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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
Sun Mar 31 2024
Journal Name
Iraqi Geological Journal
Permeability Prediction and Facies Distribution for Yamama Reservoir in Faihaa Oil Field: Role of Machine Learning and Cluster Analysis Approach
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Empirical and statistical methodologies have been established to acquire accurate permeability identification and reservoir characterization, based on the rock type and reservoir performance. The identification of rock facies is usually done by either using core analysis to visually interpret lithofacies or indirectly based on well-log data. The use of well-log data for traditional facies prediction is characterized by uncertainties and can be time-consuming, particularly when working with large datasets. Thus, Machine Learning can be used to predict patterns more efficiently when applied to large data. Taking into account the electrofacies distribution, this work was conducted to predict permeability for the four wells, FH1, FH2, F

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Publication Date
Tue Aug 15 2023
Journal Name
Journal Of Economics And Administrative Sciences
Relationship Analysis Between Monetary Policy and Financial Sustainability in Iraq For the Period 2015–2021
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This research aims to study and analyze the reality of monetary policy and financial sustainability in Iraq through either a descriptive or analytical approach by trying to link and coordinate between monetary policy and fiscal policy to enhance economic sustainability. The research is based on the hypothesis that the monetary policy of Iraq contributes to achieving financial stability, which improves economic sustainability by providing aid and assistance to the state to reduce the budget deficit and exacerbate indebtedness. The author used the monetary policy indicators, the re-deduction of Treasury transfers by the central bank and the money supply, and financial sustainability indicators, including the public debt indicators and the

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Publication Date
Fri Mar 27 2020
Journal Name
Solid State Technology
Seepage and Slope Stability Analysis for Hemrin Earth Dam in Iraq Using Geo-Studio Software
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Publication Date
Wed Jun 01 2016
Journal Name
Journal Of Engineering
Seismic Effects and Static Analysis for the Artificial Damped Outrigger Systems in Tall R.C Buildings
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This paper studies the combination fluid viscous dampers in the outrigger system to add supplementary damping into the structure, which purpose to remove the dependability of the structure to lower variable intrinsic damping. It works by connecting the central core, comprising either shear walls or braced frames, to the outer perimeter columns.

     The modal considered is a 36 storey square high rise reinforced concrete building. By constructing a discrete lumped mass model, and using frequency-based response function, two systems of dampers, parallel and series systems are studied. The maximum lateral load at the top of the building is calculated, and  this load  w

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Publication Date
Tue Dec 01 2015
Journal Name
Journal Of Economics And Administrative Sciences
Analysis of some of the success factors and product strategies Applied Research in the industrial sector of the Iraqi
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This research deals with the study of the relationship between the success factors as the independent variable and product strategies as the dependent variable , has reacted to these variables to form the frame , which is the research which centered research problem about the extent to which industrial companies the vision and knowledge of Muslim women survive and develop in the business market , which can be expressed about the extent of awareness of corporate success factors and the use of product strategies and what the relationship between the factors and strategies , while expressing the importance of research to make the focus on the product occupies a paramount importance in the industrial sector companies in relation to t

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Publication Date
Tue Jan 01 2019
Journal Name
Izvestiya Of Saratov University. New Series. Series: Philology. Journalism
To the Question of Internal Inflection of the Roots in Arabic and Russian (Inflected Analysis of the Root Structure)
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Publication Date
Fri Apr 01 2016
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Arthroscopic micro fracture and intra articular whole bone marrow injection for the treatment of articular cartilage lesions in the knee joint. Authors
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Abstract Background: Articular cartilage lesions in the knee joint are frequently seen,its treatment represents a challenge for orthopedic surgeons especially in young age patients and if left untreated,then they can progress to advanced osteoarthritis that may affect the functional status of the patients.Many treatment modalities had developed for these lesions, in the current study arthroscopic micro fracture plus intra articular whole bone marrow(WBM) injection was used as modality of treating these lesions. Objectives: to assess the effectiveness of arthroscopic micro fracture plus WBM intra articular injection as a treatment modality for knee articular cartilage lesions. Patients and Methods : a prospective experimental study was perf

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Publication Date
Sun Dec 02 2012
Journal Name
Baghdad Science Journal
Effect of magnetic treatment of irrigation water and seed on some vegetative characteristics and production of black seed "Nigella sativa
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Seeds of Nigella sativa were sown in containers containing 15kg Loamy soil. The seeds were divided before sewing into two groups. The first group was soaked with ordinary tap water end the second group was treated with magnetized water for 24hrs. The irrigation process was completed until 75% of capacity field with two types of water (tap water of magnetized water with three replications).The magnetized water was obtained from special electric device designed for this purposeRecorded measurements (plants height, the number of branches/ plant, dry weight ofplant, number of flowers, 1000 seed weight) during the harvest period.Results indicated that the seed group which was treated with magnetized water was more significant than the one which

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Publication Date
Thu Jan 31 2019
Journal Name
Journal Of The College Of Education For Women
The Quantitative Analysis for Road networks in Karbala Governorate
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The road networks is considered to be one of the determinants that controls to specify the areas of human activities, which it depend on to specify the arrival cost , in addition it is useful to achieve the connectivity for interaction and human activities , and shorten the distance and time between the population and places of service. The density of the road network in any space directly affected by the density of population and the type of economic activities and administrative functions performed by the space. On this basis, the subject of this study is reflected in the quantitative analysis of the roads network in the Governorate of Karbala. The study consists the quantitative analysis for the roads network and the Urban Nodes in th

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Publication Date
Thu Jun 01 2023
Journal Name
Iraqi Journal Of Physics
Geomorphological Analysis Methodologies for Houran Valley Basin in Iraq
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Extracting, studying and interpreting the morphological database of a basin is a basic building block for building a correct geomorphological understanding of this basin. In this work, Arc GIS 10.8 software and SRTM DEM satellite images were used. The principle of data integration was adopted by extracting the quantitative values of the morphometric characteristics that are affected by the geomorphological condition of the studied basin, then eliciting an optimal conception of the geomorphological condition of the basin from the meanings and connotations of these combined transactions. Hypsometric integration was extracted for each region in the basin separately with the value of integration of the plot curve for the relative heights of

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