Chemicals and Drugs Commons^™

Comparative Mass Spectrometry Analysis Of High And Low Centrifugation Extracellular Vesicle (Ev) Pellets From Healthy Urine Following Tamm-Horsfall Protein Removal, Dana Bielopolski, Luca Musante, Henrik Molina, Douglas Barrows, Samantha Upson, Lifang Yang, Thomas Carrol, Jonathan N. Tobin, Rhonda G. Kost, U. Erdbrügger

Department of Biomedical and Translational Sciences Faculty Publications

Objectives

Urinary extracellular vesicles (uEVs) are potential biomarkers for renal physiology and disease. Their isolation is challenged by Tamm-Horsfall protein (THP) contamination, particularly in high-speed ultracentrifugation (P100) fractions. Low-speed (P20) fractions contain biologically relevant uEVs, yet their proteomic composition is underexplored. This study evaluates strategies for THP removal to optimize mass spectrometry analysis and characterizes P20 and P100 uEV proteomes and its combination in healthy urine.

Methods

Urine from a healthy volunteer was processed via sequential centrifugation at 21,200 g (P20) and 164,244 g (P100). THP removal was performed using low ionic strength buffer (P20) and size-exclusion chromatography (P100). Western …

Absolute Quantification And Identification Of Rna From Rna-Lipid Nanoparticles Using High Resolution Mass Spectrometry, Jason C. Funderburk

Theses and Dissertations

RNA therapeutics are a rising drug category with potential use for a range of conditions encompassing infectious diseases to therapies for cancer, diseases, and genetic disorders. RNA-lipid nanoparticles (RNA-LNPs) are the prominent delivery method for these therapeutics approved products include mRNA vaccines and polyneuropathy treatments. The emergency use authorizations and orphan drug status of current RNA-LNP drugs has allowed approval without finalization of the regulatory analytical procedures for quality monitoring. The objective of the study was to develop an LC-MS assay to simultaneously measure identity and concentration of two therapeutically relevant intact RNA constructs extracted from RNA-LNPs to enhance quality …

The Myopia Epidemic: Integrating Genetic, Environmental, And Epigenetic Pathways To Define A Critical Window For Intervention, Pranavika Balaji

Undergraduate Research Posters

Myopia, or nearsightedness, has increased rapidly worldwide and is now a major public health concern caused by both genetic and environmental factors. Current understanding shows that too much near work, limited time spent outdoors, and prolonged screen use contribute to abnormal eye growth in individuals who may already have a genetic predisposition. At the molecular level, epigenetic changes and shifts in DNA activity, often influenced by environmental conditions, affect the signaling pathways that regulate eye development and may help explain why myopia is increasingly common among children. This paper synthesizes recent environmental, genetic, and epigenetic research to explain how these …

A Unified Automated And Explainable Ai Framework For Drug Discovery, Clinical Diagnostics, And Public Health Data Prediction, Lord Coffie

College of Graduate Studies: Theses & Dissertations

This thesis investigates the development of automated, explainable artificial intelligence systems to improve automated scientific discovery, clinical diagnostic support, and public health decision-making. Three independent yet thematically aligned studies were conducted across cheminformatics, radiology, and population health. Study A introduces an automated and explainable machine learning pipeline for Quantitative Structure–Activity Relationship (QSAR) modeling using RDKit-derived molecular descriptors. The pipeline performs systematic preprocessing, consensus-based feature selection (mutual information, random forest importance, RFECV), and benchmarks six supervised models—Random Forest, XGBoost, Support Vector Machine, Balanced Random Forest, EasyEnsembleClassifier, and a blended meta-ensemble, achieving AUC = 0.90 and accuracy = 0.83, while ensuring interpretability …

Partial Post-Exposure Protection By Topical Inserts Containing Tenofovir Alafenamide Fumarate/Elvitegravir In A Macaque Model Of Rectal Simian Hiv (Shiv) Infection, Natalia Makarova, Tyana Singletary, M. Melissa Peet, Kristen Kelley, Ryan Johnson, Vivek Agrahari, Maria Mendoza, Yi Pan, Walid Heneine, Meredith R. Clark, J. Gerardo García Lerma, Gustavo F. Doncel, James W. Smith

CONRAD Publications

On-demand topical inserts for HIV prevention may be a good option for people who have a low frequency of sexual activity. We recently demonstrated in a preclinical macaque model that rectal application of inserts containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) conferred protection against SHIV infection (93% efficacy) when applied as pre-exposure prophylaxis 4 hours before SHIV exposure. Here, we show that the same inserts provide significant postexposure protection (82.9% efficacy) when applied 4 hours after SHIV exposure. Our findings further support the ongoing clinical development of TAF/EVG inserts for on-demand HIV prevention.

Cold-Sensitive Acral Hand Lesions, Avery H. Seward, Jocelyn H. Larocque

Department of Medicine Faculty Publications

[Case description] An otherwise healthy woman in her 60s presented with a 2-year history of a persistent, itchy, and tender rash on the dorsal hands. The rash fluctuated in severity with the seasons, worsening during the colder months. The patient denied joint pain and fatigue, or lesions elsewhere.

Examination revealed partially blanchable violaceous plaques on the dorsal hands with partial sparing of the proximal and distal interphalangeal joints (Fig 1). A few punctate, crusted erosions and purpuric macules were present on the dorsal and volar distal phalanges (Figs 2 and 3).

Antibody-Drug Conjugates Beyond Her2 In Non-Small Cell Lung Cancer (Nsclc): Mechanisms, Emerging Targets, And Future Directions, Ahmed Ismail, Akash Desai, George R. Simon, Yanis Boumber

Department of Medicine Faculty Publications

Antibody–drug conjugates (ADCs) are a rapidly evolving class of oncology therapeutics that enable precise delivery of potent cytotoxic agents to tumor cells while minimizing systemic toxicity. While HER2-targeted ADCs such as trastuzumab deruxtecan (T-DXd) in HER2-mutant, Datopotamab deruxtecan (Dato-Dxd) in EGFR-mutant, and telisotumumab vedotin (Teliso-V) in MET IHC 3+ expressing lung cancer have already established a clinical role in non-small cell lung cancer (NSCLC), multiple ADCs targeting alternative antigens, including additional TROP2 ADCs, HER3, MET, CEACAM5, B7-H3, Nectin-4, and others, are now in advanced clinical development. This review synthesizes the current evidence for non-HER2 ADCs in NSCLC, highlighting mechanisms of …

Localization And Functional Exploration Of Leiomodin-2'S C-Terminal Binding Sites, Mason D. Summers, Madison Little, Robert P. Young, Brayan Osegueda, Alan Palma Guillen, Garry E. Smith Jr., John R. Cart, Vitold E. Galkin, Alla S. Kostyukova

Department of Biomedical and Translational Sciences Faculty Publications

Striated muscle contraction occurs through interactions between overlapping myosin-based thick and actin-based thin filaments within the sarcomere. For effective contraction to occur, the length of the thin filament must be maintained to ensure sufficient overlap with the thick filament. The proteins leiomodin and tropomodulin compete for binding at the pointed ends of thin filaments to regulate their length, using their homologous N-terminal actin and tropomyosin binding sites. Leiomodin also contains a region called the C-terminal extension, absent in tropomodulin. In this region, the cardiac isoform (leiomodin-2) contains additional actin-binding sites that enable it to bind along the sides of thin …

Cervicovaginal Lavage Fluid Iron And Manganese Levels In Women With And Without Vaginitis, Barbara Kozma, David Ratonyi, Bence Kozma, Peter Takacs, Attila G. Sipos

Department of Obstetrics & Gynecology Faculty Publications

Transition metals such as iron and manganese are critical for cellular metabolism, redox balance, and immune function, and they also influence host–pathogen interactions. Vaginitis is characterized by mucosal inflammation that may alter local trace-element homeostasis. We hypothesize that inflammatory conditions such as vaginitis may be associated with altered cervicovaginal iron and manganese levels. We performed a prospective, single-center cohort study at the University of Debrecen (Hungary) between April 2023 and April 2024, enrolling 80 women ≥ 18 years with vulvovaginal complaints. Participants were assessed at baseline and at weeks 4, 8, and 12 with clinical evaluation and cervicovaginal lavage (CVL) …

Inflammatory Co-Regulation Of Voltage-Gated Sodium Channels And Na,K-Atpase In Metastatic Breast Cancer, Steven D. Scahill, Kelly Jean Sherman, Dennis Paul

School of Graduate Studies Faculty Publications

Sodium regulation is a potentially major driver of cancer metastasis. Voltage-gated sodium channels (VGSCs) and Na,K-ATPase are sodium transporters that are upregulated in many advanced carcinomas and are implicated as metastatic drivers. However, little is known about what drives this overexpression, how these proteins influence metastatic behavior, or whether these complementary sodium transporters are co-regulated in cancer. Using sodium transporter regulation in healthy neurons as a model, the present study demonstrated that the inflammatory mediator tumor necrosis factor alpha (TNFα) affects the expression of VGSCs and Na,K-ATPase in an in vitro model of metastatic breast cancer. Acute TNFα challenge increased …

Microglial Expression Of Serotonin Receptors Reveals Parallel Regulation Of 5-Ht2b And Bdnf In The Rat Hippocampus, Andrei Turkin, Maria Sidorova, Ekaterina Kurilova, Natalia Alenina, Oksana Tuchina, Friederike Klempin

School of Graduate Studies Faculty Publications

Growing evidence suggests that psychiatric disorders are characterized by a prolonged inflammatory state, which may influence the efficacy of compounds targeting serotonin. Serotonin is a key signaling molecule in neuroplasticity of the adult hippocampus and involved in antidepressant action. Recent in vitro studies indicate the neurotransmitter may also facilitate the response to inflammation and potentially modulate microglial function towards neuroprotection. Using Tph2−/− rats depleted of brain serotonin, we examined microglial expression of various serotonin receptors (5-HTRs) in vivo in both the hippocampus and prefrontal cortex and assessed mRNA levels of cytokines and brain-derived neurotrophic factor (BDNF). We observed age-dependent and …

Radiogenomic Profiling Of Prostate Tumors Prior To External Beam Radiotherapy Converges On A Transcriptomic Signature Of Tgf-Β Activity Driving Tumor Recurrence, Anson T. Ku, Uma Shankavaram, Shana Y. Trostel, Hong Zhang, Sumeyra Kartal, Houssein A. Sater, Stephanie A. Harmon, Nicole V. Carrabba, Yang Liu, Hyunnam Ryu, James A. Proudfoot, Boon Hao Hong, Bradford J. Wood, Peter A. Pinto, Peter L. Choyke, Mack Roach, Howard M. Sandler, Stephanie L. Pugh, Kenneth L. Zeitzer, Lucas C. Mendez, Nirav S. Kapadia, William A. Hall, Anand B. Desai, Radka S. Stoyanova, Alan Pollack, Elai Davicioni, Melvin L. K. Chua, Baris Turkbey, Adam G. Sowalsky, Deborah E. Citrin

Einstein Health Papers

PURPOSE: Clinical risk grouping based on PSA, tumor grade, and disease extent guides treatment intensity for localized prostate cancer. However, many patients with intermediate- or high-risk disease treated with external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) still develop biochemical recurrence (BCR). Early identification of patients at high risk for BCR could enable personalized treatment strategies.

EXPERIMENTAL DESIGN: We prospectively enrolled 29 patients with intermediate- or high-risk prostate cancer undergoing EBRT and ADT. Pretreatment biopsies (n = 60) underwent whole-transcriptome microarray and whole-exome sequencing. Patients received multiparametric MRI at baseline and 6 months after treatment, with a median follow-up …

Vasoactive Drug Use In Children With Community Acquired Septic Shock In Australia And New Zealand, Elliot Long, Stephen Hearps, Amanda Williams, Ben Gelbart, Warwick Butt, Thomas Rozen, Sarah Mcnab, Meredith Borland, Simon Erickson, Shefali Jani, Marino Festa, Eunicia Tan, Natalie Phillips, Sainath Raman, Amit Kochar, Subodh Ganu, Simon Craig, Anna Lithgow, Arjun Rao, Emma Whyte, Stuart Dalziel, Shane George, Fran Balamuth, Scott Weiss, Nathan Kuppermann, Franz Babl

Department of Medicine Faculty Papers

BACKGROUND: Vasoactive agents are a critical supportive therapy for children with sepsis. We describe the choice and use patterns of vasoactive agents in children with sepsis.

METHODS: Prospective observational study conducted in 11 hospitals in Australia and New Zealand through the Paediatric Research in Emergency Departments International Collaborative (PREDICT) Network from April 2021 to December 2023. Children aged 0-< 18 years with suspected sepsis were included. Children admitted to hospital and treated with parenteral antibiotics and either 1) a provisional diagnosis of sepsis, and/or 2) treatment for suspected sepsis (fluid bolus to treat poor perfusion). The frequency and sequence of use of vasoactive agents, and contributors to the choice of initial vasoactive were collected.

FINDINGS: 6232 children with suspected sepsis were included; median age of 2.1 years (IQR 0.3-7.1 years), in-hospital mortality of 60 (1.0%), in whom a subset of 306 (4.9%) met Phoenix sepsis criteria. Vasoactive agents were used in 179 (2.9%) children overall …

Genomic Ascertainment Of Chek2 -Related Cancer Predisposition, Sunyoung Kim, Jung Kim, Mark Ramos, Jeremy Haley, Diane Smelser, H. Shanker Rao, Uyenlinh L. Mirshahi, Katherine L. Nathanson, Barry I. Graubard, Hormuzd A. Katki, David Carey, Douglas R. Stewart

School of Graduate Studies Faculty Publications

Importance: There is clear evidence that deleterious germline variants in CHEK2 increase risk for breast and prostate cancers; there is limited or conflicting evidence for other cancers. Objective: To quantify the prevalence of as well as cancer risk and survival associated with CHEK2 germline pathogenic and likely pathogenic variants using genomic ascertainment. Design, Setting, and Participants: This case-control study used 2 electronic health record-linked and exome-sequenced biobanks: UK Biobank (n = 469765) and Geisinger MyCode (adults only; n = 167050). Variants were classified according to American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Cases …

Treating Atopic Dermatitis: Oral Jak1 Inhibitor Vs. Monoclonal Antibody, Abby Craft, Nicolle Holgate

Physician Assistant Capstones, 2020-current

Objective: To compare symptom management of atopic dermatitis between injectable monoclonal antibodies and an oral Janus kinase 1 (JAK1) inhibitor. Design: Literature review. Methods: Searches were done in PubMed and CINAHL using the following terms: abrocitinib, Cibinqo, dupilumab, Dupixent, and atopic dermatitis. Filters included: randomized controlled trials, clinical trials, and scholarly journal. Results: Three studies met all criteria including Bieber et al, Reich et al, and Huang et al. Conclusion: Oral JAK1 inhibitor abrocitinib has been shown to have similar efficacy in symptom management of moderate-to-severe atopic dermatitis compared to monoclonal antibody dupilumab and should be considered when prescribing treatment.

Identification Of Predictive Pretreatment Biomarkers For Neoadjuvant Chemotherapy Response In Latino Invasive Breast Cancer Patients, Hedda Michelle Guevara-Nieto, Rafael Parra-Medina, Carlos A. Orozco, Sandra Diaz-Casas, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba L. Combita

School of Medicine Faculty Publications

Background: Breast cancer (BC) exhibits significant heterogeneity in incidence and mortality worldwide. Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced BC; however, its efficacy varies by subtype. This study examined the gene expression profiles associated with NAC response in Colombian women with invasive BC. Methods: RNA sequencing of pre-treatment tissues from 58 patients (29 responders and 29 non-responders) identified differentially expressed genes (DEGs) for each molecular subtype, and prognostic performance was evaluated using risk scores. Results: Functional enrichment analysis highlighted the immune system pathways in non-responders. Changes in cytokine target activity and immune cell populations were analyzed to …

Safety Evaluation Of Epicertin, An Oral Biotherapeutic Candidate For Treating Ulcerative Colitis: A 28-Day Repeated Dose Toxicity Study., Jimmy Fernando Cifuentes Jimenez

Electronic Theses and Dissertations

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic, relapsing inflammation of the colon and rectum with limited treatment options. Among them, immunosuppressive agents have a high rate of adverse side effects and do not cure the disease. EPICERTIN (EPT), a recombinant variant of the cholera toxin B subunit (CTB) with a C-terminal hexapeptide extension consisting of a KDEL endoplasmic reticulum (ER) retention motif, is a promising oral biotherapeutic candidate for the treatment of UC. EPT has demonstrated mucosal healing activity in mouse models of colitis and human colonic explants. EPT's mechanism of action involves binding to GM1 …

Overview Of Huntington's Disease And Emerging Treatment Strategies: A Narrative Review, Alexis J. Vega, Gabriel V. Hernandez, Pearse A. O'Malley, Connor J. Robin, Amanda N. Parra, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder caused by a cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin (HTT) gene. The symptoms of HD include severe motor dysfunction, cognitive issues, and emotional dysregulation. These combined issues are not only debilitating but also lead to depression/anxiety, increased suicide rates, and caregiver burnout. Our narrative review summarizes several recent studies examining the efficacy and differences among emerging treatment strategies for HD. A systematic search of peer-reviewed literature was conducted, focusing on recent studies that describe molecular genetic manipulation of the HTT gene/huntingtin protein. The results of our narrative review reveal …

Nirsevimab Effectiveness Against Intensive Care Unit Admission For Respiratory Syncytial Virus In Infants - 24 States, December 2024-April 2025, Laura D. Zambrano, Regina M. Simeone, Margaret M. Newhams, Amanda B. Payne, Natasha B. Halasa, Amber O. Orzel-Lockwood, Jemima M. Calixte, Satoshi Kamidani, Hillary Crandall, Melissa A. Cameron, Jennifer E. Schuster, Aline B. Maddux, Kathleen Chiotos, Katherine Irby, Steven L. Shein, Mary Allen Staat, Lora M. Martin, Samina S. Bhumbra, Ryan A. Nofziger, Jigar C. Chauhan, Danielle M. Zerr, Shira J. Gertz, Judith A. Guzman-Cottrill, Michele Kong, Janet R. Hume, Bria M. Coates, Kelly N. Michelson, Tamara T. Bradford, Et Al

School of Medicine Faculty Publications

Respiratory syncytial virus (RSV) is a leading cause of intensive care unit (ICU) admission and respiratory failure among infants (children aged < year) in the United States. In August 2023, CDC’s Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, to protect against RSV-associated lower respiratory tract infection among all infants aged < 8 months born during or entering their first RSV season. Following licensure, nirsevimab effectiveness has been demonstrated against RSV-associated infant hospitalization, but evidence regarding effectiveness against RSV-associated critical illness is limited. In a 27-hospital case-control investigation, nirsevimab effectiveness against both RSV-associated infant ICU admission and acute respiratory failure (illness requiring continuous positive airway pressure, bilevel positive airway pressure, or invasive mechanical ventilation) after hospital admission was evaluated during December 1, 2024-April 15, 2025. Among 457 case-patients who received a positive RSV test result and 302 control patients who received a negative RSV test result admitted to an ICU with respiratory symptoms, 14% and 45%, respectively, had received nirsevimab ≥ 7 days before symptom onset. Nirsevimab was 80% effective (95% CI = 70%-86%) against RSV-associated ICU admission and 83% effective (95% CI = 74%-90%) against acute respiratory failure when received a median of 52 days (IQR = 32-89 days) and 50 days (IQR = 32-86 days) before onset for each respective endpoint. These estimates support the recommendation for use of nirsevimab as a prevention strategy to protect infants against severe outcomes from RSV infection.

Colorectal Cancer: Differential Gene Expression And In Vitro Response To 5-Fluorouracil, Novel Fluoropyrimidine F10, And Potential Synergy With Lupeol, Shrey D. Thaker, Jenny Paredes, Jone Garai, Laura A. Martello, William H. Gmeiner, Jovanny Zabaleta, Jennie Williams

School of Medicine Faculty Publications

Colorectal cancer (CRC) remains one of the most lethal malignancies in the United States, with African American (AA) patients experiencing disproportionately higher incidence and mortality compared to Caucasian Americans (CAs). These disparities have been linked to tumor-intrinsic genomic differences, including microsatellite instability (MSI) and p53 mutation status, which may influence chemotherapeutic response, particularly to the standard-of-care agent 5-fluorouracil (5-FU). However, mechanistic insights have been limited by the lack of racially diverse preclinical models. Here, we evaluated the efficacy of F10 (a novel fluoropyrimidine polymer) vs. 5-FU using AA- and CA-derived CRC cell lines with distinct MSI and p53 profiles. MTT …

Citronellol Reduces Sepsis-Induced Renal Inflammation Via Ap-1/Nf-Κb/Tnf-Α Pathway, Huda Rashid Atiyah, Sarmed H. Kathem, Surya M. Nauli

Pharmacy Faculty Articles and Research

Sepsis is characterized by the over-production of pro-inflammatory cytokines. Cecal ligation and puncture (CLP) is a well-accepted model for recreating sepsis-induced renal injury in mice. The current study investigates how citronellol, a naturally occurring substance with a variety of biological characteristics, can prevent acute kidney inflammation brought on by CLP. In the CLP mouse model, citronellol was administered orally at doses of 50 and 100 mg/kg. Serum levels of creatinine and urea were used as markers of renal function, and the Murine Sepsis Score (MSS) was used to assess the severity of sepsis. According to our findings, CLP caused a …

Intercellular Signaling And Synaptic Deconstruction Uncovered By Single-Cell And Spatial Transcriptomics In An Ad Tauopathy Model, Jeff X. Ji, Brian L. Giles, Surjyadipta Bhattacharjee, Marie-Audrey I. Kautzmann, Alasdair P. Masson, Sonia Do Carmo, A Claudio Cuello, Nicolas G. Bazan

School of Medicine Faculty Publications

Alzheimer's disease (AD) is the leading cause of dementia in elderly individuals worldwide; however, all mechanisms leading to disease onset and progression are not well understood. Here, we report brain single-cell multiome and spatial transcriptomics in a transgenic rat model of human-like tauopathy. We have identified new markers of tau-driven AD pathology and provided single-cell evidence for genes implicated in AD. Our findings reveal how tau hyperphosphorylation and aging alter ligand-receptor communication, transcription factor regulatory networks, and specific cellular networks. Notably, we found intriguing changes in cell communication involving glutamatergic transmission and Netrin signaling as a taupathy consequence. Overall, this …

Sulindac Sulfide Suppresses Oncogenic Transformation Through Let-7b-Mediated Repression Of K-Ras Signaling, Zhipin Liang, Ruixia Ma, Bin Yi, Adam I. Riker, Yaguang Xi

School of Graduate Studies Faculty Publications

No abstract provided.

In Situ-Generated Volumetric Dried Plasma Spots For The Analysis Of Edaravone And Metabolites In Animal Models, Michele Protti, Roberta Di Lecce, Jiri Adamec, Luca G. Regazzoni, Valeria Valsecchi, Claudia Volpi, Roberto Mandrioli, Laura Mercolini

School of Graduate Studies Faculty Publications

In this study, for the first time rat plasma microsampling was carried out by means of in situ-generated volumetric dried plasma spot (vDPS) technology and applied to the determination of the neuroprotective agent edaravone and its sulphate and glucuronide metabolites. Sampling was performed using Telimmune® plasma separation cards (vPSC), which allow the formation of volumetrically accurate dried plasma spots (3 µL) from blood drops deposited on them. After accelerated forced drying and solvent extraction in methanol, drying and redissolution, analytes were baseline separated and quantified through an original HPLC-MS/MS analytical method. Validation assays provided excellent results, with detection limits between …

Roux-En-Y Gastric Bypass Is Associated With Increased Intestinal Glucose Uptake In Humans, Florina Corpodean, Maryam Naseri, Michael Kachmar, Julia St Amant, Denis P. Blondin, Owen T. Carmichael, Vance L. Albaugh

School of Medicine Faculty Publications

CONTEXT: In animal models, Roux-en-Y gastric bypass (RYGB) is associated with increased Roux limb intestinal glucose uptake that may contribute to early metabolic benefits, though prospective clinical studies are lacking. OBJECTIVE: The present study aimed to test the hypothesis that Roux limb glucose uptake would increase relative to baseline in a cohort of patients undergoing RYGB. METHODS: RYGB patients underwent preoperative baseline, and 3- and 6-month positron emission tomography/computed tomography postoperative imaging. Maximum and mean standardized uptake values (SUV) were measured from the following predefined regions of interest: cecum, hepatic flexure, splenic flexure, sigmoid colon, duodenal bulb, Roux limb, and …

Real-World Impact Of Amiodarone On Apixaban Population Pharmacokinetics In Hospitalized Patients, Samantha Kolowrat, Chazmyn Riley, Kevin Lam, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite common coadministration in nonvalvular atrial fibrillation (NVAF), there is minimal evidence regarding the impact of concomitant amiodarone use on apixaban pharmacokinetics (PK). We described the population PK of apixaban (2.5 and 5mg twice daily) in 106 hospitalized patients with and without concomitant amiodarone administration at steady state. Apixaban PK was reasonably described by a one-compartment model with first-order absorption and linear elimination. Aside from the receipt of amiodarone, age was retained as a statistically significant covariate on apparent clearance. Model-based simulations depicted concomitant amiodarone use increasing AUCT for both 2.5mg (1.58, 90% CI [1.28, 1.87]) and 5mg (1.12, 90% …

Assessing The Tumor Suppressive Impact And Regulatory Mechanisms Of Spdef Expression In Breast Cancer, Maansi Solanky, Maninder Khosla, Suresh K. Alahari

School of Graduate Studies Faculty Publications

Background/Objectives: Breast cancer is a heterogeneous disease, and the role of the transcription factor SPDEF remains controversial. We aimed to clarify the prognostic value of SPDEF, explore demographic and molecular correlates of its expression, and investigate potential regulatory mechanisms underlying its dysregulation. Methods: Genomic and clinical data for 1218 breast cancer tumors were obtained from The Cancer Genome Atlas (TCGA). SPDEF mRNA expression was compared across intrinsic subtypes, age, and race, and prognostic significance was evaluated by Kaplan–Meier analysis. Promoter methylation patterns and DNA methyltransferase (DNMT) expression were examined as potential regulatory drivers. Co-expression analysis was performed using gene panels …

Atypical Abdominal Pain: Uncovering Malignant Peritoneal Mesothelioma In Suspected Crohn's Disease: A Case Report, Catherine Loehr, Lara Boudreaux, Ann Porter Uhlhorn, Nisha Loganantharaj

School of Medicine Faculty Publications

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare and aggressive cancer from the serosal membranes of the abdominal cavity. In the United States, MPM accounts for about 10-15% of all mesothelioma cases, and translates into approximately 600 new cases diagnosed annually. It is typically diagnosed in Caucasian individuals, and while asbestos exposure is a well-established risk factor for pleural mesothelioma, its association with peritoneal mesothelioma remains less clear. Clinical symptoms of MPM, such as abdominal pain, bloating, and weight loss, overlap with other gastrointestinal disorders, which often leads to delayed diagnosis. This case report presents a unique instance of MPM …

Overview Of Exosomal Non-Coding Rnas In Cardiovascular Disease Using High Throughput Sequencing, Mortaza Eivazi, Leila Abkhooie, Kamran Hosseini, Parnia Mobasheran, Tahereh Ebrahimi, Vahideh Tarhriz, Eric Lazartigues

School of Graduate Studies Faculty Publications

Non-coding RNAs including miRNAs, long-ncRNAs, and circular RNAs play crucial roles in cell-to-cell communication and epigenetic regulation. They control gene expression at multiple levels, including transcriptional, post-transcriptional, and translational, thereby influencing associated signaling pathways. Encapsulated within exosomes, micro-vesicles, and apoptotic bodies, ncRNAs can be transported between cells while being protected from harsh environmental conditions. Studies have shown various expression patterns across different cell types and in various physiological and pathological states. However, the precise correlations and extent of their contribution to diseases are still under investigation. Recent studies have reported the involvement of extracellular vesicle-associated ncRNAs in the pathogenesis of …

Predicting Intravitreal Treatment Response Using Ultrawide-Field Angiographic Biomarkers In Diabetic Retinopathy, Karthik Reddy, Callie Deng, Boonkit Purt, Yue Liang, Nikhil Bommakanti, Gina Yu, Julie Rosenthal, Yannis M. Paulus

Wills Eye Hospital Papers

BACKGROUND: Diabetic retinopathy (DR) is a sight-threatening retinal disease with pathological mediation by vascular endothelial growth factor (VEGF). Intravitreal anti-VEGF injections are commonly used to manage DR. Ultra-wide-field fluorescein angiography (UWF-FA) can assess DR severity and characterize the amount of non-perfused retina (non-perfusion area, NP), neovascularization (neovascular area, NV), and foveal avascular zone (FAZ). However, the association between anti-VEGF treatment and NP, NV, and FAZ characterized by UWF-FA is not well established.

METHODS: A retrospective, single-center cohort study involved eyes of patients with Type 1 or 2 diabetes mellitus with at least one UWF-FA image. The area of the FAZ, …