Digital Commons Network^™

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

Faculty, Staff and Student Publications

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

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

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

Sleep, Sedentary Time, And Physical Activity In Heart Failure Subtypes: Multi-Ethnic Study Of Atherosclerosis (Mesa), Demi M. Nott

UNF Graduate Theses and Dissertations

INTRODUCTION: Previous studies have examined the associations between physical activity (PA), sedentary time (ST), and sleep on the risk of heart failure (HF). The primary aim of this study was to examine PA, ST, and sleep quality (SQ) in those diagnosed with preserved ejection fraction HF (HFpEF) and reduced ejection fraction HF (HFrEF). The secondary aim of this study was to examine these relationships in those with and without HF, independent of sub-type.

METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) collected data from 6,814 adults from a diversified cohort who range in age from 45 to 84. Subjects were classified …

Fitness Consequences Of Depressive Symptoms Vary Between Generations: Evidence From A Large Cohort Of Women Across The 20th Century, Christopher I Gurguis, Renée A Duckworth, Nicole M Bucaro, Consuelo Walss-Bass

Faculty, Staff and Student Publications

Depression has strong negative impacts on how individuals function, leading to the assumption that there is strong negative selection on this trait that should deplete genetic variation and decrease its prevalence in human populations. Yet, depressive symptoms remain common. While there has been a large body of work trying to resolve this paradox by mapping genetic variation of this complex trait, there have been few direct empirical tests of the core assumption that there is consistent negative selection on depression in human populations. Here, we use a unique long-term dataset from the National Health and Nutrition Examination Survey that spans …

Genetic Knowledge And Causal Beliefs: Implications For Health Behavior In Clinical And Non-Clinical Samples, Jamey T. Brumbaugh

Graduate Theses, Dissertations, and Problem Reports (ETD)

Objective: As the genomic era in healthcare continues to surge, it is vital to examine genetically-related psychological concepts, such as genetic knowledge and genetic causal beliefs, in genetically relevant clinical groups. Parents /caregivers of children born with cleft lip and/or palate represent a population whose knowledge and beliefs about genetics may be influenced by their frequent utilization of genetically-related healthcare services (e.g., genetic testing and genetic counseling). To date, little is known about how such beliefs vary across disease types. Even less is known regarding how disease-specific genetic causal beliefs relate to perceived behavioral control for disease development. Method: A …

Changes In Psychiatric Diagnosis Associated With Sars-Cov-2 Infection And Predicting The Development Of New Psychiatric Illness In Covid Patients By Using Machine Learning Approach: A Study Using The Us National Covid Cohort Collaborative (N3c), Asif Rahman

Graduate Theses, Dissertations, and Problem Reports (ETD)

The enduring impact of COVID-19 extends beyond acute illness, with potential long-term psychiatric consequences raising significant concern among healthcare professionals and researchers alike. Emerging evidence suggests a multifaceted relationship between COVID-19 and the development of different psychiatric illnesses like Schizophrenia Spectrum and Psychotic Disorders (SSPD), Depression, Bipolar disorder, Personality disorder, Trauma, and a range of other mental health conditions. Considering these emerging connections, our study endeavors to rigorously assess the associations between COVID-19 and various psychiatric illnesses while simultaneously employing machine learning techniques to predict the development of new psychiatric disorders in individuals affected by the virus. Leveraging the extensive …

An Appalachian Perspective On Suicide: A Focus On West Virginia’S Unique Context, Erin Delaney Caswell

Graduate Theses, Dissertations, and Problem Reports (ETD)

INTRODUCTION: The Appalachian region, spanning 13 states from New York to northern Mississippi, experiences the suicide rates in the United States (U.S.), underscoring a public health crisis exacerbated by persistent socioeconomic challenges. West Virginia (WV), the only state entirely within Appalachia, serves as a focal point for understanding the broader suicide crisis in the region, as WV has the highest suicide rates in the region. Moreover, the state has several unique socioeconomic factors, like increased poverty, lower educational attainment, limited access to healthcare, and a high prevalence of chronic pain and substance that may contribute to elevated rates of suicide. …

Resting Heart Rate Mediates The Association Between Circulating Neutrophil Count And Arterial Stiffness Progression: The Kailuan Study, Zhaogui Wu, Dan Wu, Shuohua Chen, Sichi Xu, Shunming Zhang, Shouling Wu

Research outputs 2022 to 2026

Objective: This study aimed to longitudinally investigate the association between circulating neutrophil count and the progression of arterial stiffness and to ascertain whether resting heart rate (RHR) mediates this association. Methods: The current study included 56,760 participants with brachial-ankle pulse wave velocity (baPWV) measurements from a real-life, prospective cohort in China. The associations of circulating neutrophil (exposure) with baseline baPWV, baPWV progression, and arterial stiffness (outcomes), as well as RHR (mediator) were assessed using multivariable linear and Cox regression models and mediation analysis. Results: After adjusting for cardiometabolic risk factors, for each 1-SD increase in neutrophil count, the corresponding increase …

Music As A Determinant Of Health Among First Nations People In Australia: A Scoping Narrative Review, Brigitta Scarfe, Kristy Apps, Naomi Sunderland, Phil Graham, Brydie Leigh Bartleet, Glenn Barry, Darren Garvey, Rae Cooper, Clint Bracknell

Research outputs 2022 to 2026

Issue Addressed:

While social determinants frameworks are still popular in research about First Nations health in Australia, a growing body of research prefers cultural determinants of health models. Cultural determinants models provide a holistic, strength-based framework to explain connections between health and contextual factors, including the potential role of music and its impact on social and emotional well-being. Given the growing international recognition of links between music, health, and wellbeing through bodies such as the World Health Organisation, this article examines whether and how music practices are acknowledged in First Nations determinants of health literature.

Methods:

We conducted a scoping …

Lessons Learned: Drive-Through Covid-19 Clinic Testing During An Adaptive Epidemic Response And A Point-Of-Care Test Assessment Of A Computer-Read Rapid Lateral Flow Immunoassay With Fluorescence-Based Detection, Leah Rankine-Wilson, Teresa Oncken, Irshan Basrewan, Courtney Jeffery, Todd M. Pryce, Rebecca Wake, Aus A.L. Molan, T. F. Paton, Tim J.J. Inglis

Research outputs 2022 to 2026

Background. The COVID-19 pandemic demonstrated a need for robust SARS-CoV-2 test evaluation infrastructure to underpin biosecurity and protect the population during a pandemic health emergency. Gap statement. The first generation of rapid antigen tests was less accurate than molecular methods due to their inherent sensitivity and specificity shortfalls, compounded by the consequences of self-testing. This created a need for more accurate point-of-care SARS-CoV-2 detection methods. Aim. Here we present the lessons-learned during the COVID-19 emergency response in Western Australia including the detailed set-up, evaluation and operation of rapid antigen test in a state-run drive-through sample collection service during the COVID-19 …

Demonstrating The Need For Intergenerational Trauma-Specific Substance Use Treatment For Mothers Receiving Substance Use Treatment And Their Children, Brittany Ti-Esha Smith

Graduate Theses, Dissertations, and Problem Reports (ETD)

For decades the United States has faced substance use epidemics that have devastating public health consequences, with the most recent epidemic being the opioid epidemic. While the substance that is the center of the epidemic’s changes over time, one factor that has been found to be positively related to substance use has remained consistent, that preventable risk factor is adverse childhood experiences (ACEs). Those who experience ACEs are at elevated risk for developing SUD. If the trauma that is a result of experiencing ACE is not treated it can complicate recovery and impact the individuals’ families. The children of individuals …

Factors Associated With The Prevalence Of Iron Deficiency And Anemia In Women Of Reproductive Age In The U.S.: Nhanes 2015-2020, Catherine Wise

All Master's Theses

Iron deficiency (ID) is well recognized as the most prevalent nutrient insufficiency and a leading cause of anemia. Women of reproductive age (WRA), females 15 to 49, are at an increased risk of ID and anemia. This is due to the heightened iron demands of this life stage, including puberty, menstruation, and pregnancy, which require iron intakes ranging from 15 to 27 mg/day. Poor health and nutrition increase the risk of ID and progression to anemia. Consequences of ID and anemia range from exhaustion and decreased cognitive function to an increased risk of mortality. This study aimed to assess the …

A Descriptive Analysis Of Depressive Symptoms And Body Image By Race/Ethnicity And Nativity Status Among Adolescents, Radhika Prasad

Electronic Theses & Dissertations (2024 - present)

Previous research on the immigrant health paradox among children and adolescents show a mental health advantage yet it is unclear if this applies in a similar magnitude to females (Fillion et al., 2018; Zarei et al., 2023). Immigrants may be exposed to stressors related to immigration and acculturation. Some research suggests that females respond more to stress through internalizing symptoms relative to males (Hall-Lande et al., 2007; Adkins et al., 2009). Given these gender differences in stress response, female immigrants may be particularly vulnerable to the psychological consequences of immigration related stressors. The immigrant health paradox has also overlooked subjective …

Characterizing 4,4’-Methylene Diphenyl Diisocyanate Exposure In Primary Human Epidermal Keratinocytes: A Multi-Omics Approach, Brandon F. Law

Graduate Theses, Dissertations, and Problem Reports (ETD)

Exploring the routes of exposure and biological fate of 4,4’-methylene diphenyl diisocyanate (MDI) has been a challenge for many years. Occupational exposure to MDI can result in the development of occupational asthma (MDI-OA) which results in loss of productivity, large economic costs, and costs to the individual worker. Initially, it was thought that respiratory exposure to MDI was the most likely route leading to MDI-OA. Industries utilizing MDI have been successful at controlling airborne concentrations according to industrial hygiene assessment and newly diagnosed cases of MDI-OA decreased and plateaued. New research suggests that dermal exposures to MDI may explain this …

Assessing Associations Between Emergency Room Visits For Respiratory And Cardiovascular Diseases And Criteria Air Pollutants Exposure In New York State, Tamba Solomon Lebbie

Electronic Theses & Dissertations (2024 - present)

Abstract

Air pollution is a major environmental health hazard for the general population. Approximately 90% of the global population is at risk of both indoor and outdoor air pollution, and it accounts for an estimated 7 million premature deaths every year according to the World Health Organization (WHO). Multiple studies including epidemiological and molecular analyses have confirmed the negative effects of air pollutants on human health even at levels within the WHO guidelines. This study examines the health impacts of releases of criteria air pollution from point sources in New York State (NYS). There is evidence from population studies that …

Ribosome Hibernation Factor Induces Antibiotic Persisters Of Mycobacterium Tuberculosis In Neutrophil-Rich Lung Lesions, Jamie Corro

Electronic Theses & Dissertations (2024 - present)

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is a prescient global health threat and the leading cause of death by an infectious agent. Treatment of Mtb infection involves administering 2-4 antibiotics for a minimum of 6 months. This extended drug regimen is required to target a subpopulation of persistent bacilli. As their name implies, these bacteria can “persist” by acquiring nonhereditary and transient antibiotic tolerance. Although the precise mechanism is unknown, it’s often attributed to slowing cellular growth and metabolic processes. During zinc deprivation, bacteria can remodel their ribosomes by replacing their zinc-binding paralogues containing the CXXC motif (C+) …

An Interactive, Case-Based Workshop On The Patient Experience For Internal Medicine Residents, Julian Swanson, Doris Lin, Kristen A Staggers, Priti Dangayach

Faculty, Staff and Students Publications

INTRODUCTION: The technological revolution has narrowed the information gap between physician and patient. This has led to an evolution in medicine from paternalistic to patient-centric, with health care systems now prioritizing patient experience to achieve higher satisfaction scores. Therefore, it is imperative to start early in educating trainees on how to best address the holistic needs of the patient while also delivering high-quality care.

METHODS: We implemented a 1-hour workshop that was repeated weekly over 8 weeks to capture all internal medicine residents in our program. During the workshop, we reviewed the historical evolution of patient care from paternalistic to …

Prevalence Of Congenital Anomalies According To Maternal Race And Ethnicity, Texas, 1999–2018, Jeremy M Schraw, Elwin Jaime, Charles J Shumate, Mark A Canfield, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Few studies of congenital anomalies provide prevalence estimates stratified by maternal race/ethnicity. We sought to determine whether the prevalence of a broad spectrum of anomalies varies among offspring of women from different race/ethnic groups.

METHODS: We obtained information on cases with anomalies from the population-based Texas Birth Defects Registry, and denominator data on livebirths among Texas residents during 1999-2018 from the Texas Center for Health Statistics. We estimated the prevalence ratio (PR) and 95% confidence interval (CI) of N = 145 anomalies among offspring of Hispanic and non-Hispanic Black relative to non-Hispanic White women using Poisson regression, adjusting for …

Achieving Surgical, Obstetric, Trauma, And Anesthesia (Sota) Care For All In South Asia, Siddhesh Zadey, Shirish Rao, Isha Gondi, Natalie Sheneman, Chaitrali Patil, Anveshi Nayan, Himanshu Iyer, Arti Raj Kumar, Arun Prasad, G Allen Finley, Chellapuram Raja Krishna Prasad, Chintamani, Dhananjaya Sharma, Dhruva Ghosh, Gnanaraj Jesudian, Irum Fatima, Jogi Pattisapu, Justin Sangwook Ko, Lovenish Bains, Mashal Shah, Mohammed Shadrul Alam, Narmada Hadigal, Naveen Malhotra, Nilmini Wijesuriya, Prateek Shukla, Sadaf Khan, Sunil Pandya, Tariq Khan, Tashi Tenzin, Venkat Raja Hadiga, Daniel Peterson

Faculty, Staff and Students Publications

South Asia is a demographically crucial, economically aspiring, and socio-culturally diverse region in the world. The region contributes to a large burden of surgically-treatable disease conditions. A large number of people in South Asia cannot access safe and affordable surgical, obstetric, trauma, and anesthesia (SOTA) care when in need. Yet, attention to the region in Global Surgery and Global Health is limited. Here, we assess the status of SOTA care in South Asia. We summarize the evidence on SOTA care indicators and planning. Region-wide, as well as country-specific challenges are highlighted. We also discuss potential directions-initiatives and innovations-toward addressing these …

Effects Of Covid-19 On Sleep Services Use And Its Recovery, Amin Ramezani, Amir Sharafkhaneh, Ahmed S Bahammam, Samuel T Kuna, Javad Razjouyan

Faculty, Staff and Students Publications

PURPOSE: The COVID-19 pandemic affected the utilization of various healthcare services differentially. Sleep testing services utilization (STU), including Home Sleep Apnea Testing (HSAT) and Polysomnography (PSG), were uniquely affected. We assessed the effects of the pandemic on STU and its recovery using the Veterans Health Administration (VHA) data.

PATIENTS AND METHODS: A retrospective cohort study from the VHA between 01/2019 and 10/2023 of veterans with age ≥ 50. We extracted STU data using Current Procedural Terminology codes for five periods based on STU and vaccination status: pre-pandemic (Pre-Pan), pandemic sleep test moratorium (Pan-Mor), and pandemic pre-vaccination (Pan-Pre-Vax), vaccination (Pan-Vax), and …

Vaccines Against Extraintestinal Pathogenic Escherichia Coli (Expec): Progress And Challenges, Ling Qiu, Dylan Chirman, Justin R Clark, Yikun Xing, Haroldo Hernandez Santos, Ellen E Vaughan, Anthony W Maresso

Faculty, Staff and Students Publications

The emergence of antimicrobial resistance (AMR) is a principal global health crisis projected to cause 10 million deaths annually worldwide by 2050. While the Gram-negative bacteria Escherichia coli is commonly found as a commensal microbe in the human gut, some strains are dangerously pathogenic, contributing to the highest AMR-associated mortality. Strains of E. coli that can translocate from the gastrointestinal tract to distal sites, called extraintestinal E. coli (ExPEC), are particularly problematic and predominantly afflict women, the elderly, and immunocompromised populations. Despite nearly 40 years of clinical trials, there is still no vaccine against ExPEC. One reason for this is …

Applying Market Basket Analysis To Determine Complex Coassociations Among Food Allergens In Children With Food Protein-Induced Enterocolitis Syndrome (Fpies), Ankona Banerjee, Kenneth Nobleza, Cynthia Haddad, Joshua Eubanks, Ruchit Rana, Nicholas L Rider, Lisa Pompeii, Duc Nguyen, Sara Anvari

Faculty, Staff and Students Publications

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy, characterized by delayed onset of repetitive vomiting occurring 1 to 4 h following ingestion of a food allergen. Managing FPIES requires strict avoidance of the food trigger. The concern with FPIES is determining the risk of another FPIES food trigger reaction due to potential coassociations with other foods or food groups. An effective statistical approach for analyzing FPIES-related data is essential to identify common coallergens and their associations.

METHODS: This study employed Market Basket Analysis, a data-mining technique, to examine correlations and patterns among allergens in FPIES patients at …

Autophagy Determines Distinct Cell Fates In Human Amnion And Chorion Cells, Mary Elise L Severino, Lauren Richardson, Ananth Kumar Kammala, Enkhtuya Radnaa, Kamil Khanipov, Leslie Michelle M Dalmacio, Indira U Mysorekar, Marian Kacerovsky, Ramkumar Menon

Faculty, Staff and Students Publications

Human fetal membranes (amniochorion) that line the intrauterine cavity consist of two distinct cell layers; single-layer amnion epithelial cells (AEC) and multilayer chorion trophoblast cells (CTC). These layers are connected through a collagen-rich extracellular matrix. Cellular remodeling helps support membrane growth and integrity during gestation and helps to maintain pregnancy. Preterm prelabor rupture of the human amniochorionic (fetal) membrane (pPROM) is antecedent to 40% of all spontaneous preterm birth. Oxidative stress (OS) induced activation of the p38 MAPK due to various maternal risk exposures and the amniochorion cells' senescence are reported pathological features of pPROM. Our transcriptomics analysis implicated dysregulated …

Nutritional Importance Of Animal-Sourced Foods In A Healthy Diet, Sydney Sheffield, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

Animal-sourced foods, such as meats, poultry, eggs, milk, and fish are nutrient-dense foods that are rich sources of protein, essential amino acids, and micronutrients that can be challenging to obtain solely through plant-based foods. Animal-sourced protein foods provide crucial nutrients that support the growth and development in children, maintenance of muscle mass and function in adults, gain in muscle mass and strength in exercising individuals, and mitigation of sarcopenia in the elderly. The 2020–2025 Dietary Guidelines for Americans have identified the important role of animal-sourced foods in the diet at every stage of life. Animal-sourced foods are consumed worldwide and …

Targeting Sars-Cov-2 Nonstructural Protein 3: Function, Structure, Inhibition, And Perspective In Drug Discovery, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

As a highly contagious human pathogen, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has infected billions of people worldwide with more than 6 million deaths. With several effective vaccines and antiviral drugs now available, the SARS-CoV-2 pandemic been brought under control. However, a new pathogenic coronavirus could emerge in the future, given the zoonotic nature of this virus. Natural evolution and drug-induced mutations of SARS-CoV-2 also require continued efforts for new anti-coronavirus drugs. Nonstructural protein (nsp) 3 of CoVs is a large, multifunctional protein, containing a papain-like protease (PLpro) and a macrodomain (Mac1), which are essential for viral replication. Here, we …

Preclinical Evaluation Of A Novel Antibiotic-Eluting Bioenvelope For Cied Infection Prevention, Zerelda Esquer Garrigos, John N Catanzaro, Daniel Deegan, Ji Zhang, M Rizwan Sohail

Faculty, Staff and Students Publications

The risk of infection remains a significant concern with cardiovascular implantable electronic devices, necessitating the development of new strategies. This study explores the efficacy of a novel antibiotic-eluting biologic envelope designed to mitigate infection risk through localized antibiotic delivery while preserving the regenerative properties of biological matrix. Antibiotics, rifampin and minocycline, are released through polymer discs, ensuring extended drug release. Utilizing an established model of infection in a New Zealand White rabbit, the study assessed performance against Gram-positive bacterial strains, including common pathogens such as Staphylococcus aureus and S. epidermidis associated with CIED infections, and Gram-negative bacterial strains. Results demonstrated …

Profile Of Caregiving Activities And Association With Physical Health Among Dementia Spousal Caregivers, Jinmyoung Cho, Laura P Sands, Alan B Stevens, Heather G Allore, Molly J Horstman

Faculty, Staff and Students Publications

Background and objectives: This study aims to identify patterns of caregiving intensity and assess associations between caregiving intensity and multidimensional physical health indicators and health behaviors among spousal caregivers of persons with Alzheimer's disease and related dementia.

Research design and methods: Using data from 152 spousal caregivers aged 65 and older, the intensity of their caregiving experience was measured as the number and frequency of health- and medical-related helping activities for their care recipient. Multidimensional health indicators included self-reported fatigue, sleep disturbance, physical functioning, pain interference, general health, and the number of chronic conditions from the electronic health records. Self-reported …

Twenty Years Of Epithelial-Mesenchymal Transition: A State Of The Field From Temtia X, Pierre Savagner, Thomas Brabletz, Chonghui Cheng, Christine Gilles, Tian Hong, Myriam Polette, Guojun Sheng, Marc P Stemmler, Erik W Thompson

Faculty, Staff and Students Publications

This report summarizes the 10th biennial meeting of The Epithelial Mesenchymal Transition International Association (TEMTIA), that took place in Paris on November 7-10, 2022. It provides a short but comprehensive introduction to the presentations and discussions that took place during the 3-day meeting. Similarly to previous TEMTIA meetings, TEMTIA X reviewed the most recent aspects of the epithelial-mesenchymal transition (EMT), a cellular process involved during distinct stages of development but also during wound healing and fibrosis to some degree. EMT has also been associated at various levels during tumor cell progression and metastasis. The meeting emphasized the intermediate stages of …

Branched-Chain Amino Acid Accumulation Fuels The Senescence-Associated Secretory Phenotype, Yaosi Liang, Christopher Pan, Tao Yin, Lu Wang, Xia Gao, Ergang Wang, Holly Quang, De Huang, Lianmei Tan, Kun Xiang, Yu Wang, Peter B Alexander, Qi-Jing Li, Tso-Pang Yao, Zhao Zhang, Xiao-Fan Wang

Faculty, Staff and Students Publications

The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine play critical roles in protein synthesis and energy metabolism. Despite their widespread use as nutritional supplements, BCAAs' full effects on mammalian physiology remain uncertain due to the complexities of BCAA metabolic regulation. Here a novel mechanism linking intrinsic alterations in BCAA metabolism is identified to cellular senescence and the senescence-associated secretory phenotype (SASP), both of which contribute to organismal aging and inflammation-related diseases. Altered BCAA metabolism driving the SASP is mediated by robust activation of the BCAA transporters Solute Carrier Family 6 Members 14 and 15 as well as downregulation …

Artificial Intelligence-Powered Discovery Of Small Molecules Inhibiting Ctla-4 In Cancer, Navid Sobhani, Dana Rae Tardiel-Cyril, Dafei Chai, Daniele Generali, Jian-Rong Li, Jonathan Vazquez-Perez, Jing Ming Lim, Rachel Morris, Zaniqua N Bullock, Aram Davtyan, Chao Cheng, William K Decker, Yong Li

Faculty, Staff and Students Publications

BACKGROUND/OBJECTIVES: Checkpoint inhibitors, which generate durable responses in many cancer patients, have revolutionized cancer immunotherapy. However, their therapeutic efficacy is limited, and immune-related adverse events are severe, especially for monoclonal antibody treatment directed against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which plays a pivotal role in preventing autoimmunity and fostering anticancer immunity by interacting with the B7 proteins CD80 and CD86. Small molecules impairing the CTLA-4/CD80 interaction have been developed; however, they directly target CD80, not CTLA-4.

SUBJECTS/METHODS: In this study, we performed artificial intelligence (AI)-powered virtual screening of approximately ten million compounds to identify those targeting CTLA-4. We validated the …

Dna Mismatch Repair Defect And Intratumor Heterogeneous Deficiency Differently Impact Immune Responses In Diffuse Large B-Cell Lymphoma, Zijun Y Xu-Monette, Cancan Luo, Li Yu, Yong Li, Govind Bhagat, Alexandar Tzankov, Carlo Visco, Xiangshan Fan, Karen Dybkaer, Ali Sakhdari, Nicholas T Wang, Alyssa F Yuan, April Chiu, Wayne Tam, Youli Zu, Eric D Hsi, Anamarija M Perry, Wenting Song, Dennis O'Malley, Qingyan Au, Harry Nunns, Heounjeong Go, Michael B Møller, Benjamin M Parsons, Santiago Montes-Moreno, Maurilio Ponzoni, Andrés J M Ferreri, Aliyah R Sohani, Jeremy S Abramson, Bing Xu, Ken H Young

Faculty, Staff and Students Publications

Deficient (d) DNA mismatch repair (MMR) is a biomarker predictive of better response to PD-1 blockade immunotherapy in solid tumors. dMMR can be caused by mutations in MMR genes or by protein inactivation, which can be detected by sequencing and immunohistochemistry, respectively. To investigate the role of dMMR in diffuse large B-cell lymphoma (DLBCL), MMR gene mutations and expression of MSH6, MSH2, MLH1, and PMS2 proteins were evaluated by targeted next-generation sequencing and immunohistochemistry in a large cohort of DLBCL patients treated with standard chemoimmunotherapy, and correlated with the tumor immune microenvironment characteristics quantified by fluorescent multiplex immunohistochemistry and gene-expression …