Digital Commons Network^™

Periumbilical Perforating Pseudoxanthoma Elasticum, Ana L. Duarte-Summers, Anna Chen, Morgan E. Sussman-Mccrea, Shayan Waseh, Jason B. Lee, Sylvia Hsu

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Machine Learning Quantification Of High-Resolution Tissue Microarray (Tma) Image On Muc13 Ihc Analysis, Beibei Huang, Aiko Yamaguchi, Jianbo Wang, Shilpa Sharma, Zhiwen Liu, Henry Charles Manning

Research Symposium

Background High-resolution tissue microarray (TMA) technology allows prompt molecular profiling of multiple tissue specimens, making it ideal for analyzing candidate biomarkers quickly and effectively [1, 2]. Integrating TMA with digital pathology and machine learning enhances high-throughput, cost-effective studies, offering advanced image analysis and improved diagnostic accuracy. MUC13 (Mucin 13) is a transmembrane glycoprotein frequently overexpressed in colorectal cancer (CRC) [3]. MUC13 contributes to colonic tumorigenesis, progression and metastasis [4, 5], making it an attractive target for antibody-guided radiotheranostics in CRC. This study investigates the expression pattern of MUC13 and its association with patients' clinical characteristics in primary and metastatic CRC …

Utilidad De La Combinación De Los Biomarcadores: Procalcitonina, Proteína C Reactiva Y Volumen Plaquetario Medio En El Diagnóstico Temprano De Sepsis Neonatal [Usefulness Of The Combination Of Biomarkers: Procalcitonin, C-Reactive Protein And Mean Platelet Volume In The Early Diagnosis Of Neonatal Sepsis], Oscar Manuel Berlanga Bolado Jr, Patricia Rivera Vazquez, Arely Socorro Hernández García, Angelica Lizbeth Martinez Ortiz

Research Symposium

Introducción: La sepsis neonatal es una causa frecuente de morbilidad y mortalidad infantil. Se le ha definido como un síndrome clínico caracterizado por signos sistémicos de infección, acompañado de bacteriemia en el primer mes de vida. Por lo tanto, el diagnóstico temprano es fundamental.

Objetivo: Conocer la sensibilidad y especificidad de la combinación de biomarcadores séricos como procalcitonina, proteína C reactiva y volumen plaquetario medio en el diagnóstico temprano de sepsis neonatal.

Material y métodos: Estudio clínico, de tipo prospectivo, predictivo, observacional, analítico, longitudinal y conveniencia. Se analizaron los biomarcadores como PCT, PCR, VPM para diagnosticar sepsis neonatal. Se incluyeron …

Non-Dre Voided Urine Test To Diagnose Prostate Cancer: Updated Results, Patrick T. Gomella, Joon Yau Leong, Leonard G. Gomella, Vivek S. Tomar, Hector Teran, Edouard J. Trabulsi, Mathew L. Thakur

Department of Urology Faculty Papers

Background: The standard diagnostic approach for prostate cancer (PCa) diagnosis consists of serum prostate-specific antigen (PSA) testing, digital rectal examination (DRE) and image-guided targeted biopsies. Given the invasive nature, potential adverse events and costs associated with these techniques, alternative approaches have been investigated, specifically with serum and urine assays. The work presented here is intended to further validate a novel noninvasive optical technique for PCa detection, targeting the VPAC genomic receptors that are overexpressed on prostate cancer's malignant cells (MC), in non-DRE voided urine. Methods: Patients (N = 62) who had image-guided biopsy and histologically confirmed localized PCa, and …

Somatic Acupressure For The Management Of The Fatigue-Sleep Disturbance-Depression Symptom Cluster In Breast Cancer Survivors: A Study Protocol For A Phase Iii Randomised Controlled Trial, Mengyuan Li, Tao Wang, Xian Liang Liu, Ren Li Deng, Wai Hang Kwok, Li Qun Yao, Jing Yu Benjamin Tan

Research outputs 2022 to 2026

Introduction The fatigue-sleep disturbance-depression symptom cluster (FSDSC) is commonly experienced by breast cancer (BC) survivors, leading to a deteriorated quality of life (QoL). Somatic acupressure (SA) has been recommended as a promising non-pharmacological intervention for cancer-related fatigue (the core symptom of the FSDSC) in the guidelines, showing its encouraging role in relieving cancer-related sleep disorders, fatigue and depression. This phase III randomised controlled trial (RCT) is designed to evaluate the effects, safety and cost-effectiveness of SA for managing the FSDSC in BC survivors. Methods This phase III RCT will be a partial-blinded, sham-controlled, three-arm, parallel clinical trial, involving a 7-week …

Gain-Of-Function Chromatin Remodeling Activity Of Oncogenic Foxl2c134w Reprograms Glucocorticoid Receptor Occupancy To Drive Granulosa Cell Tumors, Thomas Welte, Veena K Vuttaradhi, Eleonora Y Khlebus, Allison Brodsky, Alejandra Flores Legarreta, Joseph Celestino, Reid T Powell, Clifford C Stephan, Nghi Nguyen, Jian Li, Shiro Takamatsu, Katherine Calzoncinth, Anil K Sood, David M Gershenson, P Andrew Futreal, Barrett Lawson, R Tyler Hillman

Faculty, Staff and Student Publications

Adult type ovarian granulosa cell tumors (AGCT) are rare malignancies with the near universal c.C402G (p.Cys134Trp) somatic mutation in FOXL2, a forkhead box family transcription factor important for ovarian function. Relapsed AGCT is incurable, but the mechanism of the unique FOXL2 mutation could confer therapeutic vulnerabilities. To identify FOXL2C134W-dependent pharmacologic synergies, we created and characterized endogenous FOXL2 isogenic AGCT cells and an AGCT tumoroid biobank. A drug screen identified that glucocorticoids promote FOXL2C134W-dependent AGCT growth. Epigenetic investigation revealed that the Cys134Trp mutation exposes latent DNA sequence-specific chromatin remodeling activity in FOXL2. FOXL2C134W-dependent chromatin remodeling activity redirected glucocorticoid receptor chromatin occupancy …

Antibody-Drug Conjugates Targeting The Egfr Ligand Epiregulin Elicit Robust Antitumor Activity In Colorectal Cancer, Joan Jacob, Yasuaki Anami, Peyton C High, Zhengdong Liang, Shraddha Subramanian, Sukhen C Ghosh, Solmaz Aghaamiri, Cara Guernsey-Biddle, Ha Tran, Julie Rowe, Ali Azhdarinia, Kyoji Tsuchikama, Kendra S Carmon

Faculty, Staff and Student Publications

As colorectal cancer remains a leading cause of cancer-related death, identifying therapeutic targets and approaches is essential to improve patient outcomes. The EGFR ligand epiregulin (EREG) is highly expressed in RAS wild-type (WT) and mutant colorectal cancer, with minimal expression in normal tissues, making it an attractive target for antibody-drug conjugate (ADC) development. In this study, we produced and purified an EREG mAb, H231, which had high specificity and affinity for human and mouse EREG. H231 also internalized to lysosomes, which is important for ADC payload release. ImmunoPET and ex vivo biodistribution studies showed significant tumor uptake of zirconium-89-labeled H231, …

Epigenetic Landscapes Of Aging In Breast Cancer Survivors: Unraveling The Impact Of Therapeutic Interventions-A Scoping Review, Nikita Nikita, Zhengyang Sun, Swapnil Sharma, Amy L Shaver, Victoria Seewaldt, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

Breast cancer therapies have dramatically improved survival rates, but their long-term effects, especially on aging survivors, need careful consideration. This review delves into how breast cancer treatments and aging intersect, focusing on the epigenetic changes triggered by chemotherapy, radiation, hormonal treatments, and targeted therapies. Treatments can speed up biological aging by altering DNA methylation, histone modifications, and chromatin remodeling, affecting gene expression without changing the DNA sequence itself. The review explains the double-edged sword effect of therapy-induced epigenetic modifications, which help fight cancer but also accelerate aging. Chemotherapy and targeted therapies, in particular, impact DNA methylation and histone modifications, promoting …

First-In-Human Clinical Trial Of A Small-Molecule Ebna1 Inhibitor, Vk-2019, In Patients With Epstein-Barr-Positive Nasopharyngeal Cancer, With Pharmacokinetic And Pharmacodynamic Studies, A Dimitrios Colevas, Zahra Talebi, Elizabeth Winters, Caroline Even, Victor Ho-Fun Lee, Maura L Gillison, Saad A Khan, Rong Lu, Benjamin A Pinsky, Samantha S Soldan, Olga Vladmirova, Paul M Lieberman, Troy E Messick

Faculty, Staff and Student Publications

Purpose: A first-in-human phase I study was conducted in patients with nasopharyngeal carcinoma to assess the safety and tolerability of VK-2019, a small-molecule selective inhibitor of Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1).

Patients and methods: Pharmacokinetic and pharmacodynamic studies were performed, including the measurement of EBV DNA plasma levels. Twenty-three patients received VK-2019 orally once daily at doses ranging from 60 to 1,800 mg using an accelerated titration design, with cohort expansion at 1,800 mg. EBV genome copy number and spatial transcriptomic analyses were conducted on biopsies collected from three patients at baseline and after treatment.

Results: VK-2019 was …

Ancestral Differences In Anticancer Treatment Efficacy And Their Underlying Genomic And Molecular Alterations, Mei Luo, Jingwen Yang, Alejandro A Schäffer, Chengxuan Chen, Yuan Liu, Yamei Chen, Chunru Lin, Lixia Diao, Yong Zang, Yanyan Lou, Huda Salman, Gordon B Mills, Eytan Ruppin, Leng Han

Faculty, Staff and Student Publications

Systematic multi-omics analysis revealed ancestry-dependent molecular alterations, but their impact on the efficacy of anti-cancer treatment is yet largely unknown. Here, we analyzed clinical trials from ClinicalTrials.gov and found that only 8,779/102,721 (8.5%) oncology clinical trials posted information on enrollment by race/ethnicity. The underrepresentation of non-White populations suggests that it remains challenging to determine differences in the efficacy of anti-tumor treatments among different racial groups. Through a comprehensive analysis of clinically actionable genes, imputed drug responses, and immune features, we identified potential differences in treatment response to targeted, chemo and immunotherapies between different ancestral populations. Further analysis of multiple independent …

Pleural Effusion: Shedding Light On Pleural Disease Beyond Infection And Malignancy, William C Harding, Abdul R Halawa, Mazen M Aiche, Bilal Zafar, Hyeon-Ju R Ali, Lara Bashoura, Saadia A Faiz

Faculty, Staff and Student Publications

Background and Objectives: Non-malignant pleural effusions (NMPEs) are the most frequently encountered pleural disease. They arise from various non-malignant, non-infectious clinical conditions, including cardiac, renal, and hepatic organ dysfunction. Despite their wide prevalence, there is a lack of literature for NMPE. This publication aims to provide an updated overview of the causes, diagnostic strategies, and management options for NMPE.

Materials and Methods: This review synthesizes findings from studies published on NMPE, focusing on the presentation, diagnosis (such as imaging and pleural fluid analysis), and management strategies. Studies were selected based on relevance and were analyzed to provide a comprehensive summary …

Accumulation Of Cd38 In Hybrid Epithelial/Mesenchymal Cells Promotes Immune Remodeling And Metastasis In Breast Cancer, Tanvi H Visal, Recep Bayraktar, Petra Den Hollander, Michael A Attathikhun, Tieling Zhou, Jing Wang, Li Shen, Corina-Elena Minciuna, Meng Chen, Elizve Barrientos-Toro, Harsh Batra, Maria Gabriela Raso, Fei Yang, Edwin R Parra, Aysegul A Sahin, George A Calin, Sendurai A Mani

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer. The epithelial-to-mesenchymal transition is a nonbinary process in the metastatic cascade that generates tumor cells with both epithelial and mesenchymal traits known as hybrid EM cells. Recent studies have elucidated the enhanced metastatic potential of cancers featuring the hybrid EM phenotype, highlighting the need to uncover molecular drivers and targetable vulnerabilities of the hybrid EM state. Here, we discovered that hybrid EM breast tumors are enriched in CD38, an immunosuppressive molecule associated with worse clinical outcomes in liquid malignancies. Altering CD38 expression in tumor cell impacted migratory, invasive, …

Recovery Potential In Patients After Cardiac Arrest Who Die After Limitations Or Withdrawal Of Life Support, Jonathan Elmer, Patrick J Coppler, Cecelia Ratay, Alexis Steinberg, Sara Difiore-Sprouse, Nicholas Case, Baruch Fischhoff, Maria De-Arteaga, Alain Cariou, Alejandro A Rabinstein, Andrea O Rossetti, Ankur A Doshi, Bradley J Molyneaux, Cameron Dezfulian, Carolina B Maciel, Christoph Leithner, Cindy H Hsu, Claudio Sandroni, David M Greer, David B Seder, Francis X Guyette, Fabio Silvio Taccone, Hiromichi Naito, Jasmeet Soar, Jean-Baptiste Lascarrou, Jerry P Nolan, Karen G Hirsch, Katherine M Berg, Marion Moseby-Knappe, Markus B Skrifvars, Michael C Kurz, Min Jung Kathy Chae, Mypinder S Sekhon, Nicholas J Johnson, Pedro Kurtz, Romergryko G Geocadin, Sachin Agarwal, Teresa L May, Theresa M Olasveengen, Clifton W Callaway, Optimizing Recovery Prediction After Cardiac Arrest (Orca) Study Group

Faculty, Staff and Students Publications

Importance: Understanding the relationship between patients' clinical characteristics and outcomes is fundamental to medicine. When critically ill patients die after withdrawal of life-sustaining therapy (WLST), the inability to observe the potential for recovery with continued aggressive care could bias future clinical decisions and research.

Objective: To quantify the frequency with which experts consider patients who died after WLST following resuscitated cardiac arrest to have had recovery potential if life-sustaining therapy had been continued.

Design, setting, and participants: This prospective cohort study included comatose adult patients (aged ≥18 years) treated following resuscitation from cardiac arrest at a single academic medical center …

Comparative Analysis Of Oxygenators And Anticoagulation Strategies In Neonatal And Pediatric Ecmo Patients, Debra E. Newton, Johanna I. Orrick

Presentations

Background: Due to supply chain challenges, our institution transitioned from Pediatric Quadrox oxygenators to Nautilus oxygenators for neonatal and pediatric extracorporeal membrane oxygenation (ECMO) patients. During this transition, variations in anticoagulation results were observed with bivalirudin, the first-line anticoagulant, in patients weighing less than 8 kg. This study aimed to evaluate heparin as an alternative anticoagulant in this patient population utilizing Nautilus oxygenators. Methods: A retrospective analysis was conducted on 29 neonatal and pediatric ECMO patients (weight range: 2.3–6.1 kg). Patients were divided into three groups based on oxygenator and anticoagulant type: · Group 1: Quadrox with bivalirudin (n=11) · …

Neurocognitive Gains Among Ugandan Children With Sickle Cell Anemia On Hydroxyurea: 18-Month Trial Interim Results, Shubaya Kasule Naggayi, Dennis Kalibbala, Vincent Mboizi, John M. Ssenkusu, Zhezhen Jin, Caterina Rosano, Deogratias Munube, Bill Wambaka, Ruth Namazzi, Robert Opoka

Paediatrics and Child Health, East Africa

Children with sickle cell anemia (SCA) frequently develop progressive neurocognitive impairment. We aimed to determine effects of hydroxyurea therapy on neurocognitive function in Ugandan children with SCA by comparing levels at enrollment to a planned 18-month interim assessment. Ugandan children (N=264) ages 3-9 years were enrolled from a SCA clinic and treated in a 30-month singlearm open-label trial with escalation to maximum tolerated dose (MTD). Primary outcome was the effects of hydroxyurea on cognition, attention and executive function, along with transcranial doppler ultrasound (TCD) blood flow velocity. Sibling controls (N=110) without SCA underwent neurocognitive testing in parallel to establish age-normalized …

A Preliminary Report Of The Carotenoid Assessment In Adults 50 Years Of Age And Older In Louisiana, Mary-Catherine Feazell

Master's Theses

Fruits and vegetables are at the core of a healthy, balanced diet. They assist in preventing the development of chronic diseases such as hypertension, diabetes, cardiovascular disease, and cancer (Fadnes, et al., 2022). Aging is a natural biological process followed by disease, cognitive impairment, and a natural decline of the body’s ability to perform at its best. The older adult population is currently the fastest-growing population globally (El-Shebiney et al., 2022). Vitamin A is crucial for several parts of the body to function correctly. Despite the positive effects of Vitamin A on the body, the recommended dietary intake is not …

Detection Rate And Patterns Of Biochemical Recurrence Of Prostate Cancer Using 18f-Psma-1007 Pet/Ct At A Tertiary Teaching Hospital In Sub-Saharan Africa., Lynet Wairimu Barasa

Master of Medicine in Imaging and Diagnostic Radiology

Background: Rising PSA levels following local therapy with curative intent are seen in about one third of men previously treated for prostate cancer, indicative of disease recurrence. This is usually not detectable through imaging modalities like computed tomography (CT) or magnetic resonance imaging (MRI). Several studies show high detection rates of recurrence with 18F-PSMA-1007 PET/CT, one of the novel PET imaging modalities for prostate cancer. No studies, however, have been done to show the patterns of recurrence in the Sub-Saharan African population in whom prostate cancer is known to occur earlier and be more aggressive. Biochemical recurrence almost always …

Comparison Of Positivity Rate Of Dual Phase Sestamibi Versus Dual Tracer Pertechnetate/Sestamibi In Identification Of Parathyroid Adenomas., Naomi Chirindo Chikuro

Master of Medicine in Imaging and Diagnostic Radiology

Background 

Parathyroid adenomas are the commonest cause of primary hyperparathyroidism. The primary mode of treatment is surgical excision which can only be achieved with pre surgical localization of adenomas. Ultrasound, CT and MRI can be used but the most sensitive and specific imaging modality is parathyroid scintigraphy with use of Sestamibi labelled with technetium 99 metastable radionuclide. A few studies have been done comparing dual phase, dual tracer and combined dual phase/tracer protocols with an apparent lack of consensus on which is superior.

Objectives

This study aimed to compare the positivity rates of the mentioned parathyroid scintigraphy protocols and identify …

The Prevalence And The Predictors Of Diabetes Distress In Patients With Type 2 Diabetes Attending Diabetes Clinics At A Tertiary Private Hospital In Nairobi, Kenya., Soulthy Azamkhan Mohamed

Master of Medicine in Family Medicine

Background Diabetes distress encompasses a spectrum of emotional and psychological challenges faced by individuals managing diabetes, including anxiety, stress, depression, frustration, and feelings of helplessness. This distress arises from the constant demands of monitoring blood sugar levels, managing medications, adhering to dietary restrictions, engaging in regular physical activity, and navigating potential complications. Social and emotional factors such as stigma, discrimination, and concerns about future health further contribute to this burden. Factors like fear of hypoglycemia, financial strain, fluctuating blood sugar levels, anxiety about complications, and impacts on personal relationships exacerbate diabetes distress. Left unaddressed, diabetes distress can lead to poor …

Comparison Of The Use Of Therapeutic Plasma Exchange To Intravenous Immunoglobulin For Autoimmune Neurological Conditions At A Tertiary Hospital In Kenya., Swafiya Salim Busaidy

Master of Medicine in Internal Medicine

Background 

Plasma exchange (Barth et al.) and Intravenous Immunoglobulin (Barth et al.) have emerged as favored therapeutic options for autoimmune neurological conditions. Neurological conditions cause high morbidity and mortality in the sub-Saharan region. The utilization of these treatment options in Sub-Saharan Africa remains relatively unknown. We can determine the most efficient treatments with minimal cost implications by comparing the two treatment modalities in our setup.

Methods 

This retrospective descriptive chart review took place at Aga Khan University Hospital. It encompassed all patients admitted between 1st January 2011 and 31st December 2023 who had a neurological condition that necessitated treatment with …

Diagnostic Accuracy Of 18f-Fdg Pet-Ct Compared To Ultrasound In Identification Of Metastatic Axillary Lymph Nodes In Newly Diagnosed Breast Cancer Patients., Sarah Muthii Kibe

Master of Medicine in Imaging and Diagnostic Radiology

Background: Determination of axillary lymph node metastasis is a crucial part of breast cancer staging as it is the most important marker of overall recurrence and survival. Although axillary ultrasound (AUS) is the imaging reference standard, it has a wide range of sensitivity necessitating evaluation of other imaging modalities that may be used as adjuncts.18F-FDG PET-CT is recommended for use in metastatic and recurrent breast cancer with infrequent use in early disease due to its low spatial resolution for small axillary lymph nodes. The aim of this it study is to evaluate the diagnostic accuracy of axillary ultrasound compared …

Insulin Receptor Responsiveness Governs Tgfβ-Induced Hepatic Stellate Cell Activation: Insulin Resistance Instigates Liver Fibrosis, Wang-Hsin Lee, Evelyn A. Bates, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Cheavar A. Blair, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

The insulin receptor (INSR) has been shown to be hyperactive in hepatic stellate cells (HSCs) in humans and rodents with liver fibrosis. To explore HSC cellular mechanisms that INSR regulates during pro-fibrotic stimulation, we used CRISPR-Cas9 technology. We knocked out a portion of the INSR gene in human LX2 HSC cells (INSRe5- 8 KO) that regulates insulin responsiveness but not the insulin-like growth factor (IGF) or transforming growth factor-β (TGFβ) signaling. The INSRe5- 8 KO HSCs had significantly higher cell growth, BrdU incorporation, and lower TP53 expression that suppresses growth, and they also exhibited increased migration compared to the Scramble …

Exploring Oxylipins In Host–Microbe Interactions And Their Impact On Infection And Immunity, Robert J. Neff, Christopher D. Radka

Markey Cancer Center Faculty Publications

Plasma lipids are essential components of biological systems, transported through interactions with proteins to maintain cellular functions. These lipids exist in various forms, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenol lipids, derived from dietary intake, adipose tissue, and biosynthesis. While the association between certain fatty acids and cardiovascular diseases has been widely recognized, polyunsaturated fatty acids (PUFAs) exhibit cardioprotective effects, reducing risks of arrhythmias and heart-related mortality. This is due to their role in the production of eicosanoids, which modulate inflammation. Chronic inflammation, particularly in obesity, is significantly influenced by fatty acids, with saturated fatty acids promoting …

Predicting The Pathway Involvement Of Compounds Annotated In The Reactome Knowledgebase, Erik D. Huckvale, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

Background/Objectives: Pathway annotations of non-macromolecular (relatively small) biomolecules facilitate biological and biomedical interpretation of metabolomics datasets. However, low pathway annotation levels of detected biomolecules hinder this type of interpretation. Thus, predicting the pathway involvement of detected but unannotated biomolecules has a high potential to improve metabolomics data analysis and omics integration. Past publications have only made use of the Kyoto Encyclopedia of Genes and Genomes-derived datasets to develop machine learning models to predict pathway involvement. However, to our knowledge, the Reactome knowledgebase has not been utilized to develop these types of predictive models.

Methods: We created a dataset ready for …

Characterization, Performance, And Toxicological Assessment Of Polysulfone-Sulfonated Polyether Ether Ketone Membranes For Water Separation Applications, Muhammad Usman Yousaf, Lucca Madeo Cortarelli, Nerissa I. Jebet, Jason M. Unrine, Nirupam Aich, Olga V. Tsyusko, Isabel C. Escobar

Markey Cancer Center Faculty Publications

The removal of small molecular weight charged compounds from aqueous solutions using membrane remains a challenge. In this study, polysulfone (PSf)- and sulfonated polyether ether ketone (SPEEK)-based membranes were fabricated via non- solvent induced phase separation process (NIPS) using N-Methyl-2-Pyrrolidone (NMP) as solvent and water as non-solvent. Membranes were characterized structurally and morphologically, followed by toxicity assessment conducted before and after filtration, both with and without annealing at various pH values to evaluate potential leaching of trapped solvent from the membrane pores. Additionally, membrane performance was characterized using binary mixtures of cationic and anionic dyes. The results demonstrated selective filtration …

Computational Design And In Vitro And In Vivo Characterization Of An Apoe-Based Synthetic High-Density Lipoprotein For Sepsis Therapy, Ling Guo, Yaxia Yuan, Fang Zhang, Chang-Guo Zhan, Xiangan Li

Markey Cancer Center Faculty Publications

Introduction: Septic patients have low levels of high-density lipoproteins (HDLs), which is a risk factor. Replenishing HDLs with synthetic HDLs (sHDLs) has shown promise as a therapy for sepsis. This study aimed to develop a computational approach to design and test new types of sHDLs for sepsis treatment. Methods: We used a three-step computational approach to design sHDL nanoparticles based on the structure of HDLs and their binding to endotoxins. We tested the efficacy of these sHDLs in two sepsis mouse models—cecal ligation and puncture (CLP)-induced and P. aeruginosa-induced sepsis models—and assessed their impact on inflammatory signaling in cells. Results: …

Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Prostate cancer (PCa) is one of the leading causes of death among men worldwide. Treatments targeting the androgen receptor pathway remain the standard therapy for PCa patients. Enzalutamide (ENZ), a second-generation androgen receptor inhibitor, was developed to treat castration-resistant prostate cancer. However, while patients initially respond to ENZ, drug resistance typically develops within a few months. Artesunate (ART), a semisynthetic derivative of the Artemisinin plant, is approved for antimalaria treatment. In this study, we conducted an FDA-approved drug screening and identified ART as a potential candidate for overcoming ENZ resistance in PCa. Mechanistically, ART induces the degradation of c-Myc, enhancing …

Case Series On Prosthetic Valve Thromboses Treated With Intravenous Thrombolysis At A Tertiary Teaching Hospital In Nairobi – Kenya, John Odhiambo, Salim Abdallah, Mzee Ngunga

Internal Medicine, East Africa

Valvular heart disease is a significant global health issue, particularly in developing countries where Rheumatic Heart Disease (RHD) is the leading cause. Valve replacement surgeries have increased, with mechanical prostheses favored for their durability. However, thromboembolism remains a critical complication post-surgery, with prosthetic valve thrombosis rates of 0.03% for bioprosthetic valves and between 0.5% to 8% for mechanical valves in the aortic and mitral position. This report details two cases of heart failure following valve replacement due to rheumatic heart disease. The first case involves a 42-year-old female who developed prosthetic valve thrombosis after discontinuing warfarin for menorrhagia postmechanical mitral …

Experiences Among Parents Caring For Children With Juvenile Idiopathic Arthritis At A Tertiary Referral Hospital In Kenya, Hassan Silim, Susan Wamithi, Roselyter Riang’A, Angela Migowa

Paediatrics and Child Health, East Africa

Background: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. Despite the availability of effective treatment strategies such as disease-modifying antirheumatic drugs (DMARDs), JIA is reported to have a negative impact on the quality of life of the patients and their caregivers. Ascertaining the perceptions of the parents will help facilitate more effective management strategies and improve outcomes for these patients. This study aimed to ascertain parental experiences and perceptions of caring for children with juvenile idiopathic arthritis (JIA).

Methods: This was a single-center facility-based qualitative study. An in-depth interview guide was used to collect …

Functional Investigation Of A Putative Calcium-Binding Site Involved In The Inhibition Of Inositol 1,4, 5-Trisphosphate Receptor Activity, Vikas Arige, Larry E Wagner, Sundeep Malik, Mariah R Baker, Guizhen Fan, Irina I Serysheva, David I Yule

Faculty, Staff and Student Publications

The regulation of inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) activity is thought to define the spatiotemporal patterns of Ca2+ signals necessary for the appropriate activation of downstream effectors. The binding of both IP3 and Ca2+ is obligatory for IP3R channel opening. Ca2+ however regulates IP3R activity in a biphasic manner. Ca2+ binding to a high-affinity pocket formed by the third armadillo repeat domain and linker domain promotes IP3R channel opening without altering the Ca2+ dependency for channel inactivation. These data suggest that a distinct low-affinity Ca2+-binding site is responsible for the reduction in IP3R activity at higher [Ca2+]. We mutated a …