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Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Myeloid cells contribute to the etiology of multiple sclerosis (MS), but the dynamics of myelopoiesis during disease progression is still unclear. Here the authors show, in both mouse models and clinical data, that myelopoiesis is differentially regulated via M-CSF modulation in different organs at distinct stages of MS, with diet and lifestyle being potential modifiers.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

One picosecond after photoactivation, isomerized retinal pulls away from half of its numerous interactions with its binding pocket, and the excess of the photon energy is released through an anisotropic protein breathing motion in the direction of the extracellular space.

Analysing data on the relative abundance of basal area of ectomycorrhizal trees from lowland tropical forests, the authors show that their distribution and abundance are independent of soil quality.

Multiple variants of SARS-CoV-2 are inhibited by a trispecific DARPin.

In the final analysis of all cohorts in the phase 2 ROAR basket trial, dabrafenib plus trametinib exhibited tumor-agnostic clinical activity in patients with rare BRAFV800E-mutated cancers, including anaplastic thyroid carcinoma, biliary tract cancer, low-grade glioma and hairy cell leukemia.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

SnRK1 is a key metabolic sensor that controls plant development and stress responses. This study integrates phosphoproteomics, affinity purification coupled to mass spectrometry, proximity labelling and crosslinking mass spectrometry to obtain more insight into its upstream regulation and downstream target processes.

A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the ___location and organization of major intracellular structures.

Frequent dispersal and short-lived local transmission clusters fuelled the 2013–2016 Ebola virus epidemic in Guinea, Liberia and Sierra Leone.

The authors study Andreev bound states (ABSs) in 3-terminal InAs/Al Josephson-junction devices. They find signatures of hybridization between two ABSs, with band structure tunable by electric currents that generate magnetic fluxes threading superconducting loops in the device.

The authors study conductance replicas emerging under microwave irradiation in the tunnelling spectrum of Josephson junctions in InAs/Al heterostructures, focusing on distinguishing the signatures of Floquet-Andreev states (FASs) from those of photon-assisted tunneling (PAT). They establish that PAT largely dominates the response to microwave radiation in their device.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

Systemically injected lipid–polymer nanoparticles encapsulating small interfering RNA for silencing genes in bone-marrow endothelial cells of mice improved the healing of the mice after myocardial infarction.

Analyses of the proportions of individuals who have completed key levels of schooling across all low- and middle-income countries from 2000 to 2017 reveal inequalities across countries as well as within populations.

iGluSnFR variants with improved signal-to-noise ratios and targeting to postsynaptic sites have been developed, enabling the analysis of glutamatergic neurotransmission in vivo as illustrated in the mouse visual and somatosensory cortex.

A practical, fully synthetic route to macrolide antibiotics via the convergent assembly of simple chemical building blocks is described; more than 300 new macrolide antibiotic candidates have been synthesized using this approach, a number of which are active against bacterial strains that are resistant to currently used antibiotics.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

This Registered Report presents evidence from 87 countries and regions showing that brief emotion-regulation interventions consistently reduced negative emotions and increased positive emotions during the COVID-19 pandemic.

Adaptation to new environments often involves changes in gene expression. This study shows a role of ancestral gene expression plasticity in heavy metal adaptation of two independent lineages of Silene uniflora.

High-resolution subnational mapping of child growth failure indicators for 105 low- and middle-income countries between 2000 and 2017 shows that, despite considerable progress, substantial geographical inequalities still exist in some countries.

Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

An international consortium reports the genomic sequence for ten Drosophila species, and compares them to two other previously published Drosophila species. These data are invaluable for drawing evolutionary conclusions across an entire phylogeny of species at once.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Synthetic biology can be used to create rationally designed living therapeutics. Here the authors engineer E. coli Nissle to target STING activation in antigen presenting cells for the treatment of solid tumors and demonstrate preclinical activity in murine models.

Integration of GWAS and single-cell transcriptomic data from the entire nervous system systematically identifies cell types underlying brain complex traits and provides insights into the etiology of Parkinson’s disease.

Integrin β7-dependent Glp1r^high natural gut intraepithelial T lymphocytes that reside in the small intestine modulate dietary metabolism in mice by restricting the bioavailability of GLP-1.

In this Stage 2 Registered Report, Coles et al. present the results of a multicentre global adversarial collaboration on the facial feedback hypothesis.

In high-risk neuroblastoma cases, gains in chromosome 17q are common. Here, the authors investigate the epigenomics and transcriptomics of neuroblastoma, identifying TBX2 as a core regulatory circuitry component enhancing the reactivation of DREAM targets by MYCN/FOXM1.

The rational design of catalysts is crucial to make power-to-X technologies viable. Here the authors introduce the delafossite PdCoO₂ as a highly active hydrogen evolution reaction catalyst due to the growth of a tensile-strained Pd-rich capping layer under reductive conditions. Image credit: Christop Hohmann.