Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study.

Allergen-specific immunotherapy (AIT) induces immune tolerance, showing the highest success rate (>95%) for insect venom while a much lower chance for pollen allergy. However, the molecular switches leading to successful durable tolerance restoration remain elusive. The primary outcome of this observational study is the comprehensive immunological cellular characterization during the AIT initiation phase, whereas the secondary outcomes are the serological and Th2-cell-type-specific transcriptomic analyses.

Exercise limitations in amyloid cardiomyopathy assessed by cardiopulmonary exercise testing-A multicentre study.

Aims: Amyloid cardiomyopathy is caused by the deposition of light chain (AL) or transthyretin amyloid (ATTR) fibrils, that leads to a restrictive cardiomyopathy, often resulting in heart failure (HF) with preserved or reduced ejection fraction. This study aimed to determine whether cardiac output reduction or ventilation inefficiency plays a predominant role in limiting exercise in patients with amyloid cardiomyopathy.

Methods: We conducted a multicentre prospective study in patients with AL or ATTR cardiomyopathy who underwent cardiopulmonary exercise testing across four centres.

Inferring upstream regulatory genes of FOXP3 in human regulatory T cells from time-series transcriptomic data.

The discovery of upstream regulatory genes of a gene of interest still remains challenging. Here we applied a scalable computational method to unbiasedly predict candidate regulatory genes of critical transcription factors by searching the whole genome. We illustrated our approach with a case study on the master regulator FOXP3 of human primary regulatory T cells (Tregs).

The outer kinetochore components KNL-1 and Ndc80 complex regulate axon and neuronal cell body positioning in the nervous system.

The KMN (Knl1/Mis12/Ndc80) network at the kinetochore, primarily known for its role in chromosome segregation, has been shown to be repurposed during neurodevelopment. Here, we investigate the underlying neuronal mechanism and show that the KMN network promotes the proper axonal organization within the head nervous system. Postmitotic degradation of KNL-1, which acts as a scaffold for signaling and has microtubule-binding activities at the kinetochore, led to disorganized ganglia and aberrant placement and organization of axons in the nerve ring - an interconnected axonal network.

Severe COVID-19 and its cardiopulmonary effects 6 and 18 months after hospital discharge.

Introduction: SARS-CoV-2 infection affects the cardiopulmonary system in the acute as well as long-term phase. The aim of the present study was to comprehensively assess symptoms and possible long-term impairments 6 and 18 months after hospitalization for severe COVID-19 infection.

Methods: This prospective registry included patients with PCR-confirmed COVID-19 infection requiring hospitalization.