Biomedical Informatics Commons^™

Evaluating The Use Of Blood Pressure Polygenic Risk Scores Across Race/Ethnic Background Groups, Nuzulul Kurniansyah, Matthew O Goodman, Alyna T Khan, Jiongming Wang, Elena Feofanova, Joshua C Bis, Kerri L Wiggins, Jennifer E Huffman, Tanika Kelly, Tali Elfassy, Xiuqing Guo, Walter Palmas, Henry J Lin, Shih-Jen Hwang, Yan Gao, Kendra Young, Gregory L Kinney, Jennifer A Smith, Bing Yu, Simin Liu, Sylvia Wassertheil-Smoller, Joann E Manson, Xiaofeng Zhu, Yii-Der Ida Chen, I-Te Lee, C Charles Gu, Donald M Lloyd-Jones, Sebastian Zöllner, Myriam Fornage, Charles Kooperberg, Adolfo Correa, Bruce M Psaty, Donna K Arnett, Carmen R Isasi, Stephen S Rich, Robert C Kaplan, Susan Redline, Braxton D Mitchell, Nora Franceschini, Daniel Levy, Jerome I Rotter, Alanna C Morrison, Tamar Sofer

Faculty, Staff and Student Publications

We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare "clumping-and-thresholding" (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs …

Association Of Circulating Markers With Cognitive Decline After Radiation Therapy For Brain Metastasis, Kristin Huntoon, S Keith Anderson, Karla V Ballman, Erin Twohy, Katharine Dooley, Wen Jiang, Yi An, Jing Li, Christina Von Roemeling, Yaqing Qie, Owen A Ross, Jane H Cerhan, Anthony C Whitton, Jeffrey N Greenspoon, Ian F Parney, Jonathan B Ashman, Jean-Paul Bahary, Constantinos Hadjipanayis, James J Urbanic, Elana Farace, Deepak Khuntia, Nadia N Laack, Paul D Brown, David Roberge, Betty Y S Kim

Faculty, Staff and Student Publications

BACKGROUND: A recent phase III trial (NCT01372774) comparing use of stereotactic radiosurgery [SRS] versus whole-brain radiation therapy [WBRT] after surgical resection of a single brain metastasis revealed that declines in cognitive function were more common with WBRT than with SRS. A secondary endpoint in that trial, and the primary objective in this secondary analysis, was to identify baseline biomarkers associated with cognitive impairment after either form of radiotherapy for brain metastasis. Here we report our findings on APOE genotype and serum levels of associated proteins and their association with radiation-induced neurocognitive decline.

METHODS: In this retrospective analysis of prospectively collected …

Machine Learning Reveals Lipidome Remodeling Dynamics In A Mouse Model Of Ovarian Cancer, Olatomiwa O Bifarin, Samyukta Sah, David A Gaul, Samuel G Moore, Ruihong Chen, Murugesan Palaniappan, Jaeyeon Kim, Martin M Matzuk, Facundo M Fernández

Faculty, Staff and Students Publications

Ovarian cancer (OC) is one of the deadliest cancers affecting the female reproductive system. It may present little or no symptoms at the early stages and typically unspecific symptoms at later stages. High-grade serous ovarian cancer (HGSC) is the subtype responsible for most ovarian cancer deaths. However, very little is known about the metabolic course of this disease, particularly in its early stages. In this longitudinal study, we examined the temporal course of serum lipidome changes using a robust HGSC mouse model and machine learning data analysis. Early progression of HGSC was marked by increased levels of phosphatidylcholines and phosphatidylethanolamines. …

A Guide To The Brain Initiative Cell Census Network Data Ecosystem, Michael Hawrylycz, Maryann E Martone, Giorgio A Ascoli, Jan G Bjaalie, Hong-Wei Dong, Satrajit S Ghosh, Jesse Gillis, Ronna Hertzano, David R Haynor, Patrick R Hof, Yongsoo Kim, Ed Lein, Yufeng Liu, Jeremy A Miller, Partha P Mitra, Eran Mukamel, Lydia Ng, David Osumi-Sutherland, Hanchuan Peng, Patrick L Ray, Raymond Sanchez, Aviv Regev, Alex Ropelewski, Richard H Scheuermann, Shawn Zheng Kai Tan, Carol L Thompson, Timothy Tickle, Hagen Tilgner, Merina Varghese, Brock Wester, Owen White, Hongkui Zeng, Brian Aevermann, David Allemang, Seth Ament, Thomas L Athey, Cody Baker, Katherine S Baker, Pamela M Baker, Anita Bandrowski, Samik Banerjee, Prajal Bishwakarma, Ambrose Carr, Min Chen, Roni Choudhury, Jonah Cool, Heather Creasy, Florence D'Orazi, Kylee Degatano, Benjamin Dichter, Song-Lin Ding, Tim Dolbeare, Joseph R Ecker, Rongxin Fang, Jean-Christophe Fillion-Robin, Timothy P Fliss, James Gee, Tom Gillespie, Nathan Gouwens, Guo-Qiang Zhang, Yaroslav O Halchenko, Nomi L Harris, Brian R Herb, Houri Hintiryan, Gregory Hood, Sam Horvath, Bingxing Huo, Dorota Jarecka, Shengdian Jiang, Farzaneh Khajouei, Elizabeth A Kiernan, Huseyin Kir, Lauren Kruse, Changkyu Lee, Boudewijn Lelieveldt, Yang Li, Hanqing Liu, Lijuan Liu, Anup Markuhar, James Mathews, Kaylee L Mathews, Chris Mezias, Michael I Miller, Tyler Mollenkopf, Shoaib Mufti, Christopher J Mungall, Joshua Orvis, Maja A Puchades, Lei Qu, Joseph P Receveur, Bing Ren, Nathan Sjoquist, Brian Staats, Daniel Tward, Cindy T J Van Velthoven, Quanxin Wang, Fangming Xie, Hua Xu, Zizhen Yao, Zhixi Yun, Yun Renee Zhang, W Jim Zheng, Brian Zingg

Faculty, Staff and Student Publications

Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also essential to manipulate cell types in controlled ways and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data-generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization. Emphasis of the BICCN is on the whole mouse brain with demonstration of prototype feasibility for human and nonhuman …

Rapid-Query For Fast Identity By Descent Search And Genealogical Analysis, Yuan Wei, Ardalan Naseri, Degui Zhi, Shaojie Zhang

Faculty, Staff and Student Publications

MOTIVATION: Due to the rapid growth of the genetic database size, genealogical search, a process of inferring familial relatedness by identifying DNA matches, has become a viable approach to help individuals finding missing family members or law enforcement agencies locating suspects. A fast and accurate method is needed to search an out-of-database individual against millions of individuals. Most existing approaches only offer all-versus-all within panel match. Some prototype algorithms offer one-versus-all query from out-of-panel individual, but they do not tolerate errors.

RESULTS: A new method, random projection-based identity-by-descent (IBD) detection (RaPID) query, is introduced to make fast genealogical search possible. …

5s Rrna Pseudogene Transcripts Are Associated With Interferon Production And Inflammatory Responses In Alcohol-Associated Hepatitis, Jianguo Wu, Adam Kim, Xiaoqin Wu, Semanti Ray, Daniela S Allende, Nicole Welch, Annette Bellar, Jaividhya Dasarathy, Srinivasan Dasarathy, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Interferon (IFN) signaling is critical to the pathogenesis of alcohol-associated hepatitis (AH), yet the mechanisms for activation of this system are elusive. We hypothesize that host-derived 5S rRNA pseudogene (RNA5SP) transcripts regulate IFN production and modify immunity in AH.

APPROACH AND RESULTS: Mining of transcriptomic datasets revealed that in patients with severe alcohol-associated hepatitis (sAH), hepatic expression of genes regulated by IFNs was perturbed and gene sets involved in IFN production were enriched. RNA5SP transcripts were also increased and correlated with expression of type I IFNs. Interestingly, inflammatory mediators upregulated in sAH, but not in other liver …

Camonsertib In Dna Damage Response-Deficient Advanced Solid Tumors: Phase 1 Trial Results, Timothy A Yap, Elisa Fontana, Elizabeth K Lee, David R Spigel, Martin Højgaard, Stephanie Lheureux, Niharika B Mettu, Benedito A Carneiro, Louise Carter, Ruth Plummer, Gregory M Cote, Funda Meric-Bernstam, Joseph O'Connell, Joseph D Schonhoft, Marisa Wainszelbaum, Adrian J Fretland, Peter Manley, Yi Xu, Danielle Ulanet, Victoria Rimkunas, Mike Zinda, Maria Koehler, Ian M Silverman, Jorge S Reis-Filho, Ezra Rosen

Faculty, Staff and Student Publications

Predictive biomarkers of response are essential to effectively guide targeted cancer treatment. Ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) have been shown to be synthetic lethal with loss of function (LOF) of ataxia telangiectasia-mutated (ATM) kinase, and preclinical studies have identified ATRi-sensitizing alterations in other DNA damage response (DDR) genes. Here we report the results from module 1 of an ongoing phase 1 trial of the ATRi camonsertib (RP-3500) in 120 patients with advanced solid tumors harboring LOF alterations in DDR genes, predicted by chemogenomic CRISPR screens to sensitize tumors to ATRi. Primary objectives were to determine safety and propose …

Phase Ii Trial Of Nelipepimut-S Peptide Vaccine In Women With Ductal Carcinoma In Situ, Anne E O'Shea, Guy T Clifton, Na Qiao, Brandy M Heckman-Stoddard, Malgorzata Wojtowicz, Eileen Dimond, Isabelle Bedrosian, Diane Weber, Judy E Garber, Alexander Husband, Ricardo Pastorello, J Jack Lee, Mike Hernandez, Diane D Liu, Lana A Vornik, Powel H Brown, Gheath Alatrash, George E Peoples, Elizabeth A Mittendorf

Faculty, Staff and Student Publications

UNLABELLED: NeuVax is a vaccine comprised of the HER2-derived MHC class I peptide E75 (nelipepimut-S, NPS) combined with GM-CSF. We completed a randomized trial of preoperative vaccination with NeuVax versus GM-CSF alone in patients with ductal carcinoma in situ (DCIS). The primary objective was to evaluate for NPS-specific cytotoxic T lymphocyte (CTL) responses. Patients with human leukocyte antigen (HLA)-A2-positive DCIS were enrolled and randomized 2:1 to NeuVax versus GM-CSF alone and received two inoculations prior to surgery. The number of NPS-specific CTL was measured pre-vaccination, at surgery, and 1 and 3 to 6 months post-operation by dextramer assay. Differences in …

Representing And Utilizing Clinical Textual Data For Real World Studies: An Ohdsi Approach, Vipina K Keloth, Juan M Banda, Michael Gurley, Paul M Heider, Georgina Kennedy, Hongfang Liu, Feifan Liu, Timothy Miller, Karthik Natarajan, Olga V Patterson, Yifan Peng, Kalpana Raja, Ruth M Reeves, Masoud Rouhizadeh, Jianlin Shi, Xiaoyan Wang, Yanshan Wang, Wei-Qi Wei, Andrew E Williams, Rui Zhang, Rimma Belenkaya, Christian Reich, Clair Blacketer, Patrick Ryan, George Hripcsak, Noémie Elhadad, Hua Xu

Faculty, Staff and Student Publications

Clinical documentation in electronic health records contains crucial narratives and details about patients and their care. Natural language processing (NLP) can unlock the information conveyed in clinical notes and reports, and thus plays a critical role in real-world studies. The NLP Working Group at the Observational Health Data Sciences and Informatics (OHDSI) consortium was established to develop methods and tools to promote the use of textual data and NLP in real-world observational studies. In this paper, we describe a framework for representing and utilizing textual data in real-world evidence generation, including representations of information from clinical text in the Observational …

Learning Through Doing: Comprehensive Programming For A Training Program In Cancer Disparities, Kayce D Solari Williams, Kamisha Hamilton Escoto, Crystal Roberson, Kathy Le, Lorraine R Reitzel, Lorna H Mcneill, Shine Chang

Faculty, Staff and Student Publications

In the United States, preparing researchers and practitioners for careers in cancer requires multiple components for success. In this reflection article, we discuss our approach to designing a comprehensive research training program in cancer disparities. We focused on elements that provide students and early career scientists a deep understanding of disparities through first-hand experiences and skills training necessary to build a research career in the area. Our Educational Program sits within the framework of an NCI P20 program, "UHAND (University of Houston/MD Anderson Cancer Center)", jointly established by an NCI-designated comprehensive cancer center and a minority-serving university as a collaborative …

Piloting The Sexual And Gender Minority Cancer Curricular Advances For Research And Education (Sgm Cancer Care) Workshop: Research Training In The Service Of Sgm Cancer Health Equity, Miria Kano, Irene Tamí-Maury, Mandi L Pratt-Chapman, Shine Chang, Mikaela Kosich, Gwendolyn P Quinn, Tonia Poteat, Peter A Kanetsky, Ronit Elk, Ulrike Boehmer, Julian Sanchez, Charles Kamen, Nelson F Sanchez

Faculty, Staff and Student Publications

The purpose of this study is to describe the context, curriculum design, and pilot evaluation of the educational program "Sexual and Gender Minority Cancer Curricular Advances for Research and Education" (SGM Cancer CARE), a workshop for early-career researchers and healthcare providers interested in gaining knowledge and skills in sexual and gender minority (SGM) cancer research and healthcare advocacy. A needs assessment of a sample of clinicians and researchers (n = 104) and feedback from an Advisory Board informed the curriculum design of the SGM Cancer CARE workshop. Four SGM-tailored modules, focusing on epidemiology, clinical research, behavioral science and interventions, and …

Maternal Embryonic Leucine Zipper Kinase Is Associated With Metastasis In Triple-Negative Breast Cancer, Xuemei Xie, Gaurav B Chauhan, Ramakrishna Edupuganti, Takahiro Kogawa, Jihyun Park, Moises Tacam, Alex W Tan, Mohd Mughees, Fnu Vidhu, Diane D Liu, Juliana M Taliaferro, Mary Kathryn Pitner, Luke S Browning, Ju-Hyeon Lee, Yu Shen, Jian Wang, Naoto T Ueno, Savitri Krishnamurthy, Gabriel N Hortobagyi, Debu Tripathy, Steven J Van Laere, Geoffrey Bartholomeusz, Kevin N Dalby, Chandra Bartholomeusz

Faculty, Staff and Student Publications

UNLABELLED: Triple-negative breast cancer (TNBC) has high relapse and metastasis rates and a high proportion of cancer stem-like cells (CSC), which possess self-renewal and tumor initiation capacity. MELK (maternal embryonic leucine zipper kinase), a protein kinase of the Snf1/AMPK kinase family, is known to promote CSC maintenance and malignant transformation. However, the role of MELK in TNBC metastasis is unknown; we sought to address this in the current study. We found that

SIGNIFICANCE: These findings indicate that MELK is a driver of aggressiveness and metastasis in TNBC.

A Novel Integrated Approach To Predicting Cancer Immunotherapy Efficacy, Ruihan Luo, Jacqueline Chyr, Jianguo Wen, Yanfei Wang, Weiling Zhao, Xiaobo Zhou

Faculty, Staff and Student Publications

Immunotherapies have revolutionized cancer treatment modalities; however, predicting clinical response accurately and reliably remains challenging. Neoantigen load is considered as a fundamental genetic determinant of therapeutic response. However, only a few predicted neoantigens are highly immunogenic, with little focus on intratumor heterogeneity (ITH) in the neoantigen landscape and its link with different features in the tumor microenvironment. To address this issue, we comprehensively characterized neoantigens arising from nonsynonymous mutations and gene fusions in lung cancer and melanoma. We developed a composite NEO2IS to characterize interplays between cancer and CD8+ T-cell populations. NEO2IS improved prediction accuracy of patient responses to immune-checkpoint …

Comparative Analyses Define Differences Between Bhd-Associated Renal Tumour And Sporadic Chromophobe Renal Cell Carcinoma, Ryosuke Jikuya, Todd A Johnson, Kazuhiro Maejima, Jisong An, Young-Seok Ju, Hwajin Lee, Kyungsik Ha, Woojeung Song, Youngwook Kim, Yuki Okawa, Shota Sasagawa, Yuki Kanazashi, Masashi Fujita, Seiya Imoto, Taku Mitome, Shinji Ohtake, Go Noguchi, Sachi Kawaura, Yasuhiro Iribe, Kota Aomori, Tomoyuki Tatenuma, Mitsuru Komeya, Hiroki Ito, Yusuke Ito, Kentaro Muraoka, Mitsuko Furuya, Ikuma Kato, Satoshi Fujii, Haruka Hamanoue, Tomohiko Tamura, Masaya Baba, Toshio Suda, Tatsuhiko Kodama, Kazuhide Makiyama, Masahiro Yao, Brian M Shuch, Christopher J Ricketts, Laura S Schmidt, W Marston Linehan, Hidewaki Nakagawa, Hisashi Hasumi

Faculty, Staff and Student Publications

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated.

METHODS: To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated …

The Integrative Studies On The Functional A-To-I Rna Editing Events In Human Cancers, Sijia Wu, Zhiwei Fan, Pora Kim, Liyu Huang, Xiaobo Zhou

Faculty, Staff and Student Publications

Adenosine-to-inosine (A-to-I) RNA editing, constituting nearly 90% of all RNA editing events in humans, has been reported to contribute to the tumorigenesis in diverse cancers. However, the comprehensive map for functional A-to-I RNA editing events in cancers is still insufficient. To fill this gap, we systematically and intensively analyzed multiple tumorigenic mechanisms of A-to-I RNA editing events in samples across 33 cancer types from The Cancer Genome Atlas. For individual candidate among ∼ 1,500,000 quantified RNA editing events, we performed diverse types of downstream functional annotations. Finally, we identified 24,236 potentially functional A-to-I RNA editing events, including the cases …

Efficacy Of Systemic Chemotherapy In Patients With Low-Grade Mucinous Appendiceal Adenocarcinoma: A Randomized Crossover Trial, John Paul Shen, Abdelrahman M Yousef, Fadl A Zeineddine, Mohammad A Zeineddine, Rebecca S Tidwell, Karen A Beaty, Lisa C Scofield, Safia Rafeeq, Nicholas Hornstein, Elizabeth Lano, Cathy Eng, Aurelio Matamoros, Wai Chin Foo, Abhineet Uppal, Christopher Scally, Paul Mansfield, Melissa Taggart, Kanwal P Raghav, Michael J Overman, Keith Fournier

Faculty, Staff and Student Publications

IMPORTANCE: Appendiceal adenocarcinoma is a rare tumor, and given the inherent difficulties in performing prospective trials in such a rare disease, there are currently minimal high-quality data to guide treatment decisions, highlighting the need for more preclinical and clinical investigation for this disease.

OBJECTIVE: To prospectively evaluate the effectiveness of fluoropyrimidine-based systemic chemotherapy in patients with inoperable low-grade mucinous appendiceal adenocarcinoma.

DESIGN, SETTING, AND PARTICIPANTS: This open-label randomized crossover trial recruited patients at a single tertiary care comprehensive cancer center from September 2013 to January 2021. The data collection cutoff was May 2022. Enrollment of up to 30 patients was …

Practices And Views Of Us Oncologists And Genetic Counselors Regarding Patient Recontact After Variant Reclassification: Results Of A Nationwide Survey, Sukh Makhnoon, Elenita Davidson, Brian Shirts, Banu Arun, Sanjay Shete

Faculty, Staff and Student Publications

PURPOSE: Over a 5-year or 10-year period, between 6% and 15% of germline cancer genetic variants undergo reclassification. Up-to-date interpretation can clarify a variant's clinical significance and guide patient management. As the frequency of reclassifications increase, the issue of whether, how, when, and which providers should recontact patients with information about reclassification becomes important. However, the field lacks research evidence and definitive guidance from professional organizations about how providers should recontact patients. We compared the perspectives of US oncologists and cancer genetic counselors (GCs) to describe their practices and views regarding recontact.

MATERIALS AND METHODS: We developed a survey using …

Ovarian Cancer Pathology Characteristics As Predictors Of Variant Pathogenicity In Brca1 And Brca2, Denise G O'Mahony, Susan J Ramus, Melissa C Southey, Nicola S Meagher, Andreas Hadjisavvas, Esther M John, Ute Hamann, Evgeny N Imyanitov, Irene L Andrulis, Priyanka Sharma, Mary B Daly, Christopher R Hake, Jeffrey N Weitzel, Anna Jakubowska, Andrew K Godwin, Adalgeir Arason, Anita Bane, Jacques Simard, Penny Soucy, Maria A Caligo, Phuong L Mai, Kathleen B M Claes, Manuel R Teixeira, Wendy K Chung, Conxi Lazaro, Peter J Hulick, Amanda E Toland, Inge Sokilde Pedersen, Susan L Neuhausen, Ana Vega, Miguel De La Hoya, Heli Nevanlinna, Mallika Dhawan, Valentina Zampiga, Rita Danesi, Liliana Varesco, Viviana Gismondi, Valerio Gaetano Vellone, Paul A James, Ramunas Janavicius, Liene Nikitina-Zake, Finn Cilius Nielsen, Thomas Van Overeem Hansen, Tanja Pejovic, Ake Borg, Johanna Rantala, Kenneth Offit, Marco Montagna, Katherine L Nathanson, Susan M Domchek, Ana Osorio, María J García, Beth Y Karlan, Gemo Study Collaborators, Anna De Fazio, David Bowtell, Aocs Group, Lesley Mcguffog, Michael T Parsons, Thilo Dörk, Lisa-Marie Speith, Elizabeth Santana Dos Santos, Alexandre André B A Da Costa, Paolo Radice, Paolo Peterlongo, Laura Papi, Christoph Engel, Eric Hahnen, Rita K Schmutzler, Barbara Wappenschmidt, Douglas F Easton, Marc Tischkowitz, Christian F Singer, Yen Yen Tan, Alice S Whittemore, Weiva Sieh, James D Brenton, Drakoulis Yannoukakos, Florentia Fostira, Irene Konstantopoulou, Jana Soukupova, Michal Vocka, Czecanca Consortium, Georgia Chenevix-Trench, Paul D P Pharoah, Antonis C Antoniou, David E Goldgar, Amanda B Spurdle, Kyriaki Michailidou, Consortium Of Investigators Of Modifiers Of Brca1/2, Evidence-Based Network For The Interpretation Of Germline Mutant Alleles Consortium, Hebon Investigators, Goska Leslie

Faculty, Staff and Student Publications

BACKGROUND: The distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system.

METHODS: Data for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with …

Enhancement Of Immunotherapies In Head And Neck Cancers Using Biomaterial-Based Treatment Strategies, Gemalene M Sunga, Jeffrey Hartgerink, Andrew G Sikora, Simon Young

Faculty, Staff and Student Publications

Head and neck squamous cell carcinoma (HNSCC) is a challenging disease to treat because of typically late-stage diagnoses and tumor formation in difficult-to-treat areas, sensitive to aggressive or invasive treatments. To date, HNSCC treatments have been limited to surgery, radiotherapy, and chemotherapy, which may have significant morbidity and often lead to long-lasting side effects. The development of immunotherapies has revolutionized cancer treatment by providing a promising alternative to standard-of-care therapies. However, single-agent immunotherapy has been only modestly effective in the treatment of various cancers, including HNSCC, with most patients receiving no overall benefit or increased survival. In addition, single-agent immunotherapy's …

Clinical Outcomes Of Leuprolide Acetate In The Treatment Of Recurrent Ovarian Granulosa Cell Tumors, Katherine I Foster, Alejandra Flores Legarreta, Rhea Kamat, Katelyn F Handley, Deanna Glassman, Jeffrey A How, Barrett C Lawson, Shannon N Westin, Lois M Ramondetta, Michael Frumovitz, David M Gershenson, Anil K Sood, R Tyler Hillman

Faculty, Staff and Student Publications

BACKGROUND: The optimal treatment of recurrent ovarian granulosa cell tumors is not known. Preclinical studies and small case series have suggested direct antitumor activity of gonadotropin-releasing hormone agonists in the treatment of this disease, but little is known about the efficacy and safety of this approach.

OBJECTIVE: This study aimed to describe patterns of use and clinical outcomes of leuprolide acetate in a cohort of patients with recurrent granulosa cell tumors.

STUDY DESIGN: This was a retrospective cohort study of patients enrolled in the Rare Gynecologic Malignancy Registry at a large cancer referral center and affiliated county hospital. Patients meeting …

Uptake And Outcomes Of Neoadjuvant Chemotherapy Among Us Patients With Less Common Epithelial Ovarian Carcinomas, Koji Matsuo, Shinya Matsuzaki, Michihide Maeda, Alesandra R Rau, Kosuke Yoshihara, Ryo Tamura, Muneaki Shimada, Hiroko Machida, Mikio Mikami, Maximilian Klar, Lynda D Roman, Jason D Wright, Anil K Sood, David M Gershenson

Faculty, Staff and Student Publications

Importance: Randomized clinical trials examining the effectiveness of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer predominantly included patients with high-grade serous carcinomas. The use and outcomes of NACT in less common epithelial carcinomas are understudied.

Objective: To investigate the uptake and survival outcomes in treatment with NACT for less common histologic subtypes of epithelial ovarian cancer.

Design, setting, and participants: A retrospective cohort study and systematic literature review with meta-analysis was conducted using the National Cancer Database from 2006 to 2017 and the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2006 to 2019. Data analysis was performed …

Facial Analytics Based On A Coordinate Extrapolation System (Zface) For Morphometric Phenotyping Of Developing Zebrafish, Lorena Maili, Oscar E Ruiz, Philip H Kahan, Frankie Chiu, Stephen T Larson, S Shahrukh Hashmi, Jacqueline T Hecht, George T Eisenhoffer

Faculty, Staff and Student Publications

Facial development requires a complex and coordinated series of cellular events that, when perturbed, can lead to structural birth defects. A quantitative approach to quickly assess morphological changes could address how genetic or environmental inputs lead to differences in facial shape and promote malformations. Here, we report on a method to rapidly analyze craniofacial development in zebrafish embryos using facial analytics based on a coordinate extrapolation system, termed zFACE. Confocal images capture facial structures and morphometric data are quantified based on anatomical landmarks present during development. The quantitative morphometric data can detect phenotypic variation and inform on changes in facial …

Dusp22 Rearrangement Is Associated With A Distinctive Immunophenotype But Not Outcome In Patients With Systemic Alk-Negative Anaplastic Large Cell Lymphoma, Lianqun Qiu, Guilin Tang, Shaoying Li, Francisco Vega, Pei Lin, Sa A Wang, Wei Wang, Swaminathan P Iyer, Luis Malpica, Roberto N Miranda, Sergej Konoplev, Zhenya Tang, Hong Fang, L Jeffrey Medeiros, Jie Xu

Faculty, Staff and Student Publications

DUSP22 rearrangement (R) has been associated with a favorable outcome in systemic ALK-negative anaplastic large cell lymphoma (ALCL). However, a recent study found that patients with DUSP22-R ALK-negative ALCL have a poorer prognosis than was reported initially. In this study, we compared the clinicopathological features and outcomes of patients with ALKnegative ALCL with DUSP22-R (n=22) versus those without DUSP22-R (DUSP22-NR; n=59). Patients with DUSP22-R ALCL were younger than those with DUSP22-NR neoplasms (P=0.049). DUSP22-R ALK-negative ALCL cases were more often positive for CD15, CD8, and less frequently expressed pSTAT3Tyr705, PD-L1, granzyme B and EMA (all P0.05), but was significantly shorter …

Neuroaffective Reactivity Profiles Are Associated With Vulnerability To E-Cigarette Use, Francesco Versace, George Kypriotakis, Dustin Pluta

Faculty, Staff and Student Publications

BACKGROUND: We tested whether neuroaffective responses to motivationally salient stimuli are associated with vulnerability to cue-induced e-cigarette use in e-cigarette naïve adults who smoke daily. We hypothesized that individuals with stronger neuroaffective responses to nicotine-related cues than to pleasant stimuli (the C>P reactivity profile) would be more vulnerable to cue-induced nicotine self-administration than individuals with stronger neuroaffective responses to pleasant stimuli than to nicotine-related cues (the P>C reactivity profile).

METHODS: We used event-related potentials (ERPs, a direct measure of cortical activity) to measure neuroaffective reactivity to pleasant, unpleasant, neutral, and nicotine-related cues indicating the opportunity to use an …

Integration Of Remote Symptom And Biometric Monitoring Into The Care Of Adult Patients With Cancer Receiving Chemotherapy-A Decentralized Feasibility Pilot Study, Anaeze C Offodile, Domenica Delgado, Yu-Li Lin, Danielle Geyen, Christopher J Miller, Sanchita Jain, Janice P Finder, Sanjay Shete, Frank V Fossella, Michael J Overman, Susan K Peterson

Faculty, Staff and Student Publications

PURPOSE: Although electronic patient-reported outcomes (ePROs) are efficacious in symptom management, much is unknown about the utility of vital signs surveillance. We examined the feasibility of a remote patient monitoring platform that integrates ePROs and biometrics into the ambulatory management of symptom burden.

METHODS: Using a decentralized workflow, patients with gastrointestinal or thoracic cancer were approached for a 1-month study. Patients reported symptom burden via ePROs and biometrics (blood pressure, oxygen saturation, pulse, weight, and temperature) using bluetooth-enabled devices daily. Alerts on the basis of prespecified thresholds were managed via nurse-led triage. Adherence was defined as the completion of > 70% …

An Fbn1 Deep Intronic Variant Is Associated With Pseudoexon Formation And A Variable Marfan Phenotype In A Five Generation Family, Dong-Chuan Guo, Xueyan Duan, Kathleen Mimnagh, Alana C Cecchi, Isabella C Marin, Yang Yu, Walter V Velasco, Kwanghyuk Lee, Xue Zhu, David R Murdock, Suzanne M Leal, Marsha M Wheeler, Josh Smith, Michael J Bamshad, Dianna M Milewicz

Faculty, Staff and Student Publications

Exome sequencing of genes associated with heritable thoracic aortic disease (HTAD) failed to identify a pathogenic variant in a large family with Marfan syndrome (MFS). A genome-wide linkage analysis for thoracic aortic disease identified a peak at 15q21.1, and genome sequencing identified a novel deep intronic FBN1 variant that segregated with thoracic aortic disease in the family (LOD score 2.7) and was predicted to alter splicing. RT-PCR and bulk RNA sequencing of RNA harvested from fibroblasts explanted from the affected proband revealed an insertion of a pseudoexon between exons 13 and 14 of the FBN1 transcript, predicted to lead to …

Review Of Natural Compounds For Potential Psoriasis Treatment, Omali Y Elkhawaga, Mohamed M Ellety, Sheref O Mofty, Mohamed S Ghanem, Abdallah O Mohamed

Faculty, Staff and Student Publications

Psoriasis represents an immune-mediated disease with an unclear cause that's marked by inflammation triggered by dysfunction in the immune system, which results in inflammation in various parts of the skin. There could be obvious symptoms, such as elevated plaques; these plaques may appear differently depending on the type of skin. This disease can cause inflammation in the elbows, lower back, scalp, knees, or other regions of the body. It can begin at any age, although it most commonly affects individuals between the ages of 50 and 60. Specific cells (such as T cells) have been observed to play an obvious …

Bi-Allelic Variants In Hmgcr Cause An Autosomal-Recessive Progressive Limb-Girdle Muscular Dystrophy, Joel A Morales-Rosado, Tanya L Schwab, Sarah K Macklin-Mantia, A Reghan Foley, Filippo Pinto E Vairo, Davut Pehlivan, Sandra Donkervoort, Jill A Rosenfeld, Grace E Boyum, Ying Hu, Anh T Q Cong, Timothy E Lotze, Carrie A Mohila, Dimah Saade, Diana Bharucha-Goebel, Katherine R Chao, Christopher Grunseich, Christine C Bruels, Hannah R Littel, Elicia A Estrella, Lynn Pais, Peter B Kang, Michael T Zimmermann, James R Lupski, Brendan Lee, Matthew J Schellenberg, Karl J Clark, Klaas J Wierenga, Carsten G Bönnemann, Eric W Klee

Faculty, Staff and Students Publications

Statins are a mainstay intervention for cardiovascular disease prevention, yet their use can cause rare severe myopathy. HMG-CoA reductase, an essential enzyme in the mevalonate pathway, is the target of statins. We identified nine individuals from five unrelated families with unexplained limb-girdle like muscular dystrophy and bi-allelic variants in HMGCR via clinical and research exome sequencing. The clinical features resembled other genetic causes of muscular dystrophy with incidental high CPK levels (>1,000 U/L), proximal muscle weakness, variable age of onset, and progression leading to impaired ambulation. Muscle biopsies in most affected individuals showed non-specific dystrophic changes with non-diagnostic immunohistochemistry. …

Impact Of Race And Ethnicity On Presentation And Outcomes Of Patients Treated On Rhabdomyosarcoma Clinical Trials: A Report From The Children’S Oncology Group, Senna R Munnikhuysen, Princess A Ekpo, Wei Xue, Zhengya Gao, Philip J Lupo, Rajkumar Venkatramani, Christine M Heske

Faculty, Staff and Students Publications

BACKGROUND: Racial and ethnic disparities have been demonstrated in pediatric and adult cancers. However, there is no consensus on whether such disparities exist in the presentation, treatment, and outcome of patients with rhabdomyosarcoma (RMS).

METHODS: Patient information from the seven most recent RMS clinical trials was obtained from the Children's Oncology Group (COG). Chi-squared analyses were used to compare patient, tumor, and treatment characteristics across racial and ethnic groups. Pairwise analyses comparing Non-Hispanic Black (NHB) versus Non-Hispanic White (NHW) racial groups and Hispanic versus NHW ethnic groups were conducted for significant characteristics. Kaplan-Meier method and Wilcoxon signed-rank tests were performed …

Snv/Indel Hypermutator Phenotype In Biallelic Rad51c Variant: Fanconi Anemia, Roni Zemet, Haowei Du, Tomasz Gambin, James R Lupski, Pengfei Liu, Paweł Stankiewicz

Faculty, Staff and Students Publications

We previously reported a fetus with Fanconi anemia (FA), complementation group O due to compound heterozygous variants involving RAD51C. Interestingly, the trio exome sequencing analysis also detected eight apparent de novo mosaic variants with variant allele fraction (VAF) ranging between 11.5 and 37%. Here, using whole genome sequencing and a 'home-brew' variant filtering pipeline and DeepMosaic module, we investigated the number and signature of de novo heterozygous and mosaic variants and the hypothesis of a rare phenomenon of hypermutation. Eight-hundred-thirty apparent de novo SNVs and 21 de novo indels had VAFs below 37.41% and were considered postzygotic somatic mosaic variants. …