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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 Aug 01 2025
Journal Name
Microbial Pathogenesis
Antibacterial and therapeutic effects of vancomycin-resistant Staphylococcus aureus bacteriocin (VRSAcin) in the treatment of VRSA skin infection in mice
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Publication Date
Thu Feb 01 2024
Journal Name
Kurdish Studies
The Jurisprudence of Clans in the Balance of Social Jurisprudence (Criticism and Analysis)
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It is known that the science of jurisprudence is one of the most important Islamic sciences. Because it is a science that regulates the life of man and society and provides them with happiness in this world and the hereafter, if they follow its provisions with precision and care. The importance of this topic lies in the fact that it represents an urgent social need to show the compatibility of tribal customs with social jurisprudence. The job of the jurists was and still is to clarify the legal rulings according to what the Holy Qur’an has shown, and what has been reported on the authority of the Great Prophet (6) and the pure imams (:).It is no secret to everyone that the Islamic civilization is (the civilization of jurisprudence), just

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Publication Date
Sat Oct 20 2018
Journal Name
Journal Of Economics And Administrative Sciences
Analysis of the causes of poverty and progress strategy to combat in sudan
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Abstract:

   The problem of poverty is one of the most important development challenges facing developing countries including Sudan for several decades. Although many efforts have been made to reduce poverty, however, its rates are increasing, and public policies adopted by the government in this regard remain elusive in achievinging its main objectives or making any significant progress. The purpose of the present study is to analyse poverty in Sudan by identifying its measurement, causes and the factors that have contributed to the increasing poverty rates over the past two decades. Also this study aims at investigating the interim poverty reduction strategy in Sudan as well as evaluates that strategy throug

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Publication Date
Tue Nov 15 2022
Journal Name
Nasaq Journal
Componential Analysis of Hatred Synonymy in the Lexicons of English and Standard Arabic
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ABSTRACT This paper has a three-pronged objective: offering a unitary set of semantic distinctive features to the analysis of nominal “hatred synonyms” in the lexicon of both English and Standard Arabic (SA), applying it procedurally to test its scope of functionality crosslinguistically, and singling out the closest noun synonymous equivalents among the membership of the two sets in this particular lexical semantic field in both languages. The componential analysis and the matching procedures carried have been functional in identifying ten totally matching equivalents (i.e. at 55.6%), and eight partially matching ones (i.e. at %44.4%). This result shows that while total matching equivalences do exist in the translation of certain Eng

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Publication Date
Tue Jun 01 2021
Journal Name
Journal Of The College Of Languages (jcl)
A Multimodal Analysis of Hyperbolic Devices in Advertisements of Health and Beauty Products
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         This paper examines the use of one of the most common linguistic devices which is hyperbole. It shows how hyperbolic devices are used as an aspect of exaggeration or overstatement for an extra effect in which the speaker can use hyperbole to add something extra to a situation in order to exaggerate his idea or speech. It is, like other figures of speech, used to express a negative or positive attitude of a specific unit of language. Thus, this paper is set against a background of using hyperbole concerning two main fields (advertisements and propaganda). So, the use of hyperbole will be implied by analyzing them concerning their meaning) literal and non-literal).  Methodology of this

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Publication Date
Sat Jul 01 2017
Journal Name
International Journal Of Computer Networks And Wireless Communications
Performance Analysis of VoIP in Wireless Networks
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Voice over Internet Protocol (VoIP) is important technology that’s rapidly growing in the wireless networks. The Quality of Service (QoS) and Capacity are two of the most important issues that still need to be researched on wireless VoIP. The main aim of this paper is to analysis the performance of the VoIP application in wireless networks, with respect to different transport layer protocols and audio codec. Two scenarios used in the simulation stage. In the first scenario VoIP with codec G.711 transmitted over User Datagram Protocol (UDP), Stream Control Transmission Protocol (SCTP), and Real-Time Transport Protocol (RTP). While, in the second scenario VoIP with codec G.726 transmitted over UDP, SCTP, and RTP protocols. Network simulator

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Publication Date
Fri Jan 01 2021
Journal Name
Environment Asia 14(1) 2021 13-22
Synoptic analysis of dust storm in Iraq
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In this study, the synoptic analysis of dust storm for spring and summertime in Iraq were investigated. The images for dust provided by NASA are used to emphasize the dust storm days, while the composite maps of wind vector and geopotential 850hPa are mapped to investigate the pressure and wind direction patterns appearing with the dust condition in the same days. Spring has more dust frequency than summertime, especially in May. The frontal type of dust storm is dominant on spring, the cold air pushes the warm air that picking up the sand to the air through the vertical wind, but the southwestern high-speed wind and drought condition were controlled on the dust in summer. The northwestern wind is the main factor that carries the dust for l

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Publication Date
Wed Dec 30 2015
Journal Name
Al-kindy College Medical Journal
Intrauterine insemination outcome with and without ovulation induction treatment
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Background:: Infertility is a very common condition affecting approximately 13-14% of couples in the reproductive age. In general population; about 85% of couples have achieved conception within a year. Intrauterine insemination is one of the procedure which have a role in the treatment of infertile couple.Objectives:is to confirm that the use of ovulation induction in the course of intrauterine insemination elevates the pregnancy success rate.Method:This study had been conducted between December 2013 till December 2014 in AL-Elwiyah maternity hospital and AL-Samaraii hospital / Baghdad.On history and clinical examination; the chosen couple had the following criteria; primary infertility for more than one year, no previous IUI trials, hu

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Publication Date
Wed Sep 01 2021
Journal Name
Journal Of Engineering
Water Treatment With Conventional and Alternative Coagulants: A Review
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There is no access to basic sanitation for half the world's population, leading to Socioeconomic issues, such as scarcity of drinking water and the spread of diseases. In this way, it is of vital importance to develop water management technologies relevant to the target population. In addition, in the separation form of water treatment, the compound often used as a coagulant in water treatment is aluminum sulfate, which provides good results for raw water turbidity and color removal. Studies show, however, that its deposition in the human body, even Alzheimer's disease, can cause serious harm to health and disease development. The study aims to improve the coagulation/flocculation stage related to the amount of flakes, i

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Publication Date
Fri Jan 01 2021
Journal Name
E3s Web Of Conferences 318, 03006 (2021)
Effect of External Post-Tensioning Strengthening Technique on Flexural Capacity of Simple Supported Composite Castellated Beam
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This research is carried out to study the effect of the external post-tensioning technique on the flexural capacity of simply supported composite castellated beam experimentally. In this research, seven composite castellated beams having the same dimensions and material properties were cast and tested up to failure by applied two concentrated loads at 700 mm from each end. Two external strands of 12.7 mm diameter were fixed at each side of the web of strengthening beams and located at depth 180 mm from top fiber of the section (dps) at each end of the beam. The strands have been tensioned by using a hydraulic jack with a constant stress of 100 MPa. This research aims to study the effect of the strengthening by different shapes of st

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