bluuebunny/crossref_metadata_2025_split huggingface dataset:
Curation of a Multiple Myeloma Cell Surface Database for Immunotherapy Development
Authors: Adaniya Emily , Yu Christina , Perna Fabiana 
Published: December 2020

Background/Objective: Every year in the United States, 32,000 individuals are diagnosed with Multiple Myeloma (MM) and 13,000 die from the disease. MM is a cancer of the plasma cells and while treatment exists, MM remains incurable. Our overall goal is to identify biologically and therapeutically relevant cell surface targets to develop MM immunotherapy.

Methods: Given the genomic heterogeneity of MM, we performed surface analysis of seven MM cell lines by Mass-Spectrometry (MS), generating a pool of candidate proteins. Lacking specific tools for studying cell surface proteins, we developed an integrated computational tool with five distinct databases, and scored the likelihood of cell surface location for each molecule. One point was given for each database a protein appeared in. A protein receiving a score of three or more was considered a cell surface protein with high confidence. However, about one third of the candidates were not detected by the computational tool, thus requiring manual curation. We used UniProt and GeneCards to determine the subcellular locations of the unannotated IDs, and further confirmed their location with the computational tool.

Results: Of the 5,454 UniProt IDs produced by MS, 2,026 were not annotated. Causes of an unannotated ID included having an obsolete ID, being an isoform, and/or not being located on the cell surface. Through manual annotation, 8 unique cell surface IDs were added to the existing 448. The 456 targets were further analyzed based on their expression profiles in both MM and normal tissues resulting in 94 of the most promising targets, some of which would have been missed without manual curation.

Conclusion/Potential Impact: Public genomic databases are often incomplete and may contain errors making manual curation a necessary step in error reduction. Left unchecked, promising surface targets could have been overlooked hindering the creation of potentially curative immunotherapies.
Clinical Case Reports as a Tool for Medical Student Education
Authors: Ashraf Adeel , Ashraf Nabeel , Bae Taeok 
Published: December 2020

Background: The first two years of medical student education relies on textbooks and lectures for a foundation of knowledge that must be expounded upon in the latter two years. However, this doesn’t mean that students should be constrained to a narrow usage of their intelligence for exam questions, rather they can begin to think about using their knowledge in a clinical setting from the beginning. We researched eight prevalent pathogens that have a higher probability of being encountered by a physician by using real life examples from case reports from around the world. We condensed the materials into a team-based learning (TBL) activity with thought provoking questions related to the case in particular and to fundamental principles of microbiology and immunology as a whole.
Approach: We searched extensively through online databases to locate clinical case reports that weren’t too uncommon or too simple. Next, we built a TBL activity using the case report as the framework with clinical presentation, lab values, and images in a certain order that would resemble the way that the physician encountered it. A mixture of questions from simple identification to complex mechanisms were asked along with review of other similar pathogens and relevant pharmacology. Along with every activity, a small abridged review of the pathogen was written after researching and consulting appropriate literature. The review included the most clinically significant information to supplement the TBL activity such as history, epidemiology, transmission, disease, diagnosis, and treatment of the pathogen.
Future implications: These TBL activities can be utilized in future host defense course as a way for students to test their understanding while exploring a more clinically relevant scenario. Hopefully, students will appreciate the real world application of their expansive knowledge, and apply their newly developed understanding in rotations, residency, and even their medical practice.
Assessing the Role of Projections from the Ventral Hippocampus (vHIP) to the Medial Prefrontal Cortex (mPFC) in the Neural Circuitry of Social Familiarity-induced Anxiolysis (SoFiA) using Gi-DREADDs
Authors: Barron M. Regina , Truitt William 
Published: December 2020

The social interaction habituation (SI-hab) protocol has been used to demonstrate that rats acquire Social Familiarity-induced Anxiolysis (SoFiA), a form of safety learning where rats display anxiolysis in the presence of a familiar conspecific. SoFiA acquisition and expression can be simplified into four different constructs: social memory, anxiety, safety learning and anxiolysis. The neural circuitry of SoFiA; however, has not been fully identified. As a step towards elucidating the SoFiA neural circuitry we are identifying the role of projections from the ventral hippocampus (vHIP) to the medial prefrontal cortex (mPFC) in SoFiA acquisition.
Prior work from our lab has shown that the mPFC is needed for acquisition and expression of SoFiA. The mPFC may be the location of convergence of anxiety and social memory processing, making it a loci for safety learning. The goal of the current work is to identify the inputs to the mPFC that are pivotal for SoFiA acquisition. vHIP has been implicated in social memory and projects to the mPFC leading to the hypothesis that SoFiA acquisition requires vHIP projections to mPFC.
This hypothesis will be tested via intersectional genetics where neural tracts are selectively targeted through viruses. One virus is introduced at the soma of the neuron, and another is introduced at the end of the axon. The first virus, adeno-associated virus 8 (AAV8) will contain Cre-dependent code for an inhibitory DREADD (designer receptors exclusively activated by designer drugs.) The second virus, canine adenovirus 2 (CAV2) is picked up by axon terminals and transported to the soma where it will express Cre. Unfortunately, the uptake and transport of these viruses require specific receptors and the vHIP-mPFC pathway has poor CAV2 uptake. CAV2 levels will be increased by the introduction of Coxsackievirus and Adenovirus receptor (CAR) via AAV8 two weeks prior to CAV2-Cre injection.
A Collective Case Study: Parent-Child Sexual Health Communication of Current and Former Teen Parents in Lawrence County, Indiana
Authors: Betts Aislinn , Greene Allison , Sherwood-Laughlin Catherine 
Published: December 2020

Background/Objective:
In Lawrence County, Indiana, the birth rate for females ages 15-19 is 32.2 births per 1,000, which is significantly higher than the national average of 18.8. Project UNITE, a collaboration between the Lawrence County Pregnancy Coalition and the IU School of Public Health, aims to address this issue through a multifaceted evidence-based intervention. Since parent-child communication shapes values and behaviors, a collective case study was conducted with current and former teen parents to explore their perceptions of sexual health communication with their parents and, if applicable, with their children.
Methods:
Of the 58 semi-structured telephone interviews conducted through Project UNITE, eight were selected for this study based on transcript availability and identification as a current teen parent (2) or former teen parent (6). All participants recalled whether they had sexual health conversations with their parents and the extent of the discussions. Five shared experiences talking with their children. Deductive and inductive approaches were used to generate themes, which were then analyzed.
Results:
Most participants (7 of 8) reported little to no communication about sexual health with their parents due to a lack of comfortability, limited desire, and poor relationships. In contrast, all respondents with children over the age of five (5 of 5) reported open and frequent conversations with them. Several (3 of 8) recommended providing parents with resources about initiating discussions, and some suggested (2 of 8) a community program to promote sexual health communication.
Conclusions/Potential Impact:
The results revealed that while teen parents experienced a lack of sexual health conversations with their parents, they favored open and honest communication with their children. Barriers related to comfortability and knowledge could be alleviated through parental resources and parent-child programs. Medical professionals play a role in this solution by encouraging conversations about sexual health and engaging in educational programs.
Open Abdomen during Extracorporeal Membrane Oxygenation is a Safe and Effective Treatment for Abdominal Compartment Syndrome
Authors: Brown Joshua , Warnock Brielle , Turk Eamaan , Hocutt Gail , Gray Brian 
Published: December 2020

Background/Purpose
Historically, decompressive laparotomy and open abdomen for abdominal compartment syndrome has contraindicated Extracorporeal Membrane Oxygenation (ECMO) due to seemingly high risk of bleeding and infection. The literature shows few examples of this treatment, and the existing studies are inconclusive. The purpose of this study was to review the series at Riley Hospital for Children and evaluate the effectiveness of ECMO treatment for patients undergoing decompressive laparotomy with open abdomen to recommend future care guidelines.
Methods
We reviewed all pediatric (30 days to 18 years) patients treated with ECMO concurrently with decompressive laparotomy and open abdomen at Riley Hospital for Children from 2000-2019. We compared these patients with non-surgical pediatric patients supported with ECMO for respiratory failure at Riley Hospital for Children during the same period. Demographics, ECMO data, and outcomes were assessed. We performed t-test, ROC, and chi-square analyses. We defined significance as p=0.05.
Results
5 of 82 pediatric respiratory ECMO patients were treated with decompressive laparotomy and open abdomen. Survival among the surgical group was 60%, compared to 57% in the non-surgical group (p=0.9). Surgical patients had a similar incidence of bleeding complications (40%) compared to non-surgical patients (55.8%), p=0.486. Surgical patients had a significantly higher VIS (3126 vs 19.2, p=0.004), PaO2/FiO2 ratio (279.0 vs 72.9, p=0.031), and pump flow rate at 24hrs (112mL/kg/min vs 88.1mL/kg/min, p=0.045) than non-surgical patients, while receiving a similar volume of PRBCs (p=0.581) and requiring ECMO treatment for a similar amount of time (p=0.511).
Conclusion/Potential Impact
ECMO support in patients with decompressive laparotomy and open abdomen was associated with similar survival and bleeding complications compared to non-surgical ECMO patients. ECMO should be offered to or continued in eligible patients with abdominal catastrophe, as it is effective in supporting organ function while not significantly increasing the risk for complications.
Investigating Differences in Nutritional Parameters in Ugandan Children with Plasmodium falciparum Severe Malaria
Authors: Brown Lucy , Co Katrina , Opoka Robert , Datta Dibyadyuti , John Chandy 
Published: December 2020

Background: In 2018, malaria produced an estimated 272,000 deaths in children <5 years of age, accounting for 67% of all malaria deaths worldwide, with a majority in the WHO African Region. Malnutrition is an important risk factor for malaria. Wasting, Stunting and Underweight are crucial indicators of malnutrition. Annually, 14 million children <5 are classified as wasted and 59 million children are classified as stunted.
Objective: The objective of this study is to determine the association between each of the major manifestations of severe malaria (SM) and nutritional parameters – weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ) – in children from the Ugandan cities Mulago and Jinja.
Methods: To assess differences in WAZ, HAZ, and WHZ by the five types of SM and community controls (CC), we evaluated Z-scores from children <5 years old enrolled in a prospective cohort study (NDI, Neurodevelopmental Impairment in Children with Severe Malaria) at enrollment and 12-month follow-up.
Results: WAZ and WHZ at baseline were significantly lower among SM groups than in CC (p<0.001), but there were no significant differences observed at 12-month follow-up. There were no major differences in HAZ between the SM and CC groups. WAZ and HAZ at baseline were significantly lower among High Mortality (HM) versus Low Mortality (LM) groups (p<0.01). At 12-month follow-up, HAZ remained significantly lower in HM versus LM (p<0.01). There were no major differences in WHZ between the HM and LM groups. Compared to those who survived, the 27 children who died had significantly lower WAZ (p<0.05), but no major differences in HAZ or WHZ.
Conclusion: Underweight, stunting, and wasting may be risk factors for SM. Overall, a more comprehensive understanding of how SM elicits adverse effects in children is necessary. Nutrition intervention programs must be implemented to prevent child stunting, wasting, underweight, and mortality.
North Central Indiana AHEC: STEPS Program Impact
Authors: Ceglio Katie , Stout Julianne 
Published: December 2020

Background/Objective:
North Central Indiana Area Health Education Center (NCI AHEC) aims to encourage rural students in their service district to pursue healthcare. In light of rural healthcare shortages found in Indiana, they implemented the Successfully Training and Educating Pre-medical Students (STEPS) program, available to college juniors at Indiana University – Kokomo. Through MCAT prep courses, workshops about interviews, and job shadowing, the goal of the program is for more rural students to be accepted into local medical schools, to then return to practice in that rural area. This case study examines the initial impacts of the STEPS program and the path to healthcare for a student at IU – Kokomo.

Methods:
A mixed methods study was conducted. First, a survey was administered by NCI AHEC to students who participated in the STEPS program using a retrospective pre/post design. The quantitative data, representing students’ opinions and goals, was aggregated and interpreted. An interview was then done with a previous STEPS student. This student’s experience was analyzed.

Results:
Participation in the STEPS program resulted in increased knowledge about healthcare careers and plans to pursue further education for healthcare careers across all students. The STEPS program has identified strengths, including activities that increase student commitment to pursuing healthcare and mentorship for students. Areas for growth were also identified, including adding application assistance, decreasing competition for resources, and increasing efforts to keep students in Indiana.

Conclusion and Potential Impact:
Initial evaluation suggests that the STEPS program is beneficial in assisting rural students on their path to a career in healthcare. Analysis of the interviewee’s experience provides recommendations for improvements of the STEPS program in the future.
The Association of Surrogate Decision Makers’ Anxiety and Depression Levels at Baseline with End-of-Life Patient Care Decisions
Authors: Chen Andy , Slaven James , Torke Alexia 
Published: December 2020

Rationale: Little is known about how the psychological status of surrogate decision-makers (SDMs) influences their decisions regarding end-of-life patient care. Anecdotal evidence suggests high psychological distress may lead to denial of poor prognosis and continued aggressive treatments. We hypothesized that SDM psychological distress is associated with greater use of life-sustaining treatments and lower hospice use for seriously ill older adults.
Objectives: To determine the relationships between surrogate anxiety and depression levels and surrogates’ decisions regarding end-of-life treatments.
Methods: This prospective observational study enrolled patient/surrogate dyads from three Midwestern hospitals in one metropolitan area. Eligible patients were 65 years or older and admitted to the medicine or medical intensive care services. Baseline surveys between hospital days 2 and 10 assessed anxiety (GAD-7) and depression (PHQ-9) levels, and SDM preference for do-not-resuscitate (DNR) status. Chart reviews of the electronic medical record and regional health information exchange six months after enrollment identified the use of aggressive life-sustaining treatments and hospice for patients who died.
Results: There were 278 patient/surrogate dyads. After adjusting for other demographic and illness factors, anxiety (adjusted odds ratio [aOR] 1.09; 95% CI 1.02, 1.16; P=.007) and depression (aOR 1.08; 95% CI 1.02, 1.15; P=.011) were associated with greater preference for DNR status. Among patients who died (n=115), anxiety (aOR 0.89; 95% CI 0.79, 0.99; P=.039) was associated with less use of aggressive life-saving interventions within the last 30 days, and anxiety (aOR 1.23; 95% CI 1.09, 1.39; P<.001) and depression (aOR 1.14; 95% CI 1.04, 1.25; P=.004) were associated with greater hospice use.
Conclusions: Contrary to our hypothesis, heightened SDM psychological comorbidities at baseline are associated with greater DNR preference, as well as less life-sustaining treatment and more hospice use at the end of life. More research is needed to understand the impact of psychological distress on surrogate decision-making.
Comparison of Diffusion and Perfusion Techniques in Differentiating High Versus Low Grade Pediatric Brain Tumors
Authors: Chen Eric , Ho Chang , Gray Benjamin , Parker Jason , Diller Emily , Wen Qiuting , Wu Yu-Chien , Anthony Gregory , Territo Paul 
Published: December 2020

Background/Objective: Brain tumors are the most common solid cancer in children and cause significant mortality and morbidity. We compare the effectiveness of different parameters in predicting tumor grade between dynamic contrast enhancement (DCE), intravoxel incoherent motion (IVIM), dynamic susceptibility contrast (DSC) perfusion and diffusion weighted imaging (DWI).

Methods: A retrospective blinded review of pediatric brain tumors with DCE, IVIM, DWI, and DSC was performed. Parametric maps were registered to T2 weighted images. Volumetric regions of interest (ROI) were manually segmented from solid tumor components for each patient by a neuroradiologist (CH), neuroradiology fellow (BG), and medical student (EC). Resulting mean values for parameters from DCE (Ktrans, Kep, Ve, Vp,), IVIM (D, D*, f), DSC (rCBV) and DWI (ADC) were compared using Student’s t-test for high- and low-grade tumor groups based on WHO grading from pathology. For significant parameters, receiver operating characteristic (ROC) analysis with area under curve (AUC) was performed.

Results: 20 subjects were included with 9 low grade and 11 high grade tumors. Significant differences between low versus high grade were demonstrated for D (10−3 mm2/s) (1.4±0.4 vs 0.9±0.2, p=0.01), f (0.04±0.02 vs 0.07±0.02, p=0.02), ADC (10−3 mm2/s) (1.4±0.4 vs 0.9±0.3, p=0.009) and rCBV (2.2±0.9 vs 4.7±2.1, p=0.003). No significant difference was found for D* or any DCE parameter. AUC from ROC was similar for all significant parameters [D (0.81, p=0.003); f (0.80, p=0.003); ADC (0.83, p=0.001); rCBV (0.83, p=0.0005)].

Conclusion: D and f parameters from IVIM can significantly differentiate high versus low grade pediatric brain tumors similar to ADC and rCBV. Conversely, no DCE parameter was significant.

Scientific Implications: The results will assist the selection of MRI sequences that best predict tumor grade, as well as guide tumor biopsy for the most aggressive tumor portions. Further study of these techniques may correlate with molecular profiling and predict outcome.
Mortality Rates in Mechanically Ventilated Patients with COVID-19
Authors: Class Jonathan , Khan Sikandar , Khan Babar 
Published: December 2020

Background/Objective:
High mortality rates among mechanically ventilated COVID-19 intensive care unit (ICU) patients have raised concerns regarding use of mechanical ventilation in management of patients with COVID-19. Additional data is needed in this discussion to better understand treatment strategies for this vulnerable population. We conducted a study to examine length of stay, duration of mechanical ventilation, mortality, and risk factors for death in critically ill patients with COVID-19.

Methods:
Observational study in patients admitted to Eskenazi Health and Indiana University Health Methodist ICUs. Participants were 18 years and older patients admitted to the ICU from March 1 2020 to April 27, 2020 who tested positive for COVID-19. Primary outcomes for this study were in-hospital mortality, duration of mechanical ventilation, and the length of stay in the ICU.

Results:
The study cohort was made up of 242 patients. The mortality rate was 19.8% (48/242) for the overall cohort and 20.5% (38/185) for mechanically ventilated patients. Age was a significant risk factor for in-hospital mortality [increased hazard in in-hospital mortality: age 65-74 years (HR: 3.1, 95%Cl=1.2-7.9, p=0.021), age 75+ (HR: 4.1, 95%CI=1.6-10.5, p=0.003) compared to those younger than 65]. In our Cox’s proportional hazard model, ESRD (HR:5.9, 95%CI=1.3-26.9, p=0.021) along with age were the only risk factors with statistical significance. The median duration of mechanical ventilation in the overall cohort was 9.3 days (IQR=-5.7-13.7). In patients that died, median ICU length of stay was 8.7 days (IQR=4.0-14.9), compared to 9.2 days (IQR=4.0-14.0) in those discharged alive.

Conclusion/Clinical Impact:
We found lower mortality rates and longer length of stays in our cohort than in previous studies. While more data is needed, this study supports continued use of mechanical ventilation ARDS recommendations for treating patients with ARDS from COVID-19. Further, this data potentially shows a benefit to not having a strained healthcare system.