Digital Commons Network^™

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

Department of Medical Oncology Faculty Papers

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

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

Association Of Cancer Diagnosis With Disability Status Among Older Survivors Of Colorectal Cancer: A Population-Based Retrospective Cohort Study, Shiming Zhang, Lin-Na Chou, Michael D Swartz, Hemalkumar B Mehta, James S Goodwin, Yong-Fang Kuo, Sharon Hermes Giordano, Carole A Tucker, Karen M Basen-Engquist, Elizabeth J Lyons, Brian Downer, Susan K Peterson, Tru Cao, Maria C Swartz

Faculty, Staff and Student Publications

BACKGROUND: Older cancer survivors likely experience physical function limitations due to cancer and its treatments, leading to disability and early mortality. Existing studies have focused on factors associated with surgical complications and mortality risk rather than factors associated with the development of poor disability status (DS), a proxy measure of poor performance status, in cancer survivors. We aimed to identify factors associated with the development of poor DS among older survivors of colorectal cancer (CRC) and compare poor DS rates to an age-sex-matched, non-cancer cohort.

METHODS: This retrospective cohort study utilized administrative data from the Texas Cancer Registry Medicare-linked database. …

Utilizing Ai Integrated Neuroimaging Technology To Expand Upon Machine Learning In Positron Emission Tomography Technology With The Aim Of Detecting Amyloid Beta Biomarkers Early In The Onset Of Alzheimer's., Ethan S. Terman

UROP Posters

Early intervention in Alzheimer's is vital for treatment. The earlier a professional can detect symptoms and make a diagnosis the earlier a prognosis can be implemented. With the prevalence of data in our day-to-day world combined with Artificial intelligence (AI), utilizing both for machine learning can pave the way for more accurate and efficient detection of Alzheimer's and other neurodegenerative diseases. AI combined with Machine learning (ML) increases diagnostic efficiency and reduces human errors, making it a valuable resource for physicians and clinicians alike. With the increasing amount of data processing and image interpretation required, the ability to use AI …

Incorporating Variable Rbe In Impt Optimization For Ependymoma, Hadis Moazami Goudarzi, Gino Lim, David Grosshans, Radhe Mohan, Wenhua Cao

Faculty, Staff and Student Publications

PURPOSE: To study the dosimetric impact of incorporating variable relative biological effectiveness (RBE) of protons in optimizing intensity-modulated proton therapy (IMPT) treatment plans and to compare it with conventional constant RBE optimization and linear energy transfer (LET)-based optimization.

METHODS: This study included 10 pediatric ependymoma patients with challenging anatomical features for treatment planning. Four plans were generated for each patient according to different optimization strategies: (1) constant RBE optimization (ConstRBEopt) considering standard-of-care dose requirements; (2) LET optimization (LETopt) using a composite cost function simultaneously optimizing dose-averaged LET (LET

RESULTS: We found that the LETopt plans consistently achieved increased LET in …

Placental Co-Transcriptional Activator Vestigial-Like 1 (Vgll1) Drives Tumorigenesis Via Increasing Transcription Of Proliferation And Invasion Genes, Heather M Sonnemann, Barbara Pazdrak, Barbara Nassif, Yimo Sun, Lama Elzohary, Amjad H Talukder, Arjun S Katailiha, Krishna Bhat, Gregory Lizée

Faculty, Staff and Student Publications

Introduction: Vestigial-like 1 (VGLL1) is a co-transcriptional activator that binds to TEA domain-containing transcription factors (TEADs). Its expression is upregulated in a variety of aggressive cancer types, including pancreatic and basal-like breast cancer, and increased transcription of VGLL1 is strongly correlated with poor prognosis and decreased overall patient survival. In normal tissues, VGLL1 is most highly expressed within placental trophoblast cells, which share the common attributes of rapid cellular proliferation and invasion with tumor cells. The impact of VGLL1 in cancer has not been fully elucidated and no VGLL1-targeted therapy currently exists.

Methods: The aim of this study was to …

Crosstalk Between Breast Cancer-Derived Micrornas And Brain Microenvironmental Cells In Breast Cancer Brain Metastasis, Munazza S Khan, Grace L Wong, Chuling Zhuang, Mariana K Najjar, Hui-Wen Lo

Faculty, Staff and Student Publications

Breast cancer is the most frequent malignancy in women, constituting 15.2% of all new cancers diagnosed in the United States. Distant breast cancer metastasis accounts for the majority of breast cancer-related deaths; brain metastasis is the third most common site for metastatic breast cancer but is associated with worst prognosis of approximately eight months of survival. Current treatment options for breast cancer brain metastasis (BCBM) are limited and ineffective. To help identify new and effective therapies for BCBM, it is important to investigate the mechanisms by which breast cancer cells metastasize to the brain and thrive in the brain microenvironment. …

Does Varicocele Repair Improve Conventional Semen Parameters? A Meta-Analytic Study Of Before-After Data, Rossella Cannarella, Rupin Shah, Taha Abo-Almagd Abdel-Meguid Hamoda, Florence Boitrelle, Ramadan Saleh, Murat Gul, Amarnath Rambhatla, Parviz Kavoussi, Tuncay Toprak, Ahmed M Harraz, Edmund Ko, Gökhan Çeker, Damayanthi Durairajanayagam, Noora Alkahidi, Shinnosuke Kuroda, Andrea Crafa, Ralf Henkel, Gianmaria Salvio, Berk Hazir, Mahsa Darbandi, Marion Bendayan, Sara Darbandi, Marco Falcone, Nicolas Garrido, Raghavender Kosgi, Raneen Sawaid Kaiyal, Keshab Karna, Nguyen Ho Vinh Phuoc, Ponco Birowo, Giovanni M Colpi, Jean De La Rosette, Germar-Michael Pinggera, Quang Nguyen, Armand Zini, Wael Zohdy, Rajender Singh, Pallavi Saini, Sidney Glina, Haocheng Lin, Taymour Mostafa, Cesar Rojas-Cruz, Mohamed Arafa, Aldo E Calogero, Fotios Dimitriadis, Priyank Kothari, Vilvapathy Senguttuvan Karthikeyan, Keisuke Okada, Koji Chiba, Ates Kadıoglu, Baris Altay, Tahsin Turunc, Birute Zilaitiene, Fatih Gokalp, Aram Adamyan, Darren Katz, Eric Chung, Tiago Cesar Mierzwa, Daniel Suslik Zylbersztejn, Gustavo Marquesine Paul, Nikolaos Sofikitis, Ioannis Sokolakis, Vineet Malhotra, Sakti Ronggowardhana Brodjonegoro, Ricky Adriansjah, Akira Tsujimura, Toshiyasu Amano, Giancarlo Balercia, Imad Ziouziou, Isaac Ardianson Deswanto, Marlon Martinez, Hyun Jun Park, Mustafa Emre Bakırcıoglu, Erman Ceyhan, Kaan Aydos, Jonathan Ramsay, Suks Minhas, Manaf Al Hashimi, Ramy Abou Ghayda, Nicholas Tadros, Puneet Sindhwani, Christopher C K Ho, Rinaldo Indra Rachman, Marcelo Rodriguez Pena, Ahmad Motawi, Arun Karthik Ponnusamy, Satish Dipankar, Azwar Amir, Saleh Binsaleh, Ege Can Serefoglu, Ravi Banthia, Kareim Khalafalla, Ari Basukarno, Nguyen Hoai Bac, Karun Singla, Rafael F Ambar, Konstantinos Makarounis, Shivam Priyadarshi, Gede Wirya Kusuma Duarsa, Widi Atmoko, Sunil Jindal, Eko Arianto, Hamed Akhavizadegan, Haitham El Bardisi, Ohad Shoshany, Gian Maria Busetto, Mohamad Moussa, Mounir Jamali, Mohamed S Al-Marhoon, Mikhail Ruzaev, Hasan M A Farsi, Shingai Mutambirwa, Dong Sup Lee, Deniz Kulaksiz, Yu-Sheng Cheng, Abderrazak Bouzouita, Selcuk Sarikaya, Hussein Kandil, Georgios Tsampoukas, Ala'a Farkouh, Kasonde Bowa, Missy Savira, Nasser Mogharabian, Tan V Le, Maruto Harjanggi, Dang Tuan Anh, Tran Quang Tien Long, Mohammad Ayodhia Soebadi, Lukman Hakim, Marko Tanic, Umut Cagin Ari, Firuza R Parikh, Gokhan Calik, Vinod Kv, Gyem Dorji, Andri Rezano, Osvaldo Rajmil, Dung Mai Ba Tien, Yiming Yuan, Juan Francisco Lizarraga-Salas, Balantine Eze, Kay Seong Ngoo, Joe Lee, Umut Arslan, Ashok Agarwal, Global Andrology Forum

Faculty, Staff and Student Publications

Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles.

Materials and methods: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: …

Technical Aspects And Clinical Limitations Of Sperm Dna Fragmentation Testing In Male Infertility: A Global Survey, Current Guidelines, And Expert Recommendations, Ashok Agarwal, Ala'a Farkouh, Ramadan Saleh, Taha Abo-Almagd Abdel-Meguid Hamoda, Gianmaria Salvio, Florence Boitrelle, Ahmed M Harraz, Ramy Abou Ghayda, Parviz Kavoussi, Murat Gül, Tuncay Toprak, Giorgio Ivan Russo, Damayanthi Durairajanayagam, Amarnath Rambhatla, Ponco Birowo, Rossella Cannarella, Nguyen Ho Vinh Phuoc, Armand Zini, Mohamed Arafa, Christine Wyns, Kelton Tremellen, Selçuk Sarıkaya, Sheena Lewis, Donald P Evenson, Edmund Ko, Aldo E Calogero, Fahmi Bahar, Marlon Martínez, Rafael F Ambar, Giovanni M Colpi, Mustafa Emre Bakircioglu, Ralf Henkel, Hussein Kandil, Ege Can Serefoglu, Abdullah Alfakhri, Akira Tsujimura, Alireza Kheradmand, Angelo Marino, Aram Adamyan, Birute Zilaitiene, Cevahir Ozer, Edoardo Pescatori, Paraskevi Vogiatzi, Gian Maria Busetto, Giancarlo Balercia, Haitham Elbardisi, Hamed Akhavizadegan, Hesamoddin Sajadi, Hisanori Taniguchi, Hyun Jun Park, Israel Maldonado Rosas, Mohamed Al-Marhoon, Mohammad Ali Sadighi Gilani, Naif Alhathal, Nguyen Quang, Germar-Michael Pinggera, Priyank Kothari, Sava Micic, Sheryl Homa, Tran Quang Tien Long, Wael Zohdy, Widi Atmoko, Wael Ibrahim, Marjan Sabbaghian, Saad Mohammed Abumelha, Eric Chung, Muhammet Rasit Ugur, Mehmet Serkan Ozkent, Osama Selim, Mahsa Darbandi, Shinichiro Fukuhara, Mounir Jamali, Jean De La Rosette, Shinnosuke Kuroda, Ryan P Smith, Aykut Baser, Arif Kalkanli, Nicholas N Tadros, Kaan Aydos, Tiago Cesar Mierzwa, Kareim Khalafalla, Vineet Malhotra, Mohamad Moussa, Federica Finocchi, Rinaldo Indra Rachman, Carlo Giulioni, Tomer Avidor-Reiss, Oguzhan Kahraman, Gökhan Çeker, Cătălina Zenoaga-Barbăroșie, Trenton L Barrett, Mehmet Yilmaz, Ates Kadioglu, Sunil Jindal, Huda Omran, Kadir Bocu, Vilvapathy Senguttuvan Karthikeyan, Giorgio Franco, Jesús Fernando Solorzano, Ranjit B Vishwakarma, Eko Arianto, Nicolas Garrido, Divyanu Jain, Nazim Gherabi, Ioannis Sokolakis, Ayad Palani, Gokhan Calik, Deniz Kulaksiz, Vaida Simanaviciene, Mara Simopoulou, Nur Dokuzeylül Güngör, Gideon Blecher, Marco Falcone, Davor Jezek, Mirko Preto, Edouard Amar, Tan V Le, Sun Tae Ahn, Andri Rezano, Keerti Singh, Lucia Rocco, Missy Savira, Osvaldo Rajmil, Sara Darbandi, Emrullah Sogutdelen, Luca Boeri, Guadalupe Hernández, Lukman Hakim, Yoshiharu Morimoto, Andrian Japari, Nikolaos Sofikitis, Baris Altay, Asli Metin Mahmutoglu, Manaf Al Hashimi, Imad Ziouziou, Christina Anagnostopoulou, Haocheng Lin, Rupin Shah

Faculty, Staff and Student Publications

Purpose: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice.

Materials and methods: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses …

Pet Image Denoising Based On Denoising Diffusion Probabilistic Model, Kuang Gong, Keith Johnson, Georges El Fakhri, Quanzheng Li, Tinsu Pan

Faculty, Staff and Student Publications

Purpose: Due to various physical degradation factors and limited counts received, PET image quality needs further improvements. The denoising diffusion probabilistic model (DDPM) was a distribution learning-based model, which tried to transform a normal distribution into a specific data distribution based on iterative refinements. In this work, we proposed and evaluated different DDPM-based methods for PET image denoising.

Methods: Under the DDPM framework, one way to perform PET image denoising was to provide the PET image and/or the prior image as the input. Another way was to supply the prior image as the network input with the PET image included …

Transcriptomics Analysis Reveals Potential Mechanisms Underlying Mitochondrial Dysfunction And T Cell Exhaustion In Astronauts’ Blood Cells In Space, Maria Moreno-Villanueva, Luis E Jimenez-Chavez, Stephanie Krieger, Liang-Hao Ding, Ye Zhang, Adriana Babiak-Vazquez, Mark Berres, Sandra Splinter, Kristen E Pauken, Brian C Schaefer, Brian E Crucian, Honglu Wu

Faculty, Staff and Student Publications

Introduction: The impact of spaceflight on the immune system and mitochondria has been investigated for decades. However, the molecular mechanisms underlying spaceflight-induced immune dysregulations are still unclear.

Methods: In this study, blood from eleven crewmembers was collected before and during International Space Station (ISS) missions. Transcriptomic analysis was performed in isolated peripheral blood mononuclear cells (PBMCs) using RNA-sequencing. Differentially expresses genes (DEG) in space were determined by comparing of the inflight to the preflight samples. Pathways and statistical analyses of these DEG were performed using the Ingenuity Pathway Analysis (IPA) tool.

Results: In comparison to pre-flight, a total of 2030 …

Chromatin Regulation By Swi/Snf Remodelers In Somatic Stem Cell Maintenance And Transformation, Luke Thomas Deary

Dartmouth College Ph.D Dissertations

Cell identity is defined by the epigenome, whereby chromatin regulators work in concert to promote gene expression programs that serve a cell’s specialized purpose. Mutations in chromatin regulators are amongst the most frequent drivers of human disease, underscoring the importance of understanding their activities in maintaining cell identity and tissue function. In particular, mutations in subunits of the evolutionarily conserved SWI/SNF chromatin remodeling complexes drive diseases across human tissues in both development and adult tissue maintenance5. Three major SWI/SNF complexes exist: BAF, PBAF, and GBAF, which differ in their composition and genomic targeting but share an ATP-dependent catalytic activity to …

Tim/Tam Receptors: A Potential Biomarker For Predicting Sensitivity To Zika Virus-Induced Oncolysis In Non-Small Cell Lung Cancers, Shankari Somasekar

Honors Undergraduate Theses

Non-small cell lung cancers (NSCLC) constitute 80-85% of lung cancers and are the leading cause of cancer-related deaths globally. The most common cause is prolonged smoking. Current treatment options for NSCLC include surgery, radiation, chemotherapy, targeted drug therapy, and immunotherapy. Although these medications are effective in the short term, patients often face issues of drug resistance and debilitating side effects with prolonged use. Currently, the use of Zika virus (ZIKV) is being researched as a possible alternative treatment for cancer, which minimizes side effects and the risk of drug resistance. TIM/TAM proteins are identified as the putative ZIKV receptors on …

An Objective Assessment Of Neuromotor Control Using A Smartphone App After Repeated Subconcussive Blast Exposure, Charlend K. Howard, Masahiro Yamada, Marcia Dovel, Rie Leverett, Alexander Hill, Kenneth A. Manlapaz, David O. Keyser, Rene S. Hernandez, Sheilah S. Rowe, Walter S. Carr, Michael S. Roy, Christopher K. Rhea

Rehabilitation Sciences Faculty Publications

Subconcussive blast exposure has been shown to alter neurological functioning. However, the extent to which neurological dysfunction persists after blast exposure is unknown. This longitudinal study examined the potential short- and long-term effects of repeated subconcussive blast exposure on neuromotor performance from heavy weapons training in military personnel. A total of 214 participants were assessed; 137 were exposed to repeated subconcussive blasts and 77 were not exposed to blasts (controls). Participants completed a short stepping-in-place task while an Android smartphone app placed on their thigh recorded movement kinematics. We showed acute suppression of neuromotor variability 6 h after subconcussive blast …

Fgf5, Evelyn A Carrion, Malcolm M Moses, Richard R Behringer

Faculty, Staff and Student Publications

FGF5 functions as a negative regulator of the hair cycle in mammals. It is expressed in the outer root sheath of hair follicles during the late anagen phase of the hair cycle. It functions as a signaling molecule, mediating the transition of the anagen growth phase to catagen regression phase of the hair cycle. Spontaneous and engineered FGF5 mutations in mammalian animal models result in long hair phenotypes. In humans, inherited FGF5 mutations result in trichomegaly (long eyelashes). Knockdown of fgf5 in zebrafish embryos results in inner ear alterations. Alterations in FGF5 expression are also associated with various human pathologies.

Impact Of P53-Associated Acute Myeloid Leukemia Hallmarks On Metabolism And The Immune Environment, Monika Chomczyk, Luca Gazzola, Shubhankar Dash, Patryk Firmanty, Binsah S George, Vakul Mohanty, Hussein A Abbas, Natalia Baran

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML), an aggressive malignancy of hematopoietic stem cells, is characterized by the blockade of cell differentiation, uncontrolled proliferation, and cell expansion that impairs healthy hematopoiesis and results in pancytopenia and susceptibility to infections. Several genetic and chromosomal aberrations play a role in AML and influence patient outcomes. TP53 is a key tumor suppressor gene involved in a variety of cell features, such as cell-cycle regulation, genome stability, proliferation, differentiation, stem-cell homeostasis, apoptosis, metabolism, senescence, and the repair of DNA damage in response to cellular stress. In AML, TP53 alterations occur in 5%-12% of de novo AML …

Chronic Lymphocytic Leukemia: Disease Biology, Stefan Koehrer, Jan A Burger

Faculty, Staff and Student Publications

Background: B-cell receptor (BCR) signaling is crucial for normal B-cell development and adaptive immunity. In chronic lymphocytic leukemia (CLL), the malignant B cells display many features of normal mature B lymphocytes, including the expression of functional B-cell receptors (BCRs). Cross talk between CLL cells and the microenvironment in secondary lymphatic organs results in BCR signaling and BCR-driven proliferation of the CLL cells. This critical pathomechanism can be targeted by blocking BCR-related kinases (BTK, PI3K, spleen tyrosine kinase) using small-molecule inhibitors. Among these targets, Bruton tyrosine kinase (BTK) inhibitors have the highest therapeutic efficacy; they effectively block leukemia cell proliferation and …

Enhancing Associative Learning In Rats With A Computationally Designed Training Protocol, Xu O Zhang, Yili Zhang, Claire E Cho, Douglas S Engelke, Paul Smolen, John H Byrne, Fabricio H Do-Monte

Faculty, Staff and Student Publications

Background: Learning requires the activation of protein kinases with distinct temporal dynamics. In Aplysia, nonassociative learning can be enhanced by a computationally designed learning protocol with intertrial intervals (ITIs) that maximize the interaction between fast-activated PKA (protein kinase A) and slow-activated ERK (extracellular signal-regulated kinase). Whether a similar strategy can enhance associative learning in mammals is unknown.

Methods: We simulated 1000 training protocols with varying ITIs to predict an optimal protocol based on empirical data for PKA and ERK dynamics in rat hippocampus. Adult male rats received the optimal protocol or control protocols in auditory fear conditioning and fear …

Risk Stratification And Prediction Of Severity Of Covid-19 Infection In Patients With Preexisting Cardiovascular Disease, Stanislava Matejin, Igor D Gregoric, Rajko Radovancevic, Slobodan Paessler, Vladimir Perovic

Faculty, Staff and Student Publications

Introduction: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a highly contagious viral disease. Cardiovascular diseases and heart failure elevate the risk of mechanical ventilation and fatal outcomes among COVID-19 patients, while COVID-19 itself increases the likelihood of adverse cardiovascular outcomes.

Methods: We collected blood samples and clinical data from hospitalized cardiovascular patients with and without proven COVID-19 infection in the time period before the vaccine became available. Statistical correlation analysis and machine learning were used to evaluate and identify individual parameters that could predict the risk of needing mechanical ventilation and patient survival.

Results: Our results confirmed that COVID-19 …

Clinical Characteristics And Outcomes Of Adult Alveolar Rhabdomyosarcoma Patients On First-Line Systemic Therapies: A Single-Institution Cohort, Michael S Nakazawa, J Andrew Livingston, Maria A Zarzour, Andrew J Bishop, Ravin Ratan, Joseph A Ludwig, Dejka M Araujo, Neeta Somaiah, Vinod Ravi, Elise F Nassif, Christina L Roland, Alexander J Lazar, B Ashleigh Guadagnolo, Douglas J Harrison, Robert S Benjamin, Shreyaskumar R Patel, Anthony P Conley

Faculty, Staff and Student Publications

Background: Rhabdomyosarcomas are the most common soft tissue sarcoma in children, and pediatric alveolar rhabdomyosarcoma (ARMS) prognosis has improved based on cooperative studies. However, in adults, ARMS is significantly rarer, has poorer outcomes, and currently lacks optimal treatment strategies. Objective: This study aimed to evaluate the clinical outcome of an adult ARMS population with different front-line systemic chemotherapies and determine if any chemotherapy regimen is associated with improved survival. ]

Materials and methods: This is a retrospective study of histologically confirmed fusion-positive ARMS patients over 18 years of age, who were treated at MD Anderson Cancer Center (MDACC) from 2004 …

Commitment Complex Splicing Factors In Cancers Of The Gastrointestinal Tract-An In Silico Study, Yun Zhang, Alexandria Carrasquillo Simko, Uzondu Okoro, Deja Jamese Sibert, Jin Hyung Moon, Bin Liu, Angabin Matin

Faculty, Staff and Student Publications

The initial step in pre-mRNA splicing involves formation of a spliceosome commitment complex (CC) or E-complex by factors that serve to bind and mark the exon-intron boundaries that will undergo splicing. The CC component U1 snRNP assembles at the 5'-splice site (ss), whereas SF1, U2AF2, and U2AF1 define the 3'-ss of the intron. A PRP40 protein bridges U1 snRNP with factors at the 3'-ss. To determine how defects in CC components impact cancers, we analyzed human gastrointestinal (GI) cancer patient tissue and clinical data from cBioPortal. cBioPortal datasets were analyzed for CC factor alterations and patient outcomes in GI cancers …

Pancreatic Cancer Action Network's Spark: A Cloud-Based Patient Health Data And Analytics Platform For Pancreatic Cancer, Kawther Abdilleh, Omar Khalid, Dennis Ladnier, Wenshuai Wan, Sara Seepo, Garrett Rupp, Valentin Corelj, Zelia F Worman, Divya Sain, Jack Digiovanna, Bruce Press, Satty Chandrashekhar, Eric Collisson, Karen Y Cui, Anirban Maitra, Paul A Rejto, Kevin P White, Lynn Matrisian, Sudheer Doss

Faculty, Staff and Student Publications

Purpose: Pancreatic cancer currently holds the position of third deadliest cancer in the United States and the 5-year survival rate is among the lowest for major cancers at just 12%. Thus, continued research efforts to better understand the clinical and molecular underpinnings of pancreatic cancer are critical to developing both early detection methodologies as well as improved therapeutic options. This study introduces Pancreatic Cancer Action Network's (PanCAN's) SPARK, a cloud-based data and analytics platform that integrates patient health data from the PanCAN's research initiatives and aims to accelerate pancreatic cancer research by making real-world patient health data and analysis tools …

Harnessing Endoscopic Ultrasound-Guided Radiofrequency Ablation To Reshape The Pancreatic Ductal Adenocarcinoma Microenvironment And Elicit Systemic Immunomodulation, Vishali Moond, Bhumi Maniyar, Prateek Suresh Harne, Jennifer M Bailey-Lundberg, Nirav C Thosani

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognostics and substantial therapeutic challenges, with dismal survival rates. Tumor resistance in PDAC is primarily attributed to its fibrotic, hypoxic, and immune-suppressive tumor microenvironment (TME). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA), an Food and Drug Administration (FDA)-approved minimally invasive technique for treating pancreatic cancer, disrupts tumors with heat and induces coagulative necrosis, releasing tumor antigens that may trigger a systemic immune response-the abscopal effect. We aim to elucidate the roles of EUS-RFA-mediated thermal and mechanical stress in enhancing anti-tumor immunity in PDAC. A comprehensive literature review focused on radiofrequency immunomodulation and immunotherapy in …

Individual Ingredients Of Np-101 (Thymoquinone Formula) Inhibit Sars-Cov-2 Pseudovirus Infection, Abdelrahim Maen, Betul Gok Yavuz, Yehia I Mohamed, Abdullah Esmail, Jianming Lu, Amr Mohamed, Asfar S Azmi, Mohamed Kaseb, Osama Kasseb, Dan Li, Michelle Gocio, Mehmet Kocak, Abdelhafez Selim, Qing Ma, Ahmed O Kaseb

Faculty, Staff and Student Publications

Thymoquinone TQ, an active ingredient of Nigella Sativa, has been shown to inhibit COVID-19 symptoms in clinical trials. Thymoquinone Formulation (TQF or NP-101) is developed as a novel enteric-coated medication derivative from Nigella Sativa. TQF consists of TQ with a favorable concentration and fatty acids, including palmitic, oleic, and linoleic acids. In this study, we aimed to investigate the roles of individual ingredients of TQF on infection of SARS-CoV-2 variants

Leptomeningeal Disease In Melanoma: An Update On The Developments In Pathophysiology And Clinical Care, Inna Smalley, Adrienne Boire, Priscilla Brastianos, Harriet M Kluger, Eva Hernando-Monge, Peter A Forsyth, Kamran A Ahmed, Keiran S M Smalley, Sherise Ferguson, Michael A Davies, Isabella C Glitza Oliva

Faculty, Staff and Student Publications

Leptomeningeal disease (LMD) remains a major challenge in the clinical management of metastatic melanoma patients. Outcomes for patient remain poor, and patients with LMD continue to be excluded from almost all clinical trials. However, recent trials have demonstrated the feasibility of conducting prospective clinical trials in these patients. Further, new insights into the pathophysiology of LMD are identifying rational new therapeutic strategies. Here we present recent advances in the understanding of, and treatment options for, LMD from metastatic melanoma. We also annotate key areas of future focus to accelerate progress for this challenging but emerging field.

Myeloid Lineage Switch In Kmt2a- Rearranged Acute Lymphoblastic Leukemia Treated With Lymphoid Lineagedirected Therapies, Alex Bataller, Tareq Abuasab, David Mccall, Wei Wang, Branko Cuglievan, Ghayas C Issa, Elias Jabbour, Nicholas Short, Courtney D Dinardo, Guilin Tang, Guillermo Garcia-Manero, Hagop M Kantarjian, Koji Sasaki

Faculty, Staff and Student Publications

No abstract provided.

Editorial: Mathematical Modeling And Computational Predictions In Oncoimmunology, Vladimir A Kuznetsov, Heiko Enderling, Mark Chaplain

Faculty, Staff and Student Publications

No abstract provided.

Spatial Multiplexing And Omics, Julienne L Carstens, Santhoshi N Krishnan, Arvind Rao, Anna G Sorace, Erin H Seeley, Sammy Ferri-Borgogno, Jared K Burks

Faculty, Staff and Student Publications

Much like solving a game of Clue, understanding physiological mysteries involves answering who, what, when, and where. Multi-omics approaches delve into cellular and molecular identities (the who and what), while longitudinal data collection addresses the when. Spatial dimensions address the where. This Primer discusses current technologies enabling quantification across biological scales, emphasizing the importance of retaining the spatial dimension of that data. We outline experimental design considerations, including targeted versus untargeted approaches, sample types, biological scale, and four main classes of molecule detection. Spatial analytics are explored, covering questioning approaches, analytical platforms, image segmentation and sampling. Example applications, reproducibility considerations, …

Fueling Cardiac Myocyte Proliferation, Manisha Deogharia, Priyatansh Gurha

Faculty, Staff and Student Publications

No abstract provided.

Metformin In Conjunction With Stereotactic Radiotherapy For Early-Stage Non-Small Cell Lung Cancer: Long-Term Results Of A Prospective Phase Ii Clinical Trial, Molly K Tate, Mike Hernandez, Joe Y Chang, Steven H Lin, Zhongxing Liao, Suja M Koshy, Heath D Skinner, Stephen G Chun

Faculty, Staff and Student Publications

Background/aim: Non-small cell lung cancer (NSCLC) is increasingly detected in early stages and there is interest in improving outcomes with stereotactic body radiotherapy (SBRT). As metformin affects NSCLC signaling pathways, it might alter the metabolism of NSCLC treated with SBRT. This study investigated the long-term outcomes of a phase II clinical trial evaluating metformin in conjunction with SBRT for early-stage NSCLC.

Patients and methods: The trial evaluated patients with American Joint Commission on Cancer (AJCC) 7th edition Stage I-II, cT1-T2N0M0 NSCLC who were randomized 6:1 to receive metformin versus placebo in conjunction with SBRT. The outcomes analyzed included local failure …

Predicting Suicidality In Late-Life Depression By 3d Convolutional Neural Network And Cross-Sample Entropy Analysis Of Resting-State Fmri, Chemin Lin, Chih-Mao Huang, Wei Chang, You-Xun Chang, Ho-Ling Liu, Shu-Hang Ng, Huang-Li Lin, Tatia Mei-Chun Lee, Shwu-Hua Lee, Shun-Chi Wu

Faculty, Staff and Student Publications

Background: Predicting suicide is a pressing issue among older adults; however, predicting its risk is difficult. Capitalizing on the recent development of machine learning, considerable progress has been made in predicting complex behavior such as suicide. As depression remained the strongest risk for suicide, we aimed to apply deep learning algorithms to identify suicidality in a group with late-life depression (LLD).

Methods: We enrolled 83 patients with LLD, 35 of which were non-suicidal and 48 were suicidal, including 26 with only suicidal ideation and 22 with past suicide attempts, for resting-state functional magnetic resonance imaging (MRI). Cross-sample entropy (CSE) analysis …