Medicine and Health Sciences Commons^™

Elevated Level Of Extracellular Vimentin Is Associated With An Increased Fibrin Formation Potential In Sepsis: Ex Vivo Swine Study, Marina Martinez-Vargas, Arun Saini, Subhashree Pradhan, Luis Gardea, Barbara Stoll, Inka C Didelija, K Vinod Vijayan, Trung C Nguyen, Miguel A Cruz

Faculty, Staff and Students Publications

BACKGROUND: Sepsis can lead to coagulopathy and microvascular thrombosis. Prior studies, including ours, reported an increased level of extracellular vimentin in blood derived from septic patients. Moreover, we identified the contribution of extracellular vimentin to fibrin formation and to the fibrin clot structure ex vivo in plasma from septic patients. Here, we tested the status of plasma vimentin and its impact on fibrin clots using our recently described swine model of methicillin-resistant Staphylococcus aureus (MRSA) sepsis-induced coagulopathy.

RESULTS: We employed ELISA, size-exclusion chromatography, vimentin antibodies, confocal microscopy, and turbidity assays on piglet plasma obtained at pre- and post-MRSA inoculation. Plasma …

David Taylor Memorial Lecture: Insights Into The Origins Of Intracardiac Surgery, James K. Kirklin

The VAD Journal

David Taylor was an eminent luminary in the field of advanced heart failure and transplantation. As past president of the International Society for Heart and Lung Transplantation, he significantly impacted the field and was a mentor to many young heart failure cardiologists. In addition to many professional activities, David was an integral part of Brano meetings, including numerous eastern European trips promoting education and training in advanced heart failure, mechanical circulatory support, and transplantation

Time From Dose To Delivery And Efficacy Of Maternal Azithromycin Prophylaxis In Planned Vaginal Births, Rupsa Boelig, A Kavi, J Moore, B Babineau, W Carlo, A Tita

Department of Obstetrics and Gynecology Posters

Objective

• A Multicenter international placebo controlled randomized trial (APLUS) found that 2g oral azithromycin in labor reduced risk of maternal sepsis and death, but not newborn sepsis
• Efficacy in prevention of maternal or neonatal infections may be impacted by timing of antibiotics in labor

Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer …

Evolution Of The Substance Use Landscape: Implications For Contingency Management., Shelby Goodwin, Kimberly C Kirby, Bethany Raiff

College of Science & Mathematics Departmental Research

Contingency management (CM), which involves the delivery of incentives upon meeting behavioral goals, has the potential to improve substance use treatment outcomes. The intervention allows for flexibility through numerous modifiable components including changes to incentive magnitude and schedule, target behavior, and intervention structure. Unfortunately, numerous changes in the substance use landscape have occurred in the past 10 to 15 years: Substances are more potent, overdose risk has increased, new substances and methods of use have been introduced, and substance classes are increasingly being intentionally and unintentionally mixed. These developments potentially undermine CM outcomes. We explored recent substance use changes due …

Clinical Practice Guideline On Evaluating The Effectiveness Of Venipuncture Arm Simulation, Drena D. Belland

Walden Dissertations and Doctoral Studies

Venipuncture is an integral process in clinical care, and it has an indispensable role in diagnostics and determining therapeutic interventions. The process of phlebotomy has faced several challenges that have compromised patients’ safety. The risk of incorrect venipuncture, or preanalytical errors, leading to severe patient complications of hematoma and thrombosis calls for training using current, evidence-based practices. The goal of this project was to develop a clinical practice guideline (CPG) to determine the efficacy of venipuncture simulation training using an arm task trainer to enhance the phlebotomy skills of nurses. Based on the outcome, present, state, test model and Nightingale’s …

Effects Of Nursing Faculty Incivility On Nursing Student Attrition, Amber Solheim

Walden Dissertations and Doctoral Studies

Incivility in nursing academia can occur with various people in the role of the perpetrator or victim, including students, faculty, and healthcare professionals in clinical settings. Nursing faculty incivility towards students may lead to nursing student attrition in practical nursing or associate degree programs. The purposes of this study, guided by Bandura’s social learning theory and Tajfel’s social identity theory, were to determine if there is a (a) difference in perceived faculty incivility in nursing students who withdraw from nursing school and nursing students who do not withdraw and (b) the difference in the levels of perceived faculty incivility between …

Identifying The Roles Of Mir-17 In Ciliogenesis And Cell Cycle, Ashwaq Alanazi, Ayan K. Barui, Ashraf M. Mohieldin, Ankan Gupta, Ramani Ramachandran, Surya M. Nauli

Pharmacy Faculty Articles and Research

Emerging evidence suggests a significant contribution of primary cilia to cell division and proliferation. MicroRNAs, especially miR-17, contribute to cell cycle regulation and proliferation. Recent investigations have highlighted the dysregulated expression of miR-17 in various malignancies, underlining its potential role in cancer. However, the correlation between primary cilia and miR-17 has yet to be fully elucidated. The present study examines the presence of miR-17 in primary cilia. The miR-17 expression is studied in selected ciliary protein knockdown cells. Using in situ hybridization (ISH), we identified the subcellular localization of miR-17 in both cilium and cell body. We confirmed the importance …

Manifest Health Theory: A Holistic Approach To Cis-Gender Men’S Health, Julian L. Gallegos

School of Nursing Faculty Publications

Men’s health has often been overlooked in health care, with traditional gender norms and societal expectations significantly shaping men’s health behaviors and attitudes. The MANifest Health Theory (MHT) offers a comprehensive framework to address cis-gender men’s unique health needs by considering the complex interplay of biological, psychological, and social factors. Rooted in four interconnected core concepts—Biopsychosocial Model, Health Optimization, Health Synchronicity, and Ethnocultural Expression—MHT provides a holistic understanding of men’s health. This article explores how MHT integrates inductive and deductive reasoning, describing, explaining, predicting, and controlling aspects of men’s health. Key components such as Gender-Sensitive Care, Health Empowerment, Supportive Environments, …

Diet-Induced Obesity Induces Transcriptomic Changes In Neuroimmunometabolic-Related Genes In The Striatum And Olfactory Bulb, Rosario B Jaime-Lara, Claudia Colina-Prisco, Marcel De Jesus Vega, Sarah Williams, Ted Usdin, Bridget Matikainen-Ankney, Alayna Kinkead, Brianna Brooks, Yupeng Wang, Alexis T Franks, Alexxai Kravitz, Paule V Joseph

2020-Current year OA Pubs

The incidence of obesity has markedly increased globally over the last several decades and is believed to be associated with the easier availability of energy-dense foods, including high-fat foods. The reinforcing hedonic properties of high-fat foods, including olfactory cues, activate reward centers in the brain, motivating eating behavior. Thus, there is a growing interest in the understanding of the genetic changes that occur in the brain that are associated with obesity and eating behavior. This growing interest has paralleled advances in genomic methods that enable transcriptomic-wide analyses. Here, we examined the transcriptomic-level differences in the olfactory bulb and striatum, regions …

Signaling Modulation Mediated By Ligand Water Interactions With The Sodium Site At Μor, Rohini S Ople, Nokomis Ramos-Gonzalez, Sarah M Bernhard, Kevin Appourchaux, Sashrik Sribhashyam, Balazs R Varga, Susruta Majumdar, Et Al.

2020-Current year OA Pubs

The mu opioid receptor (μOR) is a target for clinically used analgesics. However, adverse effects, such as respiratory depression and physical dependence, necessitate the development of alternative treatments. Recently we reported a novel strategy to design functionally selective opioids by targeting the sodium binding allosteric site in μOR with a supraspinally active analgesic named

Feedback Inhibition By A Descending Gabaergic Neuron Regulates Timing Of Escape Behavior In Drosophila Larvae, Jiayi Zhu, Jean-Christophe Boivin, Alastair Garner, Jing Ning, Yi Q Zhao, Tomoko Ohyama

Faculty, Staff and Student Publications

Escape behaviors help animals avoid harm from predators and other threats in the environment. Successful escape relies on integrating information from multiple stimulus modalities (of external or internal origin) to compute trajectories toward safe locations, choose between actions that satisfy competing motivations, and execute other strategies that ensure survival. To this end, escape behaviors must be adaptive. When a Drosophila melanogaster larva encounters a noxious stimulus, such as the focal pressure a parasitic wasp applies to the larval cuticle via its ovipositor, it initiates a characteristic escape response. The escape sequence consists of an initial abrupt bending, lateral rolling, and …

Subjective And Objective Sleep Quality Assessment In Adolescent Patients With Inflammatory Bowel Disease, Holly Breeden, Elizabeth Mcdonough, Amanda Glinky, Rebecca Wallace, Robbie Beyl, Colleen Leblanc

School of Medicine Faculty Publications

Objectives: There is a link between inflammatory bowel disease (IBD) and poor sleep quality that is presumed to be multifactorial. The purpose of this study was to identify factors that impact sleep quality in this group including clinical disease activity, depression, anxiety, quality of life, and disordered social media use through questionnaires. Methods: This prospective study analyzed sleep quality in adolescent patients ages 13 to 18 with a diagnosis of IBD using objective data from wrist actigraphy and subjective report from the Pittsburgh Sleep Quality Index (PSQI). Additional screeners including the Short Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative …

Mechanisms And Metabolic Consequences Of Adipocyte Progenitor Replicative Senescence, Tonghui Lin, Aftab Mohammad, Mikhail G Kolonin, Kristin L Eckel-Mahan

Faculty, Staff and Student Publications

In recent decades, obesity has become a worldwide epidemic. As a result, the importance of adipose tissue (AT) as a metabolically active storage depot for lipids and a key mediator of body-wide metabolism and energy balance has been increasingly recognized. Emerging from the studies of AT in metabolic disease is a recognition of the importance of the adipocyte progenitor cell (APC) population of AT being the gatekeeper of adipocyte function. APCs have the capability to self-renew and undergo adipogenesis to propagate new adipocytes capable of lipid storage, which is important for maintaining a healthy fat pad, devoid of dysfunctional lipid …

A Metabolite-Based Liquid Biopsy For Detection Of Ovarian Cancer, Johannes F Fahrmann, Seyyed Mahmood Ghasemi, Chae Y Han, Ranran Wu, Jennifer B Dennison, Jody Vykoukal, Joseph Celestino, Karen Lu, Zhen Lu, Charles Drescher, Kim-Anh Do, Samir Hanash, Robert C Bast, Ehsan Irajizad

Faculty, Staff and Student Publications

Serial CA125 and second line transvaginal ultrasound (TVS) screening in the UKCTOCS indicated a shift towards detection of earlier stage ovarian cancer (OvCa), but did not yield a significant mortality reduction. There remains a need to establish additional biomarkers that can complement CA125 for even earlier and at a larger proportion of new cases. Using a cohort of plasma samples from 219 OvCa cases (59 stage I/II and 160 stage III/IV) and 409 female controls and a novel Sensitivity Maximization At A Given Specificity (SMAGS) method, we developed a blood-based metabolite-based test consisting of 7 metabolites together with CA125 for …

Hpi 101 Introduction To Health Care Professions, Cherryle Brown

Open Educational Resources

The document is a syllabus for the "HPI 101: Introduction to Healthcare Professions" course offered in Fall 2024 by Lehman College, City University of New York. The course is designed as a hybrid, synchronous learning experience with in-person sessions. It aims to provide students with an introductory understanding of the U.S. healthcare system, diverse healthcare careers, and the foundational skills necessary for success in the healthcare industry.

Key topics include the structure of the U.S. healthcare system, the roles and responsibilities of healthcare professionals, safety protocols, interpersonal communication, and basic medical terminology. The syllabus outlines various learning objectives, such as …

Recurrent High Grade Serous Endometrial Cancer With Brain Metastases: Immunotherapy Confers Improved Quality Of Life And Survival, Kierany B. Shelvin, Jill Vincent, Shawna Morron, Michael Morin, Aaron Mammoser, Navya Nair

School of Medicine Faculty Publications

No abstract provided.

Synergistic Effects Of Novel Penicillin-Binding Protein 1a Amino Acid Substitutions Contribute To High-Level Amoxicillin Resistance Of, Alain Cimuanga-Mukanya, Evariste Tshibangu-Kabamba, Patrick De Jesus Ngoma Kisoko, Kartika Afrida Fauzia, Fabien Mbaya Tshibangu, Antoine Tshimpi Wola, Pascal Tshiamala Kashala, Dieudonné Mumba Ngoyi, Steve Ahuka-Mundeke, Gunturu Revathi, Ghislain Disashi-Tumba, Yasutoshi Kido, Takashi Matsumoto, Junko Akada, Yoshio Yamaoka

Faculty, Staff and Students Publications

The growing resistance to amoxicillin (AMX)—one of the main antibiotics used in Helicobacter pylori eradication therapy—is an increasing health concern. Several mutations of penicillin-binding protein 1A (PBP1A) are suspected of causing AMX resistance; however, only a limited set of these mutations have been experimentally explored. This study aimed to investigate four PBP1A mutations (i.e., T558S, N562H, T593A, and G595S) carried by strain KIN76, a high-level AMX-resistant clinical H. pylori isolate with an AMX minimal inhibition concentration (MIC) of 2 µg/mL. We transformed a recipient strain 26695 with the DNA containing one to four mutation allele combinations of the pbp1 gene …

Adenovirus Vaccine Targeting Kinases Induces Potent Antitumor Immunity In Solid Tumors, Fei Zhu, Zheng Lu, Wenjing Tang, Guangya Zhao, Yingxiang Shao, Bowen Lu, Jiage Ding, Yanyan Zheng, Lin Fang, Huizhong Li, Gang Wang, Renjin Chen, Junnian Zheng, Dafei Chai

Faculty, Staff and Students Publications

BACKGROUND: Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain.

METHODS: Adenovirus (Ad) vaccines encoding Aurora kinase A (AURKA) or cyclin-dependent kinase 7 (CDK7) were developed, and their therapeutic potentials were investigated by various methods including western blot, flow cytometry, cytotoxic T lymphocyte assay, and enzyme-linked immunospot (ELISpot), in mouse and humanized solid tumor models.

RESULTS: Co-immunization with Ad-AURKA/CDK7 effectively prevented subcutaneous tumor growth in the Renca, RM-1, MC38, and Hepa1-6 tumor models. In therapeutic tumor models, Ad-AURKA/CDK7 treatment impeded tumor growth and increased immune cell infiltration. Administration of …

Systematic Transcriptomic Analysis Of Childhood Medulloblastoma Identifies N6-Methyladenosine-Dependent Lncrna Signatures Associated With Molecular Subtype, Immune Cell Infiltration, And Prognosis, Kandarp Joshi, Menglang Yuan, Keisuke Katsushima, Olivier Saulnier, Animesh Ray, Ernest Amankwah, Stacie Stapleton, George Jallo, Michael D Taylor, Charles G Eberhart, Ranjan J Perera

Faculty, Staff and Students Publications

Medulloblastoma, the most common malignant pediatric brain tumor, is classified into four main molecular subgroups, but group 3 and group 4 tumors are difficult to subclassify and have a poor prognosis. Rapid point-of-care diagnostic and prognostic assays are needed to improve medulloblastoma risk stratification and management. N6-methyladenosine (m6A) is a common RNA modification and long non-coding RNAs (lncRNAs) play a central role in tumor progression, but their impact on gene expression and associated clinical outcomes in medulloblastoma are unknown. Here we analyzed 469 medulloblastoma tumor transcriptomes to identify lncRNAs co-expressed with m6A regulators. Using LASSO-Cox analysis, we identified a five-gene …

Evaluating The Effectiveness Of A Student-Run Clinic On Reducing Cigarette Smoking In A Homeless Population, Briana Taormina, Bryson Jones, Kiah Gledhill Md, Audrey Darville Phd, Aprn, Cpaha-Tt

ePublications of Emerging Medical Research Scholars

Objective

Cigarette smoking remains a major health crisis in the United States, claiming the lives of hundreds of thousands of tobacco users each year. Access to evidence-based smoking cessation remains a challenge for many people that use tobacco products. Prior research demonstrates that the homeless population is exceedingly vulnerable to cigarette smoking and faces more barriers to quitting than their domiciled counterparts. This study explores the effectiveness of a free Smoking Cessation Clinic (SCC) within a homeless shelter for women and children, run by a nurse practitioner and a clinical nurse specialist trained as Tobacco Treatment Specialists, along with two …

Student Perception And Knowledge Of Team Science Following An Interprofessional Learning Module, Lisa Sheikovitz, Genevieve Zipp, Carolyn Goeckel, Marcia Downer

Journal of Innovation in Health Sciences Education

Introduction: Online interprofessional active learning experiences can provide health care students the opportunity to develop their skills in teamwork, communication, collaboration, and ethics with low financial burden and space cost to the institution. The purpose of this qualitative report was twofold. First, to assess the impact of an interprofessional education module on students’ knowledge and understanding of team science. Second, to provide insight regarding students’ perceptions of the module’s effectiveness in supporting their development as evidence-based professionals who collaboratively provide person-centered care. Data were collected anonymously via online surveys (pre- and post-module) and served as part of a program review …

Advancing Endovascular Neurosurgery Training With Extended Reality: Opportunities And Obstacles For The Next Decade, Shray Patel, Michael Covell, Saarang Patel, Sandeep Kandregula, Sai Krishna Palepu, Avi Gajjar, Oleg Shekhtman, Georgios Sioutas, Ali Dhanaliwala, Terence Gade, Jan-Karl Burkhardt, Visish Srinivasan

SKMC Student Presentations and Publications

Background: Extended reality (XR) includes augmented reality (AR), virtual reality (VR), and mixed reality (MR). Endovascular neurosurgery is uniquely positioned to benefit from XR due to the complexity of cerebrovascular imaging. Given the different XR modalities available, as well as unclear clinical utility and technical capabilities, we clarify opportunities and obstacles for XR in training vascular neurosurgeons. Methods: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. Studies were critically appraised using ROBINS-I. Results: 19 studies were identified. 13 studies used VR, while 3 studies used MR, and 3 studies used AR. …

“Dead Or Alive?” Regression Imputation Of The Binary End-Of-Event Outcome Indicator For The Nemsis Public Research Dataset, Mary E. Helander

Social Science - All Scholarship

Objectives: Recent studies address missing survival outcomes in the National Emergency Medical Services Information System (NEMSIS), a system that stores and shares standardized EMS data from U.S. States and Territories. This study aspired to improve imputed EMS outcome accuracy and establish benchmarks for common medical emergencies treated in prehospital care. Methods: This retrospective cohort study of ground-transported EMS patients with definitive end-of-EMS-event outcomes, based on dataset years 2017 to 2023, predicted the probability of “dead” or “alive” status using logistic regression. K-fold cross-validation assessed over-fitting and internal generalization. Threshold optimization and machine learning classification metrics enabled comparison with a …

Donor Types And Outcomes Of Transplantation In Myelofibrosis: A Cibmtr Study, Tania Jain, Noel Estrada-Merly, M Queralt Salas, Soyoung Kim, Jakob Devos, Min Chen, Xi Fang, Rajat Kumar, Marcio Andrade-Campos, Hany Elmariah, Vaibhav Agrawal, Mahmoud Aljurf, Ulrike Bacher, Talha Badar, Sherif M Badawy, Karen Ballen, Amer Beitinjaneh, Vijaya Raj Bhatt, Christopher Bredeson, Zachariah Defilipp, Bhagirathbhai Dholaria, Nosha Farhadfar, Shatha Farhan, Arpita P Gandhi, Siddhartha Ganguly, Usama Gergis, Michael R Grunwald, Nada Hamad, Betty K Hamilton, Yoshihiro Inamoto, Madiha Iqbal, Omer Jamy, Mark Juckett, Mohamed A Kharfan-Dabaja, Maxwell M Krem, Deepesh P Lad, Jane Liesveld, Monzr M Al Malki, Adriana K Malone, Hemant S Murthy, Guillermo Ortí, Sagar S Patel, Attaphol Pawarode, Miguel-Angel Perales, Marjolein Van Der Poel, Olle Ringden, David A Rizzieri, Alicia Rovó, Bipin N Savani, Mary Lynn Savoie, Sachiko Seo, Melhem Solh, Celalettin Ustun, Leo F Verdonck, John R Wingard, Baldeep Wirk, Nelli Bejanyan, Richard J Jones, Taiga Nishihori, Betul Oran, Ryotaro Nakamura, Bart Scott, Wael Saber, Vikas Gupta

Department of Medical Oncology Faculty Papers

We evaluate the impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using the Center for International Blood and Marrow Transplant Research registry data for HCTs done between 2013 and 2019. In all 1597 patients, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study-eligible 1032 patients who received peripheral blood grafts for chronic-phase myelofibrosis, 38% of recipients of haploidentical HCT were non-White/Caucasian. Matched sibling donor (MSD)-HCTs were associated with superior overall survival (OS) in the first 3 months (haploidentical hazard ratio [HR], 5.80 [95% confidence interval (CI), 2.52-13.35]; matched …

Srebp2 Restricts Osteoclast Differentiation And Activity By Regulating Irf7 And Limits Inflammatory Bone Erosion, Haemin Kim, In Ah Choi, Akio Umemoto, Seyeon Bae, Kaichi Kaneko, Masataka Mizuno, Eugenia Giannopoulou, Tania Pannellini, Liang Deng, Kyung-Hyun Park-Min

Publications and Research

Osteoclasts are multinucleated bone-resorbing cells, and their formation is tightly regulated to prevent excessive bone loss. However, the mechanisms by which osteoclast formation is restricted remain incompletely determined. Here, we found that sterol regulatory element binding protein 2 (SREBP2) functions as a negative regulator of osteoclast formation and inflammatory bone loss. Cholesterols and SREBP2, a key transcription factor for cholesterol biosynthesis, increased in the late phase of osteoclastogenesis. The ablation of SREBP2 in myeloid cells resulted in increased in vivo and in vitro osteoclastogenesis, leading to low bone mass. Moreover, deletion of SREBP2 accelerated inflammatory bone destruction in murine inflammatory …

A Rad18-Ubc13-Palb2-Rnf168 Axis Mediates Replication Fork Recovery In Brca1-Deficient Cancer Cells, Emily Cybulla, Sierra Wallace, Alice Meroni, Jessica Jackson, Sumedha Agashe, Mithila Tennakoon, Mangsi Limbu, Annabel Quinet, Elena Lomonosova, Hollie Noia, Stephanie Tirman, Matthew Wood, Alessandro Vindigni, Et Al.

2020-Current year OA Pubs

BRCA1/2 proteins function in genome stability by promoting repair of double-stranded DNA breaks through homologous recombination and by protecting stalled replication forks from nucleolytic degradation. In BRCA1/2-deficient cancer cells, extensively degraded replication forks can be rescued through distinct fork recovery mechanisms that also promote cell survival. Here, we identified a novel pathway mediated by the E3 ubiquitin ligase RAD18, the E2-conjugating enzyme UBC13, the recombination factor PALB2, the E3 ubiquitin ligase RNF168 and PCNA ubiquitination that promotes fork recovery in BRCA1- but not BRCA2-deficient cells. We show that this pathway does not promote fork recovery by preventing replication fork reversal …

Kmt2c Restricts G-Csf-Driven Hsc Mobilization And Granulocyte Production In A Methyltransferase-Independent Manner, Helen C Wang, Ran Chen, Wei Yang, Yanan Li, Rohini Muthukumar, Riddhi M Patel, Emily B Casey, Elisabeth Denby, Jeffrey A Magee

2020-Current year OA Pubs

Granulocyte colony-stimulating factor (G-CSF) is widely used to enhance myeloid recovery after chemotherapy and to mobilize hematopoietic stem cells (HSCs) for transplantation. Unfortunately, through the course of chemotherapy, cancer patients can acquire leukemogenic mutations that cause therapy-related myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). This raises the question of whether therapeutic G-CSF might potentiate therapy-related MDS/AML by disproportionately stimulating mutant HSCs and other myeloid progenitors. A common mutation in therapy-related MDS/AML involves chromosome 7 deletions that inactivate many tumor suppressor genes, including KMT2C. Here, we show that Kmt2c deletions hypersensitize murine HSCs and myeloid progenitors to G-CSF, as evidenced …

Nonreciprocity In Chikv And Mayv Vaccine-Elicited Protection, Whitney C Weber, Takeshi F Andoh, Craig N Kreklywich, Zachary J Streblow, Michael Denton, Magdalene M Streblow, John M Powers, Gauthami Sulgey, Samuel Medica, Igor Dmitriev, David T Curiel, Nicole N Haese, Daniel N Streblow

2020-Current year OA Pubs

Chikungunya virus (CHIKV) is a pathogenic arthritogenic alphavirus responsible for large-scale human epidemics for which a vaccine was recently approved for use. Mayaro virus (MAYV) is a related emerging alphavirus with epidemic potential with circulation overlap potential with CHIKV. We previously reported the ability of a non-replicating human adenovirus (AdV)-vectored vaccine expressing the MAYV structural polyprotein to protect against disease in mice following challenge with MAYV, CHIKV and UNAV. Herein, we evaluated mouse immunity and protective efficacy for an AdV-CHIKV full structural polyprotein vaccine in combination with heterologous AdV-MAYV prime/boost regimens versus vaccine coadministration. Heterologous prime/boost regimens skewed immunity toward …

Evaluating The Impact Of Laboratory-Based Eligibility Criteria By Race/Ethnicity In First-Line Clinical Trials Of Dlbcl, Arushi Khurana, Brad S Kahl, Et Al.

2020-Current year OA Pubs

Underrepresentation of racial and ethnic subgroups in cancer clinical trials remains a persistent challenge. Restrictive clinical trial eligibility criteria have been shown to exacerbate this problem. We previously identified that up to 24% of patients treated with standard immunochemotherapy would have been excluded from recent first-line trials in diffuse large B-cell lymphoma (DLBCL) based on 5 laboratory-based criteria. These ineligible patients had worse clinical outcomes and increased deaths related to lymphoma progression, suggesting the potential exclusion of patients who could have benefited most from the novel therapies being evaluated. Using data from the prospectively enrolled Lymphoma Epidemiology Outcomes cohort study, …