Digital Commons Network^™

Defective Dna Polymerase Beta Invoke A Cytosolic Dna Mediated Inflammatory Response, Shengyuan Zhao, Julia A Goewey Ruiz, Manu Sebastian, Dawit Kidane

Faculty, Staff and Student Publications

Base excision repair (BER) has evolved to maintain the genomic integrity of DNA following endogenous and exogenous agent induced DNA base damage. In contrast, aberrant BER induces genomic instability, promotes malignant transformation and can even trigger cancer development. Previously, we have shown that deoxyribo-5'-phosphate (dRP) lyase deficient DNA polymerase beta (POLB) causes replication associated genomic instability and sensitivity to both endogenous and exogenous DNA damaging agents. Specifically, it has been established that this loss of dRP lyase function promotes inflammation associated gastric cancer. However, the way that aberrant POLB impacts the immune signaling and inflammatory responses is still unknown. Here …

Update On Mri In Evaluation And Treatment Of Endometrial Cancer, Ekta Maheshwari, Stephanie Nougaret, Erica B Stein, Gaiane M Rauch, Ken-Pin Hwang, R Jason Stafford, Ann H Klopp, Pamela T Soliman, Katherine E Maturen, Andrea G Rockall, Susanna I Lee, Elizabeth A Sadowski, Aradhana M Venkatesan

Faculty, Staff and Student Publications

Endometrial cancer is the second most common gynecologic cancer worldwide and the most common gynecologic cancer in the United States, with an increasing incidence in high-income countries. Although the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer is a surgical staging system, contemporary published evidence-based data and expert opinions recommend MRI for treatment planning as it provides critical diagnostic information on tumor size and depth, extent of myometrial and cervical invasion, extrauterine extent, and lymph node status, all of which are essential in choosing the most appropriate therapy. Multiparametric MRI using a combination of T2-weighted sequences, …

A Hybrid Unsupervised And Supervised Learning Approach For Postictal Generalized Eeg Suppression Detection, Xiaojin Li, Yan Huang, Samden D Lhatoo, Shiqiang Tao, Laura Vilella Bertran, Guo-Qiang Zhang, Licong Cui

Faculty, Staff and Student Publications

Sudden unexpected death of epilepsy (SUDEP) is a catastrophic and fatal complication of epilepsy and is the primary cause of mortality in those who have uncontrolled seizures. While several multifactorial processes have been implicated including cardiac, respiratory, autonomic dysfunction leading to arrhythmia, hypoxia, and cessation of cerebral and brainstem function, the mechanisms underlying SUDEP are not completely understood. Postictal generalized electroencephalogram (EEG) suppression (PGES) is a potential risk marker for SUDEP, as studies have shown that prolonged PGES was significantly associated with a higher risk of SUDEP. Automated PGES detection techniques have been developed to efficiently obtain PGES durations for …

More Than Just Statics: Static And Temporal Dynamic Changes In Intrinsic Brain Activity In Unilateral Temporal Lobe Epilepsy, Chengru Song, Xiaonan Zhang, Shaoqiang Han, Keran Ma, Kefan Wang, Xinyue Mao, Yajun Lian, Xianchang Zhang, Jinxia Zhu, Yong Zhang, Jingliang Cheng

Faculty, Staff and Student Publications

BACKGROUND: Temporal lobe epilepsy (TLE) is the most prevalent refractory focal epilepsy and is more likely accompanied by cognitive impairment. The fully understanding of the neuronal activity underlying TLE is of great significance.

OBJECTIVE: This study aimed to comprehensively explore the potential brain activity abnormalities affected by TLE and detect whether the changes were associated with cognition.

METHODS: Six static intrinsic brain activity (IBA) indicators [amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree centrality (DC), global signal correlation (GSCorr), and voxel-mirrored homotopic connectivity (VMHC)] and their corresponding dynamic indicators, such as dynamic ALFF (dALFF), dynamic fALFF …

Somatic And Cognitive Domains Of Depression In An Underserved Region Of Ecuador: Some Cultural Considerations, Gang Wu, Iraida Sharina, Emil Martin

Faculty, Staff and Student Publications

Nitric oxide (NO), carbon monoxide (CO), oxygen (O2), hydrogen sulfide (H2S) are gaseous molecules that play important roles in the physiology and pathophysiology of eukaryotes. Tissue concentrations of these physiologically relevant gases vary remarkable from nM range for NO to high μM range of O2. Various hemoproteins play a significant role in sensing and transducing cellular signals encoded by gaseous molecules or in transporting them. Soluble guanylyl cyclase (sGC) is a hemoprotein that plays vital roles in a wide range of physiological functions and combines the functions of gaseous sensor and signal transducer. sGC uniquely evolved to sense low non-toxic …

Implementing A Robust Process Improvement Program In The Neonatal Intensive Care Unit To Reduce Harm, Klaus G Nether, Eric J Thomas, Amir Khan, Madelene J Ottosen, Lauren Yager

Faculty, Staff and Student Publications

INTRODUCTION: Preventable harm continues to occur with critically ill neonates despite efforts by hospital neonatal intensive care units (NICUs) to improve processes and reduce harm. Attaining significant and sustainable improvements will require training including leadership support, mentoring, and patient family engagement to improve care processes. This paper describes the implementation of a robust process improvement (RPI) program in the NICU to reduce harm.

METHODS: Leaders, staff, and parents were trained in RPI concepts and tools. Multidisciplinary teams including parent members applied the training and received regular mentorship for their improvement initiatives.

RESULTS: Participants (N = 67) completed pretraining and post-training …

A Message From The Trench: A Day In The Hospital During The Covid-19 Pandemic, Gabriel M Aisenberg

Faculty, Staff and Student Publications

No abstract provided.

Erythema Multiforme After Third Covid-19 Vaccination (Pfizer-Biontech), Sonali Batta, Austinn C Miller, Susuana Adjei, Laurie A Temiz, Stephen K Tyring

Faculty, Staff and Student Publications

We present a case of erythema multiforme (EM) associated with a third (booster) dose of COVID-19 vaccination in a patient who had no cutaneous reactions to previous doses. To our knowledge, this is the first documented case of vaccine-associated EM occurring after a third/booster vaccination. Furthermore, our case emphasizes the need to remain vigilant for vaccine-associated EM in any patient recently vaccinated, regardless of whether previous vaccinations were administered without cutaneous reactions.

Epigenome-Wide Association Study Of Mitochondrial Genome Copy Number, Penglong Wang, Christina A Castellani, Jie Yao, Tianxiao Huan, Lawrence F Bielak, Wei Zhao, Jeffrey Haessler, Roby Joehanes, Xianbang Sun, Xiuqing Guo, Ryan J Longchamps, Joann E Manson, Megan L Grove, Jan Bressler, Kent D Taylor, Tuuli Lappalainen, Silva Kasela, David J Van Den Berg, Lifang Hou, Alexander Reiner, Yongmei Liu, Eric Boerwinkle, Jennifer A Smith, Patricia A Peyser, Myriam Fornage, Stephen S Rich, Jerome I Rotter, Charles Kooperberg, Dan E Arking, Daniel Levy, Chunyu Liu

Faculty, Staff and Student Publications

We conducted cohort- and race-specific epigenome-wide association analyses of mitochondrial deoxyribonucleic acid (mtDNA) copy number (mtDNA CN) measured in whole blood from participants of African and European origins in five cohorts (n = 6182, mean age = 57-67 years, 65% women). In the meta-analysis of all the participants, we discovered 21 mtDNA CN-associated DNA methylation sites (CpG) (P < 1 × 10-7), with a 0.7-3.0 standard deviation increase (3 CpGs) or decrease (18 CpGs) in mtDNA CN corresponding to a 1% increase in DNA methylation. Several significant CpGs have been reported to be associated with at least two risk factors (e.g. chronological age or smoking) for cardiovascular disease (CVD). Five genes [PR/SET domain 16, nuclear receptor subfamily 1 group H member 3 (NR1H3), DNA repair protein, DNA polymerase kappa and decaprenyl-diphosphate synthase subunit 2], which harbor nine significant CpGs, are known to be involved in mitochondrial biosynthesis and functions. For example, NR1H3 encodes a transcription factor that is differentially expressed during an adipose tissue transition. The methylation level of cg09548275 in NR1H3 was negatively associated with mtDNA CN (effect size = -1.71, P = 4 × 10-8) and was positively associated with the NR1H3 expression level (effect size = 0.43, P = 0.0003), which indicates that the methylation level in NR1H3 may underlie the relationship between mtDNA CN, the NR1H3 transcription factor and energy expenditure. In summary, the study results suggest that mtDNA CN variation in whole blood is associated with DNA methylation levels in genes that are involved in a wide range of mitochondrial activities. These findings will help reveal molecular mechanisms between mtDNA CN and CVD.

Growth In Achondroplasia Including Stature, Weight, Weight-For-Height And Head Circumference From Clarity: Achondroplasia Natural History Study-A Multi-Center Retrospective Cohort Study Of Achondroplasia In The Us, Julie E Hoover-Fong, Kerry J Schulze, Adekemi Y Alade, Michael B Bober, Ethan Gough, S Shahrukh Hashmi, Jacqueline T Hecht, Janet M Legare, Mary Ellen Little, Peggy Modaff, Richard M Pauli, David F Rodriguez-Buritica, Maria E Serna, Cory Smid, Chengxin Liu, John Mcgready

Faculty, Staff and Student Publications

BACKGROUND: Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (achondroplasia natural history study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at 1 month increments …

Phase 3 Safety And Efficacy Of Azd1222 (Chadox1 Ncov-19) Covid-19 Vaccine, Ann R Falsey, Magdalena E Sobieszczyk, Ian Hirsch, Stephanie Sproule, Merlin L Robb, Lawrence Corey, Kathleen M Neuzil, William Hahn, Julie Hunt, Mark J Mulligan, Charlene Mcevoy, Edwin Dejesus, Michael Hassman, Susan J Little, Barbara A Pahud, Anna Durbin, Paul Pickrell, Eric S Daar, Larry Bush, Joel Solis, Quito Osuna Carr, Temitope Oyedele, Susan Buchbinder, Jessica Cowden, Sergio L Vargas, Alfredo Guerreros Benavides, Robert Call, Michael C Keefer, Beth D Kirkpatrick, John Pullman, Tina Tong, Margaret Brewinski Isaacs, David Benkeser, Holly E Janes, Martha C Nason, Justin A Green, Elizabeth J Kelly, Jill Maaske, Nancy Mueller, Kathryn Shoemaker, Therese Takas, Richard P Marshall, Menelas N Pangalos, Tonya Villafana, Antonio Gonzalez-Lopez

Faculty, Staff and Student Publications

BACKGROUND: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known.

METHODS: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru.

RESULTS: …

Intra-Tumoral Nerve-Tracing In A Novel Syngeneic Model Of High-Grade Serous Ovarian Carcinoma, Jeffrey L Barr, Allison Kruse, Anthony C Restaino, Natalia Tulina, Sarah Stuckelberger, Samuel J Vermeer, Caitlin S Williamson, Daniel W Vermeer, Marianna Madeo, Jillian Stamp, Maria Bell, Mark Morgan, Ju-Yoon Yoon, Marilyn A Mitchell, Anna Budina, Dalia K Omran, Lauren E Schwartz, Ronny Drapkin, Paola D Vermeer

Faculty, Staff and Student Publications

Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the normal tissue contains predominantly sympathetic input. The origin, specific nerve type, and the mechanisms promoting innervation and driving nerve-cancer cell communications in ovarian cancer remain largely unknown. The technique of neuro-tracing enhances the study of tumor innervation by offering a means for identification and mapping of nerve sources that may directly and indirectly affect the tumor microenvironment. …

Radioembolization With Chemotherapy For Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase Iii Trial, Mary F Mulcahy, Armeen Mahvash, Marc Pracht, Amir H Montazeri, Steve Bandula, Robert C G Martin, Ken Herrmann, Ewan Brown, Darryl Zuckerman, Gregory Wilson, Tae-You Kim, Andrew Weaver, Paul Ross, William P Harris, Janet Graham, Jamie Mills, Alfonso Yubero Esteban, Matthew S Johnson, Constantinos T Sofocleous, Siddharth A Padia, Robert J Lewandowski, Etienne Garin, Philip Sinclair, Riad Salem

Faculty, Staff and Student Publications

PURPOSE: To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM).

METHODS: In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and

RESULTS: Four hundred twenty-eight patients from …

Meta-Analyses Identify Dna Methylation Associated With Kidney Function And Damage, Pascal Schlosser, Adrienne Tin, Pamela R Matias-Garcia, Chris H L Thio, Roby Joehanes, Hongbo Liu, Antoine Weihs, Zhi Yu, Anselm Hoppmann, Franziska Grundner-Culemann, Josine L Min, Adebowale A Adeyemo, Charles Agyemang, Johan Ärnlöv, Nasir A Aziz, Andrea Baccarelli, Murielle Bochud, Hermann Brenner, Monique M B Breteler, Cristian Carmeli, Layal Chaker, John C Chambers, Shelley A Cole, Josef Coresh, Tanguy Corre, Adolfo Correa, Simon R Cox, Niek De Klein, Graciela E Delgado, Arce Domingo-Relloso, Kai-Uwe Eckardt, Arif B Ekici, Karlhans Endlich, Kathryn L Evans, James S Floyd, Myriam Fornage, Lude Franke, Eliza Fraszczyk, Xu Gao, Xīn Gào, Mohsen Ghanbari, Sahar Ghasemi, Christian Gieger, Philip Greenland, Megan L Grove, Sarah E Harris, Gibran Hemani, Peter Henneman, Christian Herder, Steve Horvath, Lifang Hou, Mikko A Hurme, Shih-Jen Hwang, Marjo-Riitta Jarvelin, Sharon L R Kardia, Silva Kasela, Marcus E Kleber, Wolfgang Koenig, Jaspal S Kooner, Holly Kramer, Florian Kronenberg, Brigitte Kühnel, Terho Lehtimäki, Lars Lind, Dan Liu, Yongmei Liu, Donald M Lloyd-Jones, Kurt Lohman, Stefan Lorkowski, Ake T Lu, Riccardo E Marioni, Winfried März, Daniel L Mccartney, Karlijn A C Meeks, Lili Milani, Pashupati P Mishra, Matthias Nauck, Ana Navas-Acien, Christoph Nowak, Annette Peters, Holger Prokisch, Bruce M Psaty, Olli T Raitakari, Scott M Ratliff, Alex P Reiner, Sylvia E Rosas, Ben Schöttker, Joel Schwartz, Sanaz Sedaghat, Jennifer A Smith, Nona Sotoodehnia, Hannah R Stocker, Silvia Stringhini, Johan Sundström, Brenton R Swenson, Maria Tellez-Plaza, Joyce B J Van Meurs, Jana V Van Vliet-Ostaptchouk, Andrea Venema, Niek Verweij, Rosie M Walker, Matthias Wielscher, Juliane Winkelmann, Bruce H R Wolffenbuttel, Wei Zhao, Yinan Zheng, Marie Loh, Harold Snieder, Daniel Levy, Melanie Waldenberger, Katalin Susztak, Anna Köttgen, Alexander Teumer

Faculty, Staff and Student Publications

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. to extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. …

Epigenome-Wide Association Study Of Serum Urate Reveals Insights Into Urate Co-Regulation And The Slc2a9 Locus, Adrienne Tin, Pascal Schlosser, Pamela R Matias-Garcia, Chris H L Thio, Roby Joehanes, Hongbo Liu, Zhi Yu, Antoine Weihs, Anselm Hoppmann, Franziska Grundner-Culemann, Josine L Min, Victoria L Halperin Kuhns, Adebowale A Adeyemo, Charles Agyemang, Johan Ärnlöv, Nasir A Aziz, Andrea Baccarelli, Murielle Bochud, Hermann Brenner, Jan Bressler, Monique M B Breteler, Cristian Carmeli, Layal Chaker, Josef Coresh, Tanguy Corre, Adolfo Correa, Simon R Cox, Graciela E Delgado, Kai-Uwe Eckardt, Arif B Ekici, Karlhans Endlich, James S Floyd, Eliza Fraszczyk, Xu Gao, Xīn Gào, Allan C Gelber, Mohsen Ghanbari, Sahar Ghasemi, Christian Gieger, Philip Greenland, Megan L Grove, Sarah E Harris, Gibran Hemani, Peter Henneman, Christian Herder, Steve Horvath, Lifang Hou, Mikko A Hurme, Shih-Jen Hwang, Sharon L R Kardia, Silva Kasela, Marcus E Kleber, Wolfgang Koenig, Jaspal S Kooner, Florian Kronenberg, Brigitte Kühnel, Christine Ladd-Acosta, Terho Lehtimäki, Lars Lind, Dan Liu, Donald M Lloyd-Jones, Stefan Lorkowski, Ake T Lu, Riccardo E Marioni, Winfried März, Daniel L Mccartney, Karlijn A C Meeks, Lili Milani, Pashupati P Mishra, Matthias Nauck, Christoph Nowak, Annette Peters, Holger Prokisch, Bruce M Psaty, Olli T Raitakari, Scott M Ratliff, Alex P Reiner, Ben Schöttker, Joel Schwartz, Sanaz Sedaghat, Jennifer A Smith, Nona Sotoodehnia, Hannah R Stocker, Silvia Stringhini, Johan Sundström, Brenton R Swenson, Joyce B J Van Meurs, Jana V Van Vliet-Ostaptchouk, Andrea Venema, Uwe Völker, Juliane Winkelmann, Bruce H R Wolffenbuttel, Wei Zhao, Yinan Zheng, Marie Loh, Harold Snieder, Melanie Waldenberger, Daniel Levy, Shreeram Akilesh, Owen M Woodward, Katalin Susztak, Alexander Teumer, Anna Köttgen

Faculty, Staff and Student Publications

Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E-7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.

Practical Considerations Of Dissolved Oxygen Levels For Platelet Function Under Hypoxia, Branden Kusanto, Andrew Gordon, Leigh Naylor-Adamson, Lloyd Atkinson, Charlie Coupland, Zoe Booth, Yusra Ahmed, Isabel M Pires, Graeme J Stasiuk, Roger Sturmey, Simon D J Calaminus, Mònica Arman

Faculty, Staff and Student Publications

Investigating human platelet function in low-oxygen environments is important in multiple settings, including hypobaric hypoxia (e.g., high altitude), sea level hypoxia-related disease, and thrombus stability. These studies often involve drawing blood from which platelets are isolated and analysed at atmospheric conditions or re-exposed to low oxygen levels in hypoxia chambers before testing. However, it remains unknown how the in vitro handling of the samples itself changes their dissolved oxygen concentration, which might affect platelet function and experimental results. Here, we prepared healthy donor platelet-rich plasma and washed platelet (WP) suspensions and exposed them to 2% oxygen. We found that the …

Association Of Low-Frequency And Rare Coding Variants With Information Processing Speed, Jan Bressler, Gail Davies, Albert V Smith, Yasaman Saba, Joshua C Bis, Xueqiu Jian, Caroline Hayward, Lisa Yanek, Jennifer A Smith, Saira S Mirza, Ruiqi Wang, Hieab H H Adams, Diane Becker, Eric Boerwinkle, Archie Campbell, Simon R Cox, Gudny Eiriksdottir, Chloe Fawns-Ritchie, Rebecca F Gottesman, Megan L Grove, Xiuqing Guo, Edith Hofer, Sharon L R Kardia, Maria J Knol, Marisa Koini, Oscar L Lopez, Riccardo E Marioni, Paul Nyquist, Alison Pattie, Ozren Polasek, David J Porteous, Igor Rudan, Claudia L Satizabal, Helena Schmidt, Reinhold Schmidt, Stephen Sidney, Jeannette Simino, Blair H Smith, Stephen T Turner, Sven J Van Der Lee, Erin B Ware, Rachel A Whitmer, Kristine Yaffe, Qiong Yang, Wei Zhao, Vilmundur Gudnason, Lenore J Launer, Annette L Fitzpatrick, Bruce M Psaty, Myriam Fornage, M Arfan Ikram, Cornelia M Van Duijn, Sudha Seshadri, Thomas H Mosley, Ian J Deary

Faculty, Staff and Student Publications

Measures of information processing speed vary between individuals and decline with age. Studies of aging twins suggest heritability may be as high as 67%. The Illumina HumanExome Bead Chip genotyping array was used to examine the association of rare coding variants with performance on the Digit-Symbol Substitution Test (DSST) in community-dwelling adults participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. DSST scores were available for 30,576 individuals of European ancestry from nine cohorts and for 5758 individuals of African ancestry from four cohorts who were older than 45 years and free of dementia and …

Development And Testing Of The Stakeholder Quality Improvement Perspectives Survey (Squips), Eric Fris, Emily Sedlock, Jason Etchegaray, Madelene J Ottosen, Ronald Pucio, Tejal Mistry, Tamara Saunders, Andrada Tomoaia-Cotisel, Eric J Thomas

Faculty, Staff and Student Publications

BACKGROUND: To create a theory-informed survey that quality improvement (QI) teams can use to understand stakeholder perceptions of an intervention.

METHOD: We created the survey then performed a cross-sectional survey of QI stakeholders of three QI projects. The projects sought to: (1) reduce unplanned extubations in a neonatal intensive care unit; (2) maintain normothermia during colorectal surgery and (3) reduce specimen processing errors for ambulatory gastroenterology procedures. We report frequencies of responses to survey items, results of exploratory factor analysis, and how QI team leaders used the results.

RESULTS: Overall we received surveys from 319 out of 386 eligible stakeholders …

Temperature Changes During Implant Osteotomy Preparations In Human Cadaver Tibiae Comparing Mis® Straight Drills With Densah® Burs, Andrew C Griggs, Crystal M Fausett, Richard J Simonson, Kimberly N Williams, Tiffany M Bisbey, Elizabeth H Lazzara, Joseph R Keebler, Deborah Diazgranados, Vimal K Mishra, Eric J Thomas, Eduardo Salas

Faculty, Staff and Student Publications

INTRODUCTION: Telerounding is slated to become an important avenue for future healthcare practice. As utilization of telerounding is increasing, a review of the literature is necessary to distill themes and identify critical considerations for the implementation of telerounding. We provide evidence of the utility of telerounding and considerations to support its implementation in future healthcare practice based on a scoping review.

METHOD: We collected articles from nine scientific databases from the earliest dated available articles to August 2020. We identified whether each article centered on telerounding policies, regulations, or practice. We also organized information from each article and sorted themes …

Central Line Associated Bloodstream Infection Caused By Kodamaea Ohmeri In A Young Child, Amier Haidar, Farhana Khaja, Brian Simms, Amr Issam Elgehiny, Tracy Omoegbele, Nikita Khetan

Faculty, Staff and Student Publications

INTRODUCTION:

CASE REPORT: The patient is a 5-year-old male with a history of short gut syndrome, and total parenteral nutrition (TPN) dependence who presented to the emergency room with a two-day history of productive-cough, rhinorrhea, and fever. Antibiotic therapy was initiated with cefepime and vancomycin for suspected CLABSI. However, within the first twenty-four hours of his admission, his initial blood culture from his central venous catheter became positive for yeast so fluconazole was added due to suspicion of candidemia. During his admission, his initial central line and peripheral blood culture were later speciated as

CONCLUSIONS: This case report further acknowledges …

Tavr In Older Adults: Moving Toward A Comprehensive Geriatric Assessment And Away From Chronological Age: Jacc Family Series, Joy M Schmitz, Scott D Lane, Michael F Weaver, Ponnada A Narayana, Khader M Hasan, Delisa D Russell, Robert Suchting, Charles E Green

Faculty, Staff and Student Publications

Cocaine use continues to be a significant public health problem with limited treatment options and no approved pharmacotherapies. Cognitive-behavioral therapy (CBT) remains the mainstay treatment for preventing relapse, however, people with chronic cocaine use display cognitive impairments that are associated with poor response to CBT. Emerging evidence in animal and human studies suggests that the peroxisome proliferator-activated receptor-gamma (PPAR- γ) agonist, pioglitazone, improves white matter integrity that is essential for cognitive function. This project will determine whether adjunctive use of pioglitazone enhances the effect of CBT in preventing relapse during the early phase of recovery from cocaine use disorder. This …

Modeling Recurrence In Idiopathic Subglottic Stenosis With Mobile Peak Expiratory Flow, Kyle Kimura, Liping Du, Lynn D Berry, Li-Ching Huang, Sheau-Chiann Chen, David O Francis, Alexander Gelbard

Faculty, Staff and Student Publications

OBJECTIVES/HYPOTHESIS: We sought to establish normative peak expiratory flow (PEF) data for patients with idiopathic subglottic stenosis (iSGS), evaluate whether immediate changes in PEF after a procedure predict long-term treatment response, and test if a decline in longitudinal PEF is associated with disease recurrence.

STUDY DESIGN: International, prospective, 3-year multicenter cohort study of 810 patients with untreated, newly diagnosed, or previously treated iSGS.

METHODS: iSGS patients consented and enrolled in the North American Airway Collaborative (NoAAC) iSGS

RESULTS: Within the NoAAC iSGS1000 cohort, 810 patients participated in a 3-year, prospective study comparing surgical treatment efficacy and 385 had appropriate PEF …

Nmr Spectroscopy-Based Metabolomics Of Platelets To Analyze Brain Tumors, Shivanand Pudakalakatti, Alessandra Audia, Anirudh Mukhopadhyay, José S Enriquez, Dontrey Bourgeois, Nabihah Tayob, Niki M Zacharias, Steven W Millward, Daniel Carson, Mary C Farach-Carson, Frederick F Lang, Amy B Heimberger, Krishna P Bhat, Pratip K Bhattacharya

Faculty, Staff and Student Publications

"Tumor-educated platelets" have recently generated substantial interest for the diagnosis of cancer. We hypothesized that tumor educated platelets from patients with brain tumors will reflect altered metabolism compared to platelets from healthy volunteers. Here, in a pilot study, we have employed nuclear magnetic resonance (NMR) spectroscopy in platelets from brain tumor patients to demonstrate altered metabolism compared to the platelets obtained from healthy volunteers.

Profile Of Autism Spectrum Disorder In Tuberous Sclerosis Complex: Results From A Longitudinal, Prospective, Multisite Study, Jamie K Capal, Marian E Williams, Deborah A Pearson, Robin Kissinger, Paul S Horn, Donna Murray, Kristn Currans, Bridget Kent, Martina Bebin, Hope Northrup, Joyce Y Wu, Mustafa Sahin, Darcy A Krueger, Tacern Study Group

Faculty, Staff and Student Publications

OBJECTIVE: Tuberous sclerosis complex (TSC) is highly associated with autism spectrum disorder (ASD). Objectives of the study were to characterize autistic features in young children with TSC.

METHODS: Participants included 138 children followed from ages 3 to 36 months with TSC from the Tuberous Sclerosis Complex Autism Center of Excellence Research Network (TACERN), a multicenter, prospective observational study aimed at understanding the underlying mechanisms of ASD in TSC. Developmental and autism-specific assessments were administered, and a clinical diagnosis of ASD was determined for all participants at 36 months. Further analyses were performed on 117 participants with valid autism assessments based …

Defining The Epidemiology Of Safety Risks In Neonatal Intensive Care Unit Patients Requiring Surgery, Daniel J France, Jason Slagle, Emma Schremp, Sarah Moroz, L Dupree Hatch, Peter Grubb, Timothy J Vogus, Matthew S Shotwell, Amanda Lorinc, Christoph U Lehmann, Jamie Robinson, Marlee Crankshaw, Maria Sullivan, Timothy A Newman, Tamara Wallace, Matthew B Weinger, Martin L Blakely

Faculty, Staff and Student Publications

OBJECTIVE: The aim of the study was to determine the incidence, type, severity, preventability, and contributing factors of nonroutine events (NREs)-events perceived by care providers or skilled observers as a deviations from optimal care based on the clinical situation-in the perioperative (i.e., preoperative, operative, and postoperative) care of surgical neonates in the neonatal intensive care unit and operating room.

METHODS: A prospective observational study of noncardiac surgical neonates, who received preoperative and postoperative neonatal intensive care unit care, was conducted at an urban academic children's hospital between November 1, 2016, and March 31, 2018. One hundred twenty-nine surgical cases in …

Pre-Exposure Prophylaxis With Various Doses Of Hydroxychloroquine Among Healthcare Personnel With High-Risk Exposure To Covid-19: A Randomized Controlled Trial, Fibhaa Syed, Muhammad Hassan, Mohammad Ali Arif, Sadia Batool, Rauf Niazi, Ume E Laila, Sadia Ashraf, Junaid Arshad

Faculty, Staff and Student Publications

Objective This trial aimed to evaluate the safety and efficacy of pre-exposure prophylaxis (PrEP) with various hydroxychloroquine (HCQ) doses against a placebo among healthcare personnel (HCP) with high-risk exposure to coronavirus disease 2019 (COVID 19). Methods A phase II, randomized, placebo-controlled trial was conducted including 200 subjects with no active or past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (antibody testing and reverse transcription-polymerase chain reaction (RT-PCR) were taken at the time of enrollment). Subjects of experimental groups one to three received HCQ in various doses and the control group received a placebo. The study outcomes in terms of …

Resistin Levels Decrease As Insulin Resistance Increases In A Mexican-American Cohort, Absalon D Gutierrez, Carlos A Flores, Sapna Naik, Minjae Lee, Parisa Asgarisabet, Masha Resman, Miryoung Lee, Joseph B Mccormick, Susan P Fisher-Hoch

Faculty, Staff and Student Publications

AIMS: Links between resistin, insulin resistance (IR), and resistin-stimulated cytokine signaling remain unknown in Mexican-Americans. A Mexican-American cohort was examined to determine (1) relationships between circulating resistin and IR, (2) resistin's associations with cytokines and demographic and anthropometric variables, and (3) similar measurements with other adipokines.

METHODS: For cross sectional analyses, 953 adults (367 males and 586 females) in the Cameron County Hispanic Cohort (CCHC) were stratified into three groups: normal glucose tolerance, prediabetes, and diabetes mellitus. Differences in resistin and other adipokine levels were examined using linear regression via unadjusted model (Model 1), model adjusted for cytokines (Model 2), …

Long-Term Impacts Faced By Patients And Families After Harmful Healthcare Events, Madelene J Ottosen, Emily W Sedlock, Aitebureme O Aigbe, Sigall K Bell, Thomas H Gallagher, Eric J Thomas

Faculty, Staff and Student Publications

BACKGROUND: Patients and families report experiencing a multitude of harms from medical errors resulting in physical, emotional, and financial hardships. Little is known about the duration and nature of these harms and the type of support needed to promote patient and family healing after such events. We sought to describe the long-term impacts (LTIs) reported by patients and family members who experienced harmful medical events 5 or more years ago.

METHODS: We performed a content analysis on 32 interviews originally conducted with 72 patients or family members about their views of the factors contributing to their self-reported harmful event. Interviews …

Patient-Derived Ipscs Link Elevated Mitochondrial Respiratory Complex I Function To Osteosarcoma In Rothmund-Thomson Syndrome, Brittany E Jewell, An Xu, Dandan Zhu, Mo-Fan Huang, Linchao Lu, Mo Liu, Erica L Underwood, Jun Hyoung Park, Huihui Fan, Julian A Gingold, Ruoji Zhou, Jian Tu, Zijun Huo, Ying Liu, Weidong Jin, Yi-Hung Chen, Yitian Xu, Shu-Hsia Chen, Nino Rainusso, Nathaniel K Berg, Danielle A Bazer, Christopher Vellano, Philip Jones, Holger K Eltzschig, Zhongming Zhao, Benny Abraham Kaipparettu, Ruiying Zhao, Lisa L Wang, Dung-Fang Lee

Faculty, Staff and Student Publications

Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma, small stature, skeletal anomalies, sparse brows/lashes, cataracts, and predisposition to cancer. Type 2 RTS patients with biallelic RECQL4 pathogenic variants have multiple skeletal anomalies and a significantly increased incidence of osteosarcoma. Here, we generated RTS patient-derived induced pluripotent stem cells (iPSCs) to dissect the pathological signaling leading to RTS patient-associated osteosarcoma. RTS iPSC-derived osteoblasts showed defective osteogenic differentiation and gain of in vitro tumorigenic ability. Transcriptome analysis of RTS osteoblasts validated decreased bone morphogenesis while revealing aberrantly upregulated mitochondrial respiratory complex I gene expression. RTS osteoblast metabolic assays …

Construct Validity For The Self-Reported Competency And Sub-Construct Associated Characteristics Of Romanian Physicians In Autism Spectrum Disorder, Mohammad H Rahbar, Iuliana Dobrescu, Shezeen Gillani, Manouchehr Hessabi, Sori Kim, Mihaela Stancu, Florina Rad

Faculty, Staff and Student Publications

BACKGROUND: Lack of physicians' knowledge regarding mental health, including Autism Spectrum Disorder (ASD) could have adverse effects on affected individuals' health and quality of life. The purpose of this study was to provide construct validity for a modified questionnaire in order to determine the self-reported competency for underlying sub-constructs in ASD, make inferences on perceived competence in ASD based on a sample of Romanian physicians, and identify physicians' characteristics associated with these sub-domains of competency.

METHODS: For this survey, we modified a questionnaire that was used in Pakistan and Turkey, and administered it to a sample of 383 practicing physicians …