OTTM: an automated classification tool for translational drug discovery from omics data.

Omics data from clinical samples are the predominant source of target discovery and drug development. Typically, hundreds or thousands of differentially expressed genes or proteins can be identified from omics data. This scale of possibilities is overwhelming for target discovery and validation using biochemical or cellular experiments. Most of these proteins and genes have no corresponding drugs or even active compounds. Moreover, a proportion of them may have been previously reported as being relevant to the disease of interest. To facilitate translational drug discovery from omics data, we have developed a new classification tool named Omics and Text driven Translational Medicine (OTTM). This tool can markedly narrow the range of proteins or genes that merit further validation via drug availability assessment and literature mining. For the 4489 candidate proteins identified in our previous proteomics study, OTTM recommended 40 FDA-approved or clinical trial drugs. Of these, 15 are available commercially and were tested on hepatocellular carcinoma Hep-G2 cells. Two drugs-tafenoquine succinate (an FDA-approved antimalarial drug targeting CYC1) and branaplam (a Phase 3 clinical drug targeting SMN1 for the treatment of spinal muscular atrophy)-showed potent inhibitory activity against Hep-G2 cell viability, suggesting that CYC1 and SMN1 may be potential therapeutic target proteins for hepatocellular carcinoma. In summary, OTTM is an efficient classification tool that can accelerate the discovery of effective drugs and targets using thousands of candidate proteins identified from omics data. The online and local versions of OTTM are available at http://otter-simm.com/ottm.html.

Seven Strategies to Integrate Equity within Translational Research in Neurology.

The rapidly accelerating translation of biomedical advances is leading to revolutionary therapies that are often inaccessible to historically marginalized populations. We identified and synthesized recent guidelines and statements to propose 7 strategies to integrate equity within translational research in neurology: (1) learn history; (2) learn about upstream forces; (3) diversify and liberate; (4) change narratives and adopt best communication practices; (5) study social drivers of health and lived experiences; (6) leverage health technologies; and (7) build, sustain, and lead culturally humble teams. We propose that equity should be a major goal of translational research, equally important as safety and efficacy. ANN NEUROL 2024;95:432-441.

Epigenetic Regulations in Autoimmunity and Cancer: from Basic Science to Translational Medicine.

Epigenetics, as a discipline that aims to explain the differential expression of phenotypes arising from the same gene sequence and the heritability of epigenetic expression, has received much attention in medicine. Epigenetic mechanisms are constantly being discovered, including DNA methylation, histone modifications, noncoding RNAs and m6A. The immune system mainly achieves an immune response through the differentiation and functional expression of immune cells, in which epigenetic modification will have an important impact. Because of immune infiltration in the tumor microenvironment, immunotherapy has become a research hotspot in tumor therapy. Epigenetics plays an important role in autoimmune diseases and cancers through immunology. An increasing number of drugs targeting epigenetic mechanisms, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, and drug combinations, are being evaluated in clinical trials for the treatment of various cancers (including leukemia and osteosarcoma) and autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis). This review summarizes the progress of epigenetic regulation for cancers and autoimmune diseases to date, shedding light on potential therapeutic strategies.

Translational medicine for acute lung injury.

Acute lung injury (ALI) is a complex disease with numerous causes. This review begins with a discussion of disease development from direct or indirect pulmonary insults, as well as varied pathogenesis. The heterogeneous nature of ALI is then elaborated upon, including its epidemiology, clinical manifestations, potential biomarkers, and genetic contributions. Although no medication is currently approved for this devastating illness, supportive care and pharmacological intervention for ALI treatment are summarized, followed by an assessment of the pathophysiological gap between human ALI and animal models. Lastly, current research progress on advanced nanomedicines for ALI therapeutics in preclinical and clinical settings is reviewed, demonstrating new opportunities towards developing an effective treatment for ALI.

Participatory translational science of neurodivergence: model for attention-deficit/hyperactivity disorder and autism research.

BACKGROUND: There are increasing calls for neurodivergent peoples' involvement in research into neurodevelopmental conditions. So far, however, this has tended to be achieved only through membership of external patient and public involvement (PPI) panels. The Regulating Emotions - Strengthening Adolescent Resilience (RE-STAR) programme is building a new participatory model of translational research that places young people with diagnoses of attention-deficit hyperactivity disorder (ADHD) and autism at the heart of the research team so that they can contribute to shaping and delivering its research plan. AIMS: To outline the principles on which the RE-STAR participatory model is based and describe its practical implementation and benefits, especially concerning the central role of members of the Youth Researcher Panel (Y-RPers). METHOD: The model presented is a culmination of a 24-month process during which Y-RPers moved from advisors to co-researchers integrated within RE-STAR. It is shaped by the principles of co-intentionality. The account here was agreed following multiple iterative cycles of collaborative discussion between academic researchers, Y-RPers and other stakeholders. RESULTS: Based on our collective reflections we offer general guidance on how to effectively integrate young people with diagnoses of ADHD and/or autism into the core of the translational research process. We also describe the specific theoretical, methodological and analytical benefits of Y-RPer involvement in RE-STAR. CONCLUSIONS: Although in its infancy, RE-STAR has demonstrated the model's potential to enrich translational science in a way that can change our understanding of the relationship between autism, ADHD and mental health. When appropriately adapted we believe the model can be applied to other types of neurodivergence and/or mental health conditions.

Overcoming Common Anxieties in Knowledge Translation: Advice for Scholarly Issue Advocates.

Policy Points Faced with urgent threats to human health and well-being such as climate change, calls among the academic community are getting louder to contribute more effectively to the implementation of the evidence generated by our research into public policy. As interest in knowledge translation (KT) surges, so have a number of anxieties about the field's shortcomings. Our paper is motivated by a call in the literature to render useful advice for those beginning in KT on how to advance impact at a policy level. By integrating knowledge from fields such as political science, moral psychology, and marketing, we suggest that thinking and acting like marketers, lobbyists, movements, and political scientists would help us advance on the quest to bridge the chasm between evidence and policy.

What predicts citation counts and translational impact in headache research? A machine learning analysis.

BACKGROUND: We aimed to develop the first machine learning models to predict citation counts and the translational impact, defined as inclusion in guidelines or policy documents, of headache research, and assess which factors are most predictive. METHODS: Bibliometric data and the titles, abstracts, and keywords from 8600 publications in three headache-oriented journals from their inception to 31 December 2017 were used. A series of machine learning models were implemented to predict three classes of 5-year citation count intervals (0-5, 6-14 and, >14 citations); and the translational impact of a publication. Models were evaluated out-of-sample with area under the receiver operating characteristics curve (AUC). RESULTS: The top performing gradient boosting model predicted correct citation count class with an out-of-sample AUC of 0.81. Bibliometric data such as page count, number of references, first and last author citation counts and h-index were among the most important predictors. Prediction of translational impact worked optimally when including both bibliometric data and information from the title, abstract and keywords, reaching an out-of-sample AUC of 0.71 for the top performing random forest model. CONCLUSION: Citation counts are best predicted by bibliometric data, while models incorporating both bibliometric data and publication content identifies the translational impact of headache research.

Physical and occupational therapists' perceptions of sustainability of a knowledge translation intervention to improve the use of outcome measures in inpatient rehabilitation: a qualitative study.

PURPOSE: To assess the perceptions, barriers, and facilitators of sustaining the use of outcome measures of physical and occupational therapists following a three-year knowledge translation intervention. METHODS: A phenomenological qualitative study was conducted at an inpatient rehabilitation hospital on 13 clinicians (6 physical therapists and 7 occupational therapists) participating in the knowledge translation intervention. Data collection used semi-structured interviewing during three focus groups to understand the lived experience of clinicians participating in the knowledge translation project. Data were analyzed using the Consolidated Framework for Implementation Research (CFIR) codebook. RESULTS: Two investigators coded twelve CFIR constructs into barriers and facilitators for outcome measure use. Four key themes emerged as determinants for outcome measures use: (1) Organizational support and clinician engagement; (2) the knowledge translation intervention; (3) the outcome measures themselves; and (4) the patients. Clinicians reported using outcome measures for patient education, treatment planning, and goal setting, while they found other outcome measures lacked functional significance. Facilitators included organizational support, access to knowledge, ongoing training, and clinician engagement. Ongoing barriers included the need for more training and the need to select different tests. CONCLUSIONS: This study found proper selection of outcomes measures is important and attributed the sustainability of the knowledge translation intervention to organizational support, clinician engagement and ongoing training. The clinicians wanted continued training to overcome new barriers. Barriers identified in this study were unique to the typical barriers identified for outcome measure use. Ongoing barrier assessments are needed for continued refinement of knowledge translation interventions to enhance sustainability.

Getting a "SMART START" to gestational diabetes mellitus education: a mixed-methods pilot evaluation of a knowledge translation tool in primary care.

BACKGROUND: South Asian people living in Canada face higher rates of gestational diabetes mellitus (GDM) compared to national trends. The objective of this study was to design and pilot test a knowledge translation (KT) tool to support GDM prevention counselling in primary care. METHODS: This study is a mixed-methods pilot evaluation of the "SMART START" KT tool involving 2 family physicians in separate practices and 20 pregnant South Asians in Ontario, Canada. We conducted the quantitative and qualitative components in parallel, developing a joint display to illustrate the converging and diverging elements. RESULTS: Between January and July 2020, 20 South Asian pregnant people were enrolled in this study. A high level of acceptability was received from patients and practitioners for timing, content, format, language, and interest in the interventions delivered. Quantitative findings revealed gaps in patient knowledge and behaviour in the following areas: GDM risk factors, the impact of GDM on the unborn baby, weight gain recommendations, diet, physical activity practices, and tracking of weight gain. From the qualitative component, we found that physicians valued and were keen to engage in GDM prevention counselling. Patients also expressed personal perceptions of healthy active living during pregnancy, experiences, and preferences with gathering and searching for information, and key preventative behaviours. CONCLUSIONS: Building on this knowledge can contribute to the design and implementation of other research opportunities or test new hypotheses as they relate to GDM prevention among South Asian communities.

An integrated knowledge translation (iKT) approach to advancing community-based depression care in Vietnam: lessons from an ongoing research-policy collaboration.

BACKGROUND: Evidence-based mental health policies are key to supporting the expansion of community-based mental health care and are increasingly being developed in low and middle-income countries (LMICs). Despite this, research on the process of mental health policy development in LMICs is limited. Engagement between researchers and policy makers via an integrated Knowledge Translation (iKT) approach can help to facilitate the process of evidence-based policy making. This paper provides a descriptive case study of a decade-long policy and research collaboration between partners in Vietnam, Canada and Australia to advance mental health policy for community-based depression care in Vietnam. METHODS: This descriptive case study draws on qualitative data including team meeting minutes, a focus group discussion with research team leaders, and key informant interviews with two Vietnamese policy makers. Our analysis draws on Murphy et al.'s (2021) findings and recommendations related to stakeholder engagement in global mental health research. RESULTS: Consistent with Murphy et al.'s findings, facilitating factors across three thematic categories were identified. Related to 'the importance of understanding context', engagement between researchers and policy partners from the formative research stage provided a foundation for engagement that aligned with local priorities. The COVID-19 pandemic acted as a catalyst to further advance the prioritization of mental heath by the Government of Vietnam. 'The nature of engagement' is also important, with findings demonstrating that long-term policy engagement was facilitated by continuous funding mechanisms that have enabled trust-building and allowed the research team to respond to local priorities over time. 'Communication and dissemination' are also crucial, with the research team supporting mental health awareness-raising among policy makers and the community, including via capacity building initiatives. CONCLUSIONS: This case study identifies factors influencing policy engagement for mental health system strengthening in an LMIC setting. Sustained engagement with policy leaders helps to ensure alignment with local priorities, thus facilitating uptake and scale-up. Funding agencies can play a crucial role in supporting mental health system development through longer term funding mechanisms. Increased research related to the policy engagement process in global mental health will further support policy development and improvement in mental health care in LMICs.

The impact of a regionally based translational cancer research collaborative in Australia using the FAIT methodology.

BACKGROUND: Translating research, achieving impact, and assessing impact are important aspirations for all research collaboratives but can prove challenging. The Hunter Cancer Research Alliance (HCRA) was funded from 2014 to 2021 to enhance capacity and productivity in cancer research in a regional centre in Australia. This study aimed to assess the impact and benefit of the HCRA to help inform future research investments of this type. METHOD: The Framework to Assess the Impact from Translational health research (FAIT) was selected as the preferred methodology. FAIT incorporates three validated methodologies for assessing impact: 1) Modified Payback; 2) Economic Analysis; and 3) Narrative overview and case studies. All three FAIT methods are underpinned by a Program Logic Model. Data were collected from HCRA and the University of Newcastle administrative records, directly from HCRA members, and website searches. RESULTS: In addition to advancing knowledge and providing capacity building support to members via grants, fellowships, scholarships, training, events and targeted translation support, key impacts of HCRA-member research teams included: (i) the establishment of a regional biobank that has distributed over 13,600 samples and became largely self-sustaining; (ii) conservatively leveraging $43.8 M (s.a.$20.5 M - $160.5 M) in funding and support from the initial $9.7 M investment; (iii) contributing to clinical practice guidelines and securing a patent for identification of stem cells for endometrial cell regeneration; (iv) shifting the treatment paradigm for all tumour types that rely on nerve cell innervation, (v) development and implementation of the world's first real-time patient treatment verification system (Watchdog); (vi) inventing the effective 'EAT' psychological intervention to improve nutrition and outcomes in people experiencing radiotherapy for head and neck cancer; (vi) developing effective interventions to reduce smoking rates among priority groups, currently being rolled out to disadvantaged populations in NSW; and (vii) establishing a Consumer Advisory Panel and Consumer Engagement Committee to increase consumer involvement in research. CONCLUSION: Using FAIT methodology, we have demonstrated the significant impact and downstream benefits that can be achieved by the provision of infrastructure-type funding to regional and rural research collaboratives to help address inequities in research activity and health outcomes and demonstrates a positive return on investment.

National strategies for knowledge translation in health policy-making: A scoping review of grey literature.

BACKGROUND AND OBJECTIVES: Without strategic actions in its support, the translation of scientific research evidence into health policy is often absent or delayed. This review systematically maps and assesses national-level strategic documents in the field of knowledge translation (KT) for health policy, and develops a practical template that can support Evidence-informed Policy Network (EVIPNet) Europe countries in producing national strategies for evidence-informed policy-making. METHODS: Websites of organizations with strategic responsibilities in KT were electronically searched, on the basis of pre-defined criteria, in July-August 2017, and an updated search was carried out in April-June 2021. We included national strategies or elements of national strategies that dealt with KT activities, as well as similar strategies of individual institutions with a national policy focus. Two reviewers screened the strategies for inclusion. Data were analysed using qualitative content analysis. RESULTS: A total of 65 unique documents were identified, of which 17 were eligible and analysed for their structure and content. Of the 17, 1 document was a national health KT action plan and 6 documents were institution-level KT strategies. The remaining 10 strategies, which were also included were 2 national health strategies, 5 national health research strategies and 3 national KT strategies (not specific to the field of health alone). In all, 13 structural elements and 7 major themes of health policy KT strategies were identified from the included documents. CONCLUSION: KT in health policy, as emerged from the national strategies that our mapping identified, is based on the production and accessibility of policy-relevant research, its packaging for policy-making and the activities related to knowledge exchange. KT strategies may play different roles in the complex and context-specific process of policy-making. Our findings show that the main ideas of health-specific evidence-informed policy literature appear in these strategies, but their effectiveness depends on the way stakeholders use them. Specific knowledge-brokering institutions and organizational capacity, advocacy about the use of evidence, and close collaboration and co-decision-making with key stakeholders are essential in furthering the policy uptake of research results.

Putting weight-related conversations into practice: Lessons learned from implementing a knowledge translation casebook in a disability context.

BACKGROUND: Due to reported challenges experienced by healthcare providers (HCPs) when having weight-related conversations with children with disabilities and their families, a knowledge translation (KT) casebook was developed, providing key communication principles with supportive resources. Our aim was to explore how the KT casebook could be implemented into a disability context. Study objectives were to develop and integrate needs-based implementation supports to help foster the uptake of the KT casebook communication principles. METHODS: A sample of nurses, physicians, occupational therapists and physical therapists were recruited from a Canadian paediatric rehabilitation hospital. Informed by the Theoretical Domains Framework, group interviews were conducted with participants to understand barriers to having weight-related conversations in their context. Implementation strategies were developed to deliver the KT casebook content that addressed these identified barriers, which included an education workshop, simulations, printed materials, and a huddle and email strategy. Participant experiences with the implementation supports were captured through workshop evaluations, pre-post surveys and qualitative interviews. Post-implementation interviews were analysed using descriptive content analysis. RESULTS: Ten HCPs implemented the KT casebook principles over 6 months. Participants reported that the workshop provided a clear understanding of the KT casebook content. While HCPs appreciated the breadth of the KT casebook, they found the abbreviated printed educational materials more convenient. Strategies developed to address participants' need for a sense of community and opportunities to learn from each other did not achieve their aim. Increased confidence in integrating the KT casebook principles into practice was not demonstrated, due, in part, to having few opportunities to practice. This was partly because of the increase in competing clinical demands at the onset of the COVID-19 pandemic. CONCLUSIONS: Despite positive feedback on the product itself, changes in the organisational and environmental context limited the success of the implementation plan. Monitoring and adapting implementation processes in response to unanticipated changes is critical to the success of implementation efforts.

Applications of Flow Cytometry in Drug Discovery and Translational Research.

Flow cytometry is a mainstay technique in cell biology research, where it is used for phenotypic analysis of mixed cell populations. Quantitative approaches have unlocked a deeper value of flow cytometry in drug discovery research. As the number of drug modalities and druggable mechanisms increases, there is an increasing drive to identify meaningful biomarkers, evaluate the relationship between pharmacokinetics and pharmacodynamics (PK/PD), and translate these insights into the evaluation of patients enrolled in early clinical trials. In this review, we discuss emerging roles for flow cytometry in the translational setting that supports the transition and evaluation of novel compounds in the clinic.

Spinocerebellar Ataxia Type 3 Pathophysiology-Implications for Translational Research and Clinical Studies.

The spinocerebellar ataxias (SCA) comprise a group of inherited neurodegenerative diseases. Machado-Joseph Disease (MJD) or spinocerebellar ataxia 3 (SCA3) is the most common autosomal dominant form, caused by the expansion of CAG repeats within the ataxin-3 (ATXN3) gene. This mutation results in the expression of an abnormal protein containing long polyglutamine (polyQ) stretches that confers a toxic gain of function and leads to misfolding and aggregation of ATXN3 in neurons. As a result of the neurodegenerative process, SCA3 patients are severely disabled and die prematurely. Several screening approaches, e.g., druggable genome-wide and drug library screenings have been performed, focussing on the reduction in stably overexpressed ATXN3(polyQ) protein and improvement in the resultant toxicity. Transgenic overexpression models of toxic ATXN3, however, missed potential modulators of endogenous ATXN3 regulation. In another approach to identify modifiers of endogenous ATXN3 expression using a CRISPR/Cas9-modified SK-N-SH wild-type cell line with a GFP-T2A-luciferase (LUC) cassette under the control of the endogenous ATXN3 promotor, four statins were identified as potential activators of expression. We here provide an overview of the high throughput screening approaches yet performed to find compounds or genomic modifiers of ATXN3(polyQ) toxicity in different SCA3 model organisms and cell lines to ameliorate and halt SCA3 progression in patients. Furthermore, the putative role of cholesterol in neurodegenerative diseases (NDDs) in general and SCA3 in particular is discussed.

[TRANSLATIONAL MEDICINE IN MALIGNANT HEMATOLOGY].

INTRODUCTION: Translational medicine is a relatively new field, bridging between basic research and the practice of medicine, resulting in improved patient management. The outcomes of science are applied in methods of disease prevention, diagnosis and treatment of various diseases. Malignant hematology is among the fields in which translational medicine has significantly contributed to the current practice.

[DIGITAL PATHOLOGY IN THE LENS OF TRANSLATIONAL MEDICINE - A BRIEF OVERVIEW AND A LOOK INTO THE FUTURE].

INTRODUCTION: Pathology is an integral part of the diagnostic and therapeutic continuum in the world of medicine and it is a significant part of the decision-making processes. The field of pathology leads the world of personalized medicine (also known as precision medicine) and is also important both in clinical practice and in the field of translational medicine. Digital pathology is a developing field that may occupy a significant part of the routine working flow in pathology in the future. Various ideas regarding digitalization of pathology slides have existed for decades, but significant developments have allowed digital pathology to reach the dimensions we see today (and are still growing). This growth can be traced to a little more than 20 years ago, when the first whole slide image (WSI) scanner was introduced, and ever since it continues to be developed and improved significantly.

[TRANSLATIONAL MEDICINE - THE FRONTLINE OF MEDICAL RESEARCH].

INTRODUCTION: In this journal we collected original papers and review papers in translational medicine. Translational medicine is a bio-medical field of research that translates findings discovered in the laboratory to clinical life, for example: diagnostic methods, new cutting-edge medications, high-tech tools, and novel public health policy. This research combines different fields in science using new advanced technologies to improve medical care and wellbeing. The most significant impact was accomplished by the National Institutes of Health (NIH) twenty years ago, when a National Center for Translational Research was built. One of the achievements was the opening of a genetic research center that focused on RNA, circular RNAs and interference RNA. This research discovered the importance of these RNA particles in neurological and metabolic diseases, which were found to be applicable for treatment of these diseases. In this journal, original papers and reviews will express the diversity and the capabilities of this research field that has inspired so many physicians and researchers.

[TRANSLATIONAL MEDICINE IN DERMATOLOGY- FURTHER PROMOTING PSORIASIS RESEARCH].

INTRODUCTION: Psoriasis is a chronic inflammatory skin disorder that affects approximately 2-3% of the population worldwide. Translational medicine, which focuses on treating and analyzing diseases caused by translational factors, is becoming increasingly relevant in the field of psoriasis research. This review aims to display the current literature on the role of translational medicine in the treatment and understanding of psoriasis. We found that translational factors such as protein kinases and cytokines play a key role in the development and progression of psoriasis. Additionally, current treatments for psoriasis, such as biologics, target these translational factors to reduce inflammation and improve skin condition. Furthermore, studies have shown that genetic variations in translational-related genes can also contribute to the development of psoriasis. This highlights the importance of translational medicine in understanding the underlying mechanisms of psoriasis and developing increasingly effective treatments for this debilitating disease.