Medicine and Health Sciences Commons^™

Health Equity Innovation In Precision Medicine: Data Stewardship And Agency To Expand Representation In Clinicogenomics, Patrick J Silva, Vasiliki Rahimzadeh, Reid Powell, Junaid Husain, Scott Grossman, Adam Hansen, Jennifer Hinkel, Rafael Rosengarten, Marcia G Ory, Kenneth S Ramos

Center for Medical Ethics and Health Policy Staff Publications

Most forms of clinical research examine a very minute cross section of the patient journey. Much of the knowledge and evidence base driving current genomic medicine practice entails blind spots arising from underrepresentation and lack of research participation in clinicogenomic databases. The flaws are perpetuated in AI models and clinical practice guidelines that reflect the lack of diversity in data being used. Participation in clinical research and biobanks is impeded in many populations due to a variety of factors that include knowledge, trust, healthcare access, administrative barriers, and technology gaps. A recent symposium brought industry, clinical, and research participants in …

Unraveling The Relationship Between Sleep Behaviors And Physical Activity In The United States: Insights From 2015 To 2020 Nhanes Data, Deepali K Ernest, Bipin Singh, Fathimath Shamna, Elizabeth A Onugha, Shreela V Sharma

Faculty, Staff and Student Publications

Background: Physical activity is an important component of metabolic health. However, little is known about the impact of specific types/intensities of physical activity on sleep health, especially among ethnically diverse populations. We examined the association of various sleep behaviors with moderate to vigorous work/recreational activity.

Methods: Self-reported data from the National Health and Nutrition Examination Survey 2015-2020 were cross-sectionally analyzed for a sample of 11,039 participants in the United States (U.S.). Weighted univariate logistic regressions determined unadjusted associations, while weighted multivariable regression models adjusting for age, sex, ethnicity, BMI categories, and socio-economic status assessed the multivariable associations with moderate and …

Utility Of Colposcopy For The Screening And Management Of Cervical Cancer In Africa: A Cross-Sectional Analysis Of Providers’ Training And Practices, Joël Fokom Domgue, Issimouha Dille, Freddy Gnangnon, Sharon Kapambwe, Celine Bouchard, Nomonde Mbatani, Elodie Gauroy, Nathalie Ledaga Ambounda, Robert Yu, Fatoumata Sidibe, Joseph Kamgno, Bangaly Traore, Pierre-Marie Tebeu, Gregory Halle-Ekane, Mohenou Isidore Diomande, Jean-Marie Dangou, Fabrice Lecuru, Isaac Adewole, Marie Plante, Partha Basu, Sanjay Shete

Faculty, Staff and Student Publications

Introduction: Cervical cancer is a public health issue in Africa with devastating socioeconomic consequences due to the lack of organized screening programs. The success of screening programs depends on the appropriate investigation and management of women who test positive for screening. Colposcopic assessment following positive screening results is a noteworthy issue in Africa. This study aimed to assess the utilization of colposcopy by providers in the region.

Methods: A cross-sectional study was conducted in 2021-2022 among healthcare providers involved in cervical cancer prevention activities in Africa. They were invited to report prior colposcopy training, whether they performed colposcopy and the …

Functional Properties Of Corticothalamic Circuits Targeting Paraventricular Thalamic Neurons, Guillermo Aquino-Miranda, Dounya Jalloul, Xu O Zhang, Sa Li, Gilbert J Kirouac, Michael Beierlein, Fabricio H Do Monte

Faculty, Staff and Student Publications

Corticothalamic projections to sensorimotor thalamic nuclei show modest firing rates and serve to modulate the activity of thalamic relay neurons. By contrast, here we find that high-order corticothalamic projections from the prelimbic (PL) cortex to the anterior paraventricular thalamic nucleus (aPVT) maintain high-frequency activity and evoke strong synaptic excitation of aPVT neurons in rats. In a significant fraction of aPVT cells, such high-frequency excitation of PL-aPVT projections leads to a rapid decay of action potential amplitudes, followed by a depolarization block (DB) that strongly limits aPVT maximum firing rates, thereby regulating both defensive and appetitive behaviors in a frequency-dependent manner. …

Transcriptomic Clustering Of Chronic Lymphocytic Leukemia: Molecular Subtypes Based On Bruton’S Tyrosine Kinase Expression Levels, Gorkem Kismali, Ganiraju Manyam, Nitin Jain, Cristina Ivan, Betty Lamothe, Mary L Ayres, Lakesla R Iles, William G Wierda, Varsha Gandhi

Faculty, Staff and Student Publications

Historically, CLL prognostication relied on disease burden, reflected in clinical stage. Later, chromosome abnormalities and genomics suggested several CLL subtypes which were aligned with response to therapy. Gene expression profiling data identified pathways associated with CLL progression. We hypothesized that transcriptome and proteome may identify functional omics associated with CLL nosology. As a test cohort, we utilized publicly available treatment-naïve CLL transcriptomics data (n = 130) and did consensus clustering that identified BTK-expression-based clusters. The BTK-High and BTK-Low clusters were validated in public and our in-house databases (n = >550 CLL patients). To associate with functional relevance, we took samples …

Comparison Of Vendor-Pretrained And Custom-Trained Deep Learning Segmentation Models For Head-And-Neck, Breast, And Prostate Cancers, Xinru Chen, Yao Zhao, Hana Baroudi, Mohammad D El Basha, Aji Daniel, Skylar S Gay, Cenji Yu, He Wang, Jack Phan, Seungtaek L Choi, Chelain R Goodman, Xiaodong Zhang, Joshua S Niedzielski, Sanjay S Shete, Laurence E Court, Zhongxing Liao, Fredrik Löfman, Peter A Balter, Jinzhong Yang

Faculty, Staff and Student Publications

Background/objectives: We assessed the influence of local patients and clinical characteristics on the performance of commercial deep learning (DL) segmentation models for head-and-neck (HN), breast, and prostate cancers.

Methods: Clinical computed tomography (CT) scans and clinically approved contours of 210 patients (53 HN, 49 left breast, 55 right breast, and 53 prostate cancer) were used to train and validate segmentation models integrated within a vendor-supplied DL training toolkit and to assess the performance of both vendor-pretrained and custom-trained models. Four custom models (HN, left breast, right breast, and prostate) were trained and validated with 30 (training)/5 (validation) HN, 34/5 left …

Characterization Of An Inorganic Powder-Based Scintillation Detector Under A Uhdr Electron Beam, Daline Tho, Sam Beddar

Faculty, Staff and Student Publications

(1) Background: Ultra-high dose rate (UHDR) radiation therapy needs a reliable dosimetry solution and scintillation detectors are promising candidates. In this study, we characterized an inorganic powder-based scintillation detector under a 9 MeV UHDR electron beam. (2) Methods: A mixture of ZnS:Ag powder and optic glue was coupled to an 8 m Eska GH-4001-P polymethyl methacrylate (PMMA) optical fiber. We evaluated the dependence of the detector on dose per pulse (DPP), pulse repetition frequency (PRF), and pulse width (PW). Additionally, we determined the stability and the reproducibility of the detector. (3) Results: The signal ratio between the PMMA clear optical …

Centering Autonomy And Choice To Support Oral Prep Utilization Among People Who Inject Drugs: Qualitative Lessons From Hptn 094 Integra, Amaya Perez-Brumer, Rose Schmidt, Rebecca Kennedy, Jordan E Lake, Yolanda R Villarreal, Sydney Bornstein, Irene Kuo, Omar Nieto, Julie Franks, Cecile Denis, Nabila El-Bassel, Steve Shoptaw, Peter Davidson, Laramie R Smith

Faculty, Staff and Student Publications

Background: Oral Pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission. However, despite high rates of HIV risk behaviors among people who inject drugs (PWID), this population remains underserved by current HIV prevention efforts in the United States. To address this challenge, we conducted an in-depth exploration of perspectives on using oral PrEP among PWID engaged in the HIV Prevention Trials Network (HPTN) 094 INTEGRA Study.

Methods: Guided by the Practical, Robust, Implementation, and Sustainability Model (PRISM), our qualitative study drew on semi-structured interviews conducted as part of the embedded implementation science evaluation of HPTN 094 INTEGRA. Seventy-seven PWID participants …

Targeting Corticotropin-Releasing Hormone Receptor Type 1 (Crhr1) Neurons: Validating The Specificity Of A Novel Transgenic Crhr1-Flpo Mouse, Mason Hardy, Yuncai Chen, Tallie Z Baram, Nicholas J Justice

Faculty, Staff and Student Publications

Corticotropin-releasing hormone (CRH) signaling through its cognate receptors, CRHR1 and CRHR2, contributes to diverse stress-related functions in the mammalian brain. Whereas CRHR2 is predominantly expressed in choroid plexus and blood vessels, CRHR1 is abundantly expressed in neurons in discrete brain regions, including the neocortex, hippocampus and nucleus accumbens. Activation of CRHR1 influences motivated behaviors, emotional states, and learning and memory. However, it is unknown whether alterations in CRHR1 signaling contribute to aberrant motivated behaviors observed, for example, in stressful contexts. These questions require tools to manipulate CRHR1 selectively. Here we describe and validate a novel Crhr1-FlpO mouse. Using bacterial artificial …

Structural Variant Allelic Heterogeneity In Mecp2 Duplication Syndrome Provides Insight Into Clinical Severity And Variability Of Disease Expression, Davut Pehlivan, Jesse D Bengtsson, Sameer S Bajikar, Christopher M Grochowski, Ming Yin Lun, Mira Gandhi, Angad Jolly, Alexander J Trostle, Holly K Harris, Bernhard Suter, Sukru Aras, Melissa B Ramocki, Haowei Du, Michele G Mehaffey, Kyunghee Park, Ellen Wilkey, Cemal Karakas, Jesper J Eisfeldt, Maria Pettersson, Lynn Liu, Marwan S Shinawi, Virginia E Kimonis, Wojciech Wiszniewski, Kyle Mckenzie, Timo Roser, Angela M Vianna-Morgante, Alberto S Cornier, Ahmed Abdelmoity, James P Hwang, Shalini N Jhangiani, Donna M Muzny, Tadahiro Mitani, Kazuhiro Muramatsu, Shin Nabatame, Daniel G Glaze, Jawid M Fatih, Richard A Gibbs, Zhandong Liu, Anna Lindstrand, Fritz J Sedlazeck, James R Lupski, Huda Y Zoghbi, Claudia M B Carvalho

Faculty, Staff and Students Publications

BACKGROUND: MECP2 Duplication Syndrome, also known as X-linked intellectual developmental disorder Lubs type (MRXSL; MIM: 300260), is a neurodevelopmental disorder caused by copy number gains spanning MECP2. Despite varying genomic rearrangement structures, including duplications and triplications, and a wide range of duplication sizes, no clear correlation exists between DNA rearrangement and clinical features. We had previously demonstrated that up to 38% of MRXSL families are characterized by complex genomic rearrangements (CGRs) of intermediate complexity (2 ≤ copy number variant breakpoints < 5), yet the impact of these genomic structures on regulation of gene expression and phenotypic manifestations have not been investigated.

METHODS: To study the role of the genomic rearrangement structures on an individual's clinical phenotypic variability, we employed a comprehensive …

Characterization Of An Inorganic Powder-Based Scintillation Detector Under A Uhdr Electron Beam, Daline Tho, Sam Beddar

Faculty, Staff and Student Publications

Background: Ultra-high dose rate (UHDR) radiation therapy needs a reliable dosimetry solution and scintillation detectors are promising candidates. In this study, we characterized an inorganic powder-based scintillation detector under a 9 MeV UHDR electron beam.

Methods: A mixture of ZnS:Ag powder and optic glue was coupled to an 8 m Eska GH-4001-P polymethyl methacrylate (PMMA) optical fiber. We evaluated the dependence of the detector on dose per pulse (DPP), pulse repetition frequency (PRF), and pulse width (PW). Additionally, we determined the stability and the reproducibility of the detector.

Results: The signal ratio between the PMMA clear optical fiber and the …

Macrowire For Intracranial Thrombectomy: An Early Experience Of A New Device And Technique For Anterior Circulation Large Vessel Occlusion Stroke, Kaustubh Limaye, Sami Al Kasab, Jaidevsinh Dolia, Mohamad Ezzeldin, Daniel Vela Duarte, Vinodh Doss, Sourabh Lahoti, David Hasan, Alejandro Spiotta, Khaled Asi, Vasu Saini, Tapan Mehta, Ameer Hassan, Diogo Haussen, Dileep Yavagal, Jesse Jones, Omar Tanweer, Waleed Brinjikji

Faculty, Staff and Students Publications

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) has become the standard of care for treatment of acute ischemic stroke secondary to large vessel occlusion up to 24 h from the last known normal time. With ADAPT and SOLUMBRA techniques, classically, a large bore aspiration catheter is delivered over a microcatheter and microwire crossing the clot to perform thrombectomy. Recently, a novel macrowire (Colossus 035 in.) has been introduced as a potential alternative to the use of microwire-microcatheter to allow the delivery of the aspiration catheter (ID = 0.070 in. up to 0.088 in.) over a macrowire alone.

OBJECTIVE: To test the …

Multi-Antigen Elephant Endotheliotropic Herpesvirus (Eehv) Mrna Vaccine Induces Humoral And Cell-Mediated Responses In Mice, Jessica R Watts, Jennifer L Spencer Clinton, Jeroen Pollet, Rongsheng Peng, Jie Tan, Paul D Ling

Faculty, Staff and Students Publications

Background/Objectives: Elephant endotheliotropic herpesvirus (EEHV) causes lethal hemorrhagic disease (HD) in Asian and African elephants in human care and the wild. It is the leading cause of death for young Asian elephants in North American and European zoos despite sensitive diagnostic tests and improved treatments. Thus, there is a critical need to develop an effective vaccine to prevent severe illness and reduce mortality from EEHV-HD. We generated a multi-antigenic EEHV mRNA vaccine to address this need that encodes the EEHV1A-subtype glycoproteins gB, gH, gL, and gO. These conserved proteins are the entry machinery for several herpesviruses in the betaherpesvirus subfamily …

Prenatal Identification Of Intracardiac Mass Expedites Surgical Management Of Capillary-Venous Malformation, Derek M Norton, Mounica Y Rao, Jianhong Zhang, M John Hicks, Anitha Parthiban, S Kristen Sexson Tejtel

Faculty, Staff and Students Publications

Fetal and neonatal cardiac tumors are rare and often benign. Clinical presentation is primarily related to mass effect, pericardial effusion or arrhythmia. Prenatal detection can assist with risk assessment and inform optimal delivery plan and postnatal management. We report a fetus with a right atrial mass discovered in the third trimester. After successful surgical resection, pathology confirmed the mass to be a capillary-venous malformation, which are rare and challenging to diagnose. The true incidence of these vascular malformations within cardiac spaces is difficult to discern given the historic classification of numerous different vascular malformations under the umbrella term hemangioma.

Reducing Restraints In Adolescent Psychiatric Inpatient Units Through Trauma-Informed Care, Alanna G. Mejia

Doctor of Nursing Practice Final Project Abstract

Purpose: This Doctor of Nursing Practice project explores the impact of implementing trauma-informed care (TIC) training and screening interventions within an inpatient adolescent psychiatric unit. The goal is to reduce physical restraint use and improve patient care by fostering a more compassionate and effective treatment approach.

Background: Adolescents in psychiatric settings often experience restraints, which can cause trauma and harm therapeutic relationships. Implementing TIC strategies equips staff with de-escalation techniques and structured trauma screenings, creating safer environments and improving patient outcomes.

Methodology: The Plan-Do-Study-Act (PDSA) cycle was chosen to guide improvements, aligning with best practices in quality improvement by allowing …

Pathways From Socioeconomic Factors To Major Cardiovascular Events Among Postmenopausal Veteran And Nonveteran Women: Findings From The Women's Health Initiative, Hind A Beydoun, May A Beydoun, Rebecca L Kinney, Simin Liu, Rona Yu, Matthew Allison, Robert B Wallace, Qian Xiao, Longjian Liu, Philippe Gradidge, Su Yon Jung, Hilary A Tindle, Shawna Follis, Robert Brunner, Jack Tsai

Faculty, Staff and Student Publications

BACKGROUND: Cardiovascular disease (CVD) remains a leading cause of death for women in the United States, with veterans being at potentially higher risk than their nonveteran counterparts due to accelerated aging and distinct biopsychosocial mechanisms. We examined pathways between selected indicators of socioeconomic status (SES) such as education, occupation, household income, and neighborhood SES and major CVD events through lifestyle and health characteristics among veteran and nonveteran postmenopausal women.

METHODS AND RESULTS: A total of 121 286 study-eligible WHI (Women's Health Initiative) participants (3091 veterans and 118 195 nonveterans) were prospectively followed for an average of 17 years, during which …

Co-Inhibition Of Tgli1 And Gp130 Using Fda-Approved Ketoconazole And Bazedoxifene Is Synergistic Against The Growth And Metastasis Of Her2-Enriched And Triple-Negative Breast Cancers, Sara Manore, Chuling Zhuang, Mariana K Najjar, Grace L Wong, Shivani Bindal, Kounosuke Watabe, Jiayuh Lin, Hui-Wen Lo

Faculty, Staff and Student Publications

Breast cancer stem cells (CSCs) are resistant to most cancer therapeutics and contribute to tumor recurrence and metastasis. Two breast CSC-promoting transcription factors, truncated glioma-associated oncogene homolog 1 (tGLI1) and signal transducer and activator of transcription 3 (STAT3), have been reported to be frequently co-expressed in HER2-enriched breast cancer and triple-negative breast cancer (TNBC), undergo protein-protein interactions for gene regulation and activation, and functionally cooperate to promote breast CSCs. STAT3 can be activated by activated interleukin-6 receptor/glycoprotein-130 (IL-6R/GP130). Co-targeting of tGLI1 and IL-6R/GP130 has not been investigated in breast cancer or any tumor type. Here, we report that tGLI1 and …

Pleural Empyema: Etiology And Pathogenesis, Daniel M Musher, Sherwood Gorbach, Joshua Fierer

Faculty, Staff and Students Publications

No abstract provided.

Skin Lesions, Weight Loss, And Facial Swelling After A Hand Injury, Yuriko Fukuta, Cindy Qinyang Wu, Todd Michael Lasco, Abdul Hafeez Diwan

Faculty, Staff and Students Publications

No abstract provided.

Uba1 Inhibition Sensitizes Cancer Cells To Parp Inhibitors, Sharad Awasthi, Lacey E Dobrolecki, Christina Sallas, Xudong Zhang, Yang Li, Sima Khazaei, Sumanta Ghosh, Collene R Jeter, Jinsong Liu, Gordon B Mills, Shannon N Westin, Michael T Lewis, Weiyi Peng, Anil K Sood, Timothy A Yap, S Stephen Yi, Daniel J Mcgrail, Nidhi Sahni

Faculty, Staff and Students Publications

Therapeutic strategies targeting the DNA damage response, such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi), have revolutionized cancer treatment in tumors deficient in homologous recombination (HR). However, overcoming innate and acquired resistance to PARPi remains a significant challenge. Here, we employ a genome-wide CRISPR knockout screen and discover that the depletion of ubiquitin-activating enzyme E1 (UBA1) enhances sensitivity to PARPi in HR-proficient ovarian cancer cells. We show that silencing or pharmacological inhibition of UBA1 sensitizes multiple cell lines and organoid models to PARPi. Mechanistic studies uncover that UBA1 inhibition not only impedes HR repair to sensitize cells to PARP inhibition …

Large-Scale Crispr/Cas9 Deletions Within The Wfdc Gene Cluster Uncover Gene Functionality And Critical Roles In Mammalian Reproduction, Katarzyna Kent, Kaori Nozawa, Rachel Parkes, Laura Dean, Frey Daniel, Mei Leng, Antrix Jain, Anna Malovannaya, Martin M Matzuk, Thomas X Garcia

Faculty, Staff and Students Publications

Despite 96 million years of evolution separating humans and rodents, 11 closely related reproductive tract-specific genes in humans—SPINT3, WFDC6, EPPIN, WFDC8, WFDC9, WFDC10A, WFDC11, WFDC10B, WFDC13, SPINT4, and WFDC3—and the 13 reproductive tract-specific orthologous genes in mice, form highly conserved syntenic gene clusters indicative of conserved, combined critical functions. Further, despite significant progress toward a nonhormonal male contraceptive targeting the protein encoded by one of these genes, epididymal peptidase inhibitor (EPPIN), and associations found between mutations in EPPIN and an increased risk of male infertility, neither EPPIN nor …

Evaluation Of An Artificial Intelligence-Based Intraocular Lens Calculator: Ai-Based Iol-Optimized Formula, Li Wang, Hendrik Burwinkel, Nicolas Bensaid, Douglas D Koch

Faculty, Staff and Students Publications

Purpose: To evaluate the ZEISS AI IOL Calculator (ZEISS AI) and compare its accuracy in refractive prediction to the Barrett Universal II (BUII) and Kane formulas.

Setting: Cullen Eye Institute, Baylor College of Medicine, Houston, TX.

Design: Retrospective case series.

Methods: The ZEISS AI IOL Calculator (ZEISS AI) is an artificial intelligence (AI) based IOL-optimized formula. The refractive prediction errors (PEs) were calculated in the entire dataset and subgroups of short eyes (axial length (AL) ≤ 22.5 mm) and long eyes (AL ≥ 25.0 mm). The standard deviation (SD), root-mean-square absolute error (RMSAE), mean absolute error (MAE), median absolute error …

Blinatumomab Maintenance After Allogeneic Hematopoietic Cell Transplantation For B-Lineage Acute Lymphoblastic Leukemia, Yuanxin Wang, Merve Dede, Vakul Mohanty, Jinzhuang Dou, Ziyi Li, Ken Chen

Faculty, Staff and Student Publications

Decoding cellular state transitions is crucial for understanding complex biological processes in development and disease. While recent advancements in single-cell RNA sequencing (scRNA-seq) offer insights into cellular trajectories, existing tools primarily study expressional rather than regulatory state shifts. We present CellTran, a statistical approach utilizing paired-gene expression correlations to detect transition cells from scRNA-seq data without explicitly resolving gene regulatory networks. Applying our approach to various contexts, including tissue regeneration, embryonic development, preinvasive lesions, and humoral responses post-vaccination, reveals transition cells and their distinct gene expression profiles. Our study sheds light on the underlying molecular mechanisms driving cellular state transitions, …

A Statistical Approach For Systematic Identification Of Transition Cells From Scrna-Seq Data, Yuanxin Wang, Merve Dede, Vakul Mohanty, Jinzhuang Dou, Ziyi Li, Ken Chen

Faculty, Staff and Student Publications

Decoding cellular state transitions is crucial for understanding complex biological processes in development and disease. While recent advancements in single-cell RNA sequencing (scRNA-seq) offer insights into cellular trajectories, existing tools primarily study expressional rather than regulatory state shifts. We present CellTran, a statistical approach utilizing paired-gene expression correlations to detect transition cells from scRNA-seq data without explicitly resolving gene regulatory networks. Applying our approach to various contexts, including tissue regeneration, embryonic development, preinvasive lesions, and humoral responses post-vaccination, reveals transition cells and their distinct gene expression profiles. Our study sheds light on the underlying molecular mechanisms driving cellular state transitions, …

Identification Of An Early Subset Of Cerebellar Nuclei Neurons In Mice, Maryam Rahimi-Balaei, Shayan Amiri, Thomas Lamonerie, Sih-Rong Wu, Huda Y Zoghbi, G Giacomo Consalez, Daniel Goldowitz, Hassan Marzban

Duncan NRI Faculty and Staff Publications

Cerebellar nuclei (CN) neurons serve as the primary output of the cerebellum and originate from the cerebellar primordium at early stages of cerebellar development. These neurons are diverse, integrating information from the cerebellar cortex and relaying it to various brain regions. Employing various methodologies, we have characterized a specific subset of CN neurons that do not originate from the rhombic lip or ventricular zone of the cerebellar primordium. Embryos were collected at early stages of development and processed for immunohistochemistry (IHC), western blotting, in situ hybridization (ISH), embryonic culture, DiI labeling, and flow cytometry analysis (FCM). Our findings indicate that …

Correlation Of Genogroup I, Genotype 1 (Gi.1) Norovirus Neutralizing Antibody Levels With Gi.1 Histo-Blood Group Antigen-Blocking Antibody Levels, Robert L Atmar, Khalil Ettayebi, Frederick H Neill, Ralph P Braun, James Sherwood, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

Background: The in vitro cultivation of human noroviruses allows a comparison of antibody levels measured in neutralization and histo-blood group antigen (HBGA)-blocking assays.

Methods: Serum samples collected during the evaluation of an investigational norovirus vaccine (HIL-214 [formerly TAK-214]) were assayed for neutralizing antibody levels against the vaccine's prototype Norwalk virus/genogroup I, genotype 1 (GI.1) (P1) virus strain. Results were compared with those previously determined using HBGA-blocking assays.

Results: Neutralizing antibody seroresponses were observed in 83% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.81; P < .001) with those measured by HBGA blocking.

Conclusions: Genogroup I, genotype 1 (GI.1)-specific HBGA-blocking antibodies are a surrogate …

Detection Of Kmt2a Partial Tandem Duplication By Optical Genome Mapping In Myeloid Neoplasms: Associated Cytogenetics, Gene Mutations, Treatment Responses, And Patient Outcomes, Qing Wei, Shimin Hu, Jie Xu, Sanam Loghavi, Naval Daver, Gokce A Toruner, Wei Wang, L Jeffrey Medeiros, Guilin Tang

Faculty, Staff and Student Publications

KMT2A partial tandem duplication (PTD) involves intragenic KMT2A duplications and has been associated with poorer prognosis. In this study, we evaluated KMT2A PTD in 1277 patients with hematological malignancies using optical genome mapping (OGM). KMT2A PTD was detected in 35 patients with acute myeloid leukemia (AML) (7%), 5 patients with myelodysplastic syndrome (MDS) (2.2%), and 5 patients with chronic myelomonocytic leukemia (CMML) (7.1%). The PTDs varied in size, region, and copy number. An Archer RNA fusion assay confirmed KMT2A PTD in all 25 patients tested: 15 spanning exons 2 to 8 and 10 spanning exons 2 to 10. Most patients …

Pharmacologic Blockade Of A Pioneer Transcription Factor, Katerina Cermakova, H Courtney Hodges

Faculty, Staff and Students Publications

Cancers frequently co-opt lineage-specific transcription factors (TF) utilized in normal development to sustain proliferation. However, the effects of these TFs on tumor development depend considerably on where in the genome they bind. A new article by Taylor and colleagues expands on previously developed diamidine compounds that obstruct the DNA binding sites of the pioneer TF PU.1 (SPI1) in acute myeloid leukemia. Immobilization and sequencing of genomic DNA targeted by these compounds revealed that these inhibitors alter the genomic binding patterns of PU.1. The authors report that their strategy constrains the genomic binding preferences of PU.1, leading to redistribution of PU.1 …

Development Of A Ripk1 Degrader To Enhance Antitumor Immunity, Xin Yu, Dong Lu, Xiaoli Qi, Rishi Ram Paudel, Hanfeng Lin, Bryan L Holloman, Feng Jin, Longyong Xu, Lang Ding, Weiyi Peng, Meng C Wang, Xi Chen, Jin Wang

Faculty, Staff and Students Publications

The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo. Degradation of RIPK1 by LD4172 triggers immunogenic cell death, enhances tumor-infiltrating lymphocyte responses, and sensitizes tumors to anti-PD1 therapy in female C57BL/6J mice. This work reports …

Whispers In The Wind: Face Mask Sampling For Mycobacterium Tuberculosis Detection In Children With Pulmonary Tuberculosis, Lennard Meiwes, Irina Kontsevaya, Dumitru Chesov, Stela Kulciţkaia, Viola Dreyer, Doris Hillemann, Qiniso Dlamini, Caroline Williams, Michael Barer, Folke Brinkmann, Renate Krüger, Stephanie Thee, Alexander Kay, Anna Maria Mandalakas, Christoph Lange

Faculty, Staff and Students Publications

Background: Recently, face mask sampling (FMS) confirmed detection of Mycobacterium tuberculosis DNA from exhaled breath in adults with tuberculosis. To date, no study has evaluated the use of FMS to detect pulmonary tuberculosis in children. We developed a method for FMS of M. tuberculosis-specific DNA in children and performed a clinical exploration to assess feasibility in children.

Methods: Face masks were spiked, analyzed on GeneXpert-Ultra, quantitative polymerase chain reaction, and targeted next-generation sequencing. Children with pulmonary tuberculosis were asked to wear 3 modified FFP2 masks for 30 minutes as part of an exploratory clinical study.

Results: Experiments with H37Ra M. …