Diseases Commons^™

Recent Advances In The Prevention And Treatment Of Decompensated Cirrhosis And Acute-On-Chronic Liver Failure (Aclf) And The Role Of Biomarkers, Jonel Trebicka, Ruben Hernaez, Debbie Lindsay Shawcross, Alexander L Gerbes

Faculty, Staff and Students Publications

The progression of cirrhosis with clinically significant portal hypertension towards decompensated cirrhosis remains clinically challenging and the evolution towards acute-on-chronic liver failure (ACLF), with one or more extrahepatic organ failures, is associated with very high mortality. In the last decade, significant progress has been made in the understanding of the mechanisms leading to decompensation and ACLF. As portal hypertension advances, bacterial translocation across an impaired gut barrier culminates in endotoxaemia, systemic inflammation and cirrhosis-associated immune dysfunction (CAID). Gut-derived systemic inflammation and CAID have become the logical targets for innovative therapies that prevent hepatic decompensation episodes and the progression to ACLF.Furthermore, …

Endotrophin, A Key Marker And Driver For Fibroinflammatory Disease, Kim Henriksen, Federica Genovese, Alexander Reese-Petersen, Laurent P Audoly, Kai Sun, Morten A Karsdal, Philipp E Scherer

Faculty, Staff and Student Publications

Our overview covers several key areas related to recent results obtained for collagen type VI and endotrophin (ETP). (1) An introduction to the history of ETP, including how it was identified, how it is released, and its function and potential receptors. (2) An introduction to the collagen family, with a focus on what differentiates collagen type VI from an evolutionary standpoint. (3) An overview of collagen type VI, the 6 individual chains (COL6A1, A2, A3, A4, A5, and A6), their differences and similarities, as well as their expression profiles and function. (4) A detailed analysis of COL6A3, including the cleaved …

Early Screening Of Colorectal Cancer Using Feature Engineering With Artificial Intelligence-Enhanced Analysis Of Nanoscale Chromatin Modifications, Andrew Chang, Sravya Prabhala, Ali Daneshkhah, Jianan Lin, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman

Faculty, Staff and Students Publications

Colonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~ 7 to 8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~ 5 to 20 nm, ~1 kbp) fold into chromatin packing domains (~ 100 to 200 nm, ~ 100 to 1000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity …

Biomarkers For Managing Neurodegenerative Diseases, Lara Cheslow, Adam E. Snook, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. …

Metabolomic Association And Risk Prediction With Heart Failure In Older Adults, Guning Liu, Ngoc Quynh H Nguyen, Kari E Wong, Sunil K Agarwal, Eric Boerwinkle, Patricia P Chang, Brian L Claggett, Laura R Loehr, Jianzhong Ma, Kunihiro Matsushita, Carlos J Rodriguez, Joseph S Rossi, Stuart D Russell, R Brandon Stacey, Amil M Shah, Bing Yu

Faculty, Staff and Student Publications

Background: Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults.

Methods: Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score …

Omics-Based Profiles And Biomarkers Of Respiratory Infections: Are We There Yet?, Jezreel Pantaleon Garcia, Scott E Evans

Faculty, Staff and Student Publications

Descriptive omics-based clinical research provides valuable early steps in understanding host immune responses to respiratory pathogens in our global efforts to mitigate the impacts of severe respiratory infections with rapidly evolving technologies https://bit.ly/4bjJsvL

Biomarker-Directed Targeted Therapy Plus Durvalumab In Advanced Non-Small-Cell Lung Cancer: A Phase 2 Umbrella Trial, Benjamin Besse, Elvire Pons-Tostivint, Keunchil Park, Sylvia Hartl, Patrick M Forde, Maximilian J Hochmair, Mark M Awad, Michael Thomas, Glenwood Goss, Paul Wheatley-Price, Frances A Shepherd, Marie Florescu, Parneet Cheema, Quincy S C Chu, Sang-We Kim, Daniel Morgensztern, Melissa L Johnson, Sophie Cousin, Dong-Wan Kim, Mor T Moskovitz, David Vicente, Boaz Aronson, Rosalind Hobson, Helen J Ambrose, Sajan Khosla, Avinash Reddy, Deanna L Russell, Mohamed Reda Keddar, James P Conway, J Carl Barrett, Emma Dean, Rakesh Kumar, Marlene Dressman, Philip J Jewsbury, Sonia Iyer, Simon T Barry, Jan Cosaert, John V Heymach

Faculty, Staff and Student Publications

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance—which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment—and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure …

Deep Phenotyping Of Post-Infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Brian Walitt, Komudi Singh, Samuel R. Lamunion, Mark Hallett, Steve Jacobson, Kong Chen, Yoshimi Enose-Akahata, Richard Apps, Jennifer J. Barb, Patrick Bedard, Robert J. Brychta, Ashura Williams Buckley, Peter D. Burbelo, Brice Calco, Brianna Cathay, Li Chen, Snigdha Chigurupati, Jinguo Chen, Foo Cheung, Lisa M.K. Chin, Benjamin W. Coleman, Amber B. Courville, Madeleine S. Deming, Bart Drinkard, Li Rebekah Feng, Luigi Ferrucci, Scott A. Gabel, Angelique Gavin, David S. Goldstein, Shahin Hassanzadeh, Sean C. Horan, Silvina G. Horovitz, Kory R. Johnson, Anita Jones Govan, Kristine M. Knutson, Joy D. Kreskow, Mark Levin, Jonathan J. Lyons, Nicholas Madian, Nasir Malik, Andrew L. Mammen, John A. Mcculloch, Patrick M. Mcgurrin, Joshua D. Milner, Ruin Moaddel, Geoffrey A. Mueller, Amrita Mukherjee, Sandra Muñoz-Braceras, Gina Norato, Katherine Pak, Iago Pinal-Fernandez, Traian Popa, Lauren B. Reoma, Michael N. Sack, Farinaz Safavi, Leorey N. Saligan, Brian A. Sellers, Stephen Sinclair, Bryan Smith, Joseph Snow, Stacey Solin, Barbara J. Stussman, Giorgio Trinchieri, Sara A. Turner, C. Stephenie Vetter, Felipe Vial, Carlotta Vizioli, Ashley Williams, Shanna B. Yang, Avindra Nath

Student Papers, Posters & Projects

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease …

Evaluation Of Ar, Ar-V7, And P160 Family As Biomarkers For Prostate Cancer: Insights Into The Clinical Significance And Disease Progression, Ruan Pimenta, Feres Camargo Malulf, Poliana Romão, Giovana Vilas Boas Caetano, Karina Serafim Da Silva, Vitoria Ghazarian, Gabriel A Dos Santos, Vanessa Guimarães, Iran Amorim Silva, Juliana Alves De Camargo, Saulo Recuero, Bárbara V Lima Aguiar Melão, Alberto Azoubel Antunes, Miguel Srougi, William Nahas, Katia R M Leite, Sabrina T Reis

Faculty, Staff and Student Publications

PURPOSE: To assess the role of the p160 family, AR, and AR-V7 in different initial presentations of prostate cancer and their association with clinical endpoints related to tumor progression.

METHODS: The study sample comprises 155 patients who underwent radical prostatectomy and 11 healthy peripheral zone biopsies as the control group. Gene expression was quantified by qPCR from the tissue specimens. The statistical analysis investigated correlations between gene expression levels, associations with disease presence, and clinicopathological features. Additionally, ROC curves were applied for distinct PCa presentations, and time-to-event analysis was used for clinical endpoints.

RESULTS: The AR-V7 diagnostic performance for any …

Examining The Association Between Posttraumatic Stress Disorder And Disruptions In Cortical Networks Identified Using Data-Driven Methods, Jin Yang, Ashley A Huggins, Delin Sun, C Lexi Baird, Courtney C Haswell, Jessie L Frijling, Miranda Olff, Mirjam Van Zuiden, Saskia B J Koch, Laura Nawijn, Dick J Veltman, Benjamin Suarez-Jimenez, Xi Zhu, Yuval Neria, Anna R Hudson, Sven C Mueller, Justin T Baker, Lauren A M Lebois, Milissa L Kaufman, Rongfeng Qi, Guang Ming Lu, Pavel Říha, Ivan Rektor, Emily L Dennis, Christopher R K Ching, Sophia I Thomopoulos, Lauren E Salminen, Neda Jahanshad, Paul M Thompson, Dan J Stein, Sheri M Koopowitz, Jonathan C Ipser, Soraya Seedat, Stefan Du Plessis, Leigh L Van Den Heuvel, Li Wang, Ye Zhu, Gen Li, Anika Sierk, Antje Manthey, Henrik Walter, Judith K Daniels, Christian Schmahl, Julia I Herzog, Israel Liberzon, Anthony King, Mike Angstadt, Nicholas D Davenport, Scott R Sponheim, Seth G Disner, Thomas Straube, David Hofmann, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine L Larson, Terri A Deroon-Cassini, Jennifer U Blackford, Bunmi O Olatunji, Evan M Gordon, Geoffrey May, Steven M Nelson, Chadi G Abdallah, Ifat Levy, Ilan Harpaz-Rotem, John H Krystal, Rajendra A Morey, Aristeidis Sotiras

Faculty, Staff and Students Publications

Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD …

Glucose Metabolism In Posterior Cingulate Cortex Has Supplementary Value To Predict The Progression Of Cognitively Unimpaired To Dementia Due To Alzheimer’S Disease: An Exploratory Study Of 18f-Fdg-Pet, Qi Zhang, Chunqiu Fan, Luyao Wang, Taoran Li, Min Wang, Ying Han, Jiehui Jiang, Alzheimer’S Disease Neuroimaging Initiative

Faculty, Staff and Student Publications

Amyloid-β (Aβ) and tau are important biomarkers to predict the progression of cognitively unimpaired (CU) to dementia due to Alzheimer's disease (AD), according to the diagnosis framework from the US National Institute on Aging and the Alzheimer's Association (NIA-AA). However, it is clinically difficult to predict those subjects who were already with Aβ positive (A +) or tau positive (T +). As a typical characteristic of neurodegeneration in the diagnosis framework, the hypometabolism of the posterior cingulate cortex (PCC) has significant clinical value in the early prediction and prevention of AD. In this paper, we proposed the glucose metabolism in …

Role Of Polyunsaturated Fat In Modifying Cardiovascular Risk Associated With Family History Of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies, Federica Laguzzi, Agneta Åkesson, Matti Marklund, Frank Qian, Bruna Gigante, Traci M Bartz, Julie K Bassett, Anna Birukov, Hannia Campos, Yoichiro Hirakawa, Fumiaki Imamura, Susanne Jäger, Maria Lankinen, Rachel A Murphy, Mackenzie Senn, Toshiko Tanaka, Nathan Tintle, Jyrki K Virtanen, Kazumasa Yamagishi, Matthew Allison, Ingeborg A Brouwer, Ulf De Faire, Gudny Eiriksdottir, Luigi Ferrucci, Nita G Forouhi, Johanna M Geleijnse, Allison M Hodge, Hitomi Kimura, Markku Laakso, Ulf Risérus, Anniek C Van Westing, Stefania Bandinelli, Ana Baylin, Graham G Giles, Vilmundur Gudnason, Hiroyasu Iso, Rozenn N Lemaitre, Toshiharu Ninomiya, Wendy S Post, Bruce M Psaty, Jukka T Salonen, Matthias B Schulze, Michael Y Tsai, Matti Uusitupa, Nicholas J Wareham, Seung-Won Oh, Alexis C Wood, William S Harris, David Siscovick, Dariush Mozaffarian, Karin Leander, Fatty Acids And Outcomes Research Consortium (Force)

Faculty, Staff and Students Publications

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.

METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were …

Digital Clock Drawing As An Alzheimer's Disease Susceptibility Biomarker: Associations With Genetic Risk Score And Apoe In Older Adults, L I Thompson, M Cummings, S Emrani, David J. Libon, A Ang, C Karjadi, R Au, C Liu

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection.

OBJECTIVE: We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker.

DESIGN: We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures.

SETTING: We used existing data …

Non-Coding Rnas Involved In The Molecular Pathology Of Alzheimer’S Disease: A Systematic Review, Reynand Jay Canoy, Jenica Clarisse Sy, Christian Deo Deguit, Caitlin Bridgette Castro, Lyoneil James Dimaapi, Beatrice Gabrielle Panlaqui, Wenzel Perian, Justine Yu, John Mark Velasco, Jesus Emmanuel Sevilleja, Anna Gibson

Ateneo School of Medicine and Public Health Publications

Alzheimer’s disease (AD) is the leading cause of dementia globally, having a pathophysiology that is complex and multifactorial. Recent findings highlight the significant role of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and piwi-interacting RNAs (piRNAs) in the molecular mechanisms underlying AD. These ncRNAs are involved in critical biological processes such as cell proliferation, apoptosis, oxidative stress, amyloid-beta aggregation, tau phosphorylation, neuroinflammation, and autophagy, which are pivotal in AD development and progression. This systematic review aims to consolidate current scientific knowledge on the role of ncRNAs in AD, making it the first to encompass …

Selecting And Evaluating Key Mds-Updrs Activities Using Wearable Devices For Parkinson's Disease Self-Assessment, Yuting Zhao, Xulong Wang, Xiyang Peng, Ziheng Li, Fengtao Nan, Menghui Zhuo, Jun Qi, Yun Yang, Zhong Zhao, Lida Xu, Po Yang

Information Technology & Decision Sciences Faculty Publications

Parkinson's disease (PD) is a complex neurodegenerative disease in the elderly. This disease has no cure, but assessing these motor symptoms will help slow down that progression. Inertial sensing-based wearable devices (ISWDs) such as mobile phones and smartwatches have been widely employed to analyse the condition of PD patients. However, most studies purely focused on a single activity or symptom, which may ignore the correlation between activities and complementary characteristics. In this paper, a novel technical pipeline is proposed for fine-grained classification of PD severity grades, which identify the most representative activities. We also propose a multi-activities combination scheme based …

Exploring Drivers Of Sex-Based Disparities In Relapsing Multiple Sclerosis, Stephanie K. Buxhoeveden

Theses and Dissertations

Females are three times more susceptible to relapsing multiple sclerosis (MS) and males typically have more severe disease, but the molecular underpinnings of these sex-based disease disparities are unknown and represent a critical knowledge gap.Subject Population: Blood samples from a demographically homogenous group of treatment naïve males and females with relapsing-MS and healthy controls. Research Design: Cross-sectional combinatorial omics pilot study. Instruments: Whole transcriptomic analysis with messenger RNA (mRNA) expression profiling using next generation sequencing (RNA-seq) and micro-RNA (miRNA) expression using NanoString technology. Aim 1) Identify and compare the actively expressed mRNAs in the transcriptome of males and …

Polygenic And Transcriptional Risk Scores Identify Chronic Obstructive Pulmonary Disease Subtypes In The Copdgene And Eclipse Cohort Studies, Matthew Moll, Julian Hecker, John Platig, Jingzhou Zhang, Auyon J. Ghosh, Katherine A. Pratte, Rui-Sheng Wang, Davin Hill, Iain R. Konigsberg, Joe W. Chiles, Craig P. Hersh, Peter J. Castaldi, Kimberly Glass, Jennifer G. Dy, Don D. Sin, Ruth Tal-Singer, Majd Mouded, Stephen I. Rennard, Gary P. Anderson, Gregory L. Kinney, Russell P. Bowler, Jeffrey L. Curtis, Merry-Lynn Mcdonald, Edwin K. Silverman, Brian D. Hobbs, Michael H. Cho

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics.

METHODS: We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein-protein interaction networks and drug repurposing …

Protein Biomarkers Gdf15 And Fgf21 To Differentiate Mitochondrial Hepatopathies From Other Pediatric Liver Diseases, Johan L K Van Hove, Marisa W Friederich, Dana K Strode, Roxanne A Van Hove, Kristen R Miller, Rohit Sharma, Hardik Shah, Jane Estrella, Linda Gabel, Simon Horslen, Rohit Kohli, Mark A Lovell, Alexander G Miethke, Jean P Molleston, Rene Romero, James E Squires, Estella M Alonso, Stephen L Guthery, Binita M Kamath, Kathleen M Loomes, Philip Rosenthal, Krupa R Mysore, Laurel A Cavallo, Pamela L Valentino, John C Magee, Shikha S Sundaram, Ronald J Sokol, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

BACKGROUND: Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies. We evaluated these biomarkers to determine if they discriminate MH from other liver diseases in children.

METHODS: Serum biomarkers were measured in 36 children with MH (17 had a genetic diagnosis); 38 each with biliary atresia, α1-antitrypsin deficiency, and Alagille syndrome; 20 with NASH; and 186 controls.

RESULTS: GDF15 levels compared to controls were …

Advances In The Clinical Application Of High-Throughput Proteomics, Miao Cui, Fei Deng, Mary L Disis, Chao Cheng, Lanjing Zhang

Faculty, Staff and Students Publications

High-throughput proteomics has become an exciting field and a potential frontier of modern medicine since the early 2000s. While significant progress has been made in the technical aspects of the field, translating proteomics to clinical applications has been challenging. This review summarizes recent advances in clinical applications of high-throughput proteomics and discusses the associated challenges, advantages, and future directions. We focus on research progress and clinical applications of high-throughput proteomics in breast cancer, bladder cancer, laryngeal squamous cell carcinoma, gastric cancer, colorectal cancer, and coronavirus disease 2019. The future application of high-throughput proteomics will face challenges such as varying protein …

Dna Mismatch Repair Defect And Intratumor Heterogeneous Deficiency Differently Impact Immune Responses In Diffuse Large B-Cell Lymphoma, Zijun Y Xu-Monette, Cancan Luo, Li Yu, Yong Li, Govind Bhagat, Alexandar Tzankov, Carlo Visco, Xiangshan Fan, Karen Dybkaer, Ali Sakhdari, Nicholas T Wang, Alyssa F Yuan, April Chiu, Wayne Tam, Youli Zu, Eric D Hsi, Anamarija M Perry, Wenting Song, Dennis O'Malley, Qingyan Au, Harry Nunns, Heounjeong Go, Michael B Møller, Benjamin M Parsons, Santiago Montes-Moreno, Maurilio Ponzoni, Andrés J M Ferreri, Aliyah R Sohani, Jeremy S Abramson, Bing Xu, Ken H Young

Faculty, Staff and Students Publications

Deficient (d) DNA mismatch repair (MMR) is a biomarker predictive of better response to PD-1 blockade immunotherapy in solid tumors. dMMR can be caused by mutations in MMR genes or by protein inactivation, which can be detected by sequencing and immunohistochemistry, respectively. To investigate the role of dMMR in diffuse large B-cell lymphoma (DLBCL), MMR gene mutations and expression of MSH6, MSH2, MLH1, and PMS2 proteins were evaluated by targeted next-generation sequencing and immunohistochemistry in a large cohort of DLBCL patients treated with standard chemoimmunotherapy, and correlated with the tumor immune microenvironment characteristics quantified by fluorescent multiplex immunohistochemistry and gene-expression …

Evaluation Of Potential Biomarkers For Lenvatinib Plus Pembrolizumab Among Patients With Advanced Endometrial Cancer: Results From Study 111/Keynote-146, Vicky Makker, Matthew H. Taylor, Carol Aghajanian, Allen L. Cohn, Marcia S. Brose, Christopher Di Simone, Zhu Alexander Cao, Leah Suttner, Andrey Loboda, Razvan Cristescu, Petar Jelinic, Robert Orlowski, Lea Dutta, Junji Matsui, Corina E. Dutcus, Yukinori Minoshima, Mark J. Messing

Department of Medical Oncology Faculty Papers

Background Lenvatinib plus pembrolizumab demonstrated clinically meaningful benefit in patients with previously treated advanced endometrial carcinoma in Study 111/KEYNOTE-146 (NCT02501096). In these exploratory analyses from this study, we evaluated the associations between clinical outcomes and gene expression signature scores and descriptively summarized response in biomarker subpopulations defined by tumor mutational burden (TMB) and DNA variants for individual genes of interest.

Methods Patients with histologically confirmed metastatic endometrial carcinoma received oral lenvatinib 20 mg once daily plus intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles. Archived formalin-fixed paraffin-embedded tissue was obtained from all patients. T-cell–inflamed gene expression …

Does Serum Uric Acid To Creatinine Ratio Predict Mortality Risk In Patients With Heart Failure, Xiaoqing Xi, Jinfeng Cai, Chen Zhang, Xuefei Wang

The Texas Heart Institute Journal

BACKGROUND: Previous studies have established a positive correlation between serum uric acid to creatinine (SUA/Cr) ratio and cardiovascular disease, but the relationship between SUA/Cr ratio and the prognosis of heart failure (HF) remains unknown. This study investigated the potential of SUA/Cr ratio as a prognostic predictor for patients with HF.

METHODS: This single-center prospective cohort study enrolled 2,122 patients with HF between March 2013 and June 2017. All patients were divided into 3 groups according to SUA/Cr ratio tertiles and were followed up with until December 31, 2022. The association between SUA/Cr ratio and the prognosis of HF was assessed …

Diagnostic Value Of Soluble Urokinase-Type Plasminogen Activator Receptor In Patients With Acute Coronary Syndrome: A Systematic Review And Meta-Analysis, Michal Pruc, Iwona Jannasz, Damian Swieczkowski, Grzegorz Procyk, Aleksandra Gasecka, Zubaid Rafique, Francesco Chirico, Nicola Luigi Bragazzi, Milosz J Jaguszewski, Jaroslaw Wysocki, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: In contemporary clinical practice, there is an increasing need for new clinically relevant biomarkers potentially optimizing management strategies in patients with suspected acute coronary syndrome (ACS). This study aimed to determine the diagnostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) levels in individuals with suspected ACS.

METHODS: A literature search was performed in Web of Science, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials databases, for studies comparing suPAR levels among patients with and without ACS groups. The methodological quality of the included papers was assessed using the Newcastle-Ottawa Scale (NOS). A fixed-effects model was used …

Meta-Analysis Of Postoperative Myocardial Injury As A Predictor Of Mortality After Living Donor Liver Transplantation, Krzysztof Jankowski, Frank W Peacock, Michal Pruc, Teresa Malecka-Massalska, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: The purpose of this study was to perform a systematic review and meta-analysis to investigate postoperative myocardial injury, as expressed by the postoperative concentration of high-sensitivity cardiac troponin I (hs-cTnI) as a predictor of mortality among living donor liver transplantation (LDLT) patients.

METHODS: PubMed, Scopus, Embase and the Cochrane Library were searched through to September 1st 2022. The primary endpoint included in-hospital mortality. Secondary endpoints were 1-year mortality and re-transplantation occurrence. Estimates are expressed as risk ratios (RRs) and 95% confidence intervals (95% CIs). Heterogeneity was assessed with the I² test.

RESULTS: During the search, 2 studies were found …

Predictive Metabolites For Incident Myocardial Infarction: A Two-Step Meta-Analysis Of Individual Patient Data From Six Cohorts Comprising 7897 Individuals From The Consortium Of Metabolomics Studies, Ana Nogal, Taryn Alkis, Yura Lee, Domagoj Kifer, Jie Hu, Rachel A Murphy, Zhe Huang, Rui Wang-Sattler, Gabi Kastenmüler, Birgit Linkohr, Clara Barrios, Marta Crespo, Christian Gieger, Annette Peters, Jackie Price, Kathryn M Rexrode, Bing Yu, Cristina Menni

Faculty, Staff and Student Publications

AIMS: Myocardial infarction (MI) is a major cause of death and disability worldwide. Most metabolomics studies investigating metabolites predicting MI are limited by the participant number and/or the demographic diversity. We sought to identify biomarkers of incident MI in the COnsortium of METabolomics Studies.

METHODS AND RESULTS: We included 7897 individuals aged on average 66 years from six intercontinental cohorts with blood metabolomic profiling (n = 1428 metabolites, of which 168 were present in at least three cohorts with over 80% prevalence) and MI information (1373 cases). We performed a two-stage individual patient data meta-analysis. We first assessed the associations …

Altered Outer Retinal Structure, Electrophysiology And Visual Perception In Parkinson's Disease, Katie K N Tran, Pei Ying Lee, David I Finkelstein, Allison M Mckendrick, Bao N Nguyen, Bang V Bui, Christine T O Nguyen

Faculty, Staff and Student Publications

BACKGROUND: Visual biomarkers of Parkinson's disease (PD) are attractive as the retina is an outpouching of the brain. Although inner retinal neurodegeneration in PD is well-established this has overlap with other neurodegenerative diseases and thus outer retinal (photoreceptor) measures warrant further investigation.

OBJECTIVE: To examine in a cross-sectional study whether clinically implementable measures targeting outer retinal function and structure can differentiate PD from healthy ageing and whether these are sensitive to intraday levodopa (L-DOPA) dosing.

METHODS: Centre-surround perceptual contrast suppression, macular visual field sensitivity, colour discrimination, light-adapted electroretinography and optical coherence tomography (OCT) were tested in PD participants (n = …

Biomarkers For Heart Failure Prediction And Prevention, Prasanti Alekhya Kotta, Vijay Nambi, Biykem Bozkurt

Faculty, Staff and Students Publications

Heart failure (HF) is a global pandemic affecting over 64 million people worldwide. Its prevalence is on an upward trajectory, with associated increasing healthcare expenditure. Organizations including the American College of Cardiology (ACC) and the American Heart Association (AHA) have identified HF prevention as an important focus. Recently, the ACC/AHA/Heart Failure Society of America (HFSA) Guidelines on heart failure were updated with a new Class IIa, Level of Evidence B recommendation for biomarker-based screening in patients at risk of developing heart failure. In this review, we evaluate the studies that have assessed the various roles and contributions of biomarkers in …

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 …

Serum Biomarkers Of Nociceptive And Neuropathic Pain In Chronic Pancreatitis, Jami L Saloman, Yan Li, Kimberly Stello, Wenhao Li, Shuang Li, Anna Evans Phillips, Kristen Hall, Evan L Fogel, Santhi Swaroop Vege, Liang Li, Dana K Andersen, William E Fisher, Christopher E Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Mark D Topazian, Stephen K Van Den Eeden, Jose Serrano, Darwin L Conwell, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were …

Alignment Between 24-H Light-Dark And Activity-Rest Rhythms Is Associated With Diabetes And Glucose Metabolism In A Nationally Representative Sample Of American Adults, Qian Xiao, John Durbin, Cici Bauer, Chris Ho Ching Yeung, Mariana G Figueiro

Faculty, Staff and Student Publications

OBJECTIVE: The alignment between environmental stimuli (e.g., dark, light) and behavior cycles (e.g., rest, activity) is an essential feature of the circadian timing system, a key contributor to metabolic health. However, no previous studies have investigated light-activity alignment in relation to glycemic control in human populations.

RESEARCH DESIGN AND METHODS: The analysis included ∼7,000 adults (aged 20-80 years) from the National Health and Nutrition Examination Survey (NHANES) (2011-2014) with actigraphy-measured, multiday, 24-h activity and light data. We used phasor analysis to derive phasor magnitude and phasor angle, which measures coupling strength and phase difference between the activity-rest and light-dark cycles, …