Medicine and Health Sciences Commons^™

Distinct Tumor-Associated Macrophage Signatures Shape The Immune Microenvironment And Patient Prognosis In Renal Cell Carcinoma, Youngsoo Han, Aidan Shen, Cheng-Chi Chao, Lucas Yeung, Aliesha Garrett, Jianming Zeng, Satoru Kawakita, Jesse Wang, Zhaohui Wang, Alireza Hassani, Xiling Shen, Chongming Jiang

Faculty, Staff and Student Publications

Renal cell carcinoma (RCC) accounts for 90% of adult renal cancer cases and is characterized by significant heterogeneity within its tumor microenvironment. This study tests the hypothesis that tumor-associated macrophages (TAMs) influence RCC progression and patient response to treatment by investigating the prognostic implications of TAM signatures. Utilizing independent single-cell RNA sequencing data from RCC patients, we developed eight distinct TAM signatures reflective of TAM presence. A LASSO Cox regression model was constructed to predict survival outcomes, evaluated using the TCGA dataset, and validated across independent RCC cohorts. Model performance was assessed through Kaplan-Meier survival plots, receiver operating characteristic (ROC) …

Distinguishing Syndromic And Nonsyndromic Cleft Palate Through Analysis Of Protein-Altering De Novo Variants In 818 Trios, Kelsey R Robinson, Sarah W Curtis, Justin E Paschall, Wasiu Lanre Adeyemo, Terri H Beaty, Azeez Butali, Carmen J Buxó, David J Cutler, Michael P Epstein, Lord J J Gowans, Jacqueline T Hecht, Gary M Shaw, Lina Moreno Uribe, Jeffrey C Murray, Harrison Brand, Seth M Weinberg, Mary L Marazita, Kimberly F Doheny, Elizabeth J Leslie-Clarkson

Faculty, Staff and Student Publications

De novo variants (DNs) are sporadically occurring variants found in an offspring but absent in both parents. DNs most commonly arise in the germline and are not under selective pressure; therefore, they may be enriched for disease-causing alleles. In fact, DNs have been implicated in multiple rare genetic disorders. Cleft palate (CP) is a craniofacial congenital anomaly occurring in ∼1 in 1,700 live births. Genome-wide association studies have found fewer than a dozen CP-specific loci, while exome and targeted sequencing studies in family-based and case-control cohorts often lack statistical power to conclusively identify causal variants. We therefore hypothesized that CP …

Compadre: Combined Pedigree-Aware Distant Relatedness Estimation For Improved Pedigree Reconstruction, Grahame F Evans, James T Baker, Lauren E Petty, Alexander S Petty, Hannah G Polikowsky, Ryan J Bohlender, Hung-Hsin Chen, Che-Yu Chou, Kathryn Z Viljoen, Janet M Beilby, Shelly Jo Kraft, Wanying Zhu, Joshua M Landman, Autumn R Morrow, Dayi Bian, Alyssa C Scartozzi, Chad D Huff, Jennifer E Below

Faculty, Staff and Student Publications

Designing powerful and unbiased genomic studies requires accurate assessment of familial relatedness even when this information is not captured from participants. Characterization of pairwise degrees of relatedness from participants' genetic data enables reconstruction of pedigrees, and several pedigree reconstruction tools have emerged in the last decade. However, limitations of these tools include high computational burden in large datasets, reliance on external information, reduced accuracy in admixed populations, and most notably, an inability to accurately reconstruct pedigrees when only a subset of family members is represented in the genetic data. To improve pedigree reconstruction in large-scale data and in pedigrees with …

Management Of Patients Post-Stroke: An Evidence Update, Stacie Mae Larreau Christensen

Posters and Presentations: Physical Therapy

No abstract provided.

Menin Inhibitor Ds-1594b Drives Differentiation And Induces Synergistic Lethality In Combination With Venetoclax In Acute Myeloid Leukemia Cells With Rearranged Mixed-Lineage Leukemia And Mutated Nucleophosmin-1, Valerio Ciaurro, Vassilena Sharlandjieva, Anna Skwarska, Catherine Chahrour, Natalia Baran, Zhihong Zeng, Cassandra Ramage, Naval Daver, Bing Z Carter, Sovira Chaundhry, Palaniraja Thandapani, Maria Paola Martelli, Thomas A Milne, Marina Konopleva

Faculty, Staff and Student Publications

Mixed-lineage leukemia (MLL) rearrangements and Nucleophosmin-1 (NPM1) mutations are associated with acute leukemias whose pathogenesis is critically influenced by protein-protein interactions between menin and MLL. We hypothesized that targeting the menin-MLL interaction using DS-1594b and blocking the antiapoptotic BCL-2 protein using venetoclax may promote differentiation and enhance eradication of MLL-rearranged and NPM1-mutated leukemias models. We treated acute myeloid leukemia (AML) cell lines with MLL rearrangements, NPM1 mutations, other leukemias and primary samples from AML patients with venetoclax alone, DS- 1594b alone, and their combination. We measured proliferation, viability, apoptosis, and differentiation using a variety of cellular assays, Western blotting, and …

Genetic Architecture And Analysis Practices Of Circulating Metabolites In The Nhlbi Trans-Omics For Precision Medicine Program, Nannan Wang, Franklin P Ockerman, Laura Y Zhou, Megan L Grove, Taryn Alkis, John Barnard, Russell P Bowler, Clary B Clish, Shinhye Chung, Emily Drzymalla, Anne M Evans, Nora Franceschini, Robert E Gerszten, Madeline G Gillman, Scott R Hutton, Rachel S Kelly, Charles Kooperberg, Martin G Larson, Jessica Lasky-Su, Deborah A Meyers, Prescott G Woodruff, Alexander P Reiner, Stephen S Rich, Jerome I Rotter, Edwin K Silverman, Ramachandran S Vasan, Scott T Weiss, Kari E Wong, Alexis C Wood, Lang Wu, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Ronit Yarden, Thomas W Blackwell, Albert V Smith, Han Chen, Laura M Raffield, Bing Yu

Faculty, Staff and Students Publications

Circulating metabolite levels partly reflect the state of human health and diseases and can be impacted by genetic determinants. Hundreds of loci associated with circulating metabolites have been identified; however, most findings focus on predominantly European ancestry or single-study analyses. Leveraging the rich metabolomics resources generated by the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) Program, we harmonized and accessibly cataloged 1,729 circulating metabolites among 25,058 ancestrally diverse samples. From our comparison of multiple methods, we provided a set of reasonable strategies for outlier and imputation handling to process metabolite data and show that inverse …

A Socioecological Needs Assessment Of Alternative Learning Environments: Implications For Occupational And Mental Well-Being In School Settings, Glenda Hux, Sydney Rice, Lexus Brettell Wicinski, John V. Rider

Communication Disorders and Occupational Therapy Faculty Publications and Presentations

Alternative learning environments (ALEs) support students with complex behavioral, emotional, and social needs, yet only a small amount of research has examined their occupational and mental health needs using a socioecological approach. This study aimed to demonstrate the process of conducting a socioecological needs assessment in an ALE and identify needs from multiple stakeholder perspectives. A qualitative descriptive design was employed. Semi-structured interviews and focus groups were conducted with 24 stakeholders, including students, educators, counselors, administrators, and a dietitian. Data were analyzed thematically by stakeholder group. Four overarching themes emerged: This School is a Shelter, We Believe in Resilience, We …

The Utility Of Ultra-Deep Rna Sequencing In Mendelian Disorder Diagnostics, Sen Zhao, Jefferson C Sinson, Shenglan Li, Jill A Rosenfeld, Gladys Zapata, Kristina Macakova, Mezthly Pena, Becky Maywald, Kim C Worley, Lindsay C Burrage, Monika Weisz-Hubshman, Shamika Ketkar, William Craigen, Lisa Emrick, Undiagnosed Diseases Network, Tyson Clark, Gila Yanai Lithwick, Zohar Shipony, Christine Eng, Brendan Lee, Pengfei Liu

Faculty, Staff and Students Publications

RNA sequencing (RNA-seq) has emerged as a powerful tool for resolving variants of uncertain significance (VUSs), particularly those affecting gene expression and splicing. However, most reference datasets and diagnostic protocols employ relatively modest sequencing depths (∼50-150 million reads), which may fail to detect low-abundance transcripts and rare splicing events critical for accurate diagnosis. We evaluated the diagnostic and translational utility of ultra-high-depth (up to ∼1 billion unique reads) RNA-seq in four clinically accessible tissues using the Ultima sequencing platform. After validating the performance of Ultima RNA-seq, we investigated how increasing sequencing depth affects gene and isoform detection, splicing variant discovery, …

Survival Analysis Of Breast Cancer Patients In Texas Using Classical And Machine Learning Methods, Sidketa Fofana, Tamer Oraby, Salique H. Shaham, Everardo Cobos, Manish K. Tripathi

School of Medicine Publications

Background

Breast cancer is considered one of the most common cancers in women worldwide. In this study, we used an 11-year cohort of malignant breast cancer survival data in Texas to investigate the factors that might explain why some breast cancer patients live longer than others.

Methods

We performed standard survival analyses, including generating Kaplan‒Meier survival curves, using the log-rank test, and applying Cox proportional hazards regression to identify the unique features of breast cancer patients and determine the main factors influencing long-term survival. We also conducted a Random Survival Forest analysis for classification and prediction. Finally, we used Mahalanobis …

Influenza Vaccine Effectiveness Against Medically Attended Outpatients Illness, United States, 2023-2024 Season, Jessie R Chung, Stacey L House, Tara Curley, Et Al.

2020-Current year OA Pubs

BACKGROUND: The 2023-2024 US influenza season was characterized by a predominance of A(H1N1)pdm09 virus circulation with cocirculation of A(H3N2) and B/Victoria viruses. We estimated vaccine effectiveness (VE) in the United States against mild-to-moderate medically attended influenza illness in the 2023-2024 season.

METHODS: We enrolled outpatients aged ≥8 months with acute respiratory illness in 7 states. Respiratory specimens were tested for influenza type/subtype by reverse-transcriptase polymerase chain reaction. Influenza VE was estimated with a test-negative design comparing odds of testing positive for influenza among vaccinated versus unvaccinated participants. We estimated VE by virus subtype/lineage and A(H1N1)pdm09 genetic subclades.

RESULTS: Among 6629 …

Volume 8 (2025) The Spanish Language, Language Variations, Cultures And Responsibility

International Journal on Responsibility

This issue reflects an intentional and profound commitment to linguistic inclusion, cultural diversity, and the shared responsibility of scholars to broaden the scope of academic dialogue beyond the boundaries of English. The essays collected here invite us to reimagine bilingualism not only as a communicative skill but also as a moral, social, and institutional responsibility.

Esta edición representa un compromiso intencional y profundo con la inclusión lingüística, la diversidad cultural y la responsabilidad compartida de ampliar los horizontes del diálogo académico más allá de los límites del inglés. Los ensayos aquí reunidos nos invitan a reimaginar el bilingüismo no solo …

Religion's Role In Shaping Psychopathological Narratives, Andrea Gonzalez Mendoza

The Graduate Review

Understanding the interplay between religion and psychopathology is essential for clinicians navigating the complexities of mental health diagnosis and treatment. This paper explores the nuanced relationship between belief systems and diagnostic frameworks, shedding light on how religious beliefs influence the perception, assessment, and treatment of mental disorders. Drawing upon historical and current-day research, this paper examines how religious interpretations shape the presentation and understanding of psychopathological symptoms. In doing so, this paper argues that psychopathology cannot be understood without considering the influence of religion on its conceptualization. The latter is illustrated by looking at historical diagnostic patterns and how they …

Focal Constrictive Pericarditis, An Unusual Cause For Biventricular Failure, Farhan Parachikkottil, Harikishore U, Shijoy P, Sajeer Kalathingathodika, Krishnakumar Prabhakaran, Kader Muneer

Journal of the Saudi Heart Association

A 34 year old male who had undergone surgical closure of a ventricular septal defect at the age of 4 years, after a long asymptomatic period, presented with heart failure and was diagnosed with atrial flutter and biventricular dysfunction. Chest X-ray showed a band-like calcification in the atrioventricular groove. Echocardiography revealed dilated atria, focal calcification with constriction at the atrioventricular groove, and biventricular systolic dysfunction. Focal constrictive pericarditis occurring in post-cardiac surgery patients is very rare. Here we report a case of focal variant of constrictive pericarditis manifesting in a young male after 3 decades of ventricular septal defect repair.

Executive Summary: Staff Education Project Staff Education To Close A Knowledge Gap Regarding Restraints, Aaron Ross Ledbetter

Walden Dissertations and Doctoral Studies

The purpose of this Executive Summary is to address a gap in knowledge that I attempted to close regarding restraint utilization. Restraints, both physical and chemical, have been prevalent over the past ten years and with their increased utilization during the pandemic which has continued post-pandemic. Nursing as a culture has become more reliant on restraints as it allows more time for nurses to provide care elsewhere. Both physical and psychological complications have been recognized during the utilization of physical restraints. Their prominence, although helpful with time constraints for nurses, have shown to negatively impact the patients who they are …

Staff Education To Improve Medicare Lung Cancer Screening And Processes, Ashley Mccammon

Walden Dissertations and Doctoral Studies

The doctoral project was a staff education initiative to address underutilization of low-dose computed tomography (LDCT) lung cancer screening among Medicare-eligible patients at the project site. Lung cancer is the leading cause of cancer death, and LDCT screening reduces mortality by up to 20%. Internal data from the project site revealed that only 20.13% of eligible patients completed screening, underscoring the need for structured staff education to improve knowledge and support early detection. The practice focused question asked: Will a staff education on Medicare LDCT screening and processes increase staff knowledge towards the ultimate goal of increasing LDCT screening rates? …

Ethnobotanical Surveys And Morphological Analysis Of Medicinal Plant Names In Lɔ́Mɔngo (Lomongo) C60 At The Elandisha Mavaolo Protected Area In Northeastern Democratic Republic Of Congo, Jean-Baptiste Grodya Musafiri, Jean-Bosco Njango Ngonda, Reddy Shutcha Ehata, Charles Kumbatulu Sita, Chrispina Alphonce, Helene B. Mavar Manga Sodila

Journal of Humanities and Social Sciences

The aim of this research is to contribute to the documentation of Lomongo, a Bantu language spoken in the Democratic Republic of Congo (DRC). In this study, we focused on two morphological aspects of medicinal plant names in Lomongo: nominal morphology and morpho-syntax. To collect data, we engaged with two categories of informants: primary informants (traditional healers) and secondary informants (native Lomongo speakers). Ethnobotanical and ethnolinguistic surveys were conducted in the “Elandisha” Mavaolo area through participant observation, semi-structured interview guides, audio recordings, and photographs. The plants identified were documented in situ with the assistance of botanists from "Matiti-Lisanga," an interdisciplinary …

Low Dose Cone Beam Computed Tomography Versus High Dose Cone Beam Computed Tomography In Measuring Furcation Involvements: (Diagnostic Accuracy Study), Marwa Ezz, Cairo University, Misr University For Science & Technology

Dentistry

Accurate diagnosis of furcation defect is essential in periodontal therapy planning. Cone beam computed tomography (CBCT) provides three-dimensional visualization, but higher radiation doses remain a concern. This study aims to assess and compare the diagnostic accuracy of low-dose CBCT (LD-CBCT) and high-dose CBCT (HD-CBCT) in detecting and measuring furcation defect using a pig mandible. Detection and accurate assessment of periodontal disease is important to determine the tooth prognosis and treatment. Radiographic assessment provides information about the pattern and extent of the furcation defect. CBCT provides unique 3D images used for diagnosis and treatment plans, but its use in periodontology not …

Strengthening The Utah Diabetes Cook Along Program For Statewide Extension Delivery: Curriculum Refinement And Randomized Controlled Trial, Carrie Durward

Funded Research Records

No abstract provided.

Development Of A Clinically Relevant Rabbit Model Of Acute Laryngeal Injury, Ryan Stepp, Naushin Ali, Areli A. Rodriguez, Ethan Nicklow, Noah Thornton, Adithya Reddy, Hannah L. Kenny, Patrick S. Cottler, Donald R. Griffin, James J. Daniero

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES: Acute laryngeal injury (ALgI) is created as a result of endotracheal tube pressure ulcer formation leading to fibrosis and inflammation. This condition often leads to airway obstruction and voice and swallowing dysfunction. This study demonstrates a reliable animal model of ALgI to reproduce the acute wound process seen clinically, to explore the pathophysiology of this disease process, and to serve as a reproducible injury suitable for the evaluation of therapeutic interventions.

METHODS: An ALgI model was developed in New Zealand White rabbits using precise mucosal stripping of the posterior larynx, followed by intubation with an oversized 4.0 endotracheal tube …

A Confucian Response To Stoic Perspectives On Physician Burnout, Charlene Tan, Ruth Neo

Journal of Wellness

Aimed at promoting cross-cultural dialogue and exchange of ideas in the humanities, this article provides a Confucian response to the Stoic viewpoints expounded by Kutch in this journal. Two arguments are made in this paper: first, Confucius shares the Stoics’ emphasis on being mindful. Secondly, a significant difference between Confucius and the Stoics is that the former replaces the Stoics’ fate with Heaven (tian), which is a central Confucian spiritual ideal. Applying Confucian and Stoic insights to burnout, medical professionals are encouraged to (re)gain strength by reflecting on and embracing spiritual ideals, whether it is fate or Heaven. …

Development Of An Evidence-Based Clinical Practice Guideline For Discharging Patients With Substance Use Disorder (Sud) From Outpatient Treatment To Community Care, Emmanuel Onyeani

Walden Dissertations and Doctoral Studies

This Doctor of Nursing Practice (DNP) project addressed a gap in practice in an outpatient treatment center for discharging patients with substance use disorder (SUD), addressing the need for follow-up care and relapse prevention due to the widespread impact of SUD. Clinical practice guidelines (CPG) help healthcare professionals make informed decisions for specific clinical situations. The guiding question asked whether an expert panel would evaluate and validate a CPG developed from current, evidence-based literature and recommendations with 70% agreement using the AGREE II tool. The CPG focused on continuity of care, access to resources, and relapse prevention strategies. Seven expert …

Google Search Trends And Their Correlation With Covid-19 Cases And Vaccination Rates In Austria, Stefanie Wendell

Walden Dissertations and Doctoral Studies

Timely digital surveillance is essential because clinical reporting often lags. This quantitative, longitudinal correlational study tested whether weekly Google searches in Austria signal changes in COVID-19 cases and vaccination uptake, and short-term case-vaccination dynamics, guided by Rogers’ Diffusion of Innovations Theory. Weekly Google Trends indices (0-100) and nationally reported surveillance totals (weekly counts of new cases and vaccine doses) were aggregated; cases: N = 175 weeks (Feb 2020–Jun 2023); vaccinations: N = 132 weeks (Dec 2020–Jun 2023). Time series correlations and lagged growth models showed that symptom-related searches consistently rose 1 week before reported cases (Δlog cases_t on Δlog searches_{t−1}: …

Enhancing Home Health Nursing Knowledge Through Targeted Education On Polypharmacy Risk Awareness In Older Adults, Chinyeaka Linda Ogbonna

Walden Dissertations and Doctoral Studies

This Doctor of Nursing Practice (DNP) staff education initiative addressed the problem of polypharmacy, a common issue in home health care that increases the risk of drug interactions, side effects, and hospitalizations. Nurses and aides often provide daily care but may not recognize high-risk medications or warning symptoms. Addressing this gap was vital to nursing practice because staff are on the front line of patient monitoring and safety. The practice-focused question asked whether structured education for home health staff would improve knowledge of polypharmacy risks by 20%, increase recognition of high-risk medications by 75%, and result in at least 75% …

Circulating Levels Of Insulin-Like Growth Factor I (Igf-I) And Risk Ofmultiple Myeloma: An Observational And Mendelian Randomisation Study, Yolanda Benavente, Sara Hermosa, Nikos Papadimitriou, Alyssa I. Clay-Gilmour Ph.D., Elizabeth E. Brown, Jonathan N. Hofmann, Nathaniel Rothman, Qing Lan, Sonja I. Berndt, Demetrius Albanes, Mark Purdue, Mitchell J. Machiela, Stephen J. Chanock, Parveen Bhatti, Wendy Cozen, Aaron Norman, Susan L. Slager, James R. Cerhan, Vincent Rajkumar, Shaji J. Kumar, Et. Al.

Faculty Publications

Evidence for an association between insulin-like growth factors (IGF) and multiple myeloma (MM) is inconsistent. We examined total IGF-I concentrations and risk of MM by combining baseline serological data among UK Biobank participants (n = 444 187; 732 incident MM) with a two-sample Mendelian randomisation (MR) analysis using identified genetic variants associated with circulating total IGF-I and IGF-binding protein 3 (IGFBP-3) in the InterLymph consortium (2434 MM and their 2567 controls). Finally, additional lymphoid neoplasm (LN) subtypes were included for comparison with the main hypothesis. Circulating IGF-I level was positively associated with MM risk Hazard ratio-HR-per one standard deviation-SD-increase …

A Rare Case Of Chilaiditi Syndrome As A Driver Of Chronic Respiratory Failure, Paige C. Adams, Daniel Kramer

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Chilaiditi sign is a rare radiographic finding demonstrating interposition of the colon between the liver and the diaphragm; Chilaiditi syndrome is the manifestation of gastrointestinal or respiratory symptoms secondary to this finding. This syndrome rarely can be associated with acute and chronic respiratory failure. We report a case of a 66-year-old woman with chronic hypercapnic and hypoxemic respiratory failure due to severe restrictive pulmonary mechanics in the setting of Chilaiditi syndrome. Imaging showed an elevated right hemidiaphragm initially concerning for hemidiaphragm paralysis; however a fluoroscopic Sniff test suggested normal diaphragm function. Despite hospitalisation for aggressive bowel decompression combined with noninvasive …

Incidence And Risk Factors For Pneumonitis Due To Trastuzumab Deruxtecan In Metastatic Breast Cancer: A Retrospective Cohort Study, Maria Azhar, Felipe Soto, Amber Su, Norma Alicia Vazquez Gonzalez, Kevin Bernal Medina, Alejandro Lizarraga Madrigal, Cesar Chavez Duran, Carlos Ignacio Rodriguez Reyna, Colin Chan, Girish S Shroff, Roland L Bassett, Sarah Pasyar, David Zhang, Vickie R Shannon, Mehmet Altan, Melissa P Mitchell, Funda Meric-Bernstam, Jason Mouabbi, Rashmi K Murthy, Saadia A Faiz, Lara Bashoura, Bora Lim, Ajay Sheshadri

Faculty, Staff and Student Publications

Background: Fam-trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) that targets human epidermal growth factor receptor 2 (HER2) and delivers a topoisomerase inhibitor payload. T-DXd has been effectively used to treat metastatic breast cancer but causes pneumonitis in 10–15% of cases. Risk factors associated with T-DXd pneumonitis are not well described.

Research question: What are the major clinical risk factors for T-DXd pneumonitis?

Study design and methods: We conducted a retrospective study of women with metastatic breast cancer at our institution treated with T-DXd as standard of care between 2020 and 2024. We collected clinical data, including demographics, relevant review …

The Barriers And Facilitators Of Maternal Influenza Vaccination, Rashida Karida Jones

USF Tampa Graduate Theses and Dissertations

Influenza remains a leading cause of morbidity and mortality in the United States, with Black individuals disproportionately affected. Pregnant women are particularly vulnerable due to their modulated immune state, placing them at increased risk of complications, hospitalization, and intensive care admission. Despite strong evidence supporting the safety and efficacy of maternal seasonal influenza vaccination (SIV), uptake remains suboptimal. This study employed a multi-method design to identify barriers and facilitators of maternal SIV uptake, with a particular focus on racial disparities.

Quantitative analyses utilized the Florida Pregnancy Risk Assessment Monitoring System (FL PRAMS) dataset from the years 2018–2022. In the fully …

Prospective Phase Ii Clinical Trial Of Molecular Glioblastoma (Historical Grade 2 And 3 Idh Wildtype Gliomas) Preliminary Novel Exploratory Analyses: Treatment Intensification, Margin Reduction And Epigenetic Stratified Outcomes With Radiation Therapy And Chemotherapy, Debra Nana Yeboa, Benjamin T Whitfield, Ruitao Lin, Chinenye Lynette Ejezie, Todd A Swanson, Thomas H Beckham, Chenyang Wang, Brian De, Subha Perni, Martin C Tom, Jing Li, Susan L Mcgovern, Rebecca Harrison, Nazanin K Majd, Vinay K Puduvalli, Ashley E Aaroe, Monica Loghin, Barbara J O'Brien, Anuj D Patel, Chirag B Patel, Jeffrey S Wefel, Ceylan Altintas Taslicay, Maria Gule-Monroe, Arnold C Paulino, Mary Frances Mcaleer, David R Grosshans, Amol J Ghia, Wen Jiang, Caroline Chung, Moshe Maor, Cheng-Han Yang, Maria A Gubbiotti, Carlos Kamiya-Matsuoka, Leomar Y Ballester, Shiao-Pei Weathers, Jason T Huse

Faculty, Staff and Student Publications

Purpose: Molecular glioblastoma (molGBM) is a variant lacking the full histopathological profile of glioblastoma. We report a trial aimed at addressing the optimal management of this newly recognized rarer form of glioma.

Methods: In this phase II study, molGBM patients were treated with radiation to a dose of 60Gy to the gross tumor volume (GTV) only, and a single smaller margin potentially as low as 1cm to the clinical tumor volume (CTV). As the trial is ongoing, we report on important exploratory biomarker findings correlating with median overall survival (mOS). Analysis included Kaplan-Meier and univariable/multivariable cox proportional hazard models. Available …

Cofilin Inhibition Ameliorates Piezo2 And Ampa Dysfunction In A Mouse Model Of Angelman Syndrome, Luis O Romero, Manisha Bade, Elisa Carrillo, Sonia Paz-López, Syed A M Hasan, William James Antonisamy, Vasanthi Jayaraman, Zahoor A Shah, Valeria Vásquez, Julio F Cordero-Morales

Faculty, Staff and Student Publications

Angelman syndrome (AS) is a neurogenetic disorder characterized by motor coordination and cognitive deficits. In AS, hippocampal neurons show reduced filamentous (F-)actin, a decrease we also reported in dorsal root ganglia (DRG) neurons, along with impaired mechanosensitive ion channel activity. Currently, there are no pharmacological targets to prevent the decrease of F-actin in AS. Here, we utilize a first-in-class selective cofilin inhibitor (SZ-3) to restore PIEZO2 function in DRG neurons and glutamate-evoked currents in hippocampal neurons from AS mice. Using atomic force microscopy, we demonstrate that inhibiting cofilin, an actin-severing protein, with SZ-3 increases cellular stiffness by stabilizing the actin …

Targeting Gd2 With Naxitamab Overcomes Gd3 Synthase-Driven Immune Suppression In Triple-Negative Breast Cancer, Vivek Anand, Bolutyfe Oderinde, Maryam Siddiqui, Anudishi Tyagi, Jenny Borgman, Chong Wu, Michael Andreeff, V Lokesh Battula

Faculty, Staff and Student Publications

Gangliosides are acidic glycosphingolipids involved in cell-adhesion, signal-transduction and tumor progression. GD3 synthase (GD3S/ST8SIA1), a key enzyme in ganglioside biosynthesis, is upregulated in many cancers, including GD2+ breast cancer stem-like cells (BCSCs) in triple-negative breast cancer (TNBC). Here, we demonstrated the immunomodulatory role of GD3S and identified a fully humanized anti-GD2 antibody, naxitamab, as a therapeutic tool to target GD3S/GD2+ breast tumors. GD3S expression correlates with immune-checkpoint activation and reduced immune infiltration. Ectopic overexpression of GD3S suppressed macrophage-mediated phagocytosis and NK or T cell-induced cell death in BC cells. Lipidomic analysis identified GD2 as the major effector ganglioside …