Diseases Commons^™

Role Of Biomarkers (Sflt-1/Plgf) In Cases Of Covid-19 For Distinguishing Preeclampsia And Guiding Clinical Management, Guilherme M Nobrega, Jose P Guida, Juliana M Novaes, Larissa M Solda, Luciana Pietro, Adriana G Luz, Giuliane J Lajos, Carolina C Ribeiro-Do-Valle, Renato T Souza, Jose G Cecatti, Indira U Mysorekar, Tabata Z Dias, Maria Laura Costa

Faculty, Staff and Students Publications

OBJECTIVES: To analyze soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factors (PlGF) concentrations and their ratio in pregnant and postpartum women with suspected COVID-19, and further investigate conditions associated with an increased ratio (sFlt-1/PlGF > 38), including preeclampsia (PE) and severe acute respiratory syndrome (SARS).

STUDY DESIGN: The present study is a secondary analysis of a prospective cohort. Blood samples were collected at time of COVID-19 investigation and the serum measurements of sFlt-1 and PlGF were performed. Clinical background, SARS-CoV-2 infection characteristics, maternal and perinatal outcomes were further analyzed.

MAIN OUTCOME MEASURES: Serum measurements of sFlt-1 and PlGF; obstetrics …

From Tuberculosis Bedside To Bench: Ube2b Splicing As A Potential Biomarker And Its Regulatory Mechanism, Mengyuan Lyu, Jian Zhou, Yanbing Zhou, Weelic Chong, Wei Xu, Hongli Lai, Lu Niu, Yang Hai, Xiaojun Yao, Sheng Gong, Qinglan Wang, Yi Chen, Yili Wang, Liyu Chen, Ganzi People's Hospital, Jiongjiong Zeng, Chengdi Wang, Binwu Ying

Student Papers, Posters & Projects

Alternative splicing (AS) is an important approach for pathogens and hosts to remodel transcriptome. However, tuberculosis (TB)-related AS has not been sufficiently explored. Here we presented the first landscape of TB-related AS by long-read sequencing, and screened four AS events (S100A8-intron1-retention intron, RPS20-exon1-alternaitve promoter, KIF13B-exon4-skipping exon (SE) and UBE2B-exon7-SE) as potential biomarkers in an in-house cohort-1. The validations in an in-house cohort-2 (2274 samples) and public datasets (1557 samples) indicated that the latter three AS events are potential promising biomarkers for TB diagnosis, but not for TB progression and prognosis. The excellent performance of classifiers further underscored the diagnostic value …

Association Of Circulating Mtdna With Cvd In Hemodialysis Patients And In Vitro Effect Of Exogenous Mtdna On Cardiac Microvascular Inflammation, Zhen Fan, Ya Feng, Li Zang, Yi Guo, Xiao-Yi Zhong

Faculty, Staff and Student Publications

BACKGROUND: Chronic kidney disease (CKD) patients sustain a fairly high prevalence of cardiovascular disease (CVD). Microvascular inflammation is an early manifestation of CVD, and the released mitochondrial DNA (MtDNA) has been proposed to be a crucial integrator of inflammatory signals. Herein, the aim of this study was to determine the relationship between CVD, microvessel, and circulating MtDNA in the settings of uremia.

METHODS: Forty-two maintenance hemodialysis (MHD) patients and 36 health controls were enrolled in this study. Plasma cell-free MtDNA was detected by TaqMan-based qPCR assay. CVD risk markers including high-sensitive C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), fibrinogen, and …

Capture Als: The Comprehensive Analysis Platform To Understand, Remedy And Eliminate Als, Vincent Picher-Martel, Claire Magnussen, Mathieu Blais, Tania M. Bubela, Samir Das, Annie Dionne, Alan C. Evans, Angela Genge, Russell Greiner, Yasser Iturria-Medina

Office of the Provost

The absence of disease modifying treatments for amyotrophic lateral sclerosis (ALS) is in large part a consequence of its complexity and heterogeneity. Deep clinical and biological phenotyping of people living with ALS would assist in the development of effective treatments and target specific biomarkers to monitor disease progression and inform on treatment efficacy. The objective of this paper is to present the Comprehensive Analysis Platform To Understand Remedy and Eliminate ALS (CAPTURE ALS), an open and translational platform for the scientific community currently in development. CAPTURE ALS is a Canadian-based platform designed to include participants' voices in its development and …

The Performance Of Afp, Afp-3, Dcp As Biomarkers For Detection Of Hepatocellular Carcinoma (Hcc): A Phase 3 Biomarker Study In The United States, Nabihah Tayob, Fasiha Kanwal, Abeer Alsarraj, Ruben Hernaez, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: α-fetoprotein (AFP), AFP Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP) in combination or in GALAD (Gender, Age, AFP-L3, AFP, and DCP) were tested for hepatocellular carcinoma (HCC) surveillance in retrospective cohort and case-control studies. However, there is a paucity of prospective data and no phase III biomarker studies from North American populations.

METHODS: We conducted a prospective specimen collection, retrospective blinded evaluation (PRoBE) cohort study in patients with cirrhosis enrolled in a 6-monthly surveillance with liver imaging and AFP. Blood samples were prospectively collected every 6 months and analyzed in a retrospective blinded …

Serum Biomarkers Correlated With Liver Stiffness Assessed In A Multicenter Study Of Pediatric Cholestatic Liver Disease, Daniel H Leung, Sridevi Devaraj, Nathan P Goodrich, Xinpu Chen, Deepthi Rajapakshe, Wen Ye, Victor Andreev, Charles G Minard, Danielle Guffey, Jean P Molleston, Lee M Bass, Saul J Karpen, Binita M Kamath, Kasper S Wang, Shikha S Sundaram, Philip Rosenthal, Patrick Mckiernan, Kathleen M Loomes, M Kyle Jensen, Simon P Horslen, Jorge A Bezerra, John C Magee, Robert M Merion, Ronald J Sokol, Benjamin L Shneider, Estella Alonso, Lee Bass, Susan Kelly, Mary Riordan, Hector Melin-Aldana, Jorge Bezerra, Kevin Bove, James Heubi, Alexander Miethke, Greg Tiao, Julie Denlinger, Erin Chapman, Ronald Sokol, Amy Feldman, Cara Mack, Michael Narkewicz, Frederick Suchy, Shikha S Sundaram, Johan Van Hove, Benigno Garcia, Mikaela Kauma, Kendra Kocher, Matthew Steinbeiss, Mark Lovell, Kathleen M Loomes, David Piccoli, Elizabeth Rand, Pierre Russo, Nancy Spinner, Jessi Erlichman, Samantha Stalford, Dina Pakstis, Sakya King, Robert Squires, Rakesh Sindhi, Veena Venkat, Kathy Bukauskas, Patrick Mckiernan, Lori Haberstroh, James Squires, Philip Rosenthal, Laura Bull, Joanna Curry, Camille Langlois, Grace Kim, Jeffery Teckman, Vikki Kociela, Rosemary Nagy, Shraddha Patel, Jacqueline Cerkoski, Jean P Molleston, Molly Bozic, Girish Subbarao, Ann Klipsch, Cindy Sawyers, Oscar Cummings, Simon P Horslen, Karen Murray, Evelyn Hsu, Kara Cooper, Melissa Young, Laura Finn, Binita M Kamath, Vicky Ng, Claudia Quammie, Juan Putra, Deepika Sharma, Aishwarya Parmar, Stephen Guthery, Kyle Jensen, Ann Rutherford, Amy Lowichik, Linda Book, Rebecka Meyers, Tyler Hall, Kasper S Wang, Sonia Michail, Danny Thomas, Catherine Goodhue, Rohit Kohli, Larry Wang, Nisreen Soufi, Daniel Thomas, Saul Karpen, Nitika Gupta, Rene Romero, Miriam B Vos, Rita Tory, John-Paul Berauer, Carlos Abramowsky, Jeanette Mcfall, Benjamin L Shneider, Sanjiv Harpavat, Paula Hertel, Daniel Leung, Mary Tessier, Deborah Schady, Laurel Cavallo, Diego Olvera, Christina Banks, Cynthia Tsai, Richard Thompson, Edward Doo, Jay Hoofnagle, Averell Sherker, Rebecca Torrance, Sherry Hall, John Magee, Robert Merion, Cathie Spino, Wen Ye

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.

APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM …

A Method Using Longitudinal Laboratory Data To Predict Future Intestinal Complication In Patients With Crohn's Disease, James Irwin, Anton Lord, Emma Ferguson, Lisa A Simms, Katherine Hanigan, Carlos A Montoya, Graham Radford-Smith

Faculty, Staff and Student Publications

Background

Stenosis, fistulization, and perforation of the bowel are severe outcomes which can occur in patients with Crohn’s disease. Accurate prediction of these events may enable clinicians to alter treatment strategies and avoid these outcomes.

Aims

To study the correlation between longitudinal laboratory testing and subsequent intestinal complications in patients with Crohn’s disease.

Methods

An observational cohort of patients with Crohn’s disease at a single center were analyzed between 01/01/1994 and 06/30/2016. A complication was defined as the development of an intestinal fistula, stenosis, or perforation. Exploratory analysis using Cox regression was performed to select the best statistical method to …

Impact Of Enteropathogens On Faltering Growth In A Resource-Limited Setting, Furqan Kabir, Junaid Iqbal, Zehra Jamil, Najeeha Talat Iqbal, Fatima Aziz, Adil Kalam, Sahrish Muneer, Aneeta Hotwani, Sheraz Ahmed, Fayyaz Umrani, Sana Syed, Kamran Sadiq, Syed Asad Ali

Department of Paediatrics and Child Health

Introduction: Environmental enteropathy is an important contributor to childhood malnutrition in the developing world. Chronic exposure to fecal pathogens leads to alteration in intestinal structure and function, resulting in impaired gut immune function, malabsorption, and growth faltering leading to environmental enteropathy.
Methods: A community-based intervention study was carried out on children till 24 months of age in Matiari district, Pakistan. Blood and fecal specimens were collected from the enrolled children aged 3-6 and 9 months. A real-time PCR-based TaqMan array card (TAC) was used to detect enteropathogens.
Results: Giardia, Campylobacter spp., enteroaggregative Escherichia coli (EAEC), Enteropathogenic Escherichia coli (EPEC), …

Histopathologic And Proteogenomic Heterogeneity Reveals Features Of Clear Cell Renal Cell Carcinoma Aggressiveness, Yize Li, Tung-Shing M Lih, Saravana M Dhanasekaran, Rahul Mannan, Lijun Chen, Marcin Cieslik, Yige Wu, Rita Jiu-Hsien Lu, David J Clark, Iga Kołodziejczak, Runyu Hong, Siqi Chen, Yanyan Zhao, Seema Chugh, Wagma Caravan, Nataly Naser Al Deen, Noshad Hosseini, Chelsea J Newton, Karsten Krug, Yuanwei Xu, Kyung-Cho Cho, Yingwei Hu, Yuping Zhang, Chandan Kumar-Sinha, Weiping Ma, Anna Calinawan, Matthew A Wyczalkowski, Michael C Wendl, Yuefan Wang, Shenghao Guo, Cissy Zhang, Anne Le, Aniket Dagar, Alex Hopkins, Hanbyul Cho, Felipe Da Veiga Leprevost, Xiaojun Jing, Guo Ci Teo, Wenke Liu, Melissa A Reimers, Russell Pachynski, Alexander J Lazar, Arul M Chinnaiyan, Brian A Van Tine, Bing Zhang, Karin D Rodland, Gad Getz, D R Mani, Pei Wang, Feng Chen, Galen Hostetter, Mathangi Thiagarajan, W Marston Linehan, David Fenyö, Scott D Jewell, Gilbert S Omenn, Rohit Mehra, Maciej Wiznerowicz, Ana I Robles, Mehdi Mesri, Tara Hiltke, Eunkyung An, Henry Rodriguez, Daniel W Chan, Christopher J Ricketts, Alexey I Nesvizhskii, Hui Zhang, Li Ding, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Students Publications

Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 …

Discovery Of A Missense Mutation (Q222k) Of The Apoe Gene From The Australian Imaging, Biomarker And Lifestyle Study, Blaine R. Roberts, Scott B. Laffoon, Anne M. Roberts, Tenielle Porter, Chris Fowler, Colin L. Masters, Edward A. Dratz, Simon M. Laws

Research outputs 2022 to 2026

After age, polymorphisms of the Apolipoprotein E (APOE) gene are the biggest risk factor for the development of Alzheimer's disease (AD). During our investigation to discovery biomarkers in plasma, using 2D gel electrophoresis, we found an individual with and unusual apoE isoelectric point compared to APOE ϵ2, ϵ3, and ϵ4 carriers. Whole exome sequencing of APOE from the donor confirmed a single nucleotide polymorphism (SNP) in exon 4, translating to a rare Q222K missense mutation. The apoE ϵ4 (Q222K) mutation did not form dimers or complexes observed for apoE ϵ2 ϵ3 proteins.

Detectable Ctdna At The Time Of Treatment Cessation Of Ipilimumab And Nivolumab For Toxicity Predicts Disease Progression In Advanced Melanoma Patients, Lydia Warburton, Anna Reid, Benhur Amanuel, Leslie Calapre, Michael Millward, Elin Gray

Research outputs 2022 to 2026

Background: Immune checkpoint inhibition (ICI) has led to unprecedented outcomes for melanoma patients but is associated with toxicity. ICI resumption after high grade irAEs poses a significant challenge in the clinical management of melanoma patients and there are no biomarkers that can help identify patients that might benefit from resuming treatment. This study aims to determine if circulating tumor DNA (ctDNA) levels at the time of treatment-limiting irAE could guide treatment decisions in this clinical context. Methods: This is a retrospective exploratory biomarker study from 34 patients treated with combination ICI for stage IV melanoma. Patients had a treatment-limiting toxicity …

Association Between Immunoglobulin G N-Glycosylation And Lupus Nephritis In Female Patients With Systemic Lupus Erythematosus: A Case-Control Study, Xinxia Lu, Liangao Wang, Meng Wang, Yuejin Li, Qinqin Zhao, Yanjun Shi, Yujing Zhang, Yingjie Wang, Wei Wang, Long Ji, Haifeng Hou, Dong Li

Research outputs 2022 to 2026

Background: Lupus nephritis (LN) is a crucial complication of systemic lupus erythematosus (SLE) and has important clinical implications in guiding treatment. N-glycosylation of immunoglobulin G (IgG) plays a key role in the development of SLE by affecting the balance of anti-inflammatory and proinflammatory responses. This study aimed to evaluate the performance of IgG N-glycosylation for diagnosing LN in a sample of female SLE patients. Methods: This case-control study recruited 188 women with SLE, including 94 patients with LN and 94 age-matched patients without LN. The profiles of plasma IgG N-glycans were detected by hydrophilic interaction chromatography with ultra-performance liquid chromatography …

Ultrahigh Resolution Lipid Mass Spectrometry Imaging Of High-Grade Serous Ovarian Cancer Mouse Models, Xin Ma, Andro Botros, Sylvia R Yun, Eun Young Park, Olga Kim, Soojin Park, Thu-Huyen Pham, Ruihong Chen, Murugesan Palaniappan, Martin M Matzuk, Jaeyeon Kim, Facundo M Fernández

Faculty, Staff and Students Publications

No effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering that little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights into how metabolic and signaling alterations accompany its development. Herein, we present a comprehensive study using ultra-high-resolution Fourier transform ion cyclotron resonance matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to investigate the spatial distribution and alterations of lipids in ovarian tissues collected from double knockout (n = 4) and triple mutant mouse models (n …

Lymphangioleiomyomatosis: Circulating Levels Of Fgf23 And Pulmonary Diffusion, Anthony J Esposito, Jewel Imani, Shikshya Shrestha, Shefali Bagwe, Anthony M Lamattina, Marina Vivero, Hilary J Goldberg, Ivan O Rosas, Elizabeth P Henske, Souheil Y El-Chemaly

Faculty, Staff and Students Publications

OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM.

METHODS: This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM …

Identification And Validation Of Igg N-Glycosylation Biomarkers Of Esophageal Carcinoma, Huiying Pan, Zhiyuan Wu, Haiping Zhang, Jie Zhang, Yue Liu, Zhiwei Li, Wei Feng, Guiqi Wang, Yong Liu, Deli Zhao, Zhiyi Zhang, Yuqin Liu, Zhe Zhang, Xiangtong Liu, Lixin Tao, Yanxia Luo, Xiaonan Wang, Xinghua Yang, Feng Zhang, Xia Li, Xiuhua Guo

Research outputs 2022 to 2026

Introduction: Altered Immunoglobulin G (IgG) N-glycosylation is associated with aging, inflammation, and diseases status, while its effect on esophageal squamous cell carcinoma (ESCC) remains unknown. As far as we know, this is the first study to explore and validate the association of IgG N-glycosylation and the carcinogenesis progression of ESCC, providing innovative biomarkers for the predictive identification and targeted prevention of ESCC. Methods: In total, 496 individuals of ESCC (n=114), precancerosis (n=187) and controls (n=195) from the discovery population (n=348) and validation population (n=148) were recruited in the study. IgG N-glycosylation profile was analyzed and an ESCC-related glycan score was …

Sixteen-Year Longitudinal Evaluation Of Blood-Based Dna Methylation Biomarkers For Early Prediction Of Alzheimer's Disease, Fernanda Schäfer Hackenhaar, Maria Josefsson, Annelie Nordin Adolfsson, Mattias Landfors, Karolina Kauppi, Tenielle Porter, Lidija Milicic, Simon M. Laws, Magnus Hultdin, Rolf Adolfsson, Sofie Degerman, Sara Pudas, Australian Imaging Biomarkers And Lifestyle Study

Research outputs 2022 to 2026

BACKGROUND: DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, has shown promise for Alzheimer's disease (AD) prediction. OBJECTIVE: Testing long-term predictive ability ( > 15 years) of existing DNAm-based epigenetic age acceleration (EAA) measures and identifying novel early blood-based DNAm AD-prediction biomarkers. METHODS: EAA measures calculated from Illumina EPIC data from blood were tested with linear mixed-effects models (LMMs) in a longitudinal case-control sample (50 late-onset AD cases; 51 matched controls) with prospective data up to 16 years before clinical onset, and post-onset follow-up. Novel DNAm biomarkers were generated with epigenome-wide LMMs, and Sparse Partial Least Squares …

Machine Learning Of Plasma Metabolome Identifies Biomarker Panels For Metabolic Syndrome: Findings From The China Suboptimal Health Cohort, Hao Wang, Youxin Wang, Xingang Li, Xuan Deng, Yuanyuan Kong, Wei Wang, Yong Zhou

Research outputs 2022 to 2026

Background: Metabolic syndrome (MetS) has been proposed as a clinically identifiable high-risk state for the prediction and prevention of cardiovascular diseases and type 2 diabetes mellitus. As a promising “omics” technology, metabolomics provides an innovative strategy to gain a deeper understanding of the pathophysiology of MetS. The study aimed to systematically investigate the metabolic alterations in MetS and identify biomarker panels for the identification of MetS using machine learning methods. Methods: Nuclear magnetic resonance-based untargeted metabolomics analysis was performed on 1011 plasma samples (205 MetS patients and 806 healthy controls). Univariate and multivariate analyses were applied to identify metabolic biomarkers …

An Imaging Mass Spectrometry Investigation Into The N-Linked Glycosylation Landscape Of Pancreatic Ductal Adenocarcinoma And The Development Of Associated Tools For Enhanced Glycan Separation And Characterization, Colin Mcdowell

MUSC Theses and Dissertations

The severity of pancreatic ductal adenocarcinoma (PDAC) is largely attributed to a failure to detect the disease before metastatic spread has occurred. CA19-9, a carbohydrate biomarker, is used clinically to surveille disease progression, but due to specificity challenges is not suitable for early discovery. As CA19-9 and other prospective markers are glycan epitopes, there is great clinical interest in understanding the glycobiology of pancreatic cancer. Unfortunately, few studies have been able to link glycosylation changes directly to pancreatic tumors and instead have focused on peripheral glycan alterations in the serum of PDAC patients. To address this gap in our understanding, …

Current Insights On The Use Of Insulin And The Potential Use Of Insulin Mimetics In Targeting Insulin Signalling In Alzheimer’S Disease, Amy Woodfield, Tatiana Gonzales, Erik Helmerhorst, Simon Laws, Philip Newsholme, Tenielle Porter, Giuseppe Verdile

Research outputs 2022 to 2026

Alzheimer’s disease (AD) and type 2 diabetes (T2D) are chronic diseases that share several pathological mechanisms, including insulin resistance and impaired insulin signalling. Their shared features have prompted the evaluation of the drugs used to manage diabetes for the treatment of AD. Insulin delivery itself has been utilized, with promising effects, in improving cognition and reducing AD related neuropathology. The most recent clinical trial involving intranasal insulin reported no slowing of cognitive decline; however, several factors may have impacted the trial outcomes. Long-acting and rapid-acting insulin analogues have also been evaluated within the context of AD with a lack of …

Abnormalities In Cardiac And Inflammatory Biomarkers In Ambulatory Subjects After Covid-19 Infection, Joshua A Keefe, Vasanthi Avadhanula, Erin G Nicholson, Sridevi Devaraj, Pedro A Piedra, Biykem Bozkurt, Xander H T Wehrens

Faculty, Staff and Students Publications

BACKGROUND: Coronavirus-2019 (COVID-19) is known to affect the heart and is associated with a pro-inflammatory state. Most studies to date have focused on clinically sick subjects. Here, we report cardiac and proinflammatory biomarkers levels in ambulatory young adults with asymptomatic or mild COVID-19 infection compared to those without infection 4-8 weeks after severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) testing.

METHODS: 131 asymptomatic or mildly symptomatic subjects were enrolled following testing for SARS-COV-2. Fifty subjects tested negative, and 81 subjects tested positive. Serum samples were collected for measurement of C-reactive protein, ferritin, interleukin-6, NT-pro-B-type natriuretic peptide, and cardiac troponin 28-55 …

Identifying Voice-Based Digital Biomarkers Of Parkinson's Disease, Rachelle Beshay, Madison Gill, Michael Shiraishi, Rahul Soangra

Student Scholar Symposium Abstracts and Posters

Introduction: Parkinson's disease is a disorder in the central nervous system that causes tremors, abnormal gait and balance, and muscle rigidity due to loss of function in parts of the brain. Traditionally, Parkinson's is identified by the physical symptoms seen in a patient's gait and motor skills, but irregular speech patterns (hypokinetic dysarthria) is one of the first symptoms to be derived from the disease. Objective: The goal of this ongoing study is to use Mel Frequency Centrum Coefficients (MFCC), to diagnose Parkinson's in the early stages by identifying hypokinetic dysarthria. MFCC's process speech recognition patterns and produce …

Relationship Between Preprocedural Lipid Levels And Periprocedural Myocardial Injury In Patients Undergoing Elective Percutaneous Coronary Intervention, Mohsen Maadani, Nima Sari Sarraf, Sanam Alilou, Kamran Aeinfar, Parham Sadeghipour, Ali Zahedmehr, Mahmood Sheikh Fathollahi, Seyyed Isa Hashemi Ghadi, Abbas Zavarehee, Maryam Zolfaghari, Reza Zolfaghari

The Texas Heart Institute Journal

BACKGROUND: Periprocedural myocardial injury is a predictor of cardiovascular morbidity and mortality after percutaneous coronary intervention.

METHODS: The authors examined the effects of preprocedural lipid levels (low-density lipoprotein, high-density lipoprotein, and triglycerides) in 977 patients with coronary artery disease who underwent elective percutaneous coronary intervention.

RESULTS: Elevated cardiac troponin I level (≥5× the upper limit of normal) was used to indicate periprocedural myocardial injury. Serum lipid samples were collected 12 hours preprocedurally. Cardiac troponin I was collected 1, 6, and 12 hours postprocedurally. Correlations between preprocedural lipid levels and postprocedural cardiac troponin I were studied. Low-density lipoprotein levels were less …

Nab-Paclitaxel, Capecitabine, And Radiation Therapy After Induction Chemotherapy In Treating Patients With Locally Advanced And Borderline Resectable Pancreatic Cancer: Phase 1 Trial And Imaging-Based Biomarker Validation, Eugene J Koay, Mohamed Zaid, Maureen Aliru, Polycarpe Bagereka, Arie Van Wieren, Maria Jovie Rodriguez, Galia Jacobson, Robert A Wolff, Michael Overman, Gauri Varadhachary, Shubham Pant, Huamin Wang, Ching-Wei Tzeng, Naruhiko Ikoma, Michael Kim, Jeffrey E Lee, Matthew Hg Katz, Eric Tamm, Priya Bhosale, Cullen M Taniguchi, Emma B Holliday, Grace L Smith, Ethan B Ludmir, Bruce D Minsky, Christopher H Crane, Albert C Koong, Prajnan Das, Xuemei Wang, Milind Javle, Sunil Krishnan

Faculty, Staff and Student Publications

PURPOSE: Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response.

METHODS AND MATERIALS: Eligible patients had pathologically confirmed pancreatic ductal adenocarcinoma, underwent computed tomography-imaging, received a diagnosis of LAPC or BRPC, and received induction chemotherapy. Standard 3 + 3 study design was used, with 3 escalating nab-paclitaxel dose levels (50, 75, and 100 mg/m

RESULTS: Twenty-three patients started and finished …

Tryptophan Oxidation In Young Children With Environmental Enteric Dysfunction Classified By The Lactulose Rhamnose Ratio, Nirupama Shivakumar, Jean W Hsu, Sindhu Kashyap, Tinku Thomas, Anura V Kurpad, Farook Jahoor

Faculty, Staff and Students Publications

BACKGROUND: In young children, associations between linear growth faltering, environmental enteric dysfunction (EED), and the plasma kynurenine (Kyn)/tryptophan (Trp) ratio (KTR) have led to the proposal that higher Trp catabolism in response to intestinal/systemic inflammation limits Trp availability for protein synthesis, resulting in impaired growth.

OBJECTIVES: We sought to estimate the Trp oxidation rate and the Trp conversion rate to Kyn in young children with and without EED.

METHODS: Children aged 18-24 mo, from urban slums, were assigned to EED (n = 19) or no-EED (n = 26) groups on the basis of a urinary lactulose/rhamnose ratio (LRR) cutoff based …

Immunogenomic Profiling Of Lung Adenocarcinoma Reveals Poorly Differentiated Tumors Are Associated With An Immunogenic Tumor Microenvironment, Neal Akhave, Jiexin Zhang, Erin Bayley, Meredith Frank, Shin-Heng Chiou, Carmen Behrens, Runzhe Chen, Xin Hu, Edwin Roger Parra, Won-Chul Lee, Stephen Swisher, Luisa Solis, Annikka Weissferdt, Cesar Moran, Neda Kalhor, Jianhua Zhang, Paul Scheet, Ara A Vaporciyan, Boris Sepesi, Don L Gibbons, John V Heymach, Jack J Lee, Ignacio I Wistuba, P Andrew Futreal, Jianjun Zhang, Junya Fujimoto, Alexandre Reuben

Faculty, Staff and Student Publications

OBJECTIVES: Pathologists have routinely observed distinct histologic patterns of growth in early-stage lung adenocarcinoma (LUAD), which have been suggested to be associated with prognosis. Herein, we investigated the relationship between LUAD patterns of growth, as defined by the updated international association for the study of lung cancer (IASLC) grading criteria, and differences in the tumor immune microenvironment to identify predictors of response to immunotherapy.

METHODS: 174 resected stage I-III LUAD tumors were classified by histologic pattern of growth (i.e. solid, micropapillary, acinar, papillary, and lepidic) and then grouped as well differentiated, moderately differentiated, and poorly differentiated. Comprehensive multiplatform analysis including …

Systematically Higher Ki67 Scores On Core Biopsy Samples Compared To Corresponding Resection Specimen In Breast Cancer: A Multi-Operator And Multi-Institutional Study, Balazs Acs, Samuel C Y Leung, Kelley M Kidwell, Indu Arun, Renaldas Augulis, Sunil S Badve, Yalai Bai, Anita L Bane, John M S Bartlett, Jane Bayani, Gilbert Bigras, Annika Blank, Henk Buikema, Martin C Chang, Robin L Dietz, Andrew Dodson, Susan Fineberg, Cornelia M Focke, Dongxia Gao, Allen M Gown, Carolina Gutierrez, Johan Hartman, Zuzana Kos, Anne-Vibeke Lænkholm, Arvydas Laurinavicius, Richard M Levenson, Rustin Mahboubi-Ardakani, Mauro G Mastropasqua, Sharon Nofech-Mozes, C Kent Osborne, Frédérique M Penault-Llorca, Tammy Piper, Mary Anne Quintayo, Tilman T Rau, Stefan Reinhard, Stephanie Robertson, Roberto Salgado, Tomoharu Sugie, Bert Van Der Vegt, Giuseppe Viale, Lila A Zabaglo, Daniel F Hayes, Mitch Dowsett, Torsten O Nielsen, David L Rimm, International Ki67 In Breast Cancer Working Group Of The Breast International Group And North American Breast Cancer Group (Big-Nabcg)

Faculty, Staff and Students Publications

Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut …

Preoperative Inflammatory Markers As Prognostic Predictors After Hepatocellular Carcinoma Resection: Data From A Western Referral Center, João Paulo Maciel Silva, Fabricio Ferreira Coelho, Alex Jones Flores Cassenote, Vagner Birk Jeismann, Gilton Marques Fonseca, Jaime Arthur Pirola Kruger, José Donizeti De Meira Júnior, Sérgio Carlos Nahas, Paulo Herman

Faculty, Staff and Student Publications

BACKGROUND: Recent studies from eastern centers have demonstrate an association between inflammatory response and long-term outcomes after hepatocellular carcinoma (HCC) resection. However, the prognostic impact of inflammatory markers in western patients, with distinct tumor and epidemiologic features, is still unknown.

AIM: To evaluate the prognostic impact of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), as well as their impact according to tumor size (< 5 cm, 5-10 cm, > 10 cm) in patients undergoing HCC resection with curative intent.

METHODS: Optimal cut-off values for NLR, PLR, and MLR were determined by plotting the receiver operator curves. Overall survival (OS) and disease-free …

Metabolites From Trypanosome-Infected Cattle As Sensitive Biomarkers For Animal Trypanosomosis, Merid N. Getahun, John Ngiela, John Mark O. Makwatta, Peter Ahuya, Tawich K. Simon, Samuel K. Kamau, Baldwyn Torto, Daniel Masiga

All Peer-Reviewed Publications

Trypanosomes are important global livestock and human pathogens of public health importance. Elucidating the chemical mechanisms of trypanosome-relevant host interactions can enhance the design and development of a novel, next-generation trypanosomosis diagnostics. However, it is unknown how trypanosome infection affects livestock volatile odors. Here, we show that Trypanosoma congolense and Trypanosoma vivax infections induced dihydro-β- ionone and junenol, while abundance of dihydro-α-ionone, phenolics, p-cresol, and 3-propylphenol significantly elevated in cow urine. These biomarkers of trypanosome infection are conserved in cow breath and the urine metabolites of naturally infected cows, regardless of population, diet, or environment differences. Furthermore, treating trypanosome-infected cows …

Landscape Of Notch1 Mutations And Co-Occurring Biomarker Alterations In Chronic Lymphocytic Leukemia, Fatima Zahra Jelloul, Richard Yang, Sofia Garces, Rashmi Kanagal-Shamanna, Chi Y Ok, Sanam Loghavi, Mark J Routbort, Zhuang Zuo, C Cameron Yin, Kristen Floyd, Roland L Bassett, William Wierda, Nitin Jain, Philip Thompson, Rajyalakshmi Luthra, L Jeffrey Medeiros, Keyur P Patel

Faculty, Staff and Student Publications

NOTCH1 is one of the most frequently mutated genes in chronic lymphocytic leukemia and has emerged as a marker of poor prognosis. In addition to coding NOTCH1 mutations involving exon 34, non-coding NOTCH1 mutations involving the 3' UTR have been described in a limited number of chronic lymphocytic leukemia (CLL) patients and were associated with adverse outcomes. In this study, 1574 CLL patients were assessed using targeted sequencing with a 29 gene panel and the results were correlated with prognostic characteristics. NOTCH1 mutations were detected in 252 (16%) patients, including both coding (220/252, 14%), non-coding (24/252, 1.5%) and a mixture …

Markers Of Kidney Function, Genetic Variation Related To Cognitive Function, And Cognitive Performance In The Uk Biobank, Erin L Richard, Linda K Mcevoy, Ian J Deary, Gail Davies, Steven Y Cao, Eyal Oren, John E Alcaraz, Andrea Z Lacroix, Jan Bressler, Rany M Salem

Faculty, Staff and Student Publications

BACKGROUND: Chronic kidney disease has been linked to worse cognition. However, this association may be dependent on the marker of kidney function used, and studies assessing modification by genetics are lacking. This study examined associations between multiple measures of kidney function and assessed effect modification by a polygenic score for general cognitive function.

METHODS: In this cross-sectional study of up to 341,208 European ancestry participants from the UK Biobank study, we examined associations between albuminuria and estimated glomerular filtration rate based on creatinine (eGFRcre) or cystatin C (eGFRcys) with cognitive performance on tests of verbal-numeric reasoning, reaction time and visual …