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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
Fri Sep 01 2023
Journal Name
Journal Of Optics
Structural and optical properties of C60-ZnO thin films synthesized by spray pyrolysis technique with plasma treatment as antibacterial activity
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Spray pyrolysis technique was used to make Carbon60-Zinc oxide (C60-ZnO) thin films, and chemical, structural, antibacterial, and optical characterizations regarding such nanocomposite have been done prior to and following treatment. Fullerene peaks in C60-ZnO thin films are identical and appear at the same angles. Following the treatment of the plasma, the existence regarding fullerene peaks in the thin films investigated suggests that the crystallographic quality related to C60-ZnO thin films has enhanced. Following plasma treatment, field emission scanning electron microscopy (FESEM) images regarding a C60-ZnO thin film indicate that both zinc oxide and fullerene particles had shrunk in the size and have an even distribution. In addition

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Publication Date
Tue Sep 01 2015
Journal Name
Photomedicine And Laser Surgery
Evaluation of Temperature Elevation During Root Canal Treatment with Dual Wavelength Laser: 2780 nm Er,Cr:YSGG and 940 nm Diode
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Publication Date
Thu May 18 2023
Journal Name
Journal Of Engineering
Experimental and Numerical Analysis of Piled Raft Foundation with Different Length of Piles Under Static Loads
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In order to understand the effect of (length of pile / diameter of pile) ratio on the load carrying capacity and settlement reduction behavior of piled raft resting on loose sand, laboratory model tests were conducted on small-scale models. The parameters studied were the effect of pile length and the number of piles. The load settlement behavior obtained from the tests has been validated by using 3-D finite element in ABAQUS program, was adopted to understand the load carrying response of piled raft and settlement reduction. The results of experimental work show that the increase in (Lp/dp) ratio led to increase in load carrying capacity by piled raft from (19.75 to 29.35%), (14.18 to 28.87%) and (0 to 16.49%) , the maximum load carried

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Publication Date
Sun Dec 01 2019
Journal Name
Indian Journal Of Ecology
Evaluation of maize hybrids, their inbred lines and estimation of genetic divergence based on cluster analysis
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Publication Date
Wed Sep 01 2021
Journal Name
Baghdad Science Journal
Bioremediation Potential of Chlorella vulgaris and Nostoc paludosum on azo Dyes with Analysis of Metabolite Changes
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               Microalgae have been used widely in bioremediation processes to degrade or adsorb toxic dyes. Here, we evaluated the decolorization efficiency of Chlorella vulgaris and Nostoc paludosum against two toxic dyes, crystal violet (CV) and malachite green (MG). Furthermore, the effect of CV and MG dyes on the metabolic profiling of the studied algae has been investigated. The data showed that C. vulgaris was most efficient in decolorization of CV and MG: the highest percentage of decolorization was 93.55% in case of MG, while CV decolorization percentage was 62.98%. N. paludosum decolorized MG dye by 77.6%, and the decolorization percentage of CV was 35.1%. Metabolic profiling of

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Publication Date
Wed Oct 17 2018
Journal Name
Journal Of Economics And Administrative Sciences
The Use Of Some Parametric And Non parametric Methods For Analysis Of Factorial Experiments With Application
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summary

In this search, we examined the factorial experiments and the study of the significance of the main effects, the interaction of the factors and their simple effects by the F test (ANOVA) for analyze the data of the factorial experience. It is also known that the analysis of variance requires several assumptions to achieve them, Therefore, in case of violation of one of these conditions we conduct a transform to the data in order to match or achieve the conditions of analysis of variance, but it was noted that these transfers do not produce accurate results, so we resort to tests or non-parametric methods that work as a solution or alternative to the parametric tests , these method

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Publication Date
Thu Mar 10 2022
Journal Name
American Journal Of Economics And Business Management
Analysis and measurement of the financial sustainability of the Iraqi economy for the period 1990-2018
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The research aims to measure the sustainability of the Iraqi economy for the period 1990-2018 as well as to show the impact of fluctuations in the level of GDP on financial sustainability, where financial sustainability is the necessary and sufficient condition for achieving economic and financial balance in the country, as financial sustainability reflects the movement of the state budget and its relationship to GDP through the indicators of deficit, fiscal surplus and public debt internal and external, as well as reflecting the art of managing public debt, and the more managed public debt is achieved, the more the management of public debt is achieved financial sustainability. for the state in the sense that there is a reciprocal

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Publication Date
Sun Oct 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
Analysis the context of Uncertainty (Nature and management) under two school of strategic thinking (theoretical perspective
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Purpose: studying and analyzing the nature of uncertainty as part of strategy formulation, through analyzing the uncertainty faced by managers in the modern business environment characterized by high complexity and dynamism, though developing of an idea about the uncertainty cases and how enable the mind to understand these cases.

Methodology: It was the use of inductive and analytical approach, in order to study the accumulation of knowledge towards development areas that could contribute to strengthening the strategy formulation.

Findings: Mentoring the future will not make the success for business organization but thought business organization ability to developing share mental

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Publication Date
Sun Jun 03 2012
Journal Name
Baghdad Science Journal
A Biochemical Study for Evaluation and Analysis of Serum Protein of Patients with Different Kidney Tumors
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The amount of protein in the serum depends on the balance between the rate of its synthesis, and that of its catabolism or loss. Abnormal metabolism may result from nutritional deficiency, enzyme deficiency, abnormal secretion of hormones, or the actions of drugs and toxins. Renal cancer is the third most common malignancy of the genitourinary system, and accounts for 3% of adult malignancies globally. Total serum proteins were measured in malignant kidney tumor, benign kidney tumors, and non tumoral kidney diseases patient groups, as well as in healthy individuals. A significant decrease (p< 0.001) of total serum protein levels in patients with malignant kidney tumors when compared with those of benign tumors, non tumoral diseases, and hea

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Publication Date
Thu May 02 2013
Journal Name
Journal Of Engineering
Experimental and numerical analysis of piled raft foundation with different length of piles under static loads
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In order to understand the effect of (length of pile / diameter of pile) ratio on the load carrying capacity and settlement reduction behavior of piled raft resting on loose sand, laboratory model tests were conducted on small-scale models. The parameters studied were the effect of pile length and the number of piles. The load settlement behavior obtained from the tests has been validated by using 3-D finite element in ABAQUS program, was adopted to understand the load carrying response of piled raft and settlement reduction. The results of experimental work show that the increase in (Lp/dp) ratio led to increase in load carrying capacity by piled raft from (19.75 to 29.35%), (14.18 to 28.87%) and (0 to 16.49%) , the maximum load carr

... Show More