presumptive change in the proteolytic processing of polyproteins 1a and 1ab.

Whole-Genome Sequencing of Isolates to Track Strain Progression in a Single Patient With Recurrent Urinary Tract Infection.

is an important uropathogen that increasingly harbors broad-spectrum antibiotic resistance determinants. Evidence suggests that some same-strain recurrences in women with frequent urinary tract infections (UTIs) may emanate from a persistent intravesicular reservoir. Our objective was to analyze isolates collected over weeks from multiple body sites of a single patient with recurrent UTI in order to track ordered strain progression across body sites, as has been employed across patients in outbreak settings.

Host Gene Expression in Nose and Blood for the Diagnosis of Viral Respiratory Infection.

Background: Recently there has been a growing interest in the potential for host transcriptomic analysis to augment the diagnosis of infectious diseases.

Methods: We compared nasal and blood samples for evaluation of the host transcriptomic response in children with acute respiratory syncytial virus (RSV) infection, symptomatic non-RSV respiratory virus infection, asymptomatic rhinovirus infection, and virus-negative asymptomatic controls. We used nested leave-one-pair-out cross-validation and supervised principal components analysis to define small sets of genes whose expression patterns accurately classified subjects.

Carriage of the Toxic Shock Syndrome Toxin Gene by Contemporary Community-Associated Staphylococcus aureus Isolates.

We report here the prevalence of the tst-1 gene among 252 methicillin-susceptible Staphylococcus aureus (MSSA) isolates and 458 methicillin-resistant S aureus (MRSA) isolates collected from 531 subjects between 2008 and 2017, one of which was recovered from a child with MRSA toxic shock syndrome. tst-1 was encoded by 43 (6%) S aureus isolates overall: 42 (16.7%) MSSA isolates and 1 (0.

Detection of Viruses in Clinical Samples by Use of Metagenomic Sequencing and Targeted Sequence Capture.

Metagenomic shotgun sequencing (MSS) is a revolutionary approach to viral diagnostic testing that allows simultaneous detection of a broad range of viruses, detailed taxonomic assignment, and detection of mutations associated with antiviral drug resistance. To enhance sensitivity for virus detection, we previously developed ViroCap, a targeted sequence capture panel designed to enrich nucleic acid from a comprehensive set of eukaryotic viruses prior to sequencing. To demonstrate the utility of MSS with targeted sequence capture for detecting clinically important viruses and characterizing clinically important viral features, we used ViroCap to analyze clinical samples from a diagnostic virology laboratory containing a broad range of medically relevant viruses.

Remnant Small Bowel Length in Pediatric Short Bowel Syndrome and the Correlation with Intestinal Dysbiosis and Linear Growth.

Background: Pediatric short bowel syndrome (SBS) is a malabsorptive state placing patients at risk for malnutrition, dehydration, and bacterial overgrowth. These patients are often dependent on parenteral nutrition (PN) while intestinal adaptation is underway. The aim of this study was to characterize the effect of remnant small bowel length on the gut microbiome.