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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 Sep 01 2019
Journal Name
Baghdad Science Journal
Detection a New Antiseptic Resistant Variant of qac Gene in Some Multi Drug Resistant Staphylococcus aureus Isolated from Different Clinical Sources
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The increasing use of antiseptic compounds creates selective pressure cause emergence of antiseptic resistance among Staphylococcus aureus .Resistance mechanism of antiseptic is driven mainly by multi drug resistant (MDR) efflux protein.Sixty five isolates of S.aureuswere collected from different clinical sources and subjected to 11 antibiotics most of them are recognized by efflux systems as extruded substrates. Range of efflux activity was estimated using cartwheel method. Simultaneous discrimination of antiseptic coding genes (qacA/B, smr and norA)as well as nuc and mecA genes among multidrug resistantS.aureus(MRSA) isolates was preformed using multiplex PCR assay

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Publication Date
Wed Dec 07 2022
Journal Name
في مجلة الدراسات الللغوية والترجمية
Semantic and cultural analysis of phraseological units with the names of wild animals in Russian and Arabic
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Summary:This article discusses the topic of phraseological units with the names of wild animals in the Russian and Arabic languages in the aspect of their comparative semantic and cultural analysis, since a comparative analysis of the meanings of phraseological units of the Arabic and Russian languages, detection of coincidences and differences in the compared languages, is an important method for studying linguoculturology, since phraseological units represent a reflection of culture in the language

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Publication Date
Thu Apr 02 2020
Journal Name
Iop Conference Series: Materials Science And Engineering
The effects of additives in to heat treatment temperature and time on the crystallinity of lithium silicate glass-ceramic
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Publication Date
Sun Apr 30 2023
Journal Name
Al-kindy College Medical Journal
Persistent Intraocular Pressure Elevation after Silicon Oil Removal in Patients with Post-Pars Plana Vitrectomy: IOP Level After SO Removal
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Background: It is well-known that silicon oil (SO) injection into the vitreous cavity after pars plana vitrectomy is usually associated with high intraocular pressure.

Objectives: To determine the influence of silicon oil (SO) removal on IOP level after pars plana vitrectomy for spontaneous rhegmatogenous retinal detachment (RRD)

Subjects and Methods: A prospective study was conducted at Ibn Al-Haitham eye teaching hospital, Baghdad- Iraq. Intraocular pressure (IOP) was measured pre and post SO removal in patients who have underwent retinal detachment surgery with SO injection of 1000 centistokes (cSt) viscosity. Baseline IOP was measured for all the patient before the SO

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Publication Date
Sun Jun 07 2009
Journal Name
Baghdad Science Journal
A New Spectrophotometric Method for Analysis of Allopurinol in Aqueous Solutions and Pharmaceutical Preparations
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A new method for determination of allopurinol in microgram level depending on its ability to reduce the yellow absorption spectrum of (I-3) at maximum wavelength ( ?max 350nm) . The optimum conditions such as "concentration of reactant materials , time of sitting and order of addition were studied to get a high sensitivity ( ? = 27229 l.mole-1.cm-1) sandal sensitivity : 0.0053 µg cm-2 ,with wide range of calibration curve ( 1 – 9 µg.ml-1 ) good stability (more then24 hr.) and repeatability ( RSD % : 2.1 -2.6 % ) , the Recovery % : ( 98.17 – 100.5 % ) , the Erel % ( 0.50 -1.83 % ) and the interference's of Xanthine , Cystein , Creatinine , Urea and the Glucose in 20 , 40 , 60 fold of analyate were also studied .

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Publication Date
Thu Oct 01 2015
Journal Name
Journal Of Economics And Administrative Sciences
Analysis of the causal relationship between agricultural imports and some economic variables in Iraq
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Foreign trade receives a good deal of economists' attention for its active contribution to economic growth, and imports of goods and services that could not be produced locally constitute an important share of the local economy.  Agricultural imports constitute an important share of the total imports due to their role in fulfilling the needs of local markets; however, the agricultural sector in Iraq contributes no more than a limited share of the country's need, which has encouraged the import of a variety of fruits, vegetables and strategic crops and different types of red and white meat. For the sake of identifying the factors affecting the demand on agricultural imports in Iraq, the following factors has been analyzed: th

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Publication Date
Fri Nov 01 2019
Journal Name
Advances In Intelligent Systems And Computing
Analysis of the Relationship Between Traffic Accidents with Human and Physical Factors in Iraq
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Publication Date
Thu Mar 17 2016
Journal Name
International Journal Of Computer Applications
Analysis of Wind Speed Data and Annual Energy Potential at Three locations in Iraq
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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
Mon Oct 06 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Dental fluorosis, dental caries, and treatment needs in Al-Muthana'a governorate among 12 years old students
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Background: A case-control study design revealeda relationship between the present of fluoride, and the reduction of dental caries and the increase prevalence and severity of dental fluorosis .The aim of this study was to assess the prevalence and severity of dental caries in relation to dental fluorosis among school children in Al-Muthana'a Governorate. Materials and methods: It was conducted among primary school students aged 12 years old, the age was taken according to the criteria of World Health Organization (1997) (1).The number of students was selected in each sector of control group according to number of schools in that sector .Sectors of control group which depend on water of river as source of drinking water. Case group which inc

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