Predictive molecular tumor response through circulating DNA (cDNA) measurements and correlation with established prognostic markers in a series of solid tumors treated with multitargeted epigenetic therapy (MTET).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13015-e13015
Author(s):  
Mohammad A. Nezami ◽  
Christian Klowsowski ◽  
Steven Jeffrey Hager

e13015 Background: Epigenetic dysregulation of certain genes contribute to the progression of cancers. Plasma ctDNA concentrations can reflect these altered genes and have been shown to correlate well with tumor burden. Methods: We planned to assess the correlation value of c DNA on known factors for prediction of overall survival (OS), recognized as surrogates for survival. Ten( 10) genes of interest, namely NOTCH1, FGF2, MYC, RB1, ATM, MET, BRCA1, BRCA2, ATM and, VHL, were selected as being highly influenced by epigenetic control. We included 54 patients with reported cDNA on the genes of interest for this study evaluating the predictive impact of early changes in cDNA in response to multitargeted epigenetic treatment and the patient survival. There were 12 cases with NOTCH1 mutations, 20 cases with MYC mutations, 5 cases with RB1, 15 cases with BRCA1 or BRCA2 mutations, 26 cases with FGF2 mutations, 18 cases with MET mutations, 2 with VHL mutations and 2 cases with ATM mutations, for a total of 100 data points. Tests for statistical significance were completed using the Fisher Exact probability test calculator found at vassarstats.net/tab2x2.html. Significance level was set at α = .05. Results: There was statistically significant (p-value: .046) correlation on the response of the allele frequency of the observed NOTCH1 alteration with similar response in the angiogenesis biomarkers (Plasma VEGF) and presence of circulating tumor cells. There was a significant correlation (p-value: .014) between a decrease in AF of the observed MYC alteration and biomarker/imaging response on follow-up. In the group of 26 identified with FGF2 mutations, 22 saw cDNA alteration fraction(AF) reduction post therapy. 16/26 of them had either c Myc or NOTCH1 alterations. Also 8 /18 cases with c Met alterations shared NOTCH1 or Myc alteration. This represents a statistically significant (p-value: .0001) correlation on the response of the allele frequency of the observed FGFR2 alteration with the response of other biomarkers. Conclusions: There were a number of significant correlations observed between early changes in cDNA allele fractions of specific genes and the later observations of established prognostic markers. We conclude that changes in cDNA mutated allele fractions observed in liquid biopsy may provide an early useful independent prognostic marker for tumors carrying epigenetically influenced targets and their alterations.

2015 ◽  
Vol 105 (11) ◽  
pp. 1400-1407 ◽  
Author(s):  
L. V. Madden ◽  
D. A. Shah ◽  
P. D. Esker

The P value (significance level) is possibly the mostly widely used, and also misused, quantity in data analysis. P has been heavily criticized on philosophical and theoretical grounds, especially from a Bayesian perspective. In contrast, a properly interpreted P has been strongly defended as a measure of evidence against the null hypothesis, H0. We discuss the meaning of P and null-hypothesis statistical testing, and present some key arguments concerning their use. P is the probability of observing data as extreme as, or more extreme than, the data actually observed, conditional on H0 being true. However, P is often mistakenly equated with the posterior probability that H0 is true conditional on the data, which can lead to exaggerated claims about the effect of a treatment, experimental factor or interaction. Fortunately, a lower bound for the posterior probability of H0 can be approximated using P and the prior probability that H0 is true. When one is completely uncertain about the truth of H0 before an experiment (i.e., when the prior probability of H0 is 0.5), the posterior probability of H0 is much higher than P, which means that one needs P values lower than typically accepted for statistical significance (e.g., P = 0.05) for strong evidence against H0. When properly interpreted, we support the continued use of P as one component of a data analysis that emphasizes data visualization and estimation of effect sizes (treatment effects).


2020 ◽  
pp. 181-189

Background. Breastfeeding is the most common way of feeding infants. Human milk contains nutrients which are necessary to provide proper growth of a child. Nowadays there aren't any recommendations to follow elimination diet in order to decrease the risk of allergy or baby colic. Only the occurrence of health problems such as lactose intolerance or cow's milk protein allergy in breastfeeding mother or infant should be a reason for eliminating dairy products from diet. It seems to be important to explore the reasons and the frequency of following milk-free diet by breastfeeding women. Objectives. The main purpose of the study was to find the reasons for following milk-free diet by breastfeeding women and making an assessment of their nutrition knowledge and food habits. Material and methods. Thirty-three breastfeeding women following milk-free diet took part in the project. The women were interviewed by the Computer Assisted Web Interview (CAWI) method with an original questionnaire. The results were developed with Spearman's rank correlation, Chi2 test and the gamma coefficient. The statistical significance level for the p-value was <0.05. Results. The main reason for following milk-free diet by the breastfeeding women was the occurrence of hypersensitivity reactions of the children's gastrointestinal system after consuming milk by mother (72% responses). After excluding milk from diet only 42% respondents declared consuming new food products or dietary supplements in order to refill the potential deficiency of nutrients. The majority of respondents also eliminated from diet highly processed food products, fast-food and the carbonated drinks. The most often declared source of information about lactation was Internet (85%). Only 12% respondents asked a nutritionist in order to get the information about breastfeeding. Conclusions. It's necessary to promote a specific nutritional advice about following milk-free diet in breastfeeding women group in order to decrease the health risk connected with low calcium diet.


2020 ◽  
Vol 16 ◽  
Author(s):  
Amal A. Mohamed ◽  
Mokhtar M. El-Zawahry ◽  
Omnia I. Tantawi ◽  
Amyan Aalkhalegy ◽  
Lamiaa Abdelfattah Fathalla ◽  
...  

Background:: In the early stages of HCC, it is unsatisfactory to depend on alpha-fetoprotein for diagnosis. Objective:: The current study evaluated the possibility of the two miRNAs which are miRNA-96 and miRNA-224 to act as biomarkers for HCC diagnosis. Methods:: This study included 50 patients with HCV-induced HCC and 50 patients with HCV-induced liver cirrhosis for comparison as well as 67 healthy volunteers as controls. All participants were subjected to history taking, clinical examination, and laboratory investigations as well as quantification of serum miRNA-96 and miRNA-224 by real-time quantitative PCR. Results:: MicroRNA 224 level was significantly higher in HCC than the other two groups and was significantly higher in liver cirrhosis than the control group. MicroRNA 96 level was higher in HCC than the control group and was higher in cirrhotic group than both HCC and control groups. However, it doesn’t reach the statistical significance level. The best cut-off value of microRNA 96 for detecting HCC was 3.414 with a sensitivity of 67% and a specificity of 67%, (p-value <0.001). The best cut-off value of microRNA 224 for detecting HCC was 16.75 with a sensitivity of 88% and a specificity of 85% (p-value<0.001). Conclusion:: miRNA-224 could serve as a biomarker for the HCC diagnosis.


2020 ◽  
Author(s):  
Abay Woday ◽  
Muluken Dessalegn ◽  
Setognal Birara ◽  
Kusse Urmale ◽  
Gebeyaw Biset ◽  
...  

Abstract Background: Birth asphyxia among newborns accounted for nearly fifty percent of neonatal mortality in sub-Saharan African countries. This scenario has been worst in Ethiopia where every two out of three deaths attributed to birth asphyxia among these babies. Moreover, studies conducted in Ethiopia are highly variable and inconclusive to estimate the pooled prevalence and risk factors of birth asphyxia. Objective: This study aims to analyses collectively and systematically the prevalence of birth asphyxia and associated factors among newborns in Ethiopia.Methods: The protocol for this review is registered at PROSPERO with registration number CRD42020158224. A comprehensive online databases (PubMed, HINARI, Scopus, EMBASE, Science direct, and Cochrane library database), Google Scholar, African Journals online, other gray and online repository accessed studies will be searched using different search engines. In addition, maternity & infant care databases uploaded at Ethiopian Health Development Journal and Ethiopian Journal of Health Sciences will be searched until June 30, 2020. Newcastle-Ottawa Quality Assessment Scale (NOS) will be used for critical appraisal of studies.. Three reviewers will screen all retrieved articles, conduct data extraction, and then critically appraise all identified studies. All identified observational studies reporting the prevalence of birth asphyxia and associated factors among neonates in Ethiopia will be considered. The analysis of data will be done using STATA 11.0 statistical software. We will demonstrate pooled estimates and determinants of birth asphyxia with effect size and 95% confidence interval. Heterogeneity among the included studies will be assessed through the Cochrane Q-test statistics and I2 test. Publication bias will be checked using funnel plot and egger’s test. Finally, statistical significance level will be declared at a p-value of less than 0.05. Discussion: the result from this systematic review will inform and guide health policy planners to invest limited resources on maternal and neonatal health. Furthermore, it will be a stimulus for future cumulative meta-analysis researchers in developing nations.


Author(s):  
Heni Nurhaeni ◽  
Dinarti Dinarti ◽  
Dwi Priharti

There are four types of parenting: democratic, authoritarian, permissive, and ignored, which would affect the character of the child. But family upbringing itself influenced education, norms/cultural, environmental, social, economic and belongs to the family members. quasi-experimental study through questionnaires, observation, deep interview, and interventions against high school Students, Peers, Teachers (BK), and their Parents/Family have been conducted through a random sampling of 108 respondents in four high school set. The result met the test paired T test statistical significance level 0 and T test result of 0.05 shows that the two variables p-value of p=0.00000. Correlation tests showed that there is a relationship between two variables at-0616. This sign (-) means that the test results are negative correlation. Can be seen if the correlation between the two variables is quite high between 0.50 to 1.0 can be concluded that the direction of the relationship between the two variables is negative. These results can be displayed from "if the family provides a strict upbringing will influence behavior in high school brawls in Adolescents will tend to be low and vice versa".


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3617-3617
Author(s):  
R. Sehgal ◽  
S. Saha ◽  
D. Wiese ◽  
R. Parker ◽  
W. Huang ◽  
...  

3617 Background: p53 and LN status(S) are important prognostic markers in Cca. Our study was done to evaluate whether p53 S could predict tumor burden in LNs in Cca undergoing SLNM. Methods: Pts with Cca underwent SLNM to determine the LN S. A portion of tumor was used for detection of p53 S by IHC.p53 Histo Score (HS) was defined as (Intensity of stain in cells from 0–4 +1) × (% cells staining). HS of 180 was taken as cut off for significance based on previous studies on solid tumors. Metastatic foci in SLNs and nonSLNs were measured in greatest diameter by ocular micrometer. For overall tumor burden in SLNs and nonSLNs,all metastatic foci were added for each pt. Results: SLNM was successful in 100% of the 117 consecutive pts with Cca. Pts with distant metastasis (mets) (18) and skip mets (9) were excluded. Of the remaining 90 pts,39% were SLN positive (+ve) and 61% were SLN negative (-ve). HS of ≤ 180 was found in 66% and HS >180 was found in 34% of the pts. In 55 SLN -ve pts 76% had HS ≤ 180 while 24% had HS >180. In 35 SLN +ve pts, 49% had HS of ≤ 180 and 51% had HS >180. ( Table ) Of SLN +ve pts, size of metastatic tumor in LNs was available in 86% of pts. Average (av.) non SLN met size was 0.95 cms in pts with HS ≤ 180 and 3.4 cms in pts with HS > 180. Av. SLN met size was 0.63 cms in pts with HS ≤ 180 and 0.9 cms in pts with HS>180 ( Table ). No statistical significance was found among T stage of pts with HS >180 vs ≤ 180. Conclusion: Pts with p53 HS >180 showed significantly greater tumor burden in both SLNs and non SLNs as compared to pts with HS ≤ 180. Also probability of having SLN -ve disease is higher in pts with HS ≤ 180 as compared to pts with HS >180 in Cca. Thus,even in SLN -ve pts, high HS may indicate a worse prognosis. Hence,a high p53 HS might predict pts with Cca having higher tumor burden in LNs and thus identify an aggressive subgroup of pts. [Table: see text] No significant financial relationships to disclose.


2021 ◽  
Author(s):  
Abdelaziz Agrram

Having a clear vocabulary profile of Moroccan master students might reveal where these participants stand compared to other countries. Therefore, the study aims to investigate the effect of languages of instruction in Morocco (e.g., Arabic vs. French) on the receptive vocabulary size of EFL Moroccan master students (e.g., departments of letters, science, and law). To this end, Meara’s (2010) Yes/No test was used as an instrument to measure the overall vocabulary size of these participants. A total of 325 EFL master students took the aforementioned test. The main research question is: Does the medium of instruction have any effects on the receptive vocabulary size of these students? Descriptive statistics were employed to calculate the overall receptive vocabulary size of test-takers. It was found that Moroccan EFL master students have a total of (M= 2293) lemmas. An independent samples t-test was run to check for any statistical significance. The t-test statistic reveals that the significance level is less than the p-value (t=-4.068, p&lt; .05, df= 323). Thus, it was concluded that there was a statistically significant difference between the French group and the Arabic group. The results of this study confirm that students who were instructed in French (M= 2417, sd= 903, N=185) outperformed the other students who were taught in Arabic (M= 2058, sd= 903, N= 140). In the current study, among various suggestions, it is proposed that the volume of 30 hours in the English module is not sufficient and should be complemented with vocabulary-based activities.


2021 ◽  
Author(s):  
Fabricio Braga ◽  
Roberto Zagury ◽  
Cristiane Perroni ◽  
Victor Hugo Domecg

Background: The COVID-19 pandemic has led to a dramatic increase in the levels of sedentary lifestyle and unhealthy dietary habits. A worsening in populational obesity levels and body composition (BC) is strongly awaited but so far not documented. Objective: To compare BC profile measured by bioelectrical impedance analysis (BIA) between pre-pandemic (P1-03/15th/2017 to 03/16th/2020) and pandemic (P2-3/17th/2020 to 3/10th/2021) period of time. Materials and Methods: BIA were grouped according to the time it was performed. Two comparisons were done: an independent sample comparison (ISC) and a paired sample comparison (PSC) considering patients with at least one BIA in P1 and P2. Age, height, gender, weight, body mass index (BMI), body fat mass (BFM), free fat mass (FFM), skeletal muscle mass (SMM), percentage of body fat (PBF), visceral fat area (VFA) were compared. Statistical significance level was defined for a p value<0.05. Results and Discussion: A total of 3.358 BIA were performed, and 2.771 and 112 were selected for IS and PS, respectively. In ISC, despite an unchanged weight, BFM, FFM, PBF and VFA increased and SSM decreased on P2(p<0.015 for all). A multivariated linear regression model using PBF as dependent variable showed P2 as an independent predictor (β=0.38 95%CI 0.19 to 0.56). In the PSC, PBF also increased from P1 to P2 (p=0.015). To our knowledge this is the first documentation of worsening BC after pandemic. Health authorities should be alert for this phenomenon and their clinical consequences in the days to come.


2020 ◽  
Vol 11 (4) ◽  
pp. 194-206
Author(s):  
Abdelaziz Agrram

Having a clear vocabulary profile of Moroccan master students might reveal where these participants stand compared to other countries. Therefore, the study aims to investigate the effect of languages of instruction in Morocco (e.g., Arabic vs. French) on the receptive vocabulary size of EFL Moroccan master students (e.g., departments of letters, science, and law). To this end, Meara’s (2010) Yes/No test was used as an instrument to measure the overall vocabulary size of these participants. A total of 325 EFL master students took the aforementioned test. The main research question is: Does the medium of instruction have any effects on the receptive vocabulary size of these students? Descriptive statistics were employed to calculate the overall receptive vocabulary size of test-takers. It was found that Moroccan EFL master students have a total of (M= 2293) lemmas. An independent samples t-test was run to check for any statistical significance. The t-test statistic reveals that the significance level is less than the p-value (t=-4.068, p< .05, df= 323). Thus, it was concluded that there was a statistically significant difference between the French group and the Arabic group. The results of this study confirm that students who were instructed in French (M= 2417, sd= 903, N=185) outperformed the other students who were taught in Arabic (M= 2058, sd= 903, N= 140). In the current study, among various suggestions, it is proposed that the volume of 30 hours in the English module is not sufficient and should be complemented with vocabulary-based activities.


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