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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
Sun Jun 12 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Effectiveness of Ombitasvir with Paritaprevir/Ritonavir plus Ribavirin on the Treatment of Naïve Patients with Chronic Hepatitis C Virus Genotype 4
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Background Direct-acting antivirals (DAAs) combination therapies from various mechanisms of action and families have been revolutionized the management landscape of chronic hepatitis C virus (HCV). Ombitasvir, paritaprevir with ritonavir (OBV/PTV/r) ± ribavirin (RBV) is approved to treat HCV genotype 4 (GT4) infection. Here, our objective was to delineate the efficacy and safety of OBV/PTV/r plus RBV in treating of Egyptian naïve patients infected with HCV GT4.

Methods a cohort of 100 Egyptian patients infected with HCV GT4 was allocated and administered orally OBV/PTV/r with RBV. The primary endpoint of our study was a sustained virological response (HCV RNA < 12 IU/mL) 12 weeks after the c

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Publication Date
Sun Mar 01 2020
Journal Name
مجلة العلوم النفسية
Emotional sensitivity in children from the parents' point of view Preparation
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The current research aims to: 1- Identify the emotional sensitivity of children from the parents' point of view. 2- Identifying the differences in the emotional sensitivity of children from the parents ’point of view, according to the parents’ gender variable (father - mother). The basic research sample consisted of (285) male and female students from the sixth grade (primary school), chosen in a randomized stratified method from the districts (Al-Karkh and AlRasafa). While the sample of statistical analysis amounted to (200) father and (200) mothers of male and female students who were randomly selected from the sixth grade of the education directorates (Al-Karkh and Al-Rasafa). The two researchers also used a number of sta

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Publication Date
Fri Jun 30 2017
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Upgrading of Al-Rustamiyah Sewage Treatment Plant Through Experimental and Theoretical Analysis of Membrane Fouling
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Al-Rustamiyah plant is the oldest and biggest sewage treatment plant in Iraq; it locates in the south of Baghdad city. The plant suffers from serious problems associated with overflow and low capacity. The present work aims to upgrade the heart of biological treatment process through suggesting the use of membrane bioreactor; (MBR). In this work, fouling of membrane during sewage treatment has been analyzed experimentally and theoretically by fouling mechanisms. Aeration has been applied in order to control fouling through producing effective diameters of air bubbles close to the membrane walls. Effect of air flow rate on flux decline was investigated. Hermia's models were used to investigate the fouling mechanisms. The results showed th

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Publication Date
Tue Aug 15 2023
Journal Name
Journal Of Economics And Administrative Sciences
Machine Learning Techniques for Analyzing Survival Data of Breast Cancer Patients in Baghdad
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The Machine learning methods, which are one of the most important branches of promising artificial intelligence, have great importance in all sciences such as engineering, medical, and also recently involved widely in statistical sciences and its various branches, including analysis of survival, as it can be considered a new branch used to estimate the survival and was parallel with parametric, nonparametric and semi-parametric methods that are widely used to estimate survival in statistical research. In this paper, the estimate of survival based on medical images of patients with breast cancer who receive their treatment in Iraqi hospitals was discussed. Three algorithms for feature extraction were explained: The first principal compone

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Publication Date
Tue Jan 08 2019
Journal Name
Iraqi Journal Of Physics
Radioactivity and annual effective dose in some types of drug
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The aim of this research is to know danger of radioactive isotopes
that are found in samples of drugs traded in Iraqi markets. The
samples are Iraqi Amoxicillin, English Amoxicillin, UAE
Amoxicillin, Indian Amoxicillin, Iraqi Paracetamol, English
Paracetamol, UAE Paracetamol and Indian Paracetamol. By high
purity germanium the activity of the following isotopes 40K, 214Pb,
228Ac and 137Cs is measured and the specific activity was used to
calculate the annual effective dose. Then the calculated annual
effective dose values are compared with the allowable annual
effective dose values of each part of digestive channel. This research
concluded that the measured annual effective dose values are not
dangerous.<

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Publication Date
Wed Feb 07 2024
Journal Name
Egyptian Journal Of Chemistry
Spectrophotometric Estimation of Methyldopa Drug in pure and pharmaceutical formulations
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Publication Date
Tue Dec 06 2022
Journal Name
Iraqi National Journal Of Nursing Specialties
Quality of Life of Children age from (8- lessthan13) years with Acute Lymphocytic Leukemia Undergoing Chemotherapy at Hematology Center in Medical City
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Objective (s): To assess the QoL of children age from (8- lessthan13) years with acute lymphocytic leukemia undergoing chemotherapy and to find out the relationship between the QoL of children with acute lymphocytic leukemia and their illness history.

Methodology:  A descriptive study included (40) children with acute lymphocytic leukemia who were ranged between (8 - less than 13 years) at the Hematology Center in Medical City for the period from 4th March 2021 to 1st September 2021. The sample was non-probability (purposive) sample of children (male and female). A questionnaire designed with 2 main parts was used. The first part focused on sociodemographic characterist

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Publication Date
Thu Sep 15 2022
Journal Name
Al-academy
Color works in highlighting the functional and aesthetic aspects of interior designs
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Color is one of the most important elements involved and contributing mainly to designs and visual works, whether they are fixed or mobile, for internal spaces through what color gives it the possibilities on the physical and intellectual level, if the process is linked to the functional performance or the aesthetic value, which is thus included within the system of processors and basic works in Designing the interior spaces and highlighting the functional and aesthetic aspects of them through the executed designs that are linked to certain techniques and mechanisms. Therefore, they are processed according to the references and pressure structures or the creation and modern dealing with materials and designs to implement operations in hi

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Publication Date
Sun Jun 11 2017
Journal Name
Al-academy
Processors Functional Design In Public Interior Spaces
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It is general known that any design in various fields such as the interior design in the field of spaces interior for the public and specific buildings that is concern about the use of humans resident , as well as other considerations relating to the organization of design elements and lines of locomotors activity and the validity of appropriate receiving to provide comfort and achieve the requirements of the position in the space of restaurants field of research.
The researcher choose the title of this study (processors design career in public spaces), the analytical study of the spaces of restaurants, as one of the public spaces that are running in their general environment of people in various strata , ages and other levels , whic

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Red flour beetle survival on different food items
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Studied red beetle life on each of the yen and wheat durum wheat, barley, corn, rice, chickpeas, ground peanuts and beans in Living situation constant temperature and relative humidity of 65% for a period of 66 days was the life cycle of the insect different from one substance to another ....

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