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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 Jun 21 2025
Journal Name
Journal Of University Of Anbar For Pure Science
Semi – automated analysis for the Nanoscale determination of Chlorpheniramine maleate drug using sodium nitroprusside by continuous flow feed via homemade NAG-SSP Photometer
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This study presents a rapid, sensitive, and straightforward approach to measure chlorpheniramine maleate (CPM) by using turbidity CFIA. The method involves CPM reacting with sodium nitroprusside (Nitropress) to produce a pale white precipitate. The NAG-SSP-5S1D analyzer was used to measure turbidity at 0°–180° angle to detect the attenuation of incident light as a result of collision on the surfaces of the precipitate particles. The linear range of CPM measurements was between 0.008 and 11 m.mol/L, with correlation coefficient of 0.9983 and R2% = 99.65. The limit of detection was determined to be 0.0328 µg/sample from the lowest concentration in the calibration curve, and the repeatability of the method (RSD%) was less than 0.4% (n = 6

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Publication Date
Thu Oct 08 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Comparison of regional bond strength of post space of fiber-reinforced post luted with two types of cements at different testing times
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Back ground: This in vitro study was carried out to investigate the effect of post space regions (coronal, middle and apical), Time and the mode of polymerization (dual, self-cured) of the cements used on the bond strength between translucent fiber post and root dentin by using push-out test. Materials and Methods: Forty eight extracted mandibular first premolars (single root) were instrumented with ProTaper Universal system files (for hand use) and obturated with gutta percha for ProTaper and AH26® root canal sealer following the manufacturer instructions, after 24 hours post space was prepared using FRC postec® plus drills no.3 creating 8 mm depth post space. The prepared samples were randomly divided into two main groups (24 samples ea

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Publication Date
Fri Jan 01 2021
Journal Name
Materials Today: Proceedings
Study of some electronic and spectroscopic properties of ZnO nanostructers by density functional theory
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Publication Date
Tue Nov 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
Proposal of Using Principle of Maximizing Entropy of Generalized Gamma Distribution to Estimate the Survival probabilities of the Population in Iraq
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In this research we been estimated the survival function for data suffer from the disturbances and confusion of Iraq Household Socio-Economic Survey: IHSES II 2012 , to data from a five-year age groups follow the distribution of the Generalized Gamma: GG. It had been used two methods for the purposes of estimating and fitting which is the way the Principle of Maximizing Entropy: POME, and method of booting to nonparametric smoothing function for Kernel, to overcome the mathematical problems plaguing integrals contained in this distribution in particular of the integration of the incomplete gamma function, along with the use of traditional way in which is the Maximum Likelihood: ML. Where the comparison on the basis of the method of the Cen

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Publication Date
Sat May 01 2021
Journal Name
Journal Of Physics: Conference Series
Operational assessment of biological wastewater treatment using advanced return-mass reactors based on principal component cluster analysis
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Abstract<p>In this study, field results data were conducted, implemented in 64 biofilm reactors to analyses extract organic matter nutrients from wastewater through a laboratory level nutrient removal process, biofilm layer moving process using anaerobic aerobic units. The kinetic layer biofilm reactors were continuously operating in Turbo 4BIO for BOD COD with nitrogen phosphorous. The Barakia plant is designed to serve 200,000 resident works on biological treatment through merge two process (activated sludge process, moving bed bio reactio MBBR) with an average wastewater flow of 50,000 m3/day the data were collected annually from 2017-2020. The water samples were analysis in the central labor</p> ... Show More
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Publication Date
Thu Oct 08 2026
Journal Name
Journal Of Physical Education
Consecutive Case Study of Detraining On Some Functional, Physical, Body and Compound Skills Variables In Advance Basketball Players
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Publication Date
Thu Jan 01 2004
Journal Name
Ipmj-iraqi Postgraduate Medical Journal
Changes in alkaline phosphatase activity in rat mammary glands from virgin through pregnancy, lactation and post–lactation
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The aim of this investigation is to study the rote of alkaline phosphatase in mammogenesis and lactogenesis. A total of fortyfemalealbino rats were used and divided according to their physiological states into four groups [ten rats each]. From each deeply ether anesthetized rat, the mammary gland was removed, fixed, quenched in liquid nitrogen and sectioned using SLEE cryostat. The sections were employed for routine haematoxylin and eosin stain and alkaline phosphatase demonstration using the calcium–cobalt method. The obvious finding in the mammary glands of pregnant rat was the presence of thick black rings indicating strong alkaline phosphatase activityaround the basal part of the secretory epithelium of the alveoli. In lactating mamma

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Publication Date
Wed Jan 01 2003
Journal Name
Ipmj-iraqi Postgraduate Medical Journal
Changes in acid phosphatase activity in rat’s mammary tissue from virginity, through pregnancy, lactation and post–lactation
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Purpose: Studying the activity of acid phosphatase, which is the marker of lysosomal activity in the mammary glands of rats at different stages of the physiological maturation [virgih, pregnancy, lactation and Post lactation] Methods: Forty, female, albino rats were used in this study. They were divided into four groups according to their physiological states [virgin, pregnancy, lactation and post lactation]. The mammary glands, after suitable fixation and sectioning, were employed for routine haematoxylin and eosin stain and for acid phosphatase demonstration Results: Acid phosphatase activity was weakly diffuse in the secretory tubules of virgin rats, the diffuse and granular activity of this enzyme was increased during pregnancy in the s

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Publication Date
Tue Oct 02 2018
Journal Name
Iraqi Journal Of Physics
Gas sensitivity properties of TiO2/Ag nanocomposite films prepared by pulse laser deposition
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In this study, a double frequency Q-switching Nd:YAG laser beam (1064 nm and λ= 532 nm, repetition rate 6 Hz and the pulse duration 10ns) have been used, to deposit TiO2 pure and nanocomposites thin films with noble metal (Ag) at various concentration ratios of (0, 10, 20, 30, 40 and 50 wt.%) on glass and p-Si wafer (111) substrates using Pulse Laser Deposition (PLD) technique. Many growth parameters have been considered to specify the optimum condition, namely substrate temperature (300˚C), oxygen pressure (2.8×10-4 mbar), laser energy (700) mJ and the number of laser shots was 400 pulses with thickness of about 170 nm. The surface morphology of the thin films has been studied by using atomic force microscopes (AFM). The Root Mean Sq

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Publication Date
Fri Jul 05 2019
Journal Name
Digest Journal Of Nanomaterials And Biostructures
Improving sensitivity of In2O3 against NO2 toxic gas by loading tin oxide(Article)
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The paper discusses the structural and optical properties of In2O3 and In2O3-SnO2 gas sensor thin films were deposited on glass and silicon substrates and grown by irradiation of assistant microwave on seeded layer nucleated using spin coating technique. The X-ray diffraction revealed a polycrystalline nature of the cubic structure. Atomic Force Microscopy (AFM) used for morphology analysis that shown the grain size of the prepared thin film is less than 100 nm, surface roughness and root mean square for In2O3 where increased after loading SnO2, this addition is a challenge in gas sensing application. Sensitivity of In2O3 thin film against NO2 toxic gas is 35% at 300oC. Sensing properties were improved after adding Tin Oxide (SnO2) to be mo

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