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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
Sat Jan 01 2022
Journal Name
Journal Of Pharmaceutical Negative Results
CD49d and CD26 in chronic lymphocytic leukemia: their correlation with clinical Binet staging and clinical parameters
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The study aimed to assess the expression of CD49d and CD26 in newly diagnosed CLL patients and find their correlation with clinical Binet stage, and other clinical parameters. This study was conducted on 51 newly diagnosed CLL patients based on lymphocyte count > 5×109/L and immunophenotyping. The expression of CD49d, and CD26 were investigated using eight-color flow cytometer. The expression of CD49d and CD26 were detected in 56.9 %, 68.8 % of CLL patients, respectively. The correlation between CD49d expression and CD26 expression was statistically significant (p < 0.001) with high concordance rate between them. The positive expression of both CD49d and CD26 had statistically significant association with clinical Binet staging (p < 0.001,

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Publication Date
Sat Jun 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
NONPARAMETRIC And Semiparametric Bayesian Estimators in survival function analysis
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 Most statistical research generally relies on the study of the behaviour of different phenomena during specific time periods and the use of the results of these studies in the development of appropriate recommendations and decision-making and for the purpose of statistical inference on the parameters of the statistical distribution of life times in  The technical staff of most of the manufacturers in the research units of these companies deals with censored data, the main objective of the study of survival is the need to provide information that is the basis for decision making and must clarify the problem and then the goals and limitations of this study and that  It may have different possibilities to perform the

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Publication Date
Tue Apr 20 2021
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Parametric Models in Survival Analysis for Lung Cancer Patients
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    The aim of this study is to estimate the survival function for the data of lung cancer patients, using parametric methods (Weibull, Gumbel, exponential and log-logistic).

Comparisons between the proposed estimation method have been performed using statistical indicator Akaike information Criterion, Akaike information criterion corrected and Bayesian information Criterion, concluding that the survival function for the lung cancer by using Gumbel distribution model is the best. The expected values of the survival function of all estimation methods that are proposed in this study have been decreasing gradually with increasing failure times for lung cancer patients, which means that there is an opposite relationshi

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Publication Date
Mon Jul 27 2020
Journal Name
Water
Groundwater Flow-Modeling and Sensitivity Analysis in a Hyper Arid Region
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Groundwater modelling is particularly challenging in arid regions where limited water recharge is available. A fault zone will add a significant challenge to the modelling process. The Western Desert in Iraq has been chosen to implement the modelling concept and calculate the model sensitivity to the changes in aquifer hydraulic properties and calibration by researching 102 observations and irrigation wells. MODFLOW-NWT, which is a Newtonian formulation for MODFLOW-2005 approaches, have been used in this study. Further, the simulation run has been implemented using the Upstream-Weighting package (UPW) to treat the dry cells. The results show sensitivity to the change of the Kx value for the major groundwater discharge flow. Only abo

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Publication Date
Sun Jan 01 2017
Journal Name
Statistical Applications In Genetics And Molecular Biology
Mixture model-based association analysis with case-control data in genome wide association studies
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Abstract<p>Multilocus haplotype analysis of candidate variants with genome wide association studies (GWAS) data may provide evidence of association with disease, even when the individual loci themselves do not. Unfortunately, when a large number of candidate variants are investigated, identifying risk haplotypes can be very difficult. To meet the challenge, a number of approaches have been put forward in recent years. However, most of them are not directly linked to the disease-penetrances of haplotypes and thus may not be efficient. To fill this gap, we propose a mixture model-based approach for detecting risk haplotypes. Under the mixture model, haplotypes are clustered directly according to their estimated d</p> ... Show More
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Publication Date
Thu Jun 01 2017
Journal Name
Journal Of The College Of Languages (jcl)
Formal and Functional Perspectives in the Analysis of Hyperboles in Obama's Speeches
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     Hyperbole is an obvious and intentional exaggeration in the sense that it takes things to such an extreme that the audience goes too far and then pulls itself back to a more reasonable position, i.e. it is an extravagant statement or figure of speech not intended to be taken literally. This paper focuses on the formal and functional perspectives in the analysis of hyperbole which American candidates produce in their speeches in electoral campaigns, for it is hypothesized that candidates in their electoral campaigns use hyperbolic expressions excessively to persuade voters of the objectives of their electoral campaign programs. Hence, it aims to analyze hyperbole in context to determine the range of pragmatic func

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Publication Date
Sun Jul 02 2017
Journal Name
Journal Of Educational And Psychological Researches
Down Syndrome causes, symptoms, and most important methods of functional treatment
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This study is descriptive and theory of Dawn syndrome as the problem of research lies in the need to identify the identification of the causes of Dawn syndrome and its symptoms and methods of dealing with it, which has become a problem that needs treatment, especially after the numbers have become high in Iraq, which has not yet taken the necessary importance for treatment and care.

The objectives of the research were summarized in the identification of the most important causes of Dawn syndrome and its symptoms and diagnosis and ways or methods of dealing with people with Dawn syndrome in order to develop therapeutic plans for him.

       

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Publication Date
Fri Feb 02 2024
Journal Name
Iraqi Journal Of Science
Using Sensitivity Analysis in Linear Programming with Practical Physical Applications
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Linear programming currently occupies a prominent position in various fields and has wide applications, as its importance lies in being a means of studying the behavior of a large number of systems as well. It is also the simplest and easiest type of models that can be created to address industrial, commercial, military and other dilemmas. Through which to obtain the optimal quantitative value. In this research, we dealt with the post optimality solution, or what is known as sensitivity analysis, using the principle of shadow prices. The scientific solution to any problem is not a complete solution once the optimal solution is reached. Any change in the values of the model constants or what is known as the inputs of the model that will chan

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Publication Date
Sun Feb 10 2019
Journal Name
Iraqi National Journal Of Nursing Specialties
Functional Performance For Patients Post Heart's Valves Replacement at Cardiac Surgery Centers in Baghdad City
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Abstract
Objectives: The study is carried out to assess functional performance for heart's valve replacement patients and find out relationship with sociodemographic data and clinical data
Methodology: Descriptive design is carried out at cardiac surgery centers in Baghdad ; Ibn -Al Betar Specialized for cardiac surgery center and Al-Iraqi center for cardiac disease. its initiation from December28the 2013 to September 1st 2014,A non- probability (purposive) sample of 50 adults patients are attended cardiac surgery centers at Baghdad city and who have heart valves replacement. The data collection through development of questionnaire which is composed from three parts(socio demographic data, clinical information, functional performa

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Publication Date
Wed Jan 01 2020
Journal Name
Indian Journal Of Forensic Medicine And Toxicology
Mouse hepatocellular carcinoma sensitivity to cisplatin and docetaxel and analysis of related proteins
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