Cancer-associated fibroblasts (CAF) are essential components of the stroma that play a critical role in cancer progression. This study aimed to identify novel CAFs markers that might contribute to ...the invasion and the prognosis of colorectal cancer.
The azoxymethane/dextran sodium sulfate mouse model of sporadic colon cancer represents an adequate source for the isolation of CAFs and normal fibroblasts. By using the explants technique, we purified CAFs and normal fibroblasts from colon tissues. Whole-cell extracts and supernatants were subjected to in-depth quantitative proteomic analysis by tandem mass spectrometry. Further validations of upregulated proteins in CAFs were carried out by chemokine microarray and immunohistochemical analyses of mouse and human tissues.
Using a fold-change of 1.4 or more, we found 132 and 125 differentially expressed proteins in whole-cell extracts and supernatants, respectively. We found CAFs-associated proinflammatory and desmoplastic signatures. The proinflammatory signature was composed of several cytokines. Among them, CCL2 and CCL8 caused an increase in migration and invasion of colorectal cancer KM12 cells. The desmoplastic signature was composed of 30 secreted proteins. In mouse and human samples, expression of LTBP2, CDH11, OLFML3, and, particularly, FSTL1 was significantly increased in the tumoral stroma, without significant expression in the cancer epithelial cells. The combination of CALU and CDH11 stromal expression showed a significant association with disease-free survival and poor prognosis.
We have identified LTBP2, CDH11, OLFML3, and FSTL1 as selective biomarkers of cancer stroma, and CALU and CDH11 as candidate stromal biomarkers of prognostic significance in colon cancer.
In this work, surrogate models based on support vector regression (SVR) of a multi-resonant unit cell in a geometrical 4-D parallelotope domain are trained and used in a reflectarray antenna design. ...The multiple sharp resonances of the unit cell prevent a suitable training process in the whole orthotope defined by the available degrees of freedom (DoF). Thus, a strategy to improve the training process and obtain highly accurate models is devised. It consists in defining a parallelotope around a rectangle of stability, which is in turn defined at a lower dimensionality. The SVR models with four geometrical DoF obtained in this parallelotope are shown to provide highly accurate results for the design of a large contoured-beam reflectarray for space applications. The direct optimization with the surrogate models allows to improve the cross-polarization performance several dB while considerably increasing computational performance. Furthermore, compared to lower dimensionality models, the 4-D models offer better results when applied to wideband and dual-band reflectarray direct optimization.
Background
In recent years, disease treatment has evolved strategies that require increase in pharmaceutical agent’s efficacy and selectivity while decreasing their toxicity in normal tissues. These ...requirements have led to the development of nanoscale liposome systems for drug release. This review focuses on lipid features, pharmacological properties of liposomal formulations and the clinical studies of their application.
Main body
Several lipids are available, but their properties could affect pharmacological or clinical efficiency of drug formulations. Many liposomal formulations have been developed and are currently on the market. Proper selection of lipid is essential for the pharmacological effect to be improved. Most of the formulations use mainly zwitterionic, cationic or anionic lipids, PEG and/or cholesterol, which have different effects on stability, pharmacokinetics and delivery of the drug formulation. Clinical trials have shown that liposomes are pharmacologically and pharmacokinetically more efficient than drug-alone formulations in treating acute myeloid leukemia, hepatitis A, pain management, ovary, gastric breast and lung cancer, among others.
Conclusion
Liposomal formulations are less toxic than drugs alone and have better pharmacological parameters. Although they seem to be the first choice for drug delivery systems for various diseases, further research about dosage regimen regarding dose and time needs to be carried out.
A common approach in the literature when obtaining surrogate models of reflectarray unit cells is to include, among other variables, the angles of incidence as input variables to the model. In this ...work, we use support vector regression (SVR) to compare this approach with a new strategy which consists in grouping the refletarray elements under a small set of angles of incidence and train surrogate models per angle of incidence pair. In this case, the dimensionality of the SVR decreases in two with regard to the former approach. In both cases, two geometrical variables are considered for reflectarray design, obtaining 4-D and 2-D SVRs, respectively. In contrast to the common approach in the literature, the comparison between the 4-D and 2-D SVRs shows that a proper discretization of the angles of incidence is more competitive than introducing the angles as input variables in the SVR. The 2-D SVR offers a shorter training time, faster reflectarray analysis, and a similar accuracy than the 4-D SVR, making it more suitable for design and optimization procedures.
Cancer-associated fibroblasts (CAF) are major mediators in tumor microenvironment. We investigated the changes in protein expression in colon cancer-associated fibroblasts compared with normal ...fibroblasts (NF) in the context of searching for prognostic biomarkers, particularly for stage II patients.
CAFs and NFs isolated from colon cancer patients were used to identify differentially expressed proteins using quantitative proteomics. Stromal expression of deregulated proteins was analyzed by IHC. Prognostic impact was studied using external gene-expression datasets for training, then quantitative PCR and IHC for validation in different cohorts of patients. Combined datasets were used for prediction of risk assessment at stages II and III.
A desmoplastic signature composed of 32 proteins, highly specific for stromal components in colon cancer, was identified. These proteins were enriched for extracellular matrix organization components, TGFβ signaling pathway, fibrosis, and wound-healing proteins. The expression in CAFs of 11 upregulated proteins and four downregulated proteins, selected for biomarker validation, was verified by orthogonal techniques. LOXL2 displayed a high prognostic impact by using external independent datasets and further validation in two different cohorts of patients. High expression of LOXL2 was associated with higher recurrence P = 0.001 HR, 5.38 95% confidence interval (CI), 1.70-17.01 and overall survival P = 0.001 HR, 8.52 (95% CI, 1.90-38.29). IHC analysis revealed a prognostic value for LOXL2 in stage II patients.
We identified LOXL2 to be associated with the outcome of colon cancer patients. Furthermore, it can be used to stratify patients at stages II and III for further therapeutic decisions.
In recent years, machine learning techniques (MLTs) have been applied to accelerate the analysis and design of electromagnetic devices. Algorithms such as artificial neural networks or support vector ...machines for regression (SVRs) have been proposed for the design of large reflectarrays for space applications at a single frequency. However, multifrequency optimization of such large antennas has not been tackled with MLTs. In this letter, for the first time, we propose a technique based on the use of SVR analysis to obtain the reflection coefficients to accelerate the design of a very large shaped-beam reflectarray for direct broadcast satellite in a 15% bandwidth. An in-house method of moments based on local periodicity is employed to generate samples to train the SVRs for each considered frequency. Then, the surrogate model is used for a design at central frequency, which is used as starting point for a wideband design procedure that is accelerated more than an order of magnitude without a significant loss of accuracy. It is shown that, by the virtue of the proposed methodology, the minimum copolar gain in the coverage zone is improved more than 10 dB at the upper frequency while maintaining a computationally efficient design procedure.
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•EKPR of atrazine-polluted soils is feasible at mesocosm scale.•Atrazine was transported in the soil by electro-osmosis and electromigration.•Final distribution of atrazine in soils ...agrees with its concentration in soil pore water.•Some limitations relative to the scaling up of EKPR processes have been detected.
Phytoremediation, an ecological remediation technology based on the use of plants, can be combined with electrokinetic treatment for the removal of both inorganic and organic pollutants from soils. Electrokinetic-assisted phytoremediation (EKPR) of atrazine was tested in a mesocosm scale experiment using ryegrass (Lolium perenne L.). Two mock-ups with dimensions of 2.25 (L) × 0.49 (W) × 0.50 (H) m were initially filled with an unpolluted low plasticity clay soil and used to carry out an EKPR test and another electrokinetic remediation (EKR) one after spiking the soil with atrazine at a dose of 2 mg kg−1. Experiments were conducted for 19 days using a DC electrical field of 0.6 V cm−1 applied continuously without changing polarity. Samples of soil, plants and soil pore water corresponding to ten different soil sections of each mock-up were taken and analysed throughout the experiment. Soil pH followed an increasing profile from the anode to the cathode, although it kept moderate values in the range of 7.53–9.62. Electro-osmosis, gravity and plant roots (in the EKPR series) influenced the final distribution of water and atrazine in the soil. Additionally, the electromigration flux had a relevant role in the atrazine residues transport during the EKPR process. Concentration values of atrazine residues remaining in the different soil sections were in good agreement with those of the soil pore water, with most of the atrazine being accumulated in the cathode section. Atrazine was mainly removed from soils by biochemical degradation, which was greatly improved by ryegrass plants; the overall atrazine removal yield was increased from 40.20% (unplanted mock-up) to 61.01% (planted mock-up).
This work presents the optimization of a dual circular-polarized (CP) shaped-beam reflectarray with improved performance. To that end, the design methodology leverages surrogate models based on ...support vector regression (SVR) of the electromagnetic response of the constituent unit cell for a direct layout optimization of the antenna. The dual CP capability is achieved using a linear polarization (LP) Jerusalem cross integrated with an LP-to-CP polarization converter. A full description of the reflectarray analysis in CP is given. We also provide a missing demonstration in the literature of the fact that the direct coefficients in CP shape the copolar (CO) pattern of the corresponding polarization. This is applied to the optimization of a dual CP reflectarray with an isoflux pattern, achieving a reduction of more than 9 dB in the crosspolar (XP) pattern.
Studies on robotic interventions for gait rehabilitation after stroke require: (i) rigorous performance evidence; (ii) systematic procedures to tune the control parameters; and (iii) combination of ...control modes. In this study, we investigated how stroke individuals responded to training for two weeks with a knee exoskeleton (ABLE-KS) using both Assistance and Resistance training modes together with auditory feedback to train peak knee flexion angle. During the training, the torque provided by the ABLE-KS and the biofeedback were systematically adapted based on the subject's performance and perceived exertion level. We carried out a comprehensive experimental analysis that evaluated a wide range of biomechanical metrics, together with usability and users' perception metrics. We found significant improvements in peak knee flexion (<inline-formula> <tex-math notation="LaTeX">{p} = {0}.{0016} </tex-math></inline-formula>), minimum knee angle during stance (<inline-formula> <tex-math notation="LaTeX">{p} = {0}.{0053} </tex-math></inline-formula>), paretic single support time (<inline-formula> <tex-math notation="LaTeX">{p} = {0}.{0087} </tex-math></inline-formula>) and gait endurance (<inline-formula> <tex-math notation="LaTeX">{p} = {0}.{022} </tex-math></inline-formula>) when walking without the exoskeleton after the two weeks of training. Participants significantly (<inline-formula> <tex-math notation="LaTeX">{p} < {0}.{00025} </tex-math></inline-formula>) improved the knee angle during the stance and swing phases when walking with the exoskeleton powered in the high Assistance mode in comparison to the No Exo and the Unpowered conditions. No clinically relevant differences were found between Assistance and Resistance training sessions. Participants improved their performance with the exoskeleton (24-55 %) for the peak knee flexion angle throughout the training sessions. Moreover, participants showed a high level of acceptability of the ABLE-KS (QUEST 2.0 score: 4.5 ± 0.3 out of 5). Our preliminary findings suggest that the proposed training approach can produce similar or larger improvements in post-stroke individuals than other studies with knee exoskeletons that used higher training intensities.
The time-sensitive network paradigm envisions the integration of operation technology and information technology in the same network. One of the requirements for building time-sensitive networks is ...sharing a global time along the network. This requirement is especially critical in wireless systems, where there are few robust methods to perform accurate time transfer. In this article, the problem of time transfer over realistic wireless channels is studied, and a time distribution scheme is proposed. The time distribution scheme has three components: Precision time protocol, a novel timestamping method (enhanced timestamps) and an algorithm to implement the enhanced timestamps. The performance of the proposed scheme has been evaluated in MATLAB using the IEEE 802.11n Standard under several standard wireless local area network channel models. The results show that the system can reach subnanosecond time transfer accuracy under non-line-of-sight and time-variant conditions, but its performance greatly depends on the signal-to-noise ratio and on the channel variation rate.
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