This study reports the development of a bioprocess involving the valorization of biodiesel-derived glycerol as the main carbon source for cell proliferation of Yarrowia lipolytica strains and production of metabolic compounds, i.e., citric acid (Cit), polyols, and other bio-metabolites, the substitution of process tap water with olive mill wastewater (OMW) in batch fermentations, and partial detoxification of OMW (up to 31.1% decolorization). Increasing initial phenolics (Phen) of OMW-glycerol blends led to substantial Cit secretion. Maximum Cit values, varying between 64.1–65.1 g/L, combined with high yield (YCit/S = 0.682–0.690 g Cit/g carbon sources) and productivity (0.335–0.344 g/L/h) were achieved in the presence of Phen = 3 g/L. The notable accumulation of endopolysaccharides (EPs) on the produced biomass was determined when Y. lipolytica LMBF Y-46 (51.9%) and ACA-YC 5033 (61.5%) were cultivated on glycerol-based media. Blending with various amounts of OMW negatively affected EPs and polyols biosynthesis. The ratio of mannitol:arabitol:erythritol was significantly affected (p < 0.05) by the fermentation media. Erythritol was the major polyol in the absence of OMW (53.5–62.32%), while blends of OMW-glycerol (with Phen = 1–3 g/L) promoted mannitol production (54.5–76.6%). Nitrogen-limited conditions did not favor the production of cellular lipids (up to 16.6%). This study addressed sustainable management and resource efficiency enabling the bioconversion of high-organic-load and toxic waste streams into valuable products within a circular bioeconomy approach.
Standard systemic therapy of advanced renal cell carcinoma (RCC) involves targeting angiogenesis, mainly through tyrosine kinase inhibitors (TKI) against the vascular endothelial growth factor receptor (VEGFR) pathway and targeting the immune checkpoints, namely, programmed death-1 (PD-1) or its ligand (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). With current strategies of combining these two approaches in the front-line setting, less is known about optimal selection of therapy upon development of resistance in the second and later lines of treatment for progressive disease. This review discusses currently available therapeutic options in patients who have progressive RCC after prior treatment with double immune checkpoint inhibitors (ICIs) or ICI-TKI combinations.
"Philosophical games provide an innovative transformative structure in the learning process for all levels of formal education. The motivation is to provide elementary school teachers with an innovative methodology for Game-based-Learning of Philosophy/in Philosophy teaching. A combination and attentive collaboration of Philosophy, Art and games/ Game-based Learning provides new tools in approaching and solving the problems that education faces today. Since Game-based Learning constitutes a strong trend in technologically enhanced learning, is the, where/with the employment of gaming elements both in learning content and learning pathways, the proposed methodology leads to a series of novel applications about teaching philosophy that enable young agents to cultivate hypothetic-deductive and critical thinking with a positive attitude towards others and developing feelings of constructive antagonism. The teaching scenario proposed aims at cultivating hypothetic – deductive and critical thought/moreover, enhances the linguistic ability in the vocabulary of ancient Greek philosophy as well. The scenario is part of a game suite entitled “Entering the Socratic school” and targets 10–12-year-old children. It is easy to implement on any digital platform with open-source tools used by almost every teacher. The game elements rely on the structure of the learning content rather than on the digital tools themselves. The methodology consists in designing a concept map and defining the game narrative, the game levels and transitions between levels, the mechanics to be used, such as polls, badges, and leaderboards. Online activities include digital games such as quizzes and crossword puzzles, student generated comic stories, and a digital guide. They are complemented by physical activities involving movement and dialogue using fishbowl techniques and Socratic circles. The proposed teaching scenario will be implemented in the classroom in the following academic year and our work team applies interdisciplinary approaches inspired by at least three different fields of expertise."
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