Digital Commons Network^™

A Hemorheological Perspective On Coronary Microvascular Dysfunction: Association Of Erythrocyte Parameters With Angiography-Derived Coronary Microcirculatory Resistance, Abdulrahman Alqazzaz, Yanfeng Lu, Jasmine Bao, Gary S. Mintz, Jiahao Feng, Yong Zhang, Shanshan Gao, Qiang Song, Feifei Ning, Hytham H. Al-Samawi, Mohsen Al-Manj, Mohammed Al-Asadi, Xin Huang, Ning Guo

Student Papers, Posters & Projects

BACKGROUND: Coronary microvascular dysfunction (CMD) contributes to myocardial ischemia in patients both without obstructive coronary artery disease (e.g., MINOCA/INOCA) and in those with co-existing epicardial stenosis. While its etiology includes structural and functional causes. hematologic parameters have been linked to cardiovascular outcomes. However, the relationship between red blood cell (RBC) markers and microvascular resistance remains poorly characterized. We aim to evaluate whether RBC parameters are correlated with the angiography-derived index of microcirculatory resistance (angio-IMR).

METHODS: This retrospective study evaluated the association between red blood cell (RBC) parameters and angio-IMR in patients with intermediate coronary artery disease (30%-70% stenosis). Data were …

A Scoping Review Of Gender-Based Violence Interventions Conducted In Afghanistan, Wahiba Abu-Ras, Basil H. Aboul-Enein, Patricia J. Kelly, Dilshod Achilov

College of Nursing Faculty Papers & Presentations

BACKGROUND: Gender-based violence (GBV) remains one of the most pervasive human rights and public health challenges worldwide, with disproportionate impacts on women and girls in conflict-affected and fragile states. Afghanistan represents one of the most restrictive environments for women's rights, where structural, cultural, and political barriers severely limit the implementation and evaluation of GBV-prevention programs. This scoping review aims to identify and critically appraise GBV prevention and response interventions implemented in Afghanistan and assess their contribution to advancing gender and health equity.

METHODS: Following PRISMA-ScR guidelines and the PICOS framework, nine databases were systematically searched for studies published between 2010 …

Fasting-Based Dietary Interventions In Cancer Patients And Survivors: A Scoping Review, Kuang-Yi Wen, Julianne Freedman, Abenezer Melaku Tafese, William Kevin Kelly, Nicole L Simone

Department of Medical Oncology Faculty Papers

Background: Fasting-based interventions are increasingly investigated as adjuncts to cancer treatment for the potential to reduce therapy-related toxicities, improve metabolic health, and enhance quality of life. However, clinical evidence regarding their efficacy, tolerability, and acceptability remains limited and fragmented. This scoping review aimed to systematically map the current evidence on fasting-based interventions in cancer patients and survivors.

Methods: A literature search was conducted in PubMed, Scopus, Web of Science, and CINAHL up to 10 June 2025. Eligible interventional studies included cancer patients or survivors and evaluated fasting-based interventions, such as time-restricted eating, intermittent fasting, short-term fasting, or fasting-mimicking …

Translating Multi-Omics Into Healthcare: Requisites For Scalable And Equitable Implementation, Birute Tumiene, David R Adams, Robert Allaway, Maria J Barrero, Chun-Hung Chan, Víctor Faundes, Vanessa S Fear, Polina Glezer, Claudia Fuchs, Tudor Groza, Elisa J F Houwink, Saumya Shekhar Jamuar, Mary Catherine V Letinturier, Richa Madan Lomash, Ratna Dua Puri, Juergen K V Reichardt, Ruty Mehrian-Shai, Francois H Van Der Westhuizen, Gaurav K Varshney, Shinya Yamamoto, Gareth Baynam

Faculty, Staff and Students Publications

Multi-omics in combination with advanced computational methodologies synthesizes diverse omics data to provide deeper insights into molecular interactions and offers transformative potential for unravelling phenomenon behind disease complexities, improving diagnostics, disease prevention, and personalized treatments. This integrative strategy enables our understanding of gene-environment relationships, chronic disease progression, and the intricate molecular pathways involved in health. Effective multi-omics analyses require robust data sharing, accessibility, interoperability, and governance, which are critical for linking genomic elements to phenotypic traits. The Global Alliance for Genomics and Health advocates for responsible data-sharing practices, by promoting key principles such as transparency and equity. By emphasizing a …

Modulation Of Biomolecular Aggregate Morphology And Condensate Infectivity., Josephine C Ferreon, Kyoung-Jae Choi, My Diem Quan, Phoebe S Tsoi, Cristopher C Ferreon, Ulas Coskun, Shih-Chu Jeff Liao, Allan Chris M Ferreon

Faculty, Staff and Students Publications

Neurodegenerative diseases feature diverse pathological protein aggregates, including Lewy bodies in Alzheimer's disease (AD) and skein-like filaments in amyotrophic lateral sclerosis (ALS). The physical mechanisms underlying this morphological diversity remain unclear. Here, we demonstrate that aggregation of the prion-like domain of hnRNPA1 (A1PrD), implicated in AD and ALS, is driven by solution composition and phase transition dynamics. Utilizing 3D timelapse and fluorescence lifetime imaging microscopy, we show that solution conditions modulate phase separation, gelation, and fibrillation, resulting in distinct structures such as fibril, gel, and starburst morphologies. Homotypic and heterotypic interactions between A1PrD and RNA were observed to shift the …

Randomized Controlled Trial Outcomes For Homestyles-2, An Online Obesity Prevention Program For Families With Children In Middle Childhood, Carol Byrd-Bredbenner, Angelica A. Pozzoli, Kaitlyn M. Eck, John Worobey, Karla Pagan Shelnutt, Melissa D. Olfert, Virginia Quick

College of Health Professions Faculty Papers

Background: Parents are children’s primary role models, are food and physical activity gatekeepers, and create the home structure/lifestyle environment. Thus, parents strongly influence children’s weight-related behaviors and have the opportunity to cultivate a “culture of health” within the home. Methods: The aim of the HomeStyles-2 (also called HomeStyles-Child) RCT was to determine whether this online, novel, age-appropriate, family intervention enabled and motivated the 131 systematically randomly assigned by computer parents of children in middle childhood (ages 6 to 11) in the experimental condition to shape home environments and healthy weight-related lifestyle practices to be more supportive of optimal health and …

Molecular Characterization Of Humanized Apoe Mouse Models Reveals Source And Genotype Dependent Differences, Na Wang, Gefei Yu, Zhen Wang, Alla Alnobani, Suren Jeevaratnam, Xue Zhang, Meghan Mcreynolds, Yuzhou Chang, Fangfang Qi, William Tauer, Cassandra Rosenberg, Melissa Wren, Tadafumi C Ikezu, Yuka A Martens, Minghui Wang, Bin Zhang, Gregory W Carter, Michael Sasner, David M Holtzman, Junmin Peng, Long-Jun Wu, Takahisa Kanekiyo, Chia-Chen Liu, Guojun Bu

The Brown Foundation: Institute of Molecular Medicine

Background

Humanized APOE targeted-replacement (TR) mice are essential tools for studying apoE isoform effects in Alzheimer’s disease (AD) and other apoE-related disorders. Despite their widespread use, existing APOE mouse models, generated with different gene targeting strategies, have not been directly compared in terms of apoE isoform expression, lipid profiles, and transcriptomic signatures. Such differences could impact how we interpret APOE genotype-related outcomes, as well as related underlying molecular mechanisms.

Methods

We conducted a comprehensive molecular comparison of humanized APOE mouse models from three sources: Taconic Biosciences (TAC), the Cure Alzheimer’s Fund (CAF), and The Jackson Laboratory (JAX). We assessed apoE …

Synthetic Lethality Between Rb-Loss And E2f3 Inhibition In Small Cell Cancers Targeted By Pyrimidine Synthesis Blockade, Evan R. Abt, Liang Wang, Grigor Varuzhanyan, Jack Freeland, Tian He, Guadalupe M. Peña-Garcia, Lauryn Ruegg, Jami Mclaughlin, Donghui Cheng, Nikolas G. Balanis, Chia-Chun Chen, Yang Xu, Yi Xing, Sanaz Memarzadeh, Caius G. Radu, Thomas G. Graeber, Owen N. Witte

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Small cell carcinoma is a highly lethal cancer variant often found with neuroendocrine (NE) features, as exemplified by small cell lung cancer and small cell NE prostate cancer (SCPC). A genome-wide CRISPR dependency screen using SCPC models generated through human prostate cell transformation identifies a requirement for the transcription factor E2F3. E2F3 dependency is linked to RB inactivation, a near universal occurrence across small cell cancers. The requirement for E2F3 is shared by RB-deficient cells originating from the prostate, lung, and adnexa. In RB-deficient cancer cells, E2F3 inhibition restrains cell cycle progression, proliferation, and tumor growth in vivo. Inhibition of …

Cystic Fibrosis And Sickle Cell Disease Associated With Nonadministration Of Vte Prophylaxis In Hospitalized Adults, Kiera Caparon, Matthew J. Lankiewicz, Jessica Crow, Jennifer C. Yui, John Lindsley, Brandyn D. Lau, Michael B. Streiff, Rakhi P. Naik, Sophie Lanzkron, Lydia H. Pecker, Peggy Kraus, Elliott R. Haut, Jiangxia Wang, Kathryn E. Dane

Cardeza Foundation for Hematologic Research

Cystic fibrosis (CF) and sickle cell disease (SCD) are associated with an increased risk of venous thromboembolism (VTE), and this risk is exacerbated by hospitalization. VTE prophylaxis nonadministration is a VTE risk factor. The objective of this study was to characterize VTE prophylaxis nonadministration among patients with either CF or SCD compared with medically ill patients without CF or SCD. We conducted a single-center retrospective cohort study of hospitalized patients who were prescribed at least 2 doses of pharmacologic VTE prophylaxis. The primary outcome was the proportion of nonadministered VTE prophylaxis doses by cohort. Multivariable logistic regression was used to …

Fecal Carbohydrate-Degrading Bacteria Are Associated With Reduced Incidence Of Lower Gastrointestinal Gvhd, Christopher Fan, Tomo Hayase, Chia-Chi Chang, Israel K Glover, Ivonne I Flores, Lauren K Mcdaniel, Miriam R Ortega, Christopher A Sanchez, Rawan K El-Himri, Alexandria N Brown, Jennifer L Karmouch, Mohamed A Jamal, Saira S Ahmed, Taylor M Halsey, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Altai Enkhbayar, Aqsa Mohammed, Maren Schmiester, Ashish Damania, Nadim J Ajami, Jennifer A Wargo, Christine B Peterson, Gabriela Rondon, Taha Al-Juhaishi, Amin M Alousi, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Eric Martens, Cesar A Arias, Robert R Jenq, Eiko Hayase

Faculty, Staff and Student Publications

Lower gastrointestinal graft-versus-host disease (LGI-GVHD) carries morbidity and mortality for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), with critical contributions from the intestinal microbiome. In a retrospective cohort of metagenomic sequencing of stool from patients with allo-HSCT (N = 90), we found that a reduction in specific Parabacteroides and Bacteroides species around the time of engraftment contributes to LGI-GVHD risk. Given the known diverse carbohydrate-degrading functionality of these bacteria, we investigated gene abundances for carbohydrate-active enzymes (CAZymes) and found that Parabacteroides merdae, P distasonis, and Bacteroides ovatus abundances were significantly correlated with CAZymes in patients who did not develop …

Heterogeneity And Plasticity Of The Naive Cd4+ T Cell Compartment, Alia Sajani, Evelien Schaafsma, Walburga Croteau, Mohamed Eltanbouly, Elizabeth C Nowak, Chao Cheng, Christopher M Burns, Mary Jo Turk, Randolph J Noelle, J Louise Lines

Faculty, Staff and Students Publications

This study describes the transcriptional heterogeneity of murine and human naive CD4+ T cells as comprising multiple discrete clusters that impact CD4+ T cell fate and trajectories. Naive CD4+ T cells experiencing inflammatory environments exhibit an altered transcriptional state that biases their differentiation trajectories.

Tulane Virus Protease As A Structural Surrogate For Inhibitor Screening Of Human Norovirus Proteases, Son Pham, Nikhil Sharma, Banumathi Sankaran, Jalen Nguyen, Mary K Estes, Joseph M Hyser, B V Venkataram Prasad

Faculty, Staff and Students Publications

Human norovirus (HuNoV) is a significant cause of gastroenteritis worldwide, affecting people of all age groups. There are currently no vaccines or drugs available, leaving susceptible populations vulnerable to severe or protracted illness. A HuNoV cultivation system is pivotal for screening norovirus antivirals. While the human intestinal enteroid cultivation system allows robust replication of multiple HuNoV strains, it presents technical and cost barriers. Tulane virus (TV), a surrogate for HuNoV, replicates well in monkey kidney cell lines and is closely related to norovirus in cellular biology. Here, we determined the structures of TV protease (TV-Pro) alone and in complex with …

Γδ T Cells At The Interface Of Innate And Adaptive Immunity In Cancer, Arnau Solé Casaramona, Martin F Bachmann, Eva Sevick-Muraca, Mona O Mohsen

The Brown Foundation: Institute of Molecular Medicine

γδ T cells are unconventional lymphocytes that bridge innate and adaptive immunity by combining recognition of stress-induced ligands independently of classical major histocompatibility complex molecules with the capacity to undergo clonal expansion and long-term adaptation. Their unusual ability to detect malignant transformation using semi-invariant T-cell receptors, butyrophilin recognition and natural killer-like receptors positions them as powerful effector cells in tumors that evade classical immune escape mechanisms. Furthermore, distinct γδ subsets have distinct phenotyping and specific tissue-residencies, which could be leveraged to modulate immunological responses. We evaluate engineered therapies and different experimental platforms for studying γδ T cell biology. We conclude …

Therapeutic Plasma Exchange For Uncontrollable Bleeding After Platelet Inhibition With Ticagrelor: A Report Of 2 Cases, Amanda Herrmann, Brenda Mai, Yu Bai, Brian Castillo, Biswajit Kar, Kimberly Klein, Ismael A Salas De Armas, Eric Salazar, Hlaing Tint, Igor D Gregoric

Faculty, Staff and Student Publications

Case series

Patients: Male, 52-year-old Male, 66-year-old

Final Diagnosis: Uncontrolled bleeding following ticagrelor associated with cardiac surgery

Symptoms: Bleeding

Clinical Procedure: —

Specialty: Cardiology Critical Care Medicine Pathology

Objective: Unusual clinical course

Background

Acute coronary syndrome is the most common cause of death in the United States. Successful intervention often requires a multi-therapeutic approach, including percutaneous coronary intervention (PCI) and antiplatelet agents such as ticagrelor. However, the use of antiplatelet agents can cause life-threatening bleeding, particularly during emergency procedures. Therapeutic plasma exchange (TPE) is a procedure that selectively removes the patient’s plasma to eliminate harmful substances. Here, we present 2 …

Chatgpt Versus Uptodate In Preclinical Medical Education: Cross-Sectional Analysis Using Term Frequency-Inverse Document Frequency Cosine Similarity, Shankar S. Thiru, Nicholas E. Aksu, Matthew Chiang, Daniel O. Gallagher, Mary Furlong, Elizabeth R. Prevou, Akhil Jay Khanna

Rothman Institute Papers

BACKGROUND: Generative artificial intelligence tools such as ChatGPT are increasingly used by medical students for self-directed learning. Although these models demonstrate linguistic fluency, their reliability as supplementary resources for preclinical education remains uncertain. In particular, comparisons with evidence-based references such as UpToDate are lacking.

OBJECTIVE: This study evaluated the similarity between responses generated by ChatGPT (with GPT-4o mini) and those from UpToDate to preclinical medical education questions to assess ChatGPT's potential as an adjunctive learning tool.

METHODS: We conducted a cross-sectional comparison study using 150 first-order questions derived from a preclinical question bank at a single allopathic institution under the …

Photobiomodulation In Treatment Of Head And Neck Cancer-Related Chronic Lymphedema: A Pilot Randomized Controlled Trial, Jie Deng, John N. Lukens, Barbara A. Murphy, Erin Mcmenamin, Karthik Rajasekaran, Ryan J. Quinn, Joy C. Cohn, Wendy Schlessinger, Lucy P. Andersen, Bryan A. Spinelli, Alexander Lin

Department of Physical Therapy Faculty Papers

BACKGROUND: Chronic lymphedema is a common late effect after completion of head and neck cancer (HNC) treatment, contributing to substantial symptom burden and negatively impacting quality of life. No effective approaches are available to treat this progressive condition. This study aimed to evaluate the preliminary efficacy of photobiomodulation (PBM) therapy for chronic lymphedema in HNC survivors.

METHODS: This was a pilot, randomized, wait-list controlled trial. Eligible HNC survivors included those with chronic lymphedema after completion of complete decongestive therapy. Participants were randomized (1:1) to 1 of 2 arms: intervention group (active) or wait-list control group (control). The active group received …

Pulmonary Complications Of Cancer Therapy: Clinical Presentations, Imaging Patterns, And Management Strategies, Bilal Zafar, Tasmea Haque, Miranda Tan, Ritika Singh, Lara Bashoura, Ajay Sheshadri, Maria Azhar, Saadia A Faiz

Faculty, Staff and Student Publications

Background and objectives: Therapeutic agents for cancer can cause unique pulmonary toxicities and mimic other conditions. The advent of new targeted molecular and immune therapies has changed the landscape of cancer treatment. These adverse events pose diagnostic and therapeutic challenges. This review aims to summarize the clinical presentations, radiographic patterns, and management strategies for noninfectious pulmonary complications associated with cancer therapies.

Materials and methods: A literature review was conducted focusing on drug-induced lung injury (DILI), radiation-induced lung injury (RILI), pleural disease, pulmonary vascular complications, and other inflammatory conditions in patients with cancer. The data sources included clinical trials, guideline recommendations, …

Fibrinogen-Bmal1 Signaling As A Therapeutic Target To Limit Aortic Dissection By Preserving Vsmc Contractility, Xiaohan Zhong, Dongjie Li, Yuanfei Zhao, Lu Dai, Jinzhang Li, Zhiqi Ji, Bojing Zuo, Hongshan Liu, Haixia Huang, Wei Wang, Haiyang Li, Yuyong Liu, Ming Gong, Xin-Liang Ma, Wenjian Jiang, Meili Wang, Hongjia Zhang

Department of Emergency Medicine Faculty Papers

Aortic dissection (AD) is a life-threatening vascular disease with a high mortality rate. Surgery is essential in the acute phase but carries significant risks, whereas elective surgery during the chronic phase yields better outcomes. However, no pharmacological therapy has been proven effective in slowing AD progression. In our recent pilot clinical study, an association between higher plasma fibrinogen levels and improved clinical outcomes was observed in AD patients, suggesting a potential protective role of fibrinogen. However, direct evidence supporting this hypothesis is lacking. In this study, a population-based analysis of nonsurgically managed patients with acute AD revealed a distinct association: …

Patient Perceptions And Knowledge Of Corticosteroid Injections: A Cross-Sectional Survey Study, Juliet Chung, Sina Ramtin, Philip Koehler, Stephen Stache, Charles Langman, Bryan Hozack, Asif M. Ilyas

Rothman Institute Papers

INTRODUCTION: Although cortisone injections are commonly used, patient understanding of cortisone is variable and often affected by misconceptions. This study explores patient perspectives, identifies misconceptions, and emphasizes the importance of improved patient education to enhance patient-centered care.

METHODS: A cross-sectional survey study was conducted from April to August 2024 among patients aged 18 and older presenting to an orthopedic physicians' office. Patients completed a novel anonymous questionnaire designed to assess their knowledge and perceptions of cortisone injections. A total of 246 patients participated, with responses collected electronically via SurveyMonkey.

RESULTS: Among 246 respondents, individuals with history of prior cortisone infections …

Impact Of Long-Term Nitrogen Scavenger Therapy On Clinical Outcome In Individuals With Urea Cycle Disorders, Roland Posset, Friederike Epp, Sven F Garbade, Florian Gleich, Andrea L Gropman, Sandesh C S Nagamani, Georg F Hoffmann, Stefan Kölker, Matthias Zielonka

Faculty, Staff and Students Publications

Principles of long-term medical management in individuals with urea cycle disorders (UCDs) encompass (1) a low protein diet, (2) supplementation of arginine and/or citrulline along with essential amino acids, nutrients, vitamins and trace elements, and (3) use of nitrogen scavenging agents to reduce recurrent hyperammonemic events (HAEs). These principles aim at providing metabolic stability, elimimation of chronic complications, and achievement of normal development as well as growth. A retrospective comparative analysis was performed by studying 138 individuals with male ornithine transcarbamylase deficiency (mOTC-D), citrullinemia type 1 (CTLN1) and argininosuccinic aciduria (ASA) based on in vitro residual enzymatic activity for severity-adjustment. …

Development And Validation Of The Emergency Department Transitions Measure, Sara Beachy, Danielle M. Mccarthy, Julianna Lenoir, Alexzandra Gentsch, Richard W. Hass, Marissa Witmer, Paula Ostroff, Melissa Tupas, Lindsey Shughart, Hailey Shughart, Kristin L. Rising

Jefferson Center for Connected Care Faculty Papers

BACKGROUND: Transitions of care are high-risk periods for patient safety in the emergency department (ED), particularly for patients who are still in the diagnostic process and are discharged with diagnostic uncertainty. Care transitions must be improved for these patients, as one third of discharged ED patients have diagnostic uncertainty. Yet there are no validated measures that assess the quality of care transitions from the ED, limiting the ability to assess the impact of interventions. Thus, we developed and validated the ED Transitions (EDT) measure.

METHODS: This mixed methods study was conducted across a large healthcare system in three phases: item …

Fungal Meningitis In Us Patients Who Received Epidural Anesthesia In Matamoros, Mexico, Dallas J Smith, Elizabeth Misas, Jeremy A W Gold, Nicole Evert, Thi Dang, Emilie Prot, Simone Godwin, Julieanna Rivas, Jessica Pearson, Lori Koenecke, Nirma D Bustamante, Maria Julia Marinissen, Gabriel Garcia Rodriquez, Irma López-Martínez, Caitlyn Lutfy, Samantha Williams, Axel A Vazquez Deida, Katrina M Byrd, Julian A Villalba, Sarah Reagan-Steiner, Lindsay Parnell, Lalitha Gade, Romney M Humphries, Nathan P Wiederhold, Charles Y Chiu, Joshua A Lieberman, Anastasia P Litvintseva, Tom Chiller, Luis Ostrosky-Zeichner, Fungal Meningitis Response Team

Faculty, Staff and Student Publications

Background: Fungal meningitis outbreaks are rare and entail high mortality rates. Beginning May 2023, we investigated fungal meningitis caused by Fusarium solani species complex occurring in US patients who received epidural anesthesia in Matamoros, Mexico.

Methods: Early epidemiological information suggested US patients with suspected fungal meningitis had undergone mostly cosmetic procedures under epidural anesthesia performed in 2 Matamoros clinics. US patients known to have received surgery at these clinics during 1 January-13 May 2023 (clinic closures date) were identified and notified by public health officials. Epidemiological and clinical data were used to update diagnostic and clinical guidance for outbreak response, …

Factors Associated With Telemedicine Use By Cardiologists For Medicare Beneficiaries In 2022 To 2023: An Observational Study, Samantha Harris, R J Waken, Fengxian Wang, Khavya C Avula, Rishi K Wadhera, Jose F Figueroa, E John Orav, Uchenna Ofoma, Karen E Joynt Maddox

2020-Current year OA Pubs

BACKGROUND: During the COVID-19 pandemic, the Centers for Medicare and Medicaid Services created a waiver to reimburse telemedicine services. It is important to understand factors that facilitate incorporation of telemedicine into ongoing cardiovascular practice.

METHODS: This was a retrospective cohort study of telemedicine and office visits delivered by cardiologists between January 1, 2022, and December 31, 2023, for Medicare beneficiaries. We calculated the adjusted incidence rate ratio (aIRR) of telemedicine visits, representing the proportion of a physician's visits delivered by telemedicine, to identify factors associated with telemedicine use.

RESULTS: There were 23 334 physicians in our cohort; they were predominantly …

Polθ Activity Modulates Sensitivity To Standard Therapies In Dnmt3a-Deficient Leukemia, Bac Viet Le, Umeshkumar Vekariya, Monika M. Toma, Margaret Nieborowska-Skorska, Marie-Christine Caron, Malgorzata Gozdecka, Zayd Haydar, Martin Walsh, Jayashri Ghosh, Elaine Vaughan-Williams, Paulina Podszywalow-Bartnicka, Anna-Mariya Kukuyan, Sylwia Ziolkowska, Jessica Atkins, Emir Hadzijusufovic, Gurushankar Chandramouly, Reza Nejati, Katarzyna Piwocka, Richard T. Pomerantz, George S. Vassiliou, Brian J.P. Huntly, Peter Valent, Mariusz Wasik, Alfonso Bellacosa, Jean-Yves Masson, Gaorav P. Gupta, Grant A. Challen, Tomasz Skorski

Department of Biochemistry and Molecular Biology Faculty Papers

Myeloid malignancies carrying somatic DNMT3A mutations (DNMT3Amut) are refractory to standard therapy. DNMT3Amut leukemia cells accumulate toxic DNA double-strand breaks (DSBs) and stalled replication forks, rendering them dependent on DNA damage response (DDR). We report here that DNA polymerase theta (Polθ), a key element in DSB repair by end-joining (Polθ-mediated end-joining [TMEJ]) and in fork restarting, promotes survival and proliferation of DNMT3Amut leukemia cells. Polθ is overexpressed in DNMT3Amut leukemia cells due to abrogation of PARP1 PARylation-dependent UBE2O E3 ligase-mediated ubiquitination and proteasomal degradation of Polθ. In addition, PARP1-mediated recruitment of the SMARCAD1-MSH2/MSH3 repressive complex to DSBs is diminished in …

Ifnγ-Induced Antigen Loss In Chimeric Antigen Receptor-T Cell Therapy, Miao Cao, Jasmine Alvarez, Ramkrishna Mitra, Michael Xu, Trevor R. Baybutt, Zhengyang Sun, Oluwatobiloba Taylor, Allison Doermann, Ross E Staudt, Scott A. Waldman, Adam E. Snook

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: FDA-approved chimeric antigen receptor (CAR)-expressing T cell therapies (CARTs) have revolutionized the treatment of blood cancers. Yet none have been successful for "solid" tumors, such as colorectal cancer (CRC), the 2nd leading cause of cancer deaths. Guanylyl cyclase C (GUCY2C) has emerged as a clinical-stage target for CART and bispecific T-cell engager (BiTE) therapies in CRC. IFNγ has been canonically recognized as beneficial for the effector functions of T cells by enhancing antigen processing and HLA presentation and is essential for CART targeting of solid malignancies by inducing adhesion molecule expression for synapse stabilization.

METHODS: Using

RESULTS: We identified …

High Dietary Fiber Is Associated With Improved Outcomes In Patients With Melanoma And Sarcoma Treated With Immunotherapy Regardless Of Gut Microbiome Dysbiosis And Social Vulnerability, Brittany C Fields, Raymond S Traweek, Kai Jiang, Russell G Witt, Ashish Damania, Yi-Ju Chiang, Nadim Ajami, Elise Nassif-Haddad, Emily Z Keung, Manoj Chelvanambi, Xiaotao Zhang, Christine B Peterson, Jennifer A Wargo, Carrie R Daniel, Christina L Roland, Ashley M Holder

Faculty, Staff and Student Publications

Background: Social vulnerability, dietary fiber, and the gut microbiome have been individually implicated in clinical outcomes for melanoma and sarcoma patients. This study hypothesized that increasing social vulnerability is associated with insufficient dietary fiber intake and negatively associated with microbiome composition and clinical outcomes.

Methods: Clinicopathologic data, baseline fiber intake, and gut microbiome profiles were assessed in 153 patients with melanoma or sarcoma treated with immune checkpoint blockade (ICB) and prospectively followed. Patients' social vulnerability index (SVI) and fiber intake were evaluated for associations with microbiome composition, treatment response, and overall survival (OS).

Results: SVI percentile was 0.4 (interquartile ratio …

Radiation Doses To Cardiac Substructures Predict Elevation In High-Sensitivity Cardiac Troponin T Levels In Radiation Therapy For Lung Cancer, Xinru Chen, Xiaodong Zhang, Ting Xu, Radhe Mohan, Ruitao Lin, Mei Chen, Rachel C Maguire, Yao Zhao, Efstratios Koutroumpakis, Nicolas L Palaskas, Anita Deswal, Ali Ajdari, Joshua S Niedzielski, Sanjay S Shete, Laurence E Court, Jinzhong Yang, Zhongxing Liao

Faculty, Staff and Student Publications

Purpose: Cardiotoxicity is a major concern for patients undergoing thoracic radiation therapy. This study compared the predictive power of radiation dose-volume histogram (DVH) parameters and radiomic/dosiomic features of the whole heart (WH) and cardiac substructures for elevated circulating high-sensitivity cardiac troponin T (hs-cTnT), a biomarker for early detection of cardiac adverse events.

Methods and materials: A retrospective cohort of 160 patients with non-small cell lung cancer (NSCLC) from a completed prospective trial and a prospective cohort of 57 patients with NSCLC enrolled in an ongoing trial were analyzed. The endpoint was hs-cTnT elevation, indicated by an increase of ≥5 ng/L …

Pimicotinib Versus Placebo For Tenosynovial Giant Cell Tumour (Maneuver): An International, Randomised, Placebo-Controlled, Phase 3 Trial, Hairong Xu, Xiaohui Niu, Vinod Ravi, Javier Martin-Broto, Albiruni Abdul Razak, Ramy Saleh, Yong Zhou, Jingnan Shen, Tang Liu, Kamlesh Kumar Sankhala, César Serrano, Silvia Stacchiotti, Jing Wang, Giacomo G Baldi, Yi Feng, Yingqi Hua, Tao Li, Piotr Rutkowski, Xiaojing Zhang, Gabriel Tinoco, Qingping Zou, Boyao Shan, Xiangyu Zhu, Hans Gelderblom

Faculty, Staff and Student Publications

Background: Tenosynovial giant cell tumour (TGCT) is a rare, locally aggressive neoplasm that affects otherwise healthy adults. There are few systemic treatment options, highlighting an unmet need. We report the results of part 1 of the MANEUVER trial, which aimed to evaluate the efficacy and safety of pimicotinib, a highly selective, potent, colony-stimulating factor-1 receptor inhibitor, in patients with TGCT.

Methods: MANEUVER is a randomised, placebo-controlled, phase 3 study done in 40 specialised hospitals in Asia, Europe, and North America. Patients aged 18 years and older with unresectable, symptomatic TGCT (patient-reported worse stiffness or worst pain of at least 4 …

Gastrointestinal Symptoms After Sport-Related Concussion In Irish Athletes, Emma Finnegan, Ed Daly, Katherine Hunzinger, Lisa Ryan

Department of Exercise Science Faculty Papers

Background/Objectives: Sport-related concussion (SRC) elicits multi-systemic symptoms, including nausea, fatigue, and cognitive changes. Gastrointestinal (GI) symptoms are not well captured in current concussion assessments and may be under-recognised in clinical follow-up. GI disturbances may influence intake tolerance and day-to-day fuelling during post-SRC recovery. This study investigated the prevalence and severity of self-reported GI symptoms in Irish athletes after their most recent SRC, examined sex-based patterns, and evaluated the rationale for integrating GI symptom checks into standard concussion tools (e.g., SCAT6) and post-injury monitoring. Methods: An online survey was completed by recreational, competitive, and elite athletes who retrospectively self-reported concussion history, …

Breaking Into Hiv-1'S Epigenetic Vault: Cure Strategies To Eliminate The Viral Reservoir, Joanna Jones, Chelsea Gunderson, Brian Wigdahl, Michael Nonnemacher

Kimmel Cancer Center Faculty Papers

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that integrates into the host cell's DNA as a provirus. Transcription from the provirus is regulated in large part by cellular proteins and epigenetic factors. These may be repressive or permissive to productive infection. The host factors that regulate this balance are therefore attractive targets for HIV-1 therapeutics. Indeed, proviral chromatin is the focus of two of the current HIV-1 cure strategies. "Shock and Kill" uses latency reversal agents to open the provirus's chromatin, promoting high levels of gene expression that induce the killing of infected cells. "Block and Lock" uses …