ObjectiveBone marrow(BM)-derived cell-based therapies for critical limb ischamia showed less clinical benefit than expected. While this might be due to patient-specific factors, it remains possible that important details were lost in the bench-to-clinic translation. The hindlimb ischaemia model is the golden standard to evaluate cell-based therapies aimed at promoting neovascularisation. To inform future trial design and identify potential knowledge gaps, we propose a systematic review and meta-analysis of preclinical evidence to assess the efficacy of BM-derived cell administration in restoring relative perfusion in the hind limb model and identify determinants of therapeutic efficacy.Search strategyPubMed and EMBASE were searched for prospective studies in which the hindlimb ischaemia model was used to assess BM-derived therapies.Screening and annotationStudies with an outcome measure related to relative perfusion of the hindlimb will be included. Study characteristics which include model-related factors as well as details on BM therapy will be extracted.Data management and reportingFor the primary analysis, a random effects model will be constructed using the mean difference calculated from the maximum relative perfusion for each study arm in each study. A separate model will be constructed using the relative perfusion at the latest time point in each study. We will also assess the risk of bias using the SYRCLE tool for internal validity. Subgroup analysis will be performed on animal characteristics, administration route, dose and cell characteristics such as the cell donor.PROSPERO registration numberThis protocol has been registered at PROSPERO (CRD2021226592).

Introduction and objectiveThe Western diet that comprises high levels of long-chain saturated fats and sugar is associated not only with metabolic disorders such as obesity and type 2 diabetes but also has been recently linked to brain changes and cognitive dysfunction. However, in animal studies, reported effects are variable, and the mechanisms underlying these effects are unclear. In the proposed review, we aim to summarise the diverse evidence of the effects of so-called ‘high-fat’ and ketogenic diets on behavioural measures of cognition in postweaning mice and rats, relative to animals on standard diets and to determine potential underlying mechanisms of high-fat diet-induced effects.Search strategyA comprehensive search strategy was designed to retrieve studies reporting use of a high-fat or ketogenic diet in postweaning mice and rats that included cognitive assessments. Three databases (Medline, SCOPUS and Web of Science) were searched and 4487 unique references were retrieved.Screening and annotationStudies were screened for inclusion by two independent reviewers, with 330 studies retained for analysis. Characteristics of disease model choice, experimental design, intervention use and outcome assessment are to be extracted using the Systematic Review Facility (http://syrf.org.uk/) tool. Studies will be assessed for study quality and risk of bias and confidence of mechanistic involvement.Data management and reportingFor cognitive outcomes, effect sizes will be calculated using normalised mean difference and summarised using a random effects model. The contribution of potential sources of heterogeneity to the observed effects of diet on cognition will be assessed using multivariable meta-regression, with partitioning of heterogeneity as a sensitivity analysis. A preliminary version of this protocol was published on 9 April 2019 on the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies website (http://www.dcn.ed.ac.uk/camarades/research.html%23protocols).Ethics and disseminationNo ethical approval is required as there are no subjects in the proposed study.

ObjectiveTo determine whether a change in editorial policy, including the implementation of a checklist, has been associated with improved reporting of measures which might reduce the risk of bias.MethodsThe study protocol has been published at doi: 10.1007/s11192-016-1964-8.DesignObservational cohort study.PopulationArticles describing research in the life sciences published in Nature journals, submitted after 1 May 2013.InterventionMandatory completion of a checklist during manuscript revision.Comparators(1) Articles describing research in the life sciences published in Nature journals, submitted before May 2013; and (2) similar articles in other journals matched for date and topic.Primary outcomeThe primary outcome is change in the proportion of Nature articles describing in vivo research published before and after May 2013 reporting the ‘Landis 4’ items (randomisation, blinding, sample size calculation and exclusions). We included 448 Nature Publishing Group (NPG) articles (223 published before May 2013, and 225 after) identified by an individual hired by NPG for this specific task, working to a standard procedure; and an independent investigator used PubMed ‘Related Citations’ to identify 448 non-NPG articles with a similar topic and date of publication from other journals; and then redacted all articles for time-sensitive information and journal name. Redacted articles were assessed by two trained reviewers against a 74-item checklist, with discrepancies resolved by a third.Results394 NPG and 353 matching non-NPG articles described in vivo research. The number of NPG articles meeting all relevant Landis 4 criteria increased from 0/203 prior to May 2013 to 31/181 (16.4%) after (two-sample test for equality of proportions without continuity correction, Χ²=36.2, df=1, p=1.8×10−9). There was no change in the proportion of non-NPG articles meeting all relevant Landis 4 criteria (1/164 before, 1/189 after). There were more substantial improvements in the individual prevalences of reporting of randomisation, blinding, exclusions and sample size calculations for in vivo experiments, and less substantial improvements for in vitro experiments.ConclusionThere was an improvement in the reporting of risks of bias in in vivo research in NPG journals following a change in editorial policy, to a level that to our knowledge has not been previously observed. However, there remain opportunities for further improvement.