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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
Mon Apr 01 2019
Journal Name
Biochemical & Cellular Archives
The impact of follicular fluid growth differentiation factor 8 levels on IVF /ICSI outcomes
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Clinical index is needed to predict the outcome of pregnancy after in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) for infertile patients. Growth differentiation factor-8 (GDF-8), also known as myostatin, is one of transforming growth factor-â superfamily localized in antral follicles in normal and PCOS ovaries but its function in female reproductive system is still unknown. Aim of the study is to assess the correlation between levels of GDF8 in follicular fluid (FF) with outcomes of in vitro fertilization (IVF/ICSI) in women with and without PCOS. A prospective case control study was performed enrolling (40) patients with PCOS and (40) non-PCOS women (male infertility) undergoing IVF/ICSI. The collect

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Publication Date
Wed Apr 30 2025
Journal Name
Iraqi Journal Of Science
Calculating the Variation of the Universal Parameter (Variable) Using Kepler's Equation for Different Orbits
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Stumpff functions are an infinite series that depends on the value of z. This value results from multiplying the reciprocal semi-major axis with a universal anomaly. The purpose from those functions is to calculate the variation of the universal parameter (variable) using Kepler's equation for different orbits. In this paper, each range for the reciprocal of the semi-major axis, universal anomaly, and z is calculated in order to study the behavior of Stumpff functions C(z) and S(z). The results showed that when z grew, Stumpff functions for hyperbola, parabola, and elliptical orbits were also growing. They intersected and had a tendency towards zero for both hyperbola and parabola orbits, but for elliptical orbits, Stumpff functions

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Publication Date
Mon Aug 04 2025
Journal Name
Al-rafidain Journal Of Medical Sciences ( Issn 2789-3219 )
Exploring the Current Situation of Cancer Patients’ Management from Physicians’ Perspective: A qualitative Study
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Background: Cancer is rising as a significant global public health concern. The global cancer burden is escalating, exerting considerable physical, emotional, and financial strain on people, families, communities, and healthcare systems. Objective: To explore the challenges faced in cancer management from the perspectives of physicians. Methods: A qualitative study was conducted between November 2024 and February 2025. Physicians were recruited from three different centers in Baghdad and Karbala using purposive and snowball sampling. The data collection was concluded upon reaching a saturation point. Results: This study included twenty-six oncologists. There was about parity between the two genders, with a slight male predominance.

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Publication Date
Wed Jun 27 2018
Journal Name
Journal Of The College Of Education For Women
The Referential Aspect of the Quranic Text Az-Zahraa’s)Peace Be Upon Her( Speech
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In the present paper, the researcher attempts to shed some light on the objective behind inserting some Qur'anic verses by Al-Zahraa (Peace Be Upon Her) in her revered speech. Besides, it tries to investigate the hidden meaning of these verses and to study them in the light of pragmaticreferences. This task is supported by Books of Tafseer as well as the books that explained this speech to arrive at its intended meaning. It is possible say that this is astep towards studying speeches of 'Ahlul Bayt' (People of the Prophet's household) in terms of modern linguistic studies, as well as employing modern methods to explore the aesthetic values of these texts.

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Publication Date
Mon Jan 01 2024
Journal Name
International Journal Of Hydrogen Energy
Modeling of electrocatalytic hydrogen evolution via high voltage alkaline electrolyzer with different nano-electrocatalysts
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Publication Date
Thu Dec 01 2022
Journal Name
Structural Concrete
Enhancement of RC T‐beams toughness using laced stirrups reinforcement for blast response predictions
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Publication Date
Wed Sep 01 2021
Journal Name
Iraqi Journal Of Physics
The Thermal Properties of Gliding arc Plasma Produced by Laboratory Reverse Vortex Flow System
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A low-cost reverse flow plasma system powered by argon gas pumping was built using homemade materials in this paper. The length of the resulting arc change was directly proportional to the flow rate, while using the thermal camera to examine the thermal intensity distribution and demonstrating that it is concentrated in the centre, away from the walls at various flow rates, the resulting arc's spectra were also measured. The results show that as the gas flow rate increased, so did the ambient temperature. The results show that the medium containing the arc has a maximum temperature of 34.1 ˚C at a flow rate of 14 L/min and a minimum temperature of 22.6 ˚C at a flow rate of 6 L/min.

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Publication Date
Mon Feb 04 2019
Journal Name
Iraqi Journal Of Physics
Microscopic study of nuclear structure for some Si-isotopes using Skyrme-Hartree-Fock-method
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In this paper the nuclear structure of some of Si-isotopes namely, 28,32,36,40Si have been studied by calculating the static ground state properties of these isotopes such as charge, proton, neutron and mass densities together with their associated rms radii, neutron skin thicknesses, binding energies, and charge form factors. In performing these investigations, the Skyrme-Hartree-Fock method has been used with different parameterizations; SkM*, S1, S3, SkM, and SkX. The effects of these different parameterizations on the above mentioned properties of the selected isotopes have also been studied so as to specify which of these parameterizations achieves the best agreement between calculated and experimental data. It can be ded

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Publication Date
Sun Jun 01 2025
Journal Name
Iop Conference Series: Earth And Environmental Science
Study the Impact of Soil Texture on Subsurface Trickle Irrigation Shifting towards Sustainable Sources
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Abstract<p>One of the most effective systems for managing water is subsurface trickle irrigation. Finding empirical formulas and studying the effect of soil texture are the main purposes of this paper. In order to reach an ideal irrigation system as a modern technique to save water, especially in arid regions, soil textures of loam, silt, and silt loam were studied on a subsurface trickle irrigation system by utilizing HYDRUS/2D. The trickle system is usually operated at low pressure, in this paper the used pressure is 30 cm with an emitter buried at 10, 15, and 20 cm at different diameters. Patterns of wetting fronts in both directions at various times depending on soil texture are gathered to </p> ... Show More
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Publication Date
Fri Dec 01 2023
Journal Name
Case Studies In Chemical And Environmental Engineering
Kinetic modeling of a solar photo-electro-Fenton process for treating petroleum refinery wastewater
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