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Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

Antibody mediated prevention (AMP) trials with the broadly neutralizing antibody VRC01 showed protection against VRC01-sensitive viruses. Here, by deep sequencing plasma samples from 172 participants of the AMP trials, the authors show a high frequency of multilineage HIV infections (38%), including coinfection with both sensitive and resistant viruses, and demonstrate that VRC01 doesn’t alter the transmission bottleneck.

Coronary artery disease has several genetic risk factors. Here, the authors develop a model that combines germline and somatic genetic drivers to predict coronary artery disease risk, identifying high-risk individuals not detected by polygenic risk scores alone.

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.

Effective target engagement of drugs relies on them achieving sufficient intracellular concentrations. Here, using a multimodal imaging pipeline the authors demonstrate that uneven distribution and uptake of PARP inhibitors in ovarian cancer patient-derived explant models correlates with therapeutic response.

Chemistry that forms an omnipresent type of carbon–carbon bond enables the modular synthesis of 3D organic molecules — a boon for drug discovery and materials design.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

The authors have applied an eight-tissue rat multi-omic dataset to analyze the gene regulatory landscape of endurance exercise training, identifying tissue-specific regulatory patterns involved in muscle function, metabolism and immune response.

Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.

High-resolution satellite data enables a unique verification of national methane emissions worldwide. Global estimates are 63 Tg a⁻¹ for oil-gas, 30% higher than the UNFCCC reports due to under-reporting by four largest emitters, and 33 Tg a⁻¹ for coal, consistent with previous estimates.

A study of reproducibility in a stratified random sample of 600 papers published from 2009 to 2018 in 62 journals spanning the social and behavioural sciences finds higher reproducibility among more recent papers and papers from journals that require data sharing.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Wafer-scale lithium tantalate-on-silicon nitride modulators achieve 100 GHz bandwidth and 581 Gbit/s data rates. With low loss and high stability, this hybrid platform offers a robust solution for next-generation optical communications.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

A fair exchange?

Interfacial charge recombination losses limit solar cell efficiency. Gao et al. mitigate these losses through front and rear-contact engineering, achieving efficiencies of 26.34% and 32.73% in tunnel oxide passivating contact single-junction and tandem solar cells.

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.

A bioelectronic device incorporating triphylite (LiFePO₄) as electrode is used for lithium-ion-specific inhibition of peripheral and central nervous system activities in rats and in mice.

Mass spectrometry (MS)-based proteomics is increasingly central to systems biology. Here, the authors present a high-throughput, multi-organ workflow that profiles 11,472 proteins in 507 mouse samples, enabling rapid, system-level evaluation of drug efficacy and toxicity.

In a phase 1b trial, patients with treatment-naive metastatic pancreatic adenocarcinoma received the CD73 inhibitor quemliclustat plus gemcitabine and nabpaclitaxel with or without the anti-PD1 antibody zimberelimab, showing encouraging clinical response rates and survival in quemliclustat-treated patients.

Colonic stem cells retain a memory of inflammation following disease resolution and there is a mechanistic link between chronic inflammation and malignancy, suggesting potential strategies to mitigate cancer risk in patients with chronic inflammatory conditions.

Endocrine-exocrine pancreas crosstalk is known to play a role in pancreatic ductal adenocarcinoma. Here, the authors discover that obesity induces the expression of the peptide hormone cholecystokinin (CCK) in β cells, affecting the peri-islet acinar cells and promoting islet-proximal tumor formation.

At present, only 13.4% of the global land surface meets the World Meteorological Organization requirements for annual precipitation monitoring.

A population genomic analysis of 1,854 Listeria soil isolates collected across the contiguous United States identifies geographically prevalent phylogroups with increased pangenome openness and recombination, as a result of adaptation to variable environments.

Simultaneous profiling of adenylated and non-adenylated RNAs reveals regulatory programs across diverse cell types.

Mower, Wan et al. introduce ROS-LLM, an open-source system that lets non-experts control robots with natural language, learn new skills from demonstrations and feedback, and automatically tune actions for reliable performance in real-world tasks.

A synthetic genetic circuit made up of recombinase-based cell-fate branching devices enables precise control over the ratios of cell types in an offspring population derived from one founder strain, and could be used to build user-defined multicellular aggregates.

Results of the phase 2 POLAR trial show that biomarker-guided treatment in patients with metastatic pancreatic cancer based on homologous repair deficiency leads to encouraging clinical response rates in immune cell-infiltrated tumors.

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.

Evo 2 is an artificial intelligence-based biological foundation model trained on 9 trillion DNA base pairs spanning all domains of life that predicts functional properties from genomic sequences and provides a rich generative model for researchers in biology.

Researchers demonstrate a photonic quantum reservoir computing platform that uses spectral and temporal multiplexing in a continuous-variable setting. Real-time memory is implemented, and nonlinear temporal tasks are enabled.

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.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Splicing factors shape how genes are stitched into RNA, but their activity is hard to measure. Here, the authors benchmark network methods and show exon-inclusion signatures infer splicing factor activity, uncovering cancer programs linked to survival and hallmarks.

The susceptibility of mouse and human T cells to ferroptosis is determined by the balance of systemic polyunsaturated and monounsaturated fatty acids, highlighting a key role for lipid metabolism and dietary composition in regulating T cell function.

Dysregulation of H3K4 methylation is associated with neurodevelopmental disorders. Here, the authors perturb H3K4 methylation in the MGE and hypothalamus, resulting in altered gene expression and cell fate as well as changes in behavior that mimic NDD symptoms.

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.

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.

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.

The role of normally silenced transposable elements (TEs) in tumorigenesis remains unclear. Here, the authors show that increased expression of TEs in both patients and mice with colitis or by DNA hypomethylating drugs elicits a viral mimicry response that suppresses tumorigenesis. This viral mimicry response inhibits the stemness of cancer initiating cells in a cell autonomous manner.

Here, the authors show that bile salt hydrolase activity is common among human gut bacterial isolates spanning seven major phyla and identify strains capable of directly dehydrogenating conjugated bile acids via hydroxysteroid dehydrogenases to produce conjugated secondary bile acids, challenging the notion that deconjugation is a prerequisite for further bile acid modifications.

Meningiomas are common brain tumors with variable behavior. This study reveals high STING expression across multiple cell types in the meningioma microenvironment. STING agonism triggers tumor cell death via programmed necrosis and pyroptosis, enhancing survival in preclinical models.

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.

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 a randomized study involving 9 general cardiologists and 107 real-world patient cases, assistance from a specifically tailored large language model resulted in preferable responses on complex case management compared to physicians alone, as rated by specialist cardiologists using a multidimensional scoring rubric.

A model is devised to investigate free charge generation in neat acceptor domains and at donor–acceptor heterojunctions. Efficient photocurrent generation in organic heterojunctions at low energetic offsets can be related to key molecular parameters and to electronic state delocalization.

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.