Digital Commons Network^™

Measuring The Impact Of A Delay In Care On Pediatric Otolaryngologic Surgery Completion, Geethanjeli N Mahendran, Ching Siong Tey, Mary Frances Musso, Grace Shebha Anand, Jeffrey Larson, Mitesh Mehta, Lara Reichert, Kara Prickett, Nikhila Pinnapureddy Raol

Faculty, Staff and Students Publications

Objective: To determine if postponement of elective pediatric otorhinolaryngology surgeries results in a change in overall healthcare utilization and if there is any commensurate impact on disease progression.

Methods: We identified patients ≤18 years of age whose surgeries were postponed at the onset of the COVID-19 pandemic-related shutdown. We then tracked patients' rate of and patterns of rescheduling surgery. Surveys were also sent to caregivers to better characterize his/her decision regarding moving forward with his/her child's surgery during COVID-19.

Results: A total of 1915 pediatric patients had elective surgeries canceled, of which 992 (51.8%) were rescheduled within 4 months. No …

Insights Into The Molecular Mechanism Of Pulmonary Vein Stenosis In Pediatric Patients With Congenital Heart Disease, Alyssa B Kalustian, Pengfei Ji, Lalita Wadhwa, Christopher A Caldarone, Manish Bansal, Athar M Qureshi, Jeffrey S Heinle, Ravi K Birla

Faculty, Staff and Students Publications

Objective: Pediatric pulmonary vein stenosis (PVS) is associated with substantial morbidity and mortality for the subset of patients with recurrent or progressive disease. The molecular mechanisms underlying the development and trajectory of PVS remain unclear. This study characterizes the transcriptome of clinical and phenotypic subtypes of PVS.

Methods: Bulk RNA sequencing analysis was performed on human pulmonary vein tissue samples obtained from surgical interventions for pediatric patients with PVS. Transcriptomic profiles were compared for primary versus postrepair PVS as well as aggressive versus nonaggressive clinical phenotypes. Principal component analysis was performed, the differential gene expression quantified, and pathway analysis conducted …

Hospital Experiences And Medical Traumatic Stress In Adults With Spina Bifida, Ellen Fremion, Nora Deibler, Juliana Abel, Monique Ridosh

Faculty, Staff and Students Publications

Purpose

This study examined hospital and emergency department (ED) experiences of adults with spina bifida (SB), medical traumatic stress (MTS) and participant characteristics including anxiety, depression, post-traumatic stress disorder (PTSD) symptoms, and resiliency scores.

Methods

Adults with SB who had a hospital or ED encounter within the last five years were recruited from a medical home clinic and completed a structured interview and validated questionnaires. Narrative inquiry was used and descriptive analyses were conducted. MTS scores were reported per participant characteristics and emotional health questionnaire score counts and percentages.

Results

Twenty-five adults with SB representing 37% of eligible patients were …

Effect Of Aerobic Or Resistance Exercise, Or Both On Insulin Secretion, Ciliary Neurotrophic Factor, And Insulin-Like Growth Factor-1 In Dieting Older Adults With Obesity, Georgia Colleluori, Viola Viola, Siresha Bathina, Reina Armamento-Villareal, Clifford Qualls, Antonio Giordano, Dennis T Villareal

Faculty, Staff and Students Publications

Background and aims: Obesity exacerbates age-related changes in metabolic and physical function. The effect of distinct exercise modalities combined with diet-induced weight loss on insulin secretion in older adults with obesity and frailty is unknown, and the potential mediators of the metabolic and functional improvements induced by lifestyle therapy still need to be identified. We aimed to assess the effects of various exercise therapies coupled with diet-induced weight loss on insulin secretion and sensitivity and on the levels of circulating Ciliary Neurotrophic Factor (CNTF), its receptor (CNTFRα), and Insulin-like Growth Factor-1 (IGF-1) in older adults with both obesity and frailty. …

Anaphylaxis Definition, Overview, And Clinical Support Tool: 2024 Consensus Report-A Ga2len Project, Timothy E Dribin, Antonella Muraro, Carlos A Camargo, Paul J Turner, Julie Wang, Graham Roberts, Aikaterini Anagnostou, Susanne Halken, Jay Liebermann, Margitta Worm, Torsten Zuberbier, Hugh A Sampson, Ga(2)Len Anaphylaxis Study Team

Faculty, Staff and Students Publications

Background: The 2006 National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network anaphylaxis criteria are widely used in clinical care and research. In 2020, the World Allergy Organization published modified criteria that have not been uniformly adopted. Different criteria contribute to inconsistent care and research outcomes.

Objective: We sought to develop a consensus anaphylaxis definition, overview, and clinical support tool.

Methods: A 12-member writing group developed draft outputs modified with input from a 46-member international expert panel, 31 medical stakeholder organizations, and 15 patient advocacy organizations. The expert panel participated in a modified Delphi process to seek consensus …

Evolution Of Esophageal Adenocarcinoma From Precursor Lesion Stem Cells, Wa Xian, Shan Wang, Jingzhong Xie, Yusuke Yamamoto, Melina Khorrami, Yanting Zhang, Raul Caballero Montes, Caycel Desales, Melika Khorrami, Zaal Mory, Ashley Hoffman, Amber Su, Crystal Nguyen, Peter J A Davies, Clifford Stephan, Shuang Pan, Wengen Wu, Yuxin Liu, Jeremy Siegelman, Rebecca E Waters, William A Ross, Shumei Song, Mark Metersky, David G Beer, Christopher P Crum, Alexander J Stewart, Matthew Vincent, Richard Russell, Robert A Izard, Khek Yu Ho, Jack Hung-Sen Lai, William W Bachovchin, Jaffer A Ajani, Frank D Mckeon

Faculty, Staff and Student Publications

Background & aims: Metastatic cancers arise from a decades-long succession of increasingly virulent precursor lesions, each of which represents prospective targets for therapeutic intervention. This evolutionary process has been particularly vivid in esophageal adenocarcinoma (EAC), as this cancer and associated precursor lesions, including Barrett's esophagus (BE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD), coexist in an accessible, 2-dimensional pattern in esophageal mucosa. Given the durability of these precursor lesions, it is likely that they, like EAC, rely on stem cells for their regenerative growth. To assess the role of stem cells in the evolution of EAC, we apply technology that …

The Microrna Mir-30a Blocks Adipose Tissue Fibrosis Accumulation In Obesity, Pradip K Saha, Robert Sharp, Aaron R Cox, Rabie Habib, Michael J Bolt, Jessica B Felix, Claudia E Ramirez Bustamante, Xin Li, Sung Yun Jung, Kang Ho Kim, Kai Sun, Huaizhu Wu, Samuel Klein, Sean M Hartig

Faculty, Staff and Student Publications

White adipose tissue (WAT) fibrosis occurring in obesity contributes to the inflammatory and metabolic comorbidities of insulin resistance and type 2 diabetes, yet the mechanisms involved remain poorly understood. Here, we report a role for the broadly conserved miRNA miR-30a as a regulator of WAT fibrosis and systemic glucose metabolism. Mice modified to express miR-30a at elevated levels in adipose tissues maintain insulin sensitivity coupled with reduced fatty liver disease when fed a high-fat diet. These effects were attributable to cell-autonomous functions of miR-30a that potently increase expression of adipocyte-specific genes. Proteomic screening revealed miR-30a limits profibrotic programs in subcutaneous …

Crispr-Cas9 Engineering Of Human T Regulatory Cells – Design And Optimization Of A Manufacturing Process, Ortal Shimon, Adam M Dean, Shoshana Cohen, Aiden L Moser, Clifford C Dacso, Yosi Gilad, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Regulatory T cells (Tregs) are a subset of CD4 + T cells that comprise 5-10 % of the total CD4 + T cell population. Tregs, which are critically important for the maintenance of immune tolerance and immune homeostasis, are distinguished from other subtypes of CD4 + T cells by the expression of the transcription factor FOXP3. Because of the centrality to immunoregulation, Tregs have gained increasing attention as promising targets for clinical applications in autoimmune diseases, transplant rejection and graft-versus-host disease (GvHD). However, the essential role of Tregs in the complex network of the immune system implies their targeting as …

A Simple, Interpretable Machine Learning Model Based On Clinical Factors Accurately Predicts Incident Dysplasia Or Malignancy In Barrett's Esophagus, Ashwin Rao, Jasmine Haydel, Samuel Ma, Aaron P Thrift, Theresa Nguyen-Wenker, Hashem B El-Serag

Faculty, Staff and Students Publications

Purpose: Identifying patients likely to develop dysplasia or malignancy is critical for effective surveillance in patients with Barrett's Esophagus (BE). However, current predictive models are limited. We evaluated the performance of machine learning (ML) models in predicting incident dysplasia or malignancy in a cohort of veteran patients with BE.

Methods: We analyzed data from 598 patients newly diagnosed with non-dysplastic BE (NDBE), BE indefinite for dysplasia (BE-IND), and BE with non-persistent low-grade dysplasia (LGD) at the Michael DeBakey Veterans Affairs Medical Center from November 1990 to January 2019 with follow-up through January 2024. Progressors were patients who developed persistent LGD, …

Diagnostic Value Of Cell-Free Dna Fetal Fraction In Patients With Prenatally Suspected Placenta Accreta Spectrum Disorder, Danielle Chirumbole, Christian M Parobek, Alex Tai, Haleh Sangi-Haghpeykar, Yamely H Mendez, Spoorthi Kamepalli, Christina C Reed, Arthur Ladron De Guevara, Keneshia Lane, Claire Hoppenot, Amir A Shamshirsaz, Michael A Belfort, Jessian L Munoz, Hendrik A Lombaard

Faculty, Staff and Students Publications

Objective: The purpose of this study was to investigate the relationship between fetal fraction (FF) and placenta accreta spectrum (PAS) pathology in patients with prenatally suspected PAS.

Methods: This was a case-control study utilizing a database of pregnancies with suspected or proven PAS delivered between 6/2012 and 7/2024 at a single institution. Pregnancies were excluded if FF was not reported. The primary outcome was mean FF in pregnancies with a final clinical diagnosis of low FIGO grade (no PAS or FIGO1-2) versus high FIGO grade (FIGO3) placenta accreta. Results were reported as mean FF ± standard error of the mean. …

Parabolic Flight As A Research Platform To Investigate Ophthalmic Changes In Microgravity, Tuan Nguyen, Joshua Ong, Sarah Aman, Alex Weaver, Ana Garcia, Amy Song, Fatma Shakarchi, Ethan Waisberg, Andrew G Lee

Faculty, Staff and Students Publications

Parabolic flight serves as an important terrestrial analog to study acute physiological changes in microgravity without the need for space travel. During a parabolic flight, alternating hypergravity and microgravity phases, lasting up to 40 seconds, enable research into ophthalmic changes. In this review, we discuss the application of parabolic flight as a platform to study microgravity-related changes that might impact ophthalmology including intraocular pressure, intracranial pressure, choroidal blood flow, and modified eye movement patterns. We further highlight how these insights could aid our understanding of vestibulo-ocular reflexes and conditions such as Spaceflight Associated Neuro-ocular Syndrome (SANS). While the brief duration …

Left Bundle Branch Area Pacing Compared With Biventricular Pacing For Cardiac Resynchronization Therapy In Patients With Left Ventricular Ejection Fraction ≤50%: Results From The International Collaborative Lbbap Study (I-Clas), Ramez Morcos, Pugazhendhi Vijayaraman, Óscar Cano, Francesco Zanon, Shunmuga Sundaram Ponnusamy, Bengt Herweg, Parikshit S Sharma, Marek Jastrzebski, Manuel Molina-Lerma, Zachary I Whinnett, Kevin Vernooy, Jiangang Zou, Girish M Nair, Rajeev K Pathak, Roderick Tung, Gaurav A Upadhyay, Karol Curila, Mihail G Chelu, Kenneth A Ellenbogen

Faculty, Staff and Students Publications

Background: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is an established treatment of heart failure with reduced ejection fraction and wide QRS. Left bundle branch area pacing (LBBAP) has emerged as a physiologic alternative by directly engaging the His-Purkinje system, potentially improving electrical resynchronization and clinical outcomes.

Objective: The aim of the study was to compare the clinical outcomes between BVP and LBBAP in patients with left ventricular ejection fraction (LVEF) ≤50% undergoing CRT.

Methods: This multicenter observational study included patients with LVEF ≤50% receiving CRT with either LBBAP or BVP at 18 centers from January 2018 to June …

Relapse Patterns Among Children And Adolescents With Kaposi Sarcoma In Malawi, Toni Chanroo, Allison Silverstein, Casey L Mcatee, William Kamiyango, Jimmy Villiera, Parth S Mehta, Erin Peckham-Gregory, Mark Zobeck, Michael E Scheurer, Carl E Allen, Rizine Mzikamanda, Nmazuo W Ozuah, Nader Kim El-Mallawany

Faculty, Staff and Students Publications

Kaposi Sarcoma (KS) is a common childhood cancer in Malawi, but few studies have exploredclinical characteristicsofrelapsed disease. We aimed to characterize clinical patterns of relapse to improve treatment and, ultimately, long-term survival in patients with pediatric KS.A retrospective cohort study was conducted among patients ages < 19 years of age at time of KS diagnosis in Lilongwe, Malawi between August 1, 2010 and March 15, 2020. Specifically, emphasis was placed on patients who had relapsed disease and excluded patients with refractory disease or those who died whilst receiving front-line treatment. Salvage therapy typically involved an intensified chemotherapy regimen compared to front-line therapy—namely nonliposomaldoxorubicin plus bleomycin/vincristine or paclitaxel monotherapy.One-hundred and ninety patients with pediatric KS were included in this analysis, 50 of whom experienced relapse (26%).Older median age was associated with occurrence of relapse (10 vs 6.7 years, p-value = 0.004). Median time from diagnosis to first relapse was 10.6 months (range 2.3–49 months). Three-year post-relapse overall survival (OS) for the entire cohort was 60% with a median follow-up time of 4.7 years after relapse.Survival was significantly higher for patients who relapsed with the woody edema clinical phenotype of pediatric KS versus those with visceral/disseminated disease—3-year OS 79% (95% CI 62–100) versus 29% (14–61).These data demonstrate potential for continued survival after KS relapse in the pediatric population and identify subsets of high-risk patients. The higher mortality observed in patients with visceral/disseminated KS highlights the need for improved therapeutic strategies.

Domains Of Housing Instability And Intimate Partner Violence Risk Among U.S. Tenants, Anairany Zapata, Leila G Wood, Annalynn M Galvin, Wenyaw Chan, Timothy A Thomas, Jack Tsai, Heather K Way, Elizabeth J Mueller, Daphne C Hernandez

Faculty, Staff and Student Publications

While IPV is often studied as a predictor of housing insecurity, few U.S. studies explore how different forms of housing instability may contribute to intimate partner violence (IPV) risk. Using a mixed-methods approach and a cross-sectional design, this study examined the association between four housing instability domains and IPV among a sample of tenants that had either experienced eviction or were at high risk for eviction. Tenants in Harris and Travis counties (Texas, USA) completed an online survey (n = 1085; March–July 2024). Housing instability was assessed across four domains: homelessness, lease violations, utility hardship, and poor housing quality. …

Exploring Tricine As A Novel Red Cell Cryopreservative: Lessons And Future Directions, Thomas Bailey-Schmidt, Christine V Saunders, Chloë E George, Thomas G Scorer, Lynn M R Mccallum, Tracey E Madgett

School of Biomedical Sciences

BACKGROUND AND OBJECTIVES: Cryopreservation allows for storage of red blood cells (RBCs) beyond the standard 35-day period. Current glycerol-based methods are labour-intensive and scale-limited in application. Tricine has been identified as a potential alternative cryoprotectant (CPA), demonstrating efficacy in sheep RBC. This study aims to evaluate the biocompatibility and efficacy of tricine in human RBC cryopreservation.

MATERIALS AND METHODS: Human and sheep RBCs were exposed to varying concentrations of tricine (2.0-20.0% w/v) or glycerol (20.0-40.0% w/v). Biocompatibility was assessed via 24-h incubation at 4°C, while cryoprotective efficacy was evaluated following freezing in liquid nitrogen, storage at -80°C and thawing at …

Role And Use Of Race In Artificial Intelligence And Machine Learning Models Related To Health, Martin C Were, Ang Li, Bradley A Malin, Zhijun Yin, Joseph R Coco, Benjamin X Collins, Ellen Wright Clayton, Laurie L Novak, Rachele Hendricks-Sturrup, Abiodun O Oluyomi, Shilo Anders, Chao Yan

Faculty, Staff and Students Publications

The role and use of race within health-related artificial intelligence (AI) and machine learning (ML) models have sparked increasing attention and controversy. Despite the complexity and breadth of related issues, a robust and holistic framework to guide stakeholders in their examination and resolution remains lacking. This perspective provides a broad-based, systematic, and crosscutting landscape analysis of race-related challenges, structured around the AI and ML life cycle and framed through "points to consider" to support inquiry and decision-making.

Biotechnology Research Incubator For Teachers (Brite) Pilot Program: Advancing Technology Research Education For Secondary School Teachers, Zhongcheng Shi, Katherine A Harris, Alana D Newell, Michael Nguyen, Yuan Yao, Joel Sederstrom, Cynthia C Hallmark, Sherita Love, Fred A Pereira, Shixia Huang

Faculty, Staff and Students Publications

Introduction: Advanced technologies have transformed diagnostics and therapeutics, improving disease management. Secondary school educators play a vital role in fostering critical thinking, problem-solving, and inspiring students in science, technology, engineering, math, and medicine (STEMM) innovations. Comprehensive teacher training enhances education delivery and ensures long-term advancements in science education, empowering future generations.

Materials and methods: We launched the Biotechnology Research Incubator for Teachers (BRITE) pilot program to train secondary school teachers. This 3-week program immerses teachers in Advanced Technology Core facilities, providing hands-on experience with cutting-edge technologies, such as protein array technology, next-generation sequencing, and flow cytometry. It also offers collaborative …

Optimal Treatment Duration In Metastatic Renal Cell Carcinoma Patients Responding To Immune Checkpoint Inhibitors: Should We Treat Beyond Two Years?, Alexander Decruyenaere, Gennigens Christine, Rottey Sylvie, Laenen Annouschka, Emmanuel Seront, Els Everaert, Philip R Debruyne, Heidi Van Den Bulck, Julie Bastin, Verbiest Annelies, Christof Vulsteke, Peter Schatteman, Daisy Luyten, Sandrine Aspeslagh, Nieves Martinez-Chanza, Marlies De Bock, Thomas Meyskens, Jolanda Verheezen, Barbara Brouwers, Benoit Beuselinck

School of Nursing and Midwifery

BACKGROUND AND PURPOSE: Optimal treatment duration is unknown in metastatic renal cell carcinoma (mRCC) responding to immune checkpoint inhibitors (ICPIs). Prolonged treatment can lead to late toxicity, burden for day clinics and financial impact.

PATIENTS AND METHODS: This multicenter retrospective study included mRCC patients responding to ipilimumab/nivolumab in first-line or nivolumab in later lines, who were treated for at least 21 months and did not stop for toxicity. Progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) were modeled non- and semi-parametrically. The effect of elective ICPI discontinuation (i.e. treatment interruption at the clinician's discretion) between 21 and 25 …

Retrotransposon Methylation Profiles And Survival In Black Women With High-Grade Serous Ovarian Carcinoma., Christelle Colin-Leitzinger, Katherine A. Lawson-Michod, Courtney E. Johnson, Irma M. Vlasac, Sean Yoder, Tania Mesa, Dana Roeber, Chad Huff, Michelle A T Hildebrandt, Kristin Haller, Anthony J. Alberg, Elisa V. Bandera, Melissa Bondy, Michele L. Cote, Theresa Hastert, Edward S. Peters, Paul D. Terry, Andrew B. Lawson, Andrew Berchuck, Brooke L. Fridley, Jing-Yi Chern, Jennifer A. Doherty, Jeffrey R. Marks, Joellen M. Schildkraut, Brock C. Christensen, Lucas A. Salas, Lauren C. Peres

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Retrotransposons (REs) constitute nearly half of the genome and include long terminal repeat (LTR) elements, Long INterspersed Elements (LINE), and Short INterspersed Elements (SINE). REs are typically silenced in somatic tissues via DNA methylation but can be reactivated through DNA hypomethylation, potentially impacting gene regulation. Here, we investigate genome-scale profiles of RE methylation in high-grade serous ovarian carcinoma (HGSOC) and associations with survival among Black women.

METHODS: Methylation levels of LTR, LINE-1, and Alu (type of SINE) in 200 HGSOC tumors were predicted using a random forest approach and clustered using multiple consensus algorithms. Associations between RE methylation clusters …

Retrotransposon Methylation Profiles And Survival In Black Women With High-Grade Serous Ovarian Carcinoma, Christelle Colin-Leitzinger, Katherine A Lawson-Michod, Courtney E Johnson, Irma M Vlasac, Sean Yoder, Tania Mesa, Dana Roeber, Chad Huff, Michelle A T Hildebrandt, Kristin Haller, Anthony J Alberg, Elisa V Bandera, Melissa Bondy, Michele L Cote, Theresa Hastert, Edward S Peters, Paul D Terry, Andrew B Lawson, Andrew Berchuck, Brooke L Fridley, Jing-Yi Chern, Jennifer A Doherty, Jeffrey R Marks, Joellen M Schildkraut, Brock C Christensen, Lucas A Salas, Lauren C Peres

Faculty, Staff and Student Publications

Introduction: Retrotransposons (REs) constitute nearly half of the genome and include long terminal repeat (LTR) elements, Long INterspersed Elements (LINE), and Short INterspersed Elements (SINE). REs are typically silenced in somatic tissues via DNA methylation but can be reactivated through DNA hypomethylation, potentially impacting gene regulation. Here, we investigate genome-scale profiles of RE methylation in high-grade serous ovarian carcinoma (HGSOC) and associations with survival among Black women.

Methods: Methylation levels of LTR, LINE-1, and Alu (type of SINE) in 200 HGSOC tumors were predicted using a random forest approach and clustered using multiple consensus algorithms. Associations between RE methylation clusters …

Efficacy And Safety Of Dapagliflozin In Patients Hospitalized With Covid-19 With And Without Type 2 Diabetes: A Prespecified Analysis Of The Dare-19 Randomized Trial, Mohammad Abdel Jawad, Ali Javaheri, Et Al.

2020-Current year OA Pubs

BACKGROUND: Although several previous studies tested SGLT2 inhibitors in the setting of an acute, non-cardiovascular illness, detailed information on their efficacy and safety among participants with and without type 2 diabetes (T2D) from double-blind randomized trials is lacking. In this secondary prespecified analysis of the Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial, we sought to evaluate the safety and efficacy of initiating dapagliflozin during acute illness with COVID-19 in patients with and without T2D.

METHODS: The DARE-19 trial randomized 1250 patients hospitalized with COVID-19 and cardiometabolic risk factors to dapagliflozin or placebo. T2D was present in 636/1250 …

Unveiling Spatial Heterogeneity In Medulloblastoma: A Multi-Omics Analysis Of Cellular State And Geographical Organization, Jiankang Li, Hailong Liu, Ziwei Wang, Jiao Zhang, Xuan Chen, Craig Daniels, Xiaochong Wu, Olivier Saulnier, Hiromichi Suzuki, Pasqualino De Antonellis, Alexandra Rasnitsyn, Winnie Ong, Evan Y Wang, Liam D Hendrikse, Yu Su, Yu Tian, Dongming Han, Ruohan Wang, Jialin Mo, Fei Liu, Kaiwen Deng, Dongyang Wang, Zhaoyang Feng, Yifei Jiang, Yanong Li, Yuting Ma, Zijia Liu, Meiyu Li, Peiyi Tian, Yanfeng Shi, Yong Jiang, Tao Yang, Shouwei Li, Jianfeng Liang, Jingchuan Wu, Ying Wang, Wanjing Zou, Yina Jiang, Lusheng Wang, Fang Chen, Xin Jin, Shuaicheng Li, Xiaoguang Qiu, Chunde Li, Ya Gao, Yujie Tang, Michael D Taylor, Tao Jiang

Faculty, Staff and Students Publications

Background: Despite numerous studies on medulloblastoma (MB) cell heterogeneity, the spatial characteristics of cellular states remain unclear.

Methods: We analyze single-nucleus and spatial transcriptomes and chromatin accessibility from human MB spanning four subgroups, to identify malignant cell populations and describe the spatial evolutionary trajectories. The spatial copy number variations (CNVs) patterns and niches were analyzed to investigate the cellular interactions.

Results: Three main malignant cell populations were identified, including progenitor-like, cycling, and differentiated populations. Gene signatures of cell populations strongly correlate to clinical outcomes. These tumor cell populations are geographically organized as stem-like and mature regions, highlighting their spatially heterogeneous …

Effects Of Neoadjuvant Immunotherapy On Hearing In Patients With Head And Neck Squamous Cell Carcinoma, Bryce Hambach, Anhelina Bilokon, John Lee, L. Noelle Allemang, Jennifer Chisholm, Chris K. Zalewski, Julie Christensen, Carmen C. Brewer, James L. Gulley, Clint T. Allen, Lisa L. Cunningham, Katharine A. Fernandez

SKMC Student Presentations and Publications

Immune checkpoint blockade (ICB) is a commonly used treatment modality for cancer with a growing list of oncologic indications. Ototoxicity is a potential immune-related adverse event of ICB treatment, but the risk of hearing loss after ICB remains unknown. This retrospective chart review sought to identify individuals who received ICB and had available audiometric data before and after treatment in order to identify clinically meaningful changes in hearing. This single center, institutional chart review examined hearing function data in patients who underwent audiometry before and after ICB treatment. Measures included pure tone thresholds, distortion product otoacoustic emissions (DPOAEs), tympanometry, and …

Refinement Of Hyams Grading Criteria For Olfactory Neuroblastoma In An Endoscopic Sinus Surgery Predominant Cohort With Extended Follow-Up: Worth The Effort?, Stacey Gargano, Vincent Cracolici, Carl Snyderman, Eric Wang, Garret Choby, Aron Pollack, Paul Gardner, Diana Bell, Raja Seethala

Computational Medicine Center Faculty Papers

BACKGROUND: Hyams grading is considered prognostic in olfactory neuroblastoma (ONB), but grading criteria are subjective and predate modern classification and surgical approach. We evaluate the application of granular grading criteria to an endoscopic surgery predominant cohort with extended follow-up.

METHODS: 78 ONB patients were identified (1994-2019) with original diagnoses dating to 1979. Original Hyams grade, Modified Hyams grade incorporating more detailed criteria and other histologic features (i.e. divergent differentiation, clear cell/oncocytic change, and spindling) were assessed if feasible, evaluated for distribution by grade and correlated with outcomes.

RESULTS: Original Hyams grade (n = 43) distribution was: I: 4 (9%), II: …

Elevated Nr2f1 Underlies The Persistence Of Invasive Disease After Treatment Of Braf-Mutant Melanoma, Manoela Tiago, Timothy J. Purwin, Casey D. Stefanski, Renaira Oliveira Da Silva, Mitchell E. Fane, Yash Chhabra, Jelan I. Haj, Jessica L. F. Teh, Rama Kadamb, Weijia Cai, Sheera Rosenbaum, Vivian Chua, Nir Hacohen, Michael A. Davies, Jessie Villanueva, Inna Chervoneva, Ashani T. Weeraratna, Dan A. Erkes, Claudia Capparelli, Julio A. Aguirre-Ghiso, Andrew E. Aplin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite the success of targeted inhibitors in cutaneous melanoma, therapeutic responses are limited by the aged tumor microenvironment and drug-tolerant residual cells. Given the similarities between drug tolerance and cellular dormancy, we studied the dormancy marker, nuclear receptor subfamily 2 group F member 1 (NR2F1), in response to BRAF-V600E inhibitors (BRAFi) plus MEK inhibitors (MEKi) in BRAF-mutant melanoma models. Transcriptomic analysis of melanoma patient samples treated with BRAFi + MEKi showed increased NR2F1. NR2F1 was highly expressed in the drug-tolerant invasive cell state of minimal residual disease in patient-derived and mouse-derived xenografts on BRAFi + MEKi. NR2F1 over-expression was sufficient …

Epigenomic Diagnosis And Prognosis Of Acute Myeloid Leukemia., Francisco Marchi, Vivek M. Shastri, Richard J. Marrero, Nam H K Nguyen, Antonella Öttl, Ann-Kathrin Schade, Marieke Landwehr, Olga Krali, Jessica Nordlund, Matin Ghavami, Fernando Sckaff, Vikash K. Mansinghka, Xueyuan Cao, William Slayton, Petr Starostik, Christopher R. Cogle, Raul C. Ribeiro, Jeffrey E. Rubnitz, Jeffery Klco, Abdelrahman Elsayed, Alan S. Gamis, Timothy J. Triche, Rhonda Ries, E Anders Kolb, Richard Aplenc, Todd Alonzo, Stanley Pounds, Soheil Meshinchi, Jatinder K. Lamba

Manuscripts, Articles, Book Chapters and Other Papers

Despite the critical role of DNA methylation, clinical implementations harnessing its promise have not been described in acute myeloid leukemia. Utilizing DNA methylation from 3314 leukemia patient samples across 11 harmonized cohorts, we describe the Acute Leukemia Methylome Atlas, which includes robust models capable of accurately predicting AML subtypes. A genome-wide prognostic model as well as a targeted panel of 38 CpGs significantly predict five-year survival in our pediatric and adult test cohorts. To accelerate rapid clinical utility, we develop a specimen-to-result protocol that uses long-read nanopore sequencing and machine learning to characterize patients' whole genomes and epigenomes. Clinical validation …

Glucose Metabolism And Its Direct Action In Cancer And Immune Regulation: Opportunities And Challenges For Metabolic Targeting, Bo-Syong Pan, Che-Chia Hsu, Hsin-En Wu, Yuan-Ru Chen, Xiaobo Zhou, Shu-Chi Wang, Chia-Yang Li, Hui-Kuan Lin

Faculty, Staff and Student Publications

Glucose metabolism is a pivotal hub for cellular energy production and the generation of building blocks that support cell growth, survival, and differentiation. Cancer cells undergo metabolic reprogramming to sustain rapid proliferation, survive in harsh microenvironments, and resist therapies. Beyond producing energy and building blocks to meet cancer cell demands, glucose metabolism generates numerous metabolites that serve as signaling molecules, orchestrating signaling pathways and epigenetic modifications that regulate cancer cell phenotypes and immunity. In this review, we discuss how glucose, through its metabolism and direct actions, influences diverse biological processes driving cancer progression and therapeutic resistance, while also exploring metabolic …

A Data Assimilation Framework For Predicting The Spatiotemporal Response Of High-Grade Gliomas To Chemoradiation, Hugo J M Miniere, David A Hormuth, Ernesto A B F Lima, Maguy Farhat, Bikash Panthi, Holly Langshaw, Mihir D Shanker, Wasif Talpur, Sara Thrower, Jodi Goldman, Sophia Ty, Caroline Chung, Thomas E Yankeelov

Faculty, Staff and Student Publications

Background: High-grade gliomas are highly invasive and respond variably to chemoradiation. Accurate, patient-specific predictions of tumor response could enhance treatment planning. We present a novel computational platform that assimilates MRI data to continually predict spatiotemporal tumor changes during chemoradiotherapy.

Methods: Tumor growth and response to chemoradiation was described using a two-species reaction-diffusion model of enhancing and non-enhancing regions of the tumor. Two evaluation scenarios were used to test the predictive accuracy of this model. In scenario 1, the model was calibrated on a patient-specific basis (n = 21) to weekly MRI data during the course of chemoradiotherapy. A data assimilation …

Neighborhood Environment And Incident Diabetes, A Neighborhood Environment-Wide Association Study ('Ne-Was'): Results From The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol)., Cara M. Smith, Elizabeth W. Spalt, Linda C. Gallo, Jordan A. Carlson, Matthew Allison, Daniela Sotres-Alvarez, Christina Cordero, Qibin Qi, Earle C. Chambers, Martha Daviglus, Amber Pirzada, Gregory A. Talavera, Robert Kaplan, Joel D. Kaufman, Stephen J. Mooney

Manuscripts, Articles, Book Chapters and Other Papers

The prevalence of type 2 diabetes is increasing among the Hispanic/Latino population. Type 2 diabetes incidence rates vary between neighborhoods, but no single aspect of the neighborhood environment is known to cause type 2 diabetes. Using data from the Hispanic Community Health Study/Study of Latinos cohort of 16,415 Hispanic/Latino adults in four major US cities, we conducted a neighborhood environment-wide association study to identify neighborhood measures or clusters of measures associated with diabetes incidence. Two-hundred and four neighborhood measures were calculated at the census tract level or within a 1-km buffer of participants' residential addresses. Independent covariate-adjusted and survey-weighted Poisson …

Non-Mutated Human Tau Stimulates Alzheimer’S Disease-Relevant Neurodegeneration In A Microglia-Dependent Manner, Ethan R Roy, Qiang Wang, Kexin Huang, Sanming Li, Yuanyuan Fan, Estrella Escobar, Constance L Atkins, Shuning Huang, Juan J Herrera, Wenbo Li, Clare Pridans, Xiaobo Zhou, Cynthia Ju, Wei Cao

Faculty, Staff and Student Publications

The accumulation of abnormal, non-mutated tau protein is a key pathological hallmark of Alzheimer's disease (AD). Despite its strong association with disease progression, the mechanisms by which tau drives neurodegeneration in the brain remain poorly understood. Here, we selectively expressed non-mutated or mutated human microtubule-associated protein tau (hMAPT) in neurons across the mouse brain and observed neurodegeneration in the hippocampus, especially associated with non-mutated human tau. Single-nuclei RNA sequencing confirmed a selective loss of hippocampal excitatory neurons by the wild-type tau and revealed the upregulation of neurodegeneration-related pathways in the affected populations. The accumulation of phosphorylated tau was accompanied by …