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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
Thu Sep 13 2018
Journal Name
Baghdad Science Journal
An Efficient Numerical Method for Solving Volterra-Fredholm Integro-Differential Equations of Fractional Order by Using Shifted Jacobi-Spectral Collocation Method
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The aim of this article is to solve the Volterra-Fredholm integro-differential equations of fractional order numerically by using the shifted Jacobi polynomial collocation method. The Jacobi polynomial and collocation method properties are presented. This technique is used to convert the problem into the solution of linear algebraic equations. The fractional derivatives are considered in the Caputo sense. Numerical examples are given to show the accuracy and reliability of the proposed technique.

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Publication Date
Wed May 10 2023
Journal Name
Journal Of Engineering
REMOVAL OF PHENOLIC COMPUNDS FROM AQUEOUS SOLUTIONS BY ADSOPTION ONTO ACTIVTED CARBONS PREPARED FROM DATE STONES BY CHEMICAL ACTIVATION WITH FeCl3
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Activated carbon prepared from date stones by chemical activation with ferric chloride (FAC) was used an adsorbent to remove phenolic compounds such as phenol (Ph) and p-nitro phenol (PNPh) from aqueous solutions. The influence of process variables represented by solution pH value (2-12), adsorbent to adsorbate weight ratio (0.2-1.8), and contact time (30-150 min) on removal percentage and adsorbed amount of Ph and PNPh onto FAC was studied. For PNPh adsorption,( 97.43 %) maximum removal percentage and (48.71 mg/g) adsorbed amount was achieved at (5) solution pH,( 1) adsorbent to adsorbate weight ratio, and (90 min) contact time. While for Ph adsorption, at (4) solution pH, (1.4) absorbent to adsorbate weight ratio, and (120 min) contact

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Publication Date
Fri Mar 17 2017
Journal Name
Elixir Mech. Engg. 109 (2017) 47879-47881, Www. Elixirpublishers. Com …‏
Effect of Cutting Angle for a Locally Assembling Motorized Vibration Cutter on Some Operational Characteristics Used for Date Palm Fronds Cutting
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Publication Date
Mon Mar 07 2022
Journal Name
Journal Of Educational And Psychological Researches
The Effect of Teaching According to the Augmented Reality Technique on theVisual Thinking Skills to Scientific Fifth-Grade Students for Biology
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The research aims to identify the effect of teaching according to the augmented reality on the technique of the visual thinking skills among scientific fifth-grade students in a biology course. In order to achieve the goal of the research, the researcher adopted the experimental approach with the partial set of the two equal groups with the dimensional test of visual thinking skills, The research population represented all the scientific students of the fifth grade for morning government schools affiliated to the General Directorate of Education of Baghdad / Karkh II, alshakerin preparatory for boys was chosen intentionally, in which two groups were chosen for this study, one group is chosen randomly as the control group via lottery, whe

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Publication Date
Thu Dec 14 2023
Journal Name
Optical And Quantum Electronics
Enhancing response characteristics of palladium-doped vanadium pentoxide on a porous silicon substrate as gas sensor synthesized by pulsed laser deposition
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Publication Date
Mon Sep 30 2024
Journal Name
Open Veterinary Journal
Crude aqueous Proteus mirabilis extract with quorum sensing inhibitory activity can increase the susceptibility of multidrug resistant Pseudomonas aeruginosa to antimicrobials
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Background: Suppression of quorum sensing (QS) that regulates many virulence factors, including antimicrobial resistance, in bacteria may subject the pathogenic microbes to the harmful consequences of the antibiotics, increasing their susceptibility to such drugs. Aim: The current study aimed to make an aqueous crude extract from the soil Proteus mirabilis isolate with the use of the gas chromatography-mass spectrometry (GC-MS) technique for its analysis, and then, study the impact of the extract on clinical isolates of Pseudomonas aeruginosa. Methods: Preparation of crude extracts from P. mirabilis (both organic and aqueous), which were then analyzed by GC-MS to detect the bioactive ingredients. Furthermore, the extract’s capability to i

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Publication Date
Mon Nov 01 2021
Journal Name
Iop Conference Series: Earth And Environmental Science
Treatability influence of municipal sewage effluent on surface water quality assessment based on Nemerow pollution index using an artificial neural network
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Abstract<p>Assessing water quality provides a scientific foundation for the development and management of water resources. The objective of the research is to evaluate the impact treated effluent from North Rustumiyia wastewater treatment plant (WWTP) on the quality of Diyala river. The model of the artificial neural network (ANN) and factor analysis (FA) based on Nemerow pollution index (NPI). To define important water quality parameters for North Al-Rustumiyia for the line(F2), the Nemerow Pollution Index was introduced. The most important parameters of assessment of water variation quality of wastewater were the parameter used in the model: biochemical oxygen demand (BOD), chemical oxygen dem</p> ... Show More
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Publication Date
Tue Oct 25 2022
Journal Name
Aip Conference Proceedings
The structural properties of mawsoniteCu6Fe2 S8Sn[CFTS] thin films effected by violet laser irradiation deposited via semi-computerized spray pyrolysis technique
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Publication Date
Sun Dec 22 2019
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Ex-vivo Ex-Vivo Absorption Study of a Novel Dabigatran Etexilate Loaded Nanostructured Lipid Carrier Using Non-Everted Intestinal Sac Model
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Abstract

The purpose of our study was to develop Dabigatran Etexilate loaded nanostructured lipid carriers (DE-NLCs) using Glyceryl monostearate and Oleic acid as lipid matrix, and to estimate the potential of the developed delivery system to improve oral absorption of low bioavailability drug, different Oleic acid ratios effect on particle size, zeta potential, entrapment efficiency and loading capacity were studied, the optimized DE-NLCs shows a particle size within the nanorange, the zeta potential (ZP) was 33.81±0.73mV with drug entrapment efficiency (EE%) of  92.42±2.31% and a loading capacity (DL%) of 7.69±0.17%. about 92% of drug was released in 24hr in a controlled manner, the ex-vivo intestinal p

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Publication Date
Fri Jul 10 2026
Journal Name
Mathematical And Computational Applications
A Regularized Numerical Solution to an Inverse Coefficient Problem for the Forced Vibrations of a Cantilever Beam Equation Under Nonlocal Conditions
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This study tackles a fourth-order inverse problem involving a cantilever beam with nonlocal conditions to simultaneously calculate the beam’s displacement and an unknown time-dependent coefficient. A finite difference approach is suggested to discretize the hyperbolic fourth-order equation. A stability analysis for the proposed scheme is also provided. The indirect problem is the minimization of the misfit function. The goal of the minimization algorithm is to reduce the gap between the measured (noisy) data and the numerical computed solution provided by the model. To achieve stable results, Tikhonov’s regularization technique is employed, and two numerical test examples are shown to illustrate the suggested scheme's reliabilit

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