Medicine and Health Sciences Commons^™

A Deep Learning Strategy To Identify Cell Types Across Species From High-Density Extracellular Recordings, Maxime Beau, David J Herzfeld, Francisco Naveros, Marie E Hemelt, Federico D'Agostino, Marlies Oostland, Alvaro Sánchez-López, Young Yoon Chung, Michael Maibach, Stephen Kyranakis, Hannah N Stabb, M Gabriela Martínez Lopera, Agoston Lajko, Marie Zedler, Shogo Ohmae, Nathan J Hall, Beverley A Clark, Dana Cohen, Stephen G Lisberger, Dimitar Kostadinov, Court Hull, Michael Häusser, Javier F Medina

Faculty, Staff and Students Publications

High-density probes allow electrophysiological recordings from many neurons simultaneously across entire brain circuits but fail to reveal cell type. Here, we develop a strategy to identify cell types from extracellular recordings in awake animals and reveal the computational roles of neurons with distinct functional, molecular, and anatomical properties. We combine optogenetics and pharmacology using the cerebellum as a testbed to generate a curated ground-truth library of electrophysiological properties for Purkinje cells, molecular layer interneurons, Golgi cells, and mossy fibers. We train a semi-supervised deep learning classifier that predicts cell types with greater than 95% accuracy based on the waveform, discharge …

The Geographic Identification Of Elevated Suicide Risk Model: Evaluating A Method For Examining Suicide-Related Behaviors At The Neighborhood Level In Harris County, Texas, Ryan M Hill, Sam C Cacace, Austin Starkey, Tyler Hendley, Jackson Bolner, Angela Cummings, Angie Hayes, Robert J Cramer

Faculty, Staff and Students Publications

Background: The 2024 National Strategy for Suicide Prevention has called for the development of community-based suicide prevention resources, and improved existing prevention efforts. In line with such efforts, Hill and colleagues developed the Geospatial Identification of Elevated Suicide Risk model that estimates the relative prevalence of adolescent suicide risk within specific geographical areas. The current study seeks to further evaluate and refine the model for use as a tool to evaluate risk and protective factors at the neighborhood level.

Method: Drawing from multiple sources, data was collected detailing adolescent suicidal ideation, suicide attempts, suicide fatalities, and census tract characteristics. Utilizing …

Age-Related Meningeal Extracellular Matrix Remodeling Compromises Cns Lymphatic Function, Kate Hitpass Romero, Taylor J Stevenson, Leon C D Smyth, Ben Watkin, Samuel J C Mccullough, Luca Vinnell, Amy M Smith, Patrick Schweder, Jason A Correia, Jonathan Kipnis, Mike Dragunow, Justin Rustenhoven

2020-Current year OA Pubs

Efficient clearance of central nervous system (CNS) waste proteins and appropriate immune surveillance is essential for brain health. These processes are facilitated by lymphatic networks present in the meninges that drain cerebrospinal fluid (CSF). Age-related impairments to meningeal lymphatic drainage contribute to CNS waste accumulation and immune dysfunction, yet the underlying mechanisms remain poorly understood. Here, we identify extracellular matrix (ECM) remodeling in the aged dura as a key driver of CSF clearance deficits, demonstrating that peri-lymphatic collagen accumulation disrupts lymphatic function. Exploring immune-derived factors contributing to this ECM remodeling, we identify transforming growth factor beta 1 (TGFβ1) as a …

Developing An Online Community Advisory Board (Cab) Of Parents From Social Media To Co-Design An Human Papillomavirus Vaccine Intervention: Participatory Research Study, Regan M. Murray, Shawn C. Chiang, Ann C. Klassen, Jennifer A. Manganello, Amy E. Leader, Wen-Juo Lo, Philip M. Massey

Department of Medical Oncology Faculty Papers

BACKGROUND: Social media health interventions have grown significantly in recent years. However, researchers are still developing innovative methods to meaningfully engage online communities to inform research activities. Little has been documented describing this approach of using online community advisory boards (CABs) to co-create health communication interventions on social media.

OBJECTIVE: This study describes the formation, engagement, and maintenance of an online CAB focused on co-creating a health education intervention for parents regarding the human papillomavirus (HPV) vaccine. The study provides guiding principles for public health researchers implementing such CABs in future digital health interventions.

METHODS: In May 2020, Twitter was …

Using The Healthy Native Youth Implementation Toolbox To Provide Web-Based Adolescent Health Promotion Decision Support To American Indian And Alaska Native Communities: Implementation Study, Amrita Sidhu, Ross Shegog, Stephanie Craig-Rushing, Nicole Trevino, Michelle Singer, Cornelia Jessen, Gwenda Gorman, Sean Simpson, Melissa Peskin, Belinda Hernandez, Christine Markham

Faculty, Staff and Student Publications

Background: American Indian and Alaska Native (AI/AN) youth experience numerous health inequities, including those in sexual, reproductive, and mental health. Implementation of culturally relevant, age-appropriate evidence-based programs may mitigate these inequities. However, numerous barriers limit the adoption and implementation of evidence-based adolescent health promotion programs in AI/AN communities.

Objective: This study examines user reach and engagement from 2022 to 2024 of web-based decision support (the Healthy Native Youth [HNY] website and the embedded HNY Implementation Toolbox), designed to increase the implementation of evidence-based adolescent health promotion programming in AI/AN communities.

Methods: Promotional strategies were designed for optimal geographic reach to …

Elevated Mitochondrial Membrane Potential Is A Therapeutic Vulnerability In Dnmt3a-Mutant Clonal Hematopoiesis, Kira A Young, Grant A Challen, Et Al.

2020-Current year OA Pubs

The competitive advantage of mutant hematopoietic stem and progenitor cells (HSPCs) underlies clonal hematopoiesis (CH). Drivers of CH include aging and inflammation; however, how CH-mutant cells gain a selective advantage in these contexts is an unresolved question. Using a murine model of CH (Dnmt3a

Mri Distance Measures As A Predictor Of Subsequent Clinical Status During The Preclinical Phase Of Alzheimer's Disease And Related Disorders, Xinyi Zhang, John C Morris, Tammie L S Benzinger, Et Al.

2020-Current year OA Pubs

Brain atrophy over time, as measured by magnetic resonance imaging (MRI), has been shown to predict subsequent cognitive impairment among individuals who were cognitively normal when first evaluated, indicating that subtle brain atrophy associated with Alzheimer's disease (AD) may begin years before clinical symptoms appear. Traditionally, atrophy has been quantified by differences in brain volume or thickness over a specified timeframe. Research indicates that the rate of atrophy varies across different brain regions, which themselves exhibit complex spatial and hierarchical organizations. These characteristics collectively emphasize the need for diverse summary measures that can effectively capture the multidimensional nature of degeneration. …

Plasma Proteomic Biomarkers Of Physical Frailty In Heart Failure: A Propensity Score Matched Discovery-Based Pilot Study, Quin Denfeld, Noelle Pavlovic, Christopher Lee, Jon Jacobs, Mary Roberts Davis, Samantha Powell, Marina Gritsenko, Susan Joseph, Beth Habecker

Division of Cardiology Faculty Papers

BACKGROUND: Physical frailty is highly prevalent in heart failure (HF), but we lack an understanding of the underlying pathophysiology. Proteomic evaluation of plasma samples may elucidate potential mechanisms and biomarkers of physical frailty in HF.

OBJECTIVES: We aimed to identify plasma proteomic biomarkers that are differentially expressed between physically frail and non-physically frail adults with HF.

METHODS: This was a secondary analysis of a subset of data and plasma samples from a study of frailty among patients with New York Heart Association (NYHA) Functional Classification I-IV HF. Physical frailty was measured using the Frailty Phenotype Criteria. Propensity score matching was …

Evolution Of The Tumor Immune Landscape During Treatment With Tebentafusp, A T Cell Receptor-Cd3 Bispecific, Joseph Sacco, Peter Kirk, Emma Leach, Alexander Shoushtari, Richard Carvajal, Camille Britton-Rivet, Sophie Khakoo, Laura Collins, Luis De La Cruz-Merino, Zeynep Eroglu, Alexandra Ikeguchi, Paul Nathan, Omid Hamid, Marcus Butler, Sarah Stanhope, Koustubh Ranade, Takami Sato

Department of Medical Oncology Faculty Papers

Metastatic uveal melanoma is an aggressive disease with poor outcome, which is refractory to immune checkpoint inhibitors. A T cell receptor (TCR)-based CD3 bispecific, tebentafusp, delivers clinical benefit in patients with metastatic uveal melanoma. Understanding the molecular basis for the anti-tumor activity of tebentafusp in an indication where checkpoint inhibitors are ineffective could aid in identification of other solid tumor indications where CD3 bispecifics may serve an unmet need. By analyzing tumor biopsies taken prior to treatment, early on-treatment, and at progression (NCT02570308), using RNA sequencing (RNA-seq) and immunohistochemistry (IHC), we show that expression of interferon-related genes in the tumor …

Integrated Analysis Of Molecular And Clinical Features Associated With Overall Survival In Melanoma Patients With Brain Metastasis, Swaminathan Kumar, Meredith S Pelster, Merve Hasanov, Renato A Guerrieri, Courtney W Hudgens, Debora A Ledesma, Fuchenchu Wang, Grant M Fischer, Julie M Simon, Lauren E Haydu, Kalman V Katlowitz, Y N Vashisht Gopal, Jennifer L Mcquade, Lawrence N Kwong, Jason T Huse, Alexander J Lazar, Michael T Tetzlaff, Jeffrey E Gershenwald, Aron Y Joon, Ken Chen, Ziyi Li, Prahlad T Ram, Sherise D Ferguson, Michael A Davies

Faculty, Staff and Student Publications

Melanoma brain metastases (MBMs) are diagnosed in up to 60% of metastatic melanoma patients. Previous studies have identified clinical factors that correlate with overall survival (OS) after MBM diagnosis. However, molecular and immune features associated with OS are poorly understood. An improved understanding of the molecular and immune correlates of OS could provide insights into MBM patient outcomes and guide therapeutic development. Thus, we analyzed clinical features and outcomes of 74 melanoma patients who underwent surgical resection (via craniotomy) between 1991 and 2015 at our institution with RNA-seq data generated from their MBMs. The median post-operative OS was 8.6 months …

Single-Cell Analyses Reveal A Functionally Heterogeneous Exhausted Cd8+ T-Cell Subpopulation That Is Correlated With Response To Checkpoint Therapy In Melanoma, Kelly M Mahuron, Osmaan Shahid, Prachi Sao, Clinton Wu, Alexandra M Haugh, Laura A Huppert, Lauren S Levine, Margaret M Lowe, Michael Alvarado, Markee Micu, Katy K Tsai, Melissa Chow, Meromit Singer, Jason M Schenkel, Arlene H Sharpe, Michael D Rosenblum, Kristen E Pauken, Adil I Daud

Faculty, Staff and Student Publications

PD-1 pathway inhibitors have revolutionized cancer therapy. However, most patients do not durably benefit, highlighting the need for biomarkers to stratify patients as responders or nonresponders. Although CD8+ tumor-infiltrating lymphocytes (TIL) have been associated with immune checkpoint therapy response, there is no consensus on which CD8+ TIL subpopulations have the most prognostic value. Preclinical studies have focused on progenitor-like exhausted CD8+ T cells (TPEX) because TPEX proliferate more in response to PD-1 inhibitors than other exhausted T-cell (TEX) subpopulations. However, immune checkpoint inhibitor treatment drives TPEX differentiation into other TEX populations that can mediate antitumor immunity. These data complicate the …

Distinguishing Multisystem Inflammatory Syndrome In Children From Typhus Using Artificial Intelligence: Mis-C Versus Endemic Typhus (Ai-Met), Angela Chun, Abraham Bautista-Castillo, Isabella Osuna, Kristiana Nasto, Flor M Munoz, Gordon E Schutze, Sridevi Devaraj, Eyal Muscal, Marietta M De Guzman, Kristen Sexson Tejtel, Tiphanie P Vogel, Ioannis A Kakadiaris

Faculty, Staff and Students Publications

Background: The pandemic emergent disease multisystem inflammatory syndrome in children (MIS-C) following coronavirus disease-19 infection can mimic endemic typhus. We aimed to use artificial intelligence (AI) to develop a clinical decision support system that accurately distinguishes MIS-C versus endemic typhus (MET).

Methods: Demographic, clinical, and laboratory features rapidly available following presentation were extracted for 133 patients with MIS-C and 87 patients hospitalized due to typhus. An attention module assigned importance to inputs used to create the 2-phase AI-MET. Phase 1 uses 17 features to arrive at a classification manually (MET-17). If the confidence level is not surpassed, 13 additional features …

Volumetric Changes In Cerebellar Transverse Zones: Age And Sex Effects In Health And Neurological Disorders, Farshid Ghiyamihoor, Payam Paymani, Jarrad Perron, Azam Asemi-Rad, Mehdi Marzban, Aashka Mohite, Karen Ardila, Bara Aljada, Asghar Marzban, Mehnosh Toback, Sherif Eltonsy, Ji Hyun Ko, Tabrez J Siddiqui, Christopher J Steele, Jiming Kong, Mario Manto, M Ethan Macdonald, Jason S Gill, Roy V Sillitoe, Fuat Balcı, Iman Beheshti, Hassan Marzban

Duncan NRI Faculty and Staff Publications

Cerebellar volumetric changes are intricately linked to aging, with distinct patterns across its transverse zones, the functional subdivisions characterized by unique cytoarchitectural and connectivity profiles. Despite research efforts, the cerebellar aging process in health and neurological disorders remains poorly understood. In this study, we investigated the effects of age and sex on total cerebellum, transverse zone, and lobule volumes using MRI data from over 45,000 participants compiled from six neuroimaging datasets. We also propose a framework for estimating cerebellum age as an indicator of cerebellar health. Significant age‐dependent volume reductions were observed across transverse zones, with the …

A Screening Question To Assess Risk Of Using Antibiotics Without A Prescription: A Diagnostic Study, Ashley Collazo, Eva Amenta, Kiara Olmeda, Marissa Valentine-King, Lindsey Laytner, Azalia Mancera, Roger Zoorob, Michael K Paasche-Orlow, Richard L Street, Barbara W Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

Objectives: Non-prescription antibiotic use (using antibiotics without medical advice) is potentially unsafe and promotes antimicrobial resistance. We studied predictors of prior non-prescription use and whether screening for prior non-prescription antibiotic use predicted intention of future non-prescription antibiotic use.

Methods: The survey was performed from January 2020 - June 2021 in six public primary care clinics and two private emergency departments. Prior non-prescription users were respondents who reported taking oral antibiotics for symptoms without contacting a clinician. Intended use was defined by answering yes to the question, "would you use antibiotics without contacting a doctor/nurse/dentist/clinic." We examined predictors for prior non-prescription …

Nitrate Ameliorates Alcohol-Induced Cognitive Impairment Via Oral Microbiota, Xiangxue Li, Zhaojun Ni, Weixiong Shi, Kangqing Zhao, Yanjie Zhang, Lina Liu, Zhong Wang, Jie Chen, Zhoulong Yu, Xuejiao Gao, Ying Qin, Jingwen Zhao, Wenjuan Peng, Jie Shi, Thomas R Kosten, Lin Lu, Lei Su, Yanxue Xue, Hongqiang Sun

Faculty, Staff and Students Publications

Alcohol use is associated with cognitive impairment and dysregulated inflammation. Oral nitrate may benefit cognitive impairment in aging through altering the oral microbiota. Similarly, the beneficial effects of nitrate on alcohol-induced cognitive decline and the roles of the oral microbiota merit investigation. Here we found that nitrate supplementation effectively mitigated cognitive impairment induced by chronic alcohol exposure in mice, reducing both systemic and neuroinflammation. Furthermore, nitrate restored the dysbiosis of the oral microbiota caused by alcohol consumption. Notably, removing the oral microbiota led to a subsequent loss of the beneficial effects of nitrate. Oral microbiota from donor alcohol use disordered …

Left Ventricular Entry To Reduce Brain Lesions During Catheter Ablation: A Randomized Trial, Gregory M Marcus, Roderick Tung, Edward P Gerstenfeld, Trisha F Hue, Feng Lin, Jing Cheng, J Peter Weiss, Wendy S Tzou, Henry Hsia, Ashkan Ehdaie, Daniel H Cooper, T Jared Bunch, Jeffrey Arkles, Babak Nazer, Adam Lee, Alexios Hadjis, Duy T Nguyen, Mihail G Chelu, Joshua Moss, Jonathan C Hsu, Miguel Valderrábano, Prashant D Bhave, Andrew D Beaser, Arvindh Kanagasundram, Oussama Wazni, Jason Bradfield, Grace Wall, Kathleen Chang, Michelle Yang, Gabrielle Montenegro, Sabrina Jarrott, Joel H Kramer, Anthony S Kim, Yvonne M Morris, William P Dillon

Faculty, Staff and Students Publications

Background: Catheter ablation of ventricular arrhythmias, one of the most rapidly growing procedures in cardiac electrophysiology, is associated with magnetic resonance imaging-detected brain lesions in more than half of cases. Although a retrograde aortic approach is conventional, modern tools enable entry through a transseptal approach that may avoid embolization of debris from the arterial system. We sought to test the hypothesis that a transseptal puncture would mitigate brain injury compared with a retrograde aortic approach.

Methods: The TRAVERSE trial (Transseptal Versus Retrograde Aortic Ventricular Entry to Reduce Systemic Emboli) was a multicenter randomized controlled comparative effectiveness trial. Patients with left …

Atm-Dependent Dna Damage Response Constrains Cell Growth And Drives Clonal Hematopoiesis In Telomere Biology Disorders, Christopher M. Sande, Karolyn A. Oetjen, Daniel C. Link, Andrew E. Gelman, Laneshia K. Tague, Et Al.

2020-Current year OA Pubs

Telomere biology disorders (TBDs) are genetic diseases caused by defective telomere maintenance. TBD patients often develop bone marrow failure and have an increased risk of myeloid neoplasms. To better understand the factors underlying hematopoietic outcomes in TBD, we comprehensively evaluated acquired genetic alterations in hematopoietic cells from 166 pediatric and adult TBD patients. Of these patients, 47.6% (28.8% of children, 56.1% of adults) had clonal hematopoiesis. Recurrent somatic alterations involved telomere maintenance genes (7.6%), spliceosome genes (10.4%, mainly U2AF1 p.S34), and chromosomal alterations (20.2%), including 1q gain (5.9%). Somatic variants affecting the DNA damage response (DDR) were identified in 21.5% …

Cerebrospinal Fluid Proteomics Identification Of Biomarkers For Amyloid And Tau Pet Stages, Zhibo Wang, Yuhan Chen, Katherine Gong, Bote Zhao, Yuye Ning, Meilin Chen, Yan Li, Muhammad Ali, Jigyasha Timsina, Menghan Liu, Carlos Cruchaga, Jianping Jia

2020-Current year OA Pubs

Accurate staging of Alzheimer's disease (AD) pathology is crucial for therapeutic trials and prognosis, but existing fluid biomarkers lack specificity, especially for assessing tau deposition severity, in amyloid-beta (Aβ)-positive patients. We analyze cerebrospinal fluid (CSF) samples from 136 participants in the Alzheimer's Disease Neuroimaging Initiative using more than 6,000 proteins. We apply machine learning to predict AD pathological stages defined by amyloid and tau positron emission tomography (PET). We identify two distinct protein panels: 16 proteins, including neurofilament heavy chain (NEFH) and SPARC-related modular calcium-binding protein 1 (SMOC1), that distinguished Aβ-negative/tau-negative (A-T-) from A+ individuals and nine proteins, such as …

Attitudes Of Female Carriers Of X-Linked Hypohidrotic Ectodermal Dysplasia Towards Prenatal Treatment And Their Decisions During A Pregnancy With A Male Fetus, Holm Schneider, Michael Schneider, Massimiliano Lia, Dorothy K Grange, Smail Hadj-Rabia, Angus Clarke, Mary Fete, Agnes Jaulent, Marlene Guiraud, Anthony Odibo, Florian Faschingbauer

2020-Current year OA Pubs

BACKGROUND: X-linked hypohidrotic ectodermal dysplasia (XLHED) is a severe genetic disorder that may be treatable with short-term protein replacement therapy during fetal development. This is currently being investigated in a multicenter clinical trial. Affected fetuses can be identified by the number of tooth germs during a routine ultrasound scan in mid-gestation. To understand the attitudes of female XLHED carriers towards prenatal treatment and ultrasonographic screening of the fetus, we analyzed an earlier and a very recent survey among those women and the actual decisions of potential trial participants.

METHODS: Initial analyses were based on a self-administered survey of 167 female …

Association Between High Triglyceride-Glucose Index And Macce In Hypertriglyceridemia Patients Undergoing Percutaneous Coronary Intervention, Yichuan Wang, Yanfeng Lu, Shanshan Gao, Zhong Zhong, Jasmine Bao, Bo Liu, Ruihan Fan, Ning Guo

SKMC Student Presentations and Publications

BACKGROUND: With a focus on metabolism-related cardiovascular diseases, the triglyceride-glucose (TyG) index has been used as a surrogate marker of insulin resistance in the prognosis of coronary heart disease. However, the prognostic role of the TyG index in patients with elevated triglycerides, still requires further research. This study aimed to investigate the association between the TyG index and Major Adverse Cardiac and Cerebrovascular Events (MACCE) in patients with hypertriglyceridemia undergoing drug-eluting stent percutaneous coronary intervention (DES-PCI).

METHODS: Out of 2250 patients, 813 with hypertriglyceridemia who underwent DES-PCI were retrospectively analyzed. MACCE was regarded as the primary endpoint. Kaplan-Meier (KM) curves …

Left Ventricular Hypertrophy Among Adults In A Population-Based Cohort In Haiti, Anju Ogyu, Lisa De Las Fuentes, Victor G Dávila-Román, Et Al.

2020-Current year OA Pubs

Left ventricular hypertrophy (LVH) is one of the strongest predictors of cardiovascular disease (CVD) and mortality; yet the means to diagnose LVH in resource-constrained settings remain limited. The objectives of this study were to determine LVH prevalence by transthoracic echocardiography (TTE) in a high-risk group, and compare TTE vs. electrocardiography (ECG-LVH) for LVH detection. We analyzed enrollment data from the Haiti cardiovascular disease cohort study on adults (≥ 18 years, n = 3,005) in Port-au-Prince between 2019 and 2021. All participants underwent questionnaires, vital signs, physical exams, and 12-lead ECGs. TTEs were acquired on those with hypertension or exhibiting CVD …

Vacuum Erectile Devices For Erectile Dysfunction: Recommendations From The 5th International Consultation On Sexual Medicine, Run Wang, Francisco E Martins, David Ralph, Georgios Hatzichristodoulou, Daniar Osmonov, Justin Parker, Sung Hun Sean Park, Ignacio Moncada, Carlo Bettocchi, Ricardo Munarriz, Tobias Köhler

Faculty, Staff and Student Publications

Introduction: Vacuum erectile device (VED) is 1 of the main approved therapies for erectile dysfunction (ED). The introduction of phosphodiesterase type 5 inhibitor (PDE5i) for ED significantly changed the roles of VED in contemporary sexual medicine.

Objective: To provide updated clinical evidence to inform health care providers on best practices with VED.

Methods: A consensus panel was held with leading sexual medicine experts during the 5th International Consultation on Sexual Medicine (ICSM). Relevant peer-reviewed literature was reviewed with focus on research from the last 10 years, but not limited to the last 10 years. The expert panel generated consensus statements …

Results Of The Phase I/Ii Study And Preliminary B-Cell Gene Signature Of Combined Inhibition Of Glutamine Metabolism And Egfr In Colorectal Cancer, Kristen K Ciombor, Seong-Woo Bae, Jennifer G Whisenant, Gregory D Ayers, Quanhu Sheng, Todd E Peterson, Gary T Smith, Kangyu Lin, Saikat Chowdhury, Preeti Kanikarla Marie, Alexey Sorokin, Allison S Cohen, Laura W Goff, Dana B Cardin, John Paul Shen, Scott Kopetz, Cathy Eng, Yu Shyr, Jordan Berlin, H Charles Manning

Faculty, Staff and Student Publications

Purpose: EGFR-targeting mAbs are essential for managing rat sarcoma virus wild-type metastatic colorectal cancer (mCRC), but their limited efficacy necessitates exploring immunologic and metabolic factors influencing response. This study evaluated glutamine metabolism targeting with EGFR inhibition to identify response biomarkers in patients with prior anti-EGFR treatment progression.

Patients and methods: We conducted a phase I/II trial in patients with KRAS wild-type mCRC, combining panitumumab (6 mg/kg) and CB-839 (600 mg/kg or 800 mg/kg), hypothesizing that the dual inhibition of glutamine metabolism and MAPK signaling would enhance outcomes. As study correlatives, we investigated the B-cell activation signature "B-score" and glutamine PET …

Germline Pathogenic Drosha Variants Are Linked To Pineoblastoma And Wilms Tumor Predisposition, Peter N Fiorica, Lisa Golmard, Jung Kim, Riyue Bao, Frank Y Lin, Angshumoy Roy, Allison Pribnow, Melissa R Perrino, Julien Masliah-Planchon, Sophie Michalak-Provost, Jennifer Wong, Mathilde Filser, Dominique Stoppa-Lyonnet, Franck Bourdeaut, Afane Brahimi, Olivier Ingster, Giselle Saulnier Sholler, Sarah A Jackson, Mark M Sasaki, Trent Fowler, Anita Ng, Ryan J Corbett, Rebecca S Kaufman, Jeremy S Haley, David J Carey, Kuan-Lin Huang, Sharon J Diskin, Jo Lynne Rokita, Hussam Al-Kateb, Rose B Mcgee, Joshua D Schiffman, Kenneth S Chen, Douglas R Stewart, D Williams Parsons, Sharon E Plon, Kris Ann P Schultz, Kenan Onel

Center for Medical Ethics and Health Policy Staff Publications

Purpose: DROSHA, DGCR8, and DICER1 regulate miRNA biogenesis and are commonly mutated in cancer. Although DGCR8 and DICER1 germline pathogenic variants (GPV) cause autosomal dominant tumor predisposition, no association between DROSHA GPVs and clinical phenotypes has been reported.

Experimental design: After obtaining informed consent, sequencing was performed on germline and tumor samples from all patients. The occurrence of germline DROSHA GPVs was investigated in large pediatric and adult cancer datasets. The population prevalence of DROSHA GPVs was investigated in the UK Biobank and Geisinger DiscovEHR cohorts.

Results: We describe nine children from eight families with heterozygous DROSHA GPVs and a …

Proteogenomic Characterization Of Non-Functional Pancreatic Neuroendocrine Tumors Unravels Clinically Relevant Subgroups, Shunrong Ji, Lihua Cao, Jing Gao, Yang Du, Zeng Ye, Xin Lou, Fen Liu, Yehan Zhang, Junfeng Xu, Xiaohan Shi, Huan Wang, Penghao Li, Yikai Li, Hongxu Chen, Zhicheng Yang, Suizhi Gao, Wuhu Zhang, Dan Huang, Shujuan Ni, Miaoyan Wei, Fei Wang, Yan Wang, Tian Ding, Desheng Jing, Guixiong Fan, Zhiyun Gong, Renquan Lu, Yi Qin, Jie Chen, Xiaowu Xu, Pei Wang, Bing Zhang, Li Ding, Ana I Robles, Henry Rodriguez, David K Chang, Ralph H Hruban, Dong Gao, Daming Gao, Gang Jin, Hu Zhou, Jianmin Wu, Xianjun Yu

Faculty, Staff and Students Publications

The majority of neuroendocrine neoplasms in pancreas are non-functional pancreatic neuroendocrine tumors (NF-PanNETs), which exhibit a high occurrence of distant metastases with limited therapeutic options. Here, we perform a comprehensive molecular characterization of 108 NF-PanNETs through integrative analysis of genomic, transcriptomic, proteomic, and phosphoproteomic profiles. Proteogenomic analysis provides functional insights into the genomic driver alterations of NF-PanNETs, revealing a potential mediator of MEN1 alterations using Men1-conditional knockout mice. Machine-learning-based modeling uncovers a three-protein signature as an independent prognostic factor, which is validated by an independent external cohort. Proteomic and phosphoproteomic-based stratification identifies four subtypes with distinct molecular characteristics, immune microenvironments, …

Somatodendritic Orientation Determines Tdcs-Induced Neuromodulation Of Purkinje Cell Activity In Awake Mice, Carlos A Sánchez-León, Guillermo Sánchez-Garrido Campos, Marta Fernández, Álvaro Sánchez-López, Javier F Medina, Javier Márquez-Ruiz

Faculty, Staff and Students Publications

Transcranial direct-current stimulation (tDCS) of the cerebellum is a promising non-invasive neuromodulatory technique being proposed for the treatment of neurological and neuropsychiatric disorders. However, there is a lack of knowledge about how externally applied currents affect neuronal spiking activity in cerebellar circuits in vivo. We investigated how Cb-tDCS affects the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex to understand the underlying mechanisms behind the polarity-dependent modulation of neuronal activity induced by tDCS. Mice (n=9) were prepared for the chronic recording of local field potentials (LFPs) to assess the actual electric field gradient imposed by …

Surgical Mitral Valve Repair Vs Replacement After Failed Mitral Transcatheter Edge-To-Edge Repair: The Cutting-Edge Registry., Mateo Marin-Cuartas, Jagdip Kang, Thilo Noack, Manuela De La Cuesta, Markus Krane, Volkmar Falk, Lenard Conradi, Christian Hagl, Maurizio Taramasso, Tom C Nguyen, D Scott Lim, Gorav Ailawadi, Michael J Mack, Robert L Smith, Anita W Asgar, Kendra J Grubb, Luigi Pirelli, Paolo Denti, Thomas Modine, Michael J Reardon, Tamim M Nazif, Vinayak N Bapat, Tsuyoshi Kaneko, Philipp Kiefer, Michael A Borger, Gilbert H L Tang, Syed Zaid

Faculty, Staff and Students Publications

Background: The impact of mitral valve (MV) surgery type after failed mitral transcatheter edge-to-edge repair (M-TEER) has not been well studied.

Objectives: The aim of this study was to compare the outcomes of MV repair vs replacement after failed M-TEER.

Methods: From 2009 to 2020, a total of 332 patients across 34 centers from the CUTTING-EDGE registry underwent MV surgery after M-TEER. Outcomes were compared between MV repair and replacement. Primary outcomes included 30-day mortality and 1-year survival after MV surgery.

Results: Among enrolled patients (mean age 73.8 ± 10.1 years, median Society of Thoracic Surgeons Predicted Risk of Mortality …

Pilot First-In-Human Ccr2 Pet/Ct To Detect Abdominal Aortic Aneurysm Wall Instability, Santiago Elizondo-Benedetto, Deborah Sultan, Ryan Wahidi, Mahdjoub Hamdi, Mohamed S Zaghloul, Shahab Hafezi, Batool Arif, Laura K Mcdonald, Kitty Harrison, Dakkota Thies, Gyu Seong Heo, Hannah Luehmann, Lisa Detering, J Westley Ohman, Zachary J Wanken, Luis A Sanchez, Joseph E Ippolito, Jie Zheng, Robert J Gropler, Richard Laforest, Yongjian Liu, Mohamed A Zayed

2020-Current year OA Pubs

No abstract provided.

Disc Edema Secondary To Sleep Apnea: A Case Report, Jeannette A. Wong-Powell Od

Optometric Clinical Practice

Background: Bilateral optic disc edema is associated with multiple systemic conditions of potentially dire consequences. Idiopathic intracranial hypertension (IIH) is a common culprit and diagnosis of exclusion, which has been observed in multiple patients with obstructive sleep apnea (OSA) and raised questions of a pathophysiological link between the two.

Case Report: A 28-year-old Caucasian male with history of transient ischemic attack-like symptoms presented with bilateral disc edema prompting a multi-disciplinary work up that included imaging, lumbar puncture, laboratory analysis, neuroophthalmological, cardiological, and pulmonary evaluations that ultimately led to a diagnosis of OSA. The case is unique in that it followed …

A Space-Occupying Lesion Manifesting As Unilateral Optic Disc Edema, Len V. Koh Od, Phd, Anna Wells Od, Lindsay Jansen Od

Optometric Clinical Practice

Background: Primary and secondary orbital diseases can arise from different tissues in the periorbital regions as space-occupying lesion leading to ophthalmic symptoms. Therefore, eye care providers are often the first encounter for these patients.

Case report: A 54-year-old Caucasian male presented as a new patient at the eye clinic with an incidental finding of edema of the left optic disc. After a thorough optometric evaluation, a referral was made to a local ear-nose-throat (ENT) specialist who confirmed a diagnosis of cavernous hemangioma by further neuroimaging. Surgical removal eventuated in resolution of disc edema with restoration of vision.

Conclusion: An insidious …