Systemic inflammation and lymphocyte activation precede rheumatoid arthritis.

Some autoimmune diseases, including rheumatoid arthritis (RA), are preceded by a critical subclinical phase of disease activity. Proactive clinical management is hampered by a lack of biological understanding of this subclinical 'at-risk' state and the changes underlying disease development. In a cross-sectional and longitudinal multi-omics study of peripheral immunity in the autoantibody-positive at-risk for RA period, we identified systemic inflammation, proinflammatory-skewed B cells, expanded Tfh17-like cells, epigenetic bias in naive T cells, TNF+IL1B+ monocytes resembling a synovial macrophage population, and CD4 T cell transcriptional features resembling those suppressed by abatacept (CTLA4-Ig) in RA patients.

Transition towards cancer mortality predominance over cardiovascular disease mortality in Brazil, 2000-2019: a population-based study.

Background: Cardiovascular disease (CVD) and cancer are the first and second leading causes of death in Brazil and worldwide. However, an ongoing epidemiological transition in which cancer surpasses CVD has been observed in many high and middle-income countries. In this study, we provided a nationwide analysis of the transition towards cancer mortality predominance over CVD mortality in Brazil.

Longitudinal Multi-omic Immune Profiling Reveals Age-Related Immune Cell Dynamics in Healthy Adults.

The generation and maintenance of protective immunity is a dynamic interplay between host and environment that is impacted by age. Understanding fundamental changes in the healthy immune system that occur over a lifespan is critical in developing interventions for age-related susceptibility to infections and diseases. Here, we use multi-omic profiling (scRNA-seq, proteomics, flow cytometry) to examined human peripheral immunity in over 300 healthy adults, with 96 young and older adults followed over two years with yearly vaccination.

MOCHA's advanced statistical modeling of scATAC-seq data enables functional genomic inference in large human cohorts.

Single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) is being increasingly used to study gene regulation. However, major analytical gaps limit its utility in studying gene regulatory programs in complex diseases. In response, MOCHA (Model-based single cell Open CHromatin Analysis) presents major advances over existing analysis tools, including: 1) improving identification of sample-specific open chromatin, 2) statistical modeling of technical drop-out with zero-inflated methods, 3) mitigation of false positives in single cell analysis, 4) identification of alternative transcription-starting-site regulation, and 5) modules for inferring temporal gene regulatory networks from longitudinal data.

Association between ultra-processed dietary pattern and bullying: the role of deviant behaviors.

Background: Ultra-processed foods have been associated with several negative outcomes, but it is not clear whether they are related to bullying perpetration. Moreover, no previous study has investigated the potential role of deviant behaviors as a mediator of this association. Our objective was to evaluate the association between ultra-processed dietary pattern and bullying, and the mediating effect of deviant behaviors in this association, among school adolescents.