The survey of Italian springs by the National Hydrographic Service, a forgotten database. Structuring and analysis of a dataset of Campania springs (southern Italy)|Il censimento delle sorgenti italiane del Servizio Idrografico, un database dimenticatoStrutturazione e analisi del dataset delle sorgenti della Campania (Italia meridionale)

The analysis of groundwater resources is a particularly significant aspect of the economic, social and environmental development of the national territory. This is particularly relevant for the Campania region which, although characterized by the most significant aquifer systems of southern Italy, suffers from critical issues related to the progressive increase in demand and climatic variability at different time scales. In this framework, the lack of data concerning the survey of springs, including the minor ones, and of historical discharge easurements represents the main limitation to a more comprehensive regional hydrogeological characterization. The only source of historical data regarding the systematic and comprehensive survey of springs and discharge measurement is the Publication No. 14 of the National Hydrographic Service of the Ministry of Public Works “The Italian springs. List and description” reporting measures made between the 1920s and 1940s which was published in distinct volumes for each compartment. Despite its potential relevance, this source has so far been little used in regional hydrogeological studies. In this paper, a comparative analysis among data of springs derived from the Publication No. 14 and from measurement campaigns made by the Cassa per il Mezzogiorno (Special Project 26), between the 1960s and 1980s for main springs, was carried out for the Campania region. The information available from each source was validated through a cross-check, by means of a comparison of coordinates and a statistical analysis of the characterizing parameters. The new dataset allowed to expand the hydrogeological regional characterization with a higher number of springs, including the minor ones. The results obtained recognize the Publication No. 14 of the National Hydrographic Service as an important source of data to not be overlooked, especially in a condition of historical data shortage, by which can be both carried out regional hydrogeological and temporal analyses as well as identified integrative groundwater resources

Timely Supplementation of Hydrogels Containing Sulfated or Unsulfated Chondroitin and Hyaluronic Acid Affects Mesenchymal Stromal Cells Commitment Toward Chondrogenic Differentiation

Mesenchymal stromal cells (MSCs) are currently used for cartilage cell therapy because of their well proven capacity to differentiate in chondrocytes. The advantage of MSC-based therapy is the possibility of producing a high number of chondrocytes for implants. The transplant procedure, however, has some limitations, since MSCs may produce non-functional chondrocytes. This limit has been challenged by cultivating MSC in media with hydrogels containing hyaluronic acid (HA), extractive chondroitin sulfate (CS), or bio-fermentative unsulphated chondroitin (BC) alone or in combination. Nevertheless, a clear study of the effect of glycosaminoglycans (GAGs) on chondrocyte differentiation is still lacking, especially for the newly obtained unsulfated chondroitin of biotechnological origin. Are these GAGs playing a role in the commitment of stem cells to chondrocyte progenitors and in the differentiation of progenitors to mature chondrocytes? Alternatively, do they have a role only in one of these biological processes? We evaluated the role of HA, CS, and – above all – BC in cell commitment and chondrocyte differentiation of MSCs by supplementing these GAGs in different phases of in vitro cultivation. Our data provided evidence that a combination of HA and CS or of HA and BC supplemented during the terminal in vitro differentiation and not during cell commitment of MSCs improved chondrocytes differentiation without the presence of fibrosis (reduced expression of Type I collagen). This result suggests that a careful evaluation of extracellular cues for chondrocyte differentiation is fundamental to obtaining a proper maturation process

Deep learning to segment liver metastases on CT images: Impact on a radiomics method to predict response to chemotherapy

Predicting response to neo-adjuvant chemotherapy of liver metastases (mts) using CT images is of key importance to provide personalized treatments. However, manual segmentation of mts should be avoid to develop methods that could be integrated into the clinical practice. The aim of this study is to evaluate if and how much automatic segmentation can affect a radiomics-based method to predict response to neoadjuvant chemotherapy of individual liver mts. To this scope, we developed an automatic deep learning method to segment liver mts, based on the U-net architecture, and we compared the classification results of a classifier fed with manual and automatic masks. In the validation set composed of 39 liver mts, the automatic deeplearning algorithm was able to detect 82% of mts, with a median precision of 67%. Using manual and automatic masks, we obtained the same classification in 19/32 mts. In case of mts with largest diameter > 20 mm, the precision of the segmentation does not impact the classification results and we obtained the same classification with both masks. Conversely, with smaller mts, we showed that a Dice coefficient of at least 0.5 should be obtained to extract the same information from the two segmentations. This are very important results in the perspective of using radiomics-based approach to predict response to therapy into clinical practice. Indeed, either precisely manually segment all lesions or refine them after automatic segmentation is a time-consuming task that cannot be performed on a daily basis

Unsulfated biotechnological chondroitin by itself as well as in combination with high molecular weight hyaluronan improves the inflammation profile in osteoarthritis in vitro model

Several studies suggest that inflammation has a pivotal role during the progression of osteoarthritis (OA) and cytokines have been identified as the main process mediators. This study aimed to explore the ability to modulate the main OA pro-inflammatory biomarkers of novel gels (H-HA/BC) based on high molecular weight hyaluronan (H-HA) and unsulfated biotechnological chondroitin (BC). For the first time, BC was tested also in combination with H-HA on human primary cells isolated from pathological knee joints. Specifically, the experiments were performed using an OA in vitro model based on human chondrocytes and synoviocytes. To evaluate the anti-inflammatory effects of H-HA/BC in comparison with H-HA and BC single gels, NF-kB, COMP-2, MyD88, MMP-13 and a wide range of cytokines, known to be specific biomarkers in OA (e.g., IL-6, IL-8, and TNF-α), were evaluated. In addition, cell morphology and proliferation occurring in the presence of either H-HA/BC or single components were assessed using time-lapse video microscopy. It was shown that synovial fluids and cells isolated from OA suffering patients, presented a cytokine pattern respondent to an ongoing inflammation status. H-HA and BC significantly reduced the levels of 23 biomarkers associated with cartilage damage. However, H-HA/BC decreased significantly 24 biological mediators and downregulated 19 of them more efficiently than the single components. In synoviocytes cultures, cytokine analyses proved that H-HA/BC gels re-established an extracellular environment more similar to a healthy condition reducing considerably the concentration of 11 analytes. Instead, H-HA and BC significantly modulated 7 (5 only with a longer treatment) and 8 biological cytokines, respectively. Our results suggest that H-HA/BC beyond the viscosupplementation effect typical for HA-based gels, can improve the inflammation status in joints and thus could be introduced as a valid protective and anti-inflammatory intraarticular device in the field of Class III medical devices for OA treatments

PEGylated Liposomes Loaded with Carbamate Inhibitor ANP0903 Trigger Apoptosis by Enhancing ER Stress in HepG2 Cancer Cells

Liver cancer is one of the most common causes of cancer death worldwide. In recent years, substantial progress has been made in the development of systemic therapies, but there is still the need for new drugs and technologies that can increase the survival and quality of life of patients. The present investigation reports the development of a liposomal formulation of a carbamate molecule, reported as ANP0903, previously tested as an inhibitor of HIV-1 protease and now evaluated for its ability to induce cytotoxicity in hepatocellular carcinoma cell lines. PEGylated liposomes were prepared and characterized. Small, oligolamellar vesicles were produced, as demonstrated by light scattering results and TEM images. The physical stability of the vesicles in biological fluids was demonstrated in vitro, alongside the stability during storage. An enhanced cellular uptake was verified in HepG2 cells treated with liposomal ANP0903, resulting in a greater cytotoxicity. Several biological assays were performed to elucidate the molecular mechanisms explaining the proapoptotic effect of ANP0903. Our results allow us to hypothesize that the cytotoxic action in tumor cells is probably due to the inhibition of the proteasome, resulting in an increase in the amount of ubiquitinated proteins within the cells, which in turn triggers activation of autophagy and apoptosis processes, resulting in cell death. The proposed liposomal formulation represents a promising approach to deliver a novel antitumor agent to cancer cells and enhance its activity

Deuterium retention and erosion in liquid Sn samples exposed to D2 and Ar plasmas in GyM device

The use of tin (Sn) as a liquid metal for plasma facing components has been recently proposed as a solution to the high heat load issue on the divertor target plates in nuclear fusion reactors. Due to its low vapor pressure, low reactivity with hydrogen and good resilience to neutron impact, tin is a good candidate as plasma facing component. However its high atomic number poses concerns about plasma contamination.In this paper two fundamental aspects have been investigated: deuterium retention and erosion fluxes from the Sn surface towards the plasma. The samples were exposed to plasma inside the linear machine GyM in magnetic cusp configuration. This setup permits to expose free liquid specimens without the need for the Capillary Porous System. Moreover it permits to lower the magnetic field in order to increase Sn Larmor radius and consequently limit Sn re-deposition in erosion experiments.Ex-situ analyses by ion beam diagnostics on solid samples exposed to deuterium plasma have proved that the amount of retained atomic deuterium is very low, approximately 0.18 at% estimated by Nuclear Reaction Analysis and 0.25 at% estimated by Elastic Recoil Detection Analysis.In the framework of erosion studies, the spectroscopic parameter S/XB was evaluated in Ar plasma for the SnI line at 380.1 nm by Optical Emission Spectroscopy and mass loss measurements in the 5–11 eV Te range, at a density ne ∼ 1.5 × 1011 cm−3. An average value of 150 ± 23 was obtained. Keywords: Liquid metals, Deuterium retention, Erosion, Double-cusp magnetic configuration, Ion beam diagnostics, S/XB spectroscopic paramete

Radiomics predicts response of individual HER2-amplified colorectal cancer liver metastases in patients treated with HER2-targeted therapy

The aim of our study was to develop and validate a machine learning algorithm to predict response of individual HER2-amplified colorectal cancer liver metastases (lmCRC) undergoing dual HER2-targeted therapy. Twenty-four radiomics features were extracted after 3D manual segmentation of 141 lmCRC on pretreatment portal CT scans of a cohort including 38 HER2-amplified patients; feature selection was then performed using genetic algorithms. lmCRC were classified as nonresponders (R−), if their largest diameter increased more than 10% at a CT scan performed after 3 months of treatment, responders (R+) otherwise. Sensitivity, specificity, negative (NPV) and positive (PPV) predictive values in correctly classifying individual lesion and overall patient response were assessed on a training dataset and then validated on a second dataset using a Gaussian naïve Bayesian classifier. Per-lesion sensitivity, specificity, NPV and PPV were 89%, 85%, 93%, 78% and 90%, 42%, 73%, 71% respectively in the testing and validation datasets. Per-patient sensitivity and specificity were 92% and 86%. Heterogeneous response was observed in 9 of 38 patients (24%). Five of nine patients were carriers of nonresponder lesions correctly classified as such by our radiomics signature, including four of seven harboring only one nonresponder lesion. The developed method has been proven effective in predicting behavior of individual metastases to targeted treatment in a cohort of HER2 amplified patients. The model accurately detects responder lesions and identifies nonresponder lesions in patients with heterogeneous response, potentially paving the way to multimodal treatment in selected patients. Further validation will be needed to confirm our findings