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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.

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 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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Wartewig et al. show that PDCD1 in T cell lymphoma restricts glycolytic energy and acetyl-CoA production. Inhibition of PD-1 signaling enforces ACLY activity and generates extramitochondrial acetyl-CoA for histone acetylation to enable AP-1 hyperactivation.

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 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.

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.

Josephson junctions composed of graphene are limited by incomplete gate control of the supercurrent, impeding their development for superconducting quantum devices. Here, the authors fabricate bipolar Josephson junctions of graphene, allowing supercurrent on/off switching through electrostatic gating.

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

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.

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.

Quantum vacuum fluctuations can create pairs of virtual particles that annihilate each other. Here, the authors show that the conventional theory that these particles have no measurable effect on real particles does not apply to anyons, exotic quasiparticles that are intermediate between fermions and bosons.

Acid sphingomyelinase (ASM) is a sphingolipid metabolizing enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide, and previous work has shown it is upregulated in models of Alzheimer’s disease. Here the authors demonstrate in a mouse model of Alzheimer’s disease that antibody-based immunotherapy targeting plasma ASM resulted in attenuated neuropathological features by suppressing pathogenic Th17 cells.

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.

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.

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

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.

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.

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.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

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.

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.

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.

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.

The relationship between striatal vascular and neural activity is not fully understood. Here the authors found neuronal activity inadequately explains striatal hemodynamic polarity, challenging classic fMRI interpretations.

Bcl-xL is an anti-apoptotic protein that has also been implicated in metastasis. In this study, the authors show that nuclear Bcl-xL promotes metastasis by regulating TGFβ signaling, which is independent of the anti-apoptotic activity of Bcl-xL.