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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 Jan 01 2020
Journal Name
Annals Of Tropical Medicine And Public Health
The use of eggplant peel powder in the treatment of hyperlipidemia caused by antibiotics administration in male local rabbits
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Publication Date
Sat Apr 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
Estimation & Analysis Relationship between Growth rate GDP and Unemployment Rate In Iraqi Economic in Period (1990-2014)
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It reflects the gross domestic product in any country total output of goods and services by the size of the country's citizens and foreign residents during the period of the year and reflect the contribution of the commodity sectors of the economy and the distribution and service in the composition of output. And gross domestic product in Iraq as an indicator dominated in the composition of oil output, along with the contribution of the service sector, as the gross domestic product is the output of a yield lien   and subjected GDP in Iraq to a series of declines succession due to vibrations of the oil market during the economic blockade on the one hand and stop imported production inputs, lack of arriving in commodity s

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Publication Date
Mon Dec 01 2008
Journal Name
Saudi Medical Journal
Treatment of perniosis with oral pentoxyfylline in comparison with oral prednisolone plus topical clobetasol ointment in Iraqi patients.
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AA Noaimi, BM Fadheel, Saudi medical journal, 2008 - Cited by 25

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Publication Date
Thu Oct 01 2020
Journal Name
Journal Of Engineering
Electrocoagulation for Treatment of Simulated Blowdown Water Of Cooling Tower
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This study investigates the results of electrocoagulation (EC) using aluminum (Al) electrodes as anode and stainless steel (grade 316) as a cathode for removing silica, calcium, and magnesium ions from simulated cooling tower blowdown waters. The simulated water contains (50 mg/l silica, 508 mg/l calcium, and 292 mg/l magnesium). The influence of different experimental parameters, such as current density (0.5, 1, and 2 mA/cm2), initial pH(5,7, and 10), the temperature of the simulated solution(250C and 35 0C), and electrolysis time was studied. The highest removal efficiency of 80.183%, 99.21%, and 98.06% for calcium, silica, and magnesium ions, respectively, were obtained at a current de

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Publication Date
Tue Jan 01 2002
Journal Name
Annals Of Saudi Medicine
Treatment of viral warts by intralesional injection of zinc sulphate
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KA Sharquie, AA Al-Nuaimy, Annals of Saudi Medicine, 2002 - Cited by 48

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Publication Date
Sun Mar 03 2013
Journal Name
Baghdad Science Journal
Effect of Magnetic Water Treatment on Prevention of CaCO3 Scales
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Permanent magnets of different intensities were used to investigate the effect of a magnetic field in the process of preventing deposits of calcium carbonate. The magnets were fixed on the water line from the tap outside. Then heating a sample of this water in flasks and measuring the amount of sediment in a manner weighted differences. These experiments comprise to the change of the velocity of water flow, which amounted to (0.5, 0.75, 1) m/sec through the magnetic fields that are of magnetic strength (2200, 6000, 9250, 11000) Gauss, and conduct measurements, tests and compare them with those obtained from the use of ordinary water.The results showed the effectiveness of magnetic treatment in reducing the rate of deposition of calcium carb

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Publication Date
Wed Jul 05 2023
Journal Name
Journal Of Pragmatics Research
Analysis of Impoliteness Strategies Used in Putin's Speech at Annexation Ceremony
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This study aims to investigate the types of impoliteness strategies used in Putin's speech at the annexation ceremony. All of Putin's speeches were intentionally delivered to cause damage to the hearers' negative and positive faces. Culpeper's (2011) classifications of impoliteness, which consist of five strategies that are the opposite of politeness, were adopted. The data were collected from the President of Russia, providing a rich source for analysis. Qualitative and quantitative analyses were employed to achieve the study objectives. Qualitative analysis allowed for a detailed examination of the impoliteness strategies employed, while quantitative analysis provided a broader understanding of their frequency and distribution. Putin most

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Publication Date
Tue Oct 23 2018
Journal Name
Journal Of Economics And Administrative Sciences
The Role of Financial Analysis in Investors Decisions ( Iraqi Stock Exchange )
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  The research aims to reveal the role of financial analysis in rationalizing the investor decision on the Iraqi stock Exchange market, by studying the relationship and impact techniques and methods of financial analysis on the decisions of investors in the market. The most important techniques and methods discussed in this study were: analysis (financial ratios analysis, comparison of financial statements analysis, cash flow statement analysis) for companies listed in the Iraqi stock Exchange market. The researcher adopted the analytical descriptive method which depends on the collection of data on the phenomenon and its interpretation. The questionnaire wa

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Publication Date
Sat Feb 02 2019
Journal Name
Journal Of The College Of Education For Women
content Analysis for Some Type of Pillows used in Iraqi houses
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content Analysis for Some Type of Pillows used in Iraqi houses

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Publication Date
Tue Dec 20 2022
Journal Name
Journal Of Language Studies
A Rhetorical Analysis of Fallacy in a Selected English Drama Movie
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Fallacies are incorrect reasoning that make an argument seem less logically credible and easier to be identified as unsound. They are widespread; individuals commit them while engaging in various activities, including at work, at home, while creating advertisements, and in the media. This study aims to investigate the rhetorical strategies accompanied with producing the fallacious arguments selected from the American Film “12 Angry Men (1957)”. The study adopts Damer’s (2009) model for the identification of fallacy. As for rhetorical analysis, the study adopts Aristotle’s triangle of rhetoric and McGuigan’s (2007) taxonomy of rhetorical devices. The results uncover that the most violated criteria are relevance, acceptabili

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