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A new sparse Bayesian quantile neural network-based approach and its application to discover physiological sweet spots in the Canadian Longitudinal Study on Aging
Identifying physiological sweet spots (optimal ranges for homeostasis) is essential for precision medicine. However, traditional statistical methods often rely on globally linear or locally jagged models that struggle to capture the smooth, non-linear nature of biological regulation in high-dimensional data. We present the Quantile Feature Selection Network (Q‑FSNet), a neural network-based framework that integrates quantile regression, feature selection, and uncertainty estimation to identify...
Impact of an online-guided physical activity intervention on cognition, resting-state brain connectivity, and the gut microbiome in healthy older adults-a randomized controlled trial
INTRODUCTION: Physical activity may enhance cognition in older adults, yet evidence from randomized controlled trials (RCTs) on mechanistic pathways remains inconclusive.
Illuminating proinflammatory myeloid cells with PET tracers targeting GPR84
Innate immunity mediated by myeloid cells defends against infection and injury, but when chronically activated, it drives tissue damage and neurodegeneration. Molecular imaging with positron emission tomography (PET) enables noninvasive, real-time monitoring of such processes in vivo. However, most current neuroinflammation PET tracers lack specificity for activated myeloid cells. G protein-coupled receptor 84 (GPR84) is a promising biomarker that is selectively upregulated on activated...
Knockout of the LRRK2-counteracting RAB phosphatase PPM1H disrupts axonal autophagy and exacerbates alpha-synuclein aggregation
Parkinson disease (PD)-associated mutations in the LRRK2 gene hyperactivate LRRK2 kinase activity, leading to increased phosphorylation of a subset of RAB GTPases, which are master regulators of intracellular trafficking. In neurons, processive retrograde transport of autophagosomes is essential for autophagosome maturation and effective degradation of autophagosomal cargo in the axon. Here, we show that knockout of the LRRK2-counteracting RAB phosphatase PPM1H causes a gene-dose-dependent...
The oscillatory biology of sleep: Linkage to dementia
During wakefulness, neuromodulators operate largely independently to support behavior and cognition. By contrast, sleep reorganizes their activity into a coordinated brain rhythm. During sleep, the major neuromodulators-norepinephrine, acetylcholine, serotonin, and dopamine-exhibit synchronized fluctuations with a periodicity of ~50 seconds. These oscillations appear as recurrent bursts of fast (10 to 30 hertz) electroencephalography activity and are phase-coupled to cerebrospinal fluid flow....
Supplements and Drugs Are Associated With Biological Age in a Cohort of Exceptionally Healthy Individuals
In this cross-sectional cohort we analyzed data from 4260 "health enthusiasts" who purchased at least one saliva-based DNA epigenetic test between 2020 and 2025 and completed detailed lifestyle and supplement questionnaires. A proprietary 9-CpG clock with a mean absolute error of 5.4 years served as the primary biomarker of biological age. High prevalence (71%) of supplement use in this cohort increased our power to study the effects of supplements compared to earlier studies that focused on the...
Have astronomers spotted an exploding primordial star?
Puzzling JWST observation could instead be one of the universe's first galaxies—or something more mundane
T-cell mechanobiology: How molecular forces shape immune function
T cells are central to adaptive immunity, and continuously sense, generate, and respond to mechanical forces. Advances in mechanoimmunology show that T-cell behavior is tightly shaped by the physical properties of their environment, including stiffness, viscoelasticity, ligand arrangement, and tissue topography. T-cell activation depends not only on biochemical signals but also on forces transmitted through the T-cell receptor, coreceptors, and mechanosensitive ion channels, which converge on...
Identifying the factors influencing long-term care utilization by older adults in China: machine learning analysis
CONCLUSIONS: Living arrangement, social activity and residence were the most significant factors associated with the types of LTC utilization by older adults in China. Overall, enabling and predisposing factors had a greater influence than the need factors. These findings not only demonstrate the potential value of ML for LTC policy development, but also provide empirical support for the Chinese government to adopt targeted interventions that enhance LTC service accessibility and affordability.
ChEA-KG and ChEA-KG-TS: a network-based transcription factor enrichment analysis tool with an accompanying time-series workflow
Transcription factor (TF) modules interact to regulate key biological processes and cell-state transitions in normal physiology and disease. Understanding these modules and how they evolve over time can be accomplished by constructing gene regulatory networks (GRNs). To identify context-specific TF subnetworks, we developed ChEA-KG, which generates enriched TF regulatory subnetworks for input gene sets. ChEA-KG is based on a GRN connecting 1559 human TFs via 131 181 signed and directed edges...
Daily briefing: Wearable robot could help kids with neuromuscular disease stand
Did a boy’s life-saving gene therapy cause his brain tumour?
How we’re using AI tools to improve psychedelic-drug research
Ebola outbreak: the data that show why researchers are so alarmed
Ebola outbreak spirals out of control: how might it have started?
See the clouds streaming and vanishing around this planet — 690 light years away
De novo design of miniproteins targeting GPCRs
Should I get a dog? What to know about pet ownership as a scientist
A star gone rogue tears through the Galaxy
DNA polymerization activates RNA cleavage of a reverse transcriptase–like antiviral enzyme
Science, Ahead of Print.