Translational Science Award Program Research Articles

Metabolic syndrome reduces cerebral blood flow more in women than men

One in three adults in the United States suffers from metabolic syndrome (MetSyn), a state of insulin resistance associated with reduced cerebral blood flow (CBF) and increased risk of stroke and neurologic diseases. Notably, females are at greater risk for cardiovascular and metabolic complications derived from insulin resistance. Still, it remains unclear whether the reduction in CBF seen in MetSyn is sex-specific or uniform between various brain regions. Additionally, fasting triglyceride (TG) levels are stronger predictors of cognitive disease in females than in males. However, little data exist examining the relationship between TG and CBF in females with MetSyn. Therefore, we aimed to examine the interaction between sex and MetSyn on global and regional CBF in young adults and to explore the relationship between fasting TG levels and CBF. We predict that males and females with MetSyn will have lower global and regional CBF compared to healthy controls of the same sex, but to a greater extent in females with MetSyn. Additionally, we predict fasting TG levels will have stronger relationships with CBF in females than in males with MetSyn. Twenty-five healthy controls (CON; 7 females; 24 ± 4 y) and 13 individuals with MetSyn (5 females; 27 ± 8 y) completed this study. Subjects were unmedicated, and females were studied on days 1-5 of their menstrual cycle. A metabolic panel, blood pressure, and waist circumference were collected in a fasted state. Magnetic resonance imaging (MRI, 3 Tesla) with arterial spin labeling was used to quantify global and regional CBF. Two-way (Group x Sex) linear models with Shaffer’s correction and Tukey adjusted post hocs were used to determine differences in CBF. In the MetSyn groups, Pearson correlation coeffcients were assessed between fasting TG levels and each global and regional CBF value. Global CBF was greater in female CON compared to all groups (p ≤ 0.01), and male CON had greater CBF than male MetSyn (p = 0.03), whereas there was no difference between male and female MetSyn (p = 0.43). Regional analyses resulted in the same pattern of between-group differences in the parietal lobe (p = 0.03), the precuneus (p = 0.01), and the frontal lobe (p = 0.01), outside of a nonsignificant difference between male CON and male MetSyn in the frontal lobe (p = 0.12). No interactions existed for the temporal lobe, occipital lobe, or thalamus (p ≥ 0.06). In females with MetSyn, fasting TG levels were moderately negatively correlated with CBF (r = -0.65), whereas a moderate positive relationship existed in males with MetSyn (r = 0.71). These data suggest that MetSyn reduces CBF to a greater extent in females than males, abolishing sex-dependent differences in CBF present in healthy young adults. While female sex is protective against cardiovascular disease in healthy young adults, this is not the case in individuals with MetSyn. Additionally, males and females with MetSyn had opposing relationships between fasting TG levels and CBF. These findings may help explain the greater cardiovascular risk in females with insulin resistance. American Diabetes Association (ADA1-16-ICTS-099 and ADA 1-12-IN-39); Clinical and Translational Science Award program (UL1TR002373); Wisconsin National Primate Research Center (P51OD011106). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

531 Transforming a Pilot Grant Program to Advance Clinical & Translational Science

OBJECTIVES/GOALS: A new mandate for Clinical & Translational Science Award (CTSA) Programs is for pilot grant funding to support clinical and translational science (CTS) projects that study challenges in the translational research pipeline. This pivot requires new structures and supports to help investigators design and implement high-quality CTS projects. METHODS/STUDY POPULATION: The Michigan Institute for Clinical & Health Research (MICHR) at the University of Michigan (U-M) has launched two rounds of pilot funding since March 2023. Faculty and staff across U-M’s three campuses, community members, and those at collaborating institutions and hospitals were eligible to apply. New pre-award supports included a CTS project framework; a recorded webinar that educated about CTS and the funding opportunity; office hours to provide tailored project feedback; a letter of intent to screen for alignment with CTS; and reviewer training for academic and community reviewers. Funded projects operate like 'mini cooperative agreements”, with MICHR experts partnering with awardees to refine evaluation plans, prepare work products, advise on dissemination, and navigate emergent challenges. RESULTS/ANTICIPATED RESULTS: The first round of funding was launched in the absence of pre-award supports; ten applications we received from faculty proposing translational research rather than CTS. We quickly re-released the FOA, expanding eligibility to staff. We received nine applications, ultimately funding four staff and one faculty studying operational challenges in translation and helping them create robust evaluation plans. We piloted the pre-award supports in our second round, with 40 individuals viewing our webinar and 11 attending office hours. Those who watched the webinar before attending office hours better understood how to embed CTS questions within their programs of research. We recently received 19 letters of intent, addressing both operational and scientific challenges, with 16 eligible to submit applications. DISCUSSION/SIGNIFICANCE: Education and personalized feedback seem to elicit a higher yield of CTS projects. Staff are already adept at solving operational challenges, so the pre-award supports were most critical for faculty accustomed to writing traditional translational research proposals. Staff have most benefited from guidance in evaluation and dissemination.

Development of the Dissemination and Implementation Science Collaborative (DISC): Opportunities to enhance implementation science capacity among researchers and practitioners in South Carolina.

This paper explores the development of the Dissemination and Implementation Science Collaborative (DISC) at the Medical University of South Carolina, established through the Clinical and Translational Science Award program. DISC aims to accelerate clinical and translational science by providing training, mentorship, and collaboration opportunities in dissemination and implementation (D&I) science. Through DISC, investigators, trainees, and community partners are equipped with the knowledge and skills to conduct D&I research and translate findings into practice, particularly in South Carolina's public health and healthcare landscape. We describe efforts to achieve the major overarching aims of DISC, which include conducting scientific workforce training, providing mentorship and consultation, and advancing methods and processes for D&I research. By sharing DISC experiences, successes, and challenges, this paper aims to support the growth of D&I research and capacity-building programs, fostering collaboration and shared resources in the field.

The role of information science within the clinical translational science ecosystem.

Academic health sciences libraries ("libraries") offer services that span the entire research lifecycle, positioning them as natural partners in advancing clinical and translational science. Many libraries enjoy active and productive collaborations with Clinical and Translational Science Award (CTSA) Program hubs and other translational initiatives like the IDeA Clinical & Translational Research Network. This article explores areas of potential partnership between libraries and Translational Science Hubs (TSH), highlighting areas where libraries can support the CTSA Program's five functional areas outlined in the Notice of Funding Opportunity. It serves as a primer for TSH and libraries to explore potential collaborations, demonstrating how libraries can connect researchers to services and resources that support the information needs of TSH.

Optimizing external advisory committee meetings of Clinical and Translational Science Awards through focused pre-review.

External advisory committees (EACs) are critical peer-review meetings that drive improvement at Clinical and Translational Science Award Program Hubs. Despite their ubiquity, evaluations of EAC optimization and effective implementation remain scarce. We present a two-tiered approach to optimizing EAC meetings through (1) in-depth, topically focused "pre-review" meetings comprised of external topic experts and at least one standing "full-board" EAC member, followed by (2) a traditional "full-board" EAC meeting. This approach allowed pre-review discussion of program-focused topics and specific recommendations, later delivered to the full-board for review and direction. To evaluate this approach, we interviewed 18 people who planned, administered, or attended pre-review and/or full-board meetings, including internal Hub staff, external topic experts, and standing EAC members. Thematic analysis was used to explore planning, implementation, and value of our two-tiered approach versus the traditional single full-board approach. Interviewees preferred the two-tiered approach, noting benefits including additional time to reflect, shared identification of strengths and challenges, and discussion of solutions to share later with the full-board. Those who attended pre-review meetings described building "transformational," rather than "transactional," relationships with invitees through more discussion and inter-hub sharing. That increased sharing invited more exploration, discussion, and planning of next steps toward innovation.

Clinical research resource support for off-site research coordinators in intensive and specialty care units.

Clinical Research Coordinators (CRCs) are vital collaborators in a clinical research project. They often are the primary liaisons between investigators and human participants in studies and are involved in every aspect of many protocols, including participant recruitment, care (both usual medical care and specific study-related monitoring and procedures), data collection, specimen processing, and follow-up. The Clinical Translational Science Award program, which was created by the National Institutes of Health in 2006, has significantly expanded the venues in which Clinical Research Resource (CRR) - based CRCs are embedded. CRCs functioning in these areas, outside of the research-focused in-patient environment of the CRR, are designated as "off-site" CRCs. Many of these locations, such as intensive care units and emergency departments, require that CRCs interact regularly with healthcare providers whose primary functions are focused on providing optimal patient care rather than research and often involving very complex patients. These off-site CRCs require additional training and support outside of the usual research-oriented environment of the CRR. They are required to function within the context of the patient-care team while fostering implementation of collaborative research. This is a description of such a program specifically geared to off-site CRCs with the goal of enhancing the quality of research and experiences of CRCs.

Weight cycling may induce lipid handling in mast cells

Abstract Weight cycling worsens diabetes risk in both humans and mice. We recently found that weight loss and weight cycling induce many immunological changes in the adipose tissue of mice by single cell RNA-sequencing. We also found a substantial increase in adipose mast cells with weight cycling, but not weight loss. The purpose of this study was to confirm and characterize the changes in mast cells with weight cycling. However, using flow cytometry (cKit+FcER1+) and Toluidine blue staining, we found that adipose mast cells are greatest in the weight loss group, in contrast to our prior study using single cell RNA-sequencing. Upon further analysis, we found two unique mast cell populations in our single cell sequencing dataset: one that we consider traditional mast cells and one with lower expression of mast cell surface and protease genes and elevated expression of lipid handling and antigen presentation genes. The second fraction appeared similar to lipid-associated macrophages and accounted for most of the mast cells in the weight cycled group. By flow cytometry, we confirmed the %CD9+, MHCII (I-A/I-E)+, and CD74+ mast cells were highest in weight cycled mice. We also found two mast cell populations in human subcutaneous adipose tissue that appear similar to the murine populations in our dataset, with one population significantly correlating with weight variability. Together, these data suggest that weight cycling may induce a population of lipid-associated mast cells. We next aim to to induce lipid handling in bone marrow derived mast cells by repeated exposure to adipose conditioned media in order to understand the mechanisms which induce lipid handling. This project was funded by a Veterans Affairs Merit Award 5I01BX002195 to AHH. AHH is also supported by a Career Scientist Award from the Veterans Affairs (IK6 BX005649). HLC was funded by an American Heart Association Postdoctoral Fellowship (20POST35120547), MAC was funded by an NIH F31 Predoctoral Fellowship (1F31DK123881), and both were previously supported by the Molecular Endocrinology Training Program (T32 DK07563). Additionally, the human mast cell work was funded by VICTR grants to HLC and MM. The Vanderbilt Institute for Clinical and Translational Research (VICTR) is funded by the National Center for Advancing Translational Sciences (NCATS) Clinical Translational Science Award (CTSA) Program, Award Number 5UL1TR002243-03.

Learn Labial Salivary Gland Biopsy Online.

From the *Division of Rheumatology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI †Division of Rheumatology, Department of Medicine, University of Wisconsin–Madison, Madison, WI Robert W. Ike ORCiD ID https://orcid.org/0000-0003-4715-4384 Sara S. McCoy ORCiD ID: 0000-0002-5293-4185 R.W.I. and S.S.M. declare no conflict of interest. S.S.M. does basic research into aspects of Sjögren disease, supported by the Clinical and Translational Science Award program, through the NIH National Center for Advancing Translational Sciences (grant 1KL2TR002374), the National Institutes of Dental and Craniofacial Research (grant 1R03DE031340), and the National Cancer Institute (grant P50 CA278595). Correspondence: Robert W. Ike, MD, 1611 Harbal Dr, Ann Arbor MI 48105. E-mail: [email protected].

Translating Scientific Discovery Into Health Policy Impact: Innovative Bibliometrics Bridge Translational Research Publications to Policy Literature.

To understand how translational science efforts lead to outcomes, it is common to examine publications as a key step in the translational process. The National Institutes of Health's Clinical and Translational Science Awards (CTSA) program aims to accelerate that process by providing support to investigators. Although it is challenging to measure the impact of such support on translational outcomes, CTSA-supported research that arises in research publications can advance translation through use of these publications in public policy and guideline documents from government health agencies, intergovernmental organizations, and other outlets. Using cutting-edge bibliometric tools, the authors evaluated how CTSA-supported research has extended its impact beyond academic silos to influence public policy literature. The authors identified approximately 118,490 publications that acknowledged receiving support from a CTSA hub, from the inception of the program in 2006 through 2021. Articles were queried in the Overton policy database, which indexes references to publications in global policy literature. The search revealed 13% of CTSA-supported articles were referenced in policy documents, significantly more than the expected proportion (10%) calculated by Overton. References came from 576 policy source outlets across 87 countries, predominantly the United States and Europe. The most frequent sources included guidelines in PubMed Central, the World Health Organization, and the Centers for Disease Control and Prevention. The authors illustrate the bridge from translational research to public policy with case studies of 6 articles based on CTSA-supported research and having notable policy impact. They found articles with greater clinical relevance, altmetric attention (i.e., nonacademic community/public attention), and academic citation influence were more likely to be referenced in policy literature. Study findings help to characterize the kinds of research that have influenced and may be expected to influence health policy in the future.

Susan S. Smyth (1965-2022).

Susan S. Smyth (1965-2022).

The rocky road to translational science: An analysis of Clinical and Translational Science Awards

Abstract Studies point out that the productivity decline in biomedicine is in significant part due to difficulties in translating basic science into clinical application. To promote translational research, the US NIH launched the Clinical and Translational Science Awards (CTSA) program in 2006. Prior evaluations of the CTSA program often assumed that the key to translation is inter-organizational collaboration or multidisciplinarity; hence, changes in either of these were measured as evidence of translational science. However, using novel measures of translational science, this study examines the relationship between CTSAs and translational science per se. We define ‘translational science’ as basic science that has translational features, and we employ two distinct, complementary measures of translational science based on publication data. Using 115 Carnegie R1 universities and their translational science publications, we find that receiving a CTSA does not obviously cause receiving institutions to conduct more translational science. Furthermore, our Principal Investigator-level analysis shows that those who received direct support from the CTSA program had already generated more translational science than others and that their research behavior did not change significantly after receiving a CTSA. Future evaluation research can adopt our novel measures of translational science and evaluation research design in the assessment of translational research activities. Finally, we conclude with a discussion of the implications of our findings for science governance.

Utilizing the Un-Meeting model to advance innovative translational and team science.

Advances in translational science require innovative solutions, and engagement of productive transdisciplinary teams play a critical role. While various forms of scientific meetings have long provided venues for sharing scientific findings and generating new collaborations, many conferences lack opportunities for active discussions. We describe the use of an Un-Meeting to foster innovative translational science teams through engaged discussions across multidisciplinary groups addressing a shared theme. The Un-Meeting was delivered by the University of Rochester Center for Leading Innovation and Collaboration, the national coordinating center for the National Institutes of Health Clinical and Translational Science Awards (CTSA) program. This pilot CTSA program Un-Meeting focused on engaging translational scientists, policy-makers, community members, advocates, and public health professionals to address the opioid crisis. The participant-driven format leveraged lightning talks, attendee-led idea generation, and extensive breakout discussions to foster multidisciplinary networking. Results indicated participation by a broad set of attendees and a high level of networking during the meeting. These results, coupled with the growth of the Un-Meeting across the CTSA Consortium, provide practices and models to potentially advance team and translational science. While future work will further assess the impact of Un-Meetings, this format presents a promising approach to enhance translational science.

Challenges in catalyzing and sustaining research in translational science.

Advancing the new field of translational science and developing innovative solutions to overcome translational roadblocks are key priorities of the Clinical and Translational Science Awards (CTSA) Program of the National Center for Advancing Translational Science (NCATS). However, interpreting this emerging concept of "translational science" (TS) as a field of inquiry distinct from "translational research" (TR) and developing real-world investigations in TS can be challenging. The goal of this paper is to share the obstacles the Einstein-Montefiore CTSA hub has faced in generating institutional interest and research in TS and to present potential strategies for addressing them. The aim is to stimulate dialog within the wider CTSA community and beyond about the need to systematically examine how TS should be efficiently and effectively pursued, that is, the science of translational science. The collective sharing of experiences and innovative approaches to overcoming TS challenges that arise at CTSA hubs is critical if the field is to grow and gain wider recognition and acceptance by the scientific and broader communities.

Building an infrastructure to support the development, conduct, and reporting of informative clinical studies: The Rockefeller University experience.

Clinical trials are a vital component of translational science, providing crucial information on the efficacy and safety of new interventions and forming the basis for regulatory approval and/or clinical adoption. At the same time, they are complex to design, conduct, monitor, and report successfully. Concerns over the last two decades about the quality of the design and the lack of completion and reporting of clinical trials, characterized as a lack of "informativeness," highlighted by the experience during the COVID-19 pandemic, have led to several initiatives to address the serious shortcomings of the United States clinical research enterprise. Against this background, we detail the policies, procedures, and programs that we have developed in The Rockefeller University Center for Clinical and Translational Science (CCTS), supported by a Clinical and Translational Science Award (CTSA) program grant since 2006, to support the development, conduct, and reporting of informative clinical studies. We have focused on building a data-driven infrastructure to both assist individual investigators and bring translational science to each element of the clinical investigation process, with the goal of both generating new knowledge and accelerating the uptake of that knowledge into practice.

Developing a Translational Team Training Program using the Wisconsin Interventions in Team Science Framework.

The Clinical and Translational Science Awards (CTSA) Program supports a national network of medical research institutions working to improve the translational process. High-performing translational teams (TTs) are critical for advancing evidence-based approaches that improve human health. When focused on content-appropriate knowledge, skills, and attitudes, targeted training results in the substantial internalization of training content, producing new skills that can be applied to improve team outputs, outcomes, and benefits. More rigorous approaches to develop, test, and evaluate interventions are needed, and we used the Wisconsin Interventions in Team Science framework as a model to systematize our efforts. We designed, built, and tested a five-session TT Training Program for translational researchers. The 90-minute sessions were pilot-tested with 47 postdoctoral fellows and evaluated through a structured evaluation plan. Ninety-five percent of post-session survey respondents indicated that the content and skills provided would make them more effective collaborators, and one hundred percent would recommend the sessions to colleagues. Respondents' scores increased from pretest to posttest for most learning outcomes. Refinements from participant feedback are described. This work provides a foundation for the continued evolution of evidence-based training programs in the CTSA environment.

Attitudes towards diversity, equity, and inclusion across the CTSA Programs: Strong but not uniform support and commitment.

This study describes attitudes towards diversity, equity, and inclusion (DEI) among members of the Clinical and Translational Science Awards (CTSA) Program. It also explores associations between program members' roles and their perceived importance of and commitment to improving DEI and assesses the link between perceived importance of and commitment to improving DEI. Lastly, it ascertains barriers and priorities concerning health equity research, workforce development, CTSA consortium leadership, and clinical trials participation among respondents. A survey was administered to registrants of the virtual CTSA Program 2020 Fall Meeting. Respondents reported their roles, perceived importance of and commitment to improving DEI. Bivariate cross-tabulations and structural equation modeling examined associations between respondents' roles, perceived importance of DEI, and commitment to improving DEI. Grounded theory was used to code and analyze open-ended questions. Among 796 registrants, 231 individuals completed the survey. DEI was "extremely important" among 72.7 percent of respondents and lowest among UL1 PIs (66.7%). Being "extremely committed" to improving DEI was reported by 56.3 percent of respondents and lowest among "other staff" (49.6%). Perceived importance of DEI was positively associated with commitment to improve DEI. Institutional and CTSA Commitment, Support, and Prioritization of DEI represented a key theme for improving DEI among respondents. Clinical and translational science organizations must take bold steps to transform individual perceptions of DEI into commitment and commitment into action. Institutions must set visionary objectives spanning leadership, training, research, and clinical trials research to meet the promise and benefits of a diverse NIH-supported workforce.

The community voices program to facilitate community-academic researcher partnerships: Stakeholder perspectives on the program's usefulness.

The Institute of Translational Health Sciences (Clinical and Translational Science Awards Program hub) developed a program coined Community Voices to invite communities to submit project ideas and be matched with academic researchers. We describe formative research to understand community and academic researcher perspectives on how the program could facilitate collaborations addressing community priorities. We conducted four focus groups with 31 community-based organization (CBO) representatives and 11 semi-structured interviews with academic researchers in the Washington, Wyoming, Alaska, Montana, and Idaho regions. Questions included the appeal of Community Voices to engage community and academic partners, potential program usefulness, and Community Voices' potential role in building community-academic partnerships. We used an inductive, constant comparison approach to code transcripts and thematic analysis to generate themes. Most CBO representatives were female (87.1%) and Hispanic/Latino (61.3%). Most academic researchers had a PhD (63.6%) and worked at a university (81.8%). The themes were: (1) community-academic partnerships built on trust will offer mutual benefit, (2) community-initiated project ideas should prioritize community needs, (3) matchmaking will accelerate connections but should not replace time to foster partnership, (4) Community Voices should go beyond matchmaking and provide ongoing support/training, and (5) fostering effective communication is key to partnership success. Community Voices is a novel, bidirectional community engagement program model that advances current practices of prioritizing researchers' project ideas. This community-driven program may shift the future direction of community engagement practices where prioritizing community's ideas becomes the norm of community-academic partnerships in clinical and translational science.

Integrating dissemination and implementation sciences within Clinical and Translational Science Award programs to advance translational research: Recommendations to national and local leaders - ADDENDUM.

Integrating dissemination and implementation sciences within Clinical and Translational Science Award programs to advance translational research: Recommendations to national and local leaders – ADDENDUM - Volume 7 Issue 1

Development of a clinical and translational research curriculum for undergraduate students.

Research participation during undergraduate years has a powerful influence on career selection and attitudes toward scientific research. Most undergraduate research programs in academic health centers are oriented toward basic research or address a particular disease focus or research discipline. Undergraduate research programs that expose students to clinical and translational research may alter student perceptions about research and influence career selection. We developed an undergraduate summer research curriculum, anchored upon a clinical and translational research study developed to address a common unmet needs in neonatal nurseries (e.g., assessment of neonatal opioid withdrawal syndrome). Program topics reflected the cross-disciplinary expertise that contributed to the development of this "bedside to bench" study, including opioid addiction, vulnerable populations, research ethics, statistics, data collection and management, assay development, analytical laboratory analysis, and pharmacokinetics. The curriculum was delivered through three offerings over 12 months, using Zoom video-conferencing due to restrictions imposed by the COVID-19 pandemic. Nine students participated in the program. Two-thirds reported the course enhanced their understanding of clinical and translational research. Over three-quarters reported the curriculum topics were very good or excellent. In open-ended questions, students reported that the cross-disciplinary nature of the curriculum was the strongest aspect of the program. The curriculum could be readily adapted by other Clinical and Translational Science Award programs seeking to provide clinical and translational research-oriented programs to undergraduate students. Application of cross-disciplinary research approaches to a specific clinical and translational research question provides students with relevant examples of translational research and translational science.

The CTSA Diversity, Equity, Inclusion, and Accessibility (DEIA) Task Force's recommendations for the CTSA program consortium.

The Clinical and Translational Science Award (CTSA) Program recognizes that advancing diversity, equity, inclusion, and accessibility (DEIA) requires moving beyond statements of commitment to transformative actions. In 2021, the CTSA Program created a Task Force (TF) to initiate work in support of structural and transformational initiatives that advance DEIA for the consortium and its individual hubs. We describe the process of forming the expertise-driven (DEIA) TF and our activities to date. We 1) developed and adopted the DEIA Learning Systems Framework to guide our approach; 2) defined a set of recommendations across four focus areas (Institutional; Programmatic; Community-Centered; and Social, Cultural, Environmental); and 3) designed and disseminated a survey to capture the CTSA Program's baseline demographic, community, infrastructural, and leadership diversity. The CTSA Consortium also elevated the TF to a standing Committee to extend our understanding, development, and implementation of DEIA approaches to translational and clinical science. These initial steps provide a foundation for collectively fostering environment that support DEIA across the research continuum.