The vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) play crucial roles in vasculogenesis and angiogenesis. Angiogenesis is an important mechanism in many physiological and ...pathological processes, and is involved in endothelial cell proliferation, migration, and survival, then leads to further tubulogenesis, and finally promotes formation of vessels. This series of signaling cascade pathways are precisely mediated by VEGF/VEGFR-2 system. The VEGF binding to the IgD2 and IgD3 of VEGFR-2 induces the dimerization of the receptor, subsequently the activation and trans-autophosphorylation of the tyrosine kinase, and then the initiation of the intracellular signaling cascades. Finally the VEGF-activated VEGFR-2 stimulates and mediates variety of signaling transduction, biological responses, and pathological processes in angiogenesis. Several crucial phosphorylated sites Tyr801, Try951, Try1175, and Try1214 in the VEGFR-2 intracellular domains mediate several key signaling processes including PLCγ-PKC, TSAd-Src-PI3K-Akt, SHB-FAK-paxillin, SHB-PI3K-Akt, and NCK-p38-MAPKAPK2/3 pathways. Based on the molecular structure and signaling pathways of VEGFR-2, the strategy of the VEGFR-2-targeted therapy should be considered to employ in the treatment of the VEGF/VEGFR-2-associated diseases by blocking the VEGF/VEGFR-2 signaling pathway, inhibiting VEGF and VEGFR-2 gene expression, blocking the binding of VEGF and VEGFR-2, and preventing the proliferation, migration, and survival of vascular endothelial cells expressing VEGFR-2.
Two separate artificial sensors, an electronic eye (EE) and an electronic tongue (ET), were recently developed to monitor grape ripening based on the analysis of must. The aim of this research is to ...exploit the complementary information obtained by means of EE and ET sensing systems using different data fusion strategies, in order to develop an integrated device able to quickly and easily quantify the physico-chemical parameters that are used to assess phenolic ripeness. To this purpose, both low-level and mid-level data fusion approaches were investigated. Partial Least Squares (PLS) regression was applied to the fused data, with the aim of relating the information brought by the two sensors with twelve physico-chemical parameters measured on the must samples by standard analytical methods. The results achieved with mid-level data fusion outperformed those obtained using EE and ET separately, and highlighted that both the artificial sensors have made a significant contribution to the prediction of each one of the considered physico-chemical parameters.
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•Data fusion was used to improve the performance of a device to monitor grape ripening.•Data from an electronic tongue (ET) and an electronic eye (EE) were combined.•Low-level and mid-level data fusion were used to build PLS calibration models.•The use of data fusion allowed to increase significantly the prediction performances.•Mid-level data fusion of PLS latent variables gave generally the best results.
Vesical Imaging Reporting and Data System (VI-RADS) score is adopted to provide preoperative bladder cancer (BCa) staging. Repeated transurethral resection of bladder tumor (Re-TURBT) is recommended ...in most of high-risk non–muscle-invasive bladder cancers (HR-NMIBCs) due to possibility of persistent/understaged disease after initial TURBT. No diagnostic tools able to improve patient’s stratification for such recommendation exist.
To (1) prospectively validate VI-RADS for discriminating between NMIBC and muscle-invasive bladder cancer (MIBC) at TURBT, and (2) evaluate the accuracy of VI-RADS for identifying HR-NMIBC patients who could avoid Re-TURBT and detecting those at higher risk for understaging after TURBT.
Patients with BCa suspicion were offered multiparametric magnetic resonance imaging (mpMRI) before TURBT. According to VI-RADS, a cutoff of ≥3 to define MIBC was assumed. TURBT reports were compared with preoperative VI-RADS scores to assess accuracy of mpMRI for discriminating between NMIBC and MIBC. HR-NMIBC Re-TURBT reports were compared with preoperatively recorded VI-RADS scores to assess mpMRI accuracy in predicting Re-TURBT outcomes.
Multiparametric MRI of the bladder before TURBT.
Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated for mpMRI performance in patients undergoing TURBT and for HR-NMIBC patients candidate for Re-TURBT. Performance of mpMRI was assessed by receiver operating characteristic curve analysis. Ƙ statistics was used to estimate inter- and intrareader variability.
A total of 231 patients were enrolled. Multiparametric MRI showed sensitivity, specificity, PPV, and NPV for discriminating NMIBC from MIBC at initial TURBT of 91.9% (95% confidence interval CI: 82.2–97.3), 91.1% (95% CI: 85.8–94.9), 77.5% (95% CI: 65.8–86.7), and 97.1% (95% CI: 93.3–99.1), respectively. The area under the curve (AUC) was 0.94 (95% CI: 0.91–0.97). Among HR-NMIBC patients (n=114), mpMRI before TURBT showed sensitivity, specificity, PPV, and NPV of 85% (95% CI: 62.1–96.8), 93.6% (95% CI: 86.6–97.6), 74.5% (95% CI: 52.4–90.1), and 96.6% (95% CI: 90.5–99.3) respectively, to identify patients with MIBC at Re-TURBT. The AUC was 0.93 (95% CI: 0.87–0.97).
VI-RADS is accurate for discriminating between NMIBC and MIBC. Within HR-NMIBC cases, VI-RADS could, in future, improve the selection of patients who are candidate for Re-TURBT.
We investigated the accuracy of Vesical Imaging Reporting and Data System (VI-RADS) score to asses bladder cancer staging before transurethral resection of bladder tumors, and we explored the performance of VI-RADS score as a future preoperative predictive tool for the selection of high-risk non–muscle-invasive bladder cancer patients who are candidate for undergoing early repeated transurethral resection of the primary tumor site.
Vesical Imaging Reporting and Data System (VI-RADS) score is a novel imaging tool able to differentiate superficial from muscle-invasive bladder cancer before transurethral resection of bladder tumor (TURBT). Within the category of high-risk non–muscle-invasive bladder cancers, VI-RADS could differentiate those not needing repeated TURBT (Re-TURBT) from those who should definitely not miss Re-TURBT.
No clear consensus on the need to perform an intracorporeal anastomosis (IA) after laparoscopic right colectomy is currently available. One of the potential benefits of intracorporeal anastomosis may ...be a reduction in surgical stress. Herein, we evaluated the surgical stress response and the metabolic response in patients who underwent right colonic resection for colon cancer. Fifty-nine patients who underwent laparoscopic resection for right colon cancer were randomized to receive an intracorporeal or an extracorporeal anastomosis (EA). Data including demographics (age, sex, BMI and ASA score), pathological (AJCC tumour stage and tumour localization) and surgical results were recorded. Moreover, to determine the levels of the inflammatory response, mediators, such as C-reactive protein (CRP), tumour necrosis factor (TNF), interleukin 1β (IL-1β), IL-6, IL-10, and IL-13, were evaluated. Similarly, cortisol and insulin levels were evaluated as hormonal responses to surgical stress. We found that the proinflammatory mediator IL-6, CRP, TNF and IL-1β levels, were significantly reduced in IA compared to EA. Concurrently, an improved profile of the anti-inflammatory cytokines IL-10 and IL-13 was observed in the IA group. Relative to the hormone response to surgical stress, cortisol was increased in patients who underwent EA, while insulin was reduced in the EA group. Based on these results, surgical stress and metabolic response to IA justify advocating the adoption of a totally laparoscopic approach when performing a right colectomy for cancer.This trial is registered on ClinicalTrials.gov (ID: NCT03422588).
Off-clamp partial nephrectomy represents one of the latest developments in nephron-sparing surgery, with the goal of preserving renal function and reducing ischemia time. The aim of this study was to ...evaluate and compare the functional, oncologic, and perioperative outcomes between off-clamp robot-assisted partial nephrectomy (off-C RAPN) and off-clamp open partial nephrectomy (off-C OPN) through a propensity score-matched (PSM) analysis. A 1:1 PSM analysis was used to balance variables potentially affecting postoperative outcomes. To report surgical quality, 1 year trifecta was used. Univariable Cox regression analysis was performed to identify predictors of trifecta achievement. The Kaplan-Meier method was used to compare cancer-specific survival (CSS), overall survival (OS), disease-free survival (DFS), and metastasis-free survival (MFS) probabilities between groups. Overall, 542 patients were included. After PSM analysis, two homogeneous cohorts of 147 patients were obtained. The off-C RAPN cohort experienced shorter length of stay (LoS) (3.4 days vs. 5.4 days;
< 0.001), increased likelihoods of achieving 1 year trifecta (89.8% vs. 80.3%;
= 0.03), lower postoperative Clavien-Dindo ≤ 2 complications (1.3% vs. 18.3%,
< 0.001), and lower postoperative transfusion rates (3.4% vs. 12.2%,
= 0.008). At univariable analysis, the surgical approach (off-C RAPN vs. off-C OPN, OR 2.22, 95% CI 1.09-4.46,
= 0.02) was the only predictor of 1 year trifecta achievement. At Kaplan-Meier analysis, no differences were observed between the two groups in terms of OS (log-rank
= 0.451), CSS (log-rank
= 0.476), DFS (log-rank
= 0.678), and MFS (log-rank
= 0.226). Comparing RAPN and OPN in a purely off-clamp scenario, the minimally invasive approach proved to be a feasible and safe surgical approach, with a significantly lower LoS and minor rate of postoperative complications and transfusions as a result of improved surgical quality expressed by higher 1 year trifecta achievement.
•It is necessary to limit contaminants such as phthalates esters (PAEs)•The behaviour of PAEs during distillation was investigated using a lab still.•DBP and DEHP were carried over into the ...distillate, DINP accumulated in the stillage.•Rectification of the secondes is effective to considerably reduce PAEs concentration.
Due to health concerns and legal matters, an investigation to limit phthalates esters (PEAs) in spirits is necessary. A lab still was used to perform pilot distillations according to the official method for brandy production in order to explore the repartition into the distilled fractions of each PAE. The process was divided in two steps: a première chauffe and a bonne chauffe. The former step included the cut into heads, heart and tails, while the latter into heads, brandy, secondes, and tails. The behaviour of each PAE during distillation was affected by its own chemical nature. Dibutyl phthalate (DBP) was entirely carried over into the distillate, while bis(2-ethylhexyl) phthalate (DEHP) only partially, and diisononyl phthalate (DINP) accumulated in the stillage. During the bonne chauffe, DBP and DEHP accumulated in the secondes more than in the brandy. A rectification step of the secondes was demonstrated to considerably reduce PAEs concentration.
Precision agriculture has emerged as a promising approach to improve crop productivity and reduce the environmental impact. However, effective decision making in precision agriculture relies on ...accurate and timely data acquisition, management, and analysis. The collection of multisource and heterogeneous data for soil characteristics estimation is a critical component of precision agriculture, as it provides insights into key factors, such as soil nutrient levels, moisture content, and texture. To address these challenges, this work proposes a software platform that facilitates the collection, visualization, management, and analysis of soil data. The platform is designed to handle data from various sources, including proximity, airborne, and spaceborne data, to enable precision agriculture. The proposed software allows for the integration of new data, including data that can be collected directly on-board the acquisition device, and it also allows for the incorporation of custom predictive systems for soil digital mapping. The usability experiments conducted on the proposed software platform demonstrate that it is easy to use and effective. Overall, this work highlights the importance of decision support systems in the field of precision agriculture and the potential benefits of using such systems for soil data management and analysis.
Schizophrenia is a severe psychiatric illness affecting almost 25 million people worldwide and is conceptualized as a disorder of synaptic plasticity and brain connectivity. Antipsychotics are the ...primary pharmacological treatment after more than sixty years after their introduction in therapy. Two findings hold true for all presently available antipsychotics. First, all antipsychotics occupy the dopamine D2 receptor (D2R) as an antagonist or partial agonist, even if with different affinity; second, D2R occupancy is the necessary and probably the sufficient mechanism for antipsychotic effect despite the complexity of antipsychotics' receptor profile. D2R occupancy is followed by coincident or divergent intracellular mechanisms, implying the contribution of cAMP regulation, β-arrestin recruitment, and phospholipase A activation, to quote some of the mechanisms considered canonical. However, in recent years, novel mechanisms related to dopamine function beyond or together with D2R occupancy have emerged. Among these potentially non-canonical mechanisms, the role of Na
channels at the dopamine at the presynaptic site, dopamine transporter (DAT) involvement as the main regulator of dopamine concentration at synaptic clefts, and the putative role of antipsychotics as chaperones for intracellular D2R sequestration, should be included. These mechanisms expand the fundamental role of dopamine in schizophrenia therapy and may have relevance to considering putatively new strategies for treatment-resistant schizophrenia (TRS), an extremely severe condition epidemiologically relevant and affecting almost 30% of schizophrenia patients. Here, we performed a critical evaluation of the role of antipsychotics in synaptic plasticity, focusing on their canonical and non-canonical mechanisms of action relevant to the treatment of schizophrenia and their subsequent implication for the pathophysiology and potential therapy of TRS.
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