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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
Mon Sep 29 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Interleukine-6 Level in Saliva of Patients with Chronic Periodontitis: A Case-Control Study
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Background:Periodontal diseases are infectious diseases in which periodontalpathogens trigger chronic inflammatory and immune responses. Interleukine-6 is a multifunctional cytokine playing a central role in inflammation and tissue injury.The aim of the study IS to determine the level of Interleukin-6(IL-6) in saliva of patients with chronic periodontitis compared to healthy subjects. Materials and Methods:The total subjects of the present study is 60, divided into 3 groups; 20 patients with chronic periodontitis with pocket depth(PD ≥4 mm)(group I), 20 patients with pocket depth(PD <4 mm) with clinical attachment loss (group II), and 20 healthy controls with pocket probing depth (PPD ≤ 3 mm) without clinical attachment loss (g

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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)
Dose Dependent Anti-inflammatory Effect of Ammi majus Alcoholic Extract in Rat: Chronic Study
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During treatment of inflammatory diseases, many conventional therapies (non-steroidal anti-inflammatory drugs) used to relief pain and inflammation. Chronic use of  the intended drugs is frequently associated with serious side effect, which may lead to discontinuation of treatment . The efficacy and dose- response effect of ammi majus extraxt  (2 , 4, 8 , 16, and 32 mg/rat) were assessed using  formalin to induce paw edema in rats as a model of chronic inflammation respectively. In this study,  42 rats were used and allocated into 7  groups each containing 6 rats, representing control (Distilled  water) , standard (piroxicam ) and test extract ( 2 , 4 , 8 , 16 and 32 mg/rat of Ammi majus alcoholic e

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Publication Date
Sun Dec 22 2019
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of Knowledge, Attitudes and Experience of off-label Drug Prescribing Practice among Physicians in Baghdad City Hospitals
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Abstract

The present study aims to assess the knowledge, attitude, and experience of off-label prescribing practice among physicians in Baghdad city hospitals. This cross-sectional study was performed through the period from November 1st 2018 to March 2019 at 17 hospitals, a self-administered questionnaire was utilized to collect data from the physicians, and the targeted hospitals were randomly selected at different regions in Baghdad City area. Out of the 400 distributed questionnaires to the physicians, 383 of them were returned completed, 57.2% indicated that they were reasonably familiar with the term “off label drug”, 57.7% mentioned that the most common medical reasons for the prescribing o

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Publication Date
Sat Jan 01 2022
Journal Name
Materials Today: Proceedings
Application of levofloxacin and doxycycline in treatment of vaginal chlamydial infection
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Doxycycline and levofloxacin are heterocyclic organic compounds that are now popularly used to treat some bacterial infections. In this study which was conducted on patients from a private clinic, we compared the use of two commonly used antibiotics for the treatment of diagnosed cases with vaginal chlamydial infection: levofloxacin and doxycycline. Vaginal chlamydial infection is considered to be a very common sexually transmitted infection. It may have minimal symptoms which can lead to neglect by the patient until it leads to some important complications among which is the inability to become pregnant. This indicates early diagnosis and treatment of this infection. By comparing the results of treatment we concluded that there is no much

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Publication Date
Tue Feb 26 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Income Tax in Iraq and the Treatment of Married Women in Charge
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   Iraqi legislator taxation  married women in charge of the income tax treatment of the man in charge of tax and the application of the principle of equality of individuals to bear public burdens. The factor legislator women in charge of special treatment in some cases, taking into account the circumstances family allow  tax in the case of whether she was married to a man is unable to completely work and does not have a resource, as well as giving the legislator allow for her children. it observed that the amount of allowing still little is notcommensurate with the high cost of living in addition to limiting the tax allowances granted within the limits of the taxpayer and his immediate family did not take the legisla

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Publication Date
Wed Dec 20 2023
Journal Name
Al-esraa University College Journal For Medical Sciences
Nanoparticles Used in Treatment and Diagnosis of Leishmaniasis in Iraq: A Review
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The aim of this paper is to identify Nano-particles that have been used in diagnosis and treatment of leishmaniasis in Iraq. All experiments conducted in this field were based on the following nanoparticles: gold nanoparticles, silver nanoparticles, zinc nanoparticles, and sodium chloride nanoparticles. Most of these experiments were reviewed in terms of differences in the concentrations of nanoparticles and the method that was used in the experiments whether it was in vivo or in vitro. These particles used in most experiments succeeded in inhibiting the growth of Leishmania parasites.

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Publication Date
Sun Sep 03 2023
Journal Name
Al-mansour Journal
Biometrics Systems Challenges in a Post-COVID-19 Pandemic World: A review
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One of the most serious health disasters in recent memory is the COVID-19 epidemic. Several restriction rules have been forced to reduce the virus spreading. Masks that are properly fitted can help prevent the virus from spreading from the person wearing the mask to others. Masks alone will not protect against COVID-19; they must be used in conjunction with physical separation and avoidance of direct contact. The fast spread of this disease, as well as the growing usage of prevention methods, underscore the critical need for a shift in biometrics-based authentication schemes. Biometrics systems are affected differently depending on whether are used as one of the preventive techniques based on COVID-19 pandemic rules. This study provides an

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Publication Date
Thu Jun 30 2022
Journal Name
Journal Of Economics And Administrative Sciences
Estimation of Time of Survival Rate by Using Clayton Function for the Exponential Distribution with Practical Application
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Each phenomenon contains several variables. Studying these variables, we find mathematical formula to get the joint distribution and the copula that are a useful and good tool to find the amount of correlation, where the survival function was used to measure the relationship of age with the level of cretonne in the remaining blood of the person. The Spss program was also used to extract the influencing variables from a group of variables using factor analysis and then using the Clayton copula function that is used to find the shared binary distributions using multivariate distributions, where the bivariate distribution was calculated, and then the survival function value was calculated for a sample size (50) drawn from Yarmouk Ho

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Publication Date
Wed Jul 01 2020
Journal Name
International Journal Of Drug Delivery Technology
Gold nanoparticle: Synthesis, functionalization, enhancement, drug delivery and therapy: A review
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Publication Date
Fri Jan 01 2021
Journal Name
International Journal Of Agricultural And Statistical Sciences
DYNAMIC MODELING FOR DISCRETE SURVIVAL DATA BY USING ARTIFICIAL NEURAL NETWORKS AND ITERATIVELY WEIGHTED KALMAN FILTER SMOOTHING WITH COMPARISON
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Survival analysis is widely applied in data describing for the life time of item until the occurrence of an event of interest such as death or another event of understudy . The purpose of this paper is to use the dynamic approach in the deep learning neural network method, where in this method a dynamic neural network that suits the nature of discrete survival data and time varying effect. This neural network is based on the Levenberg-Marquardt (L-M) algorithm in training, and the method is called Proposed Dynamic Artificial Neural Network (PDANN). Then a comparison was made with another method that depends entirely on the Bayes methodology is called Maximum A Posterior (MAP) method. This method was carried out using numerical algorithms re

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