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https://www.readbyqxmd.com/read/30126942/targeting-myddosome-signaling-in-waldenstr%C3%A3-m-s-macroglobulinemia-with-the-interleukin-1-receptor-associated-kinase-1-4-inhibitor-r191
#1
Haiwen Ni, Fazal Shirazi, Veerabhadran Baladandayuthapani, Heather Lin, Isere Kuiatse, Hua Wang, Richard J Jones, Zuzana Berkova, Yasumichi Hitoshi, Stephen M Ansell, Steven P Treon, Sheeba K Thomas, Hans C Lee, Zhiqiang Wang, R Eric Davis, Robert Z Orlowski
Purpose: Waldenström's macroglobulinemia is an incurable lymphoproliferative disorder driven by an L265P mutation in the myeloid differentiation primary response gene 88 ( MYD88 ), which activates downstream NF-κB signaling through the Myddosome. As this pathway depends in part on activity of interleukin-1 receptor-associated kinases (IRAKs)-1 and -4, we sought to evaluate the potential of the IRAK1/4 inhibitor R191 in preclinical models. Experimental Design: Patient-derived cell lines and primary samples were used in both in vitro and in vivo experiments to model Waldenström's macroglobulinemia and its response to IRAK1/4 inhibitors...
August 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30117104/cd73-downregulation-decreases-in-vitro-and-in-vivo-glioblastoma-growth
#2
J H Azambuja, N E Gelsleichter, L R Beckenkamp, I C Iser, M C Fernandes, F Figueiró, A M O Battastini, J N Scholl, F H de Oliveira, R M Spanevello, Jean Sévigny, M R Wink, M A Stefani, H F Teixeira, Elizandra Braganhol
Glioblastoma is the worst and most common primary brain tumor. Here, we demonstrated the role of CD73, an enzyme responsible for adenosine (ADO) production, in glioblastoma progression. ADO increased glioma cell viability via A1 receptor sensitization. CD73 downregulation decreased glioma cell migration and invasion by reducing metalloproteinase-2 and vimentin expression and reduced cell proliferation by 40%, which was related to necrosis and sub-G1 phase blockage of cell cycle. Those effects also involved the stimulation of Akt/NF-kB pathways...
August 16, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30094105/lessons-learnt-from-epidemiological-investigation-of-lassa-fever-outbreak-in-a-southwest-state-of-nigeria-december-2015-to-april-2016
#3
Elvis Efe Isere, Akinola Ayoola Fatiregun, Olayinka Ilesanmi, Ibidolapo Ijarotimi, Beatrice Egube, Adewale Adejugbagbe, Gboyega Adekunle Famokun
INTRODUCTION: An outbreak of Lassa Fever (LF) reported and confirmed in Ondo state, Southwest Nigeria in January 2016 was investigated. This paper provides the epidemiology of the LF and lessons learnt from the investigation of the outbreak. METHODS: The incidence management system (IMS) model was used for the outbreak coordination. Cases and deaths were identified through the routine surveillance system using standard definitions for suspected and confirmed cases and deaths respectively...
June 29, 2018: PLoS Currents
https://www.readbyqxmd.com/read/30048940/incidence-of-prostate-cancer-and-net-survival-by-grade-in-a-geriatric-population-a-population-based-study-in-a-french-administrative-entity-from-1991-to-2013
#4
Alexandre Bellier, Marc Colonna, Patricia Delafosse, Arnaud Seigneurin
BACKGROUND: Prostate cancer is the leading type of cancer among men in more developed countries. Incidence trends and survival rates could differ by age groups considering potential differences in the frequency of PSA testing, types of cancers and medical management. Our objective was to compare incidence trends and survival rates of prostate cancer between men aged ≥75 and 60-74 years. METHOD: We analyzed data from a population-based cancer registry in Isère, France...
October 2018: Cancer Epidemiology
https://www.readbyqxmd.com/read/30012192/community-based-provision-of-direct-acting-antiviral-therapy-for-hepatitis-c-study-protocol-and-challenges-of-a-randomized-controlled-trial
#5
A J Wade, J S Doyle, E Gane, C Stedman, B Draper, D Iser, S K Roberts, W Kemp, D Petrie, N Scott, P Higgs, P A Agius, J Roney, L Stothers, A J Thompson, M E Hellard
BACKGROUND: To achieve the World Health Organization hepatitis C virus (HCV) elimination targets, it is essential to increase access to treatment. Direct-acting antiviral (DAA) treatment can be provided in primary healthcare services (PHCS), improving accessibility, and, potentially, retention in care. Here, we describe our protocol for assessing the effectiveness of providing DAAs in PHCS, and the impact on the HCV care cascade. In addition, we reflect on the challenges of conducting a model of care study during a period of unprecedented change in HCV care and treatment...
July 16, 2018: Trials
https://www.readbyqxmd.com/read/29666758/-rhinochelys-amaberti-moret-1935-a-protostegid-turtle-from-the-early-cretaceous-of-france
#6
Isaure Scavezzoni, Valentin Fischer
Modern marine turtles (chelonioids) are the remnants of an ancient radiation that roots in the Cretaceous. The oldest members of that radiation are first recorded from the Early Cretaceous and a series of species are known from the Albian-Cenomanian interval, many of which have been allocated to the widespread but poorly defined genus Rhinochelys , possibly concealing the diversity and the evolution of early marine turtles. In order to better understand the radiation of chelonioids, we redescribe the holotype and assess the taxonomy of Rhinochelys amaberti Moret (1935) (UJF-ID...
2018: PeerJ
https://www.readbyqxmd.com/read/29581547/protein-targeting-chimeric-molecules-specific-for-bromodomain-and-extra-terminal-motif-family-proteins-are-active-against-pre-clinical-models-of-multiple-myeloma
#7
Xiaohui Zhang, Hans C Lee, Fazal Shirazi, Veerabhadran Baladandayuthapani, Heather Lin, Isere Kuiatse, Hua Wang, Richard J Jones, Zuzana Berkova, Ram Kumar Singh, Jing Lu, Yimin Qian, Kanak Raina, Kevin G Coleman, Craig M Crews, Bingzong Li, Huihan Wang, Yared Hailemichael, Sheeba K Thomas, Zhiqiang Wang, R Eric Davis, Robert Z Orlowski
Bromodomain and extraterminal (BET) domain containing protein (BRD)-4 modulates the expression of oncogenes such as c-myc, and is a promising therapeutic target in diverse cancer types. We performed pre-clinical studies in myeloma models with bi-functional protein-targeting chimeric molecules (PROTACs) which target BRD4 and other BET family members for ubiquitination and proteasomal degradation. PROTACs potently reduced the viability of myeloma cell lines in a time-dependent and concentration-dependent manner associated with G0 /G1 arrest, reduced levels of CDKs 4 and 6, increased p21 levels, and induction of apoptosis...
October 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29536535/does-preference-rank-predict-substitution-for-the-reinforcer-for-problem-behavior-a-behavioral-economic-analysis
#8
Michelle A Frank-Crawford, Mariana I Castillo, Iser G DeLeon
Predictions made under low response requirements inherent in most preference assessments (PAs) do not guarantee the utility of stimuli in treatments. We examined whether PA rank would predict how well stimuli supported compliance for children with escape-maintained problem behavior by examining the relation between PA rank and demand elasticity across five fixed-ratio values. Three patterns were observed: All stimuli were selected equally across values, higher ranked stimuli were selected more at higher values, and something other than the highest ranked stimulus was selected more at higher values (i...
April 2018: Journal of Applied Behavior Analysis
https://www.readbyqxmd.com/read/29380436/additional-free-reinforcers-increase-persistence-of-problem-behavior-in-a-clinical-context-a-partial-replication-of-laboratory-findings
#9
Gregory A Lieving, Iser G DeLeon, Abbey B Carreau-Webster, Michelle A Frank-Crawford, Mandy M Triggs
Behavioral momentum theory is a quantitative framework used to characterize the persistence of behavior during response disruptors as a function of baseline stimulus-reinforcer relations. Results of several investigations have shown that alternative reinforcement can increase the resistance to change of a target response during extinction. In the present study, concomitant variable-interval fixed-time schedules of reinforcement for problem behavior were employed to simulate naturalistic situations involving the superimposition of response-independent reinforcers on a baseline schedule of reinforcement for problem behavior, as in the common use of noncontingent reinforcement treatments...
January 2018: Journal of the Experimental Analysis of Behavior
https://www.readbyqxmd.com/read/29359370/descriptive-assessment-of-problem-behavior-during-transitions-of-children-with-intellectual-and-developmental-disabilities
#10
Mariana I Castillo, Daniel R Clark, Erin A Schaller, Jeanne M Donaldson, Iser G DeLeon, SungWoo Kahng
Transitions from one activity to another may evoke problem behavior from individuals with intellectual disabilities. One explanation for the occurrence of problem behavior could be the change in relative densities of reinforcement between the two activities. We conducted a descriptive assessment of problem behavior with four children during transitions to and from several different contexts. We observed that, in most cases, the probability of problem behavior was greater during a transition to an activity with a lower density of reinforcement than during a transition to an activity with a higher density of reinforcement...
January 2018: Journal of Applied Behavior Analysis
https://www.readbyqxmd.com/read/29248321/-evaluation-of-knowledge-and-practices-regarding-heterozygous-familial-hypercholesterolemia-in-children
#11
A Jeangeorges, A Rubio
INTRODUCTION: Dominant heterozygous familial hypercholesterolemia (FH) is frequent (prevalence, 1/500 to 1/250) and leads to severe and premature cardiovascular complications. It is easily detected, and its treatment is effective. However, recommendations for screening are not followed worldwide. OBJECTIVES: The aim of this study was to evaluate the knowledge and practices of doctors in the Isère department, France, regarding screening and treatment of FH in children...
February 2018: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/29242512/synthetic-integrin-binding-immune-stimulators-target-cancer-cells-and-prevent-tumor-formation
#12
Manuel Brehs, André J G Pötgens, Julia Steitz, Karine Thewes, Janett Schwarz, Anne C Conibear, Matthias Bartneck, Frank Tacke, Christian F W Becker
Immuno-oncology approaches mainly utilize monoclonal antibodies or protein-based scaffolds that bind with high affinity to cancer cells and can generate an immune response. Peptides can also bind with high affinity to cancer cells and are intermediate in size between antibodies and small molecules. They are also synthetically accessible and therefore easily modified to optimize their stability, binding affinity and selectivity. Here we describe the design of immune system engagers (ISErs), a novel class of synthetic peptide-based compounds that bind specifically to cancer cells and stimulate the immune system...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29238121/epidemic-preparedness-and-management-a-guide-on-lassa-fever-outbreak-preparedness-plan
#13
REVIEW
Akinola Ayoola Fatiregun, Elvis Efe Isere
Epidemic prone diseases threaten public health security. These include diseases such as cholera, meningitis, and hemorrhagic fevers, especially Lassa fever for which Nigeria reports considerable morbidity and mortality annually. Interestingly, where emergency epidemic preparedness plans are in place, timely detection of outbreaks is followed by a prompt and appropriate response. Furthermore, due to the nature of spread of Lassa fever in an outbreak setting, there is the need for health-care workers to be familiar with the emerging epidemic management framework that has worked in other settings for effective preparedness and response...
January 2017: Nigerian Medical Journal: Journal of the Nigeria Medical Association
https://www.readbyqxmd.com/read/29230922/synthetic-cancer-targeting-innate-immune-stimulators-give-insights-into-avidity-effects
#14
Anne C Conibear, André J G Pötgens, Karine Thewes, Claudia Altdorf, Clarissa Hilzendeger, Christian F W Becker
Multispecific and multivalent antibodies are seen as promising cancer therapeutics, and numerous antibody fragments and derivatives have been developed to exploit avidity effects that result in increased selectivity. Most of these multispecific and multivalent antibody strategies make use of recombinant expression of antigen-binding modules. In contrast, chemical synthesis and chemoselective ligations can be used to generate a variety of molecules with different numbers and combinations of binding moieties in a modular and homogeneous fashion...
March 2, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29216338/transcriptome-states-reflect-imaging-of-aging-states
#15
D Mark Eckley, Christopher E Coletta, Nikita V Orlov, Mark A Wilson, Wendy Iser, Paul Bastian, Elin Lehrmann, Yonqing Zhang, Kevin G Becker, Ilya G Goldberg
In this study, we describe a morphological biomarker that detects multiple discrete subpopulations (or "age-states") at several chronological ages in a population of nematodes (Caenorhabditis elegans). We determined the frequencies of three healthy adult states and the timing of the transitions between them across the lifespan. We used short-lived and long-lived strains to confirm the general applicability of the state classifier and to monitor state progression. This exploration revealed healthy and unhealthy states, the former being favored in long-lived strains and the latter showing delayed onset...
June 14, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29211136/surveillance-system-for-risk-and-protective-factors-for-chronic-diseases-by-telephone-survey-vigitel-changes-in-weighting-methodology
#16
Regina Tomie Ivata Bernal, Betine Pinto Moehlecke Iser, Deborah Carvalho Malta, Rafael Moreira Claro
OBJECTIVE: to introduce the methodology used to calculate post-stratification weights of the 2012 Surveillance System for Risk and Protective Factors for Chronic Diseases by Telephone Survey (Vigitel) and to compare the trends of indicators estimated by cell-by-cell weighting and raking methods. METHODS: in this panel of cross-sectional studies, the prevalences of smokers, overweight, and intake of fruits and vegetables from 2006 to 2012 were estimated using the cell-by-cell weighting and raking methods...
October 2017: Epidemiologia e Servicos de Saude: Revista do Sistema Unico de Saude do Brasil
https://www.readbyqxmd.com/read/29129474/-screening-program-for-tuberculosis-among-international-exchange-students-in-the-department-of-is%C3%A3-re
#17
M-V Albahary, F Blanc-Jouvan, C Recule, C Dubey, P Pavese
INTRODUCTION: France is a low-incidence country for tuberculosis (TB). Consequently screening is focused on high-risk populations, in particular migrants. The aim of this study was to evaluate the epidemiology of TB among international exchange students in the Department of Isère and the screening programs used. METHODS: We carried out an organizational audit based on interviews with physicians involved in the management of TB in Isère. We conducted a retrospective descriptive study based on a case series of foreign students treated for TB from 2003 to 2013 inclusively...
January 2018: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/29105901/a-comparative-study-of-synthetic-and-semisynthetic-approaches-for-ligating-the-epidermal-growth-factor-to-a-bivalent-scaffold
#18
COMPARATIVE STUDY
Anna Lena Gell, Nadja Groysbeck, Christian F W Becker, Anne C Conibear
A prominent target of monoclonal antibodies as targeted therapies for cancer is the epidermal growth factor receptor, which is overexpressed on the surface of various cancer cell types. Its natural binder, the epidermal growth factor (EGF), is a 53 amino acid polypeptide. Anticancer synthetic targeted immune system engagers (ISErs) comprising two 'binder' peptides, which are attached to a scaffold conveying immune stimulating 'effector' properties, via monodisperse polyethylene glycol chains. So far, preparation of ISErs has been limited to the use of small peptides (8-20 amino acids) as binding functionalities, and they have been entirely synthesized by solid phase peptide synthesis...
December 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29065124/sustained-virological-response-halts-fibrosis-progression-a-long-term-follow-up-study-of-people-with-chronic-hepatitis-c-infection
#19
Swee Lin G Chen Yi Mei, Alexander J Thompson, Britt Christensen, Georgina Cunningham, Lucy McDonald, Sally Bell, David Iser, Tin Nguyen, Paul V Desmond
BACKGROUND/AIMS: Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR) in people with chronic hepatitis C (CHC) infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart. METHODS: CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM) using transient elastography [FibroScan]) were identified...
2017: PloS One
https://www.readbyqxmd.com/read/28902197/fast-and-reproducible-isers-microscopy-of-single-her2-positive-breast-cancer-cells-using-gold-nanostars-as-sers-nanotags
#20
Xin-Ping Wang, Bernd Walkenfort, Matthias König, Lisa König, Sabine Kasimir-Bauer, Sebastian Schlücker
Speed is often a bottleneck in conventional Raman microscopy on biological specimens. In immuno-Raman microspectroscopy, or for short iSERS microscopy, the acquisition times per pixel have been reduced by more than one order of magnitude over the past decade since its proof of concept. Typically rather high laser power densities are employed with the intention of compensating for the shorter acquisition times, without checking the reproducibility of the results in repeated experiments on the same sample. Here, we systematically analyze this aspect at the single-cell level since it forms the basis of quantification and is very important for reinspection of the same specimen...
December 4, 2017: Faraday Discussions
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