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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 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
Wed Dec 30 2020
Journal Name
Al-kindy College Medical Journal
Iraqi women Attitude towards Immediate Post-partum/ Post-abortion Contraception: a multi-institutional study
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Background: Immediate postpartum contraceptive and post abortion contraception methods are effective safe methods and are becoming a standard practice in many countries, yet it is not widely used in Iraq.

Aims: this study: is designed to assess the attitude and willingness of women to immediate contraception after giving birth or abortion and their satisfaction to previous use.

Methods and Material: Four hundred thirty-four women were surveyed in the labor word immediately after giving birth/ abortion. Their knowledge, attitude and contraception use were assessed according to the response they reported to a given questionnaire.

Results: women were not sure abo

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Changes in the serum level of the trace elements in chronic renal
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Were studied changes in the concentration of copper, iron and zinc in blood serum of one hundred patients with chronic kidney and treated dialysis blood were also measured the level of calcium kidney and phosphate Calciotropic in serum of these patients took samples of blood from these patients before and after treatment dialysis vessels as well as the statement of changes in those standards Alkimaahiatih Results were compared with twenty-five healthy people (control group)

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Publication Date
Mon Mar 01 2021
Journal Name
Iraqi Journal Of Agricultural Sciences
CORRELATION STUDY BETWEEN THREE DIFFERENT GENES EXPRESSION AND CHRONIC MYELOID LEUKEMIA IN IRAQ
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The following study was conducted to investigate the correlation between the expression of three different genes (NOB1, DDX47, CD101( with the occurrence and development of chronic myeloid leukemia (CML) in Iraq. The difference in the expression of these genes between patients and healthy controls was studied. Moreover the correlation of age and gender with CML occurrence and comparing with control was also examined. Results showed significant increases in mean of gene expression level (ΔCt) of patient groups for all genes compared to the corresponding ΔCt means in control group, also the gene expression folding (2-ΔΔCt) reflect significant differences in the expression of these genes and CD101, mRNA showed the highest level in CML pati

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Publication Date
Sun Mar 07 2010
Journal Name
Baghdad Science Journal
Free Fatty Acids and Biochemical Changes in Iraqi patients with Chronic Renal Failure
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Chronic renal failure (CRF) is progressive irreversible destruction of kidney tissue by disease which, if not treated by dialysis or transplant, will result in patient's death. This study was carried out on 30 patients (17 male and 13 female) with chronic renal failure. The aim of this research was studied the changes in the level of total protein ,albumin, calcium ,ionized calcium, phosphorous , iron ,ALP, LDH ,CK and FFA in patients with CRF before and after hemodialysis .The obtained results have been compared with 30 healthy subjects as control group (18male and 12 female). The results showed that there was significant increase in the level of calcium ,ionized calcium, phosphorous ,iron ,ALP,LDH,CK and FFA ,while there was a signifi

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Publication Date
Tue Sep 01 2020
Journal Name
Baghdad Science Journal
Improving the Durability of Streak and Thermal Insulation of Petroleum Pipes by Using Polymeric Based Paint System: Polymer Matrix Composites have several and wide applications
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This research deals with increasing the hardening and insulating the petroleum pipes against the conditions and erosion of different environments. So, basic material of epoxy has been mixed with Ceramic Nano Zirconia reinforcement material 35 nm with the percentages  (0,1,2,3,4,5) %, whereas the paint basis of broken petroleum pipes was used  to paint on it, then it was cut into dimensions (2 cm. × 2 cm.) and 0.3cm high. After the paint and percentages are completed, the samples were immersed into the paint. Then, the micro-hardness was checked according to Vickers method and thermal inspection of paint, which contained (Thermal conduction, thermal flux and Thermal diffusivity), the density of the painted samples was calculate

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Publication Date
Mon May 15 2023
Journal Name
Gsc Advanced Research And Reviews
Teratoma induced by amlodipine drug in fetus rats
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The current study, performed during the period from February 2021 to June 2022 at the University of Thi- Qar/ College of Education for Pure Sciences, and aimed to follow the changes in external morphological features at different Embryonic developmental stages in pregnant rats treated with different doses of amlodipine. Usage In this study, 18 pregnant rats were randomly divided into three groups, each with six pregnant rats. Each group received different concentrations of amlodipine (0.3, 0.5) in oral doses until the 20th day of gestation, while the control group was injected with 0.9% normal saline. Teratomas are bizarre tumors derived from embryonic tissue that are normally found only in the gonadal and sacral regions of adults. Primary

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Publication Date
Thu Jun 25 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Comparing the Efficacy of Paracetamol, Diclofenac, and Ketorolac on Post-Appendectomy Outcomes in Children and Adolescents
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Abstract

urgent surgical intervention and appendectomy until now represent standard treatment for uncomplicated cases of appendicitis. Nausea, vomiting and pain after surgery are the most frequent issues facing patients and affecting patient quality of life and responsible for many cases of readmission after surgery. Ketorolac and diclofenac represent the most commonly prescribed non-steroidal anti-inflammatory used in postoperative setting and they cause many side effects as gastrointestinal, kidney and cardiac adverse effect in addition to increased risk of bleeding. Paracetamol is currently among the most frequently prescribed medication worldwide and it can be used safely for all age groups. This study aimed

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Publication Date
Mon Mar 01 2021
Journal Name
Journal Of Physics: Conference Series
Evaluation of total oxidant status and antioxidant capacity in sera of acute-and chronic-renal failure patients
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Abstract<p>Renal failure is a disease of the kidney, in which the renal excretory function is failed to process due to depression of the GFR. Renal failure is divided into acute and chronic depending on the period of the disease. The study was designed to investigate the level of oxidative stress in RF patients. Seventy-five subjects had enrolled in the study, who divided into three groups equally, in which they are healthy control, ARF patients, and CRF patients. The results had shown a significant <italic>(P<0.01)</italic> increase in the level of TOS for RF patients when compared with control. Also, a significant difference in the level of TOS has been observed between ARF and CR</p> ... Show More
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Publication Date
Sat Feb 01 2014
Journal Name
World Journal Of Pharmaceutical Sciences
Detection of JAK2V617F Mutation and Serum Levels of Alkaline Phosphatase and Lactate Dehydrogenase in Chronic Myelogenous Leukemia.
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Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm arises from Bcr-Abl gene translocation (called Ph chromosome) in hematopoietic stem cells (HSCs). This genetic abnormality results in constitutive activation of tyrosine kinase and subsequent uncontrol growth and multiplication of granulocytes. The cornerstone in treatment of CML are tyrosine kinase inhibitors, of which imatinib is the most effectively used. JAK2V617F mutation is an acquired single nucleotide polymorphism (SNP) occurs in JAK2 gene and is associated with many hematological malignancy other than CML. It was thought that the two genetic abnormalities (Bcr-Abl and JAK2V617F) occur mutually; however, growing body of evidences suggested the reverse. This study a

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