Medical Specialties Commons^™

Pexidartinib And Standard Neoadjuvant Therapy In The Adaptively Randomized I-Spy2 Trial For Early Breast Cancer, Hope S Rugo, Mike Campbell, Christina Yau, A Jo Chien, Anne M Wallace, Claudine Isaacs, Judy C Boughey, Hyo S Han, Meredith Buxton, Julia L Clennell, Smita M Asare, Katherine Steeg, Amy Wilson, Ruby Singhrao, Jeffrey B Matthews, Jane Perlmutter, W Fraser Symmans, Nola M Hylton, Angela M Demichele, Douglas Yee, Laura J Van't Veer, Donald A Berry, Laura J Esserman

Faculty, Staff and Student Publications

Purpose: We investigated the small-molecule receptor tyrosine kinase-inhibitor of colony-stimulating factor-1 receptor pexidartinib in the stage II/III breast cancer in the I-SPY2 platform trial.

Methods: I-SPY2 is an adaptive platform trial that features multiple arms of experimental agents administered on a background of standard neoadjuvant therapy with paclitaxel and adriamycin/cyclophosphamide, followed by definitive surgery. The adaptive randomization engine preferentially assigns patients based upon cumulative performance of each agent in a given breast cancer subtype based on hormone receptor and HER2 receptor status. The study endpoint is pathologic complete response.

Results: A total of 9 participants were randomized to receive pexidartinib …

Decoding Cancer Etiology With Cellular Reprogramming, Mo-Fan Huang, Megan E Fisher, Trinh T T Phan, Ruiying Zhao, Dung-Fang Lee

Faculty, Staff and Student Publications

Cancer research remains clinically unmet in many areas due to limited access to patient samples and the lack of reliable model systems that truly reflect human cancer biology. The emergence of patient-derived induced pluripotent stem cells and engineered human pluripotent stem cells (hPSCs) has helped overcome these challenges, offering a versatile alternative platform for advancing cancer research. These hPSCs are already proving to be valuable models for studying specific cancer driver mutations, offering insights into cancer origins, pathogenesis, tumor heterogeneity, clonal evolution, and facilitating drug discovery and testing. This article reviews recent progress in utilizing hPSCs for clinically relevant cancer …

Chemoresistance-Motility Signature Of Molecular Evolution To Chemotherapy In Non-Muscle-Invasive Bladder Cancer And Its Clinical Implications, Mi-So Jeong, Seung-Woo Baek, Gi-Eun Yang, Jeong-Yeon Mun, Jeong Ah Kim, Tae-Nam Kim, Jong-Kil Nam, Yung-Hyun Choi, Ju-Seog Lee, In-Sun Chu, Sun-Hee Leem

Faculty, Staff and Student Publications

Non-muscle-invasive bladder cancer (NMIBC) often recurs and can progress to MIBC due to resistance to treatments like intravesical chemotherapy or Bacillus Calmette-Guérin (BCG). Therefore, we established the Gemcitabine-Resistant Cells (GRCs) to study the molecular evolution under external pressure. A 63-gene Chemoresistance-Motility (CrM) signature was created to identify stage-specific traits of GRCs. This signature was tested on 1846 samples using log-rank tests and Cox regression to evaluate clinical utility. Early and intermediate resistance stages showed increased cell motility and metastatic potential. FAK, PI3K-AKT, and TGFβ pathways were activated first, followed by MAPK signaling. Single-cell analysis and experiments utilizing the CrM signature …

Selinexor (Kpt-330) In Combination With Immune Checkpoint Inhibition In Uveal Melanoma: A Phase 1b Trial, Mohamed A Gouda, Abdulrazzak Zarifa, Yali Yang, Bettzy Stephen, Serdar A Gurses, Ashabari Sprenger, Yanyan Tian, Mohamed H Derbala, Isabella Glitza Oliva, Funda Meric-Bernstam, Sapna P Patel

Faculty, Staff and Student Publications

Introduction: Uveal melanoma remains a disease with aggressive behavior and poor prognosis despite advances in clinical management. Because monotherapy with immune checkpoint inhibitors has led to limited improvement in response rates, combination with other agents that act on the biological basis of oncogenesis has been proposed as a possible therapeutic strategy.

Methods: We designed a phase 1b trial to test the safety and tolerability of selinexor in combination with immune checkpoint inhibitors in patients with advanced uveal melanoma. Patients received selinexor 60 mg PO twice weekly with standard of care, commercially available immune checkpoint inhibitor of the investigator's choice. In …

Imaging Lung Tumor Motion Using Integrated-Mode Proton Radiography-A Phantom Study Towards Tumor Tracking In Proton Radiotherapy, Ryan Fullarton, Mikaël Simard, Lennart Volz, Allison Toltz, Savanna Chung, Christoph Schuy, Daniel G Robertson, Gary Royle, Sam Beddar, Colin Baker, Christian Graeff, Charles-Antoine Collins-Fekete

Faculty, Staff and Student Publications

BACKGROUND: Motion of lung tumors during radiotherapy leads to decreased accuracy of the delivered dose distribution. This is especially true for proton radiotherapy due to the finite range of the proton beam. Methods for mitigating motion rely on knowing the position of the tumor during treatment.

PURPOSE: Proton radiography uses the treatment beam, at an energy high enough to traverse the patient, to produce a radiograph. This work shows the first results of using an integrated-mode proton radiography system to track the position of moving objects in an experimental phantom study; demonstrating the potential of using this method for measuring …

Rapidbrachyivbt: A Dosimetry Software For Patient-Specific Intravascular Brachytherapy Dose Calculations On Optical Coherence Tomography Images, Maryam Rahbaran, Jonathan Kalinowski, Joseph M Decunha, Kevin J Croce, Brian A Bergmark, James M G Tsui, Phillip M Devlin, Shirin A Enger

Faculty, Staff and Student Publications

Background: Coronary artery disease is the most common form of cardiovascular disease. It is caused by excess plaque along the arterial wall, blocking blood flow to the heart (stenosis). A percutaneous coronary intervention widens the arterial wall with the inflation of a balloon inside the lesion area and leaves behind a metal stent to prevent re-narrowing of the artery (restenosis). However, in-stent restenosis may occur due to damage to the arterial wall tissue, triggering neointimal hyperplasia, producing fibrotic and calcified plaques and narrowing the artery again. Drug-eluting stents, which slowly release medication to inhibit neointimal hyperplasia, are used to prevent …

Open-Chest Cardiac Ultrasound-Mediated Imaging With A Vacuum Coupler, Nilesh Mathuria, Krithik Vishwanath, Giorgio Brero, Blake C Fallon, Antonio Martino, Richard C Willson, Carly S Filgueira, Richard R Bouchard

Faculty, Staff and Student Publications

BACKGROUND: A fundamental obstacle for the preclinical development of ultrasound-(US) mediated cardiac imaging remains cardiac motion, which limits interframe correlation during extended acquisition periods.

PURPOSE: To address this need, we present the design and implementation of a 3D-printed vacuum coupler that stabilizes a US transducer on the epicardial surface of the heart for feasibility assessment and development of advanced, cardiac, US-mediated imaging approaches.

METHODS: The vacuum coupler was 3D printed with biocompatible resins and secured with a standard intraoperative suction aspirator. US-mediated imaging (i.e., B-mode and photoacoustic [PA] imaging) was performed in an open-chest porcine model with and without the …

Outcomes Of Patients With Treated Secondary Acute Myeloid Leukemia: A High-Risk Subtype That Warrants An Independent Prognostic Designation, Jayastu Senapati, Hagop M Kantarjian, Fadi G Haddad, Nicholas J Short, Gautam Borthakur, Rashmi Kanagal-Shamanna, Guilin Tang, Elias Jabbour, Courtney D Dinardo, Naval Daver, Guillermo Montalban-Bravo, Vishrut Shah, Amin Alousi, Elizabeth Shpall, Uday Popat, Guillermo Garcia-Manero, Farhad Ravandi, Tapan M Kadia

Faculty, Staff and Student Publications

Patients who develop acute myeloid leukemia (AML) after having received treatment for myelodysplastic syndrome (MDS) or related conditions have particularly poor outcomes. This study analyzed adult patients with newly diagnosed AML who previously had MDS, chronic myelomonocytic leukemia (CMML), or MDS/myeloproliferative neoplasm (MPN) overlap syndrome, and who had received hypomethylating agents, chemotherapy, and/or allogeneic stem cell transplantation (HSCT) for these antecedent disorders. From January 2012 to August 2023, we included 673 patients with a median age of 70 years (range, 19-94); 536 (80%) had transformed from MDS, and the remainder from CMML or MDS-MPN. Additionally, 149 patients (22%) had prior …

Incidence Of Heterotopic Ossification Without Additional Long-Term Nsaid Prophylaxis After Periacetabular Osteotomy And Concomitant Hip Arthroscopy, J Matthew Helm, Omar Stocks, Brian Crowley, Alexis Aboulafia, Jacob Siahaan, Alfred A Mansour

Faculty, Staff and Student Publications

Background: Periacetabular osteotomy (PAO) is an established treatment for hip dysplasia and has been increasingly combined with concomitant hip arthroscopy to address additional intra-articular hip pathology. Heterotopic ossification (HO) is a complication of arthroscopic and open hip procedures. Nonsteroidal anti-inflammatory drugs (NSAIDs) have become an established form of HO prophylaxis, but their use may delay bone healing.

Purpose: To examine the incidence of HO without NSAID prophylaxis in patients after PAO with concomitant hip arthroscopy and to evaluate the impact of other variables on the development of HO in these patients.

Study design: Case series; Level of evidence, 4.

Methods: …

American Society For Gastrointestinal Endoscopy Guideline On The Diagnosis And Management Of Gerd: Methodology And Review Of Evidence, Asge Standards Of Practice Committee, Madhav Desai, Wenly Ruan, Nirav C Thosani, Manuel Amaris, J Stephen Scott, Ahmed Saeed, Barham Abu Dayyeh, Marcia Irene Canto, Wasif Abidi, Omeed Alipour, Stuart K Amateau, Natalie Cosgrove, Sherif E Elhanafi, Nauzer Forbes, Divyanshoo R Kohli, Richard S Kwon, Larissa L Fujii-Lau, Jorge D Machicado, Neil B Marya, Saowanee Ngamruengphong, Swati Pawa, Sunil G Sheth, Nikhil R Thiruvengadam, Bashar J Qumseya

Faculty, Staff and Student Publications

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for strategies to diagnose and manage GERD. This document was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework and serves as an update to the prior ASGE guideline on the role of endoscopy in the management of GERD (2014). The updated guideline addresses the indications for endoscopy in patients with GERD, including patients who have undergone sleeve gastrectomy (SG) and peroral endoscopic myotomy (POEM). It also discusses endoscopic evaluation of gastroesophageal junctional integrity comprehensively and uniformly. Important, this guideline discusses …

Frailty And Sleep In Adult Survivors Of Childhood Cancer: A Childhood Cancer Survivor Study Report, Lauren C Daniel, Margaret M Lubas, Huiqi Wang, Mariana Szklo-Coxe, Kirsten K Ness, Annalynn M Williams, Daniel A Mulrooney, Rebecca Howell, Wendy Leisenring, Yutaka Yasui, Leslie L Robison, Gregory T Armstrong, Eric J Chow, Kevin R Krull, Tara M Brinkman

Faculty, Staff and Student Publications

Background: Young adult survivors of childhood cancer exhibit rates of frailty similar to adults several decades older without a cancer history. Frailty has been associated with sleep disturbances in non-cancer populations, but the relationship has not been examined in childhood cancer survivors who are known to exhibit elevated rates of sleep problems.

Aims: Examine associations between frailty and poor sleep quality in long-term survivors of childhood cancer.

Methods: This study utilized data from 9044 participants (> 5 years from diagnosis, Mage = 40.8 years [SD = 9.5]) in the Childhood Cancer Survivor Study. Survivors' frailty status, chronic health conditions (CHC), …

Mutational And Co-Mutational Landscape Of Early Onset Colorectal Cancer, Jumanah Yousef Alshenaifi, Guglielmo Vetere, Giulia Maddalena, Mahmoud Yousef, Michael G White, John Paul Shen, Eduardo Vilar, Christine Parseghian, Arvind Dasari, Van Karlyle Morris, Ryan Huey, Michael J Overman, Robert Wolff, Kanwal P Raghav, Jason Willis, Kristin Alfaro, Andy Futreal, Y Nancy You, Scott Kopetz

Faculty, Staff and Student Publications

Introduction: Colorectal cancer (CRC) incidence and mortality before 50 have been rising alarmingly in the recent decades.

Methods: Using a cohort of 10,000 patients, this study investigates the clinical, mutational, and co-mutational features of CRC in early-onset (EOCRC, < 50 years) compared to late-onset (LOCRC, ≥ 50 years).

Results: EOCRC was associated with a higher prevalence of Asian and Hispanic patients, rectal or left-sided tumors (72% vs. 59%), and advanced-stage disease. Molecular analyses revealed differences in mutation patterns, with EOCRC having higher frequencies of TP53 (74% vs. 68%, p < 0.01) and SMAD4 (17% vs. 14%, p = 0.015), while BRAF (5% vs. 11%, p < 0.001) and NOTCH1 (2.7% vs. 4.1%, p = 0.01) mutations …

Rapid Whole Genome Sequencing Uncovers A Triple Diagnosis: X-Linked Chondrodysplasia Punctata, Mecp2-Related Disorder, And Mosaic Jacobs Syndrome, Megan Samuels, Kathleen Shields, Paul Hillman, Laura Farach

Faculty, Staff and Student Publications

Background: Rapid Whole Genome Sequencing (rWGS) is increasingly being used in neonatal intensive care units, as there is growing evidence that rare singe gene disorders present in the neonatal period and early identification can change management. While the diagnostic utility is increased with this broad testing, the possibility of unexpected findings also increases significantly. Here, we present a patient found to have three distinct genetic conditions through rWGS testing, with significant psychosocial and health consequences.

Methods and results: This case report describes a patient who was identified with a form of chondrodysplasia punctata, as well as incidental findings of MECP2-related …

Preclinical And Clinical-Scale Magnetic Particle Imaging Of Natural Killer Cells: In Vitro And Ex Vivo Demonstration Of Cellular Sensitivity, Resolution, And Quantification, Olivia C Sehl, Yanwen Yang, Ariana R Anjier, Dmitry Nevozhay, Donghang Cheng, Kelvin Guo, Benjamin Fellows, Abdul Rahman Mohtasebzadeh, Erica E Mason, Toby Sanders, Petrina Kim, David Trease, Dimpy Koul, Patrick W Goodwill, Konstantin Sokolov, Max Wintermark, Nancy Gordon, Joan M Greve, Vidya Gopalakrishnan

Faculty, Staff and Student Publications

Purpose: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) may have applications for the quantitative detection of NK cells.

Procedures: Human-derived NK-92 cells were labeled by co-incubation with iron oxide nanoparticles (VivoTrax™) for 24 h then excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled versus unlabeled NK-92 cells was assessed after 4 h of co-incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17). Labeled NK-92 cells at two different doses (0.5 or 1 × 106) …

Toward A Biological Definition Of Neuronal And Glial Synucleinopathies, Claudio Soto, Brit Mollenhauer, Oskar Hansson, Un Jung Kang, Roy N Alcalay, David Standaert, Claudia Trenkwalder, Kenneth Marek, Douglas Galasko, Kathleen Poston

Faculty, Staff and Student Publications

Cerebral accumulation of alpha-synuclein (αSyn) aggregates is the hallmark event in a group of neurodegenerative diseases-collectively called synucleinopathies-which include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Currently, these are diagnosed by their clinical symptoms and definitively confirmed postmortem by the presence of αSyn deposits in the brain. Here, we summarize the drawbacks of the current clinical definition of synucleinopathies and outline the rationale for moving toward an earlier, biology-anchored definition of these disorders, with or without the presence of clinical symptoms. We underscore the utility of the αSyn seed amplification assay to detect aggregated αSyn in living …

Refining Diagnostic Subtypes Of Peripheral T-Cell Lymphoma Using A Multiparameter Approach, Catalina Amador, Dennis D Weisenburger, Ana Gomez, Alyssa Bouska, Ahmad Alshomrani, Sunandini Sharma, Ab Rauf Shah, Timothy C Greiner, Francisco Vega, Andreas Rosenwald, German Ott, Andrew L Feldman, Elaine S Jaffe, Neval Ozkaya, Sarah L Ondrejka, James R Cook, Philipp W Raess, Kerry J Savage, Graham W Slack, Joo Y Song, David W Scott, Elias Campo, Lisa M Rimsza, Joseph D Khoury, Louis M Staudt, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

Peripheral T-cell lymphoma (PTCL) is a heterogeneous category, and many cases are unclassifiable and designated as PTCL-not otherwise specified (PTCL-NOS). Gene expression profiling (GEP) has delineated two prognostic subtypes within PTCL-NOS, PTCL-TBX21, and PTCL-GATA3, characterized by distinctive transcriptomes and a different prognosis. To further evaluate the pathologic features of these subgroups, 101 PTCL cases that did not meet specific criteria for well-defined T-cell lymphoma entities underwent detailed pathologic, immunophenotypic (including TFH biomarkers) and GEP analyses, separating them into PTCL-NOS (n=63) and PTCL-TFH (a.k.a. nodal PTCL-TFH, NOS, and TFH lymphoma, NOS) (n=38). PTCL-NOS cases were further categorized into PTCL-GATA3 (n=22; 34%) …

On The Acceptance, Commissioning, And Quality Assurance Of Electron Flash Units, Allison Palmiero, Kevin Liu, Julie Colnot, Nitish Chopra, Denae Neill, Luke Connell, Brett Velasquez, Albert C Koong, Steven H Lin, Peter Balter, Ramesh Tailor, Charlotte Robert, Jean-François Germond, Patrik Gonçalves Jorge, Reiner Geyer, Sam Beddar, Raphael Moeckli, Emil Schüler

Faculty, Staff and Student Publications

Background and purpose: FLASH or ultra-high dose rate (UHDR) radiation therapy (RT) has gained attention in recent years for its ability to spare normal tissues relative to conventional dose rate (CDR) RT in various preclinical trials. However, clinical implementation of this promising treatment option has been limited because of the lack of availability of accelerators capable of delivering UHDR RT. Commercial options are finally reaching the market that produce electron beams with average dose rates of up to 1000 Gy/s. We established a framework for the acceptance, commissioning, and periodic quality assurance (QA) of electron FLASH units and present an …

Magnesium Sulfate In The Management Of Acute Ischemic Stroke: A Review Of The Literature And Future Directions, Maximillian S Feygin, Alex Brenner, Omar Tanweer

Faculty, Staff and Students Publications

Background: The management of acute ischemic stroke (AIS) was revolutionized within the last 15 years with the introduction of mechanical thrombectomy (MT) to standard of care. Despite the success of mechanical thrombectomy (MT) in achieving high recanalization rates for large vessel occlusion, functional independence post-treatment remains suboptimal. The current limitations of MT prompt evaluation of the role of adjunctive pharmacologic neuroprotective therapies to prevent excitotoxicity, cellular apoptosis, and inflammation that cause irreversible neuronal damage during AIS. Magnesium (MgSO4) provides an attractive neuroprotectant profile, having many different effects, and is inexpensive, readily available, and has a long-established safety and tolerability profile …

Relationship Between Gestational Weight Gain With Fetal Body Composition And Organ Volumes In The Eunice Kennedy Shriver National Institute Of Child Health And Human Development (Nichd) Fetal Dimensional Study: A Prospective Pregnancy Cohort, Kathryn A Wagner, Zhen Chen, Stefanie N Hinkle, Jessica L Gleason, Wesley Lee, William A Grobman, John Owen, Roger B Newman, Daniel W Skupski, Dian He, Seth Sherman, Robert E Gore-Langton, Cuilin Zhang, Jagteshwar Grewal, Katherine L Grantz

Faculty, Staff and Students Publications

Background: Inadequate and excessive gestational weight gain (GWG) are associated with increased risk of newborn small- and large-for-gestational-age, respectively, and future offspring adiposity. However, the relationship between GWG and three-dimensional (3D) measures of fetal body composition and organ volumes, which may provide greater insight into fetal growth via measurement of soft tissue, remains unknown.

Objectives: The objective of this study was to examine the relationship between trimester-specific GWG and 3D fetal body composition and organ volume measurements.

Methods: In a diverse, US prospective pregnancy cohort, trimester-specific GWG was calculated as difference between maternal weight at beginning and end of each …

Minimal Clinically Important Difference In Obsessive-Compulsive Disorder, Matti Cervin, Eric A Storch, Lara Farrell, Erik Andersson, Christian Rück, Daniel A Geller, David Mataix-Cols

Faculty, Staff and Students Publications

No abstract provided.

Diagnostic Performance Of Contrast-Enhanced Ultrasound In Traumatic Solid Organ Injuries In Children: A Systematic Review And Meta-Analysis, Payam Jannatdoust, Parya Valizadeh, Amir Hassankhani, Melika Amoukhteh, Delaram J Ghadimi, Mahsa Heidari-Foroozan, Paniz Sabeghi, Paniz Adli, Jennifer H Johnston, Pauravi S Vasavada, Ali Gholamrezanezhad

Faculty, Staff and Student Publications

Background: Blunt abdominal trauma (BAT) is a significant contributor to pediatric mortality, often causing liver and spleen injuries. Contrast-enhanced computed tomography (CT), the gold standard for diagnosing solid organ injury, poses radiation risks to children. Contrast-enhanced ultrasound (CEUS) may be a promising alternative imaging modality.

Objectives: To evaluate the diagnostic utility of CEUS for detecting solid organ injuries following BAT in the pediatric population.

Methods: A systematic review and meta-analysis were conducted through a thorough literature search in PubMed, Scopus, Web of Science, and Embase databases up to October 1, 2023. Diagnostic accuracy metrics were aggregated using a bivariate model, …

Association Of Serum Endocannabinoid Levels With Pancreatitis And Pancreatitis-Related Pain, Marc T Goodman, Christina Lombardi, Alexa Torrens, Catherine Bresee, Jami L Saloman, Liang Li, Yunlong Yang, William E Fisher, Evan L Fogel, Christopher E Forsmark, Darwin L Conwell, Phil A Hart, Walter G Park, Mark Topazian, Santhi S Vege, Stephen K Van Den Eeden, Melena D Bellin, Dana K Andersen, Jose Serrano, Dhiraj Yadav, Stephen J Pandol, Daniele Piomelli

Faculty, Staff and Student Publications

No abstract provided.

Prediction Models Of Basal Energy Expenditure In Children And Adolescents Across The Bmi Spectrum Based On Room Calorimetry: A Cross-Sectional Cohort Study, Maurice Puyau, Roman Shypailo, Nancy F Butte, Salma Musaad, Fida Bacha

Children’s Nutrition Research Center Staff Publications

Background: Existing equations for prediction of basal energy expenditure (BEE) may not be accurate in children with overweight or obesity (OW/OB).

Objectives: We aimed to develop BEE prediction equations applicable to children and adolescents across a wide BMI spectrum using gold standard room calorimetry.

Methods: We measured weight, height, waist and hip circumferences, body composition (DXA), and BEE (whole room calorimetry) in a cross-sectional cohort of 1155 healthy children, 5-19 years of age. 67% of the males and 51% of the females were classified as OW/OB. We applied multiple linear regression analyses to develop BEE prediction models for each sex. …

Superior Vena Cava Stenting Complicated By Perforation And Cardiac Tamponade, Arusa Macnojia, Jacy Gressen, Claudia Wei, Kevin Tzan, Amy Lee, Jamal Hasoon, Giustino Varrassi, Anvinh Nguyen

Faculty, Staff and Student Publications

Superior vena cava (SVC) syndrome is a clinical condition characterized by impaired venous return from the upper body due to intrinsic or extrinsic obstruction of the SVC. Endovascular stenting has become an effective intervention for symptomatic relief. However, the procedure carries a rare risk of life-threatening complications, including SVC perforation and cardiac tamponade. This study describes a 60-year-old male with SVC syndrome secondary to squamous cell carcinoma of the lung who developed SVC perforation and cardiac tamponade during endovascular stenting. Despite initial hemodynamic compromise and cardiac arrest, prompt intervention with pericardiocentesis, aggressive resuscitation, and deployment of a covered stent resulted …

A Statistical Framework For Multi-Trait Rare Variant Analysis In Large-Scale Whole-Genome Sequencing Studies, Xihao Li, Han Chen, Margaret Sunitha Selvaraj, Eric Van Buren, Hufeng Zhou, Yuxuan Wang, Ryan Sun, Zachary R Mccaw, Zhi Yu, Min-Zhi Jiang, Daniel Dicorpo, Sheila M Gaynor, Rounak Dey, Donna K Arnett, Emelia J Benjamin, Joshua C Bis, John Blangero, Eric Boerwinkle, Donald W Bowden, Jennifer A Brody, Brian E Cade, April P Carson, Jenna C Carlson, Nathalie Chami, Yii-Der Ida Chen, Joanne E Curran, Paul S De Vries, Myriam Fornage, Nora Franceschini, Barry I Freedman, Charles Gu, Nancy L Heard-Costa, Jiang He, Lifang Hou, Yi-Jen Hung, Marguerite R Irvin, Robert C Kaplan, Sharon L R Kardia, Tanika N Kelly, Iain Konigsberg, Charles Kooperberg, Brian G Kral, Changwei Li, Yun Li, Honghuang Lin, Ching-Ti Liu, Ruth J F Loos, Michael C Mahaney, Lisa W Martin, Rasika A Mathias, Braxton D Mitchell, May E Montasser, Alanna C Morrison, Take Naseri, Kari E North, Nicholette D Palmer, Patricia A Peyser, Bruce M Psaty, Susan Redline, Alexander P Reiner, Stephen S Rich, Colleen M Sitlani, Jennifer A Smith, Kent D Taylor, Hemant K Tiwari, Ramachandran S Vasan, Satupa'itea Viali, Zhe Wang, Jennifer Wessel, Lisa R Yanek, Bing Yu, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Josée Dupuis, James B Meigs, Paul L Auer, Laura M Raffield, Alisa K Manning, Kenneth M Rice, Jerome I Rotter, Gina M Peloso, Pradeep Natarajan, Zilin Li, Zhonghua Liu, Xihong Lin

Faculty, Staff and Student Publications

Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally scalable analytical pipeline for functionally informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple …

Exploring Individual Differences In Amygdala-Mediated Memory Modulation, Martina K Hollearn, Joseph R Manns, Lou T Blanpain, Stephan B Hamann, Kelly Bijanki, Robert E Gross, Daniel L Drane, Justin M Campbell, Krista L Wahlstrom, Griffin F Light, Aydin Tasevac, Phillip Demarest, Peter Brunner, Jon T Willie, Cory S Inman

Faculty, Staff and Students Publications

Amygdala activation by emotional arousal during memory formation can prioritize events for long-term memory. Building upon our prior demonstration that brief electrical stimulation to the human amygdala reliably improved long-term recognition memory for images of neutral objects without eliciting an emotional response, our study aims to explore and describe individual differences and stimulation-related factors in amygdala-mediated memory modulation. Thirty-one patients undergoing intracranial monitoring for intractable epilepsy were shown neutral object images paired with direct amygdala stimulation during encoding with recognition memory tested immediately and one day later. Adding to our prior sample, we found an overall memory enhancement effect without …

Implementation Of In Utero Laparotomy-Assisted Fetoscopic Spina Bifida Repair In Two Centers In Latin America: Rationale For This Approach In This Region, Jezid Miranda, Miguel A Parra-Saavedra, William O Contreras-Lopez, Cristóbal Abello, Guido Parra, Juan Hernandez, Amanda Barrero, Isabela Leones, Adriana Nieto-Sanjuanero, Gerardo Sepúlveda-Gonzalez, Magdalena Sanz-Cortes

Faculty, Staff and Students Publications

Background: Spina bifida (SB) is a severe congenital malformation that affects approximately 150,000 infants annually, predominantly in low- and middle-income countries, leading to significant morbidity and lifelong disabilities. In Latin America, the birth prevalence of SB is notably high, often exacerbated by limited healthcare resources and poor access to advanced medical care. The implementation of laparotomy-assisted fetoscopic in-utero SB repair programs in Latin America targets reducing prematurity rates and enabling vaginal births while preserving the benefits of decreased need for hydrocephalus treatment and improved mobility in children.

Objective: This study evaluated the safety, efficacy, and outcomes of laparotomy-assisted fetoscopic in-utero …

Polygenic Score For Clinicopathologic Features And Survival Outcomes In Papillary Thyroid Carcinoma, Sophie Li, Guibin Zheng, Li Xu, Maitrayee Goswami, Mark E Zafereo, Steven I Sherman, Guojun Li, Erich M Sturgis, Jennifer R Wang

Faculty, Staff and Students Publications

Importance: Genome-wide association studies have identified germline variants associated with the development of papillary thyroid carcinoma (PTC) that can be used to construct a polygenic score (PGS). It is important to determine whether patients with higher germline genetic risk, as summarized using PGS, present with more aggressive disease and/or develop worse clinical outcomes.

Objective: To assess whether germline risk defined by PGS is associated with clinicopathologic features and survival outcomes for patients with PTC.

Design, setting, and participants: This retrospective cohort study included patients with newly diagnosed PTC who presented to The University of Texas MD Anderson Cancer Center for …

Pediatric Participation In Biobanking Related To Inflammatory Bowel Diseases, Jennifer Saccente Thompson, Sahna Reddy, Alison Shaw, Antone R Opekun, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

Parasite-Microbiota Interactions: A Pathway To Innovative Interventions For Chagas Disease, Leishmaniasis, And Ascariasis, Juan David Ramírez, Sergio Castañeda, Jill Weatherhead, Cristina Poveda

Faculty, Staff and Students Publications

Parasitic infections are a major global health challenge, driven in part by complex interactions between parasites, host microbiota, and immune responses. Recent advances in microbiome research highlight the critical role of microbiota in influencing disease outcomes and treatment effectiveness. This review examines how changes in the microbiota impact parasite transmission, disease progression, and responses to treatment, focusing on key parasitic diseases such as Chagas disease, leishmaniasis, and ascariasis. The microbiota can either exacerbate or mitigate disease severity, depending on its composition, providing critical insights for novel therapeutic strategies. Emerging approaches discussed include the use of targeted probiotics, prebiotics, and microbiota-modulating …