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MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Platinum-group-metal-free, non-iron catalysts are highly desirable for the oxygen reduction reaction at proton exchange membrane (PEM) fuel cell cathodes, as they avoid the detrimental Fenton reactions. Now, a cobalt and nitrogen co-doped carbon catalyst with atomically dispersed porphyrin-like CoN₄C₁₂ sites is reported with an improved activity and durability in PEM fuel cell conditions.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

The Kondo effect from magnetic impurities has been proposed as a probe of fractionalized excitations in a topological quantum spin liquid. Lee et al. experimentally demonstrate the Kondo effect in a Kitaev candidate material α-RuCl3 with dilute Cr impurities.

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.

An array of optical tweezers trapping 6,100 neutral-atom qubits in 12,000 sites is experimentally realized, demonstrating performance exceeding present technologies and enabling the prospect of large-scale quantum computing and quantum error correction.

It is challenging to realize doping and surface passivation simultaneously in colloidal quantum dot inks. Here Choi et al. employ a cascade surface modification approach to solve the problem and obtain record high efficiency of 13.3% for bulk homojunction solar cells based on these inks.

Despite the development of inhibitors targeting active GTP-bound (ON) KRAS(G12C) for the treatment of KRAS G12C-driven non-small cell lung cancer (NSCLC), resistance remains an issue. Here, the authors show that despite inhibition of KRAS G12C ON, there is residual mTOR activity driving resistance, which was successfully targeted by combining with a selective mTOR inhibitor.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

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.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

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.

Superfluid ³He is a quantum condensate in which the He atoms are paired in an unconventional way. Yet despite extensive research on the collective modes of superfluid ³He, one mode has remained undiscovered, until now.

Frustration-induced dimensional reduction is manifested in lower dimensionality of magnetic correlations compared to that of the magnetic structure. Here the authors demonstrate the role of the uniform Dzyaloshinskii-Moriya interaction in the recently synthesized material Ca3ReO5Cl2 exhibiting dimensional reduction.

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.

Magnetic field induced competing phases in high-temperature superconductors provide a testbed for various theoretical scenarios. Here, Choi et al. report evidence of inhomogeneous superconducting state due to the different competition strength between two charge density wave orders in YBa₂Cu₃O_6.67.

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.

In order to be practical, schemes for characterizing quantum operations should require the simplest possible gate sequences and measurements. Here, the authors show how random gate sequences and native measurements (followed by classical post-processing) are sufficient for estimating several gate set properties.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

In human spinal ligament tissue exposed to high stress, fibrotic regions displaying elevated Rho-associated kinase signalling and an increased density of myofibroblasts expressing smooth muscle actin α contribute to degenerative spinal disease.

Here, Rathnasinghe et al. characterize the pathogenesis of a mouse-adapted SARS-CoV-2 in infected obese and aged mice, and identify mutations that are present in SARS-CoV-2 variants of concern, associated with higher transmissibility.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

RAMP3, a component of the receptor for the neuropeptide CGRP, has a cell-intrinsic role in T helper type 1 cell fate determination.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Metabolic Dysfunction-Associated Steatohepatitis (MASH), an advanced form of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), can progress to liver fibrosis. Here, the authors develop a peripheral 5HT_2A antagonist for the treatment of MASLD and MASH.

Electron optics draws upon the resemblance between electron and optical waves. Here, the authors report on the observation of electron mode formation in open cavity resonators realized in a GaAs/AlGaAs two-dimensional electronic gas.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

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.

Upon inflammation and targeted gene mutation, some fully differentiated secretory and postmitotic intestinal epithelial lineages dedifferentiate to acquire stem-like features and promote tumor formation.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Glycogen Storage Disease 1a (Gsd1a) is an inherited disorder caused by glucose 6-phosphatase (G6Pase-α) deficiency and characterized by hypoglycaemia and high risk of liver cancer. Here the authors develop a mRNA-based G6Pase-α delivery therapy that is efficacious and safe in a mouse model of GSD1a.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

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.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Immune checkpoint therapies (ICT) are promising for treating various cancers, but response rates vary. Here the authors show, in mouse models, that tumor-infiltrating mast cells colocalize with regulatory T cells, coincide with local reduction of MHC-I and CD8 T cells, and is associated with resistance to ICT, which can be reversed by c-kit inhibitor treatment.

Carbon nanotube yarns with high loadings of pseudocapacitive material are desirable, e.g., for emerging wearable technologies. Here authors make biscrolled yarns with high loadings of MnO₂nanoparticles confined in carbon nanotube galleries, demonstrating very high linear and areal capacitances.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

Combining results from 76 studies, Kunin et al. find evidence for two distinct drivers of infant looking: the degree to which a stimulus is unexpected and the degree to which it is visually unfamiliar.

Pyruvate carboxylases are homotetrameric enzymes in eukaryotes and most bacteria. Here, the authors report the structure of an unusual two-subunit form of the enzyme from the Gram-negative bacterium Methylobacillus flagellates, revealing an unexpected α₂β₄stoichiometry.

Isotope tracing, kinetics and transcriptomics show how members of the four AOM lineages employ different nitrogen use strategies that minimize competition for nitrogen substrates.