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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
Journal Of Engineering
Removal of Methyl Orange from Aqueous Solutions by Adsorption Using Corn Leaves as Adsorbent Material
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A comparative study was done on the adsorption of methyl orange dye (MO) using non-activated and activated corn leaves with hydrochloric acid as an adsorbent material. Scanning electron microscopy (SEM) and Fourier Transform Infrared spectroscopy (FTIR) were utilized to specify the properties of adsorbent material. The effect of several variables (pH, initial dye concentration, temperature, amount of adsorbent and contact time) on the removal efficiency was studied and the results indicated that the adsorption efficiency increases with the increase in the concentration of dye, adsorbent dosage and contact time, while inversely proportional to the increase in pH and temperature for both the treated and untreated corn leaves. The equi

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Publication Date
Tue Jan 01 2019
Journal Name
Energy Procedia
Studying the effect of adding buffer gases to CO2 gas on the electron transport parameter
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Publication Date
Wed Apr 25 2018
Journal Name
Earthquake And Structures
Response of circular footing on dry dense sand to impact load with different embedment depths
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Publication Date
Sat Apr 01 2023
Journal Name
Baghdad Science Journal
Characterization of a novel pathway for xanthene degradation by the engineered strain Sphingobium yanoikuyae B1DR
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Polyaromatic hydrocarbons (PAHs) are a group of aromatic compounds that contain at least two rings. These compounds are found naturally in petroleum products and are considered the most prevalent pollutants in the environment. The lack of microorganism capable of degrading some PAHs led to their accumulation in the environment which usually causes major health problems as many of these compounds are known carcinogens. Xanthene is one of the small PAHs which has three rings. Many xanthene derivatives are useful dyes that are used for dyeing wood and cosmetic articles. However, several studies have illustrated that these compounds have toxic and carcinogenic effects. The first step of the bacterial degradation of xanthene is conducted by d

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Publication Date
Fri Mar 31 2017
Journal Name
Al-khwarizmi Engineering Journal
Active Vibration Suppression of Smart Cantilever Beam with Sliding Mode Observer Using Two Piezoelectric Patches
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This paper presents a vibration suppression control design of cantilever beam using two piezoelectric ‎patches. One patch was used as ‎an actuator element, while the other was used as a sensor. The controller design was designed via the balance realization reduction method to elect the reduced order model that is most controllable and observable. ‎the sliding mode observer was designed to estimate six states from the reduced order model but three states are only used in the control law. Estimating a number of states larger than that used is in order to increase the estimation accuracy. Moreover, the state ‎estimation error is proved bounded. An ‎optimal LQR controller is designed then using the ‎estimated states with the slid

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Publication Date
Mon Dec 01 2025
Journal Name
Case Studies In Construction Materials
Optimized stress-strain modeling of eco-friendly fiber-reinforced concrete members using meta-heuristic algorithms
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Eco-friendly concrete is produced using the waste of many industries. It reduces the fears concerning energy utilization, raw materials, and mass-produced cost of common concrete. Several stress-strain models documented in the literature can be utilized to estimate the ultimate strength of concrete components reinforced with fibers. Unfortunately, there is a lack of data on how non-metallic fibers, such as polypropylene (PP), affect the properties of concrete, especially eco-friendly concrete. This study presents a novel approach to modeling the stress-strain behavior of eco-friendly polypropylene fiber-reinforced concrete (PFRC) using meta-heuristic particle swarm optimization (PSO) employing 26 PFRC various mixtures. The cement was partia

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Publication Date
Wed Apr 01 2026
Journal Name
Case Studies In Construction Materials
Performance Evaluation of Modified Hard-Grade Asphalt Binder Using Waste PVC Derived from Flex Banners
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Hard-grade asphalt binders, such as AC 20–30, offer excellent resistance to permanent deformation but are inherently brittle, making them highly susceptible to fatigue and low-temperature cracking. While polymer modification addresses these issues, virgin polymers remain expensive. Despite the growing interest in recycled plastics, the rheological impact of complex waste streams, specifically polyvinyl chloride (PVC) derived from flex banners containing plasticizers, on excessively stiff binders within the complete Superpave Performance Grading (PG) framework remains critically underexplored. This study introduces a novel valorization approach by utilizing solvent-extracted flex banner waste (WPVC) as a dual-action modifier. It leverages

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Publication Date
Thu Sep 15 2022
Journal Name
Journal Of Baghdad College Of Dentistry
Immunohistochemical evaluation for integrin binding sialoprotein on healing process of intrabony defect treated by bone sialoprotein
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Background: Bone defect healing is a multidimensional procedure with an overlapping timeline that involves the regeneration of bone tissue. Due to bone's ability to regenerate, the vast majority of bone abnormalities can be restored intuitively under the right physiological conditions. The goal of this study is to examine the immunohistochemistry of bone sialoprotein in order to determine the effect of local application of bone sialoprotein on the healing of a rat tibia generated bone defect. Materials and Methods: In this experiment, 48 albino male rats weighing 300-400 grams and aged 6-8 months will be employed under controlled temperature, drinking, and food consumption settings. The animals will be subjected to a surgical procedure o

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Publication Date
Wed Apr 01 2015
Journal Name
((المؤتمر العلمي الدولي لجمعية صيانة المصادر الوراثية والبيئية العراقية ((مؤتمر الوراثة والبيئة الثالث
Ecofriendly Synthesis Of Silver Nanoparticles By Naringe Leaf Extract, Study The Antimicrobial Activityal Against Pathogenic Bacteria
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Publication Date
Mon Mar 30 2020
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Adsorptive Desulfurization of Iraqi Heavy Naphtha Using Different Metals over Nano Y Zeolite on Carbon Nanotube
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The present research was conducted to reduce the sulfur content of Iraqi heavy naphtha by adsorption using different metals oxides over Y-Zeolite. The Y-Zeolite was synthesized by a sol-gel technique. The average size of zeolite was 92.39 nm, surface area 558 m2/g, and pore volume 0.231 cm3/g. The metals of nickel, zinc, and copper were dispersed by an impregnation method to prepare Ni/HY, Zn/HY, Cu/HY, and Ni + Zn /HY catalysts for desulfurization. The adsorptive desulfurization was carried out in a batch mode at different operating conditions such as mixing time (10,15,30,60, and 600 min) and catalyst dosage (0.2,0.4,0.6,0.8,1, and 1.2 g). The most of the sulfur compounds were removed at 10 min for all catalyst ty

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