SynthesisScientific reports2015
A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation.
Synthesis in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- Dysconnectivity of Multiple Brain Networks in Schizophrenia: A Meta-Analysis of Resting-State Functional Connectivity.Frontiers in psychiatry · 2019Pooled it
- Pooled it
- Embracing Heterogeneity in The Multicenter Stroke Preclinical Assessment Network (SPAN) Trial.Stroke · 2023Review
- Preclinical Stroke Research and Translational Failure: A Bird's Eye View on Preventable Variables.Cellular and molecular neurobiology · 2022Review
- NOX Inhibitors: From Bench to Naxibs to Bedside.Handbook of experimental pharmacology · 2021Article
- Network and Systems Medicine: Position Paper of the European Collaboration on Science and Technology Action on Open Multiscale Systems Medicine.Network and systems medicine · 2020Review
- Shift in the paradigm towards next-generation microbiology.FEMS microbiology letters · 2019Review
- From single drug targets to synergistic network pharmacology in ischemic stroke.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The use of digital pathology and image analysis in clinical trials.The journal of pathology. Clinical research · 2019Article
- Calcium-dependent blood-brain barrier breakdown by NOX5 limits postreperfusion benefit in stroke.The Journal of clinical investigation · 2019Article
- Neuroprotective Effect of SCM-198 through Stabilizing Endothelial Cell Function.Oxidative medicine and cellular longevity · 2019Article
- Reframing the Biological Basis of Neuroprotection Using Functional Genomics: Differentially Weighted, Time-Dependent Multifactor Pathogenesis of Human Ischemic Brain Damage.Frontiers in neurology · 2018Article
- A diseasome cluster-based drug repurposing of soluble guanylate cyclase activators from smooth muscle relaxation to direct neuroprotection.NPJ systems biology and applications · 2018Article
- Review
- NOX4-dependent neuronal autotoxicity and BBB breakdown explain the superior sensitivity of the brain to ischemic damage.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).Redox biology · 2017Review
- Standardized mean differences cause funnel plot distortion in publication bias assessments.eLife · 2017Article
- Reliability of infarct volumetry: Its relevance and the improvement by a software-assisted approach.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- Article
- NOS knockout or inhibition but not disrupting PSD-95-NOS interaction protect against ischemic brain damage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Biomedical research suffers from a dramatically poor translational success. For example, in ischemic stroke, a condition with a high medical need, over a thousand experimental drug targets were unsuccessful. Here, we adopt methods from clinical research for a late-stage pre-clinical meta-analysis (MA) and randomized confirmatory trial (pRCT) approach. A profound body of literature suggests NOX2 to be a major therapeutic target in stroke. Systematic review and MA of all available NOX2(-/y) studies revealed a positive publication bias and lack of statistical power to detect a relevant reduction in infarct size. A fully powered multi-center pRCT rejects NOX2 as a target to improve neurofunctional outcomes or achieve a translationally relevant infarct size reduction. Thus stringent statistical thresholds, reporting negative data and a MA-pRCT approach can ensure biomedical data validity and overcome risks of bias.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.