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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
Sat Sep 01 2018
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Functional rotation and its impact on tax performance: Applied research in the General Authority for Taxation
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The research aimed at finding out the effect of functional rotation on the tax performance of the employees of the General Authority for Taxes through the five-meter questionnaire prepared according to the required data. The data obtained from the research sample were analyzed. The results showed a significant effect of recycling In the tax performance, and this is evident from the proportion of his contribution to the interpretation of the total variation, which is a good indicator of the impact of functional rotation in the performance of the body sample research.

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Publication Date
Sat Jul 01 2023
Journal Name
Analytical Science & Technology
A Review: Synthesis and characterization of metals complexes with paracetamol drug
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In this review, previous studies on the synthesis and characterization of the metal Complexes with paracetamol by elemental analysis, thermal analysis, (IR, NMR and UV-Vis (spectroscopy and conductivity. In reviewing these studies, the authors found that paracetamol can be coordinated through the pair of electrons on the hydroxyl O-atom, carbonyl O-atom, and N-atom of the amide group. If the paracetamol was a monodentate ligand, it will be coordinated by one of the following atoms O-hydroxyl, O-carbonyl or N-amide. But if the paracetamol was bidentate, it is coordinated by atoms (O-carbonyl and N-amide), (O-hydroxyl and N-amide) or (O-carbonyl and O-hydroxyl). The authors also found that free paracetamol and its complexes have antimicrobial

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Publication Date
Tue May 24 2022
Journal Name
Analytical Science& Technology
A Review: Synthesis and characterization of metals complexes with paracetamol drug
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In this review, previous studies on the synthesis and characterization of the metal Complexes with paracetamol by elemental analysis, thermal analysis, (IR, NMR and UV-Vis (spectroscopy and conductivity. In reviewing these studies, the authors found that paracetamol can be coordinated through the pair of electrons on the hydroxyl O-atom, carbonyl O-atom, and N-atom of the amide group. If the paracetamol was a monodentate ligand, it will be coordinated by one of the following atoms O-hydroxyl, O-carbonyl or N-amide. But if the paracetamol was bidentate, it is coordinated by atoms (O-carbonyl and N-amide), (O-hydroxyl and N-amide) or (O-carbonyl and O-hydroxyl). The authors also found that free paracetamol and its complexes have antimicrobial

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Publication Date
Wed Mar 07 2018
Journal Name
International Journal Of Applied Pharmaceutics
FORMULATION AND CHARACTERIZATION OF LAFUTIDINE NANOSUSPENSION FOR ORAL DRUG DELIVERY SYSTEM
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Objective: The objective of this study was to prepare nanosuspension of a practical water insoluble antiulcer drug which is lafutidine to enhance the solubility, dissolution rate with studying the effect of different formulation variables to obtain the best formula with appropriate physical properties and higher dissolution rate.Methods: Nanosuspension of lafutidine was prepared using solvent anti-solvent precipitation method using Polyvinylpyrrolidone K-90(PVP K-90) as the stabilizer. Ten formulations were prepared to show the effect of different variables in which two formulations showed the effect of stabilizer type, three formulations showed the effect of stabilizer concentration, two formulations showed the effect of combinatio

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Publication Date
Tue Jan 01 2019
Wide-range tunable subwavelength band-stop filter for the far-infrared wavelengths based on single-layer graphene sheet
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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
The Chronic Effects of Salinity in the Biology of ?? Rotifers Brachionus calyciflorus Pallas
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The present study included the effect of chronic exposure for two concentrations of NaC? salt on the biology of fresh water zooplankton species Brachionus calyciflorus (from ^otifera). The concentrations 0.5 , 0.75%o were used for chronic exposure to investigate its effects on the life tables, range of the rate of expectation for further life and reproduction. The rotifer B. calyciflorus was sensitive to salinity and may tried to protect the species by increasing the size (2.22 ind./clutch lor control group and 2.9? for 0.5%o concentration) and number of clutches produced ?.1? clutch/female for control group and 2.9 ' ' ' for 0.75 %0 concentration) beside stimulation the animal to produce the first clutch of eggs earlier? ? small reduction

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Publication Date
Fri Jan 01 2021
Journal Name
Materials Today: Proceedings
Study of some electronic and spectroscopic properties of ZnO nanostructers by density functional theory
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Publication Date
Sun Jun 01 2014
Journal Name
Baghdad Science Journal
Survival estimation for singly type one censored sample based on generalized Rayleigh distribution
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This paper interest to estimation the unknown parameters for generalized Rayleigh distribution model based on censored samples of singly type one . In this paper the probability density function for generalized Rayleigh is defined with its properties . The maximum likelihood estimator method is used to derive the point estimation for all unknown parameters based on iterative method , as Newton – Raphson method , then derive confidence interval estimation which based on Fisher information matrix . Finally , testing whether the current model ( GRD ) fits to a set of real data , then compute the survival function and hazard function for this real data.

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Publication Date
Fri Jan 01 2021
Journal Name
International Journal Of Innovation, Creativity And Change
The importance of using the World Wide Web (the Internet) for professors of Arabic Language Department at the University of Baghdad‏
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Publication Date
Sun Dec 05 2010
Journal Name
Baghdad Science Journal
Immunoglobulins assessment (IgE,G,A,M) in some Iraqi patients with acute and chronic urticaria
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60 patients diagnosed as having urticaria were included in the study ; 30 patients were effected with acute urticaria and 30 patients were affected with chronic urticaria. In addition, 30 healthy adult volunteers were selected as control group .The patients and control groups sera were examined with enzyme linked immunosorbent assay ( ELISA) to detect total level IgE and radial immunodiffusion (RID) to detect levels of IgG , IgA and IgM . The total level of IgE in acute urticaria ( 1.45±0.13) IU/mL and chronic urticaria (2.12 ± 0.10) IU/mL patients were significantly higher than the control groups ( 0.85 ± 0.10)IU/mL (p<0.05). The level of IgG in acute urticaria ( 12.5± 0.42) g/L and chronic (13.16±0.40) g/L patients , IgA in acute (2.

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