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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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
Wed Jan 02 2008
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Hypolipidemic effect of Silymarin in Dyslipidaemia of Different Etiologies

Background: Many drug and non drug approaches are utilized for the treatment of dyslipidemia; flavonoids, the major constituents of silymarin, have been proved to
positively modify lipoproteins in experimentally – induced dyslipidemia. 
Objective: This study was designed to evaluate the effect of silymarin, when used alone or in combination with other hypolipidemic agents, on the lipid profile in
dyslipidemic patients. 
Patients and Methods: Fifty seven patients with dyslipidaemia of various etiologies are involved in this clinical trial. They are randomized into three groups treated with
either 400mg / day silymarin (gr. A) or 20 mg / day lovastatin (gr. B) or a combination of 200 mg/day si

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Publication Date
Thu Dec 13 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of Adolescents' Quality of life in Hilla City

Objective(s): The present study describes the quality of life (QOL) among adolescents with age of (12-22) year old and identifies factors that may be associated with it. Methodology: A cross-sectional design is carried throughout to evaluate adolescents' quality of life in Hilla City for the period of September 2nd 2016 to November 6th 2016. The present study is conducted in different settings that include schools and colleges in Hilla City. A non-probability "purposive" sample of (144) participant is selected and comprised of (50%) males and (50%) females. An instrument is constructed for the intent of the st

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Publication Date
Fri Jan 05 2024
Journal Name
Al-academy
THE SYSTEM OF SHAPE IN SOME OF PICASSOS CERAMICS

Picasso ceramics represented illuminated sign in ceramic art and excelled in accord ceramic art dimension aesthetically, and put it in a new prospects, despite the simplicity of the forms turn into a magical images and multiple interpretations.
So the search deliberately to choose purposive (37) samples divided into four groups, as follows: -
A flat shapes / palets or saucers / the vases /modified vases .
benefiting from indicators were spawned from literature ,to analyzing samples within the totals for the identification systems act forming art work`s:-
(1)Picasso's ceramic work product of a deliberate process represented a capacity of technical experience, and formal
(2)The system configuration in the ceramic art works c

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Publication Date
Thu Jan 10 2019
Journal Name
Journal Of The College Of Education For Women
Types of parallelism in the poetry of Mahmoud Darwish

This research deals with the study of types of parallelism in contemporary Arabic poetry and took the hair Mahmoud Darwish, a model for the study has been the goal of research to clarify the term parallelism and the statement of the most important types, said evidence of that in the poetry of Mahmoud Darwish

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Publication Date
Fri Mar 30 2001
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
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Publication Date
Mon Dec 01 2008
Journal Name
Political Sciences Journal
The role of Japan in the reconstruction of Iraq

The Role of Japan in the Reconstruction of Iraq 

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Publication Date
Mon Apr 01 2019
Journal Name
Journal Of Legal Sciences
The Role of motive in the criminalization of terrorism

The roll of motive in the legal model of terrorist crimes. It's important to define the roll of motives in modern criminal policy as whole and terrorist crimes in specific Motives are important mental elements regarding the criminals, criminalization, deterrent, and criminal charges.

Modern terrorist crimes are national and international immediate and dangerous threat to individuals lives, properties, and their Holly believes. Terrorists acts aimed to spreading fears, and desperation in hearts of persons and social institutions in order to enforce ideological system. This is explaining legislative attention toward Terrorists motives in the construction of criminal intent. Motives is the core of any Effective criminal justice syst

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Publication Date
Tue Nov 30 2021
Journal Name
Research Journal Of Pharmacy And Technology
Effect of Palliative Radiotherapy in controlling pain of Malignancy

Background: Radiation therapy reported to be an effective in palliating pain. Objective: To describe roles of palliative radiotherapy in controlling pain in metastatic cancerous patients, and evaluation of radio-therapy doses in pain management. Methods: A prospective observational study carried out at the Baghdad Radiotherapy and Nuclear Medicine Center/Baghdad Medical City Complex, Baghdad, Iraq, from 1st of December 2018 to 30th of May 2019. 88 Patients, were included. Patients were assessed before applying radiotherapy, and at the end of treatment. Pain scoring used from 0 to 10. Kaplan Meier survival curve used. Result: The mean±SD of age was 55.44±11.1 years, and the most frequent age group was 41-50years as 37(42.1%). Breas

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Publication Date
Mon Jan 21 2019
Journal Name
International Journal Of Pharmaceutical Quality Assurance
Genetic Assessment of Antibiotic Resistance in Salmonella Enteric a Serovar Typhi in Kirkuk Province

Around fifty isolates of Salmonella enterica serovar Typhi were isolated from blood specimens of patients referring to several hospitals in Kirkuk province, Iraq. The results revealed that all isolates developed resistance to trimethoprim-sulfamethoxazole and chloramphenicol. However, neither sul2 nor tem genes were detected. Moreover, only ten isolates were positive for catP. Our data suggested participation of other genes or mechanisms allow these multidrug isolates to resist the antibiotics in question.

Publication Date
Mon Aug 01 2016
Journal Name
Journal Of Engineering
Prediction of Monthly Fluoride Content in Tigris River using SARIMA Model in R Software

The need to create the optimal water quality management process has motivated researchers to pursue prediction modeling development. One of the widely important forecasting models is the sessional autoregressive integrated moving average (SARIMA) model. In the present study, a SARIMA model was developed in R software to fit a time series data of monthly fluoride content collected from six stations on Tigris River for the period from 2004 to 2014. The adequate SARIMA model that has the least Akaike's information criterion (AIC) and mean squared error (MSE) was found to be SARIMA (2,0,0) (0,1,1). The model parameters were identified and diagnosed to derive the forecasting equations at each selected location. The correlation coefficien

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