PD-1 is requisite for skin T cell formation and specification by TGFβ.

Tissue-resident memory T (T) cells provide infectious, cancer and vaccine-trained immunity across barrier sites. T cells are implicated in autoimmunity, successful response to immune checkpoint blockade in the tumor microenvironment and toxicities that occur after immune checkpoint blockade in peripheral tissues. Here, we identified that signaling through the immune checkpoint programmed death receptor 1 (PD-1) strongly impacts the early specification of CD8 T cells in the skin.

Kinetics of early peanut allergy development and resolution in the EAT, LEAP, and PAS cohorts.

Background: Little is known about the development and resolution of early peanut allergy (PA).

Objective: We examined the natural history and biomarkers of PA longitudinally in 3 cohorts.

Methods: PA development was examined in the Enquiring About Tolerance (EAT), Learning Early About Peanut (LEAP), and Peanut Allergy Sensitization (PAS) cohorts.

Kinetics of epitope-specific IgE and IgG in early peanut allergy development and resolution.

Background: The development and resolution of peanut allergy (PA) was evaluated in children enrolled or screened for the Learning Early About Peanut (LEAP) intervention trial. The development of epitope-specific (es) IgE and es-IgG antibodies was evaluated in a subset of these children to determine whether their PA status could be predicted at 4-11 months of age.

Methods: Sera from 386 children enrolled or screened as part of the LEAP trial were assayed at 4-11 months (baseline) and 60 months of age, and final allergy status was established by oral food challenge at 60 months.

Wearable Devices Identify Altered Sleep Characteristics and Sleep Trajectories in Active Inflammatory Bowel Disease.

Background And Aims: Poor sleep is associated with flares of inflammatory bowel disease (IBD). Studies often rely on subjective assessments of sleep and disease activity. Our aim is to use wearable devices to objectively assess the impact of inflammation and symptoms on sleep architecture in IBD.

ORAKLE: Optimal Risk prediction for mAke30 in patients with sepsis associated AKI using deep LEarning.

Background: Major Adverse Kidney Events within 30 days (MAKE30) is an important patient-centered outcome for assessing the impact of acute kidney injury (AKI). Existing prediction models for MAKE30 are static and overlook dynamic changes in clinical status. We introduce ORAKLE, a novel deep-learning model that utilizes evolving time-series data to predict MAKE30, enabling personalized, patient-centered approaches to AKI management and outcome improvement.

Distinct perturbances in metabolic pathways associate with disease progression in inflammatory bowel disease.

Background And Aims: Patients with inflammatory bowel disease (IBD) exhibit distinct shifts in circulating metabolite levels linked to disease activity and phenotype, but associations with disease progression remain unexplored. Our aim was to investigate relationships between circulating metabolites and metabolic pathways with disease progression risk in patients with IBD.

Methods: We performed an observational cohort study using the Mount Sinai Crohn's and Colitis Registry.

A foundational transformer leveraging full night, multichannel sleep study data accurately classifies sleep stages.

Study Objectives: To evaluate whether a foundational transformer using 8-hour, multichannel polysomnogram (PSG) data can effectively encode signals and classify sleep stages with state-of-the-art performance.

Methods: The Sleep Heart Health Study, Wisconsin Sleep Cohort, and Osteoporotic Fractures in Men (MrOS) Study visit 1 were used for training, and the Multi-Ethnic Study of Atherosclerosis (MESA), Apnea Positive Pressure Long-term Efficacy Study (APPLES), and MrOS visit 2 served as independent test sets. We developed PFTSleep, a self-supervised foundational transformer that encodes full-night sleep studies with brain, movement, cardiac, oxygen, and respiratory channels.

Immunological biomarkers of response and resistance to treatment with cabozantinib and nivolumab in recurrent endometrial cancer.

Background: Antiangiogenics combined with immune checkpoint blockade have become standard of care for recurrent endometrial cancer after standard platinum-based chemotherapy. To dissect mechanisms and define biomarkers associated with clinical outcomes to these combinations, we applied multidimensional immune monitoring to peripheral blood specimens collected from a randomized phase 2 trial of nivolumab with or without cabozantinib in 75 evaluable patients with recurrent endometrial cancer (NCI ETCTN 10104, NCT03367741). This trial demonstrated superiority of the combination to nivolumab alone.

To explore the causal association between the serum lipid profile and inflammatory bowel disease using bidirectional Mendelian randomisation analysis.

Background: Despite studies confirming that patients with inflammatory bowel disease (IBD) present with dyslipidaemia, the associations between IBD and the serum lipid profile have not been determined. The present study aimed to investigate the causal relationship between the serum lipid profile and IBD risk and elucidate the nature of the interactions between them.

Methods: Two-sample Mendelian randomisation (MR) analysis was performed to investigate the causal links between total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (Apo A), apolipoprotein B (Apo B) and lipoprotein (a) (Lp(a)) and IBD.

Gut IgA functionally interacts with systemic IgG to enhance antipneumococcal vaccine responses.

The gut microbiota enhances systemic immunoglobulin G (IgG) responses to vaccines, but it is unknown whether this effect involves IgA, which coats intestinal microbes. That IgA may amplify postimmune IgG production is suggested by the impaired IgG response to pneumococcal vaccines in some IgA-deficient patients. Here, we found that antipneumococcal but not total IgG production was impaired in mice with IgA deficiency.

Peanut Oral Immunotherapy in Children with High-Threshold Peanut Allergy.

Background: Approved therapeutics for peanut allergy are not designed for the many patients with allergic reactions to more than one peanut.

Methods: We randomly assigned (1:1) participants 4 to 14 years of age reacting to a challenge of between 443 mg and 5043 mg of peanut protein to peanut oral immunotherapy (P-OIT) using home-measured peanut butter versus peanut avoidance. The primary end point was the difference between groups in the proportion tolerating a two-dose-level increase or 9043 mg of peanut protein.

Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV-2 Infection.

Key Points: AKI in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is linked to mitochondrial dysfunction and cellular stress, highlighting novel biomarkers for severe AKI. Molecular similarities between AKI in SARS-CoV-2 and sepsis suggest that current therapeutic strategies may be applicable across both conditions. Molecular changes in acute SARS-CoV-2 infection are tied to long-term inflammation, immune dysregulation, and lasting cardiac and renal dysfunction.

NutriSighT: Interpretable Transformer Model for Dynamic Prediction of Hypocaloric Enteral Nutrition in Mechanically Ventilated Patients.

Achieving adequate enteral nutrition among mechanically ventilated patients is challenging, yet critical. We developed NutriSighT, a transformer model using learnable positional coding to predict which patients would achieve hypocaloric nutrition between days 3-7 of mechanical ventilation. Using retrospective data from two large ICU databases (3,284 patients from AmsterdamUMCdb - development set, and 6,456 from MIMIC-IV - external validation set), we included adult patients intubated for at least 72 hours.

Physiological Data Collected From Wearable Devices Identify and Predict Inflammatory Bowel Disease Flares.

Background & Aims: Wearable devices capture physiological signals noninvasively and passively. Many of these parameters have been linked to inflammatory bowel disease (IBD) activity. We evaluated the associative ability of several physiological metrics with IBD flares and how they change before the development of flare.

Exploring the Relationship Between Sleep Apnea, Myocardial Infarct Size, and Coronary Collaterals in Acute Myocardial Infarction: A Multidisciplinary Study.

Purpose: We designed a study investigating the cardioprotective role of sleep apnea (SA) in patients with acute myocardial infarction (AMI), focusing on its association with infarct size and coronary collateral circulation.

Methods: We recruited adults with AMI, who underwent Level-III SA testing during hospitalization. Delayed-enhancement cardiac magnetic resonance (CMR) imaging was performed to quantify AMI size (percent-infarcted myocardium).

The Great Controversy of Obstructive Sleep Apnea Treatment for Cardiovascular Risk Benefit: Advancing the Science Through Expert Consensus. An Official American Thoracic Society Workshop Report.

The prevalence of obstructive sleep apnea (OSA) is on the rise, driven by various factors including more sensitive diagnostic criteria, increased awareness, enhanced technology through at-home testing enabling easy and cost-effective diagnosis, and a growing incidence of comorbid conditions such as obesity. Treating symptomatic patients with OSA syndrome to enhance quality of life remains a cornerstone approach. However, there is a lack of consensus regarding treatment to improve cardiovascular disease (CVD) outcomes, particularly in light of overall negative results from several randomized controlled trials (RCT) indicating no benefit of positive airway pressure (PAP) therapy on primary and secondary CVD events.

Gastrointestinal germinal center B cell depletion and reduction in IgA plasma cells in HIV-1 infection.

Gastrointestinal (GI) B cells and plasma cells (PCs) are critical to mucosal homeostasis and the host response to HIV-1 infection. Here, high-resolution mapping of human B cells and PCs sampled from the colon and ileum during both viremic and suppressed HIV-1 infection identified a reduction in germinal center (GC) B cells and follicular dendritic cells (FDCs) during HIV-1 viremia. Immunoglobulin A-positive (IgA) PCs are the major cellular output of intestinal GCs and were significantly reduced during viremic HIV-1 infection.

A Streamlined Strategy for Basophil Activation Testing in a Multicenter Phase III Clinical Trial.

Background: The basophil activation test (BAT) has been limited to research settings owing to technical issues. Novel approaches using dry, ready-to-use reagents and streamlined protocols offer greater flexibility and may open opportunities for easier implementation in clinical research.

Objective: Using a streamlined basophil activation test (sBAT) strategy and the settings of the baseline study of the Epicutaneous Immunotherapy in Toddlers with Peanut Allergy (EPITOPE) trial of EPicutaneous ImmunoTherapy, we aimed to assess the feasibility of implementing BAT in a multicenter trial and to evaluate its utility in predicting the outcomes of peanut double-blind placebo-controlled food challenge (DBPCFC).

Utility of epitope-specific IgE, IgG4, and IgG1 antibodies for the diagnosis of wheat allergy.

Background: The bead-based epitope assay has been used to identify epitope-specific (es) antibodies and successfully used to diagnose clinical allergy to milk, egg, and peanut.

Objective: We sought to identify es-IgE, es-IgG4, and es-IgG1 of wheat proteins and determine the optimal peptides to differentiate wheat-allergic from wheat-tolerant using the bead-based epitope assay.

Methods: Children and adolescents who underwent an oral food challenge to confirm their wheat allergy status were enrolled.

Gastrointestinal germinal center B cell depletion and reduction in IgA plasma cells in HIV-1 infection.

Unlabelled: Gastrointestinal (GI) B cells and plasma cells (PCs) are critical to mucosal homeostasis and the host response to HIV-1 infection. Here, high resolution mapping of human B cells and PCs sampled from the colon and ileum during both viremic and suppressed HIV-1 infection identified a reduction in germinal center (GC) B cells and follicular dendritic cells (FDCs) during HIV-1 viremia. IgA PCs are the major cellular output of intestinal GCs and were significantly reduced during viremic HIV-1 infection.

Multimodal single-cell analyses reveal mechanisms of perianal fistula in diverse patients with Crohn's disease.

Background: Crohn's disease complicated by perianal fistulae is more prevalent and severe in patients of African ancestry.

Methods: We profiled single cells from diverse patients with Crohn's disease with perianal fistula from colorectal mucosa and fistulous tracts. Immunofluorescence was performed to validate predicted cell-cell interactions.

Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis.

Vedolizumab (VDZ) is a first-line treatment in ulcerative colitis (UC) that targets the α4β7- mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) axis. To determine the mechanisms of action of VDZ, we examined five distinct cohorts of patients with UC. A decrease in naïve B and T cells in the intestines and gut-homing (β7) plasmablasts in circulation of VDZ-treated patients suggested that VDZ targets gut-associated lymphoid tissue (GALT).

Achieving Better Understanding of Obstructive Sleep Apnea Treatment Effects on Cardiovascular Disease Outcomes through Machine Learning Approaches: A Narrative Review.

Obstructive sleep apnea (OSA) affects almost a billion people worldwide and is associated with a myriad of adverse health outcomes. Among the most prevalent and morbid are cardiovascular diseases (CVDs). Nonetheless, randomized controlled trials (RCTs) of OSA treatment have failed to show improvements in CVD outcomes.