Ulrich Dirnagl

Ulrich Dirnagl
See my · ORCID https://orcid.org/0000-0003-0755-6119

MD

About

617
Publications
78,632
Reads
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46,106
Citations
Introduction
Check out http://dirnagl.com (blog) | ORCID https://orcid.org/0000-0003-0755-6119 (cv etc.) | Twitter @dirnagl | QUEST Center BIH https://quest.bihealth.org/ | Dept. of Exp. Neurology Charite http://expneuro.charite.de/en/

Publications

Publications (617)
Article
The EQIPD framework for rigor in animal experiments aims to unify current recommendations based on evidence behind their rationale and was prospectively tested for feasibility in multicenter animal experiments.
Article
Full-text available
Lessons from implementing quality control systems in an academic research consortium to improve Good Scientific Practice and reproducibility.
Preprint
Background Mandates and recommendations related to embedding open science practices within the research lifecycle are increasingly common. Few stakeholders, however, are monitoring compliance to their mandates or recommendations. It is necessary to monitor the current state of open science to track changes over time and to identify areas to create...
Article
Full-text available
Aims Carotid artery disease is frequent and can result in chronic modest hypoperfusion of the brain. If no transient ischemic attack or stroke occur, it is classified asymptomatic. In the long-term, though, it can lead to cognitive impairment. Fostering cerebral remodeling after carotid artery occlusion might be a new concept of treatment. Paracrin...
Article
Promoting translational research as a means to overcoming chasms in the translation of knowledge through successive fields of research from basic science to public health impacts and back is a central challenge for research managers and policymakers. Organizational leaders need to assess baseline conditions, identify areas needing improvement, and...
Article
Biomedical research accuracy and relevance for improving healthcare are increasingly identified as costly problems. Basic research data quality, reporting and methodology, and reproducibility are common factors implicated in this challenge. Preclinical models of disease and therapy, largely conducted in rodents, have known deficiencies in replicati...
Preprint
The success of scientific discovery in preclinical research is based on the different roles of exploration and confirmation. Exploration involves identifying potential effects (high sensitivity), which are then tested more rigorously during confirmation (high specificity). Here, we examine different experimental strategies and their ability to bala...
Article
Full-text available
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...
Data
Introduction to the EQIPD quality system
Article
Full-text available
While high risk of failure is an inherent part of developing innovative therapies, it can be reduced by adherence to evidence-based rigorous research practices. Numerous analyses conducted to date have clearly identified measures that need to be taken to improve research rigor. Supported through the European Union's Innovative Medicines Initiative,...
Article
Full-text available
Recently, several genome-wide association studies identified PHACTR1 as key locus for five diverse vascular disorders: coronary artery disease, migraine, fibromuscular dysplasia, cervical artery dissection and hypertension. Although these represent significant risk factors or comorbidities for ischemic stroke, PHACTR1 role in brain small vessel isc...
Article
Full-text available
The purpose of preclinical research is to inform the development of novel diagnostics or therapeutics, and the results of experiments on animal models of disease often inform the decision to conduct studies in humans. However, a substantial number of clinical trials fail, even when preclinical studies have apparently demonstrated the efficacy of a...
Article
Full-text available
Promoting translational research as a means to overcoming chasms in the translation of knowledge through successive fields of research from basic science to public health impacts and back is a central challenge for research managers and policymakers. Organizational leaders need to assess baseline conditions, identify areas needing improvement, and...
Article
Full-text available
Academic research plays a key role in identifying new drug targets, including understanding target biology and links between targets and disease states. To lead to new drugs, however, research must progress from purely academic exploration to the initiation of efforts to identify and test a drug candidate in clinical trials, which are typically con...
Preprint
Full-text available
Connectome analysis of neuroimaging data is a rapidly expanding field to identify disease specific biomarkers. Structural diffusion MRI connectivity has been useful in individuals with radiological features of small vessel disease, such as white matter hyperintensities. Global efficiency, a network metric calculated from the structural connectome,...
Article
Full-text available
Statistically significant findings are more likely to be published than non-significant or null findings, leaving scientists and healthcare personnel to make decisions based on distorted scientific evidence. Continuously expanding ´file drawers’ of unpublished data from well-designed experiments waste resources creates problems for researchers, the...
Article
Full-text available
Background : Never before have clinical trials drawn as much public attention as those testing interventions for COVID-19. We aimed to describe the worldwide COVID-19 clinical research response and its evolution over the first 100 days of the pandemic. Methods: Descriptive analysis of planned, ongoing or completed trials by April 9, 2020 testing an...
Article
Full-text available
Numerous studies on experimental ischemic stroke use the filament middle cerebral artery occlusion (fMCAo) model in C57BL/6 mice, but lesion sizes in this strain are highly variable. A known contributor is variation in the posterior communicating artery (PcomA) patency. We therefore aimed to provide a semiquantitative non-invasive in vivo method to...
Preprint
Full-text available
While high risk of failure is an inherent part of developing innovative therapies, it can be reduced by adherence to evidence-based rigorous research practices. Numerous analyses conducted to date have clearly identified measures that need to be taken to improve research rigor. Supported through the European Union’s Innovative Medicines Initiative,...
Article
Full-text available
Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...
Article
Full-text available
Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...
Article
Full-text available
Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...
Article
Full-text available
Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...
Article
Full-text available
Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting is vital to this process; it allows readers to assess the reliability of the findings and repeat or build upon the work of other researchers. The ARRIVE guidelines (Animal Research: Reporting In Vivo Experiments) were developed in 2010 to h...
Article
Full-text available
Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...
Article
Full-text available
Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...
Article
Full-text available
Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...
Article
Objective To explore the accuracy of combined neurology expert forecasts in predicting primary endpoints for trials. Methods We identified one major randomized trial each in stroke, multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) that was closing within 6 months. After recruiting a sample of neurology experts for each disease, we...
Article
Full-text available
Alzheimer’s disease and small vessel ischemic disease frequently co-exist in the aging brain. However, pathogenic links between these 2 disorders are yet to be identified. Therefore we used Taqman genotyping, exome and RNA sequencing to investigate Alzheimer’s disease known pathogenic variants and pathways: APOE ε4 allele, APP-Aβ metabolism and lat...
Article
Full-text available
Over the last two decades, awareness of the negative repercussions of flaws in the planning, conduct and reporting of preclinical research involving experimental animals has been growing. Several initiatives have set out to increase transparency and internal validity of preclinical studies, mostly publishing expert consensus and experience. While m...
Article
Full-text available
Preregistration of study protocols and, in particular, Registered Reports are novel publishing formats that are currently gaining substantial traction. Besides rating the research question and soundness of methodology over outstanding significance of the results, they can help with antagonizing inadequate statistical power, selective reporting of r...
Preprint
Full-text available
How much can we rely on whether what was reported in a study was actually done? Systematic and independent examination of records, documents and processes through audits are a central element of quality management systems. In the context of current concerns about the robustness and reproducibility of experimental biomedical research audits have bee...
Article
Full-text available
The reproducibility crisis triggered worldwide initiatives to improve rigor, reproducibility, and transparency in biomedical research. There are many examples of scientists, journals, and funding agencies adopting responsible research practices. The QUEST (Quality-Ethics-Open Science-Translation) Center offers a unique opportunity to examine the ro...
Article
Full-text available
SorCS2 is an intracellular sorting receptor of the VPS10P domain receptor gene family recently implicated in oxidative stress response. Here, we interrogated the relevance of stress‐related activities of SorCS2 in the brain by exploring its role in ischemic stroke in mouse models and in patients. Although primarily seen in neurons in the healthy br...
Chapter
Full-text available
Confirmation through competent replication is a founding principle of modern science. However, biomedical researchers are rewarded for innovation, and not for confirmation, and confirmatory research is often stigmatized as unoriginal and as a consequence faces barriers to publication. As a result, the current biomedical literature is dominated by e...
Preprint
Full-text available
This preprint introduces a new open source tool (fiddle - file drawer data liberation effort; available at: http://s-quest.bihealth.org/fiddle/) that aims to help researchers to identify the most appropriate publication format for their dataset. Formats include data repositories, micropublications, preprints, data journals, publishing platforms and...
Preprint
Full-text available
Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting are vital to this process; it allows readers to assess the reliability of the findings, and repeat or build upon the work of other researchers. The NC3Rs developed the ARRIVE guidelines in 2010 to help authors and journals identify the mini...
Preprint
Full-text available
Reproducible science requires transparent reporting. The ARRIVE guidelines were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and rep...
Article
Full-text available
Objective: Maternal autoantibodies are a risk factor for impaired brain development in the offspring. Antibodies (AB) against the NR1 (GluN1) subunit of the N-Methyl-D-Aspartate-receptor (NMDAR) are among the most frequently diagnosed anti-neuronal surface AB, yet little is known about effects on fetal development during pregnancy. Methods: We e...
Article
Objective: To determine whether and to what degree bias and underestimated variability undermine the predictive value of preclinical research for clinical translation. Methods: We investigated experimental spinal cord injury (SCI) studies for outcome heterogeneity and the impact of bias. Data from 549 preclinical SCI studies including 9,535 anim...
Article
Objectives: Timely and comprehensive reporting of clinical trial results builds the backbone of evidence-based medicine and responsible research. The proportion of timely disseminated trial results can inform alternative national and international benchmarking of university medical centers (UMCs). Study design and setting: For all German UMCs, w...
Article
Full-text available
The current, widely established 3R framework for the ethical use of animals in research consists of three guiding principles, that is, R eplacement, R eduction and R efinement, all aiming to safeguard the overarching ethical principle of animal welfare. However, animal welfare alone does not suffice to make animal research ethical if the research d...
Article
Full-text available
The need for replication of initial results has been rediscovered only recently in many fields of research. In preclinical biomedical research, it is common practice to conduct exact replications with the same sample sizes as those used in the initial experiments. Such replication attempts, however, have lower probability of replication than is gen...
Article
Full-text available
Phosphatase and tensin homolog (PTEN) signalling might influence neuronal survival after brain ischemia. However, the influence of the less studied longer variant termed PTEN-L (or PTENα) has not been studied to date. Therefore, we examined the translational variant PTEN-L in the context of neuronal survival. We identified PTEN-L by proteomics in m...
Preprint
Promoting biomedical translation from bench to bedside and back in organizational settings is a central challenge for research managers and policymakers. For this, organizational leaders need to assess baseline conditions, identify areas needing improvement, and to judge the impact of specific initiatives to sustain or improve translational researc...
Article
Full-text available
Brain collateral circulation is an essential compensatory mechanism in response to acute brain ischemia. To study the temporal evolution of brain macro and microcollateral recruitment and their reciprocal interactions in response to different ischemic conditions, we applied a combination of complementary techniques (T2-weighted magnetic resonance i...
Article
Full-text available
Background: Several meta-research studies and benchmarking activities have assessed how comprehensively and timely, academic institutions and private companies publish their clinical studies. These current “clinical trial tracking” activities differ substantially in how they sample relevant studies, and how they follow up on their publication. Meth...
Article
Full-text available
Background and Purpose: The gut communicates with the brain bidirectionally via neural, humoral and immune pathways. All these pathways are affected by acute brain lesions, such as stroke. Brain-gut communication may therefore impact on the overall outcome after CNS-injury. Until now, contradictory reports on intestinal function and translocation o...
Preprint
Full-text available
Objective Timely and comprehensive reporting of clinical trial results build the backbone of evidence-based medicine and responsible research. The proportion of timely disseminated trial results can inform alternative national and international benchmarking of university medical centers (UMCs). Study Design and Setting For all German UMCs we track...
Article
Introduction We explored the use of a perfluoro-15-crown-5 ether nanoemulsion (PFC) for measuring tissue oxygenation using a mouse model of vascular cognitive impairment. Methods Seventeen C57BL/6 mice underwent stereotactic injection of PFC coupled to a fluorophore into the striatum and corpus callosum. Combined 1H/19F magnetic resonance imaging...
Article
Full-text available
Objective Within the last years, there has been growing awareness of the negative repercussions of unstandardized planning, conduct and reporting of preclinical and biomedical research. Several initiatives have set the aim of increasing validity and reliability in reporting of studies and publications, and publishers have formed similar groups. Add...
Chapter
The authors put a much-needed focus on the validity of biomedical research results that has come under scrutiny. However, as they make clear, due to the complexity of the experiments involved, errors quite naturally occur frequently. A way of managing these errors is the “Laboratory Critical Incident and Error Reporting System” (LabCIRS), a softwar...
Article
Full-text available
Millions of people worldwide currently suffer from serious neurological diseases and injuries for which there are few, and often no, effective treatments. The paucity of effective interventions is, no doubt, due in large part to the complexity of the disorders, as well as our currently limited understanding of their pathophysiology. The bleak pictu...