Digital Commons Network^™

Enl Mutation And Aml: A New Model That Reveals Oncogenic Condensate’S Function In Leukemogenesis, Zhong Fan, Yanan Jiang, Xiaotian Zhang

Faculty, Staff and Student Publications

Precise regulation of gene expression is essential for proper development and the maintenance of homeostasis in organisms. Studies have shown that some transcriptional regulatory proteins influence gene expression through the formation of dynamic, locally concentrated assemblies known as condensates, while dysregulation of transcriptional condensates was associated with several cancers, such as Ewing sarcoma and AML [Wang Y et al. (2023) Nat Chem Biol 19, 1223-1234; Chandra B et al. (2022) Cancer Discov 12, 1152-1169]. Mutations in the histone acetylation "reader" eleven-nineteen-leukemia (ENL) have been shown to form discrete condensates at endogenous genomic targets, but it remains unclear how ENL mutations …

Stat3 Inhibition In Combination With Cd47 Blockade Inhibits Osteosarcoma Lung Metastasis, Pradeep Shrestha, Rejeena Shrestha, You Zhou, Rafal Zielinski, Waldemar Priebe, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Background: New therapies are urgently needed for patients with osteosarcoma (OS). STAT3 and CD47 are potential therapeutic target in OS. Here we investigated the therapeutic activity of the orally bioavailable STAT3 inhibitor, WP1066, and anti-CD47 antibody using OS mouse models.

Methods: Cytotoxic effect of WP1066 against OS cell lines and its immunomodulatory effects were evaluated in vitro. Experimental metastasis and orthotopic syngeneic mouse models were used to investigate the therapeutic efficacy of WP1066 and anti-CD47 antibody. Further flow cytometric analysis was performed.

Results: STAT3 was constitutively activated in multiple human and mouse OS cell lines. WP1066 suppressed STAT3 activation …

Novel Use And Value Of Contrast-Enhanced Susceptibility-Weighted Imaging Morphologic And Radiomic Features In Predicting Extremity Soft Tissue Undifferentiated Pleomorphic Sarcoma Treatment Response, Raul F Valenzuela, Elvis De Jesus Duran Sierra, Mathew A Canjirathinkal, Behrang Amini, Ken-Pin Hwang, Jingfei Ma, Keila E Torres, R Jason Stafford, Wei-Lien Wang, Robert S Benjamin, Andrew J Bishop, John E Madewell, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Purpose: Undifferentiated pleomorphic sarcomas (UPSs) demonstrate therapy-induced hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. We aimed to determine the treatment-assessment value of morphologic tumoral hemorrhage patterns and first- and high-order radiomic features extracted from contrast-enhanced susceptibility-weighted imaging (CE-SWI).

Materials and methods: This retrospective institutional review board-authorized study included 33 patients with extremity UPS with magnetic resonance imaging and resection performed from February 2021 to May 2023. Volumetric tumor segmentation was obtained at baseline, postsystemic chemotherapy (PC), and postradiation therapy (PRT). The pathology-assessed treatment effect (PATE) in surgical specimens separated patients into responders (R; ≥90%, n = 16), partial responders …

Prrx1 Has Functional Roles In Pancreatic Acinar To Ductal Metaplasia And Carcinogenesis, Noriyuki Nishiwaki, Kensuke Sugiura, Kensuke Suzuki, Alina L Li, Constanza Tapia Contreras, Gizem Efe, Alice E Shin, Dorsay Sadeghian, Jun Zhao, Anirban Maitra, Jason R Pitarresi, Peter A Sims, Rohit Chandwani, Anil K Rustgi

Faculty, Staff and Student Publications

No abstract provided.

Building Boundary-Crossers In Clinical-Translational Research: An Exploratory Study Of A Novel Communication Intervention, Carrie Cameron, Irene Rull-Garcia, Laura G Meyer, Jose-Armando Fernandez-Guerrero, Erin K Dahlstrom, Christine Bell, Christine Pribbenow

Faculty, Staff and Student Publications

INTRODUCTION: Integrating scientific research across multiple disciplines to advance breakthroughs is at the heart of clinical-translational science (CTS); among competencies that have been identified as essential for progress, skillful communication is critical. Few tools are available to address the social dynamics of the multidimensional diversity characteristics of CTS. We created the "Building a Diverse Biomedical Workforce Through Communication Across Difference (CAD)" workshop intervention. Based on principles of intercultural communication, CAD taught novel situationally-based communication skills to dyads of near-peer mentors and their undergraduate mentees. This study reports on the effectiveness of the operative mechanisms employed in CAD workshops for helping …

Cord Blood-Derived Ink T Cells As A Platform For Allogeneic Car T Cell Therapy, Maison Grefe, Abel Trujillo-Ocampo, Jelita Clinton, Hong He, Ling Yu, Dan Li, Qing Ma, Elizabeth J Shpall, Jeffrey J Molldrem, Jin S Im

Faculty, Staff and Student Publications

CD1d-restricted invariant Natural Killer (iNK) T cells are a suitable candidate for allogeneic Chimeric Antigen Receptor (CAR) T cell therapy as they do not cause graft-versus-host disease (GvHD) due to the monomorphic nature of CD1d proteins. However, the phenotypic and functional heterogeneity of iNK T cells from adult donors (AD) may lead to the inconstant CAR-iNK T cell products. Cord blood-derived (CB) iNK T cells, in contrast, exhibit inter-donor homogeneity in phenotype including uniform CD4 expression and are enriched in memory iNK T cell populations. Thus, we evaluated the preclinical therapeutic potential of iNK T cells derived from cord blood …

Ganglioside Gd2 Contributes To A Stem-Like Phenotype In Intrahepatic Cholangiocarcinoma, Antonella Mannini, Mirella Pastore, Alessia Giachi, Margherita Correnti, Elena Spínola Lasso, Tiziano Lottini, Benedetta Piombanti, Ignazia Tusa, Elisabetta Rovida, Cédric Coulouarn, Jesper B Andersen, Monika Lewinska, Claudia Campani, V Lokesh Battula, Bin Yuan, Massimo Aureli, Emma V Carsana, Caterina Peraldo Neia, Paola Ostano, Alessia Tani, Daniele Nosi, Anna Vanni, Laura Maggi, Luca Di Tommaso, Giuseppina Comito, Stefania Madiai, Annarosa Arcangeli, Fabio Marra, Chiara Raggi

Faculty, Staff and Student Publications

BACKGROUND & AIMS: GD2, a member of the ganglioside (GS) family (sialic acid-containing glycosphingolipids), is a potential biomarker of cancer stem cells (CSC) in several tumours. However, the possible role of GD2 and its biosynthetic enzyme, GD3 synthase (GD3S), in intrahepatic cholangiocarcinoma (iCCA) has not been explored.

METHODS: The stem-like subset of two iCCA cell lines was enriched by sphere culture (SPH) and compared to monolayer parental cells (MON). GS profiles were evaluated by chromatography, after feeding with radioactive sphingosine. Membrane GD2 expression was evaluated by FACS, and the expression of enzymes of GS biosynthesis was analysed by RT-qPCR. The …

Development And Validation Of Natural Language Processing Algorithms In The National Enact Network, Yanshan Wang, Jordan Hilsman, Chenyu Li, Michele Morris, Paul M Heider, Sunyang Fu, Min Ji Kwak, Andrew Wen, Joseph R Applegate, Liwei Wang, Elmer Bernstam, Hongfang Liu, Jack Chang, Daniel R Harris, Alexandria Corbeau, Darren Henderson, John Osborne, Richard E Kennedy, Nelly-Estefanie Garduno-Rapp, Justin F Rousseau, Chao Yan, You Chen, Mayur B Patel, Tyler J Murphy, Bradley A Malin, Chan Mi Park, Jungwei W Fan, Sunghwan Sohn, Sandeep Pagali, Yifan Peng, Aman Pathak, Yonghui Wu, Zongqi Xia, Salvatore Loguercio, Steven E Reis, Shyam Visweswaran

Faculty, Staff and Student Publications

Objective: Electronic Health Record (EHR) data are critical for advancing translational research and AI technologies. The ENACT network offers access to structured EHR data across 57 CTSA hubs. However, substantial information is contained in clinical narratives, requiring natural language processing (NLP) for research. The ENACT NLP Working Group was formed to make NLP-derived clinical information accessible and queryable across the network.

Methods: We established the ENACT NLP Working Group with 13 sites selected based on criteria including clinical notes access, IT infrastructure, NLP expertise, and institutional support. We divided sites into five focus groups targeting clinical tasks within disease contexts. …

Epidemiology Of Patient Record Duplication, Onur Sahin, Audrey Zhao, Reuben Joseph Applegate, Todd R Johnson, Elmer V Bernstam

Faculty, Staff and Student Publications

Objectives: Duplicate patient records can increase costs and medical errors. We assessed the association between demographic factors, comorbidities, health care usage, and duplicate electronic health records.

Methods: We analyzed the association between duplicate patient records and multiple demographic variables (race, Hispanic ethnicity, sex, and age) as well as the Charlson Comorbidity Index (CCI), number of diagnoses, and number of health care encounters. The study population included 3,018,413 patients seen at a large urban academic medical center with at least one recorded diagnosis. Duplication of patient medical records was determined by using a previously validated enterprise Master Person Index.

Results: Unknown …

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Alexander M Xu, Dylan Jochum, Issa Ismail Issa, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

Plasma Dna Methylation-Based Biomarkers For Mpnst Detection In Patients With Neurofibromatosis Type 1, Katarzyna Tomczak, Manishkumar S Patel, Angela D Bhalla, Christine B Peterson, Sharon M Landers, S Carson Callahan, Di Zhang, Justin Wong, Jace P Landry, Alexander J Lazar, J Andrew Livingston, B Ashleigh Guadagnolo, Heather G Lyu, Heather Lillemoe, Christina L Roland, Emily Z Keung, Christopher P Scally, Kelly K Hunt, Ian E Mccutcheon, John M Slopis, Jian Gu, Paul Scheet, Liang Wang, Kunal Rai, Keila E Torres

Faculty, Staff and Student Publications

Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST-specific biomarkers for screening patients with NF1. Genome-wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1-MPNST cell lines was performed to identify and validate candidate MPNST-specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST-specific CpGs distinct from adjacent neurofibromas and normal tissues. To test if hypermethylation at selected CpGs can also be detected in plasma from patients with MPNST, …

Approach To Determining Etiology Of Hypophosphatemia In A Patient With Coexisting Phosphaturic Mesenchymal Tumor And Fibrous Dysplasia, Madhuri D Patil, Sintawat Wangsiricharoen, Alexander J Lazar, Bryan Moon, John E Madewell, Michael T Collins, Theresa A Guise

Faculty, Staff and Student Publications

Dysregulated FGF23 production is a demonstrated cause of hypophosphatemia and osteomalacia. Diseases associated with these conditions include phosphaturic mesenchymal tumor (PMT) causing tumor induced osteomalacia, various forms of rickets, and fibrous dysplasia (FD). Coexistence of 2 conditions that can increase FGF23 concentrations is rare. We report a case of a 79-yr-old man who presented with rib and right flank pain. Imaging revealed bone lesions in the right iliac wing, left supra-acetabular area, and L4 vertebral body. Biopsies showed a right iliac PMT and left supra-acetabular FD. Cryoablation of both lesions resolved the phosphaturia with normalization of phosphorus level. Coexistence of …

Intelligent Biology And Medicine: Accelerating Innovative Computational Approaches, Fuhai Li, Li Liu, Kai Wang, Xiaoming Liu, Zhongming Zhao

Faculty, Staff and Student Publications

In this editorial, we summarize the 2023 International Conference on Intelligent Biology and Medicine (ICIBM 2023) conference which was held on July 16-19, 2023 in Tampa, Florida, USA. We then briefly describe the nine research articles included in this special issue. ICIBM 2023 scientific program included four tutorials and workshops, four keynote lectures, four eminent scholars' presentations, 11 concurrent scientific sessions, and a poster session. We had total of 88 scientific oral presentations, including 62 regular oral presentations and 26 flash talks, as well as 46 poster presentations. The topics of these presentations covered artificial intelligence (AI), data sciences, bioinformatics, …

Deep5mc: Predicting 5-Methylcytosine (5mc) Methylation Status Using A Deep Learning Transformer Approach, Evan Kinnear, Houssemeddine Derbel, Zhongming Zhao, Qian Liu

Faculty, Staff and Student Publications

DNA methylations, such as 5-methylcytosine (5mC), are crucial in biological processes, and aberrant methylations are strongly linked to various human diseases. Genomic 5mC is not randomly distributed but exhibits a strong association with genomic sequences. Thus, various computational methods were developed to predict 5mC status based on DNA sequences. These methods generated promising achievements and overcome the limitations of experimental approaches. However, few studies have comprehensively investigated the dependency of 5mC on genomic sequences, and most existing methods focus on specific genomic regions. In this work, we introduce Deep5mC, a deep learning transformer-based method designed to predict 5mC methylations. Deep5mC …

Mmrt: Multimut Recursive Tree For Predicting Functional Effects Of High-Order Protein Variants From Low-Order Variants, Bryce Forrest, Houssemeddine Derbel, Zhongming Zhao, Qian Liu

Faculty, Staff and Student Publications

Protein sequences primarily determine their stability and functions. Mutations may occur at one, two, or three positions at the same time (low-order variants) or at multiple positions simultaneously (high-order variants), which affect protein functions. So far, low-order variants, such as single variants, double variants, and triple variants, have been well-studied through high-throughput experimental scanning techniques and computational prediction methods. However, research on high-order variants remains limited because of the difficulty of scanning an exponentially large number of potential variant combinations. Nonetheless, studying higher-order variants is crucial for understanding the pathogenesis of complex diseases, advancing protein engineering, and driving precision medicine. …

Enhancing The Utility Of Polygenic Scores In Alzheimer’S Disease Through Systematic Curation And Annotation, Savannah Mwesigwa, Yulin Dai, Nitesh Enduru, Zhongming Zhao

Faculty, Staff and Student Publications

Introduction: Polygenic Scores (PGSs) assess cumulative genetic risk variants that contribute to the association with complex diseases like Alzheimer's Disease (AD). The PGS Catalog is a valuable repository of PGSs of various complex diseases, but it lacks standardized annotations and harmonization, making the information difficult to integrate for a specific disease.

Methods: In this study, we curated 44 PGS datasets for AD from the PGS Catalog, categorized them into five methodological groups, and annotated 813,257 variants to nearby genes. We aligned the scores based on the "GWAS significant variants" (GWAS-SV) method with the GWAS Catalog and flagged redundant files and …

Lp-118 Is A Novel B-Cell Lymphoma 2 / Extra-Large Inhibitor That Demonstrates Efficacy In Models Of Venetoclaxresistant Chronic Lymphocytic Leukemia, Janani Ravikrishnan, Daisy Y Diaz-Rohena, Elizabeth Muhowski, Xiaokui Mo, Tzung-Huei Lai, Shrilekha Misra, Charmelle D Williams, John Sanchez, Andrew Mitchell, Suresh Satpati, Elizabeth Perry, Tierney Kaufman, Chaomei Liu, Arletta Lozanski, Gerard Lozanski, Kerrya Rogers, Adam S Kittai, Seema A Bhat, Mary C Collins, Matthew S Davids, Nitin Jain, William G Wierda, Rosa Lapalombella, John C Byrd, Fenlai Tan, Yi Chen, Yu Chen, Yue Shen, Stephen P Anthony, Jennifer A Woyach, Deepa Sampath

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis …

Optimal Timing Of Organs-At-Risk-Sparing Adaptive Radiation Therapy For Head-And-Neck Cancer Under Re-Planning Resource Constraints, Fatemeh Nosrat, Cem Dede, Lucas B Mccullum, Raul Garcia, Abdallah S R Mohamed, Jacob G Scott, James E Bates, Brigid A Mcdonald, Kareem A Wahid, Mohamed A Naser, Renjie He, Aysenur Karagoz, Amy C Moreno, Lisanne V Van Dijk, Kristy K Brock, Jolien Heukelom, Seyedmohammadhossein Hosseinian, Mehdi Hemmati, Andrew J Schaefer, Clifton D Fuller

Faculty, Staff and Student Publications

Background and purpose: Prior work on adaptive organ-at-risk (OAR)-sparing radiation therapy has typically reported outcomes based on fixed-number or fixed-interval re-planning, which represent one-size-fits-all approaches and do not account for the variable progression of individual patients' toxicities. The purpose of this study was to determine the personalized optimal timing of re-planning in adaptive OAR-sparing radiation therapy, considering limited re-planning resources, for patients with head and neck cancer (HNC).

Materials and methods: A novel Markov decision process (MDP) model was developed to determine optimal timing of re-planning based on the patient's expected toxicity, characterized by normal tissue complication probability (NTCP), for …

Micrornas As Key Regulators Of Cancer Drug Resistance: Insights And Future Directions In Chemotherapy, Targeted-Therapy, Radiotherapy, And Immunotherapy, Michael Attathikhun, Ancuta Jurj, George A Calin

Faculty, Staff and Student Publications

Cancer therapy remains an active field of investigation, particularly in understanding and overcoming therapy resistance. Small non-coding RNAs, such as microRNAs (miRNAs), are emerging as key regulators of cancer survival, progression, proliferation, invasion, migration, and metastasis. Although many studies have linked miRNAs to cancer therapy outcomes, significant questions remain regarding their precise molecular and cellular roles in therapy resistance. Increasing evidence shows that miRNAs influence critical pathways such as apoptosis, immune evasion, and other signaling cascades. However, there have been many setbacks because of the limitations in knowledge of each specific miRNA's function. A deeper understanding of miRNA expression and …

Burden Of Seasonal Human Coronavirus Infections In Hematopoietic Cell Transplant Recipients, Fareed Khawaja, Terri Lynn Shigle, Layale Yaghi, May Daher, Jeremy L Ramdial, Ella Ariza-Heredia, Ying Jiang, Roy F Chemaly

Faculty, Staff and Student Publications

Background: Community respiratory viruses, such as seasonal human coronavirus (HCoV), commonly infect hematopoietic cell transplant (HCT) recipients. Recognizing the risk factors and outcomes of HCoV infections in HCT recipients is essential for the future development of potentially lifesaving therapeutics.

Methods: We performed a retrospective review of all HCoV-infected HCT recipients from September 1, 2015 to August 31, 2017, at our institution. Patients were classified with upper respiratory tract infection (URI) or lower respiratory infection (LRI) based on predefined definitions for respiratory viral infections in HCT recipients. Patient data were collected to identify risk factors for HCoV LRI, and to calculate …

Partial Agonism In Heteromeric Gluk2/Gluk5 Kainate Receptor, Nabina Paudyal, Anindita Das, Elisa Carrillo, Vladimir Berka, Vasanthi Jayaraman

Faculty, Staff and Student Publications

Kainate receptors are a subtype of ionotropic glutamate receptors that form transmembrane channels upon binding glutamate. Here, we have investigated the mechanism of partial agonism in heteromeric GluK2/K5 receptors, where the GluK2 and GluK5 subunits have distinct agonist binding profiles. Using single-molecule Förster resonance energy transfer, we found that at the bi-lobed agonist-binding domain, the partial agonist AMPA-bound receptor occupied intermediate cleft closure conformational states at the GluK2 cleft, compared to the more open cleft conformations in apo form and more closed cleft conformations in the full agonist glutamate-bound form. In contrast, there is no significant difference in cleft closure …

Tnik-Driven Regulation Of Erk5 Transcriptional Activity In Endothelial Cells, Venkata Subrahmanya Kumar Samanthapudi, Sivareddy Kotla, Nhat-Tu Le

Faculty, Staff and Student Publications

Extracellular signal-regulated kinase 5 (ERK5) is essential for cardiovascular development and endothelial cell (EC) function. Activation of ERK5 through MEK5-mediated phosphorylation at threonine 218 and tyrosine 220 (T218/Y220) drives the transcriptional activation of myocyte enhancer factor-2 (MEF2), promoting the expression of KLF2 and KLF4—key transcription factors that maintain vascular homeostasis. We previously demonstrated that ponatinib suppresses ERK5 transcriptional activity without affecting laminar-flow (l-flow)-induced T218/Y220 phosphorylation, suggesting a non-canonical regulatory mechanism. Since ponatinib inhibits Traf2- and Nck-interacting kinase (TNIK), we hypothesized that TNIK modulates ERK5 transcriptional activity. Using a mammalian one-hybrid assay and quantitative RT-PCR (qRT-PCR), we show that TNIK …

Anti-Cd137 Agonist Antibody-Independent And Clinically Feasible Preparation Of Tumor-Infiltrating Lymphocytes From Soft Tissue Sarcoma And Osteosarcoma, Yining Jin, Zhiliang Jia, Xueqing Xia, Nancy B Gordon, Joseph A Ludwig, Neeta Somaiah, Shulin Li

Faculty, Staff and Student Publications

Background: Tumor infiltrating lymphocytes (TILs) therapy has been proved for treatment of metastatic melanoma and is under investigation for other types of solid tumors. However, these successes are threatened by discontinued supply of GMP-grade anti-CD137 agonist, a key TIL preparation reagent. Therefore, exploring a GMP-adherent method for expanding endogenous TILs without anti-CD137 agonist is urgent. Toward this end, we aimed to establish an anti-CD137-independent and clinically feasible TIL expansion protocol to prepare TILs from under investigated sarcoma tumors.

Methods: We collected resected tumors from patients and cut tissues into fragments. We used IL-2 and T-cell activator CD3/CD28 without anti-CD137 agonist …

Intrapartum Glycemic Control And Clinical Outcomes, Ghamar Bitar, Michal Fishel Bartal

Faculty, Staff and Student Publications

Current recommendations encourage strict intrapartum glycemic control for individuals with diabetes in pregnancy to optimize maternal and neonatal outcomes. However, established evidence is limited in providing a strong association between strict maternal blood glucose control and neonatal outcomes.

Using Content Validity Index Methodology For Cross-Cultural Translation Of A Patient-Reported Outcome Measure For Head And Neck Cancer, Janet H Van Cleave, Alizendie Guerra, Eva Liang, Carolina Gutiérrez, Ron J Karni, Marcely Tsikis, Geanise Pearl C Nguyen, Allison P Squires

Faculty, Staff and Student Publications

Introduction: Translations of patient-reported measures may not account for structural and cultural differences in shared languages spoken in multiple countries, such as English, Spanish, Arabic, or Russian. The objective of this research was to create a cross-cultural Spanish translation of the New York University (NYU) Electronic Patient Visit Assessment (ePVA)© for head and neck cancer (HNC), a patient-reported symptom measure available only in English.

Methods: Using the Content Validity Index (CVI) methodology, an expert panel of nurses (n = 6) proficient in Spanish and English independently reviewed and rated a forward translation of the ePVA, a measure consisting of …

Correspondence To Editorial 2 On "Genomic Biomarkers To Predict Response To Atezolizumab Plus Bevacizumab Immunotherapy In Hepatocellular Carcinoma: Insights From The Imbrave150 Trial", Sun Young Yim, Sung Hwan Lee, Ji Hoon Kim, Sunyoung S Lee, Ahmed O Kaseb, Ju-Seog Lee

Faculty, Staff and Student Publications

No abstract provided.

A Phase Ib/Ii Trial Of Neoadjuvant Neratinib Added To Standard Therapy In Patients With Her2-Positive Or Hr-Positive/Her2-Negative Inflammatory Breast Cancer (Including Stage Iii And Iv Disease), Bora Lim, Angela Marx, Megumi Kai, Angela Alexander, Roland Bassett, Wencai Ma, Jie Willey, Huiming Sun, Azadeh Nasrazadani, Mohammad M Mohammad, Jianhua Zhang, Anthony Lucci, Susie X Sun, Michael C Stauder, Gary J Whitman, Huong Le-Petross, Vicente Valero, Wendy A Woodward, Rachel M Layman

Faculty, Staff and Student Publications

Background: Inflammatory breast cancer (IBC) is rare but aggressive, characterized by the rapid onset of diffuse skin erythema, edema, tenderness, induration, and fast metastasis. Both hormone receptor positive (HR+) and human epidermal receptor 2 positive (HER2+) are associated with inferior response after neoadjuvant systemic therapy (NAST) compared to non-IBC. Despite multimodal treatment approaches, the 3-year overall survival rate for stage III IBC remains low at approximately 74%, around 10% lower than the 83% for non-IBC.

Objectives: To evaluate whether the addition of neratinib, an irreversible pan-ErbB receptor small molecule tyrosine kinase inhibitor, improves the rate of pathological complete response in …

Combining Biology-Based And Mri Data-Driven Modeling To Predict Response To Neoadjuvant Chemotherapy In Patients With Triple-Negative Breast Cancer, Casey E Stowers, Chengyue Wu, Zhan Xu, Sidharth Kumar, Clinton Yam, Jong Bum Son, Jingfei Ma, Jonathan I Tamir, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with limited targeted treatment options, heterogeneous treatment response, and high risk of early recurrence. Artificial intelligence (AI) has rapidly emerged as a powerful tool to address key clinical challenges in TNBC across diagnosis, treatment response assessment, and prognosis. Diagnostic and staging challenges persist due to variable imaging features in TNBC and limitations in conventional modalities, increasing the risk of delayed detection. Predicting response to neoadjuvant systemic therapy remains difficult, as patient responses are heterogeneous, and existing clinical markers provide limited early predictive value. Prognostication in TNBC is similarly constrained …

Isotonic Phase I Cancer Clinical Trial Design Utilizing Patient-Reported Outcomes, Nolan A Wages, Ruitao Lin

Faculty, Staff and Student Publications

This article considers the concept of designing Phase I clinical trials using both clinician- and patient-reported outcomes to adaptively allocate study participants to tolerable doses and determine the maximum tolerated dose (MTD) at the study conclusion. We describe a new isotonic patient-reported outcome (PRO-ISO) Phase I design with the flexibility of allocating patients to lower, more tolerable regimens if a large number of PRO-DLT events are seen at higher doses. We conduct simulation studies of the operating characteristics of the design and compared them to the patient-reported outcomes continual reassessment method (PRO-CRM). We illustrate that the PRO-ISO makes appropriate dose …

Bismuth-Infused Perivascular Wrap Facilitates Delivery Of Mesenchymal Stem Cells And Attenuation Of Neointimal Hyperplasia In Rat Arteriovenous Fistulas, Allan John R Barcena, Joy Vanessa D Perez, Marvin R Bernardino, Jossana A Damasco, Erin Marie D San Valentin, Carleigh Klusman, Benjamin Martin, Gino Martin Canlas, Francisco M Heralde, Natalie Fowlkes, Richard R Bouchard, Jizhong Cheng, Steven Y Huang, Marites P Melancon

Faculty, Staff and Student Publications

BACKGROUND: Mesenchymal stem cells (MSCs) have emerged as novel therapies for supporting arteriovenous fistula (AVF) maturation, and bioresorbable polymeric scaffolds have enabled sustained MSC delivery into maturing AVFs. However, the radiolucency of biopolymeric wraps prevents in vivo monitoring of their integrity and location, hindering long-term preclinical investigations.

METHODS: We infused bismuth nanoparticles (BiNPs) into polycaprolactone (PCL) to fabricate an electrospun perivascular wrap capable of MSC delivery and conducive to longitudinal monitoring using conventional imaging. We tested the wraps' effects on the attenuation of markers of neointimal hyperplasia (i.e., endothelial dysfunction, hypoxia, and inflammation), the leading cause of AVF failure, in …