Medical Specialties Commons^™

Addressing Artificial Intelligence Bias In Retinal Diagnostics, Philippe Burlina, Neil Joshi, William Paul, Katia D Pacheco, Neil M Bressler

Faculty, Staff and Students Publications

PURPOSE: This study evaluated generative methods to potentially mitigate artificial intelligence (AI) bias when diagnosing diabetic retinopathy (DR) resulting from training data imbalance or domain generalization, which occurs when deep learning systems (DLSs) face concepts at test/inference time they were not initially trained on.

METHODS: The public domain Kaggle EyePACS dataset (88,692 fundi and 44,346 individuals, originally diverse for ethnicity) was modified by adding clinician-annotated labels and constructing an artificial scenario of data imbalance and domain generalization by disallowing training (but not testing) exemplars for images of retinas with DR warranting referral (DR-referable) from darker-skin individuals, who presumably have greater …

Efficacy And Safety Of The Mrna-1273 Sars-Cov-2 Vaccine, Lindsey R Baden, Hana M El Sahly, Brandon Essink, Karen Kotloff, Sharon Frey, Rick Novak, David Diemert, Stephen A Spector, Nadine Rouphael, C Buddy Creech, John Mcgettigan, Shishir Khetan, Nathan Segall, Joel Solis, Adam Brosz, Carlos Fierro, Howard Schwartz, Kathleen Neuzil, Larry Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, John Mascola, Laura Polakowski, Julie Ledgerwood, Barney S Graham, Hamilton Bennett, Rolando Pajon, Conor Knightly, Brett Leav, Weiping Deng, Honghong Zhou, Shu Han, Melanie Ivarsson, Jacqueline Miller, Tal Zaks, Cove Study Group

Faculty, Staff and Students Publications

BACKGROUND: Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.

METHODS: This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. …

Eosinophils Attenuate Hepatic Ischemia-Reperfusion Injury In Mice Through St2-Dependent Il-13 Production, Yaochun Wang, Yang Yang, Meng Wang, Shuhong Wang, Jong-Min Jeong, Long Xu, Yankai Wen, Christoph Emontzpohl, Constance Lynn Atkins, Kevin Duong, Nicolas F Moreno, Xiaoyi Yuan, David R Hall, Wasim Dar, Dechun Feng, Bin Gao, Yong Xu, Zoltan Czigany, Sean P Colgan, J Steve Bynon, Shizuo Akira, Jared M Brown, Holger K Eltzschig, Elizabeth A Jacobsen, Cynthia Ju

Faculty, Staff and Students Publications

Eosinophils are a myeloid cell subpopulation that mediates type 2 T helper cell immune responses. Unexpectedly, we identified a rapid accumulation of eosinophils in 22 human liver grafts after hepatic transplantation. In contrast, no eosinophils were detectable in healthy liver tissues before transplantation. Studies with two genetic mouse models of eosinophil deficiency and a mouse model of antibody-mediated eosinophil depletion revealed exacerbated liver injury after hepatic ischemia and reperfusion. Adoptive transfer of bone marrow-derived eosinophils normalized liver injury of eosinophil-deficient mice and reduced hepatic ischemia and reperfusion injury in wild-type mice. Mechanistic studies combining genetic and adoptive transfer approaches identified …

Pandemic Makes Chronic Disease Prevention A Priority., Karen S. Kmetik, Alexis Skoufalos, David B. Nash

College of Population Health Faculty Papers

This article is the authors' final version prior to publication in Population Health Management, Volume 24, Issue 1, February 2021, Pages 1-2

Final publication is available from Mary Ann Liebert, Inc., publishers https://doi.org/10.1089/pop.2020.0126

Defining The Genotypic And Phenotypic Spectrum Of X-Linked Msl3-Related Disorder, Theresa Brunet, Kirsty Mcwalter, Katharina Mayerhanser, Grace M Anbouba, Amy Armstrong-Javors, Ingrid Bader, Evan Baugh, Amber Begtrup, Caleb P Bupp, Bert L Callewaert, Anna Cereda, Margot A Cousin, Juan C Del Rey Jimenez, Laurie Demmer, Nikita R Dsouza, Nicole Fleischer, Ralitza H Gavrilova, Sumedha Ghate, Elisabeth Graf, Andrew Green, Sarah R Green, Maria Iascone, Ameni Kdissa, Dirk Klee, Eric W Klee, Emily Lancaster, Kristin Lindstrom, Johannes A Mayr, Meriel Mcentagart, Naomi J L Meeks, Dana Mittag, Harrison Moore, Anne K Olsen, Damara Ortiz, Gretchen Parsons, Loren D M Pena, Richard E Person, Sumit Punj, Gonzalo Alonso Ramos-Rivera, Maria J Guillen Sacoto, G Bradley Schaefer, Rhonda E Schnur, Tiana M Scott, Daryl A Scott, Carolyn R Serbinski, Vandana Shashi, Victoria Mok Siu, Barbro Fossøy Stadheim, Jennifer A Sullivan, Jana Švantnerová, Lea Velsher, David S Wargowski, Ingrid M Wentzensen, Dagmar Wieczorek, Juliane Winkelmann, Patrick Yap, Michael Zech, Michael T Zimmermann, Thomas Meitinger, Felix Distelmaier, Matias Wagner

Paediatrics Publications

PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome).

METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers.

RESULTS: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of …

Rapid Decline In Telestroke Consults In The Setting Of Covid-19., Syed O. Shah., Robin Dharia, Jaime Stazi, Maureen Deprince, Robert H. Rosenwasswer

Farber Institute for Neuroscience Faculty Papers

Background and Purpose: As coronavirus disease 2019 (COVID-19) continues to be a global pandemic, there is a growing body of evidence suggesting that incidence of diseases that require emergent care, particularly myocardial infarction and ischemic stroke, has declined rapidly. The objective of this study is to quantify our experience of telestroke (TS) consults at a large tertiary comprehensive stroke center during the COVID-19 pandemic.

Methods: We retrospectively reviewed TS consults of patients presenting to our neuroscience network. Those with a confirmed diagnosis of acute ischemic stroke or transient ischemia attack were included. Data were compared from April 1, 2019, to …

Computer Automation For Physics Chart Check Should Be Adopted In Clinic To Replace Manual Chart Checking For Radiotherapy, Edward L. Clouser, Quan Chen, Yi Rong

Radiation Medicine Faculty Publications

No abstract provided.

The Quest For Conquering Covid-19: Updates From The Laboratory, David B. Nash

College of Population Health Faculty Papers

No abstract provided.

Hyperlipasemia And Potential Pancreatic Injury Patterns In Covid-19: A Marker Of Severity Or Innocent Bystander?, Hemant Goyal, Sonali Sachdeva, Abhilash Perisetti Md, Rupinder Mann, Sumant Inamdar, Benjamin Tharian

Other Specialties

No abstract provided.

Parenteral Lipid Emulsions Induce Unique Ileal Fatty Acid And Metabolomic Profiles But Do Not Increase The Risk Of Necrotizing Enterocolitis In Preterm Pigs, William Yakah, Pratibha Singh, Joanne Brown, Barbara Stoll, Doug Burrin, Muralidhar H Premkumar, Hasan H Otu, Xuesong Gu, Simon T Dillon, Towia A Libermann, Steven D Freedman, Camilia R Martin

Children’s Nutrition Research Center Staff Publications

Necrotizing enterocolitis (NEC) is a manifestation of maladaptive intestinal responses in preterm infants centrally medicated by unattenuated inflammation. Early in the postnatal period, preterm infants develop a deficit in arachidonic and docosahexaenoic acid, both potent regulators of inflammation. We hypothesized that the fatty acid composition of parenteral lipid emulsions uniquely induces blood and intestinal fatty acid profiles which, in turn, modifies the risk of NEC development. Forty-two preterm pigs were randomized to receive one of three lipid emulsions containing 100% soybean oil (SO), 15% fish oil (MO15), or 100% fish oil (FO100) with enteral feedings over an 8-day protocol. Blood …

Fructan-Sensitive Children With Irritable Bowel Syndrome Have Distinct Gut Microbiome Signatures, Bruno P Chumpitazi, Kristi L Hoffman, Daniel P Smith, Ann R Mcmeans, Salma Musaad, James Versalovic, Joseph F Petrosino, Robert J Shulman

Children’s Nutrition Research Center Staff Publications

Background: Dietary fructans may worsen gastrointestinal symptoms in children with irritable bowel syndrome (IBS).

Aim: To determine whether gut microbiome composition and function are associated with childhood IBS fructan-induced symptoms.

Methods: Faecal samples were collected from 38 children aged 7-17 years with paediatric Rome III IBS, who previously completied a double-blind, randomised, placebo-controlled crossover (fructan vs maltodextrin) trial. Fructan sensitivity was defined as an increase of ≥30% in abdominal pain frequency during the fructan diet. Gut microbial composition was determined via 16Sv4 rDNA sequencing. LEfSe evaluated taxonomic composition differences. Tax4Fun2 predicted microbial fructan metabolic pathways.

Results: At baseline, 17 fructan-sensitive …

Acute Respiratory Distress Syndrome, George W Williams, Nathaniel K Berg, Alexander Reskallah, Xiaoyi Yuan, Holger K Eltzschig

Faculty, Staff and Student Publications

Acute Respiratory Distress Syndrome (ARDS) is defined as the rapid onset of non-cardiogenic pulmonary edema resulting in respiratory failure and hypoxemia. Efforts over the past 25 years, such as those of the ARDS and Prevention and Early Treatment of Acute Lung Injury (PETAL) Networks, have demonstrated a praiseworthy collaboration to further optimize the management of ARDS. However, improvements have been only moderate and ARDS remains a leading cause of mortality in the perioperative and critical care setting. Recently, the significant morbidity and mortality of ARDS have been emphasized by its high incidence in Coronavirus Disease 2019 (COVID-19) patients. A major …

Prediction Model For Freedom From Tlr From A Multi-Study Analysis Of Long-Term Results With The Zilver Ptx Drug-Eluting Peripheral Stent., Michael D Dake, Fabrizio Fanelli, Aaron E Lottes, Erin E O'Leary, Heidi Reichert, Xiaohui Jiang, Weiguo Fu, Osamu Iida, Kan Zen, Marc Schermerhorn, Thomas Zeller, Gary M Ansel

Heart and Vascular Articles

PURPOSE: Develop a prediction model to determine the impact of patient and lesion factors on freedom from target lesion revascularization (ffTLR) for patients who are candidates for Zilver PTX drug-eluting stent (DES) treatment for femoropopliteal lesions.

METHODS: Patient factors, lesion characteristics, and TLR results from five global studies were utilized for model development. Factors potentially associated with TLR (sex, age, diabetes, hypertension, hypercholesterolemia, renal disease, smoking status, Rutherford classification, lesion length, reference vessel diameter (RVD), popliteal involvement, total occlusion, calcification severity, prior interventions, and number of runoff vessels) were analyzed in a Cox proportional hazards model. Probability of ffTLR was …

Levonorgestrel Intrauterine Device Use For Medical Indications In Nulliparous Adolescents And Young Adults., Beth I Schwartz, Morgan Alexander, Lesley L Breech

Department of Obstetrics and Gynecology Faculty Papers

PURPOSE: Intrauterine devices (IUDs) are highly effective at preventing pregnancy. Levonorgestrel (LNG) IUDs also have beneficial effects on menstrual bleeding and abdominal and pelvic pain. Although there are increasing data on use of IUDs for contraception in adolescents and for medical indications in adults, there are extremely limited data on LNG IUD use for medical indications in adolescents. Our objective is to describe the characteristics and experiences of LNG IUD use in nulliparous adolescents and young women using IUDs for medical indications.

METHODS: We conducted a retrospective chart review of all nulliparous patients aged 22 years and younger who underwent …

Intestinal Stem Cell-Derived Enteroids From Morbidly Obese Patients Preserve Obesity-Related Phenotypes: Elevated Glucose Absorption And Gluconeogenesis, Nesrin M Hasan, Kelli F Johnson, Jianyi Yin, Nicholas W Baetz, Lea Fayad, Vadim Sherman, Sarah E Blutt, Mary K Estes, Vivek Kumbhari, Nicholas C Zachos, Olga Kovbasnjuk

Faculty, Staff and Students Publications

OBJECTIVE: The mechanisms behind the efficacy of bariatric surgery (BS) for treating obesity and type 2 diabetes, particularly with respect to the influence of the small bowel, remain poorly understood. In vitro and animal models are suboptimal with respect to their ability to replicate the human intestinal epithelium under conditions induced by obesity. Human enteroids have the potential to accelerate the development of less invasive anti-obesity therapeutics if they can recapitulate the pathophysiology of obesity. Our aim was to determine whether adult stem cell-derived enteroids preserve obesity-characteristic patient-specific abnormalities in carbohydrate absorption and metabolism.

METHODS: We established 24 enteroid lines …

Relation Of Magnetic Resonance Imaging Based Arterial Signal Enhancement To Markers Of Peripheral Artery Disease, Olga A Gimnich, Jonathan Holbrook, Tatiana Belousova, Christina M Short, Addison A Taylor, Vijay Nambi, Joel D Morrisett, Christie M Ballantyne, Jean Bismuth, Dipan J Shah, Gerd Brunner

Faculty, Staff and Students Publications

Peripheral artery disease (PAD) is associated with impaired lower extremity function. We hypothesized that contrast-enhanced magnetic resonance imaging (CE-MRI) based arterial signal enhancement (SE) measures are associated with markers of PAD. A total of 66 participants were enrolled, 10 were excluded due to incomplete data, resulting in 56 participants for the final analyses (36 PAD, 20 matched controls). MR imaging was performed postreactive hyperemia using bilateral thigh blood-pressure cuffs. First pass-perfusion images were acquired at the mid-calf region with a high-resolution saturation recovery gradient echo pulse sequence, and arterial SE was measured for the lower extremity arteries. As expected, peak …

Prevalence Of Gastric Intestinal Metaplasia In A Multiethnic Us Veterans Population, Theresa H Nguyen, Mimi C Tan, Yan Liu, Massimo Rugge, Aaron P Thrift, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: There is a need to identify individuals with gastric intestinal metaplasia, a precursor to gastric cancer, so they can be offered screening and surveillance. We examined the prevalence of gastric intestinal metaplasia, detected by upper endoscopy biopsy analysis, in different race and ethnic subgroups. We also investigated the extent to which Helicobacter pylori infection, with or without acute and chronic gastritis, accounts for observed associations between race or ethnicity and risk of gastric intestinal metaplasia.

METHODS: We used data from a cross-sectional study of consecutively recruited patients at the Michael E. DeBakey Veterans Affairs Medical Center in …

Links Between Thrombosis And Inflammation In Traumatic Brain Injury, W Brad Hubbard, Jing-Fei Dong, Miguel A Cruz, Rolando E Rumbaut

Faculty, Staff and Students Publications

Traumatic brain injury (TBI) continues to be a major healthcare problem and there is much to be explored regarding the secondary pathobiology to identify early predictive markers and new therapeutic targets. While documented changes in thrombosis and inflammation in major trauma have been well described, growing evidence suggests that isolated TBI also results in systemic alterations in these mechanisms. Here, we review recent experimental and clinical findings that demonstrate how blood-brain barrier dysfunction, systemic immune response, inflammation, platelet activation, and thrombosis contribute significantly to the pathogenesis of TBI. Despite advances in the links between thrombosis and inflammation, there is a …

X-Aptamers Targeting Thy-1 Membrane Glycoprotein In Pancreatic Ductal Adenocarcinoma, Hongyu Wang, Xin Li, Lisa A Lai, Teresa A Brentnall, David W Dawson, Kimberly A Kelly, Ru Chen, Sheng Pan

Faculty, Staff and Students Publications

Modified DNA aptamers incorporated with amino-acid like side chains or drug-like ligands can offer unique advantages and enhance specificity as affinity ligands. Thy-1 membrane glycoprotein (THY1 or CD90) was previously identified as a biomarker candidate of neovasculature in pancreatic ductal adenocarcinoma (PDAC). The current study developed and evaluated modified DNA X-aptamers targeting THY1 in PDAC. The expression and glycosylation of THY1 in PDAC tumor tissues were assessed using immunohistochemistry and quantitative proteomics. Bead-based X-aptamer library that contains 108 different sequences was used to screen for high affinity THY1 X-aptamers. The sequences of the X-aptamers were analyzed with the next-generation sequencing. …

Association Of Baseline Characteristics With Insulin Sensitivity And Β-Cell Function In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study Cohort, Neda Rasouli, Naji Younes, Kristina M Utzschneider, Silvio E Inzucchi, Ashok Balasubramanyam, Andrea L Cherrington, Faramarz Ismail-Beigi, Robert M Cohen, Darin E Olson, Ralph A Defronzo, William H Herman, John M Lachin, Steven E Kahn, Grade Research Group

Faculty, Staff and Students Publications

OBJECTIVE: We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA

RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosedβ-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI).

RESULTS: The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m

CONCLUSIONS: In the …

Prevalence Of Barrett’S Esophagus And Performance Of Societal Screening Guidelines In An Unreferred Primary Care Population Of Us Veterans, Theresa H Nguyen, Aaron P Thrift, Massimo Rugge, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Less than 10% of patients diagnosed with esophageal adenocarcinoma have a pre-existing Barrett's esophagus (BE) diagnosis, possibly because of suboptimal performance of guidelines. We examined the prevalence of BE in a previously unscreened primary care population and the potential yield of practice BE screening guidelines.

METHODS: This was a retrospective analysis of a prospective cross-sectional study of consecutively recruited unreferred patients from primary care clinics who underwent study upper endoscopy. We examined the performance of BE screening guidelines of the European Society of Gastrointestinal Endoscopy (ESGE), British Society of Gastroenterology (BSG), American Society for Gastrointestinal Endoscopy (ASGE), …

Association Of Baseline Characteristics With Insulin Sensitivity And Β-Cell Function In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study Cohort, Neda Rasouli, Naji Younes, Kristina M Utzschneider, Silvio E Inzucchi, Ashok Balasubramanyam, Andrea L Cherrington, Faramarz Ismail-Beigi, Robert M Cohen, Darin E Olson, Ralph A Defronzo, William H Herman, John M Lachin, Steven E Kahn

Faculty, Staff and Students Publications

OBJECTIVE: We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA

RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosedβ-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI).

RESULTS: The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m

CONCLUSIONS: In the …

Prevalence Of Functional Limitation In Covid-19 Recovered Patients Using The Post Covid-19 Functional Status Scale, Pankaj Pant, Aishana Joshi, Babin Basnet, Bibek Man Shrestha, Navindra Raj Bista, Niraj Bam, Santa Kumar Das

Faculty, Staff and Student Publications

INTRODUCTION: COVID-19 is an emerging global health pandemic causing tremendous morbidity and mortality worldwide. Chronic symptoms progressing to poor functional status have been reported in a substantial proportion of COVID-19 patients worldwide. This study aimed to determine the prevalence of functional limitation in COVID-19 recovered patients using the post-COVID-19 functional status scale.

METHODS: A descriptive cross-sectional study was conducted at Tribhuvan University Teaching Hospital. COVID-19 recovered patients with reverse transcription-polymerase chain reaction negative status were included and assessed using the post-COVID-19 functional status scale. Data entry and analysis was done in Statistical Package for the Social Sciences version 20.0. Descriptive …

Conformation-Dependent Blockage Of Activated Vwf Improves Outcomes Of Traumatic Brain Injury In Mice, Xin Xu, Chenyu Wang, Yingang Wu, Katie Houck, Tristan Hilton, Ashley Zhou, Xiaoping Wu, Cha Han, Mengchen Yang, Wei Yang, Fu-Dong Shi, Moritz Stolla, Miguel A Cruz, Min Li, Jianning Zhang, Jing-Fei Dong

Faculty, Staff and Students Publications

Traumatic brain injury-induced coagulopathy (TBI-IC) causes life-threatening secondary intracranial bleeding. Its pathogenesis differs mechanistically from that of coagulopathy arising from extracranial injuries and hemorrhagic shock, but it remains poorly understood. We report results of a study designed to test the hypothesis that von Willebrand factor (VWF) released during acute TBI is intrinsically hyperadhesive because its platelet-binding A1-domain is exposed and contributes to TBI-induced vascular leakage and consumptive coagulopathy. This hyperadhesive VWF can be selectively blocked by a VWF A2-domain protein to prevent TBI-IC and to improve neurological function with a minimal risk of bleeding. We demonstrated that A2 given through …

New Insights And Enhanced Human Norovirus Cultivation In Human Intestinal Enteroids, Khalil Ettayebi, Victoria R Tenge, Nicolas W Cortes-Penfield, Sue E Crawford, Frederick H Neill, Xi-Lei Zeng, Xiaomin Yu, B Vijayalakshmi Ayyar, Douglas Burrin, Sasirekha Ramani, Robert L Atmar, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are the leading cause of epidemic and sporadic acute gastroenteritis worldwide. We previously demonstrated human intestinal stem cell-derived enteroids (HIEs) support cultivation of several HuNoV strains. However, HIEs did not support virus replication from every HuNoV-positive stool sample, which led us to test and optimize new medium conditions, identify characteristics of stool samples that allow replication, and evaluate consistency of replication over time. Optimization of our HIE-HuNoV culture system has shown the following: (i) a new HIE culture medium made with conditioned medium from a single cell line and commercial media promotes robust replication of HuNoV strains …

An Analytical Expression For R50% Dependent On Ptv Surface Area And Volume: A Cranial Srs Comparison, Dharmin D. Desai, Ellis Lee Johnson, Ivan L. Cordrey

Radiation Medicine Faculty Publications

The intermediate dose spill for a stereotactic radiosurgery (SRS) plan can be quantified with the metric R50%, defined as the 50% isodose cloud volume (V_IDC50%) divided by the volume of the planning target volume (PTV). By coupling sound physical principles with the basic definition of R50%, we derive an analytical expression for R50% for a spherical PTV. Our analytical expression depends on three quantities: the surface area of PTV (SA_PTV), the volume of PTV (V_PTV), and the distance of dose drop-off to 50% (Δr). The value of ∆r was obtained from a simple set …

Clinical Performance Of The Point-Of-Care Cobas Liat For Detection Of Sars-Cov-2 In 20 Minutes: A Multicenter Study., Glen Hansen, Jamie Marino, Zi-Xuan Wang, Kathleen G Beavis, John Rodrigo, Kylie Labog, Lars F Westblade, Run Jin, Nedra Love, Karen Ding, Sachin Garg, Alan Huang, Joanna Sickler, Nam K Tran

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Highly accurate testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the point of care (POC) is an unmet diagnostic need in emergency care and time-sensitive outpatient care settings. Reverse transcription-PCR (RT-PCR) technology is the gold standard for SARS-CoV-2 diagnostics. We performed a multisite U.S. study comparing the clinical performance of the first U.S. Food and Drug Administration (FDA)-authorized POC RT-PCR for detection of SARS-CoV-2 in 20 min, the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test, to the most widely used RT-PCR laboratory test, the cobas 68/8800 SARS-CoV-2 test. Clinical nasopharyngeal swab specimens from 444 patients with …

Spliceosome-Targeted Therapies Trigger An Antiviral Immune Response In Triple-Negative Breast Cancer, Elizabeth A Bowling, Jarey H Wang, Fade Gong, William Wu, Nicholas J Neill, Ik Sun Kim, Siddhartha Tyagi, Mayra Orellana, Sarah J Kurley, Rocio Dominguez-Vidaña, Hsiang-Ching Chung, Tiffany Y-T Hsu, Julien Dubrulle, Alexander B Saltzman, Heyuan Li, Jitendra K Meena, Gino M Canlas, Srinivas Chamakuri, Swarnima Singh, Lukas M Simon, Calla M Olson, Lacey E Dobrolecki, Michael T Lewis, Bing Zhang, Ido Golding, Jeffrey M Rosen, Damian W Young, Anna Malovannaya, Fabio Stossi, George Miles, Matthew J Ellis, Lihua Yu, Silvia Buonamici, Charles Y Lin, Kristen L Karlin, Xiang H-F Zhang, Thomas F Westbrook

Faculty, Staff and Students Publications

Many oncogenic insults deregulate RNA splicing, often leading to hypersensitivity of tumors to spliceosome-targeted therapies (STTs). However, the mechanisms by which STTs selectively kill cancers remain largely unknown. Herein, we discover that mis-spliced RNA itself is a molecular trigger for tumor killing through viral mimicry. In MYC-driven triple-negative breast cancer, STTs cause widespread cytoplasmic accumulation of mis-spliced mRNAs, many of which form double-stranded structures. Double-stranded RNA (dsRNA)-binding proteins recognize these endogenous dsRNAs, triggering antiviral signaling and extrinsic apoptosis. In immune-competent models of breast cancer, STTs cause tumor cell-intrinsic antiviral signaling, downstream adaptive immune signaling, and tumor cell death. Furthermore, RNA …

Identification Of 3-Chymotrypsin Like Protease (3clpro) Inhibitors As Potential Anti-Sars-Cov-2 Agents., Vicky Mody, Joanna Ho, Savannah Wills, Ahmed Mawri, Latasha Lawson, Maximilian C C J C Ebert, Guillaume M Fortin, Srujana Rayalam, Shashidharamurthy Taval

PCOM Scholarly Works

Emerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 …

Houston Hurricane Harvey Health (Houston-3h) Study: Assessment Of Allergic Symptoms And Stress After Hurricane Harvey Flooding, Abiodun O Oluyomi, Kristen Panthagani, Jesus Sotelo, Xiangjun Gu, Georgina Armstrong, Dan Na Luo, Kristi L Hoffman, Diana Rohlman, Lane Tidwell, Winifred J Hamilton, Elaine Symanski, Kimberly Anderson, Joseph F Petrosino, Cheryl Lyn Walker, Melissa Bondy

Faculty, Staff and Students Publications

BACKGROUND: In August 2017, Hurricane Harvey caused unprecedented flooding across the greater Houston area. Given the potential for widespread flood-related exposures, including mold and sewage, and the emotional and mental toll caused by the flooding, we sought to evaluate the short- and long-term impact of flood-related exposures on the health of Houstonians. Our objectives were to assess the association of flood-related exposures with allergic symptoms and stress among Houston-area residents at two time points: within approximately 30 days (T1) and 12 months (T2) after Hurricane Harvey's landfall.

METHODS: The Houston Hurricane Harvey Health (Houston-3H) Study enrolled a total of 347 …