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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
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 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
Mon Jan 01 2018
Journal Name
The Journal Of Academic Social Sciences
BETWEEN TRIBULATION AND SURVIVAL: WOMEN IN LUTFIYA AL-DULAIMIS SATURN LADIES
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Publication Date
Sun Jan 01 2017
Journal Name
Journal Of The College Of Languages (jcl)
The Literary Animal and the Grotesque Survival in Ted Hughes’s “Thrushes”
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In his opus, Ted Hughes has annexed new and fresh territories of signification to the very notion of the literary animal. Building on the earlier modernist example of the Lawrencian legacy that dwells upon the question of animalism, Hughes seems to have stepped further into the terrain of the sheer struggle when, in his hands, the grotesquerie of survival and violence energizes the topos of the literary animal in his postmodern bestiary. In Hughes’s elemental poetic process this grotesquerie and violence stages the literary animal as a vital poetic device or motif that is finally restored to the primitive power of poetry. In his “Thrushes”, he thus defamiliarizes these tiny creatures’ acts of being to bring upfront into focus thi

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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
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
Sun Dec 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
Use Generalized Pareto Survival Models to Estimation Optimal Survival Time for Myocardial Infarction Patients
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The survival analysis is one of the modern methods of analysis that is based on the fact that the dependent variable represents time until the event concerned in the study. There are many survival models that deal with the impact of explanatory factors on the likelihood of survival, including the models proposed by the world, David Cox, one of the most important and common models of survival, where it consists of two functions, one of which is a parametric function that does not depend on the survival time and the other a nonparametric function that depends on times of survival, which the Cox model is defined as a semi parametric model, The set of parametric models that depend on the time-to-event distribution parameters such as

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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 Dec 12 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Assessment of Weight Gain Post Treatment with Biological Compounds among A Sample of Patients Attending Baghdad Teaching Hospital
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Objective: to evaluate the increase in weight after biological agents and the association of weight gain with the body mass index among a sample of patients attending Baghdad Teaching Hospital Methods: A prospective study is carried out in Baghdad teaching hospital biological units and outpatient clinic of rheumatology for a period of one year starting On April 2015 and ending on March 2016. 120 patients were included in the study 40 psoriatic arthritis .40 ankylosing spondylitis and 40 rheumatoid arthritis Results : The study findings indicate that significance differences are seen regarding weight gain and b

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Publication Date
Tue Jan 19 2021
Journal Name
Sn Applied Sciences
Post-fire serviceability and residual strength of composite post-tensioned concrete T-beams
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Abstract<p>In this study, the response of ten composite post-tensioned concrete beams topped by a reinforced concrete deck with adequate reinforcing shear connectors is investigated. Depending on the concrete compressive strength of the deck slab (20, 30, and 40 MPa), beams are grouped into three categories. Seven of these beams are exposed to a fire attack of 700 and 800 °C temperature simultaneously with or without the presence of a uniformly distributed sustained static loading. After cooling back to ambient temperature, these composite beams are loaded up to failure, using a force control module, by monotonic static loading in a four-point-bending setup with two symmetrical concentrated loads applied in </p> ... Show More
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