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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
Fri Sep 26 2025
Journal Name
Journal Of Baghdad College Of Dentistry
The association of crevicular albumin level with the severity of periodontal destruction in chronic periodontitis patients after initial periodontal treatment
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Background: Gingival crevice fluid (GCF) is a mixture of substances derived from serum, leukocytes, and structural cells of periodontium and oral bacteria. These substances possess a great potential for serving as indicators of periodontal disease and healing after therapy the main purpose of this study was to find if there is a difference in albumin concentration between healthy and diseased periodontal tissues and to compare between diseased group according to pocket depth Materials and methods: total sample composed of 60 pockets found in 35 patients all of them had no history of any systemic disease, The samples were divided in to three main group that include two diseased groups divided according to the depth of the periodontal pocket

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Publication Date
Sun Jan 01 2017
Journal Name
Journal Of Clinical And Diagnostic Research
Treatment of Fistula-In-Ano with Tight (Cutting) Seton: Analysis of Outcomes and Efficacy Assessment
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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
Tue Oct 02 2018
Journal Name
Iraqi Journal Of Physics
Sensitivity of gold nanoparticles doped in porous silicon
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In this work gold nanoparticles (AuNPs), were prepared. Chemical method (Seed-Growth) was used to prepare it, then doping AuNPs with porous silicon (PS), used silicon wafer p-type to produce (PS) the processes doping achieved by electrochemical etching, the solution etching consist of HF, ethanol and AuNPs suspension, the result UV-visible absorption for AuNPs suspension showed the single peak located at ~(530 – 521) nm that related to SPR, the single peak is confirmed that the NPs present in the suspension is spherical shape and non-aggregated. X-ray diffraction analysis indicated growth AuNPs with PS. compare the PS layer without AuNPs and with AuNPs doped for electrical properties and sensitivity properties we found AuNPs:PS is more

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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 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
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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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
Fri Nov 15 2024
Journal Name
Scientific Reports
Ag@WO3 core–shell nanocomposite for wide range photo detection
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This study successfully synthesized high-performance photodetectors based on Ag-WO3 core–shell heterostructures using a simple and economical two-step pulsed laser ablation in water method and has investigated the electrical characteristics of the Ag@WO3 nanocomposite heterojunction. The Hall effect tests indicate that the synthesized Ag@WO3 exhibits n-type conduction with a Hall mobility of 1.25 × 103 cm2V-1S-1. Dark current–voltage properties indicated that the created heterojunctions displayed rectification capabilities, with the highest rectification factor of around 1.71 seen at a 5 V bias. A photodetector’s responsivity reveals the existence of two response peaks, which are situated in the ultraviolet and visible region. The ph

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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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