Medical Specialties Commons^™

Chemohormonal Therapy In Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis Of The Randomized Phase Iii E3805 Chaarted Trial, Christos E. Kyriakopoulos, Yu-Hui Chen, Michael A. Carducci, Glenn Liu, David F. Jarrard, Noah M. Hahn, Daniel H. Shevrin, Robert Dreicer, Maha Hussain, Mario Eisenberger, Manish Kohli, Elizabeth R. Plimack, Nicholas J. Vogelzang, Joel Picus, Matthew M. Cooney, Jorge A. Garcia, Robert S. Dipaola, Christopher J. Sweeney

Internal Medicine Faculty Publications

Purpose

Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume.

Patients and Methods

In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/mm² for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional …

Insufficiency Of Dna Repair Enzyme Atm Promotes Naive Cd4 T-Cell Loss In Chronic Hepatitis C Virus Infection, Juan Zhao, Xindi Dang, Peixin Zhang, Lam Nhat Nguyen, Dechao Cao, Lin Wang, Xiaoyuan Wu, Zheng D. Morrison, Ying Zhang, Zhansheng Jia, Qian Xie, Ling Wang, Shunbin Ning, Mohamed El Gazzar, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

T cells have a crucial role in viral clearance and vaccine response; however, the mechanisms regulating their responses to viral infections or vaccinations remain elusive. In this study, we investigated T-cell homeostasis, apoptosis, DNA damage, and repair machineries in a large cohort of subjects with hepatitis C virus (HCV) infection. We found that naive CD4 T cells in chronically HCV-infected individuals (HCV T cells) were significantly reduced compared with age-matched healthy subjects. In addition, HCV T cells were prone to apoptosis and DNA damage, as evidenced by increased 8-oxoguanine expression and γH2AX/53BP1-formed DNA damage foci—hallmarks of DNA damage responses. Mechanistically, …

Global Burden Of Neuroendocrine Tumors And Changing Incidence In Kentucky, Aman Chauhan, Qian Yu, Neha Ray, Zainab Farooqui, Bin Huang, Eric B. Durbin, Thomas Tucker, B. Mark Evers, Susanne Arnold, Lowell B. Anthony

Markey Cancer Center Faculty Publications

Background: Neuroendocrine tumors (NETs) have a low incidence but relatively high prevalence. Over the last three decades, the incidence of NETs has risen 6-fold in the United States. We conducted an observational study to compare the incidence of NETs reported to the Kentucky Cancer Registry (KCR) versus that reported to Surveillance, Epidemiology, and End Results Program (SEER). We also provide a systematic review of the state of neuroendocrine tumors worldwide, and compare the available global and local published data.

Methods: KCR and SEER databases were queried for NET cases between 1995 and 2015. A detailed literature review of epidemiological data …

Optimizing Vaccine Immunotherapy For Prostate Cancer, G. Hattier, E. K. Bongiorno, C. Portocarrero, Trevor R. Baybutt, Adam E. Snook, U. Rodeck

Sigma Xi Student Research Day

Introduction: Treatment options for metastatic prostate cancer are limited and cures are rare. In other cancers immunotherapy has shown remarkable efficacy in certain patient subsets particularly when combined with other treatment modalities. Our previous work showed that combining radiation and vaccine therapy slows the growth of syngeneic prostate cancer in mice more effectively than single modality treatment arms. Here we tested the hypothesis that addition of immune checkpoint inhibitors targeting the PD1/PD-L1 axis further improves efficacy of the dual radiation/vaccine treatment.

Methods: Mice were injected with tumor cells expressing human prostate specific antigen (TPSA-23). The mice were divided into six …

Near-Infrared Spectroscopy’S Predictive Ability Of Neurological Injury In Ecmo Patients, Spencer Liem, Bs, Nicholas Cavarocchi, Md, Hitoshi Hirose, Md, Phd

Sigma Xi Student Research Day

Objectives

• Elucidate sensitivity and specificity of NIRS in detecting neurological injury
• Determine magnitude of NIRS decline in ECMO patients with neurologic injury
• Explore how effective cerebral O2 monitoring is regionally and globally

Incidence Of Ocular Hypertension After Intravitreal Injection Of 2 Mg Triamcinolone Acetonide (Ivt), Jake Goodman, Bs, Maitri Pancholy, Bs, Philip Storey, Md, Mph, Anthony Obeid, Md, Durga Borkar, Md, Carl Regillo, Md, Daniel Su, Md

Sigma Xi Student Research Day

Purpose

To report the incidence of OHT following injection of 2mg IVT

Radiomic Features From Muti-Institutional Glioblastoma Mri Offers Additive Prognostic Value To Clinical And Genomic Markers, Spencer Liem, Bs, Gaurav Shukla, Md, Phd, Spyridon Bakas, Phd, Sung Min Ha, Ms, Saima Rathore, Phd, Christos Davatzikos, Phd

Sigma Xi Student Research Day

Objective

Synergies between clinical, genomic, and radiomic features should improve the predictive value of each group of features and their combinations through a prognostic classifier based on machine learning in patients with glioblastoma.

Long-Term Visual Outcomes In Optic Nerve Sheath Meningiomas Following Fractionated Stereotactic Radiotherapy, Sana Dastgheyb, Christian Fernandez, Md, Maria Werner-Wasik, Md, Voichita Bar-Ad, Md, David Andrews Md, James Evans, Md, Kevin Judy, Md, Sara Lally, Md, Carol Shields, Md, Arman Mashayekhi, Md, Wenyin Shi, Md, Phd, Christopher Farrell, Md

Sigma Xi Student Research Day

Introduction

Radiation therapy is often used for tumors of the optic nerve. The challenge with irradiating tumors surrounding structures associated with the eye is the risk of exposing the optic nerve, or other structures important to maintaining vision to potentially damaging radiation.

Fractionated stereotactic radiotherapy (FSRT) is commonly used for the treatment of optic nerve sheath meningiomas (ONSMs) for vision preservation. However, long term visual data in the literature is limited. We investigated visual outcomes in 27 patients with ONSMs after FSRT.

A Behavioral Lifestyle Intervention Enhanced With Multiple-Behavior Self-Monitoring Using Mobile And Connected Tools For Underserved Individuals With Type 2 Diabetes And Comorbid Overweight Or Obesity: Pilot Comparative Effectiveness Trial, Jing Wang, Chunyan Cai, Nikhil Padhye, Philip Orlander, Mohammad Zare

Faculty, Staff and Student Publications

BACKGROUND: Self-monitoring is a cornerstone of behavioral lifestyle interventions for obesity and type 2 diabetes mellitus. Mobile technology has the potential to improve adherence to self-monitoring and patient outcomes. However, no study has tested the use of a smartphone to facilitate self-monitoring in overweight or obese adults with type 2 diabetes mellitus living in the underserved community.

OBJECTIVE: The aim of this study was to examine the feasibility of and compare preliminary efficacy of a behavioral lifestyle intervention using smartphone- or paper-based self-monitoring of multiple behaviors on weight loss and glycemic control in a sample of overweight or obese adults …

Evaluating The Effectiveness Of Text Messaging And Phone Call Reminders To Minimize No Show At Pediatric Outpatient Clinics In Pakistan: Protocol For A Mixed-Methods Study, Sana Saeed, Noureen Somani, Fatima Sharif, Abdul Momin Kazi

Department of Paediatrics and Child Health

Background: Missing health care appointments without canceling in advance results in a no show, a vacant appointment slot that cannot be offered to others. No show can be reduced by reminding patients about their appointment in advance. In this regard, mobile health (mHealth) strategy is to use text messaging (short message service, SMS), which is available on all cellular phones, including cheap low-end handsets. Nonattendance for appointments in health care results in wasted resources and disturbs the planned work schedules.
Objectives: The purpose of this study is to evaluate the efficacy of the current text messaging (SMS) and call-based …

Markers Of Cardiometabolic Risk And Thyroid Dysfunction In U.S. Adolescents: Nhanes Iii, Jonathan Austin

Theses and Dissertations

The global prevalence of metabolic syndrome (MetS) and its associated components (high fasting glucose, waist circumference, blood pressure, triglycerides, and low HDL) have increased over the past few decades. In addition, abnormal thyroid hormone levels have been found to manifest in a cascade of metabolic dysfunction, which may be linked to MetS in youth. PURPOSE: The purpose of the study is to investigate the association between MetS, its components, and markers of thyroid function in a nationally-representative sample of adolescents. METHODS: The National Health and Nutrition Examination Survey III (1988-1994) collected data on the components of metabolic syndrome and thyroid …

Antibody-Drug Conjugates For Cancer Therapy: Chemistry To Clinical Implications, Nirnoy Dan, Saini Setua, Vivek K. Kashyap, Sheema Khan, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan

School of Medicine Publications

Chemotherapy is one of themajor therapeutic options for cancer treatment. Chemotherapy is often associated with a low therapeutic window due to its poor specificity towards tumor cells/tissues. Antibody-drug conjugate (ADC) technology may provide a potentially new therapeutic solution for cancer treatment. ADC technology uses an antibody-mediated delivery of cytotoxic drugs to the tumors in a targeted manner, while sparing normal cells. Such a targeted approach can improve the tumor-to-normal tissue selectivity and specificity in chemotherapy. Considering its importance in cancer treatment, we aim to review recent efforts for the design and development of ADCs. ADCs are mainly composed of an …

Twist Promotes Tumor Metastasis In Basal-Like Breast Cancer By Transcriptionally Upregulating Ror1, Jingying Cao, Xin Wang, Tao Dai, Yuanzhong Wu, Meifang Zhang, Renxian Cao, Ruhua Zhang, Gang Wang, Rou Jiang, Binhua P. Zhou, Jian Shi, Tiebang Kang

Markey Cancer Center Faculty Publications

Rationale: Twist is a key transcription factor for induction of epithelial-mesenchymal transition (EMT), which promotes cell migration, invasion, and cancer metastasis, confers cancer cells with stem cell-like characteristics, and provides therapeutic resistance. However, the functional roles and targeted genes of Twist in EMT and cancer progression remain elusive.

Methods: The potential targeted genes of Twist were identified from the global transcriptomes of T47D/Twist cells by microarray analysis. EMT phenotype was detected by western blotting and immunofluorescence of marker proteins. The dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the direct transcriptional induction of ROR1 by Twist. A lung …

Network Specialization During Adolescence: Hippocampal Effective Connectivity In Boys And Girls, Jeffrey D. Riley, E. Elinor Chen, Jessica Winsell, Elyssia Poggi Davis, Laura M. Glynn, Tallie Z. Baram, Curt A. Sandman, Steven L. Small, Ana Solodkin

Psychology Faculty Articles and Research

Adolescence is a complex period of concurrent mental and physical development that facilitates adult functioning at multiple levels. Despite the growing number of neuroimaging studies of cognitive development in adolescence focusing on regional activation patterns, there remains a paucity of information about the functional interactions across these participating regions that are critical for cognitive functioning, including memory. The current study used structural equation modeling (SEM) to determine how interactions among brain regions critical for memory change over the course of adolescence. We obtained functional MRI in 77 individuals aged 8–16 years old, divided into younger (ages 8–10) and older (ages …

Dealing With Deans And Academic Medical Center Leadership: Advice From Leaders., Fred Sanfilippo, Deborah Powell, Robert Folberg, Mark Tykocinski

Department of Medicine Faculty Papers

The 2017 Association of Pathology Chairs Annual Meeting included a session for department chairs and other department leaders on "how to deal with deans and academic medical center leadership." The session was focused on discussing ways to foster positive relationships with university, medical school, and health system leaders, and productively address issues and opportunities with them. Presentations and a panel discussion were provided by 4 former pathology chairs who subsequently have served as medical deans and in other leadership positions including university provost, medical center CEO, and health system board chair. There was a strong consensus among the participants on …

Geospatial Inequalities And Determinants Of Nutritional Status Among Women And Children In Afghanistan: An Observational Study, Nadia Akseer, Zaid Ahmad Bhatti, Taufiq Mashal, Sajid Bashir Soofi, Rahim Moineddin, Robert E Black Md, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Background: Undernutrition is a pervasive condition in Afghanistan, and prevalence is among the highest in the world. We aimed to comprehensively assess district-level geographical disparities and determinants of nutritional status (stunting, wasting, or underweight) among women and children in Afghanistan.
Methods: The study used individualised data from the recent Afghanistan National Nutrition Survey 2013. Outcome variables were based on growth and weight anthropometry data, which we analysed linearly as Z scores and as dichotomous categories. We analysed data from a total of almost 14 000 index mother–child pairs using Bayesian spatial and generalised least squares regression models accounting for the …

Differential Diagnosis Of Pan-Uveitis: Behçet’S Disease, Peter Blosser, Remil Simon, Courtney Ridner

Appalachian Student Research Forum

This report describes the case of a 56-year-old man who presented with blurry vision, increased intraocular pressure, and conjunctival injection after posterior chamber intraocular lens implantation. Initially post-operative endophalmitis and foreign body inflammation were considered as differential diagnoses, but after further examination pan-uveitis was diagnosed. Uveitis is an ocular finding that may indicate several diseases, one of which is Behçet’s Disease. During the interview, the patient mentioned a history of apthous ulcers and genital ulcers which then lead to the clinical diagnosis of Behçet’s Disease. This report emphasizes that Behçet’s Disease is rare in Caucasians. Therefore, is frequently misdiagnosed in …

Refrigerated Stability Of Diluted Cisatracurium, Rocuronium, And Vecuronium For Skin Testing After Perioperative Anaphylaxis, Kristen Dinsmore, Bethany Campbell, Timothy Archibald, Greg Mosier, Stacy Brown Phd, Alexei Gonzalez-Estrada Md

Appalachian Student Research Forum

Rationale: The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely cisatracurium, rocuronium, and vecuronium, for skin prick/intradermal testing.

Methods: Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, 10,000x, and 100,000x as sensitivity of the assay allowed. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days, aliquots of each dilution were removed and compared to a freshly prepared set of reference dilutions.

Results: The results …

Does Specialist Physician Supply Affect Pediatric Asthma Health Outcomes?, Guido Filler, Tom Kovesi, Erik Bourdon, Sarah Ann Jones, Laurentiu Givelichian, Cheryl Rockman-Greenberg, Jason Gilliland, Marion Williams, Elaine Orrbine, Bruno Piedboeuf

Paediatrics Publications

Background

Pediatrician and pediatric subspecialist density varies substantially among the various Canadian provinces, as well as among various states in the US. It is unknown whether this variability impacts health outcomes. To study this knowledge gap, we evaluated pediatric asthma admission rates within the 2 Canadian provinces of Manitoba and Saskatchewan, which have similarly sized pediatric populations and substantially different physician densities.

Methods

This was a retrospective cross-sectional cohort study. Health regions defined by the provincial governments, have, in turn, been classified into "peer groups" by Statistics Canada, on the basis of common socio-economic characteristics and socio-demographic determinants of health. …

Multiple Sclerosis Identification Based On Fractional Fourier Entropy And A Modified Jaya Algorithm, Shui-Hua Wang, Hong Cheng, Preetha Phillips, Yu-Dong Zhang

Publications and Research

Aim: Currently, identifying multiple sclerosis (MS) by human experts may come across the problem of “normal-appearing white matter”, which causes a low sensitivity. Methods: In this study, we presented a computer vision based approached to identify MS in an automatic way. This proposed method first extracted the fractional Fourier entropy map from a specified brain image. Afterwards, it sent the features to a multilayer perceptron trained by a proposed improved parameter-free Jaya algorithm. We used cost-sensitivity learning to handle the imbalanced data problem. Results: The 10 × 10-fold cross validation showed our method yielded a sensitivity of 97.40 ± 0.60%, …

Coordinated Responses To Individual Tumor Antigens By Igg Antibody And Cd8+ T Cells Following Cancer Vaccination., Tyler W Hulett, Shawn M. Jensen, Phillip A Wilmarth, Ashok P Reddy, Carmen Ballesteros-Merino, Michael E Afentoulis, Christopher Dubay, Larry L David, Bernard A Fox

Articles, Abstracts, and Reports

BACKGROUND: One of today's greatest hurdles for cancer immunotherapy is the absence of information regarding which tumor antigens are already recognized by patients receiving immunotherapies, and whether those therapies then boost or generate an immune response against tumor proteins. For CD8+ T cells in particular, patient-specific immune recognition and responses at the level of individual tumor antigens are rarely characterized. Because of this, some immunologists have turned to serum antibodies as an alternative measure of antigen-specific anti-tumor immunity. In this work, we sought to simultaneously interrogate serum IgG and CD8+ T cell recognition of individual tumor antigens to determine whether …

Integrating Telehealth Emergency Department Follow-Up Visits Into Residency Training., Dimitrios Papanagnou, Danica Stone, Shruti Chandra, Phillip Watts, Anna Marie Chang, Judd E. Hollander

Department of Emergency Medicine Faculty Papers

Introduction: Given the rapid expansion of telehealth (TH), there is an emerging need for trained professionals who can effectively deliver TH services. As there is no formal TH training program for residents, the Department of Emergency Medicine (DEM) at Thomas Jefferson University (TJU) developed a pilot training program for senior post-graduate-year three (PGY-3) residents that exposed them to TH practices. The objective of the study was to determine the feasibility of developing a resident-led, post-Emergency-Department (ED) visit TH follow-up program as an educational opportunity to 1) address patient satisfaction; and 2) expose senior residents to TH delivery.

Methods: During …

Seroprevalence Of Anti-Polio Antibodies In Children From Polio High Risk Area Of Afghanistan: A Cross Sectional Survey 2017, Imtiaz Hussain, Ondrej Mach, Nasir A. Hamid, Zaid Bhatti, Deborah D. Moore, Shahid Khan, Hasan Khan, William C. Weldon, Zulfiqar Ahmed Bhutta, Sajid Bashir Soofi

Department of Paediatrics and Child Health

Background: Afghanistan is one of the remaining wild-poliovirus (WPV) endemic countries. We conducted a seroprevalence survey of anti-poliovirus antibodies in Kandahar Province.
Methods: Children in two age groups (6–11 months and 36–48 months) visiting Mirwais hospital in Kandahar for minor ailments unrelated to polio were enrolled. After obtaining informed consent, we collected venous blood and conducted neutralization assay to detect poliovirus neutralizing antibodies.
Results: A total of 420 children were enrolled and 409/420 (97%) were analysed. Seroprevalence to poliovirus type 1 (PV1) was 97% and 100% in the younger and older age groups respectively; it was 71% and 91% for …

Effects On Recovery And Neuroplasticity In Brain Injury Patients, Rebekkah Mclellan

Student Scholar Showcase

Abstract

According to the Centers for Disease Control, approximately 1.7 million people sustain a Traumatic Brain Injury each year, making the topic of brain plasticity and patient recovery an important area of study. An added element is understanding whether biological, social, and environmental factors can impact the recovery and plasticity of the patient’s brain.The purpose of this literature review was to evaluate if the environment surrounding an individual who has sustained a brain injury affects their recovery and neuroplasticity. The databases used for the scope of this review included LC OneSearch, Medline, EBSCOhost, and Google Scholar. Keywords included brain injury, …

The Effectiveness Of A "Patient Discharge Information" Booklet In Patient Education Program In Saudi Arabia, Amani Al Rebeh

Annual Graduate Student Symposium

The purpose of this research was to investigate the effectiveness of the Patient Discharge Information (PDI) booklet on the knowledge, attitude, and behaviors of participants who were cesarean patients in local hospitals in Saudi Arabia. This study investigated the following two research questions: (1) does the participant have information, resources, and understand basic personal health information regarding her health conditions including diagnosis, treatment, self-care management, medication instructions, normal expected symptoms, dangerous signs and what to do, as well as lifestyle changes?; and (2) how does patient discharge information provided by the hospital make a difference in participants’ knowledge, attitude, and …

Characterization Of Sex-Based Dna Methylation Signatures In The Airways During Early Life., Cesar L Nino, Geovanny F Perez, Natalia Isaza, Maria J Gutierrez, Jose L Gomez, Gustavo Nino

Pediatrics Faculty Publications

Human respiratory conditions are largely influenced by the individual's sex resulting in overall higher risk for males. Sex-based respiratory differences are present at birth suggesting a strong genetic component. Our objective was to characterize early life sex-based genomic signatures determined by variable X-chromosome methylation in the airways. We compared male versus female genome-wide DNA methylation in nasal airway samples from newborns and infants aged 1-6 months (N = 12). We analyzed methylation signals across CpG sites mapped to each X-linked gene using an unsupervised classifier (principal components) followed by an internal evaluation and an exhaustive cross-validation. Results were validated in …

Driver Fusions And Their Implications In The Development And Treatment Of Human Cancers., Qingsong Gao, Wen-Wei Liang, Steven M Foltz, Gnanavel Mutharasu, Reyka G Jayasinghe, Song Cao, Wen-Wei Liao, Sheila M Reynolds, Matthew A Wyczalkowski, Lijun Yao, Lihua Yu, Sam Q Sun, Ken Chen, Alexander J Lazar, Ryan C Fields, Michael C Wendl, Brian A Van Tine, Ravi Vij, Feng Chen, Matti Nykter, Ilya Shmulevich, Li Ding

Articles, Abstracts, and Reports

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of …

Genomic And Molecular Landscape Of Dna Damage Repair Deficiency Across The Cancer Genome Atlas., Theo A Knijnenburg, Linghua Wang, Michael T Zimmermann, Nyasha Chambwe, Galen F Gao, Andrew D Cherniack, Huihui Fan, Hui Shen, Gregory P Way, Casey S Greene, Yuexin Liu, Rehan Akbani, Bin Feng, Lawrence A Donehower, Chase Miller, Yang Shen, Mostafa Karimi, Haoran Chen, Pora Kim, Peilin Jia, Eve Shinbrot, Shaojun Zhang, Jianfang Liu, Hai Hu, Matthew H Bailey, Christina Yau, Denise Wolf, Zhongming Zhao, John N Weinstein, Lei Li, Li Ding, Gordon B Mills, Peter W Laird, David A Wheeler, Ilya Shmulevich, Raymond J Monnat, Yonghong Xiao, Chen Wang

Articles, Abstracts, and Reports

DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in ∼20% of samples. Homologous recombination deficiency (HRD) was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein …

Systematic Analysis Of Splice-Site-Creating Mutations In Cancer., Reyka G Jayasinghe, Song Cao, Qingsong Gao, Michael C Wendl, Nam Sy Vo, Sheila M Reynolds, Yanyan Zhao, Héctor Climente-González, Shengjie Chai, Fang Wang, Rajees Varghese, Mo Huang, Wen-Wei Liang, Matthew A Wyczalkowski, Sohini Sengupta, Zhi Li, Samuel H Payne, David Fenyö, Jeffrey H Miner, Matthew J Walter, Benjamin Vincent, Eduardo Eyras, Ken Chen, Ilya Shmulevich, Feng Chen, Li Ding

Articles, Abstracts, and Reports

For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs) across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function. Notably, we found that neoantigens induced by SCMs are likely several folds more immunogenic compared to …

Spatial Organization And Molecular Correlation Of Tumor-Infiltrating Lymphocytes Using Deep Learning On Pathology Images., Joel Saltz, Rajarsi Gupta, Le Hou, Tahsin Kurc, Pankaj Singh, Vu Nguyen, Dimitris Samaras, Kenneth R Shroyer, Tianhao Zhao, Rebecca Batiste, John Van Arnam, Ilya Shmulevich, Arvind U K Rao, Alexander J Lazar, Ashish Sharma, Vésteinn Thorsson

Articles, Abstracts, and Reports

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumor-infiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched …