Digital Commons Network^™

Increases In Group A Streptococcal Infections In The Pediatric Population In Houston, Tx, 2022, Aya Aboulhosn, Misu A Sanson, Luis Alberto Vega, Maria G Segura, Lauren M Summer, Marritta Joseph, J Chase Mcneil, Anthony R Flores

Faculty, Staff and Student Publications

Beginning in October 2022, we observed a substantial increase in the total number of cases of invasive GAS disease (iGAS) in the pediatric population in Houston, TX. Emm12 GAS strains were disproportionately represented but the overall proportion of iGAS infections observed during the current spike was similar to pre-pandemic years.

Increases In Group A Streptococcal Infections In The Pediatric Population In Houston, Tx, 2022, Aya Aboulhosn, Misu A Sanson, Luis Alberto Vega, Maria G Segura, Lauren M Summer, Marritta Joseph, J Chase Mcneil, Anthony R Flores

Faculty, Staff and Student Publications

Beginning in October 2022, we observed a substantial increase in the total number of cases of invasive GAS disease (iGAS) in the pediatric population in Houston, TX. Emm12 GAS strains were disproportionately represented but the overall proportion of iGAS infections observed during the current spike was similar to pre-pandemic years.

In Vitro Activity Of Eravacycline And Comparator Agents Against Bacterial Pathogens Isolated From Patients With Cancer, Kenneth Rolston, Bahgat Gerges, Lior Nesher, Samuel A Shelburne, Randall Prince, Issam Raad

Faculty, Staff and Student Publications

BACKGROUND: Bacterial infections are common in patients with cancer, and many bacteria have developed resistance to currently used antibiotics.

OBJECTIVES: We evaluated the

METHODS: Antimicrobial susceptibility testing was performed using CLSI-approved methodology and interpretive criteria for 255 Gram-positive and 310 Gram-negative bacteria. MIC and susceptibility percentage were calculated according to CLSI and FDA breakpoints when available.

RESULTS: Eravacycline had potent activity against most Gram-positive bacteria, including MRSA. Of 80 Gram-positive isolates with available breakpoints, 74 (92.5%) were susceptible to eravacycline. Eravacycline had potent activity against most Enterobacterales, including ESBL-producing organisms. Of 230 Gram-negative isolates with available breakpoints, 201 (87.4%) were …

The In Vitro Activity Of Delafloxacin And Comparator Agents Against Bacterial Pathogens Isolated From Patients With Cancer, Bahgat Gerges, Kenneth Rolston, Samuel A Shelburne, Joel Rosenblatt, Randall Prince, Issam Raad

Faculty, Staff and Student Publications

BACKGROUND: Fluoroquinolones are used for infection prevention in high-risk patients with haematological malignancies. Fluoroquinolones are active against many Gram-negative bacilli (GNB) but are less active against Gram-positive organisms. We evaluated the

METHODS: Antimicrobial susceptibility testing and time-kill studies were performed using CLSI-approved methodology and interpretive criteria for 350 Gram-positive organisms and 210 GNB that had been recently isolated from patients with cancer.

RESULTS: Delafloxacin was more active than ciprofloxacin and levofloxacin against

CONCLUSIONS: Delafloxacin is more active than ciprofloxacin and levofloxacin against

Monogenic Early-Onset Lymphoproliferation And Autoimmunity: Natural History Of Stat3 Gain-Of-Function Syndrome, Jennifer W Leiding, Tiphanie P Vogel, Valentine G J Santarlas, Rahul Mhaskar, Madison R Smith, Alexandre Carisey, Alexander Vargas-Hernández, Manuel Silva-Carmona, Maximilian Heeg, Anne Rensing-Ehl, Bénédicte Neven, Jérôme Hadjadj, Sophie Hambleton, Timothy Ronan Leahy, Kornvalee Meesilpavikai, Charlotte Cunningham-Rundles, Cullen M Dutmer, Svetlana O Sharapova, Mervi Taskinen, Ignatius Chua, Rosie Hague, Christian Klemann, Larysa Kostyuchenko, Tomohiro Morio, Akaluck Thatayatikom, Ahmet Ozen, Anna Scherbina, Cindy S Bauer, Sarah E Flanagan, Eleonora Gambineri, Lisa Giovannini-Chami, Jennifer Heimall, Kathleen E Sullivan, Eric Allenspach, Neil Romberg, Sean G Deane, Benjamin T Prince, Melissa J Rose, John Bohnsack, Talal Mousallem, Rohith Jesudas, Maria Marluce Dos Santos Vilela, Michael O'Sullivan, Jana Pachlopnik Schmid, Štěpánka Průhová, Adam Klocperk, Matthew Rees, Helen Su, Sami Bahna, Safa Baris, Lisa M Bartnikas, Amy Chang Berger, Tracy A Briggs, Shannon Brothers, Vanessa Bundy, Alice Y Chan, Shanmuganathan Chandrakasan, Mette Christiansen, Theresa Cole, Matthew C Cook, Mukesh M Desai, Ute Fischer, David A Fulcher, Silvanna Gallo, Amelie Gauthier, Andrew R Gennery, José Gonçalo Marques, Frédéric Gottrand, Bodo Grimbacher, Eyal Grunebaum, Emma Haapaniemi, Sari Hämäläinen, Kaarina Heiskanen, Tarja Heiskanen-Kosma, Hal M Hoffman, Luis Ignacio Gonzalez-Granado, Anthony L Guerrerio, Leena Kainulainen, Ashish Kumar, Monica G Lawrence, Carina Levin, Timi Martelius, Olaf Neth, Peter Olbrich, Alejandro Palma, Niraj C Patel, Tamara Pozos, Kahn Preece, Saúl Oswaldo Lugo Reyes, Mark A Russell, Yael Schejter, Christine Seroogy, Jan Sinclair, Effie Skevofilax, Daniel Suan, Daniel Suez, Paul Szabolcs, Helena Velasco, Klaus Warnatz, Kelly Walkovich, Austen Worth, Stat3 Gof Working Group Members, Mikko R J Seppänen, Troy R Torgerson, Georgios Sogkas, Stephan Ehl, Stuart G Tangye, Megan A Cooper, Joshua D Milner, Lisa R Forbes Satter

Faculty, Staff and Students Publications

BACKGROUND: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity.

OBJECTIVE: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants.

METHODS: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3.

RESULTS: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median …

Potentiation Of The Immune Checkpoint Blockade Response By Metabolic Modulation Is Predictable Using Molecular Imaging, Renee L. Chin

Dissertations and Theses (Open Access)

Unregulated cell division is a hallmark of cancer. The high metabolic needs of the tumor cells result in nutrient depletion and produce a hostile tumor microenvironment (TME) for antitumor immune cells, protecting the tumor from immune cell-mediated control and immunotherapy. Two of these environmental factors, acidosis and hypoxia, are commonly found in solid cancers. In my thesis, I posited that modulation of tumor acidosis and hypoxia can serve as biomarkers by indicating immunogenicity and tumor sensitivity to immune checkpoint blockade (ICB) as monitored using molecular imaging. Esomeprazole was found to promote tumor immunogenicity and induce tumor control when used to …

A Randomized Clinical Trial Of Transgender Women Switching To B/F/Taf: The (Mo)Betta Trial, Jordan E Lake, Ana N Hyatt, Han Feng, Paula Debroy, Aaren Kettelhut, Hongyu Miao, Liming Peng, Shalender Bhasin, Susan Bell, Nahid Rianon, Todd T Brown, Nicholas T Funderburg

Faculty, Staff and Student Publications

Background: Cardiometabolic disease in transgender women (TW) is affected by gender-affirming hormonal therapies (GAHTs), HIV, and antiretroviral therapy (ART). We evaluated the 48-week safety/tolerability of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs continued ART in TW on GAHT.

Methods: TW on GAHT and suppressive ART were randomized 1:1 to switch to B/F/TAF (Arm A) or continue current ART (Arm B). Cardiometabolic biomarkers, sex hormones, bone mineral density (BMD) and lean/fat mass by DXA scan, and hepatic fat (controlled continuation parameter [CAP]) were measured. Wilcoxon rank-sum/signed-rank and χ2 tests compared continuous and categorical variables.

Results: TW (Arm A n = 12, Arm …

Letter To The Editor: Quality Criteria For Computational Models Predicting Individual Outcomes In Car-T Cell Therapy, Anna M Mc Laughlin, Cassian Yee

Faculty, Staff and Student Publications

No abstract provided.

A Non-Antibiotic-Disrupted Gut Microbiome Is Associated With Clinical Responses To Cd19-Car-T Cell Cancer Immunotherapy, Christoph K Stein-Thoeringer, Neeraj Y Saini, Eli Zamir, Viktoria Blumenberg, Maria-Luisa Schubert, Uria Mor, Matthias A Fante, Sabine Schmidt, Eiko Hayase, Tomo Hayase, Roman Rohrbach, Chia-Chi Chang, Lauren Mcdaniel, Ivonne Flores, Rogier Gaiser, Matthias Edinger, Daniel Wolff, Martin Heidenreich, Paolo Strati, Ranjit Nair, Dai Chihara, Luis E Fayad, Sairah Ahmed, Swaminathan P Iyer, Raphael E Steiner, Preetesh Jain, Loretta J Nastoupil, Jason Westin, Reetakshi Arora, Michael L Wang, Joel Turner, Meghan Menges, Melanie Hidalgo-Vargas, Kayla Reid, Peter Dreger, Anita Schmitt, Carsten Müller-Tidow, Frederick L Locke, Marco L Davila, Richard E Champlin, Christopher R Flowers, Elizabeth J Shpall, Hendrik Poeck, Sattva S Neelapu, Michael Schmitt, Marion Subklewe, Michael D Jain, Robert R Jenq, Eran Elinav

Faculty, Staff and Student Publications

Increasing evidence suggests that the gut microbiome may modulate the efficacy of cancer immunotherapy. In a B cell lymphoma patient cohort from five centers in Germany and the United States (Germany, n = 66; United States, n = 106; total, n = 172), we demonstrate that wide-spectrum antibiotics treatment ('high-risk antibiotics') prior to CD19-targeted chimeric antigen receptor (CAR)-T cell therapy is associated with adverse outcomes, but this effect is likely to be confounded by an increased pretreatment tumor burden and systemic inflammation in patients pretreated with high-risk antibiotics. To resolve this confounding effect and gain insights into antibiotics-masked microbiome signals …

Clinical Outcomes Of Immune Checkpoint Inhibitor Diabetes Mellitus At A Comprehensive Cancer Center, Rebecca Jeun, Priyanka C Iyer, Conor Best, Victor Lavis, Jeena M Varghese, Sireesha Yedururi, Veronica Brady, Isabella C Glitza Oliva, Ramona Dadu, Denai R Milton, Kristy Brock, Sonali Thosani

Faculty, Staff and Student Publications

Introduction: Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a rare adverse event. In this study, we characterize clinical outcomes of patients with ICI-DM and evaluate survival impact of this complication on melanoma patients.

Research design & methods: We conducted a retrospective review of 76 patients diagnosed with ICI-DM from April 2014 to December 2020.

Results: 68% of patients presented in diabetic ketoacidosis, 16% had readmissions for hyperglycemia, and hypoglycemia occurred in 70% of patients after diagnosis. Development of ICI-DM did not impact overall survival or progression-free survival in melanoma patients.

Conclusion: Development of ICI-DM is associated with long-term insulin dependence …

Sars-Cov-2 Restructures Host Chromatin Architecture, Ruoyu Wang, Joo-Hyung Lee, Jieun Kim, Feng Xiong, Lana Al Hasani, Yuqiang Shi, Erin N Simpson, Xiaoyu Zhu, Yi-Ting Chen, Pooja Shivshankar, Joanna Krakowiak, Yanyu Wang, David M Gilbert, Xiaoyi Yuan, Holger K Eltzschig, Wenbo Li

Faculty, Staff and Student Publications

Some viruses restructure host chromatin, influencing gene expression, with implications for disease outcome. Whether this occurs for SARS-CoV-2, the virus causing COVID-19, is largely unknown. Here we characterized the 3D genome and epigenome of human cells after SARS-CoV-2 infection, finding widespread host chromatin restructuring that features widespread compartment A weakening, A-B mixing, reduced intra-TAD contacts and decreased H3K27ac euchromatin modification levels. Such changes were not found following common-cold-virus HCoV-OC43 infection. Intriguingly, the cohesin complex was notably depleted from intra-TAD regions, indicating that SARS-CoV-2 disrupts cohesin loop extrusion. These altered 3D genome/epigenome structures correlated with transcriptional suppression of interferon response genes …

Clinical Implications Of Molecular Drug Resistance Testing For Mycobacterium Tuberculosis: A 2023 Tbnet/Resist-Tb Consensus Statement, José Domínguez, Martin J Boeree, Emmanuelle Cambau, Dumitru Chesov, Francesca Conradie, Vivian Cox, Keertan Dheda, Andrii Dudnyk, Maha R Farhat, Sebastien Gagneux, Martin P Grobusch, Matthias I Gröschel, Lorenzo Guglielmetti, Irina Kontsevaya, Berit Lange, Frank Van Leth, Christian Lienhardt, Anna M Mandalakas, Florian P Maurer, Matthias Merker, Paolo Miotto, Barbara Molina-Moya, Florence Morel, Stefan Niemann, Nicolas Veziris, Andrew Whitelaw, Charles R Horsburgh, Christoph Lange

Faculty, Staff and Students Publications

Drug-resistant tuberculosis is a substantial health-care concern worldwide. Despite culture-based methods being considered the gold standard for drug susceptibility testing, molecular methods provide rapid information about the Mycobacterium tuberculosis mutations associated with resistance to anti-tuberculosis drugs. This consensus document was developed on the basis of a comprehensive literature search, by the TBnet and RESIST-TB networks, about reporting standards for the clinical use of molecular drug susceptibility testing. Review and the search for evidence included hand-searching journals and searching electronic databases. The panel identified studies that linked mutations in genomic regions of M tuberculosis with treatment outcome data. Implementation of molecular …

Genomic Analysis Of Two Phlebotomine Sand Fly Vectors Of Leishmania From The New And Old World, Frédéric Labbé, Maha Abdeladhim, Jenica Abrudan, Alejandra Saori Araki, Ricardo N Araujo, Peter Arensburger, Joshua B Benoit, Reginaldo Pecanha Brazil, Rafaela V Bruno, Gustavo Bueno Da Silva Rivas, Vinicius Carvalho De Abreu, Jason Charamis, Iliano V Coutinho-Abreu, Samara G Da Costa-Latgé, Alistair Darby, Viv M Dillon, Scott J Emrich, Daniela Fernandez-Medina, Nelder Figueiredo Gontijo, Catherine M Flanley, Derek Gatherer, Fernando A Genta, Sandra Gesing, Gloria I Giraldo-Calderón, Bruno Gomes, Eric Roberto Guimaraes Rocha Aguiar, James G C Hamilton, Omar Hamarsheh, Mallory Hawksworth, Jacob M Hendershot, Paul V Hickner, Jean-Luc Imler, Panagiotis Ioannidis, Emily C Jennings, Shaden Kamhawi, Charikleia Karageorgiou, Ryan C Kennedy, Andreas Krueger, José M Latorre-Estivalis, Petros Ligoxygakis, Antonio Carlos A Meireles-Filho, Patrick Minx, Jose Carlos Miranda, Michael J Montague, Ronald J Nowling, Fabiano Oliveira, João Ortigão-Farias, Marcio G Pavan, Marcos Horacio Pereira, Andre Nobrega Pitaluga, Roenick Proveti Olmo, Marcelo Ramalho-Ortigao, José M C Ribeiro, Andrew J Rosendale, Mauricio R V Sant'anna, Steven E Scherer, Nágila F C Secundino, Douglas A Shoue, Caroline Da Silva Moraes, João Silveira Moledo Gesto, Nataly Araujo Souza, Zainulabueddin Syed, Samuel Tadros, Rayane Teles-De-Freitas, Erich L Telleria, Chad Tomlinson, Yara M Traub-Csekö, João Trindade Marques, Zhijian Tu, Maria F Unger, Jesus Valenzuela, Flávia V Ferreira, Karla P V De Oliveira, Felipe M Vigoder, John Vontas, Lihui Wang, Gareth D Weedall, Elyes Zhioua, Stephen Richards, Wesley C Warren, Robert M Waterhouse, Rod J Dillon, Mary Ann Mcdowell

Faculty, Staff and Students Publications

Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the kinetoplastid parasites of the genus Leishmania, the causative agents of devastating diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. No approved efficacious vaccine exists for leishmaniasis and available therapeutic drugs are either toxic and/or expensive, or the parasites are becoming resistant to the more recently developed drugs. Therefore, sand fly and/or reservoir control …

Incidence Rates Of Medically Attended Covid-19 In Infants Less Than 6 Months Of Age, Isabel Griffin, Stephanie A Irving, Carmen Sofia Arriola, Angela P Campbell, De-Kun Li, Fatimah S Dawood, Caroline Doughty-Skierski, Jeannette R Ferber, Nickolas Ferguson, Louise Hadden, Jillian T Henderson, Mary Juergens, Venkatesh Kancharla, Allison L Naleway, Gabriella Newes-Adeyi, Erin Nicholson, Roxana Odouli, Lawrence Reichle, Mo Sanyang, Kate Woodworth, Flor M Munoz

Faculty, Staff and Students Publications

BACKGROUND: Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age.

METHODS: We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test …

Efficacy And Safety Of Azithromycin Versus Placebo To Treat Lower Respiratory Tract Infections Associated With Low Procalcitonin: A Randomised, Placebo-Controlled, Double-Blind, Non-Inferiority Trial, Ephraim L Tsalik, Nadine G Rouphael, Ruxana T Sadikot, Maria C Rodriguez-Barradas, Micah T Mcclain, Dana M Wilkins, Christopher W Woods, Geeta K Swamy, Emmanuel B Walter, Hana M El Sahly, Wendy A Keitel, Mark J Mulligan, Bonifride Tuyishimire, Elisavet Serti, Toshimitsu Hamasaki, Scott R Evans, Varduhi Ghazaryan, Marina S Lee, Ebbing Lautenbach, Antibacterial Resistance Leadership Group, Trap-Lrti Study Group

Faculty, Staff and Student Publications

BACKGROUND: Lower respiratory tract infections are frequently treated with antibiotics, despite a viral cause in many cases. It remains unknown whether low procalcitonin concentrations can identify patients with lower respiratory tract infection who are unlikely to benefit from antibiotics. We aimed to compare the efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections in patients with low procalcitonin.

METHODS: We conducted a randomised, placebo-controlled, double-blind, non-inferiority trial at five health centres in the USA. Adults aged 18 years or older with clinically suspected non-pneumonia lower respiratory tract infection and symptom duration from 24 h to 28 …

In-Hospital Mortality Risk Stratification In Children Aged Under 5 Years With Pneumonia With Or Without Pulse Oximetry: A Secondary Analysis Of The Pneumonia Research Partnership To Assess Who Recommendations (Prepare) Dataset, Shubhada Hooli, Carina King, Eric D Mccollum, Tim Colbourn, Norman Lufesi, Charles Mwansambo, Christopher J Gregory, Somsak Thamthitiwat, Clare Cutland, Shabir Ahmed Madhi, Marta C Nunes, Bradford D Gessner, Tabish Hazir, Joseph L Mathew, Emmanuel Addo-Yobo, Noel Chisaka, Mumtaz Hassan, Patricia L Hibberd, Prakash Jeena, Juan M Lozano, William B Macleod, Archana Patel, Donald M Thea, Ngoc Tuong Vy Nguyen, Syed Ma Zaman, Raul O Ruvinsky, Marilla Lucero, Cissy B Kartasasmita, Claudia Turner, Rai Asghar, Salem Banajeh, Imran Iqbal, Irene Maulen-Radovan, Greta Mino-Leon, Samir K Saha, Mathuram Santosham, Sunit Singhi, Shally Awasthi, Ashish Bavdekar, Monidarin Chou, Pagbajabyn Nymadawa, Jean-William Pape, Glaucia Paranhos-Baccala, Valentina Sanchez Picot, Mala Rakoto-Andrianarivelo, Vanessa Rouzier, Graciela Russomando, Mariam Sylla, Philippe Vanhems, Jianwei Wang, Sudha Basnet, Tor A Strand, Mark I Neuman, Luis Martinez Arroyo, Marcela Echavarria, Shinjini Bhatnagar, Nitya Wadhwa, Rakesh Lodha, Satinder Aneja, Angela Gentile, Mandeep Chadha, Siddhivinayak Hirve, Kerry-Ann F O'Grady, Alexey W Clara, Chris A Rees, Harry Campbell, Harish Nair, Jennifer Falconer, Linda J Williams, Margaret Horne, Shamim A Qazi, Yasir Bin Nisar, Pneumonia Research Partnership To Assess Who Recommendations (Prepare) Study Group

Faculty, Staff and Students Publications

OBJECTIVES: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors.

METHODS: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors.

RESULTS: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five …

A Randomized Phase I/Ii Safety And Immunogenicity Study Of The Montanide-Adjuvanted Sars-Cov-2 Spike Protein-Rbd-Fc Vaccine, Aks-452, Eline A Feitsma, Yester F Janssen, Hendrikus H Boersma, Yannick Van Sleen, Debbie Van Baarle, David G Alleva, Thomas M Lancaster, Thillainaygam Sathiyaseelan, Sylaja Murikipudi, Andrea R Delpero, Melanie M Scully, Ramya Ragupathy, Sravya Kotha, Jeffrey R Haworth, Nishit J Shah, Vidhya Rao, Shashikant Nagre, Shannon E Ronca, Freedom M Green, Ari Aminetzah, Frans Sollie, Schelto Kruijff, Maarten Brom, Gooitzen M Van Dam, Todd C Zion

Faculty, Staff and Students Publications

BACKGROUND: Previous interim data from a phase I study of AKS-452, a subunit vaccine comprising an Fc fusion of the respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (SP/RBD) emulsified in the water-in-oil adjuvant, Montanide™ ISA 720, suggested a good safety and immunogenicity profile in healthy adults. This phase I study was completed and two dosing regimens were further evaluated in this phase II study.

METHODS: This phase II randomized, open-labelled, parallel group study was conducted at a single site in The Netherlands with 52 healthy adults (18 - 72 years) receiving AKS-452 subcutaneously at one 90 µg …

Aberrant Function Of Pathogenic Stat3 Mutant Proteins Is Linked To Altered Stability Of Monomers And Homodimers, Moses M Kasembeli, Efiyenia Kaparos, Uddalak Bharadwaj, Ahmad Allaw, Alain Khouri, Bianca Acot, David J Tweardy

Faculty, Staff and Student Publications

STAT3 mutations, predominantly in the DNA-binding domain (DBD) and Src-homology 2 domain (SH2D), cause rare cases of immunodeficiency, malignancy, and autoimmunity. The exact mechanisms by which these mutations abrogate or enhance STAT3 function are not completely understood. Here, we examined how loss-of-function (LOF) and gain-of-function (GOF) STAT3 mutations within the DBD and SH2D affect monomer and homodimer protein stability as well as their effect on key STAT3 activation events, including recruitment to phosphotyrosine (pY) sites within peptide hormone receptors, tyrosine phosphorylation at Y705, dimerization, nuclear translocation, and DNA binding. The DBD LOF mutants showed reduced DNA binding when homodimerized, whereas …

A Mast Cell-Thermoregulatory Neuron Circuit Axis Regulates Hypothermia In Anaphylaxis, Chunjing Bao, Ouyang Chen, Huaxin Sheng, Jeffrey Zhang, Yikai Luo, Byron W Hayes, Han Liang, Wolfgang Liedtke, Ru-Rong Ji, Soman N Abraham

Faculty, Staff and Student Publications

IgE-mediated anaphylaxis is an acute life-threatening systemic reaction to allergens, including certain foods and venoms. Anaphylaxis is triggered when blood-borne allergens activate IgE-bound perivascular mast cells (MCs) throughout the body, causing an extensive systemic release of MC mediators. Through precipitating vasodilatation and vascular leakage, these mediators are believed to trigger a sharp drop in blood pressure in humans and in core body temperature in animals. We report that the IgE/MC-mediated drop in body temperature in mice associated with anaphylaxis also requires the body's thermoregulatory neural circuit. This circuit is activated when granule-borne chymase from MCs is deposited on proximal TRPV1+ …

Ferroptosis Hijacking By Mycobacterium Tuberculosis, Boyi Gan

Faculty, Staff and Student Publications

A recent study from Nature Communications reveals that Mycobacterium tuberculosis can hijack epigenetic machinery in host cells and induce host cell ferroptosis, which promotes pathogen pathogenicity and spread. These findings also suggest new therapeutic strategies to treat tuberculosis.

Ms 083 Guide To Harold Pruessner, Md Papers (1964-1998), Harold Pruessner (1925-2007)

Manuscript Finding Aids

The Harold Pruessner, MD papers contains documents relating to his role at the University of Texas Medical School at Houston, particularly in the Department of Family Practice. Contents include articles, curricula, training material, information about family practice, and other administrative materials. There is also an audio recording of an interview with Dr. Pruessner from 1998. Items date from 1964 to 1998, with most of them corresponding to his time in Houston, Texas. See more at MS 083.

How Have Researchers Defined Institutions, Politics, Organizations And Governance In Research Related To Epidemic And Pandemic Response? A Scoping Review To Map Current Concepts, Austin Wu, Shivangi Khanna, Shelly Keidar, Peter Berman, Laura Jane Brubacher

Faculty, Staff and Student Publications

In recent years, the literature on public health interventions and health outcomes in the context of epidemic and pandemic response has grown immensely. However, relatively few of these studies have situated their findings within the institutional, political, organizational and governmental (IPOG) context in which interventions and outcomes exist. This conceptual mapping scoping study synthesized the published literature on the impact of IPOG factors on epidemic and pandemic response and critically examined definitions and uses of the terms IPOG in this literature. This research involved a comprehensive search of four databases across the social, health and biomedical sciences as well as …

Partnering With Patients And Families Living With Chronic Conditions To Coproduce Diagnostic Safety Through Ourdx: A Previsit Online Engagement Tool, Sigall K Bell, Zhiyong J Dong, Catherine M Desroches, Nicholas Hart, Stephen Liu, Brianna Mahon, Long H Ngo, Eric J Thomas, Fabienne Bourgeois

Faculty, Staff and Student Publications

OBJECTIVE: Patients and families are key partners in diagnosis, but methods to routinely engage them in diagnostic safety are lacking. Policy mandating patient access to electronic health information presents new opportunities. We tested a new online tool ("OurDX") that was codesigned with patients and families, to determine the types and frequencies of potential safety issues identified by patients/families with chronic health conditions and whether their contributions were integrated into the visit note.

METHODS: Patients/families at 2 US healthcare sites were invited to contribute, through an online previsit survey: (1) visit priorities, (2) recent medical history/symptoms, and (3) potential diagnostic concerns. …

T-Cell Receptor Repertoire Sequencing In The Era Of Cancer Immunotherapy, Meredith L Frank, Kaylene Lu, Can Erdogan, Yi Han, Jian Hu, Tao Wang, John V Heymach, Jianjun Zhang, Alexandre Reuben

Faculty, Staff and Student Publications

T cells are integral components of the adaptive immune system, and their responses are mediated by unique T-cell receptors (TCR) that recognize specific antigens from a variety of biological contexts. As a result, analyzing the T-cell repertoire offers a better understanding of immune responses and of diseases like cancer. Next-generation sequencing technologies have greatly enabled the high-throughput analysis of the TCR repertoire. On the basis of our extensive experience in the field from the past decade, we provide an overview of TCR sequencing, from the initial library preparation steps to sequencing and analysis methods and finally to functional validation techniques. …

Tsks Localizes To Nuage In Spermatids And Regulates Cytoplasmic Elimination During Spermiation, Keisuke Shimada, Soojin Park, Seiya Oura, Taichi Noda, Akane Morohoshi, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Spermatozoa have a streamlined shape to swim through the oviduct to fertilize oocytes. To become svelte spermatozoa, spermatid cytoplasm must be eliminated in several steps including sperm release, which is part of spermiation. Although this process has been well observed, the molecular mechanisms that underlie it remain unclear. In male germ cells, there are membraneless organelles called nuage, which are observed by electron microscopy in various forms of dense material. Reticulated body (RB) and chromatoid body remnant (CR) are two types of nuage in spermatids, but the functions of both are unknown. Using CRISPR/Cas9 technology, we deleted the entire coding …

Human Schistosomiasis Vaccines As Next Generation Control Tools, Peter J Hotez, Maria Elena Bottazzi

Faculty, Staff and Students Publications

No abstract provided.

The P323l Substitution In The Sars-Cov-2 Polymerase (Nsp12) Confers A Selective Advantage During Infection, Hannah Goldswain, Xiaofeng Dong, Rebekah Penrice-Randal, Muhannad Alruwaili, Ghada T Shawli, Tessa Prince, Maia Kavanagh Williamson, Jayna Raghwani, Nadine Randle, Benjamin Jones, I'Ah Donovan-Banfield, Francisco J Salguero, Julia A Tree, Yper Hall, Catherine Hartley, Maximilian Erdmann, James Bazire, Tuksin Jearanaiwitayakul, Malcolm G Semple, Peter J M Openshaw, J Kenneth Baillie, Isaric4c Investigators, Stevan R Emmett, Paul Digard, David A Matthews, Lance Turtle, Alistair C Darby, Andrew D Davidson, Miles W Carroll, Julian A Hiscox

Faculty, Staff and Student Publications

BACKGROUND: The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure.

RESULTS: Investigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant …

Ic090: Ken Mattox Interview, Transcript, Friends Of The Texas Medical Center Library

2023 Oral History Project

See more at Friends of the Texas Medical Center Library Records and its finding aid.

Neuronal Sirt3 Deletion Predisposes To Female-Specific Alterations In Cellular Metabolism, Memory, And Network Excitability, Jennifer N Pearson-Smith, Ruth Fulton, Christopher Q Huynh, Anna G Figueroa, Gia B Huynh, Li-Ping Liang, Lindsey B Gano, Cole R Michel, Nichole Reisdorph, Richard Reisdorph, Kristofer S Fritz, Eric Verdin, Manisha Patel

Faculty, Staff and Students Publications

Mitochondrial dysfunction is an early event in the pathogenesis of neurologic disorders and aging. Sirtuin 3 (SIRT3) regulates mitochondrial function in response to the cellular environment through the reversible deacetylation of proteins involved in metabolism and reactive oxygen species detoxification. As the primary mitochondrial deacetylase, germline, or peripheral tissue-specific deletion of SIRT3 produces mitochondrial hyperacetylation and the accelerated development of age-related diseases. Given the unique metabolic demands of neurons, the role of SIRT3 in the brain is only beginning to emerge. Using mass spectrometry-based acetylomics, high-resolution respirometry, video-EEG, and cognition testing, we report targeted deletion of SIRT3 from select neurons …

Clinically Adjudicated Reference Standards For Evaluation Of Infectious Diseases Diagnostics, Robin Patel, Ephraim L Tsalik, Scott Evans, Vance G Fowler, Sarah B Doernberg, Antibacterial Resistance Leadership Group

Faculty, Staff and Student Publications

Lack of a gold standard can present a challenge for evaluation of diagnostic test accuracy of some infectious diseases tests, particularly when the test's accuracy potentially exceeds that of its predecessors. This approach may measure agreement with an imperfect reference, rather than correctness, because the right answer is unknown. Solutions consist of multitest comparators, including those that involve a test under evaluation if multiple new tests are being evaluated together, using latent class modeling, and clinically adjudicated reference standards. Clinically adjudicated reference standards may be considered as comparator methods when no predefined test or composite of tests is sufficiently accurate; …