Promoting research quality.

Plenty of awards recognize scientific contributions, but a unique and important one honors those whose efforts significantly enhance the quality and robustness of research. We discuss why this is important to promote trust in science.

Community consensus on core open science practices to monitor in biomedicine.

The state of open science needs to be monitored to track changes over time and identify areas to create interventions to drive improvements. In order to monitor open science practices, they first need to be well defined and operationalized. To reach consensus on what open science practices to monitor at biomedical research institutions, we conducted a modified 3-round Delphi study. Participants were research administrators, researchers, specialists in dedicated open science roles, and librarians. In rounds 1 and 2, participants completed an online survey evaluating a set of potential open science practices, and for round 3, we hosted two half-day virtual meetings to discuss and vote on items that had not reached consensus. Ultimately, participants reached consensus on 19 open science practices. This core set of open science practices will form the foundation for institutional dashboards and may also be of value for the development of policy, education, and interventions.

Incorporating equity, diversity, and inclusiveness into the Hong Kong Principles.

In this response to Labib and Evans, authors of the Hong Kong Principles look forward to collaborating with those from the broad research integrity community to ensure that issues of equity, diversity and inclusion will become part of the ecosystem of research integrity.

#IchbinHannah and the fight for permanent jobs for postdocs: How a fictitious postdoc (almost) triggered a fundamental reform of German academia: How a fictitious postdoc (almost) triggered a fundamental reform of German academia.

Regarding postdocs as disposable labour with limited contracts is damaging for science. Universities need to offer them better career perspectives.

Introducing quality measures in an academic research consortium: Lessons and recommendation from implementing an ad hoc quality management system for organ model research: Lessons and recommendation from implementing an ad hoc quality management system for organ model research.

Lessons from implementing quality control systems in an academic research consortium to improve Good Scientific Practice and reproducibility.

The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study.

Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI.

Prediction of Stroke Outcome in Mice Based on Noninvasive MRI and Behavioral Testing.

BACKGROUND: Prediction of poststroke outcome using the degree of subacute deficit or magnetic resonance imaging is well studied in humans. While mice are the most commonly used animals in preclinical stroke research, systematic analysis of outcome predictors is lacking. METHODS: We intended to incorporate heterogeneity into our retrospective study to broaden the applicability of our findings and prediction tools. We therefore analyzed the effect of 30, 45, and 60 minutes of arterial occlusion on the variance of stroke volumes. Next, we built a heterogeneous cohort of 215 mice using data from 15 studies that included 45 minutes of middle cerebral artery occlusion and various genotypes. Motor function was measured using a modified protocol for the staircase test of skilled reaching. Phases of subacute and residual deficit were defined. Magnetic resonance images of stroke lesions were coregistered on the Allen Mouse Brain Atlas to characterize stroke topology. Different random forest prediction models that either used motor-functional deficit or imaging parameters were generated for the subacute and residual deficits. RESULTS: Variance of stroke volumes was increased by 45 minutes of arterial occlusion compared with 60 minutes. The inclusion of various genotypes enhanced heterogeneity further. We detected both a subacute and residual motor-functional deficit after stroke in mice and different recovery trajectories could be observed. In mice with small cortical lesions, lesion volume was the best predictor of the subacute deficit. The residual deficit could be predicted most accurately by the degree of the subacute deficit. When using imaging parameters for the prediction of the residual deficit, including information about the lesion topology increased prediction accuracy. A subset of anatomic regions within the ischemic lesion had particular impact on the prediction of long-term outcomes. Prediction accuracy depended on the degree of functional impairment. CONCLUSIONS: For the first time, we developed and validated a robust tool for the prediction of functional outcomes after experimental stroke in mice using a large and genetically heterogeneous cohort. These results are discussed in light of study design and imaging limitations. In the future, using outcome prediction can improve the design of preclinical studies and guide intervention decisions.

Preregistration of exploratory research: Learning from the golden age of discovery.

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 results, undisclosed analytic flexibility, as well as publication bias. Preregistration works well when a clear hypothesis, primary outcome, and mode of analysis can be formulated. But is it also applicable and useful in discovery research, which develops theories and hypotheses, measurement techniques, and generates evidence that justifies further research? I will argue that only slight modifications are needed to harness the potential of preregistration and make exploratory research more trustworthy and useful.

Improving the trustworthiness, usefulness, and ethics of biomedical research through an innovative and comprehensive institutional initiative.

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 role of institutions. The Berlin Institute of Health founded QUEST to increase the likelihood that research conducted at this large academic medical center would be trustworthy, useful for scientists and society, and ethical. QUEST researchers perform "science of science" studies to understand problems with standard practices and develop targeted solutions. The staff work with institutional leadership and local scientists to incentivize and support responsible practices in research, funding, and hiring. Some activities described in this paper focus on the institution, whereas others may benefit the national and international scientific community. Our experience, approaches, and recommendations will be informative for faculty leadership, administrators, and researchers interested in improving scientific practice.

The Hong Kong Principles for assessing researchers: Fostering research integrity.

For knowledge to benefit research and society, it must be trustworthy. Trustworthy research is robust, rigorous, and transparent at all stages of design, execution, and reporting. Assessment of researchers still rarely includes considerations related to trustworthiness, rigor, and transparency. We have developed the Hong Kong Principles (HKPs) as part of the 6th World Conference on Research Integrity with a specific focus on the need to drive research improvement through ensuring that researchers are explicitly recognized and rewarded for behaviors that strengthen research integrity. We present five principles: responsible research practices; transparent reporting; open science (open research); valuing a diversity of types of research; and recognizing all contributions to research and scholarly activity. For each principle, we provide a rationale for its inclusion and provide examples where these principles are already being adopted.