Digital Commons Network^™

Leveraging Chorionic Villus Biopsies For The Derivation Of Patient-Specific Trophoblast Stem Cells., Kaela Varberg, Ayelen Moreno-Irusta, Allynson Novoa, Brynne Musser, Joseph M. Varberg, Jeremy P. Goering, Irfan Saadi, Khursheed Iqbal, Hiroaki Okae, Takahiro Arima, John Williams, Margareta D. Pisarska, Michael J. Soares

Manuscripts, Articles, Book Chapters and Other Papers

Human trophoblast stem (TS) cells are informative in vitro models for the generation and testing of biologically meaningful hypotheses. The goal of this project was to derive patient-specific TS cell lines from clinically available chorionic villus biopsies. Cell outgrowths were captured from human chorionic villus tissue specimens cultured in modified human TS cell medium. Cell colonies emerged early during the culture and cell lines were established and passaged for several generations. Karyotypes of the newly established chorionic villus-derived trophoblast stem (TS^CV) cell lines were determined and compared to initial genetic diagnoses from freshly isolated chorionic villi. Phenotypes of …

Determining Falls Risk In People With Parkinson's Disease Using Wearable Sensors: A Systematic Review, Maeve Bradley, Sarah O'Loughlin, Eoghan Donlon, Amy Gallagher, Clodagh O'Keeffe, John Inocentes, Federica Ruggieri, Richard B Reilly, Richard Walsh, Tim Lynch, Daniel G Di Luca, Conor Fearon

2020-Current year OA Pubs

A prior history of falls remains the strongest predictor of future falls in individuals with Parkinson's disease (PD). There are limited biomarkers available to identify falls risk before falls begin to occur. The aim of this review is to investigate if features associated with falls risk may be detected by wearable sensors in patients with PD. A systematic search of the MEDLINE, EMBASE, Cochrane, and Cinahl databases was performed. Key quality criteria include sample size adequacy, data collection procedures, and the clarity of statistical analyses. The data from each included study were extracted into defined data extraction spreadsheets. Results were …

Phase Ii Basket Trial Of Dual Anti-Ctla-4 And Anti-Pd-1 Blockade In Rare Tumors (Dart) Swog S1609: Pancreatic Neuroendocrine Neoplasm (Pnen) Cohort, Sandip Pravin Patel, Jillian Fisher, Young Kwang Chae, Luisa Solis Soto, Anup Kasi, Bhavana Konda, Mark Walshauser, Edwin Parra, Jiexin Zhang, Caroline Duault, Edgar Gonzalez-Kozlova, Ganiraju Manyam, Jianhua Zhang, Hong Chen, Dzifa Yawa Duose, Caddie Laberiano Fernandez, Raja Luthra, Gheath Al-Atrash, Seunghee Kim-Schulze, Holden T Maecker, Ignacio I Wistuba, Sacha Gnjatic, J Jack Lee, Jianjun Zhang, Christine M Magner, Helen X Chen, Elad Sharon, Megan Othus, Christopher W Ryan, Charles Blanke, Cara L Haymaker, Razelle Kurzrock

Faculty, Staff and Student Publications

Purpose: SWOG S1609 Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) studied the efficacy of ipilimumab combined with nivolumab across multiple rare tumor types. We report the results of the pancreatic neuroendocrine neoplasm (PNEN) cohort.

Experimental design: Treatment consisted of ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously every 2 weeks. The primary endpoint was overall response rate (ORR) (Response Evaluation Criteria In Solid TumorsRECIST V.1.1). Secondary endpoints include progression-free survival (PFS), overall survival (OS), and toxicity. Clinical benefit rate (includes ORR plus stable disease (SD)>6 months was examined. Correlative …

The Epilepsy Centers Of Excellence At The Veterans Health Administration, Zulfi Haneef, Caleb A Casanova, Vincent Zhang, Jennifer R Bonds King, Rizwana Rehman, Nina I Garga, Glenn D Graham, Alan R Towne

Faculty, Staff and Students Publications

Introduction: The Veterans Health Administration (VHA) Epilepsy Centers of Excellence (ECoE) was established in 2008 to provide specialized care for veterans with epilepsy. Although established more than a decade ago, there has been no systematic evaluation of the ECoE's performance in key mission areas. We evaluated their performance in several key mission areas-clinical care, research, education, and outreach-since inception to evaluate their success in meeting the initial mandate.

Materials and methods: We analyzed available data from relevant literature, ECoE annual reports, and the ECoE website between 2011 and 2023. Clinical care is the primary mission of the ECoE and was …

"Holy Cow, Where Do I Sign Up?" Attitudes Of Military Veterans Toward Epigenomic Biomarker Toxic Exposure Testing, Stacey Pereira, Calvin Apodaca, Kyle Slominski, Rachele K Lipsky, Cristian Coarfa, Cheryl L Walker, Amy L Mcguire, Lea Steele, Drew A Helmer

Center for Medical Ethics and Health Policy Staff Publications

Introduction: After the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics Promise to Address Comprehensive Toxics (PACT) Act in 2022, there has been a great interest in studying toxic exposures encountered during military service. Development of epigenomic biomarkers for exposures could facilitate understanding of exposure-related health effects, but such testing could also provide unwanted information.

Materials and methods: We explored attitudes toward epigenomic biomarker research and the potential to test for past exposures using semistructured interviews with Veterans (n = 22) who experienced potentially harmful exposures.

Results: Twenty Veterans said they would hypothetically want to receive …

Hydration Status And Acute Kidney Injury Biomarkers In Ncaa Female Soccer Athletes During Preseason Conditioning, Daniel E Newmire, Erica M Filep, Jordan B Wainwright, Heather E Webb, Darryn S Willoughby

Faculty, Staff and Students Publications

Exercise training in extreme temperatures concurrent with hypohydration status may potentiate the development of acute kidney injury (AKI) in young, healthy persons.

Background/Objectives: It is unknown how repeated training bouts in ambient higher temperatures and humidity may influence measures of AKI. The purpose of this study was to investigate hydration status and renal biomarkers related to AKI in NCAA Division I female soccer athletes during preseason conditioning.

Methods: A convenience sample of n = 21 athletes were recruited (mean ± SEM; age: 19.3 ± 0.25 y; height: 169.6 ± 1.36 cm; mass: 68.43 ± 2.46 kg; lean body …

Letter Of Concern From The Association Of Academic Chairs Of Emergency Medicine Regarding Acgme Proposed Changes, Richard J Hamilton, Lance B Becker, Richard E Wolfe, D Adam Algren, Thomas Arnold, Michael Baumann, Ross P Berkeley, Terrell S Caffery, Chad M Cannon, Theodore J Corbin, Michael E Chansky, Harinder S Dhindsa, Charles L Emerman, David A Farcy, Chris Fox, Michael A Gibbs, Christopher S Goode, Steven Andy Godwin, Dietrich Jehle, David Johnson, Samuel M Keim, Babak Khazaeni, Barry J Knapp, Clint Hawthorne, John D Hoyle, Michael Christopher Kurz, Evan Leibner, Robert Mcnamara, Robert F Mccormack, Edward A Michelson, Chadwick Miller, Ashley Norse, Andrew Nugent, Brian J O'Neil, David T Overton, Edward A Panacek, William F Paolo, Denis R Pauzé, Amanda L Perez, Ralph J Riviello, Scott W Rodi, Peter S Pang, Juan A Gonzalez Sanchez, David Seaberg, Adam Schwartz, Stephen A Shiver, David P Sklar, Ben C Smith, Jeffrey R Stowell, Marc D Squillante, J Jeremy Thomas, Terry Vanden Hoek, Gregory A Volturo, E Lea Walters, Thomas E Wyatt, Donald M Yealy

Faculty, Staff and Student Publications

This letter, signed by over 50 academic chairs of emergency medicine, urges the ACGME to reconsider a proposed mandate requiring all emergency medicine residency programs to adopt a four-year training model. The authors argue that current three-year programs are supported by data demonstrating equivalent educational and clinical outcomes compared to four-year formats. They criticize the flawed survey methodology underpinning the proposal, note the loss of milestone-based training flexibility, and highlight the lack of added scholarly or clinical value in the fourth year. The letter also outlines negative consequences for fellowship participation, workforce development, trainee debt, and diversity. The signatories advocate …

Mis-Splicing-Derived Neoantigens And Cognate Tcrs In Splicing Factor Mutant Leukemias., Won Jun Kim, Edie I Crosse, Emma De Neef, Inaki Etxeberria, Erich Y Sabio, Eric Wang, Jan Philipp Bewersdorf, Kuan-Ting Lin, Sydney X Lu, Andrea Belleville, Nina Fox, Cynthia Castro, Pu Zhang, Takeshi Fujino, Jennifer Lewis, Jahan Rahman, Beatrice Zhang, Jacob H Winick, Alexander M Lewis, Robert F Stanley, Susan Dewolf, Brigita Meškauskaitė Urben, Meril Takizawa, Tobias Krause, Henrik Molina, Ronan Chaligne, Priya Koppikar, Jeffrey Molldrem, Mathieu Gigoux, Taha Merghoub, Anthony Daniyan, Smita S Chandran, Benjamin D Greenbaum, Christopher A Klebanoff, Robert K Bradley, Omar Abdel-Wahab

Faculty Research 2025

Mutations in RNA splicing factors are prevalent across cancers and generate recurrently mis-spliced mRNA isoforms. Here, we identified a series of bona fide neoantigens translated from highly stereotyped splicing alterations promoted by neomorphic, leukemia-associated somatic splicing machinery mutations. We utilized feature-barcoded peptide-major histocompatibility complex (MHC) dextramers to isolate neoantigen-reactive T cell receptors (TCRs) from healthy donors, patients with active myeloid malignancy, and following curative allogeneic stem cell transplant. Neoantigen-reactive CD8⁺ T cells were present in the blood of patients with active cancer and had a distinct phenotype from virus-reactive T cells with evidence of impaired cytotoxic function. T cells …

Unveiling Endoscopic Procedures In Maude: An Etl-Llm Method, Yuheng Shi, Eric Yang, Yang Gong

Faculty, Staff and Student Publications

The increased dependence on patient safety studies using the MAUDE database underscores the critical need to define and standardize the methods for extracting and analyzing event reports. The lack of reproducible methods leads to an inconsistent understanding of reported events and diminishes their effectiveness in informing clinicians. Thus, an ETL pipeline combined with LLMs was proposed to standardize the identification and interpretation of the reports. Using endoscopic clip reports as an example, the ETL-LLM method demonstrates the effectiveness of extracting and analyzing categorical and narrative reports, helping uncover insights related to patient complications, surgical procedures, and device uses. This innovative …

Mis-Splicing-Derived Neoantigens And Cognate Tcrs In Splicing Factor Mutant Leukemias, Won Jun Kim, Edie I Crosse, Emma De Neef, Inaki Etxeberria, Erich Y Sabio, Eric Wang, Jan Philipp Bewersdorf, Kuan-Ting Lin, Sydney X Lu, Andrea Belleville, Nina Fox, Cynthia Castro, Pu Zhang, Takeshi Fujino, Jennifer Lewis, Jahan Rahman, Beatrice Zhang, Jacob H Winick, Alexander M Lewis, Robert F Stanley, Susan Dewolf, Brigita Meškauskaitė Urben, Meril Takizawa, Tobias Krause, Henrik Molina, Ronan Chaligne, Priya Koppikar, Jeffrey Molldrem, Mathieu Gigoux, Taha Merghoub, Anthony Daniyan, Smita S Chandran, Benjamin D Greenbaum, Christopher A Klebanoff, Robert K Bradley, Omar Abdel-Wahab

Faculty, Staff and Student Publications

Mutations in RNA splicing factors are prevalent across cancers and generate recurrently mis-spliced mRNA isoforms. Here we identified a series of bona fide neoantigens translated from highly stereotyped splicing alterations promoted by neomorphic, leukemia-associated somatic splicing machinery mutations. We utilized feature-barcoded peptide-MHC dextramers to isolate neoantigen-reactive T cell receptors (TCRs) from healthy donors, patients with active myeloid malignancy, and following curative allogeneic stem cell transplant. Neoantigen-reactive CD8+ T cells were present in the blood of patients with active cancer and had a distinct phenotype from virus-reactive T cells with evidence of impaired cytotoxic function. T cells engineered with TCRs recognizing …

Visualizing Data For Diabetes Management In Patient Portals, Eric Yang, Lakeidra Salazar, Usha Rijal, Yang Gong

Faculty, Staff and Student Publications

Effectively managing diabetes requires active patient engagement in monitoring crucial health metrics, such as HbA1c and glucose levels. However, many existing patient portals present this information in complex and confusing formats, hindering understanding and communication. This study established a prototype for a user-centered dashboard for diabetes management, designed to enhance patient comprehension and interaction with their health data by utilizing principles of relational data display. By applying Gestalt principles and theories of distributed representation, our dashboard optimizes data visualization through Google Looker Studio, ultimately reducing cognitive load and aiding patients in self-management. The findings emphasize the benefits of user-friendly and …

Encorafenib, Cetuximab, And Mfolfox6 In Braf-Mutated Colorectal Cancer, Elena Elez, Takayuki Yoshino, Lin Shen, Sara Lonardi, Eric Van Cutsem, Cathy Eng, Tae Won Kim, Harpreet Singh Wasan, Jayesh Desai, Fortunato Ciardiello, Rona Yaeger, Timothy S Maughan, Van K Morris, Christina Wu, Tiziana Usari, Robert Laliberte, Samuel S Dychter, Xiaosong Zhang, Josep Tabernero, Scott Kopetz, Breakwater Trial Investigators

Faculty, Staff and Student Publications

Background: First-line treatment with encorafenib plus cetuximab (EC) with or without chemotherapy (oxaliplatin, leucovorin, and fluorouracil [mFOLFOX6]) for BRAF V600E-mutated metastatic colorectal cancer, an aggressive subtype with a poor prognosis, was compared with standard care (chemotherapy with or without bevacizumab) in an open-label, phase 3 trial, which showed significance regarding one of the two primary end points, objective response according to blinded independent central review (odds ratio for EC+mFOLFOX6 vs. standard care, 2.44; one-sided P< 0.001). This result led to accelerated Food and Drug Administration approval of this investigational combination therapy for BRAF V600E-mutated metastatic colorectal cancer, including as first-line therapy. Data on progression-free survival (the second primary end point) and an updated interim analysis of overall …

Pneumococcal Colonization Dynamics Among Young Children With And Without Respiratory Symptoms During The First Year Of The Sars-Cov-2 Pandemic., Liset Olarte, Brian R. Lee, Dithi Banerjee, Douglas Swanson, Christopher J. Harrison, Rangaraj Selvarangan

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Non-pharmaceutical interventions to mitigate the spread of SARS-CoV-2 were implemented across the United States in 2020. These public health measures might influence pneumococcal colonization in younger children and their subsequent risk of invasive pneumococcal disease. Our objective was to evaluate pneumococcal colonization rates in children ≤ 5 years of age with and without respiratory symptoms during the first 12 months of SARS-CoV-2 pandemic (April 2020 - March 2021).

STUDY DESIGN: This is a retrospective cross-sectional study evaluating pneumococcal colonization rates, density and serotype distribution across three study periods (April-July [Period 1], August-November [Period 2] and December-March [Period 3]) after …

A Rubric For Assessing Conformance To The Ten Rules For Credible Practice Of Modeling And Simulation In Healthcare, Alexandra Manchel, Ahmet Erdemir, Lealem Mulugeta, Joy Ku, Bruno Rego, Marc Horner, William Lytton, Jerry Myers, Rajanikanth Vadigepalli

Computational Medicine Center Faculty Papers

The power of computational modeling and simulation (M&S) is realized when the results are credible, and the workflow generates evidence that supports credibility for the context of use. The Committee on Credible Practice of Modeling & Simulation in Healthcare was established to help address the need for processes and procedures to support the credible use of M&S in healthcare and biomedical research. Our community efforts have led to the Ten Rules (TR) for Credible Practice of M&S in life sciences and healthcare. This framework is an outcome of a multidisciplinary investigation from a wide range of stakeholders beginning in 2012. …

What Drives Clinic Follow-Up After Traumatic Spinal Injury? An Observational Cohort Study From Tanzania, Chibuikem A Ikwuegbuenyi, Julie Woodfield, Romani Roman Sabas, Sean Inzerillo, Noah Willett, Magalie Cadieux, Scott L Zuckerman, Francois Waterkeyn, Halinder S Mangat, Hamisi K Shabani, Roger Härtl

2020-Current year OA Pubs

OBJECTIVES: To evaluate factors associated with clinic follow-up after traumatic spinal injury (TSI) in Tanzania, focusing on demographic, injury-related and hospital variables. We hypothesised that socioeconomic and injury-specific factors would predict follow-up adherence.

DESIGN: Retrospective observational cohort study.

SETTING: Tertiary government referral centre for neurosurgery and orthopaedics in Dar es Salaam, Tanzania.

PARTICIPANTS: 443 adults with TSI admitted between September 2016 and October 2021. Inclusion criteria included survival to discharge and availability of the discharge date. Patients with missing data were excluded.

PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were any clinic follow-up and 1-year follow-up post-discharge. Secondary outcome was …

Low Frequency, High Complexity: Assessing Skill Decay In Transesophageal Echocardiography Post-Simulation Training, Enyo Ablordeppey, Emily Terian, Collyn T Murray, Laura Wallace, Wendy Huang, Erica Blustein, Alexander Croft, Ernesto Romo, Mansi Agarwal, Daniel Theodoro

2020-Current year OA Pubs

INTRODUCTION: Resuscitative transesophageal echo (rTEE) is a promising adjunct to cardiac arrest resuscitation. However, it is a high-acuity diagnostic tool that is rarely used in this setting and its safety establishment is limited because of low occurrence. High-acuity, low occurrence skills such as rTEE during cardiac arrest inevitably decay. In this study we examined the content and percentage of rTEE skill decay following simulation-based education (SBE).

METHODS: Resuscitative TEE-naïve emergency physicians (EP) were trained using a combination of clinical exposure, web-based didactics, and monthly hands-on sessions with a high-fidelity rTEE simulator for four months. The COVID-19 pandemic created a natural …

A Conditional Point Cloud Diffusion Model For Deformable Liver Motion Tracking Via A Single Arbitrarily-Angled X-Ray Projection, Jiacheng Xie, Hua-Chieh Shao, Yunxiang Li, Shunyu Yan, Chenyang Shen, Jing Wang, You Zhang

Faculty, Staff and Student Publications

Objective. Deformable liver motion tracking using a single x-ray projection enables real-time motion monitoring and treatment intervention. We introduce a conditional point cloud diffusion (PCD) model-based framework for accurate and robust liver motion tracking from arbitrarily angled single x-ray projections. Approach. We propose a conditional PCD model for liver motion tracking (PCD-Liver), which estimates volumetric liver motion by solving deformable vector fields (DVFs) of a prior liver surface point cloud, based on a single x-ray image. It is a patient-specific model of two main components: a rigid alignment model to estimate the liver’s overall shifts, and a conditional PCD …

Mapping Mave Data For Use In Human Genomics Applications, Jeremy A Arbesfeld, Estelle Y Da, James S Stevenson, Kori Kuzma, Anika Paul, Tierra Farris, Benjamin J Capodanno, Sally B Grindstaff, Kevin Riehle, Nuno Saraiva-Agostinho, Jordan F Safer, Jonathan Casper, Maximilian Haeussler, Aleksandar Milosavljevic, Julia Foreman, Helen V Firth, Sarah E Hunt, Sumaiya Iqbal, Melissa S Cline, Alan F Rubin, Alex H Wagner

Faculty, Staff and Students Publications

Background: Experimental data from functional assays have a critical role in interpreting the impact of genetic variants. Assay data must be unambiguously mapped to a reference genome to make it accessible, but it is often reported relative to assay-specific sequences, complicating downstream use and integration of variant data across resources. To make multiplexed assays of variant effect (MAVE) data more broadly available to the research and clinical communities, the Atlas of Variant Effects Alliance mapped MAVE data from the MaveDB community database to human reference sequences, creating an extensive set of machine-readable homology mappings that are incorporated into widely used …

Physiological Role And Mechanisms Of Action For A Long Noncoding Haplotype Region., Hong Xue, Manoj K Mishra, Yong Liu, Pengyuan Liu, Michael Grzybowski, Rajan Pandey, Kristie Usa, Mark A Vanden Avond, Niharika Bala, Abdel A Alli, Allen W Cowley, Qiongzi Qiu, Andrew S Greene, Sridhar Rao, Caitlin C O'Meara, Aron M Geurts, Mingyu Liang

Faculty Research 2025

Direct targeting of noncoding genomic regions harboring common sequence variants associated with human traits through in vivo animal model studies and precise genome editing in human cells is essential for closing the critical gap between genetic discoveries and physiological understanding. However, such investigation has been impractical for many of these variants as they are in haplotypes containing multiple single-nucleotide polymorphisms (SNPs) spanning thousands of base pairs and have small effect sizes. We developed an integrated approach to address this challenge, combining an efficient two-step technique to precisely edit large haplotypes in human induced pluripotent stem cells and orthologous region deletion …

Apolipoprotein M Attenuates Age-Related Macular Degeneration Phenotypes Via Sphingosine-1-Phosphate Signaling And Lysosomal Lipid Catabolism, Tae Jun Lee, Andrea Santeford, Kristen M Pitts, Carla Valenzuela Ripoll, Ryo Terao, Zhen Guo, Mualla Ozcan, Dagmar Kratky, Christina Christoffersen, Ali Javaheri, Rajendra S Apte

2020-Current year OA Pubs

Age-related macular degeneration (AMD) is a leading cause of blindness in people over 50. AMD and cardiovascular disease share risk factors including age, impaired lipid metabolism, and extracellular lipid deposition. Because of its importance in age-related diseases, we hypothesize that apolipoprotein M (ApoM), a lipocalin that binds sphingosine-1-phosphate (S1P), might restore lipid homeostasis and retinal function in AMD. In support, we find that human patients with AMD demonstrate significantly reduced ApoM compared to controls. In mice with impaired retinal cholesterol efflux, ApoM improves retinal pigment epithelium (RPE) function and lipotoxicity in an S1P- and S1P receptor 3-dependent manner. Ultrastructural evidence …

A Road Map For Uniform, Comprehensive Long-Term Follow-Up After Curative Therapy For Sickle Cell Disease, Shalini Shenoy, Julie Kanter, Adetola Kassim, Courtney Fitzhugh, Elizabeth Stenger, Monica Bhatia, Lydia Pecker, Lakshmanan Krishnamurti, Allison A King

2020-Current year OA Pubs

An increasing number of allogeneic transplant and autologous gene modification transplant therapies seek to eradicate sickle hemoglobin and the consequent hemolysis, vasculopathy, functional compromise, morbidity, and mortality. Because these modalities are used in parallel, it is important to be able to define the spectrum and stability of correction, long-term effects, and the pros and cons of each modality. A comparison between interventions that will be sought by providers and patients undergoing intervention requires uniform assessments that evaluate disease- and intervention-related effects for informed decision-making. This expert summary outlines a pathway to functional evaluations with timing recommendations, provides broad management guidelines, …

Intratumoral Neutrophil-To-Lymphocyte Ratio Is Mirrored By Circulating Neutrophil-To-Lymphocyte Ratio In Non-Small Cell Lung Cancer, Kyle G Mitchell, Younghee Lee, Nathaniel Deboever, Marcelo V Negrao, Hai T Tran, Edwin Parra, Lauren Byers, Alexandre Reuben, Lorenzo Federico, Chantale Bernatchez, Jing Wang, Mara B Antonoff, Ara A Vaporciyan, Stephen G Swisher, Tina Cascone, Ignacio I Wistuba, John V Heymach, Don L Gibbons, Jianjun Zhang, Daniel J Mcgrail, Boris Sepesi, Cara L Haymaker

Faculty, Staff and Student Publications

Tumor-initiated emergency granulopoiesis results in expansion of the circulating neutrophil compartment and neutrophil recruitment into the tumor microenvironment (TME), which may in turn promote tumor progression. Although an elevated circulating neutrophil-to-lymphocyte ratio (cNLR) has repeatedly been demonstrated to be an adverse prognostic factor in patients with non-small cell lung cancer (NSCLC), whether this neutrophil expansion in circulation reflects a similar relative neutrophil abundance in the TME remains unclear. We sought to characterize the relationships between cNLR and the intratumoral neutrophil-to-lymphocyte ratio (tNLR), between tNLR and proteogenomic and immune features of NSCLC tumors, and between tNLR and prognosis.We analyzed tNLR (transcriptomic …

Differences In Arterial Events In Vascular Ehlers-Danlos, Loeys-Dietz, And Marfan Syndrome, Ernesto Calderon-Martinez, Walter V Velasco, Dongchuan Guo, Ellen H Hostetler, Zhang Xun, Sara Stephens, Sherene Shalhub, Julie De Backer, Maral Ouzounian, Scott A Lemaire, Olivier Milleron, Nadine Hanna, Pauline Arnaud, Maria Tchitchinadze, Siddharth K Prakash, Mark Lindsay, Julien Marcadier, Richmond Jeremy, Shaine A Morris, Anji T Yetman, Catherine Boileau, Alan C Braverman, Guillaume Jondeau, Dianna M Milewicz

Faculty, Staff and Students Publications

Background: Heritable thoracic aortic disease is due to altered genes that confer a highly penetrant risk for thoracic aortic aneurysm and dissection, and a subset of these genes also cause aneurysms and dissections of peripheral arteries beyond the aorta. Arterial aneurysms, dissections, and ruptures are associated with pathogenic variants (PVs) in COL3A1, which is responsible for vascular Ehlers-Danlos syndrome, but arterial events are rare in Marfan syndrome due to PVs in FBN1, and poorly characterized in Loeys-Dietz syndrome due to PVs in the transforming growth factor (TGF)-β pathway genes.

Objectives: This study sought to define the relative risk of arterial …

Modeling Reemergence Of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination In The Us, Mathew V Kiang, Kate M Bubar, Yvonne Maldonado, Peter J Hotez, Nathan C Lo

Faculty, Staff and Students Publications

Importance: Widespread childhood vaccination has eliminated many infectious diseases in the US. However, vaccination rates are declining, and there are ongoing policy debates to reduce the childhood vaccine schedule, which may risk reemergence of previously eliminated infectious diseases.

Objective: To estimate the number of cases and complications in the US under scenarios of declining childhood vaccination for measles, rubella, poliomyelitis, and diphtheria.

Design, setting, and participants: A simulation model was used to assess the importation and dynamic spread of vaccine-preventable infectious diseases across 50 US states and the District of Columbia. The model was parameterized with data on area-specific estimates …

Cholesterol Metabolism Regulated By Camkk2-Creb Signaling Promotes Castration-Resistant Prostate Cancer, Chenchu Lin, Thomas L Pulliam, Jenny J Han, Jiaqian Xu, Carlos Vera Recio, Sandi R Wilkenfeld, Yan Shi, Manoj Kushwaha, Sarah Bench, Eduardo Ruiz, Sanjanaa Senthilkumar, Jayasurya Dileep, Peter D A Shepherd, Nora M Navone, Albert R Klekers, Elizabeth M Whitley, Michael M Ittmann, Livia S Eberlin, Wenyi Wang, Daniel E Frigo

Faculty, Staff and Student Publications

Castration-resistant prostate cancer (CRPC) remains an incurable disease in need of improved treatments. CAMKK2 is an emerging therapeutic target whose oncogenic effects in prostate cancer have, to date, been largely attributed to its activation of AMP-activated protein kinase (AMPK). Here, we demonstrate that CAMKK2 promotes prostate cancer growth through an alternative downstream pathway involving CAMKI and CREB. Unbiased transcriptomics identify CREB-mediated transcription as a CAMKK2-regulated process, findings that we validate using diverse molecular, genetic, and pharmacological approaches in vitro and in vivo. CAMKK2 promotes CREB phosphorylation/activation through CAMKIα independently of AMPK, CAMKIV, or other CAMKI isoforms. Functionally, the CREB family …

Metabolic Control Of Glycosylation Forms For Establishing Glycan-Dependent Protein Interaction Networks, Xingyu Liu, Li Yi, Zongtao Lin, Siyu Chen, Shunyang Wang, Ying Sheng, Carlito B Lebrilla, Benjamin A Garcia, Yixuan Xie

2020-Current year OA Pubs

Protein-protein interactions (PPIs) are crucial for comprehending the molecular mechanisms and signaling pathways underlying diverse biological processes and disease progression. However, investigating PPIs involving membrane proteins is challenging due to the complexity and heterogeneity of glycosylation. To tackle this challenge, we developed an approach termed glycan-dependent affinity purification coupled with mass spectrometry (GAP-MS), specifically designed to characterize changes in glycoprotein PPIs under varying glycosylation conditions. GAP-MS integrates metabolic control of glycan profiles in cultured cells using small molecules referred to as glycan modifiers with affinity purification followed by mass spectrometry analysis (AP-MS). Here, GAP-MS was applied to characterize and compare …

Patterns Of Sialyl-Lewis X Expression Predict Gastric Histopathology, Nancy Vargas, Andrés Quiroga, Juan Pablo Chaves, Harold Bolaños, Ilke Nalbantoglu, Claudia Patricia Acosta Astaiza, Yuefeng Wu, José B Sáenz

2020-Current year OA Pubs

INTRODUCTION: Gastric cancer develops through a series of pre-cancerous changes over decades of chronic inflammation. Chronic atrophic gastritis (CAG) represents a critical transition in the progression to gastric cancer, though validated histologic markers are needed to more accurately detect and assess the extent of CAG. We previously identified sialyl-Lewis X (sLe

METHODS: We obtained gastric corpus and/or antrum biopsies from 149 adult patients with dyspepsia. Biopsies were stained with hematoxylin/eosin and a commercially available antibody to sLe

RESULTS: The majority of patients (70%) had gastric pathology (CNG or CAG ± IM). The presence of sLe

CONCLUSION: Patterns of sLe

Assessing The Impact Of Home Environmental Exposures On Allergic Rhinitis Using Real-Time Air Quality Monitoring And Symptom Assessment: Observational Feasibility Study., Aero Cavalier, Anthony I. Dick, Vickie Johnson Ii, Emily Cramer, Kamal Eldeirawi, Jayant Pinto, Sharmilee M. Nyenhuis, Victoria S. Lee

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Rhinitis is the most common sinonasal condition and poses a significant cost burden. Rhinitis symptom control is associated with exposure to environmental triggers (eg, aeroallergens, pollutants, and irritants). While people spend much of their time at home, studies examining the association of rhinitis symptoms with home environmental exposures, especially in low-income, urban, and racial or ethnic minorities, are limited. Frequently, 3 types of surveys are used in ecological momentary assessment (EMA): a survey conducted at a predetermined rate, an event-triggered survey, and a follow-up survey to gauge behavioral changes in response to the event.

OBJECTIVE: This study aims to …

Exploring Predictors Of Treatment Response To Glp-1 Receptor Agonists For Smoking Cessation, Luba Yammine, Constanza De Dios, Robert Suchting, Charles E Green, David A Nielsen, Consuelo Walss-Bass, Joy M Schmitz

Faculty, Staff and Student Publications

Introduction: Understanding predictors of smoking cessation medication efficacy facilitates the ability to enhance treatment effectiveness. In our pilot trial, exenatide, a glucagon-like peptide-1 receptor agonist, adjunct to nicotine patch improved smoking abstinence compared to nicotine patch alone. This secondary analysis explores potential baseline characteristics associated with differential treatment response to exenatide.

Aims and methods: The parent trial randomized (1:1) 84 smokers with prediabetes and/or overweight to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received nicotine patch (21 mg) and brief smoking cessation counseling, with biologically confirmed 7-day point prevalence abstinence at week 6 (end-of-treatment) deemed the primary outcome. …

Cancer Immunotherapy Clinical Trials To Support Urgently Needed Access In Low- And Middle-Income Countries: A Report From The Sitc Global Access And Impact Committee, Jennifer Dent, Thomas A Odeny, Et Al.

2020-Current year OA Pubs

Cancer is rapidly on the rise as a cause of morbidity and mortality in low- and middle-income countries (LMICs). However, despite the increasing importance of immune checkpoint inhibitors (ICIs) as a pillar of cancer therapy, access in these settings lags well behind that in high-income countries (HICs). Increasing the evaluation of ICIs through local clinical trials and demonstration projects, and inclusion in multinational clinical trials is the first step to improving access. In particular, the epidemiology and clinical presentation of cancer in LMICs is often distinct from that in HICs, and the impact of immune checkpoint blockade in these settings …