T2 cell compensatory effect following benralizumab treatment for eosinophilic gastritis.

Background: Eosinophil accumulation is a main feature of eosinophilic gastritis (EoG) and is associated with its histologic diagnosis and pathology. However, a recent clinical trial has demonstrated that EoG endoscopic, noneosinophil histologic, and clinical features remain persistent despite complete eosinophil depletion.

Objective: Our aim was to examine gastric T-cell composition and associated cytokine levels of patients with EoG following benralizumab-induced eosinophil depletion versus following administration of placebo.

Losartan Treatment Reduces Esophageal Eosinophilic Inflammation in a Subset of Eosinophilic Esophagitis.

Background: Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven esophageal disorder. Connective tissue disorders (CTDs) and esophageal connective tissue alterations are associated with EoE. Therefore, angiotensin II type 1 receptor blockade with losartan, an accepted CTD treatment, is a potential EoE treatment.

Identifying alterations in hand movement coordination from chronic stroke survivors using a wearable high-density EMG sleeve.

Non-invasive, high-density electromyography (HD-EMG) has emerged as a useful tool to collect a range of neurophysiological motor information. Recent studies have demonstrated changes in EMG features that occur after stroke, which correlate with functional ability, highlighting their potential use as biomarkers. However, previous studies have largely explored these EMG features in isolation with individual electrodes to assess gross movements, limiting their potential clinical utility.

An unbiased method to partition diverse neuronal responses into functional ensembles reveals interpretable population dynamics during innate social behavior.

In neuroscience, understanding how single-neuron firing contributes to distributed neural ensembles is crucial. Traditional methods of analysis have been limited to descriptions of whole population activity, or, when analyzing individual neurons, criteria for response categorization varied significantly across experiments. Current methods lack scalability for large datasets, fail to capture temporal changes and rely on parametric assumptions.

Treatment of Pediatric Eosinophilic Esophagitis: Traditional and Novel Therapies.

Purpose Of Review: This review presents and summarizes the existing studies on the treatment goals and options for pediatric eosinophilic esophagitis utilizing rigorous peer-reviewed literature.

Recent Findings: In addition to traditional treatments, emerging biologic therapies continue to evolve the approach to treating pediatric eosinophilic esophagitis. Well defined treatment goals will aid the continued development of new therapies.

Dissociation of vicarious and experienced rewards by coupling frequency within the same neural pathway.

Vicarious reward, essential to social learning and decision making, is theorized to engage select brain regions similarly to experienced reward to generate a shared experience. However, it is just as important for neural systems to also differentiate vicarious from experienced rewards for social interaction. Here, we investigated the neuronal interaction between the primate anterior cingulate cortex gyrus (ACCg) and the basolateral amygdala (BLA) when social choices made by monkeys led to either vicarious or experienced reward.

Benralizumab for eosinophilic gastritis: a single-site, randomised, double-blind, placebo-controlled, phase 2 trial.

Background: In eosinophilic gastrointestinal diseases, the role of eosinophils in disease pathogenesis and the effect of eosinophil depletion on patient outcomes are unclear. Benralizumab, an eosinophil-depleting monoclonal antibody that targets the interleukin-5 receptor α, might eliminate gastric tissue eosinophils and improve outcomes in eosinophilic gastritis. We aimed to assess the efficacy and safety of benralizumab in patients with eosinophilic gastritis.

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.

Endoscopic approach to eosinophilic esophagitis: American Society for Gastrointestinal Endoscopy Consensus Conference.

Endoscopy plays a critical role in caring for and evaluating the patient with eosinophilic esophagitis (EoE). Endoscopy is essential for diagnosis, assessment of response to therapy, treatment of esophageal strictures, and ongoing monitoring of patients in histologic remission. To date, less-invasive testing for identifying or grading EoE severity has not been established, whereas diagnostic endoscopy as integral to both remains the criterion standard.

Interplay between the oxytocin and opioid systems in regulating social behaviour.

The influence of neuromodulators on brain activity and behaviour is undeniably profound, yet our knowledge of the underlying mechanisms, or ability to reliably reproduce effects across varying conditions, is still lacking. Oxytocin, a hormone that acts as a neuromodulator in the brain, is an example of this quandary; it powerfully shapes behaviours across nearly all mammalian species, yet when manipulated exogenously can produce unreliable or sometimes unexpected behavioural results across varying contexts. While current research is rapidly expanding our understanding of oxytocin, interactions between oxytocin and other neuromodulatory systems remain underappreciated in the current literature.

Widespread implementations of interactive social gaze neurons in the primate prefrontal-amygdala networks.

Social gaze interaction powerfully shapes interpersonal communication. However, compared with social perception, very little is known about the neuronal underpinnings of real-life social gaze interaction. Here, we studied a large number of neurons spanning four regions in primate prefrontal-amygdala networks and demonstrate robust single-cell foundations of interactive social gaze in the orbitofrontal, dorsomedial prefrontal, and anterior cingulate cortices, in addition to the amygdala.

Single-cell RNA sequencing of mast cells in eosinophilic esophagitis reveals heterogeneity, local proliferation, and activation that persists in remission.

Background: Mast cells (MCs) are pleiotropic cells that accumulate in the esophagus of patients with eosinophilic esophagitis (EoE) and are thought to contribute to disease pathogenesis, yet their properties and functions in this organ are largely unknown.

Objectives: This study aimed to perform a comprehensive molecular and spatial characterization of esophageal MCs in EoE.

Methods: Esophageal biopsies obtained from patients with active EoE, patients with EoE in histologic remission, and individuals with histologically normal esophageal biopsies and no history of esophageal disease (ie, control individuals) were subject to single-cell RNA sequencing, flow cytometry, and immunofluorescence analyses.

International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature.

Background & Aims: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature.

Methods: This consensus process utilized Delphi methodology.

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.

Development and Validation of Web-Based Tool to Predict Lamina Propria Fibrosis in Eosinophilic Esophagitis.

Introduction: Approximately half of esophageal biopsies from patients with eosinophilic esophagitis (EoE) contain inadequate lamina propria, making it impossible to determine the lamina propria fibrosis (LPF). This study aimed to develop and validate a web-based tool to predict LPF in esophageal biopsies with inadequate lamina propria.

Methods: Prospectively collected demographic and clinical data and scores for 7 relevant EoE histology scoring system epithelial features from patients with EoE participating in the Consortium of Eosinophilic Gastrointestinal Disease Researchers observational study were used to build the models.

Desmoplakin and periplakin genetically and functionally contribute to eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease with a complex underlying genetic etiology. Herein, we conduct whole-exome sequencing of a multigeneration EoE pedigree (discovery set) and 61 additional multiplex families with EoE (replication set). A series of rare, heterozygous, missense variants are identified in the genes encoding the desmosome-associated proteins DSP and PPL in 21% of the multiplex families.

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).

Acquired Esophageal Strictures in Children: Morphometric and Immunohistochemical Analyses.

Background: Esophageal strictures (ES) in children are not well characterized pathologically. We report unique histopathologic analyses of resected acquired ES and control esophagi (CE).

Methods: Muscle layer thicknesses were measured in intact well-oriented areas; inflammatory cells were counted in the most inflamed high power field (hpf).

Slide Tracheoplasty for Repair of Complex Tracheoesophageal Fistulas.

Objectives/hypothesis: Repair of large, recurrent, and complex tracheoesophageal fistulas (TEFs) is challenging and numerous different surgical approaches exist. These various techniques each carry a set of risks and possible complications such as fistula recurrence, tracheal stenosis or pouches, esophageal stenosis, and recurrent laryngeal nerve injury. Slide tracheoplasty is a reconstructive technique successfully used in many different airway pathologies, including TEF repair.

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS).

Background: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments.

Objective: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE.

Toward a holistic view of value and social processing in the amygdala: Insights from primate behavioral neurophysiology.

Located medially within the temporal lobes, the amygdala is a formation of heterogenous nuclei that has emerged as a target for investigations into the neural bases of both primitive and complex behaviors. Although modern neuroscience has eschewed the practice of assigning broad functions to distinct brain regions, the amygdala has classically been associated with regulating negative emotional processes (such as fear or aggression), primarily through research performed in rodent models. Contemporary studies, particularly those in non-human primate models, have provided evidence for a role of the amygdala in other aspects of cognition such as valuation of stimuli or shaping social behaviors.

Social processing by the primate medial frontal cortex.

The primate medial frontal cortex is comprised of several brain regions that are consistently implicated in regulating complex social behaviors. The medial frontal cortex is also critically involved in many non-social behaviors, such as those involved in reward, affective, and decision-making processes, broadly implicating the fundamental role of the medial frontal cortex in internally guided cognition. An essential question therefore is what unique contributions, if any, does the medial frontal cortex make to social behaviors? In this chapter, we outline several neural algorithms necessary for mediating adaptive social interactions and discuss selected evidence from behavioral neurophysiology experiments supporting the role of the medial frontal cortex in implementing these algorithms.