Objectives/Goals: Planning research studies can be daunting for early-career investigators. The UW Madison Institute for Clinical and Translational Research (ICTR) has many services to assist, but navigating them can be convoluted. Therefore, we developed a method to streamline services for investigators. Methods/Study Population: Investigators were reaching out to ICTR research support services for assistance in the wrong order, delaying their study progress. To streamline ICTR services and improve investigator support, we developed the ICTR COllaborative Network (ICON) that meets weekly to discuss investigator needs and how best ICTR services can assist them. This group consists of members from ICTR’s Research and Protocol Development Program, the Recruitment and Retention Resource Center, and the Collaborative Center for Health Equity. After discussion and decision-making, a member of the group schedules a studio, bringing key services together at one time to help investigators more efficiently. Results/Anticipated Results: The group has worked with 22 investigators, decreasing the time to study implementation. One investigator indicated ICON saved her team over four months of work. Other investigators indicated the assistance with finding community partners and collaborators was essential to their success. We expect ICON, with its goal to streamline regulatory submissions and study planning, will continue to help investigators improve organization during study start up and execution, while enhancing recruitment strategies. This will result in quicker study completion and the capability to move forward with future projects and grant submissions. Discussion/Significance of Impact: ICON streamlined the consult process, improved efficiency of study planning, and brought together various experts for studio meetings with investigators. This efficient method can improve study function and execution for early-career investigators resulting in improved study success.

Objectives/Goals: Imaging neuromas, benign tumors of nerve tissue, can be difficult in amputees with osseointegrated (OI) prostheses, in which a metal rod is implanted into the residual limb. Magnetic resonance imaging can be inadequate due to the implanted metal. The aim of this study is to assess the use of ultrasound to detect neuromas in patients with OI prostheses. Methods/Study Population: This is a single-institutional observational study of 7 patients undergoing lower limb OI prostheses. Lower extremity nerve ultrasounds with 2-D grayscale and Doppler were completed at postoperative follow-up visits following OI prosthesis implantation. Specifically, the sciatic nerve, tibial nerve, common peroneal nerve, and sural nerve were targeted for imaging. Neuromas found on ultrasound were measured by maximal length in three planes. Results/Anticipated Results: Our study to date includes two patients with OI prostheses. The remaining patients will be accrued by the end of December. The first patient with a left below-the-knee amputation completed imaging 3 years after OI prosthesis implantation. The common peroneal nerve showed preserved fascicular architecture and morphology, with no distinct neuroma formation. However, the sural nerve demonstrated a 6 × 5 × 4 mm neuroma with minimal pain with deep palpation. The tibial nerve demonstrated a 14 × 11 × 8 mm neuroma within the medial calf musculature, with mild pain with deep palpation. The second patient with a right above-the-knee amputation was imaged 10 months after OI prosthesis implantation. The sciatic nerve demonstrated preserved fascicular morphology and terminated in a smooth taper. There was no defined neuroma. Discussion/Significance of Impact: In conclusion, we have preliminarily shown in the first two patients that ultrasound can successfully image neuromas in patients with OI prostheses in the postoperative period. Furthermore, despite a patient that was 3 years postoperative with two neuromas, the neuromas produced minimal to mild pain with targeted palpation.

Objectives/Goals: To create raciolinguistically sensitive emotion recognition assessment materials, we will (i) identify the prosodic cues that signal differences between raciolects (Black vs. White American English) and (ii) identify the prosodic cues that signal different emotions (angry, happy, and sad). Methods/Study Population: Research evaluating prosodic differences between raciolects and emotions both implicate pitch. For example, Black speakers tend to produce speech lower in pitch, and sad speech tends to be narrower in pitch range. In our study, 50 Black and 50 White American healthy adults will hear manipulated recordings of Black and White speakers uttering pseudoword strings that vary by mean pitch and pitch range. In the race task, participants will choose whether the stimulus was produced by a Black or White speaker. In the emotion task, they will choose whether the stimulus sounded happy, angry, or sad. Linear mixed-effects models will be used to determine the pitch correlates for each emotion by race. Results/Anticipated Results: If mean pitch (high, low) and pitch range (wide, narrow) function as acoustic correlates for emotions but differ by race, we expect the following: first, members in each participant group (Black, White) will converge on correlates that differentiate emotions and race; and second, the emotion correlates will differ between groups. Preliminary results using stimuli from only White speakers suggest convergence across groups for emotions (angry: low mean pitch, happy: high mean pitch, and sad: narrow pitch range) but not race. Ongoing data collection including stimuli from White and Black speakers will be used to conduct planned comparisons as well as test same-race, different-race differences. Discussion/Significance of Impact: Characterizing the prosodic differences in emotion recognition between races helps us understand disparities in post-stroke aprosodia. Additionally, developing a linguistically informed strategy for assessing deficits between dialects can be readily implemented across diverse linguistic communities.

Objectives/Goals: Despite efforts to support healthcare researchers to navigate translational gaps and achieve health impact, impact remains rare. We were interested in determining whether, when, and how researchers were taking actions to optimize the translational potential and impact of their research. We also wanted to identify ways to support optimization. Methods/Study Population: Our sample was drawn from Tufts CTSI’s annual outcomes survey respondents (2017–2022) and included tufts principal investigators who had at least one project that reported an outcome (e.g., publication, presentation, funding application, research products, intellectual property protection, and implementation) on the survey. We excluded individuals no longer based at Tufts, no longer working in research, and holding a non-leadership role in their research. We drew a random sample of 58 researchers from the database. Of these, 11 (19%) were excluded, 32 (55%) did not respond to our invitation, 3 (5%) declined to take part, and 12 (21%) were interviewed. The study was approved by Tufts IRB and semi-structured interviews were recorded via Zoom, transcribed in full, and analyzed using the qualitative software Dedoose. Results/Anticipated Results: We interviewed 12 participants, both male (5) and female (7), from 11 different fields, working in preclinical (2), clinical (6), and public health (4) research at assistant (3), associate (5), and full professor (4) rank. There was variety in the way that researchers conceptualized and anticipated pathways to impact. While researchers almost always described their motivation as connected to improved patient care, their ideas of impact were commonly described as research products or outputs, and there was little attention to planning and executing for real-world use. Researchers spoke about challenges related to competing career demands, institutional barriers, organizational culture, and lack of connections. Strategies to address these challenges included mentorship, collaboration, and policy work. Discussion/Significance of Impact: The disconnect between researchers’ ideas of output and impact was notable, and while researchers sometimes mentioned dissemination via publications and committees, use of dissemination and implementation frameworks were very infrequent. Fragmented approaches and implementation science gaps remain significant barriers to health impact.

New education and training opportunities are critical for the development of a diverse and highly skilled translational science workforce. In this special communication, the authors consider how Narratives of Discovery, an initiative to interview leading scientists about the sources of their creativity, can serve as a novel translational science teaching tool. Reporting on a project to map translational science principles onto nine Narratives of Discovery conducted to date, the authors demonstrate how translational science principles are manifested in the career trajectories of these scientists and propose that the narratives can serve as a formative model for trainees. Findings from systematic coding of the Narratives of Discovery suggest that the narrative format is particularly well suited to highlight translational science principles not well-addressed by existing education opportunities, including what it means for scientists to be creative and innovative, use bold and rigorous approaches, and prioritize diversity, equity, inclusion, and accessibility. Offering excerpts from the published Narratives of Discovery and quotations from the scientists themselves, the authors aim to create space for continued conversation about how to best crystallize the concepts of translational science and advance translational science education and training initiatives.

Objectives/Goals: To discuss the challenges faced by National Drug Early Warning System (NDEWS; PI Cottler) in monitoring emerging drug trends and disseminating data to maximize public health impact. Drug trends are constantly in flux, with various communities facing different harms. To provide salient information, NDEWS must triangulate data from multiple sources. Methods/Study Population: In 2020, NDEWS was funded at University of Florida through a cooperative agreement with NIDA. A Scientific Advisory Group meets regularly for overall guidance, and 17 Sentinel Sites provide local perspectives. Now in its fifth year, NDEWS has utilized traditional data such as death reporting and drug seizures and has launched several novel surveillance components. Rapid Street Reporting conducts anonymous surveys of drug use in a Sentinel Site or hotspot each month. Machine learning methods applied to Reddit reveal new trends and novel substances. County-level alerts are generated by analysis of 911-dispatch data accessed through biospatial.io. Wastewater-based epidemiology provides city-level data. Findings are disseminated primarily through email weekly briefings and by peer-reviewed articles. Results/Anticipated Results: In its first iteration, NDEWS has expanded available data sources and worked to integrate data to reveal trends that impact communities across the USA. These patterns vary substantially over time and by region and population, complicating analysis, but inclusion of multiple data sources is imperative for a full understanding of the landscape. NDEWS continues to explore novel routes of disseminating information to those who need it, including contacting local health departments with high overdose rates. Establishing networks for bidirectional communication with stakeholder groups such as toxicologists and educational affiliates is underway. NDEWS seeks to deepen ties with survivors unions (those with lived experience) and harm reduction organizations, which can be difficult due to mistrust of research. Discussion/Significance of Impact: Monitoring the rapidly changing drug landscape in the USA is challenging, and its importance has only grown in recent years as new substances arise and adulterated drug supply has become the norm, promulgating the rise of dangerous substances such as fentanyl and xylazine. Ensuring that information filters out to those who use substances is critical.

Objectives/Goals: To assess the feasibility, safety, and preliminary efficacy of implementing a supervised, outpatient aerobic and strength exercise regimen in newly diagnosed pediatric patients with acute lymphoblastic leukemia (ALL). We hypothesize that early implementation of exercise is feasible and may prevent well-known cardiometabolic late effects. Methods/Study Population: We will enroll 10–20 children (both males and females) with newly diagnosed ALL between the ages of 11–21 years to participate in a 12-month supervised, structured outpatient exercise regimen (STRONGER ALL). This regimen will consist of low- to moderate-intensity aerobic and strength exercises (either in person or coached virtually per patient preference) 3 times a week. This study will include 2 physical fitness assessments: 1) baseline and 2) end of study. Assessments will include resting energy expenditure, peak oxygen uptake, bone density, upper and lower extremity strength, flexibility, and questionnaires (feasibility and quality of life). Additionally, blood and urine specimens will undergo metabolomic analysis to identify biomarkers predictive of future cardiometabolic outcomes. Results/Anticipated Results: We expect that early implementation of STRONGER ALL in children undergoing chemotherapy will be feasible and preliminarily effective at mitigating risk factors for long-term cardiometabolic outcomes in survivors. Feasibility will be defined by recruitment capability (at least 50% of eligible patients agree to enroll), acceptance/compliance (at least 50% of participants complete the program with participation in at least 50% of sessions), data acquisition (collection and outcomes measures are appropriate), and practicability (program shows promise of being successful with pediatric ALL patients as measured by validated surveys administered to patients and caregivers). We anticipate that ALL patients participating in STRONGER ALL will have improved fitness and quality of life. Discussion/Significance of Impact: Evidence on the benefits of physical activity for ALL patients has not changed clinical practice. We aim to overcome the translational science barrier of patient- and system-level blockade in implementation of exercise in children with ALL. The evidence generated from this research may also be generalizable to other childhood cancer survivors.

Hidradenitis suppurativa (HS) is a chronic, painful inflammatory skin disease affecting 0.1% of the US population. Limited understanding of HS biology and ineffective treatments leave patients dissatisfied, facing misdiagnosis, and diagnostic delays. To address these challenges, the Rockefeller University Center for Clinical Translational Science, Clinical Directors Network, and the HS Foundation launched an initiative to foster engagement among stakeholders. Three full spectrum town halls (FSTH) were designed to engage patients, scientists, and clinicians bidirectionally. Topics spanned the translational research spectrum to amplify patient testimony, update the HS community on scientific and clinical research advances, and promote patient-centered research and care. The FSTH model aims to enhance empathy, foster trust, accelerate scientific discovery, and improve care. FSTH-2018 showcased patients’ experiences living with HS, the scientific and clinical state of the art, and tailored a new HS study to patient preferences. FSTH-2021 shared results of the study, including new insights into HS biology. FSTH-2023 highlighted best practices for outpatient surgical care of HS. Participant feedback underscored FSTH’s role in nurturing empathy and advancing discovery and patient engagement. FSTH serves as an effective model for uniting stakeholders, bridging gaps in knowledge and trust, and accelerating translational research to improve HS care.

Objectives/Goals: Triple-negative breast cancer (TNBC) is a highly aggressive and prevalent breast cancer subtype that lacks targeted therapies. This study aims to investigate whether the niclosamide derivative HJC0152 can modulate tumor-derived PD-L1 expression and enhance the effectiveness of anti-PD-1 immunotherapy in treating TNBC. Methods/Study Population: Niclosamide derivative HJC0152 was developed as a novel cancer therapeutic and immunomodulating agent. Human TNBC cell line (MDA-MB-231) was treated with HJC0152, and activation of the STAT3 signaling pathway was evaluated using Western blotting. RNA-Seq was employed to analyze the expression of protein-coding genes, particularly those related to immune response. To study therapeutic potential in vivo, TNBC mouse models will be treated with single agent treatments as well as a combination therapy of HJC0152 and anti-PD-1. Tumor volume and mass will be measured over time to determine growth inhibition. Results/Anticipated Results: Preliminary studies indicate that HJC0152 exhibits enhanced solubility compared to Niclosamide, along with high anticancer potency both in vitro and in vivo. HJC0152 was found to effectively inhibit the activation of phosphorylated STAT3 (p-STAT3) in MDA-MB-231 cells, a key signaling pathway associated with cancer progression and immune evasion. RNA-Seq analysis of HJC0152-treated MDA-MB-231 cells revealed a decrease in PD-L1 expression, an essential immune checkpoint protein involved in tumor immune suppression. These findings suggest that HJC0152 is a promising immune modulator that may enhance the efficacy of immune checkpoint blockade therapy for TNBC. Discussion/Significance of Impact: This study explores an innovative immunotherapy for TNBC using the Niclosamide derivative HJC0152, which inhibits STAT3 signaling and downregulates PD-L1. Results from this study will provide a foundation for HJC0152’s inclusion in clinical trials and potentially offer a new and promising therapeutic option for TNBC treatment.

The importance of mentoring for professional development in Science, Technology, Engineering, Mathematics and Medicine (STEMM) fields is well established. With the increasing prevalence of team science, mentoring that incorporates team science skills is essential. Here, we describe a novel mentoring program designed to develop technical and relational/interpersonal skills for working in multi-disciplinary team science environments and to develop networks to improve collaboration in multi-disciplinary team science. The Georgia Clinical and Translational Science Alliance Translational Education and Mentoring in Science program is a nine-month program consisting of one-on-one mentoring, peer mentoring groups, mentoring resources, and shared learning experiences. Mentees (fellows) are exposed to a wide range of learning opportunities related to the goals of the program. This multi-institutional effort, in its fifth year, has been well received by participants. To date, 95 faculty, post-doctoral fellows, and research scientists have participated in the program as mentees. Participants indicated that they enjoyed the program, identified new networking opportunities, and would recommend it to others. In addition, fellows reported improved relational, technical, and networking skills over the duration of the program. Mentor ratings were also quite favorable. The multi-institutional nature of the program enriched learning and its unique structure combining traditional one-on-one mentoring with peer learning communities has been beneficial to those participating.

Objectives/Goals: Intra-amniotic inflammation (IAI) is one of the leading causes of maternal/fetal morbidity globally, yet it is undiagnosed in 90–95% of cases. The purpose of this study was to assess precision and accuracy of a novel microsampling device for measuring cytokines in amniotic fluid (AF) to enable noninvasive evaluation of localized inflammation. Methods/Study Population: AF was obtained from discarded amniocentesis samples from 3 deidentified patients without known inflammation. Samples were spiked to 5 concentrations of interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a), then sampled using the Neoteryx Mitra volumetric microsampling device (20 µL). Dried/reconstituted samples were analyzed using the Luminex R&D Mag XL multiplex (IL-6, TNF-α) and compared to free-flowing AF. Inter-and intra-assay performances were evaluated across 5-runs in 3 standard cytokine concentrations. Recovery/linearity was assessed by a recovery curve and parameter estimates. Precision was assessed between-run and within-run using coefficients of variance (%CV). Accuracy was evaluated as agreement between microsampled and free-flowing AF using Bland–Altman plots. Results/Anticipated Results: TNF-α results were linear for all 3 patients across 5 concentrations. However, accuracy and recovery consistently failed (mean±SD percent recovery 176±21%). TNF-α results had acceptable precision with %CV within-run of 6.8–12.1% and across-runs of 14.0–15.9%. Microsampled TNF-α agreed with free-flowing sample: 16 of 18 (89%) were within 1SD of the mean difference (-24±36 pg/ml). IL-6 results were linear for 1/3 patients and had unacceptable accuracy and recovery for 13/15 samples (mean±SD percent recovery 764±469%). IL-6 results had acceptable precision (%CV within-run 6.2%, 7.5% and 11.2%; across-run .9–15.2%). Microsampled IL-6 agreed with free-flowing sample; 17 of 18 (94%) were within 1SD of the mean difference (-148±180pg/ml). Free-flowing vs. microsampling methods agreed best at low concentration. Discussion/Significance of Impact: This study provides preliminary support for noninvasive measurement of cytokines leveraging small amounts of leaking AF providing a promising alternative to amniocentesis and potential for assessing inflammation intrapartum. Clinical application requires development of reference ranges and association between cytokine levels and outcomes.

Within the Northwestern University Clinical and Translational Sciences Institute, we created a foundational and fluid mentor training curriculum to provide competency-based mentor training for faculty. Via our “Developing and Enhancing Mentoring Relationships” mentor workshop series, launched in 2020, we present eight 90-minute workshops each academic year. This series is designed for both training naive participants and previously trained mentors across ranks and tracks and offers both repeating (“required”) and new (“elective”) workshops annually. We implemented a Mentor Training Certificate Program (MTCP) in 2021 to formally recognize faculty who complete a minimum of nine hours of training, consisting of three required and at least three elective training sessions. Over the first four years of the workshop series, 345 unique faculty attended at least one workshop; 46 completed requirements for the MTCP. MTCP participants complete baseline and annual surveys focused on self-assessment of nine mentoring skills (e.g., providing feedback) and frequency of engaging in five recommended mentoring behaviors (e.g., aligning expectations). Scores increased significantly across all skills; participants reported increased frequency of mentoring behaviors and high satisfaction with the program. Our mentor workshop series, offering both repeating and new workshops annually, provides faculty the opportunity for either initial or advanced training.

Objectives/Goals: Early identification and profiling of planned studies is a critical administrative challenge in providing timely support for clinical trials. Here we describe the collaborative design and development of a clinical trial tracking dashboard to enhance support and quality improvement for investigator-initiated clinical trials at our institution. Methods/Study Population: Trial-CARE organized a workgroup with key stakeholders from WashU business units that manage grants, information technology, bioinformatics, data repository stewardship, and clinical trial support. The workgroup strategized next steps in a “proof-of-concept” effort to determine whether NIH investigator-initiated clinical trial metrics would be accessible via the WashU Data Warehouse. The WashU Data Warehouse is a data repository that pulls in pre-award and post-award data from sources such as the WashU Research-Grant Management System (RMS) and the NIH Reporter Tool. The proof-of-concept findings lead to implementing a plan for Phase 1 of the design, development, and piloting of a visual dashboard to track and offer targeted and timely support to NIH investigator-initiated clinical trials at WashU. Results/Anticipated Results: WashU currently has 217 grants submitted and 114 grants awarded for NIH clinical trials. In the proof of concept, we confirmed and successfully matched over 100 awarded NIH investigator-initiated clinical trials at WashU across RMS and the NIH Reporter Tool. We determined Phase I of the dashboard would track clinical trial data from these two sources via the WashU Data Warehouse. The pilot of Phase I of the dashboard will begin in February 2025. We also identified mission critical data elements not accessible via the WashU Data Warehouse (e.g., enrollment diversity, IND, and IDE). The plan to procure this data will require continued stakeholder support in Phase II of the dashboard to (1) expand data capture in RMS and (2) ingest additional data into the WashU Data Warehouse from RMS or new systems (e.g., ClinicalTrials.gov). Discussion/Significance of Impact: Early access to robust data about NIH investigator-initiated clinical trials via our newly created Phase I dashboard will better position our centralized service cores to support trial success, compliance, and quality improvement across the lifecycle of these clinical trials. In Phase II, we plan to expand the data available in the dashboard.

Objectives/Goals: Syncope is a common diagnosis in observation medicine, and characterization of observation patients is often limited to single unit, single center, or single payer systems. TriNetX, a federated deidentified multicenter national public database, provides an opportunity to study these patients from across the USA. Methods/Study Population: This retrospective cohort study queried data from 56 health care organizations (HCO) in TriNetX to examine differences between observation patients with syncope who required admission vs. those who were discharged. All observation stays with a diagnosis of syncope, defined by ICD-10, CPD, and SNOWMED codes, were queried. A total of 281,162 observation encounters were included in analysis, of which 46.4% (n = 130,357) were admitted and 53.6% (n = 150,805) were discharged. Data on age, gender, race, ethnicity, presence of congestive heart failure, EKG, and serum labs were collected for comparative analysis. T-test and Chi-square analyses were deployed with significance  =  p Results/Anticipated Results: The cohorts demonstrated statistically significant differences across all demographic factors, however, they were not clinically meaningful. Clinically significant differences include that only 72.8% of admitted patients and 68.3% of discharged patients had an EKG recorded in TriNetX during the period of observation (p Discussion/Significance of Impact: Patients admitted from observation status were more likely to have CHF, higher BNP, and pro-BNP values. TriNetX is a powerful tool to study patients across multiple hospital systems and payer types. Limitations, however, include incomplete data and inaccuracies among claims records.