10 research outputs found

    Mehran Andalibi

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    https://commons.erau.edu/oe-week-images/1010/thumbnail.jp

    Exploring Ethics and Obligations for Studying Digital Communities

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    Many of the most prominent and unanswered ethical questions within HCI and social computing involve our ethical obligation to the communities that we study. Some of these questions fall under the purview of more traditional human subjects research ethics, but others hinge on when, for example, studies of public data trigger similar obligations. Basic rules to do no harm are complicated in digital communities by issues of consent and privacy, and ethics review boards are struggling to keep up even as research communities are similarly struggling to form appropriate norms. The goals of this workshop are to continue seeding conversations about research ethics within the SIGCHI community, to work towards norm setting, and in the meantime, to collectively help community members make good ethical decisions about research into sociotechnical systems and digital communities. Copyright is held by the owner/author(s)

    Effects of oxidized low density lipoprotein, lipid mediators and statins on vascular cell interactions

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    The integrin heterodimer CD11b/CD18 (alpha M beta 2, Mac-1, CR3) expressed on monocytes or polymorphonuclear leukocytes (PMN) is a receptor for iC3b, fibrinogen, heparin, and for intercellular adhesion molecule (ICAM)-1 on endothelium, crucially contributing to vascular cell interactions in inflammation and atherosclerosis. In this report, we summarize our findings on the effects of lipid mediators and lipid-lowering drugs. Exposure of endothelial cells to oxidized low density lipoprotein (oxLDL) induces upregulation of ICAM-1 and increases adhesion of monocytic cells expressing Mac-1. Inhibition experiments show that monocytes use distinct ligands, i.e. ICAM-1 and heparan sulfate proteoglycans for adhesion to oxLDL-treated endothelium. An albumin-transferable oxLDL activity is inhibited by the antioxidant pyrrolidine dithiocarbamate (PDTC), while 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) or lysophosphatidylcholine had no effect, implicating yet unidentified radicals. Sequential adhesive! and signaling events lead to the firm adhesion of rolling PMN on activated and adherent platelets, which may occupy areas of endothelial denudation. Shear resistant arrest of PMN on thrombin-stimulated platelets in flow conditions requires distinct regions of Mac-1, involving its interactions with fibrinogen bound to platelet alpha llb beta 3, and with other platelet ligands. Both arrest and adhesion strengthening under flow are stimulated by platelet-activating factor and leukotriene B4, but not by the chemokine receptor CXCR2. We tested whether Mac-1-dependent monocyte adhesiveness is affected by inhibitors of hydroxy-methylglutaryl-Coenzyme A reductase (statins) which improve morbidity and survival of patients with coronary heart disease. As compared to controls, adhesion of isolated monocytes to endothelium ex vivo was increased in patients with hypercholesterolemia. Treatment with statins decreased total and low density lipoprotein (LDL) cholesterol plasma levels, surface expression of Mac-1, and resulted in a dramatic reduction of Mac,mediated monocyte adhesion to endothelium. The inhibition of monocyte adhesion was reversed by mevalonate but not LDL in vitro,indicating that isoprenoid precursors are crucial for adhesiveness of Mac-1. Such effects may crucially contribute to the clinical benefit of statins, independent of cholesterol-lowering, and may represent a paradigm for novel, anti-inflammatory mechanisms of action by this class of drugs

    A resource to empirically establish drug exposure records directly from untargeted metabolomics data

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    Despite extensive efforts, extracting medication exposure information from clinical records remains challenging. To complement this approach, here we show the Global Natural Product Social Molecular Networking (GNPS) Drug Library, a tandem mass spectrometry (MS/MS) based resource designed for drug screening with untargeted metabolomics. This resource integrates MS/MS references of drugs and their metabolites/analogs with standardized vocabularies on their exposure sources, pharmacologic classes, therapeutic indications, and mechanisms of action. It enables direct analysis of drug exposure and metabolism from untargeted metabolomics data, supporting flexible summarization at multiple ontology levels to align with different research goals. We demonstrate its application by stratifying participants in a human immunodeficiency virus (HIV) cohort based on detected drug exposures. We uncover drug-associated alterations in microbiota-derived N-acyl lipids that are not captured when stratifying by self-reported medication use. Overall, GNPS Drug Library provides a scalable resource for empirical drug screening in clinical, nutritional, environmental, and other research disciplines, facilitating insights into the ecological and health consequences of drug exposures. While not intended for immediate clinical decision-making, it supports data-driven exploration of drug exposures where traditional records are limited or unreliable.This project was enabled in part by the Alzheimer’s Gut Microbiome Project (AGMP) and the Data Infrastructure and Molecular Atlas for AD: Connection Exposome, Gut Microbiome, and Metabolome supplement funded wholly or in part by the following grants thereto: 1U19AG063744 and 3U19AG063744-04S1 and awarded to Dr. Kaddurah-Daouk at Duke University in partnership with multiple academic institutions. As such, the investigators within the AGMP and the Exposome Supplement, not listed specifically in this publication’s author list, provided data along with their pre-processing and prepared it for analysis, but did not participate in analysis or writing of this manuscript. A listing of AGMP Investigators can be found at https://alzheimergut.org/meet-the-team/. A complete listing of ADMC investigators can be found at: https://sites.duke.edu/adnimetab/team/. We also thank the support by NIH for the Maternal and Pediatric Precision in Therapeutics project P50HD106463, the development of tools for structure elucidation R01DK136117, and the Collaborative Microbial Metabolite Center U24DK133658. The HIV Neurobehavioral Research Center (HNRC) is supported by Center award P30MH062512 from NIMH. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZIC ES103363). H.N.Z. was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number K99ES037746. C.B. was supported by the Czech Academy of Sciences PPLZ fellowship number L200552251. V.C.L. is supported by Fonds de recherche du Québec - Santé (FRQS) Postdoctoral fellowship (335368). N.E.A was supported in part by the National Center for Complementary and Integrative Health of the NIH under award number F32AT011475. A.M.C.-R. and P.C.D. were supported by the Gordon and Betty Moore Foundation grant GBMF12120. M.R. was supported by the NIH grant R37 AI126277. T.P. was supported by the Czech Science Foundation (GA CR) grant 21-11563 M and by the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement No. 891397. L.C., R.G.-S., and P.G.-F. were supported by the Spanish Ministry of Science (PID2022-139446OB-C21 and PID2022-139446OB-C22). L.C. acknowledges the support from the Economy and Knowledge Department of the Catalan Government through Consolidated Research Group (ICRA-TECH 2021 SGR 01283), as well as from the CERCA programme. W.B. acknowledges support by the Research Foundation–Flanders (FWO G0AHY25N).Peer reviewe
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