Digital Commons Network^™

Are Thyrotropin-Releasing Hormone (Trh) And Analog Taltirelin Viable Reversal Agents Of Opioid-Induced Respiratory Depression?, Marieke Hyke Algera, Joseph F Cotten, Monique Van Velzen, Marieke Niesters, Martijn Boon, Daniel S Shoham, Kaye E Dandrea, Rutger Van Der Schrier, Albert Dahan

Faculty, Staff and Student Publications

Opioid-induced respiratory depression (OIRD) is a potentially life-threatening complication of opioid consumption. Apart from naloxone, an opioid antagonist that has various disadvantages, a possible reversal strategy is treatment of OIRD with the hypothalamic hormone and neuromodulator thyrotropin-releasing hormone (TRH). In this review, we performed a search in electronic databases and retrieved 52 papers on the effect of TRH and TRH-analogs on respiration and their efficacy in the reversal of OIRD in awake and anesthetized mammals, including humans. Animal studies show that TRH and its analog taltirelin stimulate breathing via an effect at the preBötzinger complex, an important respiratory rhythm generator …

Impact Of Post-Arrest Care Variation On Hospital Performance After Out-Of-Hospital Cardiac Arrest, Ryan Huebinger, Jordan Thomas, Benjamin S Abella, John Waller-Delarosa, Rabab Al-Araji, Richard Witkov, Normandy Villa, Peter Nikonowicz, Taylor Renbarger, Micah Panczyk, Bentley Bobrow

Faculty, Staff and Student Publications

BACKGROUND: Large variation exists for out-of-hospital-cardiac-arrest (OHCA) prehospital care, but less is known about variations in post-arrest care. We sought to evaluate variation in post-arrest care in Texas as well as factors associated with higher performing hospitals.

METHODS: We analyzed data in Texas Cardiac Arrest Registry to Enhance Survival (TX-CARES), including all adult, non-traumatic OHCAs from 1/1/2014 through 12/31/ 2020 that survived to hospital admission. We first evaluated variability in provisions of post-arrest care and outcomes. We then stratified hospitals into quartiles based on their rate of survival and evaluated the association between improving quartiles and care. Lastly, we evaluated …

Impact Of Covid19 On Maxillofacial Fractures In The Province Of L’Aquila, Abruzzo, Italy Review Of 296 Patients Treated With Statistical Comparison Of The Two-Year Pre-Covid19 And Covid19, Filippo Giovannetti, Ettore Lupi, Danilo Di Giorgio, Secondo Scarsella, Antonio Oliva, Desiderio Di Fabio, Paolo Prata, Giada Petricca, Valentino Valentini

Faculty, Staff and Student Publications

The aim of this study was to understand the impact of the COVID-19 pandemic on the epidemiology of maxillofacial trauma in a regional trauma center in L'Aquila, Abruzzo, Italy, during the first wave of the pandemic and comparted it to an equivalent period from 2015 to 2018. The authorshave retrospectively analyzed personal data, site of trauma, etiology, and mechanism of injury. Statistical analysis has been carried out utilizing IBM SPSS Statistics software (IBM Corp., Armonk, NY) and significance was accepted for P values of 0.05) as opposed to the etiology in which the road traffic accidents decreased in favor of …

Noninvasive Testing And Surrogate Markers In Invasive Fungal Diseases, George R Thompson, David R Boulware, Nathan C Bahr, Cornelius J Clancy, Thomas S Harrison, Carol A Kauffman, Thuy Le, Marisa H Miceli, Eleftherios Mylonakis, M Hong Nguyen, Luis Ostrosky-Zeichner, Thomas F Patterson, John R Perfect, Andrej Spec, Dimitrios P Kontoyiannis, Peter G Pappas

Faculty, Staff and Student Publications

Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandate the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival end points may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these …

Computational Analysis Of Memory Consolidation Following Inhibitory Avoidance (Ia) Training In Adult And Infant Rats: Critical Roles Of Camkiia And Mecp2, Yili Zhang, Paul Smolen, Cristina M Alberini, Douglas A Baxter, John H Byrne

Faculty, Staff and Student Publications

Key features of long-term memory (LTM), such as its stability and persistence, are acquired during processes collectively referred to as consolidation. The dynamics of biological changes during consolidation are complex. In adult rodents, consolidation exhibits distinct periods during which the engram is more or less resistant to disruption. Moreover, the ability to consolidate memories differs during developmental periods. Although the molecular mechanisms underlying consolidation are poorly understood, the initial stages rely on interacting signaling pathways that regulate gene expression, including brain-derived neurotrophic factor (BDNF) and Ca²⁺/calmodulin-dependent protein kinase II α (CaMKIIα) dependent feedback loops. We investigated the ways …

Pityriasis Rosea-Like Rash After Messenger Rna Covid-19 Vaccination: A Case Report And Review Of The Literature, Jordan E Buckley, Laura N Landis, Ronald P Rapini

Faculty, Staff and Student Publications

A spectrum of cutaneous reactions to SARs-CoV-2 (COVID-19) vaccines have been reported in the literature. We present a case of a pityriasis rosea-like rash occurring after Pfizer COVID-19 vaccination and review cases of pityriasis rosea (PR)/PR-like eruption (PR-LE) after mRNA COVID-19 vaccine published in the medical literature. Of the 30 cases found, none experienced severe adverse effects and the rash resolved in an average of 5.6 weeks. It is important for physicians to be aware of this self-limited reaction so they can reassure and appropriately counsel patients that it is safe to receive subsequent vaccine doses despite the cutaneous eruption. …

Prognosticators Of Visual Acuity After Indirect Traumatic Optic Neuropathy, Alex J Wright, Joanna H Queen, Emilio P Supsupin, Alice Z Chuang, John J Chen, Rod Foroozan, Ore-Ofe O Adesina

Faculty, Staff and Student Publications

BACKGROUND: The purpose of this study is to determine whether there are radiographic and systemic clinical characteristics that can predict final visual outcomes in patients with indirect traumatic optic neuropathy (iTON).

METHODS: This study is a retrospective, multicenter case series of adult patients with iTON treated initially at large, urban, and/or academic trauma centers with follow-up at an affiliated ophthalmology clinic. In addition to detailed cranial computed tomography characteristics, demographics, systemic comorbidities, coinjuries, blood products administered, and intracranial pressure, along with other factors, were gathered. LogMAR visual acuity (VA) at the initial presentation to the hospital and up to 12 …

Grief Symptoms Promote Inflammation During Acute Stress Among Bereaved Spouses, Ryan L Brown, Angie S Leroy, Michelle A Chen, Robert Suchting, Lisa M Jaremka, Jia Liu, Cobi Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

The death of a spouse is associated with maladaptive immune alterations; grief severity may exacerbate this link. We investigated whether high grief symptoms were associated with an amplified inflammatory response to subsequent stress among 111 recently bereaved older adults. Participants completed a standardized psychological stressor and underwent a blood draw before, 45 min after, and 2 hr after the stressor. Those experiencing high grief symptoms (i.e., scoring > 25 on the Inventory of Complicated Grief) experienced a 45% increase in interleukin-6 (IL-6; a proinflammatory cytokine) per hour, whereas those experiencing low grief symptoms demonstrated a 26% increase. In other words, high …

Cooking After Cancer: The Structure And Implementation Of A Community-Based Cooking Program For Cancer Survivors, Margaret Raber, Molly Costigan, Joya Chandra, Karen Basen-Engquist

Faculty, Staff and Student Publications

Cancer survivors are a growing population that may particularly benefit from nutrition and lifestyle interventions. Community-based programs teaching healthy cooking skills are increasingly popular and offer an opportunity to support survivors within communities. The objective of this study is to describe the curriculum and implementation of a cooking class program designed for cancer survivors, housed within an established community-based organization. First, we evaluated the class curriculum for specific constructs. An evidence-based measure of healthy cooking constructs, the Healthy Cooking Index (HCI), was used to analyze included recipes and revealed both summative cooking quality scores and individual constructs underlying the overall …

Factors Impacting Adolescent And Young Adult Cancer Patients’ Decision To Pursue Genetic Counseling And Testing, Megan Morand, Michael Roth, Susan K Peterson, Erica M Bednar, Aarti Ramdaney, J Andrew Livingston, Angela Yarbrough, Jessica Corredor

Faculty, Staff and Student Publications

Purpose: Adolescent and young adult (AYA) cancer patients face challenges when navigating cancer treatment and survivorship. Many are at risk for cancer predisposition syndromes; however, factors influencing pursuit of genetic counseling and testing have not been reported. We describe AYA cancer patients' decision-making process, including motivational factors and barriers, as it relates to utilization of genetic services.

Methods: Thirty AYAs diagnosed with cancer previously referred for cancer predisposition genetic counseling completed semi-structured interviews via audio-only Zoom calls. Thematic analysis was used to perform qualitative analysis and identify major themes.

Results: The sample comprised 21 AYAs who had genetic counseling and …

Cardiovascular Outcomes In Aortopathy: Gentac Registry Of Genetically Triggered Aortic Aneurysms And Related Conditions, Kathryn W Holmes, Sheila Markwardt, Kim A Eagle, Richard B Devereux, Jonathan W Weinsaft, Federico M Asch, Scott A Lemaire, Cheryl L Maslen, Howard K Song, Dianna M Milewicz, Siddharth K Prakash, Dongchuan Guo, Shaine A Morris, Reed E Pyeritz, Rita C Milewski, William J Ravekes, H C Dietz, Ralph V Shohet, Michael Silberbach, Mary J Roman

Faculty, Staff and Student Publications

BACKGROUND: The GenTAC (Genetically Triggered Thoracic Aortic Aneurysm and Cardiovascular Conditions) Registry enrolled patients with genetic aortopathies between 2007 and 2016.

OBJECTIVES: The purpose of this study was to compare age distribution and probability of elective surgery for proximal aortic aneurysm, any dissection surgery, and cardiovascular mortality among aortopathy etiologies.

METHODS: The GenTAC study had a retrospective/prospective design. Participants with bicuspid aortic valve (BAV) with aneurysm (n = 879), Marfan syndrome (MFS) (n = 861), nonsyndromic heritable thoracic aortic disease (nsHTAD) (n = 378), Turner syndrome (TS) (n = 298), vascular Ehlers-Danlos syndrome (vEDS) (n = 149), and Loeys-Dietz syndrome …

Detoxification Role Of Metabolic Glutathione S-Transferase (Gst) Genes In Blood Lead Concentrations Of Jamaican Children With And Without Autism Spectrum Disorder, Mohammad H Rahbar, Maureen Samms-Vaughan, Sori Kim, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakspeare-Pellington, Katherine A Loveland

Faculty, Staff and Student Publications

Glutathione S-transferases (GST) are involved in the detoxification of exogenous chemicals including lead (Pb). Using data from 344 pairs of autism spectrum disorder (ASD) cases and age- and sex-matched typically developing (TD) controls (2−8 years old) from Jamaica, we investigated the interaction between three GST genes and ASD status as determinants of blood Pb concentrations (BPbCs). We found that ASD cases had lower geometric mean BPbCs than TD children (1.74 vs. 2.27 µg/dL, p < 0.01). Using a co-dominant genetic model, ASD cases with the Ile/Val genotype for the GSTP1 Ile105Val polymorphism had lower GM BPbCs than TD controls, after adjusting for a known interaction between GSTP1 and GSTT1, child’s parish, socioeconomic status, consumption of lettuce, fried plantains, and canned fish (Ile/Val: 1.78 vs. 2.13 µg/dL, p = 0.03). Similarly, among carriers of the I/I or I/D (I*) genotype for GSTT1 and GSTM1, ASD cases had lower adjusted GM BPbCs than TD controls (GSTT1 I*: 1.61 vs. 1.91 µg/dL, p = 0.01; GSTM1 I*: 1.71 vs. 2.04 µg/dL, p = 0.01). Our findings suggest that genetic polymorphisms in GST genes may influence detoxification of Pb by the enzymes they encode in Jamaican children with and without ASD.

Food Insecurity And Health-Related Concerns Among Elementary Schoolteachers During The Covid-19 Pandemic, Fangyu Li, Nivedhitha Parthasarathy, Feng Zhang, Ru-Jye Chuang, Mallika Mathur, Mike Pomeroy, Jacqueline Noyola, Christine M Markham, Shreela V Sharma

Faculty, Staff and Student Publications

INTRODUCTION: US school systems underwent major upheaval, including closures, implementation of virtual and/or hybrid learning, and stringent infection mitigation protocols, during the initial phase of the COVID-19 pandemic. We aimed to examine the association between food insecurity and perceived health, perceived stress, and social determinants of health concerns among elementary schoolteachers serving predominantly low-income children during the COVID-19 pandemic.

METHODS: Brighter Bites, a nonprofit organization that weekly distributes fresh fruits and vegetables and nutrition education materials to more than 300 schools serving racial and ethnic minority populations with low income, conducts annual surveys of participating teachers to help determine subsequent …

Resistant Maltodextrin Consumption In A Double-Blind, Randomized, Crossover Clinical Trial Induces Specific Changes In Potentially Beneficial Gut Bacteria, Volker Mai, Alyssa M Burns, Rebecca J Solch, Jennifer C Dennis-Wall, Maria Ukhanova, Bobbi Langkamp-Henken

Faculty, Staff and Student Publications

Background: We have previously reported that the addition of resistant maltodextrin (RMD), a fermentable functional fiber, to the diet increases fecal weight as well as the amount of fecal bifidobacteria. Here, we report on the targeted analysis of changes in potentially beneficial gut bacteria associated with the intervention. Objective: The primary objective of this study was to determine the effect of adding 0, 15 and 25 g RMD to the diets of healthy free-living adults on potentially beneficial gut bacteria. Methods: We expanded on our previously reported microbiota analysis in a double-blind, placebo-controlled feeding study (NCT02733263) by performing additional qPCR …

Association Study Between Mucin 4 (Muc4) Polymorphisms And Idiopathic Recurrent Pregnancy Loss In A Korean Population, Ji-Hyang Kim, Han-Sung Park, Jeong-Yong Lee, Eun-Ju Ko, Young-Ran Kim, Hee-Young Cho, Woo-Sik Lee, Eun-Hee Ahn, Nam-Keun Kim

Faculty, Staff and Student Publications

Recurrent pregnancy loss (RPL) is the loss of two or more consecutive pregnancies before 20 weeks of gestational age. Our study investigated whether mucin 4 (MUC4) polymorphisms are associated with RPL. MUC polymorphisms (rs882605 C>A, rs1104760 A>G, rs2688513 A>G, rs2258447 C>T, and rs2291652 A>G) were genotyped in 374 women with RPL and 239 controls of Korean ethnicity using polymerase chain reaction-restriction fragment length polymorphism analysis and the TaqMan probe SNP genotyping assay. Differences in genotype frequencies between cases of RPL and the controls were compared. MUC4 rs882605 C>A and rs1104760 A>G polymorphisms were …

A Nickase Cas9 Gene-Drive System Promotes Super-Mendelian Inheritance In Drosophila, Víctor López Del Amo, Sara Sanz Juste, Valentino M Gantz

Faculty, Staff and Student Publications

CRISPR-based gene-drives have been proposed for managing insect populations, including disease-transmitting mosquitoes, due to their ability to bias their inheritance toward super-Mendelian rates (>50%). Current technologies use a Cas9 that introduces DNA double-strand breaks into the opposing wild-type allele to replace it with a copy of the gene-drive allele via DNA homology-directed repair. However, the use of different Cas9 versions is unexplored, and alternative approaches could increase the available toolkit for gene-drive designs. Here, we report a gene-drive that relies on Cas9 nickases that generate staggered paired nicks in DNA to propagate the engineered gene-drive cassette. We show that …

2022 Beijing Winter Olympics: Spotlight On Cardiac Metabolism, Heinrich Taegtmeyer, Vlad G Zaha, Darren K Mcguire

Faculty, Staff and Student Publications

No abstract provided.

Electrographic Seizures In Neonates With A High Risk Of Encephalopathy, Wan-Hsuan Chen, Oi-Wa Chan, Jainn-Jim Lin, Ming-Chou Chiang, Shao-Hsuan Hsia, Huei-Shyong Wang, En-Pei Lee, Yi-Shan Wang, Cheng-Yen Kuo, Kuang-Lin Lin, On The Behalf Of The Icns Group

Faculty, Staff and Student Publications

Background: Neonatal encephalopathy is caused by a wide variety of acute brain insults in newborns and presents with a spectrum of neurologic dysfunction, such as consciousness disturbance, seizures, and coma. The increased excitability in the neonatal brain appears to be highly susceptible to seizures after a variety of insults, and seizures may be the first clinical sign of a serious neurologic disorder. Subtle seizures are common in the neonatal period, and abnormal clinical paroxysmal events may raise the suspicion of neonatal seizures. Continuous video electroencephalographic (EEG) monitoring is the gold standard for the diagnosis of neonatal seizures. The aim of …

Tissue-Specific Variations In Transcription Factors Elucidate Complex Immune System Regulation, Hengwei Lu, Yi-Ching Tang, Assaf Gottlieb

Faculty, Staff and Student Publications

Gene expression plays a key role in health and disease. Estimating the genetic components underlying gene expression can thus help understand disease etiology. Polygenic models termed "transcriptome imputation" are used to estimate the genetic component of gene expression, but these models typically consider only the cis regions of the gene. However, these cis-based models miss large variability in expression for multiple genes. Transcription factors (TFs) that regulate gene expression are natural candidates for looking for additional sources of the missing variability. We developed a hypothesis-driven approach to identify second-tier regulation by variability in TFs. Our approach tested two models …

Impaired Gate16-Mediated Exocytosis In Exocrine Tissues Causes Sjögren’S Syndrome-Like Exocrinopathy, Akiko Suzuki, Chihiro Iwaya, Kenichi Ogata, Hiroki Yoshioka, Junbo Shim, Isei Tanida, Masaaki Komatsu, Norihiro Tada, Junichi Iwata

Faculty, Staff and Student Publications

Sjögren's syndrome (SjS) is a chronic autoimmune disease characterized by immune cell infiltration of the exocrine glands, mainly the salivary and lacrimal glands. Despite recent advances in the clinical and mechanistic characterization of the disease, its etiology remains largely unknown. Here, we report that mice with a deficiency for either Atg7 or Atg3, which are enzymes involved in the ubiquitin modification pathway, in the salivary glands exhibit a SjS-like phenotype, characterized by immune cell infiltration with autoantibody detection, acinar cell death, and dry mouth. Prior to the onset of the SjS-like phenotype in these null mice, we detected an accumulation …

Definition Of Germ Layer Cell Lineage Alternative Splicing Programs Reveals A Critical Role For Quaking In Specifying Cardiac Cell Fate, W Samuel Fagg, Naiyou Liu, Ulrich Braunschweig, Karen Larissa Pereira De Castro, Xiaoting Chen, Frederick S Ditmars, Steven G Widen, John Paul Donohue, Katalin Modis, William K Russell, Jeffrey H Fair, Matthew T Weirauch, Benjamin J Blencowe, Mariano A Garcia-Blanco

Faculty, Staff and Student Publications

Alternative splicing is critical for development; however, its role in the specification of the three embryonic germ layers is poorly understood. By performing RNA-Seq on human embryonic stem cells (hESCs) and derived definitive endoderm, cardiac mesoderm, and ectoderm cell lineages, we detect distinct alternative splicing programs associated with each lineage. The most prominent splicing program differences are observed between definitive endoderm and cardiac mesoderm. Integrative multi-omics analyses link each program with lineage-enriched RNA binding protein regulators, and further suggest a widespread role for Quaking (QKI) in the specification of cardiac mesoderm. Remarkably, knockout of QKI disrupts the cardiac mesoderm-associated alternative …

Cardiovascular Disease Prevention Education Using A Virtual Environment In Sexual-Minority Men Of Color With Hiv: Protocol For A Sequential, Mixed Method, Waitlist Randomized Controlled Trial, S Raquel Ramos, Constance Johnson, Gail Melkus, Trace Kershaw, Marya Gwadz, Harmony Reynolds, Allison Vorderstrasse

Faculty, Staff and Student Publications

Background: It is estimated that 70% of all deaths each year in the United States are due to chronic conditions. Cardiovascular disease (CVD), a chronic condition, is the leading cause of death in ethnic and racial minority males. It has been identified as the second most common cause of death in persons with HIV. By the year 2030, it is estimated that 78% of persons with HIV will be diagnosed with CVD.

Objective: We propose the first technology-based virtual environment intervention to address behavioral, modifiable risk factors associated with cardiovascular and metabolic comorbidities in sexual-minority men of color with HIV. …

Micro-Computed Tomography Assessment Of Bone Structure In Aging Mice, Junbo Shim, Chihiro Iwaya, Catherine G Ambrose, Akiko Suzuki, Junichi Iwata

Faculty, Staff and Student Publications

High-resolution computed tomography (CT) is widely used to assess bone structure under physiological and pathological conditions. Although the analytic protocols and parameters for micro-CT (μCT) analyses in mice are standardized for long bones, vertebrae, and the palms in aging mice, they have not yet been established for craniofacial bones. In this study, we conducted a morphometric assessment of craniofacial bones, in comparison with long bones, in aging mice. Although age-related changes were observed in the microarchitecture of the femur, tibia, vertebra, and basisphenoid bone, and were more pronounced in females than in males, the microarchitecture of both the interparietal bone …

An Observational Retrospective Study Of Adverse Events And Behavioral Outcomes During Pediatric Dental Sedation, Kawtar Zouaidi, Gregory Olson, Helen H Lee, Elsbeth Kalenderian, Muhammad F Walji

Faculty, Staff and Student Publications

Purpose: The purpose of this study was to examine a university-based dental electronic health records (EHR) database to identify sedation-related adverse events (AEs) and assess patients' behavioral outcomes during routine pediatric dental sedations (PDSs) in a dental school clinic.

Methods: A database was screened for patients younger than 18 years old who had received dental sedation in 2019. The qualifying EHRs were then accessed and sedations were reviewed for AEs, which were categorized using a 12-point classification system and the Tracking and Reporting Outcomes of Procedural Sedation Tool. Patient behaviors were assessed using provider progress notes and categorized as presence/ …

An Evidence-Based Lexical Pattern Approach For Quality Assurance Of Gene Ontology Relations, Rashmie Abeysinghe, Yuntao Yang, Mason Bartels, W Jim Zheng, Licong Cui

Faculty, Staff and Student Publications

Gene Ontology (GO) is widely used in the biological domain. It is the most comprehensive ontology providing formal representation of gene functions (GO concepts) and relations between them. However, unintentional quality defects (e.g. missing or erroneous relations) in GO may exist due to the large size of GO concepts and complexity of GO structures. Such quality defects would impact the results of GO-based analyses and applications. In this work, we introduce a novel evidence-based lexical pattern approach for quality assurance of GO relations. We leverage two layers of evidence to suggest potentially missing relations in GO as follows. We first …

Relational Graph Convolutional Networks For Predicting Blood-Brain Barrier Penetration Of Drug Molecules, Yan Ding, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

MOTIVATION: Evaluating the blood-brain barrier (BBB) permeability of drug molecules is a critical step in brain drug development. Traditional methods for the evaluation require complicated in vitro or in vivo testing. Alternatively, in silico predictions based on machine learning have proved to be a cost-efficient way to complement the in vitro and in vivo methods. However, the performance of the established models has been limited by their incapability of dealing with the interactions between drugs and proteins, which play an important role in the mechanism behind the BBB penetrating behaviors. To address this limitation, we employed the relational graph convolutional …

Targeting A Chemo-Induced Adaptive Signaling Circuit Confers Therapeutic Vulnerabilities In Pancreatic Cancer, Xu Feng, Mengfan Tang, Merve Dede, Dan Su, Guangsheng Pei, Dadi Jiang, Chao Wang, Zhen Chen, Mi Li, Litong Nie, Yun Xiong, Siting Li, Jeong-Min Park, Huimin Zhang, Min Huang, Klaudia Szymonowicz, Zhongming Zhao, Traver Hart, Junjie Chen

Faculty, Staff and Student Publications

Exploiting cancer vulnerabilities is critical for the discovery of anticancer drugs. However, tumor suppressors cannot be directly targeted because of their loss of function. To uncover specific vulnerabilities for cells with deficiency in any given tumor suppressor(s), we performed genome-scale CRISPR loss-of-function screens using a panel of isogenic knockout cells we generated for 12 common tumor suppressors. Here, we provide a comprehensive and comparative dataset for genetic interactions between the whole-genome protein-coding genes and a panel of tumor suppressor genes, which allows us to uncover known and new high-confidence synthetic lethal interactions. Mining this dataset, we uncover essential paralog gene …

Factors Associated With Covid-19 Death In The United States: Cohort Study, Uan-I Chen, Hua Xu, Trudy Millard Krause, Raymond Greenberg, Xiao Dong, Xiaoqian Jiang

Faculty, Staff and Student Publications

BACKGROUND: Since the initial COVID-19 cases were identified in the United States in February 2020, the United States has experienced a high incidence of the disease. Understanding the risk factors for severe outcomes identifies the most vulnerable populations and helps in decision-making.

OBJECTIVE: This study aims to assess the factors associated with COVID-19-related deaths from a large, national, individual-level data set.

METHODS: A cohort study was conducted using data from the Optum de-identified COVID-19 electronic health record (EHR) data set; 1,271,033 adult participants were observed from February 1, 2020, to August 31, 2020, until their deaths due to COVID-19, deaths …

Factors Associated With Covid-19 Death In The United States: Cohort Study, Uan-I Chen, Hua Xu, Trudy Millard Krause, Raymond Greenberg, Xiao Dong, Xiaoqian Jiang

Faculty, Staff and Student Publications

Background: Since the initial COVID-19 cases were identified in the United States in February 2020, the United States has experienced a high incidence of the disease. Understanding the risk factors for severe outcomes identifies the most vulnerable populations and helps in decision-making.

Objective: This study aims to assess the factors associated with COVID-19-related deaths from a large, national, individual-level data set.

Methods: A cohort study was conducted using data from the Optum de-identified COVID-19 electronic health record (EHR) data set; 1,271,033 adult participants were observed from February 1, 2020, to August 31, 2020, until their deaths due to COVID-19, deaths …

Prioritization Of Risk Genes In Multiple Sclerosis By A Refined Bayesian Framework Followed By Tissue-Specificity And Cell Type Feature Assessment, Andi Liu, Astrid M Manuel, Yulin Dai, Zhongming Zhao

Faculty, Staff and Student Publications

BACKGROUND: Multiple sclerosis (MS) is a debilitating immune-mediated disease of the central nervous system that affects over 2 million people worldwide, resulting in a heavy burden to families and entire communities. Understanding the genetic basis underlying MS could help decipher the pathogenesis and shed light on MS treatment. We refined a recently developed Bayesian framework, Integrative Risk Gene Selector (iRIGS), to prioritize risk genes associated with MS by integrating the summary statistics from the largest GWAS to date (n = 115,803), various genomic features, and gene-gene closeness.

RESULTS: We identified 163 MS-associated prioritized risk genes (MS-PRGenes) through the Bayesian framework. …