Medicine and Health Sciences Commons^™

Novel Tetrazolium-Based Colorimetric Assay For Helicase Nsp13 In Sars-Cov-2, Triet M. Pham, Morgan G. Howard, Shane M. Carey, Lindsey R. Baker, Edward L. D'Antonio

Natural Sciences Faculty Publications

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a human pathogenic virus that encodes for a helicase (SC2Hel) that is essential for viral replication. SC2Hel has the ability to unravel dsRNA or dsDNA in an NTP-dependent manner from the 5′ to 3′ directionality. The standard helicase assay from studies involving SARS-CoV and SARS-CoV-2 have relied on the concept of fluorescence resonance energy transfer. Adding to the collection of helicase assays, herein, we have developed a novel tetrazolium-based colorimetric assay system for the detection of ADP that is produced via SC2Hel activity. This SC2Hel assay combines three enzyme-coupled steps involving the …

Scoping Review Of Exposure Questionnaires And Surveys In Interstitial Lung Disease, Hayley Barnes, Seham Elmrayed, Christopher Michael Barber, Johanna Feary, Cathryn T. Lee, Sheiphali Gandhi, Cheryl E. Peters, Margaret L. Salisbury, Kerri A. Johannson

Faculty Journal Articles

Background Many interstitial lung diseases (ILDs) have clear causal relationships with environmental and occupational exposures. Exposure identification can assist with diagnosis, understanding disease pathogenesis, prognostication and prevention of disease progression and occurrence in others at risk. Despite the importance of exposure identification in ILD, there is no standardised assessment approach. Many questionnaires are in clinical and research use, yet their utility, applicability, relevance and performance characteristics are unknown. Objectives This scoping review aimed to summarise the available evidence relating to ILD exposure assessment questionnaires, identify research gaps and inform the content for a future single evidence-based ILD questionnaire. Methods A …

Reducing Delirium In Post-Surgical Patients Through Pre-Operative Risk Assessment Screening: A Policy Option, Skye Porter Berg Msn, Fnp

Doctor of Nursing Practice Final Manuscripts

One of the major complications and reasons for prolonged stay amongst patients who undergo surgery is related to the occurrence of hospital associated delirium. Unfamiliar environment, previous comorbidities, age and anesthesia can alter and affect cognitive status in the general population. While there is substantial evidence previously listing high risk patients through demographics as well as prior medical history, this study collectively gathers information based upon prior evidence-based practice data to determine the benefit of prescreening patients through use of a predictive indicator tool. Based on the literature review and inclusion data gathered from fifty patients undergoing surgery, it was …

Implementing Animal-Assisted Therapy During Psychiatric Intakes, Rebecca Dorne

Doctor of Nursing Practice Final Manuscripts

Introduction: The purpose of this evidence-based project is to determine if Animal-Assisted Therapy (AAT) causes improvements in veterans’ feelings of anger, anxiety, depression, and suicidality in the acute psychiatric setting during psychiatric evaluations. The project aims to provide veterans with an additional way to experience short-term relief from symptoms while discussing their symptomology with mental health providers.

Background: The prevalence of depression is 20% higher in veterans than in that of the general population. Similarly, it has been shown that 23% of all veterans using VA care have had PTSD at some point in their lives. In the Psychiatric Emergency …

Postoperative Opioid Usage And Disposal Strategies After Arthroscopic Procedures In A Young Cohort: A Prospective Observational Study, William Johns, Emma Johnson, Joseph Brutico, Matthew Sherman, Kevin Freedman, William Emper, John Salvo, Sommer Hammoud

Rothman Institute Papers

BACKGROUND: Although several studies have noted that patients are routinely overprescribed opioids, few have reported usage after arthroscopic surgery.

PURPOSE: To determine opioid consumption and allocation for unused opioids after common arthroscopic surgeries.

STUDY DESIGN: Case series; Level of evidence, 4.

METHODS: Patients between the ages of 15 and 40 years who were scheduled to undergo anterior cruciate ligament reconstruction (ACLR), labral repair of the hip or shoulder, meniscectomy, or meniscal repair were prospectively enrolled. Patients were prescribed either 5 mg hydrocodone-325 mg acetaminophen or 5 mg oxycodone-325 mg acetaminophen based on surgeon preference. Patients completed a daily opioid usage …

Age-Related Brain Atrophy And The Positive Effects Of Behavioral Enrichment In Middle-Aged Beagles., Jessica A Noche, Hamsanandini Radhakrishnan, Margo F. Ubele, Kathy Boaz, Jennifer L Mefford, Erin D Jones, Hollie Y Van Rooyen, Jessica A Perpich, Katie Mccarty, Beverly Meacham, Jeffrey R. Smiley, Stasia A Bembenek Bailey, László G Puskás, David K. Powell, Lorena Sordo, Michael J Phelan, Christopher M. Norris, Elizabeth Head, Craig E L Stark

Neuroscience Faculty Publications

Aging dogs serve as a valuable preclinical model for Alzheimer's disease (AD) due to their natural age-related development of β-amyloid (Aβ) plaques, human-like metabolism, and large brains that are ideal for studying structural brain aging trajectories from serial neuroimaging. Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment. Annual MRI was analyzed using modern, automated techniques for region-of-interest-based and voxel-based volumetric assessments. We found that …

Bad Therapy: Conceptualizing The Teaching Of “Thinking Like A Lawyer” As Cognitive Behavioral Therapy, Chelsea Baldwin

St. Mary's Law Journal

Law students and lawyers experience mental illness and substance abuse at higher rates than the general population and other learned professions. This is bad for an individual’s wellbeing as well as their clients and society because mental illness and substance abuse increases stress which in turn decreases effective decision-making and judgment, and in worst case scenarios leads to attrition as individuals choose death by suicide which has cascading social and economic impacts. This Article identifies practices in legal education that likely combine in a causal mechanism, although not a sole cause, to the higher rates of mental illness and substance …

The Enzymatic Regulation Of Contraction-Induced Toll-Like Receptor 4 Shedding From C2c12 Myotubes, Rebekah C. Gridley

Health, Exercise, and Sports Sciences ETDs

Stimulated contractions are shown to increase toll-like receptor 4 (TLR4) release from C2C12 myotubes in vitro. The purpose of this study was to determine if the release of TLR4 from myotubes is controlled by proteolytic membrane cleavage. A broad-spectrum metalloprotease inhibitor was used to test this hypothesis in a C2C12 cell culture model, and TLR4 concentrations in the cell culture supernatant were measured via enzyme-linked immunosorbent assay (ELISA) following stimulated myotube contractions.

ELISA analysis revealed TLR4 concentrations below the sensitivity threshold of the ELISA kit for all experimental conditions. In confirming the effectiveness of the electrical pulse stimulation (EPS) treatment, …

The Relationship Between Autistic Traits, Autistic Camouflaging, And Adults’ Representations Of Abstract And Social Concepts, Henry Tomiser, Katja Wiemer Dr.

Honors Capstones

Concrete concepts (e.g., BUTTON) can be experienced directly by the senses, whereas abstract concepts (e.g., FRIENDSHIP) cannot. Additionally, the mind may represent abstract concepts using more introspective, social, and emotional information than concrete concepts. Social difficulties are one defining feature of autism, and autistic individuals may use social camouflaging to hide these difficulties, but the precise nature of social processing in autism is not known. This study aims to explore possible links between autistic traits, autistic camouflaging, and mental representations of concepts. Participants gave open-ended definitions for concepts varying in concreteness and social content via an online survey. Responses were …

States’ Covid-19 Restrictions Were Associated With Increases In Drug Overdose Deaths In 2020, Douglas A. Wolf, Shannon M. Monnat, Jennifer Karas Montez, Emily E. Wiemers, Elyse Grossman

Center for Policy Research

Drug overdoses surged in the U.S. during the COVID-19 pandemic. Public health experts raised concerns in the pandemic’s early months about how the pandemic and the policies enacted to stem it might increase overdose risk. This brief summarizes the findings of a paper that used national data to identify how states’ COVID-19 policies affected drug overdose rates among U.S. adults ages 25-64 during the first year of the pandemic. Results show that counties located in states that adopted more aggressive in-person activity restrictions experienced larger increases in 2020 than counties located in states with fewer limitations. State economic support policies …

Exploring Complex Daily Tasks In Preclinical Alzheimer Disease, Audrey A. Keleman

WUSM Theses and Dissertations – All Programs

Alzheimer disease (AD) is a slowly progressive neurodegenerative disorder marked by a gradual decline in cognitive functions and ability to perform daily activities. AD begins with a clinically silent period in which pathological abnormalities accumulate in the brain before cognitive impairments occur (i.e., while individuals remain cognitively normal [CN]). This stage is known as preclinical AD and can last up to two decades. It can be identified by measuring biomarkers of AD using neuroimaging or biofluid techniques. In the United States alone, it is estimated that nearly 46 million individuals are in the preclinical stage of AD and at risk …

Improving Treatment Adherence Of Chronic Disease Management In Patients Presenting To The Interventional Pulmonary Perioperative Services With Telephone Follow-Ups, Victoria Dao, Desiree Camille Nanat

Doctor of Nursing Practice Final Manuscripts

Abstract

Purpose of Project: The purpose of this evidence-based practice (EBP) project was to review research-based evidence systematically and to implement evidence-based change in practice in the clinical setting. The goal is to improve treatment adherence in patients with obesity, hypertension (HTN), type 2 diabetes mellitus (T2DM), and obstructive sleep apnea (OSA) by providing telephone follow-ups within 30 days post-perioperative discharge.

Background: Obesity, HTN, T2DM, and OSA continue to pose significant challenges to the United States healthcare system. Nonadherence to prescribed management of these chronic diseases is prevalent among patients presenting to the perioperative department of a regional academic hospital …

Inequality And Opportunity: Ranking Community Health In Florence County, Sc, Stephen Borders, Lauren Carter, Brandy Hayden, Mary Elizabeth Magyar

Public Health

Florence County is at the heart of the seven-county Pee Dee Region of South Carolina with a diverse population of about 136,000 residents. Home to McLeod Regional Medical Center and MUSC Health Florence Medical Center, the area boasts more than 750 licensed beds. Despite being home to world-class medical care, the county faces significant health challenges, including high rates of chronic diseases, such as diabetes and obesity, and a shortage of healthcare providers in certain areas. These challenges are exacerbated by the county's socio-economic disparities, with many low-income residents lacking access to basic health services. Our approach addresses these challenges …

Best Anticoagulation Strategy With And Without Appendage Occlusion For Stroke-Prophylaxis In Postablation Atrial Fibrillation Patients With Cardiac Amyloidosis, Andrea Natale

Faculty Scholarship

Introduction: Both atrial fibrillation (AF) and amyloidosis increase stroke risk. We evaluated the best anticoagulation strategy in AF patients with coexistent amyloidosis. Methods: Consecutive AF patients with concomitant amyloidosis were divided into two groups based on the postablation stroke-prophylaxis approach; group 1: left atrial appendage occlusion (LAAO) in eligible patients and group 2: oral anticoagulation (OAC). Group 1 patients were further divided into Gr. 1A: LAAO + half-does NOAC (HD-NOAC) for 6 months followed by aspirin 81 mg/day and Gr. 1B: LAAO + HD-NOAC. In group 1 patients, with complete occlusion at the 45-day transesophageal echocardiogram, patients were switched to …

Violence Exposure And Trauma Screener For Youth (Vetsy), Daniel Joseph Flannery, Ivette Noriega, Mark Singer, Jeff Kretschmar

Faculty Scholarship

Background: Youth exposed to violence are at serious risk for physical, emotional, behavioral, and mental distress. Reliable and prompt detection is necessary to mitigate the psychological consequences of youth violence exposure and trauma. Objective: To describe the initial creation of the VETSY screener and its construct validity and potential use. Methods: From 2014 through 2022 we surveyed 20,532 at-risk youth aged 8–18 years from a diverse metropolitan community participating in the Defending Childhood Initiative (DCI). Youth completed a 17-item self-report screener. An Exploratory Factor Analysis (EFA) was used to determine the reliability and variable grouping for this brief screener. Violence …

Accelerated Somatic Mutation Calling For Whole-Genome And Whole-Exome Sequencing Data From Heterogenous Tumor Samples, Shuangxi Ji, Tong Zhu, Ankit Sethia, Wenyi Wang

Faculty, Staff and Student Publications

Accurate detection of somatic mutations in DNA sequencing data is a fundamental prerequisite for cancer research. Previous analytical challenges were overcome by consensus mutation calling from four to five popular callers. This, however, increases the already nontrivial computing time from individual callers. Here, we launch MuSE 2, powered by multistep parallelization and efficient memory allocation, to resolve the computing time bottleneck. MuSE 2 speeds up 50 times more than MuSE 1 and eight to 80 times more than other popular callers. Our benchmark study suggests combining MuSE 2 and the recently accelerated Strelka2 achieves high efficiency and accuracy in analyzing …

Ataxia-Telangiectasia Mutated Loss-Of-Function Displays Variant And Tissue-Specific Differences Across Tumor Types, Patrick G Pilié, Virginia Giuliani, Wei-Lien Wang, Daniel J Mcgrail, Christopher A Bristow, Natalie Y L Ngoi, Keith Kyewalabye, Khalida M Wani, Hung Le, Erick Campbell, Nora S Sanchez, Dong Yang, Jinesh S Gheeya, Rohit Vivek Goswamy, Vijaykumar Holla, Kenna Rael Shaw, Funda Meric-Bernstam, Chiu-Yi Liu, Xiaoyan Ma, Ningping Feng, Annette A Machado, Jennifer P Bardenhagen, Christopher P Vellano, Joseph R Marszalek, Eeson Rajendra, Desiree Piscitello, Timothy I Johnson, Maria Likhatcheva, Elias Elinati, Jayesh Majithiya, Joana Neves, Vera Grinkevich, Marco Ranzani, Marina Roy Luzarraga, Marie Boursier, Lucy Armstrong, Lerin Geo, Giorgia Lillo, Wai Yiu Tse, Alexander J Lazar, Scott E Kopetz, Mary K Geck Do, Sarah Lively, Michael G Johnson, Helen M R Robinson, Graeme C M Smith, Christopher L Carroll, M Emilia Di Francesco, Philip Jones, Timothy P Heffernan, Timothy A Yap

Faculty, Staff and Student Publications

PURPOSE: Mutations in the ATM gene are common in multiple cancers, but clinical studies of therapies targeting ATM-aberrant cancers have yielded mixed results. Refinement of ATM loss of function (LOF) as a predictive biomarker of response is urgently needed.

EXPERIMENTAL DESIGN: We present the first disclosure and preclinical development of a novel, selective ATR inhibitor, ART0380, and test its antitumor activity in multiple preclinical cancer models. To refine ATM LOF as a predictive biomarker, we performed a comprehensive pan-cancer analysis of ATM variants in patient tumors and then assessed the ATM variant-to-protein relationship. Finally, we assessed a novel ATM LOF …

Differences Between Acute Embolic And Atherosclerotic Middle Cerebral Artery Occlusion In Multiphase Arterial Spin-Labeling Imaging, Yasuhiro Ito, Taku Sugiyama, Shunsuke Terasaka, Hitoshi Matsuzawa, Kuniaki Harada, Naoki Nakayama, Masaki Ito, Katsuhiko Maruichi, Miki Fujimura

Faculty, Staff and Student Publications

Arterial spin-labeling magnetic resonance imaging (ASL-MRI) is widely used for evaluating collateral development in patients with acute ischemic stroke (AIS). This study aimed to characterize the findings of multiphase ASL-MRI between embolic and atherosclerotic large vessel occlusion (LVO) to aid in the differential diagnosis. Among 982 patients with AIS, 44 who were diagnosed with acute, symptomatic, and unilateral occlusion of the horizontal segment of the middle cerebral artery (MCA) were selected and categorized into embolic stroke (ES) and atherosclerosis (AT) groups. Using ASL-MRI (postlabeling delay [PLD] of 1.5, 2.0, and 2.5 s) at admission, the ipsilateral to contralateral ratio (ICR) …

Delivering Crispr To The Hiv-1 Reservoirs, Theodore Gurrola, Samuel Effah, Ilker Sariyer, Will Dampier, Michael Nonnemacher, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

Human immunodeficiency virus type 1 (HIV-1) infection is well known as one of the most complex and difficult viral infections to cure. The difficulty in developing curative strategies arises in large part from the development of latent viral reservoirs (LVRs) within anatomical and cellular compartments of a host. The clustered regularly interspaced short palindromic repeats/ CRISPR-associated protein 9 (CRISPR/Cas9) system shows remarkable potential for the inactivation and/or elimination of integrated proviral DNA within host cells, however, delivery of the CRISPR/Cas9 system to infected cells is still a challenge. In this review, the main factors impacting delivery, the challenges for delivery …

Disparate Outcomes In Hispanic Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease/Steatohepatitis And Type 2 Diabetes: Large Cohort Study, Joseph Matthew Gosnell, George Golovko, Esteban Arroyave, Akshata Moghe, Michael L Kueht, Omar Abdul Saldarriaga, Kevin H Mckinney, Heather L Stevenson, Monique R Ferguson

Faculty, Staff and Student Publications

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are a growing health burden across a significant portion of the global patient population. However, these conditions seem to have disparate rates and outcomes between different ethnic populations. The combination of MASLD/MASH and type 2 diabetes increases the risk of hepatocellular carcinoma (HCC), and Hispanic patients experience the greatest burden, particularly those in South Texas.

Aim: To compare outcomes between Hispanic and non-Hispanic patients in the United States, while further focusing on the Hispanic population within Southeast Texas to determine whether the documented disparity in outcomes is a …

Prevalence, Incidence, And Predictors Of Kaposi Sarcoma-Associated Herpesvirus Infection Among Young Men Who Have Sex With Men In The Southern United States, Maverick Salyards, Ank E Nijhawan, Jacky Kuo, Sheena M Knights, Susana Lazarte, Nazzarena Labo, Wendell Miley, Denise Whitby, Lu-Yu Hwang, Anna-William Kornberg, Kayo Fujimoto, Elizabeth Y Chiao

Faculty, Staff and Student Publications

Kaposi sarcoma (KS) continues to cause substantial morbidity and mortality in populations at risk in the southern United States. Utilizing biospecimens from the Houston site of the Young Men's Affiliate Project, 351 men who have sex with men had blood tested for KS-associated herpesvirus (KSHV) IgG. Seroprevalence, seroconversion between time points, and demographic and clinical correlates were measured. KSHV prevalence was 36.7% and incidence was 8.9 per 100 person-years. Furthermore, prevalence and incidence were higher among Black individuals, people living with HIV, and those with a history of syphilis. Further research on KSHV risk may improve health disparities in KS …

A Multi-Institutional Meningioma Mri Dataset For Automated Multi-Sequence Image Segmentation, Dominic Labella, Omaditya Khanna, Shan Mcburney-Lin, Ryan Mclean, Pierre Nedelec, Arif Rashid, Nourel Hoda Tahon, Talissa Altes, Ujjwal Baid, Radhika Bhalerao, Yaseen Dhemesh, Scott Floyd, Devon Godfrey, Fathi Hilal, Anastasia Janas, Anahita Kazerooni, Collin Kent, John Kirkpatrick, Florian Kofler, Kevin Leu, Nazanin Maleki, Bjoern Menze, Maxence Pajot, Zachary Reitman, Jeffrey Rudie, Rachit Saluja, Yury Velichko, Chunhao Wang, Pranav Warman, Nico Sollmann, David Diffley, Khanak Nandolia, Daniel Warren, Ali Hussain, John Pascal Fehringer, Yulia Bronstein, Lisa Deptula, Evan Stein, Mahsa Taherzadeh, Eduardo Portela De Oliveira, Aoife Haughey, Marinos Kontzialis, Luca Saba, Benjamin Turner, Melanie Brüßeler, Shehbaz Ansari, Athanasios Gkampenis, David Maximilian Weiss, Aya Mansour, Islam Shawali, Nikolay Yordanov, Joel Stein, Roula Hourani, Mohammed Yahya Moshebah, Ahmed Magdy Abouelatta, Tanvir Rizvi, Klara Willms, Dann Martin, Abdullah Okar, Gennaro D'Anna, Ahmed Taha, Yasaman Sharifi, Shahriar Faghani, Dominic Kite, Marco Pinho, Muhammad Ammar Haider, Michelle Alonso-Basanta, Javier Villanueva-Meyer, Andreas Rauschecker, Ayman Nada, Mariam Aboian, Adam Flanders, Spyridon Bakas, Evan Calabrese

Department of Radiology Faculty Papers

Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and longitudinal treatment monitoring. However, automated, objective, and quantitative tools for non-invasive assessment of meningiomas on multi-sequence MR images are not available. Here we present the BraTS Pre-operative Meningioma Dataset, as the largest multi-institutional expert annotated multilabel meningioma multi-sequence MR image dataset to date. This dataset includes 1,141 multi-sequence MR images from six sites, each with four structural MRI sequences (T2-, T2/FLAIR-, pre-contrast T1-, and post-contrast T1-weighted) accompanied by …

Targeting Ccl2/Ccr2 Signaling Overcomes Mek Inhibitor Resistance In Acute Myeloid Leukemia, Rucha V Modak, Katia G De Oliveira Rebola, John Mcclatchy, Mona Mohammadhosseini, Alisa Damnernsawad, Stephen E Kurtz, Christopher A Eide, Guanming Wu, Ted Laderas, Tamilla Nechiporuk, Marina A Gritsenko, Joshua R Hansen, Chelsea Hutchinson, Sara J C Gosline, Paul Piehowski, Daniel Bottomly, Nicholas Short, Karin Rodland, Shannon K Mcweeney, Jeffrey W Tyner, Anupriya Agarwal

Faculty, Staff and Student Publications

Purpose: Emerging evidence underscores the critical role of extrinsic factors within the microenvironment in protecting leukemia cells from therapeutic interventions, driving disease progression, and promoting drug resistance in acute myeloid leukemia (AML). This finding emphasizes the need for the identification of targeted therapies that inhibit intrinsic and extrinsic signaling to overcome drug resistance in AML.

Experimental design: We performed a comprehensive analysis utilizing a cohort of ∼300 AML patient samples. This analysis encompassed the evaluation of secreted cytokines/growth factors, gene expression, and ex vivo drug sensitivity to small molecules. Our investigation pinpointed a notable association between elevated levels of CCL2 …

When A Health Insurance Provider Says “No”: A Health Insurance Claim Navigation Tool, Dorothy Nuckols, Catherine Sorenson

Journal of Extension

The purpose of health insurance is to pay for preventative and nonpreventative health care. Unfortunately, claim denials are frequent and most people do not contested these denials. Consumers lack both knowledge and self-efficacy to challenge their health insurance decision. Conflict is stressful can occur when a health insurance claim is denied unexpectedly. Faced with uncertainty of health care cost coverage, consumers are more likely to delay or forgo healthcare and jeopardize their health. To address this challenge, increase awareness of claim appeal processes and to provide consumer guidance, [STATE] Extension developed a Health Insurance Claim Navigation Tool.

Casar Auc Community Only Lecture: Men, Women’S Body Autonomy & Gbv Crimes In Egypt, Us & Canada: Why Men Need To Step Up For The Education Of Women's Body Autonomy, The Prince Alwaleed Center For American Studies And Research Casar

Performances, Events, and Presentations

This was a hybrid CASAR AUC community only lecture titled: ‘Men, Women’s Body Autonomy & GBV crimes in Egypt, US & Canada’: Why men need to step up for the education of women’s body autonomy.

This lecture featured Tadwein from Egypt, Women’s Advocates from the US & London Abused Women's Counseling Center from Canada (via Zoom). This lecture was part of course AMST 1091 ‘Exploring Feminist Perspectives in Egypt & the US’ (core curriculum pathways two- American studies) taught by Yasmeen El-Ghazaly, CASAR Assistant to Director & Adjunct Faculty - Wednesday May 15th, 2024

The lecture pondered on the following …

Psilocybin Utilization In Alcohol Use Disorder, Hannah Hall, Sarah Turske, Hannah Blake, Abigail Carter, Connor Dains, Haylee Whyde, Brianna Lu, Joshua Honaker, Lindsey Peters

Pharmacy and Wellness Review

Alcohol use disorder (AUD) is a medical condition that arises from the inability to control alcohol consumption regardless of negative consequences. Over 10% of the US population met the diagnostic criteria for having AUD in 2022.1 Each individual presents with symptoms of AUD differently and may therefore need more personalized treatment. Research has shown that using a combination of currently available pharmacological and non-pharmacological treatment options provides the best results for patients with AUD. However, there still remains a pressing need for the development of newer treatment options. Psilocybin, a naturally occurring psychedelic compound, is currently under investigation due to …

Integrative Molecular Analyses Of The Md Anderson Prostate Cancer Patient-Derived Xenograft (Mda Pca Pdx) Series, Nicolas Anselmino, Estefania Labanca, Peter D A Shepherd, Jiabin Dong, Jun Yang, Xiaofei Song, Subhiksha Nandakumar, Ritika Kundra, Cindy Lee, Nikolaus Schultz, Jianhua Zhang, John C Araujo, Ana M Aparicio, Sumit K Subudhi, Paul G Corn, Louis L Pisters, John F Ward, John W Davis, Elba S Vazquez, Geraldine Gueron, Christopher J Logothetis, Andrew Futreal, Patricia Troncoso, Yu Chen, Nora M Navone

Faculty, Staff and Student Publications

PURPOSE: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer models. This initiative builds on the rich MD Anderson (MDA) prostate cancer (PCa) patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated models reflecting the heterogeneity of potentially lethal and lethal prostate cancer.

EXPERIMENTAL DESIGN: We performed whole-genome, targeted, and RNA sequencing in representative samples of the same tumor from 44 PDXs derived from 38 patients linked to donor tumor metadata and corresponding organoids. The cohort includes models derived …

A Gold Standard-Derived Modular Barcoding Approach To Cancer Transcriptomics, Yan Zhu, Mohamad Karim I Koleilat, Jason Roszik, Man Kam Kwong, Zhonglin Wang, Dipen M Maru, Scott Kopetz, Lawrence N Kwong

Faculty, Staff and Student Publications

A challenge with studying cancer transcriptomes is in distilling the wealth of information down into manageable portions of information. In this resource, we develop an approach that creates and assembles cancer type-specific gene expression modules into flexible barcodes, allowing for adaptation to a wide variety of uses. Specifically, we propose that modules derived organically from high-quality gold standards such as The Cancer Genome Atlas (TCGA) can accurately capture and describe functionally related genes that are relevant to specific cancer types. We show that such modules can: (1) uncover novel gene relationships and nominate new functional memberships, (2) improve and speed …

Transcriptomic Profiling Of Plasma Extracellular Vesicles Enables Reliable Annotation Of The Cancer-Specific Transcriptome And Molecular Subtype, Vahid Bahrambeigi, Jaewon J Lee, Vittorio Branchi, Kimal I Rajapakshe, Zhichao Xu, Naishu Kui, Jason T Henry, Wang Kun, Bret M Stephens, Sarah Dhebat, Mark W Hurd, Ryan Sun, Peng Yang, Eytan Ruppin, Wenyi Wang, Scott Kopetz, Anirban Maitra, Paola A Guerrero

Faculty, Staff and Student Publications

Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved transcriptomes of RNA within plasma extracellular vesicles (evRNA), we successfully predicted consensus molecular subtypes in patients with metastatic colorectal cancer. Analysis of plasma evRNA also enabled monitoring of changes in transcriptomic subtype under treatment selection pressure and identification of molecular pathways associated with recurrence. This approach …

The Calcineurin-Nfatc Pathway Modulates The Lipid Mediators In Bal Fluid Extracellular Vesicles, Thereby Regulating Microvascular Endothelial Cell Barrier Function, Manjula Karpurapu, Yunjuan Nie, Sangwoon Chung, Jiasheng Yan, Patrick Dougherty, Sonal Pannu, Jon Wisler, Ryan Harkless, Narasimham Parinandi, Evgeny Berdyshev, Dehua Pei, John W Christman

Faculty, Staff and Student Publications

Extracellular vesicles mediate intercellular communication by transporting biologically active macromolecules. Our prior studies have demonstrated that the nuclear factor of activated T cell cytoplasmic member 3 (NFATc3) is activated in mouse pulmonary macrophages in response to lipopolysaccharide (LPS). Inhibition of NFATc3 activation by a novel cell-permeable calcineurin peptide inhibitor CNI103 mitigated the development of acute lung injury (ALI) in LPS-treated mice. Although pro-inflammatory lipid mediators are known contributors to lung inflammation and injury, it remains unclear whether the calcineurin-NFATc pathway regulates extracellular vesicle (EV) lipid content and if this content contributes to ALI pathogenesis. In this study, EVs from mouse …