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Background: the reference method for detection of myositis-specific and myositis-associated antibodies (MSAs and MAAs) is considered immunoprecipitation (IP), but it is routinely replaced by semi-automated methods, like lineblot (LB). Few data are available on the consistency with clinical diagnoses; thus, we aim at analysing these aspects. Methods: sixty-nine patients with idiopathic inflammatory myopathies (IIM) were studied via LB (Myositis Antigens Profile 3 EUROLINE, Euroimmun) and IP (RNA and protein antigens). The degree of concordance between methods was calculated using Cohen's coefficient. Results: a substantial concordance was found for anti-Ku and anti-PM/Scl and a moderate concordance was found for anti-Jo1 and anti–Mi-2, while a fair concordance was found for anti-EJ, anti-SRP, and anti-Ro52 antibodies. The concordance could not be calculated for anti-OJ, anti-PL-7, anti-PL-12, anti-NXP2, anti-TIF1ɣ, and anti-MDA5, because they were only detected with one method. Multiple MSAs were found only with LB in 2/69 sera. Anti-MDA5, TIF1ɣ, NXP2 (detected via IP), and anti-Jo1 in anti-synthetase syndrome (both LB and IP) had the best concordance with clinical diagnosis. Conclusions: LB and IP show substantial concordance for PM/Scl and Ku, and moderate concordance for Jo1 and Mi-2, with a good concordance with clinical diagnoses. IP shows a high performance for DM-associated MSAs. LB seems to be more sensitive in detecting anti-Ro52 antibodies, but it identified multiple MSAs, unlike IP. [ABSTRACT FROM AUTHOR]

Probiotics are living microbes that provide benefits to the host. The growing data on health promotion, following probiotics administration, increased interest among researchers and pharmaceutical companies. Infections of the lower genital tract in females, caused by a wide range of pathogens, represent one of the main areas for the use of probiotics and postbiotics. Vulvovaginal candidiasis (VVC) affects 75% of women of reproductive age at least once during their lifetime, with 5–8% developing the recurrent form (RVVC). The disease is triggered by the overgrowth of Candida on the vaginal mucosa. Here, in order to establish its probiotic potential in the context of VVC, we evaluated the anti-fungal effects of the spore-producing Bacillus coagulans LMG S-24828 against C. albicans and C. parapsilosis as well as its beneficial effects in counteracting Candida vaginal infection in vitro. Our results show that both live B. coagulans and its Cell-Free Supernatant (CFS) exerted antifungal activity against both fungi. Moreover, live B. coagulans reduced hyphal formation, inhibited C. albicans adhesion to vaginal epithelial cells, showed co-aggregation capacity, and exerted a protective effect on vaginal epithelial cells infected with C. albicans. These data suggest that B. coagulans LMG S-24828 may provide benefits in the context of Candida vaginal infections. [ABSTRACT FROM AUTHOR]

In recent years, there has been an intensification of weather variability worldwide as a result of climate change. Some regions have been affected by drought, while others have experienced more intense rainfall. The incidence and severity of moldy grain and mycotoxin contamination during the growing and harvesting seasons have increased as a result of these weather conditions. Additionally, torrential rains and wet conditions may cause delays in grain drying, leading to mold growth in the field. In July 2023, a wheat field in Lecco (Lombardy, Italy) was affected by torrential rains that led to the development of the Claviceps fungi. In the field, dark sclerotia were identified on some ears. Wheat ears, kernels, and sclerotia were collected and analyzed by LC-MS/MS at IZSLER, Food Chemical Department, in Bologna. The wheat ears, kernels, and sclerotia were analyzed for 12 ergot alkaloids (EAs) according to (EU) Regulation 2023/915 (ergocornine/ergocorninine; ergocristine/ergocristinine; ergocryptine/ergocryptinine; ergometrine/ergometrinine; ergosine/ergosinine; ergotamine/ergotaminine), after QuEChERS (Z-Sep/C18) purification. The analyzed sclerotia showed significant differences in total alkaloid content that vary between 0.01 and 0.5% (w/w), according to the results of the 2017 EFSA scientific report. EAs detected in sclerotia were up to 4951 mg/kg, in wheat ears up to 33 mg/kg, and in kernels were 1 mg/kg. Additional mycotoxins, including ochratoxin A, deoxynivalenol, zearalenone, fumonisins, T2-HT2 toxins, and aflatoxins, were investigated in wheat kernels after purification with immunoaffinity columns (IAC). The analysis revealed the presence of deoxynivalenol in wheat kernels at a concentration of 2251 µg/kg. It is expected that climate change will increase the frequency of extreme weather events. In order to mitigate the potential risks associated with mycotoxin-producing fungi and to ensure the protection of human health, it is suggested that official controls be implemented in the field. [ABSTRACT FROM AUTHOR]

In recent years, the search for new compounds with antibacterial activity has drastically increased due to the spread of antibiotic-resistant microorganisms. In this study, we analyzed Cell-Free Supernatant (CFS) from Bacillus siamensis, assessing its potential antimicrobial activity against some of the main pathogenic microorganisms of human interest. To achieve this goal, we exploited the natural antagonism of skin-colonizing bacteria and their ability to produce compounds with antimicrobial activity. Biochemical and molecular methods were used to identify 247 strains isolated from the skin. Among these, we found that CFS from a strain of Bacillus siamensis (that we named CPAY1) showed significant antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis, Streptococcus agalactiae, and Candida spp. In this study, we gathered information on CFS's antimicrobial activity and on its sensitivity to chemical–physical parameters. Time–kill studies were performed; anti-biofilm activity, antibiotic resistance, and plasmid presence were also investigated. The antimicrobial compounds included in the CFS showed resistance to the proteolytic enzymes and were heat stable. The production of antimicrobial compounds started after 4 h of culture (20 AU/mL). CPAY1 CFS showed antimicrobial activity after 7 h of bacteria co-culture. The anti-biofilm activity of the CPAY1 CFS against all the tested strains was also remarkable. B. siamensis CPAY1 did not reveal the presence of a plasmid and showed susceptibility to all the antibiotics tested. [ABSTRACT FROM AUTHOR]

Lactic acid bacteria are considered an inexhaustible source of bioactive compounds; indeed, products from their metabolism are known to have immunomodulatory and anti-inflammatory activity. Recently, we demonstrated that Cell-Free Supernatants (CFS) obtained from Lactobacillus (L.) acidophilus, Lactiplantibacillus (L.) plantarum, Lacticaseibacillus (L.) rhamnosus, and Limosilactobacillus (L.) reuteri can impair Candida pathogenic potential in an in vitro model of epithelial vaginal infection. This effect could be ascribed to a direct effect of living lactic acid bacteria on Candida virulence and to the production of metabolites that are able to impair fungal virulence. In the present work, stemming from these data, we deepened our knowledge of CFS from these four lactic acid bacteria by performing a metabolomic analysis to better characterize their composition. By using an untargeted metabolomic approach, we detected consistent differences in the metabolites produced by these four different lactic acid bacteria. Interestingly, L. rhamnosus and L. acidophilus showed the most peculiar metabolic profiles. Specifically, after a hierarchical clustering analysis, L. rhamnosus and L. acidophilus showed specific areas of significantly overexpressed metabolites that strongly differed from the same areas in other lactic acid bacteria. From the overexpressed compounds in these areas, inosine from L. rhamnosus returned with the best identification profile. This molecule has been described as having antioxidant, anti-inflammatory, anti-infective, and neuroprotective properties. The biological significance of its overproduction by L. rhamnosus might be important in its probiotic and/or postbiotic activity. [ABSTRACT FROM AUTHOR]

Machine learning is a widespread technology that plays a crucial role in digitalisation and aims to explore rules and patterns in large datasets to autonomously solve non-linear problems, taking advantage of multiple source data. Due to its versatility, machine learning can be applied to agriculture. Better crop management, plant health assessment, and early disease detection are some of the main challenges facing the agricultural sector. Plant phenotyping can play a key role in addressing these challenges, especially when combined with machine learning techniques. Therefore, this study reviews available scientific literature on the applications of machine learning algorithms in plant phenotyping with a specific focus on sunflowers. The most common algorithms in the agricultural field are described to emphasise possible uses. Subsequently, the overview highlights machine learning application on phenotyping in three primaries areas: crop management (i.e., yield prediction, biomass estimation, and growth stage monitoring), plant health (i.e., nutritional status and water stress), and disease detection. Finally, we focus on the adoption of machine learning techniques in sunflower phenotyping. The role of machine learning in plant phenotyping has been thoroughly investigated. Artificial neural networks and stacked models seems to be the best way to analyse data. [ABSTRACT FROM AUTHOR]

Infections pose a significant threat to morbidity and mortality during treatments for pediatric cancer patients. Efforts to minimize the risk of infection necessitate preventive measures encompassing both environmental and host-focused strategies. While a substantial number of infections in oncologic patients originate from microorganisms within their native microbiological environment, such as the oral cavity, intestines, and skin, the concrete risk of bloodstream infections linked to the consumption of contaminated food and beverages in the community cannot be overlooked. Ensuring food quality and hygiene is essential to mitigating the impact of foodborne illnesses on vulnerable patients. The neutropenic diet (ND) has been proposed to minimize the risk of sepsis during neutropenic periods. The ND aims to minimize bacterial entry into the gut and bacterial translocation. However, a standardized definition for ND and consensus guidelines for specific food exclusions are lacking. Most centers adopt ND during neutropenic phases, but challenges in achieving caloric intake are common. The ND has not demonstrated any associated benefits and does not ensure improved overall survival. Consequently, providing unified and standardized food safety instructions is imperative for pediatric patients undergoing hematopoietic cell transplantation (HCT). Despite the lack of evidence, ND is still widely administered to both pediatric and adult patients as a precautionary measure. This narrative review focuses on the impact of foodborne infections in pediatric cancer patients and the role of the ND in comparison to food safety practices in patients undergoing chemotherapy or HCT. Prioritizing education regarding proper food storage, preparation, and cooking techniques proves more advantageous than merely focusing on dietary limitations. The absence of standardized guidelines underscores the necessity for further research in this field. [ABSTRACT FROM AUTHOR]

Phenotypic screenings are usually combined with deconvolution techniques to characterize the mechanism of action for the retrieved hits. These studies can be supported by various computational analyses, although docking simulations are rarely employed. The present study aims to assess if multiple docking calculations can prove successful in target prediction. In detail, the docking simulations submitted to the MEDIATE initiative are utilized to predict the viral targets involved in the hits retrieved by a recently published cytopathic screening. Multiple docking results are combined by the EFO approach to develop target-specific consensus models. The combination of multiple docking simulations enhances the performances of the developed consensus models (average increases in EF1% value of 40% and 25% when combining three and two docking runs, respectively). These models are able to propose reliable targets for about half of the retrieved hits (31 out of 59). Thus, the study emphasizes that docking simulations might be effective in target identification and provide a convincing validation for the collaborative strategies that inspire the MEDIATE initiative. Disappointingly, cross-target and cross-program correlations suggest that common scoring functions are not specific enough for the simulated target. [ABSTRACT FROM AUTHOR]

Mediterranean islands suffer from a lack of freshwater due to persistent and recursive droughts, limited groundwater availability and mass tourism. In Ibiza (Spain), private estates disconnected from the water distribution network consume about 21% of the total freshwater demand on the island. We conducted a study to evaluate the potential of ground-runoff harvesting (GRH) as a sustainable and inexpensive solution to increase freshwater availability in isolated households in Ibiza. The study involved an innovative modular tank of 40 m3 buried in the garden of a private property. The tank intercepted runoff forming in a 12,300 m2 hilly micro-catchment. We found that an extreme rainfall event with an intensity of 65 mm/h was able to create sufficient runoff to fill up the tank in one hour. A curve-number-based rainfall-runoff model was used to simulate the experimental results and to obtain a first-cut estimation of the potential of GRH at the scale of the island. The analysis indicates that, if installed in all forest areas in Ibiza with a similar slope to the study area, a volume of 1.31 × 10 6 m3 of freshwater could be harvested per year on the island just from extreme precipitation events. Such a volume of water is equivalent to about 5% of the island's total freshwater budget. The study concludes that GRH is a highly valuable, yet still unexploited opportunity to save large freshwater volumes in dry-climate areas like Ibiza. GRH should be promoted across Mediterranean islands, and it can be easily incorporated within local water regulations. [ABSTRACT FROM AUTHOR]

Increasing legume intake through dietary diversification confers nutritional and environmental benefits. This study used life cycle assessment to evaluate the environmental impacts of producing frozen green peas from conventional and organic farming. We explored two ways of treating farm data: modeling each farm (baseline) and using a uniform distribution of each farm parameter's average, maximum, and minimum values (alternative). We also assessed the indirect land-use change (iLUC) impacts by applying a deterministic model and used the EF 3.0 method to estimate the midpoint environmental impacts. The results of the two scenarios for pea cultivation (including iLUC) showed notable differences in absolute terms with minor discrepancies in the contribution analysis (e.g., climate change (CC) for the baseline and alternative were 0.98 and 2.09 kg CO2 eq./kg fresh peas, respectively). Generally, conventional peas had a higher environmental impact than organic peas, although this was not uniformly observed across all farms. When included, iLUC accounted for nearly half of the CC score. Pea cultivation was the most impactful phase due to emissions from fertilizers and field operations. The impacts of pea production can be reduced by anaerobic digestion of pea residues with energy and nutrient recycling. However, improvements in processing and nitrogen use efficiency could significantly enhance the overall environmental performance of frozen green peas. In summary, this study emphasizes the need for sustainable practices to minimize the environmental impact of frozen pea production. [ABSTRACT FROM AUTHOR]

Dogs' displacement behaviours and some facial expressions have been suggested to function as appeasement signals, reducing the occurrences of aggressive interactions. The present study had the objectives of using naturalistic videos, including their auditory stimuli, to expose a population of dogs to a standardised conflict (threatening dog) and non-conflict (neutral dog) situation and to measure the occurrence of displacement behaviours and facial expressions under the two conditions. Video stimuli were recorded in an ecologically valid situation: two different female pet dogs barking at a stranger dog passing by (threatening behaviour) or panting for thermoregulation (neutral behaviour). Video stimuli were then paired either with their natural sound or an artificial one (pink noise) matching the auditory characteristics. Fifty-six dogs were exposed repeatedly to the threatening and neutral stimuli paired with the natural or artificial sound. Regardless of the paired auditory stimuli, dogs looked significantly more at the threatening than the neutral videos (χ2(56, 1) = 138.867, p < 0.001). They kept their ears forward more in the threatening condition whereas ears were rotated more in the neutral condition. Contrary to the hypotheses, displacement behaviours of sniffing, yawning, blinking, lip-wiping (the tongue wipes the lips from the mouth midpoint to the mouth corner), and nose-licking were expressed more in the neutral than the threatening condition. The dogs tested showed socially relevant cues, suggesting that the experimental paradigm is a promising method to study dogs' intraspecific communication. Results suggest that displacement behaviours are not used as appeasement signals to interrupt an aggressive encounter but rather in potentially ambiguous contexts where the behaviour of the social partner is difficult to predict. [ABSTRACT FROM AUTHOR]

The prediction of drug metabolism is attracting great interest for the possibility of discarding molecules with unfavorable ADME/Tox profile at the early stage of the drug discovery process. In this context, artificial intelligence methods can generate highly performing predictive models if they are trained by accurate metabolic data. MetaQSAR-based datasets were collected to predict the sites of metabolism for most metabolic reactions. The models were based on a set of structural, physicochemical, and stereo-electronic descriptors and were generated by the random forest algorithm. For each considered biotransformation, two types of models were developed: the first type involved all non-reactive atoms and included atom types among the descriptors, while the second type involved only non-reactive centers having the same atom type(s) of the reactive atoms. All the models of the first type revealed very high performances; the models of the second type show on average worst performances while being almost always able to recognize the reactive centers; only conjugations with glucuronic acid are unsatisfactorily predicted by the models of the second type. Feature evaluation confirms the major role of lipophilicity, self-polarizability, and H-bonding for almost all considered reactions. The obtained results emphasize the possibility of recognizing the sites of metabolism by classification models trained on MetaQSAR database. The two types of models can be synergistically combined since the first models identify which atoms can undergo a given metabolic reactions, while the second models detect the truly reactive centers. The generated models are available as scripts for the VEGA program. [ABSTRACT FROM AUTHOR]

Vaginal ecosystem is a unique environment where, in physiological conditions, lactobacilli dominate. However, pathogenic microbial species responsible for vaginitis and vaginosis can also harbor vaginal microbiota. To extend our previously published data, we analyzed here both the anti-Candida and anti-inflammatory properties of the vaginal gel formulation, Respecta® Balance Gel (RBG), commercialized as an adjuvant to treat vaginitis and vaginosis. We evaluated its activity by an in vitro model where a monolayer of A-431 vaginal epithelial cells was infected by Candida albicans in the presence of RBG or the placebo formulation (pRBG). Specifically, we tested the RBG capacity to counteract C. albicans virulence factors and their anti-inflammatory properties. Our results show that, unlike the placebo, RBG reduces C. albicans adhesion, its capacity to form hyphae and C. albicans-induced vaginal cell damage. Interestingly, both RBG and pRBG reduce LPS-induced IL-8 secretion (with RBG being the most effective), demonstrating that also the placebo retains anti-inflammatory properties. From our experimental approach, we highlighted the possible role of farnesol on such effects, but we would like to point out that lactic acid, polydextrose and glycogen too must be relevant in the actual application. In summary, our results show that RBG impairs C. albicans virulence and is able to reduce the inflammation in the vaginal environment, ultimately allowing the establishment of a balanced vaginal ecosystem. [ABSTRACT FROM AUTHOR]

Gaucher Disease (GD) is a condition resulting from an autosomal recessive inheritance pattern, characterized by a deficiency of the lysosomal enzyme beta-glucocerebrosidase. This leads to the accumulation of glucocerebroside and other glycolipids in multiple tissues, causing damage to various organ systems. The diagnosis of GD can be challenging due to its heterogeneity, non-specific symptoms, and variability across different geographic regions and age groups. Although GD is suspected based on symptoms or signs, the diagnosis is confirmed through the measurement of deficient b-glucocerebrosidase activity and the identification of biallelic pathogenic variants in the GBA gene. Intravenous enzyme replacement therapy (ERT) is recommended for GD patients. In this paper, we report a case of a 2-year and 8-month-old girl with massive splenomegaly and radiological finding of hepatic gaucheroma, in whom a genetic study showed homozygous mutation on the GBA gene at c.1448T>C (p.Leu483Pro) and certified the diagnosis of GD. This patient represents the youngest child reported to have gaucheroma and also the first one presenting with gaucheroma at the diagnosis and not during the follow up, highlighting that GD should be routinely included in the differential diagnosis of children presenting with splenomegaly and hepatomegaly, taking into account that the early start of ERT can change the natural history of the disease-preventing serious complications. [ABSTRACT FROM AUTHOR]

Obesity and type 2 diabetes (T2DM) are major public health concerns associated with serious morbidity and increased mortality. Both obesity and T2DM are strongly associated with adiposopathy, a term that describes the pathophysiological changes of the adipose tissue. In this review, we have highlighted adipose tissue dysfunction as a major factor in the etiology of these conditions since it promotes chronic inflammation, dysregulated glucose homeostasis, and impaired adipogenesis, leading to the accumulation of ectopic fat and insulin resistance. This dysfunctional state can be effectively ameliorated by the loss of at least 15% of body weight, that is correlated with better glycemic control, decreased likelihood of cardiometabolic disease, and an improvement in overall quality of life. Weight loss can be achieved through lifestyle modifications (healthy diet, regular physical activity) and pharmacotherapy. In this review, we summarized different effective management strategies to address weight loss, such as bariatric surgery and several classes of drugs, namely metformin, GLP-1 receptor agonists, amylin analogs, and SGLT2 inhibitors. These drugs act by targeting various mechanisms involved in the pathophysiology of obesity and T2DM, and they have been shown to induce significant weight loss and improve glycemic control in obese individuals with T2DM. [ABSTRACT FROM AUTHOR]

Grapevines are one of the most intensely treated crops with a high potential risk to health and biodiversity. Thus, the distribution control of agrochemicals is crucial to obtain a high quality and sustainable product for intensive viticulture. Although the search for systems to reduce the waste of chemical products is consistent in some countries, such as Italy, the machinery used are obsolete. The development of an upgrading system for sprayers can be a good compromise to achieve the pollution reduction without requiring huge investments. Field tests were conducted using a LIDAR-based prototype coupled to a commercial sprayer. This study tested the distribution performance using water-sensitive papers and evaluated the infections of grapevine downy and powdery mildews. The results showed a distribution in the vegetation gaps with a higher frequency in the coverage classes >20% in the standard treatment and 10–15% in the LIDAR treatment. Treatments performed with LiDAR reduced the incidence of downy mildew and severity of powdery mildew. The innovative sprayer reduces the distribution of agrochemicals thanks to the on/off control of the nozzles in the voids of vegetation and, meanwhile, controls vineyard fungal disease, so it can be a good way to meet the sustainability and quality of the production. [ABSTRACT FROM AUTHOR]

Children with cancer are at high risk for developing short-term and long-term nutritional problems related to their underlying disease and side effects of multimodal treatments. Nutritional status (NS) can influence several clinical outcomes, such as overall survival (OS) and event-free survival (EFS), treatment tolerance, risk of developing infections and quality of life (QoL). However, the importance of nutrition in children with cancer is still underestimated. This review focuses on alterations of NS that occurs in children during cancer treatment. In particular, we reviewed the pathogenesis of undernutrition in oncological children, as well as how NS affects treatment tolerance and response, the immune system and the risk of infections of children with cancer. Thanks to recent advances in all types of supportive therapy and to the progress of knowledge on this topic, it has been realized that NS is a modifiable prognostic factor that can be intervened upon to improve the outcome of these patients. Currently, there is a lack of a systematic approach and standard recommendations for nutritional care in the pediatric cancer population. Literature analysis showed that it is essential to define the NS and treat any alterations in a timely manner ensuring proper growth and development. Nutritional follow-up should become an integral part of the care pathway. Regular nutritional monitoring should be performed at diagnosis, during treatment and during follow-up. A close collaboration and sharing of expertise between pediatric oncologists and nutrition specialists, combined with careful and participatory sharing of the feeding experience with the family and the child (after age 6 years), is strongly required. [ABSTRACT FROM AUTHOR]

The Nerve Growth Factor (NGF) belongs to the neurothrophins protein family involved in the survival of neurons in the nervous system. The interaction of NGF with its high-affinity receptor TrkA mediates different cellular pathways related to Alzheimer's disease, pain, ocular dysfunction, and cancer. Therefore, targeting NGF-TrkA interaction represents a valuable strategy for the development of new therapeutic agents. In recent years, experimental studies have revealed that peptides belonging to the N-terminal domain of NGF are able to partly mimic the biological activity of the whole protein paving the way towards the development of small peptides that can selectively target specific signaling pathways. Hence, understanding the molecular basis of the interaction between the N-terminal segment of NGF and TrkA is fundamental for the rational design of new peptides mimicking the NGF N-terminal domain. In this study, molecular dynamics simulation, binding free energy calculations and per-residue energy decomposition analysis were combined in order to explore the molecular recognition pattern between the experimentally active NGF(1–14) peptide and TrkA. The results highlighted the importance of His4, Arg9 and Glu11 as crucial residues for the stabilization of NGF(1–14)-TrkA interaction, thus suggesting useful insights for the structure-based design of new therapeutic peptides able to modulate NGF-TrkA interaction. [ABSTRACT FROM AUTHOR]

In recent years, the availability of induced pluripotent stem cell-based neuronal models has opened new perspectives on the study and therapy of neurological diseases such as Parkinson's disease. In particular, P. Zhang set up a protocol to efficiently generate dopaminergic neurons from induced pluripotent stem cells. Although the differentiation process of these cells has been widely investigated, there is scant information related to the variation in metabolic features during the differentiation process of pluripotent stem cells to mature dopaminergic neurons. For this reason, we analysed the metabolic profile of induced pluripotent stem cells, neuronal precursors and mature neurons by liquid chromatography–tandem mass spectrometry. We found that induced pluripotent stem cells primarily rely on fatty acid beta-oxidation as a fuel source. Upon progression to neuronal progenitors, it was observed that cells began to shut down fatty acid β-oxidation and preferentially catabolised glucose, which is the principal source of energy in fully differentiated neurons. Interestingly, in neuronal precursors, we observed an increase in amino acids that are likely the result of increased uptake or synthesis, while in mature dopaminergic neurons, we also observed an augmented content of those amino acids needed for dopamine synthesis. In summary, our study highlights a metabolic rewiring occurring during the differentiation stages of dopaminergic neurons. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most common cancer in women worldwide, with a high prevalence and incidence, configuring an important issue in cancer epidemiology. Over the years, the combination of primary and secondary prevention programs and multidisciplinary treatment approaches has improved the overall survival (OS) and quality of life (QoL) of patients. However, although treatment pathways should be standardized in evidence-based medicine, clinical practice (real-world evidence) may differ from expected. To improve OS and QoL, having a clear picture of the Patterns of Care actually applied is essential. To this aim, Breast IRRADIATA (Italian Repository of RADIotherapy dATA), a collaborative nationwide project, was developed as a simple tool to probe the current pattern of radiotherapy care in Italy and tested in a feasibility study. This pilot feasibility of IRRADIATA encourages a larger application of this tool nationwide and opens the way to the assessment of pattern of care radiotherapy directed to other cancers. Aim. Breast IRRADIATA (Italian Repository of RADIotherapy dATA) is a collaborative nationwide project supported by the Italian Society of Radiotherapy and Clinical Oncology (AIRO) and the Italian League Against Cancer (LILT). It focuses on breast cancer (BC) patients treated with radiotherapy (RT) and was developed to create a national registry and define the patterns of care in Italy. A dedicated tool for data collection was created and pilot tested. The results of this feasibility study are reported here. Methods. To validate the applicability of a user-friendly data collection tool, a feasibility study involving 17 Italian Radiation Oncology Centers was conducted from July to October 2021, generating a data repository of 335 BC patients treated between January and March 2020, with a minimum follow-up time of 6 months. A snapshot of the clinical presentation, treatment modalities and radiotherapy toxicity in these patients was obtained. A Data Entry Survey and a Satisfaction Questionnaire were also sent to all participants. Results. All institutions completed the pilot study. Regarding the Data Entry survey, all questions achieved 100% of responses and no participant reported spending more than 10 min time for either the first data entry or for the updating of follow-up. Results from the Satisfaction Questionnaire revealed that the project was described as excellent by 14 centers (82.3%) and good by 3 (17.7%). Conclusion. Current knowledge for the treatment of high-prevalence diseases, such as BC, has evolved toward patient-centered medicine, evidence-based care and real-world evidence (RWE), which means evidence obtained from real-world data (RWD). To this aim, Breast IRRADIATA was developed as a simple tool to probe the current pattern of RT care in Italy. The pilot feasibility of IRRADIATA encourages a larger application of this tool nationwide and opens the way to the assessment of the pattern of care radiotherapy directed to other cancers. [ABSTRACT FROM AUTHOR]

In the mature central nervous system (CNS), oligodendrocytes (OLs) provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, OLs require energy and building blocks for lipids, which implies a great investment of energy fuels and molecular sources of carbon. The oligodendroglial G protein-coupled receptor 17 (GPR17) has emerged as a key player in OL maturation; it reaches maximal expression in pre-OLs, but then it has to be internalized to allow terminal maturation. In this study, we aim at elucidating the role of physiological GPR17 downregulation in OL metabolism by applying transcriptomics, metabolomics and lipidomics on differentiating OLs. After GPR17 silencing, we found a significant increase in mature OL markers and alteration of several genes involved in glucose metabolism and lipid biosynthesis. We also observed an increased release of lactate, which is partially responsible for the maturation boost induced by GPR17 downregulation. Concomitantly, GPR17 depletion also changed the kinetics of specific myelin lipid classes. Globally, this study unveils a functional link between GPR17 expression, lactate release and myelin composition, and suggests that innovative interventions targeting GPR17 may help to foster endogenous myelination in demyelinating diseases. [ABSTRACT FROM AUTHOR]

Centrins are calcium (Ca2+)-binding proteins that are involved in many cellular functions including centrosome regulation. A known cellular target of centrins is SFI1, a large centrosomal protein containing multiple repeats that represent centrin-binding motifs. Recently, a protein homologous to yeast and mammalian SFI1, denominated TgSFI1, which shares SFI1-repeat organization, was shown to colocalize at centrosomes with centrin 1 from Toxoplasma gondii (TgCEN1). However, the molecular details of the interaction between TgCEN1 and TgSFI1 remain largely unknown. Herein, combining different biophysical methods, including isothermal titration calorimetry, nuclear magnetic resonance, circular dichroism, and fluorescence spectroscopy, we determined the binding properties of TgCEN1 and its individual N- and C-terminal domains to synthetic peptides derived from distinct repeats of TgSFI1. Overall, our data indicate that the repeats in TgSFI1 constitute binding sites for TgCEN1, but the binding modes of TgCEN1 to the repeats differ appreciably in terms of binding affinity, Ca2+ sensitivity, and lobe-specific interaction. These results suggest that TgCEN1 displays remarkable conformational plasticity, allowing for the distinct repeats in TgSFI1 to possess precise modes of TgCEN1 binding and regulation during Ca2+ sensing, which appears to be crucial for the dynamic association of TgCEN1 with TgSFI1 in the centrosome architecture. [ABSTRACT FROM AUTHOR]

(1) Background: Virtual screening campaigns require target structures in which the pockets are properly arranged for binding. Without these, MD simulations can be used to relax the available target structures, optimizing the fine architecture of their binding sites. Among the generated frames, the best structures can be selected based on available experimental data. Without experimental templates, the MD trajectories can be filtered by energy-based criteria or sampled by systematic analyses. (2) Methods: A blind and methodical analysis was performed on the already reported MD run of the hTRPM8 tetrameric structures; a total of 50 frames underwent docking simulations by using a set of 1000 ligands including 20 known hTRPM8 modulators. Docking runs were performed by LiGen program and involved the frames as they are and after optimization by SCRWL4.0. For each frame, all four monomers were considered. Predictive models were developed by the EFO algorithm based on the sole primary LiGen scores. (3) Results: On average, the MD simulation progressively enhances the performance of the extracted frames, and the optimized structures perform better than the non-optimized frames (EF1% mean: 21.38 vs. 23.29). There is an overall correlation between performances and volumes of the explored pockets and the combination of the best performing frames allows to develop highly performing consensus models (EF1% = 49.83). (4) Conclusions: The systematic sampling of the entire MD run provides performances roughly comparable with those previously reached by using rationally selected frames. The proposed strategy appears to be helpful when the lack of experimental data does not allow an easy selection of the optimal structures for docking simulations. Overall, the reported docking results confirm the relevance of simulating all the monomers of an oligomer structure and emphasize the efficacy of the SCRWL4.0 method to optimize the protein structures for docking calculations. [ABSTRACT FROM AUTHOR]

Simple Summary: Currently, few papers have been published regarding the possible interactions between radiotherapy and systemic agents for the treatment of multiple myeloma. In this paper, we retrospectively analyze the data from 312 patients (577 lesions) who received radiotherapy at our institution from 2005 to 2020, with the aim of clarifying the clinical impact of radiotherapy dose and concurrent systemic treatment (CST). The safety profile of the radiotherapy was excellent; high biologically effective doses (BEDs) and CST were associated with higher toxicity rates at the end of radiotherapy, but not after one and three months. The pain control rate was 87.4% at the end of treatment and further increased at three and six months. Radiological progression was reported only for 4.4% of the lesions at six months (based on the data available for 181 lesions) and was significantly more frequent for lesions treated without CST or BED < 15 Gy. Background and purpose: Although chemotherapy, biological agents, and radiotherapy (RT) are cornerstones of the treatment of multiple myeloma (MM), the literature regarding the possible interactions of concurrent systemic treatment (CST) and RT is limited, and the optimal RT dose is still unclear. Materials and methods: We retrospectively analyzed the records of patients who underwent RT for MM at our institution from 1 January 2005 to 30 June 2020. The data of 312 patients and 577 lesions (treated in 411 accesses) were retrieved. Results: Most of the treated lesions involved the vertebrae (60%) or extremities (18.9%). Radiotherapy was completed in 96.6% of the accesses and, although biologically effective doses assuming an α/β ratio of 10 (BED 10) > 38 Gy and CST were significantly associated with higher rates of toxicity, the safety profile was excellent, with side effects grade ≥2 reported only for 4.1% of the accesses; CST and BED 10 had no impact on the toxicity at one and three months. Radiotherapy resulted in significant improvements in performance status and in a pain control rate of 87.4% at the end of treatment, which further increased to 96.9% at three months and remained at 94% at six months. The radiological response rate at six months (data available for 181 lesions) was 79%, with only 4.4% of lesions in progression. Progression was significantly more frequent in the lesions treated without CST or BED 10 < 15 Gy, while concurrent biological therapy resulted in significantly lower rates of progression. Conclusion: Radiotherapy resulted in optimal pain control rates and fair toxicity, regardless of BED 10 and CST; the treatments with higher BED 10 and CST (remarkably biological agents) improved the already excellent radiological disease control. [ABSTRACT FROM AUTHOR]

Geological entropy is based on Shannon information entropy and measures order in the structure of a spatial random variable. Metrics have been defined to quantify geological entropy in multidimensional (2D and 3D) heterogeneous systems, for instance, porous and fractured geological media. This study introduces GEOENT, a toolbox that can efficiently be used to calculate geological entropy metrics for any kind of input-gridded field. Additionally, the definition of geological entropy metrics is updated to consider anisotropy in the structure of the heterogeneous system. Directional entrograms provide more accurate descriptions of spatial order over different Cartesian directions. This study presents the development of the geological entropy metrics, a description of the toolbox, and examples of its applications in different datasets, including 2D and 3D gridded fields, representing a variety of heterogeneous environments at different scales, from pore-scale microtomography (μCT) images to aquifer analogues. [ABSTRACT FROM AUTHOR]

Despite the increasing role played by artificial intelligence methods (AI) in pharmaceutical sciences, model deployment remains an issue, which only can be addressed with great difficulty. This leads to a marked discrepancy between the number of published predictive studies based on AI methods and the models, which can be used for new predictions by everyone. On these grounds, the present paper describes the Tree2C tool which automatically translates a tree-based predictive model into a source code with a view to easily generating applications which can run as a standalone software or can be inserted into an online web service. Moreover, the Tree2C tool is implemented within the VEGA environment and the generated program can include the source code to calculate the required attributes/descriptors. Tree2C supports various programming languages (i.e., C/C++, Fortran 90, Java, JavaScript, JScript, Lua, PHP, Python, REBOL and VBScript and C-Script). Along with a detailed description of the major features of this tool, the paper also describes two examples which are aimed to predict the blood–brain barrier (BBB) permeation as well as the mutagenicity. They permit a clear evaluation of the potentials of Tree2C and of its related features as implemented by the VEGA suite of programs. The Tree2C tool is available for free. [ABSTRACT FROM AUTHOR]

Background: The production of seeds for horticultural crops has seen a steady growth since 2006. Onion is one of the most widespread crops that followed this trend until 2013, undergoing a slight decline in 2016. Even though these crops are characterized by high economic value, they present some important issues such as high costs and labor required by some operations such as threshing. The purpose of this study is the evaluation of a patented and dedicated system for mechanical threshing throughout the evaluation of seed quality parameters. Methods: The study was conducted comparing seed samples mechanically threshed obtained from 12 companies and samples of the same batches manually threshed to determine the maximum qualitative potential. The chosen terms for comparison are the most important qualitative parameters included within ISTA standards for seed evaluation. Results: The mechanically threshed seeds show lower values for all the considered quality parameters compared to those found in the control samples. In the same way, there is also greater variability. Conclusions: The introduction of the dedicated mechanical systems allows the reduction of seed processing time while maintaining the quality standards within the limits of merchantability, but for obtaining higher standards, further analysis is necessary. [ABSTRACT FROM AUTHOR]

The phytotoxicity of four different composts obtained from pig slurry solid fraction composted by itself (SSFC) and mixed with sawdust (SC), woodchips (WCC) and wheat straw (WSC) was tested with bioassay methods. For each compost type, the effect of water extracts of compost on seed germination and primary root growth of cress (Lepidium Sativum L.) was investigated. Composts were also chemically analysed for total nitrogen, ammonium, electrical conductivity and heavy metal (Cu and Zn). The chemicals were correlated to phytotoxicity indices. The mean values of the germination index (GI) obtained were 160.7, 187.9, 200.9 and 264.4 for WSC, WCC, SC and SSFC, respectively. Growth index (GrI) ranged from the 229.4%, the highest value, for SSFC, followed by 201.9% for SC, and 193.1% for WCC, to the lowest value, 121.4%, for WSC. Electrical conductivity showed a significant and negative correlation with relative seed germination at the 50% and 75% concentrations. A strong positive correlation was found for water-extractable Cu with relative root growth and germination index at the 10% concentration. Water-extractable Zn showed a significant positive correlation with relative root growth and GI at the 10% concentration. These results highlighted that the four composts could be used for organic pellet production and subsequently distributed as a soil amendment with positive effects on seed germination and plant growth (GI > 80%). [ABSTRACT FROM AUTHOR]

Environmental sustainability has recently shifted towards biodiversity protection via governmental and intergovernmental initiatives (e.g., the UN Millennium Ecosystem Assessment, MA). The life cycle assessment, the widespread method for assessing environmental sustainability, was not created to evaluate impacts on biodiversity. However, several authors recognize its ability to estimate biodiversity loss drivers (impact indices on land use change and ecosystem). The study aims to apply LCA to the forest sector, precisely to the wood–energy chain of Hophornbeam, to cover suggestions of the MA for the biodiversity impact assessment. Six different scenarios for stove (3) and fireplace (3) wood production were analyzed, evaluating two baselines and four alternative scenarios, including sensitivity analyses related to transport distances for the raw materials. The functional unit is 1 MJ of energy. The fireplace combustion scenarios are relatively more sustainable than the stove ones are (2.95–3.21% less). The global warming potential (around 3 g CO2 eq/MJ) is consistent with current European directives on the sustainability of biofuels and scientific literature. The scenarios showed similarities regarding the impact of the categories related to MA drivers. Although biodiversity is protected by limiting forest management, some authors argue that for some species (e.g., Hophornbeam), a rational tree felling could produce biofuels, increasing biodiversity. [ABSTRACT FROM AUTHOR]

Replacing fossil energy sources with renewable energy sources is a key strategic action to limit environmental issues. To achieve this goal, substitution with biomass is beneficial due to its versatility in various fields. In terms of circular economy and sustainability, the possibility of energy exploitation of residual biomass is particularly desirable in small-medium enterprises. The use of supply chain by-products can improve sustainability and create opportunities for companies. The purpose of this study is to evaluate the suitability of residual biomass of conifers and broad-leaved trees to produce quality pellets using an agri-pellet machine activated by the power take-off of a tractor. This system can be employed at the farm level. Wood biomass of four species was tested; poplar, stone pine, black locust, and oak. Wood chips samples were analyzed to determine their qualitative characteristics following the technical standard ISO 17225-4. Based on the results, different wood blends were created to produce pellets, subsequently characterized according to ISO 17225-2. The analyses carried out on wood chips and pellets were bulk density, moisture, ash content, calorific value, elemental composition, chlorine, sulfur, and heavy metals. In addition, particles size was measured only for wood chips, while the length, diameter, mechanical durability, and ash melting behaviors were determined only for pellets. Some of the analyzed mixtures show acceptable values according to the current ISO technical standards. The values related to the apparent pellet bulk density and the durability test highlight that not all the mixtures are suitable to produce quality pellets. Results also represent a good starting point for future studies. [ABSTRACT FROM AUTHOR]

Centrins are a family of small, EF hand-containing proteins that are found in all eukaryotes and are often complexed with centrosome-related structures. Since their discovery, centrins have attracted increasing interest due to their multiple, diverse cellular functions. Centrins are similar to calmodulin (CaM) in size, structure and domain organization, although in contrast to CaM, the majority of centrins possess at least one calcium (Ca2+) binding site that is non-functional, thus displaying large variance in Ca2+ sensing abilities that could support their functional versatility. In this review, we summarize current knowledge on centrins from both biophysical and structural perspectives with an emphasis on centrin-target interactions. In-depth analysis of the Ca2+ sensing properties of centrins and structures of centrins complexed with target proteins can provide useful insight into the mechanisms of the different functions of centrins and how these proteins contribute to the complexity of the Ca2+ signaling cascade. Moreover, it can help to better understand the functional redundancy of centrin isoforms and centrin-binding proteins. [ABSTRACT FROM AUTHOR]

Stochastic multicomponent reactive transport modeling is a powerful approach to quantify the probability of non-exceedance (PNE) of arsenic (As) critical concentration thresholds in groundwater. The approach is applied to a well-characterized shallow alluvial aquifer near Venice, Italy. Here, As mobility depends primarily on rainfall-controlled redox-dependent precipitation-dissolution of iron hydroxides. A Monte-Carlo analysis based on a calibrated three-dimensional flow and transport model targeted the geochemical initial conditions as the main source of uncertainty of As concentrations in the studied aquifer. It was found that, during 115 simulated days, the fraction of the entire aquifer volume with As > 10 μgL−1 decreased on average from ~43% to ~39% and the average As concentration from ~32 μgL−1 to ~27 μgL−1. Meanwhile, PNE increased from 55% to 60% when 10 μgL−1 was set as target threshold, and from 71% to 78% for 50 μgL−1. The time dependence of As attenuation can be ascribed to the increase of oxidizing conditions during rainfall-dependent aquifer recharge, which causes As sorption on precipitating iron hydroxides. When computing the same statistics for the shallowest 6 m, As attenuation was even more evident. The volume fraction of aquifer with As > 10μgL−1 dropped from 40% to 28% and the average As concentration from 31 μgL−1 to 20 μgL−1, whereas PNE increased from 58% to 70% for As < 10 μgL−1 and from 71% to 86% for As < 50 μgL−1. Thus, the wells screen depth in the aquifer can be a critical aspect when estimating As risk, owing to the depth-dependent relative change in redox conditions during rainfall events. [ABSTRACT FROM AUTHOR]

(1) Background: Machine learning algorithms are finding fruitful applications in predicting the ADME profile of new molecules, with a particular focus on metabolism predictions. However, the development of comprehensive metabolism predictors is hampered by the lack of highly accurate metabolic resources. Hence, we recently proposed a manually curated metabolic database (MetaQSAR), the level of accuracy of which is well suited to the development of predictive models. (2) Methods: MetaQSAR was used to extract datasets to predict the metabolic reactions subdivided into major classes, classes and subclasses. The collected datasets comprised a total of 3788 first-generation metabolic reactions. Predictive models were developed by using standard random forest algorithms and sets of physicochemical, stereo-electronic and constitutional descriptors. (3) Results: The developed models showed satisfactory performance, especially for hydrolyses and conjugations, while redox reactions were predicted with greater difficulty, which was reasonable as they depend on many complex features that are not properly encoded by the included descriptors. (4) Conclusions: The generated models allowed a precise comparison of the propensity of each metabolic reaction to be predicted and the factors affecting their predictability were discussed in detail. Overall, the study led to the development of a freely downloadable global predictor, MetaClass, which correctly predicts 80% of the reported reactions, as assessed by an explorative validation analysis on an external dataset, with an overall MCC = 0.44. [ABSTRACT FROM AUTHOR]

The updated author contribution is as follows: Conceptualization, A.A., G.B. and G.A.; Data curation, A.A., G.B., C.B. and G.A.; Formal analysis, A.A., G.B., M.B. (Marta Balbinot), A.M.F., B.Z. and M.B. (Maura Brioschi); Funding acquisition, M.C., C.B. and G.A.; Investigation, A.A., G.B. and A.P.; Methodology, A.A., G.B., M.B. (Marta Balbinot), A.M.F. and M.B. (Maura Brioschi); Project administration, C.B. and G.A.; Resources, M.C., C.B. and G.A.; Supervision, A.A., G.B., C.B. and G.A.; Validation, A.A., G.B. and M.B. (Maura Brioschi); Writing - original draft, A.A., C.B. and G.A.; Writing - review and editing, A.A., M.C., P.A., A.P., C.B. and G.A. All authors have read and agreed to the published version of the manuscript. In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies. Reference 1 Altomare A., Baron G., Balbinot M., Martínez Fernández A., Pedretti A., Zoanni B., Brioschi M., Agostoni P., Carini M., Banfi C. In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies. [Extracted from the article]

Environmental sustainability continues to attract global interest, especially due to the issue of climate change. The agri-food sector is considered a major contributor to climate change as processes and activities within the sector can negatively impact the environment. The recent changing dietary pattern towards increased vegetable consumption implies a consequent increase in production to meet demand. This study assessed the environmental performance of 1 kg of spinach/FU (Functional Unit) cultivated by different producers in Italy under integrated and organic farming systems. The life cycle assessment was used following the CML_IA impact assessment method. The data used was mainly primary, related to 2019/2020 (harvest period), and representative of the cultivation systems of central and southern Italy. From the results obtained, impact scores for central Italy were higher (e.g., for global warming 0.56 and 0.47 kg CO2 eq. for central and southern respectively). There was high variability among the scores obtained. However, no statistically significant differences were observed at a confidence level of 95% (p < 0.05). Integrated farming was also more impacting than organic for most categories (e.g., for global warming 0.20 kg CO2 eq. for integrated and 0.075 kg CO2 eq. for organic) in Cerignola, Puglia region. Emissions from fertilizer, pesticide, tillage, and combine harvesting were major contributors to impact shares. The results of this study will be helpful to ensure sustainable spinach production and consumption. [ABSTRACT FROM AUTHOR]

Obesity is a condition characterized by uncontrolled expansion of adipose tissue mass resulting in pathological weight gain. Histone deacetylases (HDACs) have emerged as crucial players in epigenetic regulation of adipocyte metabolism. Previously, we demonstrated that selective inhibition of class I HDACs improves white adipocyte functionality and promotes the browning phenotype of murine mesenchymal stem cells (MSCs) C3H/10T1/2 differentiated to adipocytes. These effects were also observed in db/db and diet induced obesity mouse models and in mice with adipose-selective inactivation of HDAC3, a member of class I HDACs. The molecular basis of class I HDACs action in adipose tissue is not deeply characterized and it is not known whether the effects of their inhibition are exerted on adipocyte precursors or mature adipocytes. Therefore, the aim of the present work was to explore the molecular mechanism of class I HDAC action in adipocytes by evaluating the effects of HDAC3-specific silencing at different stages of differentiation. HDAC3 was silenced in C3H/10T1/2 MSCs at different stages of differentiation to adipocytes. shRNA targeting HDAC3 was used to generate the knock-down model. Proper HDAC3 silencing was assessed by measuring both mRNA and protein levels of mouse HDAC3 via qPCR and western blot, respectively. Mitochondrial DNA content and gene expression were quantified via qPCR. HDAC3 silencing at the beginning of differentiation enhanced adipocyte functionality by amplifying the expression of genes regulating differentiation, oxidative metabolism, browning and mitochondrial activity, starting from 72 h after induction of differentiation and silencing. Insulin signaling was enhanced as demonstrated by increased AKT phosphorylation following HDAC3 silencing. Mitochondrial content/density did not change, while the increased expression of the transcriptional co-activator Ppargc1b suggests the observed phenotype was related to enhanced mitochondrial activity, which was confirmed by increased maximal respiration and proton leak linked to reduced coupling efficiency. Moreover, the expression of pro-inflammatory markers increased with HDAC3 early silencing. To the contrary, no differences in terms of gene expression were found when HDAC3 silencing occurred in terminally differentiated adipocyte. Our data demonstrated that early epigenetic events mediated by class I HDAC inhibition/silencing are crucial to commit adipocyte precursors towards the above-mentioned metabolic phenotype. Moreover, our data suggest that these effects are exerted on adipocyte precursors. [ABSTRACT FROM AUTHOR]

Ghana is an important cocoa producer and exporter and this production is of high economic importance. Increasing interest in the sustainable productions of cocoa/chocolate necessitated the need to assess the environmental impacts associated with the production of different chocolate variants (extra dark (EDC), dark (DC), milk (MC) and flavoured milk (FMC) in Ghana, including the identification of environmental hotspots for improvement. The life cycle assessment tool was used following the CML_IA and CED impact assessment methods. EDC had the lowest scores for most of the impact categories while FMC was most impactful. For Global Warming Potential (GWP), EDC and FMC were estimated to be 1.61 kg CO2 eq. and 4.21 kg CO2 eq., respectively. CED ranged from 1.44 × 102 to 1.50 × 102 MJ-eq. Chocolate manufacturing phase was generally more impactful than cocoa cultivation due to high emissions from milk and sugar production. The impact scores for 100 g packaged chocolate bar were the lowest in comparison to 300 g chocolate pouches and 12.5 g packaged chocolate strips. GWP for 100 g and 12.5 g were 0.20 kg CO2 eq. and 0.39 kg CO2 eq., respectively. Comparing different destination points for the manufactured chocolate, impact scores for the international destination were similar to those recorded for local destinations. Improvement options are suggested for all phases to ensure more sustainable chocolate production and distribution. [ABSTRACT FROM AUTHOR]

In-memory computing (IMC) refers to non-von Neumann architectures where data are processed in situ within the memory by taking advantage of physical laws. Among the memory devices that have been considered for IMC, the resistive switching memory (RRAM), also known as memristor, is one of the most promising technologies due to its relatively easy integration and scaling. RRAM devices have been explored for both memory and IMC applications, such as neural network accelerators and neuromorphic processors. This work presents the status and outlook on the RRAM for analog computing, where the precision of the encoded coefficients, such as the synaptic weights of a neural network, is one of the key requirements. We show the experimental study of the cycle-to-cycle variation of set and reset processes for HfO 2 -based RRAM, which indicate that gate-controlled pulses present the least variation in conductance. Assuming a constant variation of conductance σ G , we then evaluate and compare various mapping schemes, including multilevel, binary, unary, redundant and slicing techniques. We present analytical formulas for the standard deviation of the conductance and the maximum number of bits that still satisfies a given maximum error. Finally, we discuss RRAM performance for various analog computing tasks compared to other computational memory devices. RRAM appears as one of the most promising devices in terms of scaling, accuracy and low-current operation. [ABSTRACT FROM AUTHOR]

Agricultural activities in Europe cover half of the total area of the continent and are simultaneously a cause of environmental impact and victims of the same impact. Horticultural or fruit crops are considered highly intensive and often employ many crop inputs such as fertilizers, pesticides, and various materials. Strawberry falls into this group, and it has grown in acreage and production more than others globally. The aim of this study is to compare the environmental impact of two strawberry cultivation systems in central Italy, a mulched soil tunnel and a soilless tunnel system. The method used to assess the impact is LCA, widely applied in agriculture and supported by international standards. The data used are mainly primary, related to 2018, and representative of the cultivation systems of central Italy. For impact assessment, the method selected was the CML_IA baseline version. From the results obtained, the two systems show a similar impact per kg of strawberries produced (e.g., for global warming: 0.785 kg CO2 eq for soilless, 0.778 kg CO2 eq for mulched soil tunnel). Reduced differences can be observed for the use of crop inputs (greater for the tunnel) and the use of materials and technology (greater for soilless). The mitigation measures considered concern the replacement of the packaging (excluding plastic) and the growing medium of the soilless using perlite and compost from insect breeding. [ABSTRACT FROM AUTHOR]

(1) Background: Data accuracy plays a key role in determining the model performances and the field of metabolism prediction suffers from the lack of truly reliable data. To enhance the accuracy of metabolic data, we recently proposed a manually curated database collected by a meta-analysis of the specialized literature (MetaQSAR). Here we aim to further increase data accuracy by focusing on publications reporting exhaustive metabolic trees. This selection should indeed reduce the number of false negative data. (2) Methods: A new metabolic database (MetaTREE) was thus collected and utilized to extract a dataset for metabolic data concerning glutathione conjugation (MT-dataset). After proper pre-processing, this dataset, along with the corresponding dataset extracted from MetaQSAR (MQ-dataset), was utilized to develop binary classification models using a random forest algorithm. (3) Results: The comparison of the models generated by the two collected datasets reveals the better performances reached by the MT-dataset (MCC raised from 0.63 to 0.67, sensitivity from 0.56 to 0.58). The analysis of the applicability domain also confirms that the model based on the MT-dataset shows a more robust predictive power with a larger applicability domain. (4) Conclusions: These results confirm that focusing on metabolic trees represents a convenient approach to increase data accuracy by reducing the false negative cases. The encouraging performances shown by the models developed by the MT-dataset invites to use of MetaTREE for predictive studies in the field of xenobiotic metabolism. [ABSTRACT FROM AUTHOR]

Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), particularly carboxymethyl-lysine (CML), have been largely proposed as factors involved in the establishment and progression of heart failure (HF). Despite this evidence, the current literature lacks the comprehensive identification and characterization of the plasma AGEs/ALEs involved in HF (untargeted approach). This work provides the first ex vivo high-resolution mass spectrometry (HR-MS) profiling of AGEs/ALEs occurring in human serum albumin (HSA), the most abundant protein in plasma, characterized by several nucleophilic sites and thus representing the main protein substrate for AGE/ALE formation. A set of AGE/ALE adducts in pooled HF-HSA samples was defined, and a semi-quantitative analysis was carried out in order to finally select those presenting in increased amounts in the HF samples with respect to the control condition. These adducts were statistically confirmed by monitoring their content in individual HF samples by applying a targeted approach. Selected AGEs/ALEs proved to be mostly CML derivatives on Lys residues (i.e., CML-Lys12, CML-Lys378, CML-Lys402), and one deoxy-fructosyl derivative on the Lys 389 (DFK-Lys 389). The nature of CML adducts was finally confirmed using immunological methods and in vitro production of such adducts further confirmed by mass spectrometry. [ABSTRACT FROM AUTHOR]

The 3CL-Protease appears to be a very promising medicinal target to develop anti-SARS-CoV-2 agents. The availability of resolved structures allows structure-based computational approaches to be carried out even though the lack of known inhibitors prevents a proper validation of the performed simulations. The innovative idea of the study is to exploit known inhibitors of SARS-CoV 3CL-Pro as a training set to perform and validate multiple virtual screening campaigns. Docking simulations using four different programs (Fred, Glide, LiGen, and PLANTS) were performed investigating the role of both multiple binding modes (by binding space) and multiple isomers/states (by developing the corresponding isomeric space). The computed docking scores were used to develop consensus models, which allow an in-depth comparison of the resulting performances. On average, the reached performances revealed the different sensitivity to isomeric differences and multiple binding modes between the four docking engines. In detail, Glide and LiGen are the tools that best benefit from isomeric and binding space, respectively, while Fred is the most insensitive program. The obtained results emphasize the fruitful role of combining various docking tools to optimize the predictive performances. Taken together, the performed simulations allowed the rational development of highly performing virtual screening workflows, which could be further optimized by considering different 3CL-Pro structures and, more importantly, by including true SARS-CoV-2 3CL-Pro inhibitors (as learning set) when available. [ABSTRACT FROM AUTHOR]

A computational screening for natural compounds suitable to bind the AKT protein has been performed after the generation of a pharmacophore model based on the experimental structure of AKT1 complexed with IQO, a well-known inhibitor. The compounds resulted as being most suitable from the screening have been further investigated by molecular docking, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis and toxicity profiles. Two compounds selected at the end of the computational analysis, i.e., ZINC2429155 (also named STL1) and ZINC1447881 (also named AC1), have been tested in an experimental assay, together with IQO as a positive control and quercetin as a negative control. Only STL1 clearly inhibited AKT activation negatively modulating the PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

COASY protein-associated neurodegeneration (CoPAN) is a rare but devastating genetic autosomal recessive disorder of inborn error of CoA metabolism, which shares with pantothenate kinase-associated neurodegeneration (PKAN) similar features, such as dystonia, parkinsonian traits, cognitive impairment, axonal neuropathy, and brain iron accumulation. These two disorders are part of the big group of neurodegenerations with brain iron accumulation (NBIA) for which no effective treatment is available at the moment. To date, the lack of a mammalian model, fully recapitulating the human disorder, has prevented the elucidation of pathogenesis and the development of therapeutic approaches. To gain new insights into the mechanisms linking CoA metabolism, iron dyshomeostasis, and neurodegeneration, we generated and characterized the first CoPAN disease mammalian model. Since CoA is a crucial metabolite, constitutive ablation of the Coasy gene is incompatible with life. On the contrary, a conditional neuronal-specific Coasy knock-out mouse model consistently developed a severe early onset neurological phenotype characterized by sensorimotor defects and dystonia-like movements, leading to premature death. For the first time, we highlighted defective brain iron homeostasis, elevation of iron, calcium, and magnesium, together with mitochondrial dysfunction. Surprisingly, total brain CoA levels were unchanged, and no signs of neurodegeneration were present. [ABSTRACT FROM AUTHOR]