bluuebunny/crossref_metadata_2025 huggingface dataset:
4184 Implementation of an Opt-Out recruitment policy at Duke University School of Medicine
Authors: Mack Michelle , Roberts Jamie , Mack Dalia , Shipes Steven , Freel Stephanie A. , Stroo Marissa , McDonald Roy , Snyder Denise
Published: July 2020

OBJECTIVES/GOALS: In March 2019, Duke updated recruitment guidelines and adopted an “Engagement” policy that requires patients to ‘opt-out’ of communications regarding potential research participation. This created an opportunity to evaluate recruitment for ongoing clinical studies pre and post implementation. METHODS/STUDY POPULATION: Implementation of the new policy required new training for study teams, modification to recruitment plans, and expansion of ongoing efforts to improve direct-to-patient messaging through EPIC/MyChart tools. The impact of this new policy on overall recruitment was monitored and characterized both prior to and after implementation of the policy. Customized MyChart messages have been generated for over 22 studies, with a total of 41,386 messages sent to potential participants. RESULTS/ANTICIPATED RESULTS: Only a small number of study teams have modified their recruitment plans with transition to the new policy. This may be related to lack of understanding about policy implementation, potential recruitment opportunities, required training, resource limitations, etc. However, our case study, TMIST, had an 48% improvement in average enrollment within the first 2 months of implementation, and an almost 40% improvement in recruitment efficiency. Since becoming an “opt-out” institution, 11 study teams have implemented direct-to-patient recruitment via the MyChart patient portal. One unintended consequence we’ve noted is several different study invitations to potential participants within some patient populations. DISCUSSION/SIGNIFICANCE OF IMPACT: The new policy allows study teams to engage in direct-to-patient outreach, leading to an increase in enrollment for some studies. Incorporation of direct-to-patient messaging strategies can be a cost and resource saving measure to improve recruitment. The need to recruit similar populations demonstrated that strategic, thoughtful approaches are needed.
4475 Meeting Partners Where They Are: Tailoring Community-Engaged Research Consultation Services
Authors: Paberzs Adam , Piechowski Patricia , Poll Jordan , Spiroff Meghan , Calhoun Karen , Buyuktur Ayse , McKay Athena , Vereen Donald , Woolford Susan
Published: July 2020

OBJECTIVES/GOALS: One of the most significant challenges to community engagement experienced by Clinical and Translational Science Award (CTSA) institutions is inadequate capacity of academic and community partners to engage in collaborative research. Several CTSAs within the consortium provide consultation services to help address this gap. METHODS/STUDY POPULATION: For over 10 years, the Michigan Institute for Clinical and Health Research (MICHR), a CTSA at the University of Michigan, has provided CEnR-specific consultations to partners seeking support for a variety of needs. Consultations can be requested for assistance with identifying potential partners, developing partnership infrastructure, finding CEnR funding opportunities, and incorporating CEnR approaches into research plans. When a consultation is requested, MICHR’s Community Engagement (CE) Program responds by planning a meeting with staff and faculty who have relevant skills, expertise, and connections. After the initial meeting, the CE Program provides follow-up communication and support based on the needs of the specific request, and often facilitates connections with potential partners. RESULTS/ANTICIPATED RESULTS: The two most frequent types of consultation requests involve 1) making connections with potential researchers or community partner organizations, and 2) providing guidance on research grant applications that involve community engagement. MICHR provides approximately 50 CEnR consultations each year, which have resulted in development of new partnerships, grant submissions, and research projects that utilize CEnR principles and address community-identified health priorities. DISCUSSION/SIGNIFICANCE OF IMPACT: This presentation will describe the evolution of MICHR’s CEnR consultation process and highlight successful outcomes and lessons learned over its 12-year history. CONFLICT OF INTEREST DESCRIPTION: NA
4131 Recruitment and Retention of Individuals with a Cocaine Use Disorder
Authors: Brown Kate , Capili Bernadette
Published: July 2020

OBJECTIVES/GOALS: 1) illustrate the varied challenges individuals with a cocaine use disorder experience in daily life, 2) demonstrate techniques for empathizing and building rapport with potential subjects, and 3) identify recruitment obstacles and solutions. METHODS/STUDY POPULATION: Methods: We use a multi-source strategy to recruit our participants and employ practical techniques to enhance protocol adherence. Methods include a welcoming environment, establishing a routine with flexibility, personalized attention, and incentives for participation. Study population: Individuals with a cocaine use disorder. RESULTS/ANTICIPATED RESULTS: Understanding the life of an individual with a cocaine use disorder is paramount to successful recruitment and retention in addiction research studies. Our clinicians have been able to recruit and retain participants successfully by employing empathetic interpersonal skills, personalized attention, and health-related incentives. DISCUSSION/SIGNIFICANCE OF IMPACT: The Centers for Disease Control and Prevention estimated that 69,029 people died of a drug overdose during the period from February 2018 to February 2019, with 23%, due to cocaine. While methadone and buprenorphine-naloxone maintenance treatment allow opioid-dependent individuals achieve a sense of physical and mental stability, there is no pharmaceutical treatment to help a cocaine-dependent individual cope with cravings or the depression and anxiety that typically follow a cocaine binge. The development of a cocaine use disorder is multi-factorial and presents a significant challenge in terms of discovering treatments, identifying efficient recruitment and retention strategies is the first step for effective research.
4554 Researchers’ Experiences Working With Community Advisory Boards: How Community Member and Patient Stakeholder Feedback Impacted The Research
Authors: Brockman Tabetha A. , Albertie Monica L. , Stephenson Noreen A. , Penheiter Sumedha G. , Patten Christi A.
Published: July 2020

OBJECTIVES/GOALS: To assess researchers’ experiences working with community advisory boards (CABs) and how community member/patient stakeholder feedback impacted the research. METHODS/STUDY POPULATION: Researchers (N = 34) who presented their research to a Mayo Clinic CAB (at MN, AZ, or FL) from 2014-2017 were invited to participate in an interview in-person or by phone averaging 10-15 min. Researchers were asked “In what ways did the feedback you received from the CAB influence your research?” The validated structured 7-item interview included domains assessing potential influence that CABs had on the research: 1) Pre-research (e.g., generated ideas), 2) Infrastructure (e.g., budget preparation), 3) Research design, 4) Implementation (e.g., research recruitment), 5) Analysis, 6) Dissemination, and 7) Post-research (e.g., assist in formulating next steps). RESULTS/ANTICIPATED RESULTS: 17 interviews were completed (8 no longer at Mayo, 9 no response). Researchers presented their study to a CAB a mean of 4 years (range 3-5) before the interview. Researchers reported that the CAB had influenced their research in the following domains: 24% in pre-research, 24% infrastructure, 41% study design, 41% implementation, 6% analysis, 24% dissemination, and 18% for post-research activities. The mean total score was = 1.8 (SD = 1.7, range 0-6), of a possible range of 0-7. DISCUSSION/SIGNIFICANCE OF IMPACT: Impact of CAB feedback on the research was moderate. Ways to enhance impact could include follow-up with researchers and CAB members.
4408 Using a human-centered design process to address challenges of engaging pregnant & parenting women with opioid use disorder
Authors: Wiehe Sarah , Lynch Dustin , Moore Courtney , Cockrum Brandon , Hawryluk Bridget , Claxton Gina
Published: July 2020

OBJECTIVES/GOALS: Using a human-centered approach, IDEO, a nationally-renown human-centered design team, and Research Jam, Indiana CTSI’s patient engagement core, integrated and tailored complimentary programs to address the challenges of engaging mothers with opioid misuse around the time of birth. METHODS/STUDY POPULATION: Gathered data through focus groups, site visits, and one-on-one interviews with key stakeholders: mothers in opioid use recovery, peer recovery coaches, and other people living with or directly affected by opioid use disorder (OUD). RESULTS/ANTICIPATED RESULTS: Themes emerged around stigma (e.g., constant judgment, majority of interactions focused on addiction, addiction comes from bad choices), the healthcare system (e.g., healthcare system bias and stigma, misalignment of services and timing of need, no support for support network), and relating to recovery (very variable but generally ambiguous and uncertain process and outcomes, importance of peer recovery coaches, importance of community resources). Identified themes were used to create insights that informed the underlying concepts of an engagement strategy including support and resources for recovery coaches, and education materials for mothers with OUD. One of human-centered design’s strengths is iteration, and the materials created for this have yet to be tested and refined thoroughly to be meaningful and lasting interventions. DISCUSSION/SIGNIFICANCE OF IMPACT: Considerable insights into the lived experience of those experiencing OUD and those who support these individuals yielded tangible ways to test improved engagement and recruitment of women with OUD at the time of birth.
4052 A TL1 Team Approach to Personalization of Donor Human Milk for Preterm Infants
Authors: Harrison Natalie , Bendixen Marion M , Neu Josef , Parker Leslie A. , Lorca Graciela L.
Published: July 2020

OBJECTIVES/GOALS: Feeding preterm infants with mother’s own milk (MOM) lowers rates of sepsis, decreases necrotizing enterocolitis, and shortens hospital stay. Our objective is to determine whether a similar microbial diversity to MOM can be obtained when fresh or frozen MOM is inoculated in donor human milk (DHM). METHODS/STUDY POPULATION: Subjects included 12 mothers of infants born 100ml of MOM per day and were excluded if they had taken antibiotics within 3 days of the 1-time pumped MOM sample collection. MOM sample was divided into fresh (processed immediately) and frozen (−20°C) for 24h fractions. MOM was inoculated in DHM [referred to as refaunated milk (RM)] at 10% (RM10) and 30% (RM30) dilutions, then incubated at timepoints: 0h, 2h, 4h at 37°C. At each timepoint, total viable microbial cell counts were performed in differential or selective media along with future 16S rRNA sequencing. RESULTS/ANTICIPATED RESULTS: Microbiota expansion was detected in MOM, RM10 and RM30 over time whether fresh or frozen milk was used as the inoculum. Incubated fresh and frozen MOM had similar bacterial loads when tested on nutrient agar (10^5-10^6 CFU/mL), mannitol salt (10^6 CFU/mL), MacConkey (10^2-10^5 CFU/mL), blood agar (10^6 CFU/mL) and MRS (10^4 CFU/mL) plates. Based on these CFU counts, RM30 incubated for 2h and RM10 at 4h showed similar counts to that of MOM at 0h. DISCUSSION/SIGNIFICANCE OF IMPACT: RM, inoculated with fresh or frozen MOM, obtained a similar microbial count compared to MOM at 0h indicates that fresh or frozen MOM can inoculate DHM. 16s rRNA sequencing is ongoing. Future studies are needed to support an inoculation protocol to be used in clinical practice and human milk banking.
4290 Acoustic screening for the “wet voice” in a canine laryngeal model
Authors: Rameau Anais
Published: July 2020

OBJECTIVES/GOALS: Early dysphagia detection reduces risk of pulmonary complications, length of hospital stay, and overall healthcare costs. The biggest limitation for early detection has been the lack of a sensitive, reliable, and noninvasive screening tool. The bedside swallow examination may miss silent aspiration in up to 40% of patients. The objective of this study is to evaluate if acoustic parameters can distinguish normal and wet voice in a canine laryngeal model. Ultimately, our goal is to establish whether the sensitivity of the bedside swallow examination can be augmented with the addition of an acoustic screen in humans. METHODS/STUDY POPULATION: Two excised canine larynges were used for laryngeal phonation simulations under six different conditions over 48 hours. Acoustic recordings were obtained while the larynges were in vibration at the phonation threshold pressure. Phonation was recorded under dry conditions and when the laryngeal introitius was covered with low viscosity glycerin (9.5cP) or high viscosity glycerin (950cP), as well as in adducted and abducted conditions. The latter mimics glottic insufficiency seen in presbylarynx or vocal fold paralysis. RESULTS/ANTICIPATED RESULTS: A total of 112 voice samples were generated and analyzed for pitch, sound pressure level (SPL), % shimmer, % jitter, relative average perturbation (RAP), and noise-to-harmonics using PRAAT software. A multivariate regression model showed that pitch, SPL, % shimmer, % jitter and RAP could significantly predict wetness in abducted conditions only. Could you please add numbers and p values? DISCUSSION/SIGNIFICANCE OF IMPACT: This pilot study indicates that classic acoustic perturbation measures distinguish the dry from the wet larynx only in glottic insufficiency condition in an ex vivo canine laryngeal model. Our next step is to study whether non-linear time series analysis and machine learning can differentiate dry and wet phonation in both adducted and abducted conditions in our animal model. CONFLICT OF INTEREST DESCRIPTION: Dr. Anais Rameau is a co-founder and Chief Executive Officer of MyophonX, a wearable device used to restore speech in patients with limited phonation capacity.
4503 Adaptation of Motor Action in Children with Hemiplegic Cerebral Palsy
Authors: Dimitropoulou Katherine , Gordon Andrew
Published: July 2020

OBJECTIVES/GOALS: We study the association of adaptive decision-making, motor planning, and neuromuscular constraints, in children with hemiplegia. We examine how children scale motor decisions to body mechanics and the distance of a target while reaching in sitting/standing, and if they can recalibrate motor decisions to sudden changes in body mechanics. METHODS/STUDY POPULATION: Forty-five 6-12 year-olds with hemiplegia and 45 age/gender matched typically developing controls participate in clinical tests (i.e. balance, visual perceptual skills, etc.) and 3 experiments. Children “reach to tap” toward a target while sitting with both preferred and not preferred arms under three conditions: regular elbow extension siting and standing and elbow extension range reduced by 50% via a splint while sitting. Trials are easy, ambiguous, and difficult. Motor decisions are compared to abilities and motion sensors (IMUs) worn at wrist, arm, sternum and lumbar area, record biomechanical strategies children use under different decisions. Synchronized video analysis presents biomechanical strategies under different decisions. RESULTS/ANTICIPATED RESULTS: Data collection is still underway. A mixed models analysis is used to compare 2 (group: hemiplegic/typically developing) X 2 (arms: healthy/impaired & dominant/non dominant) X 3 (difficulty levels) the children’s decisions. Functional analysis is used to capture biomechanical strategies children use under different decisions and levels of difficulty. Exploration strategies are recorded relative to levels of difficulty. We will also compute correlations between affordance thresholds for all children and measures of sensation, range of motion, cognition and balance (in each posture). Lastly, a secondary analysis will compare behaviors of children with left/right hemisphere lesions, as they differ in spatial abilities. Preliminary results show that children with hemiplegia make errors with both their affected and unaffected side. DISCUSSION/SIGNIFICANCE OF IMPACT: Motor deficits in children with hemiplegia are the primary focus of treatments. Motor learning interventions focus on biomechanical deficits. Results from these studies expand the focus to planning and cognitive control issues underlying motor deficits.
4212 An age-dependent, rescuable defect in intestinal barrier repair is associated with an immature enteric glial network in a neonatal pig model of intestinal ischemia
Authors: Ziegler Amanda , Sheridan Anastasia E. , Pridgen Tiffany A. , Odle Jack , Van Landeghem Laurianne , Blikslager Anthony T.
Published: July 2020

OBJECTIVES/GOALS: An age-dependent restitution defect in our neonatal pig intestinal ischemia model is rescued by unknown factors within homogenized mucosa of weaned pigs. A postnatally maturing network of enteric glia regulates the epithelial barrier, so we aim to show rescue is due to replacement of glial factors. METHODS/STUDY POPULATION: Jejunal tissues from suckling or weaned pigs were assessed by RNAseq and processed for immunofluorescent histology and 3-D volume imaging. Jejunal ischemia was surgically induced in weaned pigs and injured mucosa was recovered ex vivo with or without the glial inhibitor fluoroacetate (FA) while monitoring transepithelial electrical resistance (TER). RESULTS/ANTICIPATED RESULTS: Ingenuity Pathways Analysis of RNAseq data revealed significant suppression of numerous pathways critical for epithelial wound healing in suckling pigs (Z-score <−2 for of nine key pathways). Volume imaging studies confirmed lower density (P≤0.05) and complexity of the subepithelial glial network in suckling pigs. Treatment with FA inhibited TER recovery (P<0.0001) and restitution (P<0.05) in weaned pigs, mimicking the suckling pig phenotype and supporting glia as an important regulator of restitution in our model. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings provide important evidence that a developing glial network may be critical to the postnatal development of intestinal barrier repair mechanisms. Ongoing work will explore glial-epithelial interactions in vitro to further define postnatal development of barrier repair.
4530 Elucidating the Influence of Chemotherapy (melphalan) and /or C. difficile toxin B Exposure on Beta-catenin Protein Expression in Caco-2 Monolayers
Authors: Canales Jailene , Weiss Alison , Apewokin Senu
Published: July 2020

OBJECTIVES/GOALS: We previously reported that genetic polymorphisms in the beta-catenin gene (CTNNB) are associated with the development of Clostridiodes difficile colitis during autologous stem cell transplantation (https://www-ncbi-nlm-nih-gov.proxy.libraries.uc.edu/pubmed/29594489). To biological validate these findings, we sought to evaluate the development of chemotherapy-associated Clostridiodes difficile infections by assessing the effect of C.difficile toxin B (TcdB) and of using melphalan in beta-catenin protein expression in Caco2 cells. METHODS/STUDY POPULATION: To determine the effect of melphalan and/or C.difficile toxin B on expression of Beta-catenin from human gut epithelial cells:

Adenocarcinoma cells (Caco-2) cells were seeded and allowed to grow into monolayers

Monolayers were treated with PBS, TcdB, melphalan and/or TcdB + melphalan for 24 hours and then washed with PBS

Immunofluorescence was measured on the monolayers to visualize three markers -DAPI-Nuclear Stain (blue),Actin-ccytoskeletal stain (red), B-Catenin (green)

Analysis of images with ImageJ (NIH). Statistical analysis of the effect of TcdB and/or melphalan on β-catenin protein levels was determined by One-way ANOVA

Cells stained with a primary anti-β catenin antibody and an Alexa-488 secondary antibody were evaluated by flow cytometry to quantify the effect of melphalan and/or C. difficile toxin B on Caco2 cells. RESULTS/ANTICIPATED RESULTS: Immunofluorescent intensity was higher in the control (PSS exposed) cells when compared to melphalan, TcdB and mephalan+TcdB exposed cells (p = 0.026, 0.004 and 0.049 respectively) DISCUSSION/SIGNIFICANCE OF IMPACT: A significant difference was seen in β catenin expression in Caco-2 monolayers exposed to TcdB and/or melphalan. These data support the a role of β-catenin in the pathophysiology of CDI during chemotherapy and support GWAS findings reporting a difference in CDI susceptibility based on β-catenin genotype.
4225 Evaluation of Neurotransmitters in Channelopathy-Related Epilepsy
Authors: Misra Sunita N , Czech Theresa M. , Kearney Jennifer A.
Published: July 2020

OBJECTIVES/GOALS: Variants in voltage-gated sodium channels (VGSC) are a common cause of severe early onset epilepsy. Changes in CSF neurotransmitters (NT) were identified in 2 cases of VGSC-related epilepsy. Here we investigate NT changes in patients and a novel mouse model of VGSC-related epilepsy. METHODS/STUDY POPULATION: We conducted a single site IRB approved retrospective chart review of patients with VGSC-related epilepsy who underwent CSF NT testing for diagnostic purposes. In parallel, we examined NT levels from the brains of wild-type (WT) and a novel VGSC-related epilepsy mouse model after obtaining IACUC approval. We rapidly isolated forebrain, cortex, striatum, and brainstem from 5-6 animals per sex and genotype. A combination of HPLC with electrochemical detection and mass spectrometry were used to quantify NT levels from brain samples. RESULTS/ANTICIPATED RESULTS: We identified 10 patients with VGSC-related epilepsy who received CSF NT testing. Two of these patients had abnormal NT results including changes to dopamine (DA) or serotonin (5-HT) metabolites. We analyzed NT levels from four brain regions from male and female WT and VGSC-related epilepsy mice. We anticipate that most of the NT levels will be similar to WT, however subtle changes in the DA or 5-HT metabolites may be seen in VGSC-related epilepsy. DISCUSSION/SIGNIFICANCE OF IMPACT: Patients with VGSC-related epilepsy often have autism spectrum disorder, sleep, and movement disorders. Understanding the role of aberrant NT levels in VGSC-related epilepsy may provide additional therapeutic targets that address common neuropsychological comorbidities as well as seizures.
4091 Influence of Vision and Proprioception on Motor Control in ASD
Authors: Shafer Robin L , Wang Zheng , Mosconi Matthew W.
Published: July 2020

OBJECTIVES/GOALS: Sensorimotor integration deficits are common in Autism Spectrum Disorders (ASD). There is evidence for both an over-reliance on visual and proprioceptive feedback during motor control in ASD, suggesting deficits in the ability to modulate sensory feedback processing in order to use the most reliable input. This study aims to test this hypothesis. METHODS/STUDY POPULATION: 40 persons with ASD (ages 10-33 yrs) and 25 age-, sex- and nonverbal IQ-matched controls completed precision gripping tasks under multiple proprioceptive and visual feedback conditions. Participants squeezed a force sensor with their index finger and thumb and tried to match their force output to a target force. Visual feedback of the target force (stationary bar) and their force output (bar that moved up/down with increased/decreased force) were displayed on a computer screen. Visual feedback was presented across low, medium, and high gain levels; the force bar moved a greater distance per change in force at higher gains. Proprioceptive feedback was manipulated using 80Hz tendon vibration at the wrist to create an illusion that the muscle is contracted. Force regularity (approximate entropy; ApEn) was examined. RESULTS/ANTICIPATED RESULTS: We have scored data from 18 participants with ASD and 13 control participants to date. Preliminary results from these participants indicate a Group x Tendon Vibration x Visual Gain interaction for ApEn (F = 1.559, p = 0.023). Individuals with ASD show slight increases in ApEn with 80Hz tendon vibration relative to no tendon vibration in all visual conditions. Controls showed increased ApEn during 80Hz compared to no tendon vibration at low visual gain but decreased ApEn with tendon vibration at high visual gain. These preliminary results indicate that controls shift to using a secondary source of sensory feedback (e.g., proprioception) when the primary source (e.g., vision) is degraded. However, persons with ASD do not reweight different sensory feedback processes as feedback inputs are degraded or magnified. DISCUSSION/SIGNIFICANCE OF IMPACT: Our preliminary results reveal that sensorimotor issues in ASD result from deficits in the reweighting of sensory feedback. Namely, persons with ASD fail to dynamically recalibrate feedback processes across visual and proprioceptive systems when feedback conditions change. Our results may aid treatment development for sensorimotor issues in ASD.
4261 Insulin Sensitizing Effects of Vitamin D Mediated through Reduced Adipose Tissue Inflammation and Fibrosis: Evidence from a Human Randomized Trial and Mice Studies
Authors: Yimagou Eric Lontchi , Kang Sona , Zhang Kehao , Goyal Akankasha , You Jee Young , Rosen Evan , Kishore Preeti , Hawkins Meredith
Published: July 2020

OBJECTIVES/GOALS: Vitamin D [25(OH)D], known to have anti-inflammatory and anti-fibrotic effects in other tissues, may also impact adipose tissue. We designed parallel studies in humans and rodents to define the effects of vitamin D on adipose tissue inflammation and fibrosis, and on systemic insulin resistance. METHODS/STUDY POPULATION: We performed a randomized, double-blinded placebo-controlled trial to examine the effects of repleting vitamin D at to two levels (to >30 ng/ml and to > 50 ng/ml) in 25(OH)D-deficient (<20 ng/ml), insulin resistant, overweight-to-obese humans (n = 19). A comprehensive study of whole-body insulin action was undertaken with euglycemic stepped hyperinsulinemic clamp studies, both before (1st visit) and after administration of vitamin D or placebo (2nd visit and 3rd visit). Adipose tissue fibrosis and inflammation were quantified by ‘real-time’ rt-PCR and immunofluorescence. To determine whether vitamin D’s effects are mediated through adipocytes, we performed hyperinsulinemic clamp studies and adipose tissue analysis in an adipocyte-specific vitamin D receptor knockout (VDR KO) mouse model. RESULTS/ANTICIPATED RESULTS: 25(OH)D repletion (to >30 ng/ml) was associated with reductions in adipose tissue expression of inflammatory (0.6-0.7-fold decreased expression of TNF-α, IL-6, iNOS and PAI-1) and pro-fibrotic (0.4-0.8-fold decreased expression of TGF-β1, HiF1α, Collagen I, V, VI and MMP7) factors, decreased collagen VI immunofluorescence (p = 0.02) and improved hepatic insulin sensitivity in humans, with suppression of endogenous glucose production (EGP) (1.28 ± 0.20 vs 0.88 ± 0.18 mg/kg/min, p = 0.03). Compared to wild type (WT), VDR KO mice exhibited increased adipose tissue expression of several pro-inflammatory (Tnf-α, iNos, Pai-1, Mcp-1 and F4/80; 4-10 fold) and pro-fibrotic genes (Tgf-β1, Collagen VI, and Tsp1; 2-4 fold), in concert with hepatic insulin resistance (EGP 10 ± 3 vs 3 ± 2 mg/kg/min in WT, p = 0.021). DISCUSSION/SIGNIFICANCE OF IMPACT: Collectively, these complementary human and rodent studies establish a beneficial role of vitamin D to improve hepatic insulin resistance, likely by restraining adipose tissue inflammation and fibrosis. Thus, normalizing 25(OH)D levels could have metabolic benefits in targeted individuals. CONFLICT OF INTEREST DESCRIPTION: N/A
4306 Periodontal disease and the oral microbiome in antiretroviral-treated patients with HIV
Authors: Annavajhala Medini K , Shah Jayesh G. , Weidler Jessica , Kister Karolina , Demmer Ryan T. , Wadhwa Sunil , Yin Michael T. , Uhlemann Anne-Catrin
Published: July 2020

OBJECTIVES/GOALS: People living with HIV, despite antiretroviral therapy (ART), have increased burden of inflammatory and aging-related comorbidities such as periodontitis. Oral microbiota have been linked to periodontitis, but not in the context of HIV. We aim to compare relationships between the oral microbiome and periodontal disease in HIV+ vs healthy controls. METHODS/STUDY POPULATION: In an ongoing cohort study we have been recruiting pre- and post-menopausal women with HIV+ on ART for ≥6 months and HIV- controls matched by menopausal status (target n = 30 per arm; currently HIV+: n = 30 post- and 9 pre-M; HIV-: n = 15 post- and 6 pre-M). Patients age <18 or on antibiotics within 3 mos., except prophylaxis, are excluded. Patients provide saliva, then subgingival plaque collection during a dental examination through scaling from six index teeth. Standard CDC/AAP classifications of periodontitis are used. We will perform 16S rRNA and ITS sequencing to profile bacterial and fungal communities in saliva and plaque. Linear mixed effect regression and differential abundance analyses will be used to identify microbial and mycobial oral signatures of periodontal disease severity in HIV+ and HIV- populations. RESULTS/ANTICIPATED RESULTS: We found a markedly high prevalence of severe periodontal disease in HIV+ women despite ART (59%, compared to 11% in HIV- controls). In post-menopausal women with HIV, saliva bacterial α- and β-diversity in the saliva differed significantly with periodontal disease severity. Fungal α-diversity was also significantly lower in plaque from teeth with severe loss of tissue attachment (CAL ≥4 mm). We identified bacterial and fungal taxa significantly enriched in post-menopausal HIV+ women with severe compared to no or mild periodontitis. We hypothesize, similarly, associations between the oral microbiome and periodontitis in HIV- controls. However, we expect overall diversity metrics to be significantly altered in HIV+ compared to HIV- patients, indicating long-term dysbiosis despite treatment with ART. DISCUSSION/SIGNIFICANCE OF IMPACT: Contrasting associations between the oral microbiome and periodontal disease with respect to HIV will provide evidence for the role of microbiota in accelerated aging phenotype caused by HIV. Our results would also provide rationale for interventions targeting co-morbidities in people living with HIV to account for both inflammation and dysbiosis.
4362 The Utilization of Polyethylene Glycol Fusion to Improve Facial Reanimation
Authors: Suchyta Marissa , Roh Si-Gyun , Sabbagh Diya , Morsy Mohammed , Wang Huan , Mardini Samir
Published: July 2020

OBJECTIVES/GOALS: This study’s goal is to determine whether intraoperative treatment of facial nerves with polyethylene glycol (PEG) fusion technology improves facial paralysis outcomes. Improved facial nerve regeneration in facial paralysis patients would lead to improved recovery time and effectiveness. METHODS/STUDY POPULATION: 30 rats were utilized; 15 underwent facial nerve regeneration without PEG fusion, and 15 with PEG fusion. Facial paralysis was initiated on the left by transection of the buccal and marginal mandibular branches of facial nerve. The buccal branch was repaired though microsuture technique. Neurorrhaphy sites of rats in the PEG group were exposed to calcium free saline, methylene blue, and polyethylene glycol. Nerve continuity was assessed post-operative in 5 animals in each group through electron microscopy. Functionality was assessed in the other 10 per group by EMG and whisker analysis after surgery, and weekly for 8 weeks. At 8 weeks, nerves and distal muscles were histologically analyzed. RESULTS/ANTICIPATED RESULTS: PEG fusion technology immediately restored axonal continuity following surgery, demonstrated by electron microscopy. Electrophysiology was also similarly restored across the site immediately, determined through intraoperative nerve stimulation, in the PEG fusion group. The nonintervention group showed dramatically reduced functional recovery than the PEG fusion group following surgery, shown by lower whisking activity and poor electrophysiology outcomes. Furthermore, the PEG fusion group showed statistically significant higher fascicle counts, myelination diameter, axonal diameter, and distal muscle fibers histologically. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates that polyethylene fusion technology may improve facial reanimation outcomes. PEG is already a FDA-approved drug, and thus the pathway to translational clinical application of this work may thus be streamlined, bringing new options to patients with facial paralysis.
4199 A pilot randomized controlled trial of precision care for smoking cessation in the Southern Community Cohort Study
Authors: Senft Nicole , Sanderson Maureen , Selove Rebecca , Blot William J. , Tyndale Rachel F. , Cai Quiyin , Gilliam Karen , Kundu Suman , Tindle Hilary A.
Published: July 2020

OBJECTIVES/GOALS: Precision care may engage smokers and providers in treatment but is understudied in the community. We piloted guideline-based care (GBC) alone or with Respiragene, a lung cancer polygenic risk score (PRS, 1-10), or metabolism-informed choice of medication using the nicotine metabolite ratio (NMR). METHODS/STUDY POPULATION: Daily smokers (n = 58) with stored biospecimens in the Southern Community Cohort Study were randomized 1:1:1 to GBC, PRS, or NMR, counseled to quit smoking, and co-selected FDA-approved cessation medication (nicotine replacement, varenicline) with a tobacco counselor. In PRS, precision motivational counseling was guided by PRS (i.e., lung cancer risk 10-40-fold that of never-smokers). In NMR, precision medication recommendations consisted of varenicline for faster metabolizers (NMR≥0.31) and nicotine replacement for slow metabolizers (NMR<0.31). Feasibility was defined as achieving at least 50% provider engagement (med prescription) and at least 50% patient engagement (self-reported med use). RESULTS/ANTICIPATED RESULTS: Participants were median age 59, 72% female, 81% Black, 60% with incomes <$15,000; median cigarettes/day was 15 (IQR 8-20) and 52% reported time-to-first cigarette <5 minutes, illustrating moderate nicotine dependence. Providers confirmed medication prescriptions for 40% of patients (32% GBC, 50% PRS, 37% NMR) and 83% of patients reported using medication (prescribed or unprescribed) during the study (90% GBC, 80% PRS, 79% NMR). At 6-month follow-up, 27% (n = 15) reported cessation (39% GBC, 16% PRS, 26% NMR). Among persistent smokers, 46% reported smoking at least 50% fewer cigarettes/day compared to baseline (45% GBC, 38% PRS, 57% NMR). Small sample size precluded statistical comparisons. DISCUSSION/SIGNIFICANCE OF IMPACT: Precision interventions to quit smoking are feasible for community smokers, who engaged at high rates. However, only 40% of providers supported patients’ quit attempts with medication prescriptions. Future research should test strategies to raise provider engagement in precision smoking treatment. CONFLICT OF INTEREST DESCRIPTION: R.F.T. has consulted for Quinn Emmanual and Apotex on unrelated topics. H.A.T. reported providing input on design for a phase 3 trial of cytisine proposed by Achieve Life Sciences and being a principal investigator of National Institutes of Health–sponsored studies for smoking cessation that include medications donated by the manufacturers. Other authors declare no potential conflicts of interest.
4146 Establishment of Screening Methods for G6DP Deficiency – Translational and Clinical Applications
Authors: Gomez Christian , Espinoza Ingrid C. , Harrison Kerri A. , Backus Fremel J. , Ayyalasomayajula Krishna K. , Adcock Kim G. , Stempak Lisa M. , Summers Richard L. , Ross Leigh Ann , Walker Larry
Published: July 2020

OBJECTIVES/GOALS: To develop feasible screening methods for activity of the enzyme Glucose-6-phosphate dehydrogenase (G6PD) with point of care applicability. METHODS/STUDY POPULATION: Current knowledge establishes the relevance of G6PD as a critical therapeutic determinant for effective antimalarial therapy due to the occurrence of mutations that lead to post-treatment severe adverse effects. We present our findings on development of cost effective point-of-care screening methodologies to ascertain G6PD deficiency. RESULTS/ANTICIPATED RESULTS: Using Patient Cohort Explorer and data from the Department of Pathology, we established the prevalence of G6PD deficiency at the University of Mississippi Medical Center, Jackson, MS as high as 11.8% (African-American males in all population, n = 2518). Next, for selection of potential target groups, we set up a protocol for recruitment of volunteers based on ethnic background, parental ethnicity, and medical history. G6PD activity was evaluated using point of care methods [Trinity Biotech test or CareSTART Biosensor], and Gold Standard quantitative spectrophotometric assay (LabCorp). Determinations in >20 subjects have showed comparable concordance. If used with a conservative interpretation of the signal, the Trinity Biotech test showed superior potential for use in the field relative to the CareSTART Biosensor. DISCUSSION/SIGNIFICANCE OF IMPACT: We established the prevalence of G6PD deficiency in our medical center. We have also setup tests for point-of-care assessment of G6PD. Pending evaluation of the relative tests performance, we will be in position to screen individuals and select them for a prospective clinical trial to evaluate the safety of antimalarial agents on scope of G6PD deficiency.
4513 European Ancestry as a Risk Factor for Atrial Fibrillation in Puerto Rican Hispanics
Authors: Gonzalez-Cordero Ariel
Published: July 2020

OBJECTIVES/GOALS: Atrial fibrillation (AF) not only is the most common sustained cardiac arrhythmia in clinical practice placing patients at increased risk for thromboembolic events. Hispanics despite having a higher risk factor burden for developing AF have a lower overall incidence and prevalence of AF when compared to Non-HispanicWhites (NHW). European ancestry in the African American population was found to be an independent predictor for developing AF. Consequently, we have decided to evaluate if European ancestry is an independent risk factor for Puerto Rican Hispanics(PRH) METHODS/STUDY POPULATION: This project is a secondary analysis of a Puerto Rican population sample (n = 250) fromThePharmacogenetics of Warfarin in Puerto Ricans StudyandAGenomic Approach for Clopidogrel in CaribbeanHispanics; and1000GenomeProject to establish a control group of healthy PRH population. We will evaluate the presence of 111 known single nucleotide polymorphisms(SNP)associated with AF Europeans and determine the frequency in PRH population sample.Using admixture informatic markers (AIM) analysis will determine the percentage of admixture. Statistical analysis will include the use of Pearson Product-MomentCoefficient correlation analysis and multivariate regression. For admixture will use Maximum LikelihoodEstimation Markov Chain Monte Carlo models RESULTS/ANTICIPATED RESULTS: We anticipate that higher-frequency of AF associated European SNPs and overall higher percentage of European admixture will be associated with atrial fibrillation in PRH patients. DISCUSSION/SIGNIFICANCE OF IMPACT: The expected outcomes for this study are to identify the frequency of known genetic loci associated with AF Europeans and validate their use PRH population for machine learning risk factor models.
4037 Assessing Leadership Skills in Translational Science Training: The Rockefeller University Leadership Survey
Authors: Vaughan Roger , Romanick Michelle , Brassil Donna , Kost Rhonda G , Schlesinger Sarah , Coller Barry S.
Published: July 2020

OBJECTIVES/GOALS: There is universal recognition of the importance of team science and team leadership. We have developed a semi-quantitative translational science specific team leadership competency assessment tool and have begun implementation studies to assess the impact of personalized feedback on the team science leadership skills of KL2 Clinical Scholars. METHODS/STUDY POPULATION: To create the instrument, we employed a modified Delphi approach by conducting a thorough literature review on Leadership to concretize the relevant constructs, then used these extracted constructs as a springboard for the Rockefeller Team Science Educators (TSE’s) to discuss and refine the leadership domain areas, collectively create domain-specific survey items. Further discussion helped refined the number, grouping, and wording. Scholars also contributed feedback in item development. We piloted the Leadership Survey by having all of the Rockefeller TSEs rate Clinical Scholars, and having each Scholar rate themselves. Each item was answered using a six-point Likert scale where a low score indicated poor expression and a high score represented excellent expression of the specific leadership attribute. RESULTS/ANTICIPATED RESULTS: Incorporation into a REDCap data base made consenting and rating process by TSE’s and the Scholars straightforward. The a priori domains (Foundational Leadership Competencies, Professionalism, Team Building and Team Sustainability, Appropriate Resource Use and Study Execution, and Regulatory Accountability) had high internal validity and good internal factor structure. The congruence between TSE and Scholar self-ratings were uniformly high, and discordance was often a function of “confidence” and “modesty” on the part of the scholar, rather than deficiency. Supporting comments were informative about performance barriers and mechanisms for improvement. Return of results allowed for the exploration of training gaps. Scholars were surveyed to gauge their reaction to the formal feedback. DISCUSSION/SIGNIFICANCE OF IMPACT: This quantification of team science leadership constructs has allowed for A)- the articulation of constructs essential for successful Translational Scientists to acquire during their training, B)- identification of gaps in that training and skill set, and C)- mechanisms for bolstering any identified gaps in these essential leadership constructs. CONFLICT OF INTEREST DESCRIPTION: None
4164 Body mass index, not chemotherapy is the major predictor of insulin resistance in patients with hematological malignancies
Authors: Sahinoz Melis , Engelhardt Brian , Jung Dae Kwang , Luther James Matthew , Ikizler Talat Alp
Published: July 2020

OBJECTIVES/GOALS: Cancer survivors are at increased risk for type 2 diabetes mellitus.It is not clear if diabetes susceptibility is due to shared risk factors for cancer and diabetes, such as obesity, or if it is directly related to cancer and its treatment. We investigated the association between malignancy and insulin resistance, a major risk factor for diabetes. METHODS/STUDY POPULATION: 20 adult patients with treated hematological malignancies and 21 controls without cancer were included in the study. Individuals with pre-existing diabetes were excluded. All patients underwent a 2-hour 75-gram oral glucose tolerance test (OGTT). Hyperinsulinemic-euglycemic clamps were performed to measure the steady-state glucose infusion rate (M-value) as an indicator of whole-body glucose utilization during insulin stimulation. Insulin sensitivity index was calculated by dividing M-value over the steady-state plasma insulin (M/I). RESULTS/ANTICIPATED RESULTS: Fasting or postprandial plasma glucose levels during the OGTT did not differ significantly between malignancy patients and controls (Table 2). Difference in the insulin-stimulated glucose utilization (M-value) was not statistically significant among cancer patients and controls (median, 7.2 [IQR, 6.2-10.4] vs. 7.3 [IQR, 5.5-8.9] mg/kg/min; P = 0.261). M/I index was significantly higher in malignancy patients compared to controls (median, 42.4 mg/kg/min/(µU/ml) [IQR, 33.9-67.2] vs. 23.4 mg/kg/min/(µU/ml) [IQR, 12.9-29.2], P <0.001), however insulin clearance was also lower in the controls. In multivariate analysis, only BMI was significantly associated with M-value (β = −0.2 (95% CI −0.4, −0.1), P = 0.004), and M/I (β = −2 (95% CI −3.4, −0.5), P = 0.009). DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggest that the major contributor to diabetes development after diagnosis of cancer in adults is obesity-induced insulin resistance, not malignancy related factors. These findings emphasize the importance of obesity management in long-term survival of cancer patients, as diabetes is a risk factor for mortality in this patient population.
4067 Cancer-related fatigue during combined treatment of androgen deprivation therapy and radiotherapy is associated with mitochondrial dysfunction
Authors: Liwang Josephine K. , Feng Li Rebekah , Wolff Brian , Regan Jeniece , Alshawi Sarah , Saligan Leorey
Published: July 2020

OBJECTIVES/GOALS: Combined androgen deprivation therapy (ADT) and radiation therapy (RT) is the standard of care treatment for non-metastatic prostate cancer (NMPC). Despite the efficacy, treatment-related symptoms including fatigue greatly reduce the quality of life of cancer patients. The goal of the study is to examine the influence of combined ADT/RT on fatigue and understand its underlying mechanisms. METHODS/STUDY POPULATION: Sixty-four participants with NMPC were enrolled. Fatigue was assessed using the Functional Assessment of Cancer Therapy–Fatigue. Mitochondrial function parameters were measured as oxygen consumption from peripheral blood mononuclear cells (PBMCs) extracted from participants’ whole blood. An ADT/RT-induced fatigue mouse model was developed with fatigue measured as a reduction in voluntary wheel-running activity (VWRA) in 54 mice. Mitochondrial function was assessed in the ADT/RT mouse brains using Western blot analysis of Glucose transporter 4 (GLUT4) and transcription factor A, mitochondrial (TFAM). RESULTS/ANTICIPATED RESULTS: Fatigue in the ADT group was exacerbated during RT compared to the non-ADT group. This effect was specific to fatigue, as depressive symptoms were unaffected. PBMCs of fatigued subjects exhibited decreased ATP coupling efficiency compared to non-fatigued subjects, indicative of mitochondrial dysfunction. The ADT/RT mice demonstrated a synergistic effect of ADT and RT in decreasing VWRA. Brain tissues of ADT/RT mice exhibited decreased levels of GLUT4 and TFAM suggesting that impaired neuronal metabolic homeostasis may contribute to fatigue pathogenesis. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that fatigue induced by ADT/RT may be attributable to mitochondrial dysfunction both peripherally and in the central nervous system (CNS). The synergistic effect of ADT/RT is behaviorally reproducible in a mouse model, and its mechanism may be related to bioenergetics in the CNS.