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Biodegradable polymers and bioceramics give rise to composite structures that serve as scaffolds to promote tissue regeneration. The current research explores the preparation of biodegradable filaments for additive manufacturing. Bioresorbable segmented poly(ester urethanes) (SPEUs) are easily printable elastomers but lack bioactivity and present low elastic modulus, making them unsuitable for applications such as bone tissue engineering. Strategies such as blending and composite filament production still constitute an important challenge in addressing SPEU limitations. In this work, SPEU-poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) blends and SPEU-PHBV-Bioglass 45S5® (BG) composite materials were processed into filaments and 3D structures. A comprehensive characterization of their morphology and thermal and mechanical properties is presented. The production of 3D structures based on SPEU-PHBV with excellent dimensional precision was achieved. Although SPEU-PHBV-BG printed structures showed some defects associated with the printing process, the physicochemical, thermal, and mechanical properties of these materials hold promise. The blend composition, BG content and particle size, processing parameters, and blending techniques were carefully managed to ensure that the mechanical behavior of the material remained under control. The incorporation of PHBV in SPEU-PHBV at 70:30 w/w and BG (5 wt%) acted as reinforcement, enhancing both the elastic modulus of the filaments and the compressive mechanical behavior of the 3D matrices. The compressive stress of the printed scaffold was found to be 1.48 ± 0.13 MPa, which is optimal for tissues such as human proximal tibial trabecular bone. Therefore, these materials show potential for use in the design and manufacture of customized structures for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Objectives: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has gained a primary role in prostate cancer (PCa) imaging, overcoming conventional imaging and prostate-specific antigen (PSA) serum levels, and has recently emerged as a promising technique for monitoring therapy response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with novel hormonal therapy, taxanes, and radioligand therapy (RLT). In this review, we aim to provide an overview of the most relevant aspects under study and future prospects related to the prognostic role of PSMA PET/CT in mCRPC. Methods: A systematic literature search was performed in the following databases: MEDLINE, PubMed, and EMBASE databases. The study focused exclusively on English-language studies, excluding papers not pertinent to the topic. Results: PSMA PET imaging offers a higher sensitivity and specificity than conventional imaging and provides accurate staging and efficient diagnosis of distant metastases. The data presented herein highlight the usefulness of PET in risk stratification, with a prognostic potential that can have a significant impact on clinical practice. Several prospective trials are ongoing and will shortly provide more evidence supporting the prognostic potential of PET PSMA data in this clinical scenario. Conclusions: Current evidence proves the prognostic role of PSMA PET/CT in different settings, with raising relevance also in the context of mCRPC. [ABSTRACT FROM AUTHOR]

Parasitic otitis is an inflammatory process that can affect the external to internal cattle ear, causing discomfort in animals, impairing performance, and even leading to animal death. The infection was initially associated with nematodes of the Rhabditis genus in tropical and subtropical regions. Currently, the nematode species described as associated with bovine otitis are Metarhabditis costai, Metarhabditis freitasi, and, more recently, M. blumi. It is worth highlighting that there is still a lack of robust information regarding the morphological details, ultrastructural aspects, and molecular biology data of these species. The Metarhabditis genus is composed of seven species and two more have recently been added. The objective of this study is to update the morphological data using advanced microscopy techniques to emphasize and clarify the main morphological differences between three species of Metarhabditis currently associated with parasitic otitis. Samples of inflammatory exudate were collected from four adult female Gir cattle (Bos taurus indicus) on a farm in Itabira, Minas Gerais state, Brazil. Specimens were analyzed using light microscopy and scanning electron microscopy. Two species, M. costai and M. freitasi, were morphologically identified, consistent with previous reports. Scanning electron microscopy revealed new structural characteristics of the nematode species involved in parasitic otitis compared with M. blumi obtained from the CGC Center. Significant differences were observed in the male posterior region, bursa, and tail. Molecular analysis was conducted to differentiate these three species, and it was observed that the species first associated with otitis formed distinct clusters compared to M. blumi. However, it is important to note that further studies are needed to genetically characterize species of the Metarhabditis genus. [ABSTRACT FROM AUTHOR]

As climate change and decreasing precipitation worsen water scarcity, understanding farmers' willingness to reduce water usage is crucial. This study examines this issue in the Aosta Valley, a region facing unique challenges due to its mountainous terrain and high water management costs. The aim is to evaluate farmers' willingness to reduce water usage and the economic incentives needed to encourage water-saving strategies. To gather the data, 100 farmers participated in a survey that included a discrete choice experiment. The findings revealed that 75% of farmers were unwilling to reduce their water usage even with proposed monetary compensation (EUR 100–120 per hectare per year). On average, the additional compensation farmers would accept for a 10% reduction in water usage was estimated at EUR 360 per hectare per year. This high compensation demand suggests a disconnect between individual desires and economic feasibility. The key reasons for their reluctance included the belief that their current water usage is already optimized, inadequate compensation for potential economic losses and concerns about water shortage. The study highlights the need to understand the socio-cultural context when designing water management policies. Combining economic incentives with social and educational initiatives is likely more effective for promoting sustainable water practices. [ABSTRACT FROM AUTHOR]

Melanoma is one of the most aggressive forms of skin cancer, which is characterized by metastasis and poor prognosis due to the limited effectiveness of current therapies and the toxicity of conventional drugs. For this reason and in recent years, one of the most promising strategies in the treatment of this form of cancer is the use of drug delivery systems as carriers capable of conveying the therapeutic agent into the tumor microenvironment, thus preventing its degradation and improving its safety and effectiveness profiles. In the present work, microparticles based on silk fibroin and epifibroin 0039, silk-derived proteins loaded with idebenone, were created, which act as therapeutic carriers for topical use in the treatment of melanoma. The resulting particles have a spherical shape, good loading efficiency, and release capacity of idebenone. Efficacy studies have demonstrated a reduction in the proliferation of COLO-38, melanoma tumor cells, while safety tests have demonstrated that the microparticles are not cytotoxic and do not possess prosensitizing activity. Notably, transdermal release studies revealed that all particles released idebenone over more days. The analysis of the stimulatory markers of the proinflammatory process, CD54 and CD86, did not show any increase in expression, thus confirming the absence of potential prosesensitization effects of the silk fibroin-based particles. The research, therefore, found that idebenone-loaded silk protein microparticles could effectively reduce the proliferation of melanoma cells without cytotoxicity. This indicates the promise of a safe and effective treatment of melanoma. [ABSTRACT FROM AUTHOR]

The aim of this paper is to evaluate changes in Italy's competitiveness in the global wood products market, with a particular focus on wooden furniture and wood panels, both final and intermediate products of the crucial wooden furniture supply chain. The analysis is conducted through a cross-country comparison using trade flow matrices and various descriptive indices: Market Share, Trade Competitiveness Index, Balassa's Revealed Comparative Advantage Index, and the Symmetric Balassa Index. Furthermore, this study also examines intra-industry trade using the Grubel–Lloyd Index. While each index has its limitations when used individually, their combined analysis can provide a more comprehensive view. The study covers the period from 1996 to 2019, using data from FAO and COMTRADE sources. The results show that Italy maintains a significant position in the international furniture market, although this position has deteriorated over time. Conversely, Italy remains a net importer of wood panels. Trade flows have become more concentrated, with Canada and Germany still holding importance in the international market. However, Asian countries have now become the core of the commercial network. China has emerged as the leading exporting country in all product categories considered, with Vietnam and Malaysia also increasing in importance. Noteworthy progress has also been recorded by Russia and Poland in Europe. Additionally, the study discusses the implications of these findings for rural development, particularly in regions dependent on the wood-product sectors. [ABSTRACT FROM AUTHOR]

In modern agricultural production, cattle manure waste recovery is considered as a sustainable approach to agricultural waste management, reducing environmental pollution and chemical fertilizer use. This study aimed to investigate the effects of manure and digestate derived from a pilot-scale livestock waste-recycling system, in combination with a low copper concentration as a fungicide, on the physiological response of lettuce cv Rufus (Lactuca sativa L.) plants and the associated soil microbiome. A five-week microcosm experiment was conducted in a greenhouse under environmental conditions. Lettuce plant performance was assessed in terms of biomass, leaf area index, photosynthetic activity, chlorophyll measurements, lipid peroxidation, total phenolic content, and nutrient uptake. The results suggested that incorporating digestate into the potting soil mix significantly enhanced crop yields compared to the control and manure treatments. The soil microbial activity increased in the presence of fertilizers, improving the soil chemical and biological properties. The addition of copper negatively affected the growth and physiological performance of the lettuce plants under both the control and manure-treated conditions, except for those grown in the presence of digestate, where copper accumulation was reduced. These findings highlight the potential of growing horticultural crops using organic fertilization through livestock waste anaerobic digestate, establishing a waste-to-food recycling system. [ABSTRACT FROM AUTHOR]

'FalstaffPBR' is a pear variety released by CREA and New Plant in 2012. This study focused on the effects of various clonal rootstocks on the main productive and qualitative traits of 'FalstaffPBR' scion. The rootstocks used were 'EMC', 'EMH', and 'BA29' for quince (Cydonia oblonga) and pear 'Farold 40' (Pyrus communis). Plants were planted in 2009 with a layout that, depending on the used rootstock, varied between 60 and 120 cm on the row, according to the rootstock standard planting system, and 350 cm between rows. The average yield calculated in the trail field in the 4 years of production (2014–2017) was over 22.7 tons ha−1 on 'BA29', 22.8 tons ha−1 on 'EMH', 16.3 tons ha−1 on 'Farold 40', and 18.4 on 'EMC'. Fruits of the plants grafted on 'Farold 40' always had a medium-to-high size, while fruits produced by the plants grafted onto 'BA29' have been larger in size since the first years of production. The plants grafted onto 'EMH' produced fruits with the highest percentage of red overcolor. The 'EMH' rootstock is optimal for 'FalstaffPBR' as it gives the plant an intermediate vigor between 'BA29' and 'EMC', and a good yield per hectare from the first planting years; the average fruit size is excellent. [ABSTRACT FROM AUTHOR]

The Industrial Internet of Things (IIoT), which integrates sensors into the manufacturing system, provides new paradigms and technologies to industry. The massive acquisition of data, in an industrial context, brings with it a number of challenges to guarantee its quality and reliability, and to ensure that the results of data analysis and modelling are accurate, reliable, and reflect the real phenomena being studied. Common problems encountered with real industrial databases are missing data, outliers, anomalies, unbalanced classes, and non-exhaustive historical data. Unlike papers present in the literature that respond to those problems in a dissociated way, the work performed in this article aims to address all these problems at once. A comprehensive framework for data flow encompassing data acquisition, preprocessing, and machine class classification is proposed. The challenges of missing data, outliers, and anomalies are addressed with critical and novel class outliers distinguished. The study also tackles unbalanced class classification and evaluates the impact of missing data on classification accuracy. Several machine learning models for the operating state classification are implemented. The study also compares the performance of the proposed framework with two existing methods: the Histogram Gradient Boosting Classifier and the Extreme Gradient Boosting classifier. It is shown that using "hard voting" ensemble learning methods to combine several classifiers makes the final classifier more robust to missing data. An application is carried out on data from a real industrial dataset. This research contributes to narrowing the theory–practice gap in leveraging IIoT technologies, offering practical insights into data analytics implementation in real industrial scenarios. [ABSTRACT FROM AUTHOR]

Antibiotics (ABs) have made it possible to treat bacterial infections, which were in the past untreatable and consequently fatal. Regrettably, their use and abuse among humans and livestock led to antibiotic resistance, which has made them ineffective in many cases. The spread of antibiotic resistance genes (ARGs) and bacteria is not limited to nosocomial environments, but also involves water and soil ecosystems. The environmental presence of ABs and ARGs is a hot topic, and their direct and indirect effects, are still not well known or clarified. A particular concern is the presence of antibiotics in agroecosystems due to the application of agro-zootechnical waste (e.g., manure and biosolids), which can introduce antibiotic residues and ARGs to soils. This review provides an insight of recent findings of AB direct and indirect effects on terrestrial organisms, focusing on plant and invertebrates. Possible changing in viability and organism growth, AB bioaccumulation, and shifts in associated microbiome composition are reported. Oxidative stress responses of plants (such as reactive oxygen species production) to antibiotics are also described. [ABSTRACT FROM AUTHOR]

The purpose of this systematic review was to investigate the diagnostic accuracy of [18F]FDG PET/CT and breast MRI for primary breast cancer (BC) response assessment after neoadjuvant chemotherapy (NAC) and to evaluate future perspectives in this setting. We performed a critical review using three bibliographic databases (i.e., PubMed, Scopus, and Web of Science) for articles published up to the 6 June 2023, starting from 2012. The Quality Assessment of Diagnosis Accuracy Study (QUADAS-2) tool was adopted to evaluate the risk of bias. A total of 76 studies were identified and screened, while 14 articles were included in our systematic review after a full-text assessment. The total number of patients included was 842. Eight out of fourteen studies (57.1%) were prospective, while all except one study were conducted in a single center. In the majority of the included studies (71.4%), 3.0 Tesla (T) MRI scans were adopted. Three out of fourteen studies (21.4%) used both 1.5 and 3.0 T MRI and only two used 1.5 T. [18F]FDG was the radiotracer used in every study included. All patients accepted surgical treatment after NAC and each study used pathological complete response (pCR) as the reference standard. Some of the studies have demonstrated the superiority of [18F]FDG PET/CT, while others proved that MRI was superior to PET/CT. Recent studies indicate that PET/CT has a better specificity, while MRI has a superior sensitivity for assessing pCR in BC patients after NAC. The complementary value of the combined use of these modalities represents probably the most important tool to improve diagnostic performance in this setting. Overall, larger prospective studies, possibly randomized, are needed, hopefully evaluating PET/MR and allowing for new tools, such as radiomic parameters, to find a proper place in the setting of BC patients undergoing NAC. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) developed by microorganisms is considered one of the most critical public health issues worldwide. This problem is affecting the lives of millions of people and needs to be addressed promptly. Mainly, antibiotics are the substances that contribute to AMR in various strains of bacteria and other microorganisms, leading to infectious diseases that cannot be effectively treated. To avoid the use of antibiotics and similar drugs, several approaches have gained attention in the fields of materials science and engineering as well as pharmaceutics over the past five years. Our focus lies on the design and manufacture of polymeric-based materials capable of incorporating antimicrobial agents excluding the aforementioned substances. In this sense, two of the emerging techniques for materials fabrication, namely, electrospinning and 3D printing, have gained significant attraction. In this article, we provide a summary of the most important findings that contribute to the development of antimicrobial systems using these technologies to incorporate various types of nanomaterials, organic molecules, or natural compounds with the required property. Furthermore, we discuss and consider the challenges that lie ahead in this research field for the coming years. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease, and the currently available techniques for its detection are either invasive or less sensitive. To overcome this limitation, we present here a multiplexed point-of-care test that combines systemic inflammatory response biomarkers, standard laboratory tests, and nanoparticle-based blood tests. This test provides a "risk score" for each individual under investigation, allowing clinicians to distinguish between PDAC patients and healthy subjects accurately and to determine the optimal diagnostic and therapeutic care pathway for each patient. As a result, this work may help advance progress in the early detection of PDAC and contribute to the development of screening programs for high-risk populations. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease, for which mortality closely parallels incidence. So far, the available techniques for PDAC detection are either too invasive or not sensitive enough. To overcome this limitation, here we present a multiplexed point-of-care test that provides a "risk score" for each subject under investigation, by combining systemic inflammatory response biomarkers, standard laboratory tests, and the most recent nanoparticle-enabled blood (NEB) tests. The former parameters are routinely evaluated in clinical practice, whereas NEB tests have been recently proven as promising tools to assist in PDAC diagnosis. Our results revealed that PDAC patients and healthy subjects can be distinguished accurately (i.e., 88.9% specificity, 93.6% sensitivity) by the presented multiplexed point-of-care test, in a quick, non-invasive, and highly cost-efficient way. Furthermore, the test allows for the definition of a "risk threshold", which can help clinicians to trace the optimal diagnostic and therapeutic care pathway for each patient. For these reasons, we envision that this work may accelerate progress in the early detection of PDAC and contribute to the design of screening programs for high-risk populations. [ABSTRACT FROM AUTHOR]

Natural Killer (NK) cells are innate cytotoxic lymphoid cells that play a crucial role in cancer immunosurveillance. NKG2D is an activating receptor that binds to MIC and ULBP molecules typically induced on damaged, transformed, or infected cells. The secretion of NKG2D ligands (NKG2DLs) through protease-mediated cleavage or in an extracellular vesicle (EV) is a mode to control their cell surface expression and a mechanism used by cancer cells to evade NKG2D-mediated immunosurveillance. EVs are emerging as important players in mediating cell-to-cell communication due to their ability to transfer biological material to acceptor cells. Herein, we investigated the spreading of NKG2DLs of both MIC and ULBP molecules through the EV-mediated cross-dressing on multiple myeloma (MM) cells. We focused our attention on two MICA allelic variants, namely MICA*008 and MICA*019, representing the prototype of short and long MICA alleles, respectively, and on ULBP-1, ULBP-2, and ULBP-3. Our findings demonstrate that both ULBP and MICA ligands can be acquired from tumor cells through EVs enhancing NK cell recognition and killing. Moreover, besides MICA, EVs expressing ULBP-1 but not ULBP-2 and 3 were detected in bone marrow aspirates derived from a cohort of MM patients. Our findings shed light on the role of EV-associated MICA allelic variants and ULBP molecules in the modulation of NKG2D-mediated NK cell immunosurveillance in the tumor microenvironment. Moreover, the EV-mediated transfer of NKG2DLs could suggest novel therapeutic approaches based on the usage of engineered nanoparticles aimed at increasing cancer cell immunogenicity. [ABSTRACT FROM AUTHOR]

Electroactive bacteria (EAB) are natural microorganisms (mainly Bacteria and Archaea) living in various habitats (e.g., water, soil, sediment), including extreme ones, which can interact electrically each other and/or with their extracellular environments. There has been an increased interest in recent years in EAB because they can generate an electrical current in microbial fuel cells (MFCs). MFCs rely on microorganisms able to oxidize organic matter and transfer electrons to an anode. The latter electrons flow, through an external circuit, to a cathode where they react with protons and oxygen. Any source of biodegradable organic matter can be used by EAB for power generation. The plasticity of electroactive bacteria in exploiting different carbon sources makes MFCs a green technology for renewable bioelectricity generation from wastewater rich in organic carbon. This paper reports the most recent applications of this promising technology for water, wastewater, soil, and sediment recovery. The performance of MFCs in terms of electrical measurements (e.g., electric power), the extracellular electron transfer mechanisms by EAB, and MFC studies aimed at heavy metal and organic contaminant bioremediationF are all described and discussed. [ABSTRACT FROM AUTHOR]

In this work, we compared breadsticks (known as Treccine) flavoured with onions and olives and prepared with olive pomace oil (OPO) or with extra virgin olive oil (EVOO). The effect on one-year shelf life was also studied. The following physical, chemical and sensory analyses were conducted on the breadsticks: water activity, moisture content, colour, texture and sensory analysis (appearance, colour, flavour, taste, texture and overall acceptability). For the oil extracted from the Treccine, we determined acidity, peroxide value, spectrophotometric parameters, ABTS and DPPH assay on the hydrolitic fraction, DPPH on the lipid fraction, and fatty acids. We detected a progressive deterioration in the quality of breadsticks with a decrease in shelf life after 4–6 months in relation to each studied parameter. In the analysed breadsticks, water activity was 0.342 (OPO recipe) and 0.387 (EVOO recipe) after one-year storage; in the same storage period, the moisture content was 6.34 times (OPO) and 5.32 times (EVOO) greater. Appearance and colour were the only two sensory parameters which, after 12 months, remained above or equal to five stated as the minimum quality value. In the extracted oil, Free acidity increased from 0.35 to 0.56% (OPO) and from 0.71 to 0.98% (EVOO); Peroxide value ranged between 6.10 and 102.89 meq/kg oil (OPO) and between 4.41 and 20.91 meq/kg oil (EVOO). K232 was highest in OPO (2.43–3.70) and lowest in EVOO (1.76–2.92), K268 was 1.32–1.580 (OPO recipe) and 0.570–0.640 (EVOO recipe). Treccine prepared with extra virgin olive oil showed better biological properties and longer shelf life. [ABSTRACT FROM AUTHOR]

Rotavirus (RV) is among the most common vaccine-preventable diseases in children under five years of age. Despite the severity of rotavirus pathology in early childhood, rotavirus vaccination for children admitted to the neonatal intensive care unit (NICU), who are often born preterm and with various previous illnesses, is not performed. This multicenter, 3-year project aims to evaluate the safety of RV vaccine administration within the six main neonatal intensive care units of the Sicilian Region to preterm infants. Methods: Monovalent live attenuated anti-RV vaccination (RV1) was administered from April 2018 to December 2019 to preterm infants with gestational age ≥ 28 weeks. Vaccine administrations were performed in both inpatient and outpatient hospital settings as a post-discharge follow-up (NICU setting) starting at 6 weeks of age according to the official immunization schedule. Any adverse events (expected, unexpected, and serious) were monitored from vaccine administration up to 14 days (first assessment) and 28 days (second assessment) after each of the two scheduled vaccine doses. Results: At the end of December 2019, 449 preterm infants were vaccinated with both doses of rotavirus vaccine within the six participating Sicilian NICUs. Mean gestational age in weeks was 33.1 (±3.8 SD) and the first dose of RV vaccine was administered at 55 days (±12.9 SD) on average. The mean weight at the first dose was 3388 (SD ± 903) grams. Only 0.6% and 0.2% of infants reported abdominal colic and fever above 38.5 °C in the 14 days after the first dose, respectively. Overall, 1.9% EAEs were observed at 14 days and 0.4% at 28 days after the first/second dose administration. Conclusions: Data obtained from this study confirm the safety of the monovalent rotavirus vaccine even in preterm infants with gestational age ≥ 28 weeks, presenting an opportunity to improve the vaccination offer both in Sicily and in Italy by protecting the most fragile infants who are more at risk of contracting severe rotavirus gastroenteritis and nosocomial RV infection. [ABSTRACT FROM AUTHOR]

The success of senescence-based anticancer therapies relies on their anti-proliferative power and on their ability to trigger anti-tumor immune responses. Indeed, genotoxic drug-induced senescence increases the expression of NK cell-activating ligands on multiple myeloma (MM) cells, boosting NK cell recognition and effector functions. Senescent cells undergo morphological change and context-dependent functional diversification, acquiring the ability to secrete a vast pool of molecules termed the senescence-associated secretory phenotype (SASP), which affects neighboring cells. Recently, exosomes have been recognized as SASP factors, contributing to modulating a variety of cell functions. In particular, evidence suggests a key role for exosomal microRNAs in influencing many hallmarks of cancer. Herein, we demonstrate that doxorubicin treatment of MM cells leads to the enrichment of miR-433 into exosomes, which in turn induces bystander senescence. Our analysis reveals that the establishment of the senescent phenotype on neighboring MM cells is p53- and p21-independent and is related to CDK-6 down-regulation. Notably, miR-433-dependent senescence does not induce the up-regulation of activating ligands on MM cells. Altogether, our findings highlight the possibility of miR-433-enriched exosomes to reinforce doxorubicin-mediated cellular senescence. [ABSTRACT FROM AUTHOR]

Simple Summary: Sarcomas are a group of heterogeneous diseases with a poor prognosis and scarce therapeutic options. Innovative approaches based on novel therapeutic targets are eagerly awaited. AXL, a TAM family tyrosine kinase receptor, recently emerged as an interesting target for several type of sarcomas. Here, we propose an innovative immunotherapeutic strategy based on the targeting of AXL, using a first-in-class Pronectin™-based Bispecific T-Cell Engager (pAXL×CD3ε) for the treatment of sarcomas. Our results demonstrate that pAXL×CD3ε redirects T cells toward AXL-expressing sarcoma cell lines, leading a dose-dependent and T cell-mediated cytotoxicity in vitro. Moreover, pAXL×CD3ε inhibits the in vivo growth of human sarcoma xenografts and improves survival in immunocompromised mice, thus representing a new-generation strategy for the treatment of a still-incurable disease. Sarcomas are heterogeneous malignancies with limited therapeutic options and a poor prognosis. We developed an innovative immunotherapeutic agent, a first-in-class Pronectin™-based Bispecific T-Cell Engager (pAXL×CD3ε), for the targeting of AXL, a TAM family tyrosine kinase receptor highly expressed in sarcomas. AXL expression was first analyzed by flow cytometry, qRT-PCR, and Western blot on a panel of sarcoma cell lines. The T-cell-mediated pAXL×CD3ε cytotoxicity against sarcoma cells was investigated by flow cytometry, luminescence assay, and fluorescent microscopy imaging. The activation and degranulation of T cells induced by pAXL×CD3ε were evaluated by flow cytometry. The antitumor activity induced by pAXL×CD3ε in combination with trabectedin was also investigated. In vivo activity studies of pAXL×CD3ε were performed in immunocompromised mice (NSG), engrafted with human sarcoma cells and reconstituted with human peripheral blood mononuclear cells from healthy donors. Most sarcoma cells showed high expression of AXL. pAXL×CD3ε triggered T-lymphocyte activation and induced dose-dependent T-cell-mediated cytotoxicity. The combination of pAXL×CD3ε with trabectedin increased cytotoxicity. pAXL×CD3ε inhibited the in vivo growth of human sarcoma xenografts, increasing the survival of treated mice. Our data demonstrate the antitumor efficacy of pAXL×CD3ε against sarcoma cells, providing a translational framework for the clinical development of pAXL×CD3ε in the treatment of human sarcomas, aggressive and still-incurable malignancies. [ABSTRACT FROM AUTHOR]

(1) Background: The pressure that agricultural systems' intensive management exerts on the environment concerns society. For this reason, the demand for sustainable foods is growing in the market. This study investigated consumers' Willingness To Pay (WTP) for dry semolina pasta produced with raw materials from more diversified agricultural systems and which factors influence this choice. (2) Methods: The data, collected through a contingent valuation exercise, involved 185 Italian consumers. Through a Tobit model, the drivers influencing the WTP were selected. A latent class cluster analysis determined four different groups of consumers. (3) Results: The data highlighted a real social demand for sustainability. Consumers recognize a higher WTP for sustainable pasta. This value is influenced by drivers such as purchasing habits, personal characteristics, and environmental attitudes. (4) Conclusions: This work offers an approach, both from a market and political point of view, to how this higher potential WTP could be identified and redistributed among the value chain actors by structuring both marketing strategies for the different types of consumers and political tools able to help agri-food chains towards sustainability transition. [ABSTRACT FROM AUTHOR]

Background: in recent years, the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) has emerged as a reliable diagnostic tool in a wide variety of pathological conditions. This review aims to collect and review PET criteria developed for interpretation and treatment response assessment in cases of non-[18F]fluorodeoxyglucose ([18F]FDG) imaging in oncology. Methods: A wide literature search of the PubMed/MEDLINE, Scopus and Google Scholar databases was made to find relevant published articles about non-[18F]FDG PET response criteria. Results: The comprehensive computer literature search revealed 183 articles. On reviewing the titles and abstracts, 149 articles were excluded because the reported data were not within the field of interest. Finally, 34 articles were selected and retrieved in full-text versions. Conclusions: available criteria are a promising tool for the interpretation of non-FDG PET scans, but also to assess the response to therapy and therefore to predict the prognosis. However, oriented clinical trials are needed to clearly evaluate their impact on patient management. [ABSTRACT FROM AUTHOR]

Background: this study aims to explore the prognostic and predictive role of volumetric parameters on [68Ga]Ga-DOTATOC PET/CT in neuroendocrine tumors (NET) patients treated with peptide receptor radionuclide therapy (PRRT). Methods: We retrospectively evaluated 39 NET patients (21 male, 18 female; mean age 60.7 y) within the FENET-2016 trial (CTiD:NCT04790708). PRRT was proposed with [177Lu]Lu-DOTATOC alone or combined with [90Y]Y-DOTATOC. [68Ga]Ga-DOTATOC PET/CT was performed at baseline and 3 months after PRRT. For each PET/CT, we calculated SUVmax, SUVmean, somatostatin receptor expressing tumor volume (SRETV), and total lesion somatostatin receptor expression (TLSRE), as well as their percentage of changes (Δ), both for liver (_L) and for total tumor burden (_WB). Early clinical response (3 months after PRRT) and PFS were evaluated according to RECIST 1.1 and institutional NET board. Results: Early clinical response identified 9 partial response (PR), 25 stable disease (SD), and 5 progressive disease (PD). Post-SRETV_WB and ΔSRETV_WB were progressively increased among response groups (p = 0.02 and p = 0.03, respectively). Likewise, median post-SRETV_L was significantly higher in PD patients (p = 0.03). SUVmax and TLSRE did not correlate with early clinical response. Median PFS was 31 months. Patients with ΔSRETV_WB lower than −4.17% as well as those with post-SRETV_WB lower than 34.8 cm3 showed a longer PFS (p = 0.006 and p = 0.06, respectively). Finally, multivariate analysis identified ΔSRETV_WB as an independent predictor for PFS. Conclusions: our results could strengthen the importance of evaluating the burden of disease on [68Ga]Ga-DOTATOC PET/CT in NET patients treated with PRRT. [ABSTRACT FROM AUTHOR]

Black rot caused by the Gram-negative bacterial pathogen Xanthomonas campestris pv. campestris (Xcc) is considered one of the most destructive diseases affecting crucifers. Xcc is a seedborne pathogen able to infect the host at any growth stage. The management of the pathogen mainly relies on the use of copper-based products with possible negative effects on human health and the environment. Searching for protection alternatives is crucial for achieving a sustainable management of Xcc. Trichoderma spp. has been largely used as a biocontrol agent against several phytopathogens. Among Trichoderma species, Trichoderma longibrachiatum produces the peptaibol trichogin GA IV, a secondary metabolite with antimicrobial activity against Gram-positive bacteria, as well as filamentous and yeast-like fungi. In this work, we tested, at micromolar concentrations, 25 synthetic analogs of the peptaibol trichogin GA IV for their bacteriostatic and bactericidal activity toward the bacterium Xcc. One of the most effective peptides (4r) was also tested against the Gram-negative bacteria Xanthomonas arboricola, Pseudomonas corrugata, Pseudomonas savastanoi pv. savastanoi, Agrobacterium tumefaciens, Ralstonia solanacearum, and Erwinia carotovora subsp. carotovora, as well as the Gram-positive bacterium Bacillus subtilis. The peptide 4r reduced black rot symptoms on cauliflower plants when administered both before and 24 h after inoculation with Xcc. The cytotoxic activity of the peptide 4r was also evaluated towards suspensions of tobacco cells by Evans Blue assay. [ABSTRACT FROM AUTHOR]

Hydrocarbons occur in fossil fuels such as crude oil and consist mainly of hydrogen and carbon. Although they are natural chemicals, crude oil refining results in commercial products with new physico-chemical properties, which can increase their complexity and toxicity, and hamper their degradation. The presence of biodiverse natural microbial communities is a prerequisite for an effective homeostatic response to the various hydrocarbons, that contaminate ecosystems. However, their removal depends on the compartment contaminated (water, sediment, soil), their molecular weight, and their toxicity not hampering microbial activity. This paper reports different bacterial species involved in the biodegradation of aliphatic and aromatic hydrocarbons. Hydrocarbon contamination is generally due to the co-presence of a mixture of these chemicals, and their removal from the environment cannot rely on only a single species but generally requires bacterial consortia. Versatile bacterial metabolism relies on specific genes encoding the key enzymes involved in the peripheral metabolic and central metabolic pathways for degrading aliphatic and polycyclic aromatic hydrocarbons. Although microbial metabolism can have the potential for natural attenuation of these contaminants, hydrocarbon bioremediation, through biostimulation (e.g., use of surfactants, plants, earthworms, and nanoparticles) and bioaugmentation, can be a valid tool for removing them from actually contaminated soil, freshwater, groundwater, and seawater. [ABSTRACT FROM AUTHOR]

Simple Summary: In this paper we systematically evaluate the evidence regarding the role of [68Ga]PSMA PET/CT for clinical suspicions of prostate cancer in patients with or without previous negative biopsy. A critical review of PubMed and Web of Science according to the PRISMA statement was conducted. Eighteen publications were selected for inclusion in the analysis. In 8 articles, there was a direct comparison with mpMRI. [68Ga]PSMA PET/CT resulted more accurate in identifying primary prostate cancer with PSA values between 4 and 20 ng/mL than mpMRI. Moreover, its use combined with MRI improved sensitivity for csPCa detection, thus potentially avoiding unnecessary biopsies. Overall, [68Ga]PSMA PET/CT resulted a promising technique in patients with clinical suspicion of PCa and precedent negative biopsy or contraindications to MRI. The purpose of the study is to systematically evaluate the evidence regarding the role of [68Ga]PSMA PET/CT for clinical suspicions of prostate cancer in patients with or without previous negative biopsy. We performed a critical review of PubMed and Web of Science according to the PRISMA statement. Eighteen publications were selected for inclusion in this analysis. QUADAS-2 evaluation was adopted for quality analyses. [68Ga]PSMA-11 was the radiotracer of choice in 15 studies, while [68Ga]PSMA-617 was used in another 3. In 8 articles, there was a direct comparison with mpMRI. The total number of patients included was 1379, ranging from 15 to 291, with a median age of 64 years (range: 42–90). The median baseline PSA value was 12.9 ng/mL, ranging from 0.85 to 4156 ng/mL. Some studies evaluated the PSMA uptake comparing the SUVmax of suspicious lesions with the SUVmax of the normal biodistribution to find out optimal cut-off points. In addition, some studies suggested a significant association between PSA levels, PSA density, and [68Ga]PSMA PET/CT finding. [68Ga]PSMA PET/CT seems to be more accurate in identifying primary prostate cancer with PSA values between 4 and 20 ng/mL than mpMRI. Moreover, in some trials, the combination of PSMA PET/CT and MRI improved the NPV in the detection of clinically significant prostate cancer (csPCa) than MRI alone. Our findings are limited by the small numbers of studies and patient heterogeneity. [68Ga]PSMA PET/CT is a promising technique in patients with clinical suspicion of PCa and precedent negative biopsy or contraindications to MRI. Furthermore, its use combined with MRI improves sensitivity for csPCa detection and can avoid unnecessary biopsies. [ABSTRACT FROM AUTHOR]

[18F]F-FDG (FDG) PET is emerging as a relevant diagnostic and prognostic tool in neuroendocrine neoplasms (NENs), as a simultaneous decrease in [68Ga]Ga-DOTA peptides and increase in FDG uptake (the "flip-flop" phenomenon) occurs during the natural history of these tumors. The aim of this study was to evaluate the variations on FDG PET in NEN patients treated with two different schemes of radioligand therapy (RLT) and to correlate them with clinical–pathologic variables. A prospective evaluation of 108 lesions in 56 patients (33 males and 23 females; median age, 64.5 years) affected by NENs of various primary origins (28 pancreatic, 13 gastrointestinal, 9 bronchial, 6 unknown primary (CUP-NENs) and 1 pheochromocytoma) and grades (median Ki-67 = 9%) was performed. The patients were treated with RLT within the phase II clinical trial FENET-2016 (CTID: NCT04790708). RLT was offered for 32 patients with the MONO scheme (five cycles of [177Lu]Lu-DOTATOC) and for 24 with the DUO scheme (three cycles of [177Lu]Lu-DOTATOC alternated with two cycles of [90Y]Y-DOTATOC). Variations in terms of the ΔSUVmax of a maximum of three target lesions per patient (58 for MONO and 50 for DUO RLT) were assessed between baseline and 3 months post-RLT FDG PET. In patients with negative baseline FDG PET, the three most relevant lesions on [68Ga]Ga-DOTA-peptide PET were assessed and matched on post-RLT FDG PET, to check for any possible changes in FDG avidity. Thirty-five patients (62.5%) had at least one pathological FDG uptake at the baseline scans, but the number was reduced to 29 (52%) after RLT. In the patients treated with DUO-scheme RLT, 20 out of 50 lesions were FDG positive before therapy, whereas only 14 were confirmed after RLT (p = 0.03). Moreover, none of the 30 FDG-negative lesions showed an increased FDG uptake after RLT. The lesions of patients with pancreatic and CUP-NENs treated with the DUO scheme demonstrated a significant reduction in ΔSUVmax in comparison to those treated with MONO RLT (p = 0.03 and p = 0.04, respectively). Moreover, we found a mild positive correlation between the grading and ΔSUVmax in patients treated with the MONO scheme (r = 0.39, p < 0.02), while no evidence was detected for patients treated with the DUO scheme. Our results suggest that RLT, mostly with the DUO scheme, could be effective in changing NEN lesions' glycometabolism, in particular, in patients affected by pancreatic and CUP-NENs, regardless of their Ki-67 index. Probably, associating [90Y]Y-labelled peptides, which have high energy emission and a crossfire effect, and [177Lu]Lu ones, characterized by a longer half-life and a safer profile for organs at risk, might represent a valid option in FDG-positive NENs addressed to RLT. Further studies are needed to validate our preliminary findings. In our opinion, FDG PET/CT should represent a potent tool for fully assessing a patient's disease characteristics, both before and after RLT. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, a multiplexed strategy based on the combination of a nanoparticle-enabled blood test and serum levels of acute-phase proteins proved to be able to distinguish pancreatic cancer patients from healthy controls with a good and sex-dependent prediction ability. This study suggests a possible role of acute-phase proteins as pancreatic cancer biomarkers and paves the way for the development of multiplexed technologies for early cancer detection. The development of new tools for the early detection of pancreatic ductal adenocarcinoma (PDAC) represents an area of intense research. Recently, the concept has emerged that multiplexed detection of different signatures from a single biospecimen (e.g., saliva, blood, etc.) may exhibit better diagnostic capability than single biomarkers. In this work, we develop a multiplexed strategy for detecting PDAC by combining characterization of the nanoparticle (NP)-protein corona, i.e., the protein layer that surrounds NPs upon exposure to biological fluids and circulating levels of plasma proteins belonging to the acute phase protein (APPs) family. As a first step, we developed a nanoparticle-enabled blood (NEB) test that employed 600 nm graphene oxide (GO) nanosheets and human plasma (HP) (5% vol/vol) to produce 75 personalized protein coronas (25 from healthy subjects and 50 from PDAC patients). Isolation and characterization of protein corona patterns by 1-dimensional (1D) SDS-PAGE identified significant differences in the abundance of low-molecular-weight corona proteins (20–30 kDa) between healthy subjects and PDAC patients. Coupling the outcomes of the NEB test with the circulating levels of alpha 2 globulins, we detected PDAC with a global capacity of 83.3%. Notably, a version of the multiplexed detection strategy run on sex-disaggregated data provided substantially better classification accuracy for men (93.1% vs. 77.8%). Nanoliquid chromatography tandem mass spectrometry (nano-LC MS/MS) experiments allowed to correlate PDAC with an altered enrichment of Apolipoprotein A-I, Apolipoprotein D, Complement factor D, Alpha-1-antichymotrypsin and Alpha-1-antitrypsin in the personalized protein corona. Moreover, other significant changes in the protein corona of PDAC patients were found. Overall, the developed multiplexed strategy is a valid tool for PDAC detection and paves the way for the identification of new potential PDAC biomarkers. [ABSTRACT FROM AUTHOR]

Microtubule-targeting agents (MTAs) are effective drugs for cancer treatment. A novel diaryl [1,2]oxazole class of compounds binding the colchicine site was synthesized as cis-restricted-combretastatin-A-4-analogue and then chemically modified to have improved solubility and a wider therapeutic index as compared to vinca alkaloids and taxanes. On these bases, a new class of tricyclic compounds, containing the [1,2]oxazole ring and an isoindole moiety, has been synthetized, among which SIX2G emerged as improved MTA. Several findings highlighted the ability of some chemotherapeutics to induce immunogenic cell death (ICD), which is defined by the cell surface translocation of Calreticulin (CALR) via dissociation of the PP1/GADD34 complex. In this regard, we computationally predicted the ability of SIX2G to induce CALR exposure by interacting with the PP1 RVxF domain. We then assessed both the potential cytotoxic and immunogenic activity of SIX2G on in vitro models of multiple myeloma (MM), which is an incurable hematological malignancy characterized by an immunosuppressive milieu. We found that the treatment with SIX2G inhibited cell viability by inducing G2/M phase cell cycle arrest and apoptosis. Moreover, we observed the increase of hallmarks of ICD such as CALR exposure, ATP release and phospho-eIF2α protein level. Through co-culture experiments with immune cells, we demonstrated the increase of (i) CD86 maturation marker on dendritic cells, (ii) CD69 activation marker on cytotoxic T cells, and (iii) phagocytosis of tumor cells following treatment with SIX2G, confirming the onset of an immunogenic cascade. In conclusion, our findings provide a framework for further development of SIX2G as a new potential anti-MM agent. [ABSTRACT FROM AUTHOR]

Some livestock farms rely on anaerobic digestion (AD) technology for manure disposal, thus obtaining energy (biogas) and fertilizer (digestate). Mixtures of antibiotics used for animal health often occur in organic waste and their possible synergistic/antagonistic effects on microorganisms involved in AD are still poorly studied. This work focuses on the effects of adding ciprofloxacin, alone (5 mg L−1 ) and in combination with sulfamethoxazole (2.5–5–10 mg L−1 ), on AD efficiency and microbial community structure. The experiment consisted of 90-day cattle manure batch tests and antibiotic removal percentages were assessed. Adding antibiotics always promoted CH4 and H2 production compared to untreated controls; however, CH4 production was lowered with the highest ciprofloxacin (CIP) concentrations. The overall results show antibiotic degradation caused by acidogenic Bacteria, and CH4 was mainly produced through the hydrogenotrophic-pathway by methanogenic Archaea. Shifts in microbial community abundance (DAPI counts) and composition (Illumina-MiSeq and FISH analyses) were observed. [ABSTRACT FROM AUTHOR]

DNA vaccination has been extensively studied as a promising strategy for tumor treatment. Despite the efforts, the therapeutic efficacy of DNA vaccines has been limited by their intrinsic poor cellular internalization. Electroporation, which is based on the application of a controlled electric field to enhance DNA penetration into cells, has been the method of choice to produce acceptable levels of gene transfer in vivo. However, this method may cause cell damage or rupture, non-specific targeting, and even degradation of pDNA. Skin irritation, muscle contractions, pain, alterations in skin structure, and irreversible cell damage have been frequently reported. To overcome these limitations, in this work, we use a microfluidic platform to generate DNA-loaded lipid nanoparticles (LNPs) which are then characterized by a combination of dynamic light scattering (DLS), synchrotron small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). Despite the clinical successes obtained by LNPs for mRNA and siRNA delivery, little is known about LNPs encapsulating bulkier DNA molecules, the clinical application of which remains challenging. For in vitro screening, LNPs were administered to human embryonic kidney 293 (HEK-293) and Chinese hamster ovary (CHO) cell lines and ranked for their transfection efficiency (TE) and cytotoxicity. The LNP formulation exhibiting the highest TE and the lowest cytotoxicity was then tested for the delivery of the DNA vaccine pVAX-hECTM targeting the human neoantigen HER2, an oncoprotein overexpressed in several cancer types. Using fluorescence-activated cell sorting (FACS), immunofluorescence assays and fluorescence confocal microscopy (FCS), we proved that pVAX-hECTM-loaded LNPs produce massive expression of the HER2 antigen on the cell membrane of HEK-293 cells. Our results provide new insights into the structure–activity relationship of DNA-loaded LNPs and pave the way for the access of this gene delivery technology to preclinical studies. [ABSTRACT FROM AUTHOR]

Percutaneous patent foramen ovale (PFO) closure by traditional, double disc occluder devices was shown to be safe for patients with PFO, and more effective than prolonged medical therapy in preventing recurrent thromboembolic events. The novel suture-mediated "deviceless" PFO closure system overcomes most of the risks and limitations associated with the traditional PFO occluders, appearing to be feasible in most interatrial septum anatomies, even if data about its long-term effectiveness and safety are still lacking. The aim of the present review was to provide to the reader the state of the art about the traditional and newer techniques of PFO closure, focusing both on the procedural aspects and on the pivotal role of transesophageal echocardiography (TEE) in patient's selection, peri-procedural guidance, and post-interventional follow-up. [ABSTRACT FROM AUTHOR]

Magnetic levitation (MagLev) has recently emerged as a powerful method to develop diagnostic technologies based on the exploitation of the nanoparticle (NP)–protein corona. However, experimental procedures improving the robustness, reproducibility, and accuracy of this technology are largely unexplored. To contribute to filling this gap, here, we investigated the effect of total flow rate (TFR) and flow rate ratio (FRR) on the MagLev patterns of microfluidic-generated graphene oxide (GO)–protein complexes using bulk mixing of GO and human plasma (HP) as a reference. Levitating and precipitating fractions of GO-HP samples were characterized in terms of atomic force microscopy (AFM), bicinchoninic acid assay (BCA), and one-dimensional sodium dodecyl sulfate–polyacrylamide gel electrophoresis (1D SDS-PAGE), and nanoliquid chromatography–tandem mass spectrometry (nano-LC-MS/MS). We identified combinations of TFR and FRR (e.g., TFR = 35 μL/min and FRR (GO:HP) = 9:1 or TFR = 3.5 μL/min and FRR (GO:HP) = 19:1), leading to MagLev patterns dominated by levitating and precipitating fractions with bulk-like features. Since a typical MagLev experiment for disease detection is based on a sequence of optimization, exploration, and validation steps, this implies that the optimization (e.g., searching for optimal NP:HP ratios) and exploration (e.g., searching for MagLev signatures) steps can be performed using samples generated by bulk mixing. When these steps are completed, the validation step, which involves using human specimens that are often available in limited amounts, can be made by highly reproducible microfluidic mixing without any ex novo optimization process. The relevance of developing diagnostic technologies based on MagLev of coronated nanomaterials is also discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and still orphan hematologic malignancy. No effective immunotherapeutic strategies are presently available for this poor prognosis disease. We here report the development and the preclinical evaluation of a novel bispecific T-cell engager (BTCE) that simultaneously targets CD1a and CD3ε (CD1a x CD3ε), therefore recruiting T cells against T-ALL cells. We demonstrate that this CD1a x CD3ε BTCE induces activation, proliferation, and cytokine release by T cells in co-cultures with CD1a expressing T-ALL cells, resulting in a concentration-dependent killing of leukemic cells in vitro. Moreover, CD1a x CD3ε BTCE inhibits the in vivo growth of human T-ALL xenografts and improves survival of immunocompromised mice reconstituted with human PBMC from healthy donors. We believe that this BTCE is suitable for clinical development for the treatment of CD1a-expressing T-ALL patients. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy burdened by poor prognosis. While huge progress of immunotherapy has recently improved the outcome of B-cell malignancies, the lack of tumor-restricted T-cell antigens still hampers its progress in T-ALL. Therefore, innovative immunotherapeutic agents are eagerly awaited. To this end, we generated a novel asymmetric (2 + 1) bispecific T-cell engager (BTCE) targeting CD1a and CD3ε (CD1a x CD3ε) starting from the development of a novel mAb named UMG2. UMG2 mAb reacts against CD1a, a glycoprotein highly expressed by cortical T-ALL cells. Importantly, no UMG2 binding was found on normal T-cells. CD1a x CD3ε induced high T-cell mediated cytotoxicity against CD1a+ T-ALL cells in vitro, as demonstrated by the concentration-dependent increase of T-cell proliferation, degranulation, induction of cell surface activation markers, and secretion of pro-inflammatory cytokines. Most importantly, in a PBMC-reconstituted NGS mouse model bearing human T-ALL, CD1a x CD3ε significantly inhibited the growth of human T-ALL xenografts, translating into a significant survival advantage of treated animals. In conclusion, CD1a x CD3ε is a novel BTCE highly active against CD1a-expressing cortical-derived T-ALL cells suitable for clinical development as an effective therapeutic option for this rare and aggressive disease. [ABSTRACT FROM AUTHOR]

Generative Adversarial Networks have recently demonstrated the capability to synthesize photo-realistic real-world images. However, they still struggle to offer high controllability of the output image, even if several constraints are provided as input. In this work, we present a Recursive Text-Image-Conditioned GAN (aRTIC GAN), a novel approach for multi-conditional image generation under concurrent spatial and text constraints. It employs few line drawings and short descriptions to provide informative yet human-friendly conditioning. The proposed scenario is based on accessible constraints with high degrees of freedom: sketches are easy to draw and add strong restrictions on the generated objects, such as their orientation or main physical characteristics. Text on its side is so common and expressive that easily enforces information otherwise impossible to provide with minimal illustrations, such as objects components color, color shades, etc. Our aRTIC GAN is suitable for the sequential generation of multiple objects due to its compact design. In fact, the algorithm exploits the previously generated image in conjunction with the sketch and the text caption, resulting in a recurrent approach. We developed three network blocks to tackle the fundamental problems of catching captions' semantic meanings and of handling the trade-off between smoothing grid-pattern artifacts and visual detail preservation. Furthermore, a compact three-task discriminator (covering global, local and textual aspects) was developed to preserve a lightweight and robust architecture. Extensive experiments proved the validity of aRTIC GAN and show that the combined use of sketch and description allows us to avoid explicit object labeling. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic increased the complexity of the clinical management and pharmacological treatment of patients presenting with an Acute Coronary Syndrome (ACS). Aim: to explore the incidence and prognostic impact of in-hospital bleeding in patients presenting with ACS before and during the COVID-19 pandemic. Methods: We evaluated in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding among 2851 patients with ACS from 17 Italian centers during the first wave of the COVID-19 pandemic (i.e., March–April 2020) and in the same period in the previous two years. Results: The incidence of in-hospital TIMI major and minor bleeding was similar before and during the COVID-19 pandemic. TIMI major or minor bleeding was associated with a significant threefold increase in all-cause mortality, with a similar prognostic impact before and during the COVID-19 pandemic. Conclusions: the incidence and clinical impact of in-hospital bleeding in ACS patients was similar before and during the COVID-19 pandemic. We confirmed a significant and sizable negative prognostic impact of in-hospital bleeding in ACS patients. [ABSTRACT FROM AUTHOR]

Percutaneous coronary intervention (PCI) is one of the most common procedures performed in medicine. However, its net benefit among patients with chronic kidney disease (CKD) is less well established than in the general population. The prevalence of patients suffering from both CAD and CKD is high, and is likely to increase in the coming years. Planning the adequate management of this group of patients is crucial to improve their outcome after PCI. This starts with proper preparation before the procedure, the use of all available means to reduce contrast during the procedure, and the implementation of modern strategies such as radial access and drug-eluting stents. At the end of the procedure, personalized antithrombotic therapy for the patient's specific characteristics is advisable to account for the elevated ischemic and bleeding risk of these patients. [ABSTRACT FROM AUTHOR]

Unprecedented opportunities for early stage cancer detection have recently emerged from the characterization of the personalized protein corona (PC), i.e., the protein cloud that surrounds nanoparticles (NPs) upon exposure to a patients' bodily fluids. Most of these methods require "direct characterization" of the PC., i.e., they necessitate protein isolation, identification, and quantification. Each of these steps can introduce bias and affect reproducibility and inter-laboratory consistency of experimental data. To fulfill this gap, here we develop a nanoparticle-enabled blood (NEB) test based on the indirect characterization of the personalized PC by magnetic levitation (MagLev). The MagLev NEB test works by analyzing the levitation profiles of PC-coated graphene oxide (GO) NPs that migrate along a magnetic field gradient in a paramagnetic medium. For the test validation, we employed human plasma samples from 15 healthy individuals and 30 oncological patients affected by four cancer types, namely breast cancer, prostate cancer, colorectal cancer, and pancreatic ductal adenocarcinoma (PDAC). Over the last 15 years prostate cancer, colorectal cancer, and PDAC have continuously been the second, third, and fourth leading sites of cancer-related deaths in men, while breast cancer, colorectal cancer, and PDAC are the second, third and fourth leading sites for women. This proof-of-concept investigation shows that the sensitivity and specificity of the MagLev NEB test depend on the cancer type, with the global classification accuracy ranging from 70% for prostate cancer to an impressive 93.3% for PDAC. We also discuss how this tool could benefit from several tunable parameters (e.g., the intensity of magnetic field gradient, NP type, exposure conditions, etc.) that can be modulated to optimize the detection of different cancer types with high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Crystal scintillators and in particular inorganic scintillators play an important role in the investigation of Dark Matter (DM) and other rare processes. The investigation of a DM signature, as the annual modulation, or the directionality technique requires the use of highly radiopure detectors able to explore the very low energy region maintaining a high stability of the running conditions. In this paper, the cases of NaI(Tl), ZnWO4 and SrI2(Eu) crystal scintillators are described in the framework of our activities at the Gran Sasso National Laboratory of the INFN. Their role, the obtained results in DM investigation, as well as their potential and perspectives for the future are reviewed. [ABSTRACT FROM AUTHOR]

This work proposes to exploit functional redundancy as a tool to enhance the energy efficiency of a robotic system. In a functionally redundant system, i.e., one in which the number of degrees of freedom required to complete the task is smaller than the number of available degrees of freedom, the motion of the extra degrees of freedom can be tailored to enhance a performance metric. This work showcases a method that can be used to effectively enhance the energy efficiency through motion design, using a detailed dynamic model of the UR5 serial robot arm. The method is based on an optimization of the motion profile, using a parametrized description of the end-effector orientation: the results showcase an increased efficiency that allows energy savings up to 20.8%, according to the energy consumption results according to the electro-mechanical dynamic model of the robot. [ABSTRACT FROM AUTHOR]

This study evaluated the possibility of adopting haymaking farming machinery in giant reed (Arundo donax L.) harvesting. The test shows the technical and energy aspects of mechanical harvesting using only one specific machine, a shredding machine, designed and developed by an Italian constructor for large biomass herbaceous crops (giant reed, sorghums, switchgrass, Mischantus, etc). It is designed for high vegetative growth crops, as it is able to spread products over all soil surfaces or, alternatively, carry out windrowing. Tests were conducted in the south of Italy (Campania region) on the experimental farm Torre Lama in Bellizzi (SA). Biomass was shredded, dried in the field, and baled for use in a logistic chain and storage. The first step was the cutting and shredding of biomass crops with the specific shredder rear-mounted in an agricultural tractor. The biomass then was dried on the field, constantly monitored for moisture content, and finally, baled with a trailed round baler for storage (second step) and used in a specific logistic chain. The test showed good performance of the shredder machine between 1.17 and 1.77 ha h−1 with an operative speed between 3.9 and 5. 9 km h−1. To define the hourly production, a high wet production level of 60.70 t ha−1 and a low level of 56 t ha−1 were used as references. Under the climatic conditions of the experimental test, this harvesting system showed some advantages, such as the possibility of immediate and long-term biomass storage (less than 14% moisture content), the potential alternative use of the biomass, and the reduced resource use compared to that of other ordinary crops growing in the area. [ABSTRACT FROM AUTHOR]