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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.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Humans are highly efficient at recognizing manipulable objects. To understand this ability, we must uncover how the brain represents object-related information. Here, we investigated whether information within the category of manipulable objects is organized according to three distinct knowledge types: visual aspect, manner of manipulation, and functional purpose. Our findings suggest that these knowledge types are processed in different brain areas, with each region representing information based on real-world object similarity.

Motor skill acquisition decreases with age, as seen in zebra finches whose songs become fixed after a critical period. By manipulating inhibitory neurons in adult finches, the authors restored vocal plasticity, allowing the birds to learn new syllables without affecting existing ones.

Perro and colleagues develop a CD3⁺ T cell engager co-targeting BCMA and CD38 to improve immunotherapy for multiple myeloma, demonstrate cytotoxicity in patient-derived samples and murine models and develop a quantitative systems pharmacology model.

Haematopoietic stem cell (HSC) clonogenic activity, lineage output, lineage commitment and somatic mutation rates are influenced by the underlying disease, patient age, extent of genetic defect correction and hematopoietic stress imposed by the inherited disease, suggesting HSC adaptation.

A single-cell atlas of the developing mouse cortex provides a temporal and spatial assessment of the molecular logic that drives the establishment and organization of cortical cell types.

Pneumococcal carriage in the upper respiratory tract is an important determinant of influenza severity. Jochems et al. use human systems analysis to show that influenza-induced inflammation increases bacterial burden in the nasal cavity with implications for secondary bacterial pneumonia.

Using cervical explant models and cervical tissue from ART-suppressed HIV⁺ women, the authors here show that resident memory T cells (T_RM) in the cervical mucosa are preferentially infected and harbor more viral DNA, RNA and protein than non-T_RM, suggesting that T_RM may serve as viral reservoir in the cervical mucosa.

Using metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma mouse models, an ATP citrate lyase inhibitor reduces tumour burden and enhances efficacy of current standards of care.

T cell responses to spike protein from the SARS-CoV-2 Omicron variant (B.1.1.529) are broadly similar to the responses to ancestral, Beta (B.1.351) and Delta (B.1.617.2) spike protein in vaccinated, infected and unvaccinated individuals.

The blood–brain barrier was conventionally seen as a static protective structure, but a more complex, dynamic view of this barrier has now emerged. In this Review, Friedman et al. discuss the dynamic modulation of the blood–brain barrier under physiological conditions.

The cerebral cortex shows many similarities among species, whilst also enabling adaptations to a range of specific niches. By building a unified cerebral cortex map of ninety species, this study traces the intricate evolutionary history that links cortical morphology and its functional topography.

PdCO is a switchable optogenetic tool for inhibiting synaptic transmission in neuronal terminals in vivo, as demonstrated in a variety of contexts mainly in the mouse.

The management of acute migraine in the emergency department presents a therapeutic challenge for physicians, who need to provide adequate pain relief while minimizing adverse events and relapses. New research suggests that phenothiazines are effective drug therapies for acute migraine, highlighting their potential use as first-line treatments for acute migraine in the hospital setting.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Comparing clinically diagnosed adults with autism spectrum disorder (ASD) with online participants with self-reported high autistic traits, this study detected higher rates of social anxiety and avoidance symptoms in online participants, emphasizing the potential distinctions between clinically ascertained autism and self-reported trait-based samples.

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.

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.

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.

PTSD symptom severity in combat veterans was associated with enhanced sensitivity to prediction errors and lower neural tracking of value and learning rate, providing evidence for neurocomputational contributions to trauma-related psychopathology.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Effective science communication is necessary for engaging the public in scientific discourse and ensuring equitable access to knowledge. Training doctoral students in science communication will instill principles of accessibility, accountability, and adaptability in the next generation of scientific leaders, who are poised to expand science’s reach, generate public support for research funding, and counter misinformation. To this aim, we provide a guide for implementing formal science communication training for doctoral students.