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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 Jan 01 2022
Journal Name
Annals Of Parasitology
Evaluation the therapeutic efficacy of different concentration of amphotericin B drug in mice infected with visceral leishmaniosis
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Liposomal amphotericin B (Amph B) has been used effectively to treat leishmaniosis, in spite of its high toxicity appeared in some patients. In our study, Amph B was administered in Leishmania donovani that infected BALB/c male mice using different concentrations to evaluate its efficacy challenge against infection as well as its effect in modulating immunity of the host. We observed that low doses with short duration of Amph B as a therapy regime significantly enhanced the induction of Th1 cytokine (INF-γ), but suppressed Th2 cytokine (IL-10) production. Groups of mice infected with L. donovani and treated with Amph B showed clearly increasing in INF-γ level and reduction in IL-10 level in concentration (3, 4, 5 mg/ml/kg) with best resul

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Publication Date
Mon Sep 30 2002
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
The Treatment of Wastewater of Alcohol Factory by Filtration as Primary Treatment
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Publication Date
Fri Mar 01 2019
Journal Name
Al-khwarizmi Engineering Journal
Experimental Study of Drug Delivery system for Prednisolone Loaded and Released by Mesoporous Silica MCM-41
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In the present study, nanoporous material type MCM-41 was prepared by the sol-gel technique and was used as a carrier for prednisolone (PRD) drug delivery. The structural properties of mesoporous were fully characterized by X-ray diffraction (XRD), N2 adsorption /desorption and Fourier-transform infrared (FTIR). The mass transfer in term of adsorption process (loading) and desorption process (releasing) properties were investigated. The maximum drug loading efficiency was equal to 38% and 47.5% at different concentrations. The PRD released was prudently studied in water media of pH 6.8 simulated body fluid (SBF) in according to "United State Pharmacopeia (USP38)". The results proved that the release of prednisolone from MCM-41

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Publication Date
Wed Dec 01 2021
Journal Name
Baghdad Science Journal
Useing the Hierarchical Cluster Analysis and Fuzzy Cluster Analysis Methods for Classification of Some Hospitals in Basra
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In general, the importance of cluster analysis is that one can evaluate elements by clustering multiple homogeneous data; the main objective of this analysis is to collect the elements of a single, homogeneous group into different divisions, depending on many variables. This method of analysis is used to reduce data, generate hypotheses and test them, as well as predict and match models. The research aims to evaluate the fuzzy cluster analysis, which is a special case of cluster analysis, as well as to compare the two methods—classical and fuzzy cluster analysis. The research topic has been allocated to the government and private hospitals. The sampling for this research was comprised of 288 patients being treated in 10 hospitals. As t

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Publication Date
Tue Oct 23 2018
Journal Name
Journal Of Economics And Administrative Sciences
Processing of missing values in survey data using Principal Component Analysis and probabilistic Principal Component Analysis methods
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The idea of ​​carrying out research on incomplete data came from the circumstances of our dear country and the horrors of war, which resulted in the missing of many important data and in all aspects of economic, natural, health, scientific life, etc.,. The reasons for the missing are different, including what is outside the will of the concerned or be the will of the concerned, which is planned for that because of the cost or risk or because of the lack of possibilities for inspection. The missing data in this study were processed using Principal Component  Analysis and self-organizing map methods using simulation. The variables of child health and variables affecting children's health were taken into account: breastfeed

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Publication Date
Sun Sep 06 2015
Journal Name
Baghdad Science Journal
A study of the effect of new cobalt (II) complex and cyclophosphamide drug on (GPT, ALP) activity by using in vivo system
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The present work involved a study the effect of cobalt(II) complex with formula [CoL(H2O)NO3] .4ETOH where L=Nitro [5-(P-nitro phenyl) -4-phenyl-1,2,4 traizole-3-dithiocarbamato hydrazide] aqua. (4) Ethanol and anti-cancer drug - cyclophosphamide on specific activity of two liver enzymes (GPT,ALP) by utilizing an in vivo system in female mice. On the enzymatic level an inhibition in the activity of GPT was noticed in different body organs such as liver, kidney and lung. The inhibition was noticed in both test and cyclophosphamide drug (cp). Mice were treated with three doses of cyclophosphamide (90,180, 250) ?g/ mouse for three days. The same doses were used for the cobalt (II) complex. The liver shows the highest rate of(GPT) inhibition co

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Publication Date
Wed Jun 30 2021
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
ELECTROCHEMICAL PREPARATION OF A MOLECULAR IMPRINTED POLYMER ELECTRODE FOR ESTEMATION OF ASPIRIN USING TWO DIFFERENT FUNCTIONAL MONOMERS.: ELECTROCHEMICAL PREPARATION OF A MOLECULAR IMPRINTED POLYMER ELECTRODE FOR ESTEMATION OF ASPIRIN USING TWO DIFFERENT FUNCTIONAL MONOMERS.
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For aspirin estimated, a molecularly imprinted polymer MIP-ASP electrodes were generated by electro-polymerization process, the electrodes were prepared by combining the template (aspirin) with (vinyl acetate (VA), 1-vinylimidizole (VIZ) as a functional monomer and N, N-methylene bisacrylamide (MBAA) as crosslinkers using benzoyl peroxide (BPO) as an initiator. The efficiency of the membrane electrodes was analyzed by differential pulse voltammetry (DPV). Four electrodes were synthesized using two different plasticizers, di-butyl sebacate (DBS), di-octyl phthalate (DOP) in PVC matrix. Scanning electron microscopy (SEM) was used to describe the generated MIP, studying the electrodes properties, the slope, detection limit, and life

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Publication Date
Fri Jul 01 2022
Journal Name
Civil Engineering Journal
Behavior of Post-Tensioned Concrete Girders Subject to Partially Strand Damage and Strengthened by NSM-CFRP Composites
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Studies on the flexural behavior of post-tensioned beams subjected to strand damage and strengthened with near-surface mounted (NSM) technique using carbon fiber-reinforced polymer (CFRP) are limited and fail to examine the effect of CFRP laminates on strand strain and strengthening efficiency systematically. Furthermore, a design approach for UPC structures in existing design guidelines for FRP strengthening techniques is lacking. Hence, the behavior of post-tensioned beams strengthened with NSM-CFRP laminates after partial strand damage is investigated in this study. The testing program consists of seven post-tensioned beams strengthened by NSM-CFRP laminates with three partial strand damage ratios (14.3% symmetrical damage, 14.3%

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Publication Date
Sat Feb 01 2020
Journal Name
Structures
Experimental and numerical study on wrapping concrete cylinders post heating and cooling under preload using CFRP fabrics
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This paper reports test results and describes a numerical investigation of the effectiveness of using carbon fibre reinforced polymer (CFRP) fabrics for strengthening concrete cylinders that have been undamaged and damaged due to heating under preload. The purpose of this research was to investigate whether there is any difference in the performance of CFRP-wrapped cylinders if the wrapping is done under preload, and those for which neither heating, cooling nor wrapping was done under preload. The cylinders were exposed to 30% of maximum load at ambient temperature during heating and cooling before being wrapped under preload. Of 18 Ø 100 × 200 mm identical cylinders, 6 were left as control samples without heating, 12 were exposed t

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Publication Date
Mon Dec 25 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Colorimetry and Indirect X-ray Fluorescence Determination of Active Ingredients in Tetracycline Hydrochloride Drug and Injection Solution of B12 Vitamin Using of Polyurethane Foam Sorbents
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The simple and available technique of colorimetry and indirect X-ray fluorescence determination of tetracycline hydrochloride (in the form of colored complex with iron(III) ions) and cyanocobalamine (in the form of the colored thiocyanate complex with cobalt(II) ions) is offered. The analytes were separated from the accompanying components by sorption to polyurethane foam based on ethers. The conditions of sorption separation and measurement of analytical signal of these substances are optimized. The obtained results of tetracycline drugs and injection solution B12 vitamin are in satisfactory agreement with data declared by the manufacturer.

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