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Reservoir‐based irrigation schemes (RBISs) have been developed to minimize the adverse effects of moisture stress and improve the livelihoods of smallholder farmers in semi‐arid regions. However, many RBISs perform below expectations. A multistage expert elicitation approach and an indicator‐based Sustainability Assessment of Food and Agriculture System (SAFA) framework were used to identify sustainability challenges and manag...
Prediction of the Extent of Blood–Brain Barrier Transport Using Machine Learning and Integration into the LeiCNS-PK3.0 ModelNARA Subscribed
Introduction The unbound brain-to-plasma partition coefficient (K p,uu,BBB ) is an essential parameter for predicting central nervous system (CNS) drug disposition using physiologically-based pharmacokinetic (PBPK) modeling. K p,uu,BBB values for specific compounds are however often unavailable, and are moreover time consuming to obtain experimentally. The aim of this study was to develop a quantitative structure–property rela...
Sex differences in thermophysiological responses of elderly to low-intensity exercise during uncompensable heat strainNARA Subscribed
Purpose The rising frequency of extreme heat events poses an escalating threat of heat-related illnesses and fatalities, placing an additional strain on global healthcare systems. Whether the risk of heat-related issues is sex specific, particularly among the elderly, remains uncertain. Methods 16 men and 15 women of similar age (69 ± 5 years) were exposed to an air temperature of 39.1 ± 0.3 °C and a relative humidity (RH) of...
Mechanistic safety assessment via multi-omic characterisation of systemic pathway perturbations following in vivo MAT2A inhibitionNARA Subscribed
The tumour suppressor p16/CDKN2A and the metabolic gene, methyl-thio-adenosine phosphorylase (MTAP), are frequently co-deleted in some of the most aggressive and currently untreatable cancers. Cells with MTAP deletion are vulnerable to inhibition of the metabolic enzyme, methionine-adenosyl transferase 2A (MAT2A), and the protein arginine methyl transferase (PRMT5). This synthetic lethality has paved the way for the rapid deve...
Introduction Systemic inflammation and endothelial dysfunction are potentially modifiable factors implicated in Alzheimer’s disease (AD), which offer potential therapeutic targets to slow disease progression. Methods We investigated the relationship between baseline circulating levels of inflammatory (TNF-α, IL-1ß) and endothelial cell markers (VCAM-1, ICAM-1, E-selectin) and 18-month cognitive decline (ADAS-cog12) in 266 mild...
Extracerebral microvascular dysfunction is related to brain MRI markers of cerebral small vessel disease: The Maastricht StudyNARA Subscribed
Background Cerebral small vessel disease (cSVD) is a late consequence of cerebral microvascular dysfunction (MVD). MVD is hard to measure in the brain due to its limited accessibility. Extracerebral MVD (eMVD) measures can give insights in the etiology of cerebral MVD, as MVD may be a systemic process. We aim to investigate whether a compound score consisting of several eMVD measures is associated with structural cSVD MRI mark...