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Here, the authors show that packaging of bacterial DNA by phage-like particles is widespread in the gut microbiome, with activity of gene transfer agents being prominent in Oscillospiraceae and Ruminococcaceae; and identifying lateral transduction by a temperate phage in Bacteroides.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

The underlying molecular mechanisms of neuroinflammation and axonal damage in progressive multiple sclerosis remains unclear. Here, authors show proteomics results of human progressive multiple sclerosis brain tissues and found extracellular matrix proteins (annexin, S100, AHNAK families) were enriched in lesions and white matter.

Analysing the causal links of gene expression and protein abundance on type 2 diabetes risk in blood and seven tissues related to the disease from individuals of four ancestries, the authors advance our understanding of the genetic architecture of type 2 diabetes

The kākāpō is an intensively managed parrot endemic to New Zealand. Using genome sequencing data for all living kākāpō together with long-term phenotypic data, the authors devise an approach to identify genetic associations with fitness traits, which is informing species recovery plans.

The high-plasticity cell state (HPCS) is a critical hub that enables reciprocal transitions between cancer cell states, and targeting the HPCS may suppress cancer progression and eradicate treatment resistance.

Electrochemical acid-base production has attractive applications in mineral recovery and CO₂ removal, but current membrane-based designs are plagued by resistive losses. The authors report a membrane-less system generating useful acid and base solutions at high rates with less energy.

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here the authors report the results of a phase II clinical trial of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in RMC, associating the activation of a myeloid mimicry program in tumor cells to the rapid disease progression and hyper-progression observed in treated patients.

Though it is the most common joint disease, osteoarthritis has no molecular biomarkers or disease-modifying therapies. Here, the authors show miR-126-3p is a mechanistic biomarker that regulates angiogenesis and mitigates knee osteoarthritis severity.

The GLASS Consortium studies the evolutionary trajectories of 222 patients with a diffuse glioma to aid in our understanding of tumour progression and treatment failure

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

T-cell acute lymphoblastic leukemia is a highly aggressive disease with varying recurrence rates. Here, the authors build a single cell transcriptomic atlas of childhood T-cell acute lymphoblastic leukaemia (T-ALL). They identified a distinctive cancer cell state that correlates with high risk, treatment refractory T-ALL.

Parallel operation of two exchange-only qubits consisting of six quantum dots arranged linearly is shown to be achievable and maintains qubit control quality compared with sequential operation, with potential for use in scaled quantum computing.

Biocatalysis and metal catalysis often provide complimentary reactivities and selectivities. Here, the authors exploit the regioselectivity of an enzymatic C–H activation followed by palladium catalysed carbon-carbon bond formation in one pot, with membrane compartmentalization used to isolate the two chemistries.

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.

This paper presents TDAC-seq, a targeted chromatin-accessibility-profiling method using cytidine deaminases and long-read sequencing, to resolve the effects of CRISPR edits on single chromatin fibers.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

The journal and article are being superseded by algorithms that filter, rate and disseminate scholarship as it happens, argues Jason Priem.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

KDM4C regulates cathepsin L-mediated histone H3 N-terminal tail clipping through grainyhead-like 2 (GRHL2) methylation in breast cancer. This link between the cellular redox state and chromatin remodeling might represent a therapeutic target in KDM4C-amplified tumors.

The development of catalysts that operate under low concentration CO₂ resembling industrial waste gases holds promise for CO₂ reduction. Here, the authors report a vacuum calcination approach for regulating the Cu⁰/Cu¹⁺ density on Cu-based catalysts that can electro-catalyze low-concentration CO₂.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Previous work has realized a superconducting switch in heterostructures of superconductors and ferromagnetic insulators, but the effect has been smaller than originally predicted. Here, the authors report an absolute superconducting switch by inserting a heavy metal layer in the EuS/Nb/EuS heterostructure.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

RNA assembly has potential for developing biomaterials with tailored properties and functionalities. Here, the authors report on designed, angle-controllable RNA tiles for programmable 1D and 2D self-assembly of RNA, demonstrating RNA sensing and expanding the library of synthetic RNA nanostructures.

At present, there are no countermeasures against the GI genogroup of noroviruses. The authors characterize a protective human antibody that broadly recognizes this genogroup.

Group-IV color centers in diamond show promise for spin-photon interfaces, but precise positioning and activation are challenging. Here the authors combine site-controlled ion implantation with laser annealing and in-situ photoluminescence monitoring to create and tune individual tin vacancy centers in diamond.

Functional CRISPR screens in patient-matched pre-treatment and post-treatment glioblastoma models identify the PTP4A–ROBO1 axis as a driver of tumorigenicity and enriched ROBO1 expression in recurrent glioblastoma that can be targeted with CAR T cell therapy.

Jonathan Thomas and colleagues present real-time plasma effector measurements during wound treatment. In- situ monitoring enables precise plasma device control, advancing precision plasma medicine and supporting clinical translation.

PIEZO2 is expressed in the bladder urothelium and sensory neurons innervating the lower urinary tract and is a key mechanosensor for the control of urination.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

Comprehensive genomic and transcriptomics analyses of more than 1,300 cases of childhood T-lineage acute lymphoblastic leukaemia identify 15 distinct subtypes that are associated with specific outcomes.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

End-product toxicity, culture contamination, and energy efficient product recovery are long-standing issues in bioprocessing. Here, the authors address these problems using a fermentation strategy that combines microbial production of branched alcohols with supercritical carbon dioxide extraction.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Mutation of the C-terminal extension of 5′-aminolevulinate synthase 2 (ALAS2) is the molecular cause for X-linked protoporphyria, but the underlying mechanism is unclear. Based on crystal structures and MD simulations of ALAS2, the authors here show how the C-terminal extension regulates ALAS2 activity.