The urgent need to understand and control COVID-19, and to effectively treat people with the disease, has mobilized global scientific and medical communities like nothing in human history. It has also ushered in a new era in medical publishing. Notably, the desire to share results rapidly, widely and openly has led to an explosion of submissions to the preprint server medRxiv.
But even as the pandemic has demonstrated the potential for rapid, author-driven publication to democratize access and accelerate research, it has exposed the challenges of this model of scholarly communication. With intense public appetite for information about the virus and pandemic, there has been a real danger that individuals and institutions will act hastily on information about risks, mitigation strategies and treatments before it is adequately scrutinized. Such opportunities and challenges, best illustrated during the pandemic, lie ahead as medicine moves towards the goal of providing evidence-based care to patients no matter where they live. This trajectory also opens up real opportunities for speed, transparency and rich evaluation across peer review in medicine.
We are therefore excited to announce that eLife’s reinvigorated Medicine section will offer a whole new approach to publishing in medicine, including public health and health policy. We will apply our system of editorial oversight by practicing clinicians and clinician-investigators, and rigorous, consultative peer review to produce public reviews of preprints with significant potential to impact clinical practice. Our goal is to transform unrefereed manuscripts posted on medRxiv into refereed preprints that provide readers and potential users with a detailed assessment of the science, comments on its potential impact, and perspectives on its use. In essence, by providing rich and rapid evaluation of preprints, we hope that refereed preprints become a currency of trust in medicine.
We will continue to operate like a traditional journal, providing authors who submit their preprints to us with feedback from the reviewers and editors, and we will select a subset of papers for formal publication in eLife. Our scope is broad, covering all areas of the health sciences ranging from cellular and murine models of disease, to human genetics and genomic sciences, to therapeutic discovery, to all phases of clinical investigation, to population health outcomes, to health policy and clinical decision making.
eLife was launched in 2012 by three funders – Howard Hughes Medical Institute, Wellcome Trust and Max Planck Society, later joined by the Knut and Alice Wallenberg Foundation – who were eager to take a more active role in promoting best practices in scientific and medical publishing. Founding Editor-in-Chief Randy Schekman focused on improving the culture of peer review, pioneering a consultative approach in which reviewers and editors come together to discuss their assessments, reach a collective decision on whether the strengths of the work merit publication in eLife and which, if any, weaknesses need to be addressed before publication. The authors are then provided with a clear and concise decision letter that is free of the conflicting opinions and recommendations often found in reviews.
Since 2019, with one of us (MBE) as Editor-in-Chief, eLife has moved to embrace and encourage the growth of preprints even more strongly in all areas of science and medicine, and has developed a new concept of 'publish, then review' to serve readers and users, as well as authors (Eisen et al., 2020). This new system of creating public reviews of preprints, described briefly above, is the first major product of these efforts. The re-launch of eLife’s Medicine section is the second.
While eLife has traditionally focused on basic science, many of our editors are practicing clinicians who run research groups that cross the proverbial line between basic and clinical research. We have published papers in early translational research, but over the past few years have received many requests to bring our innovations in peer review and preprint review into the full spectrum of research in medicine.
To answer these calls, and to ensure we do so successfully, we have recruited two Deputy Editors in Medicine (DMH and MZ) and a group of Senior Editors that includes accomplished women and men from around the globe. These Senior Editors in turn have the responsibility of overseeing the review process through our Board of Reviewing Editors, which has also been greatly expanded (and will continue to expand) to include clinicians, public health specialists, and basic, translational and clinical researchers spanning a wide range of disciplines. In building the team, we have emphasized not only clinical expertise, scientific excellence and intellectual breadth, but also equity, diversity and inclusion, in order to ensure that we address patient-centered research for everyone.
The result is an editorial board that can truly aim to cover all areas of modern biology and medicine, with the ability to handle any paper in any discipline, especially those that span and knit together work from fields whose practitioners do not traditionally publish in or read the same journals. For example, we are now well equipped to evaluate all aspects of papers whose topics range from behavioral sciences and social determinants of health to clinical genetics, structural biology, drug discovery and early–stage efficacy studies. We are equally equipped to handle papers describing new COVID-19 virus mutations, their coverage by vaccines, and modeling future infections in different population settings.
In keeping with our desire to tackle the most difficult issues in publishing, we have also created a new Ethics Committee – a think tank of ethicists and individuals with long-standing experience in different aspects of science, medicine and publishing – to provide guidance on issues including, but not limited to, publishing, medical and animal ethics, biosecurity and biosafety, environmental justice, competing interests, data availability, and issues surrounding studies with minority populations in the developing world. These issues are of growing importance across both biology and medicine.
Over the past few years we have received many requests to bring our innovations in peer review and preprint review into the full spectrum of research in medicine.
We are also aware that the pipeline for the young physician-scientist is extremely leaky with most medical graduates who enter science being drawn into private medicine, whether or not they obtained a doctoral degree (Williams et al., 2018). We will leverage eLife’s expanded Medicine section to assist the careers of both laboratory-based physician-scientists and physicians whose interests lie in clinical investigation and health services research. In addition, we will encourage the STEM pipeline of women and underrepresented minorities in physician-scientist roles. eLife already has a program to encourage early-career researchers in all fields to become involved in the peer-review process, and we will also test novel processes for the mentorship, sponsorship and professional advancement of junior physician-scientists.
In all, eLife's ambitions in medicine are broader than just becoming a new open-access medical journal. This is a larger effort underscoring a cultural change to emphasize the importance of preprints and reviewing preprints; to focus on transparency, not just on open access but also on open data and open methods; and to encourage responsible behaviors in medical publishing – elements that are necessary for the translation of meaningful scientific investigation to the betterment of human health. Towards this aspiration, eLife’s reinvigorated Medicine section will cherish the support of the physician–scientist community around the globe.
The heterogeneity of white matter damage and symptoms in concussion has been identified as a major obstacle to therapeutic innovation. In contrast, most diffusion MRI (dMRI) studies on concussion have traditionally relied on group-comparison approaches that average out heterogeneity. To leverage, rather than average out, concussion heterogeneity, we combined dMRI and multivariate statistics to characterize multi-tract multi-symptom relationships.
Using cross-sectional data from 306 previously concussed children aged 9–10 from the Adolescent Brain Cognitive Development Study, we built connectomes weighted by classical and emerging diffusion measures. These measures were combined into two informative indices, the first representing microstructural complexity, the second representing axonal density. We deployed pattern-learning algorithms to jointly decompose these connectivity features and 19 symptom measures.
Early multi-tract multi-symptom pairs explained the most covariance and represented broad symptom categories, such as a general problems pair, or a pair representing all cognitive symptoms, and implicated more distributed networks of white matter tracts. Further pairs represented more specific symptom combinations, such as a pair representing attention problems exclusively, and were associated with more localized white matter abnormalities. Symptom representation was not systematically related to tract representation across pairs. Sleep problems were implicated across most pairs, but were related to different connections across these pairs. Expression of multi-tract features was not driven by sociodemographic and injury-related variables, as well as by clinical subgroups defined by the presence of ADHD. Analyses performed on a replication dataset showed consistent results.
Using a double-multivariate approach, we identified clinically-informative, cross-demographic multi-tract multi-symptom relationships. These results suggest that rather than clear one-to-one symptom-connectivity disturbances, concussions may be characterized by subtypes of symptom/connectivity relationships. The symptom/connectivity relationships identified in multi-tract multi-symptom pairs were not apparent in single-tract/single-symptom analyses. Future studies aiming to better understand connectivity/symptom relationships should take into account multi-tract multi-symptom heterogeneity.
Financial support for this work came from a Vanier Canada Graduate Scholarship from the Canadian Institutes of Health Research (G.I.G.), an Ontario Graduate Scholarship (S.S.), a Restracomp Research Fellowship provided by the Hospital for Sick Children (S.S.), an Institutional Research Chair in Neuroinformatics (M.D.), as well as a Natural Sciences and Engineering Research Council CREATE grant (M.D.).
Type 2 diabetes mellitus (T2DM) is known to be associated with neurobiological and cognitive deficits; however, their extent, overlap with aging effects, and the effectiveness of existing treatments in the context of the brain are currently unknown.
We characterized neurocognitive effects independently associated with T2DM and age in a large cohort of human subjects from the UK Biobank with cross-sectional neuroimaging and cognitive data. We then proceeded to evaluate the extent of overlap between the effects related to T2DM and age by applying correlation measures to the separately characterized neurocognitive changes. Our findings were complemented by meta-analyses of published reports with cognitive or neuroimaging measures for T2DM and healthy controls (HCs). We also evaluated in a cohort of T2DM-diagnosed individuals using UK Biobank how disease chronicity and metformin treatment interact with the identified neurocognitive effects.
The UK Biobank dataset included cognitive and neuroimaging data (N = 20,314), including 1012 T2DM and 19,302 HCs, aged between 50 and 80 years. Duration of T2DM ranged from 0 to 31 years (mean 8.5 ± 6.1 years); 498 were treated with metformin alone, while 352 were unmedicated. Our meta-analysis evaluated 34 cognitive studies (N = 22,231) and 60 neuroimaging studies: 30 of T2DM (N = 866) and 30 of aging (N = 1088). Compared to age, sex, education, and hypertension-matched HC, T2DM was associated with marked cognitive deficits, particularly in executive functioning and processing speed. Likewise, we found that the diagnosis of T2DM was significantly associated with gray matter atrophy, primarily within the ventral striatum, cerebellum, and putamen, with reorganization of brain activity (decreased in the caudate and premotor cortex and increased in the subgenual area, orbitofrontal cortex, brainstem, and posterior cingulate cortex). The structural and functional changes associated with T2DM show marked overlap with the effects correlating with age but appear earlier, with disease duration linked to more severe neurodegeneration. Metformin treatment status was not associated with improved neurocognitive outcomes.
The neurocognitive impact of T2DM suggests marked acceleration of normal brain aging. T2DM gray matter atrophy occurred approximately 26% ± 14% faster than seen with normal aging; disease duration was associated with increased neurodegeneration. Mechanistically, our results suggest a neurometabolic component to brain aging. Clinically, neuroimaging-based biomarkers may provide a valuable adjunctive measure of T2DM progression and treatment efficacy based on neurological effects.
The research described in this article was funded by the W. M. Keck Foundation (to LRMP), the White House Brain Research Through Advancing Innovative Technologies (BRAIN) Initiative (NSFNCS-FR 1926781 to LRMP), and the Baszucki Brain Research Fund (to LRMP). None of the funding sources played any role in the design of the experiments, data collection, analysis, interpretation of the results, the decision to publish, or any aspect relevant to the study. DJW reports serving on data monitoring committees for Novo Nordisk. None of the authors received funding or in-kind support from pharmaceutical and/or other companies to write this article.