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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 Jan 01 2021
Journal Name
International Journal Of Agricultural And Statistical Sciences
DYNAMIC MODELING OF TIME-VARYING ESTIMATION FOR DISCRETE SURVIVAL ANALYSIS FOR DIALYSIS PATIENTS IN BASRAH, IRAQ
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Survival analysis is widely applied to data that described by the length of time until the occurrence of an event under interest such as death or other important events. The purpose of this paper is to use the dynamic methodology which provides a flexible method, especially in the analysis of discrete survival time, to estimate the effect of covariate variables through time in the survival analysis on dialysis patients with kidney failure until death occurs. Where the estimations process is completely based on the Bayes approach by using two estimation methods: the maximum A Posterior (MAP) involved with Iteratively Weighted Kalman Filter Smoothing (IWKFS) and in combination with the Expectation Maximization (EM) algorithm. While the other

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Publication Date
Sat Aug 31 2019
Journal Name
Iraqi Journal Of Physics
Investigation the effect of post deposition thermal treatment on properties P3HT and P3HT:PCBM blend.
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  This work reports the study of heat treatment effect on the structural, morphological, optical and electrical properties of poly [3-hexylthiophene] and its blend with [6,6]-phenyl C61 butyric acid methyl ester ( P3HT:PC61BM). X-ray diffraction (XRD) measurements show that the crystallinity of the films increased with annealing. The evaluation of surface roughness and morphology was investigated using atomic force microscope (AFM), and field emission scanning microscope(FESEM). The optical properties were emphasized a strong optical absorption of P3HT compared with the blend. Hall effect measurement was used to study the electrical properties which revealed there is an increase in the electrical conductivity and Hall mobility of th

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Publication Date
Tue Jan 01 2019
Journal Name
Journal Of Clinical And Diagnostic Research
Thiopurine S-Methyltransferase Polymorphism in Iraqi Paediatric Patients with Acute Lymphoblastic Leukaemia
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Publication Date
Thu Apr 18 2019
Journal Name
Al-kindy College Medical Journal
Correlation of Serum Lipoproteins with the Activity of Acute Lymphoblastic Leukaemia
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Background: the activity of acute lymphoblastic leukemia had been observed to correlate with levels of serum lipoproteins

Objective: to evaluate the correlation of serum levels of different types of lipoproteins with activity of the disease in patients with acute lymphoblastic leukemia.

Type of the study: A prospective study.

Methods: A study included patients diagnosed as acute lymphoblastic leukemia, their serum levels of lipoproteins at time of diagnosis, and on relapse were obtained for comparison.

Results: there is significant inverse correlation of activity of acute lymphoblastic leukemia with serum total cholesterol

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Publication Date
Mon May 20 2019
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Effect of Metformin and Glimepiride Treatment on Some Biochemical Parameters in Diabetic Male Patients with Chronic Renal Failure
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The present study was included a measurements of fasting serum glucose, total protein, potassium, and calcium levels in the sera of 25 diabetic male patients suffer from chronic renal failure; their ages range were (32-75) and compared them with 25 healthy males as control group. The aim of this study was to study the effects of antidiabetic drugs on some biochemical parameters such as fasting serum glucose, serum total protein, serum potassium and calcium. The current results demonstrated a hyperkalemia in patients and this increasing of potassium is significantly (p = 0.03), but calcium level showed no significant variations ( p>0.05 ), and serum total protein was significantly decreased in patients as compared to t

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Publication Date
Sun Nov 01 2015
Journal Name
Journal Of Dentistry
New functional and aesthetic composite materials used as an alternative to traditional post materials for the restoration of endodontically treated teeth
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Objectives To tailor composites of polyethylene–hydroxyapatite to function as a new intracanal post for the restoration of endodontically treated teeth (ETT). Methods Silanated hydroxyapatite (HA) and zirconium dioxide (ZrO2) filled low-density polyethylene (LDPE) composites were fabricated by a melt extrusion process and characterised using infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). The flexural strength and modulus were determined in dry state and post ageing in simulated body fluid and fractured surfaces analysed by SEM. The water uptake and radiographic appearance of the experimental composites were also measured and compared with a commercially known endodontic fibre

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Publication Date
Sun Sep 06 2009
Journal Name
Baghdad Science Journal
Estimation of cellular immune response by evaluation of some cytokines in immunopathogenesis of chronic hepatitis B and C pre- and post- treated Iraqi patients (in vivo and in vitro)
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Two groups of chronic hepatitis B and C virus patients were divided into Pre-treated patients (25 CHB patients with positive HBs Ag for more than 6 months and 40 CHC patients), and post-treated patients [12 CHB patients (4, 6, and 2 were treated with lamivudine, IFN-? and combination of LMV + IFN-? respectively), and 27 patients for CHC (3, 13 and 11 patients were treated with Ribavirin, IFN-? and combination therapy (RBV+ IFN-?) respectively].These patients were followed up for 6 months. By using ELISA technique, levels of IL-6, IL-10, IFN-? and TNF-? were measured in vivo and in vitro (supernatant of PBMCs stimulated with PHA) and compared with healthy control. The mean level of IL-6, IL-10 and TNF-? in CHB patients showed significant dif

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Publication Date
Tue Feb 27 2018
Journal Name
Pharmaceutics
Ocular Drug Delivery Barriers—Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases
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Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barr

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Publication Date
Mon Jan 01 2024
Journal Name
Optical Materials
Design and analysis of a high sensitivity open microchannel PCF-based surface plasmon resonance refractometric sensor
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Publication Date
Sun Jan 01 2023
Journal Name
The Egyptian Journal Of Hospital Medicine
Association of Microrna-153-3p Expression in Response to Treatment with Imatinib in Patients with Chronic Myeloid Leukemia
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The study aimed to establish the association of miR-153-3p expression with treatment response to IM in CML patients. Sixty CML patients were included and divided into two groups consistent with their response to treatment whether sensitive or resistant to IM. Ten healthy normal participants were enrolled as control group. RNA was extracted from serum to work out miR-153-3p expression utilizing real-time quantitative reverse transcription polymerase chain reaction. The primers were supplied by Macrogen Inc. Twenty seven patients were sensitive to imatinib and 33 were resistant to imatinib. The ratio of male to female was 1.14:1. The bulk (58%) of patients were within the age range of 41-60 years. Weight and gender did not significantly diffe

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