Medical Genetics Commons^™

Kinesin Facilitates Phenotypic Targeting Of Therapeutic Resistance In Advanced Prostate Cancer, Maddison Archer, Diane Begemann, Edgar Gonzalez-Kozlova, Prerna R Nepali, Estefania Labanca, Peter Shepherd, Navneet Dogra, Nora Navone, Natasha Kyprianou

Faculty, Staff and Student Publications

Understanding the mechanisms underlying resistance is critical to improving therapeutic outcomes in patients with metastatic castration-resistant prostate cancer. Previous work showed that dynamic interconversions between epithelial-mesenchymal transition to mesenchymal-epithelial transition defines the phenotypic landscape of prostate tumors, as a potential driver of the emergence of therapeutic resistance. In this study, we use in vitro and in vivo preclinical MDA PCa patient-derived xenograft models of resistant human prostate cancer to determine molecular mechanisms of cross-resistance between antiandrogen therapy and taxane chemotherapy, underlying the therapeutically resistant phenotype. Transcriptomic profiling revealed that resistant and sensitive prostate cancer C4-2B cells have a unique differential …

Structure Of Adenylyl Cyclase 5 In Complex With Gβγ Offers Insights Into Adcy5-Related Dyskinesia, Yu-Chen Yen, Yong Li, Chun-Liang Chen, Thomas Klose, Val J Watts, Carmen W Dessauer, John J G Tesmer

Faculty, Staff and Student Publications

The nine different membrane-anchored adenylyl cyclase isoforms (AC1-9) in mammals are stimulated by the heterotrimeric G protein, Gαs, but their response to Gβγ regulation is isoform specific. In the present study, we report cryo-electron microscope structures of ligand-free AC5 in complex with Gβγ and a dimeric form of AC5 that could be involved in its regulation. Gβγ binds to a coiled-coil domain that links the AC transmembrane region to its catalytic core as well as to a region (C1b) that is known to be a hub for isoform-specific regulation. We confirmed the Gβγ interaction with both purified proteins and cell-based …

In Utero Exposure To Antihistamines And Risk Of Hepatocellular Carcinoma In A Multigenerational Cohort, Caitlin C Murphy, Karim Seif El Dahan, Amit G Singal, Piera M Cirillo, Nickilou Y Krigbaum, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: Growing evidence suggests that liver disease originates in early life. Antihistamines cross the placenta and are frequently prescribed to pregnant women to treat nausea and vomiting, as well as allergy and asthma symptoms. Exposure to antihistamines in utero may impact the developing liver by reprogramming or inducing epigenetic changes in fetal hepatocytes.

METHODS: We examined in utero exposure to antihistamines and the risk of HCC in the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in the East Bay, CA, between 1959 and 1966 (n=14,507 mothers and 18,751 liveborn offspring). We reviewed mothers' medical records …

Disparities In Exposure To Tobacco On Television Or Streaming Platforms, Henry K Onyeaka, Onyema G Chido-Amajuoyi, Itunu Sokale, Kobi V Ajayi, A Eden Evins, Hermioni L Amonoo, Sanjay Shete

Faculty, Staff and Student Publications

Importance: With the rise in popularity of streaming platforms concerns about exposure to tobacco advertising and promotion have emerged. While tobacco marketing and promotion through traditional television (TV) media channels has been extensively studied, less is known about exposure to tobacco through TV or streaming platforms and its associated factors.

Objective: To examine the prevalence and factors associated with exposure to tobacco products advertised, marketed, or promoted on TV or streaming platforms among US adults.

Design, setting, and participants: This cross-sectional study used data from the National Cancer Institute's Health Information National Trends Survey (HINTS 6), conducted from March 7 …

Social Determinants Of Long-Term Opioid Use Following Total Knee Arthroplasty, Katherine Hadlandsmyth, Brian C Lund, Yubo Gao, Andrea L Strayer, Heather Davila, Leslie R M Hausmann, Susanne Schmidt, Paula K Shireman, Michael A Jacobs, Michael J Mader, Robert A Tessler, Carly A Duncan, Daniel E Hall, Mary Vaughan Sarrazin

Faculty, Staff and Student Publications

Total knee arthroplasty (TKA) risks persistent pain and long-term opioid use (LTO). The role of social determinants of health (SDoH) in LTO is not well established. We hypothesized that SDoH would be associated with postsurgical LTO after controlling for relevant demographic and clinical variables. This study utilized data from the Veterans Affairs Surgical Quality Improvement Program, VA Corporate Data Warehouse, and Centers for Medicare and Medicaid Services, including Veterans aged ≥ 65 who underwent elective TKA between 2013 and 2019 with no postsurgical complications or history of significant opioid use. LTO was defined as > 90 days of opioid use beginning …

Care Fragmentation, Social Determinants Of Health, And Postoperative Mortality In Older Veterans, Carly A Duncan, Michael A Jacobs, Yubo Gao, Michael Mader, Susanne Schmidt, Heather Davila, Katherine Hadlandsmyth, Paula K Shireman, Leslie R M Hausmann, Robert A Tessler, Andrea Strayer, Mary Vaughan Sarrazin, Daniel E Hall

Faculty, Staff and Student Publications

Introduction: Veterans Affairs Surgical Quality Improvement Program (VASQIP) benchmarking algorithms helped the Veterans Health Administration (VHA) reduce postoperative mortality. Despite calls to consider social risk factors, these algorithms do not adjust for social determinants of health (SDoH) or account for services fragmented between the VHA and the private sector. This investigation examines how the addition of SDoH change model performance and quantifies associations between SDoH and 30-d postoperative mortality.

Methods: VASQIP (2013-2019) cohort study in patients ≥65 y old with 2-30-d inpatient stays. VASQIP was linked to other VHA and Medicare/Medicaid data. 30-d postoperative mortality was examined using multivariable logistic …

Targeting Adenosine A2b Receptor Promotes Penile Rehabilitation Of Refractory Erectile Dysfunction, Yang Xiong, Feng Qin, Shanzun Wei, Xingliang Yang, Jun Li, Changjing Wu, Fuxun Zhang, Jiuhong Yuan

Faculty, Staff and Student Publications

The mechanisms of adenosine and specific adenosine receptor subtypes in promoting penile rehabilitation remain unclear. Single‐cell RNA sequencing of human corpus cavernosum,  adenosine deaminase (ADA) and adenosine receptors knock‐out mice (ADA−/−, A1−/−, A2a−/−, A2b−/−, and A3−/−), and primary corpus cavernosum smooth muscle cells are used to determine receptor subtypes responsible for adenosine‐induced erection. Three rat models are established to characterize refractory erectile dysfunction (ED): age‐related ED, bilateral cavernous nerve crush related ED (BCNC), and diabetes mellitus‐induced ED. In single‐cell RNA sequencing data, the corpus cavernosum of ED patients show a decrease in adenosine A1, A2a and A2b receptors. In vivo, …

A 3d Dual-Echo Spiral Sequence For Simultaneous Dynamic Susceptibility Contrast And Dynamic Contrast-Enhanced Mri With Single Bolus Injection, Zhiqiang Li, Dinghui Wang, Melvyn B Ooi, Poonam Choudhary, Sudarshan Ragunathan, John P Karis, James G Pipe, C Chad Quarles, Ashley M Stokes

Faculty, Staff and Student Publications

Purpose: Perfusion MRI reveals important tumor physiological and pathophysiologic information, making it a critical component in managing brain tumor patients. This study aimed to develop a dual-echo 3D spiral technique with a single-bolus scheme to simultaneously acquire both dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) data and overcome the limitations of current EPI-based techniques.

Methods: A 3D spiral-based technique with dual-echo acquisition was implemented and optimized on a 3T MRI scanner with a spiral staircase trajectory and through-plane SENSE acceleration for improved speed and image quality, in-plane variable-density undersampling combined with a sliding-window acquisition and reconstruction approach for increased …

A Qualitative Narrative Study Of Rescue And Recovery Workers Responding To The Terrorist Bombing Of Oklahoma City's Murrah Building, E Whitney Pollio, Jennifer Wang, Edward Randle, David E Pollio, Carol S North

Faculty, Staff and Student Publications

OBJECTIVE: Much of disaster mental health research uses quantitative methods, focusing on numerical prevalence, services, and outcomes.

METHODS: Qualitative methods can provide more detailed, rich, and spontaneous insights into personal disaster experiences, yielding important insights beyond deductive methods. This large-scale qualitative narrative study examined experiences of 181 Oklahoma City bombing rescue/recovery workers.

RESULTS: Thematic narrative content of the bombing experience arose from personal accounts of the bomb blast by rescue/recovery workers proceeding chronologically from initial awareness and deployment to harrowing onsite search and rescue/recovery missions to the aftermath with reflections on the bombing.

CONCLUSIONS: Beyond disaster recovery/rescue worker stories published …

Molecular Responses In Decitabine- And Decitabine/ Venetoclax-Treated Patients With Acute Myeloid Leukemia And Myelodysplastic Syndromes, Agata Gruszczynska, Abhishek Maiti, Christopher A Miller, Sai Mukund Ramakrishnan, Daniel C Link, Geoffrey L Uy, Allegra A Petti, Kala Hayes, Courtney D Dinardo, Farhad Ravandi, Timothy J Ley, David H Spencer, Feng Gao, Marina Y Konopleva, John S Welch

Faculty, Staff and Student Publications

No abstract provided.

Outcome Of 3q262/Mecom Rearrangements In Chronic Myeloid Leukemia, Hiroki Akiyama, Hagop Kantarjian, Elias Jabbour, Ghayas Issa, Fadi G Haddad, Nicholas J Short, Shimin Hu, Jo Ishizawa, Michael Andreeff, Koji Sasaki

Faculty, Staff and Student Publications

Study aims: To evaluate the outcomes of patients with 3q26.2/MECOM-rearranged chronic myeloid leukemia (CML).

Methods: We reviewed consecutive adult patients with 3q26.2/MECOM-rearranged CML between January 1, 1998 and February 16, 2023. Rearrangements of 3q26.2/MECOM were confirmed by conventional cytogenetics, and fluorescence in situ hybridization starting in 2015.

Results: We identified 55 patients with MECOM-rearranged CML, including 23 in chronic phase (CP) or accelerated phase (AP) and 32 in blast phase (BP). Nine patients (16%) achieved a major cytogenetic response (MCyR) or deeper. At a median follow-up of 89 months, median survival was 14 months. The 5-year survival rate was 19% …

Combination Of Dasatinib And Venetoclax In Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia, Elias Jabbour, Fadi G Haddad, Koji Sasaki, Bing Z Carter, Yesid Alvarado, Cedric Nasnas, Lewis Nasr, Lucia Masarova, Naval Daver, Naveen Pemmaraju, Nicholas J Short, Jeffrey Skinner, Tapan Kadia, Gautam Borthakur, Guillermo Garcia-Manero, Farhad Ravandi, Ghayas C Issa, Michael Andreeff, Hagop Kantarjian

Faculty, Staff and Student Publications

Background: The dual inhibition of the BCR::ABL1 tyrosine kinase and BCL-2 could potentially deepen the response rates of chronic myeloid leukemia in chronic phase (CML-CP). This study evaluated the safety and efficacy of the combination of dasatinib and venetoclax.

Methods: In this phase 2 trial, patients with CML-CP or accelerated phase (clonal evolution) received dasatinib 50 mg/day for three courses; venetoclax was added in course 4 for 3 years. The initial venetoclax dose was 200 mg/day continuously but reduced later to 200 mg/day for 14 days, and to 100 mg/day for 7 days per course once a molecular response (MR)4.5 …

Acute Myeloid Leukemia With Mast Cell Differentiation Is Characterized By Interstitial Mast Cells, Complex Karyotype, Do Hwan Kim, Sa A Wang, Wei Wang, Guilin Tang, Shaoying Li, C Cameron Yin, Pei Lin, Marina Konopleva, M James You, Roberto N Miranda, Xiaoqiong Wang, Qing Wei, L Jeffrey Medeiros, Jie Xu

Faculty, Staff and Student Publications

No abstract provided.

T-Cell-Rich Hodgkin Lymphoma With Features Of Classic Hodgkin Lymphoma And Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Borderline Category With Overlapping Morphologic And Immunophenotypic Features, Siba El Hussein, Hong Fang, Fatima Zahra Jelloul, Wei Wang, Sanam Loghavi, Roberto N Miranda, Jonathan W Friedberg, W Richard Burack, Andrew G Evans, Jie Xu, L Jeffrey Medeiros

Faculty, Staff and Student Publications

Context.—: It is known that a subset of cases of classic Hodgkin lymphoma (CHL) with B-cell-rich nodules (lymphocyte-rich CHL) exhibits morphologic and immunophenotypic features that overlap with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), raising diagnostic difficulties that can be resolved in most cases by performing an adequate battery of immunohistochemical studies.

Objective.—: To fully characterize cases of T-cell-rich Hodgkin lymphoma where a specific diagnosis of NLPHL (ie, pattern D) or CHL could not be made even after complete immunophenotypic investigation.

Design.—: The clinical, immunomorphologic, and molecular (when applicable) presentation of 3 cases of T-cell-rich Hodgkin lymphoma was thoroughly investigated.

Results.—: These …

Variability In Performance Of Genetic-Enhanced Dxa-Bmd Prediction Models Across Diverse Ethnic And Geographic Populations: A Risk Prediction Study, Yong Liu, Xiang-He Meng, Chong Wu, Kuan-Jui Su, Anqi Liu, Qing Tian, Lan-Juan Zhao, Chuan Qiu, Zhe Luo, Martha I Gonzalez-Ramirez, Hui Shen, Hong-Mei Xiao, Hong-Wen Deng

Faculty, Staff and Student Publications

BACKGROUND: Osteoporosis is a major global health issue, weakening bones and increasing fracture risk. Dual-energy X-ray absorptiometry (DXA) is the standard for measuring bone mineral density (BMD) and diagnosing osteoporosis, but its costliness and complexity impede widespread screening adoption. Predictive modeling using genetic and clinical data offers a cost-effective alternative for assessing osteoporosis and fracture risk. This study aims to develop BMD prediction models using data from the UK Biobank (UKBB) and test their performance across different ethnic and geographical populations.

METHODS AND FINDINGS: We developed BMD prediction models for the femoral neck (FNK) and lumbar spine (SPN) using both …

Electrical Stimulation Of The Dorsal Motor Nucleus Of The Vagus In Male Mice Can Regulate Inflammation Without Affecting The Heart Rate, Aidan Falvey, Santhoshi P Palandira, Sangeeta S Chavan, Michael Brines, Robert Dantzer, Kevin J Tracey, Valentin A Pavlov

Faculty, Staff and Student Publications

Background: The vagus nerve plays an important role in neuroimmune interactions and in the regulation of inflammation. A major source of efferent vagus nerve fibers that contribute to the regulation of inflammation is the brainstem dorsal motor nucleus of the vagus (DMN), as recently shown using optogenetics. In contrast to optogenetics, electrical neuromodulation has broad therapeutic implications. However, the anti-inflammatory effectiveness of electrical stimulation of the DMN (eDMNS) and the possible heart rate (HR) alterations associated with this approach have not been investigated. Here, we examined the effects of eDMNS on HR and cytokine levels in mice administered with lipopolysaccharide …

Trends In Outcomes After Upfront Autologous Transplant For Multiple Myeloma Over Three Decades, Oren Pasvolsky, Curtis Marcoux, Jianliang Dai, Denái R Milton, Mark R Tanner, Naureen Syed, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Yosra Aljawai, Hans C Lee, Mahmoud R Gaballa, Krina K Patel, Partow Kebriaei, Sheeba K Thomas, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Upfront autologous stem cell transplantation (auto-SCT) remains standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM), although recently its role has been questioned. The aim of the study was to evaluate trends in patient characteristics, treatment, and outcomes of NDMM who underwent upfront auto-SCT over three decades. We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-SCT at MD Anderson Cancer Center between 1988 to 2021. Primary end points were progression-free survival (PFS) and overall survival (OS). Patients were grouped by the year of auto-SCT: 1988-2000 (n = 249), 2001-2005 (n = 373), …

Molecular Pathways And Cellular Subsets Associated With Adverse Clinical Outcomes In Overlapping Immune-Related Myocarditis And Myositis, Bilal A Siddiqui, Nicolas L Palaskas, Sreyashi Basu, Yibo Dai, Zhong He, Shalini S Yadav, James P Allison, Rahul A Sheth, Sudhakar Tummala, Maximilian Buja, Meenakshi B Bhattacharjee, Cezar Iliescu, Anishia Rawther-Karedath, Anita Deswal, Linghua Wang, Padmanee Sharma, Sumit K Subudhi

Faculty, Staff and Student Publications

Immune checkpoint therapies (ICT) can induce life-threatening immune-related adverse events, including myocarditis and myositis, which are rare but often concurrent. The molecular pathways and immune subsets underlying these toxicities remain poorly understood. To address this need, we performed single-cell RNA sequencing of heart and skeletal muscle biopsies obtained from living patients with cancers treated with ICTs and admitted to the hospital with myocarditis and/or myositis (overlapping myocarditis plus myositis, n = 10; myocarditis-only, n = 1) or ICT-exposed patients ruled out for toxicity utilized as controls (n = 9). All biopsies were obtained within 96 hours of clinical presentation. Analyses …

Auto-Segmentation Of Adult-Type Diffuse Gliomas: Comparison Of Transfer Learning-Based Convolutional Neural Network Model Vs Radiologists, Qi Wan, Jisoo Kim, Clifford Lindsay, Xin Chen, Jing Li, J Bryan Iorgulescu, Raymond Y Huang, Chenxi Zhang, David Reardon, Geoffrey S Young, Lei Qin

Faculty, Staff and Student Publications

Segmentation of glioma is crucial for quantitative brain tumor assessment, to guide therapeutic research and clinical management, but very time-consuming. Fully automated tools for the segmentation of multi-sequence MRI are needed. We developed and pretrained a deep learning (DL) model using publicly available datasets A (n = 210) and B (n = 369) containing FLAIR, T2WI, and contrast-enhanced (CE)-T1WI. This was then fine-tuned with our institutional dataset (n = 197) containing ADC, T2WI, and CE-T1WI, manually annotated by radiologists, and split into training (n = 100) and testing (n = 97) sets. The Dice similarity coefficient (DSC) was used to …

Estimating The Direct Effects Of The Genetic Liabilities To Bipolar Disorder, Schizophrenia, And Behavioral Traits On Suicide Attempt Using A Multivariable Mendelian Randomization Approach, Brenda Cabrera-Mendoza, Necla Aydin, Gabriel R Fries, Anna R Docherty, Consuelo Walss-Bass, Renato Polimanti

Faculty, Staff and Student Publications

Bipolar disorder (BD) and schizophrenia (SZ) are associated with higher odds of suicide attempt (SA). In this study, we aimed to explore the effect of BD and SZ genetic liabilities on SA, also considering the contribution of behavioral traits, socioeconomic factors, and substance use disorders. Leveraging large-scale genome-wide association data from the Psychiatric Genomics Consortium (PGC) and the UK Biobank (UKB), we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the putative causal effect of BD (41,917 cases, 371,549 controls) and SZ (53,386 cases, 77,258 controls) on SA (26,590 cases, 492,022 controls). Then, we assessed the putative causal effect …

Perioperative Nivolumab Versus Observation In Patients With Renal Cell Carcinoma Undergoing Nephrectomy (Prosper Ecog-Acrin Ea8143): An Open-Label, Randomised, Phase 3 Study, Mohamad E Allaf, Se-Eun Kim, Viraj Master, David F Mcdermott, Lauren C Harshman, Suzanne M Cole, Charles G Drake, Sabina Signoretti, Mahmut Akgul, Nicholas Baniak, Elsa Li-Ning, Matthew B Palmer, Hamid Emamekhoo, Nabil Adra, Hristos Kaimakliotis, Yasser Ged, Phillip M Pierorazio, E Jason Abel, Mehmet A Bilen, Kenneth Ogan, Helen H Moon, Krishna A Ramaswamy, Eric A Singer, Tina M Mayer, Jay Lohrey, Vitaly Margulis, Jessie Gills, Scott E Delacroix, Mark J Waples, Andrew C James, Peng Wang, Toni Choueiri, M Dror Michaelson, Anil Kapoor, Daniel Y Heng, Brian Shuch, Bradley C Leibovich, Primo N Lara, Judith Manola, Deborah Maskens, Dena Battle, Robert Uzzo, Gennady Bratslavsky, Naomi B Haas, Michael A Carducci

Faculty, Staff and Student Publications

Background: The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only.

Methods: In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or …

Safety And Efficacy Of Percutaneous Image-Guided Ablation For Soft Tissue Sarcoma Metastases To The Liver, Ahmed Awad, Koustav Pal, Steven Yevich, Joshua D Kuban, Alda Tam, Bruno C Odisio, Sanjay Gupta, Peiman Habibollahi, Andrew J Bishop, Anthony Paul Conley, Neeta Somaiah, Dejka M Araujo, Maria Alejandra Zarzour, Ravin Ratan, Christina L Roland, Emily Z Keung, Steven Y Huang, Rahul A Sheth

Faculty, Staff and Student Publications

Purpose: To evaluate outcomes following percutaneous image-guided ablation of soft tissue sarcoma metastases to the liver.

Materials and methods: A single-institution retrospective analysis of patients with a diagnosis of metastatic soft tissue sarcoma who underwent percutaneous image-guided ablation of hepatic metastases between January 2011 and December 2021 was performed. Patients with less than 60 days of follow-up after ablation were excluded. The primary outcome was local tumor progression-free survival (LPFS). Secondary outcomes included overall survival, liver-specific progression-free survival. and chemotherapy-free survival.

Results: Fifty-five patients who underwent percutaneous ablation for 84 metastatic liver lesions were included. The most common histopathological subtypes …

Patient Education Practices And Preferences Of Radiation Oncologists And Interprofessional Radiation Therapy Care Teams: A Mixed-Methods Study Exploring Strategies For Effective Patient Education Delivery, Jie Jane Chen, Anna M Brown, Allison E Garda, Ellen Kim, Sarah A Mcavoy, Subha Perni, Michael K Rooney, Kevin Shiue, Kristi L Tonning, Laura E Warren, Daniel W Golden, Jennifer M Croke

Faculty, Staff and Student Publications

Purpose: Patients' understanding of radiation therapy (RT) and data regarding optimal approaches to patient education (PE) within radiation oncology (RO) are limited. We aimed to evaluate PE practices of radiation oncologists and interprofessional RT care team members to inform recommendations for delivering inclusive and accessible PE.

Methods and materials: An anonymous survey was administered to all Radiation Oncology Education Collaborative Study Group members (10/5/22-11/23/22). Respondent demographics, individual practices/preferences, and institutional practices were collected. Qualitative items explored strategies, challenges, and desired resources for PE. Descriptive statistics summarized survey responses. The Fisher exact test compared PE practices by respondent role and PE …

Impact Of Pretreatment Body Mass Index On The Survival Of Head And Neck Cancer Patients, Zheng Yang, Jobran Mansour, Peng Sun, Peng Wei, Kristina R Dahlstrom, Mark Zafereo, Guojun Li, Neil D Gross

Faculty, Staff and Student Publications

Background: Differences in pretreatment body mass index (BMI) have been associated with survival in squamous cell carcinoma of head and neck (SCCHN). We examined effects of BMI on survival in SCCHN patients after stratifying patients by tumor human papillomavirus (HPV) status and subsite.

Methods: Totally 2204 SCCHN patients in a prospective study were included in this secondary analysis. Multivariable Cox models were used to evaluate associations between pretreatment BMI and overall survival, disease-specific survival, and disease-free survival.

Results: BMI was significantly higher among patients with HPV-positive tumors than HPV-negative tumors. BMI >25 kg/m2 was associated with improved survival, while BMI …

Adaptive Fine-Tuning Based Transfer Learning For The Identification Of Mgmt Promoter Methylation Status, Erich Schmitz, Yunhui Guo, Jing Wang

Faculty, Staff and Student Publications

Background. Glioblastoma Multiforme (GBM) is an aggressive form of malignant brain tumor with a generally poor prognosis. O 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been shown to be a predictive bio-marker for resistance to treatment of GBM, but it is invasive and time-consuming to determine methylation status. There has been effort to predict the MGMT methylation status through analyzing MRI scans using machine learning, which only requires pre-operative scans that are already part of standard-of-care for GBM patients. Purpose. To improve the performance of conventional transfer learning in the identification of MGMT promoter methylation status, we developed a 3D SpotTune …

Cerebellar Nuclei Cells Produce Distinct Pathogenic Spike Signatures In Mouse Models Of Ataxia, Dystonia, And Tremor, Meike E Van Der Heijden, Amanda M Brown, Dominic J Kizek, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

The cerebellum contributes to a diverse array of motor conditions, including ataxia, dystonia, and tremor. The neural substrates that encode this diversity are unclear. Here, we tested whether the neural spike activity of cerebellar output neurons is distinct between movement disorders with different impairments, generalizable across movement disorders with similar impairments, and capable of causing distinct movement impairments. Using in vivo awake recordings as input data, we trained a supervised classifier model to differentiate the spike parameters between mouse models for ataxia, dystonia, and tremor. The classifier model correctly assigned mouse phenotypes based on single-neuron signatures. Spike signatures were shared …

Targeting Astrogliosis In The Retrotrapezoid Nucleus: A Novel Approach To Ameliorate Respiratory Dysfunction And Alzheimer's Pathology In Mice, Zahid Iqbal, Ahmad El Hamamy, Ngoc Mai Le, Arya Ranjan, Yuxing Zhang, Li Qi, Bharti Manwani, Chunfeng Tan, Louise D Mccullough, Jun Li

Faculty, Staff and Student Publications

Alzheimer's disease (AD), a leading cause of dementia, is associated with significant respiratory dysfunctions. Our study explores the role of astrogliosis in the brainstem retrotrapezoid nucleus (RTN), a key breathing regulatory center, and its impact on breathing control and AD pathology in mice. Using Tg-2576 AD and wild-type mice, we investigated the effect of silencing the transforming growth factor-beta receptor II (TGFβR II) in the RTN. We performed behavioral tests, including the Barnes maze and novel object recognition test, along with whole-body plethysmography to assess breathing disorders. Our results showed that AD mice exhibited increased apneas and cognitive impairment, which …

Tert Activation Targets Dna Methylation And Multiple Aging Hallmarks, Hong Seok Shim, Jonathan Iaconelli, Xiaoying Shang, Jiexi Li, Zheng D Lan, Shan Jiang, Kayla Nutsch, Brittney A Beyer, Luke L Lairson, Adam T Boutin, Michael J Bollong, Peter G Schultz, Ronald A Depinho

Faculty, Staff and Student Publications

Insufficient telomerase activity, stemming from low telomerase reverse transcriptase (TERT) gene transcription, contributes to telomere dysfunction and aging pathologies. Besides its traditional function in telomere synthesis, TERT acts as a transcriptional co-regulator of genes pivotal in aging and age-associated diseases. Here, we report the identification of a TERT activator compound (TAC) that upregulates TERT transcription via the MEK/ERK/AP-1 cascade. In primary human cells and naturally aged mice, TAC-induced elevation of TERT levels promotes telomere synthesis, blunts tissue aging hallmarks with reduced cellular senescence and inflammatory cytokines, and silences p16INK4a expression via upregulation of DNMT3B-mediated promoter hypermethylation. In the brain, …

Glucose-6-Phosphate Dehydrogenase Deficiency As A Cause For Nonimmune Hydrops Fetalis And Severe Fetal Anemia: A Systematic Review, Neel S. Iyer, Matthew H. Mossayebi, Tracy J. Gao, Lylach Haizler-Cohen, Daniele Di Mascio, Rodney A. Mclaren, Huda B. Al-Kouatly

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive disorder that predisposes individuals to hemolysis due to an inborn error of metabolism. We performed a systematic literature review to evaluate G6PD deficiency as a possible etiology of nonimmune hydrops fetalis (NIHF) and severe fetal anemia.

METHODS: PubMed, OVID Medline, Scopus, and clinicaltrials.gov were queried from inception until 31 April 2023 for all published cases of NIHF and severe fetal anemia caused by G6PD deficiency. Keywords included "fetal edema," "hydrops fetalis," "glucose 6 phosphate dehydrogenase deficiency," and "fetal anemia." Cases with workup presuming G6PD deficiency as an etiology for NIHF and …

A Scaled Proteomic Discovery Study For Prostate Cancer Diagnostic Markers Using Proteograph, Matthew E K Chang, Jane Lange, Jessie May Cartier, Travis W Moore, Sophia M Soriano, Brenna Albracht, Michael Krawitzky, Harendra Guturu, Amir Alavi, Alexey Stukalov, Xiaoyuan Zhou, Eltaher M Elgierari, Jessica Chu, Ryan Benz, Juan C Cuevas, Shadi Ferdosi, Daniel Hornburg, Omid Farokhzad, Asim Siddiqui, Serafim Batzoglou, Robin J Leach, Michael A Liss, Ryan P Kopp, Mark R Flory

Faculty, Staff and Student Publications

There is a significant unmet need for clinical reflex tests that increase the specificity of prostate-specific antigen blood testing, the longstanding but imperfect tool for prostate cancer diagnosis. Towards this endpoint, we present the results from a discovery study that identifies new prostate-specific antigen reflex markers in a large-scale patient serum cohort using differentiating technologies for deep proteomic interrogation. We detect known prostate cancer blood markers as well as novel candidates. Through bioinformatic pathway enrichment and network analysis, we reveal associations of differentially abundant proteins with cytoskeletal, metabolic, and ribosomal activities, all of which have been previously associated with prostate …