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The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha 2018 University of Connecticut

The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha

Honors Scholar Theses

Immunotherapy as a form of cancer treatment has become increasingly popular in the past few decades. Researchers have worked to figure out how to best use the body’s natural defense mechanism, the immune system, to fight off and destroy cancer cells. In particular, the goal has been to manipulate checkpoint blockades such as CTLA-4 and PD-1 in order to take the breaks off of the immune system, allowing for a prolonged immune response to the cancer. This work has led to the development of human versions of anti-CTLA4 antibodies (ipilimumab, tremelimumab) and anti-PD1 antibodies (pembrolizumab and Nivolumab) that are ...


Systemic Blood Pressure Trends And Antihypertensive Utilization Following Continuous-Flow Left Ventricular Assist Device Implantation: An Analysis Of The Interagency Registry For Mechanically Assisted Circulatory Support, Adham Elmously, Andreas R. de Biasi, Donald A. Risucci, Berhane Worku, Evelyn M. Horn, Arash Salemi 2018 New York Medical College

Systemic Blood Pressure Trends And Antihypertensive Utilization Following Continuous-Flow Left Ventricular Assist Device Implantation: An Analysis Of The Interagency Registry For Mechanically Assisted Circulatory Support, Adham Elmously, Andreas R. De Biasi, Donald A. Risucci, Berhane Worku, Evelyn M. Horn, Arash Salemi

NYMC Faculty Publications

Background: Elevated systemic blood pressure (SBP) has been linked to complications in Continuous-flow left ventricular assist devices (CF-LVADs), including stroke and pump thrombosis. We queried Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) to describe the response of SBP to CF-LVAD implantation and to delineate contemporary trends in antihypertensive (AH) utilization for patients with these pumps. Methods: We identified all CF-LVAD implantations in patients older than 18 years from 2006-2014, excluding those whose durations were less than 30 days. Pre-implant patient demographics and characteristics were obtained for each record. SBPs [i.e., mean arterial pressures (MAPs)], AH-use data, and vital ...


Assessing Speech-Language Pathologists’ Knowledge And Use Of Language Acquisition Through Motor Planning, Mary Catherine Cazalas 2018 The University of Southern Mississippi

Assessing Speech-Language Pathologists’ Knowledge And Use Of Language Acquisition Through Motor Planning, Mary Catherine Cazalas

Honors Theses

Many individuals who are nonverbal require augmentative and alternative communication devices to communicate. The purpose of this research was to assess speech-language pathologists’ knowledge of a particular method of implementing augmentative and alternative communication devices known as language acquisition through motor planning (LAMP). Further, this research was designed to determine the percentage of speech pathologists who have used LAMP during their careers as well as the perceived level of success speech pathologists have found with LAMP. Mississippi speech-language pathologists were used as the sample for this study. A survey was created electronically via the online survey development software, “Survey Monkey ...


Identification Of Epigenetic Regulators Of Dux4-Fl For Targeted Therapy Of Facioscapulohumeral Muscular Dystrophy, Charis L. Himeda, Takako I. Jones, Ching-Man A. Virbasius, Lihua Julie Zhu, Michael R. Green, Peter L. Jones 2018 University of Massachusetts Medical School

Identification Of Epigenetic Regulators Of Dux4-Fl For Targeted Therapy Of Facioscapulohumeral Muscular Dystrophy, Charis L. Himeda, Takako I. Jones, Ching-Man A. Virbasius, Lihua Julie Zhu, Michael R. Green, Peter L. Jones

Open Access Articles

Facioscapulohumeral muscular dystrophy (FSHD) is caused by epigenetic de-repression of the disease locus, leading to pathogenic misexpression of the DUX4 gene in skeletal muscle. While the factors and pathways involved in normal repression of the FSHD locus in healthy cells have been well characterized, very little is known about those responsible for the aberrant activation of DUX4-fl in FSHD myocytes. Reasoning that DUX4-fl activators might represent useful targets for small molecule inhibition, we performed a highly targeted, candidate-based screen of epigenetic regulators in primary FSHD myocytes. We confirmed several of the strongest and most specific candidates (ASH1L, BRD2, KDM4C, and ...


Impact Of Lumacaftor/Ivacaftor On Pulmonary Exacerbation Rates In Members With Cystic Fibrosis In A Medicaid Population, Mark A. Tesell, Karen Stevens, Bonnie C. Greenwood, Caroline J. Alper, Kimberly J. Lenz, Paul L. Jeffrey 2018 University of Massachusetts Medical School

Impact Of Lumacaftor/Ivacaftor On Pulmonary Exacerbation Rates In Members With Cystic Fibrosis In A Medicaid Population, Mark A. Tesell, Karen Stevens, Bonnie C. Greenwood, Caroline J. Alper, Kimberly J. Lenz, Paul L. Jeffrey

Commonwealth Medicine Publications

This poster gives an overview of pulmonary exacerbation rates pre- and post-initiation of Lumacaftor/Ivacaftor (LUM/IVA) in Massachusetts' Medicaid program. Pulmonary disease is one of the leading causes of morbidity and mortality among patients with cystic fibrosis. LUM/IVA has been effective in improving pulmonary outcomes in two observational studies, but before this study, there had been no published data evaluating real-world outcomes for Medicaid patients receiving this therapy.

This poster on the impact of a drug for patients with cystic fibrosis was shared during the 2018 Academy of Managed Care Pharmacy Managed Care & Specialty Pharmacy Annual Meeting and ...


Acute-On-Chronic Liver Failure: Getting Ready For Prime-Time, Jasmohan S. Bajaj, Richard Moreau, Patrick S. Kamath, Hugo E. Vargas, Vicente Arroyo, K. Rajender Reddy, Gyongyi Szabo, Puneeta Tandon, Jody Olson, Constantine Karvellas, Thierry Gustot, Jennifer C. Lai, Florence Wong 2018 Virginia Commonwealth University

Acute-On-Chronic Liver Failure: Getting Ready For Prime-Time, Jasmohan S. Bajaj, Richard Moreau, Patrick S. Kamath, Hugo E. Vargas, Vicente Arroyo, K. Rajender Reddy, Gyongyi Szabo, Puneeta Tandon, Jody Olson, Constantine Karvellas, Thierry Gustot, Jennifer C. Lai, Florence Wong

University of Massachusetts Medical School Faculty Publications

Acute on chronic liver failure (ACLF) is a culmination of chronic liver disease and extra-hepatic organ failures, which is associated with a high short-term mortality and immense healthcare expenditure. There are varying definitions for organ failures and ACLF in Europe, North America and Asia. These differing definitions need to be reconciled to enhance progress in the field. The pathogenesis of ACLF is multi-factorial and related to interactions between the immuno-inflammatory system, microbiota and the precipitating factors. Individual organ failures related to the kidney, brain, lungs and circulation have cumulative adverse effects on mortality and are often complicated or precipitated by ...


Physical Therapy Practices Of The Us And South America, Dylan Young Vazquez 2018 Carroll College

Physical Therapy Practices Of The Us And South America, Dylan Young Vazquez

Carroll College Student Undergraduate Research Festival

The research for this presentation will explore the differences in the field of physical therapy between the United States and various countries in South America to compare and evaluate the preparation and implementation of physical therapy care, to formulate recommendations for possible improvements and pursue further research. The United States and selected South American countries have starkly different economic, social, and political backgrounds which impact the way in which physical therapy is administered and received. This allows for comparisons to be made between each respective model of physical therapy, creating a running dialog on how these programs can improve and ...


Photochemical Control Of Protein Arginine Deiminase (Pad) Activity, Santanu Mondal, Sangram S. Parelkar, Mitesh Nagar, Paul R. Thompson 2018 University of Massachusetts Medical School

Photochemical Control Of Protein Arginine Deiminase (Pad) Activity, Santanu Mondal, Sangram S. Parelkar, Mitesh Nagar, Paul R. Thompson

Thompson Lab Publications

Protein Arginine deiminases (PADs) play an important role in the pathogenesis of various diseases, including rheumatoid arthritis, multiple sclerosis, lupus, ulcerative colitis and breast cancer. Therefore, the development of PAD-inhibitors has drawn significant research interest in recent years. Herein, we describe the development of the first photoswitchable PAD-inhibitors. These compounds possess an azobenzene photoswitch to optically control PAD activity. Screening of a series of inhibitors structurally similar to BB-Cl-Amidine afforded compounds 1 and 2 as the most promising candidates for the light-controlled inhibition of PAD2; the cis-isomer of 1 is 10-fold more potent than its trans-isomer, whereas the trans-isomer of ...


Non-Hispanic Black-White Disparities In Pain And Pain Management Among Newly Admitted Nursing Home Residents With Cancer, Deborah Mack, Jacob N. Hunnicutt, William M. Jesdale, Kate L. Lapane 2018 University of Massachusetts Medical School

Non-Hispanic Black-White Disparities In Pain And Pain Management Among Newly Admitted Nursing Home Residents With Cancer, Deborah Mack, Jacob N. Hunnicutt, William M. Jesdale, Kate L. Lapane

UMass Center for Clinical and Translational Science Supported Publications

Background: Racial disparities in pain management persist across health care settings and likely extend into nursing homes. No recent studies have evaluated racial disparities in pain management among residents with cancer in nursing homes at time of admission.

Methods: Using a cross-sectional study design, we compared reported pain and pain management between non-Hispanic White and non-Hispanic Black newly admitted nursing home residents with cancer (n=342,920) using the de-identified Minimum Data Set version 3.0. Pain management strategies included the use of scheduled analgesics, pro re nata analgesics, and non-pharmacological methods. Presence of pain was based on self-report when ...


Bb-Cl-Amidine As A Novel Therapeutic For Canine And Feline Mammary Cancer Via Activation Of The Endoplasmic Reticulum Stress Pathway, Melissa M. Ledet, Robyn Anderson, Rebecca Harman, Aaron Muth, Paul R. Thompson, Scott A. Coonrod, Gerlinde R. Van de Walle 2018 Cornell University

Bb-Cl-Amidine As A Novel Therapeutic For Canine And Feline Mammary Cancer Via Activation Of The Endoplasmic Reticulum Stress Pathway, Melissa M. Ledet, Robyn Anderson, Rebecca Harman, Aaron Muth, Paul R. Thompson, Scott A. Coonrod, Gerlinde R. Van De Walle

Open Access Articles

BACKGROUND: Mammary cancer is highly prevalent in dogs and cats and results in a poor prognosis due to critically lacking viable treatment options. Recent human and mouse studies have suggested that inhibiting peptidyl arginine deiminase enzymes (PAD) may be a novel breast cancer therapy. Based on the similarities between human breast cancer and mammary cancer in dogs and cats, we hypothesized that PAD inhibitors would also be an effective treatment for mammary cancer in these animals.

METHODS: Canine and feline mammary cancer cell lines were treated with BB-Cl-Amidine (BB-CLA) and evaluated for viability and tumorigenicity. Endoplasmic reticulum stress was tested ...


Paclitaxel Enhances Oncolytic Potential Of Herpes Simplex Virus Type-1 In Cancer Cells, misagh naderi 2018 Louisiana State University and Agricultural and Mechanical College

Paclitaxel Enhances Oncolytic Potential Of Herpes Simplex Virus Type-1 In Cancer Cells, Misagh Naderi

LSU Master's Theses

Taxanes are spindle poisons that bind to and stabilize microtubules resulting in mitotic arrest. Herpes simplex Typ-1 (HSV-1) virions utilize the microtubular network for intracellular transport during both virus entry and virus egress from infected cells. It has been reported previously that taxanes may synergize with oncolytic herpes simplex viruses in the treatment of experimental prostate and breast tumors in mice. Other reports have indicated that taxanes may inhibit viral replication in infected cells. In this study the previously characterized Oncolytic Herpes Simplex Virus type 1 (OSVP), which was constructed in Kousoulas lab was used in conjugation with paclitaxel (taxol ...


Towards An Arthritis Flare-Responsive Drug Delivery System, Nitin Joshi, Ellen M. Gravallese, Joerg Ermann, Jeffrey M. Karp 2018 Massachusetts Institute of Technology

Towards An Arthritis Flare-Responsive Drug Delivery System, Nitin Joshi, Ellen M. Gravallese, Joerg Ermann, Jeffrey M. Karp

Open Access Articles

Local delivery of therapeutics for the treatment of inflammatory arthritis (IA) is limited by short intra-articular half-lives. Since IA severity often fluctuates over time, a local drug delivery method that titrates drug release to arthritis activity would represent an attractive paradigm in IA therapy. Here we report the development of a hydrogel platform that exhibits disassembly and drug release controlled by the concentration of enzymes expressed during arthritis flares. In vitro, hydrogel loaded with triamcinolone acetonide (TA) releases drug on-demand upon exposure to enzymes or synovial fluid from patients with rheumatoid arthritis. In arthritic mice, hydrogel loaded with a fluorescent ...


Comparación Evaluativa De La Preparación E Implementación De Fisioterapia Entre Los Estados Unidos Y Los Países Seleccionados De América Del Sur, Dylan Young Vazquez 2018 Carroll College

Comparación Evaluativa De La Preparación E Implementación De Fisioterapia Entre Los Estados Unidos Y Los Países Seleccionados De América Del Sur, Dylan Young Vazquez

Languages and Literature Undergraduate Student Works

The research for this comparative analysis explores the differences in the field of physical therapy between the United States and various countries in South America to compare and evaluate the forms of preparation and implementation of care, to formulate recommendations within areas for further research to be pursued. The United States and South American countries have starkly different economic, social, and political backgrounds which impact the way in which physical therapy is administered and received. This allows for comparisons to be made between each respective model of physical therapy, creating a running dialog on how these programs can improve and ...


Discovery And Effects Of Pharmacological Inhibition Of The E3 Ligase Skp2 By Small Molecule Protein-Protein Interaction Disruptors, John K. Morrow 2018 The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Discovery And Effects Of Pharmacological Inhibition Of The E3 Ligase Skp2 By Small Molecule Protein-Protein Interaction Disruptors, John K. Morrow

UT GSBS Dissertations and Theses (Open Access)

Skp2 (S-phase kinase-associated protein 2), one component of the SCF E3 ubiquitin ligase complex, directly interacts with Skp1 and indirectly associates with Cullin1 and Rbx1 to bridge the E2 conjugating enzyme with its protein substrate to execute its E3 ligase activity. Skp2 is an Fbox protein (due to it containing an Fbox domain) and it is the rate-limiting component of the SCF complex. Skp2 targets several cell-cycle regulatory proteins for ubiquitination and degradation; most notable and significant for cancer are the cyclin-dependent kinase inhibitor, p27. Skp2 is an oncogene and studies have shown that over-expression of Skp2 leads to increased ...


Oncology Section Edge Task Force On Cancer: Measures Of Cancer-Related Fatigue—A Systematic Review, Mary Insana Fisher, Claire Davies, Hannah Lacy, Deborah Doherty 2018 University of Dayton

Oncology Section Edge Task Force On Cancer: Measures Of Cancer-Related Fatigue—A Systematic Review, Mary Insana Fisher, Claire Davies, Hannah Lacy, Deborah Doherty

Physical Therapy Faculty Publications

Background: Cancer-related fatigue (CRF) is one of the most common side effects of cancer and cancer treatment. Being able to accurately screen for and assess CRF will improve access to and prescriptions for interventions. Valid and reliable measures to screen for and assess CRF need to be identified.

Purpose: To identify and recommend reliable, valid, and clinically useful tools to screen for and assess CRF among those treated for cancer.

Methods: A systematic review of the literature was conducted to assess the published psychometric properties and clinical feasibility of each method identified. Task force members independently reviewed each measure using ...


Transitioning To The Role Of A Professional Physical Therapist Through Community Engagement, Brittany L. Wentzel 2018 Virginia Wesleyan College

Transitioning To The Role Of A Professional Physical Therapist Through Community Engagement, Brittany L. Wentzel

VA Engage Journal

This article recounts the author's experiences observing and interning with physical therapists in a variety of settings.The hands-on experiences the author describes allowed the author to learn the specific procedures and requirements in a typical day as a Physical Therapist, and to gain knowledge on the protocol for different injuries, the muscles that each exercise strengthens, and how to properly perform exercises to prevent further injuries. The author also explores how these experiences fostered observational and interpersonal skills and solidified the decision to pursue Physical Therapy as a career.


Ajulemic Acid: Potential Treatment For Chronic Inflammation, Sumner Burstein 2018 University of Massachusetts Medical School

Ajulemic Acid: Potential Treatment For Chronic Inflammation, Sumner Burstein

Open Access Articles

Ajulemic acid (AJA, CT-3, IP-751, JBT-101, anabasum) is a first-in-class, synthetic, orally active, cannabinoid-derived drug that preferentially binds to the CB2 receptor and is nonpsychoactive. In preclinical studies, and in Phase 1 and 2 clinical trials, AJA showed a favorable safety, tolerability, and pharmacokinetic profile. It also demonstrated significant efficacy in preclinical models of inflammation and fibrosis. It suppresses tissue scarring and stimulates endogenous eicosanoids that resolve chronic inflammation and fibrosis without causing immunosuppression. AJA is currently being developed for use in 4 separate but related indications including systemic sclerosis (SSc), cystic fibrosis, dermatomyositis (DM), and systemic lupus erythematosus. Phase ...


Genetic Variants In Hsd17b3, Smad3, And Ipo11 Impact Circulating Lipids In Response To Fenofibrate In Individuals With Type 2 Diabetes, Daniel M. Rotroff, Sonja S. Pijut, Skylar W. Marvel, John R. Jack, Tammy M. Havener, Aurora Pujol, Agatha Schluter, Gregory A. Graf, Henry N. Ginsberg, Hetal S. Shah, He Gao, Mario-Luca Morieri, Alessandro Doria, Josyf C. Mychaleckyi, Howard L. McLeod, John B. Buse, Michael J. Wagner, Alison A. Motsinger-Reif, ACCORD/ACCORDion Investigators 2018 North Carolina State University

Genetic Variants In Hsd17b3, Smad3, And Ipo11 Impact Circulating Lipids In Response To Fenofibrate In Individuals With Type 2 Diabetes, Daniel M. Rotroff, Sonja S. Pijut, Skylar W. Marvel, John R. Jack, Tammy M. Havener, Aurora Pujol, Agatha Schluter, Gregory A. Graf, Henry N. Ginsberg, Hetal S. Shah, He Gao, Mario-Luca Morieri, Alessandro Doria, Josyf C. Mychaleckyi, Howard L. Mcleod, John B. Buse, Michael J. Wagner, Alison A. Motsinger-Reif, Accord/Accordion Investigators

Pharmaceutical Sciences Faculty Publications

Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin‐treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed‐up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10‐6). Rare variant and gene expression changes ...


Heavily And Fully Modified Rnas Guide Efficient Spycas9-Mediated Genome Editing, Aamir Mir, Julia F. Alterman, Matthew R. Hassler, Alexandre J. Debacker, Edward Hudgens, Dimas Echeverria, Michael H. Brodsky, Anastasia Khvorova, Jonathan K. Watts, Erik J. Sontheimer 2018 University of Massachusetts Medical School

Heavily And Fully Modified Rnas Guide Efficient Spycas9-Mediated Genome Editing, Aamir Mir, Julia F. Alterman, Matthew R. Hassler, Alexandre J. Debacker, Edward Hudgens, Dimas Echeverria, Michael H. Brodsky, Anastasia Khvorova, Jonathan K. Watts, Erik J. Sontheimer

University of Massachusetts Medical School Faculty Publications

RNA-based drugs depend on chemical modifications to increase potency and nuclease stability, and to decrease immunogenicity in vivo. Chemical modification will likely improve the guide RNAs involved in CRISPR-Cas9-based therapeutics as well. Cas9 orthologs are RNA-guided microbial effectors that cleave DNA. No studies have yet explored chemical modification at all positions of the crRNA guide and tracrRNA cofactor. Here, we have identified several heavily-modified versions of crRNA and tracrRNA that are more potent than their unmodified counterparts. In addition, we describe fully chemically modified crRNAs and tracrRNAs (containing no 2'-OH groups) that are functional in human cells. These designs ...


Down-Regulation Of Microrna-203-3p Initiates Type 2 Pathology During Schistosome Infection Via Elevation Of Interleukin-33, Xing He, Jun Xie, Yange Wang, Xiaobin Fan, Qin Su, Yue Sun, Nanhang Lei, Dongmei Zhang, Guangping Gao, Weiqing Pan 2018 Second Military Medical University

Down-Regulation Of Microrna-203-3p Initiates Type 2 Pathology During Schistosome Infection Via Elevation Of Interleukin-33, Xing He, Jun Xie, Yange Wang, Xiaobin Fan, Qin Su, Yue Sun, Nanhang Lei, Dongmei Zhang, Guangping Gao, Weiqing Pan

Open Access Articles

The type 2 immune response is the central mechanism of disease progression in schistosomiasis, but the signals that induce it after infection remain elusive. Aberrant microRNA (miRNA) expression is a hallmark of human diseases including schistosomiasis, and targeting the deregulated miRNA can mitigate disease outcomes. Here, we demonstrate that efficient and sustained elevation of miR-203-3p in liver tissues, using the highly hepatotropic recombinant adeno-associated virus serotype 8 (rAAV8), protects mice against lethal schistosome infection by alleviating hepatic fibrosis. We show that miR-203-3p targets interleukin-33 (IL-33), an inducer of type 2 immunity, in hepatic stellate cells to regulate the expansion and ...


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