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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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
Tue May 01 2018
Journal Name
Journal Of Physics: Conference Series
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Publication Date
Sat Aug 01 2015
Journal Name
International Journal Of Science And Research
Bacteriological and Immunological Study of Rheumatoid Arthritis

The current study included the collection of 175 samples of blood (Urea-blood) of patients with rheumatoid arthritis from Al–Al-Kindy Teaching Hospital, Baghdad Teaching Hospital and Al-Imamian Al-Kadhimyain Medical City in Baghdad from both sexes with different ages at the period between 1/10/2016-1/2/2017. Bacterial growth results showed that 80% of urea for bacterial transplantation were positive results, while the number of samples showing no bacterial growth was 20%. The bacterial isolation evaluate for morphological testes and biochemical microscopy, as well as identification by Api system. The highest frequency of inflectional bacteria was E. coli (41.97%), followed by E. cloacae (21.25%), P. aeruginosa (12.5%), Salmonella (10%), K

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Publication Date
Mon Apr 01 2019
Journal Name
Journal Of Pharmaceutical Sciences & Research
New Derivatives of Thiozolidinone, Synthesis and Characterization

The present work involved synthesis of new thiozolidinone derivatives,These derivatives could be divided into three type of compounds; quinolin-2-one[V]a,b ,Schiff bases[VI]a,b and imide compounds[VII]a-d. The reaction p-Hydroxyacetophenone with thiosemicarbazide led to formation thiosemicarbazon compound [II], the reacted of thiosemicarbazone with chloro acetic acid in CH3CO2Na led to yield 4- thiazelidinone compound[III] in addition, thiosemicarbazide was POCl3 to [III] give [IV] compound used intermediates to synthesis new compounds of reacted with two type of coumarin in glacial acetic acid to give quinolin-2-one[V]a,b, The later compound refluxing with different benzaldehyde in dry benzene and glacial acetic acid give Schiff bases[VI]a

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Publication Date
Mon Jul 04 2016
Journal Name
International Multidisciplinary Research Journal
Denotative and Connotative Meaning of Barnyard Verbs

Communication is a vital process that needs much more understanding and mutual background knowledge on the part of ESL learners in terms of grammar, meaning and context. Thus, the main aim of the current research paper is to identify and figure out the denotative and connotative meaning of barnyard verbs in English and practically analyzing these verbs to identify the dictionary meaning from connotative one. The main problem of this study is attributed to the fact that ESL learners may not be able to identify and understand the connotative meaning of barnyard verbs since these verbs are onomatopoeic (i.e,) a word that phonetically imitates, or suggests the source of sound that it describes). Consider the following example: the verb "coo" ha

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Publication Date
Thu Feb 23 2023
Journal Name
Chalcogenide Letters
Fabrication and evaluation of CuAlSe2/Si photodetector

In this work, we have examined the spectral response of (p-CuAlSe2/n-Si) detector, (CAS) thin films deposited by thermal evaporation at RT with a thickness (450) nm, and annealing temperature at (473K) for 2 h. Optical transmission measurements displayed reasonably slight transmission besides higher absorbance trendy the visible region, energy gaps were observed by annealing, were found to be direct, and decreased with the effect of annealing. The extreme responsivity value arises at wavelength 459 nm, with improvement value of specific detectivity and quantum efficiency the annealing films be situated originate as greatest suitable aimed at numerous device application.

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Synthesis of New Amide and ThioUrease Compounds.

The reaction of some new Schiff bases ( 2-[(2-Amino – ethylimino)-methyl]-R , 2-({2-[(R-benzylidene)-amino]-ethylimino}-methyl)-R with Benzoyl chloride or Acetyl chloride were carried out. Subsequent reactions of these products N-(2-Amino-ethyl)-N-[Chloro-(R) –methyl]-benzamide or N-(2-{?-[chloro-(R) –methyl]-amino}-ethyl)-N-[chloro-(R) –methyl]- benzamide with thiourea afforded thioureas compounds. The synthesized compounds were confirmed by their IR,UV,spectra and C.H.N. analysis.

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Publication Date
Sun Dec 30 2001
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
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Publication Date
Thu Feb 13 2020
Journal Name
College Of Islamic Sciences
سيا Contextual study of faces and isotopes

This is a contextual study in face and isotope science, and I have made it in one of the terms faces and isotopes, which is the word (bad). Quranic also, and that is at every aspect they mentioned.
The nature of the research required that it be divided into three sections:
The first topic: I singled it out to show the types of contextual connotations.
- The second topic: I singled it out to define the word bad and its meaning.
- The third topic: I devoted it to the study of the word bad and explaining the significance of the Quranic context on the additional meaning and the original meaning.
Conclusion: It mentioned the most important results, which are:
1- The significance of the Quranic context is one of the most impo

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Publication Date
Thu Sep 13 2018
Journal Name
Baghdad Science Journal
Design and Evaluation of a Polarizer Filter

This research includes theoretical and evaluation design of a polarizer filter of high transmission in the near IR region of (900-1200nm) for different incidence angles to obtain a long wave and short wave pass filter using analytical calculations. Results refer to a new configuration design in fewer layers than used in previous studies in the long wave pass at incidence angles (45o,50o,55o). Adopted Hafnium dioxide (HfO2) and Magnesium fluoride (MgF2) as coating material at design wavelength (933nm), the study also included design short wave pass polarizer by using the same coating material.

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Antimutagenicity of arugula(Eruca sativa) and carrot

Been studying the opposite effect of mutagenesis to juice plant watercress and compared juice carrots to induce mutations resistant Struptomaysan Palmtafr (NTG) and transactions as diverse as the use of juice before treatment Palmtafr or after using Almtafr or with Almtafr using system mutagenesis Bactra consisting of three isolates G3, G12, G27 are very sensitive to Struptomaysanstudy resulted in a user juice plants had no effect on the neighborhood number of isolates, but its effect on the watercress was clear

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