Gleason Dale (parcelpriest13)
Cell-mediated immunity is a specific target of several medications used to prevent or treat rejection in orthotopic heart transplantation. Low absolute lymphocyte count (ALC) has potential to be a useful and accessible clinical indicator of overall infection risk. Though some studies have demonstrated this association in other transplant populations, it has not been assessed in heart transplant recipients. A single-center retrospective cohort study examined adult heart transplant recipients transplanted between 2000 and 2018. The exposure of interest was ALC less than 0.75 x10 3cells/µL at one month post-transplant and the primary endpoint was a composite outcome of infection (including cytomegalovirus [CMV], herpes simplex I/II or varicella zoster virus [HSV/VZV], blood stream infection [BSI], invasive fungal infection [IFI]) or death occurring after one month and before one year post-transplant. A multivariable Cox proportional hazards model was created to control for confounders identified using clinicgher rate of the composite outcome (hazard ratio 2.26, 95% confidence interval 1.47-3.46, p-value less then 0.001) compared to patients without lymphopenia at one month. After adjustment for confounding variables, the presence of lymphopenia remained statistically significantly associated with the composite outcome (HR 1.72 95% CI 1.08-2.75, p=0.02). Conclusion ALC measured at one month post-heart transplant is associated with an increased risk of infectious outcomes or death in the ensuing 11months. This is a simple, accessible laboratory measure.Unsupervised methods, such as clustering methods, are essential to the analysis of single-cell genomic data. The most current clustering methods are designed for one data type only, such as single-cell RNA sequencing (scRNA-seq), single-cell ATAC sequencing (scATAC-seq) or sc-methylation data alone, and a few are developed for the integrative analysis of multiple data types. The integrative analysis of multimodal single-cell genomic data sets leverages the power in multiple data sets and can deepen the biological insight. In this paper, we propose a coupled co-clustering-based unsupervised transfer learning algorithm (coupleCoC) for the integrative analysis of multimodal single-cell data. Our proposed coupleCoC builds upon the information theoretic co-clustering framework. In co-clustering, both the cells and the genomic features are simultaneously clustered. Clustering similar genomic features reduces the noise in single-cell data and facilitates transfer of knowledge across single-cell datasets. We applied coupleCoC for the integrative analysis of scATAC-seq and scRNA-seq data, sc-methylation and scRNA-seq data and scRNA-seq data from mouse and human. We demonstrate that coupleCoC improves the overall clustering performance and matches the cell subpopulations across multimodal single-cell genomic datasets. Our method coupleCoC is also computationally efficient and can scale up to large datasets. Availability The software and datasets are available at https//github.com/cuhklinlab/coupleCoC.Microglial cells make extensive contacts with neural precursor cells (NPCs) and affiliate with vasculature in the developing cerebral cortex. But how vasculature contributes to cortical histogenesis is not yet fully understood. To better understand functional roles of developing vasculature in the embryonic rat cerebral cortex, we investigated the temporal and spatial relationships between vessels, microglia, and NPCs in the ventricular zone. Our results show that endothelial cells in developing cortical vessels extend numerous fine processes that directly contact mitotic NPCs and microglia; that these processes protrude from vessel walls and are distinct from tip cell processes; and that microglia, NPCs, and vessels are highly interconnected near the ventricle. These findings demonstrate the complex environment in which NPCs are embedded in cortical proliferative zones and suggest t