Reading view
RIFT: A RubrIc Failure Mode Taxonomy and Automated Diagnostics
Qiana: A First-Order Formalism to Quantify over Contexts and Formulas with Temporality
From High-Dimensional Spaces to Verifiable ODD Coverage for Safety-Critical AI-based Systems
A deep learning pipeline for PAM50 subtype classification using histopathology images and multi-objective patch selection
Towards Transparent and Efficient Anomaly Detection in Industrial Processes through ExIFFI
Unsupervised Behavioral Compression: Learning Low-Dimensional Policy Manifolds through State-Occupancy Matching
The exposome of brain aging across 34 countries
Nature Medicine, Published online: 03 April 2026; doi:10.1038/s41591-026-04302-z
Exposome analyses across 34 countries showed that social exposures were associated with faster functional brain aging and physical exposures with faster structural brain aging.Target product profiles for treatments to delay or prevent symptomatic Alzheimer’s disease
Nature Medicine, Published online: 03 April 2026; doi:10.1038/s41591-026-04305-w
To accelerate therapeutic development and equip stakeholders with clear benchmarks, the authors outline target product profiles for therapies designed to delay or prevent the onset of clinical symptoms of Alzheimer’s disease.Single-cell and spatial profiling in cancer biology and clinical oncology
Nature Cancer, Published online: 03 April 2026; doi:10.1038/s43018-026-01142-1
Izar and colleagues review the insights into cancer biology gained via single-cell analyses and spatial profiling and overview the challenges and opportunities associated with the implementation of these approaches to guide clinical discovery.Ethical Handling of Occupational Health and Safety Data in the Fire Service: Empirical Interview and Focus Group Study of Firefighter and Fire Service Leadership Privacy Preferences
Proteogenomic Analysis of Coronary Artery Calcification in Human Populations
Arterioscler Thromb Vasc Biol. 2026 Apr 2. doi: 10.1161/ATVBAHA.125.324171. Online ahead of print.
ABSTRACT
BACKGROUND: Joint use of multiple molecular layers can be useful to prioritize targets for mechanistic studies. Application of coronary disease in large populations is an emerging field.
METHODS: We used reported circulating proteomic data (Somascan aptamer-based) from ≈3000 individuals in the CARDIA study (Coronary Artery Risk Development in Young Adults), measuring association with prevalent and 10-year incident coronary artery calcium (CAC) score. We used a multiparametric approach to prioritize circulating protein-CAC associations via genomics of circulating protein levels and coronary artery transcription.
RESULTS: Proteins linked to prevalent/incident CAC in CARDIA implicated pathogenic mechanisms of vascular disease, including fibrosis and inflammation (GDF-15 [growth/differentiation factor 15], CDCP1 [CUB domain-containing protein 1], GSN [gelsolin], THBS2 [thrombospondin-2], chemokines, RNAS6), oxidative lipid metabolism (CILP2), extracellular matrix remodeling and signaling (MMPs [matrix metalloproteinases], TIMP-1, integrins), calcification (Notch 1, ARHGAP36 [Rho GTPase-activating protein 36]), and metabolism (GIP [gastric inhibitory polypeptide]), as well as new proteins not previously reported. Using protein-wide association study genetic approaches, several targets with nominal evidence in CAC proteomics were associated with atherosclerosis or myocardial infarction in over 300K individuals, including PCSK9 (proprotein convertase subtilisin/kexin type 9) and APO C1. Finally, the coronary artery-specific transcriptome-wide association study of CAC yielded genes with previously implicated mechanistic roles in vascular homeostasis, inflammation, and metabolism, as well as genes without previously described function in CAC. Overlap across CAC proteomics and transcriptome-wide association study highlighted genes involved in vascular inflammation (S100A9), cardiac development (HES1), vessel wall structure (SPARCL1), and vascular dysfunction or plaque (NOTCH3, TNFSF12, S100A12).
CONCLUSIONS: These results report population-level multiomics in human coronary calcification, presenting a method to identify disease-relevant targets through integration of human genetic approaches with multiomics.
PMID:41924874 | DOI:10.1161/ATVBAHA.125.324171
Proteogenomic Analysis of Coronary Artery Calcification in Human Populations
Arterioscler Thromb Vasc Biol. 2026 Apr 2. doi: 10.1161/ATVBAHA.125.324171. Online ahead of print.
ABSTRACT
BACKGROUND: Joint use of multiple molecular layers can be useful to prioritize targets for mechanistic studies. Application of coronary disease in large populations is an emerging field.
METHODS: We used reported circulating proteomic data (Somascan aptamer-based) from ≈3000 individuals in the CARDIA study (Coronary Artery Risk Development in Young Adults), measuring association with prevalent and 10-year incident coronary artery calcium (CAC) score. We used a multiparametric approach to prioritize circulating protein-CAC associations via genomics of circulating protein levels and coronary artery transcription.
RESULTS: Proteins linked to prevalent/incident CAC in CARDIA implicated pathogenic mechanisms of vascular disease, including fibrosis and inflammation (GDF-15 [growth/differentiation factor 15], CDCP1 [CUB domain-containing protein 1], GSN [gelsolin], THBS2 [thrombospondin-2], chemokines, RNAS6), oxidative lipid metabolism (CILP2), extracellular matrix remodeling and signaling (MMPs [matrix metalloproteinases], TIMP-1, integrins), calcification (Notch 1, ARHGAP36 [Rho GTPase-activating protein 36]), and metabolism (GIP [gastric inhibitory polypeptide]), as well as new proteins not previously reported. Using protein-wide association study genetic approaches, several targets with nominal evidence in CAC proteomics were associated with atherosclerosis or myocardial infarction in over 300K individuals, including PCSK9 (proprotein convertase subtilisin/kexin type 9) and APO C1. Finally, the coronary artery-specific transcriptome-wide association study of CAC yielded genes with previously implicated mechanistic roles in vascular homeostasis, inflammation, and metabolism, as well as genes without previously described function in CAC. Overlap across CAC proteomics and transcriptome-wide association study highlighted genes involved in vascular inflammation (S100A9), cardiac development (HES1), vessel wall structure (SPARCL1), and vascular dysfunction or plaque (NOTCH3, TNFSF12, S100A12).
CONCLUSIONS: These results report population-level multiomics in human coronary calcification, presenting a method to identify disease-relevant targets through integration of human genetic approaches with multiomics.
PMID:41924874 | DOI:10.1161/ATVBAHA.125.324171
Author Correction: Real-world clinical utility of tumor whole-genome sequencing in solid cancers
Nature Medicine, Published online: 02 April 2026; doi:10.1038/s41591-026-04379-6
Author Correction: Real-world clinical utility of tumor whole-genome sequencing in solid cancersSemaglutide on liver fibrosis and heart outcomes in patients at high risk of liver fibrosis: a prespecified analysis of the SELECT randomized trial
Nature Medicine, Published online: 02 April 2026; doi:10.1038/s41591-026-04281-1
A prespecified analysis from the SELECT trial showed that semaglutide reduces major adverse cardiovascular events by 20% compared with placebo, particularly in patients at high risk of fibrosis, as indicated by the Fibrosis-4 index.Correction: The cytotoxicity of gomesin peptides is mediated by the glycosphingolipid pathway and lipid-cholesterol interactions
Cell Death Discovery, Published online: 02 April 2026; doi:10.1038/s41420-026-03009-x
Correction: The cytotoxicity of gomesin peptides is mediated by the glycosphingolipid pathway and lipid-cholesterol interactions