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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 Jan 05 2024
Journal Name
Al-academy
Designs treatment of the internal spaces of pharmacies
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The pharmacy is the face for the health buildings and hospitals, The linking professional relationships and functional, it is been from the important places that most people go it, so according to that we must format its interior design in form that suitable with the need of most people use it or work in it, and this the search goal, dashing from the search subject which to hide finding designer treatment for the pharmacies interior spaces, to give share in the functional improvement performance or aesthetic. We define the search goals to share in educate the pharmacist in the effect of interior design for improvement of interior environment, in addition to the search consider as designer trying add to the other trying the interior desig

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Publication Date
Sat Oct 03 2020
Journal Name
International Journal Of Diabetes In Developing Countries
The efficacy of once-daily liraglutide as an add-on to oral antidiabetic agents on weight reduction and glycemic control in obese patients with inadequately controlled type 2 diabetes: a retrospective analysis in relation to liraglutide dose escalation within a 7-month treatment period
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Background This study aimed to evaluate the efficacy of once-daily liraglutide as an add-on to oral antidiabetics (OADs) on glycemic control and body weight in obese patients with inadequately controlled type 2 diabetes (T2D). Methods A total of 27 obese T2D patients who received 7 months (0.6 mg/day for the first month, 1.2 mg/day for 3 months, and 1.8 mg/day for 3 months) of liraglutide treatment as an add-on to OADs were included. Data on body weight (kg), fasting plasma glucose (FPG, mg/dL), postprandial glucose (PPG, mg/dL), and HbA1c (%), were recorded. Results Liraglutide doses of 1.2 mg/day and 1.8 mg/day were associated with significant decreases in body weight (by 8.0% and 11.9%, respectively, p < 0.01 for each) and HbA1c (by 20.0

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Publication Date
Wed Feb 01 2023
Journal Name
Colloid Journal
Application of Hydrophilic Lipophilic Difference Theory for Fenofibrate Formulation as a Self-Emulsifying Drug Delivery System
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Improved oral bioavailability of lipophilic substances can be achieved using self-emulsifying drug delivery systems. However, because the properties of self-emulsifying are greatly influenced by surfactant amount and type, type of oil used, droplet size, charge, cosolvents, and physiological variables, the synthesis of self-emulsifying is highly complex; consequently, only a small number of excipient self-emulsifying formulations has been developed so far for clinical use. This study reports a highly effective procedure for developing self-emulsifying formulations using a novel approach based on the hydrophilic-lipophilic difference theory. Microemulsion characteristics, such as the constituents and amounts of oil and surfactant electrolyte

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Publication Date
Sun Mar 01 2026
Journal Name
Journal Of Pharmaceutical Sciences
Mechanistic insights into drug loading effect on dissolution performance of Loratadine–Soluplus® amorphous solid dispersions
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Publication Date
Fri Aug 01 2025
Journal Name
Imam Jaafar Al-sadiq University Journal Of Human And Social Sciences
Examination of Identity and Alienation in Postcolonial Literature: Analysis of Nervous Conditions by Tsitsi Dangarembga
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This research explores the themes of identity and alienation in Tsitsi Dangarembga's famous novel, Nervous Conditions, through Kimberlé Crenshaw's intersectionality theory. The story takes place in postcolonial Zimbabwe and delivers a fascinating illustration of the intersecting domains of gender, race, class, and colonial legacies that shape the characters' experiences of identity and alienation. Benefitting from Crenshaw's intersectional paradigm, this article explores the multidimensional interface of societal categorizations and power relations in the novel, revealing the complex dynamics of individuals as they negotiate their identities in a postcolonial context. Through a thorough examination of Tambudzai's journey and the problems o

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Publication Date
Wed Dec 23 2020
Journal Name
Iraqi Journal Of Agricultural Sciences
THE TAXONOMICAL SIGNIFICANT OF COMPUTERD PHYLOGENETIC ANALYSIS AND MORPHOLOGICAL DATA IN SOME SPECIES OF POLYGONACEAE
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This research dealt with study of cladistics taxonomy of  five  species related to the genus Rumex L. and Polygonum L. from family polygonaceae in Iraq by using Mesquite software V.2.75. This  research support strongly delimiting  the species P. aviculare L. and P. lapathifolia L.as suggested in floras publication while R. dentatus L. is setted in single group whereas R. vesicarius L. and R. conglomeratus Murray were included in the same group. Also, this study involved characteristics of shape, dimensions, color, and ornamentation of seeds and fruits as  the seed forms were ranging from lenticular to trigonous. In terms of size calculations,  the seeds of R. vesicarius  was recorded the higher range (4.0- 4.5) mm in length w

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Publication Date
Tue Mar 01 2011
Journal Name
Journal Of Economics And Administrative Sciences
Measurement and analysis of the production function of the transport sector in the Iraqi economy
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Transportation Sector classified as one of the services sectors which is without the production activities cannot be complete its rule. Is act asmoving actions which operate at production and non production goals for the organization and individuals insides the country and with others, that is why this sector act as one of the main which is occupied an important status on the way the economic activities and on the level of the economic institutions the transportation work on transforming all the commodities and products from productions locations to consumption location then its effect the productivity process and create the location utility and on the level of economic it considered as one of the economic supportive structure an

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Publication Date
Wed Aug 01 2018
Journal Name
International Journal Of Novel Research In Electrical And Mechanical Engineering
Use of Panel Method in High Subsonic and Transonic Aerodynamic Analysis of Complex Aircraft Configuration
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The application of low order panel method with the Dirichlet boundary condition on complex aircraft configuration have been studied in high subsonic and transonic speeds. Low order panel method has been used to solve the case of the steady, inviscid and compressible flow on a forward swept wing – canard configuration with cylindrical fuselage and a vertical stabilizer with symmetrical cross section. The aerodynamic coefficients for the forward swept wing aircraft were calculated using measured wake shape from an experimental work on same model configuration. The study showed that the application of low order panel method can be used with acceptable results

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Publication Date
Wed Jan 01 2014
Journal Name
Current Research In Microbiology And Biotechnology
Cytogenetic Analysis for the Effect of Alcoholic and Water Extracts of Iraqi Propolis in Mice
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This study was conducted to study the cytogenetic effect of both alcoholic and water extracts of propolis on mice. Three different samples of propolis were collected from three different regions of Iraq (Najaf, Arbil and Baghdad) to be used in this study. The cytotoxic effect of two different doses of each extracted sample was measured by employing cytogenetic analysis which included (mitotic index (MI), chromosomal aberrations (CAs), micronucleus index (MN) and sperm abnormalities). Results showed that significant increase in MI and significant reduction in MN, CAs and sperm abnormalities percentage were seen after treatment with both alcoholic and water extract of the three samples when compared with negative control, and alcoholic extrac

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Publication Date
Mon Dec 01 2025
Journal Name
Journal Of Urban Management
Spatial configuration of urban informality: A morphological and syntactic analysis of informal settlements in Baghdad
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