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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
Sun Jul 17 2022
Journal Name
Open Access Macedonian Journal Of Medical Sciences
Clinical Characteristics and Antibiotics Sensitivity of Culture Positive Typhoid Fever Patients in Baghdad Teaching Hospital - A Single Center Study
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BACKGROUND: Enteric fever caused by Salmonella Typhi is an endemic disease in Iraq. Variations in presentations make it a diagnostic challenge. If untreated or treated inappropriately then it is a serious disease with potentially life-threatening complications. The recent emergence of drug resistant strains of S. Typhi is a rising public health problem and a clinical concern to the physician. AIM: The objectives of the study were to assess and describe the patterns of antimicrobial resistance, clinical characteristics, epidemiological distribution, and complications of typhoid fever. PATIENTS AND METHODS: Fifty cases of typhoid fever (culture proven) were collected during the period from February 2019 to November 2019 in the me

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Publication Date
Fri Dec 31 2021
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
THEEXPOSURE OF BAGHDAD SLUM RESIDENTS TO TELEVISION DRUG ADVERTISEMENTS AND ITS TRENDS: THEEXPOSURE OF BAGHDAD SLUM RESIDENTS TO TELEVISION DRUG ADVERTISEMENTS AND ITS TRENDS
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The advancement of science and technology in recent years has led to heavy and diversified production and thus market congestion in various goods and services; which led to an increase of competition among advertisers in order to meet the needs and wishes and to upgrade to the level of consumers. These upgrades have imposed an increase in the usage of the promotions, including advertising in terms of quantity and quality, to influence and persuade customers innovatively and creatively using all available mass media.

The research aims to identify the attitudes of residents of poor areas towards television advertisements for medicines, and the impact of those advertisements on them in terms of making purch

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Publication Date
Mon Jan 01 2024
Journal Name
Journal Of The College Of Languages (jcl)
Negation marker in Standard Persian : a typological analysis based on Givon’s functional model: عامل نفی در زبان فارسی معیار: بررسی رده‌شناختی براساس مدل نقش‌ گرایی گیون
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 Abstract:

Typological analysis about  the negation marker  in different languages is one of the fields of research that has attracted much attention.  In Persian language, this constituent has been analysed from different aspects. This study aimed to analyse  different aspects of negation marker  in  the adjectives,  the noun phrases and  the verb phrases based on typological analysis.  Many studies have been revealed that  the negation in adjectives has shown lexically and morphologically. In the noun phrases, /hich/  has used as a negative marker necessarily marking the verb phrase as negative too. In the verb phrases, negation occurs morphologically by the addition of the prefix /n

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Publication Date
Sat Dec 01 2012
Journal Name
Journal Of Economics And Administrative Sciences
A comparison Some of Methods for Estimating Survival Function for Truncated Exponential Distribution
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Exponential distribution is one of most common distributions in studies and scientific researches with wide application in the fields of reliability, engineering and in analyzing survival function therefore the researcher has carried on extended studies in the characteristics of this distribution.

In this research, estimation of survival function for truncated exponential distribution in the maximum likelihood  methods and Bayes first and second method, least square method and Jackknife dependent in the first place on the maximum likelihood method, then on Bayes first method then comparing then using simulation, thus to accomplish this task, different size samples have been adopted by the searcher us

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Publication Date
Mon Dec 04 2017
Journal Name
Al-qadisiyah Journal For Administrative And Economic Sciences
Survival Function Estimating of Single age Groups for Generalized Gamma Distribution with Simulation.
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The analysis of survival and reliability considered of topics and methods of vital statistics at the present time because of their importance in the various demographical, medical, industrial and engineering fields. This research focused generate random data for samples from the probability distribution Generalized Gamma: GG, known as: "Inverse Transformation" Method: ITM, which includes the distribution cycle integration function incomplete Gamma integration making it more difficult classical estimation so will be the need to illustration to the method of numerical approximation and then appreciation of the function of survival function. It was estimated survival function by simulation the way "Monte Carlo". The Entropy method used for the

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Publication Date
Tue Apr 01 2003
Journal Name
Abhath Al- Yarmouk [basic Sciences And Engineering]
Methodology for selecting Nonprestressed Steel in Post- Tensioning Beams
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Publication Date
Mon Jun 27 2022
Journal Name
Al-rafidain Journal Of Medical Sciences ( Issn: 2789-3219 )
Self-Reported Sleep Disorder, Anxiety and Depression in Iraqi Patients Post-Myocardial Infraction
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Background: Myocardial infarction (MI) is distinguished by the necrosis of myocardial cells as a result of substantial and prolonged ischemia. Anxiety, problems sleeping, and feelings of depression are some of the most common psychosocial consequences of having a myocardial infarction. Aim: The purpose of this study is to evaluate the effects of post-myocardial infarction on patients' levels of anxiety, depression, and quality of sleep. Method: The collection of data from 94 individuals with MI was carried out according to a descriptive cross-sectional design. Sleep quality, depression, and anxiety were evaluated using standard questionnaires. Results: 69.1% of the participants reported having trouble getting quality sleep. The perc

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Publication Date
Wed Oct 17 2018
Journal Name
Journal Of Economics And Administrative Sciences
Comparison of Two of (Turnbull) and (Generalization Turnbulls)non-parametric methods in estimating conditional survival function (applied study on breast cancer patients)
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   This research includes the application of non-parametric methods in estimating the conditional survival function represented in a method (Turnbull) and (Generalization Turnbull's) using data for Interval censored of breast cancer and two types of treatment, Chemotherapy and radiation therapy and age is continuous variable, The algorithm of estimators was applied through using (MATLAB) and then the use average Mean Square Error (MSE) as amusement  to the estimates and the results showed (generalization of Turnbull's) In estimating the conditional survival function and for both treatments ,The estimated survival of the patients does not show very large differences

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Publication Date
Fri Dec 15 2017
Journal Name
Journal Of Baghdad College Of Dentistry
Measurement of serum Superoxide dismutase levels in women with polycystic ovarian syndrome and chronic periodontitis
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ABSTRACT Background: Polycystic ovarian syndrome (PCOS) is one of the most important reproductive and endocrine disorders in women at reproductive age. It's associated with metabolic disorder, obesity, insulin resistance and oxidative stress chronic periodontitis and PCOS both of them associated with low chronic grade of inflammation. The prevalence of periodontal disease seems to be higher in women with PCOS. Superoxide dismutase enzyme (SOD) is an important circulating marker and protecting enzyme helping the body tissues to get rid of reactive oxygen species (ROS) that damage the tissue. Aim of the study: The aim of this study was to measure and compare the levels of (SOD) among group of chronic periodontitis patients with PCOS, group

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Publication Date
Thu Jan 30 2014
Journal Name
Al-kindy College Medical Journal
THE PREVALENCE AND ANTIMICROBIAL RESISTANCE OF PSEUDOMONAS SPECIES IN PATIENTS WITH CHRONIC SUPPURATIVE OTITIS MEDIA
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Background: Chronic suppurative otitis media (CSOM) is the result of aninitial episode of acute otitis media and is characterized by a persistent discharge from the middle ear through a tympanic perforation for at least 2 weeks duration. It is an important cause of preventable hearing loss, particularly in the developing world.Methods. 1. To get an overview on the bacterial ear infection profile in general 2. To assess the antibiotic resistance of Pseudomonal infection (PS) particularly since it is usually the commonest infection to cause otitis media and the most difficult to treat due to the problem of multi drug resistance... A cross sectional study was done which included 405 patient of CSOM patients196 (48%) case were males ,209 (52

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