Medicine and Health Sciences Commons^™

The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons Of The Transcriptomic Landscapes Across Mouse Models, Ling Cai, Fangjiang Wu, Qinbo Zhou, Ying Gao, Bo Yao, Ralph J Deberardinis, George K Acquaah-Mensah, Vassilis Aidinis, Jennifer E Beane, Shyam Biswal, Ting Chen, Carla P Concepcion-Crisol, Barbara M Grüner, Deshui Jia, Robert A Jones, Jonathan M Kurie, Min Gyu Lee, Per Lindahl, Yonathan Lissanu, Corina Lorz, David Macpherson, Rosanna Martinelli, Pawel K Mazur, Sarah A Mazzilli, Shinji Mii, Herwig P Moll, Roger A Moorehead, Edward E Morrisey, Sheng Rong Ng, Matthew G Oser, Arun R Pandiri, Charles A Powell, Giorgio Ramadori, Mirentxu Santos, Eric L Snyder, Rocio Sotillo, Kang-Yi Su, Tetsuro Taki, Kekoa Taparra, Phuoc T Tran, Yifeng Xia, J Edward Van Veen, Monte M Winslow, Guanghua Xiao, Charles M Rudin, Trudy G Oliver, Yang Xie, John D Minna

Faculty, Staff and Student Publications

Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. In this study, we established the Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors produced a robust and comprehensive database, …

G-Quadruplex Stabilizer Cx-5461 Effectively Combines With Radiotherapy To Target Α-Thalassemia/Mental Retardation X-Linked-Deficient Malignant Glioma, Sharvari Dharmaiah, Prit Benny Malgulwar, William E Johnson, Brandon A Chen, Vladislav Sharin, Benjamin T Whitfield, Christian Alvarez, Vasudev Tadimeti, Ahsan S Farooqi, Jason T Huse

Faculty, Staff and Student Publications

Background: Inactivation of α-thalassemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures, enhancing replication stress and genomic instability. Building on earlier work, we evaluated the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in ATRX-deficient preclinical glioma models.

Methods: Using the G4 stabilizer CX-5461, we treated patient-derived glioma stem cells (GSCs) in vitro and GSC flank and intracranial murine xenografts in vivo to evaluate efficacy as both a single agent and in combination with ionizing radiation (IR), the …

Long-Term Efficacy Of Pembrolizumab And The Clinical Utility Of Ctdna In Locally Advanced Dmmr/Msi-H Solid Tumors, Michael Lapelusa, Wei Qiao, Bryan Iorgulescu, Francis San Lucas, Keyur Patel, Deepak Bhamidipati, Jane Varkey Thomas, Nancy You, Wai Chin Foo, Dipen Maru, Selvi Thirumurthi, Van Morris, Scott Kopetz, Michael Overman, Kaysia Ludford

Faculty, Staff and Student Publications

Neoadjuvant immunotherapy can induce pathologic complete response (pCR) in patients with localized deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors. The long-term outcomes of these patients are unknown, as is the clinical utility of measuring circulating tumor DNA (ctDNA). Follow-up was evaluated in patients enrolled in a phase II trial (NCT04082572) that evaluated the efficacy and safety of pembrolizumab in patients with localized dMMR/MSI-H tumors. The primary outcomes of this trial have previously been reported. 3-year EFS and OS rates were 80% (95% CI: 66% - 93%) and 94% (95% CI: 86% - 100%). Patients without detectable ctDNA after pembrolizumab had …

Prevalence Of Cardiovascular-Kidney-Metabolic Stages In Us Adolescents And Relationship To Social Determinants Of Health, Carissa M. Baker-Smith, Abigail M. Gauen, Lucia C. Petito, Sadiya S. Khan, Norrina B. Allen

Department of Pediatrics Faculty Papers

BACKGROUND: Risk factors for atherosclerotic cardiovascular disease begin in youth. Knowledge of the prevalence of cardio-kidney-metabolic (CKM) syndrome in adolescents and its risk factors is critical to understanding the cause of atherosclerotic cardiovascular disease risk burden.

METHODS: We conducted a cross-sectional analysis of the 2017 to 2020 US National Health and Nutrition Examination Survey data and determined the prevalence of each CKM stage in adolescents aged 12 to 18 years. We then assessed the relationship between the family income-to-poverty ratio, health insurance, routine health care access, food security, health behaviors, and CKM stage. We quantified associations between social factors, behaviors, …

The Identification Of Xpr1 As A Voltage- And Phosphate-Activated Phosphate-Permeable Ion Channel, Hongjiang Wu, Liang Sun, Tong Huo, Theodore G Wensel, Frank T Horrigan, Zhao Wang

Faculty, Staff and Students Publications

Maintaining a balance of inorganic phosphate (Pi) is vital for cellular functionality. Proper phosphate levels are managed through Pi import and export; and the processes governing Pi export remain the least understood. Xenotropic and Polytropic retrovirus Receptor 1 (XPR1) has been identified as the only known Pi export protein in mammals. In this study, we introduce the cryogenic electron microscopy structure of human XPR1 (hXPR1), unveiling a structural arrangement distinct from that of any known ion transporter. Our structural results suggest that hXPR1 may operate as an ion channel, a hypothesis supported by patch clamp recordings revealing hXPR1's voltage- and …

Functional Brain Connectivity Of The Salience Network In Alcohol Use And Anxiety Disorders, Dhruv M Patel, Guillermo F Poblete, Alexandra Castellanos, Ramiro Salas

Staff and Researcher Publications

The interplay between alcohol use disorder (AUD) and anxiety disorders (ANX) is well-documented, yet the underlying neurobiological mechanisms remain elusive. This study aims to elucidate these mechanisms by examining the resting-state functional connectivity (RSFC) within the salience network and to the amygdala, both implicated in alcohol and anxiety disorders. We analyzed data from 264 inpatient participants culled from a wider group of 518 inpatients at The Menninger Clinic in Houston, TX, categorized into four groups (n = 66 each) based on DSM-IV diagnoses: AUD without ANX (AUD), ANX without AUD (ANX), concurrent AUD and ANX (BOTH), and neither (NEITHER). Our …

A Phase I Dose-Escalation Study Of The Hif-2 Alpha Inhibitor Dff332 In Patients With Advanced Clear-Cell Renal Cell Carcinoma, Sumanta K Pal, Joel Picus, Et Al.

2020-Current year OA Pubs

PURPOSE: Mutations or silencing of the von Hippel-Lindau tumor suppressor gene accumulate hypoxia-inducible factors (HIF). HIF-2α is implicated in the oncogenesis of ∼50% of patients with clear-cell renal cell carcinoma (ccRCC) but has been considered "undruggable." DFF332, an orally administered novel allosteric inhibitor of HIF-2α, showed dose-dependent antitumor efficacy in preclinical models of ccRCC.

PATIENTS AND METHODS: This first-in-human study evaluated the safety, tolerability, antitumor activity, pharmacokinetics, and pharmacodynamics of DFF332 in patients with heavily pretreated advanced ccRCC. Preliminary data from the dose escalation of DFF332 monotherapy, administered orally at 50 or 100 mg weekly or 25, 50, 100, or …

Identifying Distinct Subgroups With Severe Pain In Sickle Cell Disease: A Cluster Analysis Of The Grndad Multi-Center Registry, Martha O. Kenney, Samuel Wilson, Morgan Rosser, Sophie Lanzkron, Julie Kanter, Susan Padrino, Payal Desai, Deepa Manwani, Alice Cohen, Stephanie Guarino, Ward Hagar, Joshua Field, Jane Little

Department of Medicine Faculty Papers

Sickle cell disease (SCD) affects millions of individuals worldwide, and is characterized by both acute, episodic pain and chronic, persistent pain. Despite the significant burden of the disease, clinicians continue to face significant challenges in treating SCD pain due to variability in pain experiences. The objectives of this study were (1) to identify distinct pain subgroups based on demographic and biopsychosocial characteristics and (2) to evaluate the relationship between the subgroups and pain impact - a SCD-disease specific measure of pain interference. To achieve these objectives, we performed a hierarchical cluster analysis on a cross-sectional sample of adults with SCD …

Developing The Mycancergene Digital Health Portal To Improve Patients' Understanding Of Germline Cancer Genetic Test Results: Development, User, And Usability Testing Study, Phillip Trieu, Dominique Fetzer, Briana Mcleod, Kathryn Schweickert, Lauren Gutstein, Brian Egleston, Susan Domchek, Linda Fleisher, Lynne Wagner, Kuang-Yi Wen, Cara Cacioppo, Jessica E. Ebrahimzadeh, Dana Falcone, Claire Langer, Elisabeth Wood, Kelsey Karpink, Shelby Posen, Enida Selmani, Angela R. Bradbury

Department of Medical Oncology Faculty Papers

BACKGROUND: The use of multigene panels has significantly increased the likelihood that genetic testing will leave patients with uncertainties regarding test interpretation, implications, and recommendations, which will change over time. Effective longitudinal care models are needed to provide patients with updated information and to obtain patient and family history updates.

OBJECTIVE: To bridge this gap, we aimed to develop a patient- and genetic provider-informed digital genetic health portal (GHP), MyCancerGene, to improve longitudinal patient understanding of and responses to genetic testing.

METHODS: We used a 5-step process to develop MyCancerGene. To better understand their interest in and willingness to use …

Causes Of Death Among Us Medical Residents, Nicholas A. Yaghmour, William E. Bynum, Frederic W. Hafferty, Karen D. Könings, Thomas Richter, Timothy P. Brigham, Thomas J. Nasca

Division of Nephrology Faculty Papers

IMPORTANCE: From 2000 to 2014, the leading causes of medical resident death in the United States were neoplastic diseases and suicide.

OBJECTIVE: To examine whether US medical resident rates of death have changed since 2014 and whether causes of resident death differ by specialty.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, residents and fellows who were enrolled in Accreditation Council for Graduate Medical Education (ACGME)-accredited training programs and who died from January 2015 to December 2021 were submitted to the National Death Index to obtain causes of death. These decedents were compared with residents and fellows who died between …

Incorporating Latent Survival Trajectories And Covariate Heterogeneity In Time-To-Event Data Analysis: A Joint Mixture Model Approach, Fu-Wen Liang, Wenyaw Chan, Michael D Swartz, Bouthaina S Dabaja

Faculty, Staff and Student Publications

Background: Finite mixture models have been recently applied in time-to-event data to identify subgroups with distinct hazard functions, yet they often assume differing covariate effects on failure times across latent classes but homogeneous covariate distributions. This study aimed to develop a method for analyzing time-to-event data while accounting for unobserved heterogeneity within a mixture modeling framework.

Methods: A joint model was developed to incorporate latent survival trajectories and observed information for the joint analysis of time-to-event outcomes, correlated discrete and continuous covariates, and a latent class variable. It assumed covariate effects on survival times and covariate distributions vary across latent …

Multifaceted Roles Of Epac Signaling In Renal Functions, Oleh Pochynyuk, Kyrylo Pyrshev, Xiaodong Cheng

The Brown Foundation: Institute of Molecular Medicine

3',5'-cyclic adenosine monophosphate (cAMP) is a fundamental secondary messenger capable of rapidly amplifying and propagating cellular signals in response to various extracellular stimuli. cAMP plays a significant role in hormone-mediated regulation of renal fluid and electrolyte balance. Impaired signaling of cAMP has been linked to a variety of pathological ramifications in the kidneys. This review explores the physiological functions of exchange proteins directly activated by cAMP (Epac) in renal water balance and the regulation of solute transport in the renal tubule. Additionally, the involvement of Epac signaling in renal pathologies such as acute kidney injury, chronic kidney disease, and polycystic …

Molecular Characterization And Predictors Of Relapse In Patients With Ph + All After Frontline Ponatinib And Blinatumomab, Nicholas J Short, Hagop Kantarjian, Ken Furudate, Nitin Jain, Farhad Ravandi, Omer Karrar, Sanam Loghavi, Lewis Nasr, Fadi G Haddad, Jayastu Senapati, Rebecca Garris, Koichi Takahashi, Elias Jabbour

Faculty, Staff and Student Publications

Background: Several studies have suggested that chemotherapy-free regimens consisting of blinatumomab and a BCR::ABL1 tyrosine kinase inhibitor are highly effective in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, the clinical and molecular characteristics that predict for relapse with these chemotherapy-free regimens are largely unknown.

Methods: We conducted a prospective phase II clinical trial of the combination of blinatumomab and ponatinib in 76 patients with newly diagnosed Ph + ALL. Patients received 12-15 doses of intrathecal chemotherapy as central nervous systemic (CNS) prophylaxis. The patterns of relapse and the clinical and molecular predictors of relapse were analyzed.

Results: With …

Structural And Molecular Basis Of Pcna-Activated Fan1 Nuclease Function In Dna Repair, F. Li, A. S. Phadte, M. Bhatia, S. Barndt, A.R. Monte Carlo, Iii, C.F.D. Hou, R. Yang, S. Strock, A. Pluciennik

Department of Biochemistry and Molecular Biology Faculty Papers

FAN1 is a DNA dependent nuclease whose proper function is essential for maintaining human health. For example, a genetic variant in FAN1, Arg507 to His hastens onset of Huntington's disease, a repeat expansion disorder for which there is no cure. How the Arg507His mutation affects FAN1 structure and enzymatic function is unknown. Using cryo-EM and biochemistry, we have discovered that FAN1 arginine 507 is critical for its interaction with PCNA, and mutation of Arg507 to His attenuates assembly of the FAN1-PCNA complex on a disease-relevant extrahelical DNA extrusions formed within DNA repeats. This mutation concomitantly abolishes PCNA-FAN1-dependent cleavage of such …

Genome-Wide Allele-Specific Expression In Multi-Tissue Samples From Healthy Male Baboons Reveals The Transcriptional Complexity Of Mammals, Ramesh Ramasamy, Muthuswamy Raveendran, R Alan Harris, Hiep D Le, Ludovic S Mure, Giorgia Benegiamo, Ouria Dkhissi-Benyahya, Howard Cooper, Jeffrey Rogers, Satchidananda Panda

Faculty, Staff and Students Publications

Allele-specific expression (ASE) is pivotal in understanding the genetic underpinnings of phenotypic variation within species, differences in disease susceptibility, and responses to environmental factors. We processed 11 different tissue types collected from 12 age-matched healthy olive baboons (Papio anubis) for genome-wide ASE analysis. By sequencing their genomes at a minimum depth of 30×, we identified over 16 million single-nucleotide variants (SNVs). We also generated long-read sequencing data, enabling the phasing of all variants present within the coding regions of 96.5% of assayable protein-coding genes as a single haplotype block. Given the extensive heterozygosity of baboons relative to humans, we could …

Therapeutic Left-To-Right Shunting In Heart Failure, Francesco Fioretti, Ajith P Nair, Stefan D Anker, Barry A Borlaug, Dean J Kereiakes, Joann Lindenfeld, Gregg W Stone, Javed Butler

Faculty, Staff and Students Publications

Heart failure with reduced or preserved ejection fraction is associated with elevated left atrial pressure at rest due to fluid overload or during exercise, leading to pulmonary venous congestion. Even with available treatments, heart failure hospitalizations remain high, and improvements in quality-of-life scores and functional capacity are modest. Thus, there is growing interest in non-pharmacological methods to decompress the left atrium and improve heart failure symptoms and outcomes. Left-to-right shunts have emerged as a potential therapeutic option to reduce left atrial hypertension, improve quality of life, and impact long-term outcomes. This nascent field carries both potential therapeutic promise and many …

Soft, Skin-Interfaced Wireless Electrogoniometry Systems For Continuous Monitoring Of Finger And Wrist Joints, Hee-Sup Shin, Jihye Kim, Nicholas Fadell, Logan B Pewitt, Yusuf Shaaban, Claire Liu, Min-Seung Jo, Josif Bozovic, Andreas Tzavelis, Minsu Park, Kelly Koogler, Jin-Tae Kim, Jae-Young Yoo, John A Rogers, Mitchell A Pet

2020-Current year OA Pubs

Continuous kinematic biofeedback during exercise interventions can lead to improved therapeutic outcomes in hand and wrist rehabilitation. Conventional methods for measuring joint kinematics typically allow only static measurements performed by specially trained therapists. This paper introduces skin-conformal, wearable wireless systems designed to continuously and accurately capture the angles of target joints, specifically in hand and wrist. Supported by a computer vision-based calibration protocol run on a smart device, these magnetometer-based standalone systems provide patients and clinicians with continuous, real-time data on joint angles and ranges of motion through an intuitive graphical interface. Human trials in healthy volunteers demonstrate the accuracy …

Multicentre Analysis Of Seizure Outcome Predicted By Removal Of High-Frequency Oscillations, Vasileios Dimakopoulos, Jean Gotman, Petr Klimes, Nicolas Von Ellenrieder, Shi Bei Tan, Garnett Smith, Stephen V. Gliske, Margarita Maltseva, Minette Krisel Manalo, Martin Pail, Milan Brazdil, Dorien Van Blooijs, Maryse A. Van 'T Klooster, Sarah Johnson, Samantha Laboy, Debora Ledergerber, Lukas Imbach, Christos Papadelis, Michael R. Sperling, Maeike Zijlmans, Jan Cimbalnik, Julia Jacobs, William C. Stacey, Birgit Frauscher, Johannes Sarnthein

Department of Neurology Faculty Papers

In drug-resistant focal epilepsy, planning surgical resection can involve presurgical intracranial EEG (iEEG) recordings to detect seizures and other iEEG patterns to improve postsurgical seizure outcome. We hypothesized that resection of tissue generating interictal high-frequency oscillations (HFOs, 80-500 Hz) in the iEEG predicts surgical outcome. In eight international epilepsy centres, iEEG was recorded during the presurgical evaluation of patients. The patients were of all ages, had epilepsy of all types, and underwent surgical resection of a single focus aiming at seizure freedom. In a prospective analysis, we applied a fully automated definition of HFO that was independent of the dataset. …

Ovarian Cancer G Protein-Coupled Receptor-1 Signaling Bias Dictates Anti-Contractile Effect Of Benzodiazepines On Airway Smooth Muscle, Dominic R. Villalba, Arun K. Jannu, Elham Javed, Isha Dandekar, Ruping Wang, Deepak A. Deshpande, Steven S. An, Reynold A. Panettieri, Dale D. Tang, Raymond B. Penn, Ajay P. Nayak

Center for Translational Medicine Faculty Papers

BACKGROUND: We recently reported that the ovarian cancer G protein-coupled receptor-1 (OGR1) can be pharmacologically biased with specific benzodiazepines to couple with distinct heterotrimeric G proteins in human airway smooth muscle (ASM) cells. Lorazepam stimulated both G

METHODS: Models of histamine (His) -stimulated contraction included imaging of ex vivo human precision cut lung slices (hPCLS) and Magnetic Twisting Cytometry (MTC) analysis of human ASM cell stiffness. To explore mechanisms of regulation, we examined effects on myosin light chain (pMLC) phosphorylation and PKA activity in primary human ASM cultures, as well as actin cytoskeleton integrity as defined by changes in the …

Ogg1s326c Variant Frequent In Human Populations Facilitates Inflammatory Responses Due To Its Extended Interaction With Dna Substrate, Jinling Han, Meichen Zhang, Jiakun Ge, Zhihua Ji, Jianyi Zhao, Yinchao Hu, Chunshuang Li, Yaoyao Xue, Xining Li, Haiwang Zhao, Zixu Cui, Miaomiao Tian, Xu Zheng, Dapeng Wang, Jing Wang, Min Wei, Zsolt Radak, Yusaku Nakabeppu, Istvan Boldogh, Xueqing Ba

Faculty, Staff and Student Publications

8-oxoguanine (8-oxoGua) is one of the most frequent forms of oxidative DNA base lesions, repaired by 8-oxoguanine DNA glycosylase 1 (OGG1) via base excision repair (BER) pathway to maintain genome fidelity. The human allelic variant hOGG1^S326C, prevalent in Caucasians and Asians, has been regarded as a susceptibility factor for various diseases, yet its pathogenic mechanism remains elusive. In this study, we demonstrate that Ogg1^S326C/S326C mice exhibit increased and sustained airway inflammation compared with wild-type (WT) Ogg1^S326/S326 mice. Mechanistically, in response to inflammatory stimulation, OGG1S326C undergoes reactive oxygen species-induced dimerization, which impairs its base excision function, but …

A Pharmacokinetic And Safety Study Of Oral Arsenic Trioxide In Patients With Acute Promyelocytic Leukemia, Farhad Ravandi, Sravanti Rangaraju, Hagop Kantarjian, Guillermo Garcia-Manero, Musa Yilmaz, Kristen Baker, Terence Hall, Joy Grabenstein, Pourab Roy, Beth A Zamboni, William C Zamboni, Erica Warlick, Michael Kelly, David A Roth, Gabriel Ghiaur

Faculty, Staff and Student Publications

SY-2101 is a novel oral formulation of arsenic trioxide (ATO). Although IV ATO in combination with all trans retinoic acid is highly efficacious in treating acute promyelocytic leukemia (APL), there remains a significant unmet need due to the treatment burden associated with receiving daily ATO infusions for nearly a year and the risk of complications associated with indwelling central catheters. The pharmacokinetics (PK), safety, and tolerability of SY-2101 and ATO IV after single- and multiple-dose administration and the impact of food on PK for SY-2101 were evaluated in this phase 1 study in 15 participants with APL. SY-2101 in the …

Genetic, Transcriptomic, And Epigenomic Insights Into Sjögren's Disease: An Integrative Network Investigation And Immune Diseases Comparison, Nitesh Enduru, Astrid M Manuel, Zhongming Zhao

Faculty, Staff and Student Publications

Sjögren's disease (SjD) is a systemic autoimmune disorder primarily causing dry eyes and mouth. It frequently overlaps with other autoimmune diseases (AIDs), including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, the genetic basis of SjD remains underexplored, limiting our understanding of its connections to other immune-mediated conditions. In this study, we aimed to identify gene networks associated with SjD through the integration of genetic, transcriptomic, and epigenomic data. We further compared the genetic factors of SjD with other immune-mediated diseases. We analyzed genome-wide association studies (GWAS) summary statistics, DNA methylation, and transcriptomic data using our in-house network-based methods, …

Physiologically Based And Population Pharmacokinetic Modeling Of Midazolam In Children With Obesity Using Real-World Data, Sean Mccann, Victória E. Helfer, Stephen J. Balevic, William J. Muller, John N. Van Den Anker, Amira Al-Uzri, Marisa L. Meyer, Sarah G. Anderson, Sitora Turdalieva, Andrea N. Edginton, Daniel Gonzalez, Best Pharmaceuticals For Children Act Pediatric Trials Network Steering Committee

Department of Pediatrics Faculty Papers

Children represent a highly complex and variable population for treatment, including interindividual differences in drug dose-exposure. Midazolam has been used as a sedative for hospitalized children on- and off-label; however, factors affecting interindividual variability (IIV) in observed clearance for this population are not fully understood and can result in extreme under- or overexposure. Obesity has been described as a significant influence on midazolam in adolescents, which could potentially alter drug exposure. The goal of this study was to use two modeling strategies to evaluate dose-exposure of midazolam in children with and without obesity. Population pharmacokinetic modeling assessed whether measures of …

Smooth Muscle Cells And Fibroblasts In The Ascending Aorta Exhibit Minor Differences Between Embryonic Origins In Angiotensin Ii-Driven Transcriptional Alterations, Sohei Ito, David B Graf, Yuriko Katsumata, Jessica J Moorleghen, Chen Zhang, Yanming Li, Scott A Lemaire, Ying H Shen, Hong S Lu, Alan Daugherty, Hisashi Sawada

Faculty, Staff and Students Publications

Thoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the ascending aorta being particularly susceptible. In this region, smooth muscle cells (SMCs) and selected fibroblasts originate from the second heart field (SHF) and cardiac neural crest (CNC). While our previous study revealed a critical role of SHF-derived cells in AngII-mediated aortopathy, the contribution of CNC-derived cells remains unclear. To investigate lineage-specific responses to AngII, Mef2c-Cre R26RmT/mG mice were infused with AngII. Ascending aortas were harvested at baseline or after 3 days of infusion, representing the prepathological phase. Cells were sorted based on their embryonic origins and …

White Matter Connections Within The Central Sulcus Subserving The Somato-Cognitive Action Network, Georgios P Skandalakis, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

The somato-cognitive action network (SCAN) consists of three nodes interspersed within Penfield's motor effector regions. The configuration of the somato-cognitive action network nodes resembles the one of the 'plis de passage' of the central sulcus: small gyri bridging the precentral and postcentral gyri. Thus, we hypothesize that these may provide a structural substrate of the somato-cognitive action network. Using microdissections of 16 human hemispheres, we consistently identified a chain of three distinct plis de passage with increased underlying white matter in locations analogous to the somato-cognitive action network nodes. We mapped localizations of plis de passage into standard stereotactic space …

Narratives Or Not? Examining The Roles Of Message Format And Individuals' Stages Of Change In The Context Of Hpv Vaccination Promotion, Mengfei Guan, Shawn C. Chiang, Regan M. Murray, Wen-Juo Lo, Larry T. Hill, Ann C. Klassen, Jennifer A. Manganello, Amy E. Leader, Philip M. Massey

Department of Medical Oncology Faculty Papers

Narrative persuasion has been widely used in health communication campaigns and persuasive message design. However, several meta-analyses showed that the relative effectiveness of narratives in promoting behavior change was not consistently observed in the existing literature. With the goal of exploring boundary conditions of narrative effects, this study investigates the interaction effects of narrative persuasion and stages of change on promoting behavior change in the context of encouraging parents to vaccinate their children against human papillomavirus (HPV). Findings from an online experiment (N = 593) showed that non-narrative messages were more effective in bolstering behavioral intention than narrative messages among …

Risk Of Coronary Obstruction In Redo-Transcatheter Aortic Valve Replacement Between Bicuspid And Tricuspid Aortic Valves, Atsushi Okada, Syed Zaid, Miho Fukui, Evan Walser-Kuntz, Larissa I Stanberry, Marcus R Burns, John R Lesser, João L Cavalcante, Paul Sorajja, Vinayak N Bapat

Faculty, Staff and Students Publications

Background: Transcatheter aortic valve replacement (TAVR) is approved across all risk profiles, including patients with bicuspid aortic valves. These patients are generally younger, with a higher chance of reintervention.

Objectives: The aim of this study was to compare the feasibility of redo transcatheter aortic valve (TAV) between bicuspid and tricuspid aortic valves.

Methods: A computed tomographic (CT) simulation of redo-TAV was conducted using 913 post-TAVR CT studies from patients who underwent TAVR with SAPIEN 3 or SAPIEN 3 Ultra (S3; n = 623) or Evolut R, Evolut PRO, or Evolut PRO+ (Evolut; n = 290) valves. Fifty-nine cases were for …

Structural Proteomics Defines A Sequential Priming Mechanism For The Progesterone Receptor, Matthew D Mann, Min Wang, Josephine C Ferreon, Phoebe S Tsoi, Michael P Suess, Antrix Jain, Anna Malovannaya, Roberto Vera Alvarez, Bruce D Pascal, Raj Kumar, Dean P Edwards, Patrick R Griffin

Faculty, Staff and Students Publications

The progesterone receptor (PR) is a steroid-responsive nuclear receptor with two isoforms: PR-A and PR-B. Disruption of PR-A:PR-B signaling is associated with breast cancer through interactions with oncogenic co-regulatory proteins (CoRs). However, molecular details of isoform-specific PR-CoR interactions remain poorly understood. Using structural mass spectrometry, we investigate the sequential binding mechanism of purified full-length PR and intact CoRs, steroid receptor coactivator 3 (SRC3) and p300, as complexes on target DNA. Our findings reveal selective CoR NR-box binding by PR and unique interaction surfaces between PR and CoRs during complex assembly, providing a structural basis for CoR sequential binding on PR. …

Phase Ii Study Of Venetoclax Added To Bendamustine And Obinutuzumab In Patients With High-Risk Follicular Lymphoma As Front-Line Therapy: Pre0403, Craig A Portell, Opeyemi A Jegede, Nina Wagner-Johnston, Grzegorz S Nowakowski, Christopher Fletcher, Jonathon B Cohen, Andrew M Evens, Lori J Rosenstein, Jeffrey W Craig, Nishitha Reddy, Brad S Kahl

2020-Current year OA Pubs

Over-expression of BCL-2 defines follicular lymphoma (FL). Venetoclax (VEN), a selective BCL-2 inhibitor, has previously been evaluated with bendamustine-based chemoimmunotherapy. VEN was given continuously, resulting in promising efficacy but unacceptable toxicity. The Phase II PrE0403 study was designed to evaluate intermittent dosing of VEN (10 days per cycle) combined with obinutuzumab and bendamustine (VEN-OB) in untreated FL subjects with high-risk features defined as a FLIPI-1 score of ≥3 and/or high tumor burden by GELF criteria. A total of 56 subjects were planned to be accrued with a goal of having 51 subjects eligible to improve the historical 50% CR rate …

Outcomes Of 1,021 Consecutive Cases Utilizing A Triple Tapered Collared Stem And Automated Broaching System, Ravi R Agrawal, Maria T Schwabe, Helena F Barber, Ethan Blum, Joseph T Gibian, Ryan M Nunley, Ilya Bendich

2020-Current year OA Pubs

No abstract provided.