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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 01 2021
Journal Name
Baghdad Science Journal
Reactivity of O-Drug Bond in some Suggested Voltarine Carriers: Semiempirical and ab Initio Methods
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In this work, the possibility to use new suggested carriers (D= Aspirin, Ibuprofen, Paracetamol, Tramal) is discussed for diclofenac drug (voltarine) by using quantum mechanics calculations. The calculation methods (PM3) and (DFT) have been used for determination the reaction path of (O-D) bond rupture energies. Different groups of drugs as a carrier for diclofenac prodrugs (in a vacuum) have been used; at their optimized geometries. The calculations included the geometrical structure and some of the physical properties, in addition to the toxicity, biological activity, and NLO properties of the prodrugs, investigated using HF method. The calculations were done by Gaussian 09 program. The comparison was made for total energies of reactan

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Publication Date
Wed Mar 30 2022
Journal Name
Journal Of Economics And Administrative Sciences
Comparing Some Methods of Estimating the Parameters and Survival Function of a Log-logistic Distribution with a Practical Application
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The Log-Logistic distribution is one of the important statistical distributions as it can be applied in many fields and biological experiments and other experiments, and its importance comes from the importance of determining the survival function of those experiments. The research will be summarized in making a comparison between the method of maximum likelihood and the method of least squares and the method of weighted least squares to estimate the parameters and survival function of the log-logistic distribution using the comparison criteria MSE, MAPE, IMSE, and this research was applied to real data for breast cancer patients. The results showed that the method of Maximum likelihood best in the case of estimating the paramete

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Publication Date
Wed Aug 30 2023
Journal Name
Al-kindy College Medical Journal
Risk Factors influencing Post-Partum Depression Severity in Iraqi Women
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Background: Post-partum depression (PPD) is a form of postnatal depression that affects mothers. Clinical manifestations usually appear within six months after delivery. Risk factors that influence the severity of post-partum depression are not fully known in the Iraqi population.
Objectives: We aim to evaluate the risk factors and identify potential predictors that may influence the symptom levels (severity) of post-partum depression among Iraqi women from Baghdad.
Subjects and Methods: The current study is cross-sectional, and we used the Edinburgh Postnatal Depression Scale (EPDS) and a cut-off value of 13 to differentiate patients into two those with lower symptom levels (LSL) and higher symptom levels (HSL). We also explored p

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Publication Date
Sat May 30 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of some salivary biochemical parameters in cigarette smokers with chronic periodontitis
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Background: Cigarette smoking is an important risk factor that has a clear strong association with the prevalence and severity of chronic periodontitis (CP). Salivary biochemical parameters may be affected by both smoking and CP together. Materials and methods: Eighty systematically healthy male patients were included in this study. They were grouped based on their periodontal and smoking status. Unstimulated whole saliva (UWS) was collected from all subject. Salivary flow rate (FR) was measured during sample collection. Parameters such as salivary pH, total protein (TP), albumin (Alb), total fucose (TF), protein bound fucose (PBF) and C-reactive protein (CRP) were estimated. Results: Salivary flow rate was not altered regarding to smoking

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Publication Date
Fri Dec 14 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Assessment of Nurses' Exposure to Chronic Diseases in Thi-Qar Governorate Hospitals
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Objective: To assess nurses' exposure to hospitals chronic diseases hazards in Thi-Qar governorate, and to identify the association between nurses' socio-demographic characteristics of age, sex, marital status, place of work, the experience and educational attainment and their exposure to the hazards of chronic diseases. Methodology: A purposive "non-probability" sample of (433) nurses who were selected from four public hospitals in Thi-qar governorate for the period from November 4th 2013 to June 8th of 2014. Results: The study results indicated that that the vast majority of participants have mild chronic di

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Publication Date
Sun Jul 09 2017
Journal Name
Current Research In Microbiology And Biotechnology
The chronic effects of glucosamine sulfate (GS) on kidney in Albino Mice
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Publication Date
Mon Sep 11 2017
Journal Name
Journal Of Molecular Cell Biology
Sustained activation of P2X7 induces MMP-2-evoked cleavage and functional purinoceptor inhibition
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Publication Date
Wed Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Role of the Clinical Pharmacist in Reducing Preventable Adverse Drug Events
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According to so many previous studies, lack of sufficient information during prescribing steps may lead to medication errors. Thus, the presence of the clinical pharmacist during routine rounding process in the ward with intervention of patient care plan may reduce the probability of adverse drug events (ADEs).This study evaluate role of the clinical pharmacists, as a member of medical team with the physician, on ADEs and report their interventions in the internal medicine unit. This study was designed to compare between two groups of patients, those receiving care from a rounding team (physician, nurse, and clinical pharmacist) (study or intervention group with 51 patient); and those receiving c

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Publication Date
Mon Aug 01 2022
Journal Name
Journal Of Medicine And Life
Effect and benefit of percutaneous coronary intervention in chronic total occlusion on ventricular repolarization: QT correction and dispersion
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ST segment, T wave changes, QT interval changes, and QTc dispersion are among the parameters used to diagnose ischemic heart disease. The increase in the QT dispersion can be caused by myocardial ischemia, among other heart diseases, whereas cardiac diseases such as coronary artery disease (CAD) can be diagnosed by observing an abnormally high QTc dispersion. This study aimed to evaluate the variations in the QTc dispersion (depolarization and repolarization) of surface electrocardiography as a result of percutaneous coronary intervention (PCI) in patients with chronic total occlusion. This study took place in the Iraqi Center for Heart Disease from October 2020 to February 2021. 110 patients who suffered from chronic occlusion of t

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Publication Date
Sat May 01 2021
Journal Name
European Journal Of General Dentistry
Assessment of Serum Interleukin-1β and Interleukin-6 Levels in Patients with Chronic Periodontitis and Coronary Heart Disease
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Abstract<p> Objective The aim of this study was to assess whether serum cytokine levels correlate with clinical periodontal parameters in health or disease.</p><p> Materials and Methods Male subjects (40–60 years) with CP (n = 30), CP + CHD (n = 30), and healthy controls (n = 20) had plaque index (PLI), gingival index (GI), bleeding on probing, probing pocket depth (PPD), and clinical attachment level (CAL) evaluated. Serum IL-1β and IL-6 levels were quantified using enzyme-linked immunosorbent assay.</p><p> Results PLI, GI, PPD, and CAL were significantly higher in patients with CP + CHD compared to those with CP. Serum levels of IL-1β and IL-6 were also si</p> ... Show More
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