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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 Oct 01 2021
Journal Name
Saudi Pharmaceutical Journal
Organization factors influencing nurse ability to prevent and detect adverse drug events in public hospitals using a patient safety model
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Publication Date
Fri Oct 03 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Estimation of some salivary variables and oral health status of patients with chronic myeloid leukemia aged 45-55 years
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Background: Chronic myeloid leukemia is a cancer of the white blood cells characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow. This study aimed to determine the effect of chronic myeloid leukemia on Dental caries and Oral health status including Gingivitis, Loss of attachment, Plaque index and Calculus index as well as evaluation of salivary flow rate and salivary interleukins-6 and tumor necrosis factor-?. Material and methods: Study group consisted of (75) subjects, (25) were newly diagnosed with chronic myeloid leukemia, (25) were taking medications (Glevic), and (25) were control subjects, all ag

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Publication Date
Fri Jul 19 2024
Journal Name
Известия Юго-Западного государственного университета. Серия: Лингвистика и педагогика
ACOMPARATIVE ANALYSIS OF THE CONCEPT AND TYPES OF pun IN RUSSIAN AND ARABIC
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Abstract Purpose of research: The purpose of the article is to conduct a comparative analysis of the concept and types of puns in the Russian and Arabic languages. The main focus is on identifying similarities and differences in the definition of a pun, as well as analyzing its various types in both languages. The purpose of the study is to understand how puns are used to achieve comic or semantic effect in different cultural contexts. Methods: The study includes an analysis of literature providing information about puns in Russian and Arabic. For comparative analysis, methods were used to compare concepts, definitions and types of puns in both languages. The phonetic, semantic and syntactic aspects of the pun are considered, and cultural f

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Publication Date
Tue Jul 23 2024
Journal Name
Proceedings Of The Southwest State University. Series: Linguistics And Pedagogy
Acomparative Analysis of the Concept and Types of Homonyms in Russian and Arabic
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Purpose of research: The purpose of the article is to conduct a comparative analysis of the concept and types of puns in the Russian and Arabic languages. The main focus is on identifying similarities and differences in the definition of a pun, as well as analyzing its various types in both languages. The purpose of the study is to understand how puns are used to achieve comic or semantic effect in different cultural contexts.

Methods: The study includes an analysis of literature providing information about puns in Russian and Arabic. For comparative analysis, methods were used to compare concepts, definitions and types of puns in both languages. The phonetic, semantic and syntactic aspects of the pun are considered,

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Publication Date
Fri Dec 01 2023
Journal Name
Lxxvi Международная научно-практическая конференция «Научный форум: филология, искусствоведение и культурология»
Comparative analysis of the concept and types of homonyms in Russian and Arabic
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Abstract: This article is a comparative analysis of the concept and types of homonyms in Russian and Arabic. Homonyms are lexical units that have the same sound but different meanings. The study of homonymy in different languages can help reveal the features of the semantic structure and syntactic rules of each language. The article discusses the main aspects of homonymy in Russian and Arabic, as well as a comparative analysis of the types of homonyms that exist in both languages. The study includes an analysis of the semantic meanings of homonyms, their use in context, and possible differences in syntactic features that may affect their interpretation and perception by native speakers of these languages. The purpose of the article is to id

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Publication Date
Sat Jan 01 2022
Journal Name
International Journal Of Differential Equations
Dynamical Behaviours of Stage-Structured Fractional-Order Prey-Predator Model with Crowley-Martin Functional Response
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In this paper, the dynamic behaviour of the stage-structure prey-predator fractional-order derivative system is considered and discussed. In this model, the Crowley–Martin functional response describes the interaction between mature preys with a predator.  e existence, uniqueness, non-negativity, and the boundedness of solutions are proved. All possible equilibrium points of this system are investigated.  e su‰cient conditions of local stability of equilibrium points for the considered system are determined. Finally, numerical simulation results are carried out to con‹rm the theoretical results.

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Publication Date
Fri Apr 01 2022
Journal Name
International Journal Of Nanoscience
Study of the Interaction Between Reduced Graphene Oxide and NO<sub>2</sub>Gas Molecules via Density Functional Theory (DFT)
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Electronic properties such as density of state, energy gap, HOMO (the highest occupied molecular orbital) level, LUMO (the lowest unoccupied molecular orbital) level and density of bonds, as well as spectroscopic properties like infrared (IR), Raman scattering, force constant, and reduced masses for coronene C24, reduced graphene oxide (rGO) C24O5and interaction between C24O5and NO2gas molecules were investigated. Density functional theory (DFT) with the exchange hybrid function B3LYP with 6-311G** basis sets through the Gaussian 09 W software program was used to do these calculations. Gaussian view 05 was em

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Publication Date
Sun Jul 17 2022
Journal Name
Al–bahith Al–a'alami
Post-interactive communication A study to build a model for the flow of communication in social networking sites
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The issue of the research lies in the non-representation of the models developed for the communication process in the interaction and networking processes through social media, as the research sought to build a network model of communication according to the specific data and features of social media platforms in order to reach a special generalization to understand how the process of networking operates in cyberspace.

The researcher followed the analytical survey approach as she described the communication models outwardly in order to be able to build a networked communication model that represents the flow of post-reactive communication. Therefore, it has been named "Nebula - Sadeem" after the concept of post-space and cosmic g

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Publication Date
Sun Aug 18 2019
Journal Name
Political Sciences Journal
The challenges of precision axes for futuristic regional relations in the middle east (Iraq after post triumph's period)
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The research has tackled about an important transformation within the whole region of middle east, especially there were more challenges which revealed under the huge pivotal interests of global powers that ruled the new world order by United states of America ; being very affected over the international and regional relations than any situations appeared previously within political realities. So that, many of variables inside the international scene which happened during of this period of contradicting strategic policies by the process of reforming and restructuring of difficult equations that imposed by international and regional allies and blocs . This article had concentrated over various strategic and political studies which reflect

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Publication Date
Fri Jan 17 2025
Journal Name
Opera Medica Et Physiologica
ASSESSMENT OF THE HARMFUL EFFECT OF DUPROST DRUG ON TESTES OF ALBINO MICE
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