bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining Multisystem Inflammatory Syndrome in Children (MIS-C) Amidst the SARS-CoV-2 Pandemic
Authors: Harris Matthew , Datta Dibyadyuti , Co Katrina , Bhumbra Samina , John Chandy
Published: December 2020

Background/Objective: Multisystem Inflammatory Syndrome in Children (MIS-C) is a novel and rare pediatric post-infectious complication associated with SARS-CoV-2 infection. First described in April 2020, our scope of understanding is limited but rapidly growing. Our objective was to construct a literature repository containing MIS-C patient data from available publications to serve as a curated collection of literature on the topic. This collection facilitates direct comparison of data from various sources, allowing for informed discussions of MIS-C.  
 Methods: A database search strategy was developed for locating primary literature on MIS-C available on PubMed, medRxiv, and bioRxiv databases. Literature searches were conducted from June 26, 2020 to July 10, 2020. Search results were tested against several criteria before inclusion in the repository. Intrinsic limitations for each publication were identified during quality review. Data from each source was organized in a standardized format for analysis. 
 Results: 26 publications met inclusion criteria, 9 (35%) in pre-print status. 742 cases of probable or confirmed MIS-C were reported. Individuals ranged from 7 months to 20 years old and 58% were male. By SARS-CoV-2 PCR testing, 257/707 (36%) were positive while 485/597 (81%) were positive by SARS-CoV-2 serology testing. Common presenting symptoms included fever, one or more gastrointestinal symptoms, and rash. Laboratory testing varied, but elevated C-Reactive Protein was the most common finding (411/689, 60%), followed by elevated D-Dimer (214/470, 46%). Echocardiogram findings included coronary artery dilation in 38/414 (9%) and decreased ejection fraction in 177/330 (54%). Treatments offered included intravenous immunoglobulin (486/742, 65%), followed by steroids (376/742, 51%). 450/577 (78%) required ICU care. Patient outcomes were generally favorable, with 11 (1%) fatalities at the time of publication. 
Conclusion/Impact: Our repository of MIS-C literature compiled patient reports to identify common clinical presentations and laboratory findings. Future literature reviews are necessary to elucidate mechanisms associated with MIS-C and establish diagnostic criteria.
Identifying a Need for Mental Health Services Posthospitalization in Adolescent Trauma Patients
Authors: Hochstetler Alexandra , Vetor Ashley , Raymond Jodi , Bozell Hannah , Bell Teresa
Published: December 2020

Background: Nearly 150,000 children were hospitalized due to an injury in 2018. Hospitalized patients are often prescribed opioids and as a result, one in eight adolescents will continue using opioids twelve months after hospitalization. Predictors of sustained opioid use and future misuse posthospitalization have yet to be studied in adolescents. One of these predictors may be mental health disorders following hospitalization. It is known mental health disorders can lead to substance use disorders if not addressed properly. In this study we examined the associations between injury severity, mental health, and substance use among adolescents.  
 
Methods: Patients between 12 to 18 years old admitted for trauma were surveyed upon enrollment, and subsequently at 1, 3, 6, and 12 months posthospitalization. These surveys measured anxiety, depression, posttraumatic stress, prescription and non-prescription drug use, pain severity and pain interference. 
 Results: At enrollment and one-month posthospitalization, higher pain interference was associated with anxiety (p=.003), depression (p<.001), and PTSD (p=.004). Increased pain severity was also associated with higher PTSD (p=.003) However, at three months, pain severity and interference were only associated with PTSD (p=.005, p=.009). Frequent alcohol use and higher PTSD were found to be statistically significant at six and twelve months (p=.02). Regular prescription opioid use was related to higher anxiety (p=.048) and depression (p=.048) only at enrollment and higher PTSD only at one month (p=.034). Prescription opioid use was not associated with pain severity and interference at enrollment but was found significant at one month (p=.016, p=.36). 
 
Conclusion: Adolescents who reported higher pain severity and interference also more commonly had mental health disorders such as PTSD, anxiety, and depression. Higher PTSD scores and frequent alcohol use were also related post-injury. Screening for mental health after hospitalization should be further investigated in identifying adolescents who may be at risk for future opioid use disorders.
Anomalous Celiac Trunk Variation Encountered in Y-90 Radioembolization
Authors: Huang Alexander , Yedavalli Ramana
Published: December 2020

Background: 
Yttrium-90 microsphere embolization is a selective internal radiation therapy (SIRT) used in the treatment of hepatocellular carcinoma and liver metastases. Current literature recommends lobar, or more selective, infusion of SIRT to allow for precise radiation administration and to mitigate risk of non-target embolization. Lobar infusion requires knowledge of anatomical variations of hepatic arterial supply. The trifurcation of the celiac trunk into the left gastric artery, splenic artery, and common hepatic artery is the most common presentation representing 51% to 89% of patient anatomy. A replaced right hepatic artery (RHA) arising from the superior mesenteric artery (SMA) is one of the most common variants of hepatic arterial supply with a prevalence of 10.6% to 15%. Common variations such as these are well described and easily mapped using catheter angiography, but rarer variations are not as well described and more challenging to map. 
 
Project Methods: 
Mapping catheter angiogram of the celiac trunk and SMA was obtained. Additional aortogram and CT angiogram were obtained to further elucidate patient’s anatomy. 
 
Results: 
Initial mapping angiogram was only partially successful because the RHA could not be selected. Abdominal aortogram and CT angiogram of the abdomen and pelvis revealed a replaced RHA arising directly from the distal celiac trunk. Additionally, the patient had a replaced cystic artery arising from the left hepatic artery and an arc of Buhler connecting the proximal SMA to the proximal aspect of the right hepatic artery. 
 
Conclusion: 
Radiologists need to be aware of rare variations in hepatic arterial supply for the safe and effective treatment of hepatic neoplasms, whether primary or metastatic. Description of arterial variation and informed selection of arterial branches will remain a critical aspect of improving efficiency and reducing risks of hepatic embolization procedures.
Glycolysis and Lactate Dehydrogenase A in Iron-Mediated Suppression of Osteoblast Function
Authors: Hunter Pete , Edwards Daniel , Miller Christopher , Clinkenbeard Erica
Published: December 2020

Background/Objective:  
An estimated 37 million Americans have Chronic Kidney Disease (CKD), a condition in characterized by gradual decline in kidney function1. Patients with CKD are often afflicted with skeletal fractures, increasing morbidity and mortality. CKD has also shown a strong correlation with iron-deficiency anemia. The underlying mechanisms of how iron-deficiency anemia of CKD affects bone loss are not well understood. Based on RNA-sequencing results, we hypothesize that lactate dehydrogenase A (LDHA) may play a role in iron-deficiency mediated suppression of osteoblast differentiation and function. 
 
Methods:  
Mouse Progenitor Cells (MPC2) were incubated in osteogenic media along with deferoxamine (DFO) to induce differentiation in chronic iron deficiency; samples were collected after 7 and 14 days. Quantitative real-time PCR and western blot were used to validate LDHA mRNA and protein levels in DFO treated MPCs versus control cells. RNA levels of osteoblast genes and LDHA were also assessed in a pre-clinical mouse model of CKD. 
 
Results:  
In vitro, MPCs cultured in DFO media showed a significant increase of LDHA mRNA at 7 days (p=0.015) and returned to near control levels by day 14. Western blots showed a slight increase of total LDHA protein in DFO treated MPCs at 7 days and a large increase of protein at the 14-day mark (p=0.051). In vivo, CKD bone marrow showed a reduction in osteoblast gene expression (osteocalcin and type 1 collagen; p<0.05). LDHA mRNA expression was increased in CKD mice bone marrow when compared to wild-type mice (p=0.051), suggesting an inverse relationship. 
 
Conclusion and Potential Impact:  
Inappropriate activation of glycolysis and LDHA appears to play a role in iron-deficiency mediated suppression of osteoblast function in relation to CKD, both in vitro and in vivo. Further exploration of this relationship could be critical to the development of improved treatment options to maintain bone homeostasis during CKD.
Mental Health and Asthma Related Outcomes for Pediatric Patients Receiving Dupilumab Therapy
Authors: Kamran Saad , Krupp Nadia
Published: December 2020

Background and Hypothesis: Asthma can hinder the activities that pediatric patients can do in their daily lives. This could affect their mental health because they may have anxiety about when their next asthma attack is going to occur or whether or not they will be able to participate in the activities that all their classmates are able to. In order to help reduce the detriments of asthma on mental health, pediatric patients with asthma were given Dupilumab in order to see whether their asthma and mental health outcomes improved by reducing the severity of their asthma. We hypothesized that patients using Dupilumab were going to see better outcomes in their mental health by decreasing anxiety and depression while also improving their breathing by improving their FEV1, FEV1/FVC ratio, and Asthma Control Score. 
 
Project Methods: Pediatric patients with severe persistent asthma were entered into a High Risk Asthma clinic where they received treatment. The patients would take a spirometry test each visit and also answer questions in the GAD-7 and PHQ-9 mental health screens. The values were noted in their medical charts and also entered into a database. Using the database, the averages of all the patients’ scores before they began Dupilumab and after they began Dupilumab were calculated along with the standard deviation in order to determine a statistically significant difference.  
 
Results: Upon averaging the data, each category showed better outcomes after Dupilumab therapy, but the standard deviation always overlapped with the results from before Dupilumab therapy was started. 
 
Conclusion and Potential Impact: Despite not being statistically significant, Dupilumab did improve the asthma and mental health outcomes of patients. Further exploration with more data in order to eliminate outlying values could change the results. Dupilumab and other biologic treatments could potentially improve asthma outcomes in the future for pediatric patients.
Investigating the quality and completeness of medication data available within the Indiana Network for Patient Care
Authors: Khera Jaibir , Grannis Shaun , Kasthurirathne Suranga
Published: December 2020

Background and Hypothesis: Healthcare data is increasingly fragmented across multiple points of care due to increased specialization of healthcare services and mobility of patient populations [1]. The Indiana Network for Patient Care (INPC) plays a pivotal role in capturing, standardizing, and integrating comprehensive datasets[2]. Currently, the INPC receives medication data from a variety of sources. However, some of these sources are costly and may be incomplete and/or inaccurate. We aim to characterize the degree to which additional claims data can augment or replace existing INPC medication data. Our hypothesis is that the new claims datasets will provide additional medication information for patients in the INPC. 
Methods: Data analysts extracted and formatted a claims data sample for analysis. Individuals from the sample dataset were then mapped to INPC data using global person identifiers. The resulting analysis was split into two phases.  
Phase 1: To provide an initial high-level assessment of overlap and complementarity between INPC and new claims data, we computed the number of patients captured in each data source. Patients were classified into five groups as illustrated in Figure 1. To investigate Medicare usage, we also stratified datasets by patient age: less than 65 and 65 and older.  

Figure 1: Venn diagram illustrating medication claims data analysis approach. Several subgroups  among the INPC will be compared to existing pharmacy claims and new claims data sources. 
Phase 2: Investigation of data quality on a clinical use case. These datasets will be used to investigate the current state of the opioid epidemic in Indiana.  
Results: With the completion of phase 1, we expect to characterize the current state of claims data across each of the patient groups, and how they influence data quality within the INPC. 
Discussion. The quality and completeness of medication data currently available via the INPC in unclear. Our efforts add clarity to the current status of these datasets, and how they can be augmented for increased research and clinical productivity. 
 
Citations 
[1] Stange, K.C., The problem of fragmentation and the need for integrative solutions. The Annals of Family Medicine. 7(2):100-103, 2009. 
[2] McDonald, C. J., Overhage, J. M., Barnes, M., Schadow, G., Blevins, L., Dexter, P. R., ... & INPC Management Committee. (2005). The Indiana network for patient care: a working local health information infrastructure. Health affairs, 24(5), 1214-1220.
Racial Disparities in Lung Cancer Diagnosis and Treatment: A Single Center, Retrospective Study in Central Indiana
Authors: Killion Andrew , Duncan Francesca , Al Nasrallah Nawar , Sears Catherine
Published: December 2020

Background/Objective: 
Lung cancer is the second most common cancer and the leading cause of death from cancer in the United States. However, there is a disparity in incidence and mortality between African Americans and Caucasians. This study aims to analyze factors that could describe this difference, such as treatment, socioeconomic, or behavioral differences using information from an Indiana University Simon Cancer Center (IUSCC) lung cancer registry. We hypothesized that African Americans will have a higher lung cancer stage at diagnosis and mortality, associated with less timely, stage-appropriate treatment. 
Methods: 
Using data collected from patients diagnosed with lung cancer at IUSCC from 2000-2016, we compared racial differences in diagnoses and subsequent management. Patients were categorized by race and clinical stage at diagnosis. Further categorization by sex, vital status, age at diagnosis, time from diagnosis to treatment and death, tobacco use, surgery, chemotherapy, insurance coverage, and histology was performed. We determined the rates of surgery or chemotherapy by stage at diagnosis. Statistical analyses are by student t-test or 2-way ANOVA. 
Results: 
African Americans were younger than Caucasians at lung cancer diagnosis (average 63.4 vs. 61.2 years p-value < 0.001). African American race was associated with a longer time from diagnosis to treatment (36.4 vs. 32.1 days, p=0.023) and shorter time from diagnosis to death (475.1 vs. 623.7 days, p=0.001). The data suggests that African Americans have a later stage at diagnosis, are more likely to be uninsured and less likely to be covered by private insurance. The data suggests African Americans have a lower rate of surgery (Stages 1-3) and chemotherapy (Stages 3B and 4). 
Conclusion and Potential Impact: 
This data suggests racial differences in lung cancer diagnosis, treatment and outcomes. Future analyses will focus on multiple comparisons to determine possible impacts of socioeconomic and environmental factors on these outcomes at IUSCC and other university-affiliated health care systems.
Do Maternal Demographics and Prenatal History Impact the Efficacy of Betamethasone Therapy for Threatened Preterm Labor?
Authors: Kinney Mary , Haas David , Trussell Hayley , Silva Larissa , Quinney Sara
Published: December 2020

Background/Objective: Betamethasone is used to accelerate fetal lung maturation in women with threatened preterm labor, but its efficacy is variable and limited by the lack of patient individualization in its dosing and administration. To determine sources of variability and potential opportunities for individualization of therapy, the objective of this study was to evaluate maternal factors associated with development of neonatal respiratory distress syndrome (RDS) in a cohort of women who received betamethasone.  
 
Methods: This study prospectively enrolled women, gestational ages 23-34 weeks, who received betamethasone for threatened preterm labor (n=208). Maternal demographics, prenatal history, and neonatal outcomes were abstracted from Epic and Cerner records. RDS was the primary outcome. Associations between RDS diagnosis and factors such as maternal demographics, prenatal history, and betamethasone dosing were evaluated in a multivariable regression adjusted for gestational age at delivery. A secondary analysis limited the cohort to women who delivered within 2 weeks of betamethasone dosing (n=95). 
 
Results: Of 208 deliveries, 44.1% resulted in neonatal RDS. Within the overall cohort, the only significant association with RDS was the type of delivery, with 61.3% of cesarean births resulting in RDS versus 28.7% of vaginal births (adjusted OR 1.17 [1.06-1.28]). Among deliveries within 14 days of betamethasone dosing, women who experienced preterm premature rupture of membranes (PPROM) had lower RDS outcome rates than those without PPROM (52.6% vs. 78.9%, adjusted OR 0.80 [0.65-0.98]). Maternal age, BMI, race, and ethnicity were not associated with RDS. 
 
Conclusion: Maternal characteristics alone may not be useful biomarkers in predicting neonatal RDS. The association between PPROM and RDS may suggest the importance of the time frame between betamethasone dosing and delivery. The finding of higher risk for RDS among neonates born by cesarean is consistent with other studies and bears further exploration as betamethasone therapy may mediate the association.
The Combinatorial Effects of Cognitive Behavioral Therapy with Aerobic Exercise in the Treatment of Fibromyalgia
Authors: Ko Bryan , Bair Matthew
Published: December 2020

In the US alone, the chronic pain condition of fibromyalgia affects approximately 10 million people. Current treatment protocols focus heavily on pharmacological interventions; however, such treatments are unfavorable due to debilitating side effects and a lack of effectiveness in 2/3 of patients. Two non-pharmacological interventions which have been shown to produce meaningful pain relief are Cognitive Behavioral Therapy (CBT) and Aerobic Exercise. However, the combinatorial effects of these treatments have never been fully explored and it is unknown if these treatments interact in an additive manner or if the benefits of one negate the benefits of the other. In this work we conducted a literature review using the databases of Pubmed, OVID MEDLINE, PsychInfo, and Embase from 1995 to May 2020 to determine if the combinatorial effects of these two treatments on pain relief and pain interference are significantly greater than that of aerobic exercise alone. We reviewed over 200 potential articles for relevance. Seven papers were found to directly address our target question, two from the US and five from Europe with sample sizes ranging from 34 to 442. One paper showed improvement in pain intensity and two papers showed improvement in pain interference due to combinatorial treatment over aerobic exercise alone. When evaluating our results, we weighted these papers based on sample size, length of treatment and observation, method of CBT administration, and surveys chosen for data collection. We were unable to definitively show that CBT in combination with aerobic exercise is more effective than aerobic exercise alone at decreasing pain intensity and/or interference in patients with fibromyalgia. However, most of these papers identified several psychological and design based confounding factors that could influence their results. We recommend that more research be conducted in this area to further ascertain the effectiveness of this specific combinatorial treatment for fibromyalgia.
pSmad 3D Localization in Zebrafish Embryos
Authors: Ku Madeline , Wang Xu , Umulis David
Published: December 2020

Background and Hypothesis 
During embryonic development, individual cell fate is determined by morphogen gradient surrounding a particular cell. In particular, the positional information regarding dorsal-ventral pole is determined by the BMP concentration gradient and the anterior-posterior positional information is determined by Nodal concentration gradient. pSmad is a downstream product of BMP signaling that plays a role in the feedback regulation of BMP. Previously, we had taken confocal images of the immunohistochemistry labeled pSmad embryos on its side view (yolk sac facing the side, where ventral and dorsal pole is visible) to understand the localization of pSmad and its role in BMP signaling. However, signals diminished in the deeper part of the embryos making it harder to distinguish signals from the background noise. In this experiment, we decided to use wavelet segmentation method for image processing that will help us pick up the signals better and to reconstruct the embryos from 3 different views. We hypothesized by adding these 2 procedures, it will give us a more accurate localization of pSmad signaling in zebrafish embryos.   
Experimental Design or Project Methods 
We first used immunohistochemistry to label pSmad in 3 8 hours post fertilization zebrafish embryos. We then used Zeiss DM800 confocal to image the immunohistochemistry labeled pSmad embryos in 3 different views (pole – yolk facing towards camera, ventral, and side). These images are processed through wavelet segmentation method using Matlab, then reconstruct the half embryo from the 3 views rotation. We will then compare the result we obtained compare to the raw files and results we obtained from previous experiments.  
Results 
Thus far, we had obtained 3 views on 3 different embryos and complete the wavelet segmentation processing. We had yet to merge the 3 views to reconstruct the embryos and compare to previous results. 
Conclusion and Potential Impact 
This study will establish a more accurate localization studying method on immunohistochemistry labeled zebrafish embryos that is not limited to pSmad signaling. It can be used to build mathematical model of BMP feedback regulation signaling.
Efficacy of Mutant HPV-16 E6 Proteins in p53 Degradation
Authors: Lange Charles , Rietz Anne , Androphy Elliot
Published: December 2020

Background and Objective:  
High-risk human papilloma viruses (HPV) are the causative agent in the majority of anal, cervical, vaginal, vulvar, penile, and oropharyngeal cancers with an annual incidence of 630,000 cases world-wide. These viruses initially cause dysplasia that subsequently increases neoplasia risk. HPV’s encode eight major viral proteins with the E6 protein being crucial for replication. E6 binding to ubiquitin ligase E6AP initiates polyubiquitination of p53, targeting the protein for proteasomal degradation. We are taking a novel approach to inhibit HPV16+ dysplasia and cancers by designing inhibitors targeting specific amino acids of 16E6, which reside in the E6-E6AP binding pocket, thereby preventing p53 degradation. To affirm interaction with the targeted side chain, we generated E6 point mutations that serve as specificity controls. These mutations are designed to disrupt interaction with the compound. To ensure their suitability for our studies, we are herein characterizing their capacity to bind E6AP and bind and degrade p53. 
  
Methods:  
E6 mutants were generated by site-directed mutagenesis and analyzed by sequencing. H1299 cells were transfected with GFP, wild-type (WT) E6, or mutant HPV-16 E6 plasmids +/- WT p53 plasmid. After 48 hours, cells are lysed and 16E6 was immunoprecipitated. Proteins bound to 16 E6 were separated by SDS-PAGE and subjected to western blot. Binding to E6AP and p53 was analyzed and presence of 16E6 was confirmed by immunoblotting. To test for p53 degradation, H1299 cells were transfected with firefly luciferase (Fluc) (transfection control) and p53-luciferase along with WT E6, mutant E6 proteins, or empty LXSN plasmid. After 24 hours p53-luciferase was measured with Dual-Glo Luciferase Assay.  
 
Results:   
To be determined 
 
Conclusion:   
 To be determined
Possible Neuroinflammatory Mechanisms Which May Lead to Long-Term Neurological Disorders in COVID-19 Patients
Authors: Lange Michael , Shi Riyi
Published: December 2020

This review aims to provide insight into the possible long-term neurological complications that COVID-19 patients may experience after the resolution of intense acute inflammation characterized as “cytokine storm.” Neurological symptoms such as fatigue, headache, dizziness, nausea, confusion, dyspnea, anorexia, malaise, myalgia, ataxia, seizure, hypogeusia, and hyposmia are commonly seen in these patients. COVID-19 related encephalitis is also seen sporadically. However, some researchers believe neuroinflammation is more common than what is reported. Neurological abnormalities that are linked to neuroinflammation are of particular concern because neuroinflammation is hypothesized to cause neurological diseases such as Alzheimer’s Disease, Parkinson’s Disease, and Schizophrenia. Many potential routes can lead to inflammation in the nervous system and elicit neuron cell death in COVID-19 patients. These include the potential neurotropic pathway of the novel coronavirus, CNS parenchymal infectability, thrombotic ischemic stroke, cytokine storm, and blood-brain barrier breakdown. Past pandemics of similar neurotropic viruses could also offer insights regarding the long-term neurological effects of COVID-19. In support of our hypothesis, the Spanish Flu pandemic of 1918-1919 saw an increased incidence of neurodegenerative disease, Parkinson’s disease, and schizophrenia. We do not know exactly what the future will hold for COVID-19 however, it is of paramount importance to attempt to anticipate and prepare for the possible chronic neurological sequelae and mitigate or prevent their effects.
Therapeutic targeting of hypoxia and hypoxia inducible factor 1 with acriflavine in experimental esophageal adenocarcinoma
Authors: Lankford Christian , Hassan Sazzad , Von Holzen Urs
Published: December 2020

Background: Hypoxia or insufficient tissue oxygenation contributes to cancer aggressiveness and poor clinical prognosis. Typically, cancer cell lines are used in two-dimensional (2D) cultures for screening of anticancer agents, and they do not represent the hypoxic tumor microenvironment. In this study, we established a novel three dimensional (3D) spheroid co-culture model of esophageal adenocarcinoma (EAC). We then observed treatment response of chemo and hypoxia-targeting therapies in 2D, 3D and in vivo models of experimental EAC. Methods: EAC 3D spheroids were generated from co-culturing human EAC and fibroblast cell lines. NanoCulture® plates and dishes were used for 3D spheroid cultures. Hypoxic status was detected by adding hypoxia probe LOX-1 and fluorescent microscopy. Paclitaxel (PT), carboplatin (CP) and nanoparticle albumin-bound paclitaxel (NPT) were used as chemotherapeutic agents, whereas acriflavine was used as hypoxia-targeting agent. In vitro cell growth was detected by WST-1 assay, in vivo tumor growth was detected by measuring subcutaneous xenografts, apoptosis was detected by cleaved caspase 3/PARP expressions, and hypoxia-targeting was detected by HIF-1α expression. Results: 3D culture was more resistant to antiproliferative effect of chemotherapeutic agents PT, CP, NPT over 2D monolayer culture. Contrary to that, hypoxia-targeting agent acriflavine showed stronger antiproliferative effects in 3D culture than in 2D culture. We observed strong expression of hypoxia inducible factor-1α (HIF-1α) in 3D culture with no expression of HIF-1α in 2D culture, and acriflavine treatment completely abolished the HIF-1α expression in 3D culture. We also observed hypoxia inside the 3D culture spheroids, but not in cells grown in 2D culture. In addition, acriflavine showed significant in vivo antitumor efficacy both as monotherapy and in combination with NPT. Conclusion: Thus 3D cultures may be better than 2D cultures in simulating the important in vivo tumor characteristic of hypoxia, and HIF-targeting therapy acriflavine could be a novel treatment strategy for EAC.
Promoting Community-based Engagement with Pregnant and Postpartum Women with Substance Use Disorder via Human-centered Design
Authors: Liu Scott , Cockrum Brandon , Moore Courtney , Claxton Gina , Parks Lisa , Wiehe Sarah , Chambers Joanna , Denne Scott , Litzelman Debra
Published: December 2020

Background: 
Pregnant women with substance use disorder (SUD) are a vulnerable population that often contends with stigma, socioeconomic inequity, and mental health issues. The Community-based Addiction Reduction (CARE) Program connects pregnant and postpartum women with SUD in Central Indiana with addiction recovery coaches (ARCs) and attachment theory therapists, who provide linkage to community resources and mental health support. However, recruitment and retention of participants continue to be challenging. 
 
The goals of this research are to identify barriers and facilitators to recruitment/retention and to translate findings into patient engagement materials. 
 
Methods: 
ARCs are women with family or personal experience with SUD, and serve as proxies for patient perspectives. Qualitative data from nine semi-structured interviews conducted with ARCs and their supervisors were clustered thematically to identify barriers and facilitators to recruitment/retention. Rapid prototyping, a methodology within human-centered design (HCD), was then employed to iteratively develop deliverables, incorporating several rounds of critique from ARCs, weekly case conferences, and discussions with clinician-investigators and designers. 
 
Results: 
Facilitators to recruitment/retention included: (1) ability to personally relate to ARCs and (2) ARC advocacy when navigating community and health system resources. Barriers to recruitment/retention included: (1) distrust (associated with participants’ histories of adverse childhood events and other trauma); (2) overwhelming number of interactions with various agencies (DCS, clinics, counseling, etc.); (3) fluctuating phone access, (4) intensive enrollment process, and (5) overall program visibility. 
 
The following deliverables were designed: (1) introduction videos of ARCs (2) brief videos of patient advocacy stories told by ARCs, (3) personalized cards paired with existing gift card incentives, and (4) journal for self-reflection and self-motivation.  
 
Potential Impact: 
Qualitative findings underscore the importance of patient-centeredness in engagement with CARE participants, who are often overwhelmed and wary of others. HCD approaches within multidisciplinary teams can be leveraged to enhance program uptake and delivery within underserved populations.
Cell-Scale Modeling to Probe Mechanobiology during Early Cortical Development
Authors: Lonnberg Adam , Garcia Kara
Published: December 2020

Background/Objective: During early cerebral cortex development, neurons form from proliferative glial cells near the ventricular (apical) surface, then migrate along radial glial scaffolds to the cortical surface. In species with wrinkled brains, the presence of basal radial glial cells (bRGCs), radial glial cells which have detached from the ventricular surface, is correlated to the process of gyrification. While mechanical forces are also involved in gyrus creation, the link between the mechanical and biological aspects of this process remains unelucidated. In this study, we hypothesized that radial tension may lead to the production of gyri via the intermediary creation of bRGCs. 
Methods: To test this hypothesis, the cell-level modeling software CX3D was used to simulate a system in which radial tension acts on radial glial cells (RGCs), facilitating the semi-stochastic production of bRGCs during the process of neocortex development. The outcome of this model was contrasted with a control case in which bRGCs were not allowed to form, and the two models were compared based upon the presence of neurons on the basal surface. 
Results: The production of bRGCs via tension corresponded to a significant increase in the presence of neurons on the pial surface, even if the total number of glial cells—and thus total number of neurons generated—remained constant. Additionally, the likelihood of neurons moving more basally was found to be significantly greater in the presence of bRGCs. 
Conclusion and Potential Impact: These results were interpreted to be indications of early gyrus formation. Thus, this study showed that bRGCs—and, ultimately, gyri—may arise from mechanical tension, indicating a possible link between the biological and mechanical explanations of gyrus formation. By providing an alternative lens through which to understand cortical folding, this may have implications for future lines of inquiry, which may expand our understanding of neuro-pathologies associated with misfolding, such as autism and epilepsy.
Comparing Newborn Outcomes After Prenatal Exposure to Individual Antidepressants
Authors: Marks Claire , Quinney Sara , Haas David
Published: December 2020

Background:  Up to 1 out of 5 women experience depression during their childbearing years, with 20-33% treating with drugs. However, data are limited on individual drugs’ effects on pregnancy outcomes. The objective of this study was to compare associations between individual antidepressants and pregnancy outcomes. 
 
Study Methods:  Deidentified demographic, medical and obstetric data from women who received at least one antidepressant (SSRI or SNRI) prescription prior to conception through delivery were obtained from Regenstrief Institute. Drugs were were compared using standard statistics and multivariable regression.  
 
Results: A total of 3801 women took bupropion (n=311), citalopram (n=355), fluoxetine (n=520), sertraline (n=1557), duloxetine (n=112), escitalopram (n=534), venlafaxine (n=105), paroxetine (n=45), desvenlafaxine (n=12), or multiple antidepressants (n=250). Most women were white (86.5%), and had either commercial (50.3%) or government (48.1%) insurance.  
 
Race (p=0.002), hospital (p<0.001), and insurance (p<0.001) were associated with selection of drug. Incidence of diabetes (p<0.001), gestational diabetes (p=0.005), hypertension (p=0.015), and gestational hypertension (p=0.006) varied between drugs, with highest rates in women taking duloxetine.  NICU admission (p<0.001), transient tachypnea of newborn (TTN) (p=0.001), and adaptation syndrome (p<0.001) were significantly different between drugs, with duloxetine having highest NICU admission (42.9%) and TTN (20.5%).  Paroxetine was associated with higher rates of adaptation syndrome (13.3%).  
 
After controlling for maternal age, race, hospital, and insurance, adaptation syndrome was increased with citalopram OR[95%CI] = 2.358[1.147-4.849], duloxetine 3.180[1.362-7.424], escitalopram 2.832[1.418], paroxetine 3.347[1.138-9.847], and multiple drugs 2.603[1.222-5.545] compared to bupropion. Adding hypertension and diabetes to the model above, increased NICU admission rates were seen with citalopram 1.498[1.036-2.168], fluoxetine 1.565[1.109-2.208], duloxetine 2.568[1.593-4.139], escitalopram 2.045[1.458-2.869], and multiple drugs 2.009[1.362-2.964] compared to bupropion. 
 
Conclusion: Different antidepressants have associations with individual maternal and newborn outcomes. Duloxetine and paroxetine appear to have the strongest associations with NICU admission and adaptation syndromes, respectively. These outcomes require further investigation by exposure trimester.
Steroids for All
Authors: McKinzie Alexandra , Yang Ziyi , Daggy Joanne , Tepper Robert , Quinney Sarah , Rhoads Eli , Haneline Laura , Haas David
Published: December 2020

Background: Due to difficulties estimating the risk of preterm labor, many women diagnosed with threatened preterm delivery and given antenatal corticosteroids to improve neonatal outcomes do not deliver until term. Our objective was to compare the short-term outcomes of infants born at term to women who received betamethasone (BMZ) for threatened preterm labor to infants who were not exposed to BMZ in utero.  
 
Methods: We performed a retrospective cohort study of infants born at or after 37 weeks’ gestational age (GA) to mothers diagnosed with threatened preterm labor during pregnancy. Controlling for covariates, the primary neonatal outcomes of interest, including transient tachypnea of the newborn (TTN), neonatal intensive care unit (NICU) admission, and birthweight, were evaluated for their association with BMZ exposure.  
 
Results: Of 5330 women, 1459 (27.5%) women received BMZ at a mean GA of 32.2±3.3 weeks. The mean age of women was 27±5.9 years-old and the mean GA at delivery was 38.9±1.1 weeks. Women receiving BMZ had higher rates of maternal comorbidities (P<0.001 for diabetes, asthma, and hypertensive disorder) and were more likely to self-identify as white (P=0.022). BMZ-exposed neonates had lower birth weights and increased rates of oxygen usage, TTN, hyperbilirubinemia, hypoglycemia, and NICU admission rates (all P-values <0.05). 
Controlling for maternal characteristics and GA at delivery, BMZ exposure was not significantly associated with diagnosis of TTN [OR 1.09 (95% CI 0.80-1.50)], though it was associated with more NICU admissions [1.49 (1.19-1.86)] and lower birthweight by 91.5 (-122.3 to -60.6) grams.   
 
Conclusions: Compared to women evaluated for preterm labor that did not receive BMZ, women receiving BMZ had infants with higher rates of NICU admission and lower birthweights, though the rate of TTN diagnosis was similar between the two groups. While the benefits of BMZ to infants born preterm are clear, there may be negative impacts for infants delivered at term.
Mechanisms of ischemic skeletal muscle regeneration mediated by mechanically constrained human allogeneic mesenchymal stromal cells
Authors: O'Connor Alex , Miller Steven , Loke Michael , Gil Chang-Hyun , Leckie Katherin , Doiron Theresa , King Justin , Moldovan Leni , Murphy Michael
Published: December 2020

Background and Hypothesis: Critical limb threatening ischemia (CLTI) is the end stage of peripheral arterial disease (PAD). CLTI presents a significant risk for lower extremity amputation, especially in diabetic patients with poor options for revascularization. Additionally, using a novel diabetic mouse model of CLTI, we have shown that IM injection of 3D cultured MSCs (spheroids) is more effective in promoting skeletal muscle regeneration of ischemic muscle than monolayer cultured MSC. We hypothesize that this result is due to the mechanical constrained nature of the MSC in spheroid form, which has been shown to alter the cellular phenotype. Alginate encapsulated cells are another form of mechanical confinement, and have additional benefits including resistance to immunological attack, making them a practical therapy for treatment of CLTI patients. 
 
Project Methods: In this work, cells were encapsulated in 2% alginate using a centrifugation method. Media from these cells along with others were analyzed for IL-10 and IL-33 using ELISA. Mouse tissue samples were stained with WGA-555 antibody and analyzed using a scanning microscope. Effects on tissue perfusion were measured with Laser Doppler Perfusion Imaging. At the time of this abstract, the media from encapsulated and naked MSCs is being used to culture myoblasts, looking at cell growth. 
 
Results: ELISA results did not show significant increases in IL-10 or IL-33 for encapsulated vs. non-encapsulated cells. LDPI has shown an increased perfusion rate for hindlimbs treated with encapsulated MSCs vs naked MSCs. Muscle fiber analysis is ongoing, but initial data appears promising.  
 
Conclusion and Potential Impact: This experiment provides a starting point for improving and expanding cell therapy for critical limb ischemia, potentially resulting in better outcomes for diabetic patients and preventing lower limb amputations. The encapsulation process also has value in other types of cell therapy, as it could protect cells from host defenses and increase dwell time.
Black vs African American: Why are communication and clinical researchers not paying attention to what descendants of the African Diaspora want to be called, and why is that a problem?
Authors: Owusu Raiven , Ridley-Merriweather Katherine , Hoffmann-Longtin Krista
Published: December 2020

Problem: Descendants of African Diaspora (DADs) in the U.S. experience greater health disparities than other racial or ethnic minority groups. Many factors play a role, including their lack of participation in clinical trials. By refusing to participate, DADs cannot benefit from medical research. The barriers to recruiting DADs is well discussed in literature, but we found no research suggesting that mislabeling participants could be creating another barrier. This essay delves into the history of labeling DADs to illuminate the existing tensions between the use of “Black” and “African American” and the impact they may have on recruitment.  
Processes: Communication Theory of Identity and Critical Race Theory shaped our analysis of this mislabeling issue and its possible implications. Both theories offer insight into how an individual shapes and is simultaneously shaped by communication. We reviewed, summarized, and coded literature in the academic and popular press to answer the research question: How can mislabeling DADs possibly deter them from participating in clinical trials?  
Findings: Within DADs, there are several subgroups with different cultural heritages that contribute to how people identify. Therefore, no “catch-all” label can be used to accurately describe DADs. Academic and popular press literature indicate that preferences exist amongst this group for how they wish to be identified. Researchers should realize that “Black” and “African American” are not perceived the same by many DADs and should refrain from using them interchangeably.  
Conclusion: Given the current Black Lives Matter movement, it is imperative that health communication scholars and health researchers consider how language shapes participation and research outcomes for DADs. More research is needed to determine if the use of “Black” and “African American” interchangeably creates another barrier to the recruitment of DADs. However, if possible, researchers should take time to note the preferences of their target populations prior to recruitment.
Review of mechanisms of brain injury identified in severe malaria from 2010-2020
Authors: Patel Minal , Gopinadhan Adnan , Co Katrina , Belvin Amy , Opoka Robert , Bangirana Paul , Datta Dibyadyuti , John Chandy
Published: December 2020

Background: 
Severe malaria manifests as various conditions with severe malarial anemia being the most common and cerebral malaria being the most severe and affecting over 200,000 children annually. A 2010 review highlighted blood brain barrier degradation and decreased cerebral perfusion as contributors to the long-term behavioral, cognitive, and neurological sequalae of severe malaria. Since then, new research has identified various surface marker proteins and cytokines/chemokines playing a role in vascular changes and inflammation that progresses to acute kidney injury, retinopathy, and seizures. Our goal is to summarize the updated research and provide further insight into the mechanisms of brain injury and the outcomes that follow cerebral malaria.   
 
Project Methods: 
Hypotheses on future areas of study from the 2010 review were used to generate an outline for the updated review. Search strategies using the PubMed database were developed so that all relevant primary articles pertaining to human (pediatric and adult), murine, and in vitro studies done from 2010-2020 could be identified. The articles were then sorted and inputted into EndNote to generate a library. Review articles, case reports, and articles discussing the treatment of malaria were excluded from this index. 
 
Results: 
88 articles remarking on vasculopathy, 88 on leukocytes, 114 on cytokines/chemokines, 11 on seizures, 56 on acute kidney injury, and 35 on retinopathy have been identified as promising literature for this review. The results suggest that infected individuals have increased endothelial activation which promotes red blood cell adherence to vasculature and edema. This reduces blood flow to the brain, kidneys, and eyes and causes injury to the organs. 
 
Conclusion and Potential Impact: 
The EndNote library contains current literature on the mechanisms of brain injury secondary to severe malaria, which will be used to write a review article and identify new areas of research to further our understanding of severe malaria pathogenesis and how to target treatments.
Resumption of Driving after Total Hip Arthroplasty: A Systematic Review and Meta-Analysis
Authors: Patel Purva , Palma Samantha , Palan Jeya , Pandit Hemant , Van Duren Bernard
Published: December 2020

Background/Objective:  
The advice given to patients on resumption of driving after total hip arthroplasty (THA) is inconsistent. Due to a lack of clear guidelines, surgeons make recommendations in the range of waiting 4 to 8 weeks after surgery to resume driving. Driving is a crucial part of daily life thus, withholding driving longer than necessary can have a detrimental social and economic impact on the patient. However, it is equally important to ensure that patients only resume driving once safe. This study presents a systematic review of the literature and a meta-analysis of simulation studies to establish when it is safe for patients to return to driving after hip arthroplasty. 
 
Methods:  
The review was performed according to the PRISMA guidelines. Medline, EMBASE, and CENTRAL databases were searched to June 2020 for studies examining ‘return to driving’ or ‘brake reaction time’ after ‘total hip arthroplasty’. Titles and abstracts were screened for inclusion, data was extracted, and studies were assessed for risk of bias. Review Manager, Version 5.4 was used for statistical analysis.  
 
Results:  
A total of 14 articles met the inclusion criteria. Of these, 7 measured brake reaction time and were included in the meta-analysis. The pooled means of both right and left THA show a brake reaction time (BRT) around or just above baseline at 1 week, 2 weeks and 3 weeks, and below baseline at 6 weeks, 12 weeks, 32 weeks and 52 weeks. Of these, the pooled means at 6, 32, and 52 weeks were significant (p < 0.05). 
 
Conclusion:  
The mean recommended return to driving time was 4.5 weeks. Based upon the meta-analysis of BRT, it appears that it is safe to return to driving at 6 weeks post operatively. Orthopedic surgeons should use these results as a guideline when advising patients on when to resume driving.