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Abstract To uncover molecular changes underlying blood-brain-barrier dysfunction in Alzheimer’s disease, we performed single nucleus RNA sequencing in 24 Alzheimer’s disease and control brains and focused on vascular and astrocyte clusters as main cell types of blood-brain-barrier gliovascular-unit. The majority of the vascular transcriptional changes were in pericytes. Of the vascular molecular targets predicted to interact with astrocytic ligands, SMAD3, upregulated in Alzheimer’s disease pericytes, has the highest number of ligands including VEGFA, downregulated in Alzheimer’s disease astrocytes. We validated these findings with external datasets comprising 4,730 pericyte and 150,664 astrocyte nuclei. Blood SMAD3 levels are associated with Alzheimer’s disease-related neuroimaging outcomes. We determined inverse relationships between pericytic SMAD3 and astrocytic VEGFA in human iPSC and zebrafish models. Here, we detect vast transcriptome changes in Alzheimer’s disease at the gliovascular-unit, prioritize perturbed pericytic SMAD3-astrocytic VEGFA interactions, and validate these in cross-species models to provide a molecular mechanism of blood-brain-barrier disintegrity in Alzheimer’s disease.

Abstract Background Portal use has been studied among outpatients, but its utility and impact on inpatients is unclear. This study describes portal adoption and use among hospitalized cancer patients and investigates associations with selected safety, utilization, and satisfaction measures. Methods A retrospective review of 4594 adult hospitalized cancer patients was conducted between 2012 and 2014 at Mayo Clinic in Jacksonville, Florida, comparing portal adopters, who registered for a portal account prior to hospitalization, with nonadopters. Adopters were classified by their portal activity during hospitalization as active or inactive inpatient users. Univariate and several logistic and linear regression models were used for analysis. Results Of total patients, 2352 (51.2%) were portal adopters, and of them, 632 (26.8%) were active inpatient users. Portal adoption was associated with patients who were young, female, married, with higher income, and had more frequent hospitalizations (P .05). Conclusions Over half of our cancer inpatients adopted a portal prior to hospitalization, with increased adoption associated with predisposing and enabling determinants (eg: age, sex, marital status, income), and increased inpatient use associated with need (eg: nonlocal residence and disease severity). Additional research and greater effort to expand the portal functionality is needed to impact inpatient outcomes.