Meta-review on Perforation Model of Subarachnoid Hemorrhage in Mice: Filament Material as a Possible Moderator of Mortality.

Robust preclinical models are inevitable for researchers to unravel pathomechanisms of subarachnoidal hemorrhage (SAH). For the mouse perforation model of SAH, the goal of this meta-review was the determination of variances in mortality, SAH severity grade, and vasospasm, and their experimental moderators, as many researchers are facing with incomparable results. We searched on the databases PubMed, Embase, and Web of Science for articles describing in vivo experiments using the SAH perforation mouse model and measuring mortality, SAH grade, and/or vasospasm. After screening, 42 articles (total of 1964 mice) were included into systematic review and meta-analysis. Certain model characteristics were insufficiently reported, e.g., perforation location (not reported in six articles), filament (material (n = 15) and tip texture (n = 25)), mouse age (n = 14), and weight (n = 10). Used injective anesthetics and location of perforation showed large variation. In a random-effects meta-analysis, the overall animal mortality following SAH was 21.3% [95% CI: 17.5%, 25.7%] and increased with longer observational periods. Filament material significantly correlated with animal mortality (p = 0.024) after exclusion of hyperacute studies (time after SAH induction < 24 h). Reported mean SAH grade was 10.7 [9.6, 11.7] on the scale of Sugawara (J Neurosci Methods 167:327-34, 2008). Furthermore, mean diameter of large cerebral arteries after SAH was reduced by 27.6% compared to sham-operated non-SAH mice. Uniforming standards of experimental procedures and their reporting are indispensable to increase overall comparability.

Meta-analysis on reporting practices as a source of heterogeneity in in vitro cancer research.

Objectives: Heterogeneity of results of exact same research experiments oppose a significant socioeconomic burden. Insufficient methodological reporting is likely to be one of the contributors to results heterogeneity; however, little knowledge on reporting habits of in vitro cancer research and their effects on results reproducibility is available. Exemplified by a commonly performed in vitro assay, we aim to fill this knowledge gap and to derive recommendations necessary for reproducible, robust and translational preclinical science. Methods: Here, we use systematic review to describe reporting practices in in vitro glioblastoma research using the Uppsala-87 Malignant Glioma (U-87 MG) cell line and perform multilevel random-effects meta-analysis followed by meta-regression to explore sources of heterogeneity within that literature, and any associations between reporting characteristics and reported findings. Literature that includes experiments measuring the effect of temozolomide on the viability of U-87 MG cells is searched on three databases (Embase, PubMed and Web of Science). Results: In 137 identified articles, the methodological reporting is incomplete, for example, medium glucose level and cell density are reported in only 21.2% and 16.8% of the articles. After adjustments for different drug concentrations and treatment durations, the results heterogeneity across the studies (I2=68.5%) is concerningly large. Differences in culture medium glucose level are a driver of this heterogeneity. However, infrequent reporting of most experimental parameters limits the analysis of reproducibility moderating parameters. Conclusions: Our results further support the ongoing efforts of establishing consensus reporting practices to elevate durability of results. By doing so, this work can raise awareness of how stricter reporting may help to improve the frequency of successful translation of preclinical results into human application. The authors received no specific funding for this work. A preregistered protocol is available at the Open Science Framework (https://osf.io/9k3dq).