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Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

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.

Emu3 enables large-scale text, image and video learning based solely on next-token prediction, matching the generation and perception performance of task-specific methods, with implications for the development of scalable and unified multimodal intelligence systems.

In this study, the authors present that deep brain stimulation of lateral hypothalamic area activates a hypothalamic-pontine-spinal pathway, promoting locomotor initiation and functional recovery after spinal cord injury in mice.

The heterogeneity of HSPCs in response to IR stress remains poorly characterized. Here, the authors provide insights into the molecular intricacies of IR-induced BM injury and reveal the roles of BMP4-BMPR2 signaling in radiation resistance of HSCs.

Wang, Xiao and colleagues develop and validate organ-specific proteomic aging clocks across large population cohorts in the UK, the USA and China, which show strong performance in tracking organ aging and predicting the risk of morbidity and mortality.

Vapour-phase methods are promising for nanomaterial synthesis but the vaporization of different precursors for the synthesis of a broad nanomaterial space is challenging. Here electrified vapour deposition generates ultrahigh-temperature, high-flux atomic vapour at atmospheric pressure to rapidly vaporize diverse precursors, enabling the synthesis of multi-elemental nanomaterials with uniform compositions and tunable structures.

Self-healing materials promise commercial success if they can balance fatigue resistance and stiffness for industrial applications. Here, the authors develop a multiscale interlinked structure using an MXene framework within a polyurethane matrix, achieving high fatigue resistance, rapid self-healing, and enhanced stability.

Meng et al. report that lymphoid fate is programmed epigenetically rather than transcriptionally in haematopoietic stem cells and shed light on how epigenetic programming generates platelet differentiation pathways with distinct kinetics.

Glycogen phosphorylase kinase (PhK) initiates glycogen degradation by phosphorylating glycogen phosphorylase (GP), positioning itself at the core of glycogenolysis. Here, the authors utilize cryo-EM to elucidate the mechanisms by which human PhK is regulated by phosphorylation and calcium ions, and reveal its binding mode with the substrate GP.

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.

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.

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.

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.

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.

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.

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.

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.

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.

RNA modifications appear to play a role in determining RNA structure and function. Here, the authors develop a deep learning model that predicts the location of 12 RNA modifications using primary sequence, and show that several modifications are associated, which suggests dependencies between them.

This study identifies a decadal link between sea surface temperatures off Western Australia and the western-central tropical Pacific that has emerged since 1985. Driven by external forcings and the rapid changes in the Indo-Pacific warm pool, it may impact future climate.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

The emergence of tumour adaptive radioresistance can limit the success of radiation therapy and immunotherapy in breast cancer. In this study, the authors demonstrate that CD47 and HER2 are coordinating in tumor response to radiation and that co-blockage of both receptors can eliminate radiorestistant breast cancer cells.

Expansion of human hematopoietic stem cells present in cord blood or bone marrow can be achieved by cell culture in a hydrogel, potentially facilitating clinical applications of hematopoietic cell transplantation.

A swallowable X-ray dosimeter detects the absolute absorbed radiation dose alongside changes in pH and temperature in the gastrointestinal tract of rabbits.

There is a need for extensive neuroimaging datasets to facilitate the study of dynamic human visual perception. Here, the authors present a repository of whole-brain fMRI responses to over 1000 short naturalistic video clips across ten human subjects.

In this work, the authors develop a platform called AGILE or AI Guided Ionizable Lipid Engineering, which streamlines ionizable lipid development. Using AGILE, they rapidly design, synthesize, and evaluate ionizable lipids for mRNA delivery.

Twisted 2D magnets provide a rich playground for potential spintronic device architectures. Here, the authors use tunneling magnetoresistance measurements to investigate the collective spin states of twisted double bilayer CrI₃ in various configurations, providing evidence of non-volatile spin textures.

Myeloid cells contribute to the tumor microenvironment of thyroid cancers, but their functional relevance is lesser known. Here authors show that myeloid cells infiltrating non-medullary thyroid carcinomas upregulate their antigen presentation-related genes, release less cytokines and over-produce reactive oxygen species, with transcriptional changes already present in extra-tumoral myeloid cells.

The delta opioid receptor (δOR) is key in modulating sensation and emotion with a lower risk of drug dependence. Here, authors report cryo-EM structure of δOR and design probes to explore its signaling bias, with insights for drug discovery.

Lawson et al. show that genetic inactivation of Phd1 or Phd2 hinders progression of AML and compromises leukemic stem cells. They develop a selective PHD inhibitor IOX5 and show therapeutic efficacy in AML, which can be potentiated with venetoclax.

Optical neural networks face remarkable challenges in high-level integration and on-chip operation. In this work the authors enable optical convolution utilizing time-wavelength plane stretching approach on a microcomb-driven chip-based photonic processing unit.

The proposed edge detection based on ferroelectric field effect transistor does not rely on conventional convolution operation, realizing no-accuracy-loss, low-power (~10 fJ/per operation) and analogue-to-digital converter (ADC)-free edge computing.

Arboviruses are transmitted by arthropods and include a number of critical human and zoonotic pathogens. Here the authors report a phage display library, ArboScan, for evaluating antibody binding to the peptidome of 691 human and zoonotic arthropod borne viruses, and use it to profile anti-arbovirus antibodies from diverse samples.