Diseases Commons^™

Early Administration Of Steroids In The Ambulance Setting: An Observational Design Trial (Easi-As-Odt), Jennifer N Fishe, Gerard Garvan, Andrew Bertrand, Shannon Burcham, Phyllis Hendry, Manish Shah, Kathryn Kothari, David W Ashby, Daniel Ostermeyer, Lauren Riney, Olga Semenova, Benjamin Abo, Benjamin Abes, Nichole Shimko, Emily Myers, Marshall Frank, Tim Turner, Mac Kemp, Kim Landry, Greg Roland, Kathryn V Blake

Faculty, Staff and Students Publications

BACKGROUND: In the emergency department (ED), prompt administration of systemic corticosteroids for pediatric asthma exacerbations decreases hospital admission rates. However, there is sparse evidence for whether earlier administration of systemic corticosteroids by emergency medical services (EMS) clinicians, prior to ED arrival, further improves pediatric asthma outcomes.

METHODS: Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial is a multicenter, observational, nonrandomized stepped-wedge design study with seven participating EMS agencies who adopted an oral systemic corticosteroid (OCS) into their protocols for pediatric asthma treatment. Using univariate analyses and multivariable mixed-effects models, we compared hospital admission rates for pediatric …

Gene Content, Phage Cycle Regulation Model And Prophage Inactivation Disclosed By Prophage Genomics In The Helicobacter Pylori Genome Project, Filipa F Vale, Richard J Roberts, Ichizo Kobayashi, M Constanza Camargo, Charles S Rabkin, Hpgp Research Network

Faculty, Staff and Students Publications

Prophages can have major clinical implications through their ability to change pathogenic bacterial traits. There is limited understanding of the prophage role in ecological, evolutionary, adaptive processes and pathogenicity of Helicobacter pylori, a widespread bacterium causally associated with gastric cancer. Inferring the exact prophage genomic location and completeness requires complete genomes. The international Helicobacter pylori Genome Project (HpGP) dataset comprises 1011 H. pylori complete clinical genomes enriched with epigenetic data. We thoroughly evaluated the H. pylori prophage genomic content in the HpGP dataset. We investigated population evolutionary dynamics through phylogenetic and pangenome analyses. Additionally, we identified …

The Tb27 Transcriptomic Model For Predicting Mycobacterium Tuberculosis Culture Conversion, Maja Reimann, Korkut Avsar, Andrew R Dinardo, Torsten Goldmann, Gunar Günther, Michael Hoelscher, Elmira Ibraim, Barbara Kalsdorf, Stefan H E Kaufmann, Niklas Köhler, Anna M Mandalakas, Florian P Maurer, Marius Müller, Dörte Nitschkowski, Ioana D Olaru, Cristina Popa, Andrea Rachow, Thierry Rolling, Helmut J F Salzer, Patricia Sanchez-Carballo, Maren Schuhmann, Dagmar Schaub, Victor Spinu, Elena Terhalle, Markus Unnewehr, Nika J Zielinski, Jan Heyckendorf, Christoph Lange

Faculty, Staff and Students Publications

RATIONALE: Treatment monitoring of tuberculosis patients is complicated by a slow growth rate of Mycobacterium tuberculosis. Recently, host RNA signatures have been used to monitor the response to tuberculosis treatment.

OBJECTIVE: Identifying and validating a whole blood-based RNA signature model to predict microbiological treatment responses in patients on tuberculosis therapy.

METHODS: Using a multi-step machine learning algorithm to identify an RNA-based algorithm to predict the remaining time to culture conversion at flexible time points during anti-tuberculosis therapy.

RESULTS: The identification cohort included 149 patients split into a training and a test cohort, to develop a multistep algorithm consisting of …

Divergent Responses Of Human Intestinal Organoid Monolayers Using Commercial In Vitro Cytotoxicity Assays, Miranda A Lewis, Ketki Patil, Khalil Ettayebi, Mary K Estes, Robert L Atmar, Sasirekha Ramani

Faculty, Staff and Students Publications

In vitro models, such as primary cells and continuous cell lines routinely used for evaluating drug candidates, have limitations in their translational relevance to human diseases. Organotypic cultures are increasingly being used to assess therapeutics for various cancers and infectious diseases. Monitoring drug cytotoxicity in cell cultures is crucial in drug development, and several commercially available kits for cytotoxicity assessment offer distinct advantages and limitations. Given the complexity of organoid cultures, including donor-driven variability, we investigated drug-treated, tissue stem cell-derived human intestinal organoid responses with commonly used cell cytotoxicity assay kits. Using seven different compounds, we compared the cytotoxicity assay …

Editorial: Managing Cancer Metastasis By Tackling Anticancer Drug Resistance, Erxi Wu, Zhongzhi Wu, Chao-Yie Yang, Dan Qi, Xiaoxiao Hu, Wei Li

Faculty, Staff and Students Publications

No abstract provided.

Mechanistic Insight Into Maternal Electronic Cigarette Exposure And Its Effect On Offspring Cerebrovascular And Neurocognitive Health, Amber Victoria Mills

Graduate Theses, Dissertations, and Problem Reports (ETD)

Electronic cigarettes (Ecigs) have replaced smoking within the last decade as the preferred nicotine delivery system because of their advertising to the younger populations. Marketing has sold the idea that use of Ecigs are safer than smoking and this messaging has resonated with youth and other vulnerable populations such as pregnant women. Despite over 2.8 million children under 18 (Annual National Youth Tobacco Survey) deciding to vape, there is little information about what this will do to the next generation. Further, it is that same population that will soon reach an age when they will want to have children. There …

Implementation Of A Pilot Quality Improvement Project To Guide The Administration Of Intraoperative Dexamethasone For Postoperative Nausea And Vomiting Prophylaxis In Patients With Diabetes Undergoing Orthopedic Procedures, Brittany W. Hall

Graduate Theses, Dissertations, and Problem Reports (ETD)

Background: At a local tertiary care hospital, there was no recommendation to guide anesthesia providers in the administration of intraoperative dexamethasone to patients with diabetes. While dexamethasone is a highly effective antiemetic, it may promote hyperglycemia in patients with diabetes.

Purpose: The purpose of this project was to guide and educate about current recommendations for the administration of dexamethasone for PONV prophylaxis in patients with diabetes.

Intervention: 1) Examined pre-intervention practices of dexamethasone administration. 2) Educated about current and best practices to anesthesia staff. 3) Developed badge buddy cards outlining the guideline. 4) Examined post-intervention practices. 5) Evaluated the effect …

Improving Patient Self-Advocacy And Communication With Providers Through Diabetes Self-Management Education: Analyses From A Randomized Controlled Trial, Brenna Owens Kirk

Graduate Theses, Dissertations, and Problem Reports (ETD)

Background: West Virginia (WV), a rural state in Appalachia, has the highest type 2 diabetes mellitus (T2DM) prevalence in the United States. Open communication in the patient-provider relationship is an integral part of comprehensive chronic disease management. This is especially true for patients living with T2DM, a disease that requires many complex, daily self-management activities and is associated with increased emotional distress. However, patients living with T2DM are often reluctant to openly share their concerns regarding self-care with their provider. This study aimed to test the effectiveness of the Diabetes and Hypertension Self-Management Program (DHSMP), a 12-week group lifestyle …

Regulation Of Diabetic Cardiomyopathy Through Mitochondrial Import Of Long Non-Coding Rnas, Andrew Dodge Taylor

Graduate Theses, Dissertations, and Problem Reports (ETD)

Introduction: The leading cause of mortality in patients with diabetes mellitus is heart failure. When mitochondrial health and function is disrupted, cardiac contractile function is compromised. Therefore, understanding mitochondrial regulation may benefit predicting and countering diabetic cardiomyopathy. MicroRNAs (miRNAs) play a crucial role in diabetic cardiac mitochondrial protein expression. Long noncoding RNAs (lncRNAs) have been shown to regulate miRNAs, but not in the mitochondrion. Additionally, it has yet to be confirmed if lncRNAs utilize the same mechanisms for mitochondrial import that miRNAs use, or if lncRNA presence in the mitochondrion fluctuates in diabetic mitochondria like miRNA presence does. The …

Translational Approaches To Address The Metastatic/Resistant (Mr) Phenotype Of Non-Small Cell Lung Cancer Brain Metastases, Kent L. Marshall

Graduate Theses, Dissertations, and Problem Reports (ETD)

Lung cancer remains the most frequently diagnosed malignant neoplasm shared in men and women worldwide, second only to the sexually dimorphic prostate cancer in men and breast cancer in women. Overall, lung cancer was responsible for 12.5% of new cancer cases globally in the year 2022. Of these cases, 80-85% are non-small cell lung cancer (NSCLC), a highly genotypically diverse sub-type of lung cancer. Over the past three decades, extraordinary improvement in screening, smoking cessation, early diagnosis and targeted therapy have been made, improving NSCLC survival markedly. However, as patients are surviving their primary disease better, there is a temporal …

Anesthetic Management Of A Patient With Renal Cell Carcinoma-Associated Venous Thrombosis And Massive Transfusion, Gary Zhang, Ryan Palacios, Jamal Hasoon, Christopher L Robinson, Anvinh Nguyen

Faculty, Staff and Students Publications

A 53-year-old male with a history of multiple deep venous thromboses (DVTs) underwent a right open radical nephrectomy with inferior vena cava (IVC) thrombectomy in the context of renal cell carcinoma (RCC)-associated venous thrombosis. Imaging and renal biopsy revealed a diagnosis of RCC with non-occlusive thrombosis of the left renal vein and occlusive thrombosis of the infrarenal IVC. The major risks of concern for the procedure included thrombus embolization from surgical manipulation and massive bleeding. Intraoperatively, the patient experienced significant hemorrhage requiring massive transfusion protocol. The purpose of this case report is to emphasize the importance of multidisciplinary involvement, intraoperative …

Statins And The Risk Of Pancreatic Cancer: A Systematic Review And Meta-Analysis Of 2,797,186 Patients, Eryka Karbowska, Damian Swieczkowski, Aleksandra Gasecka, Michal Pruc, Kamil Safiejko, Jerzy R Ladny, Tomasz Kopiec, Milosz J Jaguszewski, Krzysztof J Filipiak, Zubaid Rafique, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: Statin use in many studies is related to the improvement of a patients' condition including reducing the risk of various malignancies. Herein, is a systematic review and meta-analysis to examine the evidence on the association between statin therapy and the risk of the occurrence of pancreatic cancer, mainly in terms of decreased risk of developing pancreatic cancer among patients using statin therapy in the long-term perspective.

METHODS: PubMed, Web of Science, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from database inception to December 1st, 2021. Random effect models were used to estimate summary odds ratios …

Associations Among Psychosocial Factors, Health-Related Quality Of Life, And Adherence In Pediatric Inflammatory Bowel Disease, Cecelia I. Nelson

Graduate Theses, Dissertations, and Problem Reports (ETD)

Inflammatory Bowel Disease (IBD) is a prevalent disorder among youth in the United States. IBD is one of the leading causes of chronic pain in adolescence and symptoms can lead to reduced quality of life, social embarrassment, and lower self-esteem. Adherence to medical regimens for IBD is incredibly important to prevent morbidity, mortality, and impaired health-related quality of life (HRQOL). However, adolescents struggle generally with adherence and the regimen for IBD can be complicated and include aversive side effects. Psychological factors, such as depressive symptoms, are key factors associated with non-adherence. Nevertheless, gut-specific anxiety (GSA) is a psychological factor that …

Limb Speed Perception Accuracy In Neurodegenerative Disease, Brandmeir Lynn Cheryl

Graduate Theses, Dissertations, and Problem Reports (ETD)

Movement is a fundamental human activity, enabling us to engage with our surroundings. Consequently, a well-operating neuromuscular system is essential for maintaining quality of life. Motion is not only integral for the basic function of daily living, but also plays a significant role in enhancing our physical, mental, and emotional health. The importance of this system becomes abundantly clear when it is compromised, such as with neurodegenerative disease.

Alzheimer’s disease (AD), followed by Parkinson’s disease (PD) are the two most common neurodegenerative diseases that profoundly affect millions of individuals worldwide (Lamptey et al., 2022). Characterized by distinct but sometimes overlapping …

Fight-Pd: A Feasibility Study Of Periodized Boxing Training For Parkinson Disease, David J. Blacker, Raimondo Fazio, Claire Tucak, Phillip Beranek, Connor Pollard, Tegan Shelley, Sanathraj Rajandran, Georgina Holbeche, Mitchell Turner, Travis Cruickshank

Research outputs 2022 to 2026

Background: Boxing training has become a popular form of exercise for people with Parkinson disease (PD). There is a dearth of high-quality feasibility, safety, and efficacy data on boxing training for PD. Feasibility of Instituting Graduated High-intensity Training (FIGHT-PD) aimed to examine these features in a periodized boxing training program featuring high-intensity physical and cognitive demands. Objective: To conduct a feasibility study, aiming to address deficiencies in the current knowledge base and to provide data for future studies. Design: Single-arm, open-label feasibility. Setting: University department and medical research institute. Participants: Ten people with early stage PD without contraindications to intense …

Predictive Modelling Of Metabolic Syndrome In Ghanaian Diabetic Patients: An Ensemble Machine Learning Approach, Emmanuel Acheampong, Eric Adua, Christian Obirikorang, Enoch Odame Anto, Emmanuel Peprah-Yamoah, Yaa Obirikorang, Evans Adu Asamoah, Victor Opoku-Yamoah, Michael Nyantakyi, John Taylor, Tonnies Abeku Buckman, Maryam Yakubu, Ebenezer Afrifa-Yamoah

Research outputs 2022 to 2026

Objectives: The burgeoning prevalence of cardiometabolic disorders, including type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) within Africa is concerning. Machine learning (ML) techniques offer a unique opportunity to leverage data-driven insights and construct predictive models for MetS risk, thereby enhancing the implementation of personalised prevention strategies. In this work, we employed ML techniques to develop predictive models for pre-MetS and MetS among diabetic patients. Methods: This multi-centre cross-sectional study comprised of 919 T2DM patients. Age, gender, novel anthropometric indices along with biochemical measures were analysed using BORUTA feature selection and an ensemble majority voting classification model, which included …

Nutrients And Polyphenols-Rich Sorghum Bicolor Genotypes As Complementary Therapy For Alzheimer’S Disease, Rasheed A. Abdulraheem, Ralph N. Martins, Prashant Bharadwaj, Zhaoyu Li, Ranil Coorey, Stuart Johnson, W. M. A. D. Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and most common cause of dementia among older people. The main pathological hallmarks of AD are formation of insoluble amyloid beta senile plaques and paired helical filaments of neurofibrillary tangles. AD features gradual memory decline, mild to severe cognitive impairment, eventually total dependence of patients on caregivers. Currently available drugs have not been able to modify AD pathology. This has drawn increasing attention to plant food materials with high nutritional and bioactive constituents as potential complementary therapy for AD. Sorghum bicolor is a widely available cost-effective source of proteins, fats, crude fibres, …

The Impact Of Exercise On Blood-Based Biomarkers Of Alzheimer’S Disease In Cognitively Unimpaired Older Adults, Kelsey R. Sewell, Stephanie R. Rainey-Smith, Steve Pedrini, Jeremiah J. Peiffer, Hamid R. Sohrabi, Kevin Taddei, Shaun J. Markovic, Ralph N. Martins, Belinda M. Brown

Research outputs 2022 to 2026

Physical activity is a promising preventative strategy for Alzheimer’s disease: it is associated with lower dementia risk, better cognition, greater brain volume and lower brain beta-amyloid. Blood-based biomarkers have emerged as a low-cost, non-invasive strategy for detecting preclinical Alzheimer’s disease, however, there is limited literature examining the effect of exercise (a structured form of physical activity) on blood-based biomarkers. The current study investigated the influence of a 6-month exercise intervention on levels of plasma beta-amyloid (A 42, A 40, A 42/40), phosphorylated tau (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) chain in cognitively unimpaired older adults, and …

Association Between The Presence Of Helicobacter Pylori And The Development Of De Novo Anemia In Adults Undergoing Sleeve Gastrectomy, Tammy S. Carrillo-Levin, Maria F. Jaramillo-Ocharan, Gustavo Salinas-Sedo, Carlos J. Toro-Huamanchumo

Research outputs 2022 to 2026

Background: Sleeve gastrectomy has gained prominence in obesity treatment, yet it is not without complications, such as the development of anemia in the medium term. Given the high prevalence of Helicobacter pylori infection in Peru, it is imperative to explore its potential association with this postoperative complication. Objective: To evaluate the association between the presence of Helicobacter pylori and the development of anemia 12 months after sleeve gastrectomy. Methods: A retrospective cohort study was carried out based on an analysis of secondary data from a private clinic in Lima, Peru, which included two groups of people over 18 years of …

Characterization Of Pain In Lipedema: Reliability And Validity Of Pain Pressure Thresholds And Hand-Held Sphygmomanometer Assessments In People With Lipedema, Francesco Bettariga, Luca Fumagalli, Daniele Aloisi, Luca Maestroni, Sara Mantovani

Research outputs 2022 to 2026

Background: Lipedema is a chronic condition characterized by abnormal deposition of subcutaneous adipose tissue, leading to pain. The lack of internationally recognized diagnostic criteria complicates the characterization of pain. Physiological parameters such as pain pressure threshold (PPT) represent promising prognostic markers for diagnosing lipedema, yet they remain understudied. This study aimed to evaluate the reliability and validity of two pain pressure measurements, PPT and the hand-held sphygmomanometer (HHS) in lipedema. Methods: A total of 28 adult females diagnosed with lipedema were recruited. Both PPT, using a digital algometer, and HHS, using a manual aneroid HHS, were performed to assess pain …

Effects Of Aerobic And Resistance Exercise For 9 Months On Serum Free Light Chains In Type 2 Diabetes, Youyoung Kim, John P. Campbell, Neil M. Johannsen, Timothy S. Church, Eunhan Cho, Jennifer Heaney, Guillaume Spielmann

Research outputs 2022 to 2026

Background and aims: Serum polyclonal free light chains (FLCs) levels are associated with overall survival in the general population, reflecting their utility as a biomarker of underlying immune activation and inflammation. Regular exercise is known to ameliorate low-grade inflammation in chronic diseases such as type 2 diabetes; however, the effects of different exercise training modalities on FLCs in adults with type 2 diabetes is unknown. This study investigated the effects of 9-month of aerobic, resistance or combined supervised exercise on serum FLCs in 164 patients with type 2 diabetes (age 58 ± 8 years; 63% female). Methods: 164 participants from …

Midline Brain Structures In Adult Niemann-Pick Type C Disease: A Cross-Sectional Study, Mark Walterfang, Tsutomu Takahashi, Maria A. Di Biase, Vanessa L. Cropley, Daiki Sasabayashi, Michio Suzuki, Dennis Velakoulis, Christos Pantelis

Research outputs 2022 to 2026

Objective: A range of neuropathological changes occur in the brains of individuals with adult Niemann-Pick type C disease (NPC), a recessive disorder of cholesterol trafficking that results in accumulation of cholesterol and gangliosides in lysosomes, particularly in neurons. One of the most significant regions of grey matter loss occurs in the thalami, which abut the midline. What is not known is whether these are neurodevelopmental in origin well prior to symptomatic onset. We aimed to examine other markers of midline developmental anomalies in adults with NPC. Method: We examined the size of adhesio interthalamica (AI) and cavum septum pellucidum (CSP) …

Cardiac Tamponade Secondary To Esophagopericardial Fistula, Caitlin T Perez-Stable, Lauren T Callaghan, Christopher K Wong, Jorge M Escobar, Mahboob Alam

Faculty, Staff and Students Publications

Esophagopericardial fistulas are an extremely rare structural defect that may arise from malignant or iatrogenic etiologies. This article reports the case of a patient with cardiac tamponade secondary to hydropneumopericardium from esophagopericardial fistula. Given the high morbidity and mortality of this condition, this article describes challenges in diagnosis and clinical decision-making to improve early identification and interdisciplinary management.

First-Line Chemoimmunotherapy And Immunotherapy In Patients With Non-Small Cell Lung Cancer And Brain Metastases: A Registry Study, Lauren J. Brown, Victor Khou, Chris Brown, Marliese Alexander, Dasantha Jayamanne, Joe Wei, Lauren Gray, Wei Chan, Samuel Smith, Susan Harden, Antony Mersiades, Lydia Warburton, Malinda Itchins, Jenny H. Lee, Nick Pavlakis, Stephen J. Clarke, Michael Boyer, Adnan Nagrial, Eric Hau, Ines Pires Da Silva, Steven Kao, Benjamin Y. Kong

Research outputs 2022 to 2026

Introduction: Brain metastases commonly occur in patients with non-small cell lung cancer (NSCLC). Standard first-line treatment for NSCLC, without an EGFR, ALK or ROS1 mutation, is either chemoimmunotherapy or anti-PD-1 monotherapy. Traditionally, patients with symptomatic or untreated brain metastases were excluded from the pivotal clinical trials that established first-line treatment recommendations. The intracranial effectiveness of these treatment protocols has only recently been elucidated in small-scale prospective trials. Methods: Patients with NSCLC and brain metastases, treated with first-line chemoimmunotherapy or anti-PD-1 monotherapy were selected from the Australian Registry and biObank of thoracic cancers (AURORA) clinical database covering seven institutions. The primary …

Weathering The Storm: Diagnosis And Treatment Of A Life-Threatening Disseminated Nocardia Otitidiscaviarum Infection, Li Yan Zhang, Liang Wang, Zeeshan Umar, Yuan Hong Huang, Bing Gu

Research outputs 2022 to 2026

Nocardiosis demonstrates a temporal categorization that includes acute, subacute, and chronic stages alongside distinct typical localizations such as pulmonary, cutaneous, and disseminated forms. Disseminated nocardiosis, commonly caused by Nocardia asteroides, N. brasiliensis, and N. farcinica, continues to result in substantial morbidity and mortality. Herein, we report a life-threatening disseminated nocardiosis caused by Nocardia otitidiscaviarum in a patient with minimal change disease. This study emphasizes the difficulty in the diagnosis and treatment of unknown infections in clinical settings and highlights the important role played by laboratories in solving infectious diseases caused by rare pathogens.

The Great Masquerade: Not All Coronary Artery Stenosis Are Created Equal, Prasanti A Kotta, Ajit K Koduri, Jeffrey Berman, Veronica V Rosen, Waleed T Kayani

Faculty, Staff and Students Publications

We present the case of a 60-year-old male, with active smoking and cocaine use disorder, who reported progressive chest pain. Various anatomical and functional cardiac imaging, performed to further evaluate chest pain etiology, revealed changing severity and distribution of left main artery (LMA) stenosis, raising suspicion for vasospasm. Intracoronary nitroglycerin relieved the vasospasm, with resolution of the LMA pseudostenosis. A diagnosis of vasospastic angina (VA) led to starting appropriate medical therapy with lifestyle modification counselling. This case highlights VA, a frequently underdiagnosed etiology of angina pectoris. We discuss when to suspect VA, its appropriate work-up, and management.

Using Noninvasive Clinical Parameters To Predict Mortality And Morbidity After Cardiac Interventions In Patients With Cirrhosis: A Systematic Review, Christo Mathew, Ankur Patel, George Cholankeril, Avegail Flores, Ruben Hernaez

Faculty, Staff and Students Publications

BACKGROUND: Cardiovascular disease commonly affects advanced liver disease patients. They undergo cardiac interventions to improve cardiac outcomes. Cirrhosis increases complication risk, including bleeding, renal and respiratory failure, and further decompensation, including death, posing a clinical dilemma to proceduralists. Predicting outcomes is crucial in managing patients with cirrhosis. Our aim was to systematically review clinical parameters to assess the mortality and complication risk in patients with cirrhosis undergoing cardiac interventions.

METHODS: We searched cirrhosis and cardiovascular intervention terminology in PubMed and Excerpta Medica Database (EMBASE) from inception to January 8, 2023. We included studies reporting clinical scores (e.g. Model for End-stage …

Targeting Histone Deacetylase In Cardiac Diseases, Jiao Lu, Sichong Qian, Zheng Sun

Faculty, Staff and Students Publications

Histone deacetylases (HDAC) catalyze the removal of acetylation modifications on histones and non-histone proteins, which regulates gene expression and other cellular processes. HDAC inhibitors (HDACi), approved anti-cancer agents, emerge as a potential new therapy for heart diseases. Cardioprotective effects of HDACi are observed in many preclinical animal models of heart diseases. Genetic mouse models have been developed to understand the role of each HDAC in cardiac functions. Some of the findings are controversial. Here, we provide an overview of how HDACi and HDAC impact cardiac functions under physiological or pathological conditions. We focus on in vivo studies of zinc-dependent classical …

A Prdm16-Driven Signal Regulates Body Composition In Testosterone-Treated Hypogonadal Men, Siresha Bathina, Georgia Colleluori, Dennis T Villareal, Lina Aguirre, Rui Chen, Reina Armamento-Villareal

Faculty, Staff and Students Publications

BACKGROUND: Testosterone (T) therapy increases lean mass and reduces total body and truncal fat mass in hypogonadal men. However, the underlying molecular mechanisms for the reciprocal changes in fat and lean mass in humans are not entirely clear.

METHODS: Secondary analysis of specimens obtained from a single-arm, open-label clinical trial on pharmacogenetics of response to T therapy in men with late-onset hypogonadism, conducted between 2011 and 2016 involving 105 men (40-74 years old), who were given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subcutaneous fat (SCF), peripheral blood mononuclear cells (PBMC) and serum were obtained from …

Artificial Intelligence-Powered Discovery Of Small Molecules Inhibiting Ctla-4 In Cancer, Navid Sobhani, Dana Rae Tardiel-Cyril, Dafei Chai, Daniele Generali, Jian-Rong Li, Jonathan Vazquez-Perez, Jing Ming Lim, Rachel Morris, Zaniqua N Bullock, Aram Davtyan, Chao Cheng, William K Decker, Yong Li

Faculty, Staff and Students Publications

BACKGROUND/OBJECTIVES: Checkpoint inhibitors, which generate durable responses in many cancer patients, have revolutionized cancer immunotherapy. However, their therapeutic efficacy is limited, and immune-related adverse events are severe, especially for monoclonal antibody treatment directed against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which plays a pivotal role in preventing autoimmunity and fostering anticancer immunity by interacting with the B7 proteins CD80 and CD86. Small molecules impairing the CTLA-4/CD80 interaction have been developed; however, they directly target CD80, not CTLA-4.

SUBJECTS/METHODS: In this study, we performed artificial intelligence (AI)-powered virtual screening of approximately ten million compounds to identify those targeting CTLA-4. We validated the …