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- Agarwal, Prasoon, et al.
(author)
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Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target.
- 2016
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:6, s. 6809-6923
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Journal article (peer-reviewed)abstract
- Multiple myeloma (MM) is a malignancy of the antibody-producing plasma cells. MM is a highly heterogeneous disease, which has hampered the identification of a common underlying mechanism for disease establishment as well as the development of targeted therapy. Here we present the first genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in MM patient samples, defining a common set of active H3K4me3-enriched genes and silent genes marked by H3K27me3 (H3K27me3 alone or bivalent) unique to primary MM cells, when compared to normal bone marrow plasma cells. Using this epigenome profile, we found increased silencing of H3K27me3 targets in MM patients at advanced stages of the disease, and the expression pattern of H3K27me3-marked genes correlated with poor patient survival. We also demonstrated that pharmacological inhibition of EZH2 had anti-myeloma effects in both MM cell lines and CD138+ MM patient cells. In addition, EZH2 inhibition decreased the global H3K27 methylation and induced apoptosis. Taken together, these data suggest an important role for the Polycomb repressive complex 2 (PRC2) in MM, and highlights the PRC2 component EZH2 as a potential therapeutic target in MM.
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| 3. |
- Agarwal, Prasoon, et al.
(author)
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Growth signals employ CGGBP1 to suppress transcription of Alu-SINEs
- 2016
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In: Cell Cycle. - : Informa UK Limited. - 1538-4101 .- 1551-4005. ; 15:12, s. 1558-1571
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Journal article (peer-reviewed)abstract
- CGGBP1 (CGG triplet repeat-binding protein 1) regulates cell proliferation, stress response,cytokinesis, telomeric integrity and transcription. It could affect these processes by modulatingtarget gene expression under different conditions. Identification of CGGBP1-target genes andtheir regulation could reveal how a transcription regulator affects such diverse cellular processes.Here we describe the mechanisms of differential gene expression regulation by CGGBP1 inquiescent or growing cells. By studying global gene expression patterns and genome-wide DNAbindingpatterns of CGGBP1, we show that a possible mechanism through which it affects theexpression of RNA Pol II-transcribed genes in trans depends on Alu RNA. We also show that itregulates Alu transcription in cis by binding to Alu promoter. Our results also indicate thatpotential phosphorylation of CGGBP1 upon growth stimulation facilitates its nuclear retention,Alu-binding and dislodging of RNA Pol III therefrom. These findings provide insights into howAlu transcription is regulated in response to growth signals.
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| 4. |
- Ahmed, Kamran, et al.
(author)
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Development of a standardised training curriculum for robotic surgery: a consensus statement from an international multidisciplinary group of experts
- 2015
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In: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 116:1, s. 93-101
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Journal article (peer-reviewed)abstract
- Objectives: To explore the views of experts about the development and validation of a robotic surgery training curriculum, and how this should be implemented. Materials and methods: An international expert panel was invited to a structured session for discussion. The study was of a mixed design, including qualitative and quantitative components based on focus group interviews during the European Association of Urology (EAU) Robotic Urology Section (ERUS) (2012), EAU (2013) and ERUS (2013) meetings. After introduction to the aims, principles and current status of the curriculum development, group responses were elicited. After content analysis of recorded interviews generated themes were discussed at the second meeting, where consensus was achieved on each theme. This discussion also underwent content analysis, and was used to draft a curriculum proposal. At the third meeting, a quantitative questionnaire about this curriculum was disseminated to attendees to assess the level of agreement with the key points. Results: In all, 150 min (19 pages) of the focus group discussion was transcribed (21 316 words). Themes were agreed by two raters (median agreement kappa 0.89) and they included: need for a training curriculum (inter-rater agreement kappa 0.85); identification of learning needs (kappa 0.83); development of the curriculum contents (kappa 0.81); an overview of available curricula (kappa 0.79); settings for robotic surgery training ((kappa 0.89); assessment and training of trainers (kappa 0.92); requirements for certification and patient safety (kappa 0.83); and need for a universally standardised curriculum (kappa 0.78). A training curriculum was proposed based on the above discussions. Conclusion: This group proposes a multi-step curriculum for robotic training. Studies are in process to validate the effectiveness of the curriculum and to assess transfer of skills to the operating room.
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- Bäck-Wiklund, Margareta, 1944, et al.
(author)
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Os hospitais são organizações saudáveis? Qualidade de vida no trabalho hospitalar no norte e no sul da Europa : Are healthcare organizations healthy? Quality of life in healthcare work in Northern and Southern Europe
- 2018
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In: Sociologia, Problemas e Práticas. - 0873-6529. ; 86, s. 45-67
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Research review (peer-reviewed)abstract
- From a gender perspective, this article analyses the concept of "healthy organization" through the study of the "dual agenda" of healthcare organizations. Based in the EU funded project "Quality of Life in a Changing Europe", which priviledged a multi-method approach, we analyse data from an extensive survey applied in eight European countries (Germany, Bulgaria, Finland, The Netherlands, Hungary, Portugal, United Kingdom and Sweden) and present two case studies undergone at university public hospitals in Sweden and in Portugal. Results show that the perceptions of what is a healthy organization are developed around the notions of social support, life satisfaction, work engagement and work-life reconciliation. Gender variations are a common feature in each of these dimensions. Organizational policies, professional trajectories and family resources are directly related to these variations.
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| 7. |
- Dehghan, Abbas, et al.
(author)
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Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies : The CHARGE Consortium
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
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Journal article (peer-reviewed)abstract
- Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5x10(-6) in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5x10(-6); 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8x10(-3)) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2x10(-9)). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2x10(-3)). Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders.
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| 8. |
- Derogar, Maryam, et al.
(author)
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Preparedness for side effects and bother in symptomatic men after radical prostatectomy in a prospective, non-randomized trial
- 2016
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 55:12, s. 1467-1476
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Journal article (peer-reviewed)abstract
- BACKGROUND: Many clinicians believe that preparedness before surgery for possible post-surgery side effects reduces the level of bother experienced from urinary incontinence and decreased sexual health after surgery. There are no published studies evaluating this belief. Therefore, we aimed to study the level of preparedness before radical prostatectomy and the level of bother experienced from urinary incontinence and decreased sexual health after surgery. MATERIAL AND METHODS: We prospectively collected data from a non-selected group of men undergoing radical prostatectomy in 14 centers between 2008 and 2011. Before surgery, we asked about preparedness for surgery-induced urinary problems and decreased sexual health. One year after surgery, we asked about bother caused by urinary incontinence and erectile dysfunction. As a measure of the association between preparedness and bothersomeness we modeled odds ratios (ORs) by means of logistic regression. RESULTS: Altogether 1372 men had urinary incontinence one year after surgery as well as had no urinary leakage or a small urinary dribble before surgery. Among these men, low preparedness was associated with bother resulting from urinary incontinence [OR 2.84; 95% confidence interval (CI) 1.59-5.10]. In a separate analysis of 1657 men we found a strong association between preparedness for decreased sexual health and experiencing bother from erectile dysfunction (OR 5.92; 95% CI 3.32-10.55). CONCLUSION: In this large-sized prospective trial, we found that preparedness before surgery for urinary problems or sexual side effects decreases bother from urinary incontinence and erectile dysfunction one year after surgery.
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| 9. |
- Goel, Sneha, 1993-, et al.
(author)
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Axial suspension plasma spraying of Al2O3 coatings for superior tribological properties
- 2017
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In: Surface & Coatings Technology. - : ELSEVIER SCIENCE SA. - 0257-8972 .- 1879-3347. ; 315, s. 80-87
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Journal article (peer-reviewed)abstract
- Suspension plasma spray is a relatively new thermal spray technique which enables feeding of fine powder to produce advanced coatings for varied applications. This work investigates the difference in structure and performance of Al2O3 coatings manufactured using conventional micron-sized powder feedstock and a suspension of sub-micron to few micron sized powder. Axial injection was implemented for deposition in both cases. The effect of feedstock size and processing on the tribological performance of the two coatings was of specific interest. The coatings were characterized by Optical and Scanning Electron Microscopy, micro-hardness and scratch resistance testing, and their dry sliding wear performance evaluated. The suspension sprayed coatings yielded significantly higher scratch resistance, lower friction coefficient and reduced wear rate compared to conventional coatings. The improved tribological behaviour of the former is attributable to finer porosity, smaller splat sizes, and improved interlamellar bonding.
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| 10. |
- Goel, Sneha, 1993-, et al.
(author)
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Hybrid powder-suspension Al2O3-ZrO2 coatings by axial plasma spraying : Processing, characteristics & tribological behaviour
- 2017
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In: Proceedings of the International Thermal Spray Conference & Exposition. - New York : Curran Associates, Inc. - 9781510858220 ; , s. 374-379
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Conference paper (peer-reviewed)abstract
- The ability of suspension plasma spraying (SPS) to overcome difficulties associated with feeding of fine (submicron or nano-sized) powders and achieve more refined microstructures than possible in atmospheric plasma spraying (APS) is well established. In recent times, the use of axial injection plasma spray systems has yielded substantial enhancement in deposition rates/efficiencies due to improved thermal exchange between the plasma plume and injected feedstock. The present paper describes utilization of both the above advances in plasma spraying to create various function-dependent coating architectures through simultaneous and/or sequential spraying of hybrid powder-suspension feedstock. A specific variant of such hybrid axial plasma spraying that enables deposition of composite coatings by simultaneous injection of a powder and a suspension is discussed in particular detail. Results obtained using an Al2O3-ZrO2 material system as a case study reveal that composite coatings combining the micron-size features arising from the spray-grade Al2O3 powder and submicron or nano-sized features attributable to the ZrO2 suspension can be conveniently realized. The surface morphology, microstructure, and composition of these coatings, as well as their tribological behaviour determined using scratch and ball-on-disc tests, are presented herein. The utility of this method to develop a wide array of composite coatings is also discussed.
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