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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 Dec 29 2021
Journal Name
Journal Of The College Of Education For Women
Spread of Private Education: An Analytical Geographical Study of the Factors of their Appearance, Prevalence and Functional Competence in Baghdad: سيناء عدنان عبد الله, و أريج بهجت أحمد
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يهدف البحث إلى تقييم الكفاءة الوظيفية لمؤسسات التعليم الأهلي في أداء وظيفتها بمستوى عالٍ لتشبع حاجة سكان المدينة الذين فضّلوا التعليم الأهلي على التعليم داخل المؤسسات الحكومية مما أدى إلى انتشارها، وصولا إلى أهم الآثار المترتبة على ذلك الانتشار إذ نافست فيه مؤسسات التعليم الحكومي، بل وتنافست المؤسسات الأهلية فيما بينها لتقديم أفضل خدمة تعليمية للصراع من أجل البقاء، وتهدف أيضا إلى  إظهار الوجه السلبي ا

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Publication Date
Fri Dec 14 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Effectiveness of Women's Self-care Instructions concerning Wound, Perineal & Urinary System Care post cesarean section in Baghdad teaching hospital
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Aim: to determine the effectiveness of women's self-care instructions on their post cesarean section care in Baghdad
teaching hospital.
Methodology: The present study used quasi-experimental study design in maternity words in Baghdad teaching
hospital. The sample was collected and follow up for the period (15) January 2014 until 15 May 2014 Nonprobability
(purposive sample) of (100) women post cesarean section divided in to two groups (50) women post
cesarean section considered as a study group, and another (50) women post cesarean section considered as the
control one, A questionnaire designed as a tool to collect data fit the purpose of the study a questionnaire include
demographic variables, Reproductive variables

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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Study the effect of a new nikel (II) Complex and anticancer drug (cp) on Liver enzyme activity (GPT,GOT) and Creatinine level in Kidney of femal mice
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This study involved the effect of anew nickel (II) complexs with formla [NiL2(H2O)2].2.5ETOH where L=Bis[5-(p-nitrophenyL)-4-phenyL-1,2,4-traizole-3-dithocarbamato hydrazide] diaqua. nickel(II). Ethanol(2.5).and anti-cancer drug cyclophosphamide on specific actifity of two Liver enzymes (GOT,GPT) in the (Liver,kidney) tissues and on the creatinine Level in the kidney byUtilizing an invivosystem in femalmice.The result showed that inhibition in the activity of GPT and GOT enzymes in theLiver and in both nickel (II) complex and cyclophosphamide drug (CP) . mice weretreated with three doses (90,180,320) µg/mouse for three days for each group.The Liver show's the highest rate of GPT inhibition was about 97.43% at180µg/mouse regarding the ki

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Publication Date
Sun Jun 12 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Understanding the Experience of Hospital Pharmacists with the Effectiveness, Safety, Adverse Drug Reaction Reporting and Interchangeability of Biopharmaceutical Medicines
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The study objectives were to 1) explore the real-world experience of hospital pharmacists with the differences in effectiveness safety, and interchangeability between biosimilar medicines and their reference biological counterparts, 2) reveal pharmacist recommendations to enhance the safety of biopharmaceutical medicines in public hospitals.

The study has a mixed-method design where the core component was qualitative (interviews) and the supplemental component was quantitative (adverse drug reaction, ADR, reports). This qualitative component included semi-structured (mostly face-to-face) interviews involving hospital pharmacists from different hospitals with experience with biological or biosimilar medicines. The interviews were c

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Publication Date
Mon Jan 01 2018
Journal Name
Journal Of Cosmetics, Dermatological Sciences And Applications
Treatment of Kaposi’s Sarcoma by Combination of Zinc Sulfate and Propranolol
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Publication Date
Mon Apr 01 2019
Journal Name
Biochem. Cell. Arch
Association Of – 1195a/g Single Nucleotide Polymorphism Of Cyclooxygenase-2 Gene With The Severity Of Chronic Periodontitis In An Iraqi Population
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Chronic periodontitis (CP) is an inflammatory disease affecting tooth supporting structures in response to bacterial dental plaque causing irreversible tissue destruction. Cyclooxygenase-2 (COX-2) is an effective mediator in the pathogenesis of periodontitis. Polymorphisms in the COX-2 gene may contribute to its overexpression and increased disease susceptibility. To evaluate the association between -1195 A/G single nucleotide polymorphism (SNP) in the promotor area of the cyclooxygenase-2(COX-2) gene and severity of chronic periodontitis in a sample of Iraqi population. -1195A/ G COX-2 SNP was investigated in 70 chronic periodontitis (CP) cases and 30 healthy controls. CP cases composed of 2 subgroups (35 moderate CP cases and 35 severe CP

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Publication Date
Wed Mar 25 2020
Journal Name
International Journal Of Drug Delivery Technology
Study of Molecular Interaction for Antibiotic Drug with Sugar Solutions at Different Temperature
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The interactions of drug amoxicillin with maltose or galactose solutions with a variation of temperature have been discussed by taking in the volumetric and viscometric procedures. Physical properties [densities (ρ) and viscosities (η)] of amoxicillin (AMOX) aqueous solutions and aqueous solutions of two type saccharides (maltose and galactose 0.05m) have been measured at T = (298.15, 303.15 and 308.15) K under atmospheric pressure. The apparent molar volume (ϕv cm3mole-1) has been evaluated from density data and fitted to a Redlich-Mayer equation. The empirical parameters of the Mayer-Redlich equation and apparent molar volume at infinite dilution ذv were explicated in terms of interactions from type solute-solvent and solute

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Publication Date
Sun Jun 30 2024
Journal Name
Malaysian Journal Of Science
SIMPLEX OPTIMIZATION FOR THE SPECTROPHOTOMETRIC DETERMINATION OF AZITHROMYCIN DRUG VIA ION-PAIR FORMATION
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A spectrophotometric determination of azithromycin was optimized using the simplex model. The approach has been proven to be accurate and sensitive. The analyte has been reacted with bromothymol blue (BTB) to form a colored ion pair which has been extracted in chloroform in a buffer medium of pH=4 of potassium phthalate. The extracted colored product was assayed at 415 nm and exhibited a linear quantification range over (1 - 20) g/ml. The excipients did not exhibit any interferences with the proposed approach for assaying azithromycin in pharmaceutical formulations.

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Publication Date
Wed Apr 28 2021
Journal Name
Journal Of Engineering
Post-occupancy evaluation Correlated with Medical Staffs' Satisfaction: A Case Study of Indoor Environments of General Hospitals in Sulaimani City
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This study aims at identifying the notion of Post-Occupancy Evaluation (POE) pertinent to the performance of three general hospitals constructed inside the Sulaimani City, tracing the relationship between the quality of the indoor environments and medical staff (doctors and nurses) satisfaction level. Using some indoor environment elements in the right way will positively influence the mood, stress level of the medical staff, and patient recovery as a result. The POE toolkits (AEDET and ASPECT) have been implemented on targeted wards at the selected hospitals. AEDET and ASPECT questionnaires were distributed among 152 medical staff to obtain their perspectives. In total, 112 valid questionnaires were received. The medica

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Publication Date
Mon Jul 03 2017
Journal Name
Iraqi New Medical Journal
Coarctation of aorta in pediatric age group: mode of presentation, early and intermediate outcomes of interventional treatment
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Although rare, coarctation of aorta is a treatable cause of hypertension, transcatheter dilatation by balloon with or without stent are a well-known treatment strategy