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Atrial Fibrillation Related Titin Truncation Is Associated With Atrial Myopathy in Patient-Derived Induced Pluripotent Stem Cell Disease Models.
Circ Genom Precis Med
January 2025
Centre for Heart Lung Innovation, University of British Columbia, Vancouver. (K.H., M.A., L.R., Y.L., A.S., H.H., L.R.B., Z.W.L.).
Background: Protein-truncating mutations in the titin gene are associated with increased risk of atrial fibrillation. However, little is known about the underlying pathophysiology.
Methods: We identified a heterozygous titin truncating variant (TTNtv) in a patient with unexplained early onset atrial fibrillation and normal ventricular function.
Microglia modulate the cerebrovascular reactivity through ectonucleotidase CD39.
Nat Commun
January 2025
Department of Neuroscience, Center for Brain Immunology and Glia, University of Virginia School of Medicine, Charlottesville, VA, USA.
Microglia and the border-associated macrophages contribute to the modulation of cerebral blood flow, but the mechanisms have remained uncertain. Here, we show that microglia regulate the cerebral blood flow baseline and the responses to whisker stimulation or intra-cisternal magna injection of adenosine triphosphate, but not intra-cisternal magna injection of adenosine in mice model. Notably, microglia repopulation corrects these cerebral blood flow anomalies.
View Article and Find Full Text PDFDetectability constraints on meso-scale structure in complex networks.
PLoS One
January 2025
Department of Computer Science, University of Exeter, Exeter, United Kingdom.
Community, core-periphery, disassortative and other node partitions allow us to understand the organisation and function of large networks. In this work we study common meso-scale structures using the idea of block modularity. We find that the configuration model imposes strong restrictions on core-periphery and related structures in directed and undirected networks.
View Article and Find Full Text PDFDecay in Physiologic Knowledge since Medical School among Critical Care Fellows (DIP Study).
ATS Sch
January 2025
Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland.
Rapid accumulation of knowledge and skills by trainees in the intensive care unit assumes prior mastery of clinically relevant core physiology concepts. However, for many fellows, their foundational physiology knowledge was acquired years earlier during their preclinical medical curricula and variably reinforced during the remainder of their undergraduate and graduate medical training. We sought to assess the retention of clinically relevant pulmonary physiology knowledge among pulmonary and critical care medicine (PCCM) and critical care medicine (CCM) fellows.
View Article and Find Full Text PDFFully automated radiosynthesis of [F]FCPPC for imaging microglia with PET.
Am J Nucl Med Mol Imaging
December 2024
Cyclotron and Radiochemistry Core, Karmanos Cancer Institute Detroit, MI, USA.
Colony-stimulating factor 1 receptor (CSF1R) is almost exclusively expressed on microglia in the human brain and thus, has promise as a biomarker for imaging microglia density as a proxy for neuroinflammation. [C]CPPC is a radiotracer with selective affinity to CSF1R, and has been evaluated for in-human microglia PET imaging. The flourine-18 labeled CPPC derivative, 5-cyano-N-(4-(4-(2-[F]fluoroethyl)piperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide ([F]FCPPC), was previously synthesized, however, with a low radiochemical yield using manual radiosynthesis.
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