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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
Fri Sep 01 2017
Journal Name
International Journal Of Science And Research
Analysis of Correlation between Mesiodistal width of the Maxillary and Mandibular Anterior and Posterior Teeth for Both Genders in Iraqi Population
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Abstract: Choosing suitable artificial teeth for partially edentulous patients and arranging these teeth in a way to look natural is difficult. An important factor in dentures construction is the mesiodistal width of anterior teeth, because a denture would not appearance natural if artificial teeth are of incorrect size. While for a successful orthodontic treatment, mesiodeistal width of teeth is important for space analysis and for establishing proper occlusion. The aim of this study is to determine the correlation between the average mesiodistal width of anterior and posterior teeth in male and female Iraqi population. 40 Iraqi subjects with normal occlusion participated in this study. Mesiodistal measurement of all teeth was carried out

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Publication Date
Wed Jun 01 2022
Journal Name
Journal Of The College Of Languages (jcl)
The Role of Gender and Culture in Dealing with the Arab Woman's Issues Embodied in Caricatures: A Cognitive Linguistic Analysis
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Gender and culture are among the factors that influence the process of understanding and interpreting different types of communication, especially images. The current study, which is a part of a master’s thesis, aims at investigating the role of gender and culture in interpreting and understanding the caricatures that deal with women’s issues in Arab societies. To this end, the researchers adopted Barthes’ (1957) concepts of denotation and connotation in his theory of mythologies in addition to Langacker’s (1987) theory of (Domains). The research concludes that the female subjects have better cognitive abilities in investing the signs within the selected caricatures. The other factor the study reached to is that the respondents

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Publication Date
Sat Jul 22 2023
Journal Name
Journal Of Engineering
Fatigue Analysis of Hip Prosthesis
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The present work covers the analytical design process of three dimensional (3-D) hip joint prosthesis with numerical fatigue stress analysis. The analytical generation equations describing the different stem constructive parts (ball, neck, tour, cone, lower ball) have been presented to reform the stem model in a mathematical feature. The generated surface has been introduced to FE solver (Ansys version 11) in order to simulate the induced dynamic stresses and investigate the effect of every design parameter (ball radius, angle of neck, radius of neck, neck ratio, main tour radius, and outer tour radius) on the max. equivalent stresses for hip prosthesis made from titanium alloy. The dynamic loading case has been studied to a stumbling ca

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Publication Date
Mon Apr 08 2024
Journal Name
Fifth International Conference On Applied Sciences: Icas2023
Bifurcation analysis of the role of good and bad bacteria in the decomposing toxins in the intestine with the impact of antibiotic and probiotics supplement
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This study presents a mathematical model describing the interaction of gut bacteria in the participation of probiotics and antibiotics, assuming that some good bacteria become harmful through mutations due to antibiotic exposure. The qualitative analysis exposes twelve equilibrium points, such as a good-bacteria equilibrium, a bad-bacteria equilibrium, and a coexisting endemic equilibrium in which both bacteria exist while being exposed to antibiotics. The theory of the Sotomayor theorem is applied to study the local bifurcation around all possible equilibrium points. It’s noticed that the transcritical and saddle-node bifurcation could occur near some of the system’s equilibrium points, while pitchfork bifurcation cannot be accrued at

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Publication Date
Fri Nov 01 2013
Journal Name
American Journal Of Dermatology And Venereology
Topical Adapalene 0.1% Gel versus Topical Combination of (Tretinoin 0.025% and Erythromycin 4%) Gel in Treatment of AcneVulgaris (A Split Face Comparative Study)
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HR Al-Hamamy, AA Noaimi, HA Salman, NAA Jabbar, American Journal of Dermatology and Venereology, 2013

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Publication Date
Tue Dec 01 2015
Journal Name
Journal Of Engineering
Experimental Evaluation Use of Semifluidized Bed Adsorber for the Treatment of P-chlorophenol and O-cresol in Wastewater using Activated Carbon as Adsorbent
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In the present work the performance of semifluidized bed adsorber was evaluated for removal of phenolic compound from wastewater using commercial activated carbon as adsorbent. P-chlorophenol (4-Chlorophenol) and o-cresol (2-methylphenol) was selected as a phenolic compound for that purpose. The phenols percent removal, in term of breakthrough curves were studied as affected by hydrodynamics limitations which include minimum and maximum semifluidization velocities and packed bed formation in the column by varying various parameters such as inlet liquid superficial velocity (from Uminsf to 8Uminsf m/s), and retaining grid (sometimes referred to as adsorbent loading) to initial static bed height ratio (from 3-4.5). In

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
The role of sialic acid in the immune response of patients with acute leukemia Almufaawi the subject and is on treatment Alkamiawi this
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The focus of this research revolves around the importance level of sialic acid in the reasoning of cases, including tumors and then evaluate the patient's response to treatment and its impact on the immune response there are a lot of evidence showing that parts Alkrbu ???????? in peptides sugary and glycoproteins play an important role in Alfalitin life and responsiveness

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Publication Date
Thu Jun 27 2024
Journal Name
Iraqi Journal Of Pharmaceutical Sciences
Synthesis, Characterization and Anticancer Activity of Chitosan Schiff Base / PEG Blend Doped with Gold and Silver Nanoparticles in Treatment of Breast Cancer Cell Line MCF-7
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In the present study, chitosan Schiff base has been prepared from chitosan reaction with p-chloro benzaldehyde. The AuNPs and AgNPs were manufactured by extract of onion peels as a reducing agent. The AuNPs and AgNPs that have been synthesized were characterized through UV-vis spectroscopy, XRD analyses and SEM microscopy. The polymer blends of the chitosan / PEG has been prepared by using the approach of solution casting. Chitosan Schiff base / PEG Au and Ag nanocomposites were synthesized, nanocomposites and polymer blends have been characterized by FTIR which confirm the formation of Schiff base by revealing a new band of absorption at 1693 cm-1 as a result of the (C=N) imine group. FESEM, DSC and TGA confirm the thermal stability

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Publication Date
Wed Nov 08 2023
Journal Name
Technologies And Materials For Renewable Energy, Environment, And Sustainability: Tmrees23fr
Analysis of x-ray diffraction lines of cuprous oxide nanoparticles by using variance analysis method
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In this study, the results of x-ray diffraction methods were used to determine the Crystallite size and Lattice strain of Cu2O nanoparticles then to compare the results obtained by using variance analysis method, Scherrer method and Williamson-Hall method. The results of these methods of the same powder which is cuprous oxide, using equations during the determination the crystallite size and lattice strain, It was found that the results obtained the values of the crystallite size (28.302nm) and the lattice strain (0.03541) of the variance analysis method respectively and for the Williamson-Hall method were the results of the crystallite size (21.678nm) and lattice strain (0.00317) respectively, and Scherrer method which gives the value of c

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Publication Date
Tue Mar 01 2016
Journal Name
Journal Of Natural Sciences Research
Spectrophotometric-Assisted Chemometric Method for the Simultaneous Analysis of Furosemide, Carbamazepine, Diazepam, and Carvedilol in Their Bulk and Marketed Formulation
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Simultaneous determination of Furosemide, Carbamazepine, Diazepam, and Carvedilol in bulk and pharmaceutical formulation using the partial least squares regression (PLS-1 and PLS-2) is described in this study. The two methods were successfully applied to estimate the four drugs in their quaternary mixture using UV spectral data of 84synthetic mixtures in the range of 200-350nm with the intervals Δλ=0.5nm. The linear concentration range were 1-20 μg.mL-1 for all, with correlation coefficient (R2) and root mean squares error for the calibration (RMSE) for FURO, CARB, DIAZ, and CARV were 0.9996, 0.9998, 0.9997, 0.9997, and 0.1128, 0.1292, 0.1868,0.1562 respectively for PLS-1, and for PLS-2 were 0.9995, 0.9999, 0.9997, 0.9998, and 0.1127, 0.

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