bluuebunny/crossref_metadata_2025 huggingface dataset:
High-affinity ammonium transport by Arabidopsis thaliana AMT1;4
Authors: Bindel Nino , Neuhäuser Benjamin
Published: March 2021

In plants high affinity transport proteins mediate the essential transport of ammonium across membranes. In Arabidopsis thaliana six of these AMmonium Transporters (AMTs) are encoded by the genome. All of them show a unique expression pattern. While most AMTs are highly expressed in the root, AtAMT1;4 expression is limited to the pollen grains and the pollen tube. Here, we addressed the transport characteristics of AtAMT1;4 in the heterologous Xenopus laevis oocytes system. The transport saturated and showed high affinity for ammonium with a Km value lower than 10 µM. Based on our electrophysiological analysis, we classified AtAMT1;4 as a high affinity ammonium transporter.
Mycotoxins in wheat cultivated in the Netherlands: results from eight years of field surveys
Authors: Van der Fels-Klerx H.J. , Focker Marlous , De Rijk Theo , Liu Cheng
Published: March 2021

In the period 2009–2018, an annual field survey with commercial arable farms in the Netherlands was held, to collect data on agronomics of wheat fields as well as mycotoxin concentrations of the specific wheat field at harvest. In total, 293 full farm field records over 8 years were obtained. This study aimed to investigate (i) the occurrence of deoxynivalenol (DON) and other mycotoxins, as well as correlations between these mycotoxins, and (ii) the relationships between agronomics and the DON concentration in wheat kernels for wheat cultivated in the Netherlands. Results showed that mycotoxins most frequently observed in concentrations above the limit of quantification were DON, enniatin B and B1, HT-2 toxin, zearalenone (ZEN) and nivalenol. On average, DON was detected in 54% of the samples (> 50 µg/kg) ranging from 19 to 92% depending on the year. Positive samples (> 50 µg/kg) had DON concentrations ranging 53–15,400 µg/kg, with a median of 228 µg/kg. Co-occurrence between DON and ZEN as well as between each of DON and ZEN with their modified forms was confirmed by the data of this study. The year influenced the DON concentration in wheat the most, followed by the region. The results of this study show that DON levels in wheat can only be influenced in a limited manner by agronomic practices such as the use of fungicides against Fusarium spp. around flowering, crop rotation, or the use of resistant wheat cultivars.
What Are Abstract Concepts? On Lexical Ambiguity and Concreteness Ratings
Authors: Löhr Guido
Published: March 2021

In psycholinguistics, concepts are considered abstract if they do not apply to physical objects that we can touch, see, feel, hear, smell or taste. Psychologists usually distinguish concrete from abstract concepts by means of so-calledconcreteness ratings. In concreteness rating studies, laypeople are asked to rate the concreteness of words based on the above criterion. The wide use of concreteness ratings motivates an assessment of them. I point out two problems: First, most current concreteness ratings test the intuited concreteness of word forms as opposed to concepts. This ignores the ubiquitous phenomenon of lexical ambiguity. Second, the criterion of abstract concepts that the instruction texts of rating studies rely on does not capture the notion that psychologists working on abstract concepts are normally interested in, i.e., concepts that could reasonably be sensorimotor representations. For many concepts that pick out physical objects, this is not reasonable. In this paper, I propose a characterization of concrete and abstract concepts that avoids these two problems and that may be useful for future studies in psychology.
Pediatric Primary Care Provider Comfort with Mental Health Practices: A Needs Assessment of Regions with Shortages of Treatment Access
Authors: Bettencourt Amie F. , Ferro Rebecca A. , Williams Jami-Lin L. , Khan Kainat N. , Platt Rheanna E. , Sweeney Sarah , Coble Kelly
Published: March 2021

Objectives

Nearly 50% of children with a mental health concern do not receive treatment. Child Psychiatry Access Programs like Behavioral Health Integration in Pediatric Primary Care (BHIPP) address regional shortages of mental health treatment access by providing training and consultation to primary care providers (PCPs) in managing mental health concerns. This study assessed PCPs’ comfort with mental health practices to inform expansion of BHIPP services.

Methods

Pediatric PCPs in 114 practices in three rural regions of Maryland were recruited to participate in a survey about their comfort with mental health practices and access to mental health providers for referral. Descriptives, Friedman’s test, and post hoc pairwise comparisons were used to examine survey responses.

Results

Participants were 107 PCPs. Most respondents were physicians (53.3%) or nurse practitioners/physician’s assistants (39.3%). Friedman’s test, χ2(7)= 210.15, p<.001, revealed significant within and between-group differences in PCP comfort with mental health practices. Post hoc pairwise comparisons indicated greater comfort providing mental health screening and referrals compared to prescribing psychiatric medications, providing psychoeducation or in-office mental health interventions. A Wilcoxon-signed rank test showed significantly more respondents agreed they could find a therapist than a psychiatrist in a timely manner, Z= −5.93, p<.001.

Conclusions

Pediatric PCPs were more comfortable with providing mental health assessment and referrals than treatment. However, PCPs reported difficulty finding therapists and psychiatrists for their patients. Findings underscore the need for longitudinal training to increase PCP comfort with mental health treatment. Additionally, strategies such as telepsychiatry are needed to address the disproportionate need for child psychiatrists.
Is God Invisible?
Authors: Taliaferro Charles , Evans Jil
Published: March 2021

In this volume, Charles Taliaferro and Jil Evans promote aesthetic personalism by examining three domains of aesthetics - the philosophy of beauty, aesthetic experience, and philosophy of art - through the lens of Judaism, Christianity, Islam, theistic Hinduism, and the all-seeing Compassionate Buddha. These religious traditions assume an inclusive, overarching God's eye, or ideal point of view, that can create an emancipatory appreciation of beauty and goodness. This appreciation also recognizes the reality and value of the aesthetic experience of persons and deepens the experience of art works. The authors also explore and contrast the invisibility of persons and God. The belief that God or the sacred is invisible does not mean God or the sacred cannot be experienced through visual and other sensory or unique modes. Conversely, the assumption that human persons are thoroughly visible, or observable in all respects, ignores how racism and other forms of bias render persons invisible to others.
Visual Control of Locomotion
Authors: Fajen Brett R.
Published: March 2021

This Element examines visual perception in the context of activities that involve moving about in complex, dynamic environments. A central theme is that the ability of humans and other animals to perceive their surroundings based on vision is profoundly shaped by the need to adaptively regulate locomotion to variations in the environment. As such, important new insights into what and how we perceive can be gleaned by investigating the connection between vision and the control of locomotion. I present an integrated summary of decades of research on the perception of self-motion and object motion based on optic flow, the perception of spatial layout and affordances, and the control strategies for guiding locomotion based on visual information. I also explore important theoretical issues and debates, including the question of whether visual control relies on internal models.
20902 Elucidation of Cardioprotective Mechanisms via Human Models of Chemotherapy-Induced Cardiotoxicity
Authors: Uche Nnamdi , Dai Qiang , Lai Shuping , Benjamin Ivor
Published: March 2021

ABSTRACT IMPACT: This work should provide further insights to mechanisms of the negative consequences of chemotherapy drugs, specifically in the cardiovascular system. OBJECTIVES/GOALS: Cardiotoxicity remains a safety concern in the development or utilization of chemotherapeutics largely due to the gap in knowledge of the mechanisms of toxicity. The pathophysiology of this cardiotoxicity has not been fully elucidated but data from our lab as well as other recent studies hint toward implications of mitochondrial (mito) biogenesis. METHODS/STUDY POPULATION: Prophylactic use of the beta-blocker carvedilol as well as the ACE inhibitor enalapril have been shown to inhibit the development of anthracycline-induced toxicity, but the mechanism of this cardio-protection remains elusive. To explore this, human stem cell-derived cardiomyocytes and endothelial cells will be either treated with the anthracycline doxorubicin or pretreated with carvedilol or enalapril followed by doxorubicin treatment before cellular lysates are harvested. Western blotting and qPCR will be performed to determine the expression of mito biogenesis markers including Nrf1, TFAM and the master regulator of mito biogenesis, PGC-1α. RESULTS/ANTICIPATED RESULTS: We anticipate that doxorubicin treatment alone will result in decreased expression of the mito biogenesis markers Nrf1, TFAM and PGC-1α and that pretreatment with either carvedilol and/or enalapril prior to doxorubicin treatment will either prevent or reverse this. DISCUSSION/SIGNIFICANCE OF FINDINGS: Doxorubicin’s role in causing mitochondrial dysfunction as well as suppression of biogenesis has already been established. Ideally, generation of new mitochondria would offset the occurrence of dysfunctional mitochondria. Confirming carvedilol/enalapril’s involvement with mito biogenesis would provide a mechanism of cardio-protection.
52500 Characterization of a Series of 1,4-diaryl-pyrazolo-pyridinones as Anti-Leishmanial Agents
Authors: Corman Hannah N. , Shoue Douglas A. , Melancon Bruce J. , McDowell Mary Ann
Published: March 2021

ABSTRACT IMPACT: The first-line chemotherapies used to treat leishmaniasis are highly toxic intravenous antimonials yet drug resistance has begun to develop, causing the use of oral treatment options with high price tags; there is a strong need for new, safe, and effective chemotherapeutic agents to treat leishmaniasis. OBJECTIVES/GOALS: This study was conducted in order to identify novel chemical compounds that exhibit anti-leishmanial activity and to further characterize their efficacy and toxicity in in vitro and in vivo systems in the hopes of future chemotherapeutic developments. METHODS/STUDY POPULATION: A total of 28 unique 1,4-diaryl-pyrazolo-pyridinone (1,4-DAPP) compounds were synthesized and anti-leishmanial efficacy and host cell toxicity were determined using L. donovani mCherry-expressing amastigotes and THP-1 macrophages. Additional pharmacokinetic analyses of a potent 1,4-DAPP compound were conducted, revealing a potential metabolite structure. A select group of the novel compounds were screened in a cutaneous leishmaniasis (CL) murine model using L. major mCherry-expressing parasites and female Balb/C mice. The treatment consisted of 10 intralesional injections of compound over a period of 4 weeks, while lesion growth was monitored via fluorescence and manual measurements. RESULTS/ANTICIPATED RESULTS: Four experimental compounds had IC50 values less than 5 micromolar, providing similar anti-leishmanial activity to Miltefosine. Compound 9279817 had a clearance almost twice the rate of normal hepatic blood flow and had a relatively high volumes of distribution, indicating this compound is rapidly cleared and distributes into tissues. In vitro rat liver microsome assays suggest a rapid metabolism of 9279817 and MS/MS results suggest this metabolite is most likely formed via oxidation of the sulfur on the lower aryl ring. This sulfoxide metabolite has similar efficacy as the parent compound and does not exhibit toxicity in vitro. Three of the experimental compounds behaved similarly to the antimony positive control in the murine CL model. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study revealed a novel structural class of compounds that have anti-leishmanial activity. Experiments show compounds with similar efficacy to Miltefosine while having significantly less cytotoxicity, suggesting that the 1,4-DAPP structural class could be further developed as a potential chemotherapeutic.
27042 Pressure-pain thresholds at baseline and in response to isometric exercise in Achilles tendinopathy
Authors: Sara Lauren , Yang Karis , Hart Meggie Rose , Bement Marie Hoeger , Hunter Sandra
Published: March 2021

ABSTRACT IMPACT: Baseline presentation in AT (higher upper trapezius PPT with no difference at calf or tendon) may suggest a mechanism for persistent symptoms: with more advantageous central pain processing and no tradeoff peripherally, they may choose to continue their usual activities without regard for further damage to the affected tendon. OBJECTIVES/GOALS: Exercise-induced hypoalgesia, a reduction in pain with exercise, is often observed in healthy populations but is not well established in Achilles tendinopathy (AT). The aim was to compare pressure-pain threshold (PPT) at baseline and after fatiguing isometric exercise in AT and healthy controls. METHODS/STUDY POPULATION: 21 participants were recruited for the study: 7 AT (26.5 ±8.8 yrs), 14 control (22.1 ±3.2 yrs). After a familiarization session, participants completed an experimental session that involved performance of intermittent maximal voluntary isometric contractions (MVICs) (2s:2s duty cycle) in a Biodex3 dynamometer (Biodex Medical, Shirley, NY) for 4 minutes. PPT was measured at the medial gastrocnemius (calf), Achilles tendon, and upper trapezius at baseline and immediately following the fatiguing isometric task using a Somedic Algometer (Somedic AB, Sweden). Data are expressed as Mean(SD). Change in PPT is expressed as a percentage of baseline PPT. Units for PPT are kPa. A priori alpha was set to 0.05. RESULTS/ANTICIPATED RESULTS: There was no change in tendon or calf PPT following isometric exercise in AT (tendon: p=0.78; calf: p=0.76), while both increased (i.e., exercise-induced hypoalgesia) in controls (tendon: 9.5(17.8), p=0.03; calf: 21.3(22.7), p<0.01). Neither group experienced a post-exercise change in upper trapezius PPT (AT: p=0.35; control: p=0.37). There was no between-group difference in baseline calf (p=0.14) or tendon (p=0.19) PPT. However, baseline and post-exercise upper trapezius PPT were significantly higher in AT (baseline: 335.6(194.8); post-exercise: 321.2(170.1)) than in controls (baseline: 193.7(75.1), p<0.01; post-exercise: 198.1(79.1), p<0.01). DISCUSSION/SIGNIFICANCE OF FINDINGS: These findings suggest: (1) in persons with AT, central pain processing is altered at baseline, but unaffected in response to isometric fatiguing exercise; and (2) in persons with AT, peripheral pain processing is unaffected at baseline, but is altered in response to this mode and dosage of fatiguing isometric exercise.
19734 L-type calcium channels in cerebellar neuron development and motor learning
Authors: O’Quinn DeAnna , Williams Aislinn , Parker Ashley , Myers Bryn , Plumb Ashley , Wen Hsiang , Lauffer Marisol
Published: March 2021

ABSTRACT IMPACT: We aim to understand how LTCCs impact cerebellar function. OBJECTIVES/GOALS: L-type calcium channels (LTCCs) are important in activity-dependent neurite outgrowth, which comprises neurite initiation and elongation. We used cerebellar granule neurons (CGNs) to differentiate between LTCC effects on neurite initiation vs elongation. We also tested cerebellar function in mice lacking specific LTCCs with behavioral assays. METHODS/STUDY POPULATION: CGNs were cultured from 129SvEv mouse pups at P4-P6. Potassum chloride (50mM) was used to stimulate neuronal cultures for 24 hours. Isradipine (20nM) was added to culture medium to inhibit all LTCCs for 1 hour. For Cav1.2 deletion, we crossed Cav1.2 conditional knockout mice (Cav1.2-cKO) to Syn-Cre mice (for deletion in most neurons) or Atoh1-Cre mice (for deletion in CGNs). The Cav1.2-cKO line was maintained on a 129SvEv background. For constitutive Cav1.3 deletion, mice were maintained on a C57BL/6NTac. Behavioral tasks included open field, rotarod, and Erasmus Ladder. Data were analyzed with sexes combined and separated to assess for sex as a biological variable. Studies were analyzed by one-way ANOVA, two-way ANOVA, or generalized linear mixed model, where appropriate. RESULTS/ANTICIPATED RESULTS: CGNs exhibited an increase in neurite initiation but not elongation when stimulated with potassium chloride, consistent with previous reports of activity-dependent neurite outgrowth in this cell type. LTCC inhibition with isradipine blunted KCl-induced neurite initiation. We observed no change in the length of either primary or secondary neurites with isradipine treatment with or without KCl stimulation. In our behavioral experiments, we observed no deficits in open field, rotarod, or Erasmus Ladder when Cav1.2 was deleted in most neurons (driven by Syn-Cre expression) or in cerebellar granule neurons (driven by Atoh1-Cre expression). In contrast, loss of Cav1.3 was associated with impaired motor learning in the rotarod task without evidence of ataxia on Erasmus Ladder. DISCUSSION/SIGNIFICANCE OF FINDINGS: We show a specific role for LTCCs in activity-dependent CGN neurite initiation. While loss of Cav1.2 does not affect motor learning, loss of Cav1.3 does impair motor learning. Our results help expand our understanding of LTCC function in cerebellar neurodevelopment and function.
34380 Cadherin complexes recruit PIWIL2 to suppress transposons and pro-tumorigenic transformation
Authors: Risner Alyssa , Nair-Menon Joyce , McDowell Colin , Gangaraju Vamsi , Kourtidis Antonis
Published: March 2021

ABSTRACT IMPACT: This study has uncovered a novel surprising mechanism involving the epithelial adherens junctions and transposon regulation that can deepen our understanding of tumorigenesis. OBJECTIVES/GOALS: Recent studies show that genomic instability in 50% of tumors can be attributed to increased transposon activity, but the the reasons for this activity are unknown. We have evidence of a novel mechanism linking adherens junctions with transposon regulation. We hypothesize that adherens junctions suppress transposons to maintain genomic integrity. METHODS/STUDY POPULATION: We observed co-localization of PIWIL2 with adherens junction components of well differentiated epithelial breast, kidney and colon cell lines MCF10A, MDCK and CACO2, respectively, through immunofluorescence staining, confocal microscopy, and co-immunoprecipitation studies. Breast cancer cell lines MCF7 and MDA-231 were also observed using immunofluorescence to determine the localization of PIWIL2 in cancer cell lines. shRNA knockdown of PIWIL2 in MCF10A cells, followed by western blot, immunofluorescence, and qRT-PCR was performed to confirm the knockdown, observe if transposons were upregulated, and determine the extent of DNA damage to the genome by the marker gamma-H2AX. RNA-seq will be performed to determine piRNA sequences and possible targets of PIWIL2. RESULTS/ANTICIPATED RESULTS: Our data have revealed an interaction of E-cadherin and p120 catenin, core components of adherens junctions, with PIWIL2, a member of the Argonaute family of proteins and a key component of the piRNA processing pathway that is responsible for transposon silencing. piRNAs (PIWI-interacting RNAs) are a distinct class of small RNAs that bind to PIWI proteins, and aid in transposon degradation. We found co-localization of PIWIL2 with E-cadherin and p120 catenin at adherens junctions of well-differentiated epithelial cells, whereas this association was lost in cancer cells. Furthermore, our data show that E-cadherin depletion results in mis-localization of PIWIL2 and TDRD1, another member of the PIWI complex. E-cadherin depletion also results in upregulation of transposons and ?-H2AX, an indicator of DNA damage. DISCUSSION/SIGNIFICANCE OF FINDINGS: Since both loss of junctional integrity and increased transposon activity are universal events in cancer, this study has the potential to further our understanding of the causes of tumorigenesis. Understanding the mechanisms of transposon regulation has the potential to lead to a therapeutic target in the future.
61892 Systemic TLR3-targeting Combinatorial Chemokine Modulation Sensitizes Murine Tumors to PD-1 Blockade
Authors: Kokolus Kathleen M. , Obermajer Nataša , Basse Per , Kalinski Pawel
Published: March 2021

ABSTRACT IMPACT: This work will lead to improved efficacy of immunotherapy directly impacting the survival of patients with hard to treat cancers. OBJECTIVES/GOALS: Immune checkpoint inhibitors (ICI) are most effective against ‘hot’ tumors highly infiltrated with cytotoxic T lymphocytes (CTLs) but have not worked well in poorly infiltrated ‘cold’ tumors. Thus, we are working to achieve a pretreatment regimen that will create a favorable immune profile allowing more effective ?PD-1 therapy. METHODS/STUDY POPULATION: BALB/c or C57BL/6 mice were inoculated with CRC murine cells CT26 or MC38, respectively. Mice were inoculated by two injection types: subcutaneous (SC), for systemic therapy, or intraperitoneal (IP), for local therapy. Tumor-bearing mice were given a two dose course of CKM consisting of IFN-? and rintatolimod via IP injection. Following CKM administration, mice were treated with three doses of ?PD-1 via IP injection. Mice were monitored for the kinetics of tumor growth and survival following treatment. The tumor microenvironment of treated mice was analyzed for production of chemokines, inflammatory cytokines and immune cell infiltration. RESULTS/ANTICIPATED RESULTS: CKM consisting of combination IFN-? and rintatolimod, but neither monotherapy alone, sensitized murine CRC tumors to subsequent ?PD-1 treatment. In both CT26 and MC38 tumor-bearing mice, tumor growth was hindered by CKM plus ?PD-1 treatment, independently on the route of treatment (local or systemic). Mice which experienced complete tumor regression were protected from re-challenge with a dose of tumor cells double that of the initial inoculation. Sensitizing tumors to ?PD-1 did not require intratumoral CKM administration and was observed with systemic application at distant sites. In accordance with these observations we expect that systemic CKM will induce strong increases of total and tumor-specific CTL counts in the tumor tissues as measured by both PCR and flow cytometry. DISCUSSION/SIGNIFICANCE OF FINDINGS: CKM sensitizing cold tumors to ?PD-1 indicates that intratumoral CTLs are an important factor dictating therapeutic effectiveness, independent of other factors such as tumor mutational load. The benefit of the sequential short-term CKM followed by routine ?PD-1 make this strategy feasible for rapid inclusion of into routine immunotherapy plans.
40008 COMBINED CRISPR/CAS9 AND AAV FOR THE GENERATION OF CONDITIONAL ISOGENIC GENE KNOCK-INS
Authors: Boddu Prajwal , Gupta Abhishek , Waldman Todd , Pillai Manoj
Published: March 2021

ABSTRACT IMPACT: We describe a novel methodology that combines CRISPR/Cas9-induced double stranded DNA breaks with homology dependent repair from an adeno associated virus (AAV) encoded template to generate single-allele edited isogenic cell line models of cancer-associated mutations with high efficiency. OBJECTIVES/GOALS: Conventional approaches to creating isogenic knock-ins, to model disease-associated mutations, are limited by poor efficiency and loss of the mutant allele on extended culture. We present an optimized editing approach combining CRISPR/Cas9 with Adeno-associated virus, using mutant SF3B1 as a prototype. METHODS/STUDY POPULATION: Left and right homology arms for SF3B1 were PCR amplified and cloned into pAAV-SEPT-Acceptor plasmid (containing a chimeric intron, neomycin resistance cassette and polyA tail). The disease-associated K700E mutation was introduced by site-directed mutagenesis. Single guide RNA (sgRNA) complexed with recombinant Cas9 along with the AAV donor were delivered into K562 cells, G418 resistant clones selected, and screened for integration by PCR. Confirmed clones were then transduced with a doxycycline-inducible Cre-recombinase containing lentiviral vector. Inducible expression of Cre-recombinase and expression of the mutant allele were confirmed by Western blot and Sanger sequencing respectively. RESULTS/ANTICIPATED RESULTS: Targeted-integration efficiencies among the Neo-resistant clones, generated by AAV-alone and AAV+CRISPR/Cas9, were 16% and 94%, respectively. Single cell cloning after Cre-mediated excision of loxp was unsuccessful presumably due to toxicity of the K700E mutation. To overcome this limitation, clones were transduced with doxycycline-inducible Cre-recombinase lentiviral vector. Doxycycline induction of Cre-recombinase resulted in reliable excision of the loxp cassette and expression of mutant allele at about 50% variable allele frequency (as determined by Sanger sequencing). The approach was validated in additional cell lines and for introduction of N-terminal FLAG tag for SF3B1. DISCUSSION/SIGNIFICANCE OF FINDINGS: Combining AAV and CRISPR/Cas9 can generate scalable single-dominant allele mutants with high precision and efficiency compared to AAV or CRISPR alone. Together with inducible Cre-recombinase, our approach can generate isogenic models where the mutation confers a growth disadvantage.
46942 Risk factors, prevention, and screening practices for human papilloma virus associated cancers in Central-Eastern Puerto Rico
Authors: Cruz-Martinez Lilibeth , Gonzalez-Galarza Darleen , De Jesus-Monge Wilfredo E.
Published: March 2021

ABSTRACT IMPACT: The impact of this study is that the results may lead to the development of effective educational programs and a comprehensive cancer control program while verifying patients and medical care providers adherence and compliance with cancer clinical guidelines. OBJECTIVES/GOALS: The objective of this study is to assess risk factors, preventive measures, and screening practices for human papilloma virus (HPV) associated cancers in a sub-population in Central-Eastern Puerto Rico (PR). METHODS/STUDY POPULATION: This is a sub-analysis from an annual descriptive cross-sectional questionnaire of risk factors, preventive measures, and screening practices for cancer in PR administered at a private hospital campus using a convenience sample of healthy and non-healthy adults. RESULTS/ANTICIPATED RESULTS: Out of 345 enrolled subjects in 2019 for the questionnaire, 67 were enrolled by the first author, from which 66 (19%) subjects qualified for this sub-analysis for completing the study: 79% females. When analyzing HPV risk factors, 5% of the participants were smokers. Eleven percent of the subjects received the preventive HPV vaccine. Among those non-vaccinated and eligible for vaccination, 95% were willing to get it. Seventy one percent of females 21-29 years old and 97% of 30-65 years olds had age-appropriate cervical cancer screening. DISCUSSION/SIGNIFICANCE OF FINDINGS: Despite the low prevalence of HPV vaccination, almost all of the subjects within the age range for HPV vaccination were willing to get it. Also, there was a lower prevalence of cervical cancer screening in females 21-29 years old when compared with 30-45 years old. In conclusion, there is a need for more education about HPV associated cancers and vaccine.
79885 Self-Weighing in Adolescents with Obesity: Attitudes of Teens and their Parents.
Authors: Bramante Carolyn
Published: March 2021

ABSTRACT IMPACT: Obesity is a quickly growing pandemic that negatively impacts health, and clinicians and clinics must employ all evidence-based tools (such as self-monitoring) to help patients control their weight. OBJECTIVES/GOALS: The objective of this study was to understand patient and parent perspectives on using daily self-weighing for adolescents with obesity who are seeking obesity treatment. The secondary objective was to understand perspectives on connecting smart-scales to the electronic medical record for messaging, feedback, and reminders between visits. METHODS/STUDY POPULATION: Thirty adolescents with obesity who were seeking obesity treatment at a tertiary pediatric weight management clinic were recruited into a single-arm feasibility study to create and assess a connection between blue-tooth scales and the electronic medical record. These adolescents and their parents were then approached about conducting exit interviews about their experience in the feasibility study -- their perspectives on connecting bluetooth scales connected to the electronic health record and using daily self-weighing at home to help them reach their healthy weight goals. The interviews were conducted by a trained interviewer who was not a PI or Co-I on the feasibility study, recorded, and transcribed. The interviews were organized on themes including technical challenges, mood, stress, clinic feedback. RESULTS/ANTICIPATED RESULTS: The main theme expressed by participants and parents was related to past experiences of their weight loss journey. Sub-themes included: technical challenges with apps, parental involvement in weighing, being told by clinicians to weigh, and intervention impact. Most parents desired more directions and help with setting up the app connection to the EHR. Most parents did not ask their child daily about their weight status as they did not want to cause stress. Some adolescents found it stressful when parents asked about daily weight status; others found it helpful or at least not stressful. Most participants had never been advised by their clinician to regularly self-weigh. Most found it helpful to monitor their weight regularly. Most asked for reminders from clinic to weight and for feedback on weight between visits. DISCUSSION/SIGNIFICANCE OF FINDINGS: Overall, adolescents with obesity reported self-weighing as being helpful and most wanted some, but not daily, involvement from parents. Most parents wanted additional technological support to create the scale set-up. Nearly all parents and adolescents wanted the weights to be connected to clinic, and for there to be feedback from clinic on weight.
92090 Novel use of REDCap to develop a Crisis Management Decision-Support Portal at an Academic Medical Center
Authors: Tafuto Barbara , Master Megha , Lechner Doreen Waldron
Published: March 2021

ABSTRACT IMPACT: Implementation of digital and mobile applications in clinical research crisis response protocols can mitigate their impact on clinical research. OBJECTIVES/GOALS: Crisis management is fundamental to ensuring the protection of human subjects during a clinical trial. Mobile apps have the capacity to allow for quick access to crisis response plans and can serve to mitigate their impact on clinical research. Electronic data capture tools can be used to create digital applications for such a response. METHODS/STUDY POPULATION: The Clinical Research Center at Rutgers University transferred a paper-based crisis management response plan to a digital mobile application format using Vanderbuilt’s Research Electronic Data Capture Tool (REDCap). REDCap’s branching logic allowed for programming a decision support functionality to guide users through 3 specific crises. (1) threatening or aggressive study subject behavior; (2) clinical research center break in or theft; and (3) adverse event observed for ongoing or closed clinical research study. Applicable U.S. Code of Federal Regulations, IRB guidelines, institutional policies and procedures were also used as a component of the mobile development. RESULTS/ANTICIPATED RESULTS: The Crisis Management Decision-Support Portal within the Clinical Research Center has an interactive structure. The use of branching logic demonstrates the ability for users to answer each question and be guided to appropriate responses specific to selected criteria related to each event. The tool contains a self-correct function by providing a reset option after answering each section. The portal itself can be accessed using any computer or cellphone with an internet connection. It provides the users with appropriate criteria to determine to exact communication and management protocols for reporting for the crisis event they are witnessing. As users access the portal, usage data can be collected, tracked, and stored. DISCUSSION/SIGNIFICANCE OF FINDINGS: The REDCap platform offers the opportunity to digitize crisis management protocols that ensure professionals have easy access to appropriate responses to crises at the center. The use a digital application rather than paper allows for a CTSA sponsored hub to mitigate damage, simply build new protocols, modify existing protocols, and track usage.
37606 Enhanced radiation therapy using chlorin-e6 conjugated gold nanoparticles
Authors: Jenkins Samir V. , Griffin Robert J.
Published: March 2021

ABSTRACT IMPACT: Improved radiation treatment will yield higher doses at the tumor site, while reducing damage to healthy tissue, which will improve clinical outcomes. OBJECTIVES/GOALS: Development of gold nanoparticles covalently linked to a photosensitizer for use to enhance radiation therapy. The particles will be thoroughly characterized and the mechanism uncovered. The efficacy of these particles will be tested in a murine system. METHODS/STUDY POPULATION: Gold nanoparticles were synthesized and coated with amine-terminated poly(ethylene) glycol then covalently conjugated to chlorin e6, a known, FDA approved photosensitizer. The system was characterized using UV-Vis spectroscopy, transmission electron microscopy, and nanoparticle tracking analysis. The generation of reactive oxygen species following X-irradiation was measured. Enhanced cell killing was measured clonogenically and in vivo efficacy and tumor pathology was assessed in a murine system. Further studies will determine the optimum combination of particle shape, photosensitizer structure, and ratio of components, as well as the optimal dosing schedule. RESULTS/ANTICIPATED RESULTS: Conjugation of the particle to the photosensitizer was successfully achieved, and the molecule was detectable by UV-Vis spectroscopy. TEM and NTA showed no aggregation of the particles, and an increase in reactive oxygen species generation was observed. The conjugates significantly increased cell killing during radiation treatment, while neither the particle alone or the photosensitizer significantly affected clonogenic survival at the same concentrations. Pathology of breast tumors grown in immunocompetent mice showed a significant increase in necrotic tissue following a single 20 gy treatment when the conjugate was present. DISCUSSION/SIGNIFICANCE OF FINDINGS: Radiation therapy is widely used clinically and it is a highly localized form of treatment. However, the total dose of radiation is limited largely to prevent injury to adjacent normal tissue. This conjugate has the potential to increase the effective dose in the tumor thereby reducing damage to healthy tissue and providing a more effective therapy.
95349 T1-T4 in 3 (Minutes)
Authors: Croisant Sharon , Goldberg Alisha , Prochaska John , Singleton Chantele , Bohn Krista , Hallberg Lance
Published: March 2021

ABSTRACT IMPACT: The purpose of the T1-T4 in 3 Minutes program is to improve trainees’ capacity for communication of complex to a non-scientific audience as well as to ensure that our community stakeholders have access to, and understanding of, ongoing clinical and translation research OBJECTIVES/GOALS: The T1-T4 in 3 Program: ο Increases knowledge of research across institution; ο Increases capacity of trainees to convey complex science to lay audiences, funders, colleagues, and the media; ο Increases health and scientific literacy; ο Bridges gaps between trainees and potential entrepreneurial mentors METHODS/STUDY POPULATION: T1-T4 in 3 (Minutes) is an adaptation of the University of Queensland’s Three Minute Thesis competition in which PhD students present their thesis in 3 minutes or less to a lay audience. The competition enables them to cogently communicate their ideas and research findings to a non-specialist audience. Our adapted version, T1-T4 in 3, requires a presentation in three minutes or less to a lay audience, but rather than a thesis, the topics are on trainees’ research, and in this particular case, an idea for a commercial venture. The competition provides awards for the first- and second-best projects as determined by a panel of judges, and a ‘people’s choice’ award determined by a lay audience. RESULTS/ANTICIPATED RESULTS: This exercise is anticipated to improve trainees’ capacity for communications as well as ensure that community stakeholders and research and business community partners have access to, and understanding of, ongoing clinical and translation research with potential commercial applications. Further, the increased ability of our faculty and trainees to effectively communicate complex science to the public and other audiences’‘ including potential funders’‘ supports additional stakeholder dissemination mechanisms by increasing their confidence in their abilities to converse with non-specialists about their research, thus increasing the likelihood of participation in other community-based activities. DISCUSSION/SIGNIFICANCE OF FINDINGS: To increase ITS commercialization efforts, we envision involving numerous external partners to educate, fund, and support new ventures. T1-T4 in 3 judges will include commercialization scholars from regional and national institutions as well as pharmaceutical entities and regional angel investors.
20184 A Hypothesis-Driven Parametric Study of a Computational Dermal Replacement Model
Authors: Sohutskay David , Tepole Adrian Buganza , Voytik-Harbin Sherry
Published: March 2021

ABSTRACT IMPACT: This work will be used to improve the design of engineered dermal replacements that can be used to treat difficult-to-heal wounds such as burns or ulcers. OBJECTIVES/GOALS: Wounds of the skin are among the most common and costly medical problems experienced. Engineered dermal replacements have been developed to improve outcomes, but the optimal design features are unknown. Here we describe a hypothesis-driven study of scaffold parameters using a computational model of wound healing to simulate a variety of treatments. METHODS/STUDY POPULATION: The computational model, which was informed by animal data, was used to simulate cell, cytokine, and collagen density fields. There are reciprocal mechanobiological interactions between the cells and collagen that guide the wound healing process. We analyzed initial wound properties such as scaffold stiffness, microstructure, degradation, and wound geometry by running a one-at-a-time order-of-magnitude parameter change. We then conducted a derivative-based local sensitivity analysis for simulated experimental conditions and constructed a surrogate model of wound contraction using Gaussian process regression. RESULTS/ANTICIPATED RESULTS: We conducted finite element model simulations of scaffolds that varied in physical properties. A sensitivity analysis demonstrated that wound contraction was highly sensitive to collagen fiber stiffness and density. Wound contraction rate was also dependent on initial wound size and surface area. Collagen fiber orientation in the scaffolds affected contraction directionality and the orientation of the final wound area. A Gaussian process regression model was fit to the simulation results for use in rapid prototyping of scaffolds for design optimization. The Gaussian process model was able to reproduce the wound contracture for training and test cases. DISCUSSION/SIGNIFICANCE OF FINDINGS: This work further analyzes a computational model of wounds treated with collagen scaffold dermal replacements. The hypothesis driven analysis of the model suggested several key design features of scaffolds. The model surrogate will further be used for the purposes of prediction and optimization of tissue regeneration outcomes.
27337 Characterizing Temporal Patterns in Glucose Dysregulation Following SARS-CoV-2 Infection
Authors: Mistry Sejal , Gouripeddi Ramkiran , Facelli Julio C.
Published: March 2021

ABSTRACT IMPACT: Understanding the longitudinal glucose changes following SARS-CoV-2 infection can inform point-of-care guidelines and elucidate the viral hypothesis of diabetes mellitus pathogenesis. OBJECTIVES/GOALS: Hyperglycemia has emerged as an important manifestation of SARS-CoV-2 infection in both diabetic and non-diabetic patients. Whether clinically-detectable glycemic changes persist following SARS-CoV-2 infection remain to be elucidated. This work aims to characterize temporal patterns in glucose dysregulation following SARS-CoV-2 infection. METHODS/STUDY POPULATION: Electronic health records of patients with a diagnosis of COVID-19, positive laboratory test for SARS-CoV-2, and negative history of Diabetes Mellitus prior to infection were extracted from the TriNetX database. 7,502 patients with at least one blood glucose value 2 years to 2 weeks before, 2 weeks before to 2 weeks after, and 2 weeks after to 1 year after COVID-19 diagnosis were used for analysis. Temporal patterns are characterized by training state-of-the-art clustering algorithms, including fuzzy short time-series clustering, k-means for longitudinal data, and spectral clustering. Clustering performance is evaluated using internal evaluation metrics of the Silhouette coefficient, Calinski-Harabasz score, and Davies Bouldin index. RESULTS/ANTICIPATED RESULTS: Based on the success of prior clustering methods with random blood glucose measurements, we anticipate that the proposed time-series clustering algorithms will appropriately characterize temporal patterns of glycemic dysregulation. The best performing algorithm based on interval evaluation metrics will be selected for further analysis. Associations between blood glucose values and cluster membership will be evaluated using Kruskal-Wallis one-way ANOVA and effect size will be calculated using unbiased Cohen’s d. Clinical phenotypes for each cluster will be characterized in terms of current diagnoses, prior medication use, pertinent laboratory tests, and vital signs. DISCUSSION/SIGNIFICANCE OF FINDINGS: A clearer understanding of the longitudinal glucose changes following SARS-CoV-2 infection can elucidate clinically-detectable patterns of glycemic dysregulation, identify sub-phenotypes of patients who are more susceptive to glycemic dysregulation, and inform appropriate point-of-care guidelines.
89976 ASSESSING PROTEIN BIOMARKERS ROLE IN CVD RISK PREDICTION IN PERSONS LIVING WITH HIV (PWH)
Authors: Safo Sandra , Haine Lillian , Baker Jason , Reilly Cavan , Duprez Daniel , Neaton Jim , Wang Jiuzhou , Jain Mamta K. , Pinto Alejandro Arenas , Staub Therese , Polizzotto Mark
Published: March 2021

ABSTRACT IMPACT: Our findings could potentially identify CVD at-risk persons living with HIV who might benefit from aggressive risk-reduction. OBJECTIVES/GOALS: PWH have higher rates of CVD than the general population yet CVD risk prediction models rely on traditional risk factors and fail to capture the heterogeneity of CVD risk in PWH. Here we identify protein biomarkers that are able to discriminate between CVD cases and controls in PWH, and we assess their added benefit beyond traditional risk factors. METHODS/STUDY POPULATION: We analyzed 459 baseline protein expression levels from five OLINK panels in a matched CVD (MI, coronary revascularization, stroke, CVD death) case-control study with 390 PWH from INSIGHT trials (131 cases, 259 controls). We formed 200 datasets via bootstrap. For each bootstrap set, a two-component partial least squares discriminant model (PLSDA) was fit. The importance of each variable in the discrimination of cases and controls in the PLSDA projection was assessed by the variable importance in projection (VIP) score. Proteins with average VIP scores > 1 were used in penalized logistic regression models with elastic net penalty, and proteins were ranked based on the number of times the protein had a nonzero coefficient. Proteins in the top 25th percentile were considered to have high discrimination. RESULTS/ANTICIPATED RESULTS: Participants had mean age 47 years, 13% were females, 4.9% had CVD at baseline and 69% were on ART at baseline. Eight proteins including the hepatocyte growth factor and interleukin-6 were identified as able to distinguish between CVD cases and controls within PWH. A protein score (PS) of the top-ranked proteins was developed using the bootstrap (for weights) and the entire data. The PS was found to be predictive of CVD independent of established CVD and HIV factors (Odds ratio: 2.17 CI: 1.58-2.99). A model with the PS and traditional risk factors had a 5.9% improvement in AUC over the baseline model (AUC=0.731 vs 0.69), which is an increase in model predictive power of 18%. Individuals with a PS above the median score were 3.1 (CI: 1.83- 5.41) times more likely to develop CVD than those with a protein score below the median score. DISCUSSION/SIGNIFICANCE OF FINDINGS: A protein score developed improved discrimination of PWH with CVD and those without, and helped identify PWH with high risk for developing CVD. If validated, this score and/or the individual proteins could be used in addition with established factors to identify CVD at-risk individuals who might benefit from aggressive risk-reduction.
74123 A Learning Health Systems approach using health record data to construct patient frailty scores and predict safety events
Authors: Bokov Alex , Espinoza Sara , Tripathy Chandana , Stevens Kathleen
Published: March 2021

ABSTRACT IMPACT: Laying the groundwork for better predictive algorithms to inform clinical decisions and planning. OBJECTIVES/GOALS: Frailty scores predict poor patient outcomes. Validated against highly relevant outcomes, such scores can be used to inform clinical and resource utilization decisions. We generated and validated an electronic Frailty Index (EFI) from real-world EHR data using the Rockwood deficit-accumulation framework to predict patient safety events. METHODS/STUDY POPULATION: To assure that the research approach reflected perspectives of multiple stakeholders, our multidisciplinary group included an implementation scientist, a geriatrician, an internist, and an informatician. From our large academic health center, we accessed EHR data for 14,844 patients randomly sampled from the data warehouse underlying our ACT/SHRINE node. The per-visit EFI scores were calculated using EHR codes in a rolling 2-year time window. EFI was used as the predictor variable in the analytic design. The primary outcomes were preventable patient-safety events derived from ICD-10 codes including hospital-acquired infections, non-operative hospital-acquired trauma, and cardiac complications. Cox proportional hazard models were used to estimate risk for each outcome. RESULTS/ANTICIPATED RESULTS: We found statistically significant associations of EFI with clinically meaningful outcomes from EHR data. For most outcomes, we found significant correlation with EFI and c-statistics indicating good calibration of the models. The EFI was a strong predictor of clinically relevant outcomes without relying on any data other than diagnoses, vital signs, and laboratory results from the EHR. In contrast to previous studies, we treated EFI as a time-varying predictor with multiple follow-ups per patient, which is more realistic than relying on one static time-point. We used a representative sample of the adult patient population rather than limiting it to older individuals and found EFI to be a useful metric even at relatively young ages. DISCUSSION/SIGNIFICANCE OF FINDINGS: The EFI predicted safety events in adult patients using only routine, structured EHR data and can offer a low-effort, scalable method of risk assessment, valuable to clinical decisions. The capability to harness EHR data and rapidly generate clinical knowledge can be transformative for complex care and contributes to Learning Health Systems.