OBJECTIVES/GOALS: Mechanisms underlying racial and ethnic disparities in rectal cancer care remain poorly understood. We aimed to identify barriers and facilitators to care among rectal cancer patients who identify as Hispanic/Latino (H/L) and to understand how these factors may differ based on rurality, social/physical context, and community support. METHODS/STUDY POPULATION: We utilized qualitative methods and a community-based participatory research framework, including partnership with a community-based organization and oversight from a community advisory board. We developed an initial semi-structured interview guide based on an ecological model of health behavior and then iteratively refined it with the assistance of our partners to incorporate unique aspects of the H/L community in a culturally appropriate manner. Eligible patients and their caregivers are invited to participate in hour-long interviews in both English and Spanish, depending on participants’ preferences. All interviews are recorded, translated, transcribed, and coded. Findings will be compiled and fed back to participantsand community stakeholders as a part of a community forum. RESULTS/ANTICIPATED RESULTS: We identified 6 areas for discussion based on our model: health beliefs (perceived severity, benefit, and barriers; self-efficacy), health literacy, others’ experiences with cancer, patient-provider relationship (patient-provider communication; provider-provider communication; language; cultural competency; discrimination), sources of support, and access to care. Participants are currently being recruited by clinical providers, through flyers in the cancer center, or via outreach from our community partner. We have interviewed 8 participants to date, with discussions ranging from the shock of the initial diagnosis, difficulties with navigating specialty care, and the complexities of shared decision making. We are expecting a total of 30-40 interviews to reach thematic saturation. DISCUSSION/SIGNIFICANCE: We hope to improve our understanding of mechanisms underlying racial and ethnic disparities in rectal cancer care and to identify potential targets for improvement. We plan to use our results to develop community-based policy interventions to improve care delivery, patient experience, and health equity.

OBJECTIVES/SPECIFIC AIMS: The goal is to understand the underlying mechanism of epicaridial fat biology and its response to cardiometabolic disease by using quantitative multi-echo Dixon (mDixon) of water and lipid sequence, T2* blood-oxygen-level-dependent (BOLD) sequence of iron content, and data analysis methods to determine the quantity of brown Versus white fat. To accomplish this goal, we propose to define the histological, genetic, and metabolite state of epicardial fat and to confirm the relationship between fat phenotype and magnetic resonance (MR) characteristics. We will then investigate whether MR is more effective in identifying patients with lower cardiovascular disease risk than computed tomography (CT). METHODS/STUDY POPULATION: We will recruit 100 patients undergoing open-heart surgery and will quantify mDixon (proton density fat fraction), BOLD (T2*), and T2/T1 maps of epicardial, extrapericardial, and subcutaneous fat before their surgery. We will then (a) validate MR findings by direct depot-specific tissue analysis for lipid content, histological, and genetic markers of inflammation and brown and white fat, (b) develop plasma and fat depot specific metabolite profiling of cardiovascular disease risk and correlate with imaging characteristics. We will categorize cardiovascular risk score (Cardiovascular Health Status) of our 100 patients on quartiles. We will then build models where the categorized cardiovascular risk score are regressed on MR measures (epicardial fat fraction, T2*, and T2/T1 maps) and CT measures (epicardial fat volume and coronary calcium score). RESULTS/ANTICIPATED RESULTS: We anticipate to learn about epicardial fat biology and the role of inflammation in cardiometabolic disease. We will validate proton density fat fraction, T2* and T2 map against histology of epicardial fat for lipid content, established markers of brown and white fat and inflammation, respectively, to help us translate imaging technique to clinical practice. In respect to our second aim we anticipate that MR identifies patients at lower cardiovascular risk quartile than CT. DISCUSSION/SIGNIFICANCE OF IMPACT: Interest in epicardial fat as a visceral fat of the heart and coronary arteries is rapidly growing as the scientific based evidence indicates that the anatomic specificity is an important contributor to the cardiovascular diseases. The transformation of epicardial fat from a cardioprotective phenotype to a pro-inflammatory, atherosclerosis-promoting state triggers inflammation that is coincident with the expansion of epicardial fat volume detected by anatomic imaging. This study will impact the management of patients at risk for cardiovascular disease because it will demonstrate that quantification of epicardial fat status by MR identifies fat tissue changes validated by histology at lower cardiovascular disease risk quartile than CT.

OBJECTIVES/SPECIFIC AIMS: To identify the most frequently reported barriers/constraints and resources by junior faculty in achieving their goals at a large medical school in the Western United States. METHODS/STUDY POPULATION: We reviewed 222 individual development plans (IDPs) from 26 departments in an academic medical center for content regarding constraints and resources to achieve activities and barriers and/or resources to achieve new goals. The content and quality of the IDPs included was ascertained using quantitative data analysis as well a review of open-ended qualitative questions. In addition to analyzing the content, the quality and percent completion of data filled out for each field in the IDP was also assessed to help identify gaps with departments in successfully completing and submitting their IDPs. RESULTS/ANTICIPATED RESULTS: Junior faculty indicated the following barriers: time/time management (55%); work/life balance (32%); funding (8%) and other (5%). Junior faculty also indicated that they had resources to help them achieve their goals, including: mentors (60%); collaborators (26%); colleagues (6%); other (8%). DISCUSSION/SIGNIFICANCE OF IMPACT: The barriers in goal achievement (e.g., time/time management & work/life balance issues) at this academic medical setting suggest that further resources regarding time management and work - life balance need to be developed and disseminated in order to assist faculty in achieving their objectives. This project also reinforces the importance of having a robust mentor or mentoring team for junior faculty. Mentors and administrators should work collaboratively with junior faculty to identify resources to improve time management and work-life balance.

OBJECTIVES/GOALS: Wild-type transthyretin amyloid (ATTRwt) deposits have been found to deposit in the ligamentum flavum (LF) of spinal stenosis patients prior to systemic and cardiac amyloidosis, and is implicated in LF hypertrophy. Currently, no precise method of quantifying amyloid deposits exists. Here, we present our machine learning quantification method. METHODS/STUDY POPULATION: Images of ligamentum flavum specimens stained with Congo red are obtained from spinal stenosis patients undergoing laminectomies and confirmed to be positive for ATTRwt. Amyloid deposits in these specimens are classified and quantified by TWS through training the algorithm via user-directed annotations on images of LF. TWS can also be automated through exposure to a set of training images with user- directed annotations, and then application to a set of new images without additional annotations. Additional methods of color thresholding and manual segmentation are also used on these images for comparison to TWS. RESULTS/ANTICIPATED RESULTS: We develop the use of TWS in images of LF and demonstrate its potential for automated quantification. TWS is strongly correlated with manual segmentation in the training set of images with user-directed annotations (R = 0.98; p = 0.0033) as well as in the application set of images where TWS was automated (R = 0.94; p = 0.016). Color thresholding was weakly correlated with manual segmentation in the training set of images (R = 0.78; p = 0.12) and in the application set of images (R = 0.65; p = 0.23). DISCUSSION/SIGNIFICANCE: Our machine learning method correlates with the gold standard comparator of manual segmentation and outperforms color thresholding. This novel machine learning quantification method is a precise, objective, accessible, high throughput, and powerful tool that will hopefully pave the way towards future research and clinical applications.

Objectives/Goals: The Clinical and Translational Research (CTR) pathway aims to increase the number of health science professionals participating in CTR in their careers throughout the WWAMI Region (Washington, Wyoming, Alaska, Montana, and Idaho). Methods/Study Population: The first cohort of thirty-one students started in January 2024 and were organized into three groups that met weekly. One in-person group of students in Anchorage, AK; one in-person group in Seattle, WA; and a group of students from across the WWAMI region convened virtually. Students completed a year-long series of elective courses addressing fundamental concepts of designing, conducting, and presenting the results of a research project. Over the summer between year 1 and year 2 of medical school, students dedicated 8 weeks to full-time research activities under the supervision of their research project mentor. In Fall 2024, students prepared and presented research posters at regional poster sessions and abstracts and oral presentations for submission to the Western Medical Research Conference in January 2025. Results/Anticipated Results: The ultimate goal of the CTR pathway is to increase the number of medical providers across the WWAMI region with significant awareness, interest, and experience in research. Many students hesitate to engage in research due to a perceived lack of necessary skills. The CTR pathway addresses this gap by equipping students with the research competencies needed to participate confidently in scientific inquiry. Feedback from the inaugural cohort has been overwhelmingly positive, with many students highlighting how the CTR pathway enhanced their confidence and knowledge, empowering them to execute their proposed research projects successfully. Our second cohort of students joined the CTR pathway in January 2025. Discussion/Significance of Impact: The CTR pathway positions early medical students to engage in research more deeply during their medical training and prepares them to seek additional training opportunities toward a career in research. The majority of students in the first cohort were located at regional sites and many have interest in practicing in rural or underserved areas.

OBJECTIVES/GOALS: We present findings of an academic-community health agency study that explored knowledge of cervical cancer and risks among Latinas. The collaboration between the UCLA School of Nursing and AltaMed, a community-based health organization provided diverse clinical training and opportunities to decrease disparities in marginalized communities. METHODS/STUDY POPULATION: We developed a 19-item open-ended survey guide (English/Spanish) to explore knowledge, beliefs and practices related to cervical cancer. Eight nursing students (females and males) completed a 10-week public health focused practicum at four clinical sites. Students interviewed volunteer Latinas (N = 51) and recorded their responses. Prior to surveying Latina clients, the nursing instructor developed a script and mentored the student through the recruitment process. The survey included items on the Papanicolaou exam (pap smear), the HPV, beliefs and knowledge of risks for cervical cancer and recommendations for health service delivery. RESULTS/ANTICIPATED RESULTS: The Latina participants ranged in age from 20-50s, 70% spoke English, most were US born (52%) and 29% were from Mexico. The majority had received a Pap exam (88%), but fewer understood the purpose for the Pap (72%) or the association between HPV and cervical cancer (6%). Five major themes emerged: (1) knowledge deficits regarding women’s preventive care, and the HPV vaccine; (2) limited Spanish language educational materials; (3) importance of respectful client-provider interactions; (4) modesty; and 5) scheduling appointments and the importance of a diverse workforce that understand cultural and language nuances. Recommendations included ways to improve health literacy, cervical cancer knowledge, and delivery of culturally specific health care. DISCUSSION/SIGNIFICANCE OF IMPACT: Finding highlight the importance of putting “personalismo” into practice; linking health behaviors, vaccines, and health care to addresses cervical cancer risks. The collaboration maximized student experiences with opportunities build evidence based sustainable programs for vulnerable communities.

OBJECTIVES/GOALS: The COVID-19 pandemic impacted health systems and exposed disparities in access to health care among underserved populations. We examined how the pandemic shaped social, mental, and physical health among Native American and Latino communities in rural and underserved areas. METHODS/STUDY POPULATION: Using Theory of Planned Behavior, Social Cognitive Theory, and Social Contextual Factor frameworks, we developed interview guides to examine perceptions of the COVID-19 pandemic on social, mental, and physical health among community members. Stakeholders of the Confederated Salish and Kootenai Tribes of the Flathead Reservation in Montana and the Hispanic/Latinx population in Yakima Valley in Washington were selected through purposeful community-engagement. A total of six focus group discussions and 30 key informant interviews were administered in both communities. A codebook was developed and deductive coding was applied to informant responses, followed by an inductive, constant comparison approach. The codebook was further refined and inter-rater agreement was completed by three analysts. RESULTS/ANTICIPATED RESULTS: Four themes were highlighted as areas impacted by the COVID-19 pandemic (mental and physical health, family dynamics, and social disruptions) with few differences among geographic areas or between focus group (n=39) and key informant (n=28) participants. Perceived impacts on mental health included increased stress, anxiety, and depression, while pandemic-related lifestyle or family changes impacted physical health. Participants reported changes to family routines and dynamics due to staying home, social distancing, and more frequent interactions inside or limited interactions outside the household respectively. Social distruptions reported included impacts on finances, employment, and household staples, though participants highlighted how many community members stepped up to help those in need. DISCUSSION/SIGNIFICANCE: The COVID-19 pandemic had similar impacts on two geographically distinct underserved communities in Montana and Washington. Understanding the community’s experience with the COVID-19 pandemic is critical to identify strategies to support families, community needs, and mental and physical health in underserved communities.

OBJECTIVES/SPECIFIC AIMS: Attention is a cognitive function that binds perception and behavior. Recent evidence suggests that attention involves phase-amplitude coupling (PAC) of neural signals. PAC occurs when the amplitude of one frequency (frequency for amplitude) is maximal at particular phases of another frequency (frequency for phase). However, some studies suggest PAC improves attention, while others maintain that PAC inhibits attention. The present study seeks to determine whether PAC promotes or inhibits neural signals that underlie attention. METHODS/STUDY POPULATION: Six adult epilepsy patients with implanted electrodes participated in a cued attention task. Subjects participated in a cued attention task where they oriented attention to one side of the screen at a time and discriminated between stimuli as fast as possible with mouse clicks. Perception-related electrodes discriminated the location and/or shape of the target. These were determined with a cluster-based permutation test. Behavior-related electrodes predicted reaction time (RT) with neural activity prior to target appearance. These were determined with correlations between PAC and RT. PAC was calculated using the modulation index (MI). RESULTS/ANTICIPATED RESULTS: We found 47 perception-related electrodes that discriminated location and/or shape of target (p<0.05, FDR corrected). We found 27 behavior-related electrodes where PAC prior to the target predicted RT (p<0.05 FDR corrected). There was little overlap between the perception-related and behavior-related electrodes (3%). PAC also did not discriminate left-sided and right-sided cues. In addition, behavior-related electrodes had less local neural activity and higher PAC during the period of cued attention than perception-related electrodes. DISCUSSION/SIGNIFICANCE OF IMPACT: PAC minimally facilitates perceptual aspect of visual attention. However, PAC facilitate response speed. We suggest that PAC might improve response speed by “quieting” task irrelevant neural activity. For the same reason, PAC is absent in electrodes that are actively processing meaningful streams of visual data. These findings highlight separable aspects of the human attention system and how PAC contributes to both. Future directions include determining differences in PAC for attentional disorders like ADHD and neurological neglect.

OBJECTIVES/SPECIFIC AIMS: A key factor for success in science is the ability to communicate clearly and succinctly using language appropriate to the audience. Most predoctoral training programs offer opportunities for students to build oral and written communication skills at local and national conferences. However, this rarely provides specific feedback and tends to be episodic. The Mayo Clinic Center for Clinical and Translational Science (CCaTS) has developed an environment for deliberate practice of presentation skills within a weekly Works in Progress and Journal Club session using a learning management system, Blackboard Collaborate. The learning management system captures the presentation that can then be viewed by the student. Watching yourself give a presentation is a powerful learning tool. The learning objectives of the sessions provide students deliberate practice to: (1) Build critical presentation skills for a 1-minute elevator talk, a 2-minute poster overview, a 10-minute oral presentation of your science to a science audience and to a non-science audience. (2) Develop constructive reviewer skills by completing peer reviews of presentations. (3) Develop critical thinking skills to ask thought provoking questions during presentations. By utilizing a curriculum that offers video-recording for reflection and self-evaluation, Mayo Clinic CCaTS has developed an environment in which predoctoral students are encouraged and supported to constantly hone their presentation skills. METHODS/STUDY POPULATION: All CCaTS predoctoral students are asked to prepare presentations in several formats for the weekly 1-hour session. The students’ presentations of their science or journal articles are recorded and saved within Blackboard; a link is provided for the student to review personally, with a mentor, and with the Education Coordinator to discuss the strengths and weaknesses of the presentation. During each session, faculty facilitators encourage students to ask thought provoking questions, and student reviewers are assigned to provide critical and constructive written feedback to the presenter. Sessions providing tools and guidelines for constructive feedback and developing critical and constructive questions are regularly interspersed. RESULTS/ANTICIPATED RESULTS: By reviewing a video recording of their presentations, CCaTS predoctoral students get the opportunity to self-evaluate their performance as an audience member. By going through this process of preparing, presenting, reflecting on their presentations, and discussing their strengths and weaknesses with mentors and classmates, the students gain both powerful presentation skills and methods to improve their delivery and reviewer skills. DISCUSSION/SIGNIFICANCE OF IMPACT: Successful scientists, whether in academia or industry, have the ability to communicate their science clearly using appropriate and common language specific to each audience they present to. By utilizing a curriculum that offers video-recording for reflection and self-evaluation, Mayo Clinic CCaTS has developed an environment in which predoctoral students are encouraged and supported to constantly hone their presentation skills.

OBJECTIVES/GOALS: Introduce students to programming and software development practices in the life sciences by analyzing standard clinical diagnostic bloodwork for differential immune responses. Including lectures and a semester project with the goal of enhancing undergraduate students’ education to prepare them for careers in translational science. METHODS/STUDY POPULATION: The educational content was taught for the first time as a component of the newly developed course BTEC 330 “Software Applications in the Life Sciences” in UMBC’s Translational Life Science Technology (TLST) Bachelor’s degree program at the Universities at Shady Grove campus. Eleven students took the course. All were beginners with no programming background. Lectures provided background on the diagnostic components of the CBC, criteria for differential diagnosis in the clinical setting, and introduction to hematology and flow cytometry, forming underpinnings for interpretation of the CBC results. Weekly computer lab practical sessions provided training fundamentals of R programming language, the R-studio integrated development environment (IDE), and the GitHub.com open-source software development platform. RESULTS/ANTICIPATED RESULTS: The graded assignment consisted of a coding project in which students were each assigned an individual parameter from the CBC results. These include, for example, relative lymphocyte count or hemoglobin readouts. Students each created their own R-language script using R-studio, with functional code which: 1) Read in data from a file provided, 2) Performed statistical testing, 3) Read out statistical results as text, and charts as image files, 4) “Diagnosed” individuals in the dataset as being inside or outside the clinical normal range for that parameter. Each student also registered their own GitHub account and published their open-source code. Grading was performed on code functionality by downloading each student repository and running the code with the instructor as an outside developer using the resource. DISCUSSION/SIGNIFICANCE OF IMPACT: In this curriculum, students with no background in programming learned to code a basic R-language script and use GitHub to automate interpretation of CBC results. With advanced automation now becoming commonplace in translational science, such course content can provide introductory level of literacy in development of clinical informatics software.

OBJECTIVES/GOALS: Our overall goal is to identify the processes used by the human visual system to encode visual stimuli into perceptual representations. In this project, our objective is (i) to collect a dataset of human neural activity in response to 1000 naturalistic color images and (ii) to determine how image parameters drive different parts of the human brain. METHODS/STUDY POPULATION: We recorded iEEG data in 4 human subjects who had been implanted for epilepsy monitoring. Each subject was presented 10 sets of 100 naturalistic stimuli, taken from the Natural Scenes Dataset (Allen et al., 2021), on a screen for 1 second each with 1 second rest intervals between stimuli. The subjects were instructed to fixate on a red dot at the center of the screen and were prompted to recall whether they had seen 3 additional test stimuli at the end of each set to encourage attentiveness. We calculated significant neural responses at each electrode by comparing evoked potentials and high frequency power changes during each stimulus vs. rest. Electrodes with significant responses were then mapped to anatomic locations in each subjects brain and then collectively to a standard brain. RESULTS/ANTICIPATED RESULTS: The natural image set elicited significant evoked potentials and high frequency responses at electrodes in each subject. Response latencies, from 80 to 300 ms after stimulus onset, portrayed the evolution of visual processing along the visual pathways, through key sites such as the early visual cortex, ventral temporal cortex, intraparietal sulcus, and frontal eye field. These responses differed significantly from those elicited by simple patterns, which drove early visual cortex but less so in later regions. DISCUSSION/SIGNIFICANCE: These data show that the human brain responds differently to more complex images. Determining the human brains response to naturalistic images is essential for encoding models that describe the processing in the human visual system. These models may further future efforts for electrical neurostimulation therapies such as for restoring vision.

ABSTRACT IMPACT: Partnering with academic offices to promote peer-mentoring in a virtual format is feasible, novel, and well-received across a major academic campus. Particularly during a pandemic, the success of this programmatic effort highlights the continued need for peer-to-peer support. OBJECTIVES/GOALS: To identify feasibility and key lessons learned from the planning and implementation of a virtual, interdisciplinary group peer-mentoring series, implemented broadly across an academic medical center in New York City. METHODS/STUDY POPULATION: ASPIRE! (Accountability & Safe-Space to Promote, Inspire, Recharge, & Empower one another!) is a group of seven interdisciplinary mid-career academic women faculty, who began collaborations as CTSA KL2 scholars. Our mission is to support interdisciplinary peer coaching for advancement of gender and racial equity among academic faculty and leaders. We designed and implemented a series of virtual symposia focused on essential struggles for clinicians and investigators at during the COVID-19 pandemic. Partnering with Columbia’s CTSA, Office for Women and Diverse Faculty, and Office for Research, we invited leaders in psychiatry/psychology, early childhood education, organization/team management, and academic advancement as keynote speakers and facilitated peer-mentoring virtual breakouts. RESULTS/ANTICIPATED RESULTS: These efforts resulted in the completion of four separate 1.5-hour symposia, each with keynote speakers, discussions with academic leaders, and 30-minute breakout peer-mentoring sessions. Session topics included Calibrating Expectations, Helping Families Thrive, Managing Remote Teams, and Faces and Phases of Stress. Enrollment ranged from 30 to 70 participants per session. Participants reported: (1) Keynotes focused on actionable solutions stimulated the most productive conversations; (2) Peers from different disciplines and career stages provided a range of actionable recommendations tested within local contexts; (3) The greatest learning came from the peer-to-peer breakout group sessions. DISCUSSION/SIGNIFICANCE OF FINDINGS: Partnering with academic offices to promote interdisciplinary, peer-mentoring in a virtual format is feasible, novel, and can be well-received across a major academic campus during the COVID-19 pandemic. The success of this programmatic effort highlights the continued need for expanded peer-to-peer support in academia.

OBJECTIVES/SPECIFIC AIMS: The Title V Cooperative Project between the University of Puerto Rico- Medical Sciences Campus (UPR-MSC) and Universidad Central del Caribe (UCC) has trained US, GS and F (participants) of HSPs to engage them in CTR. METHODS/STUDY POPULATION: First stage of the training sessions (TS) dealt with the theory of CTR. After TS and responding to their research interests, as answered in a questionnaire, the participants formed a CTMT, under the mentorship of a well-established CT researcher. This, as a prelude to their hands-on experiences in Intensive Development and Experiences in Advancement of Research and Increased Opportunities (IDEARIO), for which a research proposal is needed. RESULTS/ANTICIPATED RESULTS: Five (5) CTMTs were formed in different research areas – cardio, neuro, liver, renal, Zika–, as submitted in their research concept papers.Eight (8) CT researchers are currently mentoring 2 US, 7 GS and 6 F of HSPs through the CTMTs. They have submitted a research proposal, as a bridge between the theory in the TS and the practice in IDEARIO. Five (5) proposals were received and 2 of them approved, while the other 3 are in the evaluation process. We will present the composition, research topics, development of research and the feedback of participants in IDEARIO and CTMTs. DISCUSSION/SIGNIFICANCE OF IMPACT: The CTMTs and their respective proposals are effective strategies for the mentoring of US, GS and F in CTR.

OBJECTIVES/GOALS: This study aims to develop a method to examine whether blood-borne CNS-EV metal cargoes can serve as reliable biomarkers of CNS metal load and reveal a link between metal load and ALS development (i.e., neurodegenerative disease development). METHODS/STUDY POPULATION: CNS-EVs were isolated from human blood and plasma samples via direct immunoprecipitation using biotinylated antibodies for proteins known to be expressed in neurons (Contactin-2, i.e.) and astrocytes (glial-glutamate-aspartate-transporter, i.e., GLAST). Once isolated, protein concentrations in the EV samples were analyzed via ELISA assay, EV abundance was measured using ViewSizer Nanoparticle Tracking analysis, and EVs were visualized via Transmission Electron Microscopy. EVs were then analyzed for metal contents using a Perkin-Elmer NexION 350S via an ICP-MS/MS dynamic reaction cell method. RESULTS/ANTICIPATED RESULTS: Preliminary results demonstrate that it is feasible to quantify the metal contents of these CNS-derived EVs, particularly in terms of toxic metals known to be associated with neurodegenerative disorders, including copper, zinc, lead, aluminum, manganese, and iron. DISCUSSION/SIGNIFICANCE: CNS-derived EVs isolated from peripheral blood draws show promise as a potential biomarker of real-time metal load in the brain and spinal cord, with promising applications in predicting future development of neurodegenerative disorders (i.e., ALS) among patients with relevant elevated CNS metal loads.

OBJECTIVES/GOALS: There are notable disparities in cervical cancer screening. Theobjective of this study was to examine knowledge, screening practices, attitudes towards cervical cancer screening, and willingness to adopt screening innovations such as self-sampling and HPV rapid testing for cervical cancer among Hispanic women in Lake County, Indiana. METHODS/STUDY POPULATION: This mixed-methods study encompassed an online cross-sectional survey (n=231) and in-depth interviews (n=9) of individuals with a cervix aged 21-65 residing in Lake County, Indiana. Outcome variables focused on cervical cancer knowledge, willingness to adopt self-sampling, and willingness to adopt HPV rapid testing. Descriptive statistics included frequencies and percentages. A cervical cancer knowledge score was computed from 7 questions. Scores below the mean 3.62 were labeled ‘low’ while higher scores were ‘high’. We also examined associations between demographic and outcome variables. Quantitative analysis was conducted using SPSS software. Qualitative analysis was conducted using NVIVO software to thematically analyze interviews using deductive and inductive coding techniques. RESULTS/ANTICIPATED RESULTS: Majority of participants identified as Hispanic (58%), aged 31 or older (58%). While 80.5% reported being screened for cervical cancer, only 44.6% demonstrated ‘high' cervical cancer knowledge. 89.6% felt screening is important as emphasized in qualitative findings for its preventive value. Over half were willing to take their vaginal swab in clinic (55.8%) and at home (51.9%). However, among the Hispanic/Latinx groups reluctance to adopt self-sampling was notable (56.7% in clinic and 62.7% at home). Qualitative analysis revealed concerns about test accuracy. Willingness to use a hypothetical HPV rapid had higher acceptance (69.7%), with 52.2% in the Hispanic/Latinx group. Qualitative findings highlight benefits like increased screening access, comfort, and convenience offered by an HPV rapid test. DISCUSSION/SIGNIFICANCE: Hispanic/Latinx women in the sample were less willing to adopt cervical cancer screening methods such as self-sampling and rapid testing compared to non-Hispanic whites. Despite being considered beneficial for testing among vulnerable populations, our study found limited acceptance from these populations for various reasons.

OBJECTIVES/SPECIFIC AIMS: In this pilot case-control study, the metabolome was quantified in subjects with previously measured serum and clinical biomarkers. The serum metabolome was then integrated with existing serum and clinical biomarkers of WTC-exposed firefighters to identify pathways significant to loss of lung function following acute PM-exposure. This robust subset of metabolite and serum biomarkers may be clinically relevant to predicting progression to lung disease in a larger cohort. METHODS/STUDY POPULATION: Serum drawn within 6 months of 9/11 was analyzed in this pilot. Clinical measures were obtained from electronic medical records. Never-smoking, male, WTC-exposed firefighters with normal pre-9/11 lung function were segregated based on FEV1 percent predicted (FEV1 %Pred) at symptomatic presentation. Cases of WTC-LI (FEV1 %Pred <LLN, n=15) and controls (n=15) were identified from previous cohorts. Ultrahigh performance liquid chromatography tandem mass spectroscopy quantified the metabolomic fingerprints of a group with previously assessed (by multiplex panels; ELISA and Luminex) serum chemokines and cytokines. High-dimensional data analysis and dimension reduction techniques integrated metabolites, cytokines, chemokines, and clinical data to identify pathways of WTC-LI on curated data. Random Forest (RF) out-of-bag estimated success rates were used to measure classification utility of the refined biomarker profile. Principal components analysis (PCA) was used to visualize class separation produced by the refined profile. RESULTS/ANTICIPATED RESULTS: Of the 765 metabolites detected, 580 metabolites were quantified in more than 80% of subjects/group with relative standard deviation ≥15%. Relevant chemokines, cytokines, and clinical biomarkers were included based on previously established clinical importance. Initial PCA explained 34.7% of the variance in the first 3 components. RF was used to identify the top 5% of biomarkers important to class separation. RF of the refined biomarker profile correctly classified cases and controls with a 96.7% estimated success rate. A PCA of the refined metabolic profile now explained 46.2% of the variance in components 1–3, demonstrating improved class separation. Differentiators between cases of WTC-LI and controls included elevated sphingolipids in cases of WTC-LI. The metabolic-inflammatory serum biomarkers MDC, Apo AI, GM-CSF, and heart rate play an important role in class separation. Phospholipids and lysolipids also appeared to differentiate cases of WTC-LI from controls. Specifically, several glycero-phosphatidylcholines (GPC) were elevated in cases of WTC-LI. DISCUSSION/SIGNIFICANCE OF IMPACT: High-dimensional data analysis on the metabolic fingerprints, serum, and clinical biomarker data of a subset of WTC-exposed 9/11 rescue workers has identified pathways associated with the loss of lung function. Sphingolipids, known to function as inflammatory signaling mediators, are thought to play important roles in lung function under both physiological and pathological conditions. Changes in sphingolipid metabolism have been linked to several pulmonary disorders, including asthma, COPD, and acute lung injury. Interestingly, a relation between sphingolipid metabolism and the metabolic-inflammatory pathway is suggested by similarities observed in PCA. Findings of elevated GPCs are similar to COPD literature. Higher levels of GPCs could correspond to elevated levels of lysophosphatidic acid (LPA), a ligand of RAGE. RAGE is a known proinflammatory mediator; LPA species have well-described roles as lipid signaling molecules, function as synthetic intermediates in other metabolic pathways, and were found to be predictive of WTC-LI. Since metabolites are more proximal markers of disease processes, metabolites could capture the complexity of past exposures and, therefore, may better inform treatment. These pathways warrant further investigation into their mechanisms and therapeutic importance.

OBJECTIVES/SPECIFIC AIMS: Objective: The Rockefeller University Center for Clinical and Translational Science (RU-CCTS), Clinical Directors Network (CDN), and Carter Burden Network (CBN), a multisite senior services organization serving East Harlem, NY, formed a community-academic partnership to examine the use of a simple validated surrogate measure of overall health status and frailty in this population. Many CBN seniors are racial/ethnic minorities, low-income, and suffer from multiple chronic conditions, depression and food insecurity. Multiple biological, musculoskeletal, psychosocial and nutritional factors contribute to frailty, which has been defined variously in senior health outcomes research. The CTSA-funded Pilot Project aims to: (1) Engage CBN seniors and stakeholders in priority-setting, joint protocol development, research conduct, analysis, and dissemination; (2) Characterize the health status of the CBN seniors using validated measures; (3) Establish database infrastructure for current and future research; (4) Understand how health and senior activities information can be used to create programs to improve senior health. METHODS/STUDY POPULATION: Methods: (1) CEnR-Navigation, a collaborative program/process that consists of semistructured meetings and activities facilitated by expert Navigators, was used for partnership development and to engage Carter Burden seniors to refine priorities and research questions, provide feedback on study design and conduct, and analyze and disseminate results. (2) Standard physical measurements and validated survey instruments were used to collect health information; target enrollment is 240 seniors across 2 sites (1 hosted within a subsidized housing facility and Social Model Adult Day Program). (3) A REDCap-based platform was designed for data capture and import. Individual attendance at senior activities for the prior year was extracted from existing records. The primary outcome is frailty, as measured by validated walk/balance tests (Short Physical Performance Battery). Secondary outcomes include measures of engagement, and association of use of services/activities with the primary outcome. RESULTS/ANTICIPATED RESULTS: (1) In total, 29 residents and 14 other stakeholders engaged in partnership-building, study design and implementation. (2) From May to November 2017, 98 participants were enrolled from site 1 (a residential site). Enrollment at site 2 (a senior center), begun in November, is projected for February completion. Characteristics of site 1 participants: median age=63.6 years; Hispanic, 44.90% (44); White, 13.89% (10), Black, 62.50% (45); Asian, 4.17% (3); American Indian or Alaskan Native, 2.78% (2), and Other, 16.67% (12). Educational attainment: 51.04% (49) had not completed high school; 19.79% (19) were high school graduates; 18.75% (18) completed some college, and 10.42% (10) were college graduates. For the 85 participants reporting annual income: 64.71% (55) reported <$10,000; 28.24% (24) reported $10,000–$15,000; 7.06% (6) were among the ranges from $15,000 to $50,000. The average body mass index (BMI) was 30, which is obese. For 83.67% (82) of site 1 participants, the BMI was in the range of overweight or obese. Half of participants (49) reported health literacy barriers in the Single Item Health Literacy Survey. Demographics and Frailty assessments (walk and balance tests) for participants enrolled at both sites will be reported. (3) Activity participation data for July 2016–November 2017 were recovered for 507 sessions at site 1 and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: Here we report progress in developing a sustainable community-academic partnership, infrastructure and research capacity with the CBN senior services organization, and characterizing this at-risk population, of whom 71% have a high school education or less, 93% live in extreme poverty, and 84% are overweight or obese. A simple validated frailty measure in seniors will enable the acceleration of community-based translational research addressing senior health, and examine changes in this measure in relationship to the utilization of senior services.

Several reports have shown that doctoral and postdoctoral trainees in biomedical research pursue diverse careers that advance science meaningful to society. Several groups have proposed 3-tier career taxonomy to showcase these outcomes. This 3-tier taxonomy will be a valuable resource for institutions committed to greater transparency in reporting outcomes, to not only be transparent in reporting their own institutional data but also to lend greater power to a central repository.

The potential utilization of a cold-contact approach to research recruitment, where members of the research team are unknown to the patient, has grown with the expanded use of electronic health records (EHRs) and affiliated patient portals. Institutions that permit this strategy vary in their implementation and management of it but tend to lean towards more conservative approaches. This process paper describes the Medical University of South Carolina’s transition to an opt-out model of “cold-contact” recruitment (known as patient outreach recruitment or POR), wherein patients can be contacted so long as they do not express an unwillingness to receive such communication. The work highlights the benefits of this model by explaining how it, in many ways, supports and protects autonomy, beneficence, and justice for patients. The paper then describes the process of standing up the recruitment strategy, communicating the change to patients and the community, and documenting study team contact and patient research preference. Data supporting increased access to potentially eligible patients of greater diversity as well as initial researcher feedback on perceived success of POR is also shared. The paper ends with a discussion of next steps to enhance the POR process via more detailed data collection and reengagement with community stakeholders.