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Management Of Patients With Brain Metastases From Non-Small Cell Lung Cancer And Adverse Prognostic Features: Multi-National Radiation Treatment Recommendations Are Heterogeneous, Minesh Mehta 2019 Baptist Health Medical Group; Miami Cancer Institute

Management Of Patients With Brain Metastases From Non-Small Cell Lung Cancer And Adverse Prognostic Features: Multi-National Radiation Treatment Recommendations Are Heterogeneous, Minesh Mehta

All Publications

No abstract provided.


Toll-Like Receptor-4 Disruption Suppresses Adipose Tissue Remodeling And Increases Survival In Cancer Cachexia Syndrome, Felipe Henriques, Magno A. Lopes, Felipe O. Franco, Pamela Knobl, Kaltinaitis B. Santos, Luana L. Bueno, Victor A. Correa, Alexander H. Bedard, Adilson L. Guilherme, Alexander Birbrair, Sidney B. Peres, Stephen R. Farmer, Miguel L. Batista Jr. 2018 University of Massachusetts Medical School

Toll-Like Receptor-4 Disruption Suppresses Adipose Tissue Remodeling And Increases Survival In Cancer Cachexia Syndrome, Felipe Henriques, Magno A. Lopes, Felipe O. Franco, Pamela Knobl, Kaltinaitis B. Santos, Luana L. Bueno, Victor A. Correa, Alexander H. Bedard, Adilson L. Guilherme, Alexander Birbrair, Sidney B. Peres, Stephen R. Farmer, Miguel L. Batista Jr.

Open Access Articles

Cancer-induced cachexia, characterized by systemic inflammation, body weight loss, adipose tissue (AT) remodeling and muscle wasting, is a malignant metabolic syndrome with undefined etiology. Here, we show that both genetic ablation and pharmacological inhibition of TLR4 were able to attenuate the main clinical markers of cachexia in mice bearing Lewis lung carcinoma (LLC). AT remodelling was not found in LLC tumor-bearing (TB) TLR4(-/-) mice due to reduced macrophage infiltration and adipocyte atrophy. TLR4(-/-) mice were also resistant to cold-induced browning of subcutaneous AT (scAT). Importantly, pharmacological inhibition of TLR4 (Atorvastatin) reproduced the main protective effect against AT remodeling found in ...


Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. McCauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban 2018 University of Massachusetts Medical School

Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. Mccauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban

Open Access Articles

HIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, HIV-1 establishes proviruses in long-lived CD4(+) memory T cells, and perhaps other cell types, that preclude elimination of the virus even after years of continuous antiviral therapy. Here we show that the HIV-1 provirus activates innate immune signaling in isolated dendritic cells, macrophages, and CD4(+) T cells. Immune activation requires transcription from the HIV-1 provirus and expression of CRM1-dependent, Rev-dependent, RRE-containing, unspliced HIV-1 RNA. If rev is provided in trans, all HIV-1 coding sequences are dispensable for activation except those cis-acting sequences required ...


Joint Coordination Variability In Anterior Cruciate Ligament Reconstructed Subjects During Stair Ambulation Using A Vector Coding Technique, Bryan R. Simrak 2018 University of Tennessee Health Science Center

Joint Coordination Variability In Anterior Cruciate Ligament Reconstructed Subjects During Stair Ambulation Using A Vector Coding Technique, Bryan R. Simrak

Theses and Dissertations (ETD)

Anterior cruciate ligament (ACL) rupture is a common injury, with an estimated incidence of 120,000 to 200,000 per year in the United States. ACL reconstruction surgery is the standard treatment for this injury to restore knee joint stability and function. While surgical reconstruction has been shown to restore laxity of the knee, current literature lacks consensus on return to normal knee joint kinematics following surgery. Additionally, re-injury is a major risk for those who return to sports activity after reconstruction surgery. Dynamical systems methods for quantifying joint coordination variability have been explored as a method for detecting differences ...


Real-World Comparative Effectiveness Of Tocilizumab Monotherapy Vs. Tumor Necrosis Factor Inhibitors With Methotrexate In Patients With Rheumatoid Arthritis, Leslie R. Harrold, George W. Reed, Jennie Best, Steve Zlotnick, Joel M. Kremer 2018 University of Massachusetts Medical School

Real-World Comparative Effectiveness Of Tocilizumab Monotherapy Vs. Tumor Necrosis Factor Inhibitors With Methotrexate In Patients With Rheumatoid Arthritis, Leslie R. Harrold, George W. Reed, Jennie Best, Steve Zlotnick, Joel M. Kremer

Open Access Articles

INTRODUCTION: Controlled clinical studies have shown that the efficacy of tocilizumab (TCZ) monotherapy is superior to that of tumor necrosis factor inhibitor (TNFi) monotherapy and comparable to that of TCZ plus methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). This study compared the real-world effectiveness of TCZ monotherapy vs. TNFis plus MTX in US patients with RA.

METHODS: TCZ-naive patients from the Corrona RA registry with prior exposure to > /= 1 TNFi who initiated TCZ monotherapy or TNFi + MTX were included. Outcomes included mean change in Clinical Disease Activity Index (CDAI), achievement of low disease activity (LDA; CDAI < /= 10), achievement of modified American College of Rheumatology (mACR) 20/50 responses, and mean change in modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients initiating TNFi + MTX were grouped by MTX dose ( < /= 10 mg; > 10 to ...


Ectopic High Endothelial Venules In Pancreatic Ductal Adenocarcinoma: A Unique Site For Targeted Delivery, Baharak Bahmani, Mayuko Uehara, Farideh Ordikhani, Xiaofei Li, Liwei Jiang, Naima Banouni, Takaharu Ichimura, Vivek Kasinath, Siawosh K. Eskandari, Nasim Annabi, Jonathan S. Bromberg, Leonard D. Shultz, Dale L. Greiner, Reza Abdi 2018 Harvard Medical School

Ectopic High Endothelial Venules In Pancreatic Ductal Adenocarcinoma: A Unique Site For Targeted Delivery, Baharak Bahmani, Mayuko Uehara, Farideh Ordikhani, Xiaofei Li, Liwei Jiang, Naima Banouni, Takaharu Ichimura, Vivek Kasinath, Siawosh K. Eskandari, Nasim Annabi, Jonathan S. Bromberg, Leonard D. Shultz, Dale L. Greiner, Reza Abdi

Open Access Articles

BACKGROUND: Nanomedicine offers an excellent opportunity to tackle treatment-refractory malignancies by enhancing the delivery of therapeutics to the tumor site. High endothelial venules (HEVs) are found primarily in lymph nodes or formed de novo in peripheral tissues during inflammatory responses. They express peripheral node addressin (PNAd), which is recognized by the monoclonal antibody MECA79.

METHODS: Here, we demonstrated that HEVs form de novo in human pancreatic ductal adenocarcinoma (PDAC). We engineered MECA79 coated nanoparticles (MECA79-NPs) that recognize these ectopic HEVs in PDAC.

FINDINGS: The trafficking of MECA79-NPs following intravenous delivery to human PDAC implanted in a humanized mouse model was ...


Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman 2018 University of Michigan

Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman

Physiology Faculty Publications

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly ...


Targeted Delivery Of Bioactive Molecules For Vascular Intervention And Tissue Engineering, Hannah A. Strobel, Elisabet I. Qendro, Eben Alsberg, Marsha W. Rolle 2018 Worcester Polytechnic Institute

Targeted Delivery Of Bioactive Molecules For Vascular Intervention And Tissue Engineering, Hannah A. Strobel, Elisabet I. Qendro, Eben Alsberg, Marsha W. Rolle

Open Access Articles

Cardiovascular diseases are the leading cause of death in the United States. Treatment often requires surgical interventions to re-open occluded vessels, bypass severe occlusions, or stabilize aneurysms. Despite the short-term success of such interventions, many ultimately fail due to thrombosis or restenosis (following stent placement), or incomplete healing (such as after aneurysm coil placement). Bioactive molecules capable of modulating host tissue responses and preventing these complications have been identified, but systemic delivery is often harmful or ineffective. This review discusses the use of localized bioactive molecule delivery methods to enhance the long-term success of vascular interventions, such as drug-eluting stents ...


Orthogonal Cas9-Cas9 Chimeras Provide A Versatile Platform For Genome Editing, Mehmet F. Bolukbasi, Pengpeng Liu, Kevin Luk, Samantha F. Kwok, Ankit Gupta, Nadia Amrani, Erik J. Sontheimer, Lihua Julie Zhu, Scot A. Wolfe 2018 University of Massachusetts Medical School

Orthogonal Cas9-Cas9 Chimeras Provide A Versatile Platform For Genome Editing, Mehmet F. Bolukbasi, Pengpeng Liu, Kevin Luk, Samantha F. Kwok, Ankit Gupta, Nadia Amrani, Erik J. Sontheimer, Lihua Julie Zhu, Scot A. Wolfe

Open Access Articles

The development of robust, versatile and accurate toolsets is critical to facilitate therapeutic genome editing applications. Here we establish RNA-programmable Cas9-Cas9 chimeras, in single- and dual-nuclease formats, as versatile genome engineering systems. In both of these formats, Cas9-Cas9 fusions display an expanded targeting repertoire and achieve highly specific genome editing. Dual-nuclease Cas9-Cas9 chimeras have distinct advantages over monomeric Cas9s including higher target site activity and the generation of predictable precise deletion products between their target sites. At a therapeutically relevant site within the BCL11A erythroid enhancer, Cas9-Cas9 nucleases produced precise deletions that comprised up to 97% of all sequence alterations ...


Crispr-Delivery Particles Targeting Nuclear Receptor-Interacting Protein 1 (Nrip1) In Adipose Cells To Enhance Energy Expenditure, Yuefei Shen, Jessica L. Cohen, Sarah M. Nicoloro, Mark Kelly, Batuhan Yenilmez, Felipe Henriques, Emmanouela Tsagkaraki, Yvonne J. K. Edwards, Xiaodi Hu, Randall H. Friedline, Jason K. Kim, Michael P. Czech 2018 University of Massachusetts Medical School

Crispr-Delivery Particles Targeting Nuclear Receptor-Interacting Protein 1 (Nrip1) In Adipose Cells To Enhance Energy Expenditure, Yuefei Shen, Jessica L. Cohen, Sarah M. Nicoloro, Mark Kelly, Batuhan Yenilmez, Felipe Henriques, Emmanouela Tsagkaraki, Yvonne J. K. Edwards, Xiaodi Hu, Randall H. Friedline, Jason K. Kim, Michael P. Czech

Open Access Articles

RNA-guided, engineered nucleases derived from the prokaryotic adaptive immune system CRISPR-Cas represent a powerful platform for gene deletion and editing. When used as a therapeutic approach, direct delivery of Cas9 protein and single-guide RNA (sgRNA) could circumvent the safety issues associated with plasmid delivery and therefore represents an attractive tool for precision genome engineering. Gene deletion or editing in adipose tissue to enhance its energy expenditure, fatty acid oxidation, and secretion of bioactive factors through a "browning" process presents a potential therapeutic strategy to alleviate metabolic disease. Here, we developed "CRISPR-delivery particles," denoted CriPs, composed of nano-size complexes of Cas9 ...


Mutations In Influenza A Virus Neuraminidase And Hemagglutinin Confer Resistance Against A Broadly Neutralizing Hemagglutinin Stem Antibody, Kristina L. Prachanronarong, Aneth S. Canale, Ping Liu, Mohan Somasundaran, Shurong Hou, Yu-Ping Poh, Thomas Han, Quan Zhu, Nicholas Renzette, Konstantin B. Zeldovich, Timothy F. Kowalik, Nese Kurt Yilmaz, Jeffrey D. Jensen, Daniel N. Bolon, Wayne A. Marasco, Robert W. Finberg, Celia A. Schiffer, Jennifer P. Wang 2018 University of Massachusetts Medical School

Mutations In Influenza A Virus Neuraminidase And Hemagglutinin Confer Resistance Against A Broadly Neutralizing Hemagglutinin Stem Antibody, Kristina L. Prachanronarong, Aneth S. Canale, Ping Liu, Mohan Somasundaran, Shurong Hou, Yu-Ping Poh, Thomas Han, Quan Zhu, Nicholas Renzette, Konstantin B. Zeldovich, Timothy F. Kowalik, Nese Kurt Yilmaz, Jeffrey D. Jensen, Daniel N. Bolon, Wayne A. Marasco, Robert W. Finberg, Celia A. Schiffer, Jennifer P. Wang

Schiffer Lab Publications

Influenza A virus (IAV), a major cause of human morbidity and mortality, continuously evolves in response to selective pressures. Stem-directed, broadly neutralizing antibodies (sBnAbs) targeting influenza hemagglutinin (HA) are a promising therapeutic strategy, but neutralization escape mutants can develop. We used an integrated approach combining viral passaging, deep sequencing, and protein structural analyses to define escape mutations and mechanisms of neutralization escape in vitro for the F10 sBnAb. IAV was propagated with escalating concentrations of F10 over serial passages in cultured cells to select for escape mutations. Viral sequence analysis revealed three mutations in HA and one in neuraminidase (NA ...


Implementing Universal Lynch Syndrome Screening (Impulss): Protocol For A Multi-Site Study To Identify Strategies To Implement, Adapt, And Sustain Genomic Medicine Programs In Different Organizational Contexts, Alanna Kulchak Rahm, Mara M. Epstein 2018 Geisinger Genomic Medicine Institute

Implementing Universal Lynch Syndrome Screening (Impulss): Protocol For A Multi-Site Study To Identify Strategies To Implement, Adapt, And Sustain Genomic Medicine Programs In Different Organizational Contexts, Alanna Kulchak Rahm, Mara M. Epstein

Open Access Articles

BACKGROUND: Systematic screening of all colorectal tumors for Lynch Syndrome (LS) has been recommended since 2009. Currently, implementation of LS screening in healthcare systems remains variable, likely because LS screening involves the complex coordination of multiple departments and individuals across the healthcare system. Our specific aims are to (1) describe variation in LS screening implementation across multiple healthcare systems; (2) identify conditions associated with both practice variation and optimal implementation; (3) determine the relative effectiveness, efficiency, and costs of different LS screening protocols by healthcare system; and (4) develop and test in a real-world setting an organizational toolkit for LS ...


How To Translate Self-Management Support Tools Into Clinical Practice, Matthew J. Simpson, Jeanette M. Daly, Douglas H. Fernald, John M. Westfall, LeAnn C. Michaels, Barcey T. Levy, David L. Hahn, Lyle J. Fagnan, Donald E. Nease Jr. 2018 University of Colorado School of Medicine

How To Translate Self-Management Support Tools Into Clinical Practice, Matthew J. Simpson, Jeanette M. Daly, Douglas H. Fernald, John M. Westfall, Leann C. Michaels, Barcey T. Levy, David L. Hahn, Lyle J. Fagnan, Donald E. Nease Jr.

Journal of Patient-Centered Research and Reviews

Purpose: Patient self-management is an inevitable part of the work of being a patient, and self-management support (SMS) has become increasingly important in chronic disease management. However, the majority of SMS resources available in the Agency for Healthcare Research and Quality SMS Resource Library were developed without explicit collaboration between clinicians and patients.

Methods: Translation of SMS tools derived from the library into primary care practices occurred utilizing boot camp translation in four different practice-based research networks (PBRNs). The typical model of boot camp translation was adapted for the purpose of the Implementing Networks’ Self-management Tools Through Engaging Patients and ...


The Wilbarger Protocol, Brittany Hatlestad 2018 Augustana College, Rock Island Illinois

The Wilbarger Protocol, Brittany Hatlestad

Biology: Student Scholarship & Creative Works

Sensory processing disorder (SPD) is ever-increasing in children with and without disabilities. The prevalence of such a diagnosis has given rise to many different therapeutic practices. The most prescriptive, the Wilbarger protocol, will be the topic of this technique and literature review with discussions of what sensory problems are, the Wilbarger protocol, the deep pressure and proprioceptive portion of the protocol, oral tactile techniques, mechanisms of the protocol, the limitations, other options for treatment, and will conclude by looking to future research.


Comparison Of Prescribing Practices For Older Adults Treated By Female Versus Male Physicians: A Retrospective Cohort Study, Paula A. Rochon, Jerry H. Gurwitz 2018 University of Toronto

Comparison Of Prescribing Practices For Older Adults Treated By Female Versus Male Physicians: A Retrospective Cohort Study, Paula A. Rochon, Jerry H. Gurwitz

Open Access Articles

IMPORTANCE: Subtle but important differences have been described in the way that male and female physicians care for their patients, with some evidence suggesting women are more likely to adhere to best practice recommendations.

OBJECTIVE: To determine if male and female physicians differ in their prescribing practices as measured by the initiation of lower-than-recommended dose cholinesterase inhibitor (ChEI) drug therapy for dementia management.

DESIGN, SETTING, AND PARTICIPANTS: All community-dwelling Ontario residents aged 66 years and older with dementia and newly dispensed an oral ChEI drug (donepezil, galantamine, or rivastigmine) between April 1, 2010 and June 30, 2016 were included.

MAIN ...


First Case Of Pleural Empyema Caused By Staphylococcus Simulans: Review Of The Literature, Amos Lal, Jamal Akhtar, Ashfaq Ullah, George Abraham 2018 Saint Vincent Hospital

First Case Of Pleural Empyema Caused By Staphylococcus Simulans: Review Of The Literature, Amos Lal, Jamal Akhtar, Ashfaq Ullah, George Abraham

Open Access Articles

Staphylococcus simulans is a coagulase-negative organism, mainly an animal pathogen. Reports of human infection have been infrequent, mainly in patients with repeated animal contact. We report the first case of pleural empyema in an elderly woman. S. simulans tends to cause more severe infection because of a biofilm layer which helps in adherence and colonization of smooth surfaces, especially prosthetic devices, shunts, and catheters. The challenging problem even after CoNS isolation and identification is the assessment of their clinical relevance. Major factors that inhibit the penetration of antibiotics is the large-sized effusions/empyema, thickness of pleura, and the nature of ...


Protection Induced By A Francisella Tularensis Subunit Vaccine Delivered By Glucan Particles, Adam O. Whelan, Helen C. Flick-Smith, Jane Homan, Zu T. Shen, Zoe Carpenter, Payam Khoshkenar, Ambily Abraham, Nicola J. Walker, Stuart M. Levitz, Gary R. Ostroff, Petra C. F. Oyston 2018 Dstl Porton Down

Protection Induced By A Francisella Tularensis Subunit Vaccine Delivered By Glucan Particles, Adam O. Whelan, Helen C. Flick-Smith, Jane Homan, Zu T. Shen, Zoe Carpenter, Payam Khoshkenar, Ambily Abraham, Nicola J. Walker, Stuart M. Levitz, Gary R. Ostroff, Petra C. F. Oyston

Open Access Articles

Francisella tularensis is an intracellular pathogen causing the disease tularemia, and an organism of concern to biodefence. There is no licensed vaccine available. Subunit approaches have failed to induce protection, which requires both humoral and cellular immune memory responses, and have been hampered by a lack of understanding as to which antigens are immunoprotective. We undertook a preliminary in silico analysis to identify candidate protein antigens. These antigens were then recombinantly expressed and encapsulated into glucan particles (GPs), purified Saccharomyces cerevisiae cell walls composed primarily of beta-1,3-glucans. Immunological profiling in the mouse was used to down-selection to seven lead ...


Adeno-Associated Virus Neutralizing Antibodies In Large Animals And Their Impact On Brain Intraparenchymal Gene Transfer, Dan Wang, Li Zhong, Mengxin Li, Jia Li, Karen Tran, Lingzhi Ren, Ran He, Jun Xie, Richard P. Moser, Cara Fraser, Tim Kuchel, Miguel Sena-Esteves, Terence R. Flotte, Neil Aronin, Guangping Gao 2018 University of Massachusetts Medical School

Adeno-Associated Virus Neutralizing Antibodies In Large Animals And Their Impact On Brain Intraparenchymal Gene Transfer, Dan Wang, Li Zhong, Mengxin Li, Jia Li, Karen Tran, Lingzhi Ren, Ran He, Jun Xie, Richard P. Moser, Cara Fraser, Tim Kuchel, Miguel Sena-Esteves, Terence R. Flotte, Neil Aronin, Guangping Gao

Open Access Articles

Pre-existing neutralizing antibody (NAb) against adeno-associated virus (AAV) commonly found in primates is a major host barrier that can severely compromise in vivo gene transfer by AAV vectors. To achieve proof-of-concept success in clinical development of recombinant AAV (rAAV)-based in vivo gene therapy, it is crucial to consider the potential interference of NAb and to enroll serologically compatible study subjects. In this study, we report a large AAV NAb dataset comprising multiple large animal species and AAV serotypes and compare two NAb assays based on in vitro or in vivo transduction inhibition, respectively. Together with previously published AAV seroepidemiology ...


Regeneration Of Neurotransmission Transcriptome In A Model Of Epileptic Encephalopathy After Antiinflammatory Treatment, Dumitru A. Iacobas, Libor Velisek 2018 New York Medical College

Regeneration Of Neurotransmission Transcriptome In A Model Of Epileptic Encephalopathy After Antiinflammatory Treatment, Dumitru A. Iacobas, Libor Velisek

NYMC Faculty Publications

Inflammation is an established etiopathogenesis factor of infantile spasms (IS), a therapy-resistant epileptic syndrome of infancy. We investigated the IS-associated transcriptomic alterations of neurotransmission in rat hypothalamic arcuate nucleus, how they are corrected by antiinflamatory treatments and whether there are sex differences. IS was triggered by repeated intraperitoneal administration of N-methyl-D-aspartic acid following anti-inflammatory treatment (adreno-cortico-tropic-hormone (ACTH) or PMX53) or normal saline vehicle to prenatally exposed to betamethasone young rats. We found that treatments with both ACTH and PMX53 resulted in substantial recovery of the genomic fabrics of all types of synaptic transmission altered by IS. While ACTH represents the ...


The Implementation Process For Pharmacogenomic Testing For Cancer-Targeted Therapies, Ann Chen Wu, Kathleen M. Mazor, Rachel Ceccarelli, Stephanie Loomer, Christine Y. Lu 2018 Harvard Medical School

The Implementation Process For Pharmacogenomic Testing For Cancer-Targeted Therapies, Ann Chen Wu, Kathleen M. Mazor, Rachel Ceccarelli, Stephanie Loomer, Christine Y. Lu

Open Access Articles

Recent advances in genomic medicine have led to the availability of genomic tests that have the potential to improve population health, yet the process for obtaining these tests and getting them reimbursed by insurers has not been described. The objective of this study was to describe the process of ordering pharmacogenomic tests by interviewing providers, patients, and laboratories about cancer-related pharmacogenomic tests. We interviewed patients who were prescribed, providers who prescribed medications that should be guided by pharmacogenomic testing, and individuals from diagnostic laboratories. A total of 10 providers, 16 patients, and eight diagnostic laboratories described logistical and insurance issues ...


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