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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.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Values of choice options often change over time. Here, the authors show that during prospective decision making the entorhinal cortex encodes changing values using a grid-like representation, suggesting the formation of a cognitive value map.

Sarcomas are a group of mesenchymal malignancies which are molecularly heterogeneous. Here, the authors develop an in vivo muscle electroporation system for gene delivery to generate distinct subtypes of orthotopic genetically engineered mouse models of sarcoma, as well as syngeneic allograft models with scalability for preclinical assessment of therapeutics.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

TDP-43 aggregates are a hallmark of neurodegeneration. Wagner et al. show that SUMOylation/ubiquitylation of TDP-43, mediated by its recruitment to the promyelocytic leukemia protein nuclear bodies, prevents its aggregation under proteotoxic stresses.

Fatty liver disease exacerbates atherosclerosis, but the underlying mechanisms remain unclear. Here, the authors show that D-dopachrome tautomerase (D-DT/MIF-2) acts as an atypical chemokine, promoting both atherosclerosis and hepatic lipid accumulation.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Nominally identical materials are found to spontaneously order into triboelectric series over repeated processes, which is found to be driven by the act of contact itself using experiments as well as numerical simulations.

X-ray optics are notoriously challenging to fabricate due to the strict tolerances that result from the short wavelength of radiation. Here, Seibothet al. carefully quantify aberrations in complex X-ray lenses and correct them with an easy-to-fabricate broadband phase plate.

Exome sequencing within a structured diagnostic process for rare diseases in Germany shows how facial image analysis and machine learning can guide variant prioritization and uncover many ultrarare diseases.

In this Review, the authors present a roadmap towards achieving consensus on development, analysis and interpretation of single-cell transcriptomics data in adipose tissue, including discussion of roadblocks, best practices and ideal cell-type markers for annotation of adipose tissue cell types in mice and humans.

Second-generation oxidation boosts the production of anthropogenic organic aerosol, according to an analysis of urban haze in an experimental chamber.

How we juggle morally conflicting outcomes during learning remains unknown. Here, by comparing variants of reinforcement learning models, the authors show that participants differ substantially in their preference, with some choosing actions that benefit themselves while others choose actions that prevent harm.

In tauopathies, the microtubule-associated protein tau is hyperphosphorylated and aggregated. Here the authors identified a polypharmacological small molecule that inhibits aggregation, reduces phosphorylation, and restores microtubule interaction of tau.

Long-range magnetic order hardly ever emerges in a two-dimensional system due to the competition of fundamental magnetic interactions. Here, Girovskyet al. directly observe a long-range ferrimagnetic order emerging in a two-dimensional supramolecular Kondo lattice.

The practical use of all-solid-state batteries is hindered by lithium dendrites formed at current densities lower than the threshold suggested by industry research. Here, the authors propose a MHz-pulse-current protocol to circumvent the low-current cell failure and provide mechanistic analyses.

Many alkyl fluorides are readily available, but the synthetic applications trail behind the widely accepted utility of other halides. Here, the authors report a practical Csp3-F bond functionalization method that expands the currently restricted synthetic space of unactivated C(sp3)-F bonds, but also uses benzylic, propargylic and acyl fluorides.

Although intermetallic compounds and alloys feature metal atoms bonded solely to other metal atoms, this motif is unusual in molecular compounds. Now, three compounds with lanthanide metals surrounded by transition metal atoms have been made. Although reactive, they mimic intermetallic bonding and form a conceptual link from coordination compounds.

Vertebrate skeletogenic cells of different embryonic origins are distinct cell types, based on their lineage-specific gene regulatory logic that specifies them, and the potential for individualized evolutionary trajectories resulting therefrom.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

Zeiser and colleagues show that CAR T cell therapy results in upregulation of the TGFβ-activated kinase-1 (TAK1)–NF-κB–p38 MAPK pathway in microglia, causing neurocognitive defects, and find that TAK1 inhibition can reduce immune effector cell-associated neurotoxicity syndrome.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Paclitaxel is an important anticancer drug whose biosynthetic pathway reconstruction is hindered by the propensity of heterologously expressed pathway cytochromes P450, including taxadiene 5α-hydroxylase (T5αH), to form multiple products. Here, the authors tune the promoter strength for T5αH expression in Nicotiana plants to increase the levels of paclitaxel precursor taxadien-5α-ol by three-fold and reconstitute the six step early biosynthetic pathway of paclitaxel.

The grain boundaries between two coexisting phases in organic semiconductor pentacene are expected to obstruct charge transport in its thin-film devices. Westermeier et al. use infrared-spectroscopic nano-imaging to show an interlocking morphology, which is uncorrelated with its grain structures.

Van der Waals interactions are difficult to calculate at an atomistic level for moderate sized structures due to the many distinct atoms involved. Here, the authors measure the van der Waals force between an organic molecule and a metal surface, examining the non-additive part of these interactions.

Single-cell RNA sequencing with parallel tagging of progenitor cells is used to track clonal relationships and transcriptomic signatures during development of the mouse forebrain.

Analyses of 475 ancient horse genomes show modern horses emerged around 2200 bce, coinciding with sudden expansion across Eurasia, refuting the narrative of large horse herds accompanying earlier migrations of steppe peoples across Europe.

Inspired by motile plant structures that respond passively to external stimuli, in this work the authors validate biobased cellulosic materials and bioinspired 4D-printed hygromorphic bilayers for a weather-responsive, energy-autonomous shading system with a demonstration at an architectural scale.

Children are less likely to be infected with SARS-CoV-2 and develop less severe disease than adults, which makes estimation of infection rates challenging. Here, the authors conduct seroprevalence surveys of children in Germany, describe changes in prevalence over time, and identify risk factors for infection.

3D electron crystallography enables structure determination of submicron-sized crystals, but obtaining complete data is difficult due to preferred orientations. Here the authors develop sample supports that allow sampling nanocrystals with full data completeness, and demonstrate this with ZSM-5 zeolites.

Surface averaging techniques offer only limited access to the electrostatic potentials of nanostructures, which are determined by shape, material, and environment. Here, the authors quantify these potentials for gold and silver adatom chains, explaining the mechanisms of dipole formation.

A computationally designed antigen based on the receptor binding ___domain of the spike protein of sarbecoviruses elicits broad humoral responses against severe acute respiratory syndrome viruses in mice, rabbits and guinea pigs.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

The enzymatic breakdown of the lipid sphingomyelin is associated with various infectious diseases. Here, the authors introduce trifunctional sphingomyelin derivatives for the visualisation of sphingomyelin distribution and sphingomyelinase activity in infection processes.

The bacterium Helicobacter pylori, often found in the human stomach, can be classified into distinct subpopulations associated with the geographic origin of the host. Here, the authors provide insights into H. pylori population structure by collecting over 1,000 clinical strains from 50 countries and generating and analyzing high-quality bacterial genome sequences.