Chemicals and Drugs Commons^™

Persistent Chemotherapy-Induced Peripheral Neuropathy As A Chronic Cancer Pain Syndrome: Mechanisms, Therapeutic Limitations, And Future Directions, Reed Firestone, Jamin Morrison

Department of Medicine Faculty Papers

Background/Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting complication of cancer therapy and a major contributor to chronic neuropathic pain among cancer survivors. Although traditionally managed as a treatment-related toxicity, persistent CIPN frequently persists long after chemotherapy completion and is increasingly recognized as a major survivorship and palliative care challenge. This review synthesizes current mechanistic, clinical, and translational evidence and reframes persistent CIPN as a chronic neuropathic cancer pain syndrome. Methods: A narrative review of peer-reviewed literature was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library, supplemented by manual review of key references and clinical guidelines. Emphasis was placed …

Molecular Profiling And Tumor Biomarker Analysis Of Gog281/Logs: A Positive Late-Phase Trial Of Trametinib For Recurrent/Persistent Low-Grade Serous Ovarian Carcinoma, Robert L. Hollis, Austin Miller, Heather A. Lankes, Kwong-Kwok Wong, William Rodgers, David Millan, Karen Carty, Robert L. Coleman, Kathleen N. Moore, Angeles Alvarez Secord, David M. O'Malley, John K. Chan, Andrea R. Hagemann, Stephanie Gaillard, Saketh R. Guntupalli, Mitchell I. Edelson, Peter G. Rose, Oliver Dorigo, Susana Banerjee, Ailith Ewing, Michael Churchman, Anil K. Sood, C. Simon Herrington, Charlie Gourley, David M. Gershenson

Abington Jefferson Health Papers

PURPOSE: Low-grade serous ovarian carcinoma (LGSOC) is a distinct form of ovarian cancer characterized by younger patient age and relative chemoresistance. The GOG281/LOGS trial (NCT02101788) investigated the efficacy of the MEK inhibitor trametinib compared with physician's choice standard-of-care (SOC) in patients with LGSOC with persistent/recurrent disease. The study demonstrated significantly improved progression-free survival (PFS) in the trametinib-treated arm.

EXPERIMENTAL DESIGN: Two hundred and sixty patients with recurrent/persistent LGSOC were enrolled and randomly assigned in GOG281. We performed molecular analysis of 170 patients with available tumor specimens, comprising whole-exome sequencing and phospho-ERK (pERK) IHC, to identify biomarkers of clinical benefit from …

Apolipoprotein E4 And Its Later-Life Health Effects On The Multiple Sclerosis Population, Dean Zeldich, Chia Hsin Cheng, Yi Guan, Sriman Narain, Bang-Bon Koo

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune disease causing neuroinflammation and neurodegeneration. The apolipoprotein E4 (APOE4) allele, a major genetic risk factor for late-onset Alzheimer's Disease, accelerates cognitive decline and neuroinflammatory processes, including blood-brain-barrier disruption. This study explores the impact of APOE4 on later-life health in MS patients using biomarkers from the UK Biobank.

METHODS: MS patients were grouped by APOE4 carrier status: MS-E4 and MS-nonE4. Age- and sex-matched non-MS controls (control-E4, control-nonE4) were included for comparison. Analyses assessed retinal nerve fiber layer thickness (RNFL) from optical coherence tomography (OCT), blood biomarkers, cognitive performance, and brain magnetic …

The Role Of Extracellular Vesicles As Diagnostic Tools In Gut-Brain Axis Disorders, Patricia Marçal Da Costa, Paulo Iury Gomes Nunes, Gabriella Cunha Vieira Ciurleo, José Wagner Leonel Tavares Junior, Pedro Braga Neto, Ludmila Belayev, Reinaldo Barreto Oriá

School of Graduate Studies Faculty Publications

The gut–brain axis represents a dynamic two-way signaling network whose dysregulation has been implicated in a wide range of neurogastrointestinal disorders. In this context, extracellular vesicles (EVs) have emerged as critical mediators of intercellular signaling and as promising non-invasive biomarkers. Derived from host and microbial cells, EVs carry bioactive cargo—including proteins, lipids, nucleic acids, and metabolites—that reflect the physiological or pathological state of their cells of origin. Their ability to cross biological barriers, such as the blood–brain barrier, underscores their potential for diagnosing and monitoring gut–brain axis dysfunctions. In this mini-review, we integrate microbial and brain-derived EVs within the framework …

Micrornas In Prostate Cancer Liquid Biopsies: Early Detection, Prognosis, And Treatment Monitoring, Seyyed Mohammad Yaghoubi, Erfan Zare, Sina Jafari Dargahlou, Maryam Jafari, Mahdiye Azimi, Maedeh Khoshnazar, Solmaz Shirjang, Behzad Mansoori

Student Papers, Posters & Projects

Prostate cancer (PCa) is a common malignancy in men worldwide, with incidence projected to rise in the coming years. Traditional screening and diagnostic methods, such as prostate-specific antigen (PSA) testing and biopsy, face limitations in specificity and invasiveness. Circulating microRNAs (miRNAs) have emerged as stable, non-invasive biomarkers obtainable via liquid biopsies (blood, urine, semen) that could transform PCa management. These small regulatory RNAs reflect underlying tumor biology and are detectable at early disease stages, enabling improved early detection when used alongside or in place of PSA. Distinct miRNA expression patterns correlate with tumor aggressiveness. For example, miR-141 and miR-375 are …

Longitudinal Patterns Of Urinary Biomarkers Of Placental And Renal Function In Pregnancy And Associations With Early Pregnancy Exposure To Phthalates And Replacements, Erin E. Mcnell, Danielle R. Stevens, Barrett M. Welch, Suzanne Fenton, Antonia M. Calafat, Julianne Cook Botelho, Elena Sinkovskaya, Ann Przybylska, George Saade, Alfred Abuhamad, Kelly K. Ferguson

Department of Obstetrics & Gynecology Faculty Publications

Phthalates and replacements are endocrine-disrupting chemicals that may interfere with early pregnancy processes such as placentation and renal adaptation. Placental and renal biomarkers may help examine these toxicologic mechanisms. This study aims to characterize longitudinal changes in urinary protein biomarkers of placental angiogenesis (sFlt-1, PlGF, sEng) and renal function (KIM-1, NGAL, nephrin), and investigate associations with early pregnancy exposure to phthalates and replacements. Among 291 participants from the Human Placenta and Phthalates prospective cohort, urinary metabolites of eight phthalates and two replacements were quantified at up to 2 time points from 12 to 15 weeks gestation. Repeated measures were averaged …

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 …

Intravenous Infusion Of Nicotinamide Adenine Dinucleotide (Nad+) Versus Nicotinamide Riboside (Nr): A Retrospective Tolerability Pilot Study In A Real-World Setting, Kirsten Reyna, Greer Heinzen, Nikita Patel, Marie Ritter, Alexandra Siojo, Henry Legere, Rachele Pojednic

Research outputs 2022 to 2026

Background: Nicotinamide adenine dinucleotide (NAD⁺) is a cofactor for NAD⁺-dependent enzymes that regulate DNA repair, cellular metabolism, and immune function. Supplementation with NAD⁺ and its precursors is commonly used to prevent age-related disease and extend healthspan. Commercial clinical and wellness settings increasingly provide intravenous (IV) NAD⁺ and nicotinamide riboside (NR) despite limited evaluation of safety and effectiveness. These considerations are important, as NAD⁺ and its precursors differ in reported side effects, cellular uptake, and metabolism. This study sought to compare commercially administered NAD⁺ IV and NR IV in humans by evaluating infusion …

Short-Term Preeclampsia Prediction: Cutoff Variations For Sflt-1/Plgf In U.S. Patients With Or Without Hypertensive Disorders, Yaxin Li, Kristen Cagino, Jim Yee, Caroline Andy, Dajana Borova, Ayush Shah, Isla Racine, Tracy Grossman, Zhen Zhao

Student Papers, Posters & Projects

BACKGROUND: Preeclampsia (PE) is a complex disorder with significant maternal and fetal risks. The soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio shows promise as a diagnostic tool, but its adoption in the U.S. remains limited due to the lack of accessible testing platforms, U.S.-based studies, and evidence-based implementation guidelines.

PATIENTS/MATERIALS AND METHODS: We conducted a cohort study to evaluate the sFlt-1/PlGF ratio for predicting PE within two weeks among pregnant individuals ≥18 years, ≥20 weeks gestation. Serum samples were obtained from routine prenatal visits or triage evaluations. sFlt-1/PlGF ratios were measured using Roche Elecsys assays, and …

Biofluid Biomarkers Aid In Diagnosing And Developing Improved Treatments For People With Alzheimer's Disease, Jonatan A. Lopez

University Honors Theses

Dementia is a disease in which daily life is disrupted by a loss of cognitive function. Late-onset Alzheimer's disease (AD) is the most common dementia that largely begins to affect individuals in their mid 60s or older. AD was selected as the focus of this paper because it is the most common form of dementia, accounting for 50-70% of dementia cases. A typical diagnostic approach used by physicians starts with a simple clinical test, the Mini-Mental State Examination (MMSE), when cognitive decline is suspected in a patient. Then if there is enough evidence to suggest AD, a physician would order …

Quantile Index Predictors Using R Package Hyper.Gam, Tingting Zhan, Misung Yi, Inna Chervoneva

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

MOTIVATION: Evaluation of single-cell protein expression from immunohistochemistry images is used increasingly in biomedical research. Many proteins are used solely for phenotyping cells in the tumor microenvironment. Other proteins with meaningfully quantitative expression levels provide so-called functional protein biomarkers. There is still a limited number of methods and software tools available for utilizing the entire distributions of single-cell expression levels.

RESULTS: We present the R package hyper.gam, providing a supervised learning framework for deriving biomarkers based on single-cell distribution quantiles. The single-cell data are first converted into sample quantile functions, which are then used as predictors in scalar-on-function regression models …

Rna Sequencing Reveals Inflammatory And Metabolic Changes In The Lung And Brain After Carbon Black And Naphthalene Whole Body Inhalation Exposure In A Rodent Model Of Military Burn Pit Exposures, Allison M. Haaning, Brian J. Sandri, Henry L. Wyneken, William T. Goldsmith, Joshua P. Nixon, Timothy R. Nurkiewicz, Chris H. Wendt, Paul Barach, Janeen H. Trembley, Tammy A. Butterick

College of Population Health Faculty Papers

Military personnel deployed to Iraq and Afghanistan were exposed to emissions from open-air burn pits, where plastics, metals, and medical waste were incinerated. These exposures have been linked to deployment-related respiratory diseases (DRRD) and may also impact neurological health via the lung-brain axis. To investigate molecular mechanisms, adult male rats were exposed to filtered air, naphthalene (a representative volatile organic compound), or a combination of naphthalene and carbon black (surrogate for particulate matter; CBN) via whole-body inhalation (six hours/day, three consecutive days). Lung, brain, and plasma samples were collected 24 h after the final exposure. Pro-inflammatory biomarkers were assessed using …

Identification Of Serum Exosome Proteins In Systemic Sclerosis With Interstitial Lung Disease By Aptamer Proteomics, Sonsoles Piera-Velazquez, Simon T. Dillon, Xuesong Gu, Towia A. Libermann, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

OBJECTIVE: A major unmet need for Systemic Sclerosis (SSc) clinical management is the absence of well validated biomarkers for early diagnosis of SSc-associated interstitial lung disease (SSc-ILD). The objective of this study was to identify proteins contained within serum exosomes that may serve as potential biomarkers to differentiate patients with Diffuse SSc without SSc-ILD from patients with Diffuse SSc with SSc-ILD employing aptamer-based proteomics.

METHODS: Serum exosomes were isolated from two cohorts of patients. The first cohort included 15 patients with Diffuse SSc without SSc-ILD and 14 patients with Diffuse SSc with SSc-ILD and the second cohort included 12 patients …

Prognostic Value Of Lipoprotein(A) For Cardiovascular Events After Lower Limb Revascularization In Diabetic Patients With Chronic Limb-Threatening Ischemia, Federico Biscetti, Maria Margherita Rando, Maria Anna Nicolazzi, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

BACKGROUND: Chronic limb-threatening ischemia (CLTI) presents a major clinical challenge in patients with Type 2 Diabetes Mellitus (T2DM), requiring lower extremity revascularization (LER) to mitigate adverse cardiovascular and limb outcomes. Lipoprotein(a) (Lp(a)) has been implicated in cardiovascular risk, but its role in patients with T2DM and CLTI undergoing revascularization remains unclear. Thus, this study aimed to investigate the prognostic value of Lp(a) levels in diabetic CLTI patients for major adverse cardiovascular events (MACE), major adverse limb events (MALE), or both after LER.

METHODS: In this prospective cohort study of 158 individuals with T2DM and CLTI undergoing LER, baseline clinical data …

An Integrative Genomics Approach For The Discovery Of Potential Clinically Actionable Diagnostic And Prognostic Biomarkers In Colorectal Cancer, Mark Fertel, Duaa Mohammad Alawad, Chindo Hicks

School of Graduate Studies Faculty Publications

Background: Despite remarkable progress in clinical management of patients and intensified screening, colorectal cancer remains the second most common cause of cancer-related death in the United States. The recent surge of next generation sequencing has enabled genomic analysis of colorectal cancer genomes. However, to date, there is little information about leveraging gene expression data and integrating it with somatic mutation information to discover potential biomarkers and therapeutic targets. Here, we integrated gene expression data with somatic mutation information to discover potential diagnostic and prognostic biomarkers and molecular drivers of colorectal cancer. Methods: We used publicly available gene expression and somatic …

Refine: A Database Of Linked Clinical Data And Genomic Biomarkers In Renal Cell Carcinoma Patients Receiving Immunotherapy-Based Treatment Regimens, Jeffrey Zhong, Albert Jang, Bashar Abuqayas, Arnab Basu, David Benjamin, Vineel Bhatlapenumarthi, Mehmet Asim Bilen, Dhvani Buch, Mark Chang, Erica Chin, Sourat Darabi, Nagendra Dhanikonda, Pooja Ghatalia, Claud Grigg, Abby Grier, Tanya Jindal, Joannah Jung, Deepak Kilari, Hamsa Kumar, Suzanna Lee, Brittany Neelands, Chinmayi Pandya, Jeff Pawalek, Jaimee Staggers, Ahmet Yildirim, Yousef Zakharia, Kevin Zarrabi, Michael Zimmerman, George Sledge, David Spetzler, Andrew Elliott, Rana Mckay, Pedro Barata

Department of Medical Oncology Faculty Papers

The REnal cancer consortium for Focused Investigation of Novel biomarkers and Expression (REFINE) consortium represents an important initiative in integrating clinical data with molecular sequencing in patients with advanced renal cell carcinoma (RCC) treated with immunotherapy-based approaches. By leveraging real-world evidence and genomic analysis, this consortium aims to explore putative predictive biomarkers with the potential to inform personalized treatment strategies. Findings from the REFINE database may further contribute to our understanding of disease courses of immunotherapy-based approaches for various molecular subtypes of RCC, associations of race and ethnicity with RCC treatment and outcomes with representation of patient populations underrepresented in …

Plasma Proteomic Biomarkers Of Physical Frailty In Heart Failure: A Propensity Score Matched Discovery-Based Pilot Study, Quin Denfeld, Noelle Pavlovic, Christopher Lee, Jon Jacobs, Mary Roberts Davis, Samantha Powell, Marina Gritsenko, Susan Joseph, Beth Habecker

Division of Cardiology Faculty Papers

BACKGROUND: Physical frailty is highly prevalent in heart failure (HF), but we lack an understanding of the underlying pathophysiology. Proteomic evaluation of plasma samples may elucidate potential mechanisms and biomarkers of physical frailty in HF.

OBJECTIVES: We aimed to identify plasma proteomic biomarkers that are differentially expressed between physically frail and non-physically frail adults with HF.

METHODS: This was a secondary analysis of a subset of data and plasma samples from a study of frailty among patients with New York Heart Association (NYHA) Functional Classification I-IV HF. Physical frailty was measured using the Frailty Phenotype Criteria. Propensity score matching was …

Association Between High Triglyceride-Glucose Index And Macce In Hypertriglyceridemia Patients Undergoing Percutaneous Coronary Intervention, Yichuan Wang, Yanfeng Lu, Shanshan Gao, Zhong Zhong, Jasmine Bao, Bo Liu, Ruihan Fan, Ning Guo

SKMC Student Presentations and Publications

BACKGROUND: With a focus on metabolism-related cardiovascular diseases, the triglyceride-glucose (TyG) index has been used as a surrogate marker of insulin resistance in the prognosis of coronary heart disease. However, the prognostic role of the TyG index in patients with elevated triglycerides, still requires further research. This study aimed to investigate the association between the TyG index and Major Adverse Cardiac and Cerebrovascular Events (MACCE) in patients with hypertriglyceridemia undergoing drug-eluting stent percutaneous coronary intervention (DES-PCI).

METHODS: Out of 2250 patients, 813 with hypertriglyceridemia who underwent DES-PCI were retrospectively analyzed. MACCE was regarded as the primary endpoint. Kaplan-Meier (KM) curves …

Association Of Inflammatory Biomarkers With New Functional Morbidity At Hospital Discharge In Children Who Survive Severe Sepsis, Mallory Perry-Eaddy, Walter Faig, Martha Curley, Scott Weiss

Department of Pediatrics Faculty Papers

OBJECTIVE: New functional morbidity is common in critically ill children who survive sepsis; yet, the underlying biological mechanisms, particularly the impact of inflammation, remain unknown. We sought to test the hypothesis that increased levels of inflammatory biomarkers during the acute phase of pediatric sepsis are associated with new functional morbidity at hospital discharge.

METHODS: We conducted a post hoc secondary analysis of the MitoPSe clinical study, including N = 119 critically ill children who survived sepsis. Data collected included demographic and clinical variables and 31 inflammatory biomarkers collected at three distinct timepoints (within days 1-2 of PICU admission, days 3-5, …

Development And Validation Of Risk Stratification For Heart Failure After Acute Coronary Syndrome Based On Dynamic S100a8/A9 Levels, Jie Ma, Ke Ma, Jing Chen, Xinying Yang, Fei Gao, Hai Gao, Hui Zhang, Xin-Liang Ma, Jie Du, Ping Li, Yulin Li

Department of Emergency Medicine Faculty Papers

BACKGROUND: The early assessment of heart failure (HF) risk in patients with acute coronary syndrome (ACS) can help reduce mortality. S100A8/A9 is not only rapidly released after myocardial ischemia, but is also involved in reperfusion injury, which is an important predictor of HF after ACS. We attempted to construct a reliable HF risk stratification tool for evaluating patients with ACS after reperfusion therapy based on S100A8/A9 dynamic changes.

METHODS AND RESULTS: This prospective study included 3 independent cohorts of patients with ACS who received reperfusion therapy. The discovery cohort was divided into 2 subgroups: the longitudinal subgroup (n=264) with serum …

A Scoping Review Of Population Diversity In The Common Genomic Aberrations Of Clear Cell Renal Cell Carcinoma, Sean S. Kumar, Ninad Khandekar, Komal Dani, Saina R. Bhatt, Vinay Duddalwar, Anishka D' Souza

Department of Medicine Faculty Publications

Introduction: Previous literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: von Hippel-Lindau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C …

Evaluation Of Sirtuin 1 As A Predictor Of Cardiovascular Outcomes In Diabetic Patients With Limb-Threatening Ischemia, Federico Biscetti, Maria Margherita Rando, Maria Anna Nicolazzi, Enrica Rossini, Michele Santoro, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

Chronic limb-threatening ischemia (CLTI) significantly increases the risk of major adverse limb events (MALE) and major adverse cardiac events (MACE) after lower extremity revascularization (LER). This study aims to identify novel biomarkers that help to further reduce the risk of postoperative cardiovascular complications. In this prospective, nonrandomized, observational study, baseline serum levels of sirtuin 1 (SIRT1) were assessed in 147 diabetic patients scheduled for LER due to CLTI, and participants were followed for the occurrence of MALE and MACE over 12 months. Fifty-three patients experienced MALE, and 33 experienced MACE within the follow-up period. Lower baseline SIRT1 levels were significantly …

Noninvasive Multi-Cancer Detection Using Blood-Based Cell-Free Micrornas, Jason Zhang, Hallgeir Rui, Hai Hu

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Patients diagnosed with early-stage cancers have a substantially higher chance of survival than those with late-stage diseases. However, the option for early cancer screening is limited, with most cancer types lacking an effective screening tool. Here we report a miRNA-based blood test for multi-cancer early detection based on examination of serum microRNA microarray data from cancer patients and controls. First, a large multi-cancer training set that included 1,408 patients across 7 cancer types and 1,408 age- and gender-matched non-cancer controls was used to develop a 4-microRNA diagnostic model using 10-fold cross-validation. In three independent validation sets comprising a total of …

Keratin 17 Is A Prognostic And Predictive Biomarker In Pancreatic Ductal Adenocarcinoma, Lyanne Delgado-Coka, Lucia Roa-Peña, Sruthi Babu, Michael Horowitz, Emanuel Petricoin, Lynn Matrisian, Edik Blais, Natalia Marchenko, Felicia Allard, Ali Akalin, Wei Jiang, Md, Phd, Brent Larson, Andrew Hendifar, Vincent Picozzi, Minsig Choi, Kenneth Shroyer, Luisa Escobar-Hoyos

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVES: To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC).

METHODS: We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses.

RESULTS: …

Advancing Risk Stratification In Hfpef: Unveiling The Potential Of Cardiac Fibrosis Markers For Early Diagnosis And Enhanced Patient Outcomes, Mariam Abdeen

Rowan-Virtua Research Day

Heart failure with preserved ejection fraction (HFpEF) challenges clinicians due to its diverse presentation and limitations in traditional diagnostic criteria. This study delves into the potential of cardiac fibrosis markers like galectin-3, NT-proBNP, and trimethylamine N-oxide (TMAO) to enhance diagnostic precision and patient outcomes in HFpEF. A systematic review of sixteen relevant studies revealed that these biomarkers offer promise for early detection and improved risk assessment. For instance, TMAO indicates systemic implications of HFpEF, while galectin-3 shows predictive value across heart failure types. Additionally, machine-learning models incorporating multiple biomarkers predict significant risk of adverse outcomes. Despite these advances, challenges like …

Plasma Protein Signatures Of Adult Asthma, Gordon J. Smilnak, Yura Lee, Abhijnan Chattopadhyay, Annah B. Wyss, Julie D. White, Sinjini Sikdar, Jianping Jin, Andrew J. Grant, Alison A. Motsinger-Reif, Jian-Liang Li, Mikyeong Lee, Bing Yu, Stephanie J. London

Mathematics & Statistics Faculty Publications

Background: Adult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to identify plasma proteomic signatures of adult asthma.

Methods: Protein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non-case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non-case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta-analyzed using inverse-variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with …

Circulating Pre-Treatment T-Cell Receptor Repertoire As A Predictive Biomarker In Advanced Or Metastatic Non-Small-Cell Lung Cancer Patients Treated With Pembrolizumab Alone Or In Combination With Chemotherapy, A. Abed, Aaron B. Beasley, Anna L. Reid, N. Law, L. Calapre, M. Millward, Johnny Lo, Elin S. Gray

Research outputs 2022 to 2026

Background: The circulating T-cell receptor (TCR) repertoire is a dynamic representation of overall immune responses in an individual. Materials and methods: We prospectively collected baseline blood from patients treated with first-line pembrolizumab monotherapy or in combination with chemotherapy. TCR repertoire metrics were correlated with clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS) and immune-related adverse events (irAEs). We built a logistic regression classifier by fitting all four TCR- repertoire metrics to the immune checkpoint inhibitor (ICI) CBR data. In the subsequent receiver operating characteristic (ROC) analysis of the resulting logistic regression model probabilities, the best cut-off value was …

The Inherited Kras-Variant As A Biomarker Of Cetuximab Response In Nsclc, Joanne Weidhaas, Chen Hu, Ritsuko Komaki, Gregory Masters, George Blumenschein, Joe Chang, Bo Lu, Adam Dicker, Jeffrey Bogart, Yolanda Garces, Samir Narayan, Clifford Robinson, Vivek Kavadi, Joel S Greenberger, Christopher Koprowski, James Welsh, Elizabeth Gore, Robert Macrae, Rebecca Paulus, Jeffrey Bradley

Department of Radiation Oncology Faculty Papers

PURPOSE: RTOG 0617 was a phase III randomized trial for patients with unresectable stage IIIA/IIIB non-small cell lung cancer comparing standard-dose (60 Gy) versus high-dose (74 Gy) radiotherapy and chemotherapy, plus or minus cetuximab. Although the study was negative, based on prior evidence that patients with the KRAS-variant, an inherited germline mutation, benefit from cetuximab, we evaluated KRAS-variant patients in RTOG 0617.

EXPERIMENTAL DESIGN: From RTOG 0617, 328 of 496 (66%) of patients were included in this analysis. For time-to-event outcomes, stratified log-rank tests and multivariable Cox regression models were used. For binary outcomes, Cochran-Mantel-Haenzel tests and multivariable logistic regression …

Comparative Polar And Lipid Plasma Metabolomics Differentiate Kshv Infection And Disease States, Sara R. Privatt, Camila Pereira Braga, Alicia Johnson, Salum J. Lidenge, Luke Berry, John R. Ngowi, Owen Ngalamika, Andrew G. Chapple, Julius Mwaiselage, Charles Wood, John T. West, Jiri Adamec

School of Medicine Faculty Publications

Background: Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there. As with most viral cancers, infection with KSHV alone is insufficient to induce tumorigenesis. …

Correlation Between Gut Biomarkers And Depression, Jianle Gao

Rowan-Virtua Research Day

The correlation between the gut-microbiota- brain axis and mental state in the context of mental disorders such as Major Depressive Disorder (MDD), Schizophrenia, etc. has been well studied. Production of inflammatory and non-inflammatory metabolites by the gut- microbiota directly and indirectly affects the brain and mood. Therefore, colonization by maladaptive, pro-inflammatory bacteria may cause mood dysregulation and depressive features. Metabolites from these bacteria can be quantitatively analyzed for use as biomarkers of Major Depressive Disorder. Biomarkers studied include: serotonin, dopamine, butyrate, acetate, and propionate.