Digital Commons Network^™

Influenza-Associated Acute Necrotizing Encephalopathy In Us Children, Andrew Silverman, Rachel Walsh, Jonathan D Santoro, Katherine Thomas, Elizabeth Ballinger, Kristen S Fisher, Ajay X Thomas, Brian Appavu, Michael C Kruer, Derek Neilson, Jasmine Knoll, April N Sharp, Hannah E Edelman, Scott Otallah, Alexandra Morgan, Aniela Grzezulkowska, John Nguyen, Lekha M Rao, Shaina M Hecht, Laura Catalano, Hunter Daigle, Catherine Kronfol, Jessica Wharton, David Adams, Adam Z Kalawi, Michael Kung, Janetta L Arellano, Lauren Smith, Devorah Segal, Kristina Feja, Eileen Broomall, Anuj Jayakar, Sandra R Arnold, Hanna Retallack, Craig A Press, Grace Gombolay, Madeleine H Mclaughlin, Varun Kannan, Kavita Thakkar, Tasmia Rezwan, Erin Hulfish, Dalia Eid, Jennifer Meylor, Diane Peng, Ryan Hurtado, Taylor Nickerson, Iris Mandell, Abigail U Carbonell, Mallory Kerner-Rossi, Divya Jayaraman, Mallory Davis, Rosemary Olivero, Neel Shah, Christina M Osborne, Bo Zhang, Christopher Cortina, Adrienne G Randolph, Suchitra Rao, Thomas Larocca, Keith P Van Haren, Molly Wilson-Murphy

Faculty, Staff and Students Publications

Importance: Acute necrotizing encephalopathy (ANE) is a rare, but severe, neurologic condition for which epidemiologic and management data remain limited. During the 2024-2025 US influenza season, clinicians at large pediatric centers anecdotally reported an increased number of children with influenza-associated ANE, prompting this national investigation.

Objective: To understand the clinical presentation, interventions, and outcomes among US children diagnosed with influenza-associated ANE.

Design, setting, and participants: This study was a multicenter case series of children diagnosed with ANE with longitudinal follow-up. A call for cases was issued via academic societies, public health agencies, and by directly contacting pediatric specialists at 76 …

Outcomes Of Brexucabtagene Autoleucel In Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia With Cns Involvement, Ibrahim N Muhsen, Gregory W Roloff, Rawan Faramand, Tamer Othman, Yannis Valtis, Noam E Kopmar, Simone E Dekker, Matthew Connor, Santiago Mercadal, Timothy E O'Connor, Kaitlyn C Dykes, Mohamed Ahmed, Nikeshan Jeyakumar, Amy Zhang, Katharine Miller, Katherine C Sutherland, Caitlin Guzowski, Vishal K Gupta, Navneet Majhail, Minoo Battiwalla, Melhem M Solh, Shahbaz A Malik, John Mathews, Caspian H Oliai, Paul Shaughnessy, Luke Mountjoy, Catherine J Lee, Aaron C Logan, Stephanie B Tsai, Jessica T Leonard, Marc Schwartz, Joshua P Sasine, Muthu Kumaran, Noelle Frey, Jae H Park, Divya Koura, Ryan D Cassaday, Bijal D Shah, Ibrahim Aldoss, Lori S Muffly, Laquisa C Hill

Faculty, Staff and Students Publications

Patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system (CNS) involvement (CNS B-ALL) have poor outcomes and were frequently excluded from CD19-targeting chimeric antigen receptor (CAR) T-cell clinical trials. The efficacy and safety of brexucabtagene autoleucel (brexu-cel) in adults with R/R B-ALL was established by the ZUMA-3 trial, which excluded patients with advanced or symptomatic CNS involvement. In this retrospective multicenter analysis, we investigated the safety and efficacy of brexu-cel in patients with CNS B-ALL using data from the ROCCA (Real-World Outcomes Collaborative for CAR T in ALL) consortium. Of 189 patients who received infusion, 31 …

Pfkfb3 Activates Cad To Enhance De Novo Pyrimidine Synthesis For Cell Growth, Qingen Da, Yongfeng Cai, Qian Ma, Qiuhua Yang, Yapeng Cao, Yaqi Zhou, Dingwei Zhao, Zhiping Liu, Jiean Xu, Junming Quan, Liang Zhang, Rui Wang, Xuejun Jiang, Xiao Liu, Kunfu Ouyang, Zhen Han, Jikui Liu, Tao Wang, Chunxiang Zhang, Neal L Weintraub, David J R Fulton, Jun Zhao, Mei Hong, Zigang Li, Yuqing Huo

Faculty, Staff and Students Publications

Aerobic glycolysis, termed the Warburg effect, is one of the aberrant metabolic pathways in highly proliferating cells. Glycolysis provides glycolytic metabolites to support the generation of biomass, such as nucleotides, amino acids, and lipids. Research on the direct interactions between glycolysis and other metabolic pathways is an emerging field that has garnered significant interest. Phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) activates glycolysis by synthesizing fructose-2,6-bisphosphate (F2,6BP), which allosterically activates the rate-limiting enzyme 6-phosphofructo-1-kinase (PFK-1). In this study, we found that PFKFB3 directly interacts with and regulates the phosphorylation of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), the enzyme catalyzing the first three …

Hepcidin, Incident Heart Failure, And Cardiac Dysfunction In Older Adults: The Aric Study, Iman A F Aboelsaad, Brian L Claggett, Victoria Lamberson, Pranav Dorbala, Kunihiro Matsushita, Pamela Lutsey, Bing Yu, Brandon W Lennep, Youssef M K Farag, Amil M Shah, Leo F Buckley

Faculty, Staff and Student Publications

Aims: Hepcidin regulates plasma and tissue iron levels. We studied the association of hepcidin levels with the risk of incident heart failure (HF) and cardiac dysfunction in older adults.

Methods and results: We included adults from the ongoing, longitudinal Atherosclerosis Risk in Communities (ARIC) study, who were free from prevalent anaemia and HF at Visit 5 (2011-13) and had available hepcidin and covariate data. Associations of plasma hepcidin levels with overall adjudicated incident HF, HF with reduced ejection fraction (HFrEF), and HF with preserved ejection fraction (HFpEF) were assessed using multivariable Cox proportional hazards regression models. Cross-sectional associations of hepcidin …

An Ehealth Delivery Alternative For Cancer Genetic Testing For Hereditary Predisposition In Patients With Metastatic Cancers: Protocol For A Randomized Trial, Kimberley T. Lee, Briana Mcleod, Brian Egleston, Sarah Brown, Sarah Howe, Dominique Fetzer, Lauren Gutstein, Cara Cacioppo, Dana Clark, Susan M. Domchek, Jessica Ebrahimzadeh, Dana Falcone, Demetrios Ofidis, Hannah Griffin, Rajia Mim, Santina Hernandez, Linda Fleisher, Kelsey Karpink, Enida Selmani, Aysha Tahsin, Lynne Wagner, Michelle Weinberg, Kuang-Yi Wen, Elisabeth Wood, Angela R. Bradbury

Department of Medical Oncology Faculty Papers

Background: Germline BRCA1 and BRCA2 testing is a standard evidence-based practice, with established risk reduction and cancer screening guidelines for genetic carriers. With Food and Drug Administration approval for poly (adenosine diphosphate ribose) polymerase (PARP) inhibitors in patients with metastatic breast, ovarian, pancreatic, and prostate cancer, there is an additional therapeutic rationale for testing all patients with these cancers for germline BRCA1 and BRCA2 mutations. However, many at-risk patients do not have access to genetic services, leaving many genetic carriers unidentified.

Objective: The eREACH (A Randomized Study of an eHealth Delivery Alternative for Cancer Genetic Testing for Hereditary Predisposition in …

30-Day And 1-Year Outcomes From The Optimize Pro Tavr Evolut Fx Addendum Study., Hemal Gada, Ramzi F Khalil, Stanley J Chetcuti, G Michael Deeb, Kendra J Grubb, Adam B Greenbaum, David Lorenz, Robert D Jumper, Ibrahim Sultan, Dustin Kliner, Paul Mahoney, Deepak R Talreja, Mustafa I Ahmed, Joshua D Rovin, Lang Lin, Paul Sorajja, Douglas G W Fraser, Suneet Mittal, Tamim Nazif, Josep Rodes-Cabau, Amit N Vora, Kathleen Ertelt, Amanda C Tenhoff, Yu Jung Yeh, Steven J Yakubov

Heart and Vascular Articles

BACKGROUND: Primary results from the Optimize PRO study demonstrated that transcatheter aortic valve replacement (TAVR) with the cusp overlap technique (COT) resulted in low 30-day permanent pacemaker implantation (PPI) rates and no moderate or greater aortic regurgitation (AR).

OBJECTIVES: The aim of this study was to evaluate outcomes after Evolut FX implantation using the COT and postprocedural computed tomography (CT).

METHODS: The Optimize PRO FX Addendum study is a postmarket, prospective, multicenter, nonrandomized study. Patients with severe aortic stenosis underwent TAVR with the Evolut FX using the COT protocol. Postprocedurally, COT adherence was evaluated to identify key steps, and CT-assessed …

Single-Neuron Datasets For Linguistic And Semantic Processing In The Human Amygdala And Hippocampus, Yue Wang, Runnan Cao, Jon T Willie, Peter Brunner, Shuo Wang

2020-Current year OA Pubs

Understanding linguistic and semantic processing in the human brain involves exploring intricate neural networks. However, it remains unclear whether and how the amygdala and hippocampus are involved in these processes. Here, we recorded single-neuron activity from the human amygdala and hippocampus while neurosurgical patients with intractable epilepsy performed various language tasks. Specifically, we recorded from 68 neurons in 7 patients for the visual language localizer task, 115 neurons in 12 patients for the auditory language localizer task, 88 neurons in 9 patients for the TIMIT task, and 51 neurons in 4 patients for the natural story task. Together, our comprehensive …

Using The R = Mc2 Heuristic To Assess Whole-Of-School Physical Activity Implementation In Elementary Schools: A Cross-Sectional Study, Derek W Craig, Kevin Lanza, Christopher D Pfledderer, Andjelka Pavlovic, Kempson Onadeko, Natalia I Heredia, Jizyah Injil, Laura F Defina, Timothy J Walker

Faculty, Staff and Student Publications

Background: Schools are recommended to use a whole-of-school (WOS) approach to promote physical activity opportunities before, during, and after school. Yet, the barriers and facilitators to implementing a WOS approach successfully are not well understood. The R = MC2 heuristic, which defines readiness for implementation as a combination of an organization's motivation and capacity to implement, can enhance our understanding of implementation in the school setting. This study examines associations between constructs from the R = MC2 heuristic and schools' implementation of a WOS approach.

Methods: We conducted a secondary analysis of cross-sectional data from U.S. elementary schools participating in …

Unleashing Nk Cells For Cancer Immunotherapy In Lung Cancer: Biologic Challenges And Clinical Advances, Quinlan Mclaughlin, Dorothy K Sojka, Kathleen Kennedy, Sytse J Piersma, Nan Sethakorn

2020-Current year OA Pubs

Natural killer (NK) cells are a crucial part of the innate immune system and serve as an important effector for killing tumor cells through direct cytolytic activity or immunomodulatory signaling to T cells and antigen presenting cells. NK cells are correlated with increased tumor control and better overall patient survival across various types of cancers including non-small cell lung cancer (NSCLC). Despite their promising potential for anti-tumor killing, NK cell function is often diminished within the tumor microenvironment. There are many factors that lead to decreased tumor-infiltrating NK cell killing, including immunoinhibitory factors from tumor cells and resident tissues, acquired …

Building An Interdisciplinary Workforce In Geroscience: Aligning Perspectives And Educational Goals, Iman M Al-Naggar, Miranda E Orr, Et Al.

2020-Current year OA Pubs

The National Institute on Aging-funded Geroscience Education and Training Network held the "Building an Interdisciplinary Workforce in Geroscience: Aligning Perspectives and Educational Goals" preconference workshop at the 2023 Gerontological Society of America's Annual Meeting. Parties involved in geroscience education and interested stakeholders addressed the development of didactic educational materials, training, and career development opportunities to equip learners with the skills to meet the demands of the emerging field of geroscience, from research to clinic and industry. Recent successes were presented, existing opportunities, gaps, and challenges identified and discussed, and solutions and future directions described.

Sars-Cov-2 Antibody Responses In Children Exhibit Higher Fcr Engagement And Avidity Than In Adults, Carolyn A Cohen, Ludivine Grzelak, Susan S Chiu, David Sc Hui, Mike Yw Kwan, Owen Ty Tsang, Wai Hung Chan, Yat Sun Yau, Kelly Wk Lee, Masashi Mori, Gaya K Amarasinghe, Samuel Ms Cheng, Leo Lm Poon, Malik Peiris, Sophie A Valkenburg

2020-Current year OA Pubs

As intrinsic differences in humoral immune response to SARS-CoV-2 between children and adults remain unclear, we improved characterisation by defining the kinetics, specificity and function of antibodies to SARS-CoV-2 in children (n = 146, aged 9.4 ± 4.8 years with n = 257 samples) compared to adults (n = 85, aged 39.5 ± 15.2 years with n = 122 samples). We used plasma samples from an infection and vaccination-naive cohort study with RT-PCR confirmed ancestral B.1* SARS-CoV-2 virus infection with asymptomatic or mild disease, collected in Hong Kong between March to December 2020, from acute (0-14 days post infection) to …

Placental Polycyclic Aromatic Hydrocarbon (Pah) Levels Are Associated With Spontaneous Preterm Birth, Gwendolynn Hummel, Sohini Banerjee, Vasanta Putluri, Inaara Malick, Grace Johnson, Abu Hena Mostafa Kamal, Chandra Shekar R Ambati, Nagireddy Putluri, Lori Showalter, Cynthia D Shope, Joseph Hagan, Kjersti M Aagaard, Bhagavatula Moorthy, Melissa A Suter

Faculty, Staff and Students Publications

While the cause of preterm birth (PTB) (i.e., delivery before 37 weeks of gestation) is likely multifactorial, ambient exposure to environmental chemicals has been postulated to play a role in its etiology. Our prior studies of exposure to polycyclic aromatic hydrocarbons (PAHs) in pregnancy have shown an increased level of placental PAH-induced bulky DNA adducts with increasing levels of PAH exposures. In this investigation, we hypothesized that higher levels of placental PAHs would be associated with an increased risk of PTB. Using gas chromatography and mass spectrometry (GC-MS/MS), we measured levels of benzo(a)pyrene (BaP), benzo(b)fluoranthene (BbF) and dibenz(a,h)anthracene (DBA) from …

Multivariate Protein Landscape Of Host Response In Hospitalised Patients With Suspected Infection In The Emergency Department, Pratik Sinha, Et Al.

2020-Current year OA Pubs

Suspected infection requiring hospitalisation has highly heterogenous presentation. Yet, variances in host response and its implications are largely unknown. In this multicentre cohort of 3802 individual patients presenting to the Emergency Department (ED) with suspected infection requiring hospitalisation, we apply uniform manifold approximation and projections and K-means clustering to 29 plasma proteins to identify biologically discrete host response clusters. In this work, we first describe two large clusters, called "Dysregulated" and "Undifferentiated", with abnormal protein concentrations and adverse outcomes in the former. Through further clustering, we identify 4 sub-clusters in the Dysregulated cluster, each with discrete biological signatures, clinical correlates, …

Prolonging Lung Cancer Response To Egfr Inhibition By Targeting The Selective Advantage Of Resistant Cells, Lisa Brunet, David Alexandre, Jiyoung Lee, Maria Del Mar Blanquer-Rosselló, David Bracquemond, Alexis Guernet, Houssein Chhouri, Mathilde Goupil, Zoulika Kherrouche, Arnaud Arabo, Maicol Mancini, Dorthe Cartier, Shen Yao, David Godefroy, Julie Dehedin, Jian-Rong Li, Céline Duparc, Philippe Jamme, Audrey Vinchent, Caroline Bérard, David Tulasne, Sabrina Arena, Alberto Bardelli, Chao Cheng, Byoung Chul Cho, Olivier Wurtz, Cédric Coulouarn, Antonio Maraver, Stuart A Aaronson, Alexis B Cortot, Youssef Anouar, Luca Grumolato

Faculty, Staff and Students Publications

Non-small cell lung cancers (NSCLCs) treated with tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) almost invariably relapse in the long term, due to the emergence of subpopulations of resistant cells. Through a DNA barcoding approach, we show that the clinically approved drug sorafenib specifically abolishes the selective advantage of EGFR-TKI-resistant cells, while preserving the response of EGFR-TKI-sensitive cells. Sorafenib is active against multiple mechanisms of resistance/tolerance to EGFR-TKIs and its effects depend on early inhibition of MAPK-interacting kinase (MKNK) activity and signal transducer and activator of transcription 3 (STAT3) phosphorylation, and later down-regulation of MCL1 and …

A Case Of Adrenal Insufficiency Presenting With Seizures, Complicated By Developmental Cerebral Venous Anomaly And Takotsubo Cardiomyopathy: A Case Report, Katrina Villegas, Brittany Eason, Karolina Janiec, Alaa Musallam, Ahmed Hammouda, Samia Ammar Aldwaik, Radhika Tailor

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Adrenal insufficiency is a potentially life-threatening condition that often presents with nonspecific symptoms. While fatigue, hypotension, and electrolyte disturbances are common features, seizures and stress-induced cardiomyopathy are rare initial manifestations. This case is reported for its atypical presentation and to highlight the diagnostic challenge it posed in the absence of classic biochemical findings.

CASE PRESENTATION: We report a case of a 68-year-old Hispanic woman with diabetes, hypertension, dyslipidemia, and hypopituitarism secondary to Sheehan syndrome, who presented with new-onset seizures after abruptly discontinuing chronic steroid therapy. Her symptoms included progressive weakness and behavioral changes over several weeks. Initial evaluation revealed …

Circzfr/Ythdf3 Axis Drives Lymph Node Metastasis In Cervical Cancer Via Fasn Translation, Mingyi Zhou, Yan Gao, Yong Zhang, Lian He, Bo Gao, Yue Zhang, Francois X Claret, George A Calin, Danbo Wang

Faculty, Staff and Student Publications

Background: Lymph node metastasis is a key driver of poor outcomes in cervical cancer. However, the molecular mechanisms of circular RNAs (circRNAs) driving cervical cancer lymph node metastasis remain unclear.

Methods: We identified circZFR, fatty acid synthase (FASN) and YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) protein expression in the cervical cancer patients with long and short disease-free survival (DFS). Functional experiments were performed to investigate the function of circZFR, FASN and YTHDF3 on cell migration and invasion. MeRIP-qPCR, RNA pulldown, RNA Immunoprecipitation (RIP), and Co-Immunoprecipitation (Co-IP) assays were executed to investigate the mechanism of circZFR regulating FASN protein expression. …

Human Interpretable Grammar Encodes Multicellular Systems Biology Models To Democratize Virtual Cell Laboratories, Jeanette A I Johnson, Daniel R Bergman, Heber L Rocha, David L Zhou, Eric Cramer, Ian C Mclean, Yoseph W Dance, Max Booth, Zachary Nicholas, Tamara Lopez-Vidal, Atul Deshpande, Randy Heiland, Elmar Bucher, Fatemeh Shojaeian, Matthew Dunworth, André Forjaz, Michael Getz, Inês Godet, Furkan Kurtoglu, Melissa Lyman, John Metzcar, Jacob T Mitchell, Andrew Raddatz, Jacobo Solorzano, Aneequa Sundus, Yafei Wang, David G Denardo, Andrew J Ewald, Daniele M Gilkes, Luciane T Kagohara, Ashley L Kiemen, Elizabeth D Thompson, Denis Wirtz, Laura D Wood, Pei-Hsun Wu, Neeha Zaidi, Lei Zheng, Jacquelyn W Zimmerman, Jude M Phillip, Elizabeth M Jaffee, Joe W Gray, Lisa M Coussens, Young Hwan Chang, Laura M Heiser, Genevieve L Stein-O'Brien, Elana J Fertig, Paul Macklin

Faculty, Staff and Student Publications

Cells interact as dynamically evolving ecosystems. While recent single-cell and spatial multi-omics technologies quantify individual cell characteristics, predicting their evolution requires mathematical modeling. We propose a conceptual framework-a cell behavior hypothesis grammar-that uses natural language statements (cell rules) to create mathematical models. This enables systematic integration of biological knowledge and multi-omics data to generate in silico models, enabling virtual "thought experiments" that test and expand our understanding of multicellular systems and generate new testable hypotheses. This paper motivates and describes the grammar, offers a reference implementation, and demonstrates its use in developing both de novo mechanistic models and those informed …

Racial And Socioeconomic Disparities In Long Term Survival After Surgery And Radiation For Spinal Cord Hemangioblastoma, Abdul Karim Ghaith, Xinlan Yang, Joshua Weinberg, Shaan Bhandarkar, Taha Khalilullah, Abdel-Hameed Al-Mistarehi, Khaled Zaitoun, Meghana Bhimreddy, Arjun K. Menta, Antony A. Fuleihan, Kamel Chebaro, Jawad Khalifeh, Andrew Grossbach, Nicholas Theodore, Daniel Lubelski

Department of Medicine Faculty Papers

Spinal cord hemangioblastomas are rare, benign, intradural tumors that, despite their nonmalignant histopathology, can lead to substantial neurological morbidity. While disparities in outcomes based on race and socioeconomic status have been well-documented in other spinal tumor populations, their role in spinal cord hemangioblastoma remains poorly understood. In this study, we utilize the National Cancer Database (NCDB) to evaluate the influence of race, socioeconomic factors, and healthcare access on survival outcomes in patients with spinal cord hemangioblastoma. Additionally, we explore the utility of machine learning-based survival models to improve individualized risk prediction and to identify key clinical and sociodemographic determinants of …

Β-Catenin Functions As A Molecular Adapter For Disordered Cbaf Interactions, Yuen San Chan, Qinyu Gao, Sarah A Robinson, Wenzhi Wang, Ruzena Filandrova, Lisa-Maria Weinhold, Mario Loeza Cabrera, Miao Zhang, Chandra Shekar R Ambati, Antonio M Lerario, Nagireddy Putluri, Katja Kiseljak-Vassiliades, Margaret E Wierman, Mouhammed Amir Habra, Gary D Hammer, Vaclav Veverka, Katerina Cermakova, H Courtney Hodges

Faculty, Staff and Students Publications

BAF (SWI/SNF) chromatin remodelers engage binding partners to generate site-specific DNA accessibility. However, the basis for interaction between BAF and divergent binding partners has remained unclear. Here, we tested the hypothesis that scaffold proteins augment BAF's binding repertoire by examining β-catenin (CTNNB1) and steroidogenic factor 1 (SF-1, NR5A1), a transcription factor central to steroid production in human cells. BAF inhibition rapidly opposed SF-1/β-catenin enhancer occupancy, impairing SF-1 target activation and SF-1/β-catenin autoregulation. These effects arise due to β-catenin's role as a molecular adapter between SF-1 and an intrinsically disordered region (IDR) of the canonical BAF (cBAF) subunit ARID1A. In contrast …

Organizational Climate And Decision Aid Sustainability In Lupus Care: Mixed Methods Study, Aizhan Karabukayeva, Larry R Hearld, Nathan W Carroll, Reena Kelly, Jasvinder A Singh

Faculty, Staff and Students Publications

Background: Digital decision aids (DAs) are increasingly used in health care to support shared decision-making and promote patient engagement. In the context of systemic lupus erythematosus (SLE), a complex autoimmune disease characterized by diverse symptoms and uncertain prognoses, DAs offer guidance to patients in navigating treatment risks and benefits. Although numerous studies have examined the initial implementation of evidence-based tools, there is limited evidence on the organizational factors that influence their long-term sustainability in clinical practice. This gap is particularly salient for digital interventions, where integration into routine workflows and ongoing use require alignment with clinic readiness and culture. This …

Does Patient Age Influence Procedural Management Of Kidney Trauma?, Nizar Hakam, Behzad Abbasi, Umar Ghaffar, Kevin D Li, Hiren Patel, Charles P Jones, Joseph Cuschieri, Benjamin N Breyer

2020-Current year OA Pubs

OBJECTIVES: We aimed to examine the association between patient age and procedural intervention, especially nephrectomy, in patients with renal trauma in the National Trauma Data Bank (NTDB).

MATERIALS AND METHODS: We queried the 2013-2020 NTDB for adult renal trauma patients with an American Association for the Surgery of Trauma (AAST) grade. Patients without AAST grade or with no sign of life were excluded. We constructed a multinomial logistic regression model to demonstrate the association between age and procedural interventions (renal angioembolization, renorrhaphy and nephrectomy). Models were adjusted for patient, hospital, and clinical factors.

RESULTS: Our cohort was comprised of 49,884 …

Modeling The Importance Of Life Exposure Factors On Memory Performance In Diverse Older Adults: A Machine Learning Approach, Evan Fletcher, Marianne Chanti-Ketterl, Emily Hokett, Yi Lor, Umesh Venkatesan, Ruijia Chen, Omonigho M. Bubu, Rachel Whitmer, Paola Gilsanz, Zvinka Z. Zlatar

Moss-Magee Rehabilitation Papers

INTRODUCTION: Many health life exposure factors (LEFs) influence cognitive decline and dementia incidence, but their relative importance to episodic memory (an early indicator of cognitive decline) among diverse older adults is unclear. We used machine learning to rank LEFs for memory performance in a large and diverse US cohort.

METHODS: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) and Study of Healthy Aging in African Americans (STAR), participants underwent neuropsychological testing and answered questionnaires about multiple LEFs. XGBoost and Shapley Additive exPlanation values ranked the importance of factors influencing cross-sectional episodic memory in the full sample and by sex and …

Deep Phenotyping Of Obesity: Electronic Health Record-Based Temporal Modeling Study, Xiaoyang Ruan, Shuyu Lu, Liwei Wang, Andrew Wen, Sameer Murali, Hongfang Liu

Faculty, Staff and Student Publications

Background: Obesity affects approximately 40% of adults and 15%-20% of children and adolescents in the United States, and poses significant economic and psychosocial burdens. Currently, patient responses to any single antiobesity medication (AOM) vary significantly, making obesity deep phenotyping and associated precision medicine important targets of investigation.

Objective: This study aimed to evaluate the potential of electronic health records (EHR) as a primary data source for obesity deep phenotyping. We conducted an in-depth analysis of the data elements and quality available from obesity patients prior to pharmacotherapy and applied a multimodal longitudinal deep autoencoder to investigate the feasibility, data requirements, …

Multi-Ancestral Genome-Wide Association Study Of Clinically Defined Nicotine Dependence Reveals Strong Genetic Correlations With Other Substance Use Disorders And Health-Related Traits, Emma C Johnson, Jared V Balbona, Alexander S Hatoum, David A A Baranger, Louis Fox, Paul W Jeffries, Laura J Bierut, Andrew C Heath, Pamela A Madden, Elliot C Nelson, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

BACKGROUND: Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

METHODS: We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

RESULTS: We replicated the well-known association at the

CONCLUSIONS: Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics …

Germline Structural Variations Involving The Pediatric Brain Tumor Transcriptome Include Disease-Relevant And Ancestry-Related Genes, Fengju Chen, Yiqun Zhang, Luis F Paulin, Fritz J Sedlazeck, Chad J Creighton

Faculty, Staff and Students Publications

Background: Germline Structural Variants (SVs) represent an important source of genetic diversity, in large part due to their influence on gene transcription. It is necessary to systematically catalog germline SVs and their associated impacted genes across different cohorts and tissue and cellular contexts, including pediatric brain or Central Nervous System (CNS) tumors.

Methods: We combined RNA with whole genome sequencing across 1430 pediatric brain or CNS tumor patients from the Children's Brain Tumor Network. We set out to systematically identify genes for which the proximity of germline SVs was recurrently and significantly associated with differential expression in the tumor sample …

Dexamethasone-Eluting Cochlear Implants Reduce Inflammation And Foreign Body Response In Human And Murine Cochleae, Muhammad Taifur Rahman, Keiko Hirose, Et Al.

2020-Current year OA Pubs

The inflammatory foreign body response (FBR) following cochlear implantation (CI) can negatively impact CI outcomes, including increased electrode impedances. This study aims to investigate the long-term efficacy of dexamethasone-eluting cochlear implant and locally delivered dexamethasone, a potent anti-inflammatory glucocorticoid, on the intracochlear FBR and electrical impedance post-implantation in a murine model. Preliminary impedance data in humans are also provided as a complement to the murine data to illustrate generalizability and reinforce implications related to clinical application. The left ears of CX3CR1

Dissatisfaction And Residual Symptoms In Younger And Older Adult Patients After Total Knee Arthroplasty, Nicholas Pohl, Parker Brush, Adrian Santana, Sebastian Fras, Eleanor Jenkins, Arjun Saxena

Department of Orthopaedic Surgery Faculty Papers

INTRODUCTION: Total knee arthroplasty (TKA) is an increasingly used treatment option for younger patients with osteoarthritis. Previous research has found only 66% patients < 60 years who underwent TKA postoperatively reported that their knees felt normal. However, the prior studies did not compare underlying causes for dissatisfaction based on age. This study compared the satisfaction and residual symptom rates between patients ages < 60 and ≥60 years and identified specific reasons for their dissatisfaction between the age groups.

METHODS: Patients who underwent unilateral TKA for osteoarthritis from 2014 to 2016 were electronically sent a 15-question survey pertaining to surgery satisfaction. Following patient identification and survey completion, patient demographics, medical history, surgical time, and length of stay were collected through manual review of medical records. Patients who completed surveys were grouped by age (< 60 years or ≥60 years) for analysis.

RESULTS: In total, 1189 ≥ 60-year-old patients and 388 < 60-year-old patients were included. Most patients in both cohorts reported satisfaction with overall knee function (< 60: 68.6%; ≥60: 71.8%; P = 0.175). Fewer < 60-year patients reported normal knee function (66.5% vs. 75.2%; P < 0.001). The most common residual symptom in both cohorts was continued pain.

CONCLUSION: Patients younger than 60 years reported less satisfaction with performing normal activities …

Revisiting The Effect Of Udenafil On Exercise Performance In Patients With Fontan Circulation: Results Of A Post Hoc Analysis Of The Fuel Trial., David J. Goldberg, Victor Zak, Chenwei Hu, Adam M. Lubert, Rahul H. Rathod, Daniel J. Penny, Robert Whitehill, Kurt R. Schumacher, Salil Ginde, Michelle Ploutz, Gi Beom Kim, Todd T. Nowlen, Michael V. Dimaria, Benjamin P. Frischhertz, Jonathan B. Wagner, Kimberly E. Mchugh, Brian W. Mccrindle, Mark J. Cartoski, Jon Detterich, Anji T. Yetman, Anitha S. John, Marc E. Richmond, Matthew Files, R Mark Payne, Andrew S. Mackie, Christopher K. Davis, William B. Orr, Ruchira Garg, Kevin D. Hill, Jennifer S. Yauck, Michael G. Mcbride, James Yeager, Gail D. Pearson, Stephen M. Paridon, Bryan H. Goldstein

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In the FUEL (Fontan Udenafil Exercise Longitudinal) trial, a positive treatment effect was identified for outcomes at the ventilatory anaerobic threshold but not for the primary outcome, oxygen consumption (Vo₂ in participants with near-normal baseline exercise performance.

METHODS: Participants were divided into subgroups by baseline predicted peak Vo₂ (< 80% versus ≥80%). Treatment effect was evaluated in those with a baseline peak Vo2 < 80% predicted and linear regression was performed to examine the interaction between subgroup and response to therapy for the primary and secondary outcomes.

RESULTS: Of the 379 participants with paired exercise data, 302 (80%) had a baseline peak Vo₂ < 80% predicted. In this subgroup, the primary outcome of peak Vo₂ improved significantly after 6 months of udenafil treatment, when compared with placebo (0.23±4.17 mL/kg per min versus -0.90±3.74 mL/kg per min; P=0.021). Secondary outcome measures, including Vo₂ at …

Genomic Editing Of A Pathogenic Sequence Variant In Acta2 Rescues Multisystemic Smooth Muscle Dysfunction Syndrome In Mice, Qianqian Ding, Peiheng Gan, Zhisheng Xu, Hui Li, Lei Guo, Camryn Macdonald, Wei Tan, Efrain Sanchez-Ortiz, John R Mcanally, Yu Zhang, Dileep Karri, Lin Xu, Ning Liu, Eric N Olson

Faculty, Staff and Student Publications

Background: Vascular smooth muscle cells (SMCs), the predominant cell type in the aortic wall, play a crucial role in maintaining aortic integrity, blood pressure, and cardiovascular function. Vascular SMC contractility and function depend on ACTA2 (smooth muscle α-actin 2). The pathogenic variant ACTA2 c.536G>A (p.R179H) causes multisystemic smooth muscle dysfunction syndrome, a severe disorder marked by widespread smooth muscle abnormalities, resulting in life-threatening aortic disease and high risk of early death from aneurysms or stroke. No effective treatments exist for multisystemic smooth muscle dysfunction syndrome.

Methods: To develop a comprehensive therapy for multisystemic smooth muscle dysfunction syndrome, we used …

Lipid-Laden Microglia: Characterization And Roles In Diseases, Jiani Xing, Takese Mckenzie, Jian Hu

Faculty, Staff and Student Publications

Microglia are resident phagocytes of the central nervous system that play an essential role in brain development and homeostasis. When the intracellular lipid content exceeds the metabolic capacity of microglia, lipid droplets accumulate, giving rise to a distinct population termed lipid-laden microglia (LLMs). LLMs have been implicated in various neuroinflammatory and neurodegenerative diseases, functioning as both regulators/indicators of inflammation and potential therapeutic targets. This review summarizes the current research on LLMs, focusing on disease-specific regulators and functions, protective roles, interactions with neighboring cells, and advances in diagnostic and analytical tools. We also discuss the blurred distinction between LLMs and macrophages, …