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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 Jun 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
Periodontal health status of patients with Maxillary Chronic Rhinosinusitis (Part 1: Clinical study)
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Background: Periodontal diseases (PD) are inflammatory conditions of the tissues supporting the teeth, most often gingivitis and periodontitis. Maxillary chronic rhinosinusitis (MCRS) is the inflammation of the maxillary sinuses which is last for at least 12 consecutive weeks duration. Aims of study: Distribution of periodontal diseases among patients with Maxillary chronic rhinosinusitis according to gender and age. Materials and methods: Males and females subjects (25-45 years), divided into two groups; 150 patients suffer from MCRS and 130 subjects without MCRS. Clinical periodontal parameters; Plaque Index (PL.I), Gingival Index (G.I), Probing Pocket Depth (PPD), Clinical Attachment Level (CAL) and Bleeding On Probing (BOP) recorded f

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Publication Date
Sun Nov 01 2020
Journal Name
Annuals Of Tropical Medicine & Public Health
Topical treatment of seborrhoeic dermatitis and dandruff: An overview
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Publication Date
Mon Jan 01 2024
Journal Name
مجلة دراسات قانونية
Domain names between legal regulation and lack of treatment
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Throughout the ages,the methods of human production, exchange, and communication have not changed,and lifestyles have not witnessed rapid and comprehensive changes except since the presence of advanced and modern technologies for information and communication, which led to the emergence of new patterns of intellectual works and innovations that are dealt with and circulated through the virtual medium.These innovations are in many legal disputes, and domain names are one of the most important foundations of information networks, as they are the key to entering the virtual world and distinguishing websites. Because of the novelty of domain names,many attacks have occurred on them, which are closely related to intellectual property rights. And

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Publication Date
Sat Jan 01 2022
Journal Name
The 2nd Universitas Lampung International Conference On Science, Technology, And Environment (ulicoste) 2021
Study the effect of size variation and stability on the electronic and spectroscopic properties of BN wurtzoids- diamantane nanostructure via density functional theory
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Publication Date
Fri Dec 23 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Preparation and in-vitro Evaluation of Secnidazole as Periodontal In-situ Gel for Treatment of Periodontal Disease
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This study aims to develop a thermosensitive mucoadhesive periodontal in situ gel of secnidazole for local release of drug for treatment of periodontitis, in order to increase the drug residence time and to increase patient compliance while lowering the side effects of the drug.

Cold method was used to prepare 30 formulas of secnidazole periodontal in situ gel, using different concentrations of thermosensitive polymers (poloxamer407 alone or in combination with poloxamer 188) and methyl cellulose (MC ) or hydroxypropyl methylcellulose (HPMC K4M )in different concentrations used as mucoadhesive polymer and the resultant formulations were subjected to several tests such as   gelation temperature GT, appearance and pH value. The fo

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Publication Date
Sun Dec 12 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Gender Differences in Adverse Drug Reactions Among Adult Patients Reported to the Iraqi Pharmacovigilance Center
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For many years it was argued that there may be a gender differences in adverse drug reactions (ADRs). This assumption was based on many possible factors such as hormonal or behavior differences, and it was not clearly identified since the female gender was not preferred to be enrolled in many clinical trials. The primary aim of this study was to assess the extent of possibly relevant gender differences in drug–ADRs regarding causality, severity, preventability, seriousness, expectedness and outcome. While the secondary aim was to assess for which group of drugs and for which ADRs gender differences are identified most often. The study was a retrospective one that depends on processing a specially selected group of data obtained from th

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Publication Date
Sat Sep 30 2023
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Review of the Mechanisms for Preventing, Diagnosing, and Treatment of Pipe Sticking in Drilling Operations
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Stuck pipe is a prevalent and costly issue in drilling operations, with the potential to cost the petroleum industry billions of dollars annually. To reduce the likelihood of this issue, efforts have been made to identify the causes of stuck pipes. The main mechanisms that cause stuck pipes include drill cutting of the formation, inappropriate hole-cleaning, wellbore instability, and differential sticking forces, particularly in highly deviated wellbores. The significant consequences of a stuck pipe include an increase in well costs and Non-Productive Time (NPT), and in the worst-case scenario, the loss of a wellbore section and down-hole equipment, or the need to sidetrack, plug, or abandon the well. This paper provides a comprehensive

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Publication Date
Tue Dec 13 2005
Journal Name
Iraqi Journal Of Laser
Clinical Observation and Performance of High Power Diode Laser in the Treatment of Oral Lesions
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In this work, oral lesions belong to 17 patients, 7 males and 10 females. Their ages range between 15 and 45 years. Follow up was conducted after one day, 7 days, 14 days, one month, and finally 3 months postoperatively. The study lasted for 1.5 year. Surgical diode laser with wavelength of 810 ± 20 nm, with two power levels of 10 and 15 W were used in contact and in non-contact mode via optical fiber. The postoperative outcome revealed; greater haemostatic capability, dry, sealed wound and noticeable lack in pain sensation

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Effect of L-carnitine, Multivitamins and their Combination in the Treatment of Idiopathic Male Infertility
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The aim of the present study is to investigate and compare the efficacy of L-carnitine, multivitamins and their combination therapies on semen characteristics in idiopathic male infertility. Idiophathic infertile patients were randomly divided into three groups who had received three different treatment regimens for three months: group A (45 patients) has received 2 grams daily of L-carnitine alone; group B (55 patients) had received the combination of  L-carnitine (2 grams daily) plus one tablet daily of multivitamins (Stresstabs®); and group C (29 patients) had received one tablet daily of multivitamins alone. The study was started on 1/11/2009 and completed on 31/3/2010 and performed at Rizgari Teaching Hospital in

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Publication Date
Thu Nov 01 2012
Journal Name
Journal Of Drugs In Dermatology: Jdd
Treatment of scabies using 8% and 10% topical sulfur ointment in different regimens of application.
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KE Sharquie, JR Al-Rawi, AA Noaimi, HM Al-Hassany, Journal of drugs in dermatology: JDD, 2012 - Cited by 47

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