Connecting the dots in neuroscience research: The future of evidence synthesis.

Making progress in neuroscience research involves learning from existing data. In this perspective piece, we explore the potential of a data-driven evidence ecosystem to connect all primary data streams, and synthesis efforts to inform evidence-based research and translational success from bench to bedside. To enable this transformation, we set out how we can produce evidence designed with evidence curation in mind.

Screening for in vitro systematic reviews: a comparison of screening methods and training of a machine learning classifier.

Objective: Existing strategies to identify relevant studies for systematic review may not perform equally well across research domains. We compare four approaches based on either human or automated screening of either title and abstract or full text, and report the training of a machine learning algorithm to identify in vitro studies from bibliographic records.

Methods: We used a systematic review of oxygen-glucose deprivation (OGD) in PC-12 cells to compare approaches.

Finding the best fit for improving reproducibility: reflections from the QUEST Center for Responsible Research.

Increasing the reproducibility and trustworthiness of biomedical research requires engaging stakeholders from all levels in an institutional setting. The QUEST Center for Responsible Research aims to develop and implement new approaches to improve the culture and practice of research, tailored to the needs of these stakeholders. Members of the QUEST Center organised a brainstorm to reflect on the challenges and new opportunities encountered in implementing different projects through QUEST and share the lessons that working groups have learned over the first five years.

Effectiveness of biomaterial-based combination strategies for spinal cord repair - a systematic review and meta-analysis of preclinical literature.

Study Design: Systematic review and meta-analysis of preclinical literature.

Objectives: To assess the effects of biomaterial-based combination (BMC) strategies for the treatment of Spinal Cord Injury (SCI), the effects of individual biomaterials in the context of BMC strategies, and the factors influencing their efficacy. To assess the effects of different preclinical testing paradigms in BMC strategies.

Development and uptake of an online systematic review platform: the early years of the CAMARADES Systematic Review Facility (SyRF).

Preclinical research is a vital step in the drug discovery pipeline and more generally in helping to better understand human disease aetiology and its management. Systematic reviews (SRs) can be powerful in summarising and appraising this evidence concerning a specific research question, to highlight areas of improvements, areas for further research and areas where evidence may be sufficient to take forward to other research domains, for instance clinical trial. Guidance and tools for preclinical research synthesis remain limited despite their clear utility.

Comparison of commonly used methods in random effects meta-analysis: application to preclinical data in drug discovery research.

Background: Meta-analysis of preclinical data is used to evaluate the consistency of findings and to inform the design and conduct of future studies. Unlike clinical meta-analysis, preclinical data often involve many heterogeneous studies reporting outcomes from a small number of animals. Here, we review the methodological challenges in preclinical meta-analysis in estimating and explaining heterogeneity in treatment effects.

External validity in translational biomedicine: understanding the conditions enabling the cause to have an effect.

A spectre is haunting biomedical research: It appears that a substantial fraction of published research results cannot be reproduced, while spectacularly successful novel treatments developed in experimental models of disease too often fail in clinical trials. A reproducibility crisis has been proclaimed, and bench-to-bedside translation appears to be lost in a "valley of death". Both predicaments, non-reproducibility and translational roadblocks, are connected: Why should we expect to successfully "trans-late" results to humans, if already "cis-lation"-that is, the generalization from one experimental setting to an identical or fairly similar one-often fails?

Meta-analysis of variation suggests that embracing variability improves both replicability and generalizability in preclinical research.

The replicability of research results has been a cause of increasing concern to the scientific community. The long-held belief that experimental standardization begets replicability has also been recently challenged, with the observation that the reduction of variability within studies can lead to idiosyncratic, lab-specific results that cannot be replicated. An alternative approach is to, instead, deliberately introduce heterogeneity, known as "heterogenization" of experimental design.

Epidemiology and reporting characteristics of preclinical systematic reviews.

In an effort to better utilize published evidence obtained from animal experiments, systematic reviews of preclinical studies are increasingly more common-along with the methods and tools to appraise them (e.g., SYstematic Review Center for Laboratory animal Experimentation [SYRCLE's] risk of bias tool).

Animal models of chemotherapy-induced peripheral neuropathy: A machine-assisted systematic review and meta-analysis.

We report a systematic review and meta-analysis of research using animal models of chemotherapy-induced peripheral neuropathy (CIPN). We systematically searched 5 online databases in September 2012 and updated the search in November 2015 using machine learning and text mining to reduce the screening for inclusion workload and improve accuracy. For each comparison, we calculated a standardised mean difference (SMD) effect size, and then combined effects in a random-effects meta-analysis.

Identifying stroke therapeutics from preclinical models: A protocol for a novel application of network meta-analysis.

Globally, stroke is the second leading cause of death. Despite the burden of illness and death, few acute interventions are available to patients with ischemic stroke. Over 1,000 potential neuroprotective therapeutics have been evaluated in preclinical models.

Human Ischaemic Cascade Studies Using SH-SY5Y Cells: a Systematic Review and Meta-Analysis.

Low translational yield for stroke may reflect the focus of discovery science on rodents rather than humans. Just how little is known about human neuronal ischaemic responses is confirmed by systematic review and meta-analysis revealing that data for the most commonly used SH-SY5Y human cells comprises only 84 papers. Oxygen-glucose deprivation, HO, hypoxia, glucose-deprivation and glutamate excitotoxicity yielded - 58, - 61, - 29, - 45 and - 49% injury, respectively, with a dose-response relationship found only for HO injury (R = 29.

Correction: D-galactose-induced brain ageing model: A systematic review and meta-analysis on cognitive outcomes and oxidative stress indices.

[This corrects the article DOI: 10.1371/journal.pone.

Risk of bias reporting in the recent animal focal cerebral ischaemia literature.

Background: Findings from research may be less reliable where studies do not report measures to reduce risks of bias. The experimental stroke community has been at the forefront of implementing changes to improve reporting, but it is not known whether these efforts are associated with continuous improvements. Our aims here were firstly to validate an automated tool to assess risks of bias in published works, and secondly to assess the reporting of measures taken to reduce the risk of bias within recent literature for two experimental models of stroke.

D-galactose-induced brain ageing model: A systematic review and meta-analysis on cognitive outcomes and oxidative stress indices.

Animal models are commonly used in brain ageing research. Amongst these, models where rodents are exposed to d-galactose are held to recapitulate a number of features of ageing including neurobehavioral and neurochemical changes. However, results from animal studies are often inconsistent.

Anesthetic Neuroprotection in Experimental Stroke in Rodents: A Systematic Review and Meta-analysis.

Background: Patients undergoing endovascular therapy for acute ischemic stroke may require general anesthesia to undergo the procedure. At present, there is little clinical evidence to guide the choice of anesthetic in this acute setting. The clinical implications of experimental studies demonstrating anesthetic neuroprotection are poorly understood.

Systematic Review and Meta-Analysis of the Efficacy of Interleukin-1 Receptor Antagonist in Animal Models of Stroke: an Update.

Interleukin-1 receptor antagonist (IL-1 RA) is an anti-inflammatory protein used clinically to treat rheumatoid arthritis and is considered a promising candidate therapy for stroke. Here, we sought to update the existing systematic review and meta-analysis of IL-1 RA in models of ischaemic stroke, published in 2009, to assess efficacy, the range of circumstances in which efficacy has been tested and whether the data appear to be confounded due to reported study quality and publication bias. We included 25 sources of data, 11 of which were additional to the original review.

Intracranial pressure elevation after ischemic stroke in rats: cerebral edema is not the only cause, and short-duration mild hypothermia is a highly effective preventive therapy.

Correction to: Journal of Cerebral Blood Flow & Metabolism (2015) 35, 592–600; doi:10.1038/jcbfm.2014.

Intracranial pressure elevation after ischemic stroke in rats: cerebral edema is not the only cause, and short-duration mild hypothermia is a highly effective preventive therapy.

In both the human and animal literature, it has largely been assumed that edema is the primary cause of intracranial pressure (ICP) elevation after stroke and that more edema equates to higher ICP. We recently demonstrated a dramatic ICP elevation 24 hours after small ischemic strokes in rats, with minimal edema. This ICP elevation was completely prevented by short-duration moderate hypothermia soon after stroke.

Nox2 knockout delays infarct progression and increases vascular recovery through angiogenesis in mice following ischaemic stroke with reperfusion.

Evidence suggests the NADPH oxidases contribute to ischaemic stroke injury and Nox2 is the most widely studied subtype in the context of stroke. There is still conjecture however regarding the benefits of inhibiting Nox2 to improve stroke outcome. The current study aimed to examine the temporal effects of genetic Nox2 deletion on neuronal loss after ischaemic stroke using knockout (KO) mice with 6, 24 and 72 hour recovery.

Efficacy of antidepressants in animal models of ischemic stroke: a systematic review and meta-analysis.

Background And Purpose: Poststroke depression is a prevalent complication of stroke with unclear pathogenesis. The benefits of antidepressants in this context and their effects on stroke recovery other than effects on mood are not clearly defined, with some studies suggesting efficacy in improving functional outcome in both depressed and nondepressed stroke patients. We have analyzed the preclinical animal data on antidepressant treatment in focal cerebral ischemia, modeled±depression, to help inform clinical trial design.