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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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Abstract<sec> <title>Background

Chronic lymphocytic leukaemia (CLL) patients display a highly variable clinical course, with progressive acquisition of drug resistance. We sought to identify aberrant epigenetic traits that are enriched following exposure to treatment that could impact patient response to therapy.

Methods

Epigenome-wide analysis of DNA methylation was performed for 20 patients at two timepoints during treatment. The prognostic significance of differentially methylated regions (DMRs) was assessed in independent cohorts of 139 and 163 patients. Their functional role in drug sensitivity was assessed in vitro.

Results

We identified 490 DMRs following exposure to therapy, of which 31 were CLL-specific and independent of changes occurring in normal B-cell development. Seventeen DMR-associated genes were identified as differentially expressed following treatment in an independent cohort. Methylation of the HOXA4, MAFB and SLCO3A1 DMRs was associated with post-treatment patient survival, with HOXA4 displaying the strongest association. Re-expression of HOXA4 in cell lines and primary CLL cells significantly increased apoptosis in response to treatment with fludarabine, ibrutinib and idelalisib.

Conclusion

Our study demonstrates enrichment for multiple CLL-specific epigenetic traits in response to chemotherapy that predict patient outcomes, and particularly implicate epigenetic silencing of HOXA4 in reducing the sensitivity of CLL cells to therapy.

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Publication Date
Wed Sep 01 2021
Journal Name
Journal Of Engineering
The Effect of Adding High-Density Polyethylene Polymer on the Engineering Characteristics for Sandy Soil
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The loose sand is subject to large settlement when it is exposed to high stresses. This settlement is due to the nature of the high drainage of sand, which displays foundations and constructions to a large danger. The densification of loose sandy soils is required to provide sufficient bearing capacity for the structures. Thus soil stabilization is used to avoid failure in the facilities. Traditional methods of stabilized sandy soil such as fly ash, bituminous, and cement often require an extended curing period. The use of polymers to stabilize sandy soils is more extensive nowadays because it does not require a long curing time in addition to being chemically stable. In this study, the effect of adding different percent

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Publication Date
Sat Jun 01 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Measuring the Performance of IT Governance According to COBIT5 Framework by Using the Balanced Scorecard
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The research aims to clarify the COBIT5 framework for IT governance and to develop of a criterion based on Balanced Scorecard that contributes in measuring the performance of IT governance. To achieve these goals, the researchers adopted the deductive approach in the design of balanced scorecard to measure the IT governance at the Bank of Baghdad that was chosen because it relied heavily on IT.

The research has reached a number of conclusions, the most important of which is that the performance of IT department in the Bank of Baghdad falls within the good level that requires constant monitoring, the most committed items of Balanced Scorecard by the Bank were customer, internal operation, growth and finally the financial item; IT

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Publication Date
Sun Dec 04 2022
Journal Name
Jordan Journal Of Biological Sciences
The Biological Effect of ZnO Nanoparticles Produced by Using Petroselinum crispum Extract against Candida spp
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Non-thermal or cold plasma create many reactive species and charged particles when brought into contact with plant extracts. The major constituents involve reactive oxygen species, reactive nitrogen species and plasma ultra-violets. These species can be used to synthesize biologically important nanoparticles. The current study addressed the effect of the green method-based preparation approach on the volumetric analysis of Zn nanoparticles. Under different operating conditions, the traditional thermal method and the microwave method as well as the plasma generation in dielectric barrier discharge reactor were adopted as a preparation approach in this study. The results generally show that the type of method used plays an important rol

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Publication Date
Sat Dec 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
Measuring the Critical Success Factors for Total Quality Management Applications (Compared research of many colleges)
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ABSTRACT

This research aim to measure the critical success factors for total quality management applications, in order to know the key and important role played by these factors at applying the total quality management through a comparative study conducted in a number of a private colleges.

The research problem posed a set of questions, the most important ones are: Are the colleges (sample of research) aware of the critical success factors at applying the total quality management? What is the availability of the critical success factors at the work of the colleges (sample of research)? 

What are the critical success factors in the work of the researc

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Publication Date
Mon Dec 03 2012
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
The Effect of Window Size Changing on Satellite Image Segmentation Using 2D Fast Otsu Method
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Publication Date
Wed Dec 25 2019
Journal Name
Journal Of Engineering
Corrosion Rate Optimization of Mild-Steel under Different Cooling Tower Working Parameters Using Taguchi Design
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This study investigates the implementation of Taguchi design in the estimation of minimum corrosion rate of mild-steel in cooling tower that uses saline solution of different concentration. The experiments were set on the basis of Taguchi’s L16 orthogonal array. The runs were carried out under different condition such as inlet concentration of saline solution, temperature, and flowrate. The Signal-to- Noise ratio and ANOVA analysis were used to define the impact of cooling tower working conditions on the corrosion rate. A regression had been modelled and optimized to identify the optimum level for the working parameters that had been founded to be 13%NaCl, 35ᴼC, and 1 l/min. Also a confirmation run to establish the p

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Publication Date
Thu Oct 15 2015
Journal Name
International Journal Of Computer Applications
Experimental Investigation for Small Horizontal Portable Wind Turbine of Different Blades Profiles under Laboratory Conditions
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Experimental investigation for small horizontal portable wind turbine (SHPWT) of NACA-44, BP-44, and NACA-63, BP-63 profiles under laboratory conditions at different wind velocity range of (3.7-5.8 m/s) achieved in present work. Experimental data tabulated for 2, 3, 4, and 6- bladed rotor of both profiles within range of blade pitch angles . A mathematical model formulated and computer Code for MATLAB software developed. The least-squares regression is used to fit experimental data. As the majority of previous works have been presented for large scale wind turbines, the aims were to present the performance of (SHPWT) and also to make a comparisons between both profiles to conclude which is the best performance. The overall efficiency and el

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Publication Date
Sat Dec 01 2018
Journal Name
Indian Journal Of Natural Sciences
Determination of the Electron Density Variation for Ionosphere Layer Over Iraqi Zone Using IRI Model
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KA Hadi, AH Asma’a, IJONS, 2018 - Cited by 1

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Publication Date
Mon Jun 30 2025
Journal Name
Scripta Medica
Case Report: A Rare Presentation of Sigmoid Volvulus During Pregnancy With an Integrative Postoperative Approach
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Publication Date
Fri May 01 2015
Journal Name
Transplantation Proceedings
Prevalence of Polyomavirus Among United Arab Emirates Kidney Transplant Recipients: Results From a Single Center
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