Planetary Health Diet Index Trends and Associations with Dietary Greenhouse Gas Emissions, Disease Biomarkers, Obesity, and Mortality in the United States (2005-2018).

Background: Diet plays a vital role in human health and environmental effects. Monitoring diet quality and its relationship to both health and environment are essential for policy making.

Objectives: This study aimed to analyze trends in the Planetary Health Diet Index (PHDI) and its associations with daily greenhouse gas emissions from food (GHG), disease-related biomarkers, anthropometric measurements, obesity, and all-cause mortality in the US population.

Reproducibility and Validity of Plant-Based Dietary Indices in the Cancer Prevention Study-3 Diet Assessment Substudy.

Background: The Overall Plant-based Diet Index (PDI), the Healthful Plant-based Diet Index (hPDI), and the Unhealthful Plant-based Diet Index (uPDI) are relatively new tools for characterizing the quality of plant-based dietary patterns in epidemiologic studies. Reproducibility and validity of these indices have not been assessed across populations.

Objective: The objective of this study was to evaluate the reproducibility and validity of PDI, hPDI, and uPDI in a racially and ethnically diverse population.

Mechanisms of Germline Stem Cell Competition across Species.

In this review, we introduce the concept of cell competition, which occurs between heterogeneous neighboring cell populations. Cells with higher relative fitness become "winners" that outcompete cells of lower relative fitness ("losers"). We discuss the idea of super-competitors, mutant cells that expand at the expense of wild-type cells.

Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies.

SEA-AD is a multimodal cellular atlas and resource for Alzheimer's disease.

The Seattle Alzheimer’s Disease Brain Cell Atlas (SEA-AD) is a multifaceted open data resource designed to identify cellular and molecular pathologies that underlie Alzheimer’s disease. Integrating neuropathology, single cell and spatial genomics, and longitudinal clinical metadata, SEA-AD is a unique resource for studying the pathogenesis of Alzheimer’s and related dementias.

SIGNET: protocol for a multicentre, single-blind prospective, group sequential, randomised controlled trial to evaluate the benefits of a single dose of simvastatin given to potential organ donors declared dead by neurological criteria on outcomes in organ recipients.

Introduction: Successful organ transplantation in patients with end-stage organ failure improves long-term survival, improves quality of life and reduces costs to the NHS. Despite an increase in the number of deceased organ donors over the last decade, there remains a considerable shortfall of suitable organs available for transplantation. Over half of UK donors are certified dead by neurological criteria following brain stem compression, which leads to severe physiological stress in the donor, combined with a hyperinflammatory state.

Dietaryindex: a user-friendly and versatile R package for standardizing dietary pattern analysis in epidemiological and clinical studies.

Background: Few standardized and open-source tools exist for calculating multiple dietary pattern indexes from dietary intake data in epidemiological and clinical studies.

Objectives: The primary aim is to develop and validate dietaryindex, a user-friendly and versatile R package that standardizes the calculation of dietary indexes.

Methods: Dietaryindex can calculate multiple dietary indexes of high interest in research, including the Healthy Eating Index (HEI)-2020, the Alternative HEI 2010, the Dietary Approaches to Stop Hypertension Index, the Alternate Mediterranean Diet Score, the Dietary Inflammatory Index, the American Cancer Society 2020 dietary index, and the Planetary Health Diet Index from the EAT-Lancet Commission.

Desmopressin for prevention of bleeding for thrombocytopenic, critically ill patients undergoing invasive procedures: A randomised, double-blind, placebo-controlled feasibility trial.

Thrombocytopenic patients have an increased risk of bleeding when undergoing invasive procedures. In a multicentre, phase II, blinded, randomised, controlled feasibility trial, critically ill patients with platelet count 100 × 10/L or less were randomised 1:1 to intravenous desmopressin (0.3 µg/kg) or placebo before an invasive procedure.

Length of Overnight Fasting and 6-year Weight Change in the Cancer Prevention Study-3.

Background: Longer overnight fasting (ONF) is a potential strategy for weight control. Although promising, the evidence from large population-based studies is limited.

Objectives: To examine the association of self-reported ONF duration with 3- and 6-y weight change in the American Cancer Society's Cancer Prevention Study-3 prospective cohort.

The impact of social deprivation on rotator cuff repair outcomes.

Background: Rotator cuff tears are a common orthopedic injury, and the role of social determinants of health (SDoH) in surgical outcomes remains underexplored. The goal of this study was to investigate the correlation between social deprivation, measured by the Area Deprivation Index (ADI), and outcomes following arthroscopic rotator cuff repair.

Methods: We conducted a retrospective chart review on patients undergoing primary arthroscopic rotator cuff repair at a level 1 academic center between 2006 and 2019.

VLK drives extracellular phosphorylation of EphB2 to govern the EphB2-NMDAR interaction and injury-induced pain.

Phosphorylation of hundreds of protein extracellular domains is mediated by two kinase families, yet the significance of these kinases is underexplored. Here, we find that the presynaptic release of the tyrosine directed-ectokinase, Vertebrate Lonesome Kinase (VLK/Pkdcc), is necessary and sufficient for the direct extracellular interaction between EphB2 and GluN1 at synapses, for phosphorylation of the ectodomain of EphB2, and for injury-induced pain. is an essential gene in the nervous system, and VLK is found in synaptic vesicles, and is released from neurons in a SNARE-dependent fashion.

Somatic cancer driver mutations are enriched and associated with inflammatory states in Alzheimer's disease microglia.

Alzheimer's disease (AD) is an age-associated neurodegenerative disorder characterized by progressive neuronal loss and pathological accumulation of the misfolded proteins amyloid-β and tau. Neuroinflammation mediated by microglia and brain-resident macrophages plays a crucial role in AD pathogenesis, though the mechanisms by which age, genes, and other risk factors interact remain largely unknown. Somatic mutations accumulate with age and lead to clonal expansion of many cell types, contributing to cancer and many non-cancer diseases.

RhoU forms homo-oligomers to regulate cellular responses.

RhoU is an atypical member of the Rho family of small G-proteins, which has N- and C-terminal extensions compared to the classic Rho GTPases RhoA, Rac1 and Cdc42, and associates with membranes through C-terminal palmitoylation rather than prenylation. RhoU mRNA expression is upregulated in prostate cancer and is considered a marker for disease progression. Here, we show that RhoU overexpression in prostate cancer cells increases cell migration and invasion.

Cognitive Reappraisal and Need to Belong Predict Prosociality in Mexican-Origin Adolescents.

This two-year longitudinal study examined Mexican-origin adolescents' need to belong and cognitive reappraisal as predictors of multiple forms of prosocial behavior (i.e., general, emotional, and public prosocial behaviors).

Pan-Tumor Analytical Validation and Osimertinib Clinical Validation in EGFR Mutant Non-Small-Cell Lung Cancer, Supporting the First Next-Generation Sequencing Liquid Biopsy in Vitro Diagnostic.

Comprehensive genotyping is necessary to identify therapy options for patients with advanced cancer; however, many cancers are not tested, partly because of tissue limitations. Next-generation sequencing (NGS) liquid biopsies overcome some limitations, but clinical validity is not established and adoption is limited. Herein, clinical bridging studies used pretreatment plasma samples and data from FLAURA (NCT02296125; n = 441) and AURA3 (NCT02151981; n = 450) pivotal studies to demonstrate clinical validity of Guardant360 CDx (NGS LBx) to identify patients with advanced EGFR mutant non-small-cell lung cancer who may benefit from osimertinib.

Single-cell genomics reveals region-specific developmental trajectories underlying neuronal diversity in the human hypothalamus.

The development and diversity of neuronal subtypes in the human hypothalamus has been insufficiently characterized. To address this, we integrated transcriptomic data from 241,096 cells (126,840 newly generated) in the prenatal and adult human hypothalamus to reveal a temporal trajectory from proliferative stem cell populations to mature hypothalamic cell types. Iterative clustering of the adult neurons identified 108 robust transcriptionally distinct neuronal subtypes representing 10 hypothalamic nuclei.

Single-cell DNA methylation and 3D genome architecture in the human brain.

Delineating the gene-regulatory programs underlying complex cell types is fundamental for understanding brain function in health and disease. Here, we comprehensively examined human brain cell epigenomes by probing DNA methylation and chromatin conformation at single-cell resolution in 517 thousand cells (399 thousand neurons and 118 thousand non-neurons) from 46 regions of three adult male brains. We identified 188 cell types and characterized their molecular signatures.

Transcriptomic diversity of cell types across the adult human brain.

The human brain directs complex behaviors, ranging from fine motor skills to abstract intelligence, but the diversity of cell types that support these skills has not been fully described. In this work, we used single-nucleus RNA sequencing to systematically survey cells across the entire adult human brain. We sampled more than three million nuclei from approximately 100 dissections across the forebrain, midbrain, and hindbrain in three postmortem donors.