Medical Specialties Commons^™

Optimizing Genetic Ancestry Adjustment In Dna Methylation Studies: A Comparative Analysis Of Approaches, Kira D Höffler, Seyma Katrinli, Matthew W Halvorsen, Anne-Kristin Stavrum, Kevin S O'Connell, Alexey Shadrin, Srdjan Djurovic, Ole A Andreassen, James J Crowley, Jan Haavik, Kristen Hagen, Gerd Kvale, Kerry Ressler, Bjarne Hansen, Jair C Soares, Gabriel R Fries, Alicia K Smith, Stéphanie Le Hellard

Faculty, Staff and Student Publications

Background: Genetic ancestry is an important factor to account for in DNA methylation studies because genetic variation influences DNA methylation patterns. One approach uses principal components (PCs) calculated from CpG sites that overlap with common SNPs to adjust for ancestry when genotyping data is not available. However, this method does not remove technical and biological variations, such as sex and age, prior to calculating the PCs. The first PC is therefore often associated with factors other than ancestry.

Methods: We developed and adapted the adapted EpiAnceR+ approach, which includes (1) residualizing the CpG data overlapping with common SNPs for control …

Yx0798 Is A Highly Potent, Selective, And Orally Effective Cdk9 Inhibitor For Treating Aggressive Lymphoma, Vivian Jiang, Yu Xue, Hong Kim, Qingsong Cai, Tianci Zhang, Lei Nie, Joseph Mcintosh, Yang Liu, Haiying Chen, Jia Zhou, Michael Wang

Faculty, Staff and Student Publications

Nongenetic transcription evolution has been increasingly explored and recognized to drive tumor cell progression and therapeutic resistance. As the regulation hub of transcription machinery, cyclin-dependent kinase 9 (CDK9) is the gatekeeper of RNA polymerase II transcription, and CDK9 dysfunction results in transcriptomic reprogramming and tumor cell progression. We recently reported that the heat shock protein 90 (HSP90)-MYC-CDK9 network drives therapeutic resistance in mantle cell lymphoma (MCL) through transcriptomic reprogramming. We also showed that targeting CDK9 by AZD4573 and enitociclib is a safe and effective treatment in preclinical Mantle Cell Lymphoma (MCL) models, supporting CDK9 as a valid therapeutic target for …

Understanding The Nutrition Ecology And Related Distal And Proximal Research Gaps Impacting School-Aged Children's And Adolescents' Functioning-A Report From The "Biomarkers Of Nutrition For Development: Knowledge Indicating Dietary Sufficiency (Bond-Kids)" Project Working Group 2., Maureen M Black, Meg M Bruening, Amy Carroll-Scott, Jayna M Dave, Kristie L Ebi, Lora L Iannotti, Susan L Johnson, Lorrene D Ritchie, Elizabeth Y Jimenez, Alison L Steiber, Daniel J Raiten

Children’s Nutrition Research Center Staff Publications

Nutrition is critical to the health, development, and well-being of children and adolescents, operating through nutrients and the social and physical influences of dietary behaviors. Child and adolescent growth and development depend on complex biological systems interacting with the nutrition ecology. In this review, we focus on bidirectional interactions with the multilevel nutrition ecology, including distal systems (climate, geopolitical, and food systems) and proximal systems (community food options; health, social, and food services; and school policies and programs), all mediated by the family. Thus, the impact of nutrition on children's and adolescents' functional outcomes is dependent on understanding the multilevel …

Characterization Of Suspicious Prostate Lesions At Multiparametric Mri With Dynamic 68 Ga-Gozetotide Pet/Ct, Daniel Parrott, Qing Yuan, Daniella Pinho, Yin Xi, Daniel N Costa, Alberto Diaz De Leon, Marianna Dakanali, Xiankai Sun, Orhan K Oz, Spencer Bowen, Neil M Rofsky, Dana Mathews, Ivan Pedrosa

Faculty, Staff and Student Publications

Background: Prostate cancer (PCa) will affect approximately 12% of US men in their lifetime and remains the 2nd most common cause of cancer-specific death. However, there is a broad spectrum of severity of PCa; some require aggressive treatment and others can "watch-and-wait". Distinction of clinically significant prostate cancer (csPCa) from indolent PCA with current imaging methods remains challenging.

Objective: This study aims to evaluate dynamic prostate specific membrane antigen (PSMA) positron emission tomography (PET/CT) in the characterization of suspicious prostate lesions identified on multiparametric MRI (mpMRI).

Methods: Prospective study of biopsy-naïve patients with at least one Prostate Imaging and Reporting …

Inhibition Of Osteosarcoma Lung Metastases By Β-Glucan And Cd40 Agonist Is Mediated By Activation Of Macrophages And Nk Cells, Pradeep Shrestha, Rejeena Shrestha, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Background: Osteosarcoma (OS) lung metastases remain a significant therapeutic challenge. Innate immune activation is a promising therapeutic approach. Innate immune agonists can modulate the tumor immune microenvironment and improve therapeutic response.

Methods: Using an experimental syngeneic OS lung metastasis BALB/c mouse model with K7M3-luc OS cells, we evaluated the antitumor effects of yeast-derived particulate β-glucan in prevention and therapeutic settings. We then assessed whether the CD40 agonist (CD40a) in combination with β-glucan increased therapeutic response in two different immune-competent mouse models of OS lung tumor burden.

Results: In the pretreatment settings, mice treated with β-glucan prior to OS cell infusion …

Genetic Engineering Of Esophageal Organoids: Crispr-Based Knock-In For Cell Lineage Tracing, Kyung-Pil Ko, Jae-Il Park

Faculty, Staff and Student Publications

Esophageal organoids serve as powerful systems to study epithelial lineage hierarchies and cancer biology. Gene manipulation in these organoids has traditionally involved overexpression or knockout strategies. However, CRISPR-/Cas9-based knock-in (KI) approaches now enable precise cell lineage tracing and live imaging. Here, we describe protocols to generate fluorescent KI organoids from murine esophageal epithelium by tagging Krt13 (BFP) and Sox2 (mNeon). These dual-reporter organoids allow direct monitoring of growth dynamics and differentiation trajectories. We outline CRISPR/Cas9 design, donor construction using homology-independent approaches (CRISPaint), delivery into organoid cells, enrichment and single-clone isolation, and validation by fluorescence. For organoids, homology-directed repair (HDR) can …

Germline Determinants Of Toxicity And Efficacy In Patients With Large B-Cell Lymphoma Treated With Car T-Cell Therapy, Paolo Strati, Amanda Brandt, Anath C Lionel, Jared Henderson, Jason R Westin, Sherry Adkins, Elizabeth J Shpall, Partow Kebriaei, Jeremy Ramdial, Neeraj Saini, Sairah Ahmed, Christopher Flowers, Sattva S Neelapu, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

Background: Recent data have suggested that germline genetic aberrations can affect outcomes in patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CART). However, a comprehensive analysis of germline determinants of response and toxicity after CART has not yet been described.

Methods: Genome-wide genotyping was performed in 170 patients with LBCL treated with standard of care axicabtagene ciloleucel. Polygenic risk score instruments for blood cell traits and inflammatory markers were obtained from the PGS Catalog and analyzed using PRSice-2. Exploratory gene-based and genome-wide association study analyses were performed. Genetic ancestry of the patients with LBCL was …

Comprehensive Analysis Of The Tumor Targeting Efficiency Of Functionalized Nanoparticles In An Immunocompetent Environment, Nolan Jackson, Nasry Bouzeineddine, Daniel Cecchi, Safara Holder, Katrina Gee, Wayne Beckham, Sameh Basta, Sunil Krishnan, Devika B Chithrani

Faculty, Staff and Student Publications

The success of nanoparticle-based cancer therapeutics relies on their efficient tumor uptake and retention. Given this, improving nanoparticle localization in tumors is paramount to maximize their therapeutic potential. A common approach to achieve this is to functionalize nanoparticles with active targeting moieties that bind to specific tumor-associated receptors. Among these, arginine-glycine-aspartic acid (RGD) peptides have shown a potential to promote tumor accumulation by targeting the ανβ3 integrin receptor, a receptor commonly overexpressed by tumors owing to its role in promoting angiogenesis, metastasis and proliferation. Yet, its efficacy is commonly assessed using immunocompromised mice models. While useful, these models do not …

Polychlorinated Biphenyls Alter Estrogen Receptor Β-Mediated Epigenetic Regulation, Promoting Endometriosis, Yuri Park, Nuri Sung, Eunsu Kim, Jaeyeong Jeong, Juhee Sim, Mi Jin Park, John P Lydon, Xiaoming Guan, Sang Jun Han

Faculty, Staff and Students Publications

Endometriosis is a pathological condition characterized by the ectopic growth of endometrial cells, leading to chronic pelvic pain and infertility. Epidemiological studies have associated exposure to dioxin-like polychlorinated biphenyls, particularly PCB126, with an increased risk of endometriosis. However, the underlying mechanisms of this association remain poorly understood. We utilized a surgically induced endometriosis mouse model and human endometrial cell lines to assess the impact of PCB126 on endometriosis progression. Mice were exposed to environmentally relevant doses of PCB126. Endometriotic lesion growth, estrogen receptor signaling, receptor tyrosine kinase activity, and gene expression changes induced by PCB126-mediated elevation of DNA methyltransferase 3A …

Dual Targeting Of Orphan Nuclear Receptors Nr4a1 And Nr4a2 For Nonhormonal Endometriosis Therapy, Wai Ning Tiffany Tsui, Yuri Park, Srijana Upadhyay, Da Mi Kim, Lei Zhang, Gus Wright, Amanuel Hailemariam, Arafat Rahman Oany, Sang Jun Han, Stephen Safe

Faculty, Staff and Students Publications

Previous studies show that orphan nuclear receptor 4A1 (NR4A1) regulates endometriotic cell growth, survival, estrogen receptor β (ERβ), mechanistic target of rapamycin signaling and fibrosis. NR4A2 is also expressed in epithelial and stromal derived endometriotic cells, and in this study the effects of 1,1-bis(3'-indolyl)-(3,5-disubstitutedphenyl)methane (DIM-3,5) dual NR4A1/nuclear receptor 4A2 (NR4A2) ligands and knockdown of NR4A1 and NR4A2 were investigated. The dual NR4A1/2 DIM-3,5 analogs inhibited previously identified proendometriotic pathways and gene products, and they also inhibited TWIST1 and multiple markers associated with epithelial-to-mesenchymal transition (EMT). The results show that both NR4A1 and NR4A2 regulate the same pathways, including endometriotic cell …

A Neuroimmune Cerebral Assembloid Model To Study The Pathophysiology Of Familial Alzheimer's Disease, Andrea Becerra-Calixto, Anik Banerjee, Huihui Fan, Chunfeng Tan, Eunyoung Lee, Louise D Mccullough, Juneyoung Lee

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is the leading cause of dementia globally. The accumulation of amyloid and tau proteins, neuronal cell death and neuroinflammation are seen with AD progression, resulting in memory and cognitive impairment. Microglia are crucial for AD progression as they engage with neural cells and protein aggregates to regulate amyloid pathology and neuroinflammation. Recent studies indicate that microglia contribute to the propagation of amyloid beta (Aβ) via their immunomodulatory functions including Aβ phagocytosis and inflammatory cytokine production. Three-dimensional cell culture techniques provide the opportunity to study pathophysiological changes in AD in human-derived samples that are difficult to recapitulate in …

Synaptic Transmission Promotes Brain Metastatic Outgrowth In Breast Cancer, Jayanta Mondal, Patrick Nylund, Prit Benny Malgulwar, William E Johnson, Jason T Huse

Faculty, Staff and Student Publications

This work demonstrates that normal neuron-to-neuron signaling machinery is hijacked by metastasizing cancer cells during their outgrowth in the central nervous system.

Quiescent Oxphos-High Triple-Negative Breast Cancer Cells That Persist After Chemotherapy Depend On Bcl-Xl For Survival, Slawomir Andrzejewski, Marie Winter, Leandro Encarnacao Garcia, Olusiji Akinrinmade, Francisco Madeira Marques, Emmanouil Zacharioudakis, Anna Skwarska, Julio Aguirre-Ghiso, Marina Konopleva, Guangrong Zheng, Susan A Fineberg, Daohong Zhou, Evripidis Gavathiotis, Tao Wang, Eugen Dhimolea

Faculty, Staff and Student Publications

The persistent residual tumor cells that survive after chemotherapy are a major cause of treatment failure, but their survival mechanisms remain largely elusive. These cancer cells are typically characterized by a quiescent state with suppressed activity of MYC and MTOR. We observed that the MYC-suppressed persistent triple-negative breast cancer (TNBC) cells are metabolically flexible and can upregulate mitochondrial oxidative phosphorylation (OXPHOS) genes and respiratory function ("OXPHOS-high" cell state) in response to DNA-damaging anthracyclines such as doxorubicin, but not to taxanes. The elevated biomass and respiratory function of mitochondria in OXPHOS-high persistent cancer cells were associated with mitochondrial elongation and remodeling, …

Multimodal Reprogramming Of The Tumor Microenvironment By Mmr And Dual Checkpoint Blockade In Hepatocellular Carcinoma Models, Mulu Z. Tesfay, Aleksandra Cios, Khandoker Usran Ferdous, Randal S. Shelton, Bahaa Mustafa, Camila C. Simoes, Murat Gokden, Isabelle R. Miousse, Kimberly J. Krager, Marjan Boerma, Alicja Urbaniak, Anuradha Kunthur, Sri Obulareddy, Joshua M. Eichhorn, Steven R. Post, Jean Christopher Chamcheu, Omeed Moaven, Chiswili Y. Chabu, Dan G. Duda, Matteo Conti, Bruno Nardo, Rang Govindarajan, Martin E. Fernandez-Zapico, Lewis R. Roberts, Mitesh J. Borad, Martin J. Cannon, Alexei G. Basnakian, Bolni M. Nagalo

School of Graduate Studies Faculty Publications

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, thus, there is an urgent need to develop more effective therapeutic options for this dismal condition. Tumor-infiltrating lymphocytes (TILs) are associated with improved response to immune checkpoint blockade in HCC, but their low abundance in most cases limits their therapeutic efficacy. Here, we demonstrate, in mice, that low-dose intratumoral immunovirotherapy with the trivalent measles, mumps, and rubella vaccine (MMR) induces superior tumor-growth delay and extended host survival compared to individually administered vaccines for measles, mumps, or rubella viruses. Further, our results show that MMR therapy synergizes with PD-1 and …

Enhanced Piezo1 Function Contributes To The Pathogenesis Of Sickle Cell Disease, Luis O Romero, Manisha Bade, Laila Elsherif, Jada D Williams, Xiangmei Kong, Adebowale Adebiyi, Kenneth I Ataga, Shang Ma, Julio F Cordero-Morales, Valeria Vásquez

Faculty, Staff and Student Publications

Sickle cell disease (SCD), an inherited blood disorder caused by a mutation in the β-globin gene, is characterized by sickle erythrocytes that are prone to hemolysis, leading to anemia and vaso-occlusion crises. In sickle erythrocytes, hemoglobin aggregation is followed by altered cation permeability and subsequent dehydration. Interventions that restore cation permeability can decrease hemolysis and ameliorate the symptoms associated with SCD. PIEZO1 is a nonselective mechanosensitive cation channel that regulates erythrocyte volume. Gain-of-function (GOF) mutations in PIEZO1 cause hemolytic anemia by increasing cation permeability, leading to erythrocyte dehydration in humans and mice. Although PIEZO1 plays a key role in erythrocyte …

A Soft-Stiff Patterned Bioengineering Model Reveals Kinase Pathways Driving Directional Cell Migration In Pulmonary Arterial Hypertension, Tamanna Islam, Jacob Hooper, Xiaojun Zhang, Clarissa Garcia, Md Mahedi Hasan, David H Drewry, Mohammad Anwar Hossain, Taslim A Al-Hilal

Faculty, Staff and Student Publications

Directional cell migration by pulmonary arterial cells (PACs) is one of the important features of diseases involving arterial remodeling, such as pulmonary arterial hypertension (PAH), a disease that is often characterized by reduced arterial compliance and increased extracellular matrix (ECM) stiffening. However, there are no therapeutics that can halt the directional cell migration of PACs in PAH. The inability to identify drug targets or drugs against the directional cell migration during PAH pathogenesis stems from an incomplete understanding of the process and a lack of effective translational models for screening of candidate small molecules. Here, for the first time, we …

Advances In Fret Methodologies For Probing Molecular Interactions, Geetika Verma, Vasanthi Jayaraman

Faculty, Staff and Student Publications

Förster resonance energy transfer (FRET) has evolved into a powerful, quantitative approach for probing biomolecular structure, dynamics, and interactions. This research highlight brings together recent studies in Biophysical Journal that push the boundaries of traditional FRET. These innovations expand the spatial and temporal resolution of FRET, enabling its application to increasingly complex biological systems.

Multicenter Stroke Preclinical Assessment Network Analysis Of Cardiovascular Risk Factor Subgroups Treated With The Poly(Adp-Ribose) Polymerase Inhibitor Veliparib, Raymond C Koehler, Karni Bedirian, Mu-Hsun Chen, Yanrong Shi, Suyi Cao, Brooklyn D Avery, Senthilkumar S Karuppagounder, Kazi Akhter, Adnan Bibic, Valina L Dawson, Ted M Dawson, Márcio A Diniz, Jessica Lamb, Karisma A Nagarkatti, Anjali Chauhan, Jaroslaw Aronowski, Louise D Mccullough, Andreia Lopes De Morais, Xuyan Jin, Cenk Ayata, Mariia Kumskova, Rakesh B Patel, Anil K Chauhan, Enrique C Leira, Pradip K Kamat, Mohammad B Khan, Krishnan M Dhandapani, David C Hess, Ligia S B Boisserand, Basavaraju G Sanganahalli, Lauren H Sansing, Patrick D Lyden

Faculty, Staff and Student Publications

Background: The Stroke Preclinical Assessment Network tested 6 therapeutic interventions initiated at the time of reperfusion after focal ischemic stroke in young mice, aging mice, obese mice, and spontaneously hypertensive rats. This randomized, controlled trial was conducted across 6 sites with concealed treatment and blinded neurobehavior assessments. The trial had an adaptive design with preset levels of efficacy and futility interrogated after each of 4 stages. The primary outcome was turning preference on the corner test at 1 month. The PARP (poly(ADP-ribose) polymerase) inhibitor, veliparib, was considered futile after the second stage when pooling all animal models (n=231 …

Phosphorylation Of Ryr1 At Ser2902 Decreases Ca2+ Leak In Skeletal Muscle And Susceptibility To Malignant Hyperthermia And Heat Stroke, Rachel Sue Zhen Yee, Chang Seok Lee, Ting Chang, Sung Yun Jung, Omar Yousif, Courtney Cavazos, John Colyer, Filip Van Petegem, George G Rodney, Susan L Hamilton

Faculty, Staff and Students Publications

The ryanodine receptor 1 (RYR1) is the sarcoplasmic reticulum (SR) Ca2+ release channel required for both skeletal muscle contraction and Ca2+ leak. Mutations in RYR1 cause malignant hyperthermia susceptibility (MHS) and enhanced sensitivity to heat stroke (ESHS), which can result in death due to excessive skeletal muscle thermogenesis upon exposure to volatile anesthetics or heat. Here, we investigated the molecular and physiological functions of phosphorylation of RYR1 at Ser2902 by the kinase SPEG (striated muscle preferentially expressed protein). Muscle from SPEG-deficient mice expressing RYR1 with a Ser2902 →Asp2902 (S2902D) point mutation to mimic phosphorylation by SPEG showed decreased SR Ca2+ …

Atg16l1 Controls Mammalian Vacuolar Proton Atpase, Thabata L A Duque, Masroor Paddar, Einar Trosdal, Ruheena Javed, Lee Allers, Michal H Mudd, Prithvi Akepati, Soumya R Mishra, Michelle Salemi, Brett Phinney, Shawn B Bratton, Thomas Wileman, Vojo Deretic

Faculty, Staff and Student Publications

The mechanisms governing mammalian proton pump V-ATPase function are of fundamental and medical interest. The assembly and disassembly of cytoplasmic V1 domain with the membrane-embedded V0 domain of V-ATPase is a key aspect of V-ATPase localization and function. Here, we show that the mammalian protein ATG16L1, primarily appreciated for its role in canonical autophagy and in noncanonical membrane atg8ylation processes, controls V-ATPase. ATG16L1 knockout elevated V-ATPase activity, increased V1 presence on endomembranes, and increased the number of acidified intracellular compartments. ATG16L1's ability to efficiently bind V-ATPase was required for its inhibitory role in endolysosomal acidification and for control of Mycobacterium …

Squamous Non-Small Cell Lung Cancer: Current And Emerging Treatment Options, Paul K Paik, Jianjun Zhang, Howard Jack West, Jonathan W Riess

Faculty, Staff and Student Publications

Although the pharmacologic management of non-small cell lung cancer (NSCLC) has advanced substantially in the past 2 decades, disparities in the applicability to different histologic subtypes remain. Several treatment options are not suitable for squamous NSCLC, with use restricted to nonsquamous NSCLC (eg, bevacizumab and pemetrexed) because of safety concerns or comparative activity. Differences in mutational landscapes and a lack of matched targeted therapies specific to squamous NSCLC oncogenic aberrations present additional limitations. In the absence of suitable targeted therapies, immunotherapy with or without chemotherapy is the mainstay of squamous NSCLC treatment; however, survival-related outcomes remain poorer for patients with …

Inflammation And Mutational Burden Differentially Associated With Nivolumab Or Ipilimumab Combination Efficacy In Colorectal Cancer, Ming Lei, Michael J Overman, Jin Yao, Thierry André, Sara Lonardi, Heinz-Josef Lenz, Massimo Aglietta, Fabio Gelsomino, Ray Mcdermott, Ka Yeung Mark Wong, Michael A Morse, Eric Van Cutsem, Alain Hendlisz, Dana B Cardin, Bart Neyns, Andrew Hill, Anuradha Krishnamurthy, Franklin Chen, Samith Kochuparambil, Robert R Jenq, Sandzhar Abdullaev, Beilei He, Ruslan Novosiadly, Scott Kopetz

Faculty, Staff and Student Publications

Nivolumab alone and in combination with ipilimumab demonstrated durable clinical benefit in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer in the phase 2 CheckMate 142 study. Here, we report exploratory biomarker analyses from CheckMate 142 evaluating associations between various tissue biomarkers and the efficacy of nivolumab monotherapy and nivolumab plus ipilimumab combination in these patients. Higher expression of inflammation-related gene expression signatures is associated with improved response per investigator assessment and survival benefit with nivolumab monotherapy. In contrast, higher tumor mutational burden, tumor indel burden, and degrees of microsatellite instability are associated with improved response per investigator …

Quantitative Proteomics Identifies Conserved Proteins And Altered Regulation Of Mucin-16 In Low Grade Serous Ovarian Cancers, Christopher M Tarney, Paulette Mhawech-Fauceglia, Jonathan D Ogata, Julie Oliver, Tamara Abulez, Philip A Branton, Saeid Movahedi-Lankarani, Brian L Hood, Kelly A Conrads, Kendal Rosalik, Kwong-Kwok Wong, David M Gershenson, Sanghoon Lee, Anil K Sood, Robert C Bast, Kathleen M Darcy, Neil T Phippen, G Larry Maxwell, Thomas P Conrads, Nicholas W Bateman

Faculty, Staff and Student Publications

BACKGROUND: Low-grade serous ovarian carcinoma (LGSOC) is a rare and largely chemoresistant subtype of epithelial ovarian cancer. Unlike treatment for high-grade serous ovarian cancer (HGSOC), management options for LGSOC patients are limited, in part, due to a lack of deep molecular characterization of this disease. To address this limitation, we aimed to define highly conserved proteome alterations in LGSOC by performing deep quantitative proteomic analysis of tumors collected from LGSOC and HGSOC patients or normal fallopian tube tissues and validating proteins within two independent proteomic datasets of LGSOC and HGSOC tumors.

METHODS: Formalin-fixed, paraffin-embedded LGSOC (n = 12), HGSOC (n …

Assessing A Community Health Worker-Facilitated, Digitally Delivered, Family-Centered Diabetes Management Program: Single-Arm Quasi-Experimental Study, Zenong Yin, Vanessa L Errisuriz, Heather Cuevas, Bertha E Flores, Laura Delfausse, Christina Galvan, Jing Wang, Chengdong Li, Renata Morfin, Shiyu Li, Maysa Sapargeldiyeva, Giliane Yza Muyna, Minyu Zhang, Vanessa Sweet, Deborah Parra-Medina

Faculty, Staff and Student Publications

Background: The high prevalence of type 2 diabetes (T2D) and associated complications disproportionately affect low-income Latino populations, who also experience disparities in diabetes self-management (DSM), including poor medication adherence, physical activity, diet, and glycemic control.

Objective: This study examined, through an academic-community partnership, the effectiveness of ¡Salud, Salud! (an evidence-based, family-centered diabetes self-management education and support [DSMES] program) on primary (glycemic control and quality of life) and secondary (social, psychological, and behavioral factors related to T2D management) outcomes among low-income Latino adults with T2D or prediabetes.

Methods: In total, 81 adults (mean age 48.90 years, SD 12.57; n=57, 70.4%, female; …

Strain-Specific Variability In Viral Kinetics, Cytokine Response, And Cellular Damage In Air-Liquid Cultures Of Human Nasal Organoids After Infection With Sars-Cov-2, Gina M Aloisio, Trevor J Mcbride, Letisha Aideyan, Emily M Schultz, Ashley M Murray, Anubama Rajan, Erin G Nicholson, David Henke, Laura Ferlic-Stark, Amal Kambal, Hannah L Johnson, Elina A Mosa, Fabio Stossi, Sarah E Blutt, Pedro A Piedra, Vasanthi Avadhanula

Faculty, Staff and Students Publications

SARS-CoV-2 variants have demonstrated distinct epidemiological patterns and clinical presentations throughout the COVID-19 pandemic. Understanding variant-specific differences at the respiratory epithelium is crucial for understanding their pathogenesis. Here, we utilized human nasal organoid air-liquid interface (HNO-ALI) cell cultures to compare the viral replication kinetics, innate immune response, and epithelial damage of six different strains of SARS-CoV-2 (B.1.2, WA, Alpha, Beta, Delta, and Omicron). All variants replicated efficiently in HNO-ALIs, but with distinct replication kinetic patterns. The Delta variant exhibited delayed replication kinetics, achieving a steady state at 6 days post-infection compared to 3 days for other variants. Cytokine analysis revealed …

Causal Ai-Based Clinical And Radiomic Analysis For Optimizing Patient Selection In Combined Immunotherapy And Sabr In Early-Stage Nsclc: A Secondary Analysis Of The Phase Ii I-Sabr Trial, Maliazurina B Saad, Eman Showkatian, Vivek Verma, Qasem Al-Tashi, Muhammad Aminu, Xinyan Xu, Muhamed Qayati Mohamed, Morteza Salehjahromi, Sheeba J Sujit, Yuliya Kitsel, Steven H Lin, Zhongxing Liao, Saumil Gandhi, David Qian, David Jaffray, Caroline Chung, Natalie I Vokes, Jianjun Zhang, J Jack Lee, John V Heymach, Jia Wu, Joe Y Chang

Faculty, Staff and Student Publications

Background: The recent phase II randomized stereotactic ablative radiotherapy with and without immunotherapy (I-SABR) trial has shown improved event-free survival (EFS) when adding immunotherapy to stereotactic ablative radiotherapy (SABR) for early-stage inoperable non-small cell lung cancer (NSCLC). However, optimizing patient selection thereof is critical, because not every patient benefits from immunotherapy. Leveraging the powerful use of artificial intelligence, this secondary analysis of the I-SABR trial developed a modeling system (named "I-SABR-SELECT") based on clinical and radiomic factors to address which patients should receive additional immunotherapy.

Methods: The discovery/validation cohorts were from the I-SABR trial, with external validation from the single-arm …

Advancing Modified Barium Swallow Pre-Sorting With Deep Learning: A New Paradigm For The First Step Analysis In X-Ray Swallowing Study, Shitong Mao, Mohamed A Naser, Sheila Buoy, Kristy K Brock, Katherine A Hutcheson

Faculty, Staff and Student Publications

Purpose: Modified barium swallow (MBS) exams are pivotal for assessing swallowing function and include diagnostic video segments imaged in various planes, such as anteroposterior (AP or coronal plane) and lateral (or mid-sagittal plane), alongside non-diagnostic 'scout' image segments used for anatomic reference and image set-up that do not include bolus swallows. These variations in imaging files necessitate manual sorting and labeling, complicating the pre-analysis workflow.

Methods: Our study introduces a deep learning approach to automate the categorization of swallow videos in MBS exams, distinguishing between the different types of diagnostic videos and identifying non-diagnostic scout videos to streamline the MBS …

Post-Rt Head And Neck Dce-Mri: Association Between Mandibular Dose And Ve, Brandon Reber, Renjie He, Moamen R Abdelaal, Abdallah S R Mohamed, Samuel L Mulder, Laia Humbert Vidan, Clifton D Fuller, Stephen Y Lai, Kristy K Brock

Faculty, Staff and Student Publications

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a functional imaging modality that can quantify tissue permeability and blood flow. Due to vasculature changes resulting from radiation therapy (RT), DCE-MRI quantitative parameters should be significantly different in regions receiving a high radiation dose compared to regions receiving a low radiation dose. This study sought to determine whether a significant difference exists in post-head-and-neck-cancer (HNC)-RT DCE-MRI quantitative parameters (Ktrans and ve) between regions of the mandible receiving a high radiation dose and regions of the mandible receiving a low radiation dose.

Methods: DCE-MRI was acquired from HNC subjects post-RT. The DCE-MRI …

Assessing Spatial Variability In Observed Infectious Disease Spread In A Prospective Time-Space Series, Chih-Chieh Wu, Chien-Hsiun Chen, Shann-Rong Wang, Sanjay Shete

Faculty, Staff and Student Publications

Most of the growing prospective analytic methods in space-time disease surveillance and intended functions of disease surveillance systems focus on earlier detection of disease outbreaks, disease clusters, or increased incidence. The spread of the virus such as SARS-CoV-2 has not been spatially and temporally uniform in an outbreak. With the identification of an infectious disease outbreak, recognizing and evaluating anomalies (excess and decline) of disease incidence spread at the time of occurrence during the course of an outbreak is a logical next step. We propose and formulate a hypergeometric probability model that investigates anomalies of infectious disease incidence spread at …

A Mast Cell Receptor Mediates Post-Stroke Brain Inflammation Via A Dural-Brain Axis, Ruchita Kothari, Mostafa W Abdulrahim, Hyun Jong Oh, Daniel H Capuzzi, Collin B Kilgore, Sumil K Nair, Yaowu Zhang, Nathachit Limjunyawong, Sarbjit S Saini, Jennifer E Kim, Justin M Caplan, Fernanado L Gonzalez, Christopher M Jackson, Chetan Bettegowda, Judy Huang, Bhanu P Ganesh, Chunfeng Tan, Raymond C Koehler, Rafael J Tamargo, Louise D Mccullough, Risheng Xu, Xinzhong Dong

Faculty, Staff and Student Publications

The immune environment surrounding the brain plays a fundamental role in monitoring signs of injury. Insults, including ischemic stroke, can disrupt this balance and incite an exaggerated inflammatory response, yet the underlying mechanism remains unclear. Here, we show that the mast-cell-specific receptor Mrgprb2 regulates post-stroke brain inflammation from the meninges. Mrgprb2 causes meningeal mast cell degranulation after stroke, releasing immune mediators. This process recruits skull bone marrow neutrophils into the dura and further promotes neutrophil migration from the dura into the brain by cleaving the chemorepellent semaphorin 3a. We demonstrate that the human ortholog, MRGPRX2, is expressed in human meningeal …