Digital Commons Network^™

Catalase Produced By Candida Albicans Protects Streptococcus Mutans From H2o2 Stress-One More Piece In The Cross-Kingdom Synergism Puzzle, Callahan Katrak, Bruna A Garcia, Louise M Dornelas-Figueira, Mary Nguyen, Robert B Williams, Michael C Lorenz, Jacqueline Abranches

Faculty, Staff and Student Publications

Co-infection with Streptococcus mutans and Candida albicans is associated with dental caries, and their co-cultivation results in enhanced biofilm matrix production that contributes to increased virulence and caries risk. Moreover, the catalase-negative S. mutans demonstrates increased oxidative stress tolerance when co-cultivated in biofilms with C. albicans, a catalase-producing yeast. Here, we sought to obtain mechanistic insights into the increased H2O2 tolerance of S. mutans when co-cultivated with clinical isolates of Candida glabrata, Candida tropicalis, and C. albicans. Additionally, the C. albicans SC5314 laboratory strain, its catalase mutant (SC5314Δcat1), and S. mutans UA159 and its glucosyltransferase B/C …

Infants Exposed In Utero To Hurricane Maria Have Gut Microbiomes With Reduced Diversity And Altered Metabolic Capacity, Ai Zhang, David De Ángel Solá, Midnela Acevedo Flores, Lijuan Cao, Leran Wang, Josh G Kim, Phillip I Tarr, Barbara B Warner, Nicolás Rosario Matos, Leyao Wang

2020-Current year OA Pubs

The gut microbiome is a potentially important mechanism that links prenatal disaster exposures with increased disease risks. However, whether prenatal disaster exposures are associated with alterations in the infant's gut microbiome remains unknown. We established a birth cohort study named Hurricane as the Origin of Later Alterations in Microbiome (HOLA) after Hurricane Maria struck Puerto Rico in 2017. We enrolled vaginally born Latino term infants aged 2 to 6 months, including

Volatile Profiling Distinguishes Streptococcus Pyogenes From Other Respiratory Streptococcal Species, Amalia Z Berna, Joseph A Merriman, Leah Mellett, Danealle K Parchment, Michael G Caparon, Audrey R Odom John

2020-Current year OA Pubs

Sore throat is one of the most common complaints encountered in the ambulatory clinical setting. Rapid, culture-independent diagnostic techniques that do not rely on pharyngeal swabs would be highly valuable as a point-of-care strategy to guide outpatient antibiotic treatment. Despite the promise of this approach, efforts to detect volatiles during oropharyngeal infection have yet been limited. In our research study, we sought to evaluate for specific bacterial volatile organic compounds (VOC) biomarkers in isolated cultures

White Matter Integrity Abnormalities In Healthy Overweight Individuals Revealed By Whole Brain Meta-Analysis Of Diffusion Tensor Imaging Studies, Xiaodong Cheng, Wenchang Wang, Chen Sun, Yana Sun, Cong Zhou

Faculty, Staff and Student Publications

OBJECTIVE: This study aimed to conduct a coordinate-based meta-analysis (CBMA) to investigate white matter (WM) abnormalities in healthy individuals with overweight or obesity.

METHODS: A systematic literature search using Web of Science and PubMed datasets was performed. Original investigations that used diffusion tensor imaging (DTI) to explore fractional anisotropy (FA) differences between healthy overweight/obese individuals and normal weight controls were collected. The meta-analysis was conducted using the seed-based

RESULTS: The analysis included five studies comprising 232 overweight/obese individuals and 219 healthy normal weight controls. The findings showed that overweight/obese individuals exhibited reduced fractional anisotropy (FA) in specific regions, namely, the …

Development Of Novel Composite Data Quality Scores To Evaluate Facility-Level Data Quality In Electronic Data In Kenya: A Nationwide Retrospective Cohort Study, Beryne M Odeny, Anne Njoroge, Steve Gloyd, James P Hughes, Bradley H Wagenaar, Jacob Odhiambo, Lilly M Nyagah, Ayub Manya, Ooga Wesley Oghera, Nancy Puttkammer

2020-Current year OA Pubs

BACKGROUND: In this evaluation, we aim to strengthen Routine Health Information Systems (RHIS) through the digitization of data quality assessment (DQA) processes. We leverage electronic data from the Kenya Health Information System (KHIS) which is based on the District Health Information System version 2 (DHIS2) to perform DQAs at scale. We provide a systematic guide to developing composite data quality scores and use these scores to assess data quality in Kenya.

METHODS: We evaluated 187 HIV care facilities with electronic medical records across Kenya. Using quarterly, longitudinal KHIS data from January 2011 to June 2018 (total N = 30 quarters), …

Adaptive Design Of Mrna-Loaded Extracellular Vesicles For Targeted Immunotherapy Of Cancer, Shiyan Dong, Xuan Liu, Ye Bi, Yifan Wang, Abin Antony, Daeyong Lee, Kristin Huntoon, Seongdong Jeong, Yifan Ma, Xuefeng Li, Weiye Deng, Benjamin R Schrank, Adam J Grippin, Jonghoon Ha, Minjeong Kang, Mengyu Chang, Yarong Zhao, Rongze Sun, Xiangshi Sun, Jie Yang, Jiayi Chen, Sarah K Tang, L James Lee, Andrew S Lee, Lirong Teng, Shengnian Wang, Lesheng Teng, Betty Y S Kim, Zhaogang Yang, Wen Jiang

Faculty, Staff and Student Publications

The recent success of mRNA therapeutics against pathogenic infections has increased interest in their use for other human diseases including cancer. However, the precise delivery of the genetic cargo to cells and tissues of interest remains challenging. Here, we show an adaptive strategy that enables the docking of different targeting ligands onto the surface of mRNA-loaded small extracellular vesicles (sEVs). This is achieved by using a microfluidic electroporation approach in which a combination of nano- and milli-second pulses produces large amounts of IFN-γ mRNA-loaded sEVs with CD64 overexpressed on their surface. The CD64 molecule serves as an adaptor to dock …

Long-Term Evaluation Of Clinical Success And Safety Of Omadacycline In Nontuberculous Mycobacteria Infections: A Retrospective, Multicenter Cohort Of Real-World Health Outcomes, Amer El Ghali, Taylor Morrisette, Sara Alosaimy, Kristen Lucas, Maria G Tupayachi-Ortiz, Raaga Vemula, Carly Wadle, Julie V Philley, Carlos Mejia-Chew, Yasir Hamad, Ryan W Stevens, John D Zeuli, Andrew J Webb, Christina T Fiske, Anahit Simonyan, Christo L Cimino, Mehriban Mammadova, Virginia E Umana, Rodrigo Hasbun, Saira Butt, Kyle C Molina, Michael Thomas, Emily A Kaip, Jeannette Bouchard, Tristan W Gore, Catessa Howard, M Gabriela Cabanilla, Dana J Holger, Jeremy J Frens, Melissa Barger, Aaron Ong, Keira A Cohen, Michael J Rybak

Faculty, Staff and Student Publications

Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, …

Standardization Of An Antiviral Pipeline For Human Norovirus In Human Intestinal Enteroids Demonstrates Nitazoxanide Has No To Weak Antiviral Activity, Miranda A Lewis, Nicolás W Cortés-Penfield, Khalil Ettayebi, Ketki Patil, Gurpreet Kaur, Frederick H Neill, Robert L Atmar, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis. In immunocompetent hosts, symptoms usually resolve within 3 days; however, in immunocompromised persons, HuNoV infection can become persistent, debilitating, and sometimes life-threatening. There are no licensed therapeutics for HuNoV due to a near half-century delay in its cultivation. Treatment for chronic HuNoV infection in immunosuppressed patients anecdotally includes nitazoxanide, a broad-spectrum antimicrobial licensed for treatment of parasite-induced gastroenteritis. Despite its off-label use for chronic HuNoV infection, nitazoxanide has not been clearly demonstrated to be an effective treatment. In this study, we standardized a pipeline for antiviral testing using multiple human …

Priorities And Progress In Gram-Positive Bacterial Infection Research By The Antibacterial Resistance Leadership Group: A Narrative Review, Sarah B Doernberg, Cesar A Arias, Deena R Altman, Ahmed Babiker, Helen W Boucher, C Buddy Creech, Sara E Cosgrove, Scott R Evans, Vance G Fowler, Stephanie A Fritz, Toshimitsu Hamasaki, Brendan J Kelly, Sixto M Leal, Catherine Liu, Thomas P Lodise, Loren G Miller, Jose M Munita, Barbara E Murray, Melinda M Pettigrew, Felicia Ruffin, Marc H Scheetz, Bo Shopsin, Truc T Tran, Nicholas A Turner, Derek J Williams, Smitha Zaharoff, Thomas L Holland

Faculty, Staff and Student Publications

The Antibacterial Resistance Leadership Group (ARLG) has prioritized infections caused by gram-positive bacteria as one of its core areas of emphasis. The ARLG Gram-positive Committee has focused on studies responding to 3 main identified research priorities: (1) investigation of strategies or therapies for infections predominantly caused by gram-positive bacteria, (2) evaluation of the efficacy of novel agents for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, and (3) optimization of dosing and duration of antimicrobial agents for gram-positive infections. Herein, we summarize ARLG accomplishments in gram-positive bacterial infection research, including studies aiming to (1) inform optimal vancomycin dosing, …

A Single Nanobody Neutralizes Multiple Epochally Evolving Human Noroviruses By Modulating Capsid Plasticity, Wilhelm Salmen, Liya Hu, Marina Bok, Natthawan Chaimongkol, Khalil Ettayebi, Stanislav V Sosnovtsev, Kaundal Soni, B Vijayalakshmi Ayyar, Sreejesh Shanker, Frederick H Neill, Banumathi Sankaran, Robert L Atmar, Mary K Estes, Kim Y Green, Viviana Parreño, B V Venkataram Prasad

Faculty, Staff and Students Publications

Acute gastroenteritis caused by human noroviruses (HuNoVs) is a significant global health and economic burden and is without licensed vaccines or antiviral drugs. The GII.4 HuNoV causes most epidemics worldwide. This virus undergoes epochal evolution with periodic emergence of variants with new antigenic profiles and altered specificity for histo-blood group antigens (HBGA), the determinants of cell attachment and susceptibility, hampering the development of immunotherapeutics. Here, we show that a llama-derived nanobody M4 neutralizes multiple GII.4 variants with high potency in human intestinal enteroids. The crystal structure of M4 complexed with the protruding domain of the GII.4 capsid protein VP1 revealed …

Tuberculosis Presentation And Outcomes In Older Hispanic Adults From Tamaulipas, Mexico, Belinda A Medrano, Miryoung Lee, Gretchen Gemeinhardt, Javier E Rodríguez-Herrera, Moncerrato García-Viveros, Blanca I Restrepo

Faculty, Staff and Student Publications

Older people are at high risk of developing and dying from pulmonary infections like tuberculosis (TB), but there are few studies among them, particularly in Hispanics. To address these gaps, we sought to identify host factors associated with TB and adverse treatment outcomes in older Hispanics by conducting a cross-sectional study of TB surveillance data from Tamaulipas, Mexico (2006-2013; n = 8381). Multivariable logistic regressions were assessed for older adults (OA ≥65 years) when compared to young (YA, 18-39 years) and middle-aged adults (40-64 years). We found that the OA had features associated with a less complicated TB (e.g., lower …

A Retrospective, Observational Study Of 12 Cases Of Expanded-Access Customized Phage Therapy: Production, Characteristics, And Clinical Outcomes, Sabrina I Green, Justin R Clark, Haroldo H Santos, Kyle E Weesner, Keiko C Salazar, Saima Aslam, J William Campbell, Sarah B Doernberg, Emily Blodget, Michele I Morris, Gina A Suh, Karam Obeid, Fernanda P Silveira, Andrey A Filippov, Katrine L Whiteson, Barbara W Trautner, Austen L Terwilliger, Anthony Maresso

Faculty, Staff and Students Publications

BACKGROUND: Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution. Reported are outcomes of customized phage therapy for patients with difficult-to-treat antimicrobial resistant infections.

METHODS: We retrospectively assessed 12 cases of customized phage therapy from a phage production center. Phages were screened, purified, sequenced, characterized, and Food and Drug Administration-approved via the IND (investigational new drug) compassionate-care route. Outcomes were assessed as favorable or unfavorable by microbiologic and clinical standards. Infections were device-related …

Elevated Level Of Circulating But Not Urine S100a8/A9 Identifies Poor Covid-19 Outcomes, Leah Mellett, Gaya Amarasinghe, Christopher W Farnsworth, Shabaana A Khader

2020-Current year OA Pubs

The alarmin calprotectin (S100A8/A9) is thought to drive a cytokine storm, a hallmark of severe COVID-19. Recent studies report circulating S100A8/A9 levels can distinguish COVID-19 severity but have only been conducted in non-U.S. cohorts and mainly focus on serum S100A8/A9 levels. Thus, we quantified S100A8/A9 in serum and urine samples from a hospital cohort in St. Louis, Missouri, to expand the understanding of S100A8/A9 as a prognostic biomarker for COVID-19. Elevated S100A8/A9 serum levels were observed in ICU patients (

Shiga Toxin–Producing Escherichia Coli And The Hemolytic–Uremic Syndrome, Stephen B Freedman, Nicole C A J Van De Kar, Phillip I Tarr

2020-Current year OA Pubs

No abstract provided.

Nasal Iodophor Antiseptic Vs Nasal Mupirocin Antibiotic In The Setting Of Chlorhexidine Bathing To Prevent Infections In Adult Icus: A Randomized Clinical Trial, Susan S Huang, Edward J Septimus, Ken Kleinman, Lauren T Heim, Julia A Moody, Taliser R Avery, Laura Mclean, Syma Rashid, Katherine Haffenreffer, Lauren Shimelman, Whitney Staub-Juergens, Caren Spencer-Smith, Selsebil Sljivo, Ed Rosen, Russell E Poland, Micaela H Coady, Chi Hyun Lee, Eunice J Blanchard, Kimberly Reddish, Mary K Hayden, Robert A Weinstein, Brandon Carver, Kimberly Smith, Jason Hickok, Karen Lolans, Nadia Khan, S Gwynn Sturdevant, Sujan C Reddy, John A Jernigan, Kenneth E Sands, Jonathan B Perlin, Richard Platt

Faculty, Staff and Student Publications

IMPORTANCE: Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization.

OBJECTIVE: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing.

DESIGN, SETTING, AND PARTICIPANTS: Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) …

Social Determinants Of Health And Disparate Disability Accumulation In A Cohort Of Black, Hispanic, And White Patients With Multiple Sclerosis, Michael C Robertson, Brian Downer, Paul E Schulz, Rafael Samper-Ternent, Elizabeth J Lyons, Sadaf Arefi Milani

Faculty, Staff and Student Publications

OBJECTIVES: Mexico has a rapidly aging population at risk for cognitive impairment. Social and leisure activities may protect against cognitive decline in older adults. The benefits of these behaviors may vary by patterns of cognitive impairment. The objectives of this study were to identify latent states of cognitive functioning, model the incidence of transitions between these states, and investigate how social and leisure activities were associated with state transitions over a 6-year period in Mexican adults aged 60 and older.

METHODS: We performed latent transition analyses to identify distinct cognitive statuses in the 2012 and 2018 waves of the Mexican …

Bacillus Calmette-Guérin Vaccination As Defense Against Sars-Cov-2 (Badas): A Randomized Controlled Trial To Protect Healthcare Workers In The Usa By Enhanced Trained Immune Responses, Andrew R Dinardo, Moshe Arditi, Ashish M Kamat, Kent J Koster, Santiago Carrero, Tomoki Nishiguchi, Maxim Lebedev, Aaron B Benjamin, Pablo Avalos, Marisa Lozano, Madeleine G Moule, Brittany Mccune, Baysia Herron, Malik Ladki, Daanish Sheikh, Matthew Spears, Ivan A Herrejon, Courtney Dodge, Sathish Kumar, Robert W Hutchison, Theresa U Ofili, Lynne A Opperman, Jessica A Bernard, Seth P Lerner, George Udeani, Gabriel Neal, Mihai G Netea, Jeffrey D Cirillo

Faculty, Staff and Students Publications

BACKGROUND: A large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19. We hypothesize that BCG vaccination can reduce SARS-CoV-2 infection and disease severity.

METHODS: This will be a placebo-controlled adaptive multi-center randomized controlled trial. A total of 1800 individuals considered to be at …

High-Level Ceftazidime/Avibactam Resistance In Escherichia Coli Conferred By The Novel Plasmid-Mediated Β-Lactamase Cmy-185 Variant, William C Shropshire, Bradley T Endres, Jovan Borjan, Samuel L Aitken, William C Bachman, Christi L Mcelheny, Chin-Ting Wu, Stephanie L Egge, Ayesha Khan, William R Miller, Micah M Bhatti, Pranoti Saharasbhojane, Akito Kawai, Ryan K Shields, Samuel A Shelburne, Yohei Doi

Faculty, Staff and Student Publications

OBJECTIVES: To characterize a blaCMY variant associated with ceftazidime/avibactam resistance from a serially collected Escherichia coli isolate.

METHODS: A patient with an intra-abdominal infection due to recurrent E. coli was treated with ceftazidime/avibactam. On Day 48 of ceftazidime/avibactam therapy, E. coli with a ceftazidime/avibactam MIC of >256 mg/L was identified from abdominal drainage. Illumina and Oxford Nanopore Technologies WGS was performed on serial isolates to identify potential resistance mechanisms. Site-directed mutants of CMY β-lactamase were constructed to identify amino acid residues responsible for ceftazidime/avibactam resistance.

RESULTS: WGS revealed that all three isolates were E. coli ST410. The ceftazidime/avibactam-resistant strain uniquely …

Relationship Between Epa Level Of Supervision With Their Associated Subcompetency Milestone Levels In Pediatric Fellow Assessment., Richard B. Mink, Carol L. Carraccio, Bruce E. Herman, Pnina Weiss, David A. Turner, Diane E J Stafford, Kathleen A. Mcgann, Jennifer Kesselheim, Deborah C. Hsu, Pamela C. High, Jill J. Fussell, Megan L. Curran, Patricia R. Chess, Cary Sauer, Sarah Pitts, Angela Myers, John D. Mahan, Christiane E L Dammann, Tandy Aye, Alan Schwartz, Subspecialty Pediatrics Investigator Network

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Entrustable Professional Activities (EPA) and competencies represent components of a competency-based education framework. EPAs are assessed based on the level of supervision (LOS) necessary to perform the activity safely and effectively. The broad competencies, broken down into narrower subcompetencies, are assessed using milestones, observable behaviors of one's abilities along a developmental spectrum. Integration of the two methods, accomplished by mapping the most relevant subcompetencies to each EPA, may provide a cross check between the two forms of assessment and uncover those subcompetencies that have the greatest influence on the EPA assessment.

OBJECTIVES: We hypothesized that 1) there would be …

Comparison Of Bacterial Culture With Biofire® Filmarray® Multiplex Pcr Screening Of Archived Cerebrospinal Fluid Specimens From Children With Suspected Bacterial Meningitis In Nigeria, S Obaro, F Hassan-Hanga, N Medugu, Rasaq Olaosebikan, G Olanipekun, B Jibir, S Gambo, Theresa Ajose, Carissa Duru, B Ebruke, H D Davies

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Diagnosis of bacterial meningitis remains a challenge in most developing countries due to low yield from bacterial culture, widespread use of non-prescription antibiotics, and weak microbiology laboratories. The objective of this study was to compare the yield from standard bacterial culture with the multiplex nested PCR platform, the BioFire® FilmArray® Meningitis/Encephalitis Panel (BioFire ME Panel), for cases with suspected acute bacterial meningitis.

METHODS: Following Gram stain and bacterial culture on cerebrospinal fluid (CSF) collected from children aged less than 5 years with a clinical suspicion of acute bacterial meningitis (ABM) as defined by the WHO guidelines, residual CSF specimens …

Setd2 Loss And Atr Inhibition Synergize To Promote Cgas Signaling And Immunotherapy Response In Renal Cell Carcinoma, Xian-De Liu, Yan-Ting Zhang, Daniel J Mcgrail, Xuesong Zhang, Truong Lam, Anh Hoang, Elshad Hasanov, Ganiraju Manyam, Christine B Peterson, Haifeng Zhu, Shwetha V Kumar, Rehan Akbani, Patrick G Pilie, Nizar M Tannir, Guang Peng, Eric Jonasch

Faculty, Staff and Student Publications

PURPOSE: Immune checkpoint blockade (ICB) demonstrates durable clinical benefits in a minority of patients with renal cell carcinoma (RCC). We aimed to identify the molecular features that determine the response and develop approaches to enhance it.

EXPERIMENTAL DESIGN: We investigated the effects of SET domain-containing protein 2 (SETD2) loss on the DNA damage response pathway, the cytosolic DNA-sensing pathway, the tumor immune microenvironment, and the response to ataxia telangiectasia and rad3-related (ATR) and checkpoint inhibition in RCC.

RESULTS: ATR inhibition activated the cyclic GMP-AMP synthase (cGAS)-interferon regulatory factor 3 (IRF3)-dependent cytosolic DNA-sensing pathway, resulting in the concurrent expression of inflammatory …

Safety And Immunogenicity Of Live Viral Vaccines In A Multicenter Cohort Of Pediatric Transplant Recipients, Amy G Feldman, Brenda L Beaty, Jose A Ferrolino, Gabriela Maron, Hillary K Weidner, Saira A Ali, Leandra Bitterfeld, Mary Alice Boulware, Kathleen M Campbell, Emily Carr, Shelley Chapman, Yeh-Chung Chang, Ryan Cunningham, Ronald H Dallas, Keerti L Dantuluri, Bryanna N Domenick, Noelle H Ebel, Scott Elisofon, Rima Fawaz, Marc Foca, Hayley A Gans, Vani V Gopalareddy, Cindy Gu, Nitika A Gupta, Katherine Harmann, Jessica Hollenbeck, Anna R Huppler, Catalina Jaramillo, Nagraj Kasi, Nanda Kerkar, Stacee Lerret, Steven J Lobritto, Maclovio J Lopez, Elizabeth Marini, Alisha Mavis, Sonia Mehra, Lynnette Moats, Sindhu Mohandas, Flor M Munoz, Krupa R Mysore, Ceren Onsan, Nadia Ovchinsky, Kerrigan Perkins, Stacy Postma, Lauren Pratscher, Elizabeth B Rand, Regina K Rowe, Danielle Schultz, Katherine Sear, Megan L Sell, Tanvi Sharma, Janis Stoll, Mychoua Vang, Dominique Villarin, Carly Weaver, Phoebe Wood, Olivia Woodford-Berry, George Yanni, Lara A Danziger-Isakov

Faculty, Staff and Students Publications

IMPORTANCE: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions.

OBJECTIVE: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody …

Accuracy And Reliability Of Chatbot Responses To Physician Questions, Rachel S Goodman, Isik Turker, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Natural language processing tools, such as ChatGPT (generative pretrained transformer, hereafter referred to as chatbot), have the potential to radically enhance the accessibility of medical information for health professionals and patients. Assessing the safety and efficacy of these tools in answering physician-generated questions is critical to determining their suitability in clinical settings, facilitating complex decision-making, and optimizing health care efficiency.

OBJECTIVE: To assess the accuracy and comprehensiveness of chatbot-generated responses to physician-developed medical queries, highlighting the reliability and limitations of artificial intelligence-generated medical information.

DESIGN, SETTING, AND PARTICIPANTS: Thirty-three physicians across 17 specialties generated 284 medical questions that they …

Safety And Immunogenicity Of Live Viral Vaccines In A Multicenter Cohort Of Pediatric Transplant Recipients, Amy G Feldman, Stacy Postma, Janis Stoll, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions.

OBJECTIVE: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody …

Advances In Vaccine Development For Cancer Prevention And Treatment In Lynch Syndrome, Ana M Bolivar, Fahriye Duzagac, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

Lynch Syndrome (LS) is one of the most common hereditary cancer syndromes, and is caused by mutations in one of the four DNA mismatch repair (MMR) genes, namely MLH1, MSH2, MSH6 and PMS2. Tumors developed by LS carriers display high levels of microsatellite instability, which leads to the accumulation of large numbers of mutations, among which frameshift insertion/deletions (indels) within microsatellite (MS) loci are the most common. As a result, MMR-deficient (MMRd) cells generate increased rates of tumor-specific neoantigens (neoAgs) that can be recognized by the immune system to activate cancer cell killing. In this context, LS is an ideal …

Pd-1 Blockade In Combination With Dasatinib Potentiates Induction Of Anti-Acute Lymphocytic Leukemia Immunity, Paul Koller, Natalia Baran, Karine Harutyunyan, Antonio Cavazos, Saradhi Mallampati, Renee L Chin, Zhou Jiang, Xian Sun, Heng-Huan Lee, Jennifer L Hsu, Patrick Williams, Xuelin Huang, Michael A Curran, Mien-Chie Hung, Marina Konopleva

Faculty, Staff and Student Publications

Immunotherapy, in the form of hematopoietic stem cell transplantation (HSCT), has been part of the standard of care in the treatment of acute leukemia for over 40 years. Trials evaluating novel immunotherapeutic approaches, such as targeting the programmed death-1 (PD-1) pathway, have unfortunately not yielded comparable results to those seen in solid tumors. Major histocompatibility complex (MHC) proteins are cell surface proteins essential for the adaptive immune system to recognize self versus non-self. MHC typing is used to determine donor compatibility when evaluating patients for HSCT. Recently, loss of MHC class II (MHC II) was shown to be a mechanism …

New Insights Into The Neuraminidase-Mediated Hemagglutination Activity Of Influenza A(H3n2) Viruses, Rongyuan Gao, Philippe Noriel Q Pascua, Ha T Nguyen, Anton Chesnokov, Chloe Champion, Vasiliy P Mishin, Dave E Wentworth, Larisa V Gubareva

Faculty, Staff and Student Publications

Influenza virus neuraminidase (NA) can act as a receptor-binding protein, a role commonly attributed to hemagglutinin (HA). In influenza A(H3N2) viruses, three NA amino acid residues have previously been associated with NA-mediated hemagglutination: T148, D151, and more recently, H150. These residues are part of the 150-loop of the NA monomer. Substitutions at 148 and 151 arise from virus propagation in laboratory cell cultures, whereas changes at 150 occurred during virus evolution in the human host. In this study, we examined the effect of natural amino acid polymorphism at position 150 on NA-mediated hemagglutination. Using the A/Puerto Rico/8/34 backbone, we generated …

Human Intestinal Organoids As Models To Study Enteric Bacteria And Viruses, Grace Adeniyi-Ipadeola, Hephzibah Nwanosike, Sasirekha Ramani

Faculty, Staff and Students Publications

Laboratory studies of host-microbe interactions have historically been carried out using transformed cell lines and animal models. Although much has been learned from these models, recent advances in the development of multicellular, physiologically active, human intestinal organoid (HIO) cultures are allowing unprecedented discoveries of host-microbe interactions. Here, we review recent literature using HIOs as models to investigate the pathogenesis of clinically important enteric bacteria and viruses and study commensal intestinal microbes. We also discuss limitations of current HIO culture systems and how technical advances and innovative engineering approaches are providing new directions to improve the model. The studies discussed here …

Review Of Toxocariasis At A Children's Hospital Prompting Need For Public Health Interventions, Mary B Fortini, Timothy A Erickson, Lauren M Leining, Karina M Robinson, Megan N Carey, Sarah J Smith, Brendan Sullivan, Alisa R Nelson, Sarah M Gunter, Jill E Weatherhead

Faculty, Staff and Students Publications

BACKGROUND: Toxocariasis, caused the by dog and cat roundworm, is one of the most common zoonotic helminth infections in the United States and can lead to severe lifelong morbidity in children. Although historical seroprevalence studies have identified a high frequency of toxocariasis regionally in the United States, there are few studies linking epidemiology and clinical disease in children. The study objective was to examine the contemporary epidemiology of pediatric toxocariasis within an endemic US region.

METHODS: We conducted an epidemiologic study analyzing children diagnosed with toxocariasis presenting to a tertiary pediatric hospital in Texas from 2010 to 2021. We examined …

Texas Developmental Center For Aids Research Cfar Diversity, Equity, And Inclusion Pathway Initiative Program, Fred A Pereira, Alana D Newell, Andrew P Rice

Faculty, Staff and Students Publications

BACKGROUND: The Texas Developmental Center for AIDS Research (D-CFAR) diversity program, termed the CFAR Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI), was created in 2021 to engage high school students and graduate students from Underrepresented Minorities/Black, Indigenous, and People of Color populations.

SETTING: The Texas D-CFAR CDEIPI has partnered with 2 Texas high schools with predominantly economically disadvantaged and minority student populations-Michael E. DeBakey High School for Health Professions in Houston, TX, and the South Texas Independent School District Medical Professions High School in Olmito, TX in the Rio Grande Valley.

METHODS: A total of 370 high school student learners …