Digital Commons Network^™

The Effect Of Neighborhood Social Environment On Prostate Cancer Development In Black And White Men At High Risk For Prostate Cancer, Shannon M Lynch, Elizabeth Handorf, Kristen A Sorice, Elizabeth Blackman, Lisa Bealin, Veda N. Giri, Elias Obeid, Camille Ragin, Mary Daly

Department of Medical Oncology Faculty Papers

INTRODUCTION: Neighborhood socioeconomic (nSES) factors have been implicated in prostate cancer (PCa) disparities. In line with the Precision Medicine Initiative that suggests clinical and socioenvironmental factors can impact PCa outcomes, we determined whether nSES variables are associated with time to PCa diagnosis and could inform PCa clinical risk assessment.

MATERIALS AND METHODS: The study sample included 358 high risk men (PCa family history and/or Black race), aged 35-69 years, enrolled in an early detection program. Patient variables were linked to 78 nSES variables (employment, income, etc.) from previous literature via geocoding. Patient-level models, including baseline age, prostate specific antigen (PSA), …

White Matter Abnormalities Across Different Epilepsy Syndromes In Adults: An Enigma-Epilepsy Study, Sean N. Hatton, Khoa H. Huynh, Leonardo Bonilha, Eugenio Abela, Saud Alhusaini, Andre Altmann, Marina K. M. Alvim, Akshara R. Balachandra, Emanuele Bartolini, Benjamin Bender, Neda Bernasconi, Andrea Bernasconi, Boris Bernhardt, Núria Bargallo, Benoit Caldairou, Maria E. Caligiuri, Sarah J. A. Carr, Gianpiero L. Cavalleri, Fernando Cendes, Luis Concha, Esmaeil Davoodi-Bojd, Patricia M. Desmond, Orrin Devinsky, Colin P. Doherty, Martin Domin, John S. Duncan, Niels K. Focke, Sonya F. Foley, Antonio Gambardella, Ezequiel Gleichgerrcht, Renzo Guerrini, Khalid Hamandi, Akari Ishikawa, Simon S. Keller, Peter V. Kochunov, Raviteja Kotikalapudi, Barbara A.K. Kreilkamp, Patrick Kwan, Angelo Labate, Soenke Langner, Matteo Lenge, Min Liu, Elaine Lui, Pascal Martin, Mario Mascalchi, José C.V. Moreira, Marcia E. Morita-Sherman, Terence J. O'Brien, Heath R. Pardoe, José C. Pariente, Letícia F. Ribeiro, Mark P. Richardson, Cristiane S. Rocha, Raúl Rodríguez-Cruces, Felix Rosenow, Mariasavina Severino, Benjamin Sinclair, Hamid Soltanian-Zadeh, Pasquale Striano, Peter N. Taylor, Rhys H. Thomas, Domenico Tortora, Dennis Velakoulis, Annamaria Vezzani, Lucy Vivash, Felix Von Podewils, Sjoerd B. Vos, Bernd Weber, Gavin P. Winston, Clarissa L. Yasuda, Alyssa H. Zhu, Paul M. Thompson, Christopher D. Whelan, Neda Jahanshad, Sanjay M. Sisodiya, Carrie R. Mcdonald

Research Administration Articles

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n …

Therapeutic Plasma Exchange Taper Does Not Decrease Exacerbations In Immune Thrombotic Thrombocytopenic Purpura Patients, Jay S. Raval, Marshall A. Mazepa, Marian A. Rollins-Raval, Raj S. Kasthuri, Yara A. Park

Pathology Research and Scholarship

BACKGROUND: Despite rapid and intensive treatments with therapeutic plasma exchange (TPE) and immunosuppression, immune thrombotic thrombocytopenic purpura (TTP) patients are at risk of disease exacerbation, i.e., early recurrence of TTP within 30 days of achieving treatment response. TPE taper, a practice of performing additional TPE procedures after achieving treatment response, is commonly performed for decreasing exacerbations, although no evidence supports this practice.

STUDY DESIGN AND METHODS: In this prospective observational investigation over four years, our center switched its standard of care for treating all TTP patients from not performing TPE taper after achieving treatment response (i.e., no-taper cohort) to performance …

Real-World Cost Of Treatment For Multiple Sclerosis Patients Initiating And Receiving Infused Disease-Modifying Therapies Per Recommended Label In The United States., Jacqueline Nicholas, Rachel Halpern, Marina Ziehn, Jesse Peterson-Brandt, Michael Leszko, Chinmay Deshpande

Neuroscience Articles

Aims: The study evaluated the real-world cost of treatment in multiple sclerosis (MS) patients initiating infused disease-modifying-therapies (DMT) in the United States.Materials and Methods: This retrospective cohort study using administrative claims data included adult patients with MS initiating index infusion DMT (ocrelizumab (OCR), natalizumab (NTZ) or alemtuzumab (ATZ)) from April 2017-September 2018 with 6-months pre/12-months post-index continuous enrollment. The primary cohort included patients who had prescribed annual dosing visits indicated by the approved product label (PL): 3 OCR, 5 ATZ, and 12-13 NTZ infusion visits within the first year of initiation. Annual treatment cost was the sum of all …

Modulation Of Hedgehog Signaling By Kappa Opioids To Attenuate Osteoarthritis, Alexander E Weber, Omid Jalali, Sean Limfat, Ruzanna Shkhyan, Robert Van Der Horst, Siyoung Lee, Yucheng Lin, Liangliang Li, Erik N Mayer, Liming Wang, Nancy Q Liu, Frank A Petrigliano, Jay R Lieberman, Denis Evseenko

Faculty, Staff and Students Publications

OBJECTIVE: Inhibition of hedgehog (HH) signaling prevents cartilage degeneration and promotes repair in animal models of osteoarthritis (OA). This study, undertaken in OA models and in human OA articular cartilage, was designed to explore whether kappa opioid receptor (KOR) modulation via the inhibition of HH signaling may have therapeutic potential for achieving disease-modifying activity in OA.

METHODS: Primary human articular cartilage and synovial tissue samples from patients with knee OA undergoing total joint replacement and from healthy human subjects were obtained from the National Disease Research Interchange. For in vivo animal studies, a partial medial meniscectomy (PMM) model of knee …

The Brief Case: "Not Positive" Or "Not Sure"-Covid-19-Negative Results In A Symptomatic Patient, Bijal A Parikh, Thomas C Bailey, Patrick G Lyons, Neil W Anderson

Open Access Publications

No abstract provided.

Characterization Of A Multicenter Pediatric-Hydrocephalus Shunt Biobank, Jacob Gluski, Paul Zajciw, Prashant Hariharan, Amanda Morgan, Diego M Morales, Andrew Jea, William Whitehead, Neena Marupudi, Steven Ham, Sandeep Sood, James P Mcallister Ii, David D Limbrick Jr, Carolyn A Harris

Open Access Publications

BACKGROUND: Pediatric hydrocephalus is a devastating and costly disease. The mainstay of treatment is still surgical shunting of cerebrospinal fluid (CSF). These shunts fail at a high rate and impose a significant burden on patients, their families and society. The relationship between clinical decision making and shunt failure is poorly understood and multifaceted, but catheter occlusion remains the most frequent cause of shunt complications. In order to investigate factors that affect shunt failure, we have established the Wayne State University (WSU) shunt biobank.

METHODS: To date, four hospital centers have contributed various components of failed shunts and CSF from patients …

Trial Of Roflumilast Cream For Chronic Plaque Psoriasis, Mark G. Lebwohl, Kim A. Papp, Linda F. Stein Gold, Melinda J. Gooderham, Leon H. Kircik, Zoe D. Draelos, Steven E. Kempers, Mathew Zirwas, Kathleen Smith, David W. Osborne, Marie-Louise Trotman, Lynn Navale, Charlotte Merritt, David R. Berk, Howard Welgus

Dermatology Articles

BACKGROUND: Systemic oral phosphodiesterase type 4 (PDE-4) inhibitors have been effective in the treatment of psoriasis. Roflumilast cream contains a PDE-4 inhibitor that is being investigated for the topical treatment of psoriasis.

METHODS: In this phase 2b, double-blind trial, we randomly assigned adults with plaque psoriasis in a 1:1:1 ratio to use roflumilast 0.3% cream, roflumilast 0.15% cream, or vehicle (placebo) cream once daily for 12 weeks. The primary efficacy outcome was the investigator's global assessment (IGA) of a status of clear or almost clear at week 6 (assessed on a 5-point scale of plaque thickening, scaling, and erythema; a …

Reduced Intensity Conditioning For Acute Myeloid Leukemia Using Melphalan- Vs Busulfan-Based Regimens: A Cibmtr Report, Zheng Zhou, Rajneesh Nath, Jan Cerny, Hai-Lin Wang, Mei-Jie Zhang, Hisham Abdel-Azim, Vaibhav Agrawal, Gulrayz Ahmed, A Samer Al-Homsi, Mahmoud Aljurf, Hassan B Alkhateeb, Amer Assal, Ulrike Bacher, Ashish Bajel, Qaiser Bashir, Minocher Battiwalla, Vijaya Raj Bhatt, Michael Byrne, Jean-Yves Cahn, Mitchell Cairo, Hannah Choe, Edward Copelan, Corey Cutler, Moussab B Damlaj, Zachariah Defilipp, Marcos De Lima, Miguel Angel Diaz, Nosha Farhadfar, James Foran, César O Freytes, Aaron T Gerds, Usama Gergis, Michael R Grunwald, Zartash Gul, Mehdi Hamadani, Shahrukh Hashmi, Mark Hertzberg, Gerhard C Hildebrandt, Nasheed Hossain, Yoshihiro Inamoto, Luis Isola, Tania Jain, Rammurti T Kamble, Muhammad Waqas Khan, Mohamed A Kharfan-Dabaja, Partow Kebriaei, Natasha Kekre, Nandita Khera, Hillard M Lazarus, Jane L Liesveld, Mark Litzow, Hongtao Liu, David I Marks, Rodrigo Martino, Vikram Mathews, Asmita Mishra, Hemant S Murthy, Arnon Nagler, Ryotaro Nakamura, Sunita Nathan, Taiga Nishihori, Rebecca Olin, Richard F Olsson, Neil Palmisiano, Sagar S Patel, Mrinal M Patnaik, Attaphol Pawarode, Miguel-Angel Perales, Ioannis Politikos, Uday Popat, David Rizzieri, Brenda M Sandmaier, Bipin N Savani, Sachiko Seo, Nirav N Shah, Geoffrey L Uy, David Valcárcel, Leo F Verdonck, Edmund K Waller, Youjin Wang, Daniel Weisdorf, Baldeep Wirk, Eric Wong, Jean A Yared, Wael Saber

Faculty, Staff and Students Publications

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival …

Molecular And Clinicopathologic Features Of Gliomas Harboring Ntrk Fusions, Matthew Torre, Sonika Dahiya, Et Al

Open Access Publications

Fusions involving neurotrophic tyrosine receptor kinase (NTRK) genes are detected in ≤2% of gliomas and can promote gliomagenesis. The remarkable therapeutic efficacy of TRK inhibitors, which are among the first Food and Drug Administration-approved targeted therapies for NTRK-fused gliomas, has generated significant clinical interest in characterizing these tumors. In this multi-institutional retrospective study of 42 gliomas with NTRK fusions, next generation DNA sequencing (n = 41), next generation RNA sequencing (n = 1), RNA-sequencing fusion panel (n = 16), methylation profile analysis (n = 18), and histologic evaluation (n = 42) were performed. All infantile NTRK-fused gliomas (n = 7) …

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities In Lung Adenocarcinoma, Michael A. Gillette, Song Cao, Yize Li, Wen-Wei Liang, Michael C Wendl, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. …

Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A Nicholas, Hatice Hasturk, Jing Liu, Kai Jiang, Rui Liu, Zhenheng Guo, Jude Deeney, Caroline M Apovian, Jennifer Snyder-Cappione, Gregory S Hawk, Rebecca M Fleeman, Riley M F Pihl, Katherine Thompson, Anna C Belkina, Licong Cui, Elizabeth A Proctor, Philip A Kern, Barbara S Nikolajczyk

Faculty, Staff and Student Publications

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 …

Combined Lenvatinib And Pembrolizumab As Salvage Therapy In Advanced Adrenal Cortical Carcinoma, Sara Bedrose, Kevin Charles Miller, Lina Altameemi, Mohamed S Ali, Sameh Nassar, Naveen Garg, Marilyne Daher, Keith D Eaton, Jeffrey Thomas Yorio, Davey B Daniel, Matthew Campbell, Keith C Bible, Mabel Ryder, Ashish V Chintakuntlawar, Mouhammed Amir Habra

Faculty, Staff and Students Publications

BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.

METHODS: A retrospective case series describing the use of LEN/PEM …

Association Of Interleukin 7 Immunotherapy With Lymphocyte Counts Among Patients With Severe Coronavirus Disease 2019 (Covid-19), Pierre Francois Laterre, Bruno François, Christine Collienne, Philippe Hantson, Robin Jeannet, Kenneth E. Remy, Richard S. Hotchkiss

Open Access Publications

No abstract provided.

Prevalence, Incidence, And Clearance Of Human Papillomavirus Types Covered By Current Vaccines In Men With Human Immunodeficiency Virus In The Sun Study, Pragna Patel, Tim Bush, Lois Conley, Elizabeth R Unger, Teresa M Darragh, Keith Henry, Gerome Escota, John T Brooks, Erna Milunka Kojic

2020-Current year OA Pubs

BACKGROUND: High-risk anal human papillomavirus (HPV) infection is prevalent among men living with human immunodeficiency virus (HIV); the association between 9-valent (9v) high-risk HPV (HR-HPV) vaccine types and abnormal cytology has not been well characterized.

METHODS: We followed a prospective cohort study of persons with HIV at 7 HIV clinics in 4 US cities from March 2004 through June 2012. Annually, providers collected separate anal swabs for HPV detection and cytopathologic examination. Among men, we examined prevalence, incidence, and clearance of 9v HR-HPV vaccine types, compared with other HR types, and associations with abnormal cytology to assess potential vaccine impact. …

A Genome-Wide Association Study Identifies Two Novel Susceptible Regions For Squamous Cell Carcinoma Of The Head And Neck, Sanjay Shete, Hongliang Liu, Jian Wang, Robert Yu, Erich M Sturgis, Guojun Li, Kristina R Dahlstrom, Zhensheng Liu, Christopher I Amos, Qingyi Wei

Faculty, Staff and Students Publications

To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which 434,839 typed and 7,423,250 imputed SNPs as the discovery. SNPs with P <1×10–3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from dbGaP. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96×10–9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54×10–9 for the leading SNP rs142021700) was identified for hypo-pharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and eQTL analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of HLA loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN.

Implications Of New Understandings Of Gliomas In Children And Adults With Nf1: Report Of A Consensus Conference, Roger J Packer, David H Gutmann, Et Al.

2020-Current year OA Pubs

Gliomas are the most common primary central nervous system tumors occurring in children and adults with neurofibromatosis type 1 (NF1). Over the past decade, discoveries of the molecular basis of low-grade gliomas (LGGs) have led to new approaches for diagnosis and treatments. However, these new understandings have not been fully applied to the management of NF1-associated gliomas. A consensus panel consisting of experts in NF1 and gliomas was convened to review the current molecular knowledge of NF1-associated low-grade "transformed" and high-grade gliomas; insights gained from mouse models of NF1-LGGs; challenges in diagnosing and treating older patients with NF1-associated gliomas; and …

Posterior Cortical Atrophy: Characteristics From A Clinical Data Registry., Jennifer J Olds, William L Hills, Judith Warner, Julie Falardeau, Lori Haase Alasantro, Mark L Moster, Robert A Egan, Wayne T Cornblath, Andrew G Lee, Benjamin M Frishberg, Roger E Turbin, David M Katz, John A Charley, Victoria S Pelak

Department of Neurology Faculty Papers

No abstract provided.

Traumatic Injury Results In Prolonged Circulation Of Ultralarge Von Willebrand Factor And A Reduction In Adamts13 Activity, Mitchell R. Dyer, William E. Plautz, Margaret V. Ragni, Wyeth Alexander, Shannon Haldeman, Jason L. Sperry, Francis X. Guyette, Brian S. Zuckerbraun, Marian A. Rollins-Raval, Jay S. Raval, Matthew D. Neal

Pathology Research and Scholarship

BACKGROUND: Increases in plasma von Willebrand Factor (VWF) levels, accompanied by decreases in the metalloprotease ADAMTS13, have been demonstrated soon after traumatic injury while downstream effects remain unclear.

STUDY DESIGN AND METHODS: A cohort of 37 injured trauma patients from a randomized control trial investigating the use of prehospital plasma transfusion were analyzed for activity and antigen levels of ADAMTS13 and VWF at 0 and 24 hours after admission. Relevant clinical data were abstracted from the medical records. Trauma patient plasma was analyzed via agarose gel electrophoresis to evaluate the effects of injury on VWF multimer composition compared to healthy …

Relationships Of P16 Immunohistochemistry And Other Biomarkers With Diagnoses Of Cervical Abnormalities: Implications For Last Terminology, Philip E. Castle, Rachael Adcock, Jack Cuzick, Nicolas Wentzensen, Norah E. Torrez-Martinez, Salina M. Torres, Mark H. Stoler, Brigitte M. Ronnett, Nancy E. Joste, Teresa M. Darragh, Patti E. Gravitt, Mark Schiffman, William C. Hunt, Walter K. Kinney, Cosette M. Wheeler

Pathology Research and Scholarship

CONTEXT.—: Lower Anogenital Squamous Terminology (LAST) standardization recommended p16

OBJECTIVE.—: To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses.

DESIGN.—: A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available.

RESULTS.—: Biopsies were more likely to test p16 IHC positive with increasing severity of CP …

Friend And Spouse: Does The Level Of A Close-Knit, Same Sex Friend Affect Marital Intimacy?, Caitlyn Royal

Doctoral Dissertations and Projects

The purpose of this study is to contribute to the existing literature in the fields of Marital Intimacy and Healthy Friendships and adding empirical research about how the two constructs correlate. Currently, there is a gap in the literature regarding the effects of adult friendships on marital intimacy. Participants had to be in an ongoing heterosexual marriage for at least three years, be at least 18 years old and live within the United States in order to take an online survey that evaluated friendship levels and marital intimacy dynamics. Data was collected via the following instruments: Personal Assessment of Intimacy …

Emergency Potassium Normalization Treatment Including Sodium Zirconium Cyclosilicate: A Phase Ii, Randomized, Double-Blind, Placebo-Controlled Study (Energize), W Frank Peacock, Zubaid Rafique, Konstantin Vishnevskiy, Edward Michelson, Elena Vishneva, Tatiana Zvereva, Rajaa Nahra, Dao Li, Joseph Miller

Faculty, Staff and Students Publications

OBJECTIVES: Sodium zirconium cyclosilicate (SZC) is a novel, highly selective potassium binder currently approved in the United States and European Union for treatment of hyperkalemia. This pilot evaluation explored the efficacy of SZC with insulin and glucose as hyperkalemia treatment in the emergency department (ED).

METHODS:This exploratory, phase II, multicenter, randomized, double‐blind, placebo‐controlled study (NCT03337477) enrolled adult ED patients with blood potassium ≥ 5.8 mmol/L. Patients were randomized 1:1 to receive SZC 10 g or placebo, up to three times during a 10‐hour period, with insulin and glucose. The primary efficacy outcome was the mean change in serum …

Decomposing Loss Aversion From Gaze Allocation And Pupil Dilation, Feng Sheng, Arjun Ramakrishnan, Darsol Seok, Wenjia Joyce Zhao, Samuel Thelaus, Puti Cen, Michael Louis Platt

Faculty, Staff and Student Publications

Loss-averse decisions, in which one avoids losses at the expense of gains, are highly prevalent. However, the underlying mechanisms remain controversial. The prevailing account highlights a valuation bias that overweighs losses relative to gains, but an alternative view stresses a response bias to avoid choices involving potential losses. Here we couple a computational process model with eye-tracking and pupillometry to develop a physiologically grounded framework for the decision process leading to accepting or rejecting gambles with equal odds of winning and losing money. Overall, loss-averse decisions were accompanied by preferential gaze toward losses and increased pupil dilation for accepting gambles. …

Coronary Heart Disease And Mortality Following A Breast Cancer Diagnosis, Aixia Guo, Kathleen W Zhang, Kristi Reynolds, Randi E Foraker

Open Access Publications

BACKGROUND: Coronary heart disease (CHD) is a leading cause of morbidity and mortality for breast cancer survivors, yet the joint effect of adverse cardiovascular health (CVH) and cardiotoxic cancer treatments on post-treatment CHD and death has not been quantified.

METHODS: We conducted statistical and machine learning approaches to evaluate 10-year risk of these outcomes among 1934 women diagnosed with breast cancer during 2006 and 2007. Overall CVH scores were classified as poor, intermediate, or ideal for 5 factors, smoking, body mass index, blood pressure, glucose/hemoglobin A1c, and cholesterol from clinical data within 5 years prior to the breast cancer diagnosis. …

Transcriptional Analyses Of Adult And Pediatric Adamantinomatous Craniopharyngioma Reveals Similar Expression Signatures Regarding Potential Therapeutic Targets, Eric Prince, Chibueze Agwu, David D Limbrick, Et Al

Open Access Publications

Adamantinomatous craniopharyngioma (ACP) is a biologically benign but clinically aggressive lesion that has a significant impact on quality of life. The incidence of the disease has a bimodal distribution, with peaks occurring in children and older adults. Our group previously published the results of a transcriptome analysis of pediatric ACPs that identified several genes that were consistently overexpressed relative to other pediatric brain tumors and normal tissue. We now present the results of a transcriptome analysis comparing pediatric to adult ACP to identify biological differences between these groups that may provide novel therapeutic insights or support the assertion that potential …

Dna Methylation Signature For Ezh2 Functionally Classifies Sequence Variants In Three Prc2 Complex Genes, Sanaa Choufani, William T. Gibson, Andrei L. Turinsky, Brian H Y Chung, Tianren Wang, Kopal Garg, Alessandro Vitriolo, Ana S A Cohen, Sharri Cyrus, Sarah Goodman, Eric Chater-Diehl, Jack Brzezinski, Michael Brudno, Luk Ho Ming, Susan M. White, Sally Ann Lynch, Carol Clericuzio, I Karen Temple, Frances Flinter, Vivienne Mcconnell, Tom Cushing, Lynne M. Bird, Miranda Splitt, Bronwyn Kerr, Stephen W. Scherer, Jerry Machado, Eri Imagawa, Nobuhiko Okamoto, Naomichi Matsumoto, Guiseppe Testa, Maria Iascone, Romano Tenconi, Oana Caluseriu, Roberto Mendoza-Londono, David Chitayat, Cheryl Cytrynbaum, Katrina Tatton-Brown, Rosanna Weksberg

Pediatrics Research and Scholarship

Weaver syndrome (WS), an overgrowth/intellectual disability syndrome (OGID), is caused by pathogenic variants in the histone methyltransferase EZH2, which encodes a core component of the Polycomb repressive complex-2 (PRC2). Using genome-wide DNA methylation (DNAm) data for 187 individuals with OGID and 969 control subjects, we show that pathogenic variants in EZH2 generate a highly specific and sensitive DNAm signature reflecting the phenotype of WS. This signature can be used to distinguish loss-of-function from gain-of-function missense variants and to detect somatic mosaicism. We also show that the signature can accurately classify sequence variants in EED and SUZ12, which encode two other …

Tetraspanin Cd82 Drives Acute Myeloid Leukemia Chemoresistance By Modulating Protein Kinase C Alpha And Β1 Integrin Activation, Muskan Floren, Sebastian Restrepo Cruz, Christina M. Termini, Kristopher D. Marjon, Keith A. Lidke, Jennifer M. Gillette

Pathology Research and Scholarship

A principal challenge in treating acute myeloid leukemia (AML) is chemotherapy refractory disease. As such, there remains a critical need to identify key regulators of chemotherapy resistance in AML. In this study, we demonstrate that the membrane scaffold, CD82, contributes to the chemoresistant phenotype of AML. Using an RNA-seq approach, we identified the increased expression of the tetraspanin family member, CD82, in response to the chemotherapeutic, daunorubicin. Analysis of the TARGET and BEAT AML databases identifies a correlation between CD82 expression and overall survival of AML patients. Moreover, using a combination of cell lines and patient samples, we find that …

Characterization Of Adnexal Masses Using Contrast-Enhanced Subharmonic Imaging: A Pilot Study., Lauren J. Delaney, Priscilla Machado, Mehnoosh Torkzaban, Andrej Lyshchik, Corinne Wessner, Christine H. Kim, Md, Norman G Rosenblum, Scott D. Richard, Kirk Wallace, Flemming Forsberg

Department of Radiology Faculty Papers

OBJECTIVES: This pilot study evaluated whether contrast-enhanced subharmonic imaging (SHI) could be used to characterize adnexal masses before surgical intervention.

METHODS: Ten women (with 12 lesions) scheduled for surgery of an ovarian mass underwent an SHI examination of their adnexal region using a modified LOGIQ E9 scanner (GE Healthcare, Waukesha, WI) with an endocavitary transducer, in which digital clips were acquired by pulse destruction-replenishment SHI across the lesions. Time-intensity curves were created offline to quantitatively evaluate SHI parameters (fractional tumor perfusion, peak contrast intensity, time to peak contrast enhancement, and area under the time-intensity curve), which were compared to pathologic …

The Β3-Adrenergic Receptor Agonist Mirabegron Improves Glucose Homeostasis In Obese Humans, Brian S. Finlin, Hasiyet Memetimin, Beibei Zhu, Amy L. Confides, Hemendra J. Vekaria, Riham H. El Khouli, Zachary R. Johnson, Philip M. Westgate, Jianzhong Chen, Andrew J. Morris, Patrick G. Sullivan, Esther E. Dupont-Versteegden, Philip A. Kern

Internal Medicine Faculty Publications

BACKGROUND. Beige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains β3-adrenergic receptors (β3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the β3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.

METHODS. Before and after β3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and …

An Interdisciplinary Study To Understand Treatment Seeking Behavior Among Female Survivors Of Anorexia Nervosa, Meaghan Victoria Tipton

Graduate Theses and Dissertations

This study was done to examine what psychosocial factors influence treatment seeking behavior among female survivors of eating disorders. This study uses a mixed methods survey consisting of open-ended item questions regarding treatment experience and social environment, and close-ended items to measure constructs from the Health Belief Model. Fourteen participants were recruited for this study to retrospectively detail their experiences of treatment during their eating disorder. All fourteen participants identified as Caucasian, thirteen identified as female, one identified with other gender, each with a history of medically diagnosed anorexia nervosa. The mean of age of current participants was 29.46, and …