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Mri-Based Deep Learning Radiomics Model For Automated Classification Of Disc Degeneration In The Lumbar Spine, Shiv Patil, Om Gandhi, Mert Karabacak, Matthew Carr, Konstantinos Margetis

Student Papers, Posters & Projects

Disc degeneration in the lumbar spine is a major cause of low back pain (LBP). The accurate grading of disc degeneration on magnetic resonance imaging (MRI) is critical for clinical management and patient selection for spine surgery. This study aims to develop and evaluate machine learning (ML) models that combine features from deep learning (DL) and radiomics for the automated prediction of Pfirrmann grade (PG), a measure of disc degeneration, using multi-parametric lumbar spine MRI. Sagittal T1, T2, and T2 SPACE MRIs of 218 patients with LBP were acquired from the SPIDER dataset. For each intervertebral disc and available sequence, …

Gastrointestinal Symptoms After Sport-Related Concussion: Prevalence And Patterns In A Multi-Cohort Analysis, Emma Finnegan, Ed Daly, Katherine J. Hunzinger, Lisa Ryan

Department of Exercise Science Faculty Papers

Background/Objectives: Concussions occur across all sports globally; however, inconsistent symptom recognition continues to challenge diagnosis, management, and recovery. Although concussion effects extend beyond neurological dysfunction, gastrointestinal (GI) symptoms remain insufficiently captured within current assessment frameworks and may influence athletes’ fuelling choices and food tolerance during recovery. This study aimed to describe the prevalence and patterns of GI symptoms reported among athletes with a history of concussion and to explore whether symptom prevalence and burden differed by sex and country. Methods: A total of 401 adult athletes (225 males; mean age 32.4 ± 11.3 years) with a history of concussion were …

Patient-Reported Outcomes Following Operative And Nonoperative Management Of A3 Versus A4 Thoracolumbar Burst Fractures, Barry T. S. Kweh, Charlotte Dandurand, Alex R. Vaccaro, Klaus J. Schnake, Mohammad El-Sharkawi, Richard J J. Bransford, Andrei Fernandes Joaquim, Harvinder Singh Chhabra, Ulrich J. A. Spiegl, Dimitri Hauri, F. Cumhur Öner, Gregory D. Schroeder, Jin Wee Tee

Department of Orthopaedic Surgery Faculty Papers

OBJECTIVE: The aim of this study was to compare patient-report outcome measures in patients with thoracolumbar burst fractures managed either operatively or nonoperatively.

METHODS: A prospective multicenter observational study was conducted of neurologically intact patients who sustained traumatic thoracolumbar burst fractures managed operatively or nonoperatively. Outcome measures included scores on the EQ-5D index, EQ-5D visual analog scale (VAS), pain numerical rating scale (NRS), and AO Spine Patient Reported Outcome Spine Trauma (PROST) tool and patient satisfaction with follow-up up to 2 years. The Wilcoxon rank-sum test and Cochran-Armitage test were used to evaluate differences between continuous and ordinal variables, respectively. …

Clonal Reshaping And Clinical Outcomes After Rechallenge In Ici-Associated Myocarditis: Integrated Single-Cell And Tcr Repertoire Analysis, Jian Zhang, Xiaozhen He, Yerui Zhang, Xianling Qian, Yu Song, Shilong Zhang, Zheng Li, Zhiming Wang, Bo Lu, Qingqing Cai, Leilei Cheng, Yan Wang

Center for Translational Medicine Faculty Papers

BACKGROUND: Immune checkpoint inhibitor-associated myocarditis (ICIAM) poses significant challenges for cancer immunotherapy, particularly regarding the safety and efficacy of immune checkpoint blockade (ICB) rechallenge.

METHODS: The present study analyzed 23 cases of ICIAM by integrating longitudinal clinical data with single-cell RNA sequencing and T-cell receptor profiling of peripheral blood mononuclear cells (PBMCs) obtained from three representative patients before and after ICB rechallenge. The single-cell cohort comprised two patients who experienced recurrent irAEs upon rechallenge and one patient who did not develop recurrent irAEs.

RESULTS: Among 12 patients (52%) who experienced recurrent irAEs upon rechallenge, myocarditis recurrence occurred in 8 cases, …

Unbiased Niche Labeling Maps Immune-Excluded Niche In Bone Metastasis, Zhan Xu, Fengshuo Liu, Yunfeng Ding, Tianhong Pan, Yi-Hsuan Wu, Yujiao Han, Jun Liu, Igor L Bado, Weijie Zhang, Ling Wu, Yang Gao, Xiaoxin Hao, Liqun Yu, Xuan Li, David G Edwards, Hilda L Chan, Sergio Aguirre, Michael Warren Dieffenbach, Elina Chen, Siyue Wang, Yichao Shen, Dane Hoffman, Luis Becerra Dominguez, Charlotte Helena Rivas, Xiang Chen, Hai Wang, Yibin Kang, Zbigniew Gugala, Robert L Satcher, Xiang H-F Zhang

Faculty, Staff and Students Publications

Metastatic cancer cell fate is shaped by the local microenvironment niches. To unbiasedly define the cellular and molecular features of metastatic niches, we developed sortase A-based microenvironment niche tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastasis. Applying SAMENT across multiple cancer models and target organs revealed shared niche features, including macrophage enrichment and T cell depletion, alongside marked organ-specific phenotype heterogeneity in niche macrophages. In bone, metastatic niches are enriched for macrophages expressing estrogen receptor alpha (ERα) with active ERα signaling. Conditional deletion of Esr1 in macrophages significantly impaired bone colonization by enabling T cell infiltration. …

Pregnancy Outcomes After In Utero Exposure To Immune Checkpoint Inhibitors, Morgan Bou Zerdan, Bruna Kfoury, Eliane Aoun, Sarah Diane Hmaidan, Roni Nitecki Wilke, Jeffrey A How, Terri L Woodard, Pamela T Soliman, Laurie J Mckenzie

Faculty, Staff and Students Publications

Importance: Immune checkpoint inhibitors (ICIs) have transformed the management of cancers affecting reproductive-age patients, yet their impact on pregnancy outcomes remains incompletely understood. We describe two cases of maternal and fetal outcomes associated with ICI exposure during pregnancy and present a comprehensive literature review.

Methods: A retrospective chart review was conducted at MD Anderson Cancer Center (1 January 2015 to 31 December 2024) to identify patients exposed to ICIs during pregnancy. Clinical data including cancer type, treatment timing, pregnancy course, and maternal and neonatal outcomes were collected. A narrative literature review was also performed using PubMed to identify reported cases …

Development Of A Second-Generation Rarα Selective Antagonist As An Orally Bioavailable, Effective, Safe, And Reversible Male Contraceptive, Rui Shi, Kristen John, Xuan Qin, Ehfazul Haque, Taimeng Liang, Narsihmulu Cheryala, Feng Li, Henry L Wong, Gunda I Georg

Faculty, Staff and Students Publications

We report the design and SAR studies of benzopyran-, benzofuran-, and benzothiophene-derived inhibitors of the retinoic acid receptor alpha (RARα) for male contraception. SAR studies identified critical features influencing activity, such as the optimal positioning of antagonism moieties and substituents, leading to the discovery of (S)-4-(5-(2,8-dimethyl-5-(p-tolyl)-2H-chromen-3-yl)-1H-pyrrol-2-yl)­benzoic acid (compound 23). Compound 23 is a highly potent RARα inhibitor (IC50 = 0.051 nM) with excellent selectivity (>1650-fold over RARβ and >1960-fold over RARγ) and ADMET properties. Compound 23 is orally bioavailable and reduces sperm counts in mice for a full male contraceptive effect …

Evaluating Stroke Recognition And Prehospital Quality Metrics In Emergency Dispatch: A Retrospective Cohort Study Comparing Mimics And Confirmed Strokes, Nedim Leto, Elisabeth Farbu, Paul Barach, Conrad Arnfinn Bjørshol, Martin Kurz, Soffien Ajmi, Annette Fromm, Christopher Kalhagen Bjerkvig, Thomas Lindner

College of Population Health Faculty Papers

OBJECTIVES: Accurate identification of acute stroke by the Emergency Medical Dispatch Centre (EMDC) is essential for timely treatment and efficient resource use. However, stroke mimics-conditions resembling stroke can often lead to overtriage, complicating emergency care. We aimed to quantify EMDC stroke overtriage and compare characteristics of stroke mimics with confirmed stroke cases.

DESIGN: Retrospective cohort study.

SETTING: Patients with suspected stroke identified by the EMDC in Western Norway between 1 January 2021 and 31 December 2022.

PARTICIPANTS: A total of 8,261 patients with EMDC suspected stroke were included. Stroke suspicion was determined using the Norwegian Medical Priority Dispatch System, which …

Food Insecurity And At-Home Vegetable And Sugar-Sweetened Beverage Availability: Tx Sprouts Randomized Controlled Trial, Keally Haushalter, Shreela V Sharma, Marissa Burgermaster, Natalie S Poulos, Erin A Hudson, Jennifer M Daspin, Mariela Jimenez Rivero, Jaimie N Davis

Faculty, Staff and Student Publications

Food insecurity and the at-home availability of vegetables and sugar-sweetened beverages both influence dietary intake. However, most research on food insecurity and the at-home availability of vegetables and sugar-sweetened beverages is cross-sectional, which is problematic as both change frequently. Therefore, this study assessed how changes in food insecurity were associated with changes in the at-home availability of vegetables and sugar-sweetened beverages among those in the intervention and control groups of TX Sprouts. Parents who participated in TX Sprouts, a gardening, cooking, and nutrition cluster-randomized trial conducted with primarily Hispanic, low-income 3rd-5th-grade students, completed surveys at baseline and at the nine-month …

Mitochondria-Er Contact Sites (Mercs) In The Cell Cycle: Molecular Architecture And Functional Remodeling Across Cellular States, Eduardo Silva-Pavez, Bruno Torres-Gonzalez, Michelle Sotomayor, Benjamín Cartes-Saavedra, Dorian V. Ziegler, Yessia Hidalgo-Fadic, Ulises Ahumada-Castro

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondria–endoplasmic reticulum (ER) contact sites (MERCS) are nanoscopic, dynamic platforms integrating metabolism, signaling, and stress responses to regulate cell fate. These nanoscopic interfaces remodel continuously to meet the demands of proliferating, quiescent, and senescent cells. We synthesize evidence that MERCS actively coordinate local Ca2+ signaling, non-vesicular lipid transfer, and proteostasis to shape mitochondrial function and cellular homeostasis. We discuss how MERCS architecture changes across the cell cycle and during arrest, distinguishing adaptive from maladaptive remodeling, and consider therapeutic potential in aging and age-related disease.

Patterns Of Care And Clinical Outcomes In Systemic Peripheral T-Cell Lymphoma: The Leo-Mer Prospective Cohort Study, Jia Ruan, Neha Mehta-Shah, Brad Kahl, Et Al.

2020-Current year OA Pubs

Few prospective benchmark studies exist to characterize the evolving contemporary real-world practice for peripheral T-cell lymphoma (PTCL). We report the patterns of first-line care and outcomes for 720 patients with systemic PTCL enrolled in 2 related prospective cohort studies, Lymphoma Epidemiology of Outcomes (LEO) from 2015 to 2020 and Molecular Epidemiology Resource (MER) from 2002 to 2015, both followed to 2024. The primary end points were event-free survival (EFS) and overall survival (OS) using Kaplan-Meier estimator and Cox regression model. Secondary end points included correlations of clinical and treatment factors with survival. The most common induction regimens were CHOP (cyclophosphamide, …

Efficacy And Safety Of Avapritinib In Advanced Systemic Mastocytosis: 4-Year Follow-Up Of The Pathfinder Study, Jason Gotlib, Stephen T Oh, Et Al.

2020-Current year OA Pubs

Advanced systemic mastocytosis (AdvSM), a clonal hematologic neoplasm driven predominantly by D816V-mutant KIT, is often characterized by organ damage. Associated hematologic neoplasms (AHNs; usually myeloid) are often present, leading to poor survival. We report on the oral, highly selective, potent KIT D816V inhibitor avapritinib (200 mg once daily, starting dose) with >4 years follow-up from the fully enrolled PATHFINDER study. End points included overall response rate (ORR; primary), duration of response (DOR), progression-free survival (PFS), overall survival (OS), changes in objective biomarkers of disease, and safety (all secondary). Of 107 patients with AdvSM (including 71 [66%] with SM-AHN; overall population …

Isg15 Negatively Regulates Ripk3-Mediated Cell Death And Viral Pathogenesis, Yi-Chieh Perng, Jessica M C Warsaw, Sachendra S Bais, Bradley E Hiller, Marissa C Locke, David J Morales-Heil, Chaoqun Li, Alissa R Young, Kristen J Monte, Robert E Schmidt, Douglas R Green, Yi-Nan Gong, Deborah J Lenschow

2020-Current year OA Pubs

Necroptosis, a form of programmed, inflammatory necrosis, plays an important role in viral-host defense and inflammation. The receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like pseudokinase (MLKL) pathway mediates necroptosis. Yet, the mechanisms that control necroptosis to limit immunopathology are poorly understood. Here, we report that interferon-stimulated gene 15 (ISG15) negatively regulates RIPK3-mediated cell death, including necroptosis, and limits immunopathology during chikungunya virus (CHIKV) infection. ISG15-deficient mice infected with CHIKV display increased levels of necroptosis, resulting in elevated proinflammatory cytokine and chemokine production, leading to increased lethality. This dysregulated host response is fully prevented when MLKL or RIPK3 is ablated …

Cardiac Resynchronization Therapy: A Review, Caique M Ternes, Jitae A Kim, Anirban Basu, Kenneth A Ellenbogen, Mihail G Chelu

Faculty, Staff and Students Publications

Importance: Heart failure (HF) affects more than 64 million individuals worldwide, and acute HF is associated with 1-year mortality rates of 23.6% in North America and Europe. Cardiac dyssynchrony from conduction system disease may cause HF progression, particularly in patients with left ventricular (LV) systolic dysfunction.

Observations: Electrical dyssynchrony in HF most commonly presents as left bundle-branch block and affects 20% to 30% of patients with reduced LV ejection fraction (LVEF). Cardiac resynchronization therapy, which includes biventricular pacing and conduction system pacing, restores synchronous ventricular contraction and is recommended for patients with symptomatic HF despite optimal medical therapy, LVEF of …

Comprehensive Mass Spectrometry Screening-Derived Atlas Of Hdac Inhibitors Reveals Histone-Specific Acetylation Changes, Rashmi Karki, Francisca N De Luna Vitorino, Richard M Searfoss, Joanna K Lempiäinen, Cheryl H Arrowsmith, Benjamin A Garcia

2020-Current year OA Pubs

Histone deacetylase inhibitors (HDACis) have emerged as valuable therapeutics for cancer and other diseases; however, their effects on histone post-translational modification remain poorly characterized. Here, we applied quantitative mass spectrometry and high-throughput sequencing to systematically profile site-specific changes in histone modifications in response to a panel of HDACis. This platform enabled mapping of histone modification changes across hundreds of sites, including low-abundance histone marks. Furthermore, an integrative analysis of chromatin immunoprecipitation followed by sequencing (ChIP-seq) and RNA-sequencing (RNA-seq) data identified genome-wide binding sites for the low-abundance histone modification of H2A.Z acetylation in HeLa and MDA-MB-231 breast cancer cells, highlighting the …

Modulate Obesity And Related Metabolic Complications For Yielding Improvements In Ibd Outcomes (Modify-Ibd): Consensus On Obesity And Cardiometabolic Comorbidities In Inflammatory Bowel Disease Using Systematic Reviews And The Rand/Ucla Appropriateness Method, Jalpa Devi, Sami Samaan, Priya Sehgal, Mouhand Mohamed, Matthew Vincent, Shannon Coombs, Michelle Doering, Edward L. Barnes, Amanda M. Johnson, Andres J. Yarur, Parakkal Deepak

Division of Gastroenterology and Hepatology Faculty Papers

INTRODUCTION: Obesity and related cardiometabolic comorbidities, including hypertension, dyslipidaemia, diabetes, metabolic dysfunction-associated steatotic liver disease and atherosclerotic cardiovascular disease, are increasingly prevalent among individuals with inflammatory bowel disease (IBD). These conditions influence disease activity, therapeutic response, surgical outcomes and overall quality of life, yet evidence remains fragmented. The Modulate Obesity and relateD metabolic complIcations For Yielding improvements in IBD outcomes (MODIFY-IBD) initiative aims to synthesise evidence and generate consensus recommendations to guide practice and future research in this area. This study describes a protocol for a structured evidence synthesis and Research And Development/University of California, Los …

Smaller Right Ventricle Results In Poorer Exercise Performance In Young Patients With Repaired Tetralogy Of Fallot, Christiane Mhanna, Katerina Kourpas, Takeshi Tsuda

Department of Pediatrics Faculty Papers

BACKGROUND: Severe right ventricular (RV) dilatation and exercise intolerance are considered indications for pulmonary valve replacement in surgically repaired tetralogy of Fallot (rTOF).

METHODS AND RESULTS: Cardiopulmonary exercise testing (CPET) and cardiac magnetic resonance (CMR) were performed in rTOF patients with pulmonary insufficiency (PI). Oxygen pulse (OP), calculated as oxygen consumption (V̇O

CONCLUSIONS: A smaller RV was associated with worse exercise performance, indicating exercise intolerance is independent of RV dilatation in young rTOF with PI and represents a unique pathological entity responsible for reduced exercise performance.

Minimally Invasive Versus Burr Hole Craniostomy For Chronic Subdural Haematoma Evacuation: A Systematic Review And Meta-Analysis, Shaan Patel, Shiva A. Nischal, Angelette Mendonca, Kush M. Kale, Santosh Guru, Pious D. Patel, Kevin Hines, Jack Jallo, Srinivas K. Prasad

Department of Neurosurgery Faculty Papers

BACKGROUND: Minimally invasive surgery (MIS) has emerged as an appealing alternative to burr hole craniostomy (BHC) for chronic subdural haematoma (cSDH), offering reduced operative trauma and anaesthetic exposure. However, whether these procedural advantages translate into comparable outcomes remains uncertain. This systematic review and meta-analysis aimed to compare the safety, effectiveness, and procedural performance of MIS versus BHC for cSDH evacuation, with attention to device-specific outcomes.

METHODS: A systematic search of PubMed, Embase, and CENTRAL (10th November 2025) identified randomised and observational studies directly comparing MIS techniques, including twist-drill craniostomy (TDC), subdural evacuating port systems (SEPS), and YL-1 devices, with BHC. …

International Multi-Center Study To Quantify The Effect Of Deep Venous Drainage After Surgical Resection Of Spetzler-Martin Grade Ii-Iii Brain Arteriovenous Malformations, Avi A. Gajjar, Rashad Jabarkheel, Mohamed M. Salem, Basel Musmar, Sandeep Kandregula, Hammam Abdalrazeq, Nimer Adeeb, Assala Aslan, Nathan Ramachandran, Stavropoula Tjoumakaris, Hamza Adel Salim, Adam A. Dmytriw, Christopher S. Ogilvy, Mustafa K. Baskaya, Douglas Kondziolka, Jason Sheehan, Howard Riina, Abdallah Abushehab, Kareem El Naamani, Najib Muhammad, Ahmed Abdelsalam, Natasha Ironside, Deepak Kumbhare, Sanjeev Gummadi, Cagdas Ataoglu, Muhammed Amir Essibayi, Abdullah Keles, Sandeep Muram, Daniel Sconzo, Arwin Rezai, Omar Alwakaa, Pierce Davis, Salem M. Tos, Ufuk Erginoglu, Johannes Pöppe, Rajeev D. Sen, Alan S. Boulos, John C. Dalfino, Christoph J. Griessenauer, Robert M. Starke, Laligam N. Sekhar, Michael R. Levitt, David J. Altschul, Neil Haranhalli, Malia Mcavoy, Hussein A. Zeineddine, Adib A. Abla, Saman Sizdahkhani, Sravanthi Koduri, Michael R. Gooch, Robert H. Rosenwasswer Md, Christopher Stapleton, Matthew Koch, Peng R. Chen, Spiros Blackburn, Ketan Bulsara, Louis J. Kim, Omar Choudhri, Bryan Pukenas, Joshua S. Catapano, Darren Orbach, Edward Smith, Pascal J. Mosimann, Alexandra R. Paul, Pascal Jabbour, Ali Alaraj, Mohammad A. Aziz-Sultan, Aman B. Patel, Amey Savardekar, Christina Notarianni, Hugo H. Cuellar, Bharat Guthikonda, Jacques Morcos, Michael Lawton, Jan-Karl Burkhardt, Visish M. Srinivasan

Department of Neurosurgery Faculty Papers

Deep venous drainage (DVD) is considered a negative prognostic factor in AVM surgery, yet its effect on postoperative functional decline remains incompletely defined. This study evaluates whether DVD predicts worsened functional status after surgical resection of Spetzler-Martin Grade II-III AVMs. This retrospective multicenter study analyzed 129 patients with Spetzler-Martin Grade II-III AVMs across nine centers in North America and Europe who underwent primary surgical resection. We excluded cases with prior endovascular or stereotactic interventions. The primary outcome measured was poor functional status, defined as modified Rankin Scale (mRS) score 3-6 at last follow up. Among 129 patients with Spetzler-Martin Grade …

O-Glcnacylation As A Metabolic Integrator In Cardiovascular Physiology And Disease, Saima Shakil Malik, Xinchun Pi, Liang Xie

Faculty, Staff and Students Publications

No abstract provided.

Generalizability Of An Ai-Based Mammogram Risk Score (Mrs) For Breast Cancer Among Diverse Populations Of Women, Shu Jiang, Debbie L Bennett, Peter Kraft, Graham A Colditz

2020-Current year OA Pubs

Conventional prediction models incorporating genetic and clinical factors including breast density underperform in non-European populations. We investigated an artificial intelligence-derived mammogram risk score (MRS), a summary of texture features that captures intrinsic breast-tissue characteristics-the substrate for cancer development. This study leveraged data from two North American screening cohorts totaling >226,000 women, including non-Hispanic white, non-Hispanic Black, East Asian, South Asian, and Indigenous women. MRS distributions showed nonsignificant shifts (and similar SDs) between cohorts and across race and ethnic subgroups. MRS increased with age and was significantly associated with breast cancer risk, with hazard ratios per SD ranging from 2.24 [95% …

Holistic Management Of Epilepsy In Adults With Intellectual Development Disorders, Elena Fonseca, Antonella Riva, Samuel López‐Maza, Malin Zaddach, Marie‐Claire Porter, Ingo Borggraefe, Lance Watkins, Andreas Schulze‐Bonhage, Rohit Shankar, Pasquale Striano, Lina Nashef

Peninsula Medical School

This seminar addresses the complexity of the management of epilepsy in adults with intellectual development disorders (IDD), advocating holistic and multidisciplinary care aligned with the learning objectives of the International League Against Epilepsy. Epilepsy is significantly more prevalent in people with IDD, presenting unique diagnostic, therapeutic, and psychosocial challenges. Accurate diagnosis is hampered by limitations in communication, necessitating reliance on caregivers' observations. In adults with IDD and epilepsy, utilization of diagnostic tools, e.g., video electroencephalograph (EEG) monitoring, is helpful but can be challenging. Management requires careful consideration of cognitive and behavioral comorbidities and the effects of antiseizure medications (ASMs) on …

Variation In Baroreceptor Sensitivity Prevents Generalized Anxiety, Alexander Weaver, Jack Summers, Judy Taha, Zachary Miklja, Warren Lockette

Medical Student Research Symposium

VARIATION IN BARORECEPTOR SENSITIVITY PREVENTS GENERALIZED ANXIETY. Alexander Weaver, Jack Summers, Judy Taha, Zak Miklja, Warren Lockette. Division of Endocrinology, Wayne State University School of Medicine, Detroit, MI.

Key words: anxiety, baroreceptors, cardiovascular disease, PIEZO 1, humans, instantaneous baroreceptor sensitivity

BACKGROUND

We reported ex vivo measurements of PIEZO 1 channel activity in erythrocytes can predict those individuals with high levels of generalized anxiety. Because PIEZO 1 channels are expressed in cardiac baroreceptors, we next tested our hypothesis that contrasts in generalized anxiety in the population could be due to individual differences in PIEZO 1-dependent instantaneous baroreceptor sensitivity.

METHODS

Thirteen …

Co-Occurring Clonal Hematopoiesis Exhibits Strong Selection And High Leukemia Risk, Kara M Barnao, Irenaeus C C Chan, Duc Tran, Yin Cao, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are two types of clonal hematopoiesis (CH) associated with hematological parameters and malignancy risk. Here we show, in genomic data from 546,090 biobank participants, that co-occurring CH (≥2 CH mutations detected) is present in 1.6% of cancer-free individuals and shows strong evidence for selection (up to 804x enrichment). Co-occurrence is more frequent in those with a prior cancer (3.6%), suggesting treatment-induced selection. Acquisition of CHIP usually precedes mCAs with co-occurrences manifesting stronger phenotypic disruptions in telomere attrition and hematologic parameters than component CH events. Individuals with co-occurring CH have …

Axitinib-Pembrolizumab And Adverse Event Management In Patients With Advanced Renal Cell Carcinoma, Neil Shah, Yaa Ababio, Anthony Eccleston, Dharanija Rao, Scott Kelly, Jane Chang, Sarah Lucht, Caleb Paydar, Bryce Van Doren, Emily Bland, William John, Sarah Giegerich, Jalyna Laney, Bruce Feinberg, Kevin Zarrabi

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Understanding approaches to managing treatment-related adverse events (AEs) in immunotherapy and tyrosine kinase inhibitor-based treatments in a clinical setting is critical for reaching optimal patient outcomes.

OBJECTIVE: To investigate the management of AEs in community practices during first-line axitinib plus pembrolizumab therapy for advanced renal cell carcinoma (aRCC).

DESIGN, SETTING, AND PARTICIPANTS: This study comprised a cross-sectional electronic physician survey and a multisite, retrospective cohort study of the medical records of US patients with aRCC who initiated first-line axitinib-pembrolizumab between April 22, 2019, and January 31, 2024. Data were analyzed from September 18 to December 20, 2024.

EXPOSURE: First-line …

Co-Occurring Clonal Hematopoiesis Exhibits Strong Selection And High Leukemia Risk, Kara M Barnao, Aubrey K Hubbard, Irenaeus C C Chan, Weiyin Zhou, Yasminka A Jakubek, Giulio Genovese, Wendy S W Wong, Rebecca L Kelly, Corey D Young, Derek W Brown, Wen-Yi Huang, Neal D Freedman, Kristine Jones, Amy Hutchinson, Belynda Hicks, Duc Tran, Donna Arnett, Kathleen C Barnes, Joshua C Bis, Eric Boerwinkle, Jennifer A Brody, April P Carson, Daniel I Chasman, Michael H Cho, Pinkal Desai, Margaret F Doyle, Myriam Fornage, Xiuqing Guo, Nancy Heard-Costa, Marguerite Ryan Irvin, Andrew D Johnson, Sharon L R Kardia, Charles Kooperberg, Daniel Levy, Joshua P Lewis, Yun Li, Ruth J F Loos, Taralynn M Mack, Rasika A Mathias, Braxton D Mitchell, Kari E North, Nathan Pankratz, Patricia A Peyser, Michael H Preuss, Bruce M Psaty, Laura M Raffield, Susan Redline, Stephen S Rich, Jerome I Rotter, Edwin K Silverman, Albert V Smith, Jennifer A Smith, Adrienne Stilp, Yin Cao, Paul Scheet, Alexander P Reiner, Alexander G Bick, Stephen J Chanock, Paul L Auer, Kelly L Bolton, Mitchell J Machiela

Faculty, Staff and Student Publications

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are two types of clonal hematopoiesis (CH) associated with hematological parameters and malignancy risk. Here we show, in genomic data from 546,090 biobank participants, that co-occurring CH (≥2 CH mutations detected) is present in 1.6% of cancer-free individuals and shows strong evidence for selection (up to 804x enrichment). Co-occurrence is more frequent in those with a prior cancer (3.6%), suggesting treatment-induced selection. Acquisition of CHIP usually precedes mCAs with co-occurrences manifesting stronger phenotypic disruptions in telomere attrition and hematologic parameters than component CH events. Individuals with co-occurring CH have …

Childcare Challenges Among Surgical Trainees And Faculty: A Single-Institution Study, Emma G Burke, Sarah Peiffer, Melissa Koci, Lindsay Dean, Kristy L Rialon, Michele Loor, Alice King

Faculty, Staff and Students Publications

Background: Previous studies have demonstrated the challenges of parenthood in surgical training and careers. However, certain aspects of childrearing for surgeons remain understudied. We aim to leftacterize the complexity and costs of childcare amongst surgical trainees and faculty.

Methods: An anonymous, self-administered survey was conducted within the Department of Surgery at a large academic medical center. Both male and female trainees and faculty were included in the analysis. Chi-square or Fisher's Exact test was performed.

Results: Forty-six respondents provided information about childcare costs, with 37% of respondents being residents or fellows. Trainees worked longer workhours (p = 0.003) than their …

Mitochondrial Ca2+ Uniporter (Mcu) Variants Form Plasma-Membrane Channels, Iuliia Polina, Jyotsna Mishra, Michael Cypress, Maria Landherr, Nedyalka Valkov, Isabel Chaput, Bridget Nieto, Brian Rhee, Ameneh Ahrari, Nathan Demichaelis, Kye-Im Jeon, Ulrike Mende, Peng Zhang, Bong Sook Jhun, Jin O-Uchi

Center for Translational Medicine Faculty Papers

MCU, originally known as CCDC109A, is widely recognized as the gene responsible for encoding a pore-forming subunit of a Ca2+-selective channel, mitochondrial Ca2+ uniporter complex (mtCUC). While MCU expression is typically highly mitochondrial-specific, we report here a protein variant derived from the MCU gene, termed MCU-S, which lacks the mitochondria-targeting sequence (MTS) and forms a Ca2+-permeable channel outside of mitochondria. The mRNA of MCU-S was ubiquitously expressed in all cell types/tissues tested, with particularly high expression in human platelets. MCU-S protein formed Ca2+ channels at the plasma membrane, which exhibited similar channel properties to those observed in mtCUC. MCU-S channels …

Repurposing Semaglutide As An Adjunctive Treatment For Cocaine Use Disorder: Protocol For A Randomised Controlled Trial, Luba Yammine, Francesco Versace, Charles E Green, Heather E Webber, Jin Ho Yoon, Absalon D Gutierrez, Samuel J Leonard, Michael F Weaver, Joy Schmitz

Faculty, Staff and Student Publications

Introduction: Cocaine use disorder (CUD) is a significant public health concern in the USA, with considerable prevalence and mortality and no Food and Drug Administration (FDA)-approved pharmacotherapies. Recent advances in addiction science emphasise the need for novel, mechanism-based treatments. Glucagon-like peptide-1 receptor agonists, such as semaglutide, have shown promise in modulating reward-related behaviours and may offer therapeutic benefits for CUD. We present a study protocol evaluating semaglutide, as an adjunct to cognitive behavioural therapy (CBT), as a novel approach for treating CUD.

Methods and analysis: This is a randomised, double-blind, placebo-controlled trial enrolling 75 treatment-seeking adults with CUD. Participants will …

A Review Of Robotic Vnotes Surgery: Current Applications, Advantages, And Future Directions, Daniel Y Lovell, Qiannan Yang, Xiaoming Guan

Faculty, Staff and Students Publications

Over the past 500 years, the convergence of three distinct paths - vaginal surgery, laparoscopy, and robotic technologies - has enabled the development of robot-assisted vaginal natural orifice transluminal endoscopic surgery (RA-vNOTES). The ongoing evolution of vaginal surgery has led to contemporary procedures such as hysterectomy, myomectomy, sacrocolpopexy, adnexal interventions, and oncologic operations, applicable to a wide range of diagnoses and pathologies. This approach offers patients significant benefits, including superior cosmetic outcomes, less pain, lower infection rates, and faster recovery of baseline quality of life. Surgeons benefit from improved ergonomics, better visualization, the ability to use multiple instruments, and enhanced …