Allergy and Immunology Commons^™

Ga2len Anacare Consensus Statement: Potential Of Omalizumab In Food Allergy Management, Torsten Zuberbier, Antonella Muraro, Ulugbek Nurmatov, Stefania Arasi, Katarina Stevanovic, Aikaterini Anagnostou, Roberta Bonaguro, Sharon Chinthrajah, Gideon Lack, Alessandro Fiocchi, Thuy-My Le, Paul Turner, Montserrat Alvaro Lozano, Elizabeth Angier, Simona Barni, Phillippe Bégin, Barbara Ballmer-Weber, Victoria Cardona, Carsten Bindslev-Jensen, Antonella Cianferoni, Nicolette De Jong, Debra De Silva, Antoine Deschildre, Audrey Dunn Galvin, Motohiro Ebisawa, David M Fleischer, Jennifer Gerdts, Mattia Giovannini, Josefine Gradman, Susanne Halken, Syed Hasan Arshad, Ekaterina Khaleva, Susanne Lau, Richard Loh, Mika J Mäkelä, Mary Jane Marchisotto, Laura Morandini, Charlotte G Mortz, Caroline Nilsson, Anna Nowak-Wegrzyn, Marcia Podestà, Lars K Poulsen, Graham Roberts, Pablo Rodríguez Del Río, Hugh A Sampson, Angel Sánchez, Sabine Schnadt, Peter K Smith, Hania Szajewska, Natasa Teovska Mitrevska, Alice Toniolo, Carina Venter, Amena Warner, Gary W K Wong, Robert Wood, Margitta Worm

Faculty, Staff and Students Publications

Immunoglobulin E (IgE)‐mediated food allergies are the most common type of food allergy, often causing rapid symptoms after exposure to allergens posing a serious health risk and a high impact on patient's and caregiver's quality of life. Omalizumab, a humanized anti‐IgE monoclonal antibody, reduces allergic reactions by binding to circulating IgE. Omalizumab has been successfully used in allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic urticaria, and was recently approved for treating IgE‐mediated food allergies by the US Food and Drug Administration (FDA). This GA2LEN ANACARE Consensus Statement presents our position on the use of omalizumab for treating IgE‐mediated …

Diffuse Glioneuronal Tumor With Oligodendroglioma-Like Features And Nuclear Clusters Relapse In A Seven-Year-Old Boy: An Unusual Case Exhibiting Near-Tetraploidy And Chromosome 14 Diploidy, Francis M Torres, Thomas Denapoli, Ping-Sun Chen, Carrie Mohila, Kevin E Fisher, Kenneth Aldape, Mark R Lee, Timothy C Griffin

Faculty, Staff and Students Publications

Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) is a rare brain tumor of the central nervous system (CNS). Although only a few cases of DGONC have been reported following the initial description of the tumor, they have a distinct DNA methylation pattern and share a recurrent chromosomal finding of monosomy 14. We encountered a seven-year-old boy who presented with seizures and was found to have a left frontal and suprasellar mass. The tumor was grossly totally resected; histopathologic evaluation showed a cellular glioneuronal tumor with brisk mitotic activity. A near-tetraploid chromosome complement was detected, with associated diploidy …

Experiences Of Midwestern Obstetric Clinicians During The Coronavirus Disease 2019 Pandemic, Drishti D Sinha, Megan Foeller, Abigail S Bell, Anthony J Nixon, Darrell Hudson, Aimee S James, Amy R Scheffer, Ana A Baumann, Emily Diveley, Ebony B Carter, Nandini Raghuraman, Indira U Mysorekar, Jeannie C Kelly

Faculty, Staff and Students Publications

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic led to healthcare system changes aimed at minimizing disease transmission that impacted experiences with obstetric healthcare.

OBJECTIVE: To explore experiences of clinicians providing obstetric care during the COVID-19 pandemic.

STUDY DESIGN: Qualitative, in-depth, semi-structured interviews were conducted with five nurse practitioners and 16 obstetrical physicians providing a mix of outpatient and inpatient obstetric care during the COVID-19 pandemic in a mid-sized, Midwestern city in the United States. Interviews elucidated challenges and facilitators of obstetric care provision and vaccination of pregnant patients against COVID-19 during the pandemic. Transcripts were coded inductively then deductively using …

Perivascular Epithelioid Cell-Family Tumors In Children, Adolescents, And Young Adults: Clinicopathologic Features In 70 Cases, Phoebe M Hammer, Angus Toland, Muhammad Shaheen, Archana Shenoy, Ashwini Esnakula, M John Hicks, Mikako Warran, Alyaa Al-Ibraheemi, Jessica L Davis, Serena Y Tan

Faculty, Staff and Students Publications

Context.—: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors of uncertain histogenesis expressing smooth muscle and melanocytic markers. The clinicopathologic spectrum in young patients is not well documented.

Objective.—: To describe a multi-institutional series of PEComas in children, adolescents, and young adults.

Design.—: PEComas, not otherwise specified (NOS); angiomyolipomas (AMLs); lymphangioleiomyomatosis; and clear cell sugar tumors were retrospectively identified from 6 institutions and the authors' files.

Results.—: Seventy PEComas in 64 patients (median age, 15 years) were identified. They were more common in females (45 of 64 patients), occurring predominantly in the kidney (53 of 70), followed by the …

Opioid Use In Thoracic Surgery: A Retrospective Study On Postoperative Complications, Jerry Xiao, Duc T Nguyen, Zoe K Lichtenberg, Elsie Rizk, Leonora M Meisenbach, Ray Chihara, Edward A Graviss, Min P Kim

Faculty, Staff and Students Publications

Background: Opioids are important medications that are used to control postoperative pain. The enhanced recovery after surgery (ERAS) program has reduced opioid use after surgery. In a surgical practice with a robust ERAS program, we wanted to determine if there was a relationship between in-hospital opioid use and postoperative complications.

Methods: We performed a retrospective nested case-control study of patients who underwent thoracic surgical intervention at the Houston Methodist Hospital (HMH) between 11/2020 and 11/2021 from the thoracic surgery database with hospital morphine milligram equivalent (MME) information, comparing patients who did and did not experience postoperative complications. We determined the …

Novel Genes Of The Male Reproductive System: Potential Roles In Male Reproduction And As Non-Hormonal Male Contraceptive Targets, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

The development of novel non-hormonal male contraceptives represents a pivotal frontier in reproductive health, driven by the need for safe, effective, and reversible contraceptive methods. This comprehensive review explores the genetic underpinnings of male fertility, emphasizing the crucial roles of specific genes and structural variants (SVs) identified through advanced sequencing technologies such as long-read sequencing (LRS). LRS has revolutionized the detection of structural variants and complex genomic regions, offering unprecedented precision and resolution over traditional next-generation sequencing (NGS). Key genetic targets, including those implicated in spermatogenesis and sperm motility, are highlighted, showcasing their potential as non-hormonal contraceptive targets. The review …

Addressing Platelet Insecurity – A National Call To Action, Eric A Gehrie, Pampee P Young, Sridhar V Basavaraju, Arthur W Bracey, Andrew P Cap, Liz Culler, Nancy M Dunbar, Mary Homer, Iris Isufi, Rob Macedo, Tanya Petraszko, Glenn Ramsey, Christopher A Tormey, Richard M Kaufman, Edward L Snyder

Faculty, Staff and Students Publications

No abstract provided.

Synthesis And Optimization Of Small Molecule Inhibitors Of Prostate Specific Antigen, Jeffery A Erickson, Ravikumar Jimmidi, Prashanth Anamthathmakula, Xuan Qin, Jian Wang, Leyi Gong, Jaehyeon Park, Gary Koolpe, Caitlin Tan, Martin M Matzuk, Feng Li, Srinivas Chamakuri, Wipawee Winuthayanon

Faculty, Staff and Students Publications

Semen liquefaction is a postejaculation process that transforms semen from a gel-like (coagulated) form to a water-like consistency (liquefied). This process is primarily regulated by serine proteases from the prostate gland, most prominently, prostate-specific antigen (PSA; KLK3). Inhibiting PSA activity has the potential to impede liquefaction of human semen, presenting a promising target for nonhormonal contraception in the female reproductive tract. This study employed triazole B1 as a starting compound. Through systematic design, synthesis, and optimization, we identified compound 20 (CDD-3290) as a 216 nM inhibitor of PSA with better stability in media than triazole B1. Further, we also evaluated …

Sensory Dysfunction, Microbial Infections, And Host Responses In Alzheimer's Disease, Praveen Bathini, Emanuele Brai, Brian J Balin, Lynn Bimler, David B Corry, Davangere P Devanand, Richard L Doty, Garth D Ehrlich, William A Eimer, Tamas Fulop, David L Hahn, Christine J Hammond, Joseph Infanti, Ruth Itzhaki, Richard Lathe, Christopher Scott Little, Rima Mcleod, Shima T Moein, Amy R Nelson, George Perry, Or A Shemesh, Rudolph E Tanzi, Wilmore C Webley, Nikki M Schultek, Lavinia Alberi Auber

Faculty, Staff and Students Publications

Sensory functions of organs of the head and neck allow humans to interact with the environment and establish social bonds. With aging, smell, taste, vision, and hearing decline. Evidence suggests that accelerated impairment in sensory abilities can reflect a shift from healthy to pathological aging, including the development of Alzheimer's disease (AD) and other neurological disorders. While the drivers of early sensory alteration in AD are not elucidated, insults such as trauma and infections can affect sensory function. Herein, we review the involvement of the major head and neck sensory systems in AD, with emphasis on microbes exploiting sensory pathways …

Cyp3a-Mediated Carbon-Carbon Bond Cleavages In Drug Metabolism, Junhui Zhou, Xuan Qin, Shenzhi Zhou, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

Cytochrome P450 enzymes (P450s) play a critical role in drug metabolism, with the CYP3A subfamily being responsible for the biotransformation of over 50% of marked drugs. While CYP3A enzymes are known for their extensive catalytic versatility, one intriguing and less understood function is the ability to mediate carbon-carbon (C-C) bond cleavage. These uncommon reactions can lead to unusual metabolites and potentially influence drug safety and efficacy. This review focuses on examining examples of C-C bond cleavage catalyzed by CYP3A, exploring the mechanisms, physiological significance, and implications for drug metabolism. Additionally, examples of CYP3A-mediated ring expansion via C-C bond cleavages are …

A Systematic Review And Expert Delphi Consensus Recommendation On The Use Of Vaccines In Patients Receiving Dupilumab: A Position Paper Of The American College Of Allergy, Asthma And Immunology, Jay A Lieberman, Derek K Chu, Tasnuva Ahmed, Timothy E Dribin, Elissa M Abrams, Aikaterini Anagnostou, Kimberly G Blumenthal, Mark Boguniewicz, Nicole M Chase, David B K Golden, Nicholas L Hartog, Jennifer R Heimall, Tina Ho, Monica G Lawrence, David A Khan, Timothy Dean Minniear, S Shahzad Mustafa, John J Oppenheimer, Elizabeth J Phillips, Allison Ramsey, Nicholas L Rider, Lynda Schneider, Marcus S Shaker, Jonathan M Spergel, Cosby A Stone, David R Stukus, Julie Wang, Matthew J Greenhawt

Faculty, Staff and Students Publications

BACKGROUND: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the …

Initiation Of Metformin In Early Pregnancy Results In Fetal Bioaccumulation, Growth Restriction, And Renal Dysmorphology In A Primate Model, Erin Bolte, Tyler Dean, Brandon Garcia, Maxim D Seferovic, Kristin Sauter, Gwendolynn Hummel, Matthew Bucher, Feng Li, John Hicks, Xuan Qin, Melissa A Suter, Enrico R Barrozo, Michael Jochum, Cynthia Shope, Jacob E Friedman, Maureen Gannon, Stephanie R Wesolowski, Carrie E Mccurdy, Paul Kievit, Kjersti M Aagaard

Faculty, Staff and Students Publications

Background: In recent years, pragmatic metformin use in pregnancy has stretched to include prediabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus, and (most recently) preeclampsia. However, with its expanded use, concerns of unintended harm have been raised.

Objective: This study developed an experimental primate model and applied ultrahigh performance liquid chromatography coupled to triple-quadrupole mass spectrometry for direct quantitation of maternal and fetal tissue metformin levels with detailed fetal biometry and histopathology.

Study design: Within 30 days of confirmed conception (defined as early pregnancy), 13 time-bred (timed-mated breeding) Rhesus dams with pregnancies designated for fetal necropsy were initiated on …

Determining Predictors Of Actual Living Kidney Donation Based On Potential Donor Characteristics, Andrea M Meinders, Edward A Graviss, Duc T Nguyen, Jonathan Daw, Krista L Lentine, John Devin Peipert, Ahmed Osama Gaber, David A Axelrod, Francis L Weng, Amy D Waterman

Faculty, Staff and Students Publications

Background: Living donor kidney transplantation is the optimal treatment for end-stage kidney disease; however, few living donor candidates (LDCs) who begin evaluation actually donate. While some LDCs are deemed medically ineligible, others discontinue for potentially modifiable reasons.

Methods: At five transplant centers, we conducted a prospective cohort study measuring LDCs' clinical and psychosocial characteristics, educational preparation, readiness to donate, and social determinants of health. We followed LDCs for 12 months after evaluation to determine whether they donated a kidney, opted to discontinue, had modifiable reasons for discontinuing, were medically ineligible, or had other recipient-related reasons for discontinuing.

Results: Among 2184 …

Facilitators And Barriers To Initiating And Completing Tuberculosis Preventive Treatment Among Children And Adolescents Living With Hiv In Uganda: A Qualitative Study Of Adolescents, Caretakers And Health Workers, Pauline Mary Amuge, Denis Ndekezi, Moses Mugerwa, Dickson Bbuye, Diana Antonia Rutebarika, Lubega Kizza, Christine Namugwanya, Angella Baita, Peter James Elyanu, Patricia Nahirya Ntege, Dithan Kiragga, Carol Birungi, Adeodata Rukyalekere Kekitiinwa, Agnes Kiragga, Moorine Peninah Sekadde, Nicole-Austin Salazar, Anna Maria Mandalakas, Philippa Musoke

Faculty, Staff and Students Publications

INTRODUCTION: People living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV). We explored the facilitators and barriers to TPT initiation and completion among CALHIV among adolescents aged 10-19years and caretakers of children below 18years.

METHODS: We conducted a qualitative study …

Poly(Adp-Ribose) Polymerase-1 Regulates Pyroptosis Independent Function Of Nlrp3 Inflammasome In Neutrophil Extracellular Trap Formation, Louis J Delinois, Atul Sharma, Ashwin K Ramesh, Laurel D Boatright, Qun Li, Rong Xu, Hongbo R Luo, Bibhuti B Mishra, Jyotika Sharma

Faculty, Staff and Student Publications

Neutrophil extracellular traps (NETs) function to control infectious agents as well as to propagate inflammatory response in a variety of disease conditions. DNA damage associated with chromatin decondensation and NACHT domain-leucine-rich repeat-and pyrin domain-containing protein 3 (NLRP3) inflammasome activation have emerged as crucial events in NET formation, but the link between the two processes is unknown. In this study, we demonstrate that poly(ADP-ribose) polymerase-1 (PARP-1), a key DNA repair enzyme, regulates NET formation triggered by NLRP3 inflammasome activation in neutrophils. Activation of mouse neutrophils with canonical NLRP3 stimulants LPS and nigericin induced NET formation, which was significantly abrogated by pharmacological …

Chick Embryo Chorioallantoic Membrane As A Platform For Assessing The In Vivo Efficacy Of Chimeric Antigen Receptor T-Cell Therapy In Solid Tumors, Allison J Nipper, Emilie A K Warren, Kershena S Liao, Hsuan-Chen Liu, Chieko Michikawa, Caroline E Porter, Gabrielle A Wells, Mariana Villanueva, Fabio Henrique Brasil Da Costa, Ratna Veeramachaneni, Hugo Villanueva, Masataka Suzuki, Andrew G Sikora

Faculty, Staff and Student Publications

The fertilized chicken egg chorioallantoic membrane (CAM), a highly vascularized membrane nourishing the developing embryo, also supports rapid growth of three-dimensional vascularized tumors from engrafted cells and tumor explants. Because murine xenograft models suffer limitations of time, cost, and scalability, we propose CAM tumors as a rapid, efficient screening tool for assessing anti-tumor efficacy of chimeric Ag receptor (CAR) T cells against solid tumors. We tested the efficacy of human epidermal growth factor receptor 2 (HER2)-specific CAR T cells against luminescent, HER2-expressing (FaDu, SCC-47) or HER2-negative (MDA-MB-468) CAM-engrafted tumors. Three days after tumor engraftment, HER2-specific CAR T cells were applied …

Challenges Of Insulin-Like Growth Factor-1 Testing, Rongrong Huang, Junyan Shi, Ruhan Wei, Jieli Li

Faculty, Staff and Students Publications

Insulin-like growth factor 1 (IGF-1), primarily synthesized in the liver, was initially discovered due to its capacity to replicate the metabolic effects of insulin. Subsequently, it emerged as a key regulator of the actions of growth hormone (GH), managing critical processes like cell proliferation, differentiation, and apoptosis. Notably, IGF-1 displays a longer half-life compared to GH, making it less susceptible to factors that may affect GH concentrations. Consequently, the measurement of IGF-1 proves to be more specific and sensitive when diagnosing conditions such as acromegaly or GH deficiency. The recognition of the existence of IGFBPs and their potential to interfere …

Association Between Diabetes Mellitus And Total Hip Arthroplasty Outcomes: An Observational Study Using The Us National Inpatient Sample, Sumanth Chandrupatla, Kranti Rumalla, Jasvinder A Singh

Faculty, Staff and Students Publications

OBJECTIVES: To investigate the association of diabetes with postoperative outcomes in patients undergoing primary total hip arthroplasty (THA).

DESIGN: Retrospective cohort study using data from the US National Inpatient Sample (NIS).

SETTING: Study cohort was hospitalisations for primary THA in the USA, identified from the 2016-2020 NIS.

PARTICIPANTS: We identified 2 467 215 adults in the 2016-2020 NIS who underwent primary THA using International Classification of Diseases, 10th Revision codes. Primary THA hospitlizations were analysed as the overall group and also stratified by the underlying primary diagnosis for THA.

OUTCOME MEASURES: Outcome measures of interest were the length of hospital …

If At First We Don't Succeed, Should We Try, Try Again?, Kriti Puri, Susan W Denfield

Faculty, Staff and Students Publications

No abstract provided.

Tfeb Safeguards Trophoblast Syncytialization In Humans And Mice, Wanshan Zheng, Yue Zhang, Peiqun Xu, Zexin Wang, Xuan Shao, Chunyan Chen, Han Cai, Yinan Wang, Ming-An Sun, Wenbo Deng, Fan Liu, Jinhua Lu, Xueqin Zhang, Dunjin Cheng, Indira U Mysorekar, Haibin Wang, Yan-Ling Wang, Xiaoqian Hu, Bin Cao

Faculty, Staff and Students Publications

The formation of multinucleated syncytiotrophoblast (STB) through cell fusion of cytotrophoblast, also termed syncytialization, ensures the proper placental structure and functions. Nutrient insufficiency and inactivation of the mechanistic target of rapamycin complex 1 (mTORC1) in trophoblasts have been shown to enhance STB formation; however, the underlying mechanism remains elusive. Here, we showed that the deficiency of a mTORC1 downstream transcriptional factor, TFEB, significantly impaired STB formation in human trophoblasts and knock-out mice. TFEB conferred direct transcriptional activation of the fusogen ERVFRD-1 and thereby promoted trophoblast syncytialization. Additionally, TFEB expression positively correlated with the reinforced trophoblast syncytialization in human fetal growth …

Ultrapotent Broadly Neutralizing Human-Llama Bispecific Antibodies Against Hiv-1, Jianliang Xu, Tongqing Zhou, Krisha Mckee, Baoshan Zhang, Cuiping Liu, Alexandra F Nazzari, Amarendra Pegu, Chen-Hsiang Shen, Jordan E Becker, Michael F Bender, Payton Chan, Anita Changela, Ridhi Chaudhary, Xuejun Chen, Tal Einav, Young Do Kwon, Bob C Lin, Mark K Louder, Jonah S Merriam, Nicholas C Morano, Sijy O'Dell, Adam S Olia, Reda Rawi, Ryan S Roark, Tyler Stephens, I-Ting Teng, Emily Tourtellott-Fogt, Shuishu Wang, Eun Sung Yang, Lawrence Shapiro, Yaroslav Tsybovsky, Nicole A Doria-Rose, Rafael Casellas, Peter D Kwong

Faculty, Staff and Student Publications

Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV‐1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion‐stabilized HIV‐1 envelope (Env) trimer, BG505 DS‐SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4‐binding site (CD4bs) of vulnerability. Two of the vaccine‐elicited CD4bs‐targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a‐hinge region and human IgG1‐constant region (G36×3‐IgG2a and R27×3‐IgG2a), neutralized 96% of a multiclade 208‐strain panel at geometric mean IC80s of 0.314 and 0.033 µg mL−1, respectively. Cryo‐EM …

Utility Of Cystatin C-Based Equation For The Estimation Of Glomerular Filtration Rate In A Pediatric Population, Ridwan B Ibrahim, Poyyapakkam Srivaths, Estella Tam, Sridevi Devaraj

Faculty, Staff and Students Publications

Background: The accurate assessment of kidney function is vital for the early detection of kidney damage. The estimated glomerular filtration rate GFR (eGFR) from serum cystatin C (CysC) and creatinine-based equations are commonly used in clinical practice as an alternative to the invasive measured glomerular filtration rate (mGFR), which is the usually accepted overall best index of kidney function in health and disease. Recently the CKiD under 25 (CkiD U25) equations have been shown to perform well in children and young adults with chronic kidney disease (CKD). In this focused report, we evaluated the performance of the CkiD U25 equations …

Implementation, Evolution, And Laboratory Performance Of Methods-Based Proficiency Testing For Next-Generation Sequencing Detection Of Germline Sequence Variants, Karen D Tsuchiya, Birgit Funke, Madhuri Hegde, Avni Santani, Rhona J Souers, Szabolcs Szelinger, Jaimie Halley, Qin Zhao, Nicole Mot, Angshumoy Roy, Vanessa L Smith, Bing M Zhang, Karl Voelkerding, Ann M Moyer

Faculty, Staff and Students Publications

Context.—: Next-generation sequencing (NGS)-based assays are used for diagnosis of diverse inherited disorders. Limited data are available pertaining to interlaboratory analytical performance of these assays.

Objective.—: To report on the College of American Pathologists (CAP) NGS Germline Program, which is methods based, and explore the evolution in laboratory testing practices.

Design.—: Results from the NGS Germline Program from 2016-2020 were analyzed for interlaboratory analytical performance. Self-reported laboratory testing practices were also evaluated.

Results.—: From 2016-2020, a total of 297 laboratories participated in at least 1 program mailing. Of the 289 laboratories that provided information on tests offered, 138 (47.8%) offered …

Impact Of Gut Health And Microbiome On Autism Spectrum Disorder, Sik Yu So, Tor C Savidge

Faculty, Staff and Students Publications

No abstract provided.

Sting Agonist 8803 Reprograms The Immune Microenvironment And Increases Survival In Preclinical Models Of Glioblastoma, Hinda Najem, Spencer T Lea, Shashwat Tripathi, Lisa Hurley, Chao-Hsien Chen, Ivana William, Moloud Sooreshjani, Michelle Bowie, Genevieve Hartley, Corey Dussold, Sebastian Pacheco, Crismita Dmello, Catalina Lee-Chang, Kathleen Mccortney, Alicia Steffens, Jordain Walshon, Martina Ott, Jun Wei, Anantha Marisetty, Irina Balyasnikova, Roger Stupp, Rimas V Lukas, Jian Hu, Charles David James, Craig M Horbinski, Maciej S Lesniak, David M Ashley, Waldemar Priebe, Leonidas C Platanias, Michael A Curran, Amy B Heimberger

Faculty, Staff and Student Publications

STING agonists can reprogram the tumor microenvironment to induce immunological clearance within the central nervous system. Using multiplexed sequential immunofluorescence (SeqIF) and the Ivy Glioblastoma Atlas, STING expression was found in myeloid populations and in the perivascular space. The STING agonist 8803 increased median survival in multiple preclinical models of glioblastoma, including QPP8, an immune checkpoint blockade-resistant model, where 100% of mice were cured. Ex vivo flow cytometry profiling during the therapeutic window demonstrated increases in myeloid tumor trafficking and activation, alongside enhancement of CD8+ T cell and NK effector responses. Treatment with 8803 reprogrammed microglia to express costimulatory CD80/CD86 …

Preparing Patients For Oral Immunotherapy (Ppoint): International Delphi Consensus For Procedural Preparation And Consent, Douglas P Mack, Timothy E Dribin, Paul J Turner, Richard L Wasserman, Mariam A Hanna, Marcus Shaker, Mimi L K Tang, Pablo Rodríguez Del Río, Brad Sobolewski, Elissa M Abrams, Aikaterini Anagnostou, Stefania Arasi, Sakina Bajowala, Philippe Bégin, Scott B Cameron, Edmond S Chan, Sharon Chinthrajah, Andrew T Clark, Paul Detjen, George Du Toit, Motohiro Ebisawa, Arnon Elizur, Jeffrey M Factor, Justin Greiwe, Jonathan O'B Hourihane, Sarah W Hughes, Douglas H Jones, Antonella Muraro, Anna Nowak-Wegrzyn, Nandinee B Patel, Amy M Scurlock, Atul N Shah, Sayantani B Sindher, Stephen Tilles, Brian P Vickery, Julie Wang, Hugh H Windom, Matthew Greenhawt

Faculty, Staff and Students Publications

BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process.

OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form.

METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was …

Individual Disruption Of 12 Testis-Enriched Genes Via The Crispr/Cas9 System Does Not Affect The Fertility Of Male Mice, Akira Suzuki, Norikazu Yabuta, Keisuke Shimada, Daisuke Mashiko, Keizo Tokuhiro, Yuki Oyama, Haruhiko Miyata, Thomas X Garcia, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

More than 1200 genes have been shown in the database to be expressed predominantly in the mouse testes. Advances in genome editing technologies such as the CRISPR/Cas9 system have made it possible to create genetically engineered mice more rapidly and efficiently than with conventional methods, which can be utilized to screen genes essential for male fertility by knocking out testis-enriched genes. Finding such genes related to male fertility would not only help us understand the etiology of human infertility but also lead to the development of male contraceptives. In this study, we generated knockout mice for 12 genes (Acrv1, Adgrf3, …

Comparison Of Cefiderocol In-Vitro Susceptibility Testing Modalities, Nicholas S Teran, Linh Vuong, Kady Phe, Todd M Lasco, William R Miller, Vincent H Tam

Faculty, Staff and Students Publications

No abstract provided.

Mv140 Mucosal Vaccine Induces Targeted Immune Response For Enhanced Clearance Of Uropathogenic E Coli In Experimental Urinary Tract Infection, Paula Saz-Leal, Marianne Morris Ligon, Carmen María Diez-Rivero, Diego García-Ayuso, Soumitra Mohanty, Marcos Viñuela, Irene Real-Arévalo, Laura Conejero, Annelie Brauner, José Luis Subiza, Indira Uppugunduri Mysorekar

Faculty, Staff and Students Publications

MV140 is an inactivated whole-cell bacterial mucosal vaccine with proven clinical efficacy against recurrent urinary tract infections (UTIs). These infections are primarily caused by uropathogenic E. coli (UPEC) strains, which are unique in their virulence factors and remarkably diverse. MV140 contains a non-UPEC strain, suggesting that it may induce an immune response against different UPEC-induced UTIs in patients. To verify this, we experimentally evaluated the cellular and humoral responses to UTI89, a prototypical UPEC strain, in mice vaccinated with MV140, as well as the degree of protection achieved in a UPEC UTI89 model of acute cystitis. The results show that …

Downregulation Of Mirlet7 Mirna Family Promotes Tc17 Differentiation And Emphysema Via De-Repression Of Rorγt, Phillip A Erice, Xinyan Huang, Matthew J Seasock, Matthew J Robertson, Hui-Ying Tung, Melissa A Perez-Negron, Shivani L Lotlikar, David B Corry, Farrah Kheradmand, Antony Rodriguez

Faculty, Staff and Students Publications

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 microRNA (Mirlet7 miRNA) family is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the Mirlet7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here, we show that overall expression of the Mirlet7 clusters, Mirlet7b/Mirlet7c2 and Mirlet7a1/Mirlet7f1/Mirlet7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with …