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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
Sat Apr 01 2023
Journal Name
Science Of The Total Environment
Recent advances and applicable flexibility potential of electrochemical processes for wastewater treatment
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This study examined >140 relevant publications from the last few years (2018–2021). In this study, classification was reviewed depending on the operation's progress. Electrocoagulation (EC), electrooxidation (EO), electroflotation (EF), electrodialysis (ED), and electro-Fenton (EFN) processes have received considerable attention. The type of action (individual or hybrid) for each electrochemical procedure was evaluated, and statistical analysis was performed to compare them as a new manner of reviewing cited papers providing a massive amount of information efficiently to the readers. Individual or hybrid operation progress of the electrochemical techniques is critical issues. Their design, operation, and maintenance costs vary depending o

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Publication Date
Mon Mar 27 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Lipid Profile and Fasting Blood Sugar Analysis in Patients with Cholelithiasis
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Cholelithiasis is one of the commonest surgical problems and one of the most common gastrointestinal diseases throughout the world but its pathogenesis remains unclear. Many theories have been proposed forward to explain the mechanism of stone formation. It is not fully clear if symptomatic gallstone disease is associated with a specific pattern of some biochemical abnormalities, as lipid profile and fasting blood sugar in serum of patients.

This study was designed to estimate lipid profile and fasting blood sugar in the sera of patients with cholelithiasis in comparison with normal individuals (control).

In this study, 104(male=16, female=88) were symptomatic gallstone patients (aged 42.79± 12.18 years), and 38(male=6

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Publication Date
Wed Aug 19 2020
Journal Name
International Journal Of Research In Social Sciences And Humanities
HUMOUR IN THE AMERICAN AND BRITISH COMEDYEPISODES: A DISCOURSE ANALYSIS STUDY
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DBNRAAK Mohammed, International Journal of Research in Social Sciences and Humanities, 2020

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Publication Date
Sun Mar 03 2024
Journal Name
Mesopotamian Journal Of Cybersecurity
Using Information Technology for Comprehensive Analysis and Prediction in Forensic Evidence
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With the escalation of cybercriminal activities, the demand for forensic investigations into these crimeshas grown significantly. However, the concept of systematic pre-preparation for potential forensicexaminations during the software design phase, known as forensic readiness, has only recently gainedattention. Against the backdrop of surging urban crime rates, this study aims to conduct a rigorous andprecise analysis and forecast of crime rates in Los Angeles, employing advanced Artificial Intelligence(AI) technologies. This research amalgamates diverse datasets encompassing crime history, varioussocio-economic indicators, and geographical locations to attain a comprehensive understanding of howcrimes manifest within the city. Lev

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Publication Date
Mon Jan 01 2024
Journal Name
Explainable Artificial Intelligence In The Digital Sustainability Administration
Artificial Intelligence and Trends Using in Sustainability Audit: A Bibliometric Analysis
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Publication Date
Thu Jan 02 2020
Journal Name
Journal Of The College Of Languages (jcl)
Prepositions in the System of Analytical Unites of Modern Russian Language: Functional - Semantic Aspects: Отыменные предлоги В системе аналитических единиц русского языка: функционально-семантический аспект
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The present study deals with prepositions in the patterns of analytical unite of modern Russian language out of the functional -semantic aspects, which enhances the lexical semantics.  The study, also, sheds light on the prepositions of semantic derivation that adds value to the meaning of the unites, promotes the appearance of new forms that match the more important diverse complex analytical unit.

В статье рассмотрены отыменные предлоги в системе литических единиц русского языка с позиций функционального и семантического аспектов. Репрезентирована специфика функциониров

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Publication Date
Thu Apr 25 2019
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
FLOW INJECTION ANALYSIS AND SPECTROPHOTOMETRIC DETERMINATION OF NIFEDIPINEIN PHARMACEUTICAL FORMULATION: FLOW INJECTION ANALYSIS AND SPECTROPHOTOMETRIC DETERMINATION OF NIFEDIPINEIN PHARMACEUTICAL FORMULATION
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A new simple and sensitive spectrophotometric method is described for quantification of Nifedipine (NIF) and their pharmaceutical formulation. The selective method was performed by the reduction of NIF nitro group to yield primary amino group using zinc powder with hydrochloric acid. The produced aromatic amine was submitted to oxidative coupling reaction with pyrocatechol and ammonium ceric nitrate to form orange color product measured spectrophotometrically with maximum absorption at 467nm. The product was determined through flow injection analysis (FIA) system and all the chemical and physical parameters were optimized. The concentration range from 5.0 to 140.0 μg.mL-1 was obeyed Beer’s law with a limit of detection and quantitatio

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Publication Date
Wed Jun 29 2022
Journal Name
College Of Islamic Sciences
Obscene speech in the Qur'anic perspective An objective study based on the verses and interpretation of the Noble Qur’an in diagnosis and treatment
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t:

The most famous thing a person does is talk. He loves and hates, and continues with it confirming relationships, and with it, too, comes out of disbelief into faith. Marry a word and separate with a word. He reaches the top of the heavens with a kind word, with which he will gain the pleasure of God, and the Lord of a word that the servant speaks to which God writes with our pleasure or throws him on his face in the fire. Emotions are inflamed, the United Nations is intensified with a word, and relations between states and war continue with a word.

What comes out of a person’s mouth is a translator that expresses the repository of his conscience and reveals the place of his bed, for it is evidence of

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Publication Date
Thu Feb 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
Compare between result of analysis of variance after and before use analysis covariance to Split-blocks design
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This research aims to study the important of the effect of analysis of covariance manner for one of important of design for multifactor experiments, which called split-blocks experiments design (SBED) to deal the problem of extended measurements for a covariate variable or independent variable (X) with data of response variable or dependent variable Y in agricultural experiments that contribute to mislead the result when analyze data of Y only. Although analysis of covariance with discussed in experiments with common deign, but it is not found information that it is discussed with split-Blocks experiments design (SBED) to get rid of the impact a covariance variable. As part application actual field experiment conducted, begun at

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Publication Date
Thu Nov 02 2023
Journal Name
Journal Of Engineering
Verification and Parametric Analysis of Shear Behavior of Reinforced Concrete Beams using Non-linear Finite Element Analysis
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Many researchers have tackled the shear behavior of Reinforced Concrete (RC) beams by using different kinds of strengthening in the shear regions and steel fibers. In the current paper, the effect of multiple parameters, such as using one percentage of Steel Fibers (SF) with and without stirrups, without stirrups and steel fibers, on the shear behavior of RC beams, has been studied and compared by using Finite Element analysis (FE). Three-dimensional (3D) models of (RC) beams are developed and analyzed using ABAQUS commercial software. The models were validated by comparing their results with the experimental test. The total number of beams that were modeled for validation purposes was four. Extensive pa

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