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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
Mon Feb 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
The impact of strategic innovation components of the application Business process re-engineering: A survey Study of the consultant of a sample of managers and their assistants and consultants in the General Company for Post & Telecommunications
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Abstract:

        Organizations need today to move towards strategic innovation, which means the analysis of positions, especially the challenges faced by the change in the external environment, which makes it imperative for the organization that you reconsider their strategies and orientations and operations, a so-called re-engineering to meet those challenges and pressures. Now this research dilemma intellectual two-dimensional, yet my account in not Take writings and researchers effect strategic innovation in re-engineering business processes, according to science and to inform the researcher, and after the application represented in the non-application of such resear

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Publication Date
Wed Jun 01 2022
Journal Name
Civil Engineering Journal
Usage of EB-CFRP for Improved Flexural Capacity of Unbonded Post-Tensioned Concrete Members Exposed to Partially Damaged Strands
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The study presents the performance of flexural strengthening of concrete members exposed to partially unbonded prestressing with a particular emphasis on the amount (0, 14.2, and 28.5%) of cut strands-symmetrical and asymmetrical damage. In addition to examining the influence of cut strands on the remaining capacity of post-tensioned unbonded members and the effectiveness of carbon fiber reinforced polymer laminates restoration, The investigated results on rectangular members subjected to a four-point static bending load based on the composition of the laminate affected the stress of the CFRP, the failure mode, and flexural strength and deflection are covered in this study. The experimental results revealed that the usage of CFRP la

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Publication Date
Thu Oct 09 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Effect of post-pressing times on adaptation of maxillary heat cured acrylic denture base at posterior palatal seal area
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Background: The purpose of this study was to verify the influence of post- pressing time of acrylic resin (immediate, 6, 12 and 24 hour) on the dimensional accuracy of denture base whish is a critical factor in the retention and stability of the complete denture that may occur during polymerization shrinkage. Materials and Methods: Forty maxillary stone casts were poured in plastic mold (Columbia Dentoform corp. NEW YORK, type III dental stone (Geastone, Zeus Sri Loc.Tamburine Roccastrada, GR, Italy). The stone casts were randomly assigned into 4 groups of 10 specimens each according to the post-pressing times into (immediate, 6, 12 and 24 h.). Heat cure acrylic resin denture base was constructed according to the previously mentioned pressi

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Publication Date
Fri Nov 01 2024
Journal Name
Process Safety And Environmental Protection
Optimized ensemble deep random vector functional link with nature inspired algorithm and boruta feature selection: Multi-site intelligent model for air quality index forecasting
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Publication Date
Sun Jan 01 2006
Journal Name
Journal Of Cosmetic And Laser Therapy
Use of the pulsed infrared diode laser (904 nm) in the treatment of alopecia areata
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Publication Date
Wed Jan 01 2020
Journal Name
Research Journal Of Pharmacy And Technology
The effectiveness of topical vitamin k cream 1% in the treatment of steroid-induced rosacea
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Publication Date
Tue Jan 01 2019
Journal Name
Journal Of Global Pharma Technology
Analysis of fatty acids of liver in the embryo and adult of domesticated chicken gallus gallus domesticus
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The fatty acids in the embryo's liver at ages (7, 11, 14 and 19) days incubation, small chicken aged (14) days after hatching and adult were analyzed, and found (5) fatty acids, the highest concentration of fatty acid in the adult of domesticated chicken and lowest concentration in small chicken age (14) days after hatching. Statistically, there were high significant differences at the probability level (P≤0.001) between all ages together, and the highest concentrations of Oleic acid (C18:1) and Linoleic acid (C18:2) were in embryo age (7) days incubation, while in embryo age (11) days incubation Stearic acid (C18:0) and α-Linolenic acid (C18:3) were higher concentration and Palmitic acid (C16:0) was the highest concentration in the adul

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Publication Date
Sun Aug 07 2022
Journal Name
Engineering, Technology & Applied Science Research Etasr
The Combined Strengthening Effect of CFRP Wrapping and NSM CFRP Laminates on the Flexural Behavior of Post-Tensioning Concrete Girders Subjected to Partially Strand Damage
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The studies on unbonded post-tensioned concrete members strengthened with Carbon Fiber Reinforced Polymers (CFRPs) are limited and the effect of strengthening on the strain of unbonded pre-stressed steel is not well characterized. Estimating the flexural capacity of unbound post-tensioned members using the design methodology specified in the design guidelines for FRP strengthening techniques of bonded post-tensioned members does not provide a reliable evaluation. This study investigates the behavior of unbonded post-tensioned concrete members with partial strand damage (14.3% and 28.6% damage) and strengthened with CFRP laminates using a near-surface mounted technique with and without U-wrap anchorages. The experimental results show

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Publication Date
Mon Aug 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
Analysis of the Causal Relationship between the Financial Infrastructure and Foreign Investments in Malaysia and Indonesia 1990-2013
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Abstract\

The developed financial infrastructure is one of the most important elements for achieving stable financial system in a country. The importance of developed financial infrastructure comes from its role in create economic and financial context attractive for foreign investments. Thus, this paper aims first to measure an index of financial infrastructure, and secondly, to gauge the nexus between the developed financial infrastructure and foreign investments inflow in Malaysia and Indonesia. We estimate the index of financial infrastructure by using different indicators such as (the institutional environment, access to finance, legal environment, and others).

By using the G

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Publication Date
Thu Dec 28 2023
Journal Name
The Iraqi Journal Of Veterinary Medicine
Molecular Identification and Phylogenetic Analysis of Salmonella‎ species ‎Isolated from Diarrheal Children and Dogs in Baghdad Governorate, ‎Iraq‎
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This work aimed to use conventional PCR to identify Salmonella‎ spp. that ‎were isolated from diarrheal children and healthy and diarrheic dogs based on four ‎virulence genes, hilA, stn, spvR‎, and marT. Sixteen Salmonella‎ isolates including: 9 ‎isolated from children's diarrhea from three species (S. Typhimurium, S. Enteritidis, S. ‎Typhi) and seven isolated from dogs including (S. Typhimurium, S. Enteritidis, S. ‎Muenchen), were identified primarily by several methods. The PCR products of the 16S ‎rRNA gene were sequenced and examined using BLAST analysis to find differences and ‎similarities between these Iraqi isolates and already-known global strains in order to ‎construct the phylogenetic tree of S.

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