Digital Commons Network^™

Immune Thrombocytopenic Purpura Association With Epstein-Barr Virus, Amer Aldamouk, Bachr Masri, Ali Khan, Pulkita Uppal

Graduate Medical Education Research Journal

Immune thrombocytopenia (ITP), also referred to as idiopathic thrombocytopenic purpura, is an acquired form of thrombocytopenia caused by antibodies directed against platelet glycoproteins, particularly anti-GpIIb/IIIa antibodies. Epstein-Barr virus (EBV), a herpes virus infecting a large majority of the population before adulthood, has been implicated in various immune-mediated disorders, including ITP. In this report, we present a case of a young adult female with a history of thrombocytopenia who was found to have severe thrombocytopenia attributed to chronic EBV infection. Despite initial treatment with corticosteroids and intravenous immunoglobulin (IVIG), the patient's condition necessitated second-line therapies, including rituximab and thrombopoietin receptor agonists. …

Cars And Trucks: Driving A Paradigm Shift In Hematologic Malignancies, Christine Charek, Tia Solh

Lynchburg Journal of Medical Science

Hematologic malignancies account for a significant number of annual cancer diagnoses and deaths across the globe. Historically, the prognosis for relapsed and/or refractory disease after standard therapies, such as chemotherapy and/or radiation, was poor. Chimeric antigen receptor (CAR) T-cell therapy offers an additional treatment option. While promising, this type of immunotherapy also comes with potentially severe side effects, toxicities, and limitations. A better understanding of the development, administration, and management of patients undergoing treatment can provide the general clinician with the knowledge to assist within a multidisciplinary team to ultimately improve patient outcomes.

Binge Eating Disorder: A Clinical Review, Michell Mcdiffett Mshs, Pa-C

Lynchburg Journal of Medical Science

Binge eating disorder (BED) is the most common eating disorder (ED) in the United States (U.S.) and is characterized by recurrent episodes of eating a larger than normal amount of food in a discrete period of time and includes a sense of loss of control over food intake. BED is often comorbid with serious somatic and psychiatric disorders and is associated with reduced quality of life and excess mortality. Some consider BED a public health concern due to frequent co-occurrence with obesity and worse outcomes in those populations. The diagnosis is often delayed due to shame and underreporting of symptoms …

Self-Powered Rapid Antigen-Specific T-Cell Response Assay For Mycobacterium Tuberculosis Infections, Bo Ning, Sutapa Chandra, Yongchun Pan, Riti Sharan, Ngan Ha, Sanjay Singh, Alexandra Portillo Varela, Lin Li, Qingli Wu, Alexander Kay, Gugu P Maphalala, Clement Adu-Gyamfi, Santiago Carrero Longlax, Anna M Mandalakas, Smriti Mehra, Christopher J Lyon, Edward A Graviss, Andrew R Dinardo, Tony Hu

Faculty, Staff and Students Publications

Interferon-gamma release assays (IGRAs) that evaluate an individual’s T-cell activation response to Mycobacterium tuberculosis (M.tb)-specific peptides serve an important role in diagnosing tuberculosis (TB). However, there are substantial challenges to the use of IGRAs in resource-limited settings. Further, IGRA diagnostic performance can also be compromised in anergic individuals. Here we describe a microfluidic chip-based antigen-specific T-cell response assay (ASTRA) that automates the detection of M.tb-specific T-cell activation responses to facilitate screening for latent M.tb infection and TB. We observe that ASTRA demonstrates high specificity for M.tb infection in independent patient cohorts. Compared with IGRA, ASTRA shows greater …

Psoriasis Genomics: A Review, Magna Hutasuhut, Windy Keumala Budianti, Wresti Indriatmi, Mirawati Setyorini

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Psoriasis is a dermatological condition influenced by genetic and epigenetic factors, environmental triggers, as well as immune responses. Genomics refers to the study of individual genes (genomes) and their interactions with environmental influences. In the context of psoriasis genomics, the interplay between genetic predisposition and environmental factors contributes to the manifestation and variations of the disease. With advancements in molecular genotyping technology and genome-wide association studies (GWASs), researchers have identified 50 genetic markers linked to psoriasis.

Discussion: Several genetic loci associated with psoriasis have been identified, including PSORS 1-15. The genetics of psoriasis is also linked to its onset, …

Effectiveness Of 5% Channa Striata Extract Gel In Wound Healing: A Double-Blind Randomized Controlled Trial, Yulia Farida Yahya, Yuli Kurniawati, Erial Bahar, Theresia Lumban Toruan, Soenarto Kartowigno, Muhammad Izazi Hari Purwoko, Tiar Marina Octyvani

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Snakehead fish (Channa striata, CS) has traditionally been used in Indonesia as a nutrient to promote wound healing. It contains protein highly similar to human protein, which may be involved in wound healing via biological pathways. We aim to determine the effectiveness of the topical 5% CS extract gel in promoting wound healing.

Methods: A double-blind, placebo-controlled randomized clinical trial was conducted from June to August 2022 at the Department of Dermatology, Venereology, and Aesthetics of Dr. Mohammad Hoesin Hospital. We allocated 32 post-skin surgery participants with grade I acute superficial wounds on the face, neck, …

Topical Application Of Exosomes In A Patient With Acne Conglobata: A Case Report, Theressia Handayani, Stefani Luziani

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Acne conglobata (AC) is a rare and severe acne characterized by interconnected nodules, cysts, and abscesses. Mesenchymal stem cell-derived exosomes (MSC-exosomes) have immunosuppressive properties that alleviate inflammation and immunological reactions. We present a case of AC in a patient who received topical administration of exosomes.

Case Illustration: A 20-year-old male was diagnosed with AC, presenting as inflammatory papules and cysts covered with yellowish crusts that had been present for five months. Exosomes (ASCE+®, Seoul, South Korea) were topically administered at a dose of 5 mL, applied evenly to the face. The patient underwent three treatment sessions, with a …

Serial Excision Of A Nevus Sebaceous Of Jadassohn On The Scalp, Belladikna Brillianty Sugiatno, Arif Widiatmoko, Adinda Amalia Dani, Diah Prabawati Retnani

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Nevus sebaceous of Jadassohn (NSJ) is a non-hereditary hamartoma of the skin’s adnexal structures. The incidence of NSJ in newborns is estimated at 0.1-0.3% with no gender or ethnic propensity. Surgical excision is a common treatment for NSJ, although there is no definite consensus on the timing or recommendations for the removal. This article aims to present the advantages of serial excision therapy in a case of NSJ.

Case Illustration: A 14-year-old male presented with a complaint of a bump on the scalp since birth, which had progressively enlarged during puberty. Dermatological examination revealed a well-demarcated, yellow-orange …

Validity And Reliability Of The Indonesian Version Of Nordic Occupational Skin Questionnaire 2002 (Nosq-2002), Listya Paramita, Fajar Waskito, Dikky Prawiratama, Niken Indrastuti, Tuntas Rayinda, Sri Awalia Febriana

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Epidemiological data on occupational hand eczema in Indonesia is still limited, partly because there are no valid and reliable instruments in the Indonesian language as a means of survey. This study aims to translate the Nordic Occupational Skin Questionnaire 2002 (NOSQ-2002) into the Indonesian language and assess the validity and reliability of the Indonesian NOSQ-2002 as an instrument for epidemiological surveys and screening of occupational hand eczema.

Methods: The original English version of NOSQ-2002 was translated into the Indonesian language following the standard procedure of translation. The Indonesian NOSQ-2002 version, which had been collectively approved, was subsequently completed by …

Combination Of 1064 Nm Qs Nd:Yag Photoacoustic Technology And Exosome For Facial Rejuvenation, Stanley Setiawan, Samuel Septrian Putranto, Angela Maria Linata, Stephanie Salim, Novia Sari Andriati Mertosono, Shelly Nobel, Flora Asri Wardianti, Ita Anggraini, Zulaikha Rizqina Rahmawati

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Facial rejuvenation has become a global trend in cosmetic and aesthetic dermatology to restore youthful skin. The combination of 1064 nm Q-Switched Neodymium:Yttrium Aluminum Garnet (QS Nd:YAG) laser and exosomes as a facial rejuvenation procedure restores youthfulness by increasing collagen and elastin.

Case Illustration: This case series evaluated the effectiveness of 1064 nm QS Nd:YAG laser with and without human amniotic fluid stem cell-derived exosomes (hAFSC-exo) for facial rejuvenation in six adults aged 24–39 years with Fitzpatrick skin types III-IV. Participants were randomized to receive either laser treatment alone or combined with intradermal hAFSC-exo injections every two weeks for …

Skin Rejuvenation With Microbotox: A Review, Ifen Ayu Malinda, Nelva Karmila Jusuf

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Skin aging is characterized by a gradual loss of tissue and organ function. Skin aging can be classified into two types: intrinsic aging, associated with the aging process itself, and extrinsic aging, which is linked to external factors. Microbotox—an intradermal injection of diluted botulinum toxin—has emerged as a promising technique for rejuvenation by improving skin texture, pore size, and sebum control. This review aims to provide a comprehensive overview of the microbotox technique in the context of skin aging, emphasizing its mechanisms, indications, and clinical outcomes.

Discussion: In Asia, intradermal injection of botulinum toxin or microbotox has been widely …

Mis-Splicing-Derived Neoantigens And Cognate Tcrs In Splicing Factor Mutant Leukemias, Won Jun Kim, Edie I Crosse, Emma De Neef, Inaki Etxeberria, Erich Y Sabio, Eric Wang, Jan Philipp Bewersdorf, Kuan-Ting Lin, Sydney X Lu, Andrea Belleville, Nina Fox, Cynthia Castro, Pu Zhang, Takeshi Fujino, Jennifer Lewis, Jahan Rahman, Beatrice Zhang, Jacob H Winick, Alexander M Lewis, Robert F Stanley, Susan Dewolf, Brigita Meškauskaitė Urben, Meril Takizawa, Tobias Krause, Henrik Molina, Ronan Chaligne, Priya Koppikar, Jeffrey Molldrem, Mathieu Gigoux, Taha Merghoub, Anthony Daniyan, Smita S Chandran, Benjamin D Greenbaum, Christopher A Klebanoff, Robert K Bradley, Omar Abdel-Wahab

Faculty, Staff and Student Publications

Mutations in RNA splicing factors are prevalent across cancers and generate recurrently mis-spliced mRNA isoforms. Here we identified a series of bona fide neoantigens translated from highly stereotyped splicing alterations promoted by neomorphic, leukemia-associated somatic splicing machinery mutations. We utilized feature-barcoded peptide-MHC dextramers to isolate neoantigen-reactive T cell receptors (TCRs) from healthy donors, patients with active myeloid malignancy, and following curative allogeneic stem cell transplant. Neoantigen-reactive CD8+ T cells were present in the blood of patients with active cancer and had a distinct phenotype from virus-reactive T cells with evidence of impaired cytotoxic function. T cells engineered with TCRs recognizing …

Encorafenib, Cetuximab, And Mfolfox6 In Braf-Mutated Colorectal Cancer, Elena Elez, Takayuki Yoshino, Lin Shen, Sara Lonardi, Eric Van Cutsem, Cathy Eng, Tae Won Kim, Harpreet Singh Wasan, Jayesh Desai, Fortunato Ciardiello, Rona Yaeger, Timothy S Maughan, Van K Morris, Christina Wu, Tiziana Usari, Robert Laliberte, Samuel S Dychter, Xiaosong Zhang, Josep Tabernero, Scott Kopetz, Breakwater Trial Investigators

Faculty, Staff and Student Publications

Background: First-line treatment with encorafenib plus cetuximab (EC) with or without chemotherapy (oxaliplatin, leucovorin, and fluorouracil [mFOLFOX6]) for BRAF V600E-mutated metastatic colorectal cancer, an aggressive subtype with a poor prognosis, was compared with standard care (chemotherapy with or without bevacizumab) in an open-label, phase 3 trial, which showed significance regarding one of the two primary end points, objective response according to blinded independent central review (odds ratio for EC+mFOLFOX6 vs. standard care, 2.44; one-sided P< 0.001). This result led to accelerated Food and Drug Administration approval of this investigational combination therapy for BRAF V600E-mutated metastatic colorectal cancer, including as first-line therapy. Data on progression-free survival (the second primary end point) and an updated interim analysis of overall …

Contrast Enhancement, G-Cimp Subtype, And Cdkn2a/B Homozygous Deletion In Idh-Mutant Astrocytoma, Mehak Majid Khan, Wenyin Shi, Iyad Alnahhas

Department of Neurology Faculty Papers

No abstract provided.

The Epidemiology Of Sports And Recreation Related Toe Fractures In The United States, Dogerno Norceide, Gabriel I. Onor, Oluwatomi Akingbola, William Justice, Nana F. Amponsah, Abimbola Okulaja, Ifeanyichukwu Onor, Michael Okoronkwo, Chibuikem Nwizu, David Pedowitz, Md

Rothman Institute Papers

BACKGROUND: Fractures of the toes are among the most frequently diagnosed lower extremity fractures. In sports, toe fractures may present after diverse mechanisms of injury, varying severity, and varying implications for management. This study aimed to discern trends in toe fractures presenting to US emergency departments (EDs) particularly in association with sports and recreational activities. An additional aim of the study was to identify if rates of toe fracture presentation significantly decreased during the year 2020 at the height of the COVID-19 pandemic.

METHODS: We queried the National Electronic Injury Surveillance System (NEISS) database to identify toe fractures presented to …

Secondary Youth-Level Mechanisms Of Change In Parent Training For Anxious Youth, Jacey L Anderberg, Kelly Barry, Blake M Upshaw, Katie H Mangen, Samuel D Spencer, Andrew G Guzick, Daphne M Ayton, Amanda D Palo, Abigail E Candelari, Eric A Storch

Faculty, Staff and Students Publications

Background: Parent-focused treatments are a promising approach for addressing youth anxiety outside of traditional therapist-delivered modalities. Supportive Parenting for Anxious Childhood Emotions (SPACE) has preliminarily demonstrated efficacy for reducing family accommodation (FA), a key treatment outcome for youth anxiety.

Objective: Since the mechanisms of SPACE remain relatively understudied, we examined youth-reported distress tolerance (DT), anxiety sensitivity (AS), and negative automatic thoughts as candidate mechanisms of SPACE using data from a previously conducted clinical trial.

Methods: In a sample of N = 68 youth (M age = 10.2; 52% male; 62% White), we examined: (a) associations among candidate mechanisms and …

Impact Of Optimal Medical Therapy In Heart Failure Certification For Hospitalists On Guideline-Directed Medical Therapy Utilization, Farhan Ishaq, Duc T Nguyen, Edward A Graviss, Ebun Ebunlomo, Arvind Bhimaraj, Nadia Fida

Faculty, Staff and Students Publications

Background: Significant gaps in guideline-directed medical therapy (GDMT) for heart failure (HF) stem from shortages of cardiologists and advanced HF providers, as well as a lack of optimal HF management knowledge among hospitalists. This study compared the impact of optimal medical therapy in HF (OMT-HF) certification on GDMT implementation and patient outcomes between an intervention group (IG) of hospitalists and a standard-of-care comparison group (SOC-CG).

Aim: To evaluate if OMT-HF has a difference in GDMT and patients in outcomes between IG and SOC-CG.

Methods: This study was implemented from November 2022 to May 2023. Hospitalized cardiology patients with HF and …

Plane Xanthoma, Connor A. Sheehan, Theresa N. Tran, Jason B. Lee, Jeffrey Y. Liu, Sylvia Hsu

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

A Conditional Point Cloud Diffusion Model For Deformable Liver Motion Tracking Via A Single Arbitrarily-Angled X-Ray Projection, Jiacheng Xie, Hua-Chieh Shao, Yunxiang Li, Shunyu Yan, Chenyang Shen, Jing Wang, You Zhang

Faculty, Staff and Student Publications

Objective. Deformable liver motion tracking using a single x-ray projection enables real-time motion monitoring and treatment intervention. We introduce a conditional point cloud diffusion (PCD) model-based framework for accurate and robust liver motion tracking from arbitrarily angled single x-ray projections. Approach. We propose a conditional PCD model for liver motion tracking (PCD-Liver), which estimates volumetric liver motion by solving deformable vector fields (DVFs) of a prior liver surface point cloud, based on a single x-ray image. It is a patient-specific model of two main components: a rigid alignment model to estimate the liver’s overall shifts, and a conditional PCD …

Multimodal Imaging Directs Decision Making In Intraseptal L-Aaoca, Joseph Burns, Lindsay F Eilers, Stephen J Dolgner, Edward J Hickey, Silvana Molossi

Faculty, Staff and Students Publications

Background: Congenital coronary artery abnormalities represent an uncommon class of congenital heart disease with an associated risk of sudden cardiac death. There is a paucity of data for the evaluation and management of affected patients with an intraseptal course.

Case summary: A 27-year-old woman was found to have a single coronary trunk arising from the right sinus with a 2.7 cm intraseptal course of the left main coronary artery. She underwent stress cardiac magnetic resonance and catheterization, to assess for inducible ischemia before surgical repair with transconal unroofing. Her recovery was uneventful, and she remains free of symptoms.

Discussion: Management …

Mapping Mave Data For Use In Human Genomics Applications, Jeremy A Arbesfeld, Estelle Y Da, James S Stevenson, Kori Kuzma, Anika Paul, Tierra Farris, Benjamin J Capodanno, Sally B Grindstaff, Kevin Riehle, Nuno Saraiva-Agostinho, Jordan F Safer, Jonathan Casper, Maximilian Haeussler, Aleksandar Milosavljevic, Julia Foreman, Helen V Firth, Sarah E Hunt, Sumaiya Iqbal, Melissa S Cline, Alan F Rubin, Alex H Wagner

Faculty, Staff and Students Publications

Background: Experimental data from functional assays have a critical role in interpreting the impact of genetic variants. Assay data must be unambiguously mapped to a reference genome to make it accessible, but it is often reported relative to assay-specific sequences, complicating downstream use and integration of variant data across resources. To make multiplexed assays of variant effect (MAVE) data more broadly available to the research and clinical communities, the Atlas of Variant Effects Alliance mapped MAVE data from the MaveDB community database to human reference sequences, creating an extensive set of machine-readable homology mappings that are incorporated into widely used …

The Carsr Two-Component System Directly Controls Radd Expression As A Global Regulator That Senses Bacterial Coaggregation In Fusobacterium Nucleatum, Bibek G C, Chenggang Wu

Faculty, Staff and Student Publications

Two-component systems (TCS) enable bacteria to sense and respond to environmental signals, facilitating rapid adaptation. Fusobacterium nucleatum, a key oral pathobiont, employs the CarSR TCS to modulate coaggregation with various gram-positive partners by regulating the expression of radD, encoding a surface adhesion protein, as revealed by RNA-Seq analysis. However, the direct regulation of the radD-containing operon (radABCD) by the response regulator CarR, the broader CarR regulon, and the signals sensed by this system remain unclear. In this study, chromatin immunoprecipitation followed by high-throughput DNA sequencing (ChIP-seq) identified approximately 161 CarR-enriched loci across the genome and …

Intratumoral Neutrophil-To-Lymphocyte Ratio Is Mirrored By Circulating Neutrophil-To-Lymphocyte Ratio In Non-Small Cell Lung Cancer, Kyle G Mitchell, Younghee Lee, Nathaniel Deboever, Marcelo V Negrao, Hai T Tran, Edwin Parra, Lauren Byers, Alexandre Reuben, Lorenzo Federico, Chantale Bernatchez, Jing Wang, Mara B Antonoff, Ara A Vaporciyan, Stephen G Swisher, Tina Cascone, Ignacio I Wistuba, John V Heymach, Don L Gibbons, Jianjun Zhang, Daniel J Mcgrail, Boris Sepesi, Cara L Haymaker

Faculty, Staff and Student Publications

Tumor-initiated emergency granulopoiesis results in expansion of the circulating neutrophil compartment and neutrophil recruitment into the tumor microenvironment (TME), which may in turn promote tumor progression. Although an elevated circulating neutrophil-to-lymphocyte ratio (cNLR) has repeatedly been demonstrated to be an adverse prognostic factor in patients with non-small cell lung cancer (NSCLC), whether this neutrophil expansion in circulation reflects a similar relative neutrophil abundance in the TME remains unclear. We sought to characterize the relationships between cNLR and the intratumoral neutrophil-to-lymphocyte ratio (tNLR), between tNLR and proteogenomic and immune features of NSCLC tumors, and between tNLR and prognosis.We analyzed tNLR (transcriptomic …

Do Female Patients Experience Worse Outcomes Than Male Patients After Inguinal Hernia Repair? An Analysis Of The Abdominal Core Health Quality Collaborative Database, Amrita Iyer, Sunjay Kumar, Martina Rama, Sourav Podder, Li-Ching Huang, Sami Tannouri, Talar Tatarian, Francesco Palazzo

Department of Surgery Faculty Papers

BACKGROUND: Inguinal hernia repair is one of the most common general surgery operations. Some evidence suggests that female patients are at greater risk of chronic postoperative pain and hernia recurrence. We investigated rates of chronic inguinal pain and recurrence after inguinal hernia repair in both male and female patients using the Abdominal Core Health Quality Collaborative database.

METHODS: The Abdominal Core Health Quality Collaborative database was queried for patients undergoing elective, unilateral inguinal hernia repair who completed 30-day clinical follow-up and baseline and 1-year European Registry for Abdominal Wall Hernias Survey surveys. Both open and minimally invasive cases were included. …

Decreased Proliferation Of Hepg2 Liver Cancer Cells In Vitro And Exhibited Proteomic Changes In Vivo In Subjects With Metabolic Syndrome And Metabolic Dysfunction-Associated Steatotic Liver Disease Who Performed Four-Week Dawn-To-Dusk Dry Fasting, Ayse L Mindikoglu, Kristin Eckel-Mahan, Antone R Opekun, Mustafa M Alzubaidi, Zoe R Crochet, Prasun K Jalal, Sung Yun Jung

The Brown Foundation: Institute of Molecular Medicine

Background: Four-week dawn-to-dusk dry fasting (DDDF) was previously shown to have a potent anti-inflammatory effect and induce an anti-tumorigenic proteome in the serum and peripheral blood mononuclear cells in subjects without cancer. The study goal was to determine if serum obtained from these subjects without cancer who underwent 4-week DDDF has an anti-tumorigenic effect.

Methods: HepG2 cells were treated with serum collected from four individuals with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD) and four healthy individuals who performed 4-week DDDF. The objective was to assess cell proliferation/viability in HepG2 cells treated with non-fasted and dry-fasted serum and …

Modeling Reemergence Of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination In The Us, Mathew V Kiang, Kate M Bubar, Yvonne Maldonado, Peter J Hotez, Nathan C Lo

Faculty, Staff and Students Publications

Importance: Widespread childhood vaccination has eliminated many infectious diseases in the US. However, vaccination rates are declining, and there are ongoing policy debates to reduce the childhood vaccine schedule, which may risk reemergence of previously eliminated infectious diseases.

Objective: To estimate the number of cases and complications in the US under scenarios of declining childhood vaccination for measles, rubella, poliomyelitis, and diphtheria.

Design, setting, and participants: A simulation model was used to assess the importation and dynamic spread of vaccine-preventable infectious diseases across 50 US states and the District of Columbia. The model was parameterized with data on area-specific estimates …

Cholesterol Metabolism Regulated By Camkk2-Creb Signaling Promotes Castration-Resistant Prostate Cancer, Chenchu Lin, Thomas L Pulliam, Jenny J Han, Jiaqian Xu, Carlos Vera Recio, Sandi R Wilkenfeld, Yan Shi, Manoj Kushwaha, Sarah Bench, Eduardo Ruiz, Sanjanaa Senthilkumar, Jayasurya Dileep, Peter D A Shepherd, Nora M Navone, Albert R Klekers, Elizabeth M Whitley, Michael M Ittmann, Livia S Eberlin, Wenyi Wang, Daniel E Frigo

Faculty, Staff and Student Publications

Castration-resistant prostate cancer (CRPC) remains an incurable disease in need of improved treatments. CAMKK2 is an emerging therapeutic target whose oncogenic effects in prostate cancer have, to date, been largely attributed to its activation of AMP-activated protein kinase (AMPK). Here, we demonstrate that CAMKK2 promotes prostate cancer growth through an alternative downstream pathway involving CAMKI and CREB. Unbiased transcriptomics identify CREB-mediated transcription as a CAMKK2-regulated process, findings that we validate using diverse molecular, genetic, and pharmacological approaches in vitro and in vivo. CAMKK2 promotes CREB phosphorylation/activation through CAMKIα independently of AMPK, CAMKIV, or other CAMKI isoforms. Functionally, the CREB family …

The Only Constant Is Change: The Role Of Genetic Diversification In Cancer And Beyond, Malgorzata Tyczynska Weh

USF Tampa Graduate Theses and Dissertations

Genetic diversification, the process by which genetic variation arises in a population, is fundamental to evolution by natural selection. Mutation, a central diversification process, fuels adaptation across species, including in cancer. Yet most new mutations are neutral or deleterious on cell fitness, raising the question of how mutation-driven adaptation persists. To explore this paradox, I developed a spatial agent-based model (ABM) in which population fitness emerges from individual cells acquiring mutations at varied rates and with diverse fitness effects. I evaluated model behavior across adaptive states, mutation rates, and distributions of fitness effects. The results show that high mutation rates …

Exploring Predictors Of Treatment Response To Glp-1 Receptor Agonists For Smoking Cessation, Luba Yammine, Constanza De Dios, Robert Suchting, Charles E Green, David A Nielsen, Consuelo Walss-Bass, Joy M Schmitz

Faculty, Staff and Student Publications

Introduction: Understanding predictors of smoking cessation medication efficacy facilitates the ability to enhance treatment effectiveness. In our pilot trial, exenatide, a glucagon-like peptide-1 receptor agonist, adjunct to nicotine patch improved smoking abstinence compared to nicotine patch alone. This secondary analysis explores potential baseline characteristics associated with differential treatment response to exenatide.

Aims and methods: The parent trial randomized (1:1) 84 smokers with prediabetes and/or overweight to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received nicotine patch (21 mg) and brief smoking cessation counseling, with biologically confirmed 7-day point prevalence abstinence at week 6 (end-of-treatment) deemed the primary outcome. …

Detecting Early Changes In Cartilage Collagen And Proteoglycans Distribution Gradients In Mice Harboring The R992c Collagen Ii Mutant Using 2d Correlation Infrared Spectroscopy, Jolanta Fertala, Andrzej Steplewski, Andrzej Fertala

Department of Orthopaedic Surgery Faculty Papers

Collagen II is a vital structural component in developing bones and mature cartilage. Muta- tions in this protein cause spondyloepiphyseal dysplasia, a disease characterized primarily by altered skeletal growth and manifesting with a range of phenotypes, from lethal to mild. This study examined transgenic mice harboring the R992C (p.R1124C) substitution in colla- gen II. Previous research demonstrated significant growth abnormalities and disorganized growth plate structure in these mice, and histological signs of osteoarthritic changes in the knee joints of 9-month-old mice with the R992C mutation. Our study focuses on detecting early structural changes in the articular cartilage that occur before …