Liquid biopsy is a tool to unveil resistance mechanisms in NSCLC. We studied changes in gene expression in CTC-enriched fractions of EGFR-mutant NSCLC patients under osimertinib. Peripheral blood ...from 30 NSCLC patients before, after 1 cycle of osimertinib and at progression of disease (PD) was analyzed by size-based CTC enrichment combined with RT-qPCR for gene expression of epithelial (CK-8, CK-18, CK-19), mesenchymal/EMT (VIM, TWIST-1, AXL), stem cell (ALDH-1) markers, PD-L1 and PIM-1. CTCs were also analyzed by triple immunofluorescence for 45 identical blood samples. Epithelial and stem cell profile (p = 0.043) and mesenchymal/EMT and stem cell profile (p = 0.014) at PD were correlated. There was a strong positive correlation of VIM expression with PIM-1 expression at baseline and increased PD-L1 expression levels at PD. AXL overexpression varied among patients and high levels of PIM-1 transcripts were detected. PD-L1 expression was significantly increased at PD compared to baseline (p = 0.016). The high prevalence of VIM positive CTCs suggest a dynamic role of EMT during osimertinib treatment, while increased expression of PD-L1 at PD suggests a theoretical background for immunotherapy in EGFR-mutant NSCLC patients that develop resistance to osimertinib. This observation merits to be further evaluated in a prospective immunotherapy trial.
Carbon sequestration service of Mediterranean forest and other wooded land is threatened by their fragile, complex, and highly evolving nature, due to both human disturbances and climate change. ...Remote-sensing methods for forest biomass estimation have gained increased attention, and substantial research has been conducted worldwide over the past four decades. Yet, the literature body focused on Mediterranean forests is rather limited as a result of their small extent compared to other biomes. We discuss the remote-sensing studies over the Mediterranean forest and other wooded land, discriminating research based on the primary data source used, such as optical imagery, datasets from active sensors, and combination of multisource data. The review indicates that there is a significant research gap in terms of the studies, as well as a need for a reduction of the errors and uncertainty of estimates, which are associated with both the sensors' characteristics and the Mediterranean forest and other wooded land structure. Biomass estimates based on optical data were generally less accurate (R
2
close to 0.70, where R
2
is the coefficient of determination), however, when data from active sensors were involved, accuracy of estimations was considerably greater (usually R
2
greater than 0.80). With respect to scale, most of the local scale studies established relationships with R
2
over 0.70 and as high as 0.98, while the few regional scale studies exhibited R
2
close to 0.80. Further, in-depth analysis can provide more efficient data fusion, classification methods, and procedures for operational regional and national assessment of forest biomass over such Mediterranean areas.
PurposeThe causes for the formation of a bubble in the collateral market when agents are provided with homogeneous expectations are explored. This bubbly dynamics will define a sufficient condition ...for deleveraging.Design/methodology/approachTheoretical approach with neutral deleveraging.FindingsFindings of the study are defined sufficient conditions for a behavioral rational bubble's formation in a market of collateral and the subsequent deleveraging. The crowd-in effect of the representative bubble is caused by errors in extrapolating information and thus by representativeness, while the crowd-out effect of deleveraging is set off by reverting to a rational heuristic.Research limitations/implicationsThe limit is that it is a homogeneous expectations approach, the implication is that cannot be rational speculation.Practical implicationsEven in a simple model of homogeneous expectations a bubble may arise with serious effect on the demand side: models that detect just rational mispricings cannot account for behavioral components that have financial and real effects.Originality/valueThe paper defines how deleveraging may occur even in case of homogeneous expectations. The latter should not be seen just as a limit but also as a signal of the importance of being aware of behavioral components.
Thermodynamic and structural properties of the N-alkanoyl-substituted α-amino acids threonine and serine, differing only by one CH3 group in the head group, are determined and compared. Detailed ...characterization of the influence of stereochemistry proves that all enantiomers form an oblique monolayer lattice structure whereas the corresponding racemates build orthorhombic lattice structures due to dominating heterochiral interactions, except N-C16-dl-serine-ME as first example of dominating homochiral interactions in a racemic mixture of N-alkanoyl-substituted α-amino acids. In all cases, the liquid expanded–liquid condensed (LE/LC) transition pressure of the racemic mixtures is above that of the corresponding enantiomers. Phase diagrams are proposed. Using the program Hardpack to predict tilt angles and cross-sectional area of the alkyl chains shows reasonable agreement with the experimental grazing incidence X-ray diffraction (GIXD) data.
The overall aim of this study was to evaluate the use of seasonal time-series Landsat 8 Operational Land Imager (OLI) satellite imagery in estimating forest stand parameters in a heterogeneous ...Mediterranean environment. Within this framework, the random forest regression algorithm was used to model the relationship between spectral information and tree density, basal area, and wood volume, based on single-date, single-season (dry, wet), and multi-temporal (May–December) imagery. The variable importance (VIMP) measure and the minimal depth (MD) order statistic were also investigated with regard to improved prediction accuracy and the identification of relevant variables. In general, the multi-temporal and dry-season models were more accurate than the single-date models. The models resulting from the MD variable selection from the dry season imagery were the most accurate with a coefficient of determination of up to 0.54 for tree density, 0.72 for basal area, and 0.68 for volume.
•Random Forest regression models for single-date, seasonal and multi-temporal images•Variable importance (VIMP) and Minimal depth (MD) variable selection procedures•July imagery was most efficient in predicting basal area and wood volume•The SWIR spectral information presented as the most important variable•MD variable selection for dry season imagery indicated as the most accurate model
► The extraction yield for recovery of tomato waste carotenoids was studied. ► A mixture of ethyl acetate and hexane gave the highest carotenoid extraction yield. ► Extraction conditions were ...optimised using a statistically designed experiment. ► Maximum recovery of carotenoids was achieved with 45% hexane in solvent mixture.
Carotenoids constitute an important component of waste originating from tomato processing plants. Studies were carried out to assess the extraction yield of tomato waste carotenoids in different solvents and solvent mixtures and to optimise the extraction conditions for maximum recovery. A mixture of ethyl acetate and hexane gave the highest carotenoid extraction yield among the others examined. Extraction conditions, such as percentage of hexane in the solvent mixture of ethyl acetate and hexane, ratio of solvent to waste and particle size were optimised using a statistically designed experiment. A regression equation for predicting the carotenoid yield as a function of three extraction variables was derived by statistical analysis and a model with predictive ability of 0.97 was obtained. The optimised conditions for maximum carotenoid yield (37.5mgkg−1drywaste) were 45% hexane in solvent mixture, solvent mixture to waste ratio of 9.1:1 (v/w) and particle size 0.56mm.
Summary
Tomato waste is an important source of natural carotenoids. This study was carried out to assess the extractability of tomato waste carotenoids in different organic solvents and to optimise ...the extraction parameters (type of solvent, extraction time, temperature and extraction steps) for maximum yield. Among other solvents, we tested a new environmentally friendly one, ethyl lactate, which gave the highest carotenoid yield (243.00 mg kg−1 dry tomato waste) at 70 °C, compared to acetone (51.90 mg kg−1), ethyl acetate (46.21 mg kg−1), hexane (34.45 mg kg−1) and ethanol (17.57 mg kg−1). The carotenoid recovery was significantly (P < 0.05) affected by the number of extraction steps and temperature in all solvents. Mathematic equations predicted rather satisfactorily (R2 = 0.89–0.93) the rate of carotenoid extraction in the above‐mentioned solvents. Carotenoid concentration increased with time, approaching a quasi‐saturated condition at approximately 30 min of extraction.
Liquid biopsy provides real-time monitoring of tumor evolution and response to therapy through analysis of circulating tumor cells (CTCs) and plasma-circulating tumor DNA (ctDNA).
epigenetic ...silencing potentially affects response to endocrine treatment. We evaluated
methylation in CTCs and paired plasma ctDNA. We evaluated
methylation in CTCs and paired plasma ctDNA as a potential biomarker for response to everolimus/exemestane treatment.
A highly sensitive and specific real-time MSP assay for
methylation was developed and validated in (i) 65 primary breast tumors formalin-fixed paraffin-embedded (FFPE), (ii) EpCAM
CTC fractions (122 patients and 30 healthy donors; HD), (iii) plasma ctDNA (108 patients and 30HD), and (iv) in CTCs (CellSearch) and in paired plasma ctDNA for 58 patients with breast cancer.
methylation status was investigated in CTCs isolated from serial peripheral blood samples of 19 patients with ER
/HER2
advanced breast cancer receiving everolimus/exemestane.
methylation was detected in: (i) 25/65 (38.5%) FFPEs, (ii)
: 26/112 (23.3%) patients and 1/30 (3.3%) HD, and (iii)
8/108 (7.4%) patients and 1/30 (3.3%) HD.
methylation was highly concordant in 58 paired DNA samples, isolated from CTCs (CellSearch) and corresponding plasma. In serial peripheral blood samples of patients treated with everolimus/exemestane,
methylation was observed in 10/36 (27.8%) CTC-positive samples, and was associated with lack of response to treatment (
= 0.023, Fisher exact test).
We report for the first time the detection of
methylation in CTCs and a high concordance with paired plasma ctDNA.
methylation in CTCs was associated with lack of response to everolimus/exemestane regimen.
methylation should be further evaluated as a potential liquid biopsy-based biomarker.
.
Several wearable devices for physiological and activity monitoring are found on the market, but most of them only allow spot measurements. However, the continuous detection of physiological ...parameters without any constriction in time or space would be useful in several fields such as healthcare, fitness, and work. This can be achieved with the application of textile technologies for sensorized garments, where the sensors are completely embedded in the fabric. The complete integration of sensors in the fabric leads to several manufacturing techniques that allow dealing with both the technological challenges entailed by the physiological parameters under investigation, and the basic requirements of a garment such as perspiration, washability, and comfort. This review is intended to provide a detailed description of the textile technologies in terms of materials and manufacturing processes employed in the production of sensorized fabrics. The focus is pointed at the technical challenges and the advanced solutions introduced with respect to conventional sensors for recording different physiological parameters, and some interesting textile implementations for the acquisition of biopotentials, respiratory parameters, temperature and sweat are proposed. In the last section, an overview of the main garments on the market is depicted, also exploring some relevant projects under development.
Vegetation monitoring and mapping based on multi-temporal imagery has recently received much attention due to the plethora of medium-high spatial resolution satellites and the improved classification ...accuracies attained compared to uni-temporal approaches. Efficient image processing strategies are needed to exploit the phenological information present in temporal image sequences and to limit data redundancy and computational complexity. Within this framework, we implement the theory of Hidden Markov Models in crop classification, based on the time-series analysis of phenological states, inferred by a sequence of remote sensing observations. More specifically, we model the dynamics of vegetation over an agricultural area of Greece, characterized by spatio-temporal heterogeneity and small-sized fields, using RapidEye and Landsat ETM+ imagery. In addition, the classification performance of image sequences with variable spatial and temporal characteristics is evaluated and compared. The classification model considering one RapidEye and four pan-sharpened Landsat ETM+ images was found superior, resulting in a conditional kappa from 0.77 to 0.94 per class and an overall accuracy of 89.7%. The results highlight the potential of the method for operational crop mapping in Euro-Mediterranean areas and provide some hints for optimal image acquisition windows regarding major crop types in Greece.
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