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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
Wed Mar 15 2023
Journal Name
Al-academy
Analysis of the harmonic structure in the musical compositions of the artist Khaleel Ismail
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 The researcher was interested in studying a crucial aspect of the systematic world music culture. He highlights the analysis of the harmonic construction in the musical compositions of the artist Khalil Ismail, where harmony is a significant Western musical science, a pillar of the structure of instrumental and vocal music.
It depends on the compositions of vertical sounds performed simultaneously, as tones coincide and are sometimes dissonant to give sound resonance that enriches musical work and attracts recipients. Hence, the researcher has many questions, including: Can the composition of the writings of the artist Khalil Ismail determine in an objective research framework? Is there a study on this subject in some detail? whic

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Publication Date
Thu Jan 10 2019
Journal Name
Journal Of The College Of Education For Women
Spatial analysis of population growth in the district of Tuz Khurmatu for (1977-2012)
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The study population growth of the most important demographic phenomena upon which planners to meet changes in the size of the population increase is through knowledge of the requirements of population growth can be planned for the future. On this basis, Tuz District was chosen for the study of population growth, which set her period (1977-2012), and compared with the growth of the population of the province and the extent of the variation in population growth, according to the administrative units, has touched search numerical and proportional distribution of the population according to the administrative aspects of the judiciary, as well as environmental distribution.

The elimination of the study population growth dramatically

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Publication Date
Thu Jun 30 2022
Journal Name
Journal Of Economics And Administrative Sciences
Methods of Forecasting Credit Losses in A Sample of Iraqi Banks - A Comparative Analysis
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  The general trend in Iraqi banks is focused towards the application of international financial reporting standards, especially the international financial reporting standard IFRS 9 “Financial Instruments”, in addition to the directives issued on the Central Bank of Iraq’s instructions for the year 2018 regarding the development of expected credit losses models, and not to adhere to a specific method for calculating these losses and authorizing the banks’ departments to adopt the method of calculating losses that suits the nature of the bank’s activity and to be consistent in its use from time to time. The research problem revolves around the different methodologies for calculatin

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Publication Date
Sun Jun 30 2019
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Performance of Subsurface Flow Constructed Wetland Systems in the Treatment of Al-Rustumia Municipal Wastewater using Continuous Loading Feed
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This study aimed at comparing the performance of vertical, horizontal and hybrid subsurface flow systems in secondary treatment for the effluent wastewater from the primary basins at Al-Rustumia wastewater treatment plant, Baghdad, Iraq. The treatments were monitored for six weeks while the testsduration were from 4 to 12 September 2018 under continuous wastewater feeding for chemical oxygen demand (COD), total suspended solid (TSS),ammonia-nitrogen(NH4-N) and phosphate (PO4-P) in comparison with FAO and USEPA standards for effluent discharge to evaluate the suitability of treated water for irrigation purposes. Among the systems planted with Phragmites Australia, the hybrid subsurface flow system which cons

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Publication Date
Thu Dec 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
The relationship between oil revenues and financial sustainability in the Iraq analysis for the period (1990-2013)
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This study aimed to analyze and measure the relationship between oil revenues and financial sustainability in Iraq, the study used the stylistic approach inductive and deductive approach. Accompanied by the use of quantitative and analytical style, which was based on two variables oil revenues and net general budget on annual data covered the period (1990-2013). Among the most important findings of the study contain the time-series variables study on the root of the unit and is not stable in the general level, and become stable after the use of mathematical processors to gain access to a stable by taking the first difference of natural Ogartm of the series. The way (Johnson) to a long-term relationship between oil revenues and ne

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Publication Date
Tue Sep 07 2021
Journal Name
Journal Of Petroleum Exploration And Production Technology
Wellbore instability management using geomechanical modeling and wellbore stability analysis for Zubair shale formation in Southern Iraq
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Abstract<p>Wellbore instability problems cause nonproductive time, especially during drilling operations in the shale formations. These problems include stuck pipe, caving, lost circulation, and the tight hole, requiring more time to treat and therefore additional costs. The extensive hole collapse problem is considered one of the main challenges experienced when drilling in the Zubair shale formation. In turn, it is caused by nonproductive time and increasing well drilling expenditure. In this study, geomechanical modeling was used to determine a suitable mud weight window to overpass these problems and improve drilling performance for well development. Three failure criteria, including Mohr–Coulomb, modifie</p> ... Show More
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Publication Date
Sat Nov 01 2014
Journal Name
Our Dermatology Online
Topical erythromycin-zinc acetate complex lotion versus topical erythromycin gel in treatment of mild to moderate acne vulgaris
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HR Al-Hamamy, KE Sharquie, AA Noaimi, WN Hussein, Our Dermatology Online, 2014 - Cited by 6

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Publication Date
Tue Oct 14 2025
Journal Name
Journal Of Baghdad College Of Dentistry
The effect of ER: YAG laser on enamel resistance to caries during orthodontic treatment: An in vitro study
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Background: One common undesirable side effect of orthodontic treatment with fixed appliances is the development of incipient caries lesions around brackets, particularly in patients with poor oral hygiene. Different methods have been used to prevent demineralization; the recent effort to improve the resistance against the demineralization is by the application of lasers. Materials and method: Thirty human premolars extracted for orthodontic purposes were used to test the effect of two energy level of ER-YAG laser on enamel resistance to demineralization. The brackets were bonded on the teeth and all the labial surface excluding 2 mm area gingival to the brackets were painted with acid resistance varnish. Three groups were generated. The fi

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Publication Date
Thu Feb 15 2024
Journal Name
Al-manhaj Library
Multivariate Analysis (Second Edition)
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This Book is intended to be textbook studied for undergraduate course in multivariate analysis. This book is designed to be used in semester system. In order to achieve the goals of the book, it is divided into the following chapters (as done in the first edition 2019). Chapter One introduces matrix algebra. Chapter Two devotes to Linear Equation System Solution with quadratic forms, Characteristic roots & vectors. Chapter Three discusses Partitioned Matrices and how to get Inverse, Jacobi and Hessian matrices. Chapter Four deals with Multivariate Normal Distribution (MVN). Chapter Five concern with Joint, Marginal and Conditional Normal Distribution, independency and correlations. While the revised new chapters have been added (as the curr

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Publication Date
Sun Sep 01 2019
Journal Name
Al-dhad Book Store
Multivariate Analysis - First Edition
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This Book is intended to be textbook studied for undergraduate course in multivariate analysis. This book is designed to be used in semester system. In order to achieve the goals of the book, it is divided into the following chapters. Chapter One introduces matrix algebra. Chapter Two devotes to Linear Equation System Solution with quadratic forms, Characteristic roots & vectors. Chapter Three discusses Partitioned Matrices and how to get Inverse, Jacobi and Hessian matrices. Chapter Four deals with Multivariate Normal Distribution (MVN). Chapter Five concern with Joint, Marginal and Conditional Normal Distribution, independency and correlations. Many solved examples are intended in this book, in addition to a variety of unsolved relied pro

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