Diseases Commons^™

Standardized Definitions For Evaluation Of Acute Decompensated Heart Failure Therapies: Hf-Arc Expert Panel Paper, Anuradha Lala, Carine E Hamo, Biykem Bozkurt, Mona Fiuzat, Vanessa Blumer, Daniel Bukhoff, Javed Butler, Maria Rosa Costanzo, G Michael Felker, Gerasimos Filippatos, Marvin A Konstam, John J V Mcmurray, Robert J Mentz, Marco Metra, Mitchell A Psotka, Scott D Solomon, John Teerlink, William T Abraham, Christopher M O'Connor, Hf-Arc (Heart Failure Collaboratory And Academic Research Consortium)

Faculty, Staff and Students Publications

Acute decompensated heart failure (ADHF) is one of the most common reasons for hospitalizations or urgent care and is associated with poor outcomes. Therapies shown to improve outcomes are limited, however, and innovation in pharmacologic and device-based therapeutics are therefore actively being sought. Standardizing definitions for ADHF and its trajectory is complex, limiting the generalizability and translation of clinical trials to effect clinical care and policy change. The Heart Failure Collaboratory is a multistakeholder organization comprising clinical investigators, clinicians, patients, government representatives (including U.S. Food and Drug Administration and National Institutes of Health participants), payors, and industry collaborators. The following …

International Society For Pediatric And Adolescent Diabetes Clinical Practice Consensus Guidelines 2024: Diabetes Technologies - Insulin Delivery, Torben Biester, Cari Berget, Charlotte Boughton, Laura Cudizio, Laya Ekhlaspour, Marisa E Hilliard, Leenatha Reddy, Suzanne Sap Ngo Um, Melissa Schoelwer, Jennifer L Sherr, Klemen Dovc

Faculty, Staff and Students Publications

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This chapter builds on the 2022 ISPAD guidelines, and summarizes recent advances in the technology behind insulin administration, with special emphasis on insulin pump therapy, especially on glucose-responsive integrated technology that is feasible with the use of automated insulin delivery (AID) systems in children and adolescents. The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive …

Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery Of Cyclosporine And Dithranol: In-Vitro, Ex-Vivo, And In-Vivo Studies, Sammar Fathy Elhabal, Nashwa Abdelaal, Saeed A S Al-Zuhairy, Mohamed Fathi Mohamed Elrefai, Mohamed Mansour Khalifa, Mohammad Ahmad Khasawneh, Ahmed Mohsen Elsaid Hamdan, Passant M Mohie, Rania A Gad, Soad L Kabil, Mohamed Kandeel El-Ashery, Bhaskara R Jasti, Nahla A Elzohairy, Nehal Elfar, Tayseer Elnawawy, Fatma E Hassan, Mohamed Ahmed El-Nabarawi

Faculty, Staff and Students Publications

PURPOSE: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. …

Myasthenia Gravis And Numb Chin Syndrome With Lung Carcinoma, Rajesh Kumar Gupta, Ashutosh Gupta, Daniel S Um, Zarrin Khameh Neda

Faculty, Staff and Students Publications

No abstract provided.

Trends In Cardiovascular Disease-Related Mortality In Texas, Muhammad Shariq Usman, Adeena Jamil, Zainali Chunawala, Mahboob Alam, Vijay Nambi, Layla A Abushamat, Arunima Misra, Salim S Virani, Christie M Ballantyne, George E Taffet, Khurram Nasir, Sachin Goel, Sadeer Al-Kindi, Javed Butler, Abdul Mannan Khan Minhas

Faculty, Staff and Students Publications

BACKGROUND: Cardiovascular disease (CVD) is associated with high mortality in the United States, but the burden of CVD mortality is unevenly distributed between demographic and geographic subgroups, with poor characterization of state-specific trends. In this study, the disparities in CVD-related mortality trends in Texas and the United States from 1999 to 2019 were assessed.

METHODS: Trends in CVD-related mortality were evaluated through analysis of the Multiple Causes of Death Files from the National Center for Health Statistics. Crude and age-adjusted mortality rates (AAMRs) per 100,000 population with associated annual percentage changes were determined. Joinpoint regression was used to assess trends …

Expert Review Of Child And Caregiver Critiques Of A Therapeutic Guided Imagery Therapy Mobile Application Targeting Disorders Of Gut-Brain Interaction In Children, John M Hollier, Tiantá A Strickland, C Michael Fordis, Robert J Shulman, Debbe Thompson

Faculty, Staff and Students Publications

BACKGROUND: A guided imagery therapy mobile application (GIT App) is a novel platform for treating children with disorders of gut-brain interaction (DGBI). Previous feedback from child/caregiver dyads suggested modifications for our App prototype. However, their feedback had the potential to affect the intervention's efficacy. Thus, we aimed to have their critiques vetted by relevant experts prior to further App refinement.

OBJECTIVE: Compare expert reviews of the GIT App with end-users' (i.e., child/caregiver dyads') feedback.

METHODS: This mixed-methods study with experts included a hands-on App evaluation, a survey assessing usability, and focus groups comparing their perspectives with those previously provided by …

Pre-Left Ventricular Assist Device Endoscopic Evaluation Does Not Reduce The Risk Of Later Gastrointestinal Bleeding: A Multicenter Study, Jiahao Peng, Samanthika Devalaraju, Mohamed Azab, William T Cates, Molly Stone, Jonathan Reichstein, Sneha Shaha, Subhasis Chatterjee, Andrew B Civitello, Mourad H Senussi, B Joseph Elmunzer, Michael Volk, Wasseem Skef

Faculty, Staff and Students Publications

BACKGROUND: Gastrointestinal bleeding (GIB) is a common complication after placement of a left ventricular assist device (LVAD). Some institutions attempt to mitigate post-LVAD GIB using preoperative endoscopy. Our study evaluated whether preoperative endoscopy was associated with a lower risk of post-LVAD GIB.

METHODS: This was a multicenter cohort study of patients who underwent LVAD insertion from 2010-2019 at 3 academic sites. A total of 398 study participants were categorized based on whether they underwent preoperative endoscopy or not. The follow-up period was 1 year and the primary outcome was GIB. Secondary outcomes were severe bleeding and intraprocedural complications.

RESULTS: A …

Impact Of The Use Of Nutrition Information On Glycemic Control In Adults With Diabetes, Katelyn Richardson

All Master's Theses

The purpose of this study is to examine the association between glycemic control in adults with diabetes and the use of nutrition information (NI). A cross-sectional design evaluated adults with diabetes from the 2009-2010 and 2017-2020 NHANES databases. Use of NI was quantified based on the subject’s use of the Nutrition Facts Label, use of calorie information at restaurants, and use of either the USDA Food Guide Pyramid or My Plate. Glycemic control was established if the subject’s hemoglobin A1C concentration was 7.0% or lower. SAS Software (v. 9.4) was used for all statistical analysis. Differences between prevalences were established …

A Suspected Case Of Levetiracetam Induced Rhabdomyolysis, Luke Merrill Ms, Layne Hohn Ms, Marlee Jones Ms, Sydney Gibson Ms, Ty Moody Md, Anthony Breemo Md

Aesculapius Journal (Health Sciences & Medicine)

Background: Levetiracetam is a broad-spectrum antiseizure drug which works to terminate convulsions and is used in the treatment of certain types of seizures. It is commonly used to treat epilepsy in adults, and has proven an effective treatment for adults with focal seizures. This drug is normally well tolerated, but commonly reported adverse effects include fatigue, somnolence, and dizziness. A few less common effects have been noted as well, including behavioral disturbances, thrombocytopenia, and—in very few cases—rhabdomyolysis.

Case Report: Our case reports a 55-year-old male who presented to a rural emergency department for active convulsing and unresponsiveness. Initial …

Genetic Inactivation Of Β-Catenin Is Salubrious, Whereas Its Activation Is Deleterious In Desmoplakin Cardiomyopathy, Melis Olcum, Siyang Fan, Leila Rouhi, Sirisha Cheedipudi, Benjamin Cathcart, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

AIMS: Mutations in the DSP gene encoding desmoplakin, a constituent of the desmosomes at the intercalated discs (IDs), cause a phenotype that spans arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy. It is typically characterized by biventricular enlargement and dysfunction, myocardial fibrosis, cell death, and arrhythmias. The canonical wingless-related integration (cWNT)/β-catenin pathway is implicated in the pathogenesis of ACM. The β-catenin is an indispensable co-transcriptional regulator of the cWNT pathway and a member of the IDs. We genetically inactivated or activated β-catenin to determine its role in the pathogenesis of desmoplakin cardiomyopathy.

METHODS AND RESULTS: The Dsp gene was conditionally deleted in …

Mir-142: A Master Regulator In Hematological Malignancies And Therapeutic Opportunities, Wilson Huang, Doru Paul, George A Calin, Recep Bayraktar

Faculty, Staff and Student Publications

MicroRNAs (miRNAs) are a type of non-coding RNA whose dysregulation is frequently associated with the onset and progression of human cancers. miR-142, an ultra-conserved miRNA with both active -3p and -5p mature strands and wide-ranging physiological targets, has been the subject of countless studies over the years. Due to its preferential expression in hematopoietic cells, miR-142 has been found to be associated with numerous types of lymphomas and leukemias. This review elucidates the multifaceted role of miR-142 in human physiology, its influence on hematopoiesis and hematopoietic cells, and its intriguing involvement in exosome-mediated miR-142 transport. Moreover, we offer a comprehensive …

Altered Outer Retinal Structure, Electrophysiology And Visual Perception In Parkinson's Disease, Katie K N Tran, Pei Ying Lee, David I Finkelstein, Allison M Mckendrick, Bao N Nguyen, Bang V Bui, Christine T O Nguyen

Faculty, Staff and Student Publications

BACKGROUND: Visual biomarkers of Parkinson's disease (PD) are attractive as the retina is an outpouching of the brain. Although inner retinal neurodegeneration in PD is well-established this has overlap with other neurodegenerative diseases and thus outer retinal (photoreceptor) measures warrant further investigation.

OBJECTIVE: To examine in a cross-sectional study whether clinically implementable measures targeting outer retinal function and structure can differentiate PD from healthy ageing and whether these are sensitive to intraday levodopa (L-DOPA) dosing.

METHODS: Centre-surround perceptual contrast suppression, macular visual field sensitivity, colour discrimination, light-adapted electroretinography and optical coherence tomography (OCT) were tested in PD participants (n = …

Impact Of Cumulative Dose Of Brentuximab Vedotin On Outcomes Of Frontline Therapy For Advanced-Stage Hodgkin Lymphoma, Raphael E Steiner, Steven R Hwang, Arushi Khurana, Thomas M Habermann, Narendranath Epperla, Kaitlin Annunzio, Pamela Blair Allen, Katelin Baird, Darina Paulino, Juan Pablo Alderuccio, Izidore S Lossos, Kevin David, Andrew M Evens, Karan Pandya, Steven M Bair, Manali Kamdar, Sheeba Ba Aqeel, Pallawi Torka, Ryan Lynch, Stephen Smith, Lei Feng, Mansoor Noorani, Sairah Ahmed, Ranjit Nair, Francisco Vega, Susan Wu, Penny Fang, Chelsea C Pinnix, Jillian R Gunther, Bouthaina S Dabaja, Hun J Lee

Faculty, Staff and Student Publications

In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of advanced-stage classic Hodgkin lymphoma (cHL). However, there are minimal available data regarding the frequency of dose reductions or omission of BV during curative therapy and the potential impact on patient outcomes. In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with frontline A + AVD from January 2010 to April 2022. Treatment consisted of up to 1.2 mg/kg of BV and …

Engineered Adoptive T-Cell Therapies For Breast Cancer: Current Progress, Challenges, And Potential, Diego F Chamorro, Lauren K Somes, Valentina Hoyos

Faculty, Staff and Students Publications

Breast cancer remains a significant health challenge, and novel treatment approaches are critically needed. This review presents an in-depth analysis of engineered adoptive T-cell therapies (E-ACTs), an innovative frontier in cancer immunotherapy, focusing on their application in breast cancer. We explore the evolving landscape of chimeric antigen receptor (CAR) and T-cell receptor (TCR) T-cell therapies, highlighting their potential and challenges in targeting breast cancer. The review addresses key obstacles such as target antigen selection, the complex breast cancer tumor microenvironment, and the persistence of engineered T-cells. We discuss the advances in overcoming these barriers, including strategies to enhance T-cell efficacy. …

Co-Transmitting Interneurons In The Mouse Olfactory Bulb Regulate Olfactory Detection And Discrimination, Ariel M Lyons-Warren, Evelyne K Tantry, Elizabeth H Moss, Mikhail Y Kochukov, Benjamin D W Belfort, Joshua Ortiz-Guzman, Zachary Freyberg, Benjamin R Arenkiel

Faculty, Staff and Students Publications

Co-transmission of multiple neurotransmitters from a single neuron increases the complexity of signaling information within defined neuronal circuits. Superficial short-axon cells in the olfactory bulb release both dopamine and γ-aminobutyric acid (GABA), yet the specific targets of these neurotransmitters and their respective roles in olfaction have remained unknown. Here, we implement intersectional genetics in mice to selectively block GABA or dopamine release from superficial short-axon cells to identify their distinct cellular targets, impact on circuit function, and behavioral contribution of each neurotransmitter toward olfactory behaviors. We provide functional and anatomical evidence for divergent superficial short-axon cell signaling onto downstream neurons …

Folate Deficiency Modifies The Risk Of Cin3+ Associated With Dna Methylation Levels: A Nested Case–Control Study From The Ascus-Col Trial, María C. Agudelo, Samuel Agudelo, Attila Lorincz, Arianis Tatiana Ramírez, Kelly Melisa Castañeda, Isabel Garcés-Palacio, Arnold H. Zea, Chandrika Piyathilake, Gloria Ines Sanchez

School of Medicine Faculty Publications

Purpose: To our knowledge, there are very few studies evaluating if the levels of folate modify the risk of cervical intraepithelial neoplasia grade 2 and higher (CIN2+ and CIN3+) associated with the levels of HPV genome methylation, two cofactors related to single carbon metabolism and independently associated with cervical cancer in previous studies. We conducted a case–control study nested in a three-arm randomized clinical pragmatic trial (ASCUS-COL trial) to evaluate the risk of CIN3+ associated with methylation levels according to serum folate concentrations. Methods: Cases (n = 155) were women with histologically confirmed CIN2+ (113 CIN2, 38 CIN3, and 4 …

Assessment Of Deficits In Specific Cognitive Domains In Older Adults Living With Hiv., Andrea Reyes-Vega, Harideep Samanapally, Rishikesh Rijal, Stephen P. Furmanek, Christopher B. Shields, Brandon C. Dennis, Smita Ghare, Shirish Barve

Faculty and Staff Scholarship

A significant proportion of people living with HIV (PLWH) have cognitive impairment. Moreover, approximately 70% of PLWH in the United States will be ≥50 years old by 2030, raising concerns of a higher incidence of dementia as they age. Accordingly, there is a clinical need to monitor their cognitive status. The aim of this study was to delineate specific cognition areas impacted in OALWH with a clinical diagnosis of neurocognitive impairment. We used a comprehensive set of tests (paper and NIH Toolbox Cognition Battery), to assess different cognitive domains in a total of 25 OALWH ≥ 50 years. 64% were …

Pediatric Endocrinology Milestones 20-Guide To Their Implementation, Cara V Tillotson, Imen Becetti, Katherine Hwu, Laura Page, Sowmya Krishnan, Dianne Stafford, Takara Stanley, Patricia Vuguin, Jennifer M Barker

Faculty, Staff and Students Publications

The Milestones were initiated by the Accreditation Council for Graduate Medical Education (ACGME) to provide a framework for monitoring a trainee's progression throughout residency/fellowship. The Milestones describe stepwise skill progression through six core domains of clinical competency: Patient Care, Medical Knowledge, Interpersonal and Communication Skills, Practice-based Learning and Improvement, Professionalism, and Systems-based Practice. Since their introduction in 2013, several barriers to implementation have emerged. Thus, the ACGME launched the Milestones 2.0 project to develop updated specialty-specific milestones. The Pediatric Endocrinology Milestones 2.0 project aimed to improve upon Milestones 1.0 by addressing common limitations, providing resources for faculty to easily incorporate …

Interventricular Septal Hematoma Complicating Left Branch Bundle Lead Implantation: Treatment By Covered Stent, César Del Castillo, Jorge Van-Grieken, Marco Coello, Carlos Torres-Herrera, Barbara Clericus, Daniel Requena, Arnulfo Begazo, Franco Appiani, Boris Kuzmicic, Paola Varleta

Faculty, Staff and Students Publications

We present a female patient with heart failure with reduced ejection fraction who underwent left bundle branch cardiac resynchronization therapy. Left bundle branch lead implantation was complicated with septal branch perforation causing an iatrogenic coronary fistula complicated by septal hematoma formation and development of shock. Occlusion by covered stents was successfully achieved.

Interlaboratory Comparison Of Pseudomonas Aeruginosa Phage Susceptibility Testing, Krupa Parmar, Lauren Komarow, Damon W Ellison, Andrey A Filippov, Mikeljon P Nikolich, Joseph R Fackler, Martin Lee, Anjna Nair, Priyesh Agrawal, Pranita D Tamma, Maria Souli, Scott R Evans, Kerryl E Greenwood-Quaintance, Scott A Cunningham, Robin Patel, Antibacterial Resistance Leadership Group

Faculty, Staff and Student Publications

Standardized approaches to phage susceptibility testing (PST) are essential to inform selection of phages for study in patients with bacterial infections. There is no reference standard for assessing bacterial susceptibility to phage. We compared agreement between PST performed at three centers: two centers using a liquid assay standardized between the sites with the third, a plaque assay. Four Pseudomonas aeruginosa phages: PaWRA01ø11 (EPa11), PaWRA01ø39 (EPa39), PaWRA02ø83 (EPa83), PaWRA02ø87 (EPa87), and a cocktail of all four phages were tested against 145 P. aeruginosa isolates. Comparisons were made within measurements at the two sites performing the liquid assay and between these …

Rotavirus-Mediated Dgat1 Degradation: A Pathophysiological Mechanism Of Viral-Induced Malabsorptive Diarrhea, Zheng Liu, Hunter Smith, Jeanette M Criglar, Antonio J Valentin, Umesh Karandikar, Xi-Lei Zeng, Mary K Estes, Sue E Crawford

Faculty, Staff and Students Publications

Gastroenteritis is among the leading causes of mortality globally in infants and young children, with rotavirus (RV) causing ~258 million episodes of diarrhea and ~128,000 deaths annually in infants and children. RV-induced mechanisms that result in diarrhea are not completely understood, but malabsorption is a contributing factor. RV alters cellular lipid metabolism by inducing lipid droplet (LD) formation as a platform for replication factories named viroplasms. A link between LD formation and gastroenteritis has not been identified. We found that diacylglycerol O-acyltransferase 1 (DGAT1), the terminal step in triacylglycerol synthesis required for LD biogenesis, is degraded in RV-infected cells by …

The Role Of Point-Of-Care Ultrasound In The Assessment Of Pelvic Urine Leakage And Diagnosis Of Urinoma, Asra Moradkhani, Mona Zangi, Mobin Azami, Mohammad Ghasemi-Rad, Abdolghader Pakniyat

Faculty, Staff and Students Publications

BACKGROUND: Urinoma, a rare condition resulting from urine leakage due to trauma to the kidney, bladder, or urethra, is typically diagnosed using enhanced computed tomography urogram with delayed imaging. This report presents two cases of urinoma likely caused by overdistention of the renal pelvis following excessive fluid intake and the presence of a ureteral stone.

CASE PRESENTATION: We present two cases of 36-year-old and 38-year-old patients who presented with flank pain. point-of-care ultrasound (POCUS) played a pivotal role in identifying perinephric fluid in Morrison's space and the splenorenal space, respectively. These ultrasound findings guided further investigations, leading to definitive diagnoses …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Citrullinated And Malondialdehyde-Acetaldehyde Modified Proteins Promote Cellular Inflammatory And Fibrotic Responses Associated With Rheumatoid Arthritis, Nozima Aripova

Theses & Dissertations

Rheumatoid arthritis (RA) is a systemic, autoimmune disease primarily characterized by perpetual synovial inflammation that results in synovial tissue proliferation and fibrosis (pannus). Although joint involvement is the predominant manifestation of RA, extra-articular features, such as interstitial lung disease (ILD), contribute significantly to the elevated mortality associated with the condition. Post-translational modifications play a significant role in RA and RA-ILD pathogenesis. Circulating anti-citrullinated protein antibodies (ACPAs) are a highly diagnostic tool implicating a potential role for citrullinated antigens in RA and RA-ILD.

Recently, antibodies to malondialdehyde acetaldehyde adducts (MAA) have been markedly elevated in patients with RA and RA-ILD. MAA …

Myod-Skp2 Axis Boosts Tumorigenesis In Fusion Negative Rhabdomyosarcoma By Preventing Differentiation Through P57kip2 Targeting, Silvia Pomella, Matteo Cassandri, Lucrezia D’Archivio, Antonella Porrazzo, Cristina Cossetti, Doris Phelps, Clara Perrone, Michele Pezzella, Antonella Cardinale, Marco Wachtel, Sara Aloisi, David Milewski, Marta Colletti, Prethish Sreenivas, Zoë S. Walters, Giovanni Barillari, Angela Di Giannatale, Giuseppe Maria Milano, Cristiano De Stefanis, Rita Alaggio, Sonia Rodriguez-Rodriguez, Nadia Carlesso, Christopher R. Vakoc, Enrico Velardi, Beat W. Schafer, Ernesto Guccione, Susanne A. Gatz, Lucio Miele

School of Medicine Faculty Publications

Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Fusion Negative (FN)-RMS with frequent RAS pathway mutations. RMS express the master myogenic transcription factor MYOD that, whilst essential for survival, cannot support differentiation. Here we discover SKP2, an oncogenic E3-ubiquitin ligase, as a critical pro-tumorigenic driver in FN-RMS. We show that SKP2 is overexpressed in RMS through the binding of MYOD to an intronic enhancer. SKP2 in FN-RMS promotes cell cycle progression and prevents differentiation by directly targeting p27Kip1 and p57Kip2, respectively. SKP2 depletion unlocks a partly MYOD-dependent myogenic transcriptional program and strongly affects stemness and tumorigenic …

Timigp: An R Package To Depict The Tumor Microenvironment From Bulk Transcriptomics, Chenyang Li, Jianjun Zhang, Chao Cheng

Faculty, Staff and Students Publications

Exploring the clinical relevance of diverse immune cell types within the tumor microenvironment is pivotal for unraveling cancer intricacies and developing treatments. Here, we present a protocol for using tumor immune microenvironment illustration based on gene pairs, an R package to deduce cell-cell interactions, unveiling the association between immune cell relative abundance and patient prognoses from bulk gene expression and survival data. We describe steps for harnessing cell-type markers derived from single-cell RNA sequencing data to map the tumor immune microenvironment across a spectrum of cancer types. For complete details on the use and execution of this protocol, please refer …

Enniatin A Inhibits The Chaperone Hsp90 And Unleashes The Immune System Against Triple-Negative Breast Cancer, Nada H Eisa, Vincent M Crowley, Asif Elahi, Vamsi Krishna Kommalapati, Michael A Serwetnyk, Taoufik Llbiyi, Sumin Lu, Kashish Kainth, Yasmeen Jilani, Daniela Marasco, Abdeljabar El Andaloussi, Sukyeong Lee, Francis T F Tsai, Paulo C Rodriguez, David Munn, Esteban Celis, Hasan Korkaya, Abdessamad Debbab, Brian Blagg, Ahmed Chadli

Faculty, Staff and Students Publications

Low response rates and immune-related adverse events limit the remarkable impact of cancer immunotherapy. To improve clinical outcomes, preclinical studies have shown that combining immunotherapies with N-terminal Hsp90 inhibitors resulted in improved efficacy, even though induction of an extensive heat shock response (HSR) and less than optimal dosing of these inhibitors limited their clinical efficacy as monotherapies. We discovered that the natural product Enniatin A (EnnA) targets Hsp90 and destabilizes its client oncoproteins without inducing an HSR. EnnA triggers immunogenic cell death in triple-negative breast cancer (TNBC) syngeneic mouse models and exhibits superior antitumor activity compared to Hsp90 N-terminal inhibitors. …

Aspirin And Nonaspirin Nonsteroidal Antiinflammatory Drug Use And Occurrence Of Colorectal Adenoma In Black American Women, Lauren E Barber, Kimberly A Bertrand, Shanshan Sheehy, Laura F White, Hemant K Roy, Lynn Rosenberg, Julie R Palmer, Jessica L Petrick

Faculty, Staff and Students Publications

Evidence suggests that aspirin use reduces the occurrence of colorectal neoplasia. Few studies have investigated the association among Black Americans, who are disproportionately burdened by the disease. We assessed aspirin use in relation to colorectal adenoma among Black women. The Black Women's Health Study is a prospective cohort of self-identified Black American women established in 1995. Participants reported regular aspirin use on baseline and follow-up questionnaires. Beginning in 1999, participants reported undergoing a colonoscopy or sigmoidoscopy, the only procedures through which colorectal adenomas can be diagnosed. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals …

Early Cellular And Molecular Signatures Correlate With Severity Of West Nile Virus Infection, Ho-Joon Lee, Yujiao Zhao, Ira Fleming, Sameet Mehta, Xiaomei Wang, Brent Vander Wyk, Shannon E Ronca, Heather Kang, Chih-Hung Chou, Benoit Fatou, Kinga K Smolen, Ofer Levy, Clary B Clish, Ramnik J Xavier, Hanno Steen, David A Hafler, J Christopher Love, Alex K Shalek, Leying Guan, Kristy O Murray, Steven H Kleinstein, Ruth R Montgomery

Faculty, Staff and Students Publications

Infection with West Nile virus (WNV) drives a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To identify cellular and molecular signatures distinguishing WNV severity, we employed systems profiling of peripheral blood from asymptomatic and severely ill individuals infected with WNV. We interrogated immune responses longitudinally from acute infection through convalescence employing single-cell protein and transcriptional profiling complemented with matched serum proteomics and metabolomics as well as multi-omics analysis. At the acute time point, we detected both elevation of pro-inflammatory markers in innate immune cell types and reduction of regulatory T cell …

A Comprehensive Program Evaluation Of Colorectal Rescreening Initiatives In Rural Virginia, Sarah E. Stowell

Doctors of Nursing Practice (DNP) Final Projects, 2020-current

Background: Despite low-cost and effective screening tools, colorectal cancer (CRC) mortality remains high in the U.S., particularly in rural areas like Virginia’s Northern Shenandoah Valley, where screening rates are low. While literature highlights barriers to CRC screening in these communities and suggests improvement strategies, few studies focus on long-term adherence to screening in rural health clinics (RHCs).

Purpose: This program evaluation assessed the impact and effectiveness of the Rural Colorectal Cancer Rescreening Initiative (RCRI), a pilot program to increase colorectal cancer rescreening rates in a local RHC. It also offers recommendations for optimizing future RCRI efforts. Methods: The program evaluation …