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This study develops a climate health vulnerability index for New York State, presenting an updated modeling framework and showing through sensitivity analyses that design choices affect the identification of vulnerable populations.

Artificial neural networks face challenges of robustness and efficiency as they scale. Here, the authors show that incoherent network motifs provide greater stability and resilience to noise than coherent network motifs, offering new structural insights for designing stronger neural networks.

Large language models are starting to be used in safety-critical tasks such as controlling robots. Zhou et al. present LabSafety Bench, a benchmark evaluating the ability of large language models to identify hazards and assess laboratory risks.

Monitoring charge carrier dynamics and photocatalytic reaction rates in individual photocatalyst particles is a challenging task that can help us to understand structure–reactivity relationships. Here single-molecule fluorescence imaging is coupled with femtosecond interferometric scattering microscopy to investigate these properties in 2D InSe flakes.

Artificial assembly of small functional proteins provides effective strategies for downsizing RNA degraders. Here, authors develop STAR, a hypercompact RNA degrader with evolved toxin endoribonucleases and engineered Cas6- CBS system, enabling efficient degradation of cytoplasmic and nuclear RNAs.

Skyrmions - nanoscale, topological spin textures - are promising elements for next-generation computing due to their efficient coupling to currents in racetrack devices. Here, Tan et al. examine over 20,000 instances of current induced skyrmion motion to unveil a comprehensive picture of skyrmion dynamics across currents and fields.

Leber hereditary optic neuropathy (LHON) is caused by mtDNA mutations. Here, authors generated a mouse model with the common LHON mutation and showed that optimized TALE-like deaminases restored both phenotype and genotype via high-fidelity mitochondrial base editing.

Highly pathogenic avian influenza A H5N1 clade 2.3.4.4b virus has caused outbreaks in dairy cattle and cases in humans in the United States. Here, the authors assess levels of pre-existing cross-reactive antibodies to the epidemic virus strain in human serum samples collected in the United States.

Iron-rich oxides at the lowermost mantle conditions have ultralow thermal conductivity, which would impact regional thermochemical evolution around seismic ultralow velocity zones above Earth’s core-mantle boundary.

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.

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.

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.

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.

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.

Analyses of the genome sequences and expression data for two closely related mycoheterotrophic orchid species provide insights into the genomic basis underlying the evolution of mycoheterotrophy.

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.

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.

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.

Infection with SARS-CoV-2 causes interstitial pneumonia and viral replication in the lungs of transgenic mice that express a human version of ACE2, confirming the pathogenicity of the virus in this model.

An Ohmic contact interface engineering strategy was proposed by loading copper nano islands on indium hydroxide nanocubes, which could trigger and stabilize the polarized Cu0 -Cuδ+ active sites. Such catalyst enabled effective ammonia electrosynthesis with nitrate under ambient conditions

The spatial and temporal control of material properties at a distance have been so far achieved with light, heat, or sound. Here, the authors control chemical reactions and further polymerization of composites with an electric field via inverse piezo-effect resulting in multi-stiffness gels.

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.

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.

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.

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.

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.

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.

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.

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 persistence of myofibroblasts after wound healing is ultimately responsible for scarring. Here, the authors show that fibromodulin enhances interleukin 1β ternary complex formation, promoting myofibroblast apoptosis and providing a potential strategy to mitigate scarring.

In this phase 3 trial, first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with anti-PD-1 finotonlimab plus cisplatin plus 5-fluorouracil (C5F) prolonged overall survival compared with placebo plus C5F.

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.

Activation of lattice oxygen‒metal configurations in transition metal oxide-based capacitive deionization systems can enhance their performance but requires high voltages. Here the authors enhanced the capacitive deionization performance by developing a V₂O₅/V₂CO_2p heterostructure that can activate oxygen redox at low voltage (<2 V).

In the multicenter, phase 3 DAWNA-1 trial, the combination of dalpiciclib, a new cyclin-dependent kinase 4 and 6 inhibitor, with fulvestrant, in patients with HR⁺HER2⁻ advanced breast cancer who progressed or relapsed on endocrine therapy, improved progression-free survival with manageable safety and may represent a new treatment option.

Cryo-electron microscopy structure of heterodimeric GABA_B receptor in complex with G_i1 protein reveals that the mode of G-protein binding in this class-C G-protein-coupled receptor differs from that of other classes.

In chemical-genetic and lipidomics analyses, the clinical candidate oncology drug tegavivint induced an unconventional form of nonapoptotic cell death that required the lipid metabolic enzyme trans-2,3-enoyl-CoA reductase.

Metabotropic glutamate receptors exist as both homo- and heterodimers. Here, the authors report the mGlu2-4 receptor structures in the inactive, intermediate and active states, and reveal the reason for the partial activity of the mono-liganded dimers.

The metastatic tumour microenvironment in pancreatic ductal adenocarcinoma (PDAC) remains to be explored. Here, the authors perform single cell RNA sequencing analysis for synchronously resected PDAC primary tumours and matched liver metastases and find differences in cellular composition.

A pangenome analysis of 76 wild and domesticated barley accessions in combination with short-read sequence data of 1,315 barley genotypes indicates that allelic diversity at structurally complex loci may have helped crop plants to adapt to agricultural ecosystems.

Radiation-hardened electrostatic dielectric capacitors are critical components in advanced electronic and electrical systems. Here, the authors demonstrate a high-energy-density and radiation-tolerant capacitor by constructing a dendritic-like structured ferroelectric embedded in an insulator.

In quantum random number generation, one has generally to choose between high speed and strong security. Here, the authors show how to bound several adversarial imperfections on state preparation and measurement, generating 8192 secure random bits every 0.12 s in real time using a simple apparatus.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

The genome of the scallop Patinopecten yessoensis is sequenced. This bivalve mollusc has a slow-evolving genome with features such as karyotype and Hox gene expression that may be close to that of the ancestral bilaterian.