Editorial: Controversies In The Local Management Of Lung Cancer, 2018 University of Massachusetts Medical School
Editorial: Controversies In The Local Management Of Lung Cancer, John M. Varlotto, Giulia Veronesi
Open Access Articles
At the time we agreed to edit this special edition of Frontiers in early 2017, the immunotherapy revolution was already established in the second-line treatment of metastatic non-small cell lung cancer (NSCLC) and even to a select group of patients (those whose tumor cells expressed PD-L1 of ≥50%) in the first-line treatment of metastatic disease. We felt that the summarization and understanding of the strengths and benefits of our local modalities were needed prior to the possible integration of immunotherapy into the treatment paradigms of Stages I–III NSCLC and small cell lung cancer (SCLC).
A Rationally Engineered Capsid Variant Of Aav9 For Systemic Cns-Directed And Peripheral Tissue-Detargeted Gene Delivery In Neonates, 2018 University of Massachusetts Medical School
A Rationally Engineered Capsid Variant Of Aav9 For Systemic Cns-Directed And Peripheral Tissue-Detargeted Gene Delivery In Neonates, Dan Wang, Shaoyong Li, Dominic J. Gessler, Jun Xie, Li Zhong, Jia Li, Karen Tran, Kim Van Vliet, Lingzhi Ren, Qin Su, Ran He, Jason E. Goetzmann, Terence R. Flotte, Mavis Agbandje-Mckenna, Guangping Gao
Open Access Articles
Adeno-associated virus (AAV) has provided the gene therapy field with the most powerful in vivo gene delivery vector to realize safe, efficacious, and sustainable therapeutic gene expression. Because many clinically relevant properties of AAV-based vectors are governed by the capsid, much research effort has been devoted to the development of AAV capsids for desired features. Here, we combine AAV capsid discovery from nature and rational engineering to report an AAV9 capsid variant, designated as AAV9.HR, which retains AAV9's capability to traverse the blood-brain barrier and transduce neurons. This variant shows reduced transduction in peripheral tissues when delivered through ...
Adeno-Associated Virus Genome Population Sequencing Achieves Full Vector Genome Resolution And Reveals Human-Vector Chimeras, 2018 University of Massachusetts Medical School
Adeno-Associated Virus Genome Population Sequencing Achieves Full Vector Genome Resolution And Reveals Human-Vector Chimeras, Phillip W. L. Tai, Jun Xie, Kaiyuen Fong, Matthew Seetin, Cheryl Heiner, Qin Su, Michael Weiand, Daniella Wilmot, Maria L. Zapp, Guangping Gao
Open Access Articles
Recombinant adeno-associated virus (rAAV)-based gene therapy has entered a phase of clinical translation and commercialization. Despite this progress, vector integrity following production is often overlooked. Compromised vectors may negatively impact therapeutic efficacy and safety. Using single molecule, real-time (SMRT) sequencing, we can comprehensively profile packaged genomes as a single intact molecule and directly assess vector integrity without extensive preparation. We have exploited this methodology to profile all heterogeneic populations of self-complementary AAV genomes via bioinformatics pipelines and have coined this approach AAV-genome population sequencing (AAV-GPseq). The approach can reveal the relative distribution of truncated genomes versus full-length genomes in ...
Pd-L1 Is Expressed On Human Platelets And Is Affected By Immune Checkpoint Therapy, 2018 University of Bonn
Pd-L1 Is Expressed On Human Platelets And Is Affected By Immune Checkpoint Therapy, Verena Rolfes, Christian Idel, Ralph Pries, Kirstin Plotze-Martin, Jens Habermann, Timo Gemoll, Sabine Bohnet, Eicke Latz, Julika Ribbat-Idel, Bernardo S. Franklin, Barbara Wollenberg
Open Access Articles
Cancer immunotherapy has been revolutionised by drugs that enhance the ability of the immune system to detect and fight tumors. Immune checkpoint therapies that target the programmed death-1 receptor (PD-1), or its ligand (PD-L1) have shown unprecedented rates of durable clinical responses in patients with various cancer types. However, there is still a large fraction of patients that do not respond to checkpoint inhibitors, and the challenge remains to find cellular and molecular cues that could predict which patients would benefit from these therapies. Using a series of qualitative and quantitative methods we show here that PBMCs and platelets from ...
A Fresh Look At Huntingtin Mrna Processing In Huntington's Disease, 2018 University of Massachusetts Medical School
A Fresh Look At Huntingtin Mrna Processing In Huntington's Disease, Lindsay S. Romo, Emily S. Mohn, Neil Aronin
RNA Therapeutics Institute Publications
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a mutation that expands the polyglutamine (CAG) repeat in exon 1 of the huntingtin (HTT) gene. Wild-type HTT protein interacts with other proteins to protect cells against toxic stimuli, mediate vesicle transport and endocytosis, and modulate synaptic activity. Mutant HTT protein disrupts autophagy, vesicle transport, neurotransmitter signaling, and mitochondrial function. Although many of the activities of wild-type HTT protein and the toxicities of mutant HTT protein are characterized, less is known about the activities of HTT mRNA. Most putative HD therapies aim to target mutant HTT mRNA before it ...
Cognitive And Emotional Correlates Of Improved Gait Distance During The Course Of Physical Therapy Treatment For An Incomplete Spinal Cord Injury, Danielle Miller
The focus of spinal cord injury rehabilitation over the past four decades has shifted from medical management to issuses that affect quality of life and community participation (Gómara- Toldrà, Sliwinski, & Dijkers, 2014). However, the care team for spinal cord injury patients still need to collaberate in order to design and implement interventions that result in maximum participation to provide an individual with a spinal cord injury an effective rehabilitation program. In order to create such a rehablitation program, the care team must know how certain psychological and cognitive aspects, such as depression and implict memory, are related to the ...
Integration Of Complementary And Alternative Medicine Into The Healthcare System In The United States, 2018 University of Washington – Tacoma
Integration Of Complementary And Alternative Medicine Into The Healthcare System In The United States, Nikki Lu
Global Honors Theses
Chronic diseases are a prevalent issue around the world and chronic diseases are hard to prevent due to various systemic factors in the healthcare system. This paper mainly focused on socioeconomic issues and highlighted a few systemic factors in the US healthcare system. These factors have created various health disparities, inequities among socially constructed groups, and financial expenditures in the US healthcare system. Socioeconomic factors significantly impact the health and healthcare among socially constructed groups. Additionally, in this paper there are current approaches in addressing these healthcare factors such as social determinants of health and precision medicine as well as ...
In Vivo And In Vitro Studies Of Cry5b And Nicotinic Acetylcholine Receptor Agonist Anthelmintics Reveal A Powerful And Unique Combination Therapy Against Intestinal Nematode Parasites, 2018 University of Massachusetts Medical School
In Vivo And In Vitro Studies Of Cry5b And Nicotinic Acetylcholine Receptor Agonist Anthelmintics Reveal A Powerful And Unique Combination Therapy Against Intestinal Nematode Parasites, Yan Hu, Melanie Miller, Bo Zhang, Thanh-Thanh Nguyen, Martin K. Nielsen, Raffi V. Aroian
Open Access Articles
BACKGROUND: The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define ...
El Impacto De Las Artes Visuales En Personas Afectadas Por Cáncer, 2018 EXPLORARTE
El Impacto De Las Artes Visuales En Personas Afectadas Por Cáncer, Bettina Ingham
ICOT 18 - International Conference on Thinking - Cultivating Mindsets for Global Citizens
El impacto de las artes visuales en el bienestar y la mejora de la calidad de vida de personas afectadas por cáncer.
Un programa diseñado para poner en práctica e investigar el alcance que tienen las artes visuales y el método de Estrategias de Pensamiento Visual para el desarrollo de habilidades de pensamiento que promueven la identificación y expresión verbal de las emociones, minimizando, en el caso de las personas convalecientes, el sufrimiento que va desde el dolor de la enfermedad hasta el miedo a la muerte.
Los efectos que la contemplación (percepción estética), el análisis y la práctica(proceso ...
Structure Determination Of A Bioengineered Human/Porcine Factor Viii For Hemophilia A Treatment, And Improvements To The Human Factor Viii Model, 2018 Western Washington University
Structure Determination Of A Bioengineered Human/Porcine Factor Viii For Hemophilia A Treatment, And Improvements To The Human Factor Viii Model, Ian Smith
Graduate Student Symposium
Blood coagulation factor VIII (FVIII), is a non-enzymatic cofactor which plays a crucial role in the formation of a stable blood clot. Absence or deficiency of FVIII results in the blood disorder hemophilia A; with symptoms including internal hemorrhaging and the inability to stop bleeding from open wounds. Treatment of hemophilia A relies on infusions of blood, plasma, or protein concentrates to replace FVIII. Unfortunately, approximately 30% of patients receiving replacement FVIII generate pathologic anti-FVIII inhibitory antibodies, which both reduce the effectiveness of the FVIII therapeutic and increase the severity of hemophilia A symptoms. We have determined the molecular structure ...
Spectral Properties Of Doxorubicin Doped Rhdl Nanoparticles, 2018 University of North Texas Health Science Center at Fort Worth
Spectral Properties Of Doxorubicin Doped Rhdl Nanoparticles, Sunil Shah
Theses and Dissertations
Doxorubicin, also known as Adriamycin, is an anthracycline antibiotic which first gained clinical prominence in the early 1970’s as an effective antitumor agent. It is still used today to treat a spectrum of cancers like lymphoma, bladder, stomach, lung, breast, ovarian, and several others. Due to its production of free radicals to attack tumor cells, Doxorubicin interferes with mitochondrial phosphorylation and also induces cardiotoxicity. Thus, efficient and biocompatible delivery methods are needed for targeted drug delivery to overcome systemic toxicity. To maintain a high level of growth, tumor cells overexpress Scavenger receptors type B-1 (SR-B1). This cellular characteristic can ...
Failure Of Primary Total Knee Arthroplasty: Establishing A Baseline For Retrieval Analysis Using Well-Functioning Necropsy Specimens, 2018 University of Tennessee Health Science Center
Failure Of Primary Total Knee Arthroplasty: Establishing A Baseline For Retrieval Analysis Using Well-Functioning Necropsy Specimens, Meredith Perkins
Theses and Dissertations (ETD)
Introduction. Total knee arthroplasty (TKA) is an effective treatment for end-stage osteoarthritis of the knee. While many patients have positive functional and pain outcomes following primary TKA, a subset of patients have suboptimal outcomes, such as unexplained pain or aseptic loosening of the implant components necessitating revision of the index procedure. The understanding of the exact etiology of these suboptimal outcomes of primary TKA is in its infancy. In order to elucidate the etiology of failure in primary TKAs, a baseline for the factors contributing to arthroplasty failure and dissatisfaction must first be established. The purpose of this study was ...
The Dancing Nurse: Addressing Barriers To The Implementation Of Movement-Based Interventions In Holistic Patient Care, 2018 Oral Roberts University
The Dancing Nurse: Addressing Barriers To The Implementation Of Movement-Based Interventions In Holistic Patient Care, Jessica Collier, Audrey Thompson Phd
Nursing Undergraduate Work
The efficacy of dance movement therapy (DMT) is well demonstrated in contemporary nursing literature; however, implementation by healthcare professionals is often limited. Dance movement therapy was pioneered in the mid-20th century by classically trained modern dancer Marian Chace. Recent trends toward patient-centered care and interdisciplinary approaches render therapies such as DMT important modalities which nurses and other healthcare providers may become familiar with. This systematic research review focused on answering the question: “what are hindrances perceived by members of the healthcare team to implementing DMT as an alternative treatment modality?” Two variables were identified for the purposes of this ...
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 ...
Maturation Of Human Induced Pluripotent Stem Cell Derived Engineered Cardiac Tissues Using Chief Transfection And Chronic Optical Pacing., Marc M. Dwenger
Electronic Theses and Dissertations
The immaturity of engineered cardiac tissues (ECTs) limits their ability to regenerate damaged myocardium and to serve as in vitro disease models and surrogates for drug toxicity testing. Several chronic biomimetic conditioning protocols, including mechanical stretch, perfusion, and electrical stimulation promote ECT maturation but have significant technical limitations. Non-contacting chronic light stimulation using heterologously expressed light-sensitive ChIEF ion channels, termed optogenetics, may be an advantageous alternative to chronic electrical stimulation. As a proof of principle, we transfected ECTs using an AAV packaged ChIEF and then verified acute optical pacing (OP) by patch clamp. We then chronically OP ECTs for 7 ...
Identification Of Epigenetic Regulators Of Dux4-Fl For Targeted Therapy Of Facioscapulohumeral Muscular Dystrophy, 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 ...
Physical Therapy Practices Of The Us And South America, 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 ...
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 ...
Non-Hispanic Black-White Disparities In Pain And Pain Management Among Newly Admitted Nursing Home Residents With Cancer, 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 ...
Towards An Arthritis Flare-Responsive Drug Delivery System, 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 ...