Respiratory outcomes of onasemnogene abeparvovec treatment for spinal muscular atrophy: national real-world cohort study.

Onasemnogene abeparvovec (OA) is a novel gene replacement therapy for patients with spinal muscular atrophy (SMA). This study provides real-world respiratory data for pediatric SMA patients receiving OA who were assessed before and one year after treatment in a multicenter cohort study conducted from 2019 to 2021. Twenty-five OA-treated SMA patients (23 with type 1 and 2 with type 2; median age at treatment 6.

Nurse experiences and perspectives with missed nursing care during COVID-19: A qualitative study.

Aim: This study aimed to determine clinical nurse and nurse manager perspectives on missed nursing care (MNC) during the COVID-19 pandemic.

Design: This study utilized a qualitative exploratory descriptive design.

Methods: Data were obtained through focus groups and virtual interviews.

Amniotic fluid modifies esophageal epithelium differentiation and inflammatory responses.

The interplay between genetic and environmental factors during pregnancy can predispose to inflammatory diseases postnatally, including eosinophilic esophagitis (EoE), a chronic allergic disease triggered by food. Herein, we examined the effects of amniotic fluid (AF) on esophageal epithelial differentiation and responsiveness to proallergic stimuli. Multiplex analysis of AF revealed the expression of 66 cytokines, whereas five cytokines including IL-4 and thymic stromal lymphopoietin (TSLP) were not detected.

Single-cell RNA-sequencing of human eosinophils in allergic inflammation in the esophagus.

Background: Eosinophils are elusive cells involved in allergic inflammation. Single-cell RNA-sequencing (scRNA-seq) is an emerging approach to deeply characterize cellular properties, heterogeneity, and functionality.

Objectives: We sought to comprehensively characterize the transcriptome and biological functions of human eosinophils at a site of severe allergic inflammation in the esophagus (ie, eosinophilic esophagitis [EoE]).

Machine learning-based identification and characterization of mast cells in eosinophilic esophagitis.

Background: Eosinophilic esophagitis (EoE) is diagnosed and monitored using esophageal eosinophil levels; however, EoE also exhibits a marked, understudied esophageal mastocytosis.

Objectives: Using machine learning, we localized and characterized esophageal mast cells (MCs) to decipher their potential role in disease pathology.

Methods: Esophageal biopsy samples (EoE, control) were stained for MCs by anti-tryptase and imaged using immunofluorescence; high-resolution whole tissue images were digitally assembled.

Machine Learning Based Identification and Characterization of Mast cells in Eosinophilic Esophagitis.

Background: Eosinophilic esophagitis (EoE) is diagnosed and monitored using esophageal eosinophil levels; however, EoE also exhibits a marked, understudied esophageal mastocytosis.

Objective: Using machine learning, we localized and characterized esophageal mast cells to decipher their potential role in disease pathology.

Methods: Esophageal biopsy samples (EoE, control) were stained for mast cells by anti-tryptase and imaged using immunofluorescence; high-resolution whole tissue images were digitally assembled.

The minichromosome maintenance complex drives esophageal basal zone hyperplasia.

Eosinophilic esophagitis (EoE) is a chronic gastrointestinal disorder characterized by food antigen-driven eosinophilic inflammation and hyperproliferation of esophageal mucosa. By utilizing a large-scale, proteomic screen of esophageal biopsies, we aimed to uncover molecular drivers of the disease. Proteomic analysis by liquid chromatography-tandem mass spectrometry identified 402 differentially expressed proteins (DEPs) that correlated with the EoE transcriptome.

Genotype-phenotype correlations in RHOBTB2-associated neurodevelopmental disorders.

Purpose: Missense variants clustering in the BTB domain region of RHOBTB2 cause a developmental and epileptic encephalopathy with early-onset seizures and severe intellectual disability.

Methods: By international collaboration, we assembled individuals with pathogenic RHOBTB2 variants and a variable spectrum of neurodevelopmental disorders. By western blotting, we investigated the consequences of missense variants in vitro.

Single cell transcriptomic analysis of HPV16-infected epithelium identifies a keratinocyte subpopulation implicated in cancer.

Persistent HPV16 infection is a major cause of the global cancer burden. The viral life cycle is dependent on the differentiation program of stratified squamous epithelium, but the landscape of keratinocyte subpopulations which support distinct phases of the viral life cycle has yet to be elucidated. Here, single cell RNA sequencing of HPV16 infected compared to uninfected organoids identifies twelve distinct keratinocyte populations, with a subset mapped to reconstruct their respective 3D geography in stratified squamous epithelium.

Local type 2 immunity in eosinophilic gastritis.

Background: Eosinophilic gastritis (EoG) associates with type 2 immunity. However, the type 2 cytokine cellular source, gastric T-cell composition, and gastric T-cell relationship (or relationships) with disease pathology remain understudied.

Objective: We defined gastric T-cell populations and their association with histologic and endoscopic EoG pathology.

Molecular analysis of duodenal eosinophilia.

Background: Eosinophilic duodenitis (EoD), characterized by nonspecific gastrointestinal symptoms and increased numbers of duodenal eosinophils, may be in the eosinophilic gastrointestinal disease spectrum. However, diagnostic thresholds and pathogenic processes of duodenal tissue eosinophilia are inadequately characterized.

Objective: We aimed to define an EoD transcriptome and pathologic pathways.

Lockdown Fatigue in Pediatric Respiratory Patients: Lessons from the First COVID-19 Year.

Lockdown policies have been implemented worldwide to limit the spread of COVID-19. “Lockdown fatigue” is a state of exhaustion related to the accumulating effects of repeated lockdowns. The aim of the current study was to examine the effects of repeated lockdowns on children with respiratory disorders.

Harnessing artificial intelligence to infer novel spatial biomarkers for the diagnosis of eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory condition of the esophagus associated with elevated esophageal eosinophils. Second only to gastroesophageal reflux disease, EoE is one of the leading causes of chronic refractory dysphagia in adults and children. EoE is a clinicopathologic disorder and the histological portion of the diagnosis requires enumerating the density of esophageal eosinophils in esophageal biopsies, and evaluating additional features such as basal zone hyperplasia is helpful.

A Deep Multi-Label Segmentation Network For Eosinophilic Esophagitis Whole Slide Biopsy Diagnostics.

Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus associated with elevated numbers of eosinophils. Disease diagnosis and monitoring require determining the concentration of eosinophils in esophageal biopsies, a time-consuming, tedious and somewhat subjective task currently performed by pathologists. Here, we developed a machine learning pipeline to identify, quantitate and diagnose EoE patients' at the whole slide image level.

Epithelial cell-expressed type II IL-4 receptor mediates eosinophilic esophagitis.

Background: Eosinophilic esophagitis (EoE) is a chronic, food-driven allergic disease, characterized by eosinophil-rich inflammation in the esophagus. The histopathological and clinical features of EoE have been attributed to overproduction of the type 2 cytokines IL-4 and IL-13, which mediate profound alterations in the esophageal epithelium and neutralizing of their shared receptor component (IL-4Rα) with a human antibody drug (dupilumab) demonstrates clinical efficacy. Yet, the relative contribution of IL-4 and IL-13 and whether the type II IL-4 receptor (comprised of the IL-4Rα chain in association with IL-13Rα1) mediates this effect has not been determined.

Vitamin D receptor and STAT6 interactome governs oesophageal epithelial barrier responses to IL-13 signalling.

Objective: The contribution of vitamin D (VD) deficiency to the pathogenesis of allergic diseases remains elusive. We aimed to define the impact of VD on oesophageal allergic inflammation.

Design: We assessed the genomic distribution and function of VD receptor (VDR) and STAT6 using histology, molecular imaging, motif discovery and metagenomic analysis.

Single-cell RNA-Seq of human esophageal epithelium in homeostasis and allergic inflammation.

Inflammation of the esophageal epithelium is a hallmark of eosinophilic esophagitis (EoE), an emerging chronic allergic disease. Herein, we probed human esophageal epithelial cells at single-cell resolution during homeostasis and EoE. During allergic inflammation, the epithelial differentiation program was blocked, leading to loss of KRT6hi differentiated populations and expansion of TOP2hi proliferating, DSPhi transitioning, and SERPINB3hi transitioning populations; however, there was stability of the stem cell-enriched PDPNhi basal epithelial compartment.

A case of an unfortunate tooth fairy visit to a ventilator-dependent child.

An 8-year-old boy recently sustained a cerebellar arteriovenous malformation rupture, and subsequently suffered from severe neurological injury and became ventilator-dependent through a tracheostomy. During a routine clinic visit, the parents reported that a loose baby tooth had fallen out and disappeared 7 days earlier. The physical examination was unremarkable, but a chest X-ray demonstrated a foreign body in the left lung and secondary atelectasis.

Unforeseen changes in seasonality of pediatric respiratory illnesses during the first COVID-19 pandemic year.

Objectives: To investigate whether the three nationwide coronavirus disease 2019 (COVID-19) lockdowns imposed in Israel during the full first pandemic year altered the traditional seasonality of pediatric respiratory healthcare utilization.

Methods: Month by month pediatric emergency department (ED) visits and hospitalizations for respiratory diagnoses during the first full COVID-19 year were compared to those recorded for the six consecutive years preceding the pandemic. Data were collected from the patients' electronic files by utilizing a data extraction platform (MDClone ).

Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study.

Background & Aims: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined.

Methods: Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers.

Nonrespiratory complications of nusinersen-treated spinal muscular atrophy type 1 patients.

Background: Emergence of new treatments for spinal muscular atrophy type 1 (SMA1) has led to dramatic improvements in respiratory failure and survival. However, these "treated" patients sustain major problems in other organ systems, which may directly or indirectly affect their respiratory function. We observed three main nonrespiratory manifestations in these patients comprised of facial deformities, feeding problems, and spinal deformities.

The impact of California's staffing mandate and the economic recession on registered nurse staffing levels: A longitudinal analysis.

Background: Despite the importance of adequate hospital nurse staffing, California is the only state with minimum nurse-to-patient ratio mandates. The health care workforce is historically "countercyclical"-exhibiting growth during economic recessions when employment in other sectors is shrinking.

Purpose: This study was to examine how staffing mandates impact hospital nurse staffing during economic recessions.

Remote immune processes revealed by immune-derived circulating cell-free DNA.

Blood cell counts often fail to report on immune processes occurring in remote tissues. Here, we use immune cell type-specific methylation patterns in circulating cell-free DNA (cfDNA) for studying human immune cell dynamics. We characterized cfDNA released from specific immune cell types in healthy individuals (N = 242), cross sectionally and longitudinally.

Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell-Fibroblast Crosstalk.

Background & Aims: Eosinophilic esophagitis (EoE) can progress to fibrostenosis by unclear mechanisms. Herein, we investigated gene dysregulation in fibrostenotic EoE, its association with clinical parameters and specific pathways, and the functional consequences.

Methods: Esophageal biopsies from subjects with EoE were collected across 11 Consortium of Eosinophilic Gastrointestinal Disease Researchers sites (n = 311) and 2 independent replication cohorts (n = 83).

Host-Microbiota Interactions in the Esophagus During Homeostasis and Allergic Inflammation.

Background & Aims: Microbiota composition and mechanisms of host-microbiota interactions in the esophagus are unclear. We aimed to uncover fundamental information about the esophageal microbiome and its potential significance to eosinophilic esophagitis (EoE).

Methods: Microbiota composition, transplantation potential, and antibiotic responsiveness in the esophagus were established via 16S ribosomal RNA sequencing.