Safety and Pharmacokinetics of Intranasally Administered Heparin

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  1. SciScore for 10.1101/2021.07.05.21259936: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIACUC: Animals: All procedures were approved by the University of Mississippi Institutional Animal Care and Use Committee (protocol #19-009) or the University of Mississippi Medical Center Institutional Animal Care and Use Committee (protocol #1571).
    Field Sample Permit: All animals for toxicology studies were housed in the AALAC-accredited University of Mississippi Animal Facility and given access to rodent chow (Cat.# 7001, Envigo Teklad 4% Fat Rodent Diet) and tap water ad libitum for the duration of the experiments.
    Euthanasia Agents: Upon completion of the study, mice were anesthetized with vaporized isofluorane, perfused with phosphate buffer saline, and secondarily euthanized with decapitation.
    IRB: Human Study Population: An Early Phase 1 interventional clinical trial (NCT04490239) in a small sample population was performed under the approval and guidance of the University of Mississippi Institutional Review Board (protocol #21-004).
    Consent: All subjects submitted written informed consent prior to enrollment in the study.
    Sex as a biological variableToxicology experiments were performed on wild-type male (19-23g) and female (16-19g) C57BL6 mice from Envigo (Indianapolis, IN) in study groups of six mice for each dose (three male, three female).
    RandomizationOn test day, the subject was placed in a test chamber containing 3 cm of fresh 1/8 in corncob bedding for a 15-minute trial, with the food stimulus buried approximately 1 cm below the bedding surface in a randomly assigned corner of the cage.
    BlindingPlatelets in each image were counted by a blinded observer.
    Power AnalysisThe study was powered to preserve an 80% chance of not committing a Type II error with a 5% chance of Type I error at significant effect sizes (weight as the variable: power > 0.8 to detect a 20% change in body weight within sex (n = 3), 10% change in body weight within entire group (n = 6); aPTT time: power > 0.8 to detect a 100% change in aPTT (n = 4); buried food recovery time: power > 0.8 to detect a 100% change in recovery time (n = 5)).
    Cell Line AuthenticationAuthentication: Signs of inflammation, bleeding, and/or nasal discharge were monitored twice daily by visual inspection of the nose, body, cage, and bedding.

    Table 2: Resources

    Experimental Models: Organisms/Strains
    SentencesResources
    Toxicology experiments were performed on wild-type male (19-23g) and female (16-19g) C57BL6 mice from Envigo (Indianapolis, IN) in study groups of six mice for each dose (three male, three female).
    C57BL6
    suggested: None
    In vivo imaging experiments were performed on three female SKH1-Elite mice (Crl:SKH1-Hrhr Outbred: Charles River Laboratories, Wilmington, MA).
    SKH1-Elite
    suggested: None
    Software and Algorithms
    SentencesResources
    One-phase and two-phase exponential decay modeling was carried out using GraphPad Prism 8.4.3 and hypothesis testing using an extra sum-of-squares F test was performed.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Data were analyzed using SPSS and SyStat SigmaPlot v13 software.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    SyStat
    suggested: (SyStat, RRID:SCR_010455)
    SigmaPlot
    suggested: (SigmaPlot, RRID:SCR_003210)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04490239CompletedIntranasal Heparin Tolerability Study


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 18. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.


    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.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.