Medical Genetics Commons^™

Head And Neck Cancer Primary Tumor Auto Segmentation Using Model Ensembling Of Deep Learning In Pet/Ct Images, Mohamed A Naser, Kareem A Wahid, Lisanne V Van Dijk, Renjie He, Moamen Abobakr Abdelaal, Cem Dede, Abdallah S R Mohamed, Clifton D Fuller

Faculty, Staff and Student Publications

Auto-segmentation of primary tumors in oropharyngeal cancer using PET/CT images is an unmet need that has the potential to improve radiation oncology workflows. In this study, we develop a series of deep learning models based on a 3D Residual Unet (ResUnet) architecture that can segment oropharyngeal tumors with high performance as demonstrated through internal and external validation of large-scale datasets (training size = 224 patients, testing size = 101 patients) as part of the 2021 HECKTOR Challenge. Specifically, we leverage ResUNet models with either 256 or 512 bottleneck layer channels that demonstrate internal validation (10-fold cross-validation) mean Dice similarity coefficient …

Anatomy And Function Of Ventral Tegmental Area Glutamate Neurons, Jing Cai, Qingchun Tong

Faculty, Staff and Student Publications

The ventral tegmental area (VTA) is well known for regulating reward consumption, learning, memory, and addiction behaviors through mediating dopamine (DA) release in downstream regions. Other than DA neurons, the VTA is known to be heterogeneous and contains other types of neurons, including glutamate neurons. In contrast to the well-studied and established functions of DA neurons, the role of VTA glutamate neurons is understudied, presumably due to their relatively small quantity and a lack of effective means to study them. Yet, emerging studies have begun to reveal the importance of glutamate release from VTA neurons in regulating diverse behavioral repertoire …

A Narrative Review On Invasive Brain Stimulation For Treatment-Resistant Depression, Manoj P Dandekar, Alexandre P Diaz, Ziaur Rahman, Ritele H Silva, Ziad Nahas, Scott Aaronson, Sudhakar Selvaraj, Albert J Fenoy, Marsal Sanches, Jair C Soares, Patricio Riva-Posse, Joao Quevedo

Faculty, Staff and Student Publications

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic …

Harmonization Of Multi-Scanner In Vivo Magnetic Resonance Spectroscopy: Enigma Consortium Task Group Considerations, Ashley D Harris, Houshang Amiri, Mariana Bento, Ronald Cohen, Christopher R K Ching, Christina Cudalbu, Emily L Dennis, Arne Doose, Stefan Ehrlich, Ivan I Kirov, Ralf Mekle, Georg Oeltzschner, Eric Porges, Roberto Souza, Friederike I Tam, Brian Taylor, Paul M Thompson, Yann Quidé, Elisabeth A Wilde, John Williamson, Alexander P Lin, Brenda Bartnik-Olson

Faculty, Staff and Student Publications

Magnetic resonance spectroscopy is a powerful, non-invasive, quantitative imaging technique that allows for the measurement of brain metabolites that has demonstrated utility in diagnosing and characterizing a broad range of neurological diseases. Its impact, however, has been limited due to small sample sizes and methodological variability in addition to intrinsic limitations of the method itself such as its sensitivity to motion. The lack of standardization from a data acquisition and data processing perspective makes it difficult to pool multiple studies and/or conduct multisite studies that are necessary for supporting clinically relevant findings. Based on the experience of the ENIGMA MRS …

Landmark Mediation Survival Analysis Using Longitudinal Surrogate, Jie Zhou, Xun Jiang, H Amy Xia, Brian P Hobbs, Peng Wei

Faculty, Staff and Student Publications

Clinical cancer trials are designed to collect radiographic measurements of each patient's baseline and residual tumor burden at regular intervals over the course of study. For solid tumors, the extent of reduction in tumor size following treatment is used as a measure of a drug's antitumor activity. Statistical estimation of treatment efficacy routinely reduce the longitudinal assessment of tumor burden to a binary outcome describing the presence versus absence of an objective tumor response as defined by RECIST criteria. The objective response rate (ORR) is the predominate method for evaluating an experimental therapy in a single-arm trial. Additionally, ORR is …

Checkpoint Inhibitors As Immunotherapy For Fungal Infections: Promises, Challenges, And Unanswered Questions, Sebastian Wurster, Stephanie S Watowich, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through activation of immune checkpoint pathways. This observation gave rise to several preclinical studies and clinical case reports describing blockade of the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte Antigen 4 immune checkpoint pathways as an adjunct immune enhancement strategy to treat opportunistic fungal infections. The first part of this review summarizes the emerging evidence for contributions of checkpoint pathways to the immunopathology of fungal sepsis, opportunistic …

An Autoencoder-Based Deep Learning Method For Genotype Imputation, Meng Song, Jonathan Greenbaum, Joseph Luttrell, Weihua Zhou, Chong Wu, Zhe Luo, Chuan Qiu, Lan Juan Zhao, Kuan-Jui Su, Qing Tian, Hui Shen, Huixiao Hong, Ping Gong, Xinghua Shi, Hong-Wen Deng, Chaoyang Zhang

Faculty, Staff and Student Publications

Genotype imputation has a wide range of applications in genome-wide association study (GWAS), including increasing the statistical power of association tests, discovering trait-associated loci in meta-analyses, and prioritizing causal variants with fine-mapping. In recent years, deep learning (DL) based methods, such as sparse convolutional denoising autoencoder (SCDA), have been developed for genotype imputation. However, it remains a challenging task to optimize the learning process in DL-based methods to achieve high imputation accuracy. To address this challenge, we have developed a convolutional autoencoder (AE) model for genotype imputation and implemented a customized training loop by modifying the training process with a …

Clinical Implementation And Initial Experience With A 15 Tesla Mr-Linac For Mr-Guided Radiation Therapy For Gynecologic Cancer: An R-Ideal Stage 1 And 2a First In Humans Feasibility Study Of New Technology Implementation, David S Lakomy, Jinzhong Yang, Sastry Vedam, Jihong Wang, Belinda Lee, Angela Sobremonte, Pamela Castillo, Neil Hughes, Mustefa Mohammedsaid, Anuja Jhingran, Ann H Klopp, Seungtaek Choi, C David Fuller, Lilie L Lin

Faculty, Staff and Student Publications

PURPOSE: Magnetic resonance imaging-guided linear accelerator systems (MR-linacs) can facilitate the daily adaptation of radiation therapy plans. Here, we report our early clinical experience using a MR-linac for adaptive radiation therapy of gynecologic malignancies.

METHODS AND MATERIALS: Treatments were planned with an Elekta Monaco v5.4.01 and delivered by a 1.5 Tesla Elekta Unity MR-linac. The system offers a choice of daily adaptation based on either position (ATP) or shape (ATS) of the tumor and surrounding normal structures. The ATS approach has the option of manually editing the contours of tumors and surrounding normal structures before the plan is adapted. Here, …

Defective Dna Polymerase Beta Invoke A Cytosolic Dna Mediated Inflammatory Response, Shengyuan Zhao, Julia A Goewey Ruiz, Manu Sebastian, Dawit Kidane

Faculty, Staff and Student Publications

Base excision repair (BER) has evolved to maintain the genomic integrity of DNA following endogenous and exogenous agent induced DNA base damage. In contrast, aberrant BER induces genomic instability, promotes malignant transformation and can even trigger cancer development. Previously, we have shown that deoxyribo-5'-phosphate (dRP) lyase deficient DNA polymerase beta (POLB) causes replication associated genomic instability and sensitivity to both endogenous and exogenous DNA damaging agents. Specifically, it has been established that this loss of dRP lyase function promotes inflammation associated gastric cancer. However, the way that aberrant POLB impacts the immune signaling and inflammatory responses is still unknown. Here …

Association Of Proton Pump Inhibitor Use With Survival Outcomes In Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review And Meta-Analysis, Baoqing Chen, Chen Yang, Mihnea P Dragomir, Dongmei Chi, Wenyan Chen, David Horst, George A Calin, Qiaoqiao Li

Faculty, Staff and Student Publications

Background: Proton pump inhibitors (PPIs) have been shown to regulate the gut microbiome and affect the response to immune checkpoint inhibitors (ICIs). Contradictory results on survival have been observed in patients concomitantly treated with ICIs and PPIs. We performed a systematic review and meta-analysis to determine the association between PPI use and survival outcomes in ICI-treated cancer patients.

Methods: EMBASE, MEDLINE/PubMed, Cochrane Library databases, and major oncology conference proceedings were searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI-treated and PPI-free groups of ICI-treated cancer patients were included. Data regarding study and patient characteristics, ICI and PPI …

Translating Mentoring Interventions Research Into Practice: Evaluation Of An Evidence-Based Workshop For Research Mentors On Developing Trainees’ Scientific Communication Skills, Erin K Dahlstrom, Christine Bell, Shine Chang, Hwa Young Lee, Cheryl B Anderson, Annie Pham, Christine Maidl Pribbenow, Carrie A Cameron

Faculty, Staff and Student Publications

A key part of keeping doctoral and postdoctoral trainees in STEM research careers is mentoring. Our previous research indicates that mentoring trainees in scientific communication (SC) skill development increases research career intention through two social-cognitive constructs, self-efficacy in and outcome expectations for acquiring SC skills, as well as science identity. While many mentor training interventions exist, no programs focus on developing SC skills specifically. The "Scientific Communication Advances Research Excellence" (SCOARE) program trains mentors to address trainee scientific communication (SC) skill development as an innovative approach to increase trainee research career persistence. The SCOARE training is a half-day workshop for …

Pathogenic Tau Accelerates Aging-Associated Activation Of Transposable Elements In The Mouse Central Nervous System, Paulino Ramirez, Gabrielle Zuniga, Wenyan Sun, Adrian Beckmann, Elizabeth Ochoa, Sarah L Devos, Bradley Hyman, Gabriel Chiu, Ethan R Roy, Wei Cao, Miranda Orr, Virginie Buggia-Prevot, William J Ray, Bess Frost

Faculty, Staff and Student Publications

Transposable elements comprise almost half of the mammalian genome. A growing body of evidence suggests that transposable element dysregulation accompanies brain aging and neurodegenerative disorders, and that transposable element activation is neurotoxic. Recent studies have identified links between pathogenic forms of tau, a protein that accumulates in Alzheimer's disease and related "tauopathies," and transposable element-induced neurotoxicity. Starting with transcriptomic analyses, we find that age- and tau-induced transposable element activation occurs in the mouse brain. Among transposable elements that are activated at the RNA level in the context of brain aging and tauopathy, we find that the endogenous retrovirus (ERV) class …

Research Career Intentions Among Non-Native English-Speaking Graduate And Postdoctoral Trainees In Stem-Results From Cross-Sectional And Longitudinal Studies, Hwa Young Lee, Shine Chang, Cheryl B Anderson, Erin K Dahlstrom, Carrie Cameron

Faculty, Staff and Student Publications

International graduate trainees, many of whom are non-native English-speaking (L2) trainees, comprise more than half of graduate-level trainees in STEM, but little is known regarding factors that influence their career intentions, especially those that foster their growth as scientists to achieve their full potential in research. Thus, the purpose of our studies was to examine the relationship between L2 status and contextual factors that help shape the learning experiences and plans for research-focused careers. Study 1 collected cross-sectional survey data from doctoral and postdoctoral trainees (N=510) from research institutes in the Texas Medical Center in Houston. We examined which factors …

Transcriptomic-Assisted Immune And Neoantigen Profiling In Premalignancy, Kyle Chang, Florencia Mcallister, Eduardo Vilar

Faculty, Staff and Student Publications

Immune-based cancer therapies such as checkpoint inhibitors (CPI) and vaccines have been increasingly studied across different cancer types. Response to such therapies depends on a number of factors such as mutational burden, neoantigen load, presence of tumor infiltrating lymphocytes, among others. Next-generation sequencing (NGS) technologies are particularly attractive to interrogate the immune response compared to traditional assays such as qRT-PCR and immunohistochemistry (IHC) because they enable the discovery of neoantigens and simultaneous profiling of immune infiltration using gene expression on a large scale. Current approaches in immune profiling utilizes whole-exome sequencing (WES) for human leukocyte allele (HLA) typing and neoantigen …

Cancer Prevention Behaviors In Workers Of A Referral Cancer Center In Mexico City: A Pilot Study On Early Detection Awareness For Cancer, Nancy Reynoso-Noverón, Shine Chang, Luis Alonso Herrera-Montalvo, Abelardo Meneses-García

Faculty, Staff and Student Publications

Background: Prevention strategies for cancer are necessary. Health workers who often serve as role models bear responsibility for prevention counseling and programs. However, whether their habits and behaviors reflect prevention goals are unknown. We describe the prevalence of cancer risk factors and prevention behaviors in health workers of a referral cancer center in Mexico City.

Methods: Cross-sectional study in which workers of the National Cancer Institute were invited to participate in a prevention program, risk factor survey, and nutrition, psychological, and genetic counseling were included. The likelihood of cancer was calculated based on the presence of risk factors. Factors associated …

Evaluating A Pilot Culturally Sensitive Psychosocial Intervention On Posttraumatic Growth For Chinese American Breast Cancer Survivors, Qiao Chu, Moni Tang, Lingjun Chen, Lucy Young, Alice Loh, Carol Wang, Qian Lu

Faculty, Staff and Student Publications

This study investigated the potential benefit of a pilot culturally sensitive group support intervention, named Joy Luck Academy (JLA), in fostering posttraumatic growth among Chinese American breast cancer survivors. Eighty-six Chinese American breast cancer survivors participated in an eight-week single-arm pre-/post-test trial of an intervention program, which included educational lectures and peer mentor support. The JLA participants were compared with an independent sample of 109 Chinese American breast cancer survivors who went through routine care. Both groups completed baseline and eight-week follow-up assessments of the five facets of posttraumatic growth (meaningful interpersonal relationships, finding new possibilities in life, personal strength, …

Head-Mounted Digital Metamorphopsia Suppression As A Countermeasure For Macular-Related Visual Distortions For Prolonged Spaceflight Missions And Terrestrial Health, Joshua Ong, Nasif Zaman, Ethan Waisberg, Sharif Amit Kamran, Andrew G Lee, Alireza Tavakkoli

Faculty, Staff and Student Publications

During long-duration spaceflight, astronauts are exposed to various risks including spaceflight-associated neuro-ocular syndrome, which serves as a risk to astronaut vision and a potential physiological barrier to future spaceflight. When considering exploration missions that may expose astronauts to longer periods of microgravity, radiation exposure, and natural aging processes during spaceflight, more severe changes to functional vision may occur. The macula plays a critical role in central vision and disruptions to this key area in the eye may compromise functional vision and mission performance. In this article, we describe the development of a countermeasure technique to digitally suppress monocular central visual …

A Yeast Model For Trichohepatoenteric Syndrome Suggests Strong Loss Of Ski2 Function In Most Causative Mutations, Luisa J Orlando, Matthew K Yim, Thomson Hallmark, Michael Cotner, Sean J Johnson, Ambro Van Hoof

Faculty, Staff and Student Publications

The intestinal and immune disorder trichohepatoenteric syndrome (THES) is characterized by mutations in human Ski2 and Ski3, also known as SKIV2L and TTC37, respectively. The mechanism by which these mutations leads to the immunodeficiency, chronic diarrhea, failure to thrive and liver disease associated with THES is unknown. To what degree THES patient mutations in Ski2 affect Ski2 function and how the differences in Ski2 function could lead to varying patient outcomes has not been studied. Here, we assayed function of THES ski2 mutants in the yeast homolog. Our results show that most THES patient mutations cause severe dysfunction in Ski2. …

Comparison Of Psma-Based 18f-Dcfpyl Pet/Ct And Pelvic Multiparametric Mri For Lesion Detection In The Pelvis In Patients With Prostate Cancer, Trinh T Nguyen, Priya R Bhosale, Guofan Xu, Tinsu Pan, Peng Wei, Yang Lu

Faculty, Staff and Student Publications

Purpose: To directly compare the performance of pelvic mpMRI versus recently approved and increasingly used PSMA-based 18F-DCFPyL PET/CT in intermediate-high risk and biochemical recurrent prostate cancer patient cohort while exploring their potential differing applications in specific clinical scenarios.

Methods: A retrospective analysis was performed on patients who had 18F-DCFPyL PET/CT and pelvic mpMRI done from September 2021 to January 2022 at a single institution. The inclusion criteria were paired exams within a 3-month interval. Exclusion criteria were intervening treatment between exams, a change in PSA by more than 50% and absolute difference more than 1 ng/mL, or concurrent history of …

Serglycin Is Involved In Tgf-Β Induced Epithelial-Mesenchymal Transition And Is Highly Expressed By Immune Cells In Breast Cancer Tissue, Marta Tellez-Gabriel, Xavier Tekpli, Trine M Reine, Beate Hegge, Stephanie R Nielsen, Meng Chen, Line Moi, Lisa Svartdal Normann, Lill-Tove R Busund, George A Calin, Gunhild M Mælandsmo, Maria Perander, Achilleas D Theocharis, Svein O Kolset, Erik Knutsen

Faculty, Staff and Student Publications

Serglycin is a proteoglycan highly expressed by immune cells, in which its functions are linked to storage, secretion, transport, and protection of chemokines, proteases, histamine, growth factors, and other bioactive molecules. In recent years, it has been demonstrated that serglycin is also expressed by several other cell types, such as endothelial cells, muscle cells, and multiple types of cancer cells. Here, we show that serglycin expression is upregulated in transforming growth factor beta (TGF-β) induced epithelial-mesenchymal transition (EMT). Functional studies provide evidence that serglycin plays an important role in the regulation of the transition between the epithelial and mesenchymal phenotypes, …

The Seen And The Unseen: Molecular Classification And Image Based-Analysis Of Gastrointestinal Cancers, Corina-Elena Minciuna, Mihai Tanase, Teodora Ecaterina Manuc, Stefan Tudor, Vlad Herlea, Mihnea P Dragomir, George A Calin, Catalin Vasilescu

Faculty, Staff and Student Publications

Gastrointestinal cancers account for 22.5% of cancer related deaths worldwide and represent circa 20% of all cancers. In the last decades, we have witnessed a shift from histology-based to molecular-based classifications using genomic, epigenomic, and transcriptomic data. The molecular based classification revealed new prognostic markers and may aid the therapy selection. Because of the high-costs to perform a molecular classification, in recent years immunohistochemistry-based surrogate classification were developed which permit the stratification of patients, and in parallel multiple groups developed hematoxylin and eosin whole slide image analysis for sub-classifying these entities. Hence, we are witnessing a return to an image-based …

Recurrent Hgnet-Mn1 Altered (Astroblastoma Mn1-Altered) Of The Foramen Magnum: Case Report And Molecular Classification, Sricharan Gopakumar, Malcolm F Mcdonald, Himanshu Sharma, Claudio E Tatsui, Gregory N Fuller, Ganesh Rao

Faculty, Staff and Student Publications

Background: Astroblastoma is a rare primary brain tumor of unclear origin, often occurring in young patients less than 30-years-old. It typically arises supratentorially and is diagnosed based on histological features including vascular hyalinization and perivascular pseudorosettes. Recent molecular characterization of primary CNS high-grade neuroepithelial tumors with meningioma I alteration (HGNET-MN1) found that HGNET-MN1 and tumors with morphological signatures of astroblastoma clustered together. Further analysis revealed such astroblastomas have MN1 alteration and the 2021 WHO classification of tumors of the CNS now recognizes astroblastoma MN1-altered as a new entity.

Case description: Here, we present the case of …

Re-Thinking Therapeutic Development For Cns Metastatic Disease, Chantal Saberian, Michael A Davies

Faculty, Staff and Student Publications

There has been unprecedented progress in the development of systemic therapies for patients with metastatic melanoma over the last decade. There is now tremendous potential and momentum to further and markedly reduce the impact of this disease. However, developing more effective treatments for metastases to the CNS remains a critical challenge for patients with melanoma. Melanoma patients with active CNS metastases have largely been excluded from both early-phase and registration trials for all currently approved targeted and immune therapies for this disease. While this exclusion has generally been justified in clinical research due to concerns about poor prognosis, lack of …

Behavioural Immune Landscapes Of Inflammation, Georgiana Crainiciuc, Miguel Palomino-Segura, Miguel Molina-Moreno, Jon Sicilia, David G Aragones, Jackson Liang Yao Li, Rodrigo Madurga, José M Adrover, Alejandra Aroca-Crevillén, Sandra Martin-Salamanca, Alfonso Serrano Del Valle, Sandra D Castillo, Heidi C E Welch, Oliver Soehnlein, Mariona Graupera, Fátima Sánchez-Cabo, Alexander Zarbock, Thomas E Smithgall, Mauro Di Pilato, Thorsten R Mempel, Pierre-Louis Tharaux, Santiago F González, Angel Ayuso-Sacido, Lai Guan Ng, Gabriel F Calvo, Iván González-Díaz, Fernando Díaz-De-María, Andrés Hidalgo

Faculty, Staff and Student Publications

Transcriptional and proteomic profiling of individual cells have revolutionized interpretation of biological phenomena by providing cellular landscapes of healthy and diseased tissues1,2. These approaches, however, do not describe dynamic scenarios in which cells continuously change their biochemical properties and downstream 'behavioural' outputs3-5. Here we used 4D live imaging to record tens to hundreds of morpho-kinetic parameters describing the dynamics of individual leukocytes at sites of active inflammation. By analysing more than 100,000 reconstructions of cell shapes and tracks over time, we obtained behavioural descriptors of individual cells and used these high-dimensional datasets to build behavioural landscapes. These landscapes recognized leukocyte …

Prediction Of Early (4-Week) Mortality In Acute Myeloid Leukemia With Intensive Chemotherapy, Koji Sasaki, Tapan Kadia, Kebede Begna, Courtney D Dinardo, Gautam Borthakur, Nicholas J Short, Nitin Jain, Naval Daver, Elias Jabbour, Guillermo Garcia-Manero, Guillermo Montalban Bravo, Lucia Masarova, Sherry Pierce, Marina Konopleva, Farhad Ravandi, Ayalew Tefferi, Hagop Kantarjian

Faculty, Staff and Student Publications

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m2 during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was …

The Current Status And Shortcomings Of Stereotactic Radiosurgery, Hunter Mehrens, Trang Nguyen, Sharbacha Edward, Shannon Hartzell, Mallory Glenn, Daniela Branco, Nadia Hernandez, Paola Alvarez, Andrea Molineu, Paige Taylor, Stephen Kry

Faculty, Staff and Student Publications

Background: Stereotactic radiosurgery (SRS) is a common treatment for intracranial lesions. This work explores the state of SRS treatment delivery to characterize current treatment accuracy based on treatment parameters.

Methods: NCI clinical trials involving SRS rely on an end-to-end treatment delivery on a patient surrogate (credentialing phantom) from the Imaging and Radiation Oncology Core (IROC) to test their treatment accuracy. The results of 1072 SRS phantom irradiations between 2012 and 2020 were retrospectively analyzed. Univariate analysis and random forest models were used to associate irradiation conditions with phantom performance. The following categories were evaluated in terms of how they predicted …

A Phase I, Open-Label, Dose-Escalation Study Of The Ox40 Agonist Ivuxolimab In Patients With Locally Advanced Or Metastatic Cancers, Adi Diab, Omid Hamid, John A Thompson, Willeke Ros, Ferry A L M Eskens, Toshihiko Doi, Siwen Hu-Lieskovan, Samuel J Klempner, Bishu Ganguly, Catherine Fleener, Xiao Wang, Tenshang Joh, Ken Liao, Shahram Salek-Ardakani, Carrie Turich Taylor, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

PURPOSE: Stimulation of effector T cells is an appealing immunotherapeutic approach in oncology. OX40 (CD134) is a costimulatory receptor expressed on activated CD4

PATIENTS AND METHODS: Adult patients (

RESULTS: The most common all-causality adverse events were fatigue (46.2%), nausea (28.8%), and decreased appetite (25.0%). Of 31 treatment-related adverse events, 30 (96.8%) were grade ≤2. No dose-limiting toxicities occurred. Ivuxolimab exposure increased in a dose-proportionate manner from 0.3 to 10 mg/kg. Full peripheral blood target engagement occurred at ≥0.3 mg/kg. Three (5.8%) patients achieved a partial response, and disease control was achieved in 56% of patients. Increased CD4

CONCLUSIONS: Ivuxolimab …

Causal Inference Of Genetic Variants And Genes In Amyotrophic Lateral Sclerosis, Siyu Pan, Xinxuan Liu, Tianzi Liu, Zhongming Zhao, Yulin Dai, Yin-Ying Wang, Peilin Jia, Fan Liu

Faculty, Staff and Student Publications

Amyotrophic lateral sclerosis (ALS) is a fatal progressive multisystem disorder with limited therapeutic options. Although genome-wide association studies (GWASs) have revealed multiple ALS susceptibility loci, the exact identities of causal variants, genes, cell types, tissues, and their functional roles in the development of ALS remain largely unknown. Here, we reported a comprehensive post-GWAS analysis of the recent large ALS GWAS (n = 80,610), including functional mapping and annotation (FUMA), transcriptome-wide association study (TWAS), colocalization (COLOC), and summary data-based Mendelian randomization analyses (SMR) in extensive multi-omics datasets. Gene property analysis highlighted inhibitory neuron 6, oligodendrocytes, and GABAergic neurons (Gad1/Gad2) as …

Facilitating Federated Genomic Data Analysis By Identifying Record Correlations While Ensuring Privacy, Leonard Dervishi, Xinyue Wang, Wentao Li, Anisa Halimi, Jaideep Vaidya, Xiaoqian Jiang, Erman Ayday

Faculty, Staff and Student Publications

With the reduction of sequencing costs and the pervasiveness of computing devices, genomic data collection is continually growing. However, data collection is highly fragmented and the data is still siloed across different repositories. Analyzing all of this data would be transformative for genomics research. However, the data is sensitive, and therefore cannot be easily centralized. Furthermore, there may be correlations in the data, which if not detected, can impact the analysis. In this paper, we take the first step towards identifying correlated records across multiple data repositories in a privacy-preserving manner. The proposed framework, based on random shuffling, synthetic record …

A Novel Group Of Genes That Cause Endocrine Resistance In Breast Cancer Identified By Dynamic Gene Expression Analysis, Arvand Asghari, Katherine Wall, Michael Gill, Natascha Del Vecchio, Farnaz Allahbakhsh, Jacky Wu, Nan Deng, W Jim Zheng, Hulin Wu, Michihisa Umetani, Vahed Maroufy

Faculty, Staff and Student Publications

Breast cancer (BC) is the most common type of cancer diagnosed in women. Among female cancer deaths, BC is the second leading cause of death worldwide. For estrogen receptor-positive (ER-positive) breast cancers, endocrine therapy is an effective therapeutic approach. However, in many cases, an ER-positive tumor becomes unresponsive to endocrine therapy, and tumor regrowth occurs after treatment. While some genetic mutations contribute to resistance in some patients, the underlying causes of resistance to endocrine therapy are mostly undetermined. In this study, we utilized a recently developed statistical approach to investigate the dynamic behavior of gene expression during the development of …