For large-scale testing with graph-associated data, we present an empirical Bayes mixture technique to score local false-discovery rates (FDRs). Compared to procedures that ignore the graph, the proposed Graph-based Mixture Model (GraphMM) method gains power in settings where non-null cases form connected subgraphs, and it does so by regularizing parameter contrasts between testing units. Simulations show that GraphMM controls the FDR in a variety of settings, though it may lose control with excessive regularization. On magnetic resonance imaging data from a study of brain changes associated with the onset of Alzheimer's disease, GraphMM produces greater yield than conventional large-scale testing procedures.
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http://dx.doi.org/10.1093/biostatistics/kxab001 | DOI Listing |
Background: Although investment in biomedical and pharmaceutical research has increased significantly over the past two decades, there are no oral disease-modifying treatments for Alzheimer's disease (AD).
Method: We performed comprehensive human genetic and multi-omics data analyses to test likely causal relationship between EPHX2 (encoding soluble epoxide hydrolase [sEH]) and risk of AD. Next, we tested the effect of the oral administration of EC5026 (a first-in-class, picomolar sEH inhibitor) in a transgenic mouse model of AD-5xFAD and mechanistic pathways of EC5026 in patient induced Pluripotent Stem Cells (iPSC) derived neurons.
Alzheimers Dement
December 2024
Department of Neurology, University Medical Center Medical Faculty Mannheim, Heidelberg, Baden-Württemberg, Germany.
Background: Timely diagnosis of mild cognitive impairment (MCI) in Alzheimer's disease (AD) is crucial for early interventions, but its implementation is often challenging due to the complexity and time burden of required cognitive assessments. Remote unsupervised self-testing of cognition can potentially addres this health care challenge. We conducted the to date largest evaluation of feasibility and experienced added value of unsupervised digital remote assessment in primary and specialized health care in Germany.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Background: The National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) was developed to address the need for a brief yet comprehensive instrument to facilitate more uniform assessment in large-scale research studies. Here, we investigated whether the cognitive measures of the NIHTB detect cognitive decline in biomarker-confirmed Alzheimer's disease (AD).
Method: We used data from N = 178 participants (age 76.
Parkinsons Dis
December 2024
Department of Pulmonary and Critical Care Medicine, Zigong First People's Hospital, 42 Shangyihao Yizhi Street, Zigong, Sichuan, China.
Parkinson's disease (PD) is an important cause of neurological dysfunction, and the aim of this study was to explore whether neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory response (SIRI), and systemic immune inflammation (SII) are associated with the risk of developing PD. Based on this, we may identify people at high risk for PD and intervene early. Our study included 31,480 participants from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2018.
View Article and Find Full Text PDFPhilos Trans R Soc Lond B Biol Sci
January 2025
CEFE, University of Montpellier, CNRS, EPHE, IRD, Montpellier 34070, France.
Whereas preventing species extinctions remains a central objective of conservation efforts, it must be complemented by the long-term preservation of functional ecosystems and of the benefits humans derive from them. Here, I review recent approaches that explicitly account for functionality in setting large-scale conservation priorities, discussing their promise while highlighting challenges and pitfalls. Crossing data on species' distributions and ecological traits has enabled the mapping of global patterns of functional diversity and functional rarity and the identification of species that stand out for their functional distinctiveness.
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