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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
Wed Jan 02 2019
Journal Name
Journal Of The College Of Languages
Функциональная транспозиция причастий в прилагательное Functional Shift of Present and Past Participles from No-minal Meaning to Adjectival Meaning
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Publication Date
Wed Jan 02 2019
Journal Name
Journal Of The College Of Languages (jcl)
Functional Shift of Present and Past Participles from No-minal Meaning to Adjectival Meaning: Функциональная транспозиция причастий в прилагательное
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This paper tackles in detail the functional shift of parts of speech, such as the shift of a verbal clause to an adjectival clause, along with the types of such a shift. The researcher identified the important features of participles, as well as the concept of participles, adjectives, and their types. Also, the most important changes that affect the participles during such shifts. Further, an exposition is made of the different producers through which a verbal clause is changed into an adjectival one in Russian.

      This type of functional shift in parts of speech is seen as a process of deriving most of the new words in contemporary Russian. Russian is very rich in new words, whether by way of processe

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Publication Date
Sat Aug 10 2019
Journal Name
Engineering, Technology &amp; Applied Science Research
Performance of Segmental Post-Τensioned Concrete Beams Exposed to High Fire Temperature
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The present study illustrates observations, record accurate description and discussion about the behavior of twelve tested, simply supported, precast, prestressed, segmental, concrete beams with different segment numbers exposed to high fire temperatures of 300°C, 500°C, and 700°C. The test program included thermal tests by using a furnace manufactured for this purpose to expose to high burning temperature (fire flame) nine beams which were loaded with sustaining dead load throughout the burning process. The beams were divided into three groups depending on the precast segments number. All had an identical total length of 3150mm but each had different segment number (9, 7, and 5 segments), in other words, different segment length

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Publication Date
Tue Dec 01 2015
Journal Name
Journal Of Engineering
Strengthening of Reinforced Concrete T- Section Beams Using External Post-Tensioning Technique
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This research is carried out to investigate the externally post-tensioning technique for strengthening RC beams. In this research, four T-section  RC beams having the same dimensions and material properties were casted and tested up to failure by applying two mid-third concentrated loads. Three of these beams are strengthened by using external tendons, while the remaining beam is kept without strengthening as a control beam. Two external strands of 12 mm diameter were fixed at each side of the web of the strengthened beams and located at depth of 200 mm from top fiber of the section (dps). So that the depth of strands to overall depth of the section ratio (dps

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Publication Date
Sun Dec 07 2008
Journal Name
Baghdad Science Journal
Developing of Bacterial Mutagenic Assay System for Detection of Environmental and Food MutagensV – Using Anticancer Drug Cyclophosphamide
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G-system composed of three isolates G3 ( Bacillus),G12 ( Arthrobacter )and G27 ( Brevibacterium) was used to detect the mutagenicity of the anticancer drug, cyclophosphamide (CP) under conditions similar to that used for standard mutagen, Nitrosoguanidine (NTG). The CP effected the survival fraction of isolates after treatment for 15 mins using gradual increasing concentrations, but at less extent comparing to NTG. The mutagenic effect of CP was at higher level than that of NTG when using streptomycin as a genetic marker, but the situation was reversed when using rifampicin resistant as a report marker. The latter effect appeared upon recording the mutagen efficiency (ie., number of induced mutants/microgram of mutagen). Measuring the R

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Publication Date
Sat Jan 16 2016
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Synthesis, Characterization And Biological Evaluation of New Schiff Bases Mixed Ligand Metal Complexes of Some Drug Substances
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Publication Date
Thu Oct 31 2019
Journal Name
Al-kindy College Medical Journal
Assessment of efficacy and safety of dapsone gel 5% in the treatment of acne vulgaris
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ABSTRACTBackground : Acne vulgaris is a
common skin disease, affecting more than 85% of
adolescents and often continuing into adulthood.
People between 11 and 30 years of age and up to
5% of older adults. For most patients acne remains
a nuisance with occasional flares of unsightly
comedones, pustules and nodules. For other less
fortunate persons, the sever inflammatory response
to Propionibacterium acnes (P.acnes) results in
permanent
Methods: Disfiguring scars. (1, 2) Stigmata of sever
acne cane lead to social ostracism, withdrawal
from society and severe psychologic
depression (1-4).
Result Pathogenesis of acne Traditionally, acne
has been thought of as a multifactorial disease of
the fo

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Publication Date
Fri Jul 01 2022
Journal Name
Civil Engineering Journal
Behavior of Post-Tensioned Concrete Girders Subject to Partially Strand Damage and Strengthened by NSM-CFRP Composites
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Studies on the flexural behavior of post-tensioned beams subjected to strand damage and strengthened with near-surface mounted (NSM) technique using carbon fiber-reinforced polymer (CFRP) are limited and fail to examine the effect of CFRP laminates on strand strain and strengthening efficiency systematically. Furthermore, a design approach for UPC structures in existing design guidelines for FRP strengthening techniques is lacking. Hence, the behavior of post-tensioned beams strengthened with NSM-CFRP laminates after partial strand damage is investigated in this study. The testing program consists of seven post-tensioned beams strengthened by NSM-CFRP laminates with three partial strand damage ratios (14.3% symmetrical damage, 14.3%

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Publication Date
Sat Feb 01 2020
Journal Name
Structures
Experimental and numerical study on wrapping concrete cylinders post heating and cooling under preload using CFRP fabrics
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This paper reports test results and describes a numerical investigation of the effectiveness of using carbon fibre reinforced polymer (CFRP) fabrics for strengthening concrete cylinders that have been undamaged and damaged due to heating under preload. The purpose of this research was to investigate whether there is any difference in the performance of CFRP-wrapped cylinders if the wrapping is done under preload, and those for which neither heating, cooling nor wrapping was done under preload. The cylinders were exposed to 30% of maximum load at ambient temperature during heating and cooling before being wrapped under preload. Of 18 Ø 100 × 200 mm identical cylinders, 6 were left as control samples without heating, 12 were exposed t

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Publication Date
Wed Jul 31 2024
Journal Name
International Journal Of Health &amp; Medical Research
Review Article: Cupping Therapy in Treatment of Certain Diseases
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The research undertaken has provided a comprehensive insight into the practice of cupping therapy, a traditional treatment modality that has seen resurgence in. modern complementary medicine. This exploration, focusing on a spectrum of. Conditions such as migraines, lower back pain, neck pain, knee osteoarthritis, and chronic urticaria, highlights the potential benefits and the necessity for a deeper. Scientific understanding of cupping therapy. Cupping therapy, with its roots deeply embedded in ancient medical practices, offers a unique approach to treatment by promoting healing through increased blood flow and the release of toxins from the body. The application of this therapy in treating migraines has shown promising results, su

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