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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
Tue Dec 31 2024
Journal Name
Frontiers In Health Informatics
The Implementation Of Artificial Intelligence In Education: Systematic Analysis
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Background: The rapid evolution of Artificial Intelligence (AI) has significantly influenced Education, demonstrating substantial potential to transform traditional teaching and learning methods. AI reshapes teacher-student interactions and the relationship with knowledge. Objective: To analyze the potential benefits, ethical challenges, and limitations of AI in Education based on recent scientific literature, emphasizing the balance between technology and human interaction. Methods: A documentary research approach with a descriptive focus was employed, following the PRISMA protocol for systematic reviews. The search strategy involved analyzing evidence from 18 scientific articles published within the last six years. Results:AI o

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Publication Date
Fri Dec 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
Analysis the Impact of Corruption on Investment in Iraq
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There are different types of corruptions such as administrative, political, economic and financial corruption. The corruption forms also varied such as bribery, nepotism and extortion. All types and forms of corruption play significant role in the all economic variables generally and on investments in particular, and the corruption used to be an intermediate means in reducing the rate of economic growth.  The corruption contributes in reducing the domestic investments via pay bribery by investors to officials’ persons for supplemental contracts and tenders which finally leads to reduction in the investment efficiency. The corruption also contributes in rise of operational costs for the investment projects.  In additio

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Publication Date
Wed Sep 30 2020
Journal Name
Industrial Engineering &amp; Management Systems
Economic Analysis of the Financial Literacy Effects in G20
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ABSTRACT this paper extends the literature on the elements and effect of financial literacy by investigating the elements of financial literacy and the impact of financial literacy on financial inclusion and savings. This research confirms the results of researches of other economies but exposes some dissimilarities as well. The principal factors of financial literacy are discovered to be government efficiency, educational level, income, economic performance and infrastructure. Both education levels and financial literacy are found to be meaningfully and positively linked to financial inclusion and savings in G20 economies

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Publication Date
Wed Jan 01 2014
Journal Name
Journal Of Water Resource And Protection
Evaluating Water Stability Indices from Water Treatment Plants in Baghdad City
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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Mathematical treatment for solition-soliton interactions in mono-mode optical fiber
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There are many images you need to large Khneh space With the continued evolution of storage technology for computers, there is a continuing need and are required to reduce Alkhoznip space Pictures Zguet pictures in a good way, the way conversion Alamueja to Purifiers

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Publication Date
Thu Nov 30 2023
Journal Name
Eximia
A treatment strategy for recurrent (ankle injuries) in Muay Thai athletes
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Objective: An efficient solution for stabilization is the mobilization of the joints for the arthrokinematics affected by the positional defect of the CAI (i.e. chronic ankle instability). This study put to comparison the impacts of ankle dorsi flexion range of motion (DFROM) as well as dynamic balance ability (DBA) in the patients who have CAI using PJM (i.e. passive joint mobilization), a technique typically been used in previous works, and active joint mobilization (AJM), a technique which could have a greater impact on cortical excitability with the spontaneous movement. Design: rehabilitation program to treat recurrent ankle. Methods: A total of 10 players from the Iraqi clubs Muay Thai team were registered, 5 from each of

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Publication Date
Wed Aug 30 2023
Journal Name
Baghdad Science Journal
Adherence model to cervical cancer treatment in the Covid-19 era
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Cervical Uterine Cancer is a disease that explains the vulnerability in which women are in terms of reproductive health with an impact on occupational health and public health, even when in Mexico the prevalence rate is lower than the other member countries of the OECD, its impact on Human Development and Local Development shows the importance that the disease have in communities more than in cities where prevention policies through check-ups and medical examinations seem to curb the trend, but show the lack of opportunities and capacities of health centers in rural areas.   To establish the reliability, validity, and correlations between the variables reported in the literature with respect to their weighting in a public hospital. A

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Publication Date
Wed Jun 20 2018
Journal Name
Al-academy
Directed by Treatment for single-place events in the cinematographic medium
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The cinematographer mediates through the means of cinema and television a set of elements complementing each other in the light of developments in various sciences, culture and arts for the purpose of conveying the meaning to the recipient and achieve aesthetic taste. Despite the diversity of cinematographic media with its multiple forms, The researcher started from the principle of definition and knowledge of a technical phenomenon that emerged in the cinematographic medium through the treatment of dramatic events through the solutions of the exit line depends on the narrative of events in one place contributes to attract Mam spectator since this interesting phenomenon in the mediator, there .van question arises the adoption of that vis

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Publication Date
Thu Aug 30 2018
Journal Name
Journal Of Engineering
Mass Transfer Study for Bio-Synergy in Dairy Wastewater Treatment Plant
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The present study addresses the behavior of gases in cultivation media as an essential factor to develop the relationship between the microorganisms that are present in the same environment. This relationship was explained via mass transfer of those gases to be a reasonable driving force in changing biological trends. Stripping and dissolution of oxygen and carbon dioxide in water and dairy wastewater were investigated in this study. Bubble column bioreactor under thermal control system was constructed and used for these processes. The experimental results showed that the removal of gases from the culture media requires more time than the dissolution. For example, the volumetric mass transfer coefficient for the removal

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Publication Date
Fri Feb 01 2013
Journal Name
Proceedings Of The Institution Of Civil Engineers - Ground Improvement
Treatment of collapse of gypseous soils by grouting
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Gypseous soil is a collapsible soil, which causes large deformations in buildings that are constructed on it. Various methods have been used to minimise this effect, such as replacing the gypseous soil or using soil stabilisation (grouting or soil improvement). This study was carried out on four types of gypseous soils that have different properties and various gypsum contents. The testing was carried out on remoulded samples to evaluate the compressibility of gypseous soil under different conditions. The samples were grouted with acrylate liquid. The relationships between the injection pressure and the radius of flow, between time of injection and radius of flow, and between time and quantity of acrylate liquid are investigated on

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