Publications by authors named "J W T Heemskerk"

Comprehensive characterization of platelets requires various functional assays and analysis techniques, including omics-disciplines, each requiring an individual aliquot of a given sample. Consequently, the sample material per assay is often highly limited rendering downscaling a prerequisite for effective sample exploitation. Here we present a transfer of our recently introduced 96-well-based proteomics workflow (PF96) into the 384-well format (PF384) allowing for a significant increase in sensitivity when processing minute platelet protein amounts.

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Antithrombin and tissue factor pathway inhibitor (TFPI) provide different anticoagulant mechanisms. Having established a potent anticoagulant role of cultured human umbilical vein endothelial cells in vessel-on-a-chip microfluidic models, we now investigated how these cells modulated thrombin generation under stasis through antithrombin and TFPI pathways. We observed that endothelial monolayers in 96 well-plates strongly delayed and suppressed the thrombin generation process induced by tissue factor, regardless of the presence of whole blood, platelet-rich plasma or platelet-free plasma.

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Agonist-induced rises in cytosolic Ca control most platelet responses in thrombosis and hemostasis. In human platelets, we earlier demonstrated that the ORAI1-STIM1 pathway is a major component of extracellular Ca entry, in particular when induced via the ITAM-linked collagen receptor, glycoprotein VI (GPVI). In the present article, using functionally defective platelets from patients with a loss-of-function mutation in ORAI1 or STIM1, we show that Ca entry induced by the endoplasmic reticulum ATPase inhibitor, thapsigargin, fully relies on this pathway.

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Background: Metallic artefacts caused by metal implants, are a common problem in computed tomography (CT) imaging, degrading image quality and diagnostic accuracy. With advancements in artificial intelligence, novel deep learning (DL)-based metal artefact reduction (MAR) algorithms are entering clinical practice.

Objective: This systematic review provides an overview of the performance of the current supervised DL-based MAR algorithms for CT, focusing on three different domains: sinogram, image, and dual domain.

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Article Synopsis
  • Agonist-induced platelet activation leads to a change in the integrin αIIbβ3, essential for fibrinogen binding and subsequent platelet aggregation, with the potential for reversibility under certain conditions.
  • The study investigates how platelet signaling via collagen receptor GPVI and protease-activated receptors (PAR) affects the time-dependent activation of αIIbβ3.
  • Results indicate that specific inhibitors of protein kinase C and other signaling pathways can modulate integrin activation and P-selectin expression, impacting how platelets aggregate and shape during activation.
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