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Many hospitalised children with acute illness in low- and middle-income countries experience incomplete recovery, readmission, and post-discharge mortality despite guideline-directed care. Here the authors report multiomic profiling to investigate biological drivers of hospital in-patient and post-discharge mortality in 3,101 acutely ill children across nine sites in sub-Saharan Africa and South Asia.

Hybrid neural networks often underperform compared to conventional neural networks because of their low array utilization. Lu et al. propose a programmable spiking architecture that leverages photonic reconfigurable devices to integrate synaptic and neuronal functions without compromising performance.

Currently, little is known about the baseline burden or the clonal dynamics of cancer driver mutations in the normal human colon. Here, the authors employ targeted amplicon sequencing, computational modeling and spatial transcriptomics to characterize the prevalence, behavior and evolutionary fate of cancer driver mutant clones in the normal human colon, allowing a reassessment of the origins of colorectal cancer.

NatD is an acetyltransferase responsible for N-α-terminal acetylation of the histone H4 and H2A and has been linked to cell growth. Here the authors show that NatD-mediated acetylation of histone H4 serine 1 competes with the phosphorylation by CK2α at the same residue thus leading to the upregulation of Slug and tumor progression.

Break-induced replication (BIR) is mediated by DNA polymerase d (Pol d). Here, the authors identify a phospho-activated RPA-binding module in Pol d which promotes BIR efficiency, providing a paradigm for the dynamic regulation of DNA transactions involving single-stranded intermediates bound by RPA.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

The cellular origin and developmental trajectory of DICER1 syndrome-associated tumors are currently unknown. Here, the authors employ a lineage-traceable genetically modified mouse model for DICER1 syndrome to identify universal fibroblasts as the likely cellular origin of mouse Dicer1 sarcoma and map their developmental trajectory, findings that are validated in human DICER1 mesenchymal tumors.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

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.

A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

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.

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 foreign body response involves immune cell activation and fibrosis, understanding the connection of the two is important for the biomedical engineering field. Here the authors show in a mouse biomaterial implant model that γδ T cell interactions with stromal cells shape fibrosis with differential involvement of type-1 and type-17 effector γδ T cell subsets in the acute and chronic phases of the response.

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.

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.

A Hemostatic Tough Adhesive (HTA) is developed and evaluated, achieving hemostasis in both liver and spleen injuries within an in vivo preclinical porcine model.

In this work, authors show that alpibectir boosts ethionamide efficacy against Mycobacterium tuberculosis by enhancing its bioactivation and also shows intrinsic activity. The ethionamide-alpibectir combination (AlpE) is bactericidal in mice and active against drug-resistant strains.

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.

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.

Acute rheumatic fever (ARF) is a serious sequela of Strep A infection, for which a diagnostic biomarker is still lacking. Here, the authors demonstrate that CXCR3 directs T cells to heart valves in patients with ARF, linking inflammation to tissue damage.

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.

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.

Exposome analyses across 34 countries showed that social exposures were associated with faster functional brain aging and physical exposures with faster structural brain aging.

Photonic neuromorphic hardware is fast and energy-efficient, but large circuit footprints remain a key bottleneck for scaling. Here, Sestoft et al. demonstrate a few-nanowire artificial neuron that can reduce circuit footprints by ≥100 × .

The genomewide meta-analysis of lumbar spinal stenosis LSS identifies 73 previously unreported loci in addition to 15 known loci and highlights spinal degeneration as a key pathogenic mechanism. Overall, the findings expand knowledge of the genetic background of LSS.

Solvation dynamics shape many light-driven reactions but are challenging to observe. Time-resolved Xray scattering reveals the atomic-scale ultrafast reorganization of a polar solvent driven by charge transfer in a photoexcited organic molecule.

Plant community properties affect ecosystem functioning via energy fluxes in food webs, with the leaf and root resource economics of dominant tree species controlling soil food web multifunctionality.

Succinate acts as a competitive inhibitor of mammalian aspartate transcarbamylase (ATCase), leading to impaired pyrimidine biosynthesis and reduced proliferation under SDH inhibition.

Epithelial–stromal interactions drive inflammation, fibrosis, immune recruitment and cancer initiation in human IBD colon-on-a-chip devices, and responses are exacerbated by peristalsis-like movements and pregnancy-associated hormones in female-derived chips.

Rice is a staple food for many households; however, its cultivation can expose farming families to parasitic diseases such as schistosomiasis via freshwater snails. The authors examine how integrating native fish into rice fields can suppress snail hosts, boost yields and improve farmer livelihoods.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Some surveys of intelligence have suggested that the mean IQ is rising; others, that it is decreasing alarmingly. The explanation seems to be that the educational level of the populations has changed.

Pathological neovascularization is a leading cause of vision loss. In this study, the authors identify FRZB and its NTR domain as suppressors of ocular angiogenesis. FRZB prevents CAV1 phosphorylation at Tyr42 which enhances downstream TGFβ signaling via ALK5 retention.

Natural silk, mechanically strong and biodegradable, offers great potential for sustainable functional materials. Here the authors present a simple thermomechanical method for fabricating high-performance structural and optically active materials directly from silk fibres.

SbmA is a proton-driven transporter that imports antimicrobial peptides andstructurally resembles the transmembrane domain of ABC-transporters. Here, authors show through cryo-EM structures, EPR spectroscopy, and MD simulations that SbmA undergoes ABC-transporter-like conformational changes consistent with an alternating-access transport mechanism.

Prime editing is improved with engineered RNA-stabilizing motifs.

Endocrine therapies are the main adjuvant therapy for estrogen receptor positive breast cancer, but 30% of patients recur. Here, the authors discover that endocrine therapy upregulates Rac1 signalling component P-Rex1, and inhibition of Rac1 reduces tumour growth in refractory breast cancer models.

The authors investigated metabolic remodeling in response to stem cell activation and the effect of aging on this response. Aging muscle stem cells lose a key glutamine-fueled metabolic pathway that powers de novo lipogenesis needed for activation. This study shows that reductive TCA cycling helps preserve stem cell function and may offer a new target against sarcopenia.

This study describes that cardiolipin deficiency-induced mitochondrial dysfunction in T_reg cells impairs gut–immune tolerance.

In this study, the authors show that pulmonary fibroblasts act as dualfunction responders to the human-pathogenic fungus Aspergillus fumigatus, modulating immune responses while safeguarding tissue integrity.

Extracellular vesicles carrying diverse molecules circulate the body. Here, the authors show that blood-borne vesicles containing specific miRNAs boost synaptic function and sociability in mice, revealing a non-canonical pathway for social behavior.

Salladay-Perez and colleagues explore senescence induction in human and mouse macrophages using multiomic profiling. They characterize a p21⁺TREM2⁺ senescent macrophage population, which they functionally implicate in inflammaging and liver disease.