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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
Mon Jan 01 2018
Journal Name
The Analyst
A luminescent europium complex for wide-range pH sensors and sensor microtiterplates
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Luminescent sensor membranes and sensor microplates are presented for continuous or high-throughput wide-range measurement of pH based on a europium probe.

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Publication Date
Fri Jul 01 2022
Journal Name
Structures
Reliability analysis of deteriorated post-tensioned concrete bridges: The case study of Ynys-y-Gwas bridge in UK
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Concrete structures are exposed to aggressive environmental conditions that lead to corrosion of the embedded reinforcement and pre-stressing steel. Consequently, the safety of concrete structures may be compromised, and this requires a significant budgets to repair and maintain critical infrastructure. Prediction of structural safety can lead to significant reductions in maintenance costs by maximizing the impact of investments. The aim of this paper is to establish a framework to assess the reliability of existing post-tensioned concrete bridges. A time-dependent reliability analysis of an existing post-tensioned involving the assessment of Ynys-y-Gwas bridge has been presented in this study. The main cause of failure of this bridge was c

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Publication Date
Tue Mar 20 2018
Journal Name
Day 3 Thu, March 22, 2018
Southern Iraqi Oil Fields Drilling Problems Identification, Analysis, and Treatment
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Abstract<p>Multiple drilling problems are being faced continuously while drilling wells in the southern Iraqi oil fields. Many of which are handled poorly and inefficiently which yields longer non-productive time due to the lack of knowledge about the source of these problems. This study aims to investigate the Basra oil fields formations from Faris to Mishrif, diagnose the potential problems, and present the optimum treatment for each problem.</p><p>Gathering of field data and previous studies on the subject, in addition to the field experience of drilling supervisors were all the information bases of this study. Southern Iraqi oil fields were studied and analyzed care</p> ... Show More
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Publication Date
Thu Mar 25 2021
Journal Name
Dental Materials Journal
Mechanical and thermal stress evaluation of PEEK prefabricated post with different head design in endodontically treated tooth: 3D-finite element analysis
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Publication Date
Tue Feb 27 2024
Journal Name
Pharmacia
Association of the rs1801133 and rs1801131 polymorphisms in the MTHFR gene and the adverse drug reaction of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients
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Background: Methotrexate is one of the mainstays for treating rheumatoid arthritis (RA) with a wide range of adverse drug reactions, however, it’s the relationship between adverse drug reactions and genetic polymorphism remains to be highlighted, and there is a lack of studies concerning Arabic Iraqi population regarding this aspect.

Objective: Evaluate the association between genetic mutations in the MTHFR gene in SNPs (rs1801133G&gt;A and rs1801131T&gt;G) on the adverse drug reaction for RA Iraqi patients.

Methods: An observational study, that involved 95 Iraqi RA patients with established RA. Patien

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Publication Date
Mon Jun 30 2014
Journal Name
Al-kindy College Medical Journal
The prevalence and antimicrobial sensitivity of Esbl Escherichia Coli. in clinical isolates
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Background: The antimicrobial resistance is one of the most serious and expanding health problems world -wide in the last decades. The esbl escherichia coli. (extended – spectrum beta-lactamase e.coli) represents an important aspect of it .Objectives: To get an overview on the esbl e.coli prevalence profile in general. Also to assess the antibiotic sensitivity of esbl e. coli trying to specify the most effective antibiotics in combating this micro-organism.Methods: this study tries to focus on this problem in Iraq which through a prospective study approach by taking 35 clinical samples from various sources (urine, blood, abscess, eye ,vagina ,stool and others),and after confirming the presence of e.coli, the presence of esbl e.coli and

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Publication Date
Wed Jul 04 2012
Journal Name
J Bagh College Dentistry
Azithomycin as an adjunctive to non-surgical treatment in comparison with doxycycline in chronic periodontitis patients: 2-months randomized clinical trial
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Publication Date
Wed Jan 01 2020
Journal Name
Route Educational And Social Science Journal
SURVIVAL IN TIMES OF PANDEMICS: THE PROPHETIC VISION OF JACK LONDON
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Publication Date
Fri Mar 13 2020
Journal Name
Plant Archives
Azotobacter chroococcum and Rhizobium leguminosarum inoculums survival in soil and efficiency in enhancing plant growth
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Publication Date
Thu Jun 27 2024
Journal Name
Journal Of Image And Graphics
ALL-FABNET: Acute Lymphocytic Leukemia Segmentation Using a Flipping Attention Block Decoder-Encoder Network
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Melanoma, a highly malignant form of skin cancer, affects individuals of all genders and is associated with high mortality rates, especially in advanced stages. The use of tele-dermatology has emerged as a proficient diagnostic approach for skin lesions and is particularly beneficial in rural areas with limited access to dermatologists. However, accurately, and efficiently segmenting melanoma remains a challenging task due to the significant diversity observed in the morphology, pigmentation, and dimensions of cutaneous nevi. To address this challenge, we propose a novel approach called DenseUNet-169 with a dilated convolution encoder-decoder for automatic segmentation of RGB dermascopic images. By incorporating dilated convolution,

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