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https://www.readbyqxmd.com/read/28295484/who-2016-classification-changes-and-advancements-in-the-diagnosis-of-miscellaneous-primary-cns-tumours
#1
Felix Sahm, David E Reuss, Caterina Giannini
This short review highlights significant changes and recent findings incorporated to varying extent in the WHO 2016 definition of a variety of tumours, including peripheral nerve sheath tumours, meningiomas, mesenchymal non-meningothelial tumours, melanocytic tumours, lymphomas and histiocytic tumours, germ cell tumours and non-neuroendocrine pituitary tumours. Most notable classification changes include: adding "hybrid nerve sheath tumours" to the spectrum of benign nerve sheath tumours; an updated definition of atypical meningioma (WHO grade II), including cases with brain invasion; recognizing dural solitary fibrous tumour (SFT) and haemangiopericytoma (HPC) as a single tumour entity characterized by NAB2 and STAT6 gene fusions for which the term solitary SFT/HPC was chosen; recognizing that pituitary granular cell tumour, spindle cell oncocytoma, and pituicytoma all share nuclear expression of TTF-1, possibly representing a spectrum of a single nosological entity derived from posterior pituitary glial cells...
March 12, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28292496/the-estimation-and-inclusion-of-presenteeism-costs-in-applied-economic-evaluation-a-systematic-review
#2
REVIEW
Jesse Kigozi, Sue Jowett, Martyn Lewis, Pelham Barton, Joanna Coast
OBJECTIVE: Given the significant costs of reduced productivity (presenteeism) in comparison to absenteeism, and overall societal costs, presenteeism has a potentially important role to play in economic evaluations. However, these costs are often excluded. The objective of this study is to review applied cost of illness studies and economic evaluations to identify valuation methods used for, and impact of including presenteeism costs in practice. METHODS: A structured systematic review was carried out to explore (i) the extent to which presenteeism has been applied in cost of illness studies and economic evaluations and (ii) the overall impact of including presenteeism on overall costs and outcomes...
March 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/28277337/biomarkers-of-environmental-enteric-dysfunction-among-children-in-rural-bangladesh
#3
Rebecca K Campbell, Kerry Schulze, Saijuddin Shaikh, Sucheta Mehra, Hasmot Ali, Lee Wu, Rubhana Raqib, Sarah Baker, Alain Labrique, Keith P West, Parul Christian
OBJECTIVES: Environmental enteric dysfunction (EED) may inhibit growth and development in low- and middle-income countries, but available assessment methodologies limit its study. In rural Bangladesh, we measured EED using the widely-used lactulose mannitol ratio (L:M) test and a panel of intestinal and systemic health biomarkers to evaluate convergence among biomarkers and describe risk factors for EED. METHODS: In 539 18-month-old children finishing participation in a randomized food supplementation trial, serum, stool and urine collected after lactulose and mannitol dosing were analyzed for biomarkers of intestinal absorption, inflammation, permeability and repair, and systemic inflammation...
March 8, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28275199/natural-history-of-perihematomal-edema-and-impact-on-outcome-after-intracerebral-hemorrhage
#4
Teddy Y Wu, Gagan Sharma, Daniel Strbian, Jukka Putaala, Patricia M Desmond, Turgut Tatlisumak, Stephen M Davis, Atte Meretoja
BACKGROUND AND PURPOSE: Edema may worsen outcome after intracerebral hemorrhage (ICH). We assessed its natural history, factors influencing growth, and association with outcome. METHODS: We estimated edema volumes in ICH patients from the Helsinki ICH study using semiautomated planimetry. We assessed the correlation between edema extension distance (EED) and time from ICH onset, creating an edema growth trajectory model up to 3 weeks. We interpolated expected EED at 72 hours and identified clinical and imaging characteristics associated with faster edema growth...
March 8, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28268247/the-loss-of-the-nhs-eed-and-dare-databases-and-the-effect-on-evidence-synthesis-and-evaluation
#5
Simon Briscoe, Chris Cooper, Julie Glanville, Carol Lefebvre
No abstract text is available yet for this article.
March 7, 2017: Research Synthesis Methods
https://www.readbyqxmd.com/read/28256832/allosteric-inactivation-of-polycomb-repressive-complex-2-prc2-by-inhibiting-its-adapter-protein-embryonic-ectodomain-development-eed
#6
Chao-Yie Yang, Shaomeng Wang
Aberrant PRC2 activity produces gene repressive epigenetic marks in multiple diseases and led to identification of Ezh2 as a drug target. Recent studies have shown that the epigenetic reader protein EED, associated with Ezh2 in PRC2, has an additional function to stimulate the PRC2 activity after binding to H3K27me3. Optimizing a compound known to block the H3K27me3 site in EED discovered by in-house screening, Novartis scientists have now produced a compound that shows durable tumor regression in a lymphoma xenograft model...
March 3, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28254486/sar-of-amino-pyrrolidines-as-potent-and-novel-protein-protein-interaction-inhibitors-of-the-prc2-complex-through-eed-binding
#7
Michael L Curtin, Marina A Pliushchev, Huan-Qiu Li, Maricel Torrent, Justin D Dietrich, Clarissa G Jakob, Haizhong Zhu, Hongyu Zhao, Ying Wang, Zhiqin Ji, Richard F Clark, Kathy A Sarris, Sujatha Selvaraju, Bailin Shaw, Mikkel A Algire, Yupeng He, Paul L Richardson, Ramzi F Sweis, Chaohong Sun, Gary G Chiang, Michael R Michaelides
Herein we disclose SAR studies of a series of dimethylamino pyrrolidines which we recently reported as novel inhibitors of the PRC2 complex through disruption of EED/H3K27me3 binding. Modification of the indole and benzyl moieties of screening hit 1 provided analogs with substantially improved binding and cellular activities. This work culminated in the identification of compound 2, our nanomolar proof-of-concept (PoC) inhibitor which provided on-target tumor growth inhibition in a mouse xenograft model. X-ray crystal structures of several inhibitors bound in the EED active-site are also discussed...
April 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28245839/a-systematic-review-of-economic-evaluations-of-chw-interventions-aimed-at-improving-child-health-outcomes
#8
REVIEW
L Nkonki, A Tugendhaft, K Hofman
Evidence of the cost-effectiveness of community health worker interventions is pertinent for decision-makers and programme planners who are turning to community services in order to strengthen health systems in the context of the momentum generated by strategies to support universal health care, the post-2015 Sustainable Development Goal agenda.We conducted a systematic review of published economic evaluation studies of community health worker interventions aimed at improving child health outcomes. Four public health and economic evaluation databases were searched for studies that met the inclusion criteria: National Health Service Economic Evaluation Database (NHS EED), Cochrane, Paediatric Economic Evaluation Database (PEED), and PubMed...
February 28, 2017: Human Resources for Health
https://www.readbyqxmd.com/read/28229514/mutations-in-genes-encoding-polycomb-repressive-complex-2-subunits-cause-weaver-syndrome
#9
Eri Imagawa, Ken Higashimoto, Yasunari Sakai, Chikahiko Numakura, Nobuhiko Okamoto, Satoko Matsunaga, Akihide Ryo, Yoshinori Sato, Masafumi Sanefuji, Kenji Ihara, Yui Takada, Gen Nishimura, Hirotomo Saitsu, Takeshi Mizuguchi, Satoko Miyatake, Mitsuko Nakashima, Noriko Miyake, Hidenobu Soejima, Naomichi Matsumoto
Weaver syndrome is a rare congenital overgrowth disorder caused by heterozygous mutations in EZH2 (enhancer of zeste homolog 2) or EED (embryonic ectoderm development). EZH2 and EED are core components of the polycomb repressive complex 2 (PRC2), which possesses histone methyltransferase activity and catalyzes trimethylation of histone H3 at lysine 27. Here, we analyzed eight probands with clinically suspected Weaver syndrome by whole exome sequencing and identified three mutations: a 25.4-kb deletion partially involving EZH2 and CUL1 (individual 1), a missense mutation (c...
February 22, 2017: Human Mutation
https://www.readbyqxmd.com/read/28223321/a-non-canonical-function-of-ezh2-preserves-immune-homeostasis
#10
Ajithkumar Vasanthakumar, Dakang Xu, Aaron Tl Lun, Andrew J Kueh, Klaas Pjm van Gisbergen, Nadia Iannarella, Xiaofang Li, Liang Yu, Die Wang, Bryan Rg Williams, Stanley Cw Lee, Ian J Majewski, Dale I Godfrey, Gordon K Smyth, Warren S Alexander, Marco J Herold, Axel Kallies, Stephen L Nutt, Rhys S Allan
Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone-H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin-independent role of Ezh2 during T-cell development and immune homeostasis. T-cell-specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2-deficient T cells maintain normal levels of H3K27me3...
February 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28193775/targeting-the-eed-h3k27me3-interaction-allosterically-inhibits-prc2
#11
(no author information available yet)
EED226 and A-395 bind to the H3K27me3 binding pocket of EED to allosterically inhibit PRC2.
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28192098/anti-leukemic-effects-of-hdaci-belinostat-and-hmti-3-deazaneplanocin-a-on-human-acute-promyelocytic-leukemia-cells
#12
Giedrė Valiulienė, Ieva Stirblytė, Monika Jasnauskaitė, Veronika Borutinskaitė, Rūta Navakauskienė
Development of acute myeloid leukemia is usually sustained by deregulated epigenome. Alterations in DNA methylation and histone modifications are common manifestations of the disease. Acute promyelocytic leukemia (APL) is not an exception. Therefore, drugs that target epigenetic processes suggest an appealing strategy for APL treatment. In this study we tested the anti-leukemic activity of histone deacetylase inhibitor (HDACi) Belinostat (PXD101, (2E)-N-Hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide), and histone methyltransferase inhibitor (HMTi) 3-Deazaneplanocin A (DZNep, 5R-(4-amino-1H-imidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)-3-cyclopentene-1S,2R-diol) combined with retinoic acid (RA) in APL cells NB4 and HL-60...
February 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28174222/systematic-review-of-pathways-for-the-delivery-of-allergy-services
#13
Lavanya Diwakar, Carole Cummins, Richard Lilford, Tracy Roberts
OBJECTIVES: The incidence and prevalence of allergies worldwide has been increasing and allergy services globally are unable to keep up with this increase in demand. This systematic review aims to understand the delivery of allergy services worldwide, challenges faced and future directions for service delivery. METHODS: A systematic scoping review of Ovid, EMBASE, HMIC, CINAHL, Cochrane, DARE, NHS EED and INAHTA databases was carried out using predefined inclusion and exclusion criteria...
February 7, 2017: BMJ Open
https://www.readbyqxmd.com/read/28165227/discovery-of-peptidomimetic-ligands-of-eed-as-allosteric-inhibitors-of-prc2
#14
Kimberly D Barnash, Juliana The, Jacqueline L Norris-Drouin, Stephanie H Cholensky, Beau M Worley, Fengling Li, Jacob I Stuckey, Peter J Brown, Masoud Vedadi, Cheryl H Arrowsmith, Stephen V Frye, Lindsey I James
The function of EED within polycomb repressive complex 2 (PRC2) is mediated by a complex network of protein-protein interactions. Allosteric activation of PRC2 by binding of methylated proteins to the embryonic ectoderm development (EED) aromatic cage is essential for full catalytic activity, but details of this regulation are not fully understood. EED's recognition of the product of PRC2 activity, histone H3 lysine 27 trimethylation (H3K27me3), stimulates PRC2 methyltransferase activity at adjacent nucleosomes leading to H3K27me3 propagation and, ultimately, gene repression...
March 13, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28153450/tailored-liquid-chromatography-mass-spectrometry-analysis-improves-the-coverage-of-the-intracellular-metabolome-of-heparg-cells
#15
Matthias Cuykx, Noelia Negreira, Charlie Beirnaert, Nele Van den Eede, Robim Rodrigues, Tamara Vanhaecke, Kris Laukens, Adrian Covaci
Metabolomics protocols are often combined with Liquid Chromatography-Mass Spectrometry (LC-MS) using mostly reversed phase chromatography coupled to accurate mass spectrometry, e.g. quadrupole time-of-flight (QTOF) mass spectrometers to measure as many metabolites as possible. In this study, we optimised the LC-MS separation of cell extracts after fractionation in polar and non-polar fractions. Both phases were analysed separately in a tailored approach in four different runs (two for the non-polar and two for the polar-fraction), each of them specifically adapted to improve the separation of the metabolites present in the extract...
March 3, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28135237/the-eed-protein-protein-interaction-inhibitor-a-395-inactivates-the-prc2-complex
#16
Yupeng He, Sujatha Selvaraju, Michael L Curtin, Clarissa G Jakob, Haizhong Zhu, Kenneth M Comess, Bailin Shaw, Juliana The, Evelyne Lima-Fernandes, Magdalena M Szewczyk, Dong Cheng, Kelly L Klinge, Huan-Qiu Li, Marina Pliushchev, Mikkel A Algire, David Maag, Jun Guo, Justin Dietrich, Sanjay C Panchal, Andrew M Petros, Ramzi F Sweis, Maricel Torrent, Lance J Bigelow, Guillermo Senisterra, Fengling Li, Steven Kennedy, Qin Wu, Donald J Osterling, David J Lindley, Wenqing Gao, Scott Galasinski, Dalia Barsyte-Lovejoy, Masoud Vedadi, Fritz G Buchanan, Cheryl H Arrowsmith, Gary G Chiang, Chaohong Sun, William N Pappano
Polycomb repressive complex 2 (PRC2) is a regulator of epigenetic states required for development and homeostasis. PRC2 trimethylates histone H3 at lysine 27 (H3K27me3), which leads to gene silencing, and is dysregulated in many cancers. The embryonic ectoderm development (EED) protein is an essential subunit of PRC2 that has both a scaffolding function and an H3K27me3-binding function. Here we report the identification of A-395, a potent antagonist of the H3K27me3 binding functions of EED. Structural studies demonstrate that A-395 binds to EED in the H3K27me3-binding pocket, thereby preventing allosteric activation of the catalytic activity of PRC2...
January 30, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28135235/an-allosteric-prc2-inhibitor-targeting-the-h3k27me3-binding-pocket-of-eed
#17
Wei Qi, Kehao Zhao, Justin Gu, Ying Huang, Youzhen Wang, Hailong Zhang, Man Zhang, Jeff Zhang, Zhengtian Yu, Ling Li, Lin Teng, Shannon Chuai, Chao Zhang, Mengxi Zhao, HoMan Chan, Zijun Chen, Douglas Fang, Qi Fei, Leying Feng, Lijian Feng, Yuan Gao, Hui Ge, Xinjian Ge, Guobin Li, Andreas Lingel, Ying Lin, Yueqin Liu, Fangjun Luo, Minlong Shi, Long Wang, Zhaofu Wang, Yanyan Yu, Jue Zeng, Chenhui Zeng, Lijun Zhang, Qiong Zhang, Shaolian Zhou, Counde Oyang, Peter Atadja, En Li
Polycomb repressive complex 2 (PRC2) consists of three core subunits, EZH2, EED and SUZ12, and plays pivotal roles in transcriptional regulation. The catalytic subunit EZH2 methylates histone H3 lysine 27 (H3K27), and its activity is further enhanced by the binding of EED to trimethylated H3K27 (H3K27me3). Small-molecule inhibitors that compete with the cofactor S-adenosylmethionine (SAM) have been reported. Here we report the discovery of EED226, a potent and selective PRC2 inhibitor that directly binds to the H3K27me3 binding pocket of EED...
January 30, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28124441/confirmation-of-mutation-landscape-of-nf1-associated-malignant-peripheral-nerve-sheath-tumors
#18
Pierre Sohier, Armelle Luscan, Angharad Lloyd, Kevin Ashelford, Ingrid Laurendeau, Audrey Briand-Suleau, Dominique Vidaud, Nicolas Ortonne, Eric Pasmant, Meena Upadhyaya
The commonest tumors associated with neurofibromatosis type 1 (NF1) are benign peripheral nerve sheath tumors, called neurofibromas. Malignant transformation of neurofibromas into aggressive MPNSTs may occur with a poor patient prognosis. A cooperative role of SUZ12 or EED inactivation, along with NF1, TP53, and CDKN2A loss-of-function, has been proposed to drive progression to MPNSTs. An exome sequencing analysis of eight MPNSTs, one plexiform neurofibroma, and seven cutaneous neurofibromas was undertaken...
May 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28122695/environmental-enteric-dysfunction-is-associated-with-carnitine-deficiency-and-altered-fatty-acid-oxidation
#19
Richard D Semba, Indi Trehan, Ximin Li, Ruin Moaddel, M Isabel Ordiz, Kenneth M Maleta, Klaus Kraemer, Michelle Shardell, Luigi Ferrucci, Mark Manary
BACKGROUND: Environmental enteric dysfunction (EED), a condition characterized by small intestine inflammation and abnormal gut permeability, is widespread in children in developing countries and a major cause of growth failure. The pathophysiology of EED remains poorly understood. METHODS: We measured serum metabolites using liquid chromatography-tandem mass spectrometry in 400 children, aged 12-59months, from rural Malawi. Gut permeability was assessed by the dual-sugar absorption test...
January 18, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28119537/corrigendum-a-novel-mutation-in-eed-associated-with-overgrowth
#20
Ana S A Cohen, Beyhan Tuysuz, Yaoqing Shen, Sanjiv K Bhalla, Steven J M Jones, William T Gibson
No abstract text is available yet for this article.
February 2017: Journal of Human Genetics
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