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Global analysis of obesity trends from 1980 to 2024 in 200 countries and territories using data from 4,050 population-based studies reveals that framing obesity as a single global epidemic masks the highly varied dynamics across countries and age groups.

Difelikefalin is an FDA-approved KOR-targeted drug for chronic pruritus yet exhibits side effects. Here, researchers solve cryo-EM structure of difelikefalin KOR-Gi, identifying Y320^7.43 as a key bias residue. Substituting D-Phe1 with β-phenylalanine develops beta01 which retains analgesic/antipruritic efficacy via a unique receptor conformation that reduces adverse effects.

PDS5B, a cohesin regulatory protein, is shown to bind DNA and enhance the RAD51 recombinase in the promotion of DNA strand exchange and protection of DNA from MRE11 RAD50-NBS1. Here the authors use biochemical and cellular analyses to reveal that DNA binding by PDS5B is essential for DNA damage repair and the preservation of stressed DNA replication forks.

Phenotype switching is a key driver of melanoma progression and therapy resistance. Here, the authors identify the small MAF family transcription factor MAFG as a critical regulator of microphthalmia-associated transcription factor (MITF) activity and melanoma cell state plasticity through binding MITF to redirect its genomic occupancy and modulate its transcriptional programming.

Early human heart development is shaped by biomechanical cues that are difficult to study in vivo. Here, authors engineer a perfusable 3D-bioprinted model of the embryonic heart tube for in vitro modelling of early human heart development.

MOSAIC is a versatile multimodal microscope that allows seamless transition between various light-sheet, two-photon, label-free and super-resolution modalities. It is demonstrated in various systems ranging from cell culture to mice.

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 large-scale proteomics analysis of the dark proteome by the TransCODE Consortium reveals many translated non-canonical open reading frames to encode microproteins and peptideins.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

PTCHD1-AS, which encodes a long non-coding RNA, is associated with the aetiology of autism spectrum disorder in humans through striatal molecular and circuit-level dysregulation.

Here, in a two-phase population trial, the authors show that composite polyphenols intervention could mitigate the increase in pro-inflammatory indicators associated with high microplastic exposure by modulating gut microbiota and up-regulating glycerophospholipid metabolism pathways.

An electrothermal co-design strategy can be used to make flexible transistors based on aligned carbon nanotube arrays with current-gain cut-off frequencies of 152 GHz and power-gain cut-off frequencies of 102 GHz.

In this study, the authors develop PhysMAP, which combines multiple electrophysiological features to identify neuronal cell types in the neural circuit, advancing the ability to investigate circuit dynamics without genetic or optical access during behavior.

The study identifies novel genetic variants linked to core cerebrospinal fluid Alzheimer’s Disease biomarkers using a genome-wide analysis, showing how endophenotypes can identify genes and disease mechanisms not captured by case-control studies.

This study uses the inception loop framework to map neuronal invariances in mouse V1, revealing a bipartite receptive-field organization linked to segmentation and a synaptic-level hierarchy of increasing invariance supported by the MICrONS dataset.

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.

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.

Modular RNA nanostar motifs spontaneously assemble into programmable synthetic condensates in the nucleus and cytoplasm, with RNA design controlling localization, sequence-specific target recruitment and orthogonal assembly.

Papaya is a trioecious species with XX females, XY males, and XY^h hermaphrodites, and the combination of Y and Y^h chromosomes is lethal. Here, the authors identify the degeneration of the YY lethality gene on the Y chromosome as the causal balancing lethal factor that reenforces dioecy and stabilizes balanced sex ratios.

Crystallizing the perovskite layer on thin tunnel oxide passivated contact silicon cells is challenging due to rapid heat transfer. Zhou et al. address this issue using a 2-mercaptobenzothiazole additive, achieving a tandem cell efficiency of 32.76%.

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.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

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

This study uses two large fundus cohorts to show that retinal foundation models generalize well across populations but exhibit age-related fairness gaps. It highlights how pre-training data composition shapes model generalisability and fairness.

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.

Cryogenic electron microscopy images and micromechanical fracture modelling of mechanically soft lithium dendrites fracturing hard ceramic electrolytes suggest the mechanisms driving the phenomenon as well as design implications for solid-state lithium metal batteries.

RNA velocity is a widely used method to predict the fate of single cells. Here the authors show that the concept can be adapted to predict the fate of individual human subjects, using RNA velocity of whole blood at a single point in time to predict future clinical outcomes and treatment responses.

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.

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.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

IMiD-based PROTACs may degrade IKZF1/3 with hematologic effects. This study profiles these liabilities using hematopoietic assays showing stem cell rewiring and interferon activation and introduces a CRBN ligand that reduces them.

Using an integrative spatial Bayesian framework that merges high-resolution environmental pesticide risk modelling with comprehensive cancer registry data, this analysis reveals spatial patterns of pesticide exposure and liver tissue-derived molecular signatures across Peru, establishing links between pesticide usage and cancer insurgence at the national scale.

Here the authors present scLong, a billion parameter foundation model trained on 48M single cells, using self attention across all 28k human genes and Gene Ontology knowledge. It captures long range gene context in single Cell transcriptomics.

While therapies targeting type I BRAF mutations have been developed, there are limited options for those with type II and III mutations. Here, the authors identify a subset of BRAF-mutant non-small cell lung cancer patients and characterise the pan-RAF inhibitor exarafenib, demonstrating efficacy in preclinical models and investigating subsequent resistance mechanisms.

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 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.

In one-shot perceptual learning, what we see can be dramatically altered by a single past experience. Using psychophysics, fMRI, iEEG, and DNNs, the authors identify neural and computational mechanisms underlying this remarkable ability in humans.

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.

The biological clock model LifeClock predicts biological age across all life stages from routine clinical data, revealing distinct pediatric and adult disease risk patterns.

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.

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.

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.

Analysis of the somatic and transcriptomic profile of 123 acral melanoma samples from Mexican patients helps understand tumour origins and prognosis, and highlights the importance of including samples from diverse ancestries in cancer genomics 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 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.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.