Public Health Commons^™

From World War Ii To Covid-19: A Historical Perspective On The American Medical Supply Chain, Hunter D Bechtold, Andrea T Cruz, Brent D Kaziny

Faculty, Staff and Students Publications

COVID-19 is the latest episode of shortages of critical medical supplies. Historically and to the present day, medical supplies have been sourced from single regions in the world, thus rendering the supply chain vulnerable to a myriad of harmful circumstances. We argue that shortages in medications related and unrelated to COVID have illustrated the need for the United States to diversify its medical supply sources before future pandemics, political crises, or natural disasters occur.

Socioeconomic And Comorbid Factors Affecting Mortality And Length Of Stay In Covid-19 Patients, Adam Delora, Ashlynn Mills, David Jacobson, Brendon Cornett, William F Peacock, Anita Datta, Shane P Jenks

Faculty, Staff and Students Publications

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic exposed and exacerbated health disparities between socioeconomic groups. Our purpose was to determine if age, sex, race, insurance, and comorbidities predicted patients' length of stay (LOS) in the hospital and in-hospital mortality in patients diagnosed with coronavirus disease 2019 (COVID-19) during the early pandemic. Methods Utilizing retrospective, secondarily sourced electronic health record (EHR) data for patients who tested positive for COVID-19 from HCA Healthcare facilities, predictors of LOS and in-hospital mortality were assessed using regression. LOS and in-hospital mortality were assessed using logistic regression and negative binomial regression, respectively. All …

Covid Community-Engaged Testing In Alabama: Reaching Underserved Rural Populations Through Collaboration, Christopher Greer Mccollum, Thomas N Creger, Aadia I Rana, Lynn T Matthews, Stefan D Baral, Greer A Burkholder, William A Curry, Latesha Elopre, Faith E Fletcher, Sydney Grooms, Emily B Levitan, Max Michael, Barbara Van Der Pol, Michael J Mugavero

Faculty, Staff and Students Publications

Rural communities are often underserved by public health testing initiatives in Alabama. As part of the National Institutes of Health's Rapid Acceleration of Diagnostics‒Underserved Populations initiative, the University of Alabama at Birmingham, along with community partners, sought to address this inequity in COVID-19 testing. We describe the participatory assessment, selection, and implementation phases of this project, which administered more than 23 000 COVID-19 tests throughout the state, including nearly 4000 tests among incarcerated populations. (

Pin-Pointing The Key Hubs In The Ifn-Γ Pathway Responding To Sars-Cov-2 Infection, Ayelen Toro, Sofia Lage-Vickers, Juan Bizzotto, Felipe Vilicich, Agustina Sabater, Gaston Pascual, Sabrina Ledesma-Bazan, Pablo Sanchis, Maria Sol Ruiz, Ana Paula Arevalo, Jorge L Porfido, Mercedes Abbate, Rocio Seniuk, Estefania Labanca, Nicolas Anselmino, Nora M Navone, Daniel F Alonso, Elba Vazquez, Martina Crispo, Javier Cotignola, Geraldine Gueron

Faculty, Staff and Student Publications

Interferon gamma (IFN-γ) may be potential adjuvant immunotherapy for COVID-19 patients. In this work, we assessed gene expression profiles associated with the IFN-γ pathway in response to SARS-CoV-2 infection. Employing a case-control study from SARS-CoV-2-positive and -negative patients, we identified IFN-γ-associated pathways to be enriched in positive patients. Bioinformatics analyses showed upregulation of MAP2K6, CBL, RUNX3, STAT1, and JAK2 in COVID-19-positive vs. -negative patients. A positive correlation was observed between STAT1/JAK2, which varied alongside the patient's viral load. Expression of MX1, MX2, ISG15, and OAS1 (four well-known IFN-stimulated genes (ISGs)) …

Cov-Inception: Covid-19 Detection Tool Using Chest X-Ray, Aswini Thota, Ololade Awodipe, Rashmi Patel

SMU Data Science Review

Since the pandemic started, researchers have been trying to find a way to detect COVID-19 which is a cost-effective, fast, and reliable way to keep the economy viable and running. This research details how chest X-ray radiography can be utilized to detect the infection. This can be for implementation in Airports, Schools, and places of business. Currently, Chest imaging is not a first-line test for COVID-19 due to low diagnostic accuracy and confounding with other viral pneumonia. Different pre-trained algorithms were fine-tuned and applied to the images to train the model and the best model obtained was fine-tuned InceptionV3 model …

Veterans’ Ambulatory Care Experience During Covid-19: Veterans’ Access To And Satisfaction With Primary Care Early In The Pandemic, Brice Thomas, Aanchal Thadani, Patricia V Chen, Israel C Christie, Lisa M Kern, Mangala Rajan, Himabindu Kadiyala, Drew A Helmer

Faculty, Staff and Students Publications

BACKGROUND: The COVID-19 pandemic caused widespread changes to healthcare, but few studies focus on ambulatory care during the early phase of the pandemic. We characterize veterans' ambulatory care experience, specifically access and satisfaction, early in the pandemic.

METHODS: We employed a semi-structured telephone interview to capture quantitative and qualitative data from patients scheduled with a primary care provider between March 1 - June 30, 2020. Forty veterans were randomly identified at a single large urban Veterans Health Administration (VHA) medical center. The interview guide utilized 56 closed and open-ended questions to characterize veterans' perceptions of access to and satisfaction with …

Remission Of Liquid Tumors And Sars-Cov-2 Infection: A Literature Review, Dong Ho Shin, Andrew Gillard, Arie Van Wieren, Candelaria Gomez-Manzano, Juan Fueyo

Faculty, Staff and Student Publications

The coronavirus disease 2019 (COVID-19) pandemic has produced a new global challenge for patients with cancer. The disease and the immunosuppression induced by cancer therapies have generated a perfect storm of conditions to increase the severity of the symptoms and worsen the prognosis. However, a few clinical reports showcased the power of viruses to induce remission in some patients suffering from liquid tumors. Here, we reviewed six cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that resulted in cancer remission, simultaneously highlighting the strengths and the unique challenges of oncolytic virotherapy. Virotherapy has become a special case of cancer …

Delineating Covid-19 Immunological Features Using Single-Cell Rna Sequencing, Wendao Liu, Johnathan Jia, Yulin Dai, Wenhao Chen, Guangsheng Pei, Qiheng Yan, Zhongming Zhao

Faculty, Staff and Student Publications

Understanding the molecular mechanisms of coronavirus disease 2019 (COVID-19) pathogenesis and immune response is vital for developing therapies. Single-cell RNA sequencing has been applied to delineate the cellular heterogeneity of the host response toward COVID-19 in multiple tissues and organs. Here, we review the applications and findings from over 80 original COVID-19 single-cell RNA sequencing studies as well as many secondary analysis studies. We describe that single-cell RNA sequencing reveals multiple features of COVID-19 patients with different severity, including cell populations with proportional alteration, COVID-19-induced genes and pathways, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in single cells, and adaptation …

Whole-Exome Sequencing Of 14 389 Individuals From The Esp And Charge Consortia Identifies Novel Rare Variation Associated With Hemostatic Factors, Nathan Pankratz, Peng Wei, Jennifer A Brody, Ming-Huei Chen, Paul S De Vries, Jennifer E Huffman, Mary Rachel Stimson, Paul L Auer, Eric Boerwinkle, Mary Cushman, Moniek P M De Maat, Aaron R Folsom, Oscar H Franco, Richard A Gibbs, Kelly K Haagenson, Albert Hofman, Jill M Johnsen, Christie L Kovar, Robert Kraaij, Barbara Mcknight, Ginger A Metcalf, Donna Muzny, Bruce M Psaty, Weihong Tang, André G Uitterlinden, Jeroen G J Van Rooij, Abbas Dehghan, Christopher J O'Donnell, Alex P Reiner, Alanna C Morrison, Nicholas L Smith

Faculty, Staff and Student Publications

Plasma levels of fibrinogen, coagulation factors VII and VIII and von Willebrand factor (vWF) are four intermediate phenotypes that are heritable and have been associated with the risk of clinical thrombotic events. To identify rare and low-frequency variants associated with these hemostatic factors, we conducted whole-exome sequencing in 10 860 individuals of European ancestry (EA) and 3529 African Americans (AAs) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and the National Heart, Lung and Blood Institute's Exome Sequencing Project. Gene-based tests demonstrated significant associations with rare variation (minor allele frequency < 5%) in fibrinogen gamma chain (FGG) (with fibrinogen, P = 9.1 × 10-13), coagulation factor VII (F7) (with factor VII, P = 1.3 × 10-72; seven novel variants) and VWF (with factor VIII and vWF; P = 3.2 × 10-14; one novel variant). These eight novel rare variant associations were independent of the known common variants at these loci and tended to have much larger effect sizes. In addition, one of the rare novel variants in F7 was significantly associated with an increased risk of venous thromboembolism in AAs (Ile200Ser; rs141219108; P = 4.2 × 10-5). After restricting gene-based analyses to only loss-of-function variants, a novel significant association was detected and replicated between factor VIII levels and a stop-gain mutation exclusive to AAs (rs3211938) in CD36 molecule (CD36). This variant has previously been linked to dyslipidemia but not with the levels of a hemostatic factor. These efforts represent the largest integration of whole-exome sequence data from two national projects to identify genetic variation associated with plasma hemostatic factors.

Covid-19 And Children, Carl A Pierce, Kevan C Herold, Betsy C Herold, Janet Chou, Adrienne Randolph, Binita Kane, Sammie Mcfarland, Deepti Gurdasani, Christina Pagel, Peter Hotez, Sarah Cobey, Scott E Hensley

Center for Medical Ethics and Health Policy Staff Publications

There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in …

A Case Of Malpositioned Endotracheal Tube With Resultant Left Lung Collapse., Anushri Naga, Anushri Naga

Digital Journal of Clinical Medicine

BACKGROUND

ENDOTRACHEAL INTUBATION IS USUALLY DONE AS A PART OF EMERGENCY MANAGEMENT OF PATIENTS WITH A THREATENED AIRWAY AND GENERAL ANAESTHSIA, IN ORDER TO ENSURE PATENCY OF THE AIRWAY AS WELL AS PROPER VENTILATION. POSITIONING AN ET TUBE CORRECTLY IS OF PARAMOUNT IMPORTANCE IN ORDER TO PREVENT HYPOVENTILATION, INAPPROPRIATE VENTILATION AND ALSO COLLAPSE OF LUNG DUE TO MALPOSITIONING OF ET TUBE.

ETT POSITION IS USUALLY ASSESSED USING FRONTAL CHEST RADIOGRAPH. THE POSITION OF THE ETT IS DEPENDENT ON THE POSITION OF THE HEAD & NECK. THE MANDIBLE CAN BE USED FOR ASSESSMENT OF WHETHER THE NECK IS IN A NEUTRAL …

Post Covid-19 Cognitive Impairment In A Patient With Bipolar Disorder, Nilanjana Dutta, Raghav Gupta, Dr. M Kishor Mbbs, Md

Digital Journal of Clinical Medicine

COVID-19 has caused widespread health conditions, psychological and social distress among people and there is evidence that shows profound neuropsychiatric complications during acute and post-recovery phases of the infection. Cognitive impairment occurring after COVID-19 infection can be explained by various mechanisms, including persistent systemic inflammation, direct viral invasion, alteration in the blood-brain barrier, and cerebrovascular endothelial injury.There are few studies that have explored the impact of COVID-19 on pre-existing psychiatric conditions. This case report highlights the temporal association of cognitive impairment with COVID-19 and the need for cognitive assessment and management in post-COVID-19 patients with pre-existing psychiatric conditions.

Obsessive Compulsive Disorder With Porn Addiction During The Covid-19 Pandemic, Varuni Pragya, M Kishor Dr.

Digital Journal of Clinical Medicine

BACKGROUND:

COVID-19 Pandemic is an unprecedented humanitarian crisis that has affected the mental health of individuals immensely. OCD was among the mental health conditions that emerged with the new norm that is associated with repeated hand wash, social distancing and testing to confirm COVID-19. Nissen et al. (2020) found that there was a significant positive correlation between total OCD severity scores and the occurrence of OCD aggressive and sexual symptoms. [6] The COVID-19 lockdown translated into physical isolation, driving individuals to waste time online with no definite purpose, spending longer, abnormal durations of time online when bored, leading to increased …

Inspire Yourself: Volunteer!, Judith Sullivan

Journal of Transformative Touch

Doing volunteer short Zero Balancing sessions once a month for 13 years for staff, volunteers and sometimes "guests" at The Haven, a a multi-resource day shelter in downtown Charlottesville, Virginia supports the community in many ways.

Will Anti-Vaccine Activism In The Usa Reverse Global Goals?, Peter J Hotez

Center for Medical Ethics and Health Policy Staff Publications

In the time of the COVID-19 pandemic, anti-vaccine activism in the USA accelerated, amplified and formed an alliance with political groups and even extremists. An organized, well-funded and empowered anti-science movement now threatens to spill over and threaten all childhood immunizations in the USA and globally.

Genome-Wide Association Analyses Of Physical Activity And Sedentary Behavior Provide Insights Into Underlying Mechanisms And Roles In Disease Prevention, Zhe Wang, Andrew Emmerich, Nicolas J Pillon, Tim Moore, Daiane Hemerich, Marilyn C Cornelis, Eugenia Mazzaferro, Siacia Broos, Tarunveer S Ahluwalia, Traci M Bartz, Amy R Bentley, Lawrence F Bielak, Mike Chong, Audrey Y Chu, Diane Berry, Rajkumar Dorajoo, Nicole D Dueker, Elisa Kasbohm, Bjarke Feenstra, Mary F Feitosa, Christian Gieger, Mariaelisa Graff, Leanne M Hall, Toomas Haller, Fernando P Hartwig, David A Hillis, Ville Huikari, Nancy Heard-Costa, Christina Holzapfel, Anne U Jackson, Åsa Johansson, Anja Moltke Jørgensen, Marika A Kaakinen, Robert Karlsson, Kathleen F Kerr, Boram Kim, Chantal M Koolhaas, Zoltan Kutalik, Vasiliki Lagou, Penelope A Lind, Mattias Lorentzon, Leo-Pekka Lyytikäinen, Massimo Mangino, Christoph Metzendorf, Kristine R Monroe, Alexander Pacolet, Louis Pérusse, Rene Pool, Rebecca C Richmond, Natalia V Rivera, Sebastien Robiou-Du-Pont, Katharina E Schraut, Christina-Alexandra Schulz, Heather M Stringham, Toshiko Tanaka, Alexander Teumer, Constance Turman, Peter J Van Der Most, Mathias Vanmunster, Frank J A Van Rooij, Jana V Van Vliet-Ostaptchouk, Xiaoshuai Zhang, Jing-Hua Zhao, Wei Zhao, Zhanna Balkhiyarova, Marie N Balslev-Harder, Sebastian E Baumeister, John Beilby, John Blangero, Dorret I Boomsma, Soren Brage, Peter S Braund, Jennifer A Brody, Marcel Bruinenberg, Ulf Ekelund, Ching-Ti Liu, John W Cole, Francis S Collins, L Adrienne Cupples, Tõnu Esko, Stefan Enroth, Jessica D Faul, Lindsay Fernandez-Rhodes, Alison E Fohner, Oscar H Franco, Tessel E Galesloot, Scott D Gordon, Niels Grarup, Catharina A Hartman, Gerardo Heiss, Jennie Hui, Thomas Illig, Russell Jago, Alan James, Peter K Joshi, Taeyeong Jung, Mika Kähönen, Tuomas O Kilpeläinen, Woon-Puay Koh, Ivana Kolcic, Peter P Kraft, Johanna Kuusisto, Lenore J Launer, Aihua Li, Allan Linneberg, Jian'an Luan, Pedro Marques Vidal, Sarah E Medland, Yuri Milaneschi, Arden Moscati, Bill Musk, Christopher P Nelson, Ilja M Nolte, Nancy L Pedersen, Annette Peters, Patricia A Peyser, Christine Power, Olli T Raitakari, Mägi Reedik, Alex P Reiner, Paul M Ridker, Igor Rudan, Kathy Ryan, Mark A Sarzynski, Laura J Scott, Robert A Scott, Stephen Sidney, Kristin Siggeirsdottir, Albert V Smith, Jennifer A Smith, Emily Sonestedt, Marin Strøm, E Shyong Tai, Koon K Teo, Barbara Thorand, Anke Tönjes, Angelo Tremblay, Andre G Uitterlinden, Jagadish Vangipurapu, Natasja Van Schoor, Uwe Völker, Gonneke Willemsen, Kayleen Williams, Quenna Wong, Huichun Xu, Kristin L Young, Jian Min Yuan, M Carola Zillikens, Alan B Zonderman, Adam Ameur, Stefania Bandinelli, Joshua C Bis, Michael Boehnke, Claude Bouchard, Daniel I Chasman, George Davey Smith, Eco J C De Geus, Louise Deldicque, Marcus Dörr, Michele K Evans, Luigi Ferrucci, Myriam Fornage, Caroline Fox, Theodore Garland, Vilmundur Gudnason, Ulf Gyllensten, Torben Hansen, Caroline Hayward, Bernardo L Horta, Elina Hyppönen, Marjo-Riitta Jarvelin, W Craig Johnson, Sharon L R Kardia, Lambertus A Kiemeney, Markku Laakso, Claudia Langenberg, Terho Lehtimäki, Loic Le Marchand, Patrik K E Magnusson, Nicholas G Martin, Mads Melbye, Andres Metspalu, David Meyre, Kari E North, Claes Ohlsson, Albertine J Oldehinkel, Marju Orho-Melander, Guillaume Pare, Taesung Park, Oluf Pedersen, Brenda W J H Penninx, Tune H Pers, Ozren Polasek, Inga Prokopenko, Charles N Rotimi, Nilesh J Samani, Xueling Sim, Harold Snieder, Thorkild I A Sørensen, Tim D Spector, Nicholas J Timpson, Rob M Van Dam, Nathalie Van Der Velde, Cornelia M Van Duijn, Peter Vollenweider, Henry Völzke, Trudy Voortman, Gérard Waeber, Nicholas J Wareham, David R Weir, Heinz-Erich Wichmann, James F Wilson, Andrea L Hevener, Anna Krook, Juleen R Zierath, Martine A I Thomis, Ruth J F Loos, Marcel Den Hoed

Faculty, Staff and Student Publications

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle …

Genetic Analyses Of The Electrocardiographic Qt Interval And Its Components Identify Additional Loci And Pathways, William J Young, Najim Lahrouchi, Aaron Isaacs, Thuyvy Duong, Luisa Foco, Farah Ahmed, Jennifer A Brody, Reem Salman, Raymond Noordam, Jan-Walter Benjamins, Jeffrey Haessler, Leo-Pekka Lyytikäinen, Linda Repetto, Maria Pina Concas, Marten E Van Den Berg, Stefan Weiss, Antoine R Baldassari, Traci M Bartz, James P Cook, Daniel S Evans, Rebecca Freudling, Oliver Hines, Jonas L Isaksen, Honghuang Lin, Hao Mei, Arden Moscati, Martina Müller-Nurasyid, Casia Nursyifa, Yong Qian, Anne Richmond, Carolina Roselli, Kathleen A Ryan, Eduardo Tarazona-Santos, Sébastien Thériault, Stefan Van Duijvenboden, Helen R Warren, Jie Yao, Dania Raza, Stefanie Aeschbacher, Gustav Ahlberg, Alvaro Alonso, Laura Andreasen, Joshua C Bis, Eric Boerwinkle, Archie Campbell, Eulalia Catamo, Massimiliano Cocca, Michael J Cutler, Dawood Darbar, Alessandro De Grandi, Antonio De Luca, Jun Ding, Christina Ellervik, Patrick T Ellinor, Stephan B Felix, Philippe Froguel, Christian Fuchsberger, Martin Gögele, Claus Graff, Mariaelisa Graff, Xiuqing Guo, Torben Hansen, Susan R Heckbert, Paul L Huang, Heikki V Huikuri, Nina Hutri-Kähönen, M Arfan Ikram, Rebecca D Jackson, Juhani Junttila, Maryam Kavousi, Jan A Kors, Thiago P Leal, Rozenn N Lemaitre, Henry J Lin, Lars Lind, Allan Linneberg, Simin Liu, Peter W Macfarlane, Massimo Mangino, Thomas Meitinger, Massimo Mezzavilla, Pashupati P Mishra, Rebecca N Mitchell, Nina Mononen, May E Montasser, Alanna C Morrison, Matthias Nauck, Victor Nauffal, Pau Navarro, Kjell Nikus, Guillaume Pare, Kristen K Patton, Giulia Pelliccione, Alan Pittman, David J Porteous, Peter P Pramstaller, Michael H Preuss, Olli T Raitakari, Alexander P Reiner, Antonio Luiz P Ribeiro, Kenneth M Rice, Lorenz Risch, David Schlessinger, Ulrich Schotten, Claudia Schurmann, Xia Shen, M Benjamin Shoemaker, Gianfranco Sinagra, Moritz F Sinner, Elsayed Z Soliman, Monika Stoll, Konstantin Strauch, Kirill Tarasov, Kent D Taylor, Andrew Tinker, Stella Trompet, André Uitterlinden, Uwe Völker, Henry Völzke, Melanie Waldenberger, Lu-Chen Weng, Eric A Whitsel, James G Wilson, Christy L Avery, David Conen, Adolfo Correa, Francesco Cucca, Marcus Dörr, Sina A Gharib, Giorgia Girotto, Niels Grarup, Caroline Hayward, Yalda Jamshidi, Marjo-Riitta Järvelin, J Wouter Jukema, Stefan Kääb, Mika Kähönen, Jørgen K Kanters, Charles Kooperberg, Terho Lehtimäki, Maria Fernanda Lima-Costa, Yongmei Liu, Ruth J F Loos, Steven A Lubitz, Dennis O Mook-Kanamori, Andrew P Morris, Jeffrey R O'Connell, Morten Salling Olesen, Michele Orini, Sandosh Padmanabhan, Cristian Pattaro, Annette Peters, Bruce M Psaty, Jerome I Rotter, Bruno Stricker, Pim Van Der Harst, Cornelia M Van Duijn, Niek Verweij, James F Wilson, Dan E Arking, Julia Ramirez, Pier D Lambiase, Nona Sotoodehnia, Borbala Mifsud, Christopher Newton-Cheh, Patricia B Munroe

Faculty, Staff and Student Publications

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and …

Pivoting The Biosafety Program In Response To Covid-19: Recommendations Of Key Services And Tasks To Consider For The Next Pandemic, Robert J Emery, Scott J Patlovich, Kristin G King, Janelle Rios

Faculty, Staff and Student Publications

INTRODUCTION: With the onset of the COVID-19 pandemic, a rapid adjustment of work tasks was necessary for many biosafety programs (and other safety programs) to address drastic shifts in workload demands amid pandemic-related shutdowns and subsequent needs for supporting COVID-19-related safe work protocols, diagnostic testing, research, vaccine development, and so forth. From a program management standpoint, evaluating and understanding these tasks were critically important to ensure that appropriate support and resources were in place, especially during such unprecedented times of rapid change and significant impact to normal life and routine.

METHODS: Described here are examples of how the biosafety program …

An Empirical Model Of Proton Rbe Based On The Linear Correlation Between X-Ray And Proton Radiosensitivity, David B Flint, Chase E Ruff, Scott J Bright, Pablo Yepes, Qianxia Wang, Mandira Manandhar, Mariam Ben Kacem, Broderick X Turner, David K J Martinus, Simona F Shaitelman, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Background: Proton relative biological effectiveness (RBE) is known to depend on physical factors of the proton beam, such as its linear energy transfer (LET), as well as on cell-line specific biological factors, such as their ability to repair DNA damage. However, in a clinical setting, proton RBE is still considered to have a fixed value of 1.1 despite the existence of several empirical models that can predict proton RBE based on how a cell's survival curve (linear-quadratic model [LQM]) parameters α and β vary with the LET of the proton beam. Part of the hesitation to incorporate variable RBE models …

Repurposing Epigenetic Inhibitors To Target The Clostridioides Difficile-Specific Dna Adenine Methyltransferase And Sporulation Regulator Cama, Jujun Zhou, John R Horton, Dan Yu, Ren Ren, Robert M Blumenthal, Xing Zhang, Xiaodong Cheng

Faculty, Staff and Student Publications

Epigenetically targeted therapeutic development, particularly for SAM-dependent methylations of DNA, mRNA and histones has been proceeding rapidly for cancer treatments over the past few years. However, this approach has barely begun to be exploited for developing new antibiotics, despite an overwhelming global need to counter antimicrobial resistance. Here, we explore whether SAM analogues, some of which are in (pre)clinical studies as inhibitors of human epigenetic enzymes, can also inhibit Clostridioides difficile-specific DNA adenine methyltransferase (CamA), a sporulation regulator present in all C. difficile genomes sequenced to date, but found in almost no other bacteria. We found that SGC0946 (an …

Clinical Acceptability Of Fully Automated External Beam Radiotherapy For Cervical Cancer With Three Different Beam Delivery Techniques, Dong Joo Rhee, Anuja Jhingran, Kai Huang, Tucker J Netherton, Nazia Fakie, Ingrid White, Alicia Sherriff, Carlos E Cardenas, Lifei Zhang, Surendra Prajapati, Stephen F Kry, Beth M Beadle, William Shaw, Frederika O'Reilly, Jeannette Parkes, Hester Burger, Chris Trauernicht, Hannah Simonds, Laurence E Court

Faculty, Staff and Student Publications

Purpose: To fully automate CT-based cervical cancer radiotherapy by automating contouring and planning for three different treatment techniques.

Methods: We automated three different radiotherapy planning techniques for locally advanced cervical cancer: 2D 4-field-box (4-field-box), 3D conformal radiotherapy (3D-CRT), and volumetric modulated arc therapy (VMAT). These auto-planning algorithms were combined with a previously developed auto-contouring system. To improve the quality of the 4-field-box and 3D-CRT plans, we used an in-house, field-in-field (FIF) automation program. Thirty-five plans were generated for each technique on CT scans from multiple institutions and evaluated by five experienced radiation oncologists from three different countries. Every plan was …

Development And Validation Of A Checklist For Use With Automatically Generated Radiotherapy Plans, Kelly A Nealon, Laurence E Court, Raphael J Douglas, Lifei Zhang, Eun Young Han

Faculty, Staff and Student Publications

Purpose: To develop a checklist that improves the rate of error detection during the plan review of automatically generated radiotherapy plans.

Methods: A custom checklist was developed using guidance from American Association of Physicists in Medicine task groups 275 and 315 and the results of a failure modes and effects analysis of the Radiation Planning Assistant (RPA), an automated contouring and treatment planning tool. The preliminary checklist contained 90 review items for each automatically generated plan. In the first study, eight physicists were recruited from our institution who were familiar with the RPA. Each physicist reviewed 10 artificial intelligence-generated resident …

Metagenomes Of Rectal Swabs In Larger, Advanced Stage Cervical Cancers Have Enhanced Mucus Degrading Functionalities And Distinct Taxonomic Structure, Tatiana V Karpinets, Xiaogang Wu, Travis Solley, Molly B El Alam, Travis T Sims, Kyoko Yoshida-Court, Erica Lynn, Mustapha Ahmed-Kaddar, Greyson Biegert, Jingyan Yue, Xingzhi Song, Huandong Sun, Joseph F Petrosino, Melissa P Mezzari, Pablo Okhuysen, Patricia J Eifel, Anuja Jhingran, Lilie L Lin, Kathleen M Schmeler, Lois Ramondetta, Nadim Ajami, Robert R Jenq, Andrew Futreal, Jianhua Zhang, Ann H Klopp, Lauren E Colbert

Faculty, Staff and Student Publications

BACKGROUND: Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. We proposed that functions of specific microbial species adjoining the mucus layer may directly impact the biology of CC.

METHOD: Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics.

RESULTS: Significant association of molecular functions encoded by the metagenomes was found with initial tumor size and stage. Profiling of the molecular function abundances and their distributions identified …

Delayed Large Local Reactions To Moderna Covid-19 Vaccine: A Follow-Up Report After Booster Vaccination, Kimberly G Blumenthal, Catherine Ahola, Sara Anvari, Upeka Samarakoon, Esther E Freeman

Faculty, Staff and Students Publications

No abstract provided.

Quality Of Life, Illness Perceptions, And Parental Lived Experiences In Tango2-Related Metabolic Encephalopathy And Arrhythmias, Chaya N Murali, Seema R Lalani, Mahshid S Azamian, Christina Y Miyake, Hadley Stevens Smith

Faculty, Staff and Students Publications

TANGO2 disorder is a rare genetic disease with multi-system effects that causes episodic crises. Quality of life and psychosocial effects of this rare disease have not previously been studied. To examine health-related quality of life (HRQoL), illness perceptions, and lived experience, we surveyed 16 children and 31 parents of children with TANGO2 disorder identified via a disease-specific social media group and research foundation email distribution list. We assessed HRQoL by parent proxy-report and child self-report using the Pediatric Quality of Life Inventory (PedsQL™). Parental perceptions of their child's condition were assessed using the revised illness perceptions questionnaire adapted for TANGO2 …

Efficacy And Safety Of Ensovibep For Adults Hospitalized With Covid-19 : A Randomized Controlled Trial, Christina Barkauskas, Eleftherios Mylonakis, Garyfallia Poulakou, Barnaby E Young, David M Vock, Lianne Siegel, Nicole Engen, Greg Grandits, Nilima R Mosaly, Andrew M Vekstein, Ralph Rogers, Fadi Shehadeh, Matthew Kaczynski, Evangelia K Mylona, Konstantinos N Syrigos, Vasiliki Rapti, David C Lye, Diong Shiau Hui, Lindsay Leither, Kirk U Knowlton, Mamta K Jain, Rubria Marines-Price, Alice Osuji, J Scott Overcash, Ioannis Kalomenidis, Zafeiria Barmparessou, Michael Waters, Karla Zepeda, Peter Chen, Sam Torbati, Francis Kiweewa, Nicholus Sebudde, Eyad Almasri, Alyssa Hughes, Sanjay R Bhagani, Alison Rodger, Uriel Sandkovsky, Robert L Gottlieb, Eriobu Nnakelu, Barbara Trautner, Vidya Menon, Joseph Lutaakome, Michael Matthay, Philip Robinson, Konstantinos Protopapas, Nikolaos Koulouris, Ivan Kimuli, Amiran Baduashvili, Dominique L Braun, Huldrych F Günthard, Srikanth Ramachandruni, Robert Kidega, Kami Kim, Timothy J Hatlen, Andrew N Phillips, Daniel D Murray, Tomas O Jensen, Maria L Padilla, Evan X Accardi, Katy Shaw-Saliba, Robin L Dewar, Marc Teitelbaum, Ven Natarajan, Sylvain Laverdure, Helene C Highbarger, M Tauseef Rehman, Susan Vogel, David Vallée, Page Crew, Negin Atri, Adam J Schechner, Sarah Pett, Fleur Hudson, Jonathan Badrock, Giota Touloumi, Samuel M Brown, Wesley H Self, Crystal M North, Adit A Ginde, Christina C Chang, Anthony Kelleher, Stephanie Nagy-Agren, Shikha Vasudeva, David Looney, Hien H Nguyen, Adriana Sánchez, Amy C Weintrob, Birgit Grund, Shweta Sharma, Cavan S Reilly, Roger Paredes, Agnieszka Bednarska, Norman P Gerry, Abdel G Babiker, Victoria J Davey, Annetine C Gelijns, Elizabeth S Higgs, Virginia Kan, Gail Matthews, B Taylor Thompson, Philippe Legenne, Richa Chandra, H Clifford Lane, James D Neaton, Jens D Lundgren

Faculty, Staff and Students Publications

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.

OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.

DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978).

SETTING: Multinational, multicenter trial.

PARTICIPANTS: Adults hospitalized with COVID-19.

INTERVENTION: Intravenous ensovibep, 600 mg, or placebo.

MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day …

Cross-Sectional Study On Overweight And Obesity Associated With Fast-Food Consumption In Bangladesh, Farhana Sultana, Shafayet Ahmed Siddiqui, Md. Ashraful Islam, Mohammad Hamid Al Muktadir, Md. Shalahuddin Millat, Muhammed Mohibul Islam, Abu Montakim Tareq, Nahida Afroz, Mahabuba Rahman, Mohammad Nurul Amin, Talha Bin Emran

Makara Journal of Health Research

Background: This study aimed to investigate the risk factors and status of fast-food consumption among students in Bangladesh.

Methods: This cross-sectional study was conducted from March to November 2020. A total of 654 samples were collected from several schools, colleges, and universities during this study period.

Results: About 60.1% and 39.9% of the students were male and female, respectively. Of the students, 53.1% considered fast food as unhealthy (p < 0.001), but only 47.7% were leading a sedentary lifestyle. A significant outcome of overweight and pre-obesity was observed for student institutions, consumption frequency, daily fast-food consumption, and sedentary lifestyle (p < 0.001). In addition, positive association was observed for fast-food consumption more than three times and less than three times per week (OR and 95% CI: 11.13 [7.52–16.47], p < 0.001), higher social class and lower class (OR and 95% CI: 2.18 [1.31–3.62], p = 0.003), fast food preference and other foods (OR and 95% CI: 1.55 [1.11–2.15], p = 0.009), and sedentary and heavily active lifestyle (OR …

Virtual Global Health In Graduate Medical Education: A Systematic Review, Lisa Umphrey, Nora Lenhard, Suet Kam Lam, Nathaniel E Hayward, Shaina Hecht, Priya Agrawal, Amy Chambliss, Jessica Evert, Heather Haq, Stephanie M Lauden, George Paasi, Mary Schleicher, Megan Song Mchenry

Faculty, Staff and Students Publications

OBJECTIVES: To synthesize recent virtual global health education activities for graduate medical trainees, document gaps in the literature, suggest future study, and inform best practice recommendations for global health educators.

METHODS: We systematically reviewed articles published on virtual global health education activities from 2012-2021 by searching MEDLINE, EMBASE, Cochrane Library, ERIC, Scopus, Web of Science, and ProQuest Dissertations & Theses A&I. We performed bibliography review and search of conference and organization websites. We included articles about primarily virtual activities targeting for health professional trainees. We collected and qualitatively analyzed descriptive data about activity type, evaluation, audience, and drivers or barriers. …

Endophenotype Effect Sizes Support Variant Pathogenicity In Monogenic Disease Susceptibility Genes, Jennifer L Halford, Valerie N Morrill, Seung Hoan Choi, Sean J Jurgens, Giorgio Melloni, Nicholas A Marston, Lu-Chen Weng, Victor Nauffal, Amelia W Hall, Sophia Gunn, Christina A Austin-Tse, James P Pirruccello, Shaan Khurshid, Heidi L Rehm, Emelia J Benjamin, Eric Boerwinkle, Jennifer A Brody, Adolfo Correa, Brandon K Fornwalt, Namrata Gupta, Christopher M Haggerty, Stephanie Harris, Susan R Heckbert, Charles C Hong, Charles Kooperberg, Henry J Lin, Ruth J F Loos, Braxton D Mitchell, Alanna C Morrison, Wendy Post, Bruce M Psaty, Susan Redline, Kenneth M Rice, Stephen S Rich, Jerome I Rotter, Peter F Schnatz, Elsayed Z Soliman, Nona Sotoodehnia, Eugene K Wong, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Marc S Sabatine, Christian T Ruff, Kathryn L Lunetta, Patrick T Ellinor, Steven A Lubitz

Faculty, Staff and Student Publications

Accurate and efficient classification of variant pathogenicity is critical for research and clinical care. Using data from three large studies, we demonstrate that population-based associations between rare variants and quantitative endophenotypes for three monogenic diseases (low-density-lipoprotein cholesterol for familial hypercholesterolemia, electrocardiographic QTc interval for long QT syndrome, and glycosylated hemoglobin for maturity-onset diabetes of the young) provide evidence for variant pathogenicity. Effect sizes are associated with pathogenic ClinVar assertions (P < 0.001 for each trait) and discriminate pathogenic from non-pathogenic variants (area under the curve 0.82-0.84 across endophenotypes). An effect size threshold of ≥ 0.5 times the endophenotype standard deviation nominates up to 35% of rare variants of uncertain significance or not in ClinVar in disease susceptibility genes with pathogenic potential. We propose that variant associations with quantitative endophenotypes for monogenic diseases can provide evidence supporting pathogenicity.

Years Of Life Lost Associated With Covid-19 Deaths In The Usa During The First 2 Years Of The Pandemic, Troy Quast, Ross Andel, Sean Gregory, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Background: Prior estimates of the years of life lost (YLLs) in the USA associated with coronavirus disease 2019 (COVID-19) were 1.2 million through 11 July 2020 and 3.9 million through 31 January 2021 (which roughly coincides with the first full year of the pandemic). The aim of this study is to update YLL estimates through the first 2 years of the pandemic.

Methods: We employed data regarding COVID-19 deaths through 5 February 2022 by jurisdiction, gender and age group. We used actuarial life expectancy tables by gender and age to estimate YLLs.

Results: We estimated roughly 9.7 million YLLs due …