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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.

The epigenetic mechanisms underlying phenotypic diversity across different metastatic sites in castration-resistant prostate cancer (CRPC) remain to be characterised. Here, multi-omic profiling across metastatic lesions identifies regulatory networks driving tumour lineage programs and potential therapeutic targets.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

Analysis combining multiple global tree databases reveals that whether a ___location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Pathogen diagnostics are strong determinants of azithromycin effects on diarrhea duration, but host factors may better predict benefits for severe outcomes. In this work, authors utilise a machine learning-based approach to evaluate personalized rules for the decision to treat watery diarrhea with azithromycin.

The mechanism of macrophage cytotoxicity against cancer cells requires further illustration. By employing CRISPR screening in CAR-macrophage and cancer cell co-culture system, the authors identify depletion of ATG9A on cancer cells sensitizes them to macrophage-mediated killing, which can be synergic with CSF1R inhibition in cancer treatment.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

An integrated smart capsule that encapsulates an array of electrochemical sensors can provide real-time, continuous and multiplexed monitoring of the gastrointestinal tract.

Monomethylation of histone H4 lysine 20 (H4K20me1) contributes to DNA replication but the mechanism is not well understood. Here, the authors identify a conserved tandem Tudor ___domain of BAHCC1 as a H4K20me1-specific reader, which promotes the recruitment of MCM complex to chromatin for efficient DNA replication.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

End-of-life nonhuman primates can be used to screen pools of lipid nanoparticles for clinical safety 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.

The complexity of epithelial cell states in the fibrotic niche in the context of chronic kidney disease remains incompletely understood. Here the authors integrate snRNA and ATAC-seq with high-plex single-cell molecular imaging to generate a spatially-revolved multiomic atlas of human kidney disease.

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.

Phytochrome photoreceptors are master regulators of plant development. This paper describes 3D structures of soybean phytochrome A in both Pr (inactive) and Pfr (signalling) states, revealing changes that might transmit the light signal to the cell.

Currently, there is limited knowledge about the spatial heterogeneity of glioma-driving molecular events. Here, the authors employ a multiomics approach to characterize the spatial transcriptomic heterogeneity of various types of gliomas and identify spatially distinct tumor subclones with genomic plasticity driven by mutations on extrachromosomal DNA.

Quantum spin-ice phases are predicted to have emergent gauge fields and fractionalization. Neutron scattering and thermodynamic measurements of the quantum spin-ice candidate Ce₂Zr₂O₇ show features consistent with these predictions.

Tacto et al. uncover a key marker that enables the selection of functional, transplantable human islets derived from stem cells, potentially paving the way for more precise and effective diabetes cell therapy.

The authors show that the cell-penetrating peptide DG9 enhances PMO delivery to skeletal and cardiac muscles via multiple endocytic pathways. DG9-PMO significantly boosts dystrophin restoration and cardioprotection, addressing a key challenge in the therapy of Duchenne muscular dystrophy.

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.

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.

A genomic study of 125 individuals from the Carpathian Basin (4800–3900 BCE) reveals different kinship systems in nearby Copper Age communities, and highlights both genetic continuity and contrasting patterns of social organization.

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.

In a cluster-randomized trial conducted across 70 medical centers in six countries, a 16-week structured educational program for healthcare providers improved adherence to guidelines for rhythm control but not for stroke prevention in individuals with atrial fibrillation.

Here the authors engineer a bispecific antibody (Ab) for HIV-1 by combining a gp41 N-heptad repeat targeting Ab with a CD4 binding Ab. Prepositioning via CD4 binding results in high neutralization breadth and potency, and experiments in HIV infected humanized male mice show reduction of viral load.

From artificial intelligence to infectious diseases, top researchers in Hong Kong, Malaysia, Singapore, South Korea and Taiwan are making big impacts on the global stage.

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.

Urinary kidney injury-1 (Kim-1) outperforms serum creatinine, blood urea nitrogen and urinary N-acetyl-β-D-glucosaminidase in detecting kidney damage induced in rats by a range of nephrotoxicants. Earlier detection of renal injury, enabled by monitoring levels of urinary Kim-1, should enable elimination of nephrotoxic candidates sooner in the drug development pipeline.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Wireless bioresorbable stimulators are promising therapeutic implants that naturally dissolve after use. Here, the authors developed a device that operates for months and enables simultaneous multi-site stimulation, preventing early muscle atrophy and accelerating reinnervation in nerve injury models.

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.

A 50 microRNA-based dynamic risk score for stratifying individuals with and without type 1 diabetes was developed using samples obtained from multicenter and multiethnic cohorts.

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.

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.

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.

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

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.

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.

Optimized SORT LNPs enable precise and long-lasting base editing in dual organs in a disease mouse model.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.