Epidemiology Commons^™

Is Covid-19-Induced Platelet Activation A Cause Of Concern For Patients With Cancer?, Lenard M Lichtenberger, K Vinod Vijayan

Faculty, Staff and Students Publications

Patients with cancer are more susceptible to be infected by SARS-CoV-2 and develop severe outcomes including ICU admittance, mechanical ventilator support, and a high rate of mortality. Like mid-to late-stage cancer, SARS-CoV-2 infection is associated with platelet hyperactivity, systemic inflammation, thrombotic complications, and coagulopathy. Platelets also promote cancer cell growth, survival in circulation, and angiogenesis at sites of metastases. In this article, we will discuss the potential for platelets in the development of systemic inflammation and thrombosis in SARS-CoV-2-infected patients with cancer, with the concern that the platelet-induced pathogenic events are likely magnified in cancer patients with COVID-19.

Sars-Cov-2 Early Infection Signature Identified Potential Key Infection Mechanisms And Drug Targets, Yue Li, Ashley Duche, Michael R. Sayer, Don Roosan, Farid G. Khalafalla, Rennolds S. Ostrom, Jennifer Totonchy, Moom Roosan

Pharmacy Faculty Articles and Research

Background

The ongoing COVID-19 outbreak has caused devastating mortality and posed a significant threat to public health worldwide. Despite the severity of this illness and 2.3 million worldwide deaths, the disease mechanism is mostly unknown. Previous studies that characterized differential gene expression due to SARS-CoV-2 infection lacked robust validation. Although vaccines are now available, effective treatment options are still out of reach.

Results

To characterize the transcriptional activity of SARS-CoV-2 infection, a gene signature consisting of 25 genes was generated using a publicly available RNA-Sequencing (RNA-Seq) dataset of cultured cells infected with SARS-CoV-2. The signature estimated infection level accurately in …

Aberrant Azin2 And Polyamine Metabolism Precipitates Tau Neuropathology, Leslie A. Sandusky-Beltran, Andrii Kovalenko, Devon S. Placides, Kevin Ratnasamy, Chao Ma, Jerry B. Hunt, Huimin Liang, John Ivan T. Calahatian, Camilla Michalski, Margaret Fahnestock, Laura J. Blair, April L. Darling, Jeremy D. Baker, Sarah N. Fontaine, Chad A. Dickey, Joshua J. Gamsby, Kevin R. Nash, Erin L. Abner, Maj-Linda B. Selenica, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Tauopathies display a spectrum of phenotypes from cognitive to affective behavioral impairments; however, mechanisms promoting tau pathology and how tau elicits behavioral impairment remain unclear. We report a unique interaction between polyamine metabolism, behavioral impairment, and tau fate. Polyamines are ubiquitous aliphatic molecules that support neuronal function, axonal integrity, and cognitive processing. Transient increases in polyamine metabolism hallmark the cell’s response to various insults, known as the polyamine stress response (PSR). Dysregulation of gene transcripts associated with polyamine metabolism in Alzheimer’s disease (AD) brains were observed, and we found that ornithine decarboxylase antizyme inhibitor 2 (AZIN2) increased to …

Sex, Diabetes Status And Cognition: Findings From The Study Of Longevity In Diabetes, Chris Moran, Paola Gilsanz, Michal S. Beeri, Rachel A. Whitmer, Mary E. Lacy

Epidemiology and Environmental Health Faculty Publications

INTRODUCTION: Women comprise two-thirds of people with dementia, making female sex a significant dementia risk factor. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are known dementia risk factors with an increasing global incidence. Understanding whether subtle sex differences persist in cognitive function prior to dementia in the context of diabetes may help elucidate the magnitude of sex effects on dementia risk.

RESEARCH DESIGN AND METHODS: We examined cross-sectional data from the Study of Longevity in Diabetes (SOLID), a prospective cohort study of members of Kaiser Permanente Northern California aged 60 years and older with T1D (n=758), T2D …

The Association Of Circulating Amylin With Β-Amyloid In Familial Alzheimer's Disease, Han Gia Ly, Nirmal Verma, Savita Sharma, Deepak Kotiya, Sanda Despa, Erin L. Abner, Peter T. Nelson, Gregory A. Jicha, Donna M. Wilcock, Larry B. Goldstein, Rita Guerreiro, José Brás, Angela J. Hanson, Suzanne Craft, Andrew J. Murray, Geert Jan Biessels, Claire Troakes, Henrik Zetterberg, John Hardy, Tammaryn Lashley, Alzheimer’S Disease Exome Sequencing Group, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Introduction

This study assessed the hypothesis that circulating human amylin (amyloid‐forming) cross‐seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD).

Methods

Evidence of amylin‐AD pathology interaction was tested in brains of 31 familial AD mutation carriers and 20 cognitively unaffected individuals, in cerebrospinal fluid (CSF) (98 diseased and 117 control samples) and in genetic databases. For functional testing, we genetically manipulated amylin secretion in APP/PS1 and non‐APP/PS1 rats.

Results

Amylin‐Aβ cross‐seeding was identified in AD brains. High CSF amylin levels were associated with decreased CSF Aβ42 concentrations. AD risk and amylin gene are not correlated. Suppressed amylin secretion protected …

Implementación De Políticas De Prevención Y Control De La Obesidad Infantil En Estados Unidos Y Latinoamérica: Lecciones Para La Investigación Y La Práctica Transfronterizas, Mireya Vilar-Compte, Rafael Perez-Escamilla, Elizabeth Rhodes, Olga L. Sarmiento, Camila Corvalan, Rachel Sturke, Susan Vorkoper

Department of Public Health Scholarship and Creative Works

Aunque se han hecho avances en el desarrollo y aplicación a gran escala de inter-venciones eficaces contra la obesidad infantil, los retos siguen siendo importantes. Nuestro objetivo era comprender las causas del éxito de Estados Unidos y los países latinoamericanos en la implementación de políticas y programas (PYP) contra la obe-sidad e identificar oportunidades de mejora aplicando los principios de la ciencia de la implementación. Seleccionamos tres estudios de comparación de casos: (1) el etique-tado frontal en los envases de alimentos (México y Chile), (2) los programas de calles abiertas y calles para el juego (Colombia y Estados Unidos) y …

Multiple Proteinopathies And Their Role In Cognitive Impairment And Neurodegenerative Diseases, Shama D. Karanth

Theses and Dissertations--Epidemiology and Biostatistics

Most age-related neurodegenerative disorders are associated with the aggregation of misfolded and aberrant proteins. Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders and is highly prevalent in older adults. Neuropathologically, AD is characterized by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). Other misfolded proteins, including α-synuclein and transactive response DNA-binding protein 43 (TDP-43), are also commonly observed in aged brains. Aberrant α-synuclein has been associated with Parkinson's disease, Dementia with Lewy bodies, and multiple system atrophy, whereas TDP-43 has been associated with multiple neurological diseases, the most common of which was designated as limbic-predominant, …

Characteristics And Outcomes Of In-Hospital Cardiac Arrest In Covid-19 A Systematic Review And Meta-Analysis, Lukasz Szarpak, Magdalena Borkowska, Frank W Peacock, Zubaid Rafique, Aleksandra Gasecka, Jacek Smereka, Katarzyna Pytkowska, Marta Jachowicz, Lukasz Iskrzycki, Natasza Gilis-Malinowska, Milosz J Jaguszewski

Faculty, Staff and Students Publications

BACKGROUND: The purpose herein, was to perform a systematic review of interventional outcome studies in patients with in-hospital cardiac arrest before and during the coronavirus disease 2019 (COVID-19) pandemic period.

METHODS: A meta-analysis was performed of publications meeting the following PICOS criteria: (1) participants, patients > 18 years of age with cardiac arrest due to any causes; (2) intervention, cardiac arrest in COVID-19 period; (3) comparison, cardiac arrest in pre-COVID-19 period; (4) outcomes, detailed information for survival; (5) study design, randomized controlled trials, quasi-randomized or observational studies comparing cardiac arrest in COVID-19 and pre-COVID-19 period for their effects in patients with …

Thyroid Storm In A Patient With Covid-19, Angela N Rao, Ruaa Y Al-Ward, Ruchi Gaba

Faculty, Staff and Students Publications

OBJECTIVE: A thyroid storm is a severe exacerbation of thyrotoxicosis that can cause significant morbidity and mortality. The emergence of the novel coronavirus (SARS-CoV-2) that originated in Wuhan, China, has become a worldwide pandemic. We present the first documented case of thyroid storm (as defined by the Burch-Wartofsky criteria) in a patient with COVID-19.

METHODS: Laboratory and diagnostic studies, including thyroid function tests, thyroid antibody testing, SARS-CoV-2 nasopharyngeal polymerase chain reaction testing, and thyroid ultrasound were performed.

RESULTS: A 25-year-old woman presented to the hospital with dry cough, dyspnea, palpitations, weight loss, diarrhea, and anxiety. Physical examination revealed exophthalmos with …

Large-Scale Characterization Of Drug Responses Of Clinically Relevant Proteins In Cancer Cell Lines, Wei Zhao, Jun Li, Mei-Ju M Chen, Yikai Luo, Zhenlin Ju, Nicole K Nesser, Katie Johnson-Camacho, Christopher T Boniface, Yancey Lawrence, Nupur T Pande, Michael A Davies, Meenhard Herlyn, Taru Muranen, Ioannis K Zervantonakis, Erika Von Euw, Andre Schultz, Shwetha V Kumar, Anil Korkut, Paul T Spellman, Rehan Akbani, Dennis J Slamon, Joe W Gray, Joan S Brugge, Yiling Lu, Gordon B Mills, Han Liang

Faculty, Staff and Students Publications

Perturbation biology is a powerful approach to modeling quantitative cellular behaviors and understanding detailed disease mechanisms. However, large-scale protein response resources of cancer cell lines to perturbations are not available, resulting in a critical knowledge gap. Here we generated and compiled perturbed expression profiles of ∼210 clinically relevant proteins in >12,000 cancer cell line samples in response to ∼170 drug compounds using reverse-phase protein arrays. We show that integrating perturbed protein response signals provides mechanistic insights into drug resistance, increases the predictive power for drug sensitivity, and helps identify effective drug combinations. We build a systematic map of "protein-drug" connectivity …

Characterization Of Adiposity And Inflammation Genetic Pleiotropy Underlying Cardiovascular Risk Factors In Hispanics., Mohammad Yaser (Anwar)

Electronic Theses and Dissertations

The observed overlap between genetic variants associated with both adiposity and inflammatory markers suggests that changes in both adiposity and inflammation could be partially mediated by common pathways. The pervasive but sparsely characterized “pleiotropic” genetic variants associated with both adiposity and inflammation have been hypothesized to provide insight into the shared biology. This study explored and characterized the genetic pleiotropy underpinning adiposity and inflammation using genetic and phenotypic observations from the Cameron County Hispanic Cohort (CCHC). A total of 3,313 samples and >9 million single nucleotide polymorphisms (SNPs) were examined in this study. Mixed model genome-wide association studies (GWAS) were …

Safety And Effectiveness Of Hydroxychloroquine And Azithromycin Combination Therapy For Treatment Of Hospitalized Patients With Covid-19: A Propensity-Matched Study, Henry D Huang, Hani Jneid, Mariam Aziz, Venkatesh Ravi, Parikshit S Sharma, Timothy Larsen, Neal Chatterjee, Basil Saour, Zaid Aziz, Hemal Nayak, Richard G Trohman, Kousik Krishnan

Faculty, Staff and Students Publications

INTRODUCTION: We sought to determine the effectiveness and safety of hydroxychloroquine-azithromycin (HCQ-AZM) therapy in hospitalized patients with COVID-19.

METHODS: This was a retrospective cohort study of 613 patients hospitalized (integrated health system involving three hospitals) for RT-PCR-confirmed COVID-19 infection between March 1, 2020 and April 25, 2020. Intervention was treatment with HCQ-AZM in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Outcomes of interest were in-hospital all-cause mortality, cardiovascular mortality, pulseless electrical activity (PEA) arrest, non-lethal arrhythmias, and length of hospital stay. Secondary measures included in-hospital corrected QT (QTc) interval parameters and serum biomarkers levels.

RESULTS: Propensity-matched …

Postacute Covid-19: An Overview And Approach To Classification, Eva M Amenta, Amy Spallone, Maria C Rodriguez-Barradas, Hana M El Sahly, Robert L Atmar, Prathit A Kulkarni

Faculty, Staff and Students Publications

As the coronavirus disease 2019 (COVID-19) pandemic has progressed, a large volume of literature has developed delineating the clinical manifestations of acute infection. Recent reports have also started to describe persistent symptoms extending beyond the period of initial illness or hospitalization. Anecdotes of different signs and symptoms occurring after acute infection have also arisen in the lay press. Here we describe the current existing medical literature on the emerging concept of postacute COVID-19 and suggest an approach to classifying different manifestations of the syndrome. We also review long-term clinical manifestations observed in patients who recovered from infection due to other …

Epidemiology And Pathophysiology Of Common Skin Diseases In West Africa: An Immunodermatological Framework, Osazomon Imarenezor

All HCAS Student Capstones, Theses, and Dissertations

This capstone reviews the common skin diseases on a global scale. With these dermatoses being further funneled into Africa and then magnified into common West African dermatoses, the meta-analyses of literature available paints a clear picture of the epidemiological & pathological factors and their contribution to the skin disease. Each article analysed in this analysis was taken from a 20-year span of January 2000 to December 2019. The selection of articles was fine-tuned by identifying the distribution of skin disease, revealing the populations affected (age, gender, ethnicity, etc), the main causes, country of origin, the prognosis of disease, and the …

Donor And Transplant Candidate Selection For Solid Organ Transplantation During The Covid-19 Pandemic, N Thao N Galvan, Nicolas F Moreno, Jay E Garza, Susan Bourgeois, Marion Hemmersbach-Miller, Bhamidipati Murthy, Katherine Timmins, Christine A O'Mahony, James Anton, Andrew Civitello, Puneet Garcha, Gabe Loor, Kenneth Liao, Alexis Shaffi, John Vierling, Rise Stribling, Abbas Rana, John A Goss

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus responsible for a worldwide pandemic has forced drastic changes in medical practice in an alarmingly short period of time. Caregivers must modify their strategies as well as optimize the utilization of resources to ensure public and patient safety. For organ transplantation, in particular, the loss of lifesaving organs for transplantation could lead to increased waitlist mortality. The priority is to select uninfected donors to transplant uninfected recipients while maintaining safety for health care systems in the backdrop of a virulent pandemic. We do not yet have a standard approach to evaluating …

Genetics Of Smoking Behaviors In American Indians, Jeffrey A Henderson, Dedra S Buchwald, Barbara V Howard, Patricia Nez Henderson, Yafang Li, Rachel F Tyndale, Christopher I Amos, Olga Y Gorlova, Collaborative To Improve Native Cancer Outcomes (Cinco), A P50 Center For Population Health And Health Disparities Program Project Sponsored By The National Cancer Institute

Faculty, Staff and Students Publications

BACKGROUND: The smoking behavior of American Indians (AI) differs from that of non-Hispanic whites (NHW). Typically light smokers, cessation interventions in AIs are generally less effective. To develop more effective cessation programs for AIs, clinicians, researchers, and public health workers need a better understanding of the genetic factors involved in their smoking behavior. Our aim was to assess whether SNPs associated with smoking behavior in NHWs are also associated with smoking in AIs.

METHODS: We collected questionnaire data on smoking behaviors and analyzed blood and saliva samples from two Tribal populations with dramatically different cultures and smoking prevalence, one in …

Tumor Somatic Mutations Also Existing As Germline Polymorphisms May Help To Identify Functional Snps From Genome-Wide Association Studies, Ivan P Gorlov, Xiangjun Xia, Spiridon Tsavachidis, Olga Y Gorlova, Christopher I Amos

Faculty, Staff and Students Publications

We hypothesized that a joint analysis of cancer risk-associated single-nucleotide polymorphism (SNP) and somatic mutations in tumor samples can predict functional and potentially causal SNPs from GWASs. We used mutations reported in the Catalog of Somatic Mutations in Cancer (COSMIC). Confirmed somatic mutations were subdivided into two groups: (1) mutations reported as SNPs, which we call mutational/SNPs and (2) somatic mutations that are not reported as SNPs, which we call mutational/noSNPs. It is generally accepted that the number of times a somatic mutation is reported in COSMIC correlates with its selective advantage to tumors, with more frequently reported mutations being …

The Role Of Rapid Diagnostic Point Of Care Igg/Igm Antibody Tests In The Diagnosis Of Sars-Cov-2 Infection, Nishita Tripathi, Daniya Sheikh, Dawn Balcom

The University of Louisville Journal of Respiratory Infections

Background: Current testing of symptomatic patients for SARS-CoV-2 involves the use of nucleic acid amplification tests, also known as genetic, RNA, or polymerase chain reaction (PCR), to detect viral RNA. The initial use of point of care (POC) antibody tests, also known as serological tests, in the management of SARS-CoV-2 infection was limited. In this review, we determine the significance of POC antibody serological tests and explore their possible role in the diagnosis and management of patients infected with the SARS-CoV-2 virus.

Methods: A literature search was conducted in Google Scholar, PubMed, and Embase, supplemented by searching the Centers for …

Human Genes Differ By Their Uv Sensitivity Estimated Through Analysis Of Uv-Induced Silent Mutations In Melanoma, Ivan P Gorlov, Christopher I Amos, Spiridon Tsavachidis, Colin Begg, Eva Hernando, Chao Cheng, Ronglai Shen, Irene Orlow, Li Luo, Marc S Ernstoff, Joel Parker, Nancy E Thomas, Olga Y Gorlova, Marianne Berwick

Faculty, Staff and Students Publications

We hypothesized that human genes differ by their sensitivity to ultraviolet (UV) exposure. We used somatic mutations detected by genome-wide screens in melanoma and reported in the Catalog Of Somatic Mutations In Cancer. As a measure of UV sensitivity, we used the number of silent mutations generated by C>T transitions in pyrimidine dimers of a given transcript divided by the number of potential sites for this type of mutations in the transcript. We found that human genes varied by UV sensitivity by two orders of magnitude. We noted that the melanoma-associated tumor suppressor gene CDKN2A was among the top …

Aaim Recommendations For The 2020-2021 Internal Medicine Residency Application Cycle In Response To The Covid-19 Pandemic, Katherine C Chretien, Jaya M Raj, Reeni A Abraham, Paul Aronowitz, Donna J Astiz, Shobhina G Chheda, Ernie L Esquivel, Maria M Garcia, Nadia Ismail, Susan Lane, Suzanne E Mclaughlin, Anne Pereira, Amy W Shaheen, Abby L Spencer, Kimberly M Tartaglia, Lisa L Willett

Faculty, Staff and Students Publications

This statement was released in June 2020 by the Alliance for Academic Internal Medicine to provide guidance for the 2020-2021 residency application cycle in light of the COVID-19 pandemic. While many of the recommendations are specific to this cycle, others, such as the Department Summary Letter of Evaluation, are meant to be an enduring change to the internal medicine residency application process. AAIM realizes that some schools may not yet have the tools or resources to implement the template fully this cycle and look toward collaboration within the internal medicine education community to facilitate adoption in the cycles to come.

Intratumoral Translocation Positive Heterogeneity In Pediatric Alveolar Rhabdomyosarcoma Tumors Correlates To Patient Survival Prognosis, Katrina Gleditsch, Jorge Peñas, Danielle Mercer, Ayesha Umrigar, James Briscoe, Matthew Stark, Fern Tsien, Andrew D. Hollenbach

School of Medicine Faculty Publications

Alveolar rhabdomyosarcoma (ARMS) is characterized by one of three translocation states: t(2;13) (q35;q14) producing PAX3-FOXO1, t(1;13) (p36;q14) producing PAX7-FOXO1, or translocation-negative. Tumors with t(2;13) are associated with greater disease severity and mortality than t(1;13) positive or translocation negative patients. Consistent with this fact, previous work concluded that a molecular analysis of RMS translocation status is essential for the accurate determination of prognosis and diagnosis. However, despite this knowledge, most diagnoses rely on histology and in some cases utilize fluorescence in situ hybridization (FISH) probes unable to differentiate between translocation products. Along these same lines, diagnostic RT-PCR analysis, which can differentiate …

Comparison Of Sars-Cov-2 Detection From Nasopharyngeal Swab Samples By The Roche Cobas 6800 Sars-Cov-2 Test And A Laboratory-Developed Real-Time Rt-Pcr Test, Elisabet Pujadas, Nnaemeka Ibeh, Matthew M Hernandez, Aneta Waluszko, Tatyana Sidorenko, Vanessa Flores, Biana Shiffrin, Numthip Chiu, Alicia Young-Francois, Michael D Nowak, Alberto E Paniz-Mondolfi, Emilia M Sordillo, Carlos Cordon-Cardo, Jane Houldsworth, Melissa R Gitman

Faculty, Staff and Student Publications

The urgent need to implement and rapidly expand testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has led to the development of multiple assays. How these tests perform relative to one another is poorly understood. We evaluated the concordance between the Roche Diagnostics cobas 6800 SARS-CoV-2 test and a laboratory-developed test (LDT) real-time reverse transcription-polymerase chain reaction based on a modified Centers for Disease Control and Prevention protocol, for the detection of SARS-CoV-2 in samples submitted to the Clinical Laboratories of the Mount Sinai Health System. A total of 1006 nasopharyngeal swabs in universal transport medium from persons under …

A Novel Methodology To Identify The Primary Topics Contained Within The Covid-19 Research Corpus, Allen Crane, Brock Freidrich, William Fehlman, Igor Frolow, Daniel W. Engels

SMU Data Science Review

In this paper, we present a novel framework and system for the identification of primary research topics from within a corpus of related publications, the classification of individual publications according to these topics, and the results of the application of our framework and system to the COVID-19 Open Research Dataset (CORD-19). CORD-19 is a corpus of published peer reviewed and pre-peer reviewed articles related to the coronavirus that causes COVID-19. Using machine learning techniques, such as Non-negative Matrix Factorization for Natural Language Processing and a Bayesian classifier, we developed a novel framework and system that automatically extracts sparse and meaningful …

Limbic-Predominant Age-Related Tdp-43 Encephalopathy Differs From Frontotemporal Lobar Degeneration, John L. Robinson, Sílvia Porta, Filip G. Garrett, Panpan Zhang, Sharon X. Xie, Eunran Suh, Vivianna M. Van Deerlin, Erin L. Abner, Gregory A. Jicha, Justin M. Barber, Virginia M-Y Lee, Edward B. Lee, John Q. Trojanowski, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

TAR-DNA binding protein-43 (TDP-43) proteinopathy is seen in multiple brain diseases. A standardized terminology was recommended recently for common age-related TDP-43 proteinopathy: limbic-predominant, age-related TDP-43 encephalopathy (LATE) and the underlying neuropathological changes, LATE-NC. LATE-NC may be co-morbid with Alzheimer’s disease neuropathological changes (ADNC). However, there currently are ill-defined diagnostic classification issues among LATE-NC, ADNC, and frontotemporal lobar degeneration with TDP-43 (FTLD-TDP). A practical challenge is that different autopsy cohorts are composed of disparate groups of research volunteers: hospital- and clinic-based cohorts are enriched for FTLD-TDP cases, whereas community-based cohorts have more LATE-NC cases. Neuropathological methods also differ across laboratories. Here, …

Targeting Pd-L1 In Non-Small Cell Lung Cancer Using Car T Cells, Ming Liu, Xu Wang, Wei Li, Xinfang Yu, Pedro Flores-Villanueva, Zijun Y Xu-Monette, Ling Li, Mingzhi Zhang, Ken H Young, Xiaodong Ma, Yong Li

Faculty, Staff and Students Publications

Antibodies against programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have dramatically changed the landscape of therapies for non-small cell lung carcinoma (NSCLC); however, the majority of patients do not respond to these agents. In addition, hyperprogressive disease (HPD) develops in a larger portion of NSCLC patients treated with PD-1/PD-L1 inhibitors than in patients treated with standard chemotherapy. The use of chimeric antigen receptor (CAR) T cells has been successful to treat blood cancers but not for solid tumors like NSCLC. In this work, we constructed CAR T cells that target PD-L1 and evaluated their efficacy in NSCLC …

Prospects For Rnai Therapy Of Covid-19, Hasan Uludağ, Kylie Parent, Hamidreza Montazeri Aliabadi, Azita Haddadi

Pharmacy Faculty Articles and Research

COVID-19 caused by the SARS-CoV-2 virus is a fast emerging disease with deadly consequences. The pulmonary system and lungs in particular are most prone to damage caused by the SARS-CoV-2 infection, which leaves a destructive footprint in the lung tissue, making it incapable of conducting its respiratory functions and resulting in severe acute respiratory disease and loss of life. There were no drug treatments or vaccines approved for SARS-CoV-2 at the onset of pandemic, necessitating an urgent need to develop effective therapeutics. To this end, the innate RNA interference (RNAi) mechanism can be employed to develop front line therapies against …

Rna-Gps Predicts Sars-Cov-2 Rna Residency To Host Mitochondria And Nucleolus, Kevin E Wu, Furqan M Fazal, Kevin R Parker, James Zou, Howard Y Chang

Faculty, Staff and Students Publications

SARS-CoV-2 genomic and subgenomic RNA (sgRNA) transcripts hijack the host cell's machinery. Subcellular localization of its viral RNA could, thus, play important roles in viral replication and host antiviral immune response. We perform computational modeling of SARS-CoV-2 viral RNA subcellular residency across eight subcellular neighborhoods. We compare hundreds of SARS-CoV-2 genomes with the human transcriptome and other coronaviruses. We predict the SARS-CoV-2 RNA genome and sgRNAs to be enriched toward the host mitochondrial matrix and nucleolus, and that the 5' and 3' viral untranslated regions contain the strongest, most distinct localization signals. We interpret the mitochondrial residency signal as an …

Cardiac Surgery During The Coronavirus Disease 2019 Pandemic: Perioperative Considerations And Triage Recommendations, Vivek Patel, Ernesto Jimenez, Lorraine Cornwell, Trung Tran, David Paniagua, Ali E Denktas, Andrew Chou, Samuel J Hankins, Biykem Bozkurt, Todd K Rosengart, Hani Jneid

Faculty, Staff and Students Publications

The coronavirus disease 2019 pandemic, caused by severe acute respiratory syndrome coronavirus-2, represents the third human affliction attributed to the highly pathogenic coronavirus in the current century. Because of its highly contagious nature and unprecedented global spread, its aggressive clinical presentation, and the lack of effective treatment, severe acute respiratory syndrome coronavirus-2 infection is causing the loss of thousands of lives and imparting unparalleled strain on healthcare systems around the world. In the current report, we discuss perioperative considerations for patients undergoing cardiac surgery and provide clinicians with recommendations to effectively triage and plan these procedures during the coronavirus disease …

Foundational Research And Nih Funding Enabling Emergency Use Authorization Of Remdesivir For Covid-19, Ekaterina Galkina Cleary, Matthew J. Jackson, Zoë Folchman-Wagner, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Emergency Use Authorization for remdesivir months after discovery of COVID-19 is unprecedented. Typically, decades of research and public-sector funding are required to establish the mature body of foundational research requisite for efficient, targeted drug discovery and development. This work quantifies the body of research related to remdesivir’s biological target, RNA-dependent RNA polymerase (RdRp), or parent chemical structure, nucleoside analogs (NcAn), through 2019, as well as NIH funding for this research 2000–2019. There were 6,567 RdRp-related publications in PubMed, including 1,263 with NIH support, and 11,073 NcAn-related publications, including 2,319 with NIH support. NIH support for RdRp research comprised 2,203 Project …

Association Analysis Of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci With 20,871 Lung Cancer Cases And 15,971 Controls, Yuzhuo Wang, Olga Y Gorlova, Ivan P Gorlov, Meng Zhu, Juncheng Dai, Demetrius Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Gary E Goodman, Stig E Bojesen, Maria Teresa Landi, Mattias Johansson, Angela Risch, Heunz-Erich Wichmann, Heike Bickeboller, David C Christiani, Gad Rennert, Susanne M Arnold, Paul Brennan, John K Field, Sanjay Shete, Loïc Le Marchand, Olle Melander, Hans Brunnstrom, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil E Caporaso, Penella J Woll, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Victoria L Stevens, Hongxia Ma, Guangfu Jin, Zhibin Hu, Christopher I Amos, Hongbing Shen

Faculty, Staff and Students Publications

BACKGROUND: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.

METHODS: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data …