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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 Sep 16 2021
Journal Name
International Journal Of Clinical Practice
An overview of post‐COVID‐19 complications
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Publication Date
Fri Aug 10 2018
Journal Name
In Book: Challenges In Mechanics Of Time-dependent Materials, Volume 2edition: 1stchapter: 12
Experimental Investigation of Segmental Post-tensioned Girders
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Publication Date
Mon Dec 30 2019
Journal Name
College Of Islamic Sciences
Extremism in religion Causes, effects and treatment
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Praise be to God, Lord of the worlds, and prayers and peace be upon His messenger, the mercy of the worlds.
As for after ....
It is clear from the legal texts in the Noble Qur’an and the Sunnah of the Prophet, that Islam is a method that interferes in everything in beliefs, worship, behavior and transactions, and it forbids excess and extremism and mistrust of people and looking at them through a black lens, self-conceit and contempt of others.
In our research, we will try, God willing, to study the phenomenon of religious extremism with its comprehensive dimensions, the position of Islam on it through the verses and hadiths discussed by it, and the diagnosis of the reasons for its emergence and emergence, because if we learn

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Publication Date
Wed Jul 07 2021
Journal Name
International Journal Of Applied Pharmaceutics
APPLICATION OF 3D PRINTING IN INNOVATED DRUG DELIVERY: A REVIEW
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Increasing requests for modified and personalized pharmaceutics and medical materials makes the implementation of additive manufacturing increased rapidly in recent years. 3D printing has been involved numerous advantages in case of reduction in waste, flexibility in the design, and minimizing the high cost of intended products for bulk production of. Several of 3D printing technologies have been developed to fabricate novel solid dosage forms, including selective laser sintering, binder deposition, stereolithography, inkjet printing, extrusion-based printing, and fused deposition modeling. The selection of 3D printing techniques depends on their compatibility with the printed drug products. This review intent to provide a perspecti

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Publication Date
Tue Feb 16 2016
Journal Name
World Journal Of Pharmaceutical Research
ENDOCRINE REPRODUCTIVE EFFECTS OF PREGABALIN DRUG IN FEMALE ALBINO RATS
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The aim of present study was to investigate the effect of Pregabalin on hormonal profile of pituitary and ovarian hormones in female albino rats. Three groups of healthy adult female albino rats having fifteen rats in each group were selected for present study. The rats of groups G2 and G3 were administered with Pregabalin with two doses 150 mg and 300mg/kg b.wt/day respectively by orally route daily for 1month, 2 months, and 3 months. Animals of group G1 (Control) were given saline alone. After the experimental periods, the rats were sacrificed, and the study of hormonal profile was carried out by collecting blood samples from the heart puncture method, centrifuged sera and analyzing concentrations of estrogen, progesterone and gonadotropi

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Publication Date
Fri Jan 01 2021
Journal Name
Materials Today: Proceedings
Study of some electronic and spectroscopic properties of ZnO nanostructers by density functional theory
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Publication Date
Tue Jan 01 2019
Wide-range tunable subwavelength band-stop filter for the far-infrared wavelengths based on single-layer graphene sheet
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Publication Date
Fri Dec 24 2021
Journal Name
Oncology And Radiotherapy
The effect of different clinicopathological parameters on disease free survival in triple negative breast cancer Iraqi women
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Publication Date
Sat May 11 2024
Journal Name
Journal Of Optics
The effect of increasing temperature on the sensitivity of photonic crystal fiber
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Photonic Crystal Fiber Fabry–Perot Interferometers (FPI) based on Surface Plasmon Resonance (SPR) was investigated in this paper in order to detect changes in photonic crystal fiber sensitivity with increasing temperature. FPI is composed of a PCF (ESM-12) solid core spliced with a single-mode fiber (SMF) on one side and a 40nm thick gold Nano film on the other. In order to obtain the SPR curve, the end of PCF can be spliced with the side of SMF before covering the gold film on the PCF. SPR results are included in the suggested sensor, based on the conclusions of the investigations. Resolution (R) is 0.0871, Signal-to-Noise Ratio (SNR) is 0.1867, a figure of merit (FOM) is 0.0069, and sensitivity (S) is 1.1481 . This sensor proposed is s

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Publication Date
Wed Oct 17 2018
Journal Name
Journal Of Economics And Administrative Sciences
Comparison of Two of (Turnbull) and (Generalization Turnbulls)non-parametric methods in estimating conditional survival function (applied study on breast cancer patients)
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   This research includes the application of non-parametric methods in estimating the conditional survival function represented in a method (Turnbull) and (Generalization Turnbull's) using data for Interval censored of breast cancer and two types of treatment, Chemotherapy and radiation therapy and age is continuous variable, The algorithm of estimators was applied through using (MATLAB) and then the use average Mean Square Error (MSE) as amusement  to the estimates and the results showed (generalization of Turnbull's) In estimating the conditional survival function and for both treatments ,The estimated survival of the patients does not show very large differences

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