Reimagining the peer-review system for translational health science journals.

Retractions of coronavirus disease 2019 (COVID-19) papers in high impact journals, such as The Lancet and the New England Journal of Medicine, have been panned as major scientific fraud in public media. The initial reaction to this news was to seek out scapegoats and blame individual authors, peer-reviewers, editors, and journals for wrong doing. This paper suggests that scapegoating a few individuals for faulty science is a myopic approach to the more profound problem with peer-review. Peer-review in its current limited form cannot be expected to adequately address the scope and complexity of large interdisciplinary science research collaboration, which is central in translational research. In addition, empirical studies on the effectiveness of traditional peer-review reveal its very real potential for bias and groupthink; as such, expectations regarding the capacity and effectiveness of the current peer review process are unrealistic. This paper proposes a new vision of peer-review in translational science that, on the one hand, would allow for early release of a manuscript to ensure expediency, whereas also creating a forum or a collective of various experts to actively comment, scrutinize, and even build on the research under review. The aim would be to not only generate open discussion and oversight respecting the quality and limitations of the research, but also to assess the extent and the means for that knowledge to translate into social benefit.

A Cytometrist's Guide to Coordinating and Performing Effective COVID-19 Research.

Cytometry is playing a crucial role in addressing the COVID-19 pandemic. In this commentary-written by a variety of stakeholders in the cytometry, immunology, and infectious disease communities-we review cytometry's role in the COVID-19 response and discuss workflow issues critical to planning and executing effective research in this emerging field. We discuss sample procurement and processing, biosafety, technology options, data sharing, and the translation of research findings into clinical environments. © 2020 International Society for Advancement of Cytometry.

Health disparities: Intracellular consequences of social determinants of health.

Health disparities exist dependent on socioeconomic status, living conditions, race/ethnicity, diet, and exposures to environmental pollutants. Herein, the various exposures contributing to a person's exposome are collectively considered social determinants of health (SDOH), and the SDOH-exposome impacts health more than health care. This review discusses the extent of evidence of the physiologic consequences of these exposures at the intracellular level. We consider how the SDOH-exposome, which captures how individuals live, work and age, induces cell processes that modulate a conceptual "redox rheostat." Like an electrical resistor, the SDOH-exposome, along with genetic predisposition and age, regulate reductive and oxidative (redox) stress circuits and thereby stimulate inflammation. Regardless of the source of the SDOH-exposome that induces chronic inflammation and immunosenescence, the outcome influences cardiometabolic diseases, cancers, infections, sepsis, neurodegeneration and autoimmune diseases. The endogenous redox rheostat is connected with regulatory molecules such as NAD+/NADH and SIRT1 that drive redox pathways. In addition to these intracellular and mitochondrial processes, we discuss how the SDOH-exposome can influence the balance between metabolism and regulation of immune responsiveness involving the two main molecular drivers of inflammation, the NLRP3 inflammasome and NF-κB induction. Mitochondrial and inflammasome activities play key roles in mediating defenses against pathogens and controlling inflammation before diverse cell death pathways are induced. Specifically, pyroptosis, cell death by inflammation, is intimately associated with common disease outcomes that are influenced by the SDOH-exposome. Redox influences on immunometabolism including protein cysteines and ion fluxes are discussed regarding health outcomes. In summary, this review presents a translational research perspective, with evidence from in vitro and in vivo models as well as clinical and epidemiological studies, to outline the intracellular consequences of the SDOH-exposome that drive health disparities in patients and populations. The relevance of this conceptual and theoretical model considering the SARS-CoV-2 pandemic are highlighted. Finally, the case of asthma is presented as a chronic condition that is modified by adverse SDOH exposures and is manifested through the dysregulation of immune cell redox regulatory processes we highlight in this review.

Clinical approval of nanotechnology-based SARS-CoV-2 mRNA vaccines: impact on translational nanomedicine.

One year after the first human case of SARS-CoV-2, two nanomedicine-based mRNA vaccines have been fast-tracked, developed, and have received emergency use authorization throughout the globe with more vaccine approvals on the heels of these first two. Several SARS-CoV-2 vaccine compositions use nanotechnology-enabled formulations. A silver lining of the COVID-19 pandemic is that the fast-tracked vaccine development for SARS-CoV-2 has advanced the clinical translation pathway for nanomedicine drug delivery systems. The laboratory science of lipid-based nanoparticles was ready and rose to the clinical challenge of rapid vaccine development. The successful development and fast tracking of SARS-CoV-2 nanomedicine vaccines has exciting implications for the future of nanotechnology-enabled drug and gene delivery; it demonstrates that nanomedicine is necessary and critical to the successful delivery of advanced molecular therapeutics such as nucleic acids, it is establishing the precedent of safety and the population effect of phase four clinical trials, and it is laying the foundation for the clinical translation of more complex, non-lipid nanomedicines. The development, fast-tracking, and approval of SARS-CoV-2 nanotechnology-based vaccines has transformed the seemingly daunting challenges for clinically translating nanomedicines into measurable hurdles that can be overcome. Due to the tremendous scientific achievements that have occurred in response to the COVID-19 pandemic, years, perhaps even decades, have been streamlined for certain translational nanomedicines.

Strategic vision for improving human health at The Forefront of Genomics.

Starting with the launch of the Human Genome Project three decades ago, and continuing after its completion in 2003, genomics has progressively come to have a central and catalytic role in basic and translational research. In addition, studies increasingly demonstrate how genomic information can be effectively used in clinical care. In the future, the anticipated advances in technology development, biological insights, and clinical applications (among others) will lead to more widespread integration of genomics into almost all areas of biomedical research, the adoption of genomics into mainstream medical and public-health practices, and an increasing relevance of genomics for everyday life. On behalf of the research community, the National Human Genome Research Institute recently completed a multi-year process of strategic engagement to identify future research priorities and opportunities in human genomics, with an emphasis on health applications. Here we describe the highest-priority elements envisioned for the cutting-edge of human genomics going forward-that is, at 'The Forefront of Genomics'.

Evidence-based medicine and COVID-19: what to believe and when to change.

The COVID-19 pandemic has led to a surge of information being presented to clinicians regarding this novel and deadly disease. There is a clear urgency to collate, review, appraise and act on this information if we are to do the best for clinicians and patients. However, the speed of the pandemic is a threat to traditional models of knowledge translation and practice change. In this concepts paper, we argue that clinicians need to be agile in their thinking and practice in order to find the right time to change. Adoption of new methods should be based on clinical judgement, the weight of evidence and the balance of probabilities that any new technique, test or treatment might work. The pandemic requires all of us to reach a new level of evidence-based medicine characterised by scepticism, thoughtfulness, responsiveness and clinically agility in practice.

The future is now? Clinical and translational aspects of "Omics" technologies.

Big data has become a central part of medical research, as well as modern life generally. "Omics" technologies include genomics, proteomics, microbiomics and increasingly other omics. These have been driven by rapid advances in laboratory techniques and equipment. Crucially, improved information handling capabilities have allowed concepts such as artificial intelligence and machine learning to enter the research world. The COVID-19 pandemic has shown how quickly information can be generated and analyzed using such approaches, but also showed its limitations. This review will look at how "omics" has begun to be translated into clinical practice. While there appears almost limitless potential in using big data for "precision" or "personalized" medicine, the reality is that this remains largely aspirational. Oncology is the only field of medicine that is widely adopting such technologies, and even in this field uptake is irregular. There are practical and ethical reasons for this lack of translation of increasingly affordable techniques into the clinic. Undoubtedly, there will be increasing use of large data sets from traditional (e.g. tumor samples, patient genomics) and nontraditional (e.g. smartphone) sources. It is perhaps the greatest challenge of the health-care sector over the coming decade to integrate these resources in an effective, practical and ethical way.