Digital Commons Network^™

Fibrinolytic-Deficiencies Predispose Hosts To Septicemia From A Catheter-Associated Uti, Jonathan J Molina, Wei Xu, Karla Bergeron, Aleksandra Klim, Michael G Caparon, Scott J Hultgren, Alana Desai, Et Al.

2020-Current year OA Pubs

Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, here we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition …

S100a8/A9 As A Prognostic Biomarker With Causal Effects For Post-Acute Myocardial Infarction Heart Failure, Jie Ma, Yang Li, Ping Li, Xinying Yang, Shuolin Zhu, Ke Ma, Fei Gao, Hai Gao, Hui Zhang, Xin-Liang Ma, Jie Du, Yulin Li

Department of Emergency Medicine Faculty Papers

Heart failure is the prevalent complication of acute myocardial infarction. We aim to identify a biomarker for heart failure post-acute myocardial infarction. This observational study includes 1062 and 1043 patients with acute myocardial infarction in the discovery and validation cohorts, respectively. The outcomes are in-hospital and long-term heart failure events. S100A8/A9 is screened out through proteomic analysis, and elevated circulating S100A8/A9 is independently associated with heart failure in discovery and validation cohorts. Furthermore, the predictive value of S100A8/A9 is superior to the traditional biomarkers, and the addition of S100A8/A9 improves the risk estimation using traditional risk factors. We finally report …

Effectiveness Of The Minder Mobile Mental Health And Substance Use Intervention For University Students: Randomized Controlled Trial, Melissa Vereschagin, Angel Y Wang, Chris G Richardson, Hui Xie, Richard J Munthali, Kristen L Hudec, Calista Leung, Katharine D Wojcik, Lonna Munro, Priyanka Halli, Ronald C Kessler, Daniel V Vigo

Faculty, Staff and Students Publications

Background: University attendance represents a transition period for students that often coincides with the emergence of mental health and substance use challenges. Digital interventions have been identified as a promising means of supporting students due to their scalability, adaptability, and acceptability. Minder is a mental health and substance use mobile app that was codeveloped with university students.

Objective: This study aims to examine the effectiveness of the Minder mobile app in improving mental health and substance use outcomes in a general population of university students.

Methods: A 2-arm, parallel-assignment, single-blinded, 30-day randomized controlled trial was used to evaluate Minder using …

Fair Header Reference Genome: A Trustworthy Standard, Adam Wright, Mark D Wilkinson, Christopher Mungall, Scott Cain, Stephen Richards, Paul Sternberg, Ellen Provin, Jonathan L Jacobs, Scott Geib, Daniela Raciti, Karen Yook, Lincoln Stein, David C Molik

Faculty, Staff and Students Publications

The lack of interoperable data standards among reference genome data-sharing platforms inhibits cross-platform analysis while increasing the risk of data provenance loss. Here, we describe the FAIR bioHeaders Reference genome (FHR), a metadata standard guided by the principles of Findability, Accessibility, Interoperability and Reuse (FAIR) in addition to the principles of Transparency, Responsibility, User focus, Sustainability and Technology. The objective of FHR is to provide an extensive set of data serialisation methods and minimum data field requirements while still maintaining extensibility, flexibility and expressivity in an increasingly decentralised genomic data ecosystem. The effort needed to implement FHR is low; FHR's …

Identifying Potential Dietary Treatments For Inherited Metabolic Disorders Using Drosophila Nutrigenomics, Felipe Martelli, Jiayi Lin, Sarah Mele, Wendy Imlach, Oguz Kanca, Christopher K Barlow, Jefferson Paril, Ralf B Schittenhelm, John Christodoulou, Hugo J Bellen, Matthew D W Piper, Travis K Johnson

Faculty, Staff and Students Publications

Inherited metabolic disorders are a group of genetic conditions that can cause severe neurological impairment and child mortality. Uniquely, these disorders respond to dietary treatment; however, this option remains largely unexplored because of low disorder prevalence and the lack of a suitable paradigm for testing diets. Here, we screened 35 Drosophila amino acid disorder models for disease-diet interactions and found 26 with diet-altered development and/or survival. Using a targeted multi-nutrient array, we examine the interaction in a model of isolated sulfite oxidase deficiency, an infant-lethal disorder. We show that dietary cysteine depletion normalizes their metabolic profile and rescues development, neurophysiology, …

A Novel Machine Learning Algorithm Selects Proteome Signature To Specifically Identify Cancer Exosomes, Bingrui Li, Fernanda G Kugeratski, Raghu Kalluri

Faculty, Staff and Student Publications

Non-invasive early cancer diagnosis remains challenging due to the low sensitivity and specificity of current diagnostic approaches. Exosomes are membrane-bound nanovesicles secreted by all cells that contain DNA, RNA, and proteins that are representative of the parent cells. This property, along with the abundance of exosomes in biological fluids makes them compelling candidates as biomarkers. However, a rapid and flexible exosome-based diagnostic method to distinguish human cancers across cancer types in diverse biological fluids is yet to be defined. Here, we describe a novel machine learning-based computational method to distinguish cancers using a panel of proteins associated with exosomes. Employing …

Effect Of Early Vs Late Inguinal Hernia Repair On Serious Adverse Event Rates In Preterm Infants: A Randomized Clinical Trial, Martin L Blakely, Andrea Krzyzaniak, Melvin S Dassinger, Claudia Pedroza, Jorn-Hendrik Weitkamp, Ankush Gosain, Michael Cotten, Susan R Hintz, Henry Rice, Sherry E Courtney, Kevin P Lally, Namasivayam Ambalavanan, Catherine M Bendel, Kim Chi T Bui, Casey Calkins, Nicole M Chandler, Roshni Dasgupta, Jonathan M Davis, Katherine Deans, Daniel A Deugarte, Jeffrey Gander, Carl-Christian A Jackson, Martin Keszler, Karen Kling, Stephen J Fenton, Kimberley A Fisher, Tyler Hartman, Eunice Y Huang, Saleem Islam, Frances Koch, Shabnam Lainwala, Aaron Lesher, Monica Lopez, Meghna Misra, Jamie Overbey, Brenda Poindexter, Robert Russell, Steven Stylianos, Douglas Y Tamura, Bradley A Yoder, Donald Lucas, Donald Shaul, P Ben Ham, Colleen Fitzpatrick, Kara Calkins, Aaron Garrison, Diomel De La Cruz, Shahab Abdessalam, Charlotte Kvasnovsky, Bradley J Segura, Joel Shilyansky, Lynne M Smith, Jon E Tyson

Faculty, Staff and Student Publications

Importance: Inguinal hernia repair in preterm infants is common and is associated with considerable morbidity. Whether the inguinal hernia should be repaired prior to or after discharge from the neonatal intensive care unit is controversial.

Objective: To evaluate the safety of early vs late surgical repair for preterm infants with an inguinal hernia.

Design, setting, and participants: A multicenter randomized clinical trial including preterm infants with inguinal hernia diagnosed during initial hospitalization was conducted between September 2013 and April 2021 at 39 US hospitals. Follow-up was completed on January 3, 2023.

Interventions: In the early repair strategy, infants underwent inguinal …

Biomarkers For Managing Neurodegenerative Diseases, Lara Cheslow, Adam E. Snook, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. …

The Genomic And Evolutionary Landscapes Of Anaplastic Thyroid Carcinoma, Peter Y F Zeng, Stephenie D Prokopec, Stephen Y Lai, Nicole Pinto, Michelle A Chan-Seng-Yue, Roderick Clifton-Bligh, Michelle D Williams, Christopher J Howlett, Paul Plantinga, Matthew J Cecchini, Alfred K Lam, Iram Siddiqui, Jianxin Wang, Ren X Sun, John D Watson, Reju Korah, Tobias Carling, Nishant Agrawal, Nicole Cipriani, Douglas Ball, Barry Nelkin, Lisa M Rooper, Justin A Bishop, Cathie Garnis, Ken Berean, Norman G Nicolson, Paul Weinberger, Ying C Henderson, Christopher M Lalansingh, Mao Tian, Takafumi N Yamaguchi, Julie Livingstone, Adriana Salcedo, Krupal Patel, Frederick Vizeacoumar, Alessandro Datti, Liu Xi, Yuri E Nikiforov, Robert Smallridge, John A Copland, Laura A Marlow, Martin D Hyrcza, Leigh Delbridge, Stan Sidhu, Mark Sywak, Bruce Robinson, Kevin Fung, Farhad Ghasemi, Keith Kwan, S Danielle Macneil, Adrian Mendez, David A Palma, Mohammed I Khan, Mushfiq Shaikh, Kara M Ruicci, Bret Wehrli, Eric Winquist, John Yoo, Joe S Mymryk, James W Rocco, David Wheeler, Steve Scherer, Thomas J Giordano, John W Barrett, William C Faquin, Anthony J Gill, Gary Clayman, Paul C Boutros, Anthony C Nichols

Faculty, Staff and Student Publications

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid …

Consensus Pharmacophore Strategy For Identifying Novel Sars-Cov-2 Mpro Inhibitors From Large Chemical Libraries, Angel J Ruiz-Moreno, Raziel Cedillo-González, Luis Cordova-Bahena, Zhiqiang An, José L Medina-Franco, Marco A Velasco-Velázquez

The Brown Foundation: Institute of Molecular Medicine

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main Protease (Mpro) is an enzyme that cleaves viral polyproteins translated from the viral genome and is critical for viral replication. Mpro is a target for anti-SARS-CoV-2 drug development, and multiple Mpro crystals complexed with competitive inhibitors have been reported. In this study, we aimed to develop an Mpro consensus pharmacophore as a tool to expand the search for inhibitors. We generated a consensus model by aligning and summarizing pharmacophoric points from 152 bioactive conformers of SARS-CoV-2 Mpro inhibitors. Validation against a library of conformers from a subset of ligands showed that …

Advocacy Connection Team-Now Educational Program For Headache Fellows And Patients/Caregivers: Assessment Of Educational Objectives, Courtney Seebadri-White, Hsiangkuo Yuan, William B. Young, Karissa N. Arca

Department of Neurology Faculty Papers

OBJECTIVE: To assess for improvement in comfort in participating in advocacy for migraine and headache disorders and knowledge needed for successful advocacy.

BACKGROUND: The Advocacy Connection Team (ACT)-Now program is an educational program offered through Miles for Migraine, a non-profit advocacy organization. It is designed to teach headache fellows and patients advocacy skills.

METHODS: In a cross-sectional pre-test-post-test design, the 2021 ACT-Now cohort of 98 participants were administered a set of 11 pre-course survey questions identifying their role (healthcare provider/headache fellow or patient/caregiver), baseline knowledge of migraine-related disability and stigma, and baseline engagement and comfort with advocating. The post-course survey …

Tmem106b Coding Variant Is Protective And Deletion Detrimental In A Mouse Model Of Tauopathy, George A Edwards, Caleb A Wood, Yang He, Quynh Nguyen, Peter J Kim, Ruben Gomez-Gutierrez, Kyung-Won Park, Yong Xu, Cody Zurhellen, Ismael Al-Ramahi, Joanna L Jankowsky

Duncan NRI Faculty and Staff Publications

TMEM106B is a risk modifier of multiple neurological conditions, where a single coding variant and multiple non-coding SNPs influence the balance between susceptibility and resilience. Two key questions that emerge from past work are whether the lone T185S coding variant contributes to protection, and if the presence of TMEM106B is helpful or harmful in the context of disease. Here, we address both questions while expanding the scope of TMEM106B study from TDP-43 to models of tauopathy. We generated knockout mice with constitutive deletion of TMEM106B, alongside knock-in mice encoding the T186S knock-in mutation (equivalent to the human T185S variant), and …

Edge-Wise Analysis Reveals White Matter Connectivity Associated With Focal To Bilateral Tonic-Clonic Seizures, Sam S. Javidi, Xiaosong He, Ankeeta Ankeeta, Qirui Zhang, Salvatore Citro, Michael R. Sperling, Joseph I. Tracy

Farber Institute for Neuroscience Faculty Papers

OBJECTIVE: Focal to bilateral tonic-clonic seizures (FBTCS) represent a challenging subtype of focal temporal lobe epilepsy (TLE) in terms of both severity and treatment response. Most studies have focused on regional brain analysis that is agnostic to the distribution of white matter (WM) pathways associated with a node. We implemented a more selective, edge-wise approach that allowed for identification of the individual connections unique to FBTCS.

METHODS: T1-weighted and diffusion-weighted images were obtained from 22 patients with solely focal seizures (FS), 43 FBTCS patients, and 65 age/sex-matched healthy participants (HPs), yielding streamline (STR) connectome matrices. We used diffusion tensor-derived STRs …

Childhood Cancer Mutagenesis Caused By Transposase-Derived Pgbd5, Makiko Yamada, Ross R Keller, Rodrigo Lopez Gutierrez, Daniel Cameron, Hiromichi Suzuki, Reeti Sanghrajka, Jake Vaynshteyn, Jeffrey Gerwin, Francesco Maura, William Hooper, Minita Shah, Nicolas Robine, Phillip Demarest, N Sumru Bayin, Luz Jubierre Zapater, Casie Reed, Steven Hébert, Ignas Masilionis, Ronan Chaligne, Nicholas D Socci, Michael D Taylor, Claudia L Kleinman, Alexandra L Joyner, G Praveen Raju, Alex Kentsis

Faculty, Staff and Students Publications

Genomic rearrangements are a hallmark of most childhood tumors, including medulloblastoma, one of the most common brain tumors in children, but their causes remain largely unknown. Here, we show that PiggyBac transposable element derived 5 (Pgbd5) promotes tumor development in multiple developmentally accurate mouse models of Sonic Hedgehog (SHH) medulloblastoma. Most Pgbd5-deficient mice do not develop tumors, while maintaining normal cerebellar development. Ectopic activation of SHH signaling is sufficient to enforce cerebellar granule cell progenitor-like cell states, which exhibit Pgbd5-dependent expression of distinct DNA repair and neurodevelopmental factors. Mouse medulloblastomas expressing Pgbd5 have increased numbers of somatic structural DNA rearrangements, …

Investigating The Use Of Finerenone In Children With Chronic Kidney Disease And Proteinuria: Design Of The Fiona And Open-Label Extension Studies., Franz Schaefer, Giovanni Montini, Hee Gyung Kang, Johan Vande Walle, Joshua Zaritsky, Michiel F. Schreuder, Mieczyslaw Litwin, Andrea Scalise, Helen Scott, James Potts, Pablo Iveli, Stefanie Breitenstein, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria.

OBJECTIVE: FIONA and the associated open-label extension (OLE) study aim to demonstrate that …

Tumor Treating Fields Suppress Tumor Cell Growth And Neurologic Decline In Models Of Spinal Metastases, Daniel Ledbetter, Romulo Augusto Andrade De Almeida, Xizi Wu, Ariel Naveh, Chirag B Patel, Queena Gonzalez, Thomas H Beckham, Robert North, Laurence Rhines, Jing Li, Amol Ghia, David Aten, Claudio Tatsui, Christopher Alvarez-Breckenridge

Faculty, Staff and Student Publications

Spinal metastases can result in severe neurologic compromise and decreased overall survival. Despite treatment advances, local disease progression is frequent, highlighting the need for novel therapies. Tumor treating fields (TTFields) impair tumor cell replication and are influenced by properties of surrounding tissue. We hypothesized that bone's dielectric properties will enhance TTFields-mediated suppression of tumor growth in spinal metastasis models. Computational modeling of TTFields intensity was performed following surgical resection of a spinal metastasis and demonstrated enhanced TTFields intensity within the resected vertebral body. Additionally, luciferase-tagged human KRIB osteosarcoma and A549 lung adenocarcinoma cell lines were cultured in demineralized bone grafts …

Mapping Sca1 Regional Vulnerabilities Reveals Neural And Skeletal Muscle Contributions To Disease, Lisa Duvick, W Michael Southern, Kellie A Benzow, Zoe N Burch, Hillary P Handler, Jason S Mitchell, Hannah Kuivinen, Udaya Gadiparthi, Praseuth Yang, Alyssa Soles, Carrie A Sheeler, Orion Rainwater, Shannah Serres, Erin B Lind, Tessa Nichols-Meade, Yun You, Brennon O'Callaghan, Huda Y Zoghbi, Marija Cvetanovic, Vanessa C Wheeler, James M Ervasti, Michael D Koob, Harry T Orr

Duncan NRI Faculty and Staff Publications

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ataxin-1 (ATXN1) protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced disease phenotypes, we developed a floxed conditional knockin mouse (f-ATXN1146Q/2Q) with mouse Atxn1 coding exons replaced by human ATXN1 exons encoding 146 glutamines. f-ATXN1146Q/2Q mice manifested SCA1-like phenotypes including motor and cognitive deficits, wasting, and decreased survival. Central nervous system (CNS) contributions to disease were revealed using f-ATXN1146Q/2Q;Nestin-Cre mice, which showed improved rotarod, open field, and Barnes maze performance by 6-12 weeks of age. In contrast, …

Expression Of Als-Pfn1 Impairs Vesicular Degradation In Ipsc-Derived Microglia., Salome Funes, Jonathan Jung, Del Hayden Gadd, Michelle Mosqueda, Jianjun Zhong, Shankaracharya, Matthew Unger, Karly Stallworth, Debra Cameron, Melissa S Rotunno, Pepper Dawes, Megan Fowler-Magaw, Pamela J Keagle, Justin A Mcdonough, Sivakumar Boopathy, Miguel Sena-Esteves, Jeffrey A Nickerson, Cathleen Lutz, William C Skarnes, Elaine T Lim, Dorothy P Schafer, Francesca Massi, John E Landers, Daryl A Bosco

Faculty Research 2024

Microglia play a pivotal role in neurodegenerative disease pathogenesis, but the mechanisms underlying microglia dysfunction and toxicity remain to be elucidated. To investigate the effect of neurodegenerative disease-linked genes on the intrinsic properties of microglia, we studied microglia-like cells derived from human induced pluripotent stem cells (iPSCs), termed iMGs, harboring mutations in profilin-1 (PFN1) that are causative for amyotrophic lateral sclerosis (ALS). ALS-PFN1 iMGs exhibited evidence of lipid dysmetabolism, autophagy dysregulation and deficient phagocytosis, a canonical microglia function. Mutant PFN1 also displayed enhanced binding affinity for PI3P, a critical signaling molecule involved in autophagic and endocytic processing. Our cumulative data …

Pathogenic Variants In Crx Have Distinct Cis-Regulatory Effects On Enhancers And Silencers In Photoreceptors, James L Shepherdson, Ryan Z Friedman, Yiqiao Zheng, Chi Sun, Inez Y Oh, David M Granas, Barak A Cohen, Shiming Chen, Michael A White

2020-Current year OA Pubs

Dozens of variants in the gene for the homeodomain transcription factor (TF) cone-rod homeobox (

Mapping Human Tissues With Highly Multiplexed Rna In Situ Hybridization, Kian Kalhor, Amanda Knoten, Joseph P Gaut, Sanjay Jain, Et Al.

2020-Current year OA Pubs

In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. There has been a surge of multiplexed RNA in situ mapping techniques but their application to human tissues has been limited due to their large size, general lower tissue quality and high autofluorescence. Here we report DART-FISH, a padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections. We introduce an omni-cell type cytoplasmic stain that substantially improves the segmentation of cell bodies. Our enzyme-free isothermal decoding procedure allows us to image 121 genes in large sections from the human …

Combined Kras-Mapk Pathway Inhibitors And Her2-Directed Drug Conjugate Is Efficacious In Pancreatic Cancer, Ashenafi Bulle, Peng Liu, Kuljeet Seehra, Sapana Bansod, Yali Chen, Kiran Zahra, Vikas Somani, Iftikhar Ali Khawar, Hung-Po Chen, Paarth B Dodhiawala, Lin Li, Yutong Geng, Chia-Kuei Mo, Jay Mahsl, Li Ding, Ramaswamy Govindan, Sherri Davies, Jacqueline Mudd, William G Hawkins, Ryan C Fields, David G Denardo, Jason M Held, Patrick M Grierson, Andrea Wang-Gillam, Marianna B Ruzinova, Kian-Huat Lim, Et Al.

2020-Current year OA Pubs

Targeting the mitogen-activated protein kinase (MAPK) cascade in pancreatic ductal adenocarcinoma (PDAC) remains clinically unsuccessful. We aim to develop a MAPK inhibitor-based therapeutic combination with strong preclinical efficacy. Utilizing a reverse-phase protein array, we observe rapid phospho-activation of human epidermal growth factor receptor 2 (HER2) in PDAC cells upon pharmacological MAPK inhibition. Mechanistically, MAPK inhibitors lead to swift proteasomal degradation of dual-specificity phosphatase 6 (DUSP6). The carboxy terminus of HER2, containing a TEY motif also present in extracellular signal-regulated kinase 1/2 (ERK1/2), facilitates binding with DUSP6, enhancing its phosphatase activity to dephosphorylate HER2. In the presence of MAPK inhibitors, DUSP6 …

Summit-Fa: A New Resource For Improved Transcriptome Imputation Using Functional Annotations, Hunter J Melton, Zichen Zhang, Chong Wu

Faculty, Staff and Student Publications

Transcriptome-wide association studies (TWAS) integrate gene expression prediction models and genome-wide association studies (GWAS) to identify gene-trait associations. The power of TWAS is determined by the sample size of GWAS and the accuracy of the expression prediction model. Here, we present a new method, the Summary-level Unified Method for Modeling Integrated Transcriptome using Functional Annotations (SUMMIT-FA), which improves gene expression prediction accuracy by leveraging functional annotation resources and a large expression quantitative trait loci (eQTL) summary-level dataset. We build gene expression prediction models in whole blood using SUMMIT-FA with the comprehensive functional database MACIE and eQTL summary-level data from the …

Understanding Heterogeneity In Individual Responses To Digital Lifestyle Intervention Through Self-Monitoring Adherence Trajectories In Adults With Overweight Or Obesity: Secondary Analysis Of A 6-Month Randomized Controlled Trial, Shiyu Li, Yan Du, Hongyu Miao, Kumar Sharma, Chengdong Li, Zenong Yin, Bradley Brimhall, Jing Wang

Faculty, Staff and Student Publications

Background: Achieving clinically significant weight loss through lifestyle interventions for obesity management is challenging for most individuals. Improving intervention effectiveness involves early identification of intervention nonresponders and providing them with timely, tailored interventions. Early and frequent self-monitoring (SM) adherence predicts later weight loss success, making it a potential indicator for identifying nonresponders in the initial phase.

Objective: This study aims to identify clinically meaningful participant subgroups based on longitudinal adherence to SM of diet, activity, and weight over 6 months as well as psychological predictors of participant subgroups from a self-determination theory (SDT) perspective.

Methods: This was a secondary data …

Supporting Underrepresented Students In Health Sciences: A Fuzzy Cognitive Mapping Approach To Program Evaluation., Danielle F. Chiang, Scott A. Guerrero, Emma Sexton, Stephen S. Gardner

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The Students Training in Academia, Health, and Research (STAHR) Program at the University of Missouri-Kansas City (UMKC) strives to help students from low-income families that have experienced educational challenges due to poverty and prepare them to enter, persist, and graduate from a health sciences degree program at UMKC. Students in the program participated in fuzzy cognitive mapping (FCM) sessions to ensure that all voices of the program were heard to improve program implementation, and student success, and contribute to an equitable educational environment.

METHODS: Fuzzy Cognitive Mapping sessions for the 2020-2021 cohort of students (n = 52) were conducted …

Germline Structural Variation Globally Impacts The Cancer Transcriptome Including Disease-Relevant Genes, Fengju Chen, Yiqun Zhang, Fritz J Sedlazeck, Chad J Creighton

Faculty, Staff and Students Publications

Germline variation and somatic alterations contribute to the molecular profile of cancers. We combine RNA with whole genome sequencing across 1,218 cancer patients to determine the extent germline structural variants (SVs) impact expression of nearby genes. For hundreds of genes, recurrent and common germline SV breakpoints within 100 kb associate with increased or decreased expression in tumors spanning various tissues of origin. A significant fraction of germline SV expression associations involves duplication of intergenic enhancers or 3' UTR disruption. Genes altered by both somatic and germline SVs include ATRX and CEBPA. Genes essential in cancer cell lines include BARD1 and …

Establishment Of Murine Pregnancy Requires The Promyelocytic Leukemia Zinc Finger Transcription Factor, Lan Hai, Vineet K Maurya, Francesco J Demayo, John P Lydon

Faculty, Staff and Students Publications

Using an established human primary cell culture model, we previously demonstrated that the promyelocytic leukemia zinc finger (PLZF) transcription factor is a direct target of the progesterone receptor (PGR) and is essential for progestin-dependent decidualization of human endometrial stromal cells (HESCs). These in vitro findings were supported by immunohistochemical analysis of human endometrial tissue biopsies, which showed that the strongest immunoreactivity for endometrial PLZF is detected during the progesterone (P4)-dominant secretory phase of the menstrual cycle. While these human studies provided critical clinical support for the important role of PLZF in P4-dependent HESC decidualization, functional validation in vivo was not …

Antithrombotic Therapy In Cerebral Cavernous Malformations: A Systematic Review, Meta-Analysis, And Network Meta-Analysis, Basel Musmar, Hamza Salim, Jihad Abdelgadir, Samantha Spellicy, Nimer Adeeb, Ali Zomorodi, Allan Friedman, Issam Awad, Pascal Jabbour, David Hasan

Department of Neurosurgery Faculty Papers

BACKGROUND: Cerebral cavernous malformations are complex vascular anomalies in the central nervous system associated with a risk of intracranial hemorrhage. Traditional guidelines have been cautious about the use of antithrombotic therapy in this patient group, citing concerns about potential bleeding risk. However, recent research posits that antithrombotic therapy may actually be beneficial. This study aims to clarify the association between antithrombotic therapy, including antiplatelet and anticoagulant medications, and the risk of intracranial hemorrhage in patients with cerebral cavernous malformations.

METHODS AND RESULTS: A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus databases, following Preferred Reporting Items …

Visual Outcome And Ocular Complications In Patients With Lacrimal Gland Carcinoma After Eye-Sparing Surgery And Adjuvant Radiation Therapy, Zhenyang Zhao, Steven Jay Frank, Jing Ning, Jiawei Zhao, Xinyang Jiang, Xin A Wang, Amy C Schefler, Ehab Hanna, Amy Moreno, Brandon Gunn, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

Background: We report visual outcomes and ocular complications in patients with lacrimal gland carcinoma who had eye-sparing surgery followed by radiotherapy.

Methods: This review included consecutive patients with lacrimal gland carcinoma who underwent eye-sparing surgery and adjuvant radiotherapy or concurrent chemoradiation therapy between 2007 and 2018. Clinical data, including details of ophthalmological examinations and radiation treatment were reviewed.

Results: The study included 23 patients, 15 males and 8 females, with median age 51 years. Twenty patients (87%) received intensity-modulated proton therapy; 3 (13%) received intensity-modulated radiotherapy. Nineteen patients (83%) received concurrent chemotherapy. After a median follow-up time of 37 months …

Synthetic Pet From Ct Improves Diagnosis And Prognosis For Lung Cancer: Proof Of Concept, Morteza Salehjahromi, Tatiana V Karpinets, Sheeba J Sujit, Mohamed Qayati, Pingjun Chen, Muhammad Aminu, Maliazurina B Saad, Rukhmini Bandyopadhyay, Lingzhi Hong, Ajay Sheshadri, Julie Lin, Mara B Antonoff, Boris Sepesi, Edwin J Ostrin, Iakovos Toumazis, Peng Huang, Chao Cheng, Tina Cascone, Natalie I Vokes, Carmen Behrens, Jeffrey H Siewerdsen, John D Hazle, Joe Y Chang, Jianhua Zhang, Yang Lu, Myrna C B Godoy, Caroline Chung, David Jaffray, Ignacio Wistuba, J Jack Lee, Ara A Vaporciyan, Don L Gibbons, Gregory Gladish, John V Heymach, Carol C Wu, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

[18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are indispensable components in modern medicine. Although PET can provide additional diagnostic value, it is costly and not universally accessible, particularly in low-income countries. To bridge this gap, we have developed a conditional generative adversarial network pipeline that can produce FDG-PET from diagnostic CT scans based on multi-center multi-modal lung cancer datasets (n = 1,478). Synthetic PET images are validated across imaging, biological, and clinical aspects. Radiologists confirm comparable imaging quality and tumor contrast between synthetic and actual PET scans. Radiogenomics analysis further proves that the dysregulated cancer hallmark pathways of …

Hematopoietic Stem Cells With Granulo-Monocytic Differentiation State Overcome Venetoclax Sensitivity In Patients With Myelodysplastic Syndromes, Juan Jose Rodriguez-Sevilla, Irene Ganan-Gomez, Feiyang Ma, Kelly Chien, Monica Del Rey, Sanam Loghavi, Guillermo Montalban-Bravo, Vera Adema, Bethany Wildeman, Rashmi Kanagal-Shamanna, Alexandre Bazinet, Helen T Chifotides, Natthakan Thongon, Xavier Calvo, Jesús María Hernández-Rivas, Maria Díez-Campelo, Guillermo Garcia-Manero, Simona Colla

Faculty, Staff and Student Publications

The molecular mechanisms of venetoclax-based therapy failure in patients with acute myeloid leukemia were recently clarified, but the mechanisms by which patients with myelodysplastic syndromes (MDS) acquire secondary resistance to venetoclax after an initial response remain to be elucidated. Here, we show an expansion of MDS hematopoietic stem cells (HSCs) with a granulo-monocytic-biased transcriptional differentiation state in MDS patients who initially responded to venetoclax but eventually relapsed. While MDS HSCs in an undifferentiated cellular state are sensitive to venetoclax treatment, differentiation towards a granulo-monocytic-biased transcriptional state, through the acquisition or expansion of clones with STAG2 or RUNX1 mutations, affects HSCs' …