TNF drives aberrant BMP signaling to induce endothelial and mesenchymal dysregulation in pulmonary hypertension.

The pathobiology of pulmonary hypertension (PH) is complex and multiple cell types contribute to disease pathogenesis. We sought to characterize the molecular crosstalk between endothelial and mesenchymal cells that promote PH in the tumor necrosis factor α-transgenic (TNF-Tg) model of PH. Pulmonary endothelial and mesenchymal cells were isolated from WT and TNF-Tg mice and underwent single-cell RNA sequencing.

Ki-67 promotes inflammatory signaling governing neutrophil recruitment during respiratory infections.

Neutrophils defend against respiratory infections but cause acute lung injury (ALI) when excessively recruited to the lung. Early life environmental factors can shape lung development, but how they impact neutrophil recruitment is not known. We show that exposing newborn mice to hyperoxia increases the number of adult alveolar type 1 (AT1) epithelial cells expressing the proliferation marker Ki-67.

A Multimodal Spatial and Epigenomic Atlas of Human Adult Lung Topography.

Developing high-resolution reference maps of disease-susceptible spatial niches is a critical step to mitigating the profound effects of lung disease. Here, we present an integrated multimodal single-nucleus human lung atlas (snHLA) profiling 746,047 nuclei from 49 mapped lung blocks spanning clinically relevant distal airways, alveoli, and interstitium across 11 healthy adults. Integrating snRNA-seq and SNARE-seq2, which co-assays chromatin accessibility and gene expression from the same nucleus, we resolved 70 molecularly distinct populations and captured 332,846 accessible chromatin regions, nominating new transcriptional regulators of human lung cell diversity.

Prolonged time to treatment of biologics in inflammatory bowel disease: disparities from a retrospective study in a tertiary referral centre in the UK.

Background: Several disparities in healthcare utilisation and delivery are reported in inflammatory bowel disease (IBD). We examined disparities for delays in biologic administration.

Methods: This is a tertiary centre, retrospective, cohort study of consecutive adult IBD outpatients referred to the biologics clinic (BC) for initiation of therapy over 2 years.

ECCO Topical Review on Predictive Models on Inflammatory Bowel Disease Disease Course and Treatment Response.

Background And Aims: Inflammatory bowel disease (IBD) poses a clinical challenge due to its variable progression and treatment response. Despite the development of predictive models, their clinical application remains limited due to validation and methodological inconsistencies. The current topical review examines existing predictive models, assesses their relevance, and discusses the barriers to their clinical implementation.

A Low Dietary Quality Index in a Newly Diagnosed Inflammatory Bowel Disease Cohort: Results from a Case-Control Study.

Background: Epidemiological evidence suggests a link between the risk of IBD and diet. Macro- and micro- nutrient intake, diet quality and dietary patterns may play a pivotal role in disease pathogenesis. We aimed to study the dietary intake of newly diagnosed IBD patients compared to non-IBD controls.

Sorted-Cell Proteomics Reveals an AT1-Associated Epithelial Cornification Phenotype and Suggests Endothelial Redox Imbalance in Human Bronchopulmonary Dysplasia.

Unlabelled: Bronchopulmonary dysplasia (BPD) is a neonatal lung disease characterized by inflammation and scarring leading to long-term tissue damage. Previous whole tissue proteomics identified BPD-specific proteome changes and cell type shifts. Little is known about the proteome-level changes within specific cell populations in disease.

Human BioMolecular Atlas Program (HuBMAP): 3D Human Reference Atlas construction and usage.

The Human BioMolecular Atlas Program (HuBMAP) aims to construct a 3D Human Reference Atlas (HRA) of the healthy adult body. Experts from 20+ consortia collaborate to develop a Common Coordinate Framework (CCF), knowledge graphs and tools that describe the multiscale structure of the human body (from organs and tissues down to cells, genes and biomarkers) and to use the HRA to characterize changes that occur with aging, disease and other perturbations. HRA v.

Cell Population-resolved Multiomics Atlas of the Developing Lung.

The lung is a vital organ that undergoes extensive morphological and functional changes during postnatal development. To disambiguate how different cell populations contribute to organ development, we performed proteomic and transcriptomic analyses of four sorted cell populations from the lung of human subjects 0-8 years of age with a focus on early life. The cell populations analyzed included epithelial, endothelial, mesenchymal, and immune cells.

Perianal Fistulizing Crohn's Disease: Utilizing the TOpClass Classification in Clinical Practice to Provide Targeted Individualized Care.

Background & Aims: Perianal fistulation is a challenging phenotype of Crohn's disease, with significant impact on quality of life. Historically, fistulae have been classified anatomically in relation to the sphincter complex, and management guidelines have been generalized, with lack of attention to the clinical heterogenicity seen. The recent 'TOpClass classification system' for perianal fistulizing Crohn's disease (PFCD) addresses this issue, and classifies patients into defined groups, which provide a focus for fistula management that aligns with disease characteristics and patient goals.

Human BioMolecular Atlas Program (HuBMAP): 3D Human Reference Atlas Construction and Usage.

The Human BioMolecular Atlas Program (HuBMAP) aims to construct a reference 3D structural, cellular, and molecular atlas of the healthy adult human body. The HuBMAP Data Portal (https://portal.hubmapconsortium.

Acute Severe Ulcerative Colitis Flare Complicated by Myopericarditis and Infliximab-Induced Hepatitis.

Unlabelled: Ulcerative colitis (UC) is an autoimmune disease associated with both intestinal and extraintestinal manifestations. The latter may include heart complications, such as myopericarditis leading to life-threatening arrythmias. Nowadays, UC is commonly treated with biologic medications and infliximab is the first line therapy in an outpatient setting, while it is also used as rescue therapy in acute severe UC.

Single-Cell Transcriptomic Profiling Identifies Molecular Phenotypes of Newborn Human Lung Cells.

While animal model studies have extensively defined the mechanisms controlling cell diversity in the developing mammalian lung, there exists a significant knowledge gap with regards to late-stage human lung development. The NHLBI Molecular Atlas of Lung Development Program (LungMAP) seeks to fill this gap by creating a structural, cellular and molecular atlas of the human and mouse lung. Transcriptomic profiling at the single-cell level created a cellular atlas of newborn human lungs.

Association between maternal stress and premature milk cortisol, milk IgA, and infant health: a cohort study.

Background: Maternal stress is pervasive in the neonatal intensive care unit (NICU). Maternal stress is associated with changes in human milk (HM) immunomodulatory agents, which may impact neonatal health. We sought to determine the association between maternal stress, HM immunoglobulin A (IgA) and cortisol, and to assess how these milk components correlate with infant immune and neurodevelopmental outcomes.

Bulk RNA sequencing of human pediatric lung cell populations reveals unique transcriptomic signature associated with postnatal pulmonary development.

Postnatal lung development results in an increasingly functional organ prepared for gas exchange and pathogenic challenges. It is achieved through cellular differentiation and migration. Changes in the tissue architecture during this development process are well-documented and increasing cellular diversity associated with it are reported in recent years.

Guided construction of single cell reference for human and mouse lung.

Accurate cell type identification is a key and rate-limiting step in single-cell data analysis. Single-cell references with comprehensive cell types, reproducible and functionally validated cell identities, and common nomenclatures are much needed by the research community for automated cell type annotation, data integration, and data sharing. Here, we develop a computational pipeline utilizing the LungMAP CellCards as a dictionary to consolidate single-cell transcriptomic datasets of 104 human lungs and 17 mouse lung samples to construct LungMAP single-cell reference (CellRef) for both normal human and mouse lungs.

New insights into the natural history of bronchopulmonary dysplasia from proteomics and multiplexed immunohistochemistry.

Bronchopulmonary dysplasia (BPD) is a disease of prematurity related to the arrest of normal lung development. The objective of this study was to better understand how proteome modulation and cell-type shifts are noted in BPD pathology. Pediatric human donors aged 1-3 yr were classified based on history of prematurity and histopathology consistent with "healed" BPD (hBPD, = 3) and "established" BPD (eBPD, = 3) compared with respective full-term born ( = 6) age-matched term controls.

Influence of the irradiated pulmonary microenvironment on macrophage and T cell dynamics.

Background: The lung is sensitive to radiation, increasing normal tissue toxicity risks following radiation therapy. Adverse outcomes include pneumonitis and pulmonary fibrosis, which result from dysregulated intercellular communication within the pulmonary microenvironment. Although macrophages are implicated in these pathogenic outcomes, the impact of their microenvironment is not well understood.

Ethnicity Associated Microbial and Metabonomic Profiling in Newly Diagnosed Ulcerative Colitis.

Introduction: Ulcerative colitis (UC) differs across geography and ethnic groups. Gut microbial diversity plays a pivotal role in disease pathogenesis and differs across ethnic groups. The functional diversity in microbial-driven metabolites may have a pathophysiologic role and offer new therapeutic avenues.

An optimized approach and inflation media for obtaining complimentary mass spectrometry-based omics data from human lung tissue.

Human disease states are biomolecularly multifaceted and can span across phenotypic states, therefore it is important to understand diseases on all levels, across cell types, and within and across microanatomical tissue compartments. To obtain an accurate and representative view of the molecular landscape within human lungs, this fragile tissue must be inflated and embedded to maintain spatial fidelity of the location of molecules and minimize molecular degradation for molecular imaging experiments. Here, we evaluated agarose inflation and carboxymethyl cellulose embedding media and determined effective tissue preparation protocols for performing bulk and spatial mass spectrometry-based omics measurements.

LungMAP Portal Ecosystem: Systems-level Exploration of the Lung.

An improved understanding of the human lung necessitates advanced systems models informed by an ever-increasing repertoire of molecular omics, cellular imaging, and pathological datasets. To centralize and standardize information across broad lung research efforts, we expanded the LungMAP.net website into a new gateway portal.

A novel digital rectoscope for the triage of lower gastrointestinal symptoms in primary care: a prospective multicentre feasibility study.

Background: Access to community rectoscopy might help to ease the burden on hospital services and reduce costs for the NHS. To assess this, a prospective multicentre observational phase I feasibility study of a novel digital rectoscope and telestration software for the triage of lower gastrointestinal (GI) symptoms was undertaken.

Aim: To determine if digital rectoscopy is feasible, acceptable, and clinically safe.