bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Incident DKA in the Indiana New Onset T1D Patient Population
Authors: Beer Brianna , Moors Kelly , Evans-Molina Carmella , Sims Emily 
Published: December 2020

Background/Objective: Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes (T1D) resulting from ketone body production and metabolic acidosis occurring due to insulin deficiency. We sought to define the occurrence of DKA amongst pediatric patients presenting with new-onset T1D in Indiana and to determine whether patterns of DKA were affected by the COVID-19 pandemic.

Methods: This was a retrospective chart review for patients <18 years admitted to Riley Children’s Hospital with a clinical diagnosis of new onset T1D who had available chemistry values. Patients diagnosed from March 23- June 30, 2020 and over the same period in 2019 were included. DKA was classified as mild (bicarbonate 10-15 mmol/L) or severe (bicarbonate <10 mmol/L).

Results: Ninety-four patients met inclusion criteria. The total number of incident T1D cases in 2019 and 2020 were similar (48 vs. 46, respectively). Similarly, there was no significant difference in rates of DKA (21 in 2019 vs. 25 in 2020; p>0.05). Of the 94 patients, 49% met criteria for DKA; 79% of cases were classified as severe and 21% as mild. More males were diagnosed with DKA in both 2019 and 2020 (61% of DKA cases). Non-Hispanic whites comprised 75% of all new onset T1D patients and no differences in race or ethnicity were present amongst those presenting in DKA.

Conclusion: DKA was present in nearly half of all new onset pediatric T1D cases in Indiana in 2019 and 2020. There was no observed impact of the COVID-19 pandemic on T1D or DKA.

Impact and Implications: DKA is common amongst pediatric patients with new onset T1D in Indiana. Prompt recognition of symptoms is needed to prevent this life-threatening complication of T1D.
Patient Reported Outcomes after Local Flap Coverage for Lower Extremity Trauma
Authors: Bhagat Neel , Loewenstein Scott , Knox Kevin , Adkinson Joshua , Hassanein Aladdin , Bamba Ravinder 
Published: December 2020

Background:
Complex lower extremity trauma can result in devastating outcomes including amputation and poor quality of life. Limb salvage can be achieved with the use of local flaps like muscle flaps such as the gastrocnemius or soleus flaps, which detach muscles in order to use them for local coverage. Fasciocutaneous flaps such as reverse sural and propeller flaps are other examples of local flaps which utilize overlying soft tissue for local rearrangement. Patient-reported outcome (PRO) studies have not been reported for local flaps. Additionally, the potential for functional deficits as a result of muscle flaps in comparison to fasciocutaneous flaps has not been investigated.

Methods:
Local flap coverage for lower extremity traumas between 2014-2019 were reviewed. 248 local flaps were performed for lower extremity salvage following trauma. PROs were recorded utilizing both the Lower Extremity Functional scale (LEFS) and the 36-Item Short-Form Health Survey (SF-36).

Results:
Surveys were completed by 37 patients (response rate 18.3%, mean follow-up time 3.16 years, average age 49.72 years old). The average LEFS score was 42.09 ± 14.18, and the average physical functioning score was 43.03 ± 21.54. LEFS score and SF-36 physical functioning scores were significantly lower in patients who underwent muscle flaps compared to fasciocutaneous flaps (p=0.021 and p=0.022 respectively).

Conclusions and Impact:
Patients undergoing local flaps for lower extremity reconstruction have low quality of life scores. Patients who underwent fasciocutaneous flaps had significantly higher quality of life scores compared to muscle flap patients suggesting that fasciocutaneous flaps may cause less functional deficit in salvage operations.
Connecting Faith and Health: Improving Health Outcomes Through Congregant Networks
Authors: Campbell Meredith , Christenson Jacob , Craig David 
Published: December 2020

Background and Hypothesis: People living in areas of high social vulnerability face health disparities in part due to disconnection. Health institutions recognize the importance of treating whole persons but are disconnected from local knowledge of community health assets and social and cultural barriers. People in health-challenged neighborhoods may experience disconnection and distrust in seeking the many resources and services needed for good health. Congregations are longstanding anchor institutions in marginalized communities. They build trusted relationships among members through shared values and care for wellness. Sometimes they extend these connections through on-the-ground service to neighboring communities. We hypothesize that a network of congregations can build trusted connections and share local knowledge and cultural competence to improve health outcomes and holistic wellness in vulnerable neighborhoods.

Methods: Community-engaged participatory research requires reciprocity in mapping assets, identifying priorities, narrating shared values, designing projects and messaging results. We developed mixed-methods tools to ensure community expertise drives an iterative research process. Methods include: an initial health and wellness survey, follow-up wellness interviews to collect stories and assets, an online learning community for 14 congregations with monthly focus groups, and visual maps of health data and wellness assets.

Results: While the study is ongoing, preliminary survey data demonstrates that congregations have local knowledge of issues affecting health and wellness among their congregants and the surrounding neighborhood. Their preexisting support for health and wellness through community outreach programs indicates building on their current network could expand their reach and improve health and wellness in vulnerable neighborhoods.

Conclusion and Potential Impact: Successful community engaged research prioritizes iterative methods that allow community participants to use their voice and tell their stories.
Congregations' practice of shared values and knowledge of lived experience can forge connections for greater resilience and health supports in socially vulnerable communities.
Characterization of the Tumor Microenvironment of Neurofibromatosis Type I Plexiform Neurofibromas
Authors: Chmiel Abigail , Rhodes Steven , Angus Steve , He Yongzheng , Lu Quingbo , Sciaky Noah , Johnson Gary , Clapp Wade 
Published: December 2020

Background/Objective:
Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome caused by mutations in the NF1 tumor suppressor gene. Patients with NF1 develop tumors of the peripheral nervous system called plexiform neurofibromas (PNs). These histopathologically complex tumors are composed of various immune and inflammatory cells. Mast cells have previously been identified as one key immune cell lineage underpinning PN initiation and progression, however new technologies leveraging RNA-sequencing (RNAseq) allow for the broad and systematic characterization of the PN tumor microenvironment. Here we utilized these tools to delineate PN cellular composition.
Methods:
RNA seq was performed on murine wild type (n=6) and PN (n=6) tissues. We utilized CIBERSORT to profile the cellular constituents of the PN microenvironment. CIBERSORT is a deconvolution method that uses a reference matrix to estimate the relative proportions of various cell types. Statistical analyses were performed on cell lineage subtypes delineated by CIBERSORT. We further performed a Gene Set Enrichment Analysis (GSEA) to identify which pathways and cytokines might be upregulated in PNs.
Results:
Using a murine reference matrix, the macrophage lineage, M0 (p = 0.072), M1 (p = 0.1), were upregulated in PNs (n=6) compared to WT (n=6). A human reference matrix showed M2 (p=0.025) to be upregulated in PNs. GSEA showed IL-1, IL-6, IL-8, TNF and Type I IFN and cytokine secretion to be upregulated in PNs compared to WT.
Conclusion:
Macrophages were among the most upregulated components of the NF1 tumor microenvironment and upregulation of IL-1, IL-6, IL-8, TNF and Type I IFN production may be contributing to inflammation that is critical in the initiation and progression of PNs.
Scientific/Clinical/Policy Impact and Implications:
Pharmacotherapies that can target the macrophage lineage and/or aforementioned cytokines may have utility in the treatment of PNs. Further studies are necessary to evaluate this hypothesis.
Serum Biomarkers in Postoperative Delirium after Esophagectomy
Authors: Dalal Azhar , Khan Sikandar , Lindroth Heidi , Khan Babar 
Published: December 2020

Background: The pathophysiology of postoperative delirium in patients undergoing esophagectomy is not well understood but has been hypothesized to involve neuroinflammation. Inflammatory biomarkers may therefore be associated with delirium incidence and severity. We conducted this study to measure the association between serum inflammatory biomarkers and postoperative delirium and delirium severity.

Methods: Blood samples were obtained from patients enrolled in a randomized double-blind placebo-controlled trial undergoing elective esophagectomy at Indiana University Health University Hospital. S100 calcium-binding protein B, C-Reactive Protein (CRP), interleukins 8, 10, tumor necrosis factor-alpha, and insulin like growth factor 1 (IGF1) were analyzed at preoperative, and postoperative days 1 and 3 timepoints. Delirium status and severity were assessed using the Confusion Assessment Method for Intensive Care Unit and Delirium Rating Scale (DRS-R-98), respectively.

Results: Samples from 71 patients were included. Higher median CRP values were associated with delirium incidence at post-operative day 1 (no delirium: 22.7 IQR:2.2, 42.7; delirium: 35.4 IQR:25.0, 50.0, p=0.031) but not at post-operative day 3. Median CRP S100B serum values were correlated with mean delirium severity (-0.289, p=0.020). IGF-1 serum values were associated with delirium severity on post-operative day 1 (0.270, p=0.040).

Conclusion: Postoperative delirium incidence was associated with higher median CRP values at POD1. The findings of this study provide evidence for the early measurement of post-operative serum biomarkers to ascertain likely incidence and severity of delirium.
Decreased brain volumes in infants with prenatal opioid exposure
Authors: Dietrich Jonathan , Guckien Zoe , Picklesimer MaKayla , Sparks Christina , Haas David , Sadhasivam Senthilkumar , Radhakrishnan Rupa 
Published: December 2020

Background/Objective: Previous small studies have shown that prenatal opioid-exposed (POE) infants and older children display decreased cerebral, cerebellar, or subcortical brain volumes. However, these studies are plagued by suboptimal reference standards or were unable to correct for the influence of other environmental factors in older children. Therefore, our goal was to study differences in brain volume of POE infants when compared to a geographically matched population. We hypothesized that there will be a significant decrease in total brain volume of the POE infants in comparison to the non-opioid exposed control infants, including a reduction in the cerebellar volume.

Methods: This was an IRB approved prospective study of mothers and infants with POE and controls without POE. All recruited infants underwent MRI scans of the brain before they reached a corrected age of 2 months. The T1-weighted MRI images were analyzed by Infant FreeSurfer and segmented into ROIs. The segmentations were manually checked and edited. An ANOVA analysis was performed to compare the cerebellar and total brain volume datasets. We corrected for gender, corrected gestational age at MRI scan, and total brain volume where necessary.

Results: 42 infants were included in the study, 21 with POE and 21 control infants. There was a significant difference in the mean gestational age of POE infants (38.28±2.13) compared to control infants (39.42±0.72). On quantitative analysis, the POE group had a significantly reduced total brain and supratentorial volume in comparison to the controls. The cerebellar volume was also significantly smaller in POE, but this significance did not persist when the total brain volume was included in the model.

Conclusion: The supratentorial region is affected disproportionately more than the cerebellum in POE. Specific reductions in cortical, subcortical, and white matter volume need to be further investigated and their influence on developmental outcomes need to be studied.
An Implementation Evaluation of A Comprehensive Sex Education Program in a Rural Indiana County
Authors: Estes Lauren , Meagher Carolyn , Hensley Monique , Hunt Abby , Wuerch Cory , Ott Mary 
Published: December 2020

Background and Objective: Rural teen pregnancy is a significant public health problem, yet there are no evidence-based prevention programs (EBPs) developed for rural communities. Little is known about the process of implementing and adapting EBPs for rural communities. An implementation science framework is a useful way to methodologically examine EBPs replicated in new contexts. Specifically, the Evaluation, Preparation, Implementation, Sustainment (EPIS) framework was utilized for this project. The purpose of this study is to describe the challenges and sucesses in the implementation of EBPs in a rural community.
Project Methods: Youth RISE! is a federally funded, evidence based, community-wide sex education program implemented in Clinton County, Indiana. Qualitative interviews were conducted with key stakeholders involved in implementing the program (n=22). Participants fulfilled diverse roles such as school administrators, teachers, local program partners, and the grantor. These interviews, conducted in-person or via telephone in 2018 and via Zoom in 2020, were subsequently transcribed, coded and analyzed using thematic analysis. Codes were developed from the EPIS implementation framework and an initial review of transcripts and field notes.
Results: Participants described the Youth RISE! Program as overwhelmingly successful. Qualitative analysis revealed three central themes of Community Readiness, Transparency, and Buy-In. Community readiness included timing, involvement of trusted community partners, and framing teen pregnancy as a public health issue rather than a values issue. Transparency included frequent communication between all parties, positive messaging, and a strong presence in the community. Buy-in included parent, teacher, and school administration support as well as maintaining equal partnerships between the community, school, and partner agencies.
Conclusion and Potential Impact: Contrary to popular beliefs, this rural community was willing to implement comprehensive sex education programs in its schools. This data may be used to inform future implementation of EBPs in rural communities.
Novel Participatory Methodologies for Identifying Motivations of Minority Women to Participate in a Breast Cancer Clinical Trial
Authors: Evans Madeline , Ridley-Merriweather Katherine 
Published: December 2020

Background: The Komen Tissue Bank (KTB), a biorepository that stores healthy breast tissue for use as controls in breast cancer (BC) research, has a notable deficiency in tissue donations from racial and ethnic minority women. Though studies have documented similar disparities in many clinical trials, the reasons why minority women agree or decline to participate in clinical trials remain largely unknown. This study used two novel participatory communication methodologies with minimal researcher intervention to explore potential motivations for minority women (Latinas, Asian Americans, and Black women) to donate breast tissue to the KTB.
Methods: Two novel methodologies rooted in Grounded Practical Theory and Grounded Theory were used to study the attitudes of non-donors toward tissue donation and the reasons donors chose to donate tissue to the KTB, respectively. The non-donors (Latinas, n=14; Asian Americans, n=17) participated in interactive focus groups, and donors (Black, n=20) participated in open-ended interviews, all of which were then transcribed and coded to identify common motivations for donating breast tissue.
Results: The interactive methodology of both the focus groups and interviews yielded rich data that may not have arisen in a traditional question-driven format. Though the manifestation differed between minority groups, three common factors influencing the decision to donate breast tissue were present in all groups: altruistic tendencies, cultural norms, and personal connection to BC. Non-donors also expressed their need for more information before making the decision to donate.
Conclusion and Potential Impact: Common factors that influence the decision to donate tissue were identified using these two novel interactive methodologies, though the expression differed between minority groups. The information gleaned from this study will inform future communication efforts by the KTB and other clinical trial researchers, with the ultimate goal of distributing targeted recruitment materials to increase the representation of minority women in clinical trials.
Improving Post-Stroke Outcomes in Ischemic Stroke Animal Models Using C3a Monoclonal Antibody Treatment
Authors: Failinger David , Yen Jui-Hung 
Published: December 2020

Background
Stroke is one of the leading causes of death in the world and a majority of strokes cases are ischemic stroke. Ischemia causes tissue damage by preventing nutrient delivery, but damage is also caused by inflammation after reperfusion. The complement pathway is active during reperfusion. Our study focuses on the effects of C3a component inhibition during post stroke inflammation.

Material and Methods
A total of 30 C57BL/6 mice will be randomly divided into 3 groups (n=10/group) and subjected to a 40-minute middle cerebral artery occlusion (MCAO). The control group will receive a vehicle (saline, Group 1) and two experiment groups will receive 5 ml/kg IV injections of neutralizing C3a monoclonal antibody. The first experimental group (Group 2) will receive the injection 30 minutes after the start of occlusion and the second experimental group (Group 3) will receive two injections at 30 minutes and 3h after the start of occlusion. All groups will be subject to neurological function tests at 24h and 48h. Additionally, at 48h post-injury animals will be sacrificed and the ischemic brains harvested, followed by Triphenyl tetrazolium Chloride (TTC) staining to determine infarct volume.

Results
The infarct volumes and neurological function scores for the experimental groups are expected to have statistically smaller values and improved neurological deficient compared to the vehicle group. Group 3 mice are expected to have smaller values and lower scores compared to Group 2.

Discussion
C3a plays an important role in recruitment of inflammatory cells such as macrophages/microglia and neutrophils, which can cause brain tissue injury and neuron cell death. Limiting the presence C3a component by monoclonal antibody is expected to limit recruitment and lessen post-ischemic inflammation damage. Future studies may test combinations of complement pathway inhibition to optimize the depression of post-stroke inflammation and as well as preventing susceptibility to post-stroke infection.
Serum Proteomic Analysis in Esophagectomy Patients with Postoperative Delirium: A Case-Control Study
Authors: Fitschen Walter , Khan Sikandar , Lindroth Heidi , Wang Sophia , Imran Sundus , True Jason , Aryal Uma , Perkins Anthony , Gao Sujuan , Caplan Gideon , Twigg III Homer , Kesler Kenneth , Khan Babar 
Published: December 2020

Background: Delirium is a common post-operative complication for patients who undergo esophagectomy. The pathophysiology of delirium is poorly understood, limiting therapeutic options. To advance our pathophysiologic understanding, we conducted this study to evaluate the association of protein expression with postoperative delirium.
Methods: A case-control study was performed using blood samples from the PEPOD randomized clinical control trial (NCT02213900). 52 patients (26 cases with delirium, 26 control) who were >18 years old, spoke English, and underwent esophagectomy were included, while those with schizophrenia, Parkinson’s, alcohol abuse, neuroleptic malignant syndrome, haloperidol allergy, and severe dementia were excluded. Samples were from pre-op and post-op day 1. Delirium was assessed for using the Confusion Assessment Method for the Intensive Care Unit and Richmond Agitation Sedation Scale, while the severity was assessed using DRS-R-68. Proteomic analysis was performed using TMT 10ples isobaric labels. Proteome Discoverer and STRING web-based tools were used for bioinformatic analyses, and the Wilcoxon-Mann-Whitney Odds (WMWodds) test was used to report between-group differences in protein abundance ratios.
Results: 52 samples (26 cases, 26 controls) were analyzed for this study. Elevated protein abundance ratios of Coagulation factor IX (Median (IQR): 1.18 (1.08-1.28) p=0.047) and Mannosyl-oligosaccharide 1,2-alpha-mannosidase (Median (IQR): 1.50 (1.35-1.60) p=0.049) were noted in patients that developed delirium. Elevated protein abundance ratios of angiotensinogen (Median (IQR): 1.19 (1.14-1.23) p=0.038), ceruloplasmin (Median (IQR): 1.02 (0.98-1.08) p=0.038), and Complement C2 (Median (IQR): 1.01 (0.96-1.08) p=0.016) were noted in control patients. Protein abundance ratios for Complement C2 (Spearman rs=0.31, 95%CI [-0.55, -0.02]) and Mannosyl-oligosaccharide 1,2-alpha-mannosidase (rs=0.61, 95%CI [0.29, 0.81]) were associated with the severity of delirium in case patients.
Conclusions: Changes in proteins associated with coagulation, inflammation, and protein handling were identified. These could be evaluated in future studies to develop tools for predicting onset and severity of post-operative delirium.