Medical Sciences Commons^™

Bi-Allelic Variants In Nrdc Cause A Neurodevelopmental Disorder Characterized By Neonatal Lethality, Microcephaly, And Brain Abnormalities, Davut Pehlivan, Abigail Sandoval, Reza Maroofian, François Lecoquierre, Aisha M Al Shamsi, Gyu S Lee, Osman Yesilbas, Preston Taylor, Matthew B Mcdougal, Vahid Bahrambeigi, Omid Aryani, Juan Felipe Ramirez, Khalid Hama Salih, Chadi Al Alam, Heba Morsy, Haytham Hussien, Tarek Omar, Ibrahim M Abdelrazek, Anne Claire Brehin, Dana Marafi, Tugba Kalayci, Jubran Abu Rahma, Jawabreh Kassem Talbeya, Husein Dabbah, Eric Verspyck, Toktam Moosavian, Jawid M Fatih, Tadahiro Mitani, Gulsen Akay, Daniel G Calame, Anne-Marie Guerrot, Wendy K Chung, Henry Houlden, James R Lupski, Adel Shalata, Wan Hee Yoon

Faculty, Staff and Students Publications

Nardilysin (NRDC) plays a role in multiple cellular functions in diverse cellular compartments, including ectodomain shedding in the plasma membrane, as well as chaperoning a key Krebs cycle enzyme in mitochondria. We had previously reported limited clinical information from two individuals with homozygous frameshift variants in NRDC. With inclusion of previously published individuals, here we report 14 individuals (10 females, four males) from nine unrelated families carrying homozygous NRDC pathogenic variants. Common clinical features include severe to profound developmental delay/intellectual disability (12/12), microcephaly (13/13), prematurity (5/13), lethality in the first 3 years of life (9/14), seizures (7/11), joint contractures (4/8), …

Proteomics Analysis Of Plasma For Risk Of Sepsis: Findings From The Atherosclerosis Risk In Communities Study, Junichi Ishigami, Xiao Hu, Pascal Schlosser, Thomas R Austin, Jingsha Chen, Bruce M Psaty, David Dowdy, Christie M Ballantyne, Morgan E Grams, Josef Coresh, James S Floyd, Kunihiro Matsushita

Faculty, Staff and Students Publications

Background: Sepsis is a life-threatening complication of infection with high mortality. A high-throughput analysis of circulating blood proteins may provide mechanistic insight and potent therapeutic targets for the prevention of sepsis.

Methods: We used multivariable Cox regression analysis to examine the association of 4955 plasma proteins, measured by SomaScan, with the risk of incident sepsis among 11 065 participants of the Atherosclerosis Risk in Communities (ARIC) Study (visit 3 in 1993 to 1995; mean age, 60.1 years, 54.4% female, 21.0% Black). Proteins (false discovery rate [FDR] of P < 0.05) discovered at visit 3 were replicated using data at visit 5 (n = 4869 in 2011 to 2013: mean age, 75.5 years) and in the Cardiovascular Health Study (CHS) (n = 3512 in 1992 to 1993; mean age, 74.5 years). Canonical pathways were identified by enrichment analyses.

Results: At ARIC visit three, 669 proteins were associated with the risk …

Athletic Trainers’ Motivations For And Satisfaction With Transition To The Physician Practice Setting, Abigail G. Overstreet, Nicolette A. Harris, Cailee E. Welch Bacon

Clinical Practice in Athletic Training

An increasing number of athletic trainers are transitioning from traditional settings, such as secondary schools, colleges, universities, and professional sports, to physician practice. Although research suggests athletic trainers may be changing settings in search of better working conditions, little is known about their motivations for and satisfaction with the setting transition. The objective of this research was to explore athletic trainers’ motivations for and satisfaction with transition to the physician practice setting. A qualitative design was used to collect and interpret data. Eleven certified athletic trainers (6 women, 5 men; age 1⁄4 38.5 6 10.0 years) who transitioned from a …

Trust, Culture, And Conversation: How Athletic Training Leaders Navigate High-Stakes Interactions, Nicole A. Wilkins, Ashley B. Thrasher, Ericka P. Zimmerman

Clinical Practice in Athletic Training

Introduction: Engaging in difficult conversations is central to leadership growth and requires sustained effort to refine and strengthen these skills. Leaders not only need to navigate the complexities of their role within an organization, but also the intersectionality of interpersonal dynamics, emotional intelligence, structural hierarchies, and the nuanced environments that influence how communication occurs. Furthermore, leaders must adapt to role expectations that shift across clinical, academic, and administrative contexts, adjusting their approach to engaging in conversations based on these complexities. As part of a larger research project examining difficult conversations, this portion of the study explored how leaders in athletic …

Integrating Wearable Technologies Into Athletic Training: Bridging Innovation And Clinical Practice, Michael Douglas

Clinical Practice in Athletic Training

Athletic training is entering a transformative period driven by the convergence of wearable technologies, artificial intelligence (AI), and advanced biomechanical modeling. Historically, wearable technology in sport was primarily used for performance tracking, including workload monitoring, heart rate assessment, and movement quantification. However, advances in sensor accuracy and data analytics have expanded the clinical relevance of wearable systems, allowing athletic trainers to monitor fatigue markers, movement asymmetry, and neuromuscular control patterns that inform injury risk and rehabilitation progression. Wearable sensor technologies provide objective data that can support clinical decision-making when integrated with traditional evaluation methods.¹Despite these advancements, wearable technologies present persistent …

Recurrent Lateral Patellar Dislocation After Mpfl Repair With Subsequent Tibial Tubercle Anteromedialization And Concomiant Mpfl Reconstruction, Jacob Hardy, Anthony Thomas Drazick, Joshua Pratt, Jeremy M. Burnham

Clinical Practice in Athletic Training

Introduction: Patellar instability is a common knee pathology, particularly among adolescents and young adults, with reported incidence rates ranging from 7 to 77 per 100,000 person-years. Following an initial patellar dislocation, recurrence rates have been reported as high as 86%, particularly in patients with underlying anatomic risk factors. Identification of the multifactorial contributors to patellar instability is critical to guide appropriate management and prevent recurrent episodes. Common pathoanatomic factors associated with recurrent instability include trochlear dysplasia, patella alta, lateralized tibial tubercle, coronal or torsional malalignment, and abnormal patellar shift. This case report describes a patient who presented with a chronic …

Improving Entry-Level Athletic Training Student Confidence In Emergency Care: A Pilot Study, Michele Pye, Cade Watts, John Hunt, Kimberly Pritchard

Clinical Practice in Athletic Training

Introduction: Immediate and emergency care is essential to athletic training education and clinical practice. Athletic training students (ATS) may have limited exposure to emergencies during their clinical experiences, which can undermine their confidence. AT educators can improve ATS confidence and clinical reasoning using a simulation-based, learner-centered SNAPPS approach. SNAPPS consists of Summarizing the history and findings, Narrowing and Analyzing the differential diagnoses, Probing peers about uncertainties or confusion, Planning management, and Selecting case-related knowledge gaps for self-directed learning. This empowers students to control the learning environment while adding realism to encounters. The purpose of this pilot study was to determine …

Performance On The Timed Single-Leg Step-Down Test Is Correlated With Hip And Knee Biomechanics As Measured By 3d Markerless Motion Capture, Ghislain Aminake, Anthony Drazick, Christ Focht, Chloe Roy, Emily Clark, Savannah Knighton, Edward Austin, Jeremy Burnham

Clinical Practice in Athletic Training

Introduction: The timed single-leg step-down (SLSD) test is widely used in clinical and sports settings to assess lower extremity function and injury risk, yet the specific biomechanical determinants of performance on this test remain poorly understood. The purpose of this study is to investigate the relationship between performance on the timed SLSD test and hip and knee biomechanics captured by a markerless 3-D motion-analysis system. Methods: Twenty (20) healthy high school athletes with no recent history of lower extremity injury completed a 60-second timed single leg step down test. The number of quality SLSD repetitions (REPS) constituted their SLSD score. …

A Pocket Manual For Human Papillomavirus Vaccines, Natalie A Voss, J Brooks Jackson, Mary B Rysavy

Faculty, Staff and Student Publications

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and is responsible for the majority of cervical, anal, and vaginal cancers. The first prophylactic HPV vaccine was introduced in the United States in 2006. Extensive evidence demonstrates the HPV vaccine is highly efficacious and effective, particularly when administered prior to HPV exposure. Despite strong safety data and proven cost-effectiveness, HPV vaccine uptake in the United States and globally remains suboptimal. Barriers to vaccination include limited knowledge, safety concerns, and logistical challenges. Current advancements focus on single-dose vaccine regimens, development of therapeutic vaccines, and higher-valent formulations. Expanding HPV vaccine …

Epigenetic Activation Of Ebv Bglf4 Determines Antiviral-Based Regimen Response In Ebv+Cns Lymphoproliferative Disease, Christoph Weigel, Haley Klimaszewski, Fode Tounkara, Selamawit Addissie, Sarah Schlotter, Betsy Pray, James Dugan, Bradley Haverkos, Lynda Villagomez, Mark Lustberg, Pierluigi Porcu, Timothy Voorhees, Richard Ambinder, Shannon Kenney, Joyce Fingeroth, Henri-Jacques Delecluse, Michael Caligiuri, Lapo Alinari, Ginny Bumgardner, Christopher Oakes, Robert Baiocchi

Kimmel Cancer Center Faculty Papers

Epstein-Barr virus (EBV)–associated primary central nervous system lymphoproliferative diseases (EBV+PCNSL) are aggressive conditions with poor prognoses. We previously reported durable responses in patients with PCNSL who were treated with the antivirals ganciclovir and azidothymidine, plus rituximab and dexamethasone (GARD). Responses were associated with the detection of the lytic viral protein kinases, BGLF4 and BXLF1. These antiviral activating kinases are associated with lytic EBV, however, the mechanism for expression in latently infected EBV+CNSL is unknown. Expanding on previous work, we provide long-term clinical outcome data (N = 24) and show that RNA expression analysis in CNSL tissue biopsies (n = 12) …

Modulating Alternative Splicing Of Mecp2 Is A Potential Therapeutic Strategy For Rett Syndrome, Harini P Tirumala, Li Wang, Yan Li, Sameer S Bajikar, Ashley G Anderson, Wei Wang, Alexander J Trostle, Mahla Zahabiyon, Aleksandar Bajic, Jean J Kim, Hu Chen, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Rett syndrome (RTT) is a neurological disorder caused by loss-of-function mutations in methyl CpG binding protein 2 (MECP2), a transcriptional regulator essential for maintenance of normal neuronal function. The current FDA-approved treatment for RTT, Trofinetide, mildly alleviates some symptoms. In contrast, re-introducing MeCP2 or increasing its amount through transgenesis in mouse RTT models improves most neurological phenotypes and enhances survival. Here, we devised a therapeutic strategy to moderately increase MeCP2 protein by modulating the alternative splicing of MECP2 to switch the less efficiently translated e2 to the more efficiently translated e1 isoform. We deleted Mecp2 exon 2 (unique …

Characteristics And Incidence Of Gastric Cancer Among Patients With Autoimmune And Non-Autoimmune Atrophic Gastritis In A U.S. Population, Mimi C Tan, Kadon N Caskey, Irene Jeong-Ah Lee, Yan Liu, Juan Gomez Cifuentes, Shilpa Jain, Hashem B El-Serag

Faculty, Staff and Students Publications

Background: Autoimmune gastritis (AIG) is a risk factor for gastric neuroendocrine tumor (NET). We compared risk factors between AIG cases, non-autoimmune atrophic gastritis (NAIG) cases, and normal controls and determined the incidence of gastric malignancy, including adenocarcinoma and NET.

Methods: We included patients who underwent endoscopy with gastric biopsy between 3/2006 and 9/2021 in Harris Health (Houston, Texas). We identified AIG cases, NAIG cases (gastric atrophy or intestinal metaplasia [GIM] without autoimmune features), and normal controls (without AIG, NIAG, and GIM). A GI pathologist confirmed AIG diagnosis on histopathology report or slide. We determined risk factors of AIG compared to …

Childhood Maltreatment And Deviations From Normative Brain Structure: A Mega-Analysis Of 3,711 Individuals From The Enigma Mdd And Enigma Ptsd Working Groups, Haley R Wang, Zhen-Qi Liu, Elena Pozzi, Ahmed Hussain, Priyanka Sigar, Chadi Abdallah, Nina Alexander, Justin Baker, Jochen Bauer, Jennifer Urbano Blackford, Josh Cisler, Colm G Connolly, Andrew Cotton, Judith Daniels, Udo Dannlowski, Maria Densmore, Terri Deroon-Cassini, Danai Dima, Stefan Du Plessis, Amit Etkin, Negar Fani, Lukas Fisch, Jacklynn Fitzgerald, Thomas Frodl, Cynthia H Y Fu, Ali Saffet Gonul, Evan M Gordon, Ian Gotlib, Roberto Goya-Maldonado, Nynke A Groenewold, Dominik Grotegerd, Tim Hahn, J Paul Hamilton, Laura Han, Ilan Harpaz-Rotem, Courtney C Haswell, Ryan Herringa, Julia Herzog, Jonathan Ipser, Neda Jahanshad, Tanja Jovanovic, Milissa Kaufman, Tilo Kircher, Maximilian Konowski, Sheri-Michelle Koopowitz, Axel Krug, John Krystal, Ruth Lanius, Christine Larson, Amit Lazarov, Lauren Lebois, Elisabeth Leehr, Ifat Levy, Meng Li, Antje Manthey, Adi Maron-Katz, Andrew Mcintosh, Katie Mclaughlin, Susanne Meinert, Benson Mwangi, Steven M Nelson, Igor Nenadić, Yuval Neria, Richard Neufeld, Amar Ojha, Bunmi Olatunji, Elizabeth A Olson, Nils Opel, Matthew Peverill, Kerry Ressler, Marisa Ross, Isabelle Rosso, Matthew Sacchet, Kelly Sambrook, Christian Schmahl, Soraya Seedat, Martha E Shenton, Maurizio Sicorello, Anika Sierk, Jair C Soares, Dan J Stein, Frederike Stein, Murray B Stein, Benjamin Suarez-Jimenez, Jean Théberge, Sophia I Thomopoulos, Carissa Tomas, Paula Usemann, Leigh L Van Den Heuvel, Sanne Van Rooij, Henrik Walter, Martin Walter, Xin Wang, Heather Whalley, Nils R Winter, Mon-Ju Wu, Hong Xie, Tony Yang, Xi Zhu, Sigal Zilcha-Mano, Giovana B Zunta-Soares, Sophia Frangou, Paul M Thompson, Lauren Salminen, Delin Sun, Rajendra Morey, Jennifer S Stevens, Lianne Schmaal, Tiffany C Ho

Faculty, Staff and Student Publications

Background: Childhood maltreatment (CM), encompassing abuse and neglect, is highly prevalent and associated with elevated risk for Major Depressive Disorder (MDD), Posttraumatic Stress Disorder (PTSD), and other related conditions. The extent to which neuroanatomical alterations in MDD and PTSD are attributable to CM, however, is uncertain.

Methods: Here, we analyzed CM and whole-brain MRI data from 3,711 participants in the ENIGMA MDD and PTSD Working Groups (25 sites; 33.3±13.0 years; 59.9% female). Normative modeling estimated deviation z-scores for 14 subcortical volumes (SV), 68 cortical thickness (CT), and 68 surface area (SA) measures. To identify transdiagnostic effects, associations between CM and …

Medial Pulvinar Nucleus As A Causal Hub For Heteromodal Naming, Oscar Woolnough, Tessy Thomas, Kathryn M Snyder, Ellery Wheeler, Jay Gavvala, Nitin Tandon

Faculty, Staff and Student Publications

Our ability to retrieve the names of objects in our environment is a fundamental aspect of everyday life. This process requires a complex, dynamic network of cortical and subcortical interactions. While the cortical constituents of this network have been extensively studied with intracranial recordings, the subcortical nodes of the naming network are unclear. We probed the role of the left medial pulvinar nucleus in naming with direct intracranial recordings and stimulation in eight humans (three male, five female) as they named objects using pictures and auditory and written descriptions. We found a spectrotemporal signature of naming in the left medial …

Impact Of Physiotherapy Interventions On Pain, 6-Minute Walk Test, Civiq-20 Scores, And Edema In Patients With Varicose Veins: A Literature Review, Ganesh B.R, Aditi Avinash Samudre

Internet Journal of Allied Health Sciences and Practice

Introduction: As a result of chronic venous insufficiency, varicose veins develop in almost 30% of the adult population across the globe. It causes myriad symptoms like fatigue in legs, pain, swelling, and alteration in skin texture. Conservative physiotherapy interventions—Buerger’s exercise and Manual Lymphatic Drainage (MLD)—aim to improve venous and lymphatic return. Objective: To compare the effects of Buerger’s exercise versus MLD on limb volume, venous hemodynamics, symptom relief, and quality of life in varicose vein patients. Approach: A systematic search was carried out from February 2020 until the date this study was completed in June 2020 on PubMed, Scopus, CINAHL, …

Pregnancy, Cancer, And Radiation-A Modern Refresher, Kelly Kisling, Sandra M Meyers, Rebecca Milman, Susan Richardson, Christina Chapman, Justine Dupere, Grace Eliason, Suzanne Evans, Titania Juang, Young Lee, Jeffrey Masten, Julia Maues, Rachel Newman, Mike Silosky, Catherine Song, Catheryn Yashar, Sara Thrower

Faculty, Staff and Student Publications

Cancer occurs in ∼1 per 1000 pregnancies; thousands of patients may require radiation procedures for diagnosis and treatment each year in the United States alone. This rare but high-risk scenario, coupled with fear of radiation, has created ambiguity in the ideal management of pregnant patients. Without a comprehensive guide for the use of radiation in imaging and treatment for pregnant cancer patients, it is difficult for providers to offer optimal patient-centered care without introducing disparities. The goal of this paper is to provide guidance on the use of radiation for screening, diagnosis, staging, and treatment of cancer, while highlighting gaps …

Clinical Validation Of Perfusion Imaging With Pulmonary Function Test Data Using Voronoi-Based Discretization, Jorge Cisneros, Caleb J. Herrera, Yi-Kuan Liu, Lisa V. Du, Yevgeniy Vinogradskiy, Richard Castillo, Girish Nair, Edward Castillo

Department of Medicine Faculty Papers

Objective.Accurate lung function assessment is essential for diagnosing and managing diseases like chronic obstructive pulmonary disorder, pulmonary emboli, and lung cancer. Single-photon emission computed tomography (SPECT) provides valuable 3D functional imaging of ventilation and perfusion, but is limited by low spatial resolution, availability, additional radiation, and cost. Alternative methods, including CT-based perfusion (CT-P) and deep learning models, require large datasets to validate results that are often scarce. Pulmonary function tests (PFTs) offer rapid and noninvasive global lung function measures and are clinically widely used. While ventilation correlates well with PFTs, perfusion imaging presents challenges due to complex blood flow and …

Single-Layer Spherical (Sls) Vs Single-Layer (Sl) Woven Endobridge (Web) Device In The Treatment Of Narrow-Neck Intracranial Aneurysms: A Propensity Score-Matched Analysis, Hamza Adel Salim, Vivek Yedavalli, Fathi Milhem, Nimer Adeeb, Basel Musmar, Muhammed Amir Essibayi, Motaz Daraghma, Mahmoud Dibas, Nicole M Cancelliere, Jose Danilo Bengzon Diestro, Oktay Algin, Sherief Ghozy, Sovann V Lay, Adrien Guenego, Leonardo Renieri, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Markus Möhlenbruch, Michael Kral, Charlotte Chung, Mohamed M Salem, Ivan Lylyk, Paul M Foreman, Hamza Shaikh, Vedran Župančić, Muhammad U Hafeez, Joshua Catapano, Muhammad Waqas, Muhammet Arslan, Onur Ergun, James D Rabinov, Julian Maingard, Clemens M Schirmer, Mariangela Piano, Anna L Kühn, Caterina Michelozzi, Robert M Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie T Nawka, Marios Psychogios, Christian Ulfert, Bryan Pukenas, Jan-Karl Burkhardt, Thien Huynh, Juan Carlos Martinez-Gutierrez, Sunil A Sheth, Diana Slawski, Rabih Tawk, Benjamin Pulli, Boris Lubicz, Pietro Panni, Ajit S Puri, Guglielmo Pero, Eytan Raz, Christoph J Griessenauer, Hamed Asadi, Adnan Siddiqui, Elad I Levy, Neil Haranhalli, David Altschul, Andrew F Ducruet, Felipe C Albuquerque, Robert W Regenhardt, Christopher J Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Stavropoula I Tjoumakaris, Hugo H Cuellar-Saenz, Pascal M Jabbour, Frédéric Clarençon, Nicola Limbucci, Vitor Mendes Pereira, Aman B Patel, Max Wintermark, Adam A Dmytriw

Faculty, Staff and Student Publications

Data on the use of Woven EndoBridge (WEB) devices in the treatment of narrow-neck intracranial aneurysms (NNA) are limited. We compared the efficacy and safety of single-layer (SL) and single-layer spherical (SLS) WEB devices in treating NNA. We conducted a multicenter retrospective analysis of adult patients with NNA (neck ≤ 4 mm and width-to-neck ratio ≥ 2) treated with SL or SLS WEB devices between January 2011 and December 2022. Patients with fusiform or blister aneurysms, adjunctive treatments, or devices other than SL or SLS were excluded. Propensity score matching was used to adjust for confounding variables. Outcomes included procedural …

Pharmacologic And Oncohistone Inhibition Of Setd2 Converge On Genomic Instability, Alyssa T Paparella, Ashley G Boice, In Young Park, Rajkishor Nishad, Durga Tripathi, Seth A Nelson, Edward W Pietryk, H Josh Jang, Ian J Frew, W Kimryn Rathmell, Frank M Mason, Cristian Coarfa, Ruhee Dere, Cheryl Lyn Walker

Faculty, Staff and Students Publications

Background/objectives: SETD2 is a dual-function methyltransferase important for methylation of histone H3 at lysine 36 and α-tubulin in spindle microtubules. Genetic inactivation of SETD2 during oncogenesis drives loss of H3K36me3, genomic instability, and cancer progression. This study asked if disruption of genomic stability was a canonical feature of SETD2 inactivation via different pathways.

Methods: We evaluated the impact of EPZ-719, a pharmacologic SETD2 inhibitor, and an H3.3K36M mutant histone ("oncohistone") that binds and sequesters SETD2, on methylation activity and genomic stability in human cell lines. SETD2 activity was measured using in vitro methylation assays, H3K36me3 loss confirmed by Western analysis, …

Ten Years Real-World Experience With Sacubitril/Valsartan In Patients With Heart Failure With Reduced Ejection Fraction, Gianluigi Savarese, Christian Basile, Alexandre Mebazaa, Antoni Bayes-Genis, Seok Min Kang, Byung-Su Yoo, Carlos Eid, Biykem Bozkurt, Javed Butler

Faculty, Staff and Students Publications

Introduction: Sacubitril/valsartan (Sac/Val) represents a cornerstone of heart failure (HF) with reduced ejection fraction (HFrEF) management. This systematic review provides a comprehensive overview of real-world evidence (RWE) regarding the implementation, clinical effectiveness, and safety of Sac/Val in patients with HFrEF.

Methods: A systematic literature search of PubMed was conducted through March 2024 following PRISMA guidelines.

Results: The review included 45 manuscripts from 30 different studies, primarily from Europe (44%) and the US (30%). RWE confirmed that Sac/Val was associated with a lower risk of cardiovascular mortality (10%-16%), HF hospitalization (10%-38%), and all-cause mortality (10%-25%). Sac/Val was significantly associated with cardiac …

Circulating Ketone Bodies And Incident Cardiovascular Outcomes And Mortality: Insights From The Uk Biobank, Parag Anilkumar Chevli, Saeid Mirzai, Richard Kazibwe, Jeff Kingsley, Alexis C Wood, Joseph Yeboah, Leandro Slipczuk, Anurag Mehta, Harpreet S Bhatia, Ambarish Pandey, Michael D Shapiro

Children’s Nutrition Research Center Staff Publications

Background: Ketone bodies (KB) are endogenous energy sources synthesized by the liver in response to metabolic stress. Their associations with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and mortality and their potential beneficial or harmful effects have yet to be determined. This study aimed to examine the association between KB and incident cardiovascular outcomes and mortality in a large general population cohort free from ASCVD and HF at baseline.

Methods: This analysis included 90 987 participants (mean age 56.4 ± 8.1 years; 54.7% women) from the UK Biobank without prevalent ASCVD or HF. KB were measured by nuclear magnetic resonance …

Pd-L1 Positivity Predicts A Unique Hyperaggressive Tumor Group Within Meng C Meningiomas, Vijay Nitturi, Shervin Hosseingholi Nouri, Collin English, Hsiang-Chih Lu, Elizabeth Ledbetter, Diego Rojas, Sean Lau, Malcolm Mcdonald, Jacob J Mandel, Abdul Basit Khan, Arif O Harmanci, Akdes S Harmanci, Tiemo Klisch, Akash J Patel

Duncan NRI Faculty and Staff Publications

Molecular profiling has identified 3 groups of meningiomas, with MenG C tumors exhibiting the vast majority of recurrences. Efforts to find effective treatments for recurrent meningiomas have remained elusive. Higher WHO-grade meningiomas have exhibited greater Programmed Death Ligand 1 (PD-L1) expression through various methods, but the prognostic value of PD-L1 expression has not been described in the context of molecular profiling. Additionally, trials investigating PD-1/PD-L1-targeted immunotherapies have produced disappointing results. Here, we find that PD-L1 positivity, while prevalent in MenG C tumors, does not predict recurrence in the benign MenG A and B tumors. PD-L1 positivity also occurs independently of …

Proteomic Profiling Of Pulmonary Function And Cardiovascular Disease Risk In The Atherosclerosis Risk In Communities Study, Yura Lee, Astrid M Manuel, Ngoc Quynh H Nguyen, Christine Ladd-Acosta, Alanna C Morrison, Kari E North, Eric Boerwinkle, Amil M Shah, Zhongming Zhao, Stephanie J London, Bing Yu

Faculty, Staff and Student Publications

Background: Pulmonary function is linked to cardiovascular disease risk; however, the underlying mechanisms remain unclear. We aimed to identify protein biomarkers associated with pulmonary function and examine their impact on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and all-cause mortality.

Methods: Data from White and Black Americans in the Atherosclerosis Risk in Communities study (visit 2: N=11 354, mean age=57 years; visit 5: N=3517, mean age=75 years), a prospective cohort, were analyzed. Linear regression assessed associations between protein levels and pulmonary function measures, including forced expiratory volume in 1 second and forced vital capacity. The impact of …

Influence Of Body Composition On The Efficacy Of Nivolumab Plus Ipilimumab For Metastatic Clear Cell Renal Cell Carcinoma, Kabir Grewal, Maria Julia Moura Nascimento Santos, Pankaj Kumar Chauhan, Kai Yu, Nizar M Tannir, Sagar S Mukhida, Neha Venkatesh, Amishi Y Shah, Amado J Zurita, Andrew C Johns, Matthew T Campbell, Sangeeta Goswami, Jianjun Gao, Eric Jonasch, Jennifer L Mcquade, Omar Alhalabi, Pavlos Msaouel, Andrew W Hahn

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor therapy (ICI) with nivolumab+ipilimumab is a first-line (1L) standard for metastatic clear cell renal cell carcinoma (ccRCC), yet outcomes remain heterogeneous. Increasing evidence suggests that host factors influence the tumor microenvironment and response to ICI. Although higher body mass index (BMI) has been associated with improved outcomes in several malignancies, BMI is an imprecise surrogate for underlying adipose and muscle compartments. We evaluated the association between body composition and outcomes with 1L nivolumab+ipilimumab in metastatic ccRCC.

Methods: We retrospectively analyzed patients with mccRCC treated with 1L nivolumab+ipilimumab at MD Anderson Cancer Center between June 2015 and …

Single Ventricle Physiology May Not Preclude Cardiac Repair In The Setting Of Congenital Diaphragmatic Hernia, Kylie I Holden, Michael C Scott, Ashley H Ebanks, Amir M Khan, D Michael Mcmullan, Anthony Johnson, Charles S Cox, Matthew T Harting, Damien J Lapar

The Brown Foundation: Institute of Molecular Medicine

Objective: Management for congenital heart disease (CHD) with congenital diaphragmatic hernia (CDH), particularly in single ventricle physiology, is challenging, with limited studies showing poor outcomes. This investigation evaluated outcomes for these complex patients.

Methods: This retrospective cohort study (2007-2022) from the CDH Study Group analyzed mortality in patients with CDH and single ventricle physiology, using standard statistical methods and Cox regression for estimation.

Results: A total of 9,261 CDH patients were identified, including 1,886 with CDH + CHD and 131 with single ventricle physiology. The median gestational age was 38 weeks and birthweight was 2.8 kg. Of 131 patients, 34 …

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Metabolic Responses To Freund’S Adjuvants And Oncolytic Viruses: Implications On Vaccines And Tumor Immunity, Kiruthiga Mone

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Freund’s adjuvants have been extensively used in experimental research, and they modulate immune responses through various mechanisms. While both complete Freund’s adjuvant (CFA) and incomplete Freund’s adjuvant (IFA) contain the same mineral oil base, CFA contains the killed extract of Mycobacterium tuberculosis (M. tb) as an additional ingredient. Because the CFA contains mycobacterial content similar to that of Bacillus Calmette-Guérin (BCG), which induces trained immunity (TI), we tested the hypothesis that CFA may elicit TI-like features. To test this hypothesis, we investigated the metabolic and epigenetic reprogramming induced by CFA, with IFA and BCG as controls, in inbred …

Mechanometabolism Instructs Hematopoietic Stem Cell Specification, Paulina D Horton, Alina Syed, Michelle Winkler, Abishek B Vaidya, Michael Rariden, Neha Arora, Yong Zhou, Michihiro Kobayashi, Momoko Yoshimoto, Hyun Jung Lee, Hyun-Eui Kim, John P Hagan, Catherine Denicourt, Travis I Moore, Pamela L Wenzel

Faculty, Staff and Student Publications

Mechanical force generated by blood flow stimulates emergence of the first hematopoietic stem cells (HSCs) that populate the blood system. Force drives the transition of HSC precursors from an endothelial to hematopoietic identity, yet the molecular regulation of this fate switch remains poorly understood. We report that shear stress triggers adaptation in mitochondrial composition, ultrastructure, and function, which are essential for hematopoietic fate and engraftment potential. Shear stress remodels mitochondria in hemogenic endothelium by promoting mitochondrial gene transcription and protein synthesis. Laminar flow selectively initiates translation of 5' terminal polypyrimidine (5'TOP) motif-containing transcripts, which commonly encode ribosome and translation machinery. …

Ectopic B Lymphocyte Follicles Exacerbate Ischemic Brain Damage Via Mif-Cd74/Cxcr4 And Interferon Signaling, Sheng Yang, Hang Zhang, Lu-Lu Xu, Luo-Qi Zhou, Yun-Hui Chu, Lian Chen, Xiao-Wei Pang, Lu-Yang Zhang, Li-Fang Zhu, Ming-Hao Dong, Ke Shang, Jun Xiao, Long-Jun Wu, Wei Wang, Dai-Shi Tian, Chuan Qin

Faculty, Staff and Student Publications

Neuroinflammation, encompassing both innate and adaptive immune responses, plays a crucial role in ischemic stroke. Although B lymphocytes are central to adaptive immunity, their contributions to ischemic stroke remain poorly understood. Here, we demonstrated that B lymphocytes accumulate in ischemic lesions, forming germinal center-like structures at the later stage after stroke, which mainly depended on in situ proliferation. This accumulation correlated with worsened neuroinflammation and ischemic injury, whereas B cell depletion reduced chronic brain damage during stroke. Mechanistically, microglia recruited B cells into ischemic lesions through MIF-CD74/CXCR4 signaling during the early phase of stroke, while IFN-related pathways in B cells …

Surface Morphometrics Reveals Local Membrane Thickness Variation In Organellar Subcompartments, Michaela Medina, Ya-Ting Chang, Hamidreza Rahmani, Mark Frank, Zidan Khan, Daniel Fuentes, Frederick A Heberle, M Neal Waxham, Benjamin A Barad, Danielle A Grotjahn

Faculty, Staff and Student Publications

Lipid bilayers form the basis of organellar architecture, structure, and compartmentalization in the cell. Decades of biophysical, biochemical, and imaging studies on purified or in vitro-reconstituted liposomes have shown that variations in lipid composition influence the physical properties of membranes, such as thickness and curvature. However, similar studies characterizing these membrane properties within the native cellular context have remained technically challenging. Recent advancements in cellular cryo-electron tomography (cryo-ET) imaging enable high-resolution, three-dimensional views of native organellar membrane architecture preserved in near-native conditions. We previously developed a "Surface Morphometrics" pipeline that generates surface mesh reconstructions to model and quantify cellular membrane …