Illustration of temporal evolution in patients with metastatic renal cell carcinoma (mRCC) using both circulating tumor DNA (ctDNA) and tissue-based genomic data.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 347-347
Author(s):  
Zeynep Busra Zengin ◽  
Caroline Weipert ◽  
Joann Hsu ◽  
Nicholas Salgia ◽  
Chuck Hensel ◽  
...  
Keyword(s):  
Circulating Tumor Dna ◽  
Genomic Profiling ◽  
Temporal Separation ◽  
Tissue Samples ◽  
Sequencing Platform ◽  
Targeted Next Generation Sequencing ◽  
Paired Samples ◽  
Significant Difference ◽  
The Difference ◽  
Ctdna Analysis

347 Background: We have previously demonstrated the feasibility of ctDNA assessment in mRCC and preliminarily showed agreement between ctDNA and tissue-based genomic findings (Zengin et al ESMO 2020). Our data suggested that the degree of agreement is dependent upon the temporal separation of blood and tissue samples. We sought to further explore this temporal impact in a separate validation cohort. Methods: Patients (pts) with mRCC who underwent ctDNA genomic profiling were identified. ctDNA analysis was performed using a CLIA-certified 73-74 gene panel (Guardant360). From this cohort we identified a subset of pts who also underwent tissue-based genomic profiling using either a whole exome sequencing platform (GemExtra [TGen, Phoenix, AZ]) or a targeted next generation sequencing platform (Foundation Medicine [Cambridge, MA] or Tempus [Chicago, IL]). Only alterations covered by both assays were included for the current analysis. The difference in the proportion of alterations detected on tissue and ctDNA was compared between these cohorts and at a 6-mo landmark using the χ2 test. Results: In total, ctDNA and tissue based genomic profiling was assessed in 112 pts (M:F, 81:31); with most common histology was clear cell (85.7%). Median time between ctDNA and tissue assessments was 9.8 months (IQR 1.15-23.7). When examining paired samples in which >1 ctDNA alteration was detected, 32% (43/133) of alterations detected on tissue were also detected in ctDNA. This proportion increased to 43% (29/67) when samples collected within 6 months of each other, and was 51% (28/55) in samples collected within 3 months of each other. There was no significant difference in the frequency of shared mutations between the cohorts (P=0.09; Table). Conclusions: Our study confirms that ctDNA and tissue-based genomic profiling continue to provide consistently high levels of agreement. Notably, the percentage of samples with ≥1 ctDNA alteration detected was significantly lower in both cohorts compared to previous studies in RCC. More shared alterations were found on ctDNA when both ctDNA and tissue-based assessment were obtained at closer intervals. [Table: see text]

Genomic profiling of circulating tumor DNA (ctDNA) from patients (pts) with advanced non-small cell lung cancer (NSCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9025-9025 ◽  
Author(s):  
Ibiayi Dagogo-Jack ◽  
Eric Bernicker ◽  
Tianhong Li ◽  
Victoria Wang ◽  
Jeffrey S. Ross ◽  
...  
Keyword(s):  
Acquired Resistance ◽  
Large Cell ◽  
Circulating Tumor Dna ◽  
Genomic Profiling ◽  
Tissue Samples ◽  
Egfr Amplification ◽  
Tissue Biopsy ◽  
Not Otherwise Specified ◽  
Complementary Approach ◽  
Clinical Support

9025 Background: Tissue biopsy is the gold standard for detection of genomic alterations (GA) and selection of matched targeted therapies in NSCLC, but ctDNA assay provides a possible complementary approach for some pts. Methods: Hybrid-capture based genomic profiling of 62 genes using a ctDNA assay (FoundationACT™) was performed on blood samples from 1,019 consecutive NSCLC pts. The fraction of ctDNA in the blood was estimated using the maximum somatic allele frequency (MSAF) for each sample. Results: Pt characteristics: Median age 69 years (range 8-94); 54% were female. Histologies included adenocarcinoma (n = 720), NSCLC not otherwise specified (NSCLC NOS; n = 179), squamous cell (n = 57), LC NOS (n = 51), large cell (n = 6), and sarcomatoid (n = 6). ≥1 reportable GA was detected in 71% of all cases and in 83% of cases with evidence of ctDNA in the blood (MSAF > 0). For 22 pts with paired blood and tissue samples collected within 30 days and MSAF > 0, 33/64 (52%) GA detected in tissue were also detected in ctDNA. In 55 pts for whom tissue was insufficient for analysis, ≥1 GA was detected in ctDNA in 43 (78%) cases. For 856 cases with MSAF > 0, an average of 1.8 GA/sample were reported. GA were most frequently detected in TP53 (57%), EGFR (23%) and KRAS (17%). Comparative analysis with the tissue-based FoundationCORE™ database (n = 19,264) showed similar frequencies of GA per gene, although KRAS mutation was more frequent in tissue than ctDNA (27% vs 17%, P < 0.0001), and EGFR T790M was more frequent in ctDNA than tissue (7% vs 2%, P < 0.0001), likely reflecting use of liquid versus tissue biopsy after relapse on targeted therapy .Kinase fusions ( ALK, ROS1, RET, FGFR3, PDGFRA) were identified in 5% (39/856) of cases. Diverse and novel mechanisms of acquired resistance (AR) were detected in ctDNA including MET Y1230C and EGFR amplification post-crizotinib, FGFR3-TACC3 fusion post-EGFR inhibitor, and multiple EGFRAR mutations post-osimertinib. Conclusions: In this series, use of a rigorously validated capture-based assay revealed evidence of ctDNA in the blood in 84% of cases. Our results provide clinical support for use of this assay as a complementary technology to tissue-based genomic testing in a subset of pts with NSCLC.

scholarly journals The Effects of Test Type, Pronunciation, and Proficiency Level on EFL Learners’ Speaking Exam Scores

2020 ◽  
Vol 10 (3) ◽  
pp. 95
Author(s):  
Kardelen Kilinc ◽  
Ozgur Yildirim
Keyword(s):  
Test Scores ◽  
Intermediate Level ◽  
Test Type ◽  
Speaking Test ◽  
Paired Samples ◽  
Proficiency Level ◽  
Significant Difference ◽  
Efl Students ◽  
Bivariate Regression ◽  
The Difference

The present study aims to reveal the effects of test type, pronunciation and proficiency levels of the students on speaking test scores. A total of 147 Turkish EFL students consisting of 38 beginner, 36 elementary, 37 pre-intermediate and 36 intermediate levels participated in the study. Presentation as planned, and paired speaking test as unplanned one were used as instruments to figure out the effects of two different test types on the test scores. Being prepared for their performances, the students did their presentations lasting between 5 and 8 minutes in front of two raters. The same participants, at the end of each level, were invited to the paired-speaking tests designed for the students to show their spontaneous performances. The performances in both tests were scored through a scale with five criteria, and the criteria along with overall scores were examined through Paired Samples t-test to reveal the effects of test type, and through bivariate regression to see the proportion of pronunciation aspect on overall scores. The results showed that in beginner level, although no differences were found in the overall scores, the test type induced differences in pronunciation, vocabulary and relevance aspect of their speaking performances. Similar results were found in elementary level besides the difference found in accuracy aspect, which resulted in a significant difference in overall scores. However, in pre-intermediate level, the only significant difference was found in pronunciation. On the other hand, in intermediate level all the aspects along with the overall scores were found to be affected by the test type except for fluency and pronunciation. The bivariate regression revealed that the effect of pronunciation sub-score on overall scores is significant in each level and test type.

scholarly journals THINK-PAIR-SHARE MODEL AS SOLUTION TO DEVELOP STUDENTS’ CRITICAL THINKING IN ISLAMIC STUDIES: IS IT EFFECTIVE?

2020 ◽  
Vol 39 (1) ◽  
pp. 144-155
Author(s):  
Mohammad Kurjum ◽  
Abdul Muhid ◽  
Muhammad Thohir
Keyword(s):  
Critical Thinking ◽  
Conventional Method ◽  
Statistical Technique ◽  
Control Group ◽  
Control Group Design ◽  
Islamic Studies ◽  
Paired Samples ◽  
Significant Difference ◽  
Equivalent Control ◽  
The Difference

One type of cooperative learning methods is Think Pair Share (TPS). This study aimed at examining the contribution of the TPS method in increasing students' critical thinking in Islamic studies. Particularly, the study investigated the significances of the difference between learned students using TPS method and conventional method, and the effectiveness of TPS learning method. This study used an experimental group and a control group. It is a quasi-experiment with pre-test and post-tests non equivalent control group design. The population of this research are students who take courses in Islamic studies. Samples are taken randomly by taking two classes for an experimental class and a control class. The technique of collecting data was tests, while the technique of data analysis used the statistical technique of t-test (independent and paired samples) within the application of the SPSS release 24 program. The results of the study indicate that there is a significant difference (sig .000) between groups of students who are taught by the TPS Method and conventional Method. In addition, the TPS method has also proven to be effective for teaching Islamic studies which shows a significant difference (sig .000) between the pre-test and post-test.

Association of telomere length (TL) with clinical outcomes in patients with colorectal carcinoma (CRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 418-418
Author(s):  
Mahadi Ali Baig ◽  
Amartej Merla ◽  
Titto A Augustine ◽  
Gil Atzmon ◽  
Temuri Budagov ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Copy Number ◽  
Tandem Repeats ◽  
Progression Free Survival ◽  
Housekeeping Gene ◽  
Tissue Samples ◽  
Paired Samples ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Metastatic Sites

418 Background: Telomeres (T) consist of thousands of copies of TTAGGG tandem repeats capping the ends of the chromosome. T along with enzyme telomerase provides protection against any threats to the genome that might arise as a consequence of “end replication problem.” During aberrant cell proliferations the normal check points of cell cycle is compromised leading to unrestricted cell division with extremely short T and subsequent genomic instability. Studies have linked short TL with premalignant and malignant stages of CRC carcinogenesis. However, the relation of TL to the clinical outcomes has not been conclusively determined. In this study we evaluated the association of TL with clinical outcomes in a cohort of 75 CRC patients. Methods: Tumor DNA was isolated from formalin fixed paraffin embedded specimens. TL was measured by using a qRT-PCR method that provided the relative T copy number, compared to reference copy number of the housekeeping gene, β-Globin, which resulted in a T/S ratio. One T/S ratio unit is equivalent to a mean TL of 4,270 base pairs (BP). Results: From 75 patients, 122 tissue samples were identified (66 primary, 52 metastases, 29 matched pairs). Age at diagnosis (>/< median) had a statistically significant difference in TL (mean BP 4700 vs. 4374; p=0.05) with shorter TL in the advanced age. Females had longer TL compared to men (mean BP 4722 vs. 3669 respectively; p=0.04). Shorter TL was associated with shorter progression free survival (PFS) for patients treated with cetuximab/panitumumab (3963 vs. 5295 p=0.04). There was a trend towards increased overall survival (>/< median) with longer TL (4934 vs. 4117; p=0.08). We failed to find a difference in the TL between primary and metastatic sites in the 29 patients with paired samples. Conclusions: TL is a potential biomarker predictive of clinical outcome (PFS) for patients treated with cetuximab/panitumumab. Tumor TL reduces with advancing age and appears to be sex dependent. Further studies to validate TL’s predictive role in patient outcomes are underway.

Genomic profiling of circulating tumor DNA (ctDNA) from patients (pts) with pancreatic ductal adenocarcinoma (PDA).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4128-4128
Author(s):  
Nathan Bahary ◽  
Jie He ◽  
Mark Bailey ◽  
Shan Zhong ◽  
Gerald Li ◽  
...  
Keyword(s):  
Cancer Biology ◽  
Clinical Care ◽  
Circulating Tumor Dna ◽  
The Cancer Genome Atlas ◽  
Ductal Adenocarcinoma ◽  
Genomic Profiling ◽  
Tissue Samples ◽  
Comprehensive Genomic Profiling ◽  
Cancer Genome Atlas ◽  
Genomic Characterization

4128 Background: PDA is a lethal and increasingly common malignancy and tissue samples for genomic characterization may be limited. As PDA has a high and consistent frequency of KRAS, p53 and CDKN2A mutations it serves as a robust indication to test the utility of ctDNA in accurately characterizing genomic alterations (GA). A prior study suggested significant differences between ctDNA and tissue base profiling but assays were not conducted on the same platform (PMID27833075). We undertook this study to see whether ctDNA could recapitulate the known genomic hallmarks of tumor based profiling. Methods: Hybrid-capture based genomic profiling of 62 genes (FoundationACT) was performed on ctDNA from 78 pts with advanced PDA with samples received in the course of clinical care. The fraction of ctDNA in the blood was estimated using the maximum somatic allele frequency (MSAF) for each sample. Frequencies of alterations in these common drivers were then compared to those seen in tumors of pts who underwent comprehensive genomic profiling (CGP) tissue testing performed on the same core platform, FoundationOne, and The Cancer Genome Atlas (TCGA). Results: Pt characteristics: Median age 65 (range, 47-88); Female (33) /Male (45). FoundationACT results show that 53/78 (68%) cases had MSAF >0 (56%-78%%, 95% CI). ≥1 GA was reported in 81% of the cases with evidence of ctDNA in the blood. The most common GA detected by FoundationACT (based on cases with evidence of ctDNA in blood) vs FoundationOne were in KRAS (59% vs 89%, p< 0.0001), TP53 (69% vs.74%, p=0.19), and CDKN2A (14% vs.45%). Other detected clinically relevant GA detected by FoundationACT included: BRCA1, ERBB2, NF1, PIK3CA. Conclusions: This study demonstrates significant differences between the established driver oncogenic alterations for PDA, as assessed by ct DNA and tissue based genomic profiling which are unlikely to be explained by differences in assay, but rather novel cancer biology. At present use of ctDNA genomic profiling in PDA should not routinely replace tissue based genomic characterization. [Table: see text]

scholarly journals Association between HLA-A gene polymorphism and early-onset preeclampsia in Chinese pregnant women early-onset

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuanyuan Zheng ◽  
Cui Ma ◽  
Xiaowei Liu ◽  
Shaowen Wu ◽  
Weiyuan Zhang ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Early Onset ◽  
Venous Blood ◽  
Susceptibility Gene ◽  
Control Group ◽  
Sequencing Platform ◽  
Significant Difference ◽  
The Difference ◽  
Early Onset Preeclampsia ◽  
Idiopathic Disease

Abstract Background Preeclampsia is an idiopathic disease during pregnancy. This study explores the correlation between HLA-A polymorphism and the onset of preeclampsia. Methods The Illumina HiSeq2500 sequencing platform was used to genotyping HLA-A allele in venous blood DNA of 50 preeclampsia pregnant women and 48 normal pregnant women and umbilical cord blood DNA of their children of Han nationality in China. The frequencies and distributions of alleles and genotypes among the mothers and their children were compared between the two groups. The differences of frequencies and distributions of genotypes were compared between the two groups according to the mothers’ genotype compatibility. Results Twenty HLA-A alleles were detected in preeclampsia pregnant women and normal pregnant women; 21 HLA-A alleles were found in preeclampsia group fetuses and 22 HLA-A alleles in control group fetuses. There was no statistical difference in the HLA-A genes’ frequency between the two groups of pregnant women and their fetuses. When the sharing antigen was 1, the number of maternal-fetal pairs in the preeclampsia group was more than that in the control group; the difference was statistically significant (P < 0.05). The frequency of neither mother nor fetus carrying the HLA-A * 24: 02 gene in the preeclampsia group was significantly lower than that in the control group (P < 0.05). HLA-A gene homozygosity in fetuses of early-onset preeclampsia group was substantially higher than that of the control group (P = 0.0148); there is no significant difference in pregnant women’s genes homozygosity between early-onset preeclampsia group and the control group. Conclusions HLA-A * 24: 02 may be a susceptibility gene for early preeclampsia.

scholarly journals A Comparison of Lane Marking Detection Quality and View Range between Daytime and Night-Time Conditions by Machine Vision

Energies ◽  
2021 ◽  
Vol 14 (15) ◽  
pp. 4666
Author(s):  
Darko Babić ◽  
Dario Babić ◽  
Mario Fiolić ◽  
Arno Eichberger ◽  
Zoltan Ferenc Magosi
Keyword(s):  
Machine Vision ◽  
Lane Detection ◽  
Rank Test ◽  
Quality Level ◽  
Full Potential ◽  
Night Time ◽  
Paired Samples ◽  
Significant Difference ◽  
The Difference ◽  
Detection Quality

Lateral support systems in vehicles have a high potential for reduction of lane departure crashes. To profit from their full potential, such systems should function properly in adverse conditions. Literature indicates that their accuracy varies between day and night-time. However, detailed quantifications of the systems’ performance in these conditions are rare. The aim of this study is to investigate the differences in detection quality and view range of Mobileye 630 in dry daytime and night-time conditions. On-road tests on four rural road sections in Croatia were conducted. Wilcoxon signed-rank test was used to test the difference between the number of quality rankings while absolute average, average difference and standard deviation were used to analyse the view range. Also, a paired samples t-test was used to test the difference between conditions for each line on each road. The overall results confirm that a significant difference in lane detection quality view range exists between tested conditions. “Medium” and “high” detection confidence (quality level 3 and 2), increased by 5% and 8% during night-time compared to daytime while level 0 (“nothing detected”) decreased by 12%. The view range increased (almost 16% for middle line) during daytime compared to night-time. The findings of this study expand the existing knowledge and are valuable for research and development of machine-vision systems but also for road authorities to optimize the markings’ quality performance.

scholarly journals Utility of circulating tumor DNA for detection and monitoring of endometrial cancer recurrence and progression

2020 ◽  
Author(s):  
Esther L. Moss ◽  
Diviya N. Gorsia ◽  
Anna Collins ◽  
Pavandeep Sandhu ◽  
Nalini Foreman ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Recurrence ◽  
Circulating Tumor Dna ◽  
Plasma Dna ◽  
Poor Overall Survival ◽  
Targeted Next Generation Sequencing ◽  
Whole Exome ◽  
Ctdna Analysis ◽  
Msi Analysis ◽  
Tumor Dna

ABSTRACTDespite the increasing incidence of endometrial cancer (EC) worldwide and the poor overall survival of patients who recur, no reliable biomarker exists for detecting and monitoring EC recurrence and progression during routine follow-up. Circulating tumor DNA (ctDNA) is a sensitive method for monitoring cancer activity and stratifying patients that are likely to respond to therapy. As a pilot study, we investigated the utility of ctDNA for detecting and monitoring EC recurrence and progression in 13 patients using targeted next-generation sequencing (tNGS) and personalized ctDNA assays. Using tNGS, at least 1 somatic mutation at a variant allele frequency (VAF) >20% was detected in 69% (9/13) of patient tumors. The four patients with no detectable tumor mutations at >20% VAF were whole exome sequenced, with all four harboring mutations in genes not analyzed by tNGS. Analysis of matched and longitudinal plasma DNA revealed earlier detection of EC recurrence and progression and dynamic kinetics of ctDNA levels reflecting treatment response. We also detected acquired high microsatellite instability (MSI-H) in ctDNA from one patient whose primary tumor was MSI stable. Our study suggests that ctDNA analysis, and in particular MSI analysis in ctDNA could become a useful biomarker for early detection and monitoring of EC recurrence and progression.

KAITAN PELATIHAN DALAM UPAYA MENINGKATKAN KUALITAS KERJA KARYAWAN PT BOGOR AGRO LESTARI TAHUN 2007

2018 ◽  
Vol 3 (01) ◽  
pp. 54
Author(s):  
Dedy Mulyadi ◽  
Kartika .
Keyword(s):  
Behavioral Change ◽  
Career Planning ◽  
Short Term ◽  
Paired Samples ◽  
Statistical Computation ◽  
Significant Difference ◽  
Before And After ◽  
The Difference

Considering the major role of human resource in achieving the company’s goal the company should provide an operational skill or knowledge directly from manager to employee’s levels. The company should give the employees a better understanding that the training is provided not only to execute the pre-determined program smoothly, but also to increase the quality of their achievement in their own field that in turn will influence their income, performance and future career planning. Comparing the statistical scores gained by the employee before and after the training proves the significant difference. After the training the score was higher (3.87%) than before the training (3.08%), which means that the training gave good impact. Other statistical computation using t – paired samples with α = 0.005 and degree of freedom (df = 29) also proved the difference where t counted (-38.445) is bigger than t table (-1.669). The training was basically aiming at formulating the expected ability from the employees to change their behavior. Such a change was formulated in terms of behavioral change and a short-term educational program by using systemic and organized procedures, so that operative employees learn technical and skill knowledge for specific purpose.

Association of telomere length with clinical outcomes in patients with colorectal carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14540-e14540
Author(s):  
Mahadi Ali Baig ◽  
Titto A Augustine ◽  
Amartej Merla ◽  
Gil Atzmon ◽  
Temuri Budagov ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Copy Number ◽  
Tandem Repeats ◽  
Progression Free Survival ◽  
Housekeeping Gene ◽  
Tissue Samples ◽  
Paired Samples ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Metastatic Sites

e14540 Background: Telomeres (T) consist of thousands of copies of TTAGGG tandem repeats capping the ends of the chromosome. T along with enzyme telomerase provides protection against any threats to the genome that might arise as a consequence of “end replication problem”. Studies have linked short TL with premalignant and malignant stages of CRC carcinogenesis. However, the relation of TL to the clinical outcomes has not been conclusively determined. In this study we evaluated the association of TL with clinical outcomes in a cohort of 75 CRC patients. Methods: Tumor DNA was isolated from formalin fixed paraffin embedded specimens. TL was measured by using a qRT-PCR method that provided the relative T copy number, compared to reference copy number of the housekeeping gene, β-Globin, which resulted in a T/S ratio. One T/S ratio unit is equivalent to a mean TL of 4,270 base pairs (BP). Results: From 75 patients, 118 tissue samples were identified (66 primary, 52 metastases, 29 matched pairs). Age at diagnosis (>/< median) had a statistically significant difference in TL (mean BP 4700 vs. 4374; p=0.05) with shorter TL in the advanced age. Females had longer TL compared to men (mean BP 4722 vs. 3669 respectively; p=0.04). Stage at diagnosis (localized Vs Metastatic) had a statistically significant difference in TL (mean BP 4047 vs. 5704; p=0.03). Shorter TL was associated with shorter progression free survival (PFS) for patients treated with cetuximab/panitumumab (3963 vs 5295 p=0.022). Patients treated with cetuximab/panitumumab who had Shorter TL were also found to have significantly decreased Overall Survival (OS) (101.1 Months vs 153.02 Months p<0.0001). We failed to find a difference in the TL between primary and metastatic sites in the 29 patients with paired samples. There was no difference of TL seen with size of the tumor. Furthermore there was no difference in TL between various metastatic sites. Conclusions: TL is a potential biomarker predictive of clinical outcome (OS & PFS) for patients treated with cetuximab/panitumumab. Tumor TL reduces with advancing age and appears to be sex dependent. Further studies to validate TL’s predictive role in patient outcomes are underway.

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