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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 Nov 01 2013
Journal Name
Journal Of Cosmetics, Dermatological Sciences And Applications
Treatment of chronic paronychia: A double blind comparative clinical trial using singly vaseline, nystatin and fucidic acid ointment
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KE Sharquie, AA Noaimi, SA Galib, Journal of Cosmetics, Dermatological Sciences and Applications, 2013 - Cited by 4

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Publication Date
Mon Dec 01 2014
Journal Name
Journal Of Economics And Administrative Sciences
USING SENSITIVITY ANALYSIS IN DETERMINING THE OPTIMAL&EFFICIENT PRODUCTION PLANS IN GREENHOUSES IN ASSOCIATION OF AL-WATAN UNDER CONDITION OF RISK &UNCERTAINTY
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 The objectives of this research are to determine and find out the reality of crops structure of greenhouses in association of Al-Watan  in order to stand on the optimal use of economic resources available for the purpose of reaching a crop structure optimization of the farm that achieves maximize profit and gross and net farm incomes , using the method of linear programming to choose the farm optimal plan with the highest net income , as well as identifying production plans farm efficient with (income - deviation) optimal (E-A) of the Association and derived, which takes into account the margin risk wich derived from each plan using the model( MOTAD), as a model of models of linear programming alternative programming m

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
MEASURING OF FARMERS ADOPTION LEVEL FOR MODERN IRRIGATION SYSTEM AND THEIR WIDE APPLICATION
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74 fanners were randomily selected from the Lc:ital. of 406 fanners using the Modern Irrigation System up to November , 2000 , for the purpose of wide adoptation of such system. Rcsults indicated according to the data which has been obtained and statistically analysed by the statistical package for the Social Sciences (SPSS) program showed that the majority of the farmers adopted this new system of irrigation due to the increase in the yield up to 5" .

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Publication Date
Sat Jun 08 2024
Journal Name
Karbala International Journal Of Modern Science
Designing of Human Serum Albumin Nanoparticles for Drug Delivery: a Potential Use of Anticancer Treatment
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Human serum albumin (HSA) nanoparticles have been widely used as versatile drug delivery systems for improving the efficiency and pharmaceutical properties of drugs. The present study aimed to design HSA nanoparticle encapsulated with the hydrophobic anticancer pyridine derivative (2-((2-([1,1'-biphenyl]-4-yl)imidazo[1,2-a]pyrimidin-3-yl)methylene)hydrazine-1-carbothioamide (BIPHC)). The synthesis of HSA-BIPHC nanoparticles was achieved using a desolvation process. Atomic force microscopy (AFM) analysis showed the average size of HSA-BIPHC nanoparticles was 80.21 nm. The percentages of entrapment efficacy, loading capacity and production yield were 98.11%, 9.77% and 91.29%, respectively. An In vitro release study revealed that HSA-BIPHC nan

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Publication Date
Wed Oct 09 2019
Journal Name
Engineering, Technology &amp; Applied Science Research
Numerical Analysis of Segmental Post Tensioned Concrete Beams Exposed to High Fire Temperature
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The main objective of this study is to characterize the main factors which may affect the behavior of segmental prestressed concrete beams comprised of multi segments. The 3-D finite element program ABAQUS was utilized. The experimental work was conducted on twelve simply supported segmental prestressed concrete beams divided into three groups depending on the precast segments number. They all had an identical total length of 3150mm, but each had different segment numbers (9, 7, and 5 segments), in other words, different segment lengths. To simulate the genuine fire disasters, nine beams were exposed to high-temperature flame for one hour, the selected temperatures were 300°C (572°F), 500°C (932°F) and 700°C (1292°F) as recomm

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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
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
Tue Dec 01 2020
Journal Name
Gulf Economist
The Bayesian Estimation in Competing Risks Analysis for Discrete Survival Data under Dynamic Methodology with Application to Dialysis Patients in Basra/ Iraq
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Survival analysis is one of the types of data analysis that describes the time period until the occurrence of an event of interest such as death or other events of importance in determining what will happen to the phenomenon studied. There may be more than one endpoint for the event, in which case it is called Competing risks. The purpose of this research is to apply the dynamic approach in the analysis of discrete survival time in order to estimate the effect of covariates over time, as well as modeling the nonlinear relationship between the covariates and the discrete hazard function through the use of the multinomial logistic model and the multivariate Cox model. For the purpose of conducting the estimation process for both the discrete

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Publication Date
Wed Jun 15 2022
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of salivary immunoglobulin A, interleu-kin-6 and C-reactive protein in chronic kidney dis-ease patients on hemodialysis and on conservative treatment
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Background: Chronic kidney disease is a gradual loss of kidney function with diabetes and hypertension as the leading cause. Chronic kidney disease is one of these systemic diseases that can affect salivary contents. Aims: This study aimed to assess salivary immunoglobulin A, interleukin-6 and C- reactive protein in chronic kidney disease patients on hemodialysis and those on conservative treatment in comparison with control subjects. Materials and methods: Ninety subjects were included in this study divided into three groups: 30 patients with chronic kidney disease on hemodialysis for at least 6 months ago; 30 patients with chronic kidney disease on conservative treatment and 30 healthy control subjects. Secretory immunoglobulin A, inte

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