Building prevention research science communication and knowledge translation capacity through multidisciplinary collaboration.

OBJECTIVE: To document the outcomes of a dedicated Science Communication Community of Practice (CoP) for increasing prevention-focused knowledge translation (KT) and evidence uptake. Type of program: Shared priorities and a united vision to communicate the value of prevention research led to the formation of a dedicated Science Communication CoP within an Australian public health prevention-focused research collaboration. Members of the CoP included science communication experts and early- and mid-career researchers (EMCRs) with KT-focused roles. METHODS: The CoP met monthly, with semi-structured meetings led by an experienced science communication professional. A priority of the CoP was to develop resources that could help members and external parties to communicate their findings, especially EMCRs and those working on low-resourced projects. Insights from CoP members were synthesised to document if, and how, the CoP increased communication and KT capacity. RESULTS: CoP members found that participatory dialogue - dialogue that involves sharing perspectives and listening to others in order to develop a shared understanding - helped promote a greater understanding of science communication techniques and led to KT being embedded within projects. The CoP itself resulted in shared narratives and communication outputs that could not have been produced by individual members, primarily due to a lack of dedicated resourcing. Members found that engaging in the CoP increased their use of a range of science communication skills, tactics, and methods (e.g., targeted messaging for policy and practice, use of media and social media, and event management to engage audiences and build trust). LESSONS LEARNT: The CoP helped build a greater working knowledge of science communication among its members, leading to increased KT activities. Within an environment of low resourcing for science communication, bringing researchers together with science communication experts can help promote the communication of synthesised evidence and unified messaging on 'what works for prevention'.

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.

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.

Systematic synthesis of intersectional best practices: knowledge translation for circumpolar indigenous disability.

Numerous theories, models, and frameworks (TMFs) currently exist for knowledge translation (KT), with scholarship that is increasingly inclusive of populations experiencing health inequalities. This study proposes two objectives: 1) exploring a nine-step method for synthesising best practices, acknowledging existing syntheses in the form of tailored-databases and review-style publications; and 2) collating best practices to inform KT that is inclusive to indigenous individuals living with disabilities in circumpolar regions. The resulting synthesis emphasises 10 best practices: explicitly connect the accountability of stakeholders to the wellbeing of the people they serve; recognise entanglement with existing neoliberal systems; assess impacts of KT on indigenous treatment providers; employ personal outreach visits; rectify longstanding delegitimization; avoid assuming the target group to be homogeneous, critically examine inequitable distribution of benefits and risks; consider how emphasis on a KT initiative can distract from historical and systemic inequalities; target inequitable, systemic social and economic forces; consider how KT can also be mobilised to gain power and control; assess what is selected for KT, and how it intersects with power position of external stakeholders and internal champions; and, allow people access-to-knowledge which changes inequitable systems.

Evaluative study of a MOOC on knowledge translation in five French-speaking countries.

Over the past few years, the RENARD research team has observed a sharp increase in the need for knowledge translation (KT) training. Given the high demand, it has been nearly impossible for the team to provide training entirely in person, and so a massive open online course (MOOC) was developed. Its aim is to promote the use and appropriation of the KT process by practitioners, decision-makers, and others in the public sphere. The goal of this study was to evaluate the MOOC by collecting users' opinions, reactions, appropriation, and practice changes. A qualitative research design was used. Data were collected through semi-structured individual interviews (n = 16) with professionals from Canada, France, and three West African countries (Burkina Faso, Mali, and Senegal) who had taken the MOOC. All interviews were subjected to thematic content analysis. The MOOC content was generally appreciated and reused by the respondents. The results revealed one main motive for completing the course: the immediate opportunity to apply their learning in their practice environments. However, most respondents deplored the lack of interaction among learners and expressed the need for coaching with an instructor to deepen the topics covered during the course. The results also revealed connection and accessibility issues linked to the Internet network and unstable access to electricity in West African countries. The study highlights the potential of MOOCs for the acquisition of knowledge and competencies by KT professionals. Several recommendations and avenues of exploration were formulated to optimize and improve future designs of MOOCs on KT.

Advancing the utilization of real-world data and real-world evidence in clinical pharmacology and translational research-Proceedings from the ASCPT 2023 preconference workshop.

Real-world data (RWD) and real-world evidence (RWE) are now being routinely used in epidemiology, clinical practice, and post-approval regulatory decisions. Despite the increasing utility of the methodology and new regulatory guidelines in recent years, there remains a lack of awareness of how this approach can be applied in clinical pharmacology and translational research settings. Therefore, the American Society of Clinical Pharmacology & Therapeutics (ASCPT) held a workshop on March 21st, 2023 entitled "Advancing the Utilization of Real-World Data (RWD) and Real-World Evidence (RWE) in Clinical Pharmacology and Translational Research." The work described herein is a summary of the workshop proceedings.

Molnupiravir: Mechanism of action, clinical, and translational science.

Molnupiravir is an oral prodrug of the broadly active, antiviral ribonucleoside analog N-hydroxycytidine (NHC). The primary circulating metabolite NHC is taken up into cells and phosphorylated to NHC-triphosphate (NHC-TP). NHC-TP serves as a competitive substrate for viral RNA-dependent RNA polymerase (RdRp), which results in an accumulation of errors in the viral genome, rendering virus replication incompetent. Molnupiravir has demonstrated activity against SARS-CoV-2 both clinically and preclinically and has a high barrier to development of viral resistance. Little to no molnupiravir is observed in plasma due to rapid hydrolysis to NHC. Maximum concentrations of NHC are reached at 1.5 h following administration in a fasted state. The effective half-life of NHC is 3.3 h, reflecting minimal accumulation in the plasma following twice-daily (Q12H) dosing. The terminal half-life of NHC is 20.6 h. NHC-TP exhibits a flatter profile with a lower peak-to-trough ratio compared with NHC, which supports Q12H dosing. Renal and hepatic pathways are not major routes of elimination, as NHC is primarily cleared by metabolism to uridine and cytidine, which then mix with the endogenous nucleotide pools. In a phase III study of nonhospitalized patients with COVID-19 (MOVe-OUT), 5 days of treatment with 800 mg molnupiravir Q12H significantly reduced the incidence of hospitalization or death compared with placebo. Patients treated with molnupiravir also had a greater reduction in SARS-CoV-2 viral load and improved clinical outcomes, compared with those receiving placebo. The clinical effectiveness of molnupiravir has been further demonstrated in several real-world evidence studies. Molnupiravir is currently authorized or approved in more than 25 countries.

Translational Research and Health Equity: Gene Therapies for Sickle Cell Disease as a Case Study.

In August of 2023, the National Academies of Science, Engineering, and Medicine published a timely report titled "Toward Equitable Innovation in Health and Medicine: A Framework." Here, we review some of the key contributions of the report, focusing on two dimensions of equity: input equity and deployment equity. We then use the example of new gene therapies to treat sickle cell disease (SCD) as a case study of input and deployment equity in translational research. The SCD case study illustrates the need for a kind of translational bioethics with deep understanding of lived experiences and clinical realities as well as a high degree of economic and policy sophistication.

Through the big top: An exploratory study of circus-based artistic knowledge translation in rural healthcare services, Québec, Canada.

BACKGROUND: The conventional methods and strategies used for knowledge translation (KT) in academic research often fall short in effectively reaching stakeholders, such as citizens, practitioners, and decision makers, especially concerning complex healthcare issues. In response, a growing number of scholars have been embracing arts-based knowledge translation (ABKT) to target a more diverse audience with varying backgrounds and expectations. Despite the increased interest, utilization, and literature on arts-based knowledge translation over the past three decades, no studies have directly compared traditional knowledge translation with arts-based knowledge translation methods. Thus, our study aimed to evaluate and compare the impact of an arts-based knowledge translation intervention-a circus show-with two traditional knowledge translation interventions (webinar and research report) in terms of awareness, accessibility, engagement, advocacy/policy influence, and enjoyment. METHODS: To conduct this exploratory convergent mixed method study, we randomly assigned 162 participants to one of the three interventions. All three knowledge translation methods were used to translate the same research project: "Rural Emergency 360: Mobilization of decision-makers, healthcare professionals, patients, and citizens to improve healthcare and services in Quebec's rural emergency departments (UR360)." RESULTS: The findings revealed that the circus show outperformed the webinar and research report in terms of accessibility and enjoyment, while being equally effective in raising awareness, increasing engagement, and influencing advocacy/policy. Each intervention strategy demonstrates its unique array of strengths and weaknesses, with the circus show catering to a diverse audience, while the webinar and research report target more informed participants. These outcomes underscore the innovative and inclusive attributes of Arts-Based Knowledge translation, showcasing its capacity to facilitate researchers' engagement with a wider array of stakeholders across diverse contexts. CONCLUSION: As a relevant first step and a complementary asset, arts-based knowledge translation holds immense potential in increasing awareness and mobilization around crucial health issues.

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.

[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.

Supporting children's participation in active travel: developing an online road safety intervention through a collaborative integrated knowledge translation approach.

Even though regular engagement in physical activity (PA) among children can support their development and encourage the adoption of healthy lifelong habits, most do not achieve their recommended guidelines. Active travel (AT), or any form of human-powered travel (e.g., walking), can be a relatively accessible, manageable, and sustainable way to promote children's PA. One common barrier to children's engagement in AT, however, is a reported lack of education and training. To support children's participation in AT, this paper presents the development of a comprehensive 4-module online road safety education intervention designed to improve children's knowledge and confidence regarding AT. Using a qualitative integrated knowledge translation (iKT) approach undertaken with community collaborators (n = 50) containing expertise in health promotion, public safety, school administration, and transportation planning, our inductive thematic analysis generated fourth themes which constituted the foundation of the intervention modules: Active Travel Knowledge: Awareness of Benefits and Participation; Pedestrian Safety and Skills: Roles, Responsibilities, and Rules; Signs and Infrastructure: Identification, Literacy, and Behaviour; Wheeling Safety and Skills: Technical Training and Personal Maneuvers. Each theme/module was then linked to an explicit learning objective and connected to complementary knowledge activities, resources, and skill development exercises. Implications for research and practice are discussed.

Mobocertinib: Mechanism of action, clinical, and translational science.

Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations represent ~6%-12% of all EGFR-mutated non-small cell lung cancer (NSCLC) cases. First-, second-, and third-generation tyrosine kinase inhibitors (TKIs) have limited clinical activity against EGFR ex20ins mutations. Mobocertinib is a first-in-class oral EGFR TKI that selectively targets in-frame EGFR ex20ins mutations in NSCLC; accelerated approval in the United States was granted for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR ex20ins mutations whose disease has progressed on or after platinum-based chemotherapy. Accelerated approval was based on the results from the three-part, open-label, multicenter, pivotal phase I/II nonrandomized clinical trial (NCT02716116) that enrolled 114 patients with locally advanced or metastatic EGFR ex20ins mutation-positive NSCLC who were previously treated with platinum-based chemotherapy and received mobocertinib at the recommended dosage of 160 mg once daily. At the November 1, 2021, data cutoff date, the confirmed objective response rate per independent review committee (IRC) was 28%, median duration of response was 15.8 months, median progression-free survival per IRC was 7.3 months, and median overall survival was 20.2 months. The most common treatment-emergent adverse events were gastrointestinal- and skin-related. The phase III EXCLAIM-2 study evaluated mobocertinib versus chemotherapy as first-line therapy for locally advanced or metastatic EGFR ex20ins-positive NSCLC; however, the primary end point was not met, resulting in initiating voluntary withdrawal of mobocertinib worldwide. This mini-review article summarizes the mechanism of action, pharmacokinetic characteristics, key clinical trials, and clinical efficacy and safety data for mobocertinib.

Science as a calling and as a profession: The wider setting in Weber's scholarly endeavor.

In his 1917 lecture for Munich students (most often entitled in English translation "Science as a Vocation"), Max Weber addressed numerous issues: not only how "profession" and "calling" are related in science and scholarship, but also Entzauberung ("disenchantment"); rationality and its limits; ultimate values; and the field of tension between science and religion. The present essay locates these themes in Weber's oeuvre from 1911 onward, and analyses how they resonate and culminate in Weber's address in 1917. It is in 1911 that he decided to engage with the problem that was to stand central in his thinking until his death in 1920: the nature and causes of certain specific turns in the course of European history which, so he argued, have proven to be of "universal significance." Special attention is given in the present essay to how Weber dealt in this connection with the rise of modern science and the rise of modern tonal harmony. A concluding section explains what, over a century later, makes reading Weber still so rewarding an experience.

[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 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.