Diseases Commons^™

Landscape Of Notch1 Mutations And Co-Occurring Biomarker Alterations In Chronic Lymphocytic Leukemia, Fatima Zahra Jelloul, Richard Yang, Sofia Garces, Rashmi Kanagal-Shamanna, Chi Y Ok, Sanam Loghavi, Mark J Routbort, Zhuang Zuo, C Cameron Yin, Kristen Floyd, Roland L Bassett, William Wierda, Nitin Jain, Philip Thompson, Rajyalakshmi Luthra, L Jeffrey Medeiros, Keyur P Patel

Faculty, Staff and Student Publications

NOTCH1 is one of the most frequently mutated genes in chronic lymphocytic leukemia and has emerged as a marker of poor prognosis. In addition to coding NOTCH1 mutations involving exon 34, non-coding NOTCH1 mutations involving the 3' UTR have been described in a limited number of chronic lymphocytic leukemia (CLL) patients and were associated with adverse outcomes. In this study, 1574 CLL patients were assessed using targeted sequencing with a 29 gene panel and the results were correlated with prognostic characteristics. NOTCH1 mutations were detected in 252 (16%) patients, including both coding (220/252, 14%), non-coding (24/252, 1.5%) and a mixture …

Free Cholesterol Bioavailability And Atherosclerosis, Rei J Abe, Jun-Ichi Abe, Minh T H Nguyen, Elizabeth A Olmsted-Davis, Abrar Mamun, Priyanka Banerjee, John P Cooke, Longhou Fang, Henry Pownall, Nhat-Tu Le

Faculty, Staff and Student Publications

Purpose of review: As both a cholesterol acceptor and carrier in the reverse cholesterol transport (RCT) pathway, high-density lipoprotein (HDL) is putatively atheroprotective. However, current pharmacological therapies to increase plasma HDL cholesterol (HDL-c) concentration have paradoxically failed to prevent or reduce atherosclerosis and cardiovascular disease (CVD). Given that free cholesterol (FC) transfer between surfaces of lipoproteins and cells is reversible, excess plasma FC can be transferred to the cells of peripheral tissue sites resulting in atherosclerosis. Here, we summarize potential mechanisms contributing to this paradox and highlight the role of excess free cholesterol (FC) bioavailability in atherosclerosis vs. atheroprotection.

Recent …

Association Of Flame-Retardant Clothing With Mycosis Fungoides: A Retrospective Analysis, Katherine E Park, Vignesh Ramachandran, Jessica Tran, Tejas P Joshi, Naveen Garg, Madeleine Duvic

Faculty, Staff and Student Publications

Introduction: Mycosis fungoides (MF), the most prevalent form of cutaneous T-cell lymphoma (CTCL), has been associated with a variety of environmental and occupational exposures. Flame-retardant clothing (FRC), in contrast to flame-resistant clothing, is chemically treated and may constitute a previously unrecognized occupational hazard.

Objectives: To report an association between FRC and MF.

Methods: After encountering several young male patients whose onset of MF coincided with the occupational use of FRC and occupation as fire fighters, we did a retrospective search. Additional biopsy proven MF patients with use of FRC were identified by the EPIC electronic medical record using the search …

Primer For Development Of Guidelines For Helicobacter Pylori Therapy Using Antimicrobial Stewardship, David Y Graham, Jyh-Ming Liou

Faculty, Staff and Students Publications

We provide a primer to assist in the difficult transition of Helicobacter pylori therapy guidelines to those that adhere to the principles of antimicrobial stewardship. This transition will entail abandonment of many of the principles that heretofore formed the basis of treatment guidelines and recommendations. The goals of antimicrobial stewardship include optimization of the use of antibiotics while reducing antimicrobial resistance. The critical outcome measure is absolute cure rate which largely restricts comparative trials to those which reliably produce high cure rates (eg, ∼95%). Therapies that fail to achieve at least a 90% cure rate should be abandoned as unacceptable. …

Heightened Levels Of Plasma Growth Differentiation Factor 15 In Men Living With Hiv, Neeti Agarwal, Claudia E Ramirez Bustamante, Huaizhu Wu, Reina Armamento-Villareal, Jordan E Lake, Ashok Balasubramanyam, Sean M Hartig

Faculty, Staff and Students Publications

Plasma biomarkers that reflect energy balance disorders in people living with HIV (PLWH) remain limited. Growth differentiation factor 15 (GDF15) abundance in plasma of mice and humans induces negative energy balance but also becomes highly elevated in obesity and other metabolic diseases. We sought to compare plasma GDF15 levels in PLWH and HIV-negative persons and mouse models expressing the HIV accessory protein Vpr (that recapitulate HIV-associated metabolic disorders) and determine their relationship to metabolic parameters. We measured liver Gdf15 mRNA levels and plasma GDF15 levels in male Vpr mice and littermate controls. In parallel, we analyzed plasma GDF15 levels in …

Developing And Optimizing A Computable Phenotype For Incident Venous Thromboembolism In A Longitudinal Cohort Of Patients With Cancer, Ang Li, Wilson L Da Costa, Danielle Guffey, Emily M Milner, Anthony K Allam, Karen M Kurian, Francisco J Novoa, Marguerite D Poche, Raka Bandyo, Carolina Granada, Courtney D Wallace, Neil A Zakai, Christopher I Amos

Faculty, Staff and Students Publications

BACKGROUND: Research on venous thromboembolism (VTE) that relies only on the International Classification of Diseases (ICD) can misclassify outcomes. Our study aims to discover and validate an improved VTE computable phenotype for people with cancer.

METHODS: We used a cancer registry electronic health record (EHR)-linked longitudinal database. We derived three algorithms that were ICD/medication based, natural language processing (NLP) based, or all combined. We then randomly sampled 400 patients from patients with VTE codes (n = 1111) and 400 from those without VTE codes (n = 7396). Weighted sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were …

Health-Related Quality Of Life In Pediatric Acute Recurrent Or Chronic Pancreatitis: Association With Biopsychosocial Risk Factors, See Wan Tham, Fuchenchu Wang, Cheryl E Gariepy, Gretchen A Cress, Maisam A Abu-El-Haija, Melena D Bellin, Kate M Ellery, Douglas S Fishman, Tanja Gonska, Melvin B Heyman, Tom K Lin, Asim Maqbool, Brian A Mcferron, Veronique D Morinville, Jaimie D Nathan, Chee Y Ooi, Emily R Perito, Sarah Jane Schwarzenberg, Zachary M Sellers, Uzma Shah, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark E Lowe, Aliye Uc, Tonya M Palermo, International Study Group Of Pediatric Pancreatitis: In Search For A Cure (Insppire) And Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

OBJECTIVES: Abdominal pain, emergency department visits, and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data on health-related quality of life (HRQOL) in this population, however, remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL.

METHODS: Data were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment.

RESULTS: The sample included …

Inflammatory Links Between Hypertriglyceridemia And Atherogenesis, Xueying Peng, Huaizhu Wu

Faculty, Staff and Students Publications

Purpose of Review

Recent studies indicate an association between hypertriglyceridemia (HTG) and atherosclerotic cardiovascular disease (ASCVD). The purpose of this review is to discuss the potential mechanism connecting HTG and ASCVD risk and the potential efficacy of HTG-targeting therapies in ASCVD prevention.

Recent Findings

HTG, with elevations in triglyceride-rich lipoproteins (TGRL) and their remnants, are causal ASCVD risk factors. The mechanisms whereby HTG increases ASCVD risk are not well understood but may include multiple factors. Inflammation plays a crucial role in atherosclerosis. TGRL compared to low-density lipoproteins (LDL) correlate better with inflammation. TGRL remnants can penetrate endothelium and interact with …

Circadian Regulation Of Gene Expression And Metabolism In The Liver, Dongyin Guan, Mitchell A Lazar

Faculty, Staff and Students Publications

Circadian rhythms are approximately 24-hour cycles of variation in physiological processes, gene expression, and behavior. They result from the interplay of internal biological clocks with daily environmental rhythms, including light/dark and feeding/fasting. Note that 24-hour rhythms of liver metabolic processes have been known for almost 100 years. Modern studies reveal that, like metabolism, hepatic gene expression is highly rhythmic. Genetic or environmental changes can disrupt the circadian rhythms of the liver, leading to metabolic disorders and hepatocellular carcinoma. In this review, we summarize the current understanding of mechanisms regulating rhythmic gene expression in the liver, highlighting the roles of transcription …

Tocilizumab In Patients Hospitalised With Covid-19 Pneumonia: Efficacy, Safety, Viral Clearance, And Antibody Response From A Randomised Controlled Trial (Covacta), Ivan O Rosas, Norbert Bräu, Michael Waters, Ronaldo C Go, Atul Malhotra, Bradley D Hunter, Sanjay Bhagani, Daniel Skiest, Sinisa Savic, Ivor S Douglas, Julia Garcia-Diaz, Mariam S Aziz, Nichola Cooper, Taryn Youngstein, Lorenzo Del Sorbo, David J De La Zerda, Andrew Ustianowski, Antonio Cubillo Gracian, Kevin G Blyth, Jordi Carratalà, Bruno François, Thomas Benfield, Derrick Haslem, Paolo Bonfanti, Cor H Van Der Leest, Nidhi Rohatgi, Lothar Wiese, Charles Edouard Luyt, Rebecca N Bauer, Fang Cai, Ivan T Lee, Balpreet Matharu, Louis Metcalf, Steffen Wildum, Emily Graham, Larry Tsai, Min Bao

Faculty, Staff and Students Publications

BACKGROUND: In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated.

METHODS: Adults in Europe and North America hospitalised with COVID-19 (

FINDINGS: By day 60, 24·5% (72/294) of patients in the tocilizumab arm and 25·0% (36/144) in the placebo arm died (weighted …

Sirolimus (Rapamycin) Induced Mucosal Healing In Anti-Tumor Necrosis Factor Refractory Pediatric Ulcerative Colitis, Richard Kellermayer, Andrew Chang, Kalyani Patel

Faculty, Staff and Students Publications

Sirolimus (rapamycin) has been sparsely reported in the treatment of pediatric ulcerative colitis (PUC). Mucosal healing has not been examined in responders to the drug. We describe a case of infliximab refractory PUC where rapamycin induced sustained clinical remission along with mucosal healing. We conclude that rapamycin should be positioned into the expanding treatment repertoire of PUC.

Prevalence And Clinical Correlates Of Antinuclear Antibody In Patients With Gastroparesis, Henry P Parkman, Mark L Van Natta, Ashima Makol, Madhusudan Grover, Richard W Mccallum, Zubair Malik, Kenneth L Koch, Irene Sarosiek, Braden Kuo, Robert J Shulman, Gianrico Farrugia, Laura Miriel, James Tonascia, Frank Hamilton, Pankaj J Pasricha, Thomas L Abell, Niddk Gastroparesis Clinical Research Consortium

Faculty, Staff and Students Publications

BACKGROUND: Autoimmunity may play a role in the pathogenesis of gastroparesis in a subset of patients. Antinuclear antibody (ANA) testing is often used to screen for autoimmune disorders.

AIMS: 1) Determine prevalence of a positive ANA in patients with gastroparesis; 2) Describe characteristics of idiopathic gastroparesis patients with positive ANA.

METHODS: Patients were assessed with gastric emptying scintigraphy (GES), symptom assessment via Patient Assessment of Upper GI Symptoms [PAGI-SYM], and blood tests-ANA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP).

RESULTS: Positive ANA was seen in 148 of 893 (17%) patients with gastroparesis, being similar in idiopathic (16% of 536 patients), …

Evaluating Eosinophilic Colitis As A Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study, Tetsuo Shoda, Margaret H Collins, Mark Rochman, Ting Wen, Julie M Caldwell, Lydia E Mack, Garrett A Osswald, John A Besse, Yael Haberman, Seema S Aceves, Nicoleta C Arva, Kelley E Capocelli, Mirna Chehade, Carla M Davis, Evan S Dellon, Gary W Falk, Nirmala Gonsalves, Sandeep K Gupta, Ikuo Hirano, Paneez Khoury, Amy Klion, Calies Menard-Katcher, John Leung, Vincent A Mukkada, Philip E Putnam, Jonathan M Spergel, Joshua B Wechsler, Guang-Yu Yang, Glenn T Furuta, Lee A Denson, Marc E Rothenberg, Consortium Of Eosinophilic Gastrointestinal Diseases Researchers (Cegir)

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined.

METHODS: Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations …

Berberine Remodels Adipose Tissue To Attenuate Metabolic Disorders By Activating Sirtuin 3, Dan Li, Chao Yang, Jian-Zhong Zhu, Eduardo Lopez, Tian Zhang, Qiang Tong, Cheng Peng, Li-Gen Lin

Faculty, Staff and Students Publications

Adipose tissue remodelling is considered a critical pathophysiological hallmark of obesity and related metabolic diseases. Berberine (BBR), a natural isoquinoline alkaloid, has potent anti-hyperlipidaemic and anti-hyperglycaemic effects. This study aimed to explore the role of BBR in modulating adipose tissue remodelling and the underlying mechanisms. BBR protected high fat diet (HFD)-fed mice against adiposity, insulin resistance and hyperlipidemia. BBR alleviated adipose tissue inflammation and fibrosis by inhibiting macrophage infiltration, pro-inflammatory macrophage polarization and the abnormal deposition of extracellular matrix, and the effect was mediated by BBR directly binding and activating the deacetylase Sirtuin 3 (SIRT3) and suppressing the activation of …

Mitochondrial Sirtuin-3 (Sirt3) Prevents Doxorubicin-Induced Dilated Cardiomyopathy By Modulating Protein Acetylation And Oxidative Stress, Mateusz M Tomczyk, Kyle G Cheung, Bo Xiang, Nahid Tamanna, Ana L Fonseca Teixeira, Prasoon Agarwal, Stephanie M Kereliuk, Victor Spicer, Ligen Lin, Jason Treberg, Qiang Tong, Vernon W Dolinsky

Faculty, Staff and Students Publications

BACKGROUND: High doses of doxorubicin put cancer patients at risk for developing dilated cardiomyopathy. Previously, we showed that doxorubicin treatment decreases SIRT3 (sirtuin 3), the main mitochondrial deacetylase and increases protein acetylation in rat cardiomyocytes. Here, we hypothesize that SIRT3 expression can attenuate doxorubicin induced dilated cardiomyopathy in vivo by preventing the acetylation of mitochondrial proteins.

METHODS: Nontransgenic, M3-SIRT3 (truncated SIRT3; short isoform), and M1-SIRT3 (full-length SIRT3; mitochondrial localized) transgenic mice were treated with doxorubicin for 4 weeks (8 mg/kg body weight per week). Echocardiography was performed to assess cardiac structure and function and validated by immunohistochemistry and immunofluorescence (n=4-10). …

The Covid-19 Pandemic: Early Ripple Effects In Pediatric Palliative Care, Linda Marisol Bustamante, Regina Okhuysen-Cawley, Julia Downing, Stephen R Connor, Mary Ann Muckaden, Marianne Phillips, Andrea Icaza, Nicole Garzon, Yuriko Nakashima, Kelsi Morgan, David Mauser, Michelle Grunauer

Faculty, Staff and Students Publications

Palliative care, which aims to provide comprehensive, interdisciplinary, holistic care to children, adolescents and adults with life-threatening, and ultimately life-limiting conditions, is a discipline that has emerged as an integral component of healthcare systems throughout the world. Although the value of life-affirming palliative care (PC) has been shown across many domains, funding and acceptance of palliative care teams have been variable: some hospital systems have free-standing, dedicated interdisciplinary teams while, in many instances, palliative care services are provided "pro bono" by individuals with a special interest in the discipline, who provide PC in addition to other responsibilities. In this article, …

Author Correction: Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Correction to: Scientific Reports https://doi.org/10.1038/s41598-019-47255-9, published online 29 July 2019

The original Article contained an error in Figure 1A where the control trace for both the HEK-AMY3 and HEKWT cells was duplicated...

The original Article has been corrected.

Targeting Cd123 In Blastic Plasmacytoid Dendritic Cell Neoplasm Using Allogeneic Anti-Cd123 Car T Cells, Tianyu Cai, Agnès Gouble, Kathryn L Black, Anna Skwarska, Ammar S Naqvi, Deanne Taylor, Ming Zhao, Qi Yuan, Mayumi Sugita, Qi Zhang, Roman Galetto, Stéphanie Filipe, Antonio Cavazos, Lina Han, Vinitha Kuruvilla, Helen Ma, Connie Weng, Chang-Gong Liu, Xiuping Liu, Sergej Konoplev, Jun Gu, Guilin Tang, Xiaoping Su, Gheath Al-Atrash, Stefan Ciurea, Sattva S Neelapu, Andrew A Lane, Hagop Kantarjian, Monica L Guzman, Naveen Pemmaraju, Julianne Smith, Andrei Thomas-Tikhonenko, Marina Konopleva

Faculty, Staff and Student Publications

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with poor outcomes with conventional therapy. Nearly 100% of BPDCNs overexpress interleukin 3 receptor subunit alpha (CD123). Given that CD123 is differentially expressed on the surface of BPDCN cells, it has emerged as an attractive therapeutic target. UCART123 is an investigational product consisting of allogeneic T cells expressing an anti-CD123 chimeric antigen receptor (CAR), edited with TALEN

Ameliorative Effects Of Minor Cannabinoids Over Hiv-1 Tat-Mediated Visceral Pain, Charlie Worth

Honors Theses

As the total number of people living with HIV continues to rise across the world, an effective HIV treatment is still sought after. While modern-day advanced therapies exist for mitigating much of the negative effects of HIV, the virus remains evasive and problematic in the central nervous system. Thus, even with treatment, many people living with HIV continue to suffer from a plethora of symptoms. However, a large proportion of HIV-positive patients claim to feel a reduction in those persevering symptoms after cannabis usage. This anecdotal evidence has sparked interest in the efficacy of cannabis constituents for HIV therapy. This …

Donor-Derived Multiple Leukemia Antigen-Specific T-Cell Therapy To Prevent Relapse After Transplant In Patients With All, Swati Naik, Spyridoula Vasileiou, Ifigeneia Tzannou, Manik Kuvalekar, Ayumi Watanabe, Catherine Robertson, Natalia Lapteva, Wang Tao, Mengfen Wu, Bambi Grilley, George Carrum, Rammurti T Kamble, Laquisa Hill, Robert A Krance, Caridad Martinez, Priti Tewari, Bilal Omer, Stephen Gottschalk, Helen E Heslop, Malcom K Brenner, Cliona M Rooney, Juan F Vera, Ann M Leen, Premal D Lulla

Faculty, Staff and Students Publications

Hematopoietic stem cell transplant (HSCT) is a curative option for patients with high-risk acute lymphoblastic leukemia (ALL), but relapse remains a major cause of treatment failure. To prevent disease relapse, we prepared and infused donor-derived multiple leukemia antigen-specific T cells (mLSTs) targeting PRAME, WT1, and survivin, which are leukemia-associated antigens frequently expressed in B- and T-ALL. Our goal was to maximize the graft-versus-leukemia effect while minimizing the risk of graft-versus-host disease (GVHD). We administered mLSTs (dose range, 0.5 × 107 to 2 × 107 cells per square meter) to 11 patients with ALL (8 pediatric, 3 adult), and observed no …

Perceived Roles, Benefits And Barriers Of Virtual Global Health Partnership Initiatives: A Cross-Sectional Exploratory Study, Lisa Umphrey, George Paasi, William Windsor, Grace Abongo, Jessica Evert, Heather Haq, Elizabeth M Keating, Suet Kam Lam, Megan S Mchenry, Carolyne Ndila, Charles Nwobu, Amy Rule, Reena P Tam, Daniel Olson, Peter Olupot-Olupot

Faculty, Staff and Students Publications

BACKGROUND: Virtual global health partnership initiatives (VGHPIs) evolved rapidly during the COVID-19 pandemic to ensure partnership continuity. However the current landscape for VGHPI use and preference is unknown. This study aimed to increase understanding of GH partners' perspectives on VGHPIs.

METHODS: From 15 October to 30 November 2020, An online, international survey was conducted using snowball sampling to document pandemic-related changes in partnership activities, preferences for VGHPIs, and perceived acceptability and barriers. The survey underwent iterative development within a diverse author group, representing academic and clinical institutions, and the non-profit sector. Participants from their professional global health networks were invited, …

Markers Of Kidney Function, Genetic Variation Related To Cognitive Function, And Cognitive Performance In The Uk Biobank, Erin L Richard, Linda K Mcevoy, Ian J Deary, Gail Davies, Steven Y Cao, Eyal Oren, John E Alcaraz, Andrea Z Lacroix, Jan Bressler, Rany M Salem

Faculty, Staff and Student Publications

BACKGROUND: Chronic kidney disease has been linked to worse cognition. However, this association may be dependent on the marker of kidney function used, and studies assessing modification by genetics are lacking. This study examined associations between multiple measures of kidney function and assessed effect modification by a polygenic score for general cognitive function.

METHODS: In this cross-sectional study of up to 341,208 European ancestry participants from the UK Biobank study, we examined associations between albuminuria and estimated glomerular filtration rate based on creatinine (eGFRcre) or cystatin C (eGFRcys) with cognitive performance on tests of verbal-numeric reasoning, reaction time and visual …

Accessory Genomes Drive Independent Spread Of Carbapenem-Resistant Klebsiella Pneumoniae Clonal Groups 258 And 307 In Houston, Tx, William C Shropshire, An Q Dinh, Michelle Earley, Lauren Komarow, Diana Panesso, Kirsten Rydell, Sara I Gómez-Villegas, Hongyu Miao, Carol Hill, Liang Chen, Robin Patel, Bettina C Fries, Lilian Abbo, Eric Cober, Sara Revolinski, Courtney L Luterbach, Henry Chambers, Vance G Fowler, Robert A Bonomo, Samuel A Shelburne, Barry N Kreiswirth, David Van Duin, Blake M Hanson, Cesar A Arias

Faculty, Staff and Student Publications

Carbapenem-resistant Klebsiella pneumoniae (CRKp) is an urgent public health threat. Worldwide dissemination of CRKp has been largely attributed to clonal group (CG) 258. However, recent evidence indicates the global emergence of a CRKp CG307 lineage. Houston, TX, is the first large city in the United States with detected cocirculation of both CRKp CG307 and CG258. We sought to characterize the genomic and clinical factors contributing to the parallel endemic spread of CG258 and CG307. CRKp isolates were collected as part of the prospective, Consortium on Resistance against Carbapenems in Klebsiella and other Enterobacterales 2 …

Vampires And Other Diseases: Stochastic Infection Dynamics Of Small Populations, Marijn Jaarsma

Honors Projects in Science and Technology

Mathematical models are powerful tools often applied in the field of epidemiology. The type and shape of the model will differ between different types of diseases. In this study, stochastic dynamical models are applied to the entertaining example of vampires, and the results of this analysis are compared to real-life diseases with small populations of infected. The data used comes from pop-culture depictions of vampires in literature, television shows, movies, and fan pages associated with these depictions. The aim of this study is to serve as an educational tool for modeling diseases with small populations to predict and control the …

Genetic Susceptibility To Patient-Reported Xerostomia Among Long-Term Oropharyngeal Cancer Survivors, Puja Aggarwal, Katherine A Hutcheson, Robert Yu, Jian Wang, Clifton D Fuller, Adam S Garden, Ryan P Goepfert, Jillian Rigert, Frank E Mott, Charles Lu, Stephen Y Lai, G Brandon Gunn, Mark S Chambers, Guojun Li, Chih-Chieh Wu, Ehab Y Hanna, Erich M Sturgis, Sanjay Shete

Faculty, Staff and Students Publications

Genetic susceptibility for xerostomia, a common sequela of radiotherapy and chemoradiotherapy for head and neck cancer, is unknown. Therefore, to identify genetic variants associated with moderate to severe xerostomia, we conducted a GWAS of 359 long-term oropharyngeal cancer (OPC) survivors using 579,956 autosomal SNPs. Patient-reported cancer treatment-related xerostomia was assessed using the MD Anderson Symptom Inventory. Patient response was dichotomized as moderate to severe or none to mild symptoms. In our study, 39.2% of OPC survivors reported moderate to severe xerostomia. Our GWAS identified eight SNPs suggestively associated with higher risk of moderate to severe xerostomia in six genomic regions …

Venetoclax Combinations Delay The Time To Deterioration Of Hrqol In Unfit Patients With Acute Myeloid Leukemia, Keith W Pratz, Panayiotis Panayiotidis, Christian Recher, Xudong Wei, Brian A Jonas, Pau Montesinos, Vladimir Ivanov, Andre C Schuh, Courtney D Dinardo, Jan Novak, Vlatko Pejsa, Don Stevens, Su-Peng Yeh, Inho Kim, Mehmet Turgut, Nicola Fracchiolla, Kazuhito Yamamoto, Yishai Ofran, Andrew H Wei, Cat N Bui, Katy Benjamin, Rajesh Kamalakar, Jalaja Potluri, Wellington Mendes, Jacob Devine, Walter Fiedler

Faculty, Staff and Student Publications

Phase 3 trials Viale-A and Viale-C evaluated health-related quality of life (HRQoL) in patients with AML unfit for intensive chemotherapy who received venetoclax (VEN) + (AZA) (Viale-A) or low-dose cytarabine (LDAC) (Viale-C) or placebo (PBO) + AZA or LDAC. Patient-reported outcomes included: EORTC QLQ-C30 global health status (GHS/QoL) and physical functioning (PF), PROMIS Cancer Fatigue Short Form 7a (Fatigue), and EQ-5D-5L health status visual analog scale (HS-VAS). Time to deterioration (TTD), defined as worsening from baseline in meaningful change thresholds (MCT) of ≥10, 5, or 7 points for GHS/QoL or PF, fatigue, and HS-VAS, respectively, was assessed; differences between groups …

Temporal Trends In Outcomes In Patients With Adrenocortical Carcinoma: A Multidisciplinary Referral-Center Experience, Marilyne Daher, Jeena Varghese, Stephen K Gruschkus, Camilo Jimenez, Steven G Waguespack, Sara Bedrose, Lina Altameemi, Hadil Bazerbashi, Aung Naing, Vivek Subaiah, Matthew T Campbell, Amishi Y Shah, Miao Zhang, Rahul A Sheth, Jose A Karam, Christopher G Wood, Nancy D Perrier, Paul H Graham, Jeffery E Lee, Mouhammed Amir Habra

Faculty, Staff and Students Publications

CONTEXT: Reporting temporal trends in adrenocortical carcinoma (ACC) helps guide management strategies.

OBJECTIVE: This work aimed to report the trends in disease burden and clinical outcomes over time that cannot be adequately captured from individual clinical trials.

METHODS: A retrospective study was held of ACC patients seen at a referral cancer center between February 1998 and August 2019. Clinical outcomes were compared between an early cohort (February 1998-June 2007) and a late cohort (July 2007-August 2019).

RESULTS: A total of 621 patients included with a median age at diagnosis of 49.3 years (range, 0.5-86.6 years). There were 285 (45.9%) patients …

Stroke Network Of Wisconsin (Snow) Scale Predicts Large Vessel Occlusion Stroke In The Prehospital Setting, Kessarin Panichpisal, Sarah Erpenbeck, Paul Vilar, Reji P. Babygirija, Maharaj Singh, M. Riccardo Colella, Richard A. Rovin

Journal of Patient-Centered Research and Reviews

Purpose: In previous trials, the Stroke Network of Wisconsin (SNOW) scale accurately predicted large vessel occlusion (LVO) stroke in the hospital setting. This study evaluated SNOW scale performance in the prehospital setting and its ability to predict LVO or distal medium vessel occlusion (DMVO) in patients suspected of having acute ischemic stroke (AIS), a scenario in which transport time to an endovascular treatment-capable facility (ECSC) is critical.

Methods: All potential AIS patients with last-known-well time of ≤ 24 hours were assessed by Milwaukee County Emergency Medical Services for LVO using SNOW. Patients with a positive SNOW score were transferred to …

Associations Between Residential Greenspace, Socioeconomic Status, And Stroke: A Matched Case-Control Study, Heloise Cheruvalath, Jennifer Homa, Maharaj Singh, Paul Vilar, Amin Kassam, Richard A. Rovin

Journal of Patient-Centered Research and Reviews

Purpose: Studies have shown increased residential greenspace is associated with improved outcome following stroke. This study sought to determine if residential greenspace is an independent stroke risk factor.

Methods: A retrospective 1:4 matched case-control study involving 1174 stroke and 4696 control patients over a 3-year period from Milwaukee County, Wisconsin, was conducted. Greenspace was determined using normalized difference vegetation index (NDVI) for a 250-meter radius surrounding a subject’s residence. The area deprivation index (ADI) for the census block tract of a subject’s residence was obtained from the Neighborhood Atlas® (University of Wisconsin School of Medicine and Public Health). …

Computer Simulations And Network-Based Profiling Of Binding And Allosteric Interactions Of Sars-Cov-2 Spike Variant Complexes And The Host Receptor: Dissecting The Mechanistic Effects Of The Delta And Omicron Mutations, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we combine all-atom MD simulations and comprehensive mutational scanning of S-RBD complexes with the angiotensin-converting enzyme 2 (ACE2) host receptor in the native form as well as the S-RBD Delta and Omicron variants to (a) examine the differences in the dynamic signatures of the S-RBD complexes and (b) identify the critical binding hotspots and sensitivity of the mutational positions. We also examined the differences in allosteric interactions and communications in the S-RBD complexes for the Delta and Omicron variants. Through the perturbation-based scanning of the allosteric propensities of the SARS-CoV-2 S-RBD residues and dynamics-based network centrality and …