Medicine and Health Sciences Commons^™

Envisioning Future Urinary Tract Infection Diagnostics, Robin Patel, Christopher R Polage, Jennifer Dien Bard, Larissa May, Francesca M Lee, Valeria Fabre, Mary K Hayden, Sarah D B Doernberg, David A Haake, Barbara W Trautner, Larissa Grigoryan, Ephraim L Tsalik, Kimberly E Hanson

Faculty, Staff and Students Publications

Urinary tract infections (UTIs) are among the most common bacterial infections in the United States and are a major driver of antibiotic use, both appropriate and inappropriate, across healthcare settings. Novel UTI diagnostics are a strategy that might enable better UTI treatment. Members of the Antibacterial Resistance Leadership Group Laboratory Center and the Infectious Diseases Society of America Diagnostics Committee convened to envision ideal future UTI diagnostics, with a view towards improving delivery of healthcare, patient outcomes and experiences, and antibiotic use, addressing which types of UTI diagnostics are needed and how companies might approach development of novel UTI diagnostics.

Mechanistic Origin Of Different Binding Affinities Of Sars-Cov And Sars-Cov-2 Spike Rbds To Human Ace2, Zhi-Bi Zhang, Yuan-Ling Xia, Jian-Xin Shen, Wen-Wen Du, Yun-Xin Fu, Shu-Qun Liu

Faculty, Staff and Student Publications

The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (RBDCoV2) has a higher binding affinity to the human receptor angiotensin-converting enzyme 2 (ACE2) than the SARS-CoV RBD (RBDCoV). Here, we performed molecular dynamics (MD) simulations, binding free energy (BFE) calculations, and interface residue contact network (IRCN) analysis to explore the mechanistic origin of different ACE2-binding affinities of the two RBDs. The results demonstrate that, when compared to the RBDCoV2-ACE2 complex, RBDCoV-ACE2 features enhanced dynamicsand inter-protein positional movements and increased conformational entropy and conformational diversity. Although the inter-protein electrostatic attractive interactions are the primary determinant for the high ACE2-binding affinities of …

Alpha-Fetoprotein (Afp) And Afp-L3 Is Most Useful In Detection Of Recurrence Of Hepatocellular Carcinoma In Patients After Tumor Ablation And With Low Afp Level, Madison Force, Grace Park, Divya Chalikonda, Christopher G. Roth, Micah Cohen, Dina Halegoua-De Marzio, Hie-Won Hann

Department of Medicine Faculty Papers

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is a leading cause of mortality worldwide. While there are many risk factors for HCC including alcohol, obesity, and diabetes, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection still account for the majority of HCC worldwide. Globally, HBV is the leading risk factor for HCC. Patients with chronic hepatitis B (CHB) and advanced liver disease are at high risk for HCC. Screening for HCC is done routinely with ultrasound with or without alpha-fetoprotein (AFP) at six-month intervals. The combination of ultrasound and AFP has been …

Exploring Preventive Healthcare In A High-Risk Vulnerable Population, Trisha L Amboree, Jane R Montealegre, Kayo Fujimoto, Osaro Mgbere, Charles Darkoh, Paige Padgett Wermuth

Faculty, Staff and Student Publications

This study describes preventive care behaviors and explores opportunities to deliver preventive sexual healthcare to a high-risk vulnerable population. Data from the National HIV Behavioral Surveillance (NHBS) system high-risk heterosexuals (HET) cycle (2019) in Houston, Texas, was used to describe preventive care utilization and assess the relationship between healthcare utilization and sociodemographic characteristics. More than 47% reported having no usual source of healthcare, and 94.6% reported receiving no non-HIV STI testing in the past 12 months. Additionally, many sociodemographic factors were associated with healthcare utilization and having a usual source of healthcare. Future efforts should be targeted at increasing preventive …

Meta-Analysis Of Genome-Wide Association Studies Identifies Ancestry-Specific Associations Underlying Circulating Total Tau Levels, Chloé Sarnowski, Mohsen Ghanbari, Joshua C Bis, Mark Logue, Myriam Fornage, Aniket Mishra, Shahzad Ahmad, Alexa S Beiser, Eric Boerwinkle, Vincent Bouteloup, Vincent Chouraki, L Adrienne Cupples, Vincent Damotte, Charles S Decarli, Anita L Destefano, Luc Djoussé, Alison E Fohner, Carol E Franz, Tiffany F Kautz, Jean-Charles Lambert, Michael J Lyons, Thomas H Mosley, Kenneth J Mukamal, Matthew P Pase, Eliana C Portilla Fernandez, Robert A Rissman, Claudia L Satizabal, Ramachandran S Vasan, Amber Yaqub, Stephanie Debette, Carole Dufouil, Lenore J Launer, William S Kremen, William T Longstreth, M Arfan Ikram, Sudha Seshadri

Faculty, Staff and Student Publications

Circulating total-tau levels can be used as an endophenotype to identify genetic risk factors for tauopathies and related neurological disorders. Here, we confirmed and better characterized the association of the 17q21 MAPT locus with circulating total-tau in 14,721 European participants and identified three novel loci in 953 African American participants (4q31, 5p13, and 6q25) at P < 5 × 10-8. We additionally detected 14 novel loci at P < 5 × 10-7, specific to either Europeans or African Americans. Using whole-exome sequence data in 2,279 European participants, we identified ten genes associated with circulating total-tau when aggregating rare variants. Our genetic study sheds light on genes reported to be associated with neurological diseases including stroke, Alzheimer's, and Parkinson's (F5, MAP1B, and BCAS3), with Alzheimer's pathological hallmarks (ADAMTS12, IL15, and FHIT), or with an important function in the brain (PARD3, ELFN2, UBASH3B, SLIT3, and NSD3), and suggests that the genetic architecture of circulating total-tau may differ according to ancestry.

Exploiting 4–1bb Immune Checkpoint To Enhance The Efficacy Of Oncolytic Virotherapy For Diffuse Intrinsic Pontine Gliomas, Virginia Laspidea, Montserrat Puigdelloses, Sara Labiano, Lucía Marrodán, Marc Garcia-Moure, Marta Zalacain, Marisol Gonzalez-Huarriz, Naiara Martínez-Vélez, Iker Ausejo-Mauleon, Daniel De La Nava, Guillermo Herrador-Cañete, Javier Marco-Sanz, Elisabeth Guruceaga, Carlos E De Andrea, María Villalba, Oren Becher, Massimo Squatrito, Verónica Matía, Jaime Gállego Pérez-Larraya, Ana Patiño-García, Sumit Gupta, Candelaria Gomez-Manzano, Juan Fueyo, Marta M Alonso

Faculty, Staff and Student Publications

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors, and patient survival has not changed despite many therapeutic efforts, emphasizing the urgent need for effective treatments. Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was engineered to express the costimulatory ligand 4-1BBL to potentiate the antitumor immune response of the virus. Delta-24-ACT induced the expression of functional 4-1BBL on the membranes of infected DIPG cells, which enhanced the costimulation of CD8+ T lymphocytes. In vivo, Delta-24-ACT treatment of murine DIPG orthotopic tumors significantly improved the survival of treated mice, leading to long-term survivors that developed …

Repurposing Probenecid For The Treatment Of Heart Failure (Re-Prosper-Hf): A Study Protocol For A Randomized Placebo-Controlled Clinical Trial, Jack Rubinstein, Nathan Robbins, Karen Evans, Gabrielle Foster, Kevin Mcconeghy, Toluwalope Onadeko, Julie Bunke, Melanie Parent, Xi Luo, Jacob Joseph, Wen-Chih Wu

Faculty, Staff and Student Publications

BACKGROUND: Improving contractility in heart failure with reduced ejection fraction (HFrEF) has resurfaced as a potential treatment goal. Inotropic therapy is now better understood through its underlying mechanism as opposed to the observed effect of increasing contractility. Calcitropes are a subgroup of inotropes that largely depend on the stimulation of adenylyl cyclase to transform ATP into cyclic adenosine monophosphate (cAMP). At least two clinically relevant calcitropes-istaroxime and probenecid-improve contractility through an increase in systolic intracellular calcium without activating cAMP production. Probenecid, which has been safely used clinically for decades in non-cardiac conditions, has recently been identified as an agonist of …

Predicted Gene Expression In Ancestrally Diverse Populations Leads To Discovery Of Susceptibility Loci For Lifestyle And Cardiometabolic Traits, Heather M Highland, Genevieve L Wojcik, Mariaelisa Graff, Katherine K Nishimura, Chani J Hodonsky, Antoine R Baldassari, Alanna C Cote, Iona Cheng, Christopher R Gignoux, Ran Tao, Yuqing Li, Eric Boerwinkle, Myriam Fornage, Jeffrey Haessler, Lucia A Hindorff, Yao Hu, Anne E Justice, Bridget M Lin, Danyu Lin, Daniel O Stram, Christopher A Haiman, Charles Kooperberg, Loic Le Marchand, Tara C Matise, Eimear E Kenny, Christopher S Carlson, Eli A Stahl, Christy L Avery, Kari E North, Jose Luis Ambite, Steven Buyske, Ruth J Loos, Ulrike Peters, Kristin L Young, Stephanie A Bien, Laura M Huckins

Faculty, Staff and Student Publications

One mechanism by which genetic factors influence complex traits and diseases is altering gene expression. Direct measurement of gene expression in relevant tissues is rarely tenable; however, genetically regulated gene expression (GReX) can be estimated using prediction models derived from large multi-omic datasets. These approaches have led to the discovery of many gene-trait associations, but whether models derived from predominantly European ancestry (EA) reference panels can map novel associations in ancestrally diverse populations remains unclear. We applied PrediXcan to impute GReX in 51,520 ancestrally diverse Population Architecture using Genomics and Epidemiology (PAGE) participants (35% African American, 45% Hispanic/Latino, 10% Asian, …

Loss-Of-Function Variants In Tiam1 Are Associated With Developmental Delay, Intellectual Disability, And Seizures, Shenzhao Lu, Rebecca Hernan, Paul C Marcogliese, Yan Huang, Tracy S Gertler, Meltem Akcaboy, Shiyong Liu, Hyung-Lok Chung, Xueyang Pan, Xiaoqin Sun, Melahat Melek Oguz, Ulkühan Oztoprak, Jeroen H F De Baaij, Jelena Ivanisevic, Erin Mcginnis, Maria J Guillen Sacoto, Wendy K Chung, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

TIAM Rac1-associated GEF 1 (TIAM1) regulates RAC1 signaling pathways that affect the control of neuronal morphogenesis and neurite outgrowth by modulating the actin cytoskeletal network. To date, TIAM1 has not been associated with a Mendelian disorder. Here, we describe five individuals with bi-allelic TIAM1 missense variants who have developmental delay, intellectual disability, speech delay, and seizures. Bioinformatic analyses demonstrate that these variants are rare and likely pathogenic. We found that the Drosophila ortholog of TIAM1, still life (sif), is expressed in larval and adult central nervous system (CNS) and is mainly expressed in a subset of neurons, but not in …

Quality Of Life Impact And Recovery After Ureteroscopy And Stent Insertion: Insights From Daily Surveys In Stents, Jonathan D Harper, Alana C Desai, Jodi A Antonelli, Gregory E Tasian, Justin B Ziemba, Hussein R Al-Khalidi, H Henry Lai, Naim M Maalouf, Peter P Reese, Hunter B Wessells, Ziya Kirkali, Charles D Scales, Niddk Urinary Stone Disease Research Network (Usdrn)

2020-Current year OA Pubs

BACKGROUND: Our objective was to describe day-to-day evolution and variations in patient-reported stent-associated symptoms (SAS) in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS), a prospective multicenter observational cohort study, using multiple instruments with conceptual overlap in various domains.

METHODS: In a nested cohort of the STENTS study, the initial 40 participants having unilateral ureteroscopy (URS) and stent placement underwent daily assessment of self-reported measures using the Brief Pain Inventory short form, Patient-Reported Outcome Measurement Information System measures for pain severity and pain interference, the Urinary Score of the Ureteral Stent Symptom Questionnaire, and Symptoms of Lower Urinary Tract …

Hsp90-Cdc37 Functions As A Chaperone For The Oncogenic Fgfr3-Tacc3 Fusion, Tao Li, Farideh Mehraein-Ghomi, M Elizabeth Forbes, Sanjeev V Namjoshi, E Ashley Ballard, Qianqian Song, Ping-Chieh Chou, Xuya Wang, Brittany C Parker Kerrigan, Frederick F Lang, Glenn Lesser, Waldemar Debinski, Xuejun Yang, Wei Zhang

Faculty, Staff and Student Publications

The FGFR3-TACC3 (F3-T3) fusion gene was discovered as an oncogenic molecule in glioblastoma and bladder cancers, and has subsequently been found in many cancer types. Notably, F3-T3 was found to be highly expressed in both untreated and matched recurrence glioblastoma under the concurrent radiotherapy and temozolomide (TMZ) treatment, suggesting that targeting F3-T3 is a valid strategy for treatment. Here, we show that the F3-T3 protein is a client of heat shock protein 90 (HSP90), forming a ternary complex with the cell division cycle 37 (CDC37). Deprivation of HSP90 or CDC37 disrupts the formation of the ternary complex, which destabilizes glycosylated …

Safety And Efficacy Of Colchicine In Covid-19 Patients: A Systematic Review And Meta-Analysis Of Randomized Control Trials, Farah Yasmin, Hala Najeeb, Abdul Moeed, Wardah Hassan, Mahima Khatri, Muhammad Sohaib Asghar, Ahmed Kunwer Naveed, Waqas Ullah, Salim Surani

Department of Medicine Faculty Papers

Background: Colchicine has been used an effective anti-inflammatory drug to treat gout diseases. Owing to its pharmacodynamic of inhibiting interleukins, it has been repurposed to target the cytokine storm post-SARS-CoV-2 invasion. The goal of this meta-analysis was to evaluate the safety profile of colchicine in COVID-19 patients using the gold-standard randomised-control trials.

Methods: Electronic databases (Pubmed, Google Scholar, and Cochrane) were systematically searched until June 2021 and RCTs were extracted. Outcomes of interest included all-cause mortality, COVID-19 severity, mechanical ventilation, C-reactive protein and D-dimer levels. Using a random-effects model, dichotomous outcomes were pooled using odds ratios (OR) through the generic …

Overcrowded Housing Increases Risk For Covid-19 Mortality: An Ecological Study, Karan Varshney, Talia Glodjo, Jenna R Adalbert

College of Population Health Faculty Papers

Objectives: Overcrowded housing is a sociodemographic variable associated with increased infection and mortality rates from communicable diseases. It is not well understood if this association exists for COVID-19. Our objective was hence to determine the association between household overcrowding and risk of mortality from COVID-19, and this was done by performing bivariable and multivariable analyses using COVID-19 data from cities in Los Angeles County.

Results: Bivariate regression revealed that overcrowded households were positively associated with COVID-19 deaths (standardized β = 0.863, p < 0.001). COVID-19 case totals, people aged 60+, and the number of overcrowded households met conditions for inclusion in the backwards stepwise linear regression model. Analysis revealed all independent variables were positively associated with mortality rates, primarily for individuals 60 + (standardized β1 = 0.375, p = 0.001), followed by overcrowded households (standardized β2 = 0.346, p = 0.014), and total COVID-19 cases (standardized β3 = 0.311, p < 0.001). Our findings highlight that residing in overcrowded households may be an important risk factor for COVID-19 mortality. Public health entities should consider this population when allocating resources for prevention and control of COVID-19 mortality and future disease outbreaks.

Overcrowded Housing Increases Risk For Covid-19 Mortality: An Ecological Study., Karan Varshney, Talia Glodjo, Jenna Adalbert

College of Population Health Faculty Papers

OBJECTIVES: Overcrowded housing is a sociodemographic variable associated with increased infection and mortality rates from communicable diseases. It is not well understood if this association exists for COVID-19. Our objective was hence to determine the association between household overcrowding and risk of mortality from COVID-19, and this was done by performing bivariable and multivariable analyses using COVID-19 data from cities in Los Angeles County.

RESULTS: Bivariate regression revealed that overcrowded households were positively associated with COVID-19 deaths (standardized β = 0.863, p < 0.001). COVID-19 case totals, people aged 60+, and the number of overcrowded households met conditions for inclusion in the backwards stepwise linear regression model. Analysis revealed all independent variables were positively associated with mortality rates, primarily for individuals 60 + (standardized β

Meloxicam Versus Celecoxib For Postoperative Analgesia After Total Knee Arthroplasty: Safety, Efficacy And Cost, Amer Haffar, Yale A Fillingham, Leigham Breckenridge, D'Andrew Gursay, Jess H Lonner

Rothman Institute Papers

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as part of multimodal analgesia in total knee arthroplasty (TKA). Selective cyclooxygenase (COX)-2 inhibitors (e.g., celecoxib) are believed to have fewer gastrointestinal (GI) adverse effects than nonselective NSAIDS. Meloxicam is less selective for COX-2 than celecoxib is and partially inhibits COX-1 at higher doses. Nonetheless, some surgeons prefer using nonselective NSAIDs because of their lower expense.

METHODS: Four thousand nine hundred ninety-four patients who underwent TKA between January 2015 and February 2020 and took either celecoxib (n = 3,174), meloxicam 15 mg/d (n = 1,819), or meloxicam 7.5 mg/d (n = 451) …

Genetic Evaluation For Hereditary Cancer Syndromes Among African Americans: A Critical Review, Ambreen Khan, Charles R Rogers, Carson D Kennedy, Ana Maria Lopez, Joanne Jeter

Department of Medical Oncology Faculty Papers

While hereditary cancer syndromes have been described and studied for centuries, the completion of the human genome project fueled accelerated progress in precision medicine due to the introduction of genetic testing in the 1990s, creating avenues for tailored treatments and medical management options. However, genetic testing has not benefited everyone equitably, with nearly all of the published work based on individuals of non-Hispanic White/European ancestry. There remains a gap in knowledge regarding the prevalence, penetrance, and manifestations of common hereditary cancer syndromes in the African-American population due to significant disparities in access and uptake of genetic testing. This review summarizes …

Perceptions Of Weight Status And Energy Balance Behaviors Among Patients With Non-Alcoholic Fatty Liver Disease, Natalia I Heredia, Ruchi Gaba, Yan Liu, Shilpa Jain, Manasi Rungta, Manav Rungta, Hashem B El-Serag, Fasiha Kanwal, Aaron P Thrift, Maya Balakrishnan

Faculty, Staff and Students Publications

Weight loss through behavioral modification is central to treating non-alcoholic fatty liver disease (NAFLD). To achieve this, patients need to accurately self-perceive their health behaviors. We aimed to identify predictors of concordance between self-perception and objective measures of body weight, physical activity (PA) and dietary behaviors. We used data from the Harris County NAFLD Cohort, an ongoing prospective study in a regional safety-net healthcare system. Patients completed self-administered baseline questionnaires on demographics, diet, PA, and self-perceptions. We assessed concordance between actual and self-perceived body weight and energy-balance behaviors. Multivariable logistic regression identified predictors of concordance. Patients (n = 458; average …

Demographic And Regional Trends Of Mortality In Patients With Aortic Dissection In The United States, 1999 To 2019, Salik Nazir, Robert W Ariss, Abdul Mannan Khan Minhas, Rochell Issa, Erin D Michos, Yochai Birnbaum, George V Moukarbel, P Kasi Ramanathan, Hani Jneid

Faculty, Staff and Students Publications

Background Aortic dissection (AoD) is associated with high morbidity and mortality. However, the burden of AoD mortality is not well characterized, and contemporary data and mortality trends in different demographic and geographic subgroups have not been described. Methods and Results Trends in AoD mortality were assessed using a cross-sectional analysis of the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database. Crude and age-adjusted mortality rates (AAMR) per 1 million people with associated annual percent changes were determined. Joinpoint regression was used to assess trends in the overall sample and different demographic (sex, race and ethnicity, …

Implementing A New Emergency Department: A Qualitative Study Of Health Professionals' Change Responses And Perceptions, Nina Thórný Stefánsdóttir, Per Nilsen, Mette Bendtz Lindstroem, Ove Andersen, Byron J Powell, Tine Tjørnhøj-Thomsen, Jeanette Wassar Kirk

2020-Current year OA Pubs

BACKGROUND: The aim of the study is two-fold. It explores how managers and key employees at the Emergency Department (ED) and specialist departments in a university hospital in the Capital Region of Denmark respond to the planned change to a new ED, and how they perceive the change involved in the implementation of the new ED. The study investigates what happens when health professionals are confronted with implementation of policy that changes their organization and everyday work lives. Few studies provide in-depth investigations of health professionals' reactions to the implementation of new EDs, and particularly how they influence the implementation …

Left Ventricular Hypertrophy And Biomarkers Of Cardiac Damage And Stress In Aortic Stenosis, Elliot J Stein, Nishath Quader, Alan Zajarias, Anna Vatterott, Et Al

2020-Current year OA Pubs

Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core-laboratory-measured LV mass index, cTnT, and NT-proBNP. LVH was defined by sex-specific guideline cut-offs and elevated biomarker levels were based on age and sex cut-offs. Adjusted Cox proportional hazards models evaluated …

Harmonizing Model Organism Data In The Alliance Of Genome Resources., Alliance Of Genome Resources Consortium, Anna V. Anagnostopoulos, Susan M. Bello, Judith A. Blake, Olin Blodgett, Carol J. Bult, Karen R. Christie, Mary E. Dolan, Paul Hale, James A. Kadin, Monica S. Mcandrews, Howie Motenko, David R. Shaw, Constance M. Smith, Cynthia L. Smith, Monika Tomczuk, Laurens G. Wilming

Faculty Research 2022

The Alliance of Genome Resources (the Alliance) is a combined effort of 7 knowledgebase projects: Saccharomyces Genome Database, WormBase, FlyBase, Mouse Genome Database, the Zebrafish Information Network, Rat Genome Database, and the Gene Ontology Resource. The Alliance seeks to provide several benefits: better service to the various communities served by these projects; a harmonized view of data for all biomedical researchers, bioinformaticians, clinicians, and students; and a more sustainable infrastructure. The Alliance has harmonized cross-organism data to provide useful comparative views of gene function, gene expression, and human disease relevance. The basis of the comparative views is shared calls of …

Methylation Quantitative Trait Loci Are Largely Consistent Across Disease States In Crohn’S Disease, Suresh Venkateswaran, Hari K Somineni, Varun Kilaru, Seyma Katrinli, Jarod Prince, David T Okou, Jeffrey S Hyams, Lee A Denson, Richard Kellermayer, Greg Gibson, David J Cutler, Alicia K Smith, Subra Kugathasan, Karen N Conneely

Faculty, Staff and Students Publications

Recently, we identified 1,189 CpG sites whose DNA methylation level in blood associated with Crohn's disease. Here, we examined associations between DNA methylation and genetic variants to identify methylation quantitative trait loci across disease states in (1) 402 blood samples from 164 newly diagnosed pediatric Crohn's disease patients taken at 2 time points (diagnosis and follow-up), and 74 non-inflammatory bowel disease controls, (2) 780 blood samples from a non-Crohn's disease adult population, and (3) 40 ileal biopsies (17 Crohn's disease cases and 23 non-inflammatory bowel disease controls) from group (1). Genome-wide DNAm profiling and genotyping were performed using the Illumina …

Privacy-Preserving Logistic Regression With Secret Sharing, Ali Reza Ghavamipour, Fatih Turkmen, Xiaoqian Jiang

Faculty, Staff and Student Publications

BACKGROUND: Logistic regression (LR) is a widely used classification method for modeling binary outcomes in many medical data classification tasks. Researchers that collect and combine datasets from various data custodians and jurisdictions can greatly benefit from the increased statistical power to support their analysis goals. However, combining data from different sources creates serious privacy concerns that need to be addressed.

METHODS: In this paper, we propose two privacy-preserving protocols for performing logistic regression with the Newton-Raphson method in the estimation of parameters. Our proposals are based on secure Multi-Party Computation (MPC) and tailored to the honest majority and dishonest majority …

Epistemic Beliefs: Relationship To Future Expectancies And Quality Of Life In Cancer Patients., Paul K J Han, Elizabeth Scharnetzki, Eric Anderson, John Dipalazzo, Tania D Strout, Caitlin Gutheil, F Lee Lucas, Emily A Edelman, Jens Rueter

Faculty Research 2022

CONTEXT: Expectations about the future (future expectancies) are important determinants of psychological well-being among cancer patients, but the strategies patients use to maintain positive and cope with negative expectancies are incompletely understood.

OBJECTIVES: To obtain preliminary evidence on the potential role of one strategy for managing future expectancies: the adoption of "epistemic beliefs" in fundamental limits to medical knowledge.

METHODS: A sample of 1307 primarily advanced-stage cancer patients participating in a genomic tumor testing study in community oncology practices completed measures of epistemic beliefs, positive future expectancies, and mental and physical health-related quality of life (HRQOL). Descriptive and linear regression …

Auriculocondylar Syndrome 2 Results From The Dominant-Negative Action Of Plcb4 Variants., Stanley M Kanai, Caleb Heffner, Timothy C Cox, Michael L Cunningham, Francisco A Perez, Aaron M Bauer, Philip Reigan, Cristan Carter, Stephen A Murray, David E Clouthier

Faculty Research 2022

Auriculocondylar syndrome 2 (ARCND2) is a rare autosomal dominant craniofacial malformation syndrome linked to multiple genetic variants in the coding sequence of phospholipase C β4 (PLCB4). PLCB4 is a direct signaling effector of the endothelin receptor type A (EDNRA)-Gq/11 pathway, which establishes the identity of neural crest cells (NCCs) that form lower jaw and middle ear structures. However, the functional consequences of PLCB4 variants on EDNRA signaling is not known. Here, we show, using multiple signaling reporter assays, that known PLCB4 variants resulting from missense mutations exert a dominant-negative interference over EDNRA signaling. In addition, using CRISPR/Cas9, we find that …

Sex-Specific Alterations In Hepatic Cholesterol Metabolism In Low Birth Weight Adult Guinea Pigs., Ousseynou Sarr, Katherine E Mathers, Christina Vanderboor, Kristina Wiggers, Aditya Devgan, Daniel B Hardy, Lin Zhao, Timothy Regnault

Paediatrics Publications

BACKGROUND: Intrauterine growth restriction and low birth weight (LBW) have been widely reported as an independent risk factor for adult hypercholesterolaemia and increased hepatic cholesterol in a sex-specific manner. However, the specific impact of uteroplacental insufficiency (UPI), a leading cause of LBW in developed world, on hepatic cholesterol metabolism in later life, is ill defined and is clinically relevant in understanding later life liver metabolic health trajectories.

METHODS: Hepatic cholesterol, transcriptome, cholesterol homoeostasis regulatory proteins, and antioxidant markers were studied in UPI-induced LBW and normal birth weight (NBW) male and female guinea pigs at 150 days.

RESULTS: Hepatic free and …

Baroreflex Sensitivity In Facioscapulohumeral Muscular Dystrophy, Miguel Anselmo, Shandon Coffman, Mia Larson, Kathryn Vera, Emma Lee, Mary Mcconville, Michael Kyba, Manda L Keller-Ross

Department of Medicine Faculty Papers

Facioscapulohumeral muscular dystrophy (FSHD), a common form of muscular dystrophy, is caused by a genetic mutation that alters DUX4 gene expression. This mutation contributes to significant skeletal muscle loss. Although it is suggested that cardiac muscle may be spared, people with FSHD have demonstrated autonomic dysregulation. It is unknown if baroreflex function, an important regulator of blood pressure (BP), is impaired in people with FSHD. We examined if baroreflex sensitivity (BRS) is blunted in patients with FSHD. Thirty minutes of resting BP, heart rate, and cardiovagal BRS were measured in 13 patients with FSHD (age: 50 ± 13 years, avg …

Implementation Of Clinical Practice Guidelines For Hospitalized Patients With Covid-19 In Academic Medical Centers, Amy Chang Berger, Noa Simchoni, Andrew Auerbach, W Michael Brode, Ethan Kuperman, Katie Raffel, Alan Kubey

Department of Medicine Faculty Papers

No abstract provided.

Does Age-Related Macular Degeneration (Amd) Treatment Influence Patient Falls And Mobility? A Systematic Review., Hannah Garrigan, Jacquelyn N. Hamati, Parth Lalakia, Rosemary Frasso, Brooke Salzman, Leslie Hyman

Student Papers, Posters & Projects

PURPOSE: Age-related macular degeneration (AMD), a leading cause of irreversible blindness, increases fall risk through impaired central vision. Falls place an enormous economic burden on healthcare systems. We hypothesized that AMD treatments may reduce patients' falls risk. This systematic review (ID #: 172623) synthesized the current understanding of wet and dry AMD treatments' impact on patient falls and mobility, connecting these two public health issues.

METHODS: On April 17, 2020, PubMed, Scopus, CINAHL, and the Cochrane Central Register of Controlled Trials were queried. Clinical trials and observational studies were included, while non-English and non-primary studies were excluded. Two authors screened, …

Hepatitis B Virus-Associated Hepatocellular Carcinoma And Chronic Stress, Nicholas Noverati, Rukaiya Bashir, Dina Halegoua-De Marzio, Hie-Won Hann

Department of Medicine Faculty Papers

The Hepatitis B virus is one of the most significant hepatocarcinogens globally. The carcinogenic mechanisms of this virus are complex, and may include interactions with the host's immune system. Certain factors, such as stress on the body, can also potentiate these mechanisms. Stress, although adaptive in an acute form, is deleterious to health when chronic and can both suppress and activate the host's defense system. In hepatocellular carcinoma, this can lead to tumor initiation and progression. Those that are more prone to stress, or exposed to situations that incite stress, may be at higher risk of developing cancer. Racial disparities, …