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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 Jan 19 2021
Journal Name
Sn Applied Sciences
Post-fire serviceability and residual strength of composite post-tensioned concrete T-beams
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Abstract<p>In this study, the response of ten composite post-tensioned concrete beams topped by a reinforced concrete deck with adequate reinforcing shear connectors is investigated. Depending on the concrete compressive strength of the deck slab (20, 30, and 40 MPa), beams are grouped into three categories. Seven of these beams are exposed to a fire attack of 700 and 800 °C temperature simultaneously with or without the presence of a uniformly distributed sustained static loading. After cooling back to ambient temperature, these composite beams are loaded up to failure, using a force control module, by monotonic static loading in a four-point-bending setup with two symmetrical concentrated loads applied in </p> ... Show More
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Publication Date
Fri Aug 01 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Oral manifestations, biochemical, and IL-6 analysis of saliva in major depressive disorder patients under treatment
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Background: Major depressive disorder (MDD) is mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities. The aims of the study: were to determine the prevalence of oral manifestation among patients with major depressive disorder receiving antidepressant drugs, and detect alkaline phosphatase (ALP), Total Salivary proteins (TSP), and Interleukin-6 (IL-6) in relation to MDD patients under treatment and to compare with healthy controls. Materials and method: (50) MDD patients; between the ages of 20 years and 60 years.The depression patients are divided into (25) patients under treatment with fluoxetine (Prozac), and (25) patients under tr

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Publication Date
Mon Jun 30 2014
Journal Name
Al-kindy College Medical Journal
The prevalence and antimicrobial sensitivity of Esbl Escherichia Coli. in clinical isolates
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Background: The antimicrobial resistance is one of the most serious and expanding health problems world -wide in the last decades. The esbl escherichia coli. (extended – spectrum beta-lactamase e.coli) represents an important aspect of it .Objectives: To get an overview on the esbl e.coli prevalence profile in general. Also to assess the antibiotic sensitivity of esbl e. coli trying to specify the most effective antibiotics in combating this micro-organism.Methods: this study tries to focus on this problem in Iraq which through a prospective study approach by taking 35 clinical samples from various sources (urine, blood, abscess, eye ,vagina ,stool and others),and after confirming the presence of e.coli, the presence of esbl e.coli and

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Publication Date
Fri Aug 01 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Salivary level of RANKL and OPG in chronic periodontitis
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Background: Periodontal diseases are initiated by microbial plaque, which accumulates in the sulcular region and induces an inflammatory response. The Receptor activator of nuclear factor-kappa B ligand / osteoprotegerin (RANKL/OPG) axis is involved in the regulation of bone metabolism in periodontitis, in which an increase in receptor activator of nuclear factor-kappa B ligand or a decrease in osteoprotegerin can tip the balance in favor of osteoclastogenesis and the resorption of alveolar bone that is the hallmark of periodontitis. This study was performed to investigate the role of salivary levels of RANKL and OPG in pathogenesis of chronic periodontitis. Subjects and Methods: Fifty five subjects with chronic periodontitis with ages rang

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Publication Date
Thu Jun 27 2024
Journal Name
Journal Of Image And Graphics
ALL-FABNET: Acute Lymphocytic Leukemia Segmentation Using a Flipping Attention Block Decoder-Encoder Network
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Melanoma, a highly malignant form of skin cancer, affects individuals of all genders and is associated with high mortality rates, especially in advanced stages. The use of tele-dermatology has emerged as a proficient diagnostic approach for skin lesions and is particularly beneficial in rural areas with limited access to dermatologists. However, accurately, and efficiently segmenting melanoma remains a challenging task due to the significant diversity observed in the morphology, pigmentation, and dimensions of cutaneous nevi. To address this challenge, we propose a novel approach called DenseUNet-169 with a dilated convolution encoder-decoder for automatic segmentation of RGB dermascopic images. By incorporating dilated convolution,

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Publication Date
Fri Sep 15 2023
Journal Name
Al-academy
Space suitability and its functional implications in interior design
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The current research dealt with the study of space compatibility and its role in enhancing the functional aspect of the design of the interior spaces of isolation hospitals by finding a system or format that is compatible with the nature of the changes occurring in the structure and function of the space system, as well as contributing to enhancing compatibility between the functional aspect and the interior space. Therefore, the designer must The interior is the study of the functional and spatial aspects as they are the basic aspects for achieving suitability, and through the interaction between the person and the place, the utilitarian performance characteristics are generated that the interior designer is interested in and tries to d

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Publication Date
Sun Dec 16 2018
Journal Name
Al-academy
Graphic Design and Functional Applications in the Interior Space
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The overlap between science and knowledge is a feature of the 21st century. This integration, which crosses the traditional boundaries between academic disciplines, has occurred because of the emergence of new needs and new professions. This overlap has overshadowed the arts in general and design in particular. The Design achievements have not been far away from the attempts of integration of more than one type or design application to produce new outputs unique in its functional and aesthetic character, including the terms of internal graphic design.

The researcher raises the question of the functional dimension of graphic design in the internal space, in order to answer it through the methodological framework, which includes th

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Publication Date
Fri Mar 13 2020
Journal Name
Plant Archives
Azotobacter chroococcum and Rhizobium leguminosarum inoculums survival in soil and efficiency in enhancing plant growth
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Publication Date
Tue Apr 26 2022
Journal Name
Journal Of Contemporary Medical Sciences
Doxorubicin Immobilization on chitosan-modified silver Nanoparticles as a drug delivery method for effective anticancer treatment
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Objective: The goal of this research is to load Doxorubicin (DOX) on silver nanoparticles coupled with folic acid and test their anticancer properties against breast cancer. Methods: Chitosan-Capped silver nanoparticles (CS-AgNPs) were manufactured and loaded with folic acid as well as an anticancer drug, Doxorubicin, to form CS-AgNPs-DOX-FA conjugate. AFM, FTIR, and SEM techniques were used to characterize the samples. The produced multifunctional nano-formulation served as an intrinsic drug delivery system, allowing for effective loading and targeting of chemotherapeutics on the Breast cancer (AMJ 13) cell line. Flowcytometry was used to assess therapy efficacy by measuring apoptotic induction.  Results: DOX and CS-Ag

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Publication Date
Wed Jan 01 2014
Journal Name
Journal Of Thi – Qar Science
Enhanced of the Two photon Absorption in Nanostructure Wide Band gap Semiconductor CdS using femtosecond Laser
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We observed strong nonlinear absorption in the CdS nanoparticles of dimension in the range 50-100 nm when irradiant with femtosecond pulsed laser at 800 nm and 120 GW/cm 2 irradiance intensity. The repetition rate and average power were 250 kHz and

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