Digital Commons Network^™

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Assessing Chatgpt's Capability As A New Age Standardized Patient: Qualitative Study, Joseph Cross, Tarron Kayalackakom, Raymond E. Robinson, Andrea Vaughans, Roopa Sebastian, Ricardo Hood, Courtney Lewis, Sumanth Devaraju, Prasanna Honnavar, Nikhilesh Anand

School of Medicine Publications

Background: Standardized patients (SPs) have been crucial in medical education, offering realistic patient interactions to students. Despite their benefits, SP training is resource-intensive and access can be limited. Advances in artificial intelligence (AI), particularly with large language models such as ChatGPT, present new opportunities for virtual SPs, potentially addressing these limitations.

Objectives: This study aims to assess medical students' perceptions and experiences of using ChatGPT as an SP and to evaluate ChatGPT's effectiveness in performing as a virtual SP in a medical school setting.

Methods: This qualitative study, approved by the American University of Antigua Institutional Review Board, involved 9 …

Introducing Social Determinants Of Health To The Alzheimer's Disease Research Center Network: Development And Implementation In The Uniform Data Set, Megan Zuelsdorff, Erin L. Abner, Joyce E. Balls-Berry, Gregory A. Jicha, Serggio Lanata, Gladys Maestre, Monica Rosselli, Shana D. Stites, Rachel A. Whitmer, Consuelo H. Wilkins

School of Medicine Publications

The Alzheimer's Disease Research Centers (ADRCs) consortium represents a critical locus of research on Alzheimer's disease and related disorders (ADRD) prevention, diagnosis, and intervention. Through the National Alzheimer's Coordinating Center's (NACC) standardized protocol, the Uniform Data Set (UDS), ADRCs have collected rich, harmonizable clinical and cognitive data. However, the collection of social data has been sparse and Center specific, constraining ADRD science that addresses research priorities on social determinants of health (SDOH) and health equity. Capitalizing on the transition to a revised UDS version 4, an interdisciplinary committee representing 10 ADRCs reviewed the literature and instrumentation, ultimately creating a brief …

Differences In Blood Leukocyte Subpopulations In Schizophrenia: A Systematic Review And Meta-Analysis, Leon Dudeck, Madeleine Nussbaumer, Thomas Nickl-Jockschat, Paul C Guest, Henrik Dobrowolny, Gabriela Meyer-Lotz, Zhongming Zhao, Roland Jacobs, Kolja Schiltz, Brisa S Fernandes, Johann Steiner

Faculty, Staff and Student Publications

Importance: This study aims to provide robust evidence to support or challenge the immune hypothesis of schizophrenia.

Objective: To conduct a meta-analysis of reports on blood leukocyte subpopulations in schizophrenia vs healthy controls, examining disease- and treatment-related differences as well as potential confounders.

Data sources: Systematic database search for English and non-English peer-reviewed articles in PubMed, Web of Science, Scopus, and Cochrane Library databases, with the last search in January 2024.

Study selection: Cross-sectional, case-control, and longitudinal studies comparing leukocyte numbers in patients with schizophrenia and healthy controls. After duplicates were removed, 3691 studies were identified for screening.

Data extraction …

Gonadotropin-Releasing Hormone Ii And Its Receptor: Novel Regulators Of Semen Quality And Follicular Function In Swine, Caitlin Elizabeth Ross

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Pigs are the only mammalian livestock species encoding functional proteins for the second form of gonadotropin-releasing hormone (GnRH-II) and its receptor (GnRHR-II). In the first study, GnRHR-II localized to developing germ cells and the connecting piece of ejaculated spermatozoa. Concurrently, GnRH-II was most abundantly produced in the testis compared with other reproductive tract organs and was present within seminal plasma. Moreover, treatment of extended semen with GnRHR-II analogues altered sperm motility, morphology, and kinematics. For remaining studies, we utilized a swine line with ubiquitous knockdown of GnRHR-II (GnRHR-II KD) developed in our laboratory. The second study demonstrated that circulating GnRH-II …

Amniotic Fluid Extracellular Vesicle And Cell-Free Rna Profiling Reveals Fetal Adaptations In Twin-Twin Transfusion Syndrome, Jacqueline G Parchem, Huihui Fan, Lovepreet K Mann, Kadeshia M Campbell, Sujuan Yang, Wencai Ma, Jong H Won, Jing Wang, Ramesha Papanna, Raghu Kalluri

Faculty, Staff and Student Publications

No abstract provided.

Effect Of Very Preterm Delivery On Outcomes Following In Utero Spina Bifida Repair, Michael V Zaretsky, Jagruti Anadkat, Kelly A Bennett, Yair J Blumenfeld, Chris Buchanan, Caitlin Clifford, Timothy Crombleholme, Samer Elbabaa, Stephen P Emery, William H Goodnight, Hanmin Lee, Joseph B Lillegard, Foong-Yen Lim, Francois I Luks, Virginia Lijewski, Jena L Miller, Ueli Moehrlen, Julie Moldenhauer, Anita J Moon-Grady, Mauro Schenone, Daniel W Skupski, Aimen F Shaaban, Kuojen Tsao, Tim Van Mieghem, Amy J Wagner

Faculty, Staff and Student Publications

Objective: In utero fetal spina bifida repair decreases the risk for cerebrospinal fluid (CSF) diversion including ventriculoperitoneal (VP) shunt placement, reverses hindbrain herniation, and improves motor function with a higher likelihood of independent ambulation. Unfortunately, in utero surgery can be complicated by preterm delivery. The goal of this study was to compare pregnancy and neonatal outcomes between individuals who delivered very preterm, and those who delivered later in gestation following in-utero spina bifida repair.

Methods: Data from the North American Fetal Therapy Network (NAFTNet) Fetal Myelomeningocele Consortium (fMMC) registry collected from 2011 to 2024 were analyzed. Three cohorts of patients …

Evidence For Biomolecular Condensates Formed By The Escherichia Coli Matp Protein In Spatiotemporal Regulation Of The Bacterial Cell Division Cycle, Inés Barros-Medina, Miguel Ángel Robles-Ramos, Marta Sobrinos-Sanguino, Juan Román Luque-Ortega, Carlos Alfonso, William Margolin, Germán Rivas, Begoña Monterroso, Silvia Zorrilla

Faculty, Staff and Student Publications

An increasing number of proteins involved in bacterial cell cycle events have been recently shown to form biomolecular condensates important for their functions that may play a role in development of antibiotic-tolerant persister cells. Here we report that the E. coli chromosomal Ter macrodomain organizer MatP, a division site selection protein coordinating chromosome segregation with cell division, formed biomolecular condensates in crowding cytomimetic systems preferentially localized at the membrane of microfluidics droplets. Condensates were antagonized and partially dislodged from the membrane by DNA sequences recognized by MatP (matS), which partitioned into them. FtsZ, a core component of the division machinery …

Biophysical Studies Of Nucleic Acid - Small Molecule Recognition, Andrea Conner

All Dissertations

The presented work is a collection of studies performed to examine small molecule recognition of nucleic acids. Recognition of nucleic acids was examined using two types of small molecules: aminoglycosides and Hoechst dyes. Chapter One focuses on established experimental techniques (i.e. absorbance, isothermal titration calorimetry, flow cytometry, cell microscopy, etc.) in small molecule recognition of nucleic acids. The emphasis of studies in the group has been on two focus areas. (i) Thermodynamic characterization of mixed A-form and B-form DNA or RNA conformation with aminoglycosides, particularly neomycin-class. (ii) Characterization of new Hoechst-morpholine (HT-MO) derivatives’ interactions with nucleic acids.

Focus area (i) …

The Genomic Landscape And Prognostic Impact Of Kras, Stk11, And Smarca4 Mutations And Co-Mutations On Survival Outcomes In Non-Small Cell Lung Cancer, Peter Manolakos

All Dissertations

Non-small lung cancer (NSCLC) accounts for 85% of lung cancer cases, and Kirsten rat sarcoma viral oncogene homolog (KRAS), Serine/Threonine Kinase 11 (STK11), and SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4) mutations and co-mutations have been increasingly recognized for their potential prognostic significance. However, clear knowledge gaps remain regarding which treatments should be selected for patients who present clinically with KRAS/STK11 or KRAS/SMARCA4 co-mutations, as outlined in Chapter 1. Despite significant clinical development advancements in immunotherapy and targeted therapy, a deeper understanding of the influence of these genomic …

Exploring The Role Of The Id2 And Rab11fip3 Pathway In X-Linked Chronic Granulomatous Disease (Xcgd) Through Comparative Gene Expression Analysis, Kaili Coenen

Honors Theses

X-linked chronic granulomatous disease (XCGD) is a debilitating immunodeficiency disorder primarily affecting men. The disease results from mutations in the CYBB gene on the X chromosome, which encodes the GP91^PHOX protein responsible for electron transfer from NADPH to molecular oxygen. Despite the identification of the CYBB mutation, the pathological mechanism underlying the reduction in reactive oxygen species (ROS) generation in XCGD remains unclear. We hypothesized that comparative gene expression analysis, combined with pathway analysis, could identify genes and signaling pathways contributing to reduced reactive oxygen species (ROS) levels in XCGD. In this study, we analyzed gene expression data from four …

The Impact Of Public Health Authority On Emergency Response In State Health Departments, Jessica L. Baggett

Dissertations: Doctor of Public Health

Background

Public health authority plays a crucial role in enabling state health officials to implement emergency response measures such as isolation, quarantine, and vaccination campaigns. However, legislative changes following the COVID-19 pandemic have significantly curtailed these authorities in many states, raising concerns about the ability of public health officials to respond effectively to future health crises. The erosion of public health authority has highlighted gaps in the legal literacy of health officials and underscored the need for enhanced training in navigating political and legal challenges.

Purpose

The purpose of this study is to assess legal literacy among state health officials, …

Identifying Predictors Of Student Success During Occupational Therapy Level Ii Fieldwork, Melissa R. Foster

Graduate Theses and Dissertations

The training paradigm for new occupational therapy (OT) practitioners includes both didactic classroom learning and clinical fieldwork experiences in order for them to establish clinical competency. However, many students struggle with the theory-to-practice gap of translating classroom knowledge to clinical experiences. When students struggle in this manner, it causes stress for all stakeholders involved, including the fieldwork educator, clinic managers, OT program faculty, as well as the student.

This study aims to avoid this stress by identifying predictors of student success by analyzing data from recent graduates of the University of Arkansas/University of Arkansas for Medical Sciences OT program through …

Enhancing Fairness In Disease Prediction By Optimizing Multiple Domain Adversarial Networks, Bin Li, Xiaoqian Jiang, Kai Zhang, Arif O Harmanci, Bradley Malin, Hongchang Gao, Xinghua Shi

Faculty, Staff and Student Publications

Predictive models in biomedicine need to ensure equitable and reliable outcomes for the populations they are applied to. However, biases in AI models for medical predictions can lead to unfair treatment and widening disparities, underscoring the need for effective techniques to address these issues. However, current approaches struggle to simultaneously mitigate biases induced by multiple sensitive features in biomedical data. To enhance fairness, we introduce a framework based on a Multiple Domain Adversarial Neural Network (MDANN), which incorporates multiple adversarial components. In an MDANN, an adversarial module is applied to learn a fair pattern by negative gradients back-propagating across multiple …

Longevity Humans Have Youthful Erythrocyte Function And Metabolic Signatures, Fang Yu, Changhan Chen, Wuping Liu, Zhixiang Zhao, Yuhua Fan, Zhenjiang Li, Weilun Huang, Tingting Xie, Cheng Luo, Zhouzhou Yao, Qi Guo, Zhiyu Yang, Juan Liu, Yujin Zhang, Rodney E Kellems, Jian Xia, Ji Li, Yang Xia

Faculty, Staff and Student Publications

Longevity individuals have lower susceptibility to chronic hypoxia, inflammation, oxidative stress, and aging-related diseases. It has long been speculated that "rejuvenation molecules" exist in their blood to promote extended lifespan. We unexpectedly discovered that longevity individuals exhibit erythrocyte oxygen release function similar to young individuals, whereas most elderly show reduced oxygen release capacity. Untargeted erythrocyte metabolomics profiling revealed that longevity individuals are characterized by youth-like metabolic reprogramming and these metabolites effectively differentiate the longevity from the elderly. Quantification analyses led us to identify multiple novel longevity-related metabolites within erythrocytes including adenosine, sphingosine-1-phosphate (S1P), and glutathione (GSH) related amino acids. Mechanistically, …

Pathobiology Of Aortic Aneurysms And Dissections: Synthesis Of Recent Investigations And Evolving Insights, L Maximilian Buja, Bihong Zhao, Deborah Vela, Ana Segura, Navneet Narula

Faculty, Staff and Student Publications

The pathobiology of aortic disease is linked to aortic region: atherosclerosis for abdominal aorta, primary medial degeneration or aortitis for ascending thoracic aorta, and all causes for descending thoracic aorta and thoracoabdominal lesions. The pathogenesis of aortic dissection involves damage of the outer media from impaired perfusion from dysfunctional vasa vasorum, formation of discrete foci of disrupted vascular smooth muscle cell-elastic fiber extension-contractile units, and imbalance of radial sheer stress across the aortic wall, thereby creating an intimal tear and linear dissection. Thoracic aortic aneurysms develop from the chronic progression of medial degeneration coupled with the weakening of the remodeled …

Tumour Size Is Associated With Growth Rates Of >0.5 Cm/Year And Delayed Intervention In Small Renal Masses In Patients On Active Surveillance, Maximilian Pallauf, Michael Rezaee, Roy Elias, Tina Wlajnitz, Sean A Fletcher, Joseph Cheaib, Khalid Alkhatib, Peter Chang, Andrew A Wagner, James M Mckiernan, Mohamad E Allaf, Phillip M Pierorazio, Nirmish Singla

Faculty, Staff and Student Publications

Objective: To evaluate the association between tumour size and the growth rate (GR) of small renal masses (SRMs) in patients managed by active surveillance (AS).

Materials and methods: We queried the prospective, multi-institutional Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry for patients on AS with an imaging interval of ≥6 months, identifying 456 patients. We tracked tumour size over time; a GR >0.5 cm/year was defined as a GR event. We used multivariable recurrent events and time-to-event Cox regression modelling to evaluate the association between tumour size and GR events (primary outcome) and tumour size and delayed …

Comparing The Efficacy And Safety Of Glp-1 Receptor Agonists Versus Gastric Bypass Surgery In The Treatment Of Obesity And Type 2 Diabetes, Abir Oliver

Physician Assistant Scholarly Project Papers

Obesity and type 2 diabetes are interconnected global health challenges, contributing significantly to morbidity, mortality, and healthcare costs. This literature review compares the efficacy, safety, and applicability of glucagon-like peptide-1 (GLP-1) receptor agonists and bariatric surgery as treatment options. A literature search with defined inclusion and exclusion criteria was conducted using PubMed and EBSCOhost from May to July 2024, resulting in 14 randomized controlled trials for evaluation. This literature review supports the efficacy of both GLP-1 receptor agonists, particularly semaglutide, and bariatric surgery as effective interventions for weight loss and glycemic control in patients with obesity and type 2 diabetes. …

Adherence To Life’S Essential 8 Is Associated With Delayed White Matter Aging, Li Feng, Zhenyao Ye, Yezhi Pan, Rozalina G Mccoy, Braxton D Mitchell, Peter Kochunov, Paul M Thompson, Jie Chen, Menglu Liang, Thu T Nguyen, Edmond Shenassa, Yan Li, Travis Canida, Hongjie Ke, Hwiyoung Lee, Song Liu, L Elliot Hong, Chixiang Chen, David K Y Lei, Shuo Chen, Tianzhou Ma

Faculty, Staff and Student Publications

Background: The American Heart Association introduced Life's Essential 8 (LE8) to promote cardiovascular health and longevity. However, its impact on brain ageing and interactions with genetic risk factors of dementia, such as APOE4, remains unclear. This study investigates the relationship between LE8 and white matter brain ageing and evaluates the moderating effects of the APOE4 allele.

Methods: This cross-sectional study utilized data from the UK Biobank, including genetic, neuroimaging, and health-related data from touchscreen questionnaires, physical examinations, and biological samples. Participants were non-pregnant whites with LE8 variables, diffusion tensor imaging (DTI) data, and APOE4 genetic information available, excluding those with …

Risk Factors For Mismatches In The Art Laboratory: An Analysis Of 73,719 Electronic Witnessing Points, Maria Forbrig, Kelli Peirce, Chris Copeland, Jay Natalwala, Vincent Chapple, Yanhe Liu

Research outputs 2022 to 2026

Research question: What are the risk factors for mismatches (involving or not involving biological material) and critical mismatches (CMM; involving biological material) in an assisted reproductive technology laboratory equipped with an electronic witnessing system (EWS)? Design: In total, 73,719 witnessing points were extracted retrospectively from an EWS database, representing 11,210 consecutive treatment cycles performed at Fertility North between January 2016 and July 2023. Results: Overall, 138 (0.19%) mismatches and 16 (0.02%) CMM were identified during the study period. Significant differences were detected in both mismatch (P = 0.003) and CMM (P = 0.038) rates between different time periods of the …

Race And Clinical Outcomes In Hormone Receptor-Positive, Her2-Negative, Node-Positive Breast Cancer In The Randomized Rxponder Trial, Yara Abdou, William E Barlow, Julie R Gralow, Funda Meric-Bernstam, Kathy S Albain, Daniel F Hayes, Nancy U Lin, Edith A Perez, Lori J Goldstein, Stephen K L Chia, Sukhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Anne F Schott, Steven Shak, Priyanka Sharma, Danika L Lew, Jieling Miao, Joseph M Unger, Debasish Tripathy, Gabriel N Hortobagyi, Lajos Pusztai, Kevin Kalinsky

Faculty, Staff and Student Publications

Background: The phase III RxPONDER trial has affected treatment for node-positive (1-3), hormone receptor-positive, HER2-negative breast cancer with a 21-gene recurrence score (RS) less than 26. We investigated how these findings apply to different racial and ethnic groups within the trial.

Methods: The trial randomly assigned women to endocrine therapy (ET) or to chemotherapy plus ET. The primary clinical outcome was invasive disease-free survival (IDFS), with distant relapse-free survival (DRFS) as a secondary outcome. Multivariable Cox models were used to evaluate the association between race/ethnicity and survival outcomes, adjusting for clinicopathological characteristics, RS, and treatment.

Results: A total of 4048 …

A Quantitative Study Teaching De-Escalation With Virtual Reality Simulation To Associate Nursing Students Measuring Effectiveness, Learning, And Confidence, Michele Rene Marbet

Doctoral Dissertations and Projects

Workplace violence against nurses is a critical global public health issue, as one in four nurses reportedly experience physical assault by patients. This quantitative quasi-experimental, pretest-posttest study aimed to assess the effectiveness of virtual reality simulation as a teaching strategy for de-escalation education in associate nursing students’ (N = 29) perception in learning and confidence. The study utilized the Simulation Effectiveness Tool-Modified (SET-M) instrument to measure outcomes guided by Kolb's experiential learning theory and the NLN Jeffries simulation theory. The learning variable demonstrated significant improvement as confirmed by paired t-test analysis (p < .01). For the effectiveness and confidence variables, which violated assumptions of normality, a comprehensive statistical approach was implemented. Analysis included parametric testing via paired t-tests, supplemented by nonparametric methods (Wilcoxon Signed-ranks test and Sign test) to ensure statistical rigor. The cumulative results across all three statistical tests consistently demonstrated significant improvements (p < .001). Effect size calculations revealed medium to large significance for all variables measured by Cohen’s d. The conclusive findings of this research included a rejection of all three null hypotheses, which suggests that virtual reality simulation is an effective teaching strategy for developing de-escalation skills, enhancing both learning and confidence among associate nursing students. Future studies are needed to further validate and expand upon the findings of the current research, potentially leading to more widespread adoption of virtual reality simulation in nursing education for teaching de-escalation.

Manganese-Induced Precocious Puberty Alters Mammary Epithelial Cell Proliferation In Female Rats, Alina M. Hamilton, Vinod K. Srivastava, Jill K. Hiney, William L. Dees, Robert K. Dearth

School of Integrative Biological & Chemical Sciences Faculty Publications

Precocious puberty (PP) is an established breast cancer risk factor. In the normal mammary gland, hormone receptor-positive (HR+) cells rarely proliferate. In breast cancer, proliferating epithelial cells are often HR+. It is not known if PP can modify this population of proliferating HR+ cells. Previously, we established a manganese-induced precocious puberty (MnPP) model to study the effects of PP on mammary gland development in female rats. Here, we characterized the distribution of HR+ proliferating mammary epithelial cells in prepubertal and adult rodents, in association with precocious puberty. Female rats were exposed daily to 10 mg/kg manganese chloride or saline (control) …

A Neuroimmune Circuit Mediates Chemo Brain Pathology, Daniel Ahmadi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Chemotherapeutic agents, while effective in targeting malignant tumors, often reduce the patients’ quality of life by inducing fatigue, pain, and motivational deficits. These symptoms are collectively referred to as “chemo brain.” The mechanisms underlying these adverse effects, and specifically whether fatigue and motivational impairments share a common etiology, remain poorly understood. The neural–immune substrates of these symptoms remain obscure, in part because standard preclinical regimens either bypass key systemic signals or introduce local toxicity confounds. Here, I establish and validate a three‑day, low‑dose intravenous cisplatin protocol that avoids peritoneal inflammation and severe renal injury yet produces robust, reversible fatigue and …

Using A Surgical Risk Predictor To Estimate Percutaneous Cryoablation Adverse Event Risk: A Single Center Comparative Analysis, Prisha Patel, Koustav Pal, Hadi Ahmed, Bill Tang, Iwan Paolucci, Mohammad Khavandi, Peiman Habibollahi, Ketan Shah, Steven Y Huang, Bruno C Odisio, Sanjay Gupta, Kamran Ahrar, Steven Yevich, Joshua D Kuban, Alda Tam, Rahul A Sheth

Faculty, Staff and Student Publications

Objective: To evaluate the relevance of established surgical risk calculators for predicting complications in patients undergoing percutaneous lung cryoablation (PLC).

Methods: The institution's database was queried for PLC procedures from March 2015 to May 2024, excluding those patients with concomitant local therapies or five or more lesions treated in a single setting. Demographics, frailty metrics as defined by the surgical literature, and procedural variables were collected. To evaluate the suitability of surgical risk estimate calculators, the requisite demographic data were input into the American College of Surgery surgical risk calculator; estimates for length of stay (LOS), serious complications, 30-day readmission, …

Tumoral And Circulating Genomic Landscape Inform Survival Differences In Colorectal Carcinomatosis, Michael G White, Reed I Ayabe, Mohammad A Zeineddine, Fadl A Zeineddine, Abdelrahman M G Yousef, Mahmoud Yousef, Norman J Galbraith, J Bryan Iorgulescu, Christopher Scally, Keith Fournier, Timothy E Newhook, Nancy Y You, Jason Willis, Scott Kopetz, George J Chang, John Paul Shen, Abhineet Uppal

Faculty, Staff and Student Publications

Colorectal peritoneal metastases (CPM) are the third most common site of metastatic spread of colorectal cancer and are associated with worse survival than other sites of metastatic disease. In recent years tumoral circulating tumoral DNA (ctDNA) mutational status has been increasingly utilized in clinical decision making for metastatic colorectal cancer patients despite its utility in CPM being poorly understood. Here we describe standard of care performed mutational profiles and associated outcomes for unresectable CPM patients, with a contextual comparison to 160 unresected colorectal liver metastases (CLM) patients. Of 508 patients, 288 (57 %) had CPM alone and 220 (43 %) …

Phase Ii Trial Of Atezolizumab And Bevacizumab For Treatment Of Hpv-Positive Unresectable Or Metastatic Squamous Cell Carcinoma Of The Anal Canal, Van K Morris, Suyu Liu, Kangyu Lin, Haifeng Zhu, Seema Prasad, Armeen Mahvash, Priya Bhosale, Baohua Sun, Edwin R Parra, Ignacio Wistuba, Arjun Peddireddy, James Yao, Julia Mendoza-Perez, Mark Knafl, Scott E Woodman, Cathy Eng, Daniel Halperin

Faculty, Staff and Student Publications

Purpose: Anti-PD-L1 antibodies are associated with responses in < 25% of patients with metastatic human papillomavirus-associated malignancies. VEGF signaling causes immune evasion and immune suppression within the tumor. We evaluated the anti-PD-L1 antibody atezolizumab and anti-VEGF antibody bevacizumab for patients with unresectable, advanced anal cancer.

Patients and methods: For this phase II study, participants with previously treated, immunotherapy-naïve anal cancer received atezolizumab (1,200 mg) and bevacizumab (15 mg/kg) intravenously every 21 days. Responses were evaluated every 9 weeks (RECIST version 1.1). The primary endpoint was the best radiographic response. Median survival was estimated by Kaplan-Meier and compared for selected biomarkers (including paired pre- and on-treatment biopsies) using a log-rank test.

Results: Among 20 participants, the overall response rate was 11% [95% confidence interval (CI): 1.2-32]. Median progression-free survival and overall survival were 4.1 months (95% CI, 2.6-not …

Pembrolizumab In Patients With Advanced Miscellaneous Rare Cancers: Results From A Phase 2 Basket Trial, Mirella Nardo, Camila Braganca Xavier, Bettzy Stephen, Jeffrey A How, Justin Moyers, Vivek Subbiah, David S Hong, Aung Naing

Faculty, Staff and Student Publications

Introduction: Rare solid tumors account for one-quarter of cancers among adults in the United States, but few resources have been devoted to their treatment. We evaluated the efficacy of pembrolizumab, a programmed cell death-1 inhibitor, in patients with rare solid tumors.

Methods: We conducted a phase 2 basket trial that included patients with rare, advanced tumors. Patients were enrolled in the study in nine tumor-specific and a 10th cohort of miscellaneous rare histologies. Patients received pembrolizumab 200 mg intravenously every 21 days. The primary endpoint was the non-progression rate at 27 weeks per immune-related Response Evaluation Criteria in Solid Tumors …

Multiparametric Mri Scoring System Of The Pancreas For The Diagnosis Of Chronic Pancreatitis, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Xuandong Zhao, Anil K Dasyam, Vivek Gowdra Halappa, Aashish Patel, Zarine K Shah, Jordan Swensson, Naoki Takahashi, Sudhakar Venkatesh, Ashley Wachsman, Liang Li, Kristofer Jennings, Yunlong Yang, Phil A Hart, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Mark Topazian, Paul R Territo, Scott A Persohn, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Background: Ductal features alone may not offer high diagnostic sensitivity or most accurate disease severity of chronic pancreatitis (CP).

Purpose: Diagnose CP based on multiparametric MRI and MRCP features.

Study type: Prospective.

Population: Between February 2019 and May 2021, 46 control (23 males, 49.3 ± 14.1 years), 45 suspected (20 males, 48.7 ± 12.5 years), and 46 definite (20 males, 53.7 ± 14.6 years) CP patients were enrolled at seven hospitals enrolled in the MINIMAP study. CP classification was based on imaging findings and clinical presentation.

Field strength and sequences: 1.5 T. T1-weighted (T1W) spoiled gradient echo, T1 map with …

Justification, Margin Values, And Analysis Populations For Oncologic Noninferiority And Equivalence Trials: A Meta-Epidemiological Study, Troy J Kleber, Alexander D Sherry, Andrew J Arifin, Gabrielle S Kupferman, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Esther J Beck, Avital M Miller, Adina H Passy, Zachary R Mccaw, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Background: Noninferiority and equivalence trials evaluate whether an experimental therapy's effect on the primary endpoint is contained within an acceptable margin compared with standard of care. The reliability and impact of this conclusion, however, is largely dependent on the justification for this design, the choice of margin, and the analysis population used.

Methods: A meta-epidemiological study was performed of phase 3 randomized noninferiority and equivalence oncologic trials registered at ClinicalTrials.gov. Data were extracted from each trial's registration page and primary manuscript.

Results: We identified 65 noninferiority and 10 equivalence trials that collectively enrolled 61 632 patients. Of these, 61 (81%) …