bluuebunny/crossref_metadata_2025 huggingface dataset:
CD33 and TREM2 peripheral gene expression in relation to cortical thickness
Authors: Braun, BS Abby L. , Sanjay, MS Apoorva Bharthur , Svaldi Diana O. , Apostolova, MD Liana G.
Published: January 2019

Background and Hypothesis:  Genome-wide association and whole genome sequencing studies have uncovered over 20 novel Alzheimer’s Disease (AD) risk genes. Many of these genes are involved with neuroinflammation. Neuroinflammation plays a pivotal role in disease development. CD33 and TREM2 are two immune pathway genes implicated in AD.  We studied the association between peripheral blood expression of CD33 and TREM2, with cortical thickness – a marker of neurodegeneration in AD.  We hypothesized that expression of some these genes would correlate with cortical atrophy in our pooled sample.  
Experimental Design or Project Methods: Data from 155 subjects (50 NC and 105 MCI) were gathered from the UCLA ImaGene study. The imaging data was processed using the FreeSurfer 6.0 longitudinal pipeline and cortical anatomy was standardized for all subjects.  A GLM analysis using Surfstat investigated the associstion of gene expression levels in peripheral blood and cortical thickness controlling for age, gender, education, and diagnosis and generated 3D visualization maps of these associations. Statistical significance was determined with p set at 0.05. 
Results:  CD33 expression showed a positive correlation with cortical thickness in the right medial, inferior and lateral temporal, lateral parietal, posterior cingulate and inferior lateral frontal cortices. TREM2 did not show statistically significant association with cortical atrophy. 
Conclusion and Potential Impact:  Peripeheral blood CD33 expression level seems to be lower in individuals with greater cortical atrophy in AD-relevant areas.  This contributes to a growing body of research that indicates a role for the immune system and CD33 in particular in the pathology of AD and may contribute to future mechanism and biomarker studies.
CHARACTERIZING THE ROLE OF ORBITOFRONTAL CORTEX IN SOCIAL MEMORY
Authors: Bruce Marissa L , Andrews Katharine D. , Lungwitz Elizabeth A. , Truitt William A.
Published: January 2019

Background and Hypothesis: 
Social-enhanced safety learning is a psychosocial process used to reduce fear or anxiety by learning to discriminate fearful versus safe stimuli via a social safety cue.  Learning to associate safety with a social cue requires intact social memory. Preliminary data in rats suggests inhibiting the orbitofrontal cortex (OFC) with pharmacologic agents impairs social memory. However, the specific mechanism by which OFC regulates social memory remains unknown.  Because the OFC has broad functional implications including valuation, decision-making, social and emotional behaviors, olfaction, and non-social memory, we hypothesized that OFC inhibition was disrupting one of these specific processes, resulting in social memory impairment.    
Experimental Design or Project Methods: 
Cannulated adult male Sprague-Dawley rats were injected bilaterally in OFC with either saline vehicle, or 0.9 mM Muscimol, a GABAA agonist that transiently inhibits local neuronal activity.  At 10 minutes post-injection, rats underwent behavior testing for either: social recognition, novel object recognition, social preference (innate gregariousness), or olfactory discrimination.  
Results:  
Rats receiving Muscimol injection, but not rats receiving vehicle injection, demonstrated statistically significant impairment of social recognition, observed as a failure to discriminate between two conspecifics. Alternatively, rats receiving Muscimol injection, but not rats receiving vehicle injection, did not demonstrate statistically significant impairment of novel object (non-social) recognition, innate gregariousness, or olfaction, which were all intact in vehicle injected rats.  
Conclusion and Potential Impact: 
These data suggest OFC may be part of a unique neural circuit specific to social memory.  Delineating the circuitry of social memory from non-social memory offers exciting possibilities in the advancement of precision therapies.
The Influence of Aging on the Relationship between Retrobulbar Blood Flow and Retinal Microcirculation in Glaucoma Patients
Authors: Burgett, BS Kendall M. , Siesky, PhD Brent , Harris, MS, FARVO, PhD Alon
Published: January 2019

Background and Hypothesis: Glaucoma is a multifactorial disease; therefore, different patient populations may be more susceptible to developing glaucoma due to distinct factors. The hypothesis of this study was that the relationship between retrobulbar blood flow velocity and the amount of avascular area in the peripapillary retina in glaucoma patients differs based on patient age.  
Project Methods: Data from 18 glaucoma patients aged ≥70 years old (75.9±5.4) and 24 glaucoma patients aged <70 (60.5±8.6) were used in this analysis. Peak systolic and end diastolic velocities (PSV/EDV) of nasal and temporal posterior ciliary arteries (N/TPCA) were measured using color Doppler imaging (CDI) in order to assess retrobulbar blood flow velocities. Heidelberg Retinal Flowmetry (HRF) was used to quantify the amount of superior avascular area (SAA) and inferior avascular area (IAA) of the peripapillary retina. 
Results: In patients ≥70 years of age, a negative correlation was detected between retrobulbar blood flow velocity and IAA (r=−0.45 for NPCA-PSV, r=−0.36 for NPCA-EDV, r=−0.35 for TPCA-PSV, r=−0.45 for TPCA-EDV). This is in contrast to the positive correlation seen in patients <70 years of age (r=0.45 for NPCA-PSV, r=0.39 for NPCA-EDV, r=0.55 for TPCA-PSV, r=0.69 for TPCA-EDV). Correlation coefficients between the two age groups were significantly different (p<0.01, p<0.05, p<0.01, and p<0.0001 respectively). 
Conclusion and Potential Impact: The relationship between blood vessels supplying the eye and retinal microcirculation is significantly different based on patient age. This suggests that different age populations may have distinct risk profiles for glaucoma. A more complete understanding of population dependent risk factor profiles may assist glaucoma screening and early detection.
A Clinically Suitable Approach to Whole-Body Imaging for Quantification of Regional Perfusion: Validation of Positron Emission Tomography (PET) with 62Cu-ETS and Image-based Tracer Kinetic Modeling
Authors: Cheng Monica , Smith Nathaniel J. , Territo Wendy L. , Mathias Carla J. , Fletcher James W. , Logan Theodore F. , Green Mark A. , Hutchins Gary D.
Published: January 2019

Background & Hypothesis: We hypothesize that whole-body PET imaging with 62Cu-ETS and readily implemented tracer kinetic models, can enable absolute quantification of regional perfusion (mL•min-1•g-1) in a fashion that is reproducible; readily standardized across institutions; and logistically suitable for clinical implementation. 
Experimental Design: Thirty-five paired 62Cu-ETS and H215O studies were performed in six Göttingen minipigs to validate the use of image-derived input functions. H215O estimates of tissue perfusion served as a reference standard for comparison with 62Cu-ETS. To demonstrate quantitative whole-body perfusion imaging in humans, paired 62Cu-ETS and H215O studies were performed in 14 renal cell carcinoma patients both prior to and following sunitinib therapy. 
Results: The pig studies showed a strong correlation between regional blood flow estimates made with 62Cu-ETS and H215O, using image-derived input functions with tracer kinetic model-based corrections for 62Cu-ETS decomposition in blood (slope=0.932, R2=0.746). High quality voxel-wise 62Cu-ETS perfusion and blood volume parametric images demonstrated a strong correlation with H215O across all tissues within the imaging field-of-view. Using a same-day test-retest design, which was then repeated across two weeks, the animal study demonstrated good test-retest variability (TRV) for 62Cu-ETS and H215O with TRV of 6.3% ± 5.40% and 5.0% ± 4.77%, respectively. These findings strongly support application of the modeling methods to the human data, which is currently in progress. 
Conclusion & Potential Impact: Whole-body imaging to non-invasively quantify regional perfusion holds promising potential for clinical implementation, using 62Cu-ETS PET coupled with tracer kinetic models that rely solely on the acquired imaging data.
Assessing generalizability of a new-onset type 1 diabetes Biobank
Authors: Ciresi Colette , Wendholt Kathleen , Mullen Maureen , Evans-Molina Carmella , DiMeglio Linda
Published: January 2019

Background and Hypothesis:  
Type 1 diabetes (T1D) is characterized by insulin deficiency due to autoimmune pancreatic beta cell destruction. The Wells Center Pediatric Diabetes Research Program is collecting blood and urine samples from children with new onset T1D admitted to Riley Hospital. These samples are being used to discover biomarkers predictive of disease heterogeneity and course. Since not every newly-diagnosed child enrolls in the Biobank, we examined if persons enrolled are similar or different from the at-large population of newly-diagnosed children to know how generalizable samples collected are from our newly-diagnosed population. 
Project Methods:   
Between September 2016 and May 2018, 71 newly-diagnosed children (mean age 9.6±4.3 years) and their caregivers were approached by researchers and asked to provide blood/urine samples. Thirty-four consented/assented (as required); 21 had blood and urine collected; 13 urine only. We looked for differences in age, sex, race, BMI, socioeconomic status (based on zip code), and admission bloodwork parameters between participants and non-participants.  
Results:  
Overall, participants were more likely to be white and have higher admission bicarbonate. Children who provided blood and urine had no other significant differences from non-participants. Children who provided urine only were more likely to be male and to have higher admission bicarbonate than non-participants. Currently, we are obtaining data to make comparisons with the general population of all patients diagnosed at Riley.  
Conclusion/Potential Impact: 
Our Biobank will provide samples to explore novel biomarkers to facilitate highly-targeted therapies and to screen future preventative treatments. As we continue to collect data, it will remain important to monitor and carefully consider its generalizability.
Canines in the emergency department: a novel approach to stress reduction in emergency medicine providers
Authors: Davis Jacob C. , Van Ryzin, MD Kimberly J. , Linville Courtney T. , Pettit, MS Kate L. , Kline, MD Jeffrey A.
Published: January 2019

Background and Hypothesis: 
Cognitive stress during shiftwork contributes to burnout in emergency care. We hypothesize that if emergency care providers (physicians and nurses) were to interact with a therapy dog, their stress levels will decrease. 
Experimental Design or Project Methods: 
Consenting emergency medicine physicians and nurses provided three self-reported assessments of stress as well as saliva samples near the beginning of their shift. During peak hours in the emergency department at Eskenazi Hospital participants are randomized to interact with either a therapy dog or perform a mindfulness exercise via art therapy for five minutes. Self-perceived stress and saliva samples are obtained 30 minutes later and again near the end of shift. To assess potential change in participant behavior, patients of providers in either group receive a validated questionnaire assessing perceived empathy of the provider. Salivary cortisol will be measured at the end of the study by a vendor (Salimetrics). The sample size of 40 per group is predicated on a 25% decrease in self-reported stress in the dog group on the emergency care worker stress scale (ECWSS). 
Results: 
From June 1 to July 10, 24 participants have been randomized (12 in each group). Seven participants (58%) exposed to dogs had a mean decrease in the ECWSS of -5 (+/-1.8) compared with four participants (33%) who had a mean decrease of -2 (+/-0.8) after art therapy. The mean overall change in ECWSS after dog was -2 (+/-1.5) vs. +3 (+/-1.5) after art therapy.  Current data suggest a greater decrease of self-reported stress after interaction with a therapy dog, compared to art therapy. 
Conclusion and Potential Impact: 
Interim analysis suggests that exposure to a therapy dog decreases stress in a subset of emergency care workers. This work will help determine if human-animal interaction can modulate stress biology imposed by providing emergency medical care.
Determining the cellular localization of C.elegans Editing Enzyme
Authors: Dudley Anna , Hundley Heather , Rajendren Suba
Published: January 2019

Background and Hypothesis: 
Over two thirds of human mRNAs contain adenosine(A)-to-inosine (I) editing sites indicating that RNA editing significantly alters the flow of genetic information. RNA editing is required for normal development and proper neuronal function in all animals. Aberrant RNA editing is identified in several neurological disorders and cancers. 
 A-to-I RNA editing is catalyzed by adenosine deaminases that act on RNA (ADARs) proteins. These enzymes commonly bind to double stranded RNA (dsRNA) and catalyze the conversion of adenosine to inosine. However, it is unknown whether these different regions of mRNA are edited by ADARs in the cytoplasm or nucleus. Early research has shown that inosines are present in the nucleus, while new additional evidence shows activity in cytoplasm as well. What dictates the location of the editing is yet unknown.  
Experimental Design:  
The subcellular localization of the ADAR editing enzyme will be determined by performing western blots of fractionated Caenorhabditis elegans embryos. Unlike mammals, ADAR editing is not essential in C. elegans, thus making it an easy system to address mechanistic questions about RNA editing. Embryos will be attained from wild-type, ADR-1 and ADR-2 knockout worms, and biochemical techniques will be used to obtain nuclei and cytoplasmic fractions. These fractions will be subjected to SDS-PAGE and western blotting for the ADAR editing enzyme, ADR-2. I will also use positive controls of a nuclear protein (histone) and a cytoplasmic protein (Tubulin) to test the fractionation. 
Anticipated Results:  
That there will be more ADR-2 enzyme in the nucleus than the cytoplasm. 
Potential Impact: 
Knowing the location of the edited RNA will allow researchers to have a better idea of what mechanisms influence the editing of ADAR, and what dictates the localization of dsRNA. Current theories involve the number of inosine groups, cellular conditions which effect localization, and nuclear retention molecules other than inosine.
Quantitative Effect of Emergency Department Case Management on Visits, Diagnostics, and Cost
Authors: Nickel, MD Jeffrey , Connelly Nancy , Duffner Cameron , Pablo Xyryl , Hughes Aeleia
Published: January 2019

Background and Hypothesis: 
In 2012, Parkview Health initiated a case management (CM) program with the hypothesis that it would reduce emergency department (ED) visits, radiation exposure, and costs for patients who had visited a Parkview ED 5 or more times within 6 months. 
Experimental Design or Project Methods: 
This retrospective case series involved examining medical records of 460 CM patients from 2011 to 2018, recording the amount of Parkview ED visits, diagnostic tests, and affected cost accumulated in the year prior to CM enrollment compared to each of the next 2 years. Demographics, chief complaints, diagnoses, psychiatric and drug use history, and whether the patients had insurance and a primary care provider were also recorded. Patient data was excluded if the patient was younger than 18 at the time of CM enrollment, had not yet completed 2 years in the CM program, or if medical records were not available. ANOVA and 1-sided, paired t-testing were performed to evaluate significance of the results. 
Results: 
Comparing the year before enrollment to the 2nd year after, ED visits were reduced from 5,264 to 2,012 for 378 patients (63%, p<0.01), the affected cost was reduced from $551,734.45 to $246,248.34 for 299 patients (55%, p<0.01), and the number of diagnostic tests was reduced from 6,040 to 1,883 for 104 patients (69%, p<0.01). 
Conclusion and Potential Impact: 
Patients enrolled in Parkview’s CM program showed statistically significant reductions in ED visits, radiologic exposures, and affected costs over 2 years, with implicit improved health outcomes. Projected 10-year affected cost savings range from $3.7 million to $9.1 million.
Lung Ultrasound Proficiency Study
Authors: Fabre Katarina L. , Russell Frances M.
Published: January 2019

Background and Hypothesis: Acute heart failure (AHF) is a major public health burden, and accounts for billions of dollars in healthcare costs annually. Pulmonary congestion is a primary reason patients with AHF seek emergency care. B-lines on lung ultrasound (LUS) is an objective measurement of congestion. It has great implications on diagnosis and prognosis for patients with AHF, but is operator dependent. The goal of this study was to determine if novice sonographers, with limited training, could quantify LUS B-lines with good correlation when compared to experts. 
Methods: This was a prospective observational study of novice sonographers from three academic institutions. Sonographers received a structured 2-hour ultrasound training on LUS B-line assessment, which included lecture, B-line video review to practice counting, and hands-on patient scanning. Sonographers quantified B-lines in 4 lung zones in each hemithorax in patients with pulmonary edema. The primary objective was measured by comparing novice sonographer B-line counts to a blinded expert reviewer. We used a cumulative sum method for statistical analysis. 
Results: There were xx sonographers, who scanned xx patients with pulmonary edema. We found … (will await Eckert’s stats).  
Conclusion and Potential Impact: Will await Eckert’s stats- if successful, the quantification of B-lines by novice sonographers in patients with AHF may greatly impact diagnosis, prognosis and risk stratification.
Aspergeillus Fumigatus: The Effects of Adiponectin on Inflammatory Cytokine Production
Authors: Foust Rick , Templeton Robert
Published: January 2019

Background and Hypothesis: Although inflammatory cytokines are important for antifungal defenses, excessive production significantly increases host immune pathology. It is therefore important to identify host pathways that limit detrimental inflammation in invasive fungal infection. Our prior results showed that mice with invasive aspergillosis (IA) that were deficient in the metabolic cytokine production produced more of the cytokine Tumor Necrosis Factor (TNF) than alveolar in wild-type control mice.  Therefore, we hypothesize that adiponectin inhibits antifungal cytokine secretion in alveolar macrophages.  
Experimental Design or Project Methods: To test this hypothesis, the commonly used A. fumigatus strain Af293 was purchased from the Fungal Genetics Stock Center and grown on and harvested from agar. The alveolar macrophage cell line MH-S and cytokine ELISA kits was obtained from MilliporeSigma and ThermoFisher, respectively. MH-S cells were stimulated with swollen, fixed Af293 conidia for 24 hours in the presence or absence of recombinant mouse adiponectin. After 24 hours, supernatants and cells was were collected and assayed for ILs 1a, 6, and TNF protein and mRNA , by ELISA and quantitative RT-PCR, respectively. 
Results: Although our preliminary results suggest possible inhibition of cytokine secretion by adiponectin in response to A. fumigatus, significant differences have thus far not been observed.  
Conclusion and Potential Impact: We are therefore currently optimizing our experimental conditions to improve antifungal cytokine secretion. These studies may ultimately assist in the discovery of novel therapeutic targets and improve the prognosis of A. fumigatus infections
Assessing Student Engagement and Higher Order Skill Proficiency During the First and Second Year of Medical School – A Comparison Between the Legacy and Recently Reformed Active Learning Curricula
Authors: Francis Brandon , Hopper, PhD Mari
Published: January 2019

Background and Hypothesis: This study set-out to determine if: 

students enrolled in Indiana University’s reformed curricula (RC) demonstrate higher levels of engagement (E) and higher order skill (HOS) proficiency than students prior to reform in the legacy curriculum (LC).  

students increase E and HOS from first year of medical school (MS1) to second year (MS2). 
students performing in lowest HOS quartile during MS1 will demonstrate greater gains in HOS by MS2 than students in higher quartiles. 

Experimental Design or Project Methods: Determined E using a validated self-report survey (Ahlfeldt, 2007). Assessed HOS using the standardized Collegiate Learning Assessment (CLA+), professionally developed and validated by the Council for Aid to Education (https://cae.org/flagship-assessments-cla-cwra/cla/). Statistical analysis was preliminary; further analysis to be completed by statistician. Between group comparison of LC and RC via t test assuming unequal variance; paired t test for within group comparison MS1 to MS2 (significance p<0.05). 
Results: Students in RC increased E significantly from MS1 (39.0±7.0) to MS2 (40.8±5.3) and demonstrate significantly higher E than LC MS2 students (36.3±5.3). There were no differences in HOS proficiency when comparing RC to LC, or MS1 to MS2. Students in RC in the lowest quartile for HOS during MS1 (1688.8±53.1) significantly increased when re-tested during MS2 (1809.5±86.8). 
Conclusion and Potential Impact: Curricular reform resulted in higher E when compared to LC. Despite increased E, there were no related changes in HOS. Results from quartile analysis agreed with previous reports that active learning preferentially benefits lower performing students (Koles, 2010).
Medical Students’ Studying Approach to a Changing Medical School Anatomy Curriculum
Authors: Gibson, BA Daniel , Husmann, PhD Polly
Published: January 2019

Background and Hypothesis: 
With medical school curriculum changes, students have to reassess how they approach their studies. This study evaluates how medical students planned to study gross anatomy before and after the 2016 Indiana University School of Medicine (IUSM) curriculum change. Student study plans are hypothesized to be different before and after the curriculum change.   
Methods: 
First-year medical students from 2015-2017 were given a survey prior to their gross anatomy course. The survey integrated 37 Likert scale questions about resources the students might use, study strategies, demographics, prior anatomy and/or physiology courses, etc. T-tests were run between the curriculum and student grades as well as seven categories that grouped related questions from the survey.  Comparisons were also made between the upper and lower thirds of the class. 
Results: 
The final course and NMBE percentages were found to be significantly different between curricula (p<0.0001/p<0.0001). Differences in planned usage of text-based, lab-based, and web-based resources were also significant (p<0.0001/p=0.002/p=0.007). Analyses additionally found that students in the upper third of all classes were more likely to have a prior anatomy and physiology course (p=0.031). 
Conclusion and Potential Impact: 
Student study plans for anatomy have changed with the revision of the curriculum.  Current students are planning to use outside resources (e.g., textbooks, websites) more than previous cohorts in the traditional curriculum.  In addition, students with prior knowledge of anatomy and physiology may have an advantage in understanding medical anatomy.  These findings have implications for the long-term retention of this material and subsequent student outcomes.
Assessing lead exposure sources at the property scale in Indianapolis
Authors: Hentz, BS Emily , Filippelli, PhD Gabriel , Springer Noah , Hopkins, MA, BS, BA Emily , Orr Isheka , Smith, BA Rachel
Published: January 2019

Background and Hypothesis: 
Lead (Pb) was phased out of paint and gasoline over 40 years ago due to neurotoxicity in humans, but has persisted in soils and poses a legacy threat to many.  The Indianapolis 46218 zip code has had >10% children exhibiting Pb poisoning. This zip code has had historically high soil Pb levels, and is undergoing redevelopment. We hypothesize that redevelopment will act to re-expose new populations of people to the legacy Pb present in the area.   
Experimental Design or Project Methods: 
We sampled 5 parks and 7 playgrounds.  Stratified random sampling based on permit type was used to select properties from 25 issued and 25 closed permits from 527 identified demolition permits.  Nearby residential properties were selected, with permission of residents. Samples were taken near the dripline of the house, front yard, and street, or from each quadrant at sites without houses. Samples were dried, crushed, sieved to 150 microns, and assessed using X-Ray Fluorescence.   
Results: 
Mean Pb levels from driplines (1026 ppm) were significantly higher than streets (p=0.001), parks (p=0.002), yards (p=0.001), and demolition sites (p=0.000).  Pb concentrations for playgrounds had the lowest median lead levels (42 ppm), while dripline samples had the highest (289 ppm).  The EPA standard for children’s play areas is 400 ppm. 
Conclusion and Potential Impact: 
While all samples from playgrounds were below 400 ppm, children are also likely playing at their homes, where no legislation effectively protects them from potential Pb poisoning and values were found above 400 ppm.  An immediate outcome from this project is the education.  Residents who agreed to testing (n=42) received results of the test and guidelines to prevent Pb poisoning.  More work remains to ensure preventive rather than reactive strategies are employed to protect children’s health.
Fat Soluble Vitamin, B12 and Iron Deficiency in Patients with Coliform Small Intestinal Bacterial Overgrowth (SIBO)
Authors: Howard Gage , Wo John
Published: January 2019

Background and Hypothesis: Vitamin deficiency has been described as a clinical complication of SIBO. However, it is unclear if the type of bacterial colonization is an important determinant in vitamin and nutritional complications. Our aim was to characterize the prevalence of specific vitamin and mineral deficiencies (vitamins A, D, E, K, B12, and iron) in patients with and without coliform SIBO. We hypothesized that results would show a significant increase in the incidence of vitamin and/or mineral deficiency in patients with coliform SIBO. 
Methods: A prospective registry was formulated, consisting of patients presenting to our outpatient motility clinic with suspected SIBO. Serum levels of vitamins A, D, E, INR for K, B12 and iron studies were obtained. Upper enteroscopy-aspiration and quantitative aerobic-anaerobic cultures were performed. Primary study endpoints were prevalences of clinical vitamin/mineral deficiencies (A, D, E, K, B12, and iron) based on the final diagnosis: A) SIBO by coliform bacteria (>104 CFU/mL), B) SIBO by upper respiratory tract (URT) bacteria (>105 CFU/mL) and no SIBO. 2x3 chi square, univariate and multivariate analyses were utilized.  
Expected Results: 128 subjects were enrolled, and 96 subjects underwent aspiration. Final diagnoses were the following: coliform SIBO in 32 (33%) and no SIBO or URT SIBO in 64 (67%). The presence of any vitamin deficiency appears to be more prevalent in patients with coliform SIBO (46.7%) than those without (28.1%), but it is currently unclear if these differences reach statistical significance.  
Conclusions: 1) Fat-soluble vitamin deficiency may be more common in coliform SIBO, but its absence does not exclude the possibility of coliform SIBO being present. 2) Although a high folate and low B12 can be suggestive of SIBO, these derangements were not common in our heterogeneous group of patients.  
*Will send update following data analysis*
Developmental Toxicity of TCE Exposure in Zebrafish: Analyzing Vitamin D Metabolism
Authors: Grisby Briana M. , Thompson Kathryn M. , Freeman Jennifer L.
Published: January 2019

Background and Hypothesis: Trichloroethylene (TCE) is an industrial solvent used since the 1940s. A known carcinogen, it is found in over half of Superfund sites where levels have reached 12,000 parts per billion (ppb; µg/L), though the US Environmental Protection Agency maximum contaminant level in drinking water is 5 ppb. In this study, the zebrafish model was used to investigate the developmental toxicity of TCE by assessing its effects on metabolism. Preliminary studies have shown a reduction in gene expression of the cytochrome P450 (CYP) enzymes responsible for breakdown of vitamin D. As a result, we expected to see lower levels of downstream metabolites, namely calcitriol, as detected by an Enzyme-Linked Immunosorbent Assay (ELISA). 
Experimental Design: At 0-2 hours post fertilization (hpf), embryos were dosed with TCE at either 0 or 10 ppb. At 72 hpf, the larvae were removed from the TCE and prepared for the ELISA procedure. 
Results: ELISA revealed similar levels of calcitriol between the control and 10 ppb groups. The difference between the two groups did not show statistical significance (p>0.05). 
Conclusion: These results suggest that there may not be a direct relationship between CYP gene expression and certain downstream metabolic effects or that the organism was able to compensate for the biological changes. If the latter, additional time points for TCE exposure could be evaluated. As studies continue, we plan to evaluate CYP gene expression at higher concentrations to correlate with other biological effects and determine if there is consistency with results from lower concentrations.
Tendon transfer of pronator teres to flexor pollicis longus to restore thumb flexion in incomplete tetraplegia
Authors: Jarrett Nathan P. , Merrell Gregory A.
Published: January 2019

Background and Hypothesis: Incomplete tetraplegia creates immense barriers to autonomy for individuals with spinal cord injuries. These patients may retain control of some forearm extensors, but use of flexors is largely eliminated, affecting many movements necessary for daily activities. Although tendon transfers using brachioradialis and other muscles to restore hand function are standard practice, pronator teres has not been extensively studied as a donor for flexors. The purpose of this study is to quantify forearm pronation capability pre- and post-tendon transfer of pronator teres to flexor pollicis longus in a cadaver model. We hypothesize that tendon transfer will make thumb flexion possible, while preserving forearm pronation against gravity at a minimum. 
Experimental Design: Five cadaver arms were evaluated for pronation capability against gravity before and after tendon transfer. In both stages, the arms were also assessed for the pronation forces produced at the wrist when pulling pronator teres with 25, 50, and 75 N of force. With each force, the arms were tested in full supination and neutral position. 
Results: All five arms were capable of pronating against gravity before and after the tendon transfer. Following the transfer, pronation force decreased, but the difference was not statistically significant. 
Conclusion and Potential Impact: Pronator teres to flexor pollicis longus tendon transfer produces thumb flexion while retaining the forearm’s ability to pronate. Used in conjunction with well-established donors, such as brachioradialis, pronator teres’ expendability could offer an additional motor unit for restoring hand function in tetraplegic patients.
Resiliency in Medical Students and Residents Participating in the Global Health AMPATH Kenya Elective
Authors: Keilman Courtney L. , Baenziger, MD Jenny
Published: January 2019

Burnout has become a prominent issue among healthcare providers. The demands of working long shifts, prolonged periods of stress and increased time spent charting all contribute to this phenomenon. Current research suggests that an intrinsic sense of resilience may be key in combating this epidemic. Just as our sense of empathy and compassion can be cultivated through experience, so too can our level of resilience. We propose that engaging in an international health project during medical professional education may promote a greater sense of resiliency. To analyze this, we will use the Connor-Davidson Resilience Scale© to survey 4thyear medical students and residents at the Indiana University School of Medicine (IUSM) that have participated in the AMPATH rotation at Moi University in Kenya between June 2018 and May 2019. To determine the potential change in resilience we will ask our subjects to complete the survey prior to their trip, as well as 1-months and 1-year after their trip. This study may lead to the advocacy for such projects to be integrated into medical education curricula to combat the growing problem that is physician burnout.
Mapping Out Receptors: High Throughput Screening of Endothelial Monocyte Activating Polypeptide II (EMAPII) Using PRESTO-TANGO
Authors: Lam Nathan , Maier Bernhard , Chelvanambi Sarvesh , Hato Takashi , Clauss Matthias
Published: January 2019

Background: Secreted endothelial monocyte activating polypeptide II (EMAPII/AIMP1) is a pro-apoptotic, pro-inflammatory ligand implicated in diseases such as colorectal cancer, cardiovascular disease, and emphysema. Thus, EMAPII has been shown to induce apoptosis through CXCR3 receptor binding. However, not all EMAPII functions have been attributed to CXCR3. Discovery of new receptors interacting with EMAPII could lead to development of new therapies blocking cognate ligand-receptor binding. We hypothesize the existence of at least one unknown secondary receptor for EMAPII. 
Methods: The PRESTO-TANGO assay, a construct which converts G-protein coupled receptor (GPCR) ligand binding into luciferase activity measurable by luminometer, was validated using transfection with TANGO-modified CXCR3 and S1P1R as test receptors in HTLA cells. Protocols for cell transfection, adherence, and cultivation were optimized with IP10, EMAPII, and S1P as test ligands. 
Results: The assay was successfully validated using several GPCR activation readouts. Binding curves were generated for S1P/S1P1 (EC50= 569nM), IP10/CXCR3 (EC50= 47.1 nM), and EMAPII/CXCR3 (EC50= 628 nM). Conditions for the PRESTO-TANGO assay were further refined for maximal signal-to-noise ratio and robust inter-assay reproducibility in preparation for high-throughput screening. We are currently testing 314 TANGO-modified GPCRs for EMAPII affinity. 
Conclusion: We have validated the Tango assay for the known EMAPII-CXCR3 ligand-receptor system, a valuable tool for evaluation of anti-EMAPII therapeutics. Discovery of a novel EMAPII receptor would allow for the development of therapies including neutralizing antibodies (analogous to the PD1 receptor antibody Pembrolizumab for solid tumors) in diseases such as colorectal cancer, cardiovascular disease, and emphysema.
Evaluation of a Critical Sized Bone Defect in a Porcine Tibial Model
Authors: Milto Anthony J. , Peters Alexander W. , Tucker Aamir , Brinker Alex , Savaglio Michael , Adam Gremah , Ganesh Venkateswaran , Gunderson Zachary , Childress Paul , Natoli Roman M. , McKinley Todd O. , Kacena Melissa A.
Published: January 2019

Background/Hypothesis:
Few large animal bone injury models exist. We present a porcine tibial model of metacritical and critical sized bone defects for the simulation of traumatic bone injuries.
Project Methods:
16 pigs were used in this study. The pigs were divided into 3 groups (n=4-8/group). In 12 pigs, a 25 mm osteotomy was created in the tibia and the space was filled with a 25 mm scaffold. 8 of the 25 mm scaffolds were secured with an intramedullary (IM) nail and 4 of the scaffolds were secured with plates. In 4 pigs a 40 mm osteotomy was created, filled with a 40 mm scaffold, and secured with plates. Fracture healing was assessed 3 months post-operatively using the Radiographic Union Score for Tibial Fractures (RUST) criteria.
Results:
For the 25 mm IM group, none of the 8 pigs achieved cortical bone union at 3 months post-op. In contrast, cortical union was observed in all of the 25 mm defects secured with plates. None of the 40 mm defects secured with plates achieved cortical union.
Conclusion/Potential Impact:
The failure of the 25 mm defect secured with an IM nail and the 40 mm defect secured with plates demonstrates that these are critical sized defect models. However, because the 25 mm defect secured with bridge plates did heal, we have termed this a metacritical sized defect. Identification of a defect size that can heal or not heal based on the fixation technique is a powerful translational model for testing therapies.
Understanding the Algebraic and Logical Structure of Speech Perception
Authors: Misiolek Kalina A. , Worth Robert M. , Rubchinsky Leonid L.
Published: January 2019

Background: Although subject to much variation, the anatomy of language comprehension has become increasingly clear with the advent of fMRI; however, the steps of speech comprehension remain elusive. There are two main theories of language processing – hierarchical and sequential (or probabilistic). According to the hierarchical theory, sentences are broken down (e.g. sentence to words to syllables to phonemes) and then reconstructed while syntactic and semantic meanings are attached. Sequential theory suggests the use of “word-level statistics” and n-gram-type models to predict sequences of word meanings.1 Although evidence suggests both models play some role, as a starting point, many comprehension models focus on hierarchical theory, and many of those in turn rely on neural networks. However, in various ways, these models fall short of explaining how the brain can biologically carry out all the steps. 
Methods: We attempt to create a hierarchical model of speech comprehension using linear logic (or a related logic) or Category Theory, with the hope that such an approach may be able to explain the process more naturally. We focus on the second half of comprehension (i.e. the reconstruction) to make use of existing neuronal logic gate models.2 The goal is to construct a linear logic model or to create categories and associated functors that could explain hierarchical linguistic processing and many neurolinguistic study results.  
Potential Impact: Although this model would only account for hierarchical linguistic processing, it would be a huge step forward in understanding how our brain processes speech – and possibly other inputs – at the level of neuron bundles. 
References: 

Frank, S. L., Christiansen, M. H. (2018). Hierarchical and sequential processing of language. Language, Cognition and Neuroscience, 1-6. doi:10.1080/23273798.2018.1424347 

Goldental, A., Guberman, S., Vardi, R., & Kanter, I. (2014). A computational paradigm for dynamic logic-gates in neuronal activity. Frontiers in Computational Neuroscience, 8. doi:10.3389/fncom.2014.00052
REDUCED INFECTION RATE AFTER ASEPTIC REVISION TOTAL HIP ARTHROPLASTY WITH EXTENDED ORAL ANTIBIOTIC PROTOCOL
Authors: Mohiuddin, BS Amer , Rice, BA Justin , Ziemba-Davis, BA Mary , Meneghini, MD R. Michael
Published: January 2019

Background and Hypothesis: Periprosthetic joint infection (PJI is a leading cause of failure after aseptic revision total hip arthroplasty (RTHA). While well documented in the primary setting, perioperative antibiotic duration is not well described in RTHA where the risk of PJI was recently reported to be 8% one-year post-revision. The study purpose was to evaluate whether extended oral antibiotic prophylactic protocol minimizes PJI in aseptic RTHA patients compared to the published literature.  
Project Methods: 169 consecutive aseptic RTHAs performed with modern perioperative and infection-prevention protocols by a single surgeon at a single center were retrospectively reviewed. 80% of patients were discharged on 7-day oral antibiotic prophylaxis while intra-operative cultures were incubating. Infections and reoperations were documented.  
Results: Average age and BMI were 63 years and 30 kg/m2.  67% percent of patients were ASA-III/IV, signifying the severity of comorbidities in this revision cohort. There we no cases of PJI in the 90-day postoperative period. Ninety-eight percent of cases were infection free at mean follow-up of 45 months. Three (1.8%) cases underwent reoperation for deep infection at 110, 161 and 581 days.   
Conclusion and Potential Impact: Our observed infection rate of 0.0% is lower than published infection rates following RTHA and a 1.5% infection rate in primary THA in patients with no identifiable risk factors for PJI.  Based on this clinically meaningful decrease in PJI in this challenging cohort, we encourage further study regarding extended antibiotic protocol weighed appropriately against potential consequences.
Disease Severity in Non-alcoholic Fatty Liver Disease (NAFLD) Patients with No Prior Diagnosis of Cirrhosis – A Unique Insight Using Vibration-Controlled Transient Elastography (VCTE)
Authors: Muschi David , Vuppalanchi Dr. Raj
Published: January 2019

Background and Hypothesis: 
The severity of fibrosis is a strong prognostic indicator in patients with non-alcoholic fatty liver disease (NAFLD). However, routine evaluation with a liver biopsy in patients with NAFLD is not feasible and as such, the assessment of disease severity is often limited in small sample sizes. Vibration-controlled transient elastography (VCTE) is a non-invasive tool that can simultaneously assess for both liver fibrosis and steatosis by estimating liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) respectively.  The aim of the current study is to estimate the prevalence of (1) abnormal LSM indicative of any fibrosis based on LSM ≥ 6.5 kPa, (2) compensated Advanced Chronic Liver Disease (cACLD) – suggestive(10-15kPa) and highly suggestive (>15 kPa), and (3) severe steatosis  
Experimental Design or Project Methods: 
Patients seen at digestive and liver disorders clinic at Indiana University Hospital that underwent VCTE between 8/2013-4/2018 were identified from the Fibrocan502 Touch data table. The ICD10 codes used as the indication for performing the VCTE were extracted and confirmed with the review of electronic health records.  
Results: 
1240 patients met the criteria.  The prevalence of abnormal LSM in the study cohort was 66% with 38.5 % having LSM suggestive of cACLD and 22% having LSM highly suggestive of cACLD. The prevalence of severe steatosis was 77%. The proportion of NAFLD patients with cACLD (suggestive and highly suggestive) during the study period was not significantly different (Figure1).   
Conclusion and Potential Impact:  
There are many NAFLD patients with liver stiffness indicative of abnormal LSM and 22% have LSM that is highly suggestive of cACLD. The proportion of patients with cACLD is steady over the study duration.
Role of CCL21 on the Transcriptional Regulation of MHC II in Malignant Glioma Infiltrating Plasmacytoid Dendritic Cells
Authors: Newman Sharlé , Chintala Sreenivasulu , Henriquez Mario , Dey Mahua
Published: January 2019

Background and Hypothesis: Glioblastoma (GBM) is a malignant brain tumor characterized by high tumor heterogeneity and an immunosuppressive tumor microenvironment (TME). Immunomodulation approaches have been investigated, but outcomes remain poor. Several studies describe the functional deregulation of immune cells including, T cells, dendritic cells (DC), and macrophages. Plasmacytoid dendritic cells (pDC), which accumulate in the GBM TME, are shown to have an immunosuppressive phenotype characterized by a lack of IFN-[Symbol] secretion and upregulation of MHC II. MHC II presentation is transcriptionally regulated by several factors produced by tumor cells including, TGFβ, TNFα, and IL10 through the modulation of CIITA, the catalytic component of the enhanceosome. GBM tumor cells secrete several chemokines/cytokines, which may regulate MHC II expression in pDCs. We hypothesize that chemokine CCL21 transcriptionally upregulates MHC II through the activation of CIITA in pDC.   
Experimental Design/Project methods: We performed experiments using two GBM tumor cells models GL261 and CT2A and used western blot, PCR, immunohistochemistry, immunofluorescence, and flow cytometry to determine the levels of CCL21 and its ligands ACKR3/4 in tumor cells and pDC. 
Results:  We observed overexpression of CCL21 in GBM and upregulation of MHCII in tumor associated pDC. We predict that inhibition of CCL21 will lead to downregulation of MHC II in tumor associated pDC which could potentially lead to reversal of the immunosuppressive TME by presenting the antigens to T cells.  
Conclusions/Potential Impact: The results of this study can elucidate novel mechanisms of MHCII regulation and identify CCL21 as a potential therapeutic target for immunotherapy development in GBM.
Patient Perception of Empathy from Emergency Medicine Residents
Authors: Ofoma, MS Max , Pettit, MD Katie
Published: January 2019

Background and Hypothesis: This project analyzes the effect of years of training and gender of ED providers on patients’ perception of empathy from them. The project will also explore how patient characteristics may impact the patients’ perception of empathy from the ED providers. 
It is expected that women providers in their third year of training will exhibit higher scores of empathy. It has been previously demonstrated that white women with a college education have the worst perceptions of empathy from their ED providers. 
Experimental Design or Project Methods: Eligible patients from Eskenazi/Methodist Hospital, who have had a CT scan ordered, will be enrolled via convenience sample. Patient perceptions of physician empathy will be assessed via the “Empathy Behavior Survey for Patients” (EBS) and “Jefferson Scale of Patient Perceptions of Physician Empathy” (JSPPPE). Patient demographic data and information about the provider ordering the CT scan will be recorded as well.  
Results: On the EBS/JSPPE, 1st, 2nd, and 3rd year residents were given scores of 51/31.5, 51/31, and 51.5/33 respectively. Male residents were given a median score of 51 on the EBS and 32 on the JSPPPE. Female residents were given a median score of 50.5 and 31 on the JSPPPE. White female patients with a college education gave a score of 50.5 on the EBS and a 32.5 on the JSPPPE. 
Conclusion and Potential Impact: Years of training or gender do not seem to have an impact on patient perception of empathy nor do White female patients with a college education.