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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 Nov 30 2024
Journal Name
The Journal Of Infection In Developing Countries
Hematological profile among cutaneous leishmaniasis patients before and after treatment with sodium stibogluconate in Diyala, Iraq
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Introduction: Cutaneous leishmaniasis (CL) is a common protozoan disease in Iraq characterized by localized ulcers, primarily on exposed skin. This study aimed to investigate the hematological parameters of infected patients using a complete blood count (CBC) in the endemic area of Diyala Governorate, northeast of Baghdad. This has been studied in newly diagnosed, untreated individuals and patients receiving sodium antimony gluconate. Methodology: Hematological screening was performed on blood samples from 161 patients with microscopically diagnosed cutaneous leishmaniasis before and after treatment. Anti-Leishmania IgG was also assessed by ELISA in seropositive and seronegative subjects. Results: The newly diagnosed, untreated pati

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Publication Date
Thu Jun 15 2017
Journal Name
Journal Of Baghdad College Of Dentistry
Dental caries and treatment needs in relation to nutritional status among children with congenital heart disease
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Background: Congenital heart disease is one of the most common developmental anomalies in children. These patients commonly have poor oral health that increase caries risk. Dental management of children with congenital heart disease requires special attention, because of their heightened susceptibility to infectious endocarditis. The aims of this study were to assess the severity of dental caries of primary and permanent teeth and treatment needs in relation to nutritional indicator (Body Mass Index) among children with congenital heart disease. Materials and Methods: In this case-control study, case group consisted of 399 patients aged between 6-12 years old with congenital heart disease were examined for dental status in Ibn Al-Bitar spec

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Publication Date
Tue Dec 16 2008
Journal Name
Journal Of Planner And Development
City of Baghdad Analysis of the mechanisms of economic action in the development and development
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The economy of a city has an important role not only in its establishment but also in its development. This is quite clear in the city of Baghdad throughout its history since its building in 762 A.D. In addition, most of its problems that the city is suffering from are basically related to not giving enough importance to the economic factors in the master planning of Baghdad since 1950’s. This may explain the failiars of master plans in dealing with the actual population growth and the city's inability to absorb such increases and interrelated and diverse activities which are negatively reflected on the economic variables particularly the effect on the land values, and the strong competitions amongst the land uses without previ

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Publication Date
Thu Sep 01 2022
Journal Name
Https://www.researchgate.net/journal/university-of-baghdad-engineering-journal-1726-4073
Hazard analysis in drinking water plant
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Source, sedimentation, coagulation, flocculation, filter, and tank are parts of a water treatment plant. As a result, some issues threaten the process and affect the drinking water quality, which is required to provide clean drinking water according to special standards and international and local specifications, determined by laboratory results from physical, chemical, and biological tests. In order to keep the water safe for drinking, it is necessary to analyze the risks and assess the pollution that occurs in every part of the plant. The method is carried out in a common way, which is monitoring through laboratory tests, and it is among the standards of the global and local health regulators

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Publication Date
Thu Sep 01 2022
Journal Name
Journal Of Engineering
Hazard analysis in drinking water plant
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Source, sedimentation, coagulation, flocculation, filter, and tank are parts of a water treatment plant. As a result, some issues threaten the process and affect the drinking water quality, which is required to provide clean drinking water according to special standards and international and local specifications, determined by laboratory results from physical, chemical, and biological tests. In order to keep the water safe for drinking, it is necessary to analyze the risks and assess the pollution that occurs in every part of the plant. The method is carried out in a common way, which is monitoring through laboratory tests, and it is among the standards of the global and local health regulators

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Publication Date
Sun Apr 04 2010
Journal Name
Journal Of Educational And Psychological Researches
The effect of two treatment methods in the gaining of fourth grade students in geography object.
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research aim :
- The research aimed to investigate the effect of two treatment
methods in the gaining of fourth grade students in geography
object.
- Research hypothesis
 there are no statistically significant differences at the level of ( 0.05 )
in the average level of achievement in geography between the first
experimental group ( strengthening lessons ) and the second group
( re- teaching )
 no individual differences statically significant at the level of ( 0.05 )
in the average level achievement in geography object of the second
experimental group ( re- teaching ) and the first experimental group
( strengthening lesson )
 the research sample : the researcher selected randomly Baghdad

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Publication Date
Tue Jun 01 2021
Journal Name
Https://www.researchgate.net/journal/iop-conference-series-materials-science-and-engineering-1757-899x
Application of multivariate statistical techniques in the evaluation of large-scale water treatment plants in Baghdad.
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Abstract<p>This paper aims to evaluate large-scale water treatment plants’ performance and demonstrate that it can produce high-level effluent water. Raw water and treated water parameters of a large monitoring databank from 2016 to 2019, from eight water treatment plants located at different parts in Baghdad city, were analyzed using nonparametric and multivariate statistical tools such as principal component analysis (PCA) and hierarchical cluster analysis (HCA). The plants are Al-Karkh, Sharq-Dijlah, Al-Wathba, Al-Qadisiya Al-Karama, Al-Dora, Al-Rasheed, Al-Wehda. PCA extracted six factors as the most significant water quality parameters that can be used to evaluate the variation in drinkin</p> ... Show More
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Publication Date
Wed Jan 01 2020
Journal Name
Plant Archives
An analysis for adoption of subsurface irrigation technology and its role in agricultural development in Iraq
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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
The study of some physical and chemical characteristics in drinking water treatment plant of Jurf Al- Sakar subdestric in Babylon governorate, Iraq
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Some physical and chemical characteristics of Jurf Al- Sakar drinking water plant in Babylon governorate have been studied. Seven locations for this plant were selected. These were the drinking water treatment plant source on Euphrates River before entering the plant, precipitation, filtration and collection tanks, and also after leaving the plant at distances of one meter, 4 and 8 km. The samples were collected bimonthly from October, 2002 to August, 2003. Some results match with the national and international standard characters while the other characters (Turbidity, total hardness, calcium, nitrate, phosphate and the biological oxygen demand values) were not match. The present study showed that drinking water treatment plant is undrinka

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Publication Date
Mon Jul 15 2019
Journal Name
Journal Of Pharmaceutical And Biological Sciences
Analysis of genome variation in CEs of meningococcal isolates
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Important points were concluded from this analysis related with the presence of the same variable CEs within multiple isolates with different time points being under the selection and the location of SNPs within the conserved functional pattern of CEs. In the 40 isolates, 9 out of 39 variable CEs conducted with multiple isolates

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