Cyclophosphamide, Fluorouracil and subcutaneous Interleukin-2 in the treatment of advanced GIST: A Case Report

A male 68 years hold patient was admitted to surgical ward for hemorrhagic shock. After CT scan detection of 6x5 cm neoformation of first jejunal loop, he was submitted to segmental resection and pathological diagnosis was gastrointestinal stromal tumor. The patient was defined as high-risk according to Takahashi criteria, but refused Imatinib adjuvant therapy. After 15 months of disease-free interval, he developed bilobar liver metastases. After treatment with Imatinib 400 mg he reported G3 hepatotoxicity resolved with temporary suspension, he continue low dose with stable disease. After liver progression, he resumed Imatinib full dose with disease stabilization for 9 months. After liver progression, second line Sunitinib 37,5 mg/day was started for four months with stable disease. After further liver and lymph node mediastinal progression he was treated for four months with Regorafenib with disease stabilization. Patient developed slow but inexorable progression of liver disease with severe abdominal pain resistant to opioid and was treated with authorized compassionate program comprising Cyclophosphamide 300 mg/sqm and Fluorouracil 500 mg/sqm on day 1 intravenously followed by Interleukin-2 4.5 MUI subcutaneously on days 3–6 and 17–20 every four weeks. After three cycles the patients obtained a relevant subjective improvement with partial response on mediastinal lymph node and liver stabilization. A substantial increase on neutrophil, lymphocytes, monocytes, platelets, T regulator cells count, and a decrease on platelets/lymphocytes, CD8/T regulator cells ratio, CD8, NK count and C-reactive protein value were observed after treatment compared to basal value. The toxicity was mild represented by fever G1, flue-like-syndrome G1 during the treatment. After four cycle of chemo-immunotherapy, the patient demonstrated progression of disease and died five months after treatment. Noteworthy is the temporal disease control with significant symptomatic improvement achieved for the first time with this chemo-immunotherapeutic combination in a patient with very advanced pretreated GIST

Fly fishing no-kill zones: a possible way to conjugate conservation issues, sustainable sport enhancement and local development in Alpine areas?

The promotion of sustainable tourism and outdoor sports can represent an important way to couple environmental conservation strategies and economic enhancement in marginal and Alpine areas. In this context catch and release fly fishing zones can represent an interesting tool, although no data is available on the effectiveness of these practices on Alpine salmonid population dynamics. Salmonids are the main group of fish in alpine rivers and they are the only actively targeted by anglers. Aim of this work is filling this gap, with a pilot study on two no-kill zones (Po and Pellice rivers, NW Italy). We conducted a temporal and spatial comparison between free-fishing and catch and release management river sections, with a detailed analysis on the Po River site. Our results support the hypothesis that catch and release management allows a numerical increase in wild trout populations. In particular, we detected a massive and rapid increase in younger individuals, possibly linked to a stop on the removal of large-sized reproducers. Protecting trout by the implementation of this practice can at the same time allow the increase of sustainable economic development and sport in marginal areas

Heuristic Algorithm for the Analysis of Fast Field Cycling (FFC) NMR Dispersion Curves

Evaluation of nuclear magnetic relaxation dispersion (NMRD) curves obtained by the fast field cycling nuclear magnetic resonance (FFC-NMR) relaxometry technique is a valuable tool for analyzing the microscopic dynamics of condensed matter systems. However, quantitative data analysis involves several conceptual and practical issues. Moving forward from previous literature approaches, we propose a new analysis method, relying on the elaboration of the inverse integral transform of the NMRD curve. Our approach results in a true heuristic method, able to unambiguously individuate the dynamic domains in the system, thereby avoiding the possible introduction of any element of discretion. The analysis of some data sets relevant to real samples suggests the possibility that the results obtained with the heuristic method may be actually led back to some distinct physical/chemical features of the systems

Transferability Of Mesohabitat Suitability Criteria In Northern Italy

In the framework of water resources planning and management, the MesoHABSIM (MesoHABitat SImulation Model) approach demonstrated high potential to assess suitable environmental conditions for freshwater fish species. In the present study, the transferability capabilities of mesohabitat suitability criteria were evaluated in nine streams across Northern Italy. In particular, the Random Forest (RF) technique was used to calibrate and validate suitability criteria for adult and juvenile life stages of brown trout (Salmo trutta), marble trout (Salmo marmoratus), bullhead (Cottus gobio) Italian barbel (Barbus plebejus), and Italian vairone (Telestes muticellus). Presence/absence binary models were calibrated at the mesohabitat scale (i.e., the geomorphic unit scale) using field data collected in reference sites, selected for their natural hydro-morphological conditions and habitat characteristics. Model transferability tests were performed in streams located in different regions within the distribution area of the fish and not included in the model calibration dataset. Predictive capacities of the models were very good in terms of accuracy (ranging from 75% to 82%) and true skill statistic (ranging from 52% to 75%). The high predictive performances can be related to (i) the use of an ecologically relevant spatial resolution (mesohabitat) to predict fish presence, (ii) a robust and adequate hydro-morphological characterization of the analyzed geomorphic units, and (iii) the large number of mesohabitat descriptors provided by the MesoHABSIM approach. Results showed that mesohabitat suitability criteria based on RF can be considered transferable among streams located in different regions of Northern Italy, especially when river channels are characterized by similar hydro-morphological characteristics

1H-NMR Spectroscopy Coupled with Chemometrics to Classify Wines According to Different Grape Varieties and Different Terroirs

In this study, 1H-NMR spectroscopy coupled with chemometrics was applied to study the wine metabolome and to classify wines according to different grape varieties and different terroirs. By obtaining the metabolomic fingerprinting and profiling of the wines, it was possible to assess the metabolic biomarkers leading the classification (i.e., phenolic compounds, aroma compounds, amino acids, and organic acids). Moreover, information about the influence of the soil in shaping wine metabolome was obtained. For instance, the relationship between the soil texture and the content of amino acids and organic acids in wines was highlighted. The analysis conducted in this study allowed extraction of relevant spectral information not only from the most populated and concentrated spectral areas (e.g., aliphatic and carbinolic areas), but also from crowded spectral areas held by lowly concentrated compounds (i.e., polyphenols). This may be due to a successful combination between the parameters used for data reduction, preprocessing and elaboration. The metabolomic fingerprinting also allowed exploration of the H-bonds network inside the wines, which affects both gustatory and olfactory perceptions, by modulating the way how solutes interact with the human sensory receptors. These findings may have important implications in the context of food traceability and quality control, providing information about the chemical composition and biomolecular markers from a holistic point of view

Vegan and sugar-substituted chocolates: assessing physicochemical characteristics by NMR relaxometry, rheology, and DSC

The main physicochemical characteristics of novel artisanal chocolates (both dark and milky) intended for vegan consumers or for those requiring assumption of fewer simple sugars, were analysed. Replacement of milk (with coconut copra, almonds, and soy protein isolates), and sucrose (with coconut sugars, stevia and erythritol, respectively) in dark chocolate, were accounted for by means of texture analysis, rheology, water activity, fatty acid composition, differential scanning calorimetry (DSC) and fast field cycling (FFC) nuclear magnetic resonance (NMR) relaxometry. The vegan sample (i.e., the milk-less one) showed lower values of hardness and adhesiveness as well as a larger peak in the melting behavior at the calorimetric evaluation (DSC). Moreover, the absence of milk resulted in the halving of the yield stress and a decrease in both the apparent and Casson's viscosity. In the sample of chocolate with less sucrose, the peak temperatures measured at the DSC indicate crystallization of cocoa butter in its best form (V beta 2), unlike in dark chocolate, due to the different sugar composition. Similarly, the Casson yield stress (tau 0), increased significantly (almost 70%), with the substitution of sugar. Finally, the results of NMR FFC relaxometry made it possible to identify aggregates of different sizes, laying the basis for its use as a rapid, non-destructive method for chocolate analysis

Robust Algorithms for the Analysis of Fast-Field-Cycling Nuclear Magnetic Resonance Dispersion Curves

Fast-Field-Cycling (FFC) Nuclear Magnetic Resonance (NMR) relaxometry is a powerful, non-destructive magnetic resonance technique that enables, among other things, the investigation of slow molecular dynamics at low magnetic field intensities. FFC-NMR relaxometry measurements provide insight into molecular motion across various timescales within a single experiment. This study focuses on a model-free approach, representing the NMRD profile R1 as a linear combination of Lorentzian functions, thereby addressing the challenges of fitting data within an ill-conditioned linear least-squares framework. Tackling this problem, we present a comprehensive review and experimental validation of three regularization approaches to implement the model-free approach to analyzing NMRD profiles. These include (1) MF-UPen, utilizing locally adapted L2 regularization; (2) MF-L1, based on L1 penalties; and (3) a hybrid approach combining locally adapted L2 and global L1 penalties. Each method’s regularization parameters are determined automatically according to the Balancing and Uniform Penalty principles. Our contributions include the implementation and experimental validation of the MF-UPen and MF-MUPen algorithms, and the development of a “dispersion analysis” technique to assess the existence range of the estimated parameters. The objective of this work is to delineate the variance in fit quality and correlation time distribution yielded by each algorithm, thus broadening the set of software tools for the analysis of sample structures in FFC-NMR studies. The findings underline the efficacy and applicability of these algorithms in the analysis of NMRD profiles from samples representing different potential scenarios

Composite RGO/Ag/Nanosponge Materials for the Photodegradation of Emerging Pollutants from Wastewaters

Some composite materials have been prepared, constituted by a cyclodextrin-bis-urethane-based nanosponge matrix in which a reduced graphene oxide/silver nanoparticles photocatalyst has been dispersed. Different chain extenders were employed for designing the nanosponge supports, in such a way as to decorate their hyper-cross-linked structure with diverse functionalities. Moreover, two different strategies were explored to accomplish the silver loading. The obtained systems were successfully tested as catalysts for the photodegradation of emerging pollutants such as model dyes and drugs. Enhancement of the photoactive species performance (up to nine times), due to the synergistic local concentration effect exerted by the nanosponge, could be assessed. Overall, the best performances were shown by polyamine-decorated materials, which were able to promote the degradation of some particularly resistant drugs. Some methodological issues pertaining to data collection are also addressed

Low-Cost and High-Performance Solution for Positioning and Monitoring of Large Structures

Systems for accurate attitude and position monitoring of large structures, such as bridges, tunnels, and offshore platforms are changing in recent years thanks to the exploitation of sensors based on Micro-ElectroMechanical Systems (MEMS) as an Inertial Measurement Unit (IMU). Currently adopted solutions are, in fact, mainly based on fiber optic sensors (characterized by high performance in attitude estimation to the detriment of relevant costs large volumes and heavy weights) and integrated with a Global Position System (GPS) capable of providing low-frequency or single-update information about the position. To provide a cost-effective alternative and overcome the limitations in terms of dimensions and position update frequency, a suitable solution and a corresponding prototype, exhibiting performance very close to those of the traditional solutions, are presented and described hereinafter. The solution leverages a real-time Kalman filter that, along with the proper features of the MEMS inertial sensor and Real-Time Kinematic (RTK) GPS, allows achieving performance in terms of attitude and position estimates suitable for this kind of application. The results obtained in a number of tests underline the promising reliability and effectiveness of the solution in estimating the attitude and position of large structures. In particular, several tests carried out in the laboratory highlighted high system stability; standard deviations of attitude estimates as low as 0.04 degrees were, in fact, experienced in tests conducted in static conditions. Moreover, the prototype performance was also compared with a fiber optic sensor in tests emulating actual operating conditions; differences in the order of a few hundredths of a degree were found in the attitude measurements