Epidemiology Commons^™

Sarscov-2 Serostatus Amongst Vaccinated Employees At A Pediatric Hospital System, Sridevi Devaraj, Izmarie Poventud-Fuentes, Matthew Girotto, Jermaine Monroe, Julie Boom, George Delclos, James Versalovic

Faculty, Staff and Students Publications

To gain insights on the heterogeneity of immune responses to vaccination against SARS-CoV-2 and to identify factors that could make individuals vulnerable to infection due to lack of response to vaccination, our hospital started offering free voluntary post-antibody testing against the spike protein IgG for all fully vaccinated employees.

Post-vaccination response against SARS-CoV-2 was assessed using the FDA-EUA approved VITROS anti-SARS-CoV-2 IgG immunometric assay specific to the spike protein.

Out of a total of 3266 antibody tests performed in fully vaccinated Texas Children’s, 99.4% had a positive antibody response to the spike protein. From the 21 employees (0.6%) that had …

Identification Of Lung Cancer Drivers By Comparison Of The Observed And The Expected Numbers Of Missense And Nonsense Mutations In Individual Human Genes, Olga Y Gorlova, Marek Kimmel, Spiridon Tsavachidis, Christopher I Amos, Ivan P Gorlov

Faculty, Staff and Students Publications

Largely, cancer development is driven by acquisition and positive selection of somatic mutations that increase proliferation and survival of tumor cells. As a result, genes related to cancer development tend to have an excess of somatic mutations in them. An excess of missense and/or nonsense mutations in a gene is an indicator of its cancer relevance. To identify genes with an excess of potentially functional missense or nonsense mutations one needs to compare the observed and expected numbers of mutations in the gene. We estimated the expected numbers of missense and nonsense mutations in individual human genes using (i) the …

Germline Polymorphisms In Mgmt Associated With Temozolomide-Related Myelotoxicity Risk In Patients With Glioblastoma Treated On Nrg Oncology/Rtog 0825, Michael E Scheurer, Renke Zhou, Mark R Gilbert, Melissa L Bondy, Erik P Sulman, Ying Yuan, Yanhong Liu, Elizabeth Vera, Merideth M Wendland, Emad F Youssef, Volker W Stieber, Ritsuko R Komaki, John C Flickinger, Lawrence C Kenyon, H Ian Robins, Grant K Hunter, Ian R Crocker, Samuel T Chao, Stephanie L Pugh, Terri S Armstrong

Faculty, Staff and Students Publications

BACKGROUND: We sought to identify clinical and genetic predictors of temozolomide-related myelotoxicity among patients receiving therapy for glioblastoma.

METHODS:Patients (n = 591) receiving therapy on NRG Oncology/RTOG 0825 were included in the analysis. Cases were patients with severe myelotoxicity (grade 3 and higher leukopenia, neutropenia, and/or thrombocytopenia); controls were patients without such toxicity. A risk-prediction model was built and cross-validated by logistic regression using only clinical variables and extended using polymorphisms associated with myelotoxicity.

RESULTS: 23% of patients developed myelotoxicity (n = 134). This toxicity was first reported during the concurrent phase of therapy for 56 patients; 30 …

Analysis Of Recurrent Urinary Tract Infection Management In Women Seen In Outpatient Settings Reveals Opportunities For Antibiotic Stewardship Interventions, Marissa A Valentine-King, Barbara W Trautner, Roger J Zoorob, George Germanos, Michael Hansen, Jason L Salemi, Kalpana Gupta, Larissa Grigoryan

Faculty, Staff and Students Publications

OBJECTIVES: We characterized antibiotic prescribing patterns and management practices among recurrent urinary tract infection (rUTI) patients, and we identified factors associated with lack of guideline adherence to antibiotic choice, duration of treatment, and urine cultures obtained. We hypothesized that prior resistance to nitrofurantoin or trimethoprim-sulfamethoxazole (TMP-SMX), shorter intervals between rUTIs, and more frequent rUTIs would be associated with fluoroquinolone or β-lactam prescribing, or longer duration of therapy.

METHODS: This study was a retrospective database study of adult women with

RESULTS: Among 214 patients with 566 visits, 61.5% of prescriptions comprised first-line agents of nitrofurantoin (39.7%) and TMP-SMX (21.5%), followed by …

Exercise-Induced Myokines Downregulates The Ace2 Level In Bronchial Epithelial Cells: Implications For Sars-Cov-2 Prevention, Vaishali Bhardwaj, Mart Dela Cruz, Deepika Subramanyam, Rohit Kumar, Sandeep Markan, Beth Parker, Hemant K Roy

Faculty, Staff and Students Publications

BACKGROUND: The Covid-19 pandemic has emerged as the leading public health challenge of our time (20th century). While vaccinations have finally blunted the death rate, concern has remained about more virulent forms highlighting the need for alternative approaches. Epidemiological studies indicate that physical activity has been shown to decrease the risk of infection of some respiratory viruses. Part of the salutary effects of exercise is believed to be through the elaboration of cytokines by contracting skeletal muscles (termed myokines). The objective of this study was to investigate whether exercise-induced myokines would mitigate the SARS-CoV-2 infectivity of the bronchial epithelium through …

A Survey On Self-Medication For The Prevention Or Treatment Of Covid-19 And Distrust In Healthcare Of Veterans In A Primary Care Setting In The United States, Eva Amenta, Larissa Grigoryan, Laura Dillon, Casey Hines-Munson, John Van, Barbara Trautner

Faculty, Staff and Students Publications

BACKGROUND: The SARS-CoV-2 (COVID-19) pandemic brought the public overwhelming and conflicting information. Rates of trust in healthcare professionals have been declining among laypersons over the past five decades. In this setting, we sought to evaluate the use of medications, both with or without a prescription, to prevent and treat SARS-CoV-2 as well as trust in healthcare among patients in a primary care clinic.

DESIGN: We surveyed 150 veterans in primary care clinic waiting rooms at a large southwestern tertiary care Veterans Affairs hospital. This survey was performed in March-November 2021.

METHODS: The survey asked about respondents' demographics, use of medications, …

Variations In Medical Students' Educational Preferences, Attitudes And Volunteerism During The Covid-19 Global Pandemic, Nital P Appelbaum, Sanghamitra M Misra, Jennifer Welch, M Harrison Humphries, Sunthosh Sivam, Nadia Ismail

Faculty, Staff and Students Publications

Public health crises require individuals, often volunteers, to help minimize disasters. The COVID-19 pandemic required such activation of individuals, but little is known about medical students’ preferences of such engagement. We investigated potential variations in medical students’ educational preferences, attitudes, and volunteerism during the COVID-19 pandemic based on socio-demographics to better prepare for future activation scenarios. A web-based, anonymous survey of U.S. medical students at a single institution was conducted in May 2020. Across four training year, 518 (68% response rate) students completed the survey. During the pandemic, 42.3% (n = 215) wanted to discontinue in-person clinical experiences, 32.3% (n …

A Community-Based Management Of Covid-19 In A Mobile Container Unit, Elena Petrova, Timothy Farinholt, Tejas P Joshi, Hannah Moreno, Mayar Al Mohajer, Shital M Patel, Joseph Petrosino, Sharmila Anandasabapathy

Faculty, Staff and Students Publications

Vaccine uptake is a multifactor measure of successful immunization outcomes that includes access to healthcare and vaccine hesitancy for both healthcare workers and communities. The present coronavirus disease (COVID-19) pandemic has highlighted the need for novel strategies to expand vaccine coverage in underserved regions. Mobile clinics hold the promise of ameliorating such inequities, although there is a paucity of studies that validate environmental infection in such facilities. Here, we describe community-based management of COVID-19 through a Smart Pod mobile clinic deployed in an underserved community area in the United States (Aldine, Harris County, TX, USA). In particular, we validate infection …

Posttranslational Modifications In Pd-L1 Turnover And Function: From Cradle To Grave, Xinfang Yu, Wei Li, Ken H Young, Yong Li

Faculty, Staff and Students Publications

Programmed death-ligand 1 (PD-L1) is one of the most classic immune checkpoint molecules. Cancer cells express PD-L1 to inhibit the activity of effector T cells' cytotoxicity through programmed death 1 (PD-1) engagement in exposure to inflammatory cytokines. PD-L1 expression levels on cancer cells might affect the clinical response to anti-PD-1/PD-L1 therapies. Hence, understanding molecular mechanisms for regulating PD-L1 expression is essential for improving the clinical response rate and efficacy of PD-1/PD-L1 blockade. Posttranslational modifications (PTMs), including phosphorylation, glycosylation, ubiquitination, and acetylation, regulate PD-L1 stability, cellular translocation, and interaction with its receptor. A coordinated positive and negative regulation via PTMs is …

Efficacy Of The Mrna-1273 Sars-Cov-2 Vaccine At Completion Of Blinded Phase, Hana M El Sahly, Lindsey R Baden, Brandon Essink, Susanne Doblecki-Lewis, Judith M Martin, Evan J Anderson, Thomas B Campbell, Jesse Clark, Lisa A Jackson, Carl J Fichtenbaum, Marcus Zervos, Bruce Rankin, Frank Eder, Gregory Feldman, Christina Kennelly, Laurie Han-Conrad, Michael Levin, Kathleen M Neuzil, Lawrence Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, Laura Polakowski, John R Mascola, Julie E Ledgerwood, Barney S Graham, Allison August, Heather Clouting, Weiping Deng, Shu Han, Brett Leav, Deb Manzo, Rolando Pajon, Florian Schödel, Joanne E Tomassini, Honghong Zhou, Jacqueline Miller

Faculty, Staff and Students Publications

BACKGROUND: At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported.

METHODS: We enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo, 28 days apart, at 99 centers across the United States. …

Prevention And Screening Of Hpv Malignancies, Kristina R Dahlstrom, Andrew T Day, Erich M Sturgis

Faculty, Staff and Students Publications

It is estimated that 5% of the global cancer burden, or approximately 690,000 cancer cases annually, is attributable to human papillomavirus (HPV). Primary prevention through prophylactic vaccination is the best option for reducing the burden of HPV-related cancers. Most high-income countries (HICs) have introduced the HPV vaccine and are routinely vaccinating adolescent boys and girls. Unfortunately, although they suffer the greatest morbidity and mortality due to HPV-related cancers, many lower- and middle-income countries (LMICs) have been unable to initiate and sustain vaccination programs. Secondary prevention in the form of screening has led to substantial declines in cervical cancer incidence in …

Perspectives From The Society For Pediatric Research: Advice On Sustaining Science And Mentoring During Covid-19, Catherine S Forster, Suong T Nguyen, Weston T Powell, Daniel J Moore, Jacqueline Ho, Melvin B Heyman, Tara L Wenger, Fernando Gonzalez, Margaret Hostetter, Andrew Nowalk, Caroline E Rassbach, Debra Boyer, Pnina Weiss, Rebecca L Blankenburg, Jordan S Orange, Kate G Ackerman, Audrea M Burns, National Pediatric Physician-Scientist Collaborative Workgroup

Faculty, Staff and Students Publications

The COVID-19 pandemic will leave an indelible mark on the careers of current medical trainees. Given the disruptions to medical education, economic impact on institutions, and the uncertainties around future job prospects, trainees are facing unprecedented challenges. This situation is especially concerning for futures of pediatric physician-scientist trainees, where concerns regarding maintaining the pipeline were well documented prior to the emergence of COVID-19. In this Perspectives article, we leverage the unique expertise of our workgroup to address concerns of physician-scientist trainees and to provide suggestions on how to navigate career trajectories in the post-COVID-19 era. We identified and addressed four …

Ankyrin-Dependent Na+ Channel Clustering Prevents Neuromuscular Synapse Fatigue, Chuansheng Zhang, Abhijeet Joshi, Yanhong Liu, Ozlem Sert, Seth G Haddix, Lindsay H Teliska, Anne Rasband, George G Rodney, Matthew N Rasband

Faculty, Staff and Students Publications

Skeletal muscle contraction depends on activation of clustered acetylcholine receptors (AchRs) and muscle-specific Na+ channels (Nav1.4). Some Nav1.4 channels are highly enriched at the neuromuscular junction (NMJ) and their clustering is thought to be essential for effective muscle excitation. However, this has not been experimentally tested, and how NMJ Na+ channels are clustered is unknown. Here, using muscle-specific AnkyrinR, AnkyrinB, and AnkyrinG single, double, and triple-conditional knockout mice we show that Nav1.4 channels fail to cluster only after deletion of all three ankyrins. Remarkably, ankyrin-deficient muscles have normal NMJ morphology, AchR clustering, sarcolemmal levels of Nav1.4, and muscle force, and …

Dna-Encoded Chemistry Technology Yields Expedient Access To Sars-Cov-2m Pro Inhibitors, Srinivas Chamakuri, Shuo Lu, Melek Nihan Ucisik, Kurt M Bohren, Ying-Chu Chen, Huang-Chi Du, John C Faver, Ravikumar Jimmidi, Feng Li, Jian-Yuan Li, Pranavanand Nyshadham, Stephen S Palmer, Jeroen Pollet, Xuan Qin, Shannon E Ronca, Banumathi Sankaran, Kiran L Sharma, Zhi Tan, Leroy Versteeg, Zhifeng Yu, Martin M Matzuk, Timothy Palzkill, Damian W Young

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration–approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (Mpro) without extensive and time-consuming medicinal chemistry. CDD-1714, the initial three-building-block screening hit (molecular weight [MW] = 542.5 g/mol), was a potent inhibitor (inhibition …

Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants In The Chrebp (Carbohydrate Responsive Element Binding Protein) Locus And Hdl-C (High-Density Lipoprotein Cholesterol) And Triglyceride Concentrations, Danielle E Haslam, Gina M Peloso, Melanie Guirette, Fumiaki Imamura, Traci M Bartz, Achilleas N Pitsillides, Carol A Wang, Ruifang Li-Gao, Jason M Westra, Niina Pitkänen, Kristin L Young, Mariaelisa Graff, Alexis C Wood, Kim V E Braun, Jian'an Luan, Mika Kähönen, Jessica C Kiefte-De Jong, Mohsen Ghanbari, Nathan Tintle, Rozenn N Lemaitre, Dennis O Mook-Kanamori, Kari North, Mika Helminen, Yasmin Mossavar-Rahmani, Linda Snetselaar, Lisa W Martin, Jorma S Viikari, Wendy H Oddy, Craig E Pennell, Frits R Rosendall, M Arfan Ikram, Andre G Uitterlinden, Bruce M Psaty, Dariush Mozaffarian, Jerome I Rotter, Kent D Taylor, Terho Lehtimäki, Olli T Raitakari, Kara A Livingston, Trudy Voortman, Nita G Forouhi, Nick J Wareham, Renée De Mutsert, Steven S Rich, Joann E Manson, Samia Mora, Paul M Ridker, Jordi Merino, James B Meigs, Hassan S Dashti, Daniel I Chasman, Alice H Lichtenstein, Caren E Smith, Josée Dupuis, Mark A Herman, Nicola M Mckeown

Faculty, Staff and Students Publications

BACKGROUND: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the

METHODS: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near

RESULTS: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers …

Reducing Covid-19 Quarantine With Sars-Cov-2 Testing: A Simulation Study, Bo Peng, Wen Zhou, Rowland W Pettit, Patrick Yu, Peter G Matos, Alexander L Greninger, Julie Mccashin, Christopher I Amos

Faculty, Staff and Students Publications

OBJECTIVE: To evaluate the effectiveness of SARS-CoV-2 testing on shortening the duration of quarantines for COVID-19 and to identify the most effective choices of testing schedules.

DESIGN: We performed extensive simulations to evaluate the performance of quarantine strategies when one or more SARS-CoV-2 tests were administered during the quarantine. Simulations were based on statistical models for the transmissibility and viral loads of SARS-CoV-2 infections and the sensitivities of available testing methods. Sensitivity analyses were performed to evaluate the impact of perturbations in model assumptions on the outcomes of optimal strategies.

RESULTS: We found that SARS-CoV-2 testing can effectively reduce the …

The Detrimental Association Between Fear Of Falling And Motor Performance In Older Cancer Patients With Chemotherapy-Induced Peripheral Neuropathy, Gu Eon Kang, Tamiko K Murphy, Mark E Kunik, Hoda J Badr, Biruh T Workeneh, Sarvari V Yellapragada, Yvonne H Sada, Bijan Najafi

Faculty, Staff and Students Publications

BACKGROUND: Cancer patients with chemotherapy-induced peripheral neuropathy (CIPN) are at increased risk of falls and developing fear of falling (FoF). Although FoF may continue to impair motor performance and increase the risk of falling even further, this association remains unexplored in CIPN.

RESEARCH QUESTION: Does high FoF in patients with CIPN further deteriorate motor performance beyond the impairment from CIPN-related sensory deficits?

METHODS: In this secondary analysis of data collected from two clinical trials, gait parameters during habitual walking condition and postural sway parameters during 30-second quiet standing (eye-open and eyes-closed) were compared among older participants (≥ 65 years) with …

Population Simulations Of Covid-19 Outbreaks Provide Tools For Risk Assessment And Continuity Planning, Bo Peng, Rowland W Pettit, Christopher I Amos

Faculty, Staff and Students Publications

OBJECTIVES: We developed COVID-19 Outbreak Simulator (https://ictr.github.io/covid19-outbreak-simulator/) to quantitatively estimate the effectiveness of preventative and interventive measures to prevent and battle COVID-19 outbreaks for specific populations.

MATERIALS AND METHODS: Our simulator simulates the entire course of infection and transmission of the virus among individuals in heterogeneous populations, subject to operations and influences, such as quarantine, testing, social distancing, and community infection. It provides command-line and Jupyter notebook interfaces and a plugin system for user-defined operations.

RESULTS: The simulator provides quantitative estimates for COVID-19 outbreaks in a variety of scenarios and assists the development of public health policies, risk-reduction operations, and …

What The Pandemic Experience Taught Us About Stem Higher Education-School Partnerships, Nancy P Moreno, Dolores V Garay, Katherine A Harris, Alana D Newell, Beatriz Perez-Sweeney, Elizabeth Camacho-Lopez, Bernice A Shargey

Faculty, Staff and Students Publications

The move to virtual schooling and other measures to reduce the spread of SARS-CoV-2 infection dramatically changed the educational experience for grades K-12 populations during the years 2020 and 2021. STEM teaching and learning, and community partnerships focused on STEM education, were not exempt from the changes. Universities and other community partners had to adapt their STEM partnership programming to address new needs and assist students, teachers, families, and schools throughout periods of at-home learning and the re-reintroduction of in-person classes. Some of the changes included developing new programs, providing health-related guidance to school leaders, and converting student-focused programs to …

Microbial Science Research In The Post-Covid Environment, Nguyen K Nguyen, Carey-Ann D Burnham, Arturo Casadevall, Mary K Estes, Rebecca V Ferrell, Suzanne M J Fleiszig, Speakers, Moderators, And Panelists Of The Asm Virtual Symposium: Microbial Science Research In The Post-Covid Environment

Faculty, Staff and Students Publications

Since early 2020, the world has witnessed the unprecedented accomplishments of the scientific community in the fight against the coronavirus disease 2019 (COVID-19) pandemic. In the meantime, we also learned valuable lessons and recognized the challenges that hindered our successes. In this article, we synthesize the ideas discussed at the ASM Virtual Symposium: Microbial Science Research in the Post-COVID Environment on 10 November 2020. We propose three new approaches that microbiology researchers can embrace to overcome these challenges. Moreover, we suggest broad systematic changes to focus on social impacts, teamwork, and diversity, equity, and inclusion. We believe these values are …

Genetic Variation And Recurrent Haplotypes On Chromosome 6q23-25 Risk Locus In Familial Lung Cancer, Anthony M Musolf, Claire L Simpson, Bilal A Moiz, Claudio W Pikielny, Candace D Middlebrooks, Diptasri Mandal, Mariza De Andrade, Michael D Cole, Colette Gaba, Ping Yang, Ming You, Yafang Li, Elena Y Kupert, Marshall W Anderson, Ann G Schwartz, Susan M Pinney, Christopher I Amos, Joan E Bailey-Wilson

Faculty, Staff and Students Publications

Although lung cancer is known to be caused by environmental factors, it has also been shown to have genetic components, and the genetic etiology of lung cancer remains understudied. We previously identified a lung cancer risk locus on 6q23-25 using microsatellite data in families with a history of lung cancer. To further elucidate that signal, we performed targeted sequencing on nine of our most strongly linked families. Two-point linkage analysis of the sequencing data revealed that the signal was heterogeneous and that different families likely had different risk variants. Three specific haplotypes were shared by some of the families: 6q25.3-26 …

Evidence-Based Approach To Early Outpatient Treatment Of Sars-Cov-2 (Covid-19) Infection, J Drew Payne, Kimberly Sims, Cynthia Peacock, Tanis Welch, Ruth E Berggren

Faculty, Staff and Students Publications

Misinformation and promotion of well-intended but disproved therapies for COVID-19 have plagued evidence-based shared decision-making throughout the COVID-19 pandemic. In times of crisis, clinicians may feel that their strong inclination to prescribe potentially harmful, unproven therapies on behalf of their patients is supported by beneficence. Clinicians should mindfully identify and avoid commission bias during this pandemic, especially as more data have accumulated to assist with clinically sound decision-making. We describe a more evidence-based approach to treatment of early outpatient COVID-19, stressing the availability of Food and Drug Administration emergency use authorization therapies and considering plausibly beneficial, nonprescription supplements that are …

Invasive Therapies For Acute Coronary Syndromes In The Covid-19 Era, Sanket Borgaonkar, Joshua Hahn, Marilyne Daher, Waleed Kayani, Hani Jneid

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: To identify and address the challenges associated with the care of ACS patients during the coronavirus 2019 pandemic.

RECENT FINDINGS: The COVID-19 pandemic has had a considerable global impact with over 2.0 million deaths worldwide so far. There has been considerable evidence suggesting that COVID-19 increases the risk of acute coronary syndromes (ACS). We propose characterizing ACS patients into 3 distinct categories to better assist in appropriate triage and management: critically ill patients, non-critically ill ST elevation myocardial infarction (STEMI) patients, and non-critically ill non-ST elevation myocardial infarction (NSTEMI)/unstable angina (UA) patients. We thoroughly review treatments strategies, …

Coronavirus Disease-19 And Cardiovascular Disease: A Risk Factor Or A Risk Marker?, Jing Liu, Salim S Virani, Mahboob Alam, Ali E Denktas, Ihab Hamzeh, Umair Khalid

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to …

Coronavirus Disease-19 And Cardiovascular Disease: A Risk Factor Or A Risk Marker?, Jing Liu, Salim S Virani, Mahboob Alam, Ali E Denktas, Ihab Hamzeh, Umair Khalid

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to …

Tocilizumab In Hospitalized Patients With Severe Covid-19 Pneumonia, Ivan O Rosas, Norbert Bräu, Michael Waters, Ronaldo C Go, Bradley D Hunter, Sanjay Bhagani, Daniel Skiest, Mariam S Aziz, Nichola Cooper, Ivor S Douglas, Sinisa Savic, Taryn Youngstein, Lorenzo Del Sorbo, Antonio Cubillo Gracian, David J De La Zerda, Andrew Ustianowski, Min Bao, Sophie Dimonaco, Emily Graham, Balpreet Matharu, Helen Spotswood, Larry Tsai, Atul Malhotra

Faculty, Staff and Students Publications

BACKGROUND: Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.

METHODS: In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants …

Conditional Survival Among Patients With Oropharyngeal Cancer Treated With Radiation Therapy And Alive Without Recurrence 5 Years After Diagnosis, Kristina R Dahlstrom, Juhee Song, Peter F Thall, Clifton D Fuller, Katherine A Hutcheson, Faye M Johnson, G Brandon Gunn, Jack Phan, Steven J Frank, William H Morrison, Renata Ferrarotto, David I Rosenthal, Erich M Sturgis, Adam S Garden

Faculty, Staff and Students Publications

BACKGROUND: Risk of recurrence among patients with oropharyngeal cancer (OPC) who survive 5 years is low. The goal of this study was to assess long-term survival of patients with OPC alive without recurrence 5 years after diagnosis.

METHODS: This study included newly diagnosed patients with OPC, who had been treated with radiation and were alive without recurrence 5 years after diagnosis. Overall survival (OS) probabilities beyond 5 years were estimated using the Kaplan-Meier method. Factors associated with OS were determined using Bayesian piecewise exponential survival regression. Standardized mortality ratios for all-cause death were estimated controlling for study year, age, and …

The Impact Of Covid-19 On Kidney Transplantation And The Kidney Transplant Recipient – One Year Into The Pandemic, Pascale Khairallah, Nidhi Aggarwal, Ahmed A Awan, Chandan Vangala, Medha Airy, Jenny S Pan, Bhamidipati V R Murthy, Wolfgang C Winkelmayer, Venkat Ramanathan

Faculty, Staff and Students Publications

The COVID‐19 pandemic has significantly changed the landscape of kidney transplantation in the United States and worldwide. In addition to adversely impacting allograft and patient survival in postkidney transplant recipients, the current pandemic has affected all aspects of transplant care, including transplant referrals and listing, organ donation rates, organ procurement and shipping, and waitlist mortality. Critical decisions were made during this period by transplant centers and individual transplant physicians taking into consideration patient safety and resource utilization. As countries have begun administering the COVID vaccines, new and important considerations pertinent to our transplant population have arisen. This comprehensive review focuses …

Myd88 L265p Elicits Mutation-Specific Ubiquitination To Drive Nf-Κb Activation And Lymphomagenesis, Xinfang Yu, Wei Li, Qipan Deng, Haidan Liu, Xu Wang, Hui Hu, Ya Cao, Zijun Y Xu-Monette, Ling Li, Mingzhi Zhang, Zhongxin Lu, Ken H Young, Yong Li

Faculty, Staff and Students Publications

Myeloid differentiation primary response protein 88 (MYD88) is a critical universal adapter that transduces signaling from Toll-like and interleukin receptors to downstream nuclear factor-κB (NF-κB). MYD88L265P (leucine changed to proline at position 265) is a gain-of-function mutation that occurs frequently in B-cell malignancies such as Waldenstrom macroglobulinemia. In this study, E3 ligase RING finger protein family 138 (RNF138) catalyzed K63-linked nonproteolytic polyubiquitination of MYD88L265P, resulting in enhanced recruitment of interleukin-1 receptor-associated kinases and elevated NF-κB activation. However, RNF138 had little effect on wild-type MYD88 (MYD88WT). With either RNF138 knockdown or mutation on MYD88 ubiquitination sites, MYD88L265P did not constitutively activate …

On The Application, Reporting, And Sharing Of In Silico Simulations For Genetic Studies, Kaleigh Riggs, Huann-Sheng Chen, Melissa Rotunno, Bing Li, Naoko I Simonds, Leah E Mechanic, Bo Peng

Faculty, Staff and Students Publications

In silico simulations play an indispensable role in the development and application of statistical models and methods for genetic studies. Simulation tools allow for the evaluation of methods and investigation of models in a controlled manner. With the growing popularity of evolutionary models and simulation-based statistical methods, genetic simulations have been applied to a wide variety of research disciplines such as population genetics, evolutionary genetics, genetic epidemiology, ecology, and conservation biology. In this review, we surveyed 1409 articles from five journals that publish on major application areas of genetic simulations. We identified 432 papers in which genetic simulations were used …