Calibration of the INCA model in a Mediterranean forested catchment: the effect of hydrological inter-annual variability in an intermittent stream

International audienceMediterranean regions are characterised by a stream hydrology with a marked seasonal pattern and high inter-annual variability. Accordingly, soil N processes and leaching of solutes in Mediterranean regions also show a marked seasonality, occurring in pulses as soils re-wet following rain. The Integrated Nitrogen Catchment model (INCA) was applied to Fuirosos, a Mediterranean catchment located in NE Spain using hydrological data and streamwater nitrate and ammonium concentrations collected from 1999 to 2002. This study tested the model under Mediterranean climate conditions and assessed the effect of the high inter-annual variability on the ability of INCA to simulate discharge and N fluxes. The model was calibrated for the whole three-year period and the n coefficients of determinion (r2) between simulated and observed data were 0.54 and 0.1 for discharge and nitrate temporal dynamics, respectively. Ammonium dynamics were simulated poorly and the linear regression between observed and simulated data was not significant statistically. To assess the effect of inter-annual variability on INCA simulations, the calibration process was run separately for two contrasting hydrological years: a dry year with a total rainfall of 525 mm and a wet year with a total of 871 mm. The coefficients of determination for the correlation between observed and simulated discharge for these two periods were 0.67 (p2 = 0.13 p2 = 0.56 p Keywords: environmental modelling, intermittent stream, Mediterranean climate, Fuirosos, hydrology, nitrat

Co-design, co-learning, and co-production of an app for pancreatic cancer patients—the “Pancreas Plus” study protocol

Background: Pancreatic cancer is a malignant and complex tumor that often leads to an adverse prognosis. Patients need to face a challenging treatment path, which involves highly-specialized multidisciplinary professionals. The complexity of the disease requires the development of dedicated tools to support patients in their care journey. Co-production stands as a valuable strategy in oncological care to engage patients in understanding their care journey and behaving accordingly to get the best possible clinical outcome. Methods: The non-profit association Unipancreas, active in promoting the latest advances in pancreatic cancer care and in supporting pancreatic cancer patients, has partnered with a multidisciplinary group of professionals to conceive the brand new program “Pancreas Plus” to employ a co-design, co-learning, and co-production path to design an app devoted to pancreatic cancer patients to assist them during their treatment and follow-up journey. The app, which is the outcome of a multi-stakeholder engagement project, offers health information and medical advice specifically tailored on the pancreatic cancer disease. The article reports the research protocol, which may be replicated for the design of other e-health tools focusing on different conditions. Discussion: The study’s output will be an app that sees the pancreatic cancer patient as the main beneficiary but which can gather and address the interests and needs of all meaningful stakeholders, including clinicians, researchers, healthcare and educational institutions, and

Pinus mugo essential oil impairs STAT3 activation through oxidative stress and induces apoptosis in prostate cancer cells

Essential oils (EOs) and their components have been reported to possess anticancer properties and to increase the sensitivity of cancer cells to chemotherapy. The aim of this work was to select EOs able to downregulate STAT3 signaling using Western blot and RT-PCR analyses. The molecular mechanism of anti-STAT3 activity was evaluated through spectrophotometric and fluorometric analyses, and the biological effect of STAT3 inhibition was analyzed by flow cytometry and wound healing assay. Herein, Pinus mugo EO (PMEO) is identified as an inhibitor of constitutive STAT3 phosphorylation in human prostate cancer cells, DU145. The down-modulation of the STAT3 signaling cascade decreased the expression of anti-proliferative as well as anti-apoptotic genes and proteins, leading to the inhibition of cell migration and apoptotic cell death. PMEO treatment induced a rapid drop in glutathione (GSH) levels and an increase in reactive oxygen species (ROS) concentration, resulting in mild oxidative stress. Pretreatment of cells with N-acetyl-cysteine (NAC), a cell-permeable ROS scavenger, reverted the inhibitory action of PMEO on STAT3 phosphorylation. Moreover, combination therapy revealed that PMEO treatment displayed synergism with cisplatin in inducing the cytotoxic effect. Overall, our data highlight the importance of STAT3 signaling in PMEO cytotoxic activity, as well as the possibility of developing adjuvant therapy or sensitizing cancer cells to conventional chemotherapy

Correction: Surgeons’ perspectives on artificial intelligence to support clinical decision-making in trauma and emergency contexts: results from an international survey

Correction: Surgeons' perspectives on artificial intelligence to support clinical decision-making in trauma and emergency contexts: results from an international surve

S-Glutathionylation at Cys328 and Cys542 Impairs STAT3 Phosphorylation.

STAT3 is a latent transcription factor that promotes cell survival and proliferation and is often constitutively active in cancers. Although many reports provide evidence that STAT3 is a direct target of oxidative stress, its redox regulation is poorly understood. Under oxidative conditions STAT3 activity can be modulated by S-glutathionylation, a reversible redox modification of cysteine residues. This suggests the possible cross-talk between phosphorylation and glutathionylation and points out that STAT3 is susceptible to redox regulation. Recently, we reported that decreasing the GSH content in different cell lines induces inhibition of STAT3 activity through the reversible oxidation of thiol groups. In the present work, we demonstrate that GSH/diamide treatment induces S-glutathionylation of STAT3 in the recombinant purified form. This effect was completely reversed by treatment with the reducing agent dithiothreitol, indicating that S-glutathionylation of STAT3 was related to formation of protein-mixed disulfides. Moreover, addition of the bulky negatively charged GSH moiety impairs JAK2-mediated STAT3 phosphorylation, very likely interfering with tyrosine accessibility and thus affecting protein structure and function. Mass mapping analysis identifies two glutathionylated cysteine residues, Cys328 and Cys542, within the DNA-binding domain and the linker domain, respectively. Site direct mutagenesis and in vitro kinase assay confirm the importance of both cysteine residues in the complex redox regulatory mechanism of STAT3. Cells expressing mutant were resistant in this regard. The data presented herein confirmed the occurrence of a redox-dependent regulation of STAT3, identified the more redox-sensitive cysteines within STAT3 structure, and may have important implications for development of new drugs

Assessing the distribution of exotic egg parasitoids of Halyomorpha halys in Europe with a large-scale monitoring program

The brown marmorated stink bug Halyomorpha halys is an invasive agricultural pest with a worldwide distribution. Classical biological control has been identified as the most promising method to reduce the populations of H. halys. Adventive populations of two candidates for releases, Trissolcus japonicus and Trissolcus mitsukurii, have recently been detected in Europe. To assess their distribution and abundance, a large-scale survey was performed. From May to September 2019, a wide area covering northern Italy and parts of Switzerland was surveyed, highlighting the expanding distribution of both Tr. japonicus and Tr. mitsukurii. Within four years after their first detection in Europe, both species have rapidly spread into all types of habitats where H. halys is present, showing a wide distribution and continuous expansion. Both exotic Trissolcus showed high levels of parasitism rate towards H. halys, while parasitization of non-target species was a rare event. The generalist Anastatus bifasciatus was the predominant native parasitoid of H. halys, while the emergence of native scelionids from H. halys eggs was rarely observed. The presence of the hyperparasitoid Acroclisoides sinicus was also recorded. This study provided fundamental data that supported the development of the first inoculative release program of Tr. japonicus in Europe

FOLFIRINOX after first-line gemcitabine-based chemotherapy in advanced pancreatic cancer: a retrospective comparison with FOLFOX and FOLFIRI schedules

Background: Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death. In cases with metastasis, the combination of 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine-based chemotherapy regimens are considered the standard of care. However, the optimal sequence of these regimens is unclear. Methods: This retrospective study initially evaluated 186 patients with locally advanced/metastatic pancreatic cancer at three Italian institutions between February 2013 and October 2019. All patients had progressed after receiving gemcitabine-based first-line chemotherapy and were subsequently offered second-line FOLFIRINOX, FOLFOX-6, or FOLFIRI treatment. This study evaluated progression-free survival (PFS), overall survival from the start of second-line treatment (OS2), overall survival from the start of first-line treatment (OS1), and safety outcomes. Results: A total of 77 patients received ⩾4 cycles of second-line chemotherapy and were considered eligible: 15 patients received FOLFIRINOX, 32 patients received FOLFOX-6, and 30 patients received FOLFIRI. The FOLFIRINOX group had median PFS of 26.29 weeks and median OS2 of 47.86 weeks, while the FOLFIRI group had median PFS of 10.57 weeks and median OS2 of 25.00 weeks (p = 0.038). No significant differences were observed between the FOLFIRINOX and FOLFOX-6 groups in terms of PFS (26.29 weeks versus 23.07 weeks) or OS2 (47.86 weeks versus 42.00 weeks). The most common grade 3–4 toxicities were anemia, neutropenia, and thrombocytopenia, which occurred more frequently in the FOLFIRINOX and FOLFOX-6 groups. Conclusion: Relative to the FOLFIRI regimen, the FOLFIRINOX regimen had a favorable toxicity profile and better survival outcomes. No significant differences were observed relative to the FOLFOX-6 regimen

Surgeons’ perspectives on artificial intelligence to support clinical decision-making in trauma and emergency contexts: results from an international survey

Background: Artificial intelligence (AI) is gaining traction in medicine and surgery. AI-based applications can offer tools to examine high-volume data to inform predictive analytics that supports complex decision-making processes. Time-sensitive trauma and emergency contexts are often challenging. The study aims to investigate trauma and emergency surgeons’ knowledge and perception of using AI-based tools in clinical decision-making processes. Methods: An online survey grounded on literature regarding AI-enabled surgical decision-making aids was created by a multidisciplinary committee and endorsed by the World Society of Emergency Surgery (WSES). The survey was advertised to 917 WSES members through the society’s website and Twitter profile. Results: 650 surgeons from 71 countries in five continents participated in the survey. Results depict the presence of technology enthusiasts and skeptics and surgeons’ preference toward more classical decision-making aids like clinical guidelines, traditional training, and the support of their multidisciplinary colleagues. A lack of knowledge about several AI-related aspects emerges and is associated with mistrust. Discussion: The trauma and emergency surgical community is divided into those who firmly believe in the potential of AI and those who do not understand or trust AI-enabled surgical decision-making aids. Academic societies and surgical training programs should promote a foundational, working knowledge of clinical AI

Компетентностный подход в профессиональной подготовке будущих дизайнеров: возможности проектной деятельности

Анализ феномена "проектная деятельность" и ее возможности в развитии профессиональных компетенций будущих специалистов-дизайнеро