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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 Feb 18 2022
Journal Name
Journal Of Blood Medicine
Circulating miR-126-3p and miR-423-5p Expression in de novo Adult Acute Myeloid Leukemia: Correlations with Response to Induction Therapy and the 2-Year Overall Survival
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Abstract Background: Acute myeloid leukemia (AML) results from sequential genetic alterations in a normal hematopoietic stem cell or its progenitors giving rise to an autonomous clone that dominates the bone marrow leading to marrow failure. MicroRNAs are short non-coding nucleic acid sequences that regulate post-transcriptional gene expression by base-pairing with their target mRNAs. MiRNAs can be secreted into extracellular fluids and carried to target cells by vesicles or bound to proteins. Intracellular and circulating miRNAs are believed to be useful markers in the diagnosis, prognosis, and treatment of various cancers. Practically, circulating miRNAs are more stable at room temperatures and extreme conditions. Purpose: This study aim

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Publication Date
Sun Dec 25 2022
Journal Name
International Journal Of Drug Delivery Technology
Effect of Zinc drug on amino acid concentration in liver of white mice, Mus musculus
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Zinc is one of the essential trace elements, it plays a key role in many biochemical and functional processes. It is less harmful than many other minerals, in the case of exposure to high doses of zinc, poisoning occurs, and this poisoning may mostly result from the accidental ingestion of household products containing zinc or nutritional supplements, this study was conducted to find out the effects of zinc on the concentration of amino acid. A total of 30 adult white mouse males were taken and divided into three groups; the first group (control) of 10 mice taken with distilled water for 30 days, the second group includes 10 mice that were dose with Zn drug concentration of 50 mg/kg/day for 30 days, the third group includes 10 mice that wer

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Publication Date
Tue Feb 01 2022
Journal Name
Baghdad Science Journal
Study the Inhibition Effect of Amoxicillin Drug for Corrosion of Carbon Steel in Saline Media
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          Potentiostatic polarization and weight loss methods have been used to investigate the corrosion behavior of carbon steel in sodium chloride solution at different concentrations (0.1, 0.4 and 0.6) M under the influence of temperatures ( 293, 298, 303, 308 and 313) K. The inhibition efficiency of the amoxicillin drug on carbon steel in 0.6 M NaCl has also been studied based on concentration and temperature. The corrosion rate showed that all salt concentrations ( NaCl solution) resulted in corrosion of carbon steel in varying ratio and 0.6 M of salt solution  was the highest rate (50.46 g/m².d). The results also indicate that the rate of corrosion increases at a temperature of 313 K.. Potentiodynamic polarization studi

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Publication Date
Sun Jun 05 2016
Journal Name
Baghdad Science Journal
The formation, structure, and electronic properties of Lansoprazol drug and cucurbit [7]urils complex (Theoretical Study)
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The current study deals with host-guest complex formation between cucurbit [7] urils as host and lansoprazole as guesti using PM3 (semi empirical molecules orbital calculations) also DFT calculations. In this complex, the formation of hydrogen bonding may be occurred through portal oxygen atoms(O2) of cucurbit [7] urils and amine groups (NH 2 )of the drug. The energies of HOMO and LUMO orbital’s have been computed for the host guest complex and its components. The result of the stabilization energy explained a complex formation.

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Publication Date
Fri Nov 01 2013
Journal Name
Journal Of Engineering
Strengthening and Closing Cracks for Existing reinforced Concrete Girders Using External Post-Tensioning
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Publication Date
Thu Apr 18 2024
Journal Name
Eximia Journal
Forecasts some of functional indicators nervous system for dribbling skills in young basketball players from Baghdad Governorate
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The research study is important since it establishes predicted rates for various nervous system functional indicators.In terms of performing the skill of Dribbling in basketball for young players in Baghdad Governorate in order to reach scientific results that serve researchers, coaches, and players uniformly. The study's goal is to create predictive equations for specific functional indicators of the nervous system in relation to the Dribbling skill performance of young basketball players in Baghdad Governorate. The researchers used a descriptive approach with a survey method on (8) youth basketball league clubs in Baghdad Governorate for the 2022-2023 sports season, totaling (96) players . Three tests were used to measure the nervous sy

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Publication Date
Mon Feb 08 2021
Journal Name
Public Works Management &amp; Policy
Causes of Problems in Post-Disaster Emergency Re-Construction Projects—Iraq as a Case Study
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This study examines the causes of time delays and cost overruns in a selection of thirty post-disaster reconstruction projects in Iraq. Although delay factors have been studied in many countries and contexts, little data exists from countries under the conditions characterizing Iraq during the last 10-15 years. A case study approach was used, with thirty construction projects of different types and sizes selected from the Baghdad region. Project data was gathered from a survey which was used to build statistical relationships between time and cost delay ratios and delay factors in post disaster projects. The most important delay factors identified were contractor failure, redesigning of designs/plans and change orders, security is

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Publication Date
Mon Mar 07 2022
Journal Name
Journal Of Educational And Psychological Researches
The Impact of Cognitive Behavior Program Based on Meichenbaum Theory in Reducing the Negative Emotional Sensitivity among the Intermediate Stage Students
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The aim of this research is to construct a cognitive behavior program based on the theory of Meichenbaum in reducing the emotional sensitivity among Intermediate school students. To achieve the aims of the research, two hypotheses were formulated and the experimental design with equal groups was chosen. The population of research and its sample are determined. The test of negative emotional sensitivity, which is constructed by the researcher, was adopted. The test contains (20) items proved validity and reliability as a reliable test by presenting it to a group of arbitrators and experts in education and psychology. An educational program is constructed based on the theory of Meichenbaum. The test was applied to a sample of (60) second i

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Publication Date
Tue Jan 01 2019
Journal Name
Therapeutic Advances In Drug Safety
Deferasirox in thalassemia: a comparative study between an innovator drug and its copy among a sample of Iraqi patients
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Background:

The health care industry is witnessing an increasing trend in the use of generic medicines because of their presumed low cost compared with innovator medicines. The aim of this study was to determine and compare the performance of the copy drug Osveral®and its innovator drug deferasirox (Exjade®).

Methods:

A prospective observational study including 223 patients receiving the branded medicine Exjade®and 101 patients receiving the copy Osveral®was carried out. Data were assessed for a 1-year period and included clinical symptoms, serum ferrit

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Publication Date
Sun Jun 05 2016
Journal Name
Baghdad Science Journal
Development of an Eco-Friendly Method for Iron Extraction and Determination in Pharmaceuticals Using Ciprofloxacin Drug as Chelating agent
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A method is developed for the determination of iron (III) in pharmaceutical preparations by coupling cloud point extraction (CPE) and UV-Vis spectrophotometry. The method is based on the reaction of Fe(III) with excess drug ciprofloxacin (CIPRO) in dilute H2SO4, forming a hydrophobic Fe(III)- CIPRO complex which can be extracted into a non-ionic surfactant Triton X-114, and iron ions are determined spectrophotometrically at absorption maximum of 437 nm. Several variables which impact on the extraction and determination of Fe (III) are optimized in order to maximize the extraction efficiency and improve the sensitivity of the method. The interferences study is also considered to check the accuracy of the procedure. The results hav

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