Objectives/Goals: Understanding cognitive habits and values of individuals or groups, and providing tools to apply them to collaborative, interdisciplinary endeavors to better communicate between different industries, functions, and cultures. Methods/Study Population: Using literary research to establish groupings of common core values in interpersonal communications, applying established 5 patterns of “thought languages” to scale to group communications. Accepted psychological personality inventories for individuals will overlay into cognitive values, primarily using the current big five OCEAN model. Demonstrating these values to find common goals among interdisciplinary collaborations can identify prospective members, cultural differences in industry, patient communication, and public messaging in STEM. Integrating these tools into research groups to establish more efficacious communication between teams, governing bodies, and patient communication can be sampled via pre and post research surveys of feeling understood. Results/Anticipated Results: The results of feeling understood by various parties in collaborative research would be a measure of not just effective expressed communication, but received communication. Feeling understood is a current metric of communication that is correlated with satisfaction, trust, and interdependence. All of these results are integral to the successful operations of collaborative projects. Demonstrating a positive correlation between applying the 5 thought languages and better-surveyed outcomes of understanding will guide the effectiveness of this as a future collaborative tool for translational sciences. Discussion/Significance of Impact: The significance of effective communication based on positive reception will foster future collaborations. Encouraging familiarity between differing individuals, groups, and industries, even between subjects and researchers, patients and healthcare. More satisfaction, more trust, and more interdependence will propagate between these groups.

Objectives/Goals: Primary sclerosing cholangitis (PSC) manifests with an inflammatory milieu that leads to fibrotic scarring of the liver. Human PSC liver bile ducts are enriched with neutrophils; however, their infiltration and functional role is unexplored. Our goal is to investigate the mechanism and impact of peribiliary neutrophil infiltration observed in PSC. Methods/Study Population: Primary cholangiocytes (bile duct cells) isolated from WT and mouse models of PSC (3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed mice and Mdr2-/- mice) were analyzed by RNA-sequencing. Immunofluorescence (IF) was performed on liver tissues from PSC patients and mouse models of PSC for markers of bile ducts and neutrophils (KRT19 and MPO). Intrahepatic leukocytes (IHL) isolated from mice livers were evaluated for neutrophil abundance and activation state. Anti-Ly6G antibody-mediated neutrophil depletion in Mdr2-/- mice was analyzed by IF, histology, and cytometry by time-of-flight (CyTOF). Cholangiocytes stimulated with TNFα (to induce an inflammatory phenotype) were analyzed for neutrophil chemoattractants with genetic and pharmacological interventions. Results/Anticipated Results: RNA-seq analysis of primary cholangiocytes from PSC mouse models revealed enrichment in inflammatory and neutrophil degranulation pathways. Flow cytometry and RT-PCR analysis revealed an increase in the neutrophil population in PSC mice with activated phenotype. Peripheral depletion of neutrophils in Mdr2-/- mice alleviated liver injury and inflammation, along with a reduction in peribiliary neutrophil infiltration and attenuated bridging fibrosis. CyTOF analysis showed a significant reduction in CD8+ T cells upon neutrophil depletion, implying neutrophils sustain CD8+ T cells in PSC liver. Mechanistically in cholangiocytes, TNFα mediates expression of neutrophil chemoattractants, CXCL1 and CXCL8, through the cyclic GMP-AMP synthase stimulator of interferon genes (cGAS-STING) pathway. Discussion/Significance of Impact: Our findings suggest that activation of the STING pathway in cholangiocytes in cholestatic liver disease triggers an immune response resulting in peri-portal neutrophil infiltration via CXC chemokines. The sustained presence of these activated neutrophils engages the adaptive immune system to perpetuate the inflammation and fibrosis seen in PSC.

Learning Health Systems (LHS) iteratively implement and evaluate health improvement projects. Dissemination and implementation (D&I) science is the study of evidence-based practices in real-world settings, a critical tool for LHS. This paper explores intersections between LHS and D&I science in Clinical and Translational Science Awards (CTSAs) institutions and identifies critical components of collaboration. We conducted website scans of 34 CTSAs and their home institutions that had Dissemination, Implementation, and Knowledge Translation (DIKT) Workgroup members. We identified linkages between CTSAs and their institutions’ LHS. We interviewed six CTSA leaders experienced in LHS and D&I sciences. Nearly half of CTSAs identified an LHS structure on their websites, but only one-third indicates CTSA involvement in these efforts. Interviewees identified key components for successful integration of LHS and D&I sciences: leadership, infrastructure, balance between rigor and efficiency, and aligned incentives. The need for research integration in LHS, to improve evaluation and increase knowledge, is an emerging opportunity for D&I scientists and CTSAs. CTSAs that are engaged in D&I science can introduce and/or expand the role of D&I science in LHS. Collaboration between CTSAs and clinical leaders could result in strengthened relationships between clinical and research enterprises, effective and efficient health care delivery, and improved health.

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.

The NIH Center for Accelerated Innovations at Cleveland Clinic (NCAI-CC) was funded by the National Heart Lung and Blood Institute (NHLBI) to support academic investigators in technology development and commercialization. NCAI-CC was one of three multi-institutional Centers established in the fall of 2013. The goal of each Center was to catalyze the growth of an ecosystem of commercialization within their affiliated institutions and regions by managing a program of funding and guiding translational project development and by delivering commercialization education programs to participating investigators. NCAI-CC created and managed such a funding program, ultimately supporting 75 different projects across seven separate academic institutions and developed tailored educational content following the National Science Foundation I-Corps™ curriculum and delivered the program to 79 teams from 12 institutions. We determined early on that in establishment and implementation of projects, it is important to support the teams and principal investigators throughout the program. The support includes a change in principal investigator mindset from specific aims orientation to goals and deliverables on projects. Our skills development efforts emphasized commercialization and a deep understanding of customer needs for new technology adoption. Here, we review our experiences, outcomes, and insights, including the challenges identified in program implementation.

Objectives/Goals: Depression is common among people living with HIV (PLWH). This study explored the link between reduced metacognitive awareness and depression in PLWH. It utilized a positive emotion regulation task to compare brain activation during viewing versus upregulating positive emotions. Methods/Study Population: Depressed PLWH (N = 24; mean age  =  53; HAM-D mean  =  19) participated in an emotion regulation task while blood oxygen-level-dependent (BOLD) responses were recorded. In the emotional regulation task, participants were shown the International Affective Picture System (IAPS) a series of positive, negative, and neutral images. Participants were asked to view these images and given instructions to either negatively reappraise (RN) or positively reappraise (RP). In the RP condition, participants were no longer shown the image and asked to upregulate their positive emotional responses associated with it. Ten onset times were included for each trial. Results/Anticipated Results: A one-sample t-test was conducted to analyze contrasts between reappraisal of positive images and viewing positive images (RP > VP). Results showed significantly greater activation in the posterior cingulate and angular gyrus during the RP condition (peak MNI: 18, -52, 34; p < 0.001, uncorrected, k > 10 voxels). In comparing the reappraisal of negative images to viewing negative images (RN > VN), there was increased activation in the right supramarginal gyrus (peak MNI: 50, -28, 22; p < 0.001, uncorrected, k > 10 voxels). When contrasting the reappraisal of positive to negative images (RP > RN), BOLD signals were higher in the left dorsolateral prefrontal cortex (peak MNI: 40, -38, 32; p < 0.001, uncorrected, k > 10 voxels). Discussion/Significance of Impact: Findings underscore that depressed PLWH demonstrates BOLD responses in brain regions linked to appetitive motivation and meta-cognitive awareness during the RP condition which demands more executive resources among those with depression, highlighting the complexity of emotional regulation in this population.

The Community Research Advisory Council (C-RAC) of the Johns Hopkins Institute for Clinical and Translational Research was established in 2009 to provide community-engaged research consultation services. In 2016–2017, C-RAC members and researchers were surveyed on their consultation experiences. Survey results and a 2019 stakeholder meeting proceeding helped redesign the consultation services. Transitioning to virtual consultations during COVID-19, the redesigning involved increasing visibility, providing consultation materials in advance, expanding member training, and effective communications. An increase in consultations from 28 (2009–2017) to 114 (2020–2022) was observed. Implementing stakeholder-researcher inputs is critical to holistic and sustained community-engaged research.

Rapid whole genome sequencing (rapid WGS) is a powerful diagnostic tool that is becoming increasingly practical for widespread clinical use. However, protocols for its use are challenging to implement. A significant obstacle to clinical adoption is that laboratory certification requires an initial research development phase, which is constrained by regulations from returning results. Regulations preventing return of results have ethical implications in cases which might impact patient outcomes. Here, we describe our experience with the development of a rapid WGS research protocol, that balanced the requirements for laboratory-validated test development with the ethical needs of clinically relevant return of results.

Actively engaging community health centers (CHCs) in research is necessary to ensure evidence-based practices are relevant to all communities and get us closer to closing the health equity gap. We report here on the Boston HealthNet Research Collaborative, a partnership between health centers, Boston HealthNet and the Boston University Clinical, and Translational Science Institute with the explicit goal of supporting research partnerships early in the planning phase of the study lifecycle. We used the principles of community engagement guided by a collective impact framework to codesign, pilot, and evaluate a process for facilitating research partnerships. Accomplishments in the first 2 years include a web-based Toolkit with a step-by-step guide and an active learning collaborative with health center representatives to support research capacity building. The process resulted in 81 new research project partnerships across 50 individual research projects. Most research partnership requests were made later in the research lifecycle, after the planning phase. Partnership acceptance was largely driven by the Collaborative’s pre-defined Guiding Principles and Rules of Engagement. These lessons drive an iterative process to improve the longitudinal relationship between our translational research program and our CHC partners.

Predictive analytics in health is a complex, transdisciplinary field requiring collaboration across diverse scientific and stakeholder groups. Pilot implementation of participatory research to foster team science in predictive analytics through a partnered-symposium and funding competition. In total, 85 stakeholders were engaged across diverse translational domains, with a significant increase in perceived importance of early inclusion of patients and communities in research. Participatory research approaches may be an effective model for engaging broad stakeholders in predictive analytics.

The University of Kansas Cancer Center (KU Cancer Center) initiated an engagement program to leverage the lived experience of individuals and families with cancer. KU Cancer Center faculty, staff, and patient partners built an infrastructure to achieve a patient-designed, patient-led, and research-informed engagement program called Patient and Investigator Voices Organizing Together (PIVOT). This special communication offers an engagement roadmap that can be replicated, scaled, and adopted at other cancer centers and academic health systems. PIVOT demonstrates that collaboration among academic leaders, investigators, and people with a lived experience yields a patient-centered, vibrant environment that enriches the research enterprise.