Discovery in clinical and translational medicine.

With the rapid development of biotechnologies and deep improvement of knowledge, "Discovery" is the initial period and source of innovation of clinical and translational medicine. The international journal of Clinical and Translational Discovery serves to highlight unknown or unclear aspects of clinical and translational medicine-associated knowledge, technologies, mechanisms, and therapies (https://onlinelibrary.wiley.com/journal/27680622). The Discovery aims to define the interaction between genes, proteins, and cells, and explore molecular mechanisms of intercommunication and inter-regulation. More discoveries of technologies and equipment are expected to improve method sensitivity, specificity, stability, analysis, and clinical significance. The first priority of Clinical and Translational Discovery is to turn gene-, protein-, drug-, cell-, and interaction-based discoveries into health advancements. Clinical and Translational Discovery highly focuses on the discoveries of biological therapies and precision medicine-based therapy elicited from computational chemistry, DNA libraries, target-dependent small molecular drugs, high-throughput screening, vaccination, immune therapy, cell implantations, gene editing, and RNA- or protein-based inhibitors. Thus, Clinical and Translational Discovery sincerely welcome you to join and share the rapid development and future successes to come.

How to translate the knowledge of COVID-19 into the prevention of Omicron variants.

Omicron variants are part of the "Coronavirus disease 2019 [COVID-19] Variants of Concerns" and has the potential to spread around the world rapidly and can harm human life. We can anticipate that the endemic state of COVID-19 will be characterized by the development of new strains with surges that will predominate in unvaccinated and immunodeficient populations. Thus, there will be an important role in promoting vaccinations, boosters and accessible testing to prevent disease transmission and to rapidly detect surges. There is an urgent need to explore the virology and biology of Omicron variants, define clinical phenomes and therapies, monitor dynamics of genetic changes, and translate the knowledge of COVID-19 into new variants. Clinical and translational medicine will be impactful in addressing these challenges by providing new insights for understanding and predicting new variants-associated transmissibility, disease severity, immune escape, diagnostic or therapeutic failure.

Inferring a causal relationship between ceramide levels and COVID-19 respiratory distress.

A causal relationship between plasma ceramide concentration and respiratory distress symptoms in COVID-19 patients is inferred. In this study, plasma samples of 52 individuals infected with COVID-19 were utilized in a lipidomic analysis. Lipids belonging to the ceramide class exhibited a 400-fold increase in total plasma concentration in infected patients. Further analysis led to the demonstration of concentration dependency for severe COVID-19 respiratory symptoms in a subclass of ceramides. The subclasses Cer(d18:0/24:1), Cer(d18:1/24:1), and Cer(d18:1/22:0) were shown to be increased by 48-, 40-, and 33-fold, respectively, in infected plasma samples and to 116-, 91- and 50-fold, respectively, in plasma samples with respiratory distress. Hence, monitoring plasma ceramide concentration, can be a valuable tool for measuring effects of therapies on COVID-19 respiratory distress patients.

Translational Potential of Metabolomics on Animal Models of Inflammatory Bowel Disease-A Systematic Critical Review.

In the development of inflammatory bowel disease (IBD), the gut microbiota has been established as a key factor. Recently, metabolomics has become important for understanding the functional relevance of gut microbial changes in disease. Animal models for IBD enable the study of factors involved in disease development. However, results from animal studies may not represent the human situation. The aim of this study was to investigate whether results from metabolomics studies on animal models for IBD were similar to those from studies on IBD patients. Medline and Embase were searched for relevant studies up to May 2017. The Covidence systematic review software was used for study screening, and quality assessment was conducted for all included studies. Data showed a convergence of ~17% for metabolites differentiated between IBD and controls in human and animal studies with amino acids being the most differentiated metabolite subclass. The acute dextran sodium sulfate model appeared as a good model for analysis of systemic metabolites in IBD, but analytical platform, age, and biological sample type did not show clear correlations with any significant metabolites. In conclusion, this systematic review highlights the variation in metabolomics results, and emphasizes the importance of expanding the applied detection methods to ensure greater coverage and convergence between the various different patient phenotypes and animal models of inflammatory bowel disease.

Interrogating the World Bank's role in global health knowledge production, governance, and finance.

BACKGROUND: In the nearly half century since it began lending for population projects, the World Bank has become one of the largest financiers of global health projects and programs, a powerful voice in shaping health agendas in global governance spaces, and a mass producer of evidentiary knowledge for its preferred global health interventions. How can social scientists interrogate the role of the World Bank in shaping 'global health' in the current era? MAIN BODY: As a group of historians, social scientists, and public health officials with experience studying the effects of the institution's investment in health, we identify three challenges to this research. First, a future research agenda requires recognizing that the Bank is not a monolith, but rather has distinct inter-organizational groups that have shaped investment and discourse in complicated, and sometimes contradictory, ways. Second, we must consider how its influence on health policy and investment has changed significantly over time. Third, we must analyze its modes of engagement with other institutions within the global health landscape, and with the private sector. The unique relationships between Bank entities and countries that shape health policy, and the Bank's position as a center of research, permit it to have a formative influence on health economics as applied to international development. Addressing these challenges, we propose a future research agenda for the Bank's influence on global health through three overlapping objects of and domains for study: knowledge-based (shaping health policy knowledge), governance-based (shaping health governance), and finance-based (shaping health financing). We provide a review of case studies in each of these categories to inform this research agenda. CONCLUSIONS: As the COVID-19 pandemic continues to rage, and as state and non-state actors work to build more inclusive and robust health systems around the world, it is more important than ever to consider how to best document and analyze the impacts of Bank's financial and technical investments in the Global South.

Pharmacist dispensing of the abortion pill in Canada: Diffusion of Innovation meets integrated knowledge translation.

BACKGROUND: Since Canadian drug regulatory approval of mifepristone for medical abortion in 2015 and its market availability in January 2017, the role of pharmacists in abortion provision has changed rapidly. We sought to identify the factors that influenced the initiation and provision of medical abortion from the perspectives of Canadian pharmacists, bridging two frameworks - Diffusion of Innovation in Health Service Organizations and integrated knowledge translation. METHODS: We conducted one-on-one semi-structured interviews with pharmacists residing in Canada who intended to stock and dispense mifepristone within the first year of availability. Our data collection, analysis, and interpretation were guided by reflexive thematic analysis and supported by an integrated knowledge translation partnership with pharmacy stakeholders. RESULTS: We completed interviews with 24 participants from across Canada: 33% had stocked and 21% had dispensed mifepristone. We found that pharmacists were willing and able to integrate medical abortion care into their practice and that those who had initiated practice were satisfied with their dispensing experience. Our analysis indicated that several key Diffusion of Innovation constructs impacted the uptake of mifepristone, including: innovation (relative advantage, complexity and compatibility, technical support), system readiness (innovation-system fit, dedicated time, resources), diffusion and dissemination (expert opinion, boundary spanners, champions, social networks, peer opinions), implementation (external collaboration), and linkage. Participants' experiences suggest that integrated knowledge translation facilitated evidence-based changes to mifepristone dispensing restrictions, and communication of those changes to front line pharmacists. CONCLUSIONS: We illustrate how Diffusion of Innovation and integrated knowledge translation may work together as complimentary frameworks for implementation science research. Unlike in the USA, UK, and other highly regulated settings globally, pharmacists in Canada are permitted to dispense mifepristone for medical abortion. We contribute to literature that shows that mifepristone dispensed outside of hospitals, clinics, and medical offices is safe and acceptable to both patients and prescribers. This finding is of particular importance to the current COVID-19 pandemic response and calls for continued and equitable access to abortion care in primary practice.

Uprooting race-based assumptions in biomedical journal articles.

Coronavirus disease 2019 (COVID-19) has exacerbated the structural inequities in healthcare and the challenges of translating research into public discourse. This article highlights key antiracist considerations, presents previously noted core challenges, and provides recommendations for writing and reporting. Importantly, this article contributes to combating racialized science in the biomedical community.

Adapting Interventions for Occupational Therapy Practice: Application of the FRAME Coding Structure.

Occupational therapy practitioners often adapt evidence-based interventions for implementation into practice, yet these adaptations are seldom captured systematically. The purpose of this study was to apply the Framework for Reporting Adaptations and Modifications-Expanded (FRAME) to describe adaptations to one intervention modified for teletherapy in the wake of COVID-19. An embedded multiple case study design was used to track adaptations made to a vestibular and bilateral integration (VBI) protocol-traditionally delivered in-person-that was implemented via teletherapy in a pediatric outpatient clinic. The "Modification and Adaptation Checklist" was used to track protocol adaptations. Data were examined through descriptive analyses; 63 adaptations were made to the VBI protocol. The most frequently noted adaptation was "Repeating protocol activities," whereas the "Integrating another treatment approach with the VBI protocol" was the least common adaptation. The FRAME may be useful for tracking adaptations and evaluating how adaptations influence intervention effectiveness.

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.

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.

Conducting Translational Gastrointestinal Research in the Era of COVID-19.

Spread of the novel coronavirus SARS-CoV-2 has resulted in a global pandemic that is affecting the health and economy of all World Health Organization [WHO] regions. Clinical and translational research activities have been affected drastically by this global catastrophe. In this document we provide a suggested roadmap for resuming gastrointestinal translational research activities, emphasising physical distancing and use of personal protective equipment. We discuss modes of virus transmission in enclosed environments [including clinical workplaces and laboratories] and potential risks of exposure in the endoscopy environment for research staff. The proposed guidelines should be considered in conjunction with local institutional and government guidelines so that translational research can be resumed as safely as possible.

A Quantitative and Radiomics approach to monitoring ARDS in COVID-19 patients based on chest CT: a retrospective cohort study.

Rationale: Acute respiratory distress syndrome (ARDS) is one of the major reasons for ventilation and intubation management of COVID-19 patients but there is no noninvasive imaging monitoring protocol for ARDS. In this study, we aimed to develop a noninvasive ARDS monitoring protocol based on traditional quantitative and radiomics approaches from chest CT. Methods: Patients diagnosed with COVID-19 from Jan 20, 2020 to Mar 31, 2020 were enrolled in this study. Quantitative and radiomics data were extracted from automatically segmented regions of interest (ROIs) of infection regions in the lungs. ARDS existence was measured by Pa02/Fi02 <300 in artery blood samples. Three different models were constructed by using the traditional quantitative imaging metrics, radiomics features and their combinations, respectively. Receiver operating characteristic (ROC) curve analysis was used to assess the effectiveness of the models. Decision curve analysis (DCA) was used to test the clinical value of the proposed model. Results: The proposed models were constructed using 352 CT images from 86 patients. The median age was 49, and the male proportion was 61.9%. The training dataset and the validation dataset were generated by randomly sampling the patients with a 2:1 ratio. Chi-squared test showed that there was no significant difference in baseline of the enrolled patients between the training and validation datasets. The areas under the ROC curve (AUCs) of the traditional quantitative model, radiomics model and combined model in the validation dataset was 0.91, 0.91 and 0.94, respectively. Accordingly, the sensitivities were 0.55, 0.82 and 0.58, while the specificities were 0.97, 0.86 and 0.98. The DCA curve showed that when threshold probability for a doctor or patients is within a range of 0 to 0.83, the combined model adds more net benefit than "treat all" or "treat none" strategies, while the traditional quantitative model and radiomics model could add benefit in all threshold probability. Conclusions: It is feasible to monitor ARDS from CT images using radiomics or traditional quantitative analysis in COVID-19. The radiomics model seems to be the most practical one for possible clinical use. Multi-center validation with a larger number of samples is recommended in the future.