Tie2 activation protects against prothrombotic endothelial dysfunction in COVID-19
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SciScore for 10.1101/2021.05.13.21257070: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All enrolled patients provided either written and/or verbal informed consent, participation was entirely voluntary, and the repository studies were approved by the internal review board (IRB) at their respective institutions (BIDMC IRB 2020P000361 and MGH IRB 2020P000804).
IRB: All enrolled patients provided either written and/or verbal informed consent, participation was entirely voluntary, and the repository studies were approved by the internal review board (IRB) at their respective institutions (BIDMC IRB 2020P000361 and MGH IRB 2020P000804).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication …SciScore for 10.1101/2021.05.13.21257070: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All enrolled patients provided either written and/or verbal informed consent, participation was entirely voluntary, and the repository studies were approved by the internal review board (IRB) at their respective institutions (BIDMC IRB 2020P000361 and MGH IRB 2020P000804).
IRB: All enrolled patients provided either written and/or verbal informed consent, participation was entirely voluntary, and the repository studies were approved by the internal review board (IRB) at their respective institutions (BIDMC IRB 2020P000361 and MGH IRB 2020P000804).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Primary antibodies used for immunofluorescence microscopy are as follows: anti-VWF (clone IIIE2.34, Millipore Sigma), anti-VWFsuggested: NoneExperimental Models: Cell Lines Sentences Resources Endothelial cell culture: Human umbilical vein endothelial cells (HUVEC, pooled donor, Lonza) were grown on collagen-coated culture plates and maintained in endothelial cell growth basal media (EBM-2, Lonza), containing 2% fetal bovine serum (FBS) and contents of the EGM-2 SingleQuots growth factor supplement kit. HUVECsuggested: KCB Cat# KCB 200648YJ, RRID:CVCL_2959)Gene expression analysis: Confluent HUVECs were treated with pooled patient plasma as described above and gene expression was determined using a 2-step Cell-to-Ct Taqman kit (Thermo Fisher Scientific). HUVECssuggested: NoneSoftware and Algorithms Sentences Resources Image analysis: Fluorescent images were analyzed using Image J software (NIH). Image Jsuggested: (ImageJ, RRID:SCR_003070)All statistical analysis was performed using GraphPad Prism (version 9.0; GraphPad Software, San Diego, CA). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study has several limitations. Given the retrospective and non-consecutive nature of patient recruitment into the biorepositories, several biases may have inadvertently been introduced. It would have been useful to have readouts of gene expression and coagulation assays of individual plasmas correlated with markers detected in vivo or whether these functional assays provided additional predictive clinical information. Given the limited amount of plasma supply however, it was necessary to pool the individual plasmas. The amount of autopsy specimens were limited, which impaired our ability to perform comprehensive histopathological assessment of multiple endothelial markers. We cannot rule out that differences in specimen preparation affected antibody staining. That samples were not collected uniformly early upon hospital or ICU admission limits the applicability of our conclusions regarding endothelial biomarkers and clinical endpoints. In conclusion, the present study supports the concept that moderate and severe COVID-19 are driven at least in part by procoagulant endothelial cell dysfunction, the degree of which increases in parallel with COVID-19 disease severity. Elevated Angpt-2 levels may potentiate endothelial cell dysfunction through inhibition of antithrombotic Tie2 signaling. Activation of Tie2 through two independent mechanisms corrects the prothrombotic changes in endothelial cells induced by plasma from COVID-19 patients. Our findings support further investig...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04511650 Recruiting A Study to Evaluate the Safety and Efficacy of Razuprotafib,… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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