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Through integrated multi-omics and experimental validation, this study reveals that altered gut microbiota and bile acid metabolism activate TLR3 to induce urothelial injury in interstitial cystitis, identifying a pathway with therapeutic potential.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

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.

Immunotherapy has improved patient outcomes in those with metastatic or recurrent head and neck squamous cell carcinoma (HNSCC) but less so in the neoadjuvant setting. Here, the authors report the efficacy, safety and exploratory biomarker analysis of a phase II clinical trial investigating neoadjuvant tislelizumab (anti-PD-1) and afatinib (EGFR TKI) in patients with locally advanced HNSCC.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

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.

The synthesis of high value heterocycles from cheap starting materials remains challenging. Here, the authors develop a new strategy to realize practical and modular synthesis of N-H indoles and analogs from toluene and nitrile derivatives using naturally abundant copper salt as catalyst.

Nonlinear transport effects arising from the quantum metric have been reported in topological magnets at low temperatures. Here, the authors demonstrate a second-harmonic transport response in TbMn₆Sn₆ at room temperature, attributed to the quantum metric and controllable via an applied magnetic field.

This Resource provides a multi-omic tissue atlas of aging in nonhuman primates.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Fault-tolerant manipulation of quantum bits is demonstrated experimentally on an eight-photon cluster state using topological error correction.

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.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Understanding brain function requires integrating neuronal structure, activity, and genes. Here, authors developed an optogenetic tool they name Pisces, to enable complete labeling of individual neurons’ morphology with functional and molecular profiling, allowing multimodal single-cell analysis in vivo in zebrafish.

In a quantum simulation of a (2+1)D lattice gauge theory using a superconducting quantum processor, the dynamics of strings reveal the transition from deconfined to confined excitations as the effective electric field is increased.

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.

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.

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.

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.

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.

Excessive fibrosis triggered by bisphosphonates impairs fracture healing in osteoporotic bone. Here, the authors develop an injectable magnesium-alendronate MOF-based hydrogel adhesive and show it prevents fibrosis and enhances bone repair, improving healing strength in an osteoporotic rat model.

Single-nucleus RNA-seq was used to profile 11 retinas with varying stages of age-related macular degeneration and 6 control retinas. The authors identified shared glial states across neurodegeneration, indicating that the retina provides a human system for investigating therapeutic approaches in neurodegeneration.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

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.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

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.

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.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

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.

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.

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.

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

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.

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.

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.

Nanopore reads have been advantageous for de novo genome assembly; however these reads have high error rates. Here, the authors develop an error correction and de novo assembly tool, NECAT, which produces efficient, high quality assemblies of nanopore reads.

Colour code on a superconducting qubit quantum processor is demonstrated, reporting above-breakeven performance and logical error scaling with increased code size by a factor of 1.56 moving from distance-3 to distance-5 code.

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 jujube is a major dry fruit crop in China and is commonly used for medicinal purposes. Here the authors sequence the genome and transcriptome of the most widely cultivated jujube cultivar, Dongzao, and highlight the genetic and molecular basis of agronomically important jujube traits, such as vitamin C content.

Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.

Long-read single-cell RNA isoform sequencing can elucidate the intricate landscape of alternative RNA splicing in individual cells, but it suffers from a low read throughput. Here, the authors develop circular consensus sequencing methods to allow high-throughput and high-accuracy single-cell RNA isoform sequencing.

Subpopulations of cytokine-producing and myofibroblastic hepatic stellate cells, identified by single-cell RNA sequencing, protect against or promote the development of hepatocellular carcinoma via high expression of hepatocyte growth factor or type I collagen, respectively..

Here, the authors simultaneously capture dynamic Raman spectral evidence of Ru surfaces, interfacial water, *H and *OH intermediates, and the interactions between them, demonstrating the regulation of Ru valence state on interfacial water and intermediates for catalytic activity improvement.

The LHCb experiment at CERN has observed significant asymmetries between the decay rates of the beauty baryon and its CP-conjugated antibaryon, thus demonstrating CP violation in baryon decays.

Authors propose an entropy engineering strategy to realize the carrier-phonon decoupling in SrTiO₃-based perovskite thermoelectrics, reducing the lattice thermal conductivity nearly to the amorphous limit and improving the weighted mobility.