Digital Commons Network^™

Radiologic-Pathologic Correlation Of Covid-19-Associated Acute Disseminated Encephalomyelitis, Amy Bezold, Huda Hussain, Julum Nwanze, James T Roberts, Kuang-Chun J Hsieh

Faculty, Staff and Students Publications

A 42-year-old woman presented with drooling, slurred speech, inability to walk and talk, and a recent positive COVID-19 test. She had two prior hospital admissions within the past week for similar symptoms with inconclusive evaluation. MRI of the brain demonstrated multifocal white matter hyperintense lesions on fluid-attenuated inversion recovery (FLAIR)/diffusion with variable enhancement. These imaging findings have been described in recent literature and are associated with inflammatory demyelinating disease, such as acute disseminated encephalomyelitis. The patient subsequently underwent a brain biopsy with a final diagnosis of inflammatory demyelinating lesion. To our knowledge, this is the first radiologic-pathologic correlation of COVID-19-associated …

It Is Time For A Paradigm Shift In Design, Execution, And Publishing Of Comparative Helicobacter Pylori Treatment Trials, David Y Graham

Faculty, Staff and Students Publications

No abstract provided.

Pediatric Vitamin D: Pseudo-Hypervitaminosis, Lily Olayinka, Izmarie Poventud-Fuentes, Emily Garnett, Sridevi Devaraj

Faculty, Staff and Students Publications

BACKGROUND: Vitamin D toxicity is rare in pediatric population. Falsely elevated levels of 25-hydroxyvitamin D have been reported as a major challenge with immunoassay methods for quantifying vitamin D metabolites.

CASE PRESENTATION AND METHOD: Here, we present two pediatric cases of falsely elevated 25-hydroxyvitamin D that resulted in unnecessary further testing. We also report significant same-day variation in the measurement of 25-hydroxyvitamin D using the Abbott i2000SR immunoassay. Samples were spun twice and their values were confirmed with the gold standard liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for confirmation.

CONCLUSION: The addition of a centrifugation step prior to sample testing …

Safety Endpoints With Vadadustat Versus Darbepoetin Alfa In Patients With Non-Dialysis-Dependent Ckd: A Post Hoc Regional Analysis Of The Pro, Wolfgang C Winkelmayer, Susan Arnold, Steven K Burke, Glenn M Chertow, Kai-Uwe Eckardt, Alan G Jardine, Eldrin F Lewis, Wenli Luo, Kunihiro Matsushita, Peter A Mccullough, Todd Minga, Patrick S Parfrey

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Prespecified analyses of the PRO

STUDY DESIGN: Phase 3, global, open-label, randomized, active-controlled clinical trial.

SETTING AND PARTICIPANTS: Erythropoiesis-stimulating agent-untreated patients with anemia and NDD-CKD.

INTERVENTION: Eligible patients were randomized 1:1 to receive vadadustat or darbepoetin alfa.

OUTCOMES: The primary safety end point was time to first MACE. Secondary safety end points included time to first expanded MACE (MACE plus hospitalization for heart failure or thromboembolic event, excluding vascular access thrombosis).

RESULTS: In the non-US/non-Europe region, there was a higher proportion of patients with baseline estimated glomerular filtration rate (eGFR) level of ≤10 mL/min/1.73 m

LIMITATIONS: Different …

Pdcl2 Is Essential For Sperm Acrosome Formation And Male Fertility In Mice, Yoshitaka Fujihara, Kiyonori Kobayashi, Ferheen Abbasi, Tsutomu Endo, Zhifeng Yu, Masahito Ikawa, Martin M Matzuk

Faculty, Staff and Students Publications

BACKGROUND: Each year, infertility affects 15% of couples worldwide, with 50% of cases attributed to men. Globozoospermia is an uncommon cause of male factor infertility, characterized by defects in sperm acrosome formation, leading to round-headed spermatozoa.

OBJECTIVE: We generated Pdcl2 knockout mice to investigate the essential roles of PDCL2 in mammalian reproduction.

MATERIALS AND METHODS: We used reverse transcription-polymerase chain reaction to demonstrate that PDCL2 was expressed exclusively in the male reproductive tract in mice and humans. We created Pdcl2 knockout mice using the CRISPR-Cas9 system and analyzed their fertility. Pdcl2 null spermatozoa underwent further evaluation using computer-assisted sperm analysis, …

Hyperphosphorylation Of The Group A Streptococcal Control Of Virulence Regulator Increases Promoter Occupancy Specifically At Virulence Factor-Encoding Genes, Nicola Horstmann, Chau Nguyen Tran, Anthony R Flores, Samuel A Shelburne

Faculty, Staff and Student Publications

The control of virulence two-component gene regulatory system (CovRS) is critical to the pathogenesis of many medically important streptococci. In emm1 group A streptococci (GAS), CovR directly binds the promoters of numerous GAS virulence factor-encoding genes. Elimination of CovS phosphatase activity increases CovR phosphorylation (CovR~P) levels and abrogates GAS virulence. Given the emm type-specific diversity of CovRS function, in this study we used chromatin immunoprecipitation sequencing (ChIP-seq) to define global CovR DNA occupancy in the wild-type emm3 strain MGAS10870 (medium CovR~P) and its CovS phosphatase-negative derivative 10870-CovS-T284A (high CovR~P). In the wild-type emm3 strain, 89% of the previously identified emm1 …

Infant Isolation And Cohorting For Preventing Or Reducing Transmission Of Healthcare-Associated Infections In Neonatal Units, Morcos Hanna, Rita Shah, Lucila Marquez, Rebecca Barzegar, Adrienne Gordon, Mohan Pammi

Faculty, Staff and Students Publications

BACKGROUND: Neonatal healthcare-associated infections (HAIs) result in increased morbidity and mortality, as well as increased healthcare costs. Patient isolation measures, i.e. single-room isolation or the cohorting of patients with similar infections, remain a recommended and commonly used practice for preventing horizontal spread of infections in the neonatal intensive care unit (NICU). OBJECTIVES: Our primary objective was to assess the effect of single-room isolation or cohorting, or both for preventing transmission of HAIs or colonization with HAI-causing pathogens in newborn infants less than six months of age admitted to the neonatal intensive care unit (NICU). Our secondary objective was to assess …

Drugging Evolution Of Antibiotic Resistance At A Regulatory Network Hub, Yin Zhai, John P Pribis, Sean W Dooling, Libertad Garcia-Villada, P J Minnick, Jun Xia, Jingjing Liu, Qian Mei, Devon M Fitzgerald, Christophe Herman, P J Hastings, Mauro Costa-Mattioli, Susan M Rosenberg

Faculty, Staff and Students Publications

Evolution of antibiotic resistance is a world health crisis, fueled by new mutations. Drugs to slow mutagenesis could, as cotherapies, prolong the shelf-life of antibiotics, yet evolution-slowing drugs and drug targets have been underexplored and ineffective. Here, we used a network-based strategy to identify drugs that block hubs of fluoroquinolone antibiotic-induced mutagenesis. We identify a U.S. Food and Drug Administration- and European Medicines Agency-approved drug, dequalinium chloride (DEQ), that inhibits activation of the

Researching Covid To Enhance Recovery (Recover) Adult Study Protocol: Rationale, Objectives, And Design, Leora I Horwitz, Tanayott Thaweethai, Shari B Brosnahan, Mine S Cicek, Megan L Fitzgerald, Jason D Goldman, Rachel Hess, S L Hodder, Vanessa L Jacoby, Michael R Jordan, Jerry A Krishnan, Adeyinka O Laiyemo, Torri D Metz, Lauren Nichols, Rachel E Patzer, Anisha Sekar, Nora G Singer, Lauren E Stiles, Barbara S Taylor, Shifa Ahmed, Heather A Algren, Khamal Anglin, Lisa Aponte-Soto, Hassan Ashktorab, Ingrid V Bassett, Brahmchetna Bedi, Nahid Bhadelia, Christian Bime, Marie-Abele C Bind, Lora J Black, Andra L Blomkalns, Hassan Brim, Mario Castro, James Chan, Alexander W Charney, Benjamin K Chen, Li Qing Chen, Peter Chen, David Chestek, Lori B Chibnik, Dominic C Chow, Helen Y Chu, Rebecca G Clifton, Shelby Collins, Maged M Costantine, Sushma K Cribbs, Steven G Deeks, John D Dickinson, Sarah E Donohue, Matthew S Durstenfeld, Ivette F Emery, Kristine M Erlandson, Julio C Facelli, Rachael Farah-Abraham, Aloke V Finn, Melinda S Fischer, Valerie J Flaherman, Judes Fleurimont, Vivian Fonseca, Emily J Gallagher, Jennifer C Gander, Maria Laura Gennaro, Kelly S Gibson, Minjoung Go, Steven N Goodman, Joey P Granger, Frank L Greenway, John W Hafner, Jenny E Han, Michelle S Harkins, Kristine S P Hauser, James R Heath, Carla R Hernandez, On Ho, Matthew K Hoffman, Susan E Hoover, Carol R Horowitz, Harvey Hsu, Priscilla Y Hsue, Brenna L Hughes, Prasanna Jagannathan, Judith A James, Janice John, Sarah Jolley, S E Judd, Joy J Juskowich, Diane G Kanjilal, Elizabeth W Karlson, Stuart D Katz, J Daniel Kelly, Sara W Kelly, Arthur Y Kim, John P Kirwan, Kenneth S Knox, Andre Kumar, Michelle F Lamendola-Essel, Margaret Lanca, Joyce K Lee-Lannotti, R Craig Lefebvre, Bruce D Levy, Janet Y Lin, Brian P Logarbo, Jennifer K Logue, Michele T Longo, Carlos A Luciano, Karen Lutrick, Shahdi K Malakooti, Gail Mallett, Gabrielle Maranga, Jai G Marathe, Vincent C Marconi, Gailen D Marshall, Christopher F Martin, Jeffrey N Martin, Heidi T May, Grace A Mccomsey, Dylan Mcdonald, Hector Mendez-Figueroa, Lucio Miele, Murray A Mittleman, Sindhu Mohandas, Christian Mouchati, Janet M Mullington, Girish N Nadkarni, Erica R Nahin, Robert B Neuman, Lisa T Newman, Amber Nguyen, Janko Z Nikolich, Igho Ofotokun, Princess U Ogbogu, Anna Palatnik, Kristy T S Palomares, Tanyalak Parimon, Samuel Parry, Sairam Parthasarathy, Thomas F Patterson, Ann Pearman, Michael J Peluso, Priscilla Pemu, Christian M Pettker, Beth A Plunkett, Kristen Pogreba-Brown, Athena Poppas, J Zachary Porterfield, John G Quigley, Davin K Quinn, Hengameh Raissy, Candida J Rebello, Uma M Reddy, Rebecca Reece, Harrison T Reeder, Franz P Rischard, Johana M Rosas, Clifford J Rosen, Nadine G Rouphael, Dwight J Rouse, Adam M Ruff, Christina Saint Jean, Grecio J Sandoval, Jorge L Santana, Shannon M Schlater, Frank C Sciurba, Caitlin Selvaggi, Sudha Seshadri, Howard D Sesso, Dimpy P Shah, Eyal Shemesh, Zaki A Sherif, Daniel J Shinnick, Hyagriv N Simhan, Upinder Singh, Amber Sowles, Vignesh Subbian, Jun Sun, Mehul S Suthar, Larissa J Teunis, John M Thorp, Amberly Ticotsky, Alan T N Tita, Robin Tragus, Katherine R Tuttle, Alfredo E Urdaneta, P J Utz, Timothy M Vanwagoner, Andrew Vasey, Suzanne D Vernon, Crystal Vidal, Tiffany Walker, Honorine D Ward, David E Warren, Ryan M Weeks, Steven J Weiner, Jordan C Weyer, Jennifer L Wheeler, Sidney W Whiteheart, Zanthia Wiley, Natasha J Williams, Juan P Wisnivesky, John C Wood, Lynn M Yee, Natalie M Young, Sokratis N Zisis, Andrea S Foulkes

Faculty, Staff and Student Publications

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. …

Pentoxifylline For Treatment Of Sepsis And Necrotising Enterocolitis In Neonates, Mohan Pammi, Khalid N Haque

Faculty, Staff and Students Publications

BACKGROUND: Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015.

OBJECTIVES: To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC.

SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We …

Gata6-As1 Regulates Intestinal Epithelial Mitochondrial Functions, And Its Reduced Expression Is Linked To Intestinal Inflammation And Less Favourable Disease Course In Ulcerative Colitis, Katya E Sosnovski, Tzipi Braun, Amnon Amir, Danielle Moshel, Marina Benshoshan, Kelli L Vandussen, Nina Levhar, Haya Abbas-Egbariya, Katia Beider, Rakefet Ben-Yishay, Syed Asad Ali, Sean R Moore, Subra Kugathasan, Ifat Abramovich, Efrat Glick Saar, Batya Weiss, Iris Barshack, Eyal Gottlieb, Tamar Geiger, Shomron Ben-Horin, Igor Ulitsky, Jeffrey S Hyams, Lee A Denson, Yael Haberman

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Widespread dysregulation of long non-coding RNAs [lncRNAs] including a reduction in GATA6-AS1 was noted in inflammatory bowel disease [IBD]. We previously reported a prominent inhibition of epithelial mitochondrial functions in ulcerative colitis [UC]. However, the connection between reduction of GATA6-AS1 expression and attenuated epithelial mitochondrial functions was not defined.

METHODS: Mucosal transcriptomics was used to conform GATA6-AS1 reduction in several treatment-naïve independent human cohorts [n=673]. RNA pull-down followed by mass spectrometry was used to determine the GATA6-AS1 interactome. Metabolomics and mitochondrial respiration following GATA6-AS1 silencing in Caco-2 cells were used to elaborate on GATA6-AS1 functions.

RESULTS: GATA6-AS1 …

Tonb-Dependent Receptor Protein Displayed On Spores Of Bacillus Subtilis Stimulates Protective Immune Responses Against Acinetobacter Baumannii, Nor-Aziyah Matrahim, Kathryn Marie Jones, Brian P Keegan, Ulrich Strych, Bin Zhan, Hai-Yen Lee, Sazaly Abubakar

Faculty, Staff and Students Publications

The emergence of antibiotic-resistant Acinetobacter baumannii strains with limited treatment options has become a significant global health concern. Efforts to develop vaccines against the bacteria have centred on several potential protein targets, including the TonB-dependent receptors (TBDRs). In the present study, TBDRs from A. baumannii were displayed on the surface of Bacillus subtilis spores. The immunogenicity of the recombinant spores was evaluated in orally vaccinated mice. None of the immunized mice demonstrated signs of illness and were observed to be healthy throughout the study. Sera and the intestinal secretions from the recombinant spores-treated mice demonstrated mucosal and humoral antibody responses …

Coronavirus Disease 2019 Convalescent Plasma Outpatient Therapy To Prevent Outpatient Hospitalization: A Meta-Analysis Of Individual Participant Data From 5 Randomized Trials, Adam C Levine, Yuriko Fukuta, Moises A Huaman, Jiangda Ou, Barry R Meisenberg, Bela Patel, James H Paxton, Daniel F Hanley, Bart J A Rijnders, Arvind Gharbharan, Casper Rokx, Jaap Jan Zwaginga, Andrea Alemany, Oriol Mitjà, Dan Ouchi, Pere Millat-Martinez, Valerie Durkalski-Mauldin, Frederick K Korley, Larry J Dumont, Clifton W Callaway, Romina Libster, Gonzalo Perez Marc, Diego Wappner, Ignacio Esteban, Fernando Polack, David J Sullivan

Faculty, Staff and Students Publications

BACKGROUND: Outpatient monoclonal antibodies are no longer effective and antiviral treatments for coronavirus disease 2019 (COVID-19) disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma (CCP) is promising, clinical trials among outpatients have shown mixed results.

METHODS: We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching Medline, Embase, medRxiv, World Health Organization COVID-19 Research Database, Cochrane Library, and Web of Science from January 2020 to September 2022.

RESULTS: Five included studies from 4 …

Strict Conservation Yet Non-Essential Nature Of Plasmid Gene Bba40 In The Lyme Disease Spirochete Borrelia Burgdorferi, Irene N Kasumba, Kit Tilly, Tao Lin, Steven J Norris, Patricia A Rosa

Faculty, Staff and Student Publications

The highly segmented genome of Borrelia burgdorferi, the tick-borne bacterium that causes Lyme disease, is composed of a linear chromosome and more than 20 co-existing endogenous plasmids. Many plasmid-borne genes are unique to B. burgdorferi and some have been shown to provide essential functions at discrete points of the infectious cycle between a tick vector and rodent host. In this study, we investigated the role of

Colocalization Of Linezolid Resistance (Cfr) And Virulence Factors Cytolysin And Hemolysin (Cln And Hln) On A Plasmid In Enterococcus Faecalis, Nikita V Singh, Kavindra V Singh, An Q Dinh, Cesar A Arias, William C Shropshire, Blake M Hanson, Barbara E Murray

Faculty, Staff and Student Publications

No abstract provided.

Stroke Survivors' Telemedicine Experiences During The Covid-19 Pandemic: A Phenomenological Investigation, Irene N Kasumba, Kit Tilly, Tao Lin, Steven J Norris, Patricia A Rosa

Faculty, Staff and Student Publications

The highly segmented genome of Borrelia burgdorferi, the tick-borne bacterium that causes Lyme disease, is composed of a linear chromosome and more than 20 co-existing endogenous plasmids. Many plasmid-borne genes are unique to B. burgdorferi and some have been shown to provide essential functions at discrete points of the infectious cycle between a tick vector and rodent host. In this study, we investigated the role of bba40, a highly conserved and differentially expressed gene on a ubiquitous linear plasmid of B. burgdorferi. In a prior genome-wide analysis, inactivation of bba40 by transposon insertion was linked with a …

Contribution Of The Oral And Gastrointestinal Microbiomes To Bloodstream Infections In Leukemia Patients, Stephanie Mcmahon, Pranoti Sahasrabhojane, Jiwoong Kim, Samantha Franklin, Chia-Chi Chang, Robert R Jenq, Andrew E Hillhouse, Samuel A Shelburne, Jessica Galloway-Peña

Faculty, Staff and Student Publications

Bloodstream infections (BSIs) pose a significant mortality risk for acute myeloid leukemia (AML) patients. It has been previously reported that intestinal domination (>30% relative abundance [RA] attributed to a single taxon) with the infecting taxa often precedes BSI in stem cell transplant patients. Using 16S rRNA amplicon sequencing, we analyzed oral and stool samples from 63 AML patients with BSIs to determine the correlation between the infectious agent and microbiome composition. Whole-genome sequencing and antimicrobial susceptibilities were performed on all BSI isolates. Species-level detection of the infectious agent and presence of antibiotic resistance determinants in the stool (

Microbiome Alterations Driven By Trypanosoma Cruzi Infection In Two Disjunctive Murine Models, Sergio Castañeda, Marina Muñoz, Peter J Hotez, Maria Elena Bottazzi, Alberto E Paniz-Mondolfi, Kathryn M Jones, Rojelio Mejia, Cristina Poveda, Juan David Ramírez

Faculty, Staff and Students Publications

Alterations caused by Trypanosoma cruzi in the composition of gut microbiome may play a vital role in the host-parasite interactions that shapes physiology and immune responses against infection. Thus, a better understanding of this parasite-host-microbiome interaction may yield relevant information in the comprehension of the pathophysiology of the disease and the development of new prophylactic and therapeutic alternatives. Therefore, we implemented a murine model with two mice strains (BALB/c and C57BL/6) to evaluate the impact of Trypanosoma cruzi (Tulahuen strain) infection on the gut microbiome utilizing cytokine profiling and shotgun metagenomics. Higher parasite burdens were observed in cardiac and intestinal …

Microbiome Alteration Via Fecal Microbiota Transplantation Is Effective For Refractory Immune Checkpoint Inhibitor-Induced Colitis, Taylor M Halsey, Anusha S Thomas, Tomo Hayase, Weijie Ma, Hamzah Abu-Sbeih, Baohua Sun, Edwin Roger Parra, Zhi-Dong Jiang, Herbert L Dupont, Christopher Sanchez, Rawan El-Himri, Alexandria Brown, Ivonne Flores, Lauren Mcdaniel, Miriam Ortega Turrubiates, Matthew Hensel, Dung Pham, Stephanie S Watowich, Eiko Hayase, Chia-Chi Chang, Robert R Jenq, Yinghong Wang

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy. All 12 patients had grade 3 or 4 ICI-related diarrhea or colitis that failed to respond to standard first-line (corticosteroids) and second-line …

Neurocognitive Dysfunction With Neuronal Injury In People With Hiv On Long-Duration Antiretroviral Therapy, Cynthia Mcmahan, Devon K Dietrich, Elizabeth F Horne, Erin Kelly, Katrina Geannopoulos, Peter Selim Siyahhan Julnes, Lillian Ham, Ulisses Santamaria, Chuen-Yen Lau, Tianxia Wu, Hsing-Chuan Hsieh, Anuradha Ganesan, Catherine Berjohn, Suad Kapetanovic, Daniel S Reich, Govind Nair, Joseph Snow, Brian K Agan, Avindra Nath, Bryan R Smith

Staff and Researcher Publications

Background and objectives: Neurologic outcomes in people with HIV (PWH) on long-duration antiretroviral therapy (ART) are not fully understood, and the underlying pathophysiology is unclear. To address this, we established a cohort of such individuals and compared them with HIV-negative controls using a novel matching technique. Both groups underwent extensive cognitive testing, evaluation for psychiatric measures, and MRI and CSF analyses.

Methods: Participants underwent comprehensive neuropsychological testing and completed standardized questionnaires measuring depressive symptoms, perceptions of own functioning, and activities of daily living as part of an observational study. Brain MRI and lumbar puncture were optional. Coarsened Exact Matching was …

Plumbing Mysterious Rnas In “Dark Genome” For The Conquest Of Human Diseases, Lisa A Huang, Chunru Lin, Liuqing Yang

Faculty, Staff and Student Publications

Next-generation sequencing has revealed that less than 2% of transcribed genes are translated into proteins, with a large portion transcribed into noncoding RNAs (ncRNAs). Among these, long noncoding RNAs (lncRNAs) represent the largest group and are pervasively transcribed throughout the genome. Dysfunctions in lncRNAs have been found in various diseases, highlighting their potential as therapeutic, diagnostic, and prognostic targets. However, challenges, such as unknown molecular mechanisms and nonspecific immune responses, and issues of drug specificity and delivery present obstacles in translating lncRNAs into clinical applications. In this review, we summarize recent publications that have explored lncRNA functions in human diseases. …

Mapping Human Norovirus Antigens During Infection Reveals The Breadth Of The Humoral Immune Response, Lynn Su, Wanzhi Huang, Frederick H Neill, Mary K Estes, Robert L Atmar, Timothy Palzkill

Faculty, Staff and Students Publications

Human noroviruses (HuNoV) are the leading cause of acute gastroenteritis worldwide. The humoral immune response plays an important role in clearing HuNoV infections and elucidating the antigenic landscape of HuNoV during an infection can shed light on antibody targets to inform vaccine design. Here, we utilized Jun-Fos-assisted phage display of a HuNoV genogroup GI.1 genomic library and deep sequencing to simultaneously map the epitopes of serum antibodies of six individuals infected with GI.1 HuNoV. We found both unique and common epitopes that were widely distributed among both nonstructural proteins and the major capsid protein. Recurring epitope profiles suggest immunodominant antibody …

An Epidemic Model With Time Delays Determined By The Infectivity And Disease Durations, Masoud Saade, Samiran Ghosh, Malay Banerjee, Vitaly Volpert

Faculty, Staff and Student Publications

We propose an epidemiological model with distributed recovery and death rates. It represents an integrodifferential system of equations for susceptible, exposed, infectious, recovered and dead compartments. This model can be reduced to the conventional ODE model under the assumption that recovery and death rates are uniformly distributed in time during disease duration. Another limiting case, where recovery and death rates are given by the delta-function, leads to a new point-wise delay model with two time delays corresponding to the infectivity period and disease duration. Existence and positiveness of solutions for the distributed delay model and point-wise delay model are proved. …

Representing And Utilizing Clinical Textual Data For Real World Studies: An Ohdsi Approach, Vipina K Keloth, Juan M Banda, Michael Gurley, Paul M Heider, Georgina Kennedy, Hongfang Liu, Feifan Liu, Timothy Miller, Karthik Natarajan, Olga V Patterson, Yifan Peng, Kalpana Raja, Ruth M Reeves, Masoud Rouhizadeh, Jianlin Shi, Xiaoyan Wang, Yanshan Wang, Wei-Qi Wei, Andrew E Williams, Rui Zhang, Rimma Belenkaya, Christian Reich, Clair Blacketer, Patrick Ryan, George Hripcsak, Noémie Elhadad, Hua Xu

Faculty, Staff and Student Publications

Clinical documentation in electronic health records contains crucial narratives and details about patients and their care. Natural language processing (NLP) can unlock the information conveyed in clinical notes and reports, and thus plays a critical role in real-world studies. The NLP Working Group at the Observational Health Data Sciences and Informatics (OHDSI) consortium was established to develop methods and tools to promote the use of textual data and NLP in real-world observational studies. In this paper, we describe a framework for representing and utilizing textual data in real-world evidence generation, including representations of information from clinical text in the Observational …

A Highly Selective Humanized Ddr1 Mab Reverses Immune Exclusion By Disrupting Collagen Fiber Alignment In Breast Cancer, Junquan Liu, Huai-Chin Chiang, Wei Xiong, Victor Laurent, Samuel C Griffiths, Jasmin Dülfer, Hui Deng, Xiujie Sun, Y Whitney Yin, Wenliang Li, Laurent P Audoly, Zhiqiang An, Thomas Schürpf, Rong Li, Ningyan Zhang

Faculty, Staff and Student Publications

BACKGROUND: Immune exclusion (IE) where tumors deter the infiltration of immune cells into the tumor microenvironment has emerged as a key mechanism underlying immunotherapy resistance. We recently reported a novel role of discoidin domain-containing receptor 1 (DDR1) in promoting IE in breast cancer and validated its critical role in IE using neutralizing rabbit monoclonal antibodies (mAbs) in multiple mouse tumor models.

METHODS: To develop a DDR1-targeting mAb as a potential cancer therapeutic, we humanized mAb9 with a complementarity-determining region grafting strategy. The humanized antibody named PRTH-101 is currently being tested in a Phase 1 clinical trial. We determined the binding …

Predicting The Risk Of Alzheimer's Disease And Related Dementia In Patients With Mild Cognitive Impairment Using A Semi-Competing Risk Approach, Zhaoyi Chen, Yuchen Yang, Dazheng Zhang, Jingchuan Guo, Yi Guo, Xia Hu, Yong Chen, Jiang Bian

Faculty, Staff and Student Publications

Alzheimer's disease (AD) and AD-related dementias (AD/ADRD) are a group of progressive neurodegenerative diseases. The progression of AD can be conceptualized as a continuum in which patients progress from normal cognition to preclinical AD (i.e., no symptoms but biological changes in the brain) to mild cognitive impairment (MCI) due to AD (i.e., mild symptoms but not interfere with daily activities), followed by increasing severity of dementia due to AD. Early detection and prediction models for the transition of MCI to AD/ADRD are needed, and efforts have been made to build predictions of MCI conversion to AD/ADRD. However, most existing studies …

Ocular Toxicity Profile Of Targeted Cancer Therapy (Tct) At A Us Tertiary Cancer Center, Moe Ameri, Nagham Al Zubidi, Azadeh Razmandi, Andrew Whyte, Aung Naing, Nimisha A Patel, Dan S Gombos

Faculty, Staff and Student Publications

PURPOSE: Targeted cancer therapy (TCT) is a significant advancement in oncology with promising survival improvement in patients with cancer and remarkable effects on various cancers. There is evidence suggesting a connection between specific TCT classes and the occurrence of immune-related adverse events (irAEs). Our study aims to investigate the potential ocular toxicities of different classes of TCT, provide a better understanding of these toxicities, and aid in the future development of screening and management recommendations for ocular irAEs.

DESIGN: Retrospective observational case series.

PARTICIPANTS: Only ocular immune-related AEs were included in the study; patients on TCT who received a new …

Factors, Enablers And Challenges For Covid-19 Vaccine Development, Jean-Louis Excler, Melanie Saville, Lois Privor-Dumm, Sarah Gilbert, Peter J Hotez, Didi Thompson, Salim Abdool-Karim, Jerome H Kim

Faculty, Staff and Students Publications

The COVID-19 pandemic triggered a sense of vulnerability and urgency that led to concerted actions by governments, funders, regulators and industry to overcome traditional challenges for the development of vaccine candidates and to reach authorisation. Unprecedented financial investments, massive demand, accelerated clinical development and regulatory reviews were among the key factors that contributed to accelerating the development and approval of COVID-19 vaccines. The rapid development of COVID-19 vaccines benefited of previous scientific innovations such as mRNA and recombinant vectors and proteins. This has created a new era of vaccinology, with powerful platform technologies and a new model for vaccine development. …

The Role Of Limch1 Alternative Splicing In Skeletal Muscle Function, Matthew S Penna, Rong-Chi Hu, George G Rodney, Thomas A Cooper

Faculty, Staff and Students Publications

Postnatal skeletal muscle development is a highly dynamic period associated with widespread alternative splicing changes required to adapt tissues to adult function. These splicing events have significant implications because the reversion of adult mRNA isoforms to fetal isoforms is observed in forms of muscular dystrophy. LIMCH1 is a stress fiber–associated protein that is alternatively spliced to generate uLIMCH1, a ubiquitously expressed isoform, and mLIMCH1, a skeletal muscle–specific isoform containing six additional exons simultaneously included after birth in the mouse. CRISPR/Cas9 was used to delete the six alternatively spliced exons of LIMCH1 in mice, thereby forcing the constitutive expression of the …

Vaccine Access, Equity And Justice: Covid-19 Vaccines And Vaccination, Lois Privor-Dumm, Jean-Louis Excler, Sarah Gilbert, Salim S Abdool Karim, Peter J Hotez, Didi Thompson, Jerome H Kim

Faculty, Staff and Students Publications

Although significant progress has been made in achieving goals for COVID-19 vaccine access, the quest for equity and justice remains an unfinished agenda. Vaccine nationalism has prompted calls for new approaches to achieve equitable access and justice not only for vaccines but also for vaccination. This includes ensuring country and community participation in global discussions and that local needs to strengthen health systems, address issues related to social determinants of health, build trust and leverage acceptance to vaccines, are addressed. Regional vaccine technology and manufacturing hubs are promising approaches to address access challenges and must be integrated with efforts to …