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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 Nov 20 2024
Journal Name
Journal Of Baghdad College Of Dentistry
Orthodontic considerations of functional occlusion in Class І normal occlusion

Background: The therapeutic goal of orthodontic treatment is to establish ideal occlusion which includes both static and functional aspects. The objective of this study was to clarify functional occlusal treatment goals by analyzing functional occlusion in subjects with established normal occlusion and identify the differences between canine protected occlusion and group function occlusion. Materials and Methods: The sample consisted of 62 subjects with normal occlusion and with an age range of (18-25 years).Functional occlusal contacts during lateral excursion were identified on a fully adjustable articulator, and then the samples were classified according to: 1) Type of functional occlusion: A) Canine protected occlusion group (canine pr

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Publication Date
Wed Apr 01 2015
Journal Name
Al–bahith Al–a'alami
The Functional Construction of Advertisements in the Iraqi Press Websites

Communication and media technologies have seen several changes in the last two decades. These changes put the basis for the emergence of communicative and media practices on several levels including political, economic, technological and artistic. And these, in turn, led to the emergence of new media trends and phenomena in various areas of media worthily to be studied and researched for example online advertisings.                                                                                          Online advert

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Publication Date
Tue Dec 30 2008
Journal Name
Al-kindy College Medical Journal
The Sensitivity and Specificity of Oral Tumors and Premalignant Lesions Diagnosis by Otolaryngologists

Background: Tumors of the oral cavity are under
estimated in general dental and medical practice,
some authors describe it as the forgetting disease,
others wondering if the attention paid to this disease
compared to its fatality (The 5-year survival rate is
about 50%) is enough for disease control? However;
this disease deserves a comprehensive assessment by
all dental and medical fields assumed to examine the
oral cavity regularly, especially otolaryngologist.
Objectives: To find out the sensitivity and specificity
of clinical examination in diagnosing oral tumors and
premalignant conditions by otolaryngologist.
Methods: Across sectional retrospective study was
conducted in the:
-study design:

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Publication Date
Tue Oct 02 2018
Journal Name
Iraqi Journal Of Physics
Sensitivity of Ce doped CuO for NO2 gas

In this work the structural, optical and sensitive properties of Cerium - Copper oxide thin film prepared on silicon and glass substrate by the spray pyrolysis technique at a temperature of (200, 250, 300 °C). The results of (XRD) showed that all the prepared films were of a polycrystalline installation and monoclinic crystal structure with a preferable directions was (111) of CuO. Optical characteristics observed that the absorption coefficient has values for all the prepared CuO: Ce% (104 cm-1) in the visible spectrum, indicating that all the thin films prepared have a direct energy gap. Been fabrication of gas sensors of (CuO: Ce %) within optimum preparation conditions and study sensitivity properties were examined her exposed to ni

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Publication Date
Tue Feb 14 2023
Journal Name
Journal Of Educational And Psychological Researches
Logical Intelligence and its Relationship to the Sensitivity of Sensory Processing of Students in Distinguished Schools

Abstract

The research aims to identify the logical intelligence of distinguished students and to identify the extent of the contribution of the fields of logical intelligence to the sensitivity of students' sensory processing in distinguished schools. The research sample consisted of (400) male and female students selected by the stratified random method with the proportional method. The scale that was prepared according to the theoretical framework and the adopted theory was applied after being subject to the psychometric properties of validity and reliability, Logical thinking (observation, interpretation, mathematical and arithmetic operations) contributed to sensory processing. The results showed that disting

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Publication Date
Sat Nov 28 2020
Journal Name
Iraqi Journal Of Science
Non Bayesian estimation for survival and hazard function of weighted Rayleigh distribution (b)

In this paper, we proposed a new class of Weighted Rayleigh Distribution based on two parameters, one is scale parameter and the other is shape parameter which introduced in Rayleigh distribution. The main properties of this class are derived and investigated in . The moment method and maximum likelihood method are used to obtain estimators of parameters, survival function and hazard function. Real data sets are collected to investigate two methods which depend it in this study. A comparison was made between two methods of estimation.

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Publication Date
Sun Feb 03 2019
Journal Name
Journal Of The College Of Education For Women
The builds and functional relations Between the peopolitics and strategy

The geopolities considering as build from the basies builds of the polities
geography, participating in appointing the military geography, and submit to it
geo-polities purveyed, playing important role to appointing the builds relations
between the high strategy and the military strategy, while the foreign polities of
the state, which considering as a tool for the state outside it environment and
borders playing the role of the performance and the functional works to the
peaceful or hostile reaction according to the geopolities purveyed which
participating in amassing the recourse for the economical, political, social,
military and technology strategies and activating it to achieving the state interests
and obj

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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

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
Fri Sep 01 2023
Journal Name
Civil Engineering Journal
Fundamental Challenges and Management Opportunities in Post Disaster Reconstruction Project

The study examines the root causes of delays that the project manager is unable to resolve or how the decision-maker can identify the best opportunities to get over these obstacles by considering the project constraints defined as the project triangle (cost, time, and quality) in post-disaster reconstruction projects to review the real challenges to overcome these obstacles. The methodology relied on the exploratory description and qualitative data examined. 43 valid questionnaires were distributed to qualified experienced engineers. A list of 49 factors causes was collected from previous international and local studies. A Relative Important Index (RII) is adapted to determine the level of importance of each sub-criterion in the fou

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Publication Date
Sun May 30 2021
Journal Name
Iraqi Journal Of Science
In Vivo and In Vitro Study of the Genetic Effects of Cabergoline Drug

This study aimed to stand on genetic effects important of cabergoline drug. This toxic effect was evaluated for three different doses (0.05, 0.1, 0.5 mg/ml) in comparison with control (PBS/ phosphate buffer saline) both in vivo and in vitro. In vivo study involved the cytogenetic evaluation of cabergoline in mice by examination of mitotic index percentage (MI), micronucleus formation (MN) and chromosomal aberrations. Result indicated that all the tested doses cause significant reduction in MI percentage, while significant rise was seen with both MN formation and all studied chromosomal aberrations. While in vitro study involved measuring the effect of cabergoline on normal cell line (REF/ Rat embryonic

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