Scientific and technological innovations have become increasingly important as we face the benefits and challenges of both globalization and a knowledge-based economy. Still, enrolment rates in STEM ...degrees are low in many European countries and consequently there is a lack of adequately educated workforce in industries. We believe that this can be mainly attributed to pedagogical issues, such as the lack of engaging hands-on activities utilized for science and math education in middle and high schools. In this paper, we report our work in the SciChallenge European project, which aims at increasing the interest of pre-university students in STEM disciplines, through its distinguishing feature, the systematic use of social media for providing and evaluation of the student-generated content. A social media-aware contest and platform were thus developed and tested in a pan-European contest that attracted <inline-formula><tex-math notation="LaTeX">> {{700}}</tex-math></inline-formula> participants. The statistical analysis and results revealed that the platform and contest positively influenced participants STEM learning and motivation, while only the gender factor for the younger study group appeared to affect the outcomes (confidence level - <inline-formula><tex-math notation="LaTeX">{\text{p}}< .05</tex-math></inline-formula>).
Cloud computing offers a flexible pay-as-you-go model for provisioning application resources, which enables applications to scale on-demand based on the current workload. In many cases, though, users ...face the single vendor lock-in effect, missing opportunities for optimal and adaptive application deployment across multiple clouds. Several cloud modelling languages have been developed to support multi-cloud resource management, but still they lack holistic cloud management of all aspects and phases. This work defines the Cloud Application Modelling and Execution Language (CAMEL), which (i) allows users to specify the full set of design time aspects for multi-cloud applications, and (ii) supports the models@runtime paradigm that enables capturing an application’s current state facilitating its adaptive provisioning. CAMEL has been already used in many projects, domains and use cases due to its wide coverage of cloud management features. Finally, CAMEL has been positively evaluated in this work in terms of its usability and applicability in several domains (e.g., data farming, flight scheduling, financial services) based on the technology acceptance model (TAM).
Noninvasive prenatal testing (NIPT) using whole genome and targeted sequencing has become increasingly accepted for clinical detection of Trisomy 21 and sex chromosome aneuploidies. Few studies have ...shown that sub-chromosomal deletions or duplications associated with genetic syndromes can also be detected in the fetus noninvasively. There are still limitations on these methodologies such as the detection of variants of unknown clinical significance, high number of false positives, and difficulties to detect small aberrations. We utilized a recently developed targeted sequencing approach for the development of a NIPT assay, for large and small size deletions/duplications, which overcomes these existing limitations. Artificial pregnancies with microdeletion/microduplication syndromes were created by spiking DNA from affected samples into cell free DNA (cfDNA) from non-pregnant samples. Unaffected spiked samples and normal pregnancies were used as controls. Target Capture Sequences (TACS) for seven syndromes were designed and utilized for targeted capture enrichment followed by sequencing. Data was analyzed using a statistical pipeline to identify deletions or duplications on targeted regions. Following the assay development a proof of concept study using 33 normal pregnancies, 21 artificial affected and 17 artificial unaffected pregnancies was carried out to test the sensitivity and specificity of the assay. All 21 abnormal spiked-in samples were correctly classified as subchromosomal aneuploidies while the 33 normal pregnancies or 17 normal spiked-in samples resulted in a false positive result. We have developed an NIPT assay for the detection of sub-chromosomal deletions and duplications using the targeted capture enrichment technology. This assay demonstrates high accuracy, high read depth of the genomic region of interest, and can identify deletions/duplications as small as 0.5 Mb. NIPT of fetal microdeletion/microduplication syndromes can be of enormous benefit in the management of pregnancies at risk both for prospective parents and health care providers.
Abstract Since 2012, non-invasive prenatal testing (NIPT) using cell-free DNA from maternal plasma is applied all over the world as highly efficient first-line or contingent screening approach for ...trisomy 13, 18 and 21. With further technical development the screening has expanded to other genetic conditions such as sex chromosome anomalies (SCAs), rare autosomal trisomies (RATs), microdeletions/microduplications, structural chromosomal aberrations and monogenic diseases. Meanwhile, commercial providers are offering a number of different tests, with variable performance, the application of which needs to be carefully evaluated to apply to the true needs of clinical practice. In our review we present the different NIPT methodologies and discuss the main strengths and limitations in the context of providing a responsible pregnancy management.
Sensor networks that collect data from the environment can be utilized in the development of context-aware applications, bringing into sight the need for data collection, management, and ...distribution. Boards with microcontrollers, such as Arduino and Raspberry Pi, have gained wide acceptance and are used mainly for educational and research purposes. Utilizing the information available via sensors connected to these platforms requires extended technical knowledge. In this work, we present a sensor management framework, SensoMan, that manages a collection of sensors spread in the environment connected to microcontroller boards. We present the framework’s architecture, a method for sensor data management, and a prototype system. Sensor data can also trigger the execution of actions on actuators. Thus, we further propose a rule engine as well as social connectivity following a scheme where sensors and their data can be shared among users. Our work shows that the creation of such a system is feasible and can use simple equipment (e.g., sensors, controller plugs) that can be replicated in other environments. The use of SensoMan is demonstrated via two scenarios that show its potential in combining simple tools that do not require an extended learning curve. A small-scale user study was also performed.
DNA methylation is the most characterized epigenetic process exhibiting stochastic variation across different tissues and individuals. In non-invasive prenatal testing (NIPT) fetal specific ...methylated regions can potentially be used as biomarkers for the accurate detection of fetal aneuploidies. The aim of this study was the investigation of inter-individual methylation variability of previously reported fetal-specific markers and their implementation towards the development of a novel NIPT assay for the detection of trisomies 13, 18, and 21. Methylated DNA Immunoprecipitation (MeDIP) combined with in-solution targeted enrichment followed by NGS was performed in 29 CVS and 27 female plasma samples to assess inter-individual methylation variability of 331 fetal-specific differentially methylated regions (DMRs). The same approach was implemented for the NIPT of trisomies 13, 18 and 21 using spiked-in (n = 6) and pregnancy samples (n = 44), including one trisomy 13, one trisomy 18 and four trisomy 21. Despite the variability of DMRs, CVS samples showed statistically significant hypermethylation (p<2e-16) compared to plasma samples. Importantly, our assay correctly classified all euploid and aneuploid cases without any false positive results (n = 44). This work provides the starting point for the development of a NIPT assay based on a robust set of fetal specific biomarkers for the detection of fetal aneuploidies. Furthermore, the assay's targeted nature significantly reduces the analysis cost per sample while providing high read depth at regions of interest increasing significantly its accuracy.
The mechanisms underlying high drug resistance and relapse rates after multi-modal treatment in patients with colorectal cancer (CRC) and liver metastasis (LM) remain poorly understood.
We evaluate ...the potential translational implications of intra-patient heterogeneity (IPH) comprising primary and matched metastatic intratumor heterogeneity (ITH) coupled with circulating tumor DNA (ctDNA) variability.
A total of 122 multi-regional tumor and perioperative liquid biopsies from 18 patients were analyzed
targeted next-generation sequencing (NGS).
The proportion of patients with ITH were 53% and 56% in primary CRC and LM respectively, while 35% of patients harbored
mutations in LM indicating spatiotemporal tumor evolution and the necessity of multiregional analysis. Among the 56% of patients with alterations in liquid biopsies,
mutations in cfDNA were identified in 25% of patients, which were undetectable in both CRC and LM. All 17 patients with driver alterations harbored mutations targetable by molecularly targeted drugs, either approved or currently under evaluation.
Our proof-of-concept prospective study provides initial evidence on potential clinical superiority of IPH and warrants the conduction of precision oncology trials to evaluate the clinical utility of I PH-driven matched therapy.
Tumorigenesis is a complex, multistep process that depends on numerous alterations within the cell and contribution from the surrounding stroma. The ability to model macroscopic tumor evolution with ...high fidelity may contribute to better predictive tools for designing tumor therapy in the clinic. However, attempts to model tumor growth have mainly been developed and validated using data from xenograft mouse models, which fail to capture important aspects of tumorigenesis including tumor-initiating events and interactions with the immune system. In the present study, we investigate tumor growth and therapy dynamics in a mouse model of de novo carcinogenesis that closely recapitulates tumor initiation, progression and maintenance in vivo. We show that the rate of tumor growth and the effects of therapy are highly variable and mouse specific using a Gompertz model to describe tumor growth and a two-compartment pharmacokinetic/ pharmacodynamic model to describe the effects of therapy in mice treated with 5-FU. We show that inter-mouse growth variability is considerably larger than intra-mouse variability and that there is a correlation between tumor growth and drug kill rates. Our results show that in vivo tumor growth and regression in a double transgenic mouse model are highly variable both within and between subjects and that mathematical models can be used to capture the overall characteristics of this variability. In order for these models to become useful tools in the design of optimal therapy strategies and ultimately in clinical practice, a subject-specific modelling strategy is necessary, rather than approaches that are based on the average behavior of a given subject population which could provide erroneous results.
Non-invasive prenatal testing (NIPT) has been widely adopted for the detection of fetal aneuploidies and microdeletion syndromes, nevertheless, limited clinical utilization has been reported for the ...non-invasive prenatal screening of monogenic diseases. In this study, we present the development and validation of a single comprehensive NIPT for prenatal screening of chromosomal aneuploidies, microdeletions and 50 autosomal recessive disorders associated with severe or moderate clinical phenotype.
We employed a targeted capture enrichment technology powered by custom TArget Capture Sequences (TACS) and multi-engine bioinformatics analysis pipeline to develop and validate a novel NIPT test. This test was validated using 2033 cell-fee DNA (cfDNA) samples from maternal plasma of pregnant women referred for NIPT and paternal genomic DNA. Additionally, 200 amniotic fluid and CVS samples were used for validation purposes. All NIPT samples were correctly classified exhibiting 100% sensitivity (CI 89.7-100%) and 100% specificity (CI 99.8-100%) for chromosomal aneuploidies and microdeletions. Furthermore, 613 targeted causative mutations, of which 87 were unique, corresponding to 21 monogenic diseases, were identified. For the validation of the assay for prenatal diagnosis purposes, all aneuploidies, microdeletions and point mutations were correctly detected in all 200 amniotic fluid and CVS samples.
We present a NIPT for aneuploidies, microdeletions, and monogenic disorders. To our knowledge this is the first time that such a comprehensive NIPT is available for clinical implementation.
The cancer risk in Barrett's oesophagus (BO) is difficult to estimate. Histologic dysplasia has strong predictive power, but can be missed by random biopsies. Other clinical parameters have limited ...utility for risk stratification. We aimed to assess whether a molecular biomarker panel on targeted biopsies can predict neoplastic progression of BO.
203 patients with BO were tested at index endoscopy for 9 biomarkers (p53 and cyclin A expression; aneuploidy and tetraploidy; CDKN2A (p16), RUNX3 and HPP1 hypermethylation; 9p and 17p loss of heterozygosity) on autofluorescence-targeted biopsies and followed-up prospectively. Data comparing progressors to non-progressors were evaluated by univariate and multivariate analyses using survival curves, Cox-proportional hazards and logistic regression models.
127 patients without high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC) at index endoscopy were included, of which 42 had evidence of any histologic progression over time. Aneuploidy was the only predictor of progression from non-dysplastic BO (NDBO) to any grade of neoplasia (p = 0.013) and HGD/OAC (p = 0.002). Aberrant p53 expression correlated with risk of short-term progression within 12 months, with an odds ratio of 6.0 (95% CI: 3.1–11.2). A panel comprising aneuploidy and p53 had an area under the receiving operator characteristics curve of 0.68 (95% CI: 0.59–0.77) for prediction of any progression.
Aneuploidy is the only biomarker that predicts neoplastic progression of NDBO. Aberrant p53 expression suggests prevalent dysplasia, which might have been missed by random biopsies, and warrants early follow up.
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