Digital Commons Network^™

Prehospital Use Of A Modified Heart Pathway And Point-Of-Care Troponin To Predict Cardiovascular Events, Jason P. Stopyra, Louis Fornage, Et Al.

Open Access Publications

CLINICAL TRIAL REGISTRATION: clinicaltrials.gov (NCT02709135).

Work-Related And Personal Factors Associated With Mental Well-Being During The Covid-19 Response: Survey Of Health Care And Other Workers, Bradley A Evanoff, Jaime R Strickland, Ann Marie Dale, Lisa Hayibor, Emily Page, Jennifer G Duncan, Thomas Kannampallil, Diana L Gray

Open Access Publications

BACKGROUND: The response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created an unprecedented disruption in work conditions. This study describes the mental health and well-being of workers both with and without clinical exposure to patients with coronavirus disease (COVID-19).

OBJECTIVE: The aim of this study is to measure the prevalence of stress, anxiety, depression, work exhaustion, burnout, and decreased well-being among faculty and staff at a university and academic medical center during the SARS-CoV-2 pandemic and describe work-related and personal factors associated with their mental health and well-being.

METHODS: All faculty, staff, and postdoctoral fellows of …

Exposure To Covid-19 Patients Increases Physician Trainee Stress And Burnout, Thomas G. Kannampallil, Charles W. Goss, Bradley A. Evanoff, Jaime R. Strickland, Rebecca P. Mcalister, Jennifer Duncan

Open Access Publications

The coronavirus disease 2019 (COVID-19) pandemic has put considerable physical and emotional strain on frontline healthcare workers. Among frontline healthcare workers, physician trainees represent a unique group-functioning simultaneously as both learners and caregivers and experiencing considerable challenges during the pandemic. However, we have a limited understanding regarding the emotional effects and vulnerability experienced by trainees during the pandemic. We investigated the effects of trainee exposure to patients being tested for COVID-19 on their depression, anxiety, stress, burnout and professional fulfillment. All physician trainees at an academic medical center (n = 1375) were invited to participate in an online survey. We …

The Baby Bridge Program: A Sustainable Program That Can Improve Therapy Service Delivery For Preterm Infants Following Nicu Discharge, Roberta Pineda, Elizabeth Heiny, Patricia Nellis, Joan Smith, Jaqueline M. Mcgrath, Margaux Collins, Abigail Barker

Open Access Publications

OBJECTIVE: The aim of this project was to determine revenues and costs over time to assess the sustainability of the Baby Bridge program.

METHODS: The Baby Bridge program was developed to promote timely, consistent and high quality early therapy services for high-risk infants following neonatal intensive care unit (NICU) discharge. Key features of the Baby Bridge program were defined as: 1) having the therapist establish rapport with the family while in the NICU, 2) scheduling the first home visit within one week of discharge and continuing weekly visits until other services commence, 3) conducting comprehensive assessments to inform targeted interventions …

Smoking-By-Genotype Interaction In Type 2 Diabetes Risk And Fasting Glucose, Peitao Wu, Mary F. Feitosa, Yize Li, Michael M. Province, D C Rao, Et Al.

Open Access Publications

Smoking is a potentially causal behavioral risk factor for type 2 diabetes (T2D), but not all smokers develop T2D. It is unknown whether genetic factors partially explain this variation. We performed genome-environment-wide interaction studies to identify loci exhibiting potential interaction with baseline smoking status (ever vs. never) on incident T2D and fasting glucose (FG). Analyses were performed in participants of European (EA) and African ancestry (AA) separately. Discovery analyses were conducted using genotype data from the 50,000-single-nucleotide polymorphism (SNP) ITMAT-Broad-CARe (IBC) array in 5 cohorts from from the Candidate Gene Association Resource Consortium (n = 23,189). Replication was performed in …

Client Processing Is Altered By Novel Myopathy-Causing Mutations In The Hsp40 J Domain, Melanie Y. Pullen, Conrad C. Weihl, Heather L. True

Open Access Publications

The misfolding and aggregation of proteins is often implicated in the development and progression of degenerative diseases. Heat shock proteins (HSPs), such as the ubiquitously expressed Type II Hsp40 molecular chaperone, DNAJB6, assist in protein folding and disaggregation. Historically, mutations within the DNAJB6 G/F domain have been associated with Limb-Girdle Muscular Dystrophy type 1D, now referred to as LGMDD1, a dominantly inherited degenerative disease. Recently, novel mutations within the J domain of DNAJB6 have been reported in patients with LGMDD1. Since novel myopathy-causing mutations in the Hsp40 J domain have yet to be characterized and both the function of DNAJB6 …

Myd88-Dependent Influx Of Monocytes And Neutrophils Impairs Lymph Node B Cell Responses To Chikungunya Virus Infection Via Irf5, Nos2 And Nox2, Mary K. Mccarthy, Glennys V. Reynoso, Emma S. Winkler, Matthias Mack, Michael S. Diamond, Heather D. Hickman, Thomas E. Morrison

Open Access Publications

Humoral immune responses initiate in the lymph node draining the site of viral infection (dLN). Some viruses subvert LN B cell activation; however, our knowledge of viral hindrance of B cell responses of important human pathogens is lacking. Here, we define mechanisms whereby chikungunya virus (CHIKV), a mosquito-transmitted RNA virus that causes outbreaks of acute and chronic arthritis in humans, hinders dLN antiviral B cell responses. Infection of WT mice with pathogenic, but not acutely cleared CHIKV, induced MyD88-dependent recruitment of monocytes and neutrophils to the dLN. Blocking this influx improved lymphocyte accumulation, dLN organization, and CHIKV-specific B cell responses. …

Tourette Syndrome Research Highlights From 2019, Andreas Hartmann, Yulia Worbe, Kevin J Black

Open Access Publications

This is the sixth yearly article in the Tourette Syndrome Research Highlights series, summarizing research from 2019 relevant to Tourette syndrome and other tic disorders. The highlights from 2020 is being drafted on the Authorea online authoring platform; readers are encouraged to add references or give feedback on our selections comments feature on this page. After the calendar year ends, this article is submitted as the annual update for the Tics collection F1000Research.

Tictimer Web: Software For Measuring Tic Suppression Remotely, Jonathan K Black, Jonathan M Koller, Kevin J. Black

Open Access Publications

Woods and Himle developed a standardized tic suppression paradigm (TSP) for the experimental setting, to quantify the effects of intentional tic suppression in Tourette syndrome. We previously provided a computer program to facilitate recording tic occurrence and to automate reward delivery during the several experimental conditions of the TSP. The present article describes a web-based program that performs the same functions. Implementing this program on the web allows research sessions to be performed remotely, in tandem with a video calling program. Relevant data for each session, such as the timing of tics and dispensed rewards, are stored in plain text …

Depressogenic Self-Schemas Are Associated With Smaller Regional Grey Matter Volume In Never-Depressed Preadolescents, Pan Liu, Matthew R J Vandemeer, Marc F Joanisse, Deanna M Barch, David J A Dozois, Elizabeth P Hayden

Open Access Publications

Self-referential processing (i.e., self-schemas that guide processing of self-descriptive information) emerges early in youth, with deeper encoding of negative self-descriptors and/or shallower encoding of positive self-descriptors causally linked to depression. However, the relationship between depressogenic self-schemas and brain structure is unclear. We investigated associations between self-schemas and regional grey matter volume (GMV) in 84 never-depressed preadolescents oversampled for depression risk based on maternal depression history. Self-schemas were assessed using a Self-Referent Encoding Task (SRET) and regional GMV was indexed via voxel-based morphometry analysis of structural magnetic resonance imaging data. Youths' positive self-schemas were associated with greater regional GMV within the …

Campylobacter Colonization, Environmental Enteric Dysfunction, Stunting, And Associated Risk Factors Among Young Children In Rural Ethiopia: A Cross-Sectional Study From The Campylobacter Genomics And Environmental Enteric Dysfunction (Caged) Project, Dehao Chen, Mark J Manary, Et Al

Open Access Publications

Livestock farming provides a possible mechanism by which smallholder farmers can meet their household need for animal source foods (ASF), which may reduce the risk of stunting. However, direct/indirect contacts with domestic animals may increase colonization by

Nonmicrobial Activation Of Tlrs Controls Intestinal Growth, Wound Repair, And Radioprotection, William F Stenson, Matthew A Ciorba

Open Access Publications

TLRs, key components of the innate immune system, recognize microbial molecules. However, TLRs also recognize some nonmicrobial molecules. In particular, TLR2 and TLR4 recognize hyaluronic acid, a glycosaminoglycan in the extracellular matrix. In neonatal mice endogenous hyaluronic acid binding to TLR4 drives normal intestinal growth. Hyaluronic acid binding to TLR4 in pericryptal macrophages results in cyclooxygenase2- dependent PGE

Apurinic/Apyrimidinic Endonuclease 1 Restricts The Internalization Of Bacteria Into Human Intestinal Epithelial Cells Through The Inhibition Of Rac1, Gerco Den Hartog, Lindsay D Butcher, Amber L Ablack, Laura A Pace, Jailal N G Ablack, Richard Xiong, Soumita Das, Thaddeus S Stappenbeck, Lars Eckmann, Peter B Ernst, Sheila E Crowe

Open Access Publications

Pathogenic intestinal bacteria lead to significant disease in humans. Here we investigated the role of the multifunctional protein, Apurinic/apyrimidinic endonuclease 1 (APE1), in regulating the internalization of bacteria into the intestinal epithelium. Intestinal tumor-cell lines and primary human epithelial cells were infected with

Advances In Modeling The Immune Microenvironment Of Colorectal Cancer, Paul Sukwoo Yoon, Nuala Del Piccolo, Venktesh S Shirure, Yushuan Peng, Amanda Kirane, Robert J Canter, Ryan C Fields, Steven C George, Sepideh Gholami

Open Access Publications

Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related death in the US. CRC frequently metastasizes to the liver and these patients have a particularly poor prognosis. The infiltration of immune cells into CRC tumors and liver metastases accurately predicts disease progression and patient survival. Despite the evident influence of immune cells in the CRC tumor microenvironment (TME), efforts to identify immunotherapies for CRC patients have been limited. Here, we argue that preclinical model systems that recapitulate key features of the tumor microenvironment-including tumor, stromal, and immune cells; the extracellular matrix; and the vasculature-are …

Ige And T Cell Reactivity To A Comprehensive Panel Of Cockroach Allergens In Relation To Disease, Anna Pomés, Véronique Schulten, Jill Glesner, Ricardo Da Silva Antunes, Aaron Sutherland, Leonard B Bacharier, Avraham Beigelman, Paula Busse, April Frazier, Alessandro Sette

Open Access Publications

IgE sensitization to cockroach allergens is associated with development of allergic diseases, such as asthma. To understand the relevance of different cockroach allergens for diagnosis and immunotherapy, a comprehensive analysis of IgE antibody levels and T cell reactivity to an expanded set of cockroach allergens and their relationship to disease was performed in a cohort of USA cockroach sensitized patients. IgE antibody levels to recombinant chitinase and hemocyanin were measured for 23 subjects by custom-made ImmunoCAPs and compared with IgE levels to eight cockroach allergens we previously reported for the same cohort.

Dementia Research In The Caribbean Hispanic Islands: Present Findings And Future Trends, Daisy Acosta, Jorge J Llibre-Guerra, Ivonne Z Jiménez-Velázquez, Juan J Llibre-Rodríguez

Open Access Publications

During the last decade, the Caribbean Hispanic islands experienced accelerated demographic aging, representing the fastest aging region within Latin America. Age-related non-communicable diseases, including dementia, are now reported at high prevalence. The Caribbean islands share similar genetic ancestry, culture, migration patterns, and risk profiles, providing a unique setting to understand dementia in the Caribbean-Hispanics. This perspective article aimed to describe the impact of dementia in the Caribbean, at a local and regional level and reflect on research strategies to address dementia. We report on 10/66 project findings, described research projects and regional plans for the region. According to our results, …

Direct Tumor Visual Feedback During Free Breathing In 0.35t Mrgrt, Taeho Kim, Benjamin C Lewis, Alex Price, Thomas Mazur, H Michael Gach, Justin C Park, Bin Cai, Erin Wittland, Lauren Henke, Hyun Kim, Sasa Mutic, Olga Green

Open Access Publications

To present a tumor motion control system during free breathing using direct tumor visual feedback to patients in 0.35 T magnetic resonance-guided radiotherapy (MRgRT). We present direct tumor visualization to patients by projecting real-time cine MR images on an MR-compatible display system inside a 0.35 T MRgRT bore. The direct tumor visualization included anatomical images with a target contour and an auto-segmented gating contour. In addition, a beam-status sign was added for patient guidance. The feasibility was investigated with a six-patient clinical evaluation of the system in terms of tumor motion range and beam-on time. Seven patients without visual guidance …

Sars-Cov-2 Viral Rna Shedding For More Than 87 Days In An Individual With An Impaired Cd8+ T Cell Response, Jackson S Turner, Aaron Day, Wafaa B Alsoussi, Zhuoming Liu, Jane A O'Halloran, Rachel M Presti, Bruce K Patterson, Sean P J Whelan, Ali H Ellebedy, Philip A Mudd

Open Access Publications

Prolonged shedding of viral RNA occurs in some individuals following SARS-CoV-2 infection. We perform comprehensive immunologic evaluation of one individual with prolonged shedding. The case subject recovered from severe COVID-19 and tested positive for SARS-CoV-2 viral RNA repeatedly as many as 87 days after the first positive test, 97 days after symptom onset. The subject did not have any associated rise in anti-Spike protein antibody titers or plasma neutralization activity, arguing against re-infection. This index subject exhibited a profoundly diminished circulating CD8+ T cell population and correspondingly low SARS-CoV-2-specific CD8+ T cell responses when compared with a cohort of other …

An Atypical Brct-Brct Interaction With The Xrcc1 Scaffold Protein Compacts Human Dna Ligase Iiiα Within A Flexible Dna Repair Complex, Michal Hammel, Ishtiaque Rashid, Aleksandr Sverzhinsky, Yasin Pourfarjam, Miaw-Sheue Tsai, Tom Ellenberger, John M. Pascal, In-Kwon Kim, John A. Tainer, Alan E. Tomkinson

Open Access Publications

The XRCC1-DNA ligase IIIα complex (XL) is critical for DNA single-strand break repair, a key target for PARP inhibitors in cancer cells deficient in homologous recombination. Here, we combined biophysical approaches to gain insights into the shape and conformational flexibility of the XL as well as XRCC1 and DNA ligase IIIα (LigIIIα) alone. Structurally-guided mutational analyses based on the crystal structure of the human BRCT-BRCT heterodimer identified the network of salt bridges that together with the N-terminal extension of the XRCC1 C-terminal BRCT domain constitute the XL molecular interface. Coupling size exclusion chromatography with small angle X-ray scattering and multiangle …

Nutrition-Related Symptoms In Adult Survivors Of Critical Illness Who Are Eating Orally: A Scoping Review Protocol., Louise Albrich, Lee Anne S. Chapple, Amelia Nock, Emma J. Ridley, Mary Hickson

School of Health Professions

OBJECTIVE: This review will explore and map the current literature on the nutritional impact of symptoms reported by adult survivors of critical illness who are eating orally after discharge from the intensive care unit (ICU). INTRODUCTION: Survivors of critical care often experience ICU-acquired weakness and poor functional recovery. It is plausible that nutrition interventions throughout their recovery could improve outcomes for these patients. Although a growing number of studies aim to explore the effect of nutrition delivered in the early phases of critical illness, this is also important post-ICU discharge, particularly in already nutritionally compromised patients presenting with muscle loss …

Burden Of Rare Deleterious Variants In Wnt Signaling Genes Among 511 Myelomeningocele Patients, Luke Hebert, Paul Hillman, Craig Baker, Michael Brown, Allison Ashley-Koch, James E Hixson, Alanna C Morrison, Hope Northrup, Kit Sing Au

Faculty, Staff and Student Publications

Genes in the noncanonical WNT signaling pathway controlling planar cell polarity have been linked to the neural tube defect myelomeningocele. We hypothesized that some genes in the WNT signaling network have a higher mutational burden in myelomeningocele subjects than in reference subjects in gnomAD. Exome sequencing data from 511 myelomeningocele subjects was obtained in-house and data from 29,940 ethnically matched subjects was provided by version 2 of the publicly available Genome Aggregation Database. To compare mutational burden, we collapsed rare deleterious variants across each of 523 human WNT signaling genes in case and reference populations. Ten WNT signaling genes were …

Covid-19 Sampling From The Middle Ear And Mastoid: A Case Report, George B Wanna, Zachary G Schwam, Vivian F Kaul, Maura K Cosetti, Enrique Perez, Peter Filip, Waleed Javaid, Avi Kandel, Alberto Paniz-Mondolfi, Satish Govindaraj, Eric M Genden

Faculty, Staff and Student Publications

No abstract provided.

Microbiotyping The Sinonasal Microbiome, Ahmed Bassiouni, Sathish Paramasivan, Arron Shiffer, Matthew R Dillon, Emily K Cope, Clare Cooksley, Mahnaz Ramezanpour, Sophia Moraitis, Mohammad Javed Ali, Benjamin S Bleier, Claudio Callejas, Marjolein E Cornet, Richard G Douglas, Daniel Dutra, Christos Georgalas, Richard J Harvey, Peter H Hwang, Amber U Luong, Rodney J Schlosser, Pongsakorn Tantilipikorn, Marc A Tewfik, Sarah Vreugde, Peter-John Wormald, J Gregory Caporaso, Alkis J Psaltis

Faculty, Staff and Student Publications

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal “microbiotypes” or “states”: the first is Corynebacterium-dominated, the second is Staphylococcus-dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella, and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based …

An Ecological Momentary Assessment Of Self-Improved And Self-Evaluation Body Comparisons: Associations With College Women's Body Dissatisfaction And Exercise, Rachel I. Macintyre, Kristin E. Heron, Abby L. Braitman, Danielle Arigo

Psychology Faculty Publications

Upward body comparisons are prevalent among college women and associated with body dissatisfaction and disordered eating. However, less is known about distinguishing features of the comparisons themselves as they occur in daily life. The primary purpose of the present study was to examine whether two types of upward body comparisons previously studied experimentally (self-improvement and self-evaluation) are differentially associated with body- and exercise-related outcomes in real-life settings using ecological momentary assessment (EMA). Undergraduate women (N = 74) between 18-25 years (Mage = 20.4, SD = 1.63) completed five surveys on smartphones daily for seven days. EMA measures …

Somatic Symptoms And Binge Eating In Women's Daily Lives, Kelly A. Romano, Kristin E. Heron, Kathryn E. Smith, Ross D. Crosby, Scott G. Engel, Stephen A. Wonderlich, Raina D. Pang, Tyler B. Mason

Psychology Faculty Publications

Objective

The present study aimed to determine whether the momentary severity of women's somatic symptoms was concurrently and prospectively associated with their engagement in binge eating in naturalistic settings.

Method

Thirty women (M_age = 34.13, SD = 13.92) who had engaged in binge eating at least once over the month prior to study entry completed a 14-day ecological momentary assessment (EMA) protocol. During each of the 14 days, participants received five semi-random surveys via text message that assessed momentary somatic symptom severity (i.e., headaches, stomachaches/pain, chest/heart pain, faintness/dizziness, shortness of breath, fatigue) and disordered eating behaviors. Generalized estimating equations …

Transcriptional Insights Into Pathogenesis Of Cutaneous Systemic Sclerosis Using Pathway Driven Meta-Analysis Assisted By Machine Learning Methods, Xiao Xu, Meera Ramanujam, Sudha Visvanathan, Shervin Assassi, Zheng Liu, Li Li

Faculty, Staff and Student Publications

Pathophysiology of systemic sclerosis (SSc, Scleroderma), an autoimmune rheumatic disease, comprises of mechanisms that drive vasculopathy, inflammation and fibrosis. Understanding of the disease and associated clinical heterogeneity has advanced considerably in the past decade, highlighting the necessity of more specific targeted therapy. While many of the recent trials in SSc failed to meet the primary end points that predominantly relied on changes in modified Rodnan skin scores (MRSS), sub-group analysis, especially those focused on the basal skin transcriptomic data have provided insights into patient subsets that respond to therapies. These findings suggest that deeper understanding of the molecular changes in …

Dynamic Conformal Arcs For Lung Stereotactic Body Radiation Therapy: A Comparison With Volumetric-Modulated Arc Therapy., Rasmus Bokrantz, Minna Wedenberg, Peter Sandwall

Oncology Articles

This study constitutes a feasibility assessment of dynamic conformal arc (DCA) therapy as an alternative to volumetric-modulated arc therapy (VMAT) for stereotactic body radiation therapy (SBRT) of lung cancer. The rationale for DCA is lower geometric complexity and hence reduced risk for interplay errors induced by respiratory motion. Forward planned DCA and inverse planned DCA based on segment-weight optimization were compared to VMAT for single arc treatments of five lung patients. Analysis of dose-volume histograms and clinical goal fulfillment revealed that DCA can generate satisfactory and near equivalent dosimetric quality to VMAT, except for complex tumor geometries. Segment-weight optimized DCA …

Who Benefits From A Prostate Rectal Spacer? Secondary Analysis Of A Phase Iii Trial, Thomas J. Quinn, Walter Bosch, Et Al.

2020-Current year OA Pubs

PURPOSE: Previously a phase III trial of a hydrogel rectal spacer during prostate radiation therapy found decreased toxicity and a clinically significant improvement in bowel quality of life (QOL) at 3 years by the Expanded Prostate Cancer Index. We performed a secondary analysis to identify men less likely to benefit.

METHODS AND MATERIALS: Clinical and dosimetric data for the 222 patients enrolled on the SpaceOAR phase III trial were analyzed. The volume of rectum treated to 70 Gy (V70) and the quantitative analysis of normal tissue effects in the clinic (QUANTEC) rectal dose goals were used as surrogates for clinical …

2019 Hrs/Ehra/Aphrs/Lahrs Expert Consensus Statement On Catheter Ablation Of Ventricular Arrhythmias, Edmond M Cronin, Phillip Cuculich, Et Al.

2020-Current year OA Pubs

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the …

Adenosine At The Interphase Of Hypoxia And Inflammation In Lung Injury, Xiangyun Li, Nathanial K Berg, Tingting Mills, Kaiying Zhang, Holger K Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

Hypoxia and inflammation often coincide in pathogenic conditions such as acute respiratory distress syndrome (ARDS) and chronic lung diseases, which are significant contributors to morbidity and mortality for the general population. For example, the recent global outbreak of Coronavirus disease 2019 (COVID-19) has placed viral infection-induced ARDS under the spotlight. Moreover, chronic lung disease ranks the third leading cause of death in the United States. Hypoxia signaling plays a diverse role in both acute and chronic lung inflammation, which could partially be explained by the divergent function of downstream target pathways such as adenosine signaling. Particularly, hypoxia signaling activates adenosine …