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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 Apr 01 2020
Journal Name
Biochemical & Cellular Archives
INVESTIGATION OF VITAMIN D, ESTRADIOL AND C-REACTIVE PROTEIN LEVELS IN PRE AND POST-MENOPAUSAL IRAQI TYPE 2 DIABETES MELLITUS IN WOMEN.
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Diabetes mellitus is a metabolic chronic disease, with global estimation increase in patient (around 100 million in 2030).The aim of the current study is to investigate vitamin D, C-reactive protein and estradiol levels in pre and postmenopausal Iraqi women with type 2 diabetes (T2MD).A total of 176 female distributed into two groups: the first included 90 women withT2MD (43 pre and 47 post-menopausal); the second group included 86 healthy subjects (41 pre and 45 postmenopausal) considered as control. This study has shown that women in premenopausal (20-40 years) had highly significant difference in the estradiol and vitamin D levels in diabetes subjects (62.192 ± 17.643pg/ml, 10.522 ± 1.958ng/ml) compared with healthy (131.793 ± 1

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Publication Date
Sat Apr 01 2017
Journal Name
Diyala Journal For Pure Science
Determination of IL-35, PTH, Ferritin and Other biochemical parameters in sera of Iraqi Men with chronic kidney failure.
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Chronic kidney Failure, a progressive disease, includes both medical and biochemical features that damage kidneys and decrease their abilities to work effectively, this disease is characterized by a chronic disorders to both the innate and adaptive immune systems, generate a complex and not fully understood immune dysfunction. In the present study, (30) men suffering from chronic kidney failure with age in range (40-55) year and (30) healthy men within the same range of age were enrolled in this study. The aim of this study is to highlight the role of immunological aspect (IL-35), hormonal aspects (PTH), some functional proteins and immunological electrolytes in sera of chronic kidney failure (CKF) patients. Biochemical parameters were dete

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Publication Date
Sat Jan 01 2022
Journal Name
Iop Conference Series: Earth And Environmental Science
Residual post fire strength of non-prismatic perforated beams
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Abstract<p>The main aim of this study is to assess the performance and residual strength of post-fire non-prismatic reinforced concrete beams (NPRC) with and without openings. To do this, nine beams were cast and divided into three major groupings. These groups were classified based on the degrees of heating exposure temperature chosen (ambient, 400, and 700°C), with each group containing three non-prismatic beams (solid, 8 trapezoidal openings, and 8 circular openings). Experimentally, given the same beam geometry, increasing burning temperature caused degradation in NPRC beams, which was reflected in increased mid-span deflection throughout the fire exposure period and also residual deflectio</p> ... Show More
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Publication Date
Wed Aug 07 2019
Journal Name
Iraqi National Journal Of Nursing Specialties
Effectiveness of Post-Abortion Family Planning Counseling Program on Nurses and Midwives' Practices in Middle Euphrates Maternity Hospitals
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Objectives: To determine the effectiveness of post-abortion family planning counseling program on nurses and midwives' practices and to predict the variables which may effect on their practices Methodology: A quasi experimental study was conducted from 23th April 2017 to 14th March 2018 in three governorates in Middle Euphrates of Iraq: (Holy Karbala, Al - Najef Al Ashraf and Babylon) on nurses and midwives who work at maternity hospitals. Systematic random sampling was used to select 122 nurses and midwives, (60) of them for study group and (62) for control group. A checklist is an instrument that evaluate the practices which included 50 items. Validity of content was determined through reviewing it by (16) experts and reliability of to

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Publication Date
Sun Aug 06 2023
Journal Name
Karbala International Journal Of Modern Science
Improving the BURT’s Sensitivity using Noise Calibration Unit via Crab Nebula Observations
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Radio observations from astronomical sources like supernovae became one the most important sources of information about the physical properties of those objects. However, such radio observations are affected by various types of noise such as those from sky, background, receiver, and the system itself. Therefore, it is essential to eliminate or reduce these undesired noise from the signals in order to ensure accurate measurements and analysis of radio observations. One of the most commonly used methods for reducing the noise is to use a noise calibrator. In this study, the 3-m Baghdad University Radio Telescope (BURT) has been used to observe crab nebula with and without using a calibration unit in order to investigate its impact on the sign

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Publication Date
Sun Aug 06 2023
Journal Name
Karbala International Journal Of Modern Science
Improving the BURT’s Sensitivity using Noise Calibration Unit via Crab Nebula Observations
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Radio observations from astronomical sources like supernovae became one the most important sources of information about the physical properties of those objects. However, such radio observations are affected by various types of noise such as those from sky, background, receiver, and the system itself. Therefore, it is essential to eliminate or reduce these undesired noise from the signals in order to ensure accurate measurements and analysis of radio observations. One of the most commonly used methods for reducing the noise is to use a noise calibrator. In this study, the 3-m Baghdad University Radio Telescope (BURT) has been used to observe crab nebula with and without using a calibration unit in order to investigate its impact on the sign

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Publication Date
Tue Nov 01 2016
Journal Name
World J. Pharmaceut. Res
Histological study on kidney affected by carbamazepine drug in postnatal rat
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Background: The use of antiepileptic drugs (AEDs) during pregnancy warrants several side effects and also deleterious effects on fetal development, the antiepileptic drugs have potential to affect the fetal development throughout the pregnancy although, the majority of infants born to epileptic pregnant women are normal but more expose to the malformations. Aim: The present study aimed to investigate the effect of carbamazepine drug on the kidney development at day 7 postnatally in the Albino Rat (Rattus rattus) as a mammalian model. Material & Methods: 20 healthy pregnant female rats were divided into two groups, 10 pregnant rats in each group; group one served as control group administrated distal water while group two used as experimenta

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Publication Date
Wed Sep 30 2015
Journal Name
European Journal Of Chemistry
Reaction pathways and transition states of the C-C and C-H bond cleavage in the aromatic pyrenemolecule - A Density Functional study
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The activation and reaction energies of the C-C and C-H bonds cleavage in pyrene molecule are calculated applying the Density Functional Theory and 6-311G Gaussian basis. Different values for the energies result for the different bonds, depending on the location of the bond and the structure of the corresponding transition states. The C-C bond cleavage reactions include H atom migration, in many cases, leading to the formation of CH2 groups and H-C≡C- acetylenic fragments. The activation energy values of the C-C reactions are greater than 190.00 kcal/mol for all bonds, those for the C-H bonds are greater than 160.00 kcal/mol. The reaction energy values for the C-C bonds range between 56.497 to 191.503 kcal/mol. As for the C-H cleavage rea

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Publication Date
Mon Dec 17 2018
Journal Name
Iop Conference Series: Materials Science And Engineering
Differentiation of CD34+ Human Hair Follicle Stem Cells into Functional Melanocytes
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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Heun Method Using to Solve System of NonLinear Functional Differential Equations
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In this paper Heun method has been used to find numerical solution for first order nonlinear functional differential equation. Moreover, this method has been modified in order to treat system of nonlinear functional differential equations .two numerical examples are given for conciliated the results of this method.

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