bluuebunny/crossref_metadata_2025_split huggingface dataset:
scRNA-Seq Identifies IL-1 Responsive Cell Subsets in the Skin Injury-induced Inflammatory Response
Authors: Harpold Kayla , Zhou Hong-Ming , Slominski Radomir , Seymour Leroy , Bell Maria , Dave Priya , Atumonye Joseph , Wright III William , Dawes Avery , Griesenauer Brad , Paczesny Sophie , Kaplan Mark , Spandau Dan , Liu Yunglong , Xuei Xiaoling , Gao Hongyu , Hoki Aki , Turner Matthew 
Published: December 2020

Inflammation is an integral aspect of skin wound healing; however, the mechanisms that regulate inflammatory cascades in this context are not well defined. To better understand how skin inflammation impacts wound healing, we developed an ex vivo skin culture system to model key aspects of the inflammatory phase of wound healing. In this model, a defined set of proinflammatory cytokines and chemokines, mirroring those produced in wounds in vivo, are produced when mouse or human skin biopsies are cultured ex vivo. We refer to this pattern of cytokine and chemokine induction as the skin injury-induced inflammatory response. Previous studies in our laboratory demonstrated this response is initiated by the cytokine, interleukin 1 alpha (IL-1α). To understand the cellular sources and targets of IL-1α during the skin injury-induced inflammatory response, skin biopsies from mouse tail skin were cultured ex vivo for 8 hours followed by processing for single cell RNA sequencing (scRNAseq). Using bioinformatic software, R, and the package, Seurat, analysis of scRNAseq data from this experiment identified 22 distinct cell population clusters. While no populations exhibited significant expression of Il1a transcripts, multiple cell populations expressed Il1r1 transcripts, which encodes the ligand-specific subunit of the IL-1 receptor. Notably, fibroblast, endothelial cell and stromal cell clusters were characterized by expression of Il1r1 and the skin injury-induced inflammatory response transcripts Il6, Cxcl1 and/or Csf3. Furthermore, Reactome Pathway Analysis suggested the Il-1 signaling axis was activated in these cell populations. This information provides a basis for future studies to understand how IL-1 signaling in fibroblasts, endothelial cells and stromal cells impacts wound healing in vivo, which could in turn lead to novel therapeutic approaches to clinically relevant outcomes.
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.