Restless Legs Syndrome: Known Knowns and Known Unknowns

Although restless legs syndrome (RLS) is a common neurological disorder, it remains poorly understood from both clinical and pathophysiological perspectives. RLS is classified among sleep-related movement disorders, namely, conditions characterized by simple, often stereotyped movements occurring during sleep. However, several clinical, neurophysiological and neuroimaging observations question this view. The aim of the present review is to summarize and query some of the current concepts (known knowns) and to identify open questions (known unknowns) on RLS pathophysiology. Based on several lines of evidence, we propose that RLS should be viewed as a disorder of sensorimotor interaction with a typical circadian pattern of occurrence, possibly arising from neurochemical dysfunction and abnormal excitability in different brain structures.

The Known Unknowns: What Citizen Science Projects in Germany Know about Their Volunteers—And What They Don’t Know

The citizen science landscape in Germany offers an enormous range for participation. More than 170 projects currently present themselves on the national citizen science platform. In 2020, we conducted a survey among 140 projects (participation rate 56%), and they provided information on the organisational framework and characteristics (disciplines, initiators, funding, and project goals), as well as on the academic researchers and the volunteering citizen scientists involved. A surprising result was that the level of knowledge about the volunteers is very low overall. Many projects deliberately do not collect personal data (e.g., on socio-demographic variables, knowledge, and behaviour), partly for data-protection reasons and partly because they are unsure about how to collect it due to a lack of instruments and standards. We aim to illustrate the complexity of this issue and discuss various dilemmas arising between theoretical aspirations and the pragmatic and procedural realities in practice. We conclude with suggestions for developing project-specific strategies to increase diversity and inclusion. We argue that the task of conducting accompanying research on participant diversity cannot be borne by individual projects alone and consider the development and implementation of co-creative and qualitative approaches suitable for this purpose.

Known unknowns and unknown unknowns – An introduction to research on harms

ObjectiveMost systematic reviews of interventions focus on potential benefits. Common methods and assumptions that are appropriate for assessing benefits can be inappropriate for harms. This paper provides a primer on researching harms, particularly in systematic reviews. Study Design and SettingNarrative review to describe challenges with assessing harm.ResultsSystematic reviewers and investigators for primary studies should be familiar with various terminologies used to describe and classify harms across settings and study reports. Some classification systems facilitate grouping harms for analysis, which has both advantages and limitations for causal inference. Published reports of clinical trials include limited information about harms, so systematic reviewers should not depend on these studies and journal articles to reach conclusions about harms. Visualizations might improve communication of multiple dimensions of harms such as severity, relatedness, and timing.ConclusionThe terminology, classification, detection, collection, and reporting of harms create unique challenges that take time, expertise, and resources to navigate in both primary studies and evidence syntheses. Systematic reviewers might reach incorrect conclusions if they focus on evidence about harms found in published reports of randomized trials of a particular health problem. Systematic reviews could be improved through better identification and reporting of harms in primary studies and through better training and uptake of appropriate methods for synthesizing evidence about harms.

SARS-CoV-2 Transgressing LncRNAs Uncovers the Known Unknowns

SARS-CoV-2 harbors many known unknown regions in the form of hypothetical open reading frames (ORFs). While the mechanisms underlying the disease pathogenesis are not clearly understood, molecules such as long noncoding RNAs (lncRNAs) play a key regulatory role in the viral pathogenesis from endocytosis. We asked whether or not the lncRNAs in the host are associated with the viral proteins and argue that lncRNA-mRNA molecules related to viral infection may regulate SARS-CoV-2 pathogenesis. Towards the end of the perspective, we provide challenges and insights into investigating these transgression pathways.