Medical Specialties Commons^™

Clinical And Genetic Markers Of Vascular Toxicity In Glioblastoma Patients: Insights From Nrg Oncology Rtog-0825, Joshua D Strauss, Mark R Gilbert, Minesh Mehta, Ang Li, Renke Zhou, Melissa L Bondy, Erik P Sulman, Ying Yuan, Yanhong Liu, Elizabeth Vera, Merideth M Wendland, Volker W Stieber, Vinay K Puduvalli, Serah Choi, Nina L Martinez, H Ian Robins, Grant K Hunter, Chi-Fan Lin, Vivian A Guedes, Melissa A Richard, Stephanie L Pugh, Terri S Armstrong, Michael E Scheurer

Faculty, Staff and Students Publications

Background: Glioblastoma (GBM) is an aggressive form of brain cancer in which treatment is associated with toxicities that can result in therapy discontinuation or death. This analysis investigated clinical and genetic markers of vascular toxicities in GBM patients during active treatment.

Methods: In total, 591 non-Hispanic White GBM patients with clinical data were included in the analysis from NRG RTOG-0825. Genome-wide association studies (GWAS) were performed from genotyped blood samples (N = 367) by occurrence of thrombosis or hypertension (grade ≥ 2). A clinical prediction model was produced for each vascular toxicity. Significant GWAS variants were then added to the …

Predictors Of Perioperative Stroke In Patients With Ischemic-Type Moyamoya Disease Treated With Surgical Revascularization: A Retrospective Multicenter Study, Basel Musmar, Joanna M. Roy, Hammam Abdalrazeq, Elias Atallah, Kareem El Naamani, Ching-Jen Chen, Roland Jabre, Hassan Saad, Jonathan A. Grossberg, Adam A. Dmytriw, Aman B. Patel, Mirhojjat Khorasanizadeh, Christopher S. Ogilvy, Ajith J. Thomas, Andre Monteiro, Adnan Siddiqui, Gustavo M. Cortez, Ricardo A. Hanel, Guilherme Porto, Alejandro M. Spiotta, Anthony J. Piscopo, David M. Hasan, Mohammad Ghorbani, Joshua Weinberg, Shahid M. Nimjee, Kimon Bekelis, Mohamed M. Salem, Jan-Karl Burkhardt, Akli Zetchi, Charles Matouk, Brian M. Howard, Rosalind Lai, Rose Du, Rawad Abbas, Georgios S Sioutas, Abdelaziz Amllay, Alfredo Munoz, Nabeel A Herial, Stavropoula I Tjoumakaris, Michael Reid Gooch, Robert H Rosenwasser, Pascal Jabbour

Department of Neurosurgery Faculty Papers

INTRODUCTION: Moyamoya disease (MMD) is a chronic cerebrovascular disorder characterized by progressive stenosis or occlusion of the internal carotid arteries and the development of collateral moyamoya vessels. Surgical revascularization is commonly used to prevent future ischemic events in ischemic-type MMD, but there remains a high rate of stroke perioperatively. This study aims to analyze the predictive factors for perioperative stroke in patients with ischemic-type MMD undergoing surgical revascularization using a large multicenter database.

METHODS: We conducted a multicenter retrospective study in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. This study included patients with ischemic-type …

A Randomized Phase Ii/Iii Study Of Paclitaxel/Carboplatin/Metformin Versus Paclitaxel/Carboplatin/Placebo As Initial Therapy For Measurable Stage Iii Or Iva, Stage Ivb, Or Recurrent Endometrial Cancer: An Nrg Oncology/Gog Study, Victoria L. Bae-Jump, Michael W. Sill, Paola A. Gehrig, Jason D. Merker, David L. Corcoran, Adam D. Pfefferle, Michele C. Hayward, Joan L. Walker, Andrea R. Hagemann, Steven E. Waggoner, Roisin E. O'Cearbhaill, Megan E. Mcdonald, Mitchell I. Edelson, Paul A. Disilvestro, Amy L. Mcnally, Aimee Fleury, Ramey D. Littell, Frederick R. Ueland, Heather A. Lankes, Carol Aghajanian

Abington Jefferson Health Papers

INTRODUCTION: We evaluated the efficacy of the addition of the anti-diabetic drug metformin to standard-of-care paclitaxel and carboplatin (PC) in patients with advanced and recurrent endometrial cancer (EC).

METHODS: In this phase II/III trial, EC patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) disease were randomly assigned to PC/metformin (850 mg BID) versus PC/placebo. Metformin or placebo was continued as maintenance therapy after completion of PC until disease progression. The primary endpoint of phase II was progression-free survival (PFS). The primary endpoint of phase III was overall survival (OS). Secondary …

Consensus Recommendations For An Integrated Diagnostic Approach To Peripheral Nerve Sheath Tumors Arising In The Setting Of Neurofibromatosis Type 1, Calixto-Hope G Lucas, Andrea M Gross, Carlos G Romo, Carina A Dehner, Alexander J Lazar, Markku Miettinen, Melike Pekmezci, Martha Quezado, Fausto J Rodriguez, Anat Stemmer-Rachamimov, David Viskochil, Arie Perry

Faculty, Staff and Student Publications

Consensus recommendations published in 2017 histologically defining atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP) and malignant peripheral nerve sheath tumor (MPNST) were codified in the 2021 WHO Classification of Tumors of the Central Nervous System and the 2022 WHO Classification of Tumors of Soft Tissue and Bone. However, given the shift in diagnostic pathology toward the use of integrated histopathologic and genomic approaches, the incorporation of additional molecular strata in the classification of Neurofibromatosis Type 1 (NF1)-associated peripheral nerve sheath tumors should be formalized to aid in accurate diagnosis and early identification of malignant transformation and enable appropriate intervention …

Immunotherapy-Related Neurotoxicity In The Central Nervous System Of Children With Cancer, Jiasen He, Jeremy Connors, Andrew Meador, Shuo Xu, Heather Meador, Hong Jiang, Juan Fueyo, Candelaria Gomez-Manzano, Gregory K Friedman, Wafik Zaky, Zsila Sadighi, John M Slopis, Ali H Ahmad

Faculty, Staff and Student Publications

Significant gaps remain in our understanding of immunotherapy-related neurotoxicity in pediatric patients, largely because much of our knowledge comes from studies in adults. Accurately identifying the adverse effects of immunotherapy in children is also challenging, owing to variations in terminology and grading systems. Moreover, the manifestation of immunotherapy-related neurotoxicity differs greatly across different diseases, various modalities, dosages, and delivery methods. Combining immunotherapy with other treatments might improve outcomes but introduces new complexities and potential for increased toxicities. Additionally, pediatric patients with intracranial malignancy have unique responses to immunotherapies and distinct neurotoxicity compared to those with extracranial malignancy. Consequently, we must …

Cryptic Kmt2a::Afdn Fusion Due To Afdn Insertion Into Kmt2a In A Patient With Acute Monoblastic Leukemia, Qing Wei, Gokce A Toruner, Beenu Thakral, Keyur P Patel, Naveen Pemmaraju, Sa A Wang, Rashmi Kanagal-Shamanna, Guilin Tang, Ghayas C Issa, Sanam Loghavi, L Jeffrey Medeiros, Courtney Dinardo

Faculty, Staff and Student Publications

Background: KMT2A rearrangements occur in ~10% of acute myeloid leukemia (AML) cases and are critical for classification, risk stratification, and use of targeted therapy. However, insertions involving the KMT2A gene can evade detection using chromosomal analysis and/or fluorescence in situ hybridization (FISH).

Methods: We present a case of a 22-year-old woman with acute monoblastic leukemia harboring a cryptic KMT2A::AFDN fusion identified by RNA sequencing. Initial FISH showed a 3' KMT2A deletion, while conventional karyotyping and the automated bioinformatic pipeline for optical genome mapping (OGM) did not identify the canonical translocation.

Results: To resolve these discrepancies, metaphase KMT2A FISH (break-apart fusion …

Cryptic Kmt2a::Afdn Fusion Due To Afdn Insertion Into Kmt2a In A Patient With Acute Monoblastic Leukemia, Qing Wei, Gokce A Toruner, Beenu Thakral, Keyur P Patel, Naveen Pemmaraju, Sa A Wang, Rashmi Kanagal-Shamanna, Guilin Tang, Ghayas C Issa, Sanam Loghavi, L Jeffrey Medeiros, Courtney Dinardo

Faculty, Staff and Student Publications

Background: KMT2A rearrangements occur in ~10% of acute myeloid leukemia (AML) cases and are critical for classification, risk stratification, and use of targeted therapy. However, insertions involving the KMT2A gene can evade detection using chromosomal analysis and/or fluorescence in situ hybridization (FISH).

Methods: We present a case of a 22-year-old woman with acute monoblastic leukemia harboring a cryptic KMT2A::AFDN fusion identified by RNA sequencing. Initial FISH showed a 3' KMT2A deletion, while conventional karyotyping and the automated bioinformatic pipeline for optical genome mapping (OGM) did not identify the canonical translocation.

Results: To resolve these discrepancies, metaphase KMT2A FISH (break-apart fusion …

Outcomes Of Double Free Flap Reconstruction For Advanced Head And Neck Tumors In A Safety-Net Hospital Population, Yossef Alsabawi, John M. Gaddis, Angela D. Haskins, Jonathan Shum, David J. Hernandez

Research Symposium

Background: Double-free flap reconstruction has emerged as a viable option for addressing more complicated defects after oncologic resection. We aim to report the feasibility of this approach at a single-institutional safety net hospital.

Methods: A retrospective chart review was performed between November 2020 and October 2023 for adult patients who underwent multiple, simultaneous free tissue transfers for head and neck defects following tumor resection. This study occurs at Ben Taub Hospital, a safety net hospital in Houston, Texas. Data collected included demographics, risk factors, oncologic and operative details, complications, and functional and disease outcomes. Socioeconomic status was assessed …

Primary Care Behavioral Health Partnerships Advancing & Transforming Health Sciences (Pcbh Paths): An Initiative To Address Health Disparities And Promote Equitable Care In The Rio Grande Valley (Rgv), Deepu George, Joanna Garza, Maria G. Hernandez, Yvette K. Cantu Cazares, Monica C. Perez, Yvette K. Cantu Cazares, Mayrin A. Perez

Research Symposium

Purpose: The Rio Grande Valley (RGV) faces significant socio-economic challenges, with 35.6% of residents living in poverty and uninsured rates as high as 40%. Each year, approximately 260,000 residents experience mild to moderate behavioral health conditions. Behavioral health care in the region is particularly scarce, with only 30.1 mental health providers per 100,000 compared to the statewide average of 72.7. Furthermore, approximately 90.5% of the population identifies as Hispanic/Latino, so culturally relevant interventions are critical. The Primary Care Behavioral Health Partnerships Advancing & Transforming Health Sciences (PCBH PATHS) Initiative addresses these disparities by 1) developing a PCBH model tailored to …

Epilepsy In The Hispanic Population In The Rgv: A Five-Year Retrospective Chart Review, Megan W. Szobody, Kelsey Potter-Baker

Research Symposium

Introduction: Epilepsy is a seizure disorder characterized by abnormal electrical patterns in the brain that lead to changes in synchronization of neuronal firing patterns. Presentations of seizures vary, and include convulsions, changes in awareness, loss of consciousness, or unusual sensations. Approximately 3.4 million Americans suffer from epilepsy, with close to 15,000 in the Rio Grande Valley (RGV). The RGV is home to a vast Hispanic population, with 91% of its population identifying as Hispanic or Latino, according to the American Immigration Council’s research in 2019. However, literature on the prevalence, and presentation of epilepsy within the Hispanic population …

Superior Vena Cava Syndrome Due To Germ Cell Tumor In A Young Adult: Case Report, Manlio F. Lara Duck, Netzahualcoyotl Mayek Pérez, Juan Rosales Martínez

Research Symposium

Background: In superior vena cava syndrome (SVCS), the superior vena cava becomes mechanically obstructed by venous thrombus formation or by compression caused by intrathoracic tumors. SVCS is most common in men over 45 years of age; 22.5% of patients with SVCS have stage IV lung cancer or lymphoma. SVCS may occur secondary to extrathoracic tumors (testicular, ovarian, kidney, intestinal).

Case presentation: Male (24 years old) with a history of cancer in his maternal grandmother; denied drug addiction. Factory worker who denied being in direct contact with any chemicals and/or toxins. He reported non-productive cough; paroxysmal unilateral left facial edema without …

Clinical Relapse Versus Treatment Failure: The Case For Surveillance For Re-Appearance Of Minimal Measurable Disease In Pediatric Patients With Higher Risk B-All, Paul S. Gaynon, Linwei Li

Research Symposium

Background: Despite significant advancements in the treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL), chemotherapy has reached its end of “intensification” stage despite improvements in supportive care. Moreover, relapse remains a major challenge, particularly in high-risk populations such as adolescents and young adults (AYAs). The definition of threshold for clinical relapse as 25% presence of marrow lymphoblasts was established decades ago, which may be incoherent with current therapeutic strategies and delay the window for timely treatment for relapsed patients. Emerging data suggest that early detection of minimal residual disease (MRD) may offer an opportunity to intervene before clinical relapse, improving …

Changes In Brain Functional Connectivity Associated With Transcutaneous Auricular Vagus Nerve Stimulation In Healthy Controls, Daniel A. Monti, Nancy Wintering, Faezeh Vedaei, Alicia Steinmetz, Feroze Mohamed, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

PURPOSE: A growing number of research studies have explored the potential effects of vagus nerve stimulation (VNS) on brain physiology as well as clinical effects particularly related to stress and anxiety. However, there currently are limited studies showing functional changes during different frequencies of stimulation and laterality effects transcutaneous auricular VNS (TaVNS). In this study, we evaluated whether TaVNS alters functional connectivity in the brain of healthy controls. We hypothesized that TaVNS would significantly alter connectivity in areas involved with emotional processing and regulation including the limbic areas, insula, frontal lobe regions, and cerebellum.

METHODS: We enrolled 50 healthy controls. …

The Advancement And Utility Of Multimodal Imaging In The Diagnosis Of Degenerative Disc Disease, Eric M. Teichner, Robert C. Subtirelu, Connor R. Crutchfield, Chitra Parikh, Arjun Ashok, Sahithi Talasila, Victoria Anderson, Milan Patel, Sricharvi Mannam, Andrew Lee, Thomas Werner, William Y. Raynor, Abass Alavi, Mona-Elisabeth Revheim

SKMC Student Presentations and Publications

Degenerative disc disease (DDD) is a common spinal condition characterized by the deterioration of intervertebral discs, leading to chronic back pain and reduced mobility. While magnetic resonance imaging (MRI) has long been the standard for late-stage DDD diagnosis, its limitations in early-stage detection prompt the exploration of advanced imaging methods. Positron emission tomography/computed tomography (PET/CT) using ¹⁸F- fluorodeoxyglucose (FDG) and ¹⁸F-sodium fluoride (NaF) has shown promise in identifying metabolic imbalances and age-related spinal degeneration, thereby complementing CT grading of the disease. The novel hybrid imaging modality PET/MRI provides new opportunities and are briefly discussed. The complex pathophysiology of …

Orthopedic Frailty Risk Stratification (Ofrs): A Systematic Review Of The Frailty Indices Predicting Adverse Outcomes In Orthopedics., Nithin K Gupta, Forrest Dunivin, Hikmat R Chmait, Chase Smitterberg, Azhaan Buttar, Moiz Fazal-Ur-Rehman, Taylor Manes, Morgan Turnow, Tyler K Williamson, Benjamin C Taylor, Jack W Weick, Christian Bowers

Surgery Articles

BACKGROUND: With a growing number of elderly patients requiring elective and non-elective procedures, frailty-based preoperative risk stratification is an emerging tool in orthopedic surgery to minimize adverse postoperative outcomes. This paper sought to understand the current literature regarding preoperative Orthopedic Frailty Risk Stratification (OFRS) and describe the disparate frailty indices and their capabilities for discrimination in predicting adverse postoperative outcomes.

METHODS: A literature search was conducted in Pubmed, Cochrane, and Scopus for articles published during or prior to February 2024 assessing frailty following surgery for orthopedic pathologies. Qualitative variables including study characteristics and application of frailty were collected and synthesized. …

Genome-Wide Prediction Of Dominant And Recessive Neurodevelopmental Disorder-Associated Genes, Ryan S Dhindsa, Blake A Weido, Justin S Dhindsa, Arya J Shetty, Chloe F Sands, Slavé Petrovski, Dimitrios Vitsios, Anthony W Zoghbi

Duncan NRI Faculty and Staff Publications

Despite great progress, thousands of neurodevelopmental disorder (NDD) risk genes remain to be discovered. We present a computational approach that accelerates NDD risk gene identification using machine learning. First, we demonstrate that models trained solely on single-cell RNA sequencing data can robustly predict genes implicated in autism spectrum disorder (ASD), developmental and epileptic encephalopathy (DEE), and developmental delay (DD). Notably, we find differences in gene expression patterns of genes with monoallelic and bi-allelic inheritance patterns in the developing human cortex. We then integrate expression data with 300 orthogonal features, including intolerance metrics, protein-protein interaction data, and others, in a semi-supervised …

Evolving Trends In Retinoblastoma Management: A 16-Year Clinicopathological Analysis Of Enucleated Eyes, Ari H. August, Darcy Curtis, Maya Eiger-Moscovich, Antonio Yaghy, Sara E. Lally, Jerry A. Shields, Carol L. Shields, Ralph C. Eagle, Tatyana Milman

Wills Eye Hospital Papers

PURPOSE: New treatments for advanced retinoblastoma (RB) have offered alternatives to primary enucleation. We assessed the impact of these therapies on the indications for enucleation and the histopathological findings in enucleated eyes with RB.

MATERIALS AND METHODS: Eyes of all patients who underwent enucleation for RB at a single institution between January 2005 and August 2021 were included. Data collected retrospectively included demographics, clinical and pathologic staging, pathologic findings, and management. Statistical analysis included Kendall’s τb, Pearson χ², and Cramér’s V.

RESULTS: There were 254 eyes from 252 patients with information available for review. Annual enucleations decreased between …

Roles Of Mir-223 In Platelet Function And High On-Treatment Platelet Reactivity: A Brief Report And Review, Shayan Askari, Lawrence E. Goldfinger

Cardeza Foundation for Hematologic Research

BACKGROUND: Platelets are highly enriched in microRNAs (miRNAs), which are genomically encoded 19-25 nucleotide non-coding RNAs that target complementary mRNAs through total or near-total base pairing. MiR-223 is among the most abundant miRNAs in human and murine platelets, but despite ongoing investigations in recent years, miR-223 roles in platelet physiology and its putative roles in high on-treatment platelet reactivity (HTPR) remain controversial, as studies showed varying findings.

OBJECTIVES: In the current hybrid review/report, we aim to compare studies that investigated miR-223 in platelet function and HTPR. Additionally, we briefly report our own findings on murine miR-223-deficient platelets.

METHODS: We have …

Impact Of Primary Care Team Configuration On Access And Quality Of Care, Sylvia J Hysong, Kelley Arredondo, Houston F Lester, Richard Sorelle, Trang Pham, Frederick L Oswald, Lechauncy Woodard, Laura A Petersen, Joshua Hamer, Ashley M Hughes

Faculty, Staff and Students Publications

Background: Team-based primary care has become the norm within many large healthcare systems; however, limited guidance exists on how to optimally staff primary care teams in relationship to healthcare.

Objective: This paper examines the associations between variations in team staffing configurations on primary care access and clinical quality.

Design: Observational study linking national Veterans Health Administration (VHA) data from February 2020 on primary care team staffing configurations to data on access to and quality of care the teams delivered.

Participants: We examined data from 22,390 primary care personnel assigned to 7050 teams from 1050 VA Medical Centers and Community-Based Outpatient …

Drbioright 20: An Llm-Powered Bioinformatics Chatbot For Large-Scale Cancer Functional Proteomics Analysis, Wei Liu, Jun Li, Yitao Tang, Yining Zhao, Chaozhong Liu, Meiyi Song, Zhenlin Ju, Shwetha V Kumar, Yiling Lu, Rehan Akbani, Gordon B Mills, Han Liang

Faculty, Staff and Student Publications

Functional proteomics provides critical insights into cancer mechanisms, facilitating the discovery of novel biomarkers and therapeutic targets. We have developed a comprehensive cancer functional proteomics resource using reverse phase protein arrays, incorporating data from nearly 8000 patient samples from The Cancer Genome Atlas and approximately 900 samples from the Cancer Cell Line Encyclopedia. Our dataset includes a curated panel of nearly 500 high-quality antibodies, covering all major cancer hallmark pathways. To enhance the accessibility and analytic power of this resource, we introduce DrBioRight 2.0 ( https://drbioright.org ), an intuitive bioinformatic platform powered by state-of-the-art large language models. DrBioRight enables researchers …

Structure-Function Relationship Of Ash1l And Histone H3k36 And H3k4 Methylation, Kendra R Vann, Rajal Sharma, Chih-Chao Hsu, Maeva Devoucoux, Adam H Tencer, Lei Zeng, Kevin Lin, Li Zhu, Qin Li, Catherine Lachance, Ruben Rosas Ospina, Qiong Tong, Ka Lung Cheung, Shuai Yang, Soumi Biswas, Hongwen Xuan, Jovylyn Gatchalian, Lorena Alamillo, Jianlong Wang, Suk Min Jang, Brianna J Klein, Yue Lu, Patricia Ernst, Brian D Strahl, Scott B Rothbart, Martin J Walsh, Michael L Cleary, Jacques Côté, Xiaobing Shi, Ming-Ming Zhou, Tatiana G Kutateladze

Faculty, Staff and Student Publications

The histone H3K36-specific methyltransferase ASH1L plays a critical role in development and is frequently dysregulated in human diseases, particularly cancer. Here, we report on the biological functions of the C-terminal region of ASH1L encompassing a bromodomain (ASH1LBD), a plant homeodomain (ASH1LPHD) finger, and a bromo-adjacent homology (ASH1LBAH) domain, structurally characterize these domains, describe their mechanisms of action, and explore functional crosstalk between them. We find that ASH1LPHD recognizes H3K4me2/3, whereas the neighboring ASH1LBD and ASH1LBAH have DNA binding activities. The DNA binding function of ASH1LBAH is a driving force for the association of ASH1L with the linker DNA in the …

Identification Of Genes Associated With Testicular Germ Cell Tumor Susceptibility Through A Transcriptome-Wide Association Study, Emilio Ugalde-Morales, Rona Wilf, John Pluta, Alexander Ploner, Mengyao Fan, Mohammad Damra, Katja K Aben, Lynn Anson-Cartwright, Chu Chen, Victoria K Cortessis, Siamak Daneshmand, Alberto Ferlin, Marija Gamulin, Jourik A Gietema, Anna Gonzalez-Niera, Tom Grotmol, Robert J Hamilton, Mark Harland, Trine B Haugen, Russ Hauser, Michelle A T Hildebrandt, Robert Karlsson, Lambertus A Kiemeney, Jung Kim, Davor Lessel, Ragnhild A Lothe, Chey Loveday, Stephen J Chanock, Katherine A Mcglynn, Coby Meijer, Kevin T Nead, Jeremie Nsengimana, Maja Popovic, Thorunn Rafnar, Lorenzo Richiardi, Maria S Rocca, Stephen M Schwartz, Rolf I Skotheim, Kari Stefansson, Douglas R Stewart, Clare Turnbull, David J Vaughn, Sofia B Winge, Tongzhang Zheng, Alvaro N Monteiro, Kristian Almstrup, Peter A Kanetsky, Katherine L Nathanson, Fredrik Wiklund, Testicular Cancer Consortium

Faculty, Staff and Student Publications

Transcriptome-wide association studies (TWASs) have the potential to identify susceptibility genes associated with testicular germ cell tumors (TGCTs). We conducted a comprehensive TGCT TWAS by integrating genome-wide association study (GWAS) summary data with predicted expression models from normal testis, TGCT tissues, and a cross-tissue panel that encompasses shared regulatory features across 22 normal tissues, including the testis. Gene associations were evaluated while accounting for variant-level effects from GWASs, followed by fine-mapping analyses in regions exhibiting multiple TWAS signals, and finally supplemented by colocalization analysis. Expression and protein patterns of identified TWAS genes were further examined in relevant tissues. Our analysis …

Pspc1 Exerts An Oncogenic Role In Aml By Regulating A Leukemic Transcription Program In Cooperation With Pu1, Juyeong Hong, Pinpin Sui, Ying Li, Kerryn Y Xu, Ji-Hoon Lee, Juan Wang, Shi Chen, Peng Zhang, Noah Wingate, Asra Noor, Yaxia Yuan, Robert Hromas, Hongwei Zhou, Karina Hamamoto, Rui Su, C Cameron Yin, Fengxi Ye, Andrés E Quesada, Jianjun Chen, Suming Huang, Daohong Zhou, M James You, Feng-Chun Yang, Jianlong Wang, Mingjiang Xu

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy characterized by the blockage of myeloid cell differentiation and uncontrolled proliferation of immature myeloid cells. Here, we show that paraspeckle component 1 (PSPC1) is aberrantly overexpressed and associated with poor survival in AML patients. Using human AML cells and mouse models, we demonstrate that PSPC1 is not required for normal hematopoiesis, but it is critical and essential for AML cells to maintain their leukemic characteristics. PSPC1 loss induces robust differentiation, suppresses proliferation, and abolishes leukemogenesis in diverse AML cells. Mechanistically, PSPC1 exerts a pro-leukemia effect by regulating a unique leukemic transcription …

2024 Lifetime Achievement Award: Biology Unbalanced: Genes, Gene Dosage, And Disease Susceptibility, James R Lupski

Faculty, Staff and Students Publications

This article is based on the address given by the author at the 2024 meeting of The American Society of Human Genetics (ASHG) in Denver, CO. A video of the original address can be found at the ASHG website.

Sequence Variants In Hectd1 Result In A Variable Neurodevelopmental Disorder, Gazelle Zerafati-Jahromi, Elias Oxman, Hieu D Hoang, Wu-Lin Charng, Tanvitha Kotla, Weimin Yuan, Keito Ishibashi, Sonia Sebaoui, Kathryn Luedtke, Bryce Winrow, Rebecca D Ganetzky, Anna Ruiz, Carmen Manso-Basúz, Nino Spataro, Peter Kannu, Taryn Athey, Christina Peroutka, Caitlin Barnes, Richard Sidlow, George Anadiotis, Kari Magnussen, Irene Valenzuela, Alejandro Moles-Fernandez, Seth Berger, Christina L Grant, Eric Vilain, Gudny A Arnadottir, Patrick Sulem, Telma S Sulem, Kari Stefansson, Shavonne Massey, Natalie Ginn, Annapurna Poduri, Alissa M D'Gama, Rozalia Valentine, Sara K Trowbridge, Chaya N Murali, Rachel Franciskovich, Yen Tran, Bryn D Webb, Kim M Keppler-Noreuil, April L Hall, Bobbi Mcgivern, Kristin G Monaghan, Maria J Guillen Sacoto, Dustin Baldridge, Gary A Silverman, Sonika Dahiya, Tychele N Turner, Tim Schedl, Joshua G Corbin, Stephen C Pak, Irene E Zohn, Christina A Gurnett

Faculty, Staff and Students Publications

Dysregulation of genes encoding the homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases has been linked to cancer and structural birth defects. One member of this family, the HECT-domain-containing protein 1 (HECTD1), mediates developmental pathways, including cell signaling, gene expression, and embryogenesis. Through GeneMatcher, we identified 14 unrelated individuals with 15 different variants in HECTD1 (10 missense, 3 frameshift, 1 nonsense, and 1 splicing variant) with neurodevelopmental disorders (NDDs), including autism, attention-deficit/hyperactivity disorder, and epilepsy. Of these 15 HECTD1 variants, 10 occurred de novo, 3 had unknown inheritance, and 2 were compound heterozygous. While all individuals in this cohort displayed …

Dual Burden: Analyzing The Co-Occurrence Of Spinal Cord And Traumatic Brain Injuries In Texas, Blake C. Martin, Kevin Garcia Valdez, Daniel Salinas, Paul Bonilla, Victoria Elizondo, Anesu Karen Murambadoro, Kelsey Baker

Research Symposium

Background: An estimated 60% of people that suffer a spinal cord injury (SCI) have a co-occurring traumatic brain injury (TBI), with cervical level injuries having the greatest comorbidity. Following an accident, diagnosis of TBI may be missed as emergency responders prioritize the spinal injury. Early recognition of brain involvement in a patient with a traumatic SCI is crucial, as delayed treatment may cause irreversible neurological impairment such as deficits in concentration, memory, and learning. In this study, we analyzed the comorbidity of TBI and SCI in Texas, and the related demographics and injury characteristics. We aimed to increase awareness of …

Symptomatic Manifestations Of Hip Dysplasia In Young Adults: How Do Patients Present Before And After Surgery?, John M. Gaddis, Amanda Wheeler, Yossef Alsabawi, Erika Shults, Charles South, Joel E. Wells

Research Symposium

Background: Hip dysplasia is a common source of hip pain in young adults that can lead to early-onset osteoarthritis. The Bernese periacetabular osteotomy (PAO) and total hip arthroplasty (THA) have shown good results as surgical treatment options for this disorder, yet pain may persist after surgery. A previous study described the clinical features of pre-treated hip dysplasia in a traditional clinical cohort; however, to our knowledge, no previous studies have examined the symptomatic manifestations of hip dysplasia in young adults before and after various surgical treatments including the analysis of pain locations in numerous anatomical areas through a body pain …

Health Inequities In An Undocumented Immigrant Woman With Scleroderma: A Case Report Of Uninsured Care Challenges, Jorge A. Aboytes, Jose J. Loayza, Ismael Cantu

Research Symposium

Introduction: Systemic sclerosis (SSc), commonly known as scleroderma, is a rare connective tissue disorder involving widespread fibrosis, immune system dysregulation, and vascular abnormalities¹. The disease disproportionately affects women, with a female-to-male ratio of 4:1 to 9:1, and is marked by significant ethnic and healthcare disparities². Underserved populations often experience worse outcomes, driven by higher medical costs and increased utilization of emergency and inpatient services³. Among Hispanic patients, language and cultural barriers further exacerbate disparities in access to and quality of care⁴. These challenges underscore the need for equitable healthcare strategies. We present …

Metallosis And An Adverse Reaction To Metal Debris Following Dislocation Of A Metal-On-Metal Hip Arthroplasty: A Case Report, John M. Gaddis, Amanda Wheeler, Bretton Laboret, Joel Wells

Research Symposium

Background: Primary total hip arthroplasties have a reported survivorship exceeding 95% at 10-year data. Metal-on-metal bearing surfaces were introduced to minimize wear rate for patients undergoing THA, however, long-term data has shown an unacceptably high failure rate requiring THA revision. The metal-on-metal implants can lead to failure with the generation of the metal ions, specifically cobalt and chromium. The rise in levels of these metal ions can result in adverse reaction to metal debris (ARMD) which can consist of macroscopic necrosis, corrosive osteolysis, sterile hip effusions, and pseudotumor. There are no specific clinical signs or symptoms indicating metallosis, rather, diagnosis …

Assessing The Accuracy And Readability Of Chatgpt 4.0’S Responses To Common Patient Questions Regarding Periacetabular Osteotomy (Pao), John M. Gaddis, Elias Arellano, Yossef Alsabawi, Pablo Castaneda, Joel Wells

Research Symposium

Aims: The study aimed to evaluate the accuracy, comprehensiveness, and readability of responses generated by ChatGPT 4.0 to 30 common patient questions about the Bernese Periacetabular Osteotomy (PAO).

Methods: Two fellowship-trained orthopaedic surgeons specializing in hip preservation selected thirty questions from a prior study identifying common PAO questions on social media. Each question was entered into ChatGPT 4.0, and the surgeons independently graded responses. Responses were evaluated using an established grading system: “excellent,” “satisfactory requiring minimal clarification,” “satisfactory requiring moderate clarification,” or “unsatisfactory.” Accuracy and comprehensiveness were assessed based on the concordance of response content with current literature. Readability was …