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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
Sat Jul 01 2017
Journal Name
Journal Of Biological Chemistry
Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites
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Publication Date
Thu Nov 01 2018
Journal Name
Optical Fiber Technology
Enhancing refractive index sensitivity using micro-tapered long-period fiber grating inscribed in biconical tapered fiber
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Publication Date
Mon Jan 02 2017
Journal Name
Journal Of Educational And Psychological Researches
Frustration degree and guilt among drug addicts harmful to themselves
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This study aimed to identify the degree of frustration and guilt among addicts who hurt themselves with drug,  and to know the addicts perspective  who are in treatment clinics and rehabilitation centers  in Palestine, in order to achieve this goal aDeterminationThe study population has been identified , this study population consisted of ' (82) addict, the researcher used the descriptive analytical method which is appropriate for  this  study, so the researcher questioned the addicts who are in treatment clinics and rehabilitation centers  in Palestine and analyze their  responses  in light of some of the variables.

The study results showed that drug addicts who ar

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Publication Date
Wed Apr 01 2020
Journal Name
Biochemical & Cellular Archives
INVESTIGATION OF VITAMIN D, ESTRADIOL AND C-REACTIVE PROTEIN LEVELS IN PRE AND POST-MENOPAUSAL IRAQI TYPE 2 DIABETES MELLITUS IN WOMEN.
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Diabetes mellitus is a metabolic chronic disease, with global estimation increase in patient (around 100 million in 2030).The aim of the current study is to investigate vitamin D, C-reactive protein and estradiol levels in pre and postmenopausal Iraqi women with type 2 diabetes (T2MD).A total of 176 female distributed into two groups: the first included 90 women withT2MD (43 pre and 47 post-menopausal); the second group included 86 healthy subjects (41 pre and 45 postmenopausal) considered as control. This study has shown that women in premenopausal (20-40 years) had highly significant difference in the estradiol and vitamin D levels in diabetes subjects (62.192 ± 17.643pg/ml, 10.522 ± 1.958ng/ml) compared with healthy (131.793 ± 1

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Publication Date
Wed Aug 07 2019
Journal Name
Iraqi National Journal Of Nursing Specialties
Effectiveness of Post-Abortion Family Planning Counseling Program on Nurses and Midwives' Practices in Middle Euphrates Maternity Hospitals
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Objectives: To determine the effectiveness of post-abortion family planning counseling program on nurses and midwives' practices and to predict the variables which may effect on their practices Methodology: A quasi experimental study was conducted from 23th April 2017 to 14th March 2018 in three governorates in Middle Euphrates of Iraq: (Holy Karbala, Al - Najef Al Ashraf and Babylon) on nurses and midwives who work at maternity hospitals. Systematic random sampling was used to select 122 nurses and midwives, (60) of them for study group and (62) for control group. A checklist is an instrument that evaluate the practices which included 50 items. Validity of content was determined through reviewing it by (16) experts and reliability of to

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Publication Date
Tue Jan 02 2018
Journal Name
International Journal Of Science& Nature
HYPOTHYROIDISM IN PEDIATRIC PATIENTS: MODE OF PRESENTATION AND TREATMENT OUTCOME
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ABSTRACT The present study was conducted to determine the mode of presentation of hypothyroidism in pediatric patients and the effects of timing of diagnosis and therapy on the patient’s outcome. The study involved review and evaluation of the medical records of 41 registered patients in the Endocrine clinic of Children Welfare Teaching Hospital in Baghdad during the period from January 1991 to July 2007. Forty one patients included in this study. Twenty four (58.5%) were males and17 (41.4%) were females with a male to female ratio of 1.4:1, their age range is 40 days to12.3 years. The majority of the studied patients were infants 19(47%). The most commonly observed presenting features were growth retardation and short stature. The best t

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Publication Date
Sat Apr 01 2023
Journal Name
Journal Of Environmental Accounting And Management
On the Food Chain Model with Sokol Howell Functional Response and Prey Refuge
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The cheif aim of the present investigation is to develop Leslie Gower type three species food chain model with prey refuge. The intra-specific competition among the predators is considered in the proposed model. Besides the logistic growth rate for the prey species, Sokol Howell functional response for predation is chosen for our model formulation. The behaviour of the model system thoroughly analyses near the biologically significant equilibria. The linear stability analysis of the equilibria is carried out in order to examine the response of the system. The present model system experiences Hopf bifurcation depending on the choice of suitable model parameters. Extensive numerical simulation reveals the validity of the proposed model.

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Publication Date
Sun Sep 01 2024
Journal Name
Green Analytical Chemistry
Green methods for determination of paracetamol in drug samples: A comparative study
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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
Sat Aug 02 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of some salivary enzymes levels in type 2 diabetic patients with chronic periodontitis (Clinical and biochemical study)
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Background: Diabetic patients have been reported to be more susceptible to gingivitis and periodontitis than healthy subjects. Many intracellular enzymes like (alkaline phosphatase- (ALP), aspartate aminotransferase- (AST) and alanine aminotransferase- (ALT) that are released outside cells into the gingival crevicular fluid (GCF) and saliva after destruction of periodontal tissue during periodontitis. This study was conducted to determine the periodontal health status and the levels of salivary enzymes (ALP, AST and ALT) of the study and control groups and to correlate the levels of these enzymes with clinical periodontal parameters in each study group. Subjects, Materials and Methods: One hundred subjects were enrolled in the study, with a

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