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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.

Current short-pulse-duration neutron sources suffer from a low repetition rate, hindering applications. Here, the authors demonstrate advancements of laser-wakefield based photoneutron generation at high repetition rates and conversion efficiencies, providing an alternative to traditional pitcher-catcher methods.

The 11^th International Conference on Rare Diseases and Orphan Drugs (ICORD), South Africa, included the Africa-Rare initiative launch and facilitated multi-stakeholder engagement in the challenges facing, and opportunities for, Africans living with rare diseases. The following ICORD Global Call to Action, developed in collaboration with the International Rare Diseases Research Consortium, synthesizes the outcomes of the deliberations and emphasizes the international collaborative efforts required to address the global effects of rare diseases on public health.

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.

Aligning foundation models with human judgments enables them to more accurately approximate human behaviour and uncertainty across various levels of visual abstraction, while additionally improving their generalization performance.

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.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Impacts from a climate event can cascade through natural, anthropogenic and socio-economic systems. Here the authors assess cascading climate impacts on the EU and identify intervention points for adaptation related to water, livelihoods, agriculture, infrastructure and economy, and violent conflict.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

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.

Perfect absorption has been achieved in passive open quantum systems and is inherently linked to Parity-Time symmetry. Here, the authors experimentally and theoretically demonstrate a version beyond this paradigm using a system described by a non-Hermitian Hamiltonian, and providing a connection between Perfect Absorption and Hermitian subspaces.

The BabyScreen+ study offered genomic screening to 1,000 newborns in Australia, and showed that the approach is feasible and positively received by families, leading to molecular diagnoses in 1.6% of babies.

Here the authors identify TNIP1 as a risk factor for a fatal neurodegenerative disorder and discover specific genetic loci associated with the three main subtypes of this disorder. The findings highlight distinct disease mechanisms, emphasizing the roles of immunity and the notch signaling pathway.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

Substandard and falsified medicines are a global health threat. The fight against them is a regulatory and research challenge; here, the authors argue the importance of global and regional oversight, monitoring of, and research into the extent of the issue.

Cancer genetics has benefited from the advent of next generation sequencing, yet a comparison of sequencing and analysis techniques is lacking. Here, the authors sequence a normal-tumour pair and perform data analysis at multiple institutes and highlight some of the pitfalls associated with the different methods.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Removing fossil fuel subsidy could reduce the CO₂ emissions and improve the use of government budget, while the feasibility is in doubt. This research demonstrates the public attitudes in developing countries are not worse than that for carbon tax, and better use of the public fund is preferred.

The discovery that DNA methylation of different CpG sites can serve as digital barcodes of clonal identity led to the development of EPI-Clone, an algorithm that enables single-cell lineage tracing through cellular differentiation at scale.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

Clear cell renal cell carcinoma (ccRCC) usually metastasizes to the lungs. Here, the authors discover that SWI/SNF ATPase subunit SMARCA4 silencing of HLF regulates ccRCC lung metastasis by modulating the integration of collagen's mechanical cues with the actin cytoskeleton through leupaxin.

Analyses of data from more than 200,000 individuals identify phenotypic features associated to carrying variants in autism-associated genes, in individuals with and without a diagnosis of autism.

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.

New 43–45 ka dates for stone tool assemblages associated with anatomically modern humans (AMHs) at the southern Spanish site of Bajondillo suggest an early AMH incursion and weaken the case for late Neanderthal persistence in the region.

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.

The ankylosaurian dinosaur Spicomellus afer possessed a tail weapon and uniquely elaborate dermal armour.

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.

Gene regulatory network architecture and complex dosage effects from paralogue diversification converge to shape phenotypic space, producing the potential for both strongly buffered phenotypes and sudden bursts of phenotypic change.

Quantum mechanics predicts that objects can simultaneously exist in a superposition of two states. Kneeet al.propose and demonstrate experimentally a protocol which fully confirms this prediction, by testing the so-called Leggett–Garg inequality in a non-invasive manner.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder characterized by the functional loss of the tumor suppressor gene neurofibromin, that can lead to the development of benign and malignant tumors. Here the authors describe the development of an adeno-associated virus vector for NF1 gene replacement therapy of NF1 related tumors, showing tropism and anti-tumor activity in preclinical models

During the development of multi-cellular animals, biochemical signals control the organization of cells to set up body axes. In mouse embryonic stem cell aggregates, tissue flows are now found to amplify the formation of such body axes.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

Heat extremes threaten the health of urban residents with particularly strong impacts from day–night sustained heat. Observation and simulation data across eastern China show increasing risks of compound events attributed to anthropogenic emissions and urbanization.

A global analysis reveals regional trends of net forest ageing but also that widespread stand-replacing disturbances, such as fire and harvest, are driving declining forest age in many areas, often accompanied by substantial losses in aboveground carbon stocks and shifts in carbon sink dynamics.

The SWI/SNF chromatin remodeling complex is frequently mutated in cancer and neurodevelopmental disorders. Here, the authors performed a CRISPR screen and identified MLF2 and RBM15 as modulators of SWI/SNF assembly, revealing new therapeutic targets for diseases caused by impaired chromatin remodeling.

This study provides an evidence database on climate change in cities, highlighting that small and fast-growing cities, especially in Asia and Africa, are underresearched, which has contributed to biases and validity issues in past Intergovernmental Panel on Climate Change climate change assessments.

Plasma cells (PC) contribute to the pathogenesis of autoimmune diseases by secreting autoantibodies. Strategies to target pathogenic PCs are thus required. Here, the authors profile different PC subsets in naïve and lupus-prone mice and report the emergence and expansion of a CD19^– PC subset in diseased mice that could compromise the effectiveness of CD19-targeting therapies.

Invasive Salmonella Typhimurium bloodstream infection causes a significant public health burden in sub-Saharan Africa. Here, the authors analyse whole genome sequences of 1,302 S. Typhimurium isolates from Africa and describe its evolution, geographic spread, and antimicrobial resistance characteristics.

With over 2,000 newly identified data points, this study estimates 2,525 million m³ of wood fuel removals globally in 2019, approximately 30% higher than previously understood. Global production of wood charcoal is estimated at 70.5 million tonnes, approximately 50% higher than previous values.

Interact-omics, a high-throughput cytometry-based framework, resolves the cellular interaction landscape.

The generation of a national pan-genome, a population-specific catalogue of genetic variation, may advance the impact of clinical genetics studies. Here the Besenbacher et al. carry out deep sequencing and de novo assembly of 10 parent–child trios to generate a Danish pan-genome that provides insight into structural variation, de novomutation rates and variant calling.

Ataxia telangiectasia and Rad3-related kinase (ATR) is a rational radiosensitization target. This trial evaluates the combination of the ATR inhibitor, ceralasertib, with palliative radiotherapy in 27 patients with advanced solid tumors.

Using deep sequencing of human carotid plaque cells from male and female patients with carotid stenosis, Sukhavasi et al. identify sex-biased cell-type-specific gene-regulatory networks and different phenotypes in smooth muscle cells, including an osteogenic phenotype in females and a chondrocytic phenotype in males.