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Infantile hemangiomas (IHs) are benign vascular neoplasms of childhood (prevalence 5–10%) due to the abnormal proliferation of endothelial cells. IHs are characterized by a peculiar natural life cycle enclosing three phases: proliferative (≤12 months), involuting (≥13 months), and involuted (up to 4–7 years). The mechanisms underlying this neoplastic disease still remain uncovered. Twenty-seven IH tissue specimens (15 proliferative and 12 involuting) were subjected to hematoxylin and eosin staining and a panel of diagnostic markers by immunohistochemistry. WT1, nestin, CD133, and CD26 were also analyzed. Moreover, CD31pos/CD26pos proliferative hemangioma–derived endothelial cells (Hem-ECs) were freshly isolated, exposed to vildagliptin (a DPP-IV/CD26 inhibitor), and tested for cell survival and proliferation by MTT assay, FACS analysis, and Western blot assay. All IHs displayed positive CD31, GLUT1, WT1, and nestin immunostaining but were negative for D2-40. Increased endothelial cell proliferation in IH samples was documented by ki67 labeling. All endothelia of proliferative IHs were positive for CD26 (100%), while only 10 expressed CD133 (66.6%). Surprisingly, seven involuting IH samples (58.3%) exhibited coexisting proliferative and involuting aspects in the same hemangiomatous lesion. Importantly, proliferative areas were characterized by CD26 immunolabeling, at variance from involuting sites that were always CD26 negative. Finally, in vitro DPP-IV pharmacological inhibition by vildagliptin significantly reduced Hem-ECs proliferation through the modulation of ki67 and induced cell cycle arrest associated with the upregulation of p21 protein expression. Taken together, our findings suggest that CD26 might represent a reliable biomarker to detect proliferative sites and unveil non-regressive IHs after a 12-month life cycle.

Organic waste-to-energy (OWtE) technologies are playing a steadily increasing role in the Green Transition, thus becoming a powerful driver in the establishment of an ever more efficient and sustainable circular economy. The advantages of OWtE processes are well known: not only do they reduce the waste volumes sent to landfills or incineration plants, but also and foremost, through the energy they yield (biogenic carbon dioxide, amongst others), they reduce dependance on fossil fuels. This article gives a complete panorama of these technologies, starting from the classical methods and ending with a review of the latest modern novelties. Advantages and disadvantages of each method are highlighted, with particular focus on the formation of by-products and the relevant treatment aimed at preventing environmental pollution. Accordingly, modern techniques for increasing waste-to-energy efficiency and integrating the concept of circular economy and substitutability are analyzed from this perspective. Along with an analysis of modern scientific achievements in this area, practical examples of the implementation of technologies in European countries are given, with an emphasis on the obvious advantages, both economic and environmental.

The cacao fruit is a rich source of polyphenols, including flavonoids and phenolic acids, which possess significant health benefits. The accurate identification and quantification of these bioactive compounds extracted from different parts of the cacao fruit, such as pods, beans, nibs, and cacao shells, require specific treatment conditions and analytical techniques. This review presents a comprehensive comparison of extraction processes and analytical techniques used to identify and quantify polyphenols from various parts of the cacao fruit. Additionally, it highlights the environmental impact of these methods, exploring the challenges and opportunities in selecting and utilizing extraction, analytical, and impact assessment techniques, while considering polyphenols’ yield. The review aims to provide a thorough overview of the current knowledge that can guide future decisions for those seeking to obtain polyphenols from different parts of the cacao fruit.

Endometrial cancer (EC) is a common gynecological cancer worldwide. Treatment has been improved in recent years; however, in advanced stages, therapeutic options are still limited. The expression of galectins is increased in several tumor types and that they are involved in important cell processes. Large studies on endometrial cancer are still pending; Specimens of 225 patients with EC were immunohistochemically stained with antibodies for Gal-8 and Gal-9. Expression was correlated with histopathological variables. The cytosolic expression of both galectins is associated with grading and survival. Cytosolic Galectin-8 expression is a positive prognostic factor for overall survival (OS) and progression-free survival (PFS), while nuclear Gal-8 expression correlates only to OS. The cytosolic presence of Galectin-9 is correlated with a better prognosis regarding OS. Our results suggest that expression of both galectins is associated with OS and PFS in EC. Further studies are needed to understand the underlying molecular mechanisms.

Transition metal dichalcogenides (TMDCs), represented by MX2 (where M = Mo, W and X = S, Se, and Te), and more recently, their moiré superlattices (i.e., formed by superimposing layers of TMDCs with different rotation angles) have attracted considerable interest due to their excellent physical properties and unique nanoscale functionalities. Compared to graphene, the literature indicates that TMDCs offer a competitive advantage in optoelectronic technologies, primarily owing to their compositionally controlled non-zero bandgap. These two-dimensional (2D) nanostructured single or multiple layers exhibit remarkable properties that differ from their bulk counterparts. Moreover, stacking different TMDC monolayers also forms heterostructures and introduces unique quantum effects and extraordinary electronic properties, which is particularly promising for next-generation optoelectronic devices and photo(electro)catalytic applications. Therefore, in this review, we also highlight the new possibilities in the formation of 2D/2D heterostructures of MX2-based materials with moiré patterns and discuss the main critical challenges related to the synthesis and large-scale applications of layered MX2 and MX2-based composites to spur significant advances in emerging optoelectronic and photo(electro)catalytic applications.

In the European Union, salmonellosis is one of the most important zoonoses reported. Poultry meat and egg products are the most common food matrices associated with Salmonella presence. Moreover, wild and domestic animals could represent an important reservoir that could favour the direct and indirect transmission of pathogens to humans. Salmonella spp. can infect carnivorous or omnivorous wild birds that regularly ingest food and water exposed to faecal contamination. Birds kept in captivity can act as reservoirs of Salmonella spp. following ingestion of infected prey or feed. In this paper, we describe the isolation of different Salmonella serovars in several species of raptors hosted in aviaries in an Italian wildlife centre and in the raw chicken necks used as their feed but intended for human consumption. Characterisations of strains were carried out by integrating classical methods and whole genome sequencing analysis. The strains of S. bredeney isolated in poultry meat and birds belonged to the same cluster, with some of them being multidrug-resistant (MDR) and carrying the Col(pHAD28) plasmid-borne qnrB19 (fluoro)quinolone resistance gene, thus confirming the source of infection. Differently, the S. infantis found in feed and raptors were all MDR, carried a plasmid of emerging S. infantis (pESI)-like plasmid and belonged to different clusters, possibly suggesting a long-lasting infection or the presence of additional undetected sources. Due to the high risk of fuelling a reservoir of human pathogens, the control and treatment of feed for captive species are crucial.

Background: Knee osteoarthritis is the most prevalent type of osteoarthritis. Patients frequently encounter pain triggered by movement that evolves into impaired joint function. Needing persistent rest or having night-time pain signifies advanced disease. Qualitative research is considered the most effective method for comprehending patients’ needs and contexts. Methods: This study employed a qualitative research design, allowing the researchers to acquire insights into the patients’ beliefs and values, and the contextual factors influencing the formation and expression of these beliefs and values. Results: A cohort of nine patients awaiting total knee replacement (TKR) surgery was included and they were interviewed until data saturation was achieved. The results of the phenomenological analysis resulted in the identification of three themes: “The existence of pain impedes the capacity to participate in daily life activities”; “TKR induced fears and uncertainties regarding the progression of the disease”; “Severe nighttime pain compromising sleep quality”. Conclusions: This study analyzes the experiences of people awaiting TKR surgery, emphasizing the importance of addressing their unique needs to improve preoperative education and rehabilitation. In this way, patients’ recovery during the postoperative phase can be improved.

The standard treatment for locally advanced cervical cancer typically includes concomitant chemoradiation, a regimen known to induce severe hematologic toxicity (HT). Particularly, pelvic bone marrow dose exposure has been identified as a contributing factor to this hematologic toxicity. Chemotherapy further increases bone marrow suppression, often necessitating treatment interruptions or dose reductions. A systematic search for original articles published between 1 January 2006 and 7 January 2024 that reported on chemoradiotherapy for locally advanced cervical cancer and hematologic toxicities was conducted. Twenty-four articles comprising 1539 patients were included in the final analysis. HT of grade 2 and higher was observed across all studies and frequently exceeded 50%. When correlating active pelvic bone marrow and HT, significant correlations were found for volumes between 10 and 45 Gy and HT of grade 3 and higher. Several dose recommendations for pelvic bone and pelvic bone marrow sparing to reduce HT were established, including V10 < 90–95%, V20 < 65–86.6% and V40 < 22.8–40%. Applying dose constraints to the pelvic bone/bone marrow is a promising approach for reducing HT, and thus reliable implementation of therapy. However, prospective randomized controlled trials are needed to define precise dose constraints and optimize clinical strategies.

The rehabilitation of those who have undergone anterior cruciate ligament reconstruction (ACL-R) is a complex process that involves many factors. Physical ability recovery is not the only factor in the return to sport; psychosocial factors such as anxiety, pain response, self-esteem, locus of control, and fear of re-injury also play an important role. A systematic search was conducted on the PubMed, Medline, Cochrane, CINAHL and Embase databases using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). No randomized controlled trials (RCTs) were identified. The Methodological Index for Non-Randomized Studies (MINOR) was used to assess the quality of the identified non-RCT studies. A total of 308 studies were identified, of which 32 met the eligibility criteria. The results of these studies were obtained using the KOOS (ADL, Sport, QoL), ACL, TSK-11, K-SES, questionnaires/interviews, and other scales as instrumental approaches. This systematic review and meta-analysis revealed that psychological factors have a significant influence on the post-anterior cruciate ligament reconstruction outcomes of athletes. Fear of re-injury and pain were the primary factors that limited return to sport, whereas self-efficacy, psychological will, and age were associated with better functional outcomes and were essential for male and young patients. Clinicians should focus on both physical and psychological components to optimize rehabilitation.

Abdominal surgery is associated with high postoperative mortality and morbidity in cirrhotic patients. Despite improvements in surgical techniques, clinical management, and intensive care, the outcome could be influenced by the degree of portal hypertension, the severity of hepatopathy, or the type of surgery. Preoperative transjugular intrahepatic portosystemic shunt (TIPS) placement, in addition to medical therapy, plays an important role in managing the complications of portal hypertension such as ascites, hepatic encephalopathy, variceal bleeding or portal vein thrombosis. To date, the improvement of post-surgery outcomes in cirrhotic patients after TIPS placement remains unclear. Only observational data existing in the literature and prospective studies are urgently needed to evaluate the efficacy and safety of TIPS in this setting. This review aims to outline the role of TIPS as a tool in postoperative complications reduction in cirrhotic patients, both in the setting of emergency and elective surgery.

Ground-based infrared cameras can be used effectively and safely to provide quantitative information about small to moderate-sized volcanic eruptions. This study describes an infrared camera that has been used to measure emissions from the Mt. Etna and Stromboli (Sicily, Italy) volcanoes. The camera provides calibrated brightness temperature images in a broadband (8–14 µm) channel that is used to determine height, plume ascent rate and volcanic cloud/plume temperature and emissivity at temporal sampling rates of up to 1 Hz. The camera can be operated in the field using a portable battery and includes a microprocessor, data storage and WiFi. The processing and analyses of the data are described with examples from the field experiments. The updraft speeds of the small eruptions at Stromboli are found to decay with a timescale of ∼10 min and the volcanic plumes reach thermal equilibrium within ∼2 min. A strong eruption of Mt. Etna on 1 April 2021 was found to reach ∼9 km, with ascent speeds of 10–20 ms−1. The plume, mostly composed of the gases CO2, water vapour and SO2, became bent over by the prevailing winds at high levels, demonstrating the need for multiple cameras to accurately infer plume heights.

A series of typhoons and tropical storms have produced extreme precipitation events in Vietnam during the first part of the 2020 monsoon season: events of this magnitude pose significant challenges to remote sensing Quantitative Precipitation Estimation (QPE) techniques. The weather-monitoring needs of modern human activities require that these challenges be overcome. In order to address this issue, in this work, seven precipitation products were validated with high spatial and temporal detail against over 1200 rain gauges in Vietnam during six case studies tailored around the most intense events of 2020. The data sources included the Vietnamese weather radar network, IMERG Early run and Final run, the South Korean GEO-KOMPSAT-2A and Chinese FengYun-4A geostationary satellites, DPR on board the GPM-Core Observatory, and European ERA5-Land reanalysis. All products were resampled to a standardized 0.02° grid and compared at hourly scale with ground stations measurements. The results indicated that the radars product was the most capable of reproducing the information collected by the rain gauges during the selected extreme events, with a correlation coefficient of 0.70 and a coefficient of variation of 1.38. However, it exhibited some underestimation, approximately 30%, in both occurrence and intensity. Conversely, geostationary products tended to overestimate moderate rain rates (FY-4A) and areas with low precipitation (GK-2A). More complex products such as ERA5-Land and IMERG failed to capture the highest intensities typical of extreme events, while GPM-DPR showed promising results in detecting the highest rain rates, but its capability to observe isolated events was limited by its intermittent coverage.

Microplastics (MPs) (0.1 µm–5 mm particles) have been documented in oceans and seas. Bivalve molluscs (BMs) can accumulate MPs and transfer to humans through the food chain. BMs (especially mussels) are used to assess MPs’ contamination, but the genus Donax has not been thoroughly investigated. The aim of this study was to detect and characterize MPs in D. trunculus specimens collected along the Tuscan coast (Italy), and to assess the potential risk for consumers. The samples (~10 g of tissue and intervalval liquid from 35 specimens) were digested using a solution of 10% KOH, subjected to NaCl density separation, and filtered through 5 μm pore-size filters. All items were morphologically classified and measured, and their mean abundance (MA) was calculated. Furthermore, 20% of them were analyzed by Raman spectroscopy and, based on the obtained results, the MA was recalculated (corrected MA) and the annual human exposure was estimated. In the 39 samples analyzed, 85 items fibers (n = 45; 52.94%) and fragments (n = 40; 47.06%) were found. The MA was 0.23 ± 0.17 items/grww. Additionally, 83.33% of the items were confirmed as MPs (polyethylene and polyethylene terephthalate). Based on the correct MA (0.18 MPs/grww), D. trunculus consumers could be exposed to 19.2 MPs/per capita/year. The health risk level of MPs was classified as level III (moderate).

The Rothmund–Thomson syndrome (RTS) is a rare autosomal recessive disease associated with poikiloderma, telangiectasias, sun-sensitive rash, hair growth problems, juvenile cataracts and, for a subset of some RTS patients, a high risk of cancer, especially osteosarcoma. Most of the RTS cases are caused by biallelic mutations of the RECQL4 gene, coding for the RECQL4 DNA helicase that belongs to the RecQ family. Cellular and post-radiotherapy radiosensitivity was reported in RTS cells and patients since the 1980s. However, the molecular basis of this particular phenotype has not been documented to reliably link the biological and clinical responses to the ionizing radiation (IR) of cells from RTS patients. The aim of this study was therefore to document the specificities of the radiosensitivity associated with RTS by examining the radiation-induced nucleo-shuttling of ATM (RIANS) and the recognition and repair of the DNA double-strand breaks (DSB) in three skin fibroblasts cell lines derived from RTS patients and two derived from RTS patients’ parents. The results showed that the RTS fibroblasts tested were associated with moderate but significant radiosensitivity, a high yield of micronuclei, and impaired DSB recognition but normal DSB repair at 24 h likely caused by a delayed RIANS, supported by the sequestration of ATM by some RTS proteins overexpressed in the cytoplasm. To our knowledge, this report is the first radiobiological characterization of cells from RTS patients at both molecular and cellular scales.

Frequency-domain electromagnetic induction (FDEMI) methods are frequently used in non-invasive, area-wise mapping of the subsurface electromagnetic soil properties. A crucial part of data analysis is the geophysical inversion of the data, resulting in either conductivity and/or magnetic susceptibility subsurface distributions. We present a novel 1D stochastic optimization approach that combines dimension-adapting reversible jump Markov chain Monte Carlo (MCMC) with artificial bee colony (ABC) optimization for geophysical inversion, with specific application to frequency-domain electromagnetic induction (FDEMI) data. Several solution models of simplified model geometry and a variable number of model knots, which are found by the inversion method, are used to create re-sampled resulting average models. We present synthetic test inversions using conductivity models based on 14 direct-push (DP) EC logs from Greece, Italy, and Germany, as well as field data applications using multi-coil FDEMI devices from three sites in Azerbaijan and Germany. These examples show that the method can effectively lead to solutions that resemble the known DP input models or image reasonable stratigraphic and archaeological features in the field data. Neighboring 1D solutions on field data examples show high coherence along profiles even though each 1D inversion is independently handled. The computational effort for one 1D inversion is less than 120,000 forward calculations, which is much less than usually needed in MCMC inversions, whereas the resulting models show more plausible solutions due to the dimension-adapting properties of the inversion method.

An investigation of the Magdalenian occupation at Étiolles-Les Coudray (France) was conducted using geophysical methods. Based on ground-penetrating radar (GPR), electrical resistivity tomography (ERT), electromagnetic induction (EMI), and stratigraphic information, we present a reconstruction of the main sediment interfaces carrying the Magdalenian occupation. Étiolles-Les Coudray is one of the most important open-air campsites in the Paris Basin, where consecutive settlements distributed along the Hauldres stream were preserved by silts. The geoarchaeological goals were, in particular, the reconstruction of the ancient environment in which hunter–gatherers settled, providing spatialized known stratigraphies able to find an echo in the Seine Valley. Moreover, a focus on the capability of geophysical methods to detect archaeological features is also presented and discussed. We observed that the major reflections in the GPR records were generated from interfaces that have grain size variation: (1) the bottom of the Holocene colluvium and (2) the bottom of the upper Late Glacial silt. EMI and ERT show a very clear horizon associated with the upper Late Glacial silt, in some places even more clearly defined than with GPR. We confirmed the presence of a channel along the slope, placed under Locus 1, and a second channel of the same type globally following the paleotopography of Locus 2. We created a thickness map of the “beige sandy silt” and hypothesized a high probability of good preservation conditions of Magdalenian evidence. Finally, the detection of several localized diffraction hyperbolas in the GPR record offers the possibility to obtain the ground truth of the geophysical results in the near future and verify the nature (archaeological or geological) of these features.

Background: Hyperferritinemia (HF) is a common finding and can be considered as metabolic HF (MHF) in combination with metabolic diseases. The definition of MHF was heterogenous until a consensus statement was published recently. Our aim was to apply the definition of MHF to provide data on the prevalence and characteristics of MHF in a Central-European cohort. Methods: This study was a retrospective analysis of the Paracelsus 10,000 study, a population-based cohort study from the region of Salzburg, Austria. We included 8408 participants, aged 40–77. Participants with HF were divided into three categories according to their level of HF and evaluated for metabolic co-morbidities defined by the proposed criteria for MHF. Results: HF was present in 13% (n = 1111) with a clear male preponderance (n = 771, 69% of HF). Within the HF group, 81% (n = 901) of subjects fulfilled the metabolic criteria and were defined as MHF, of which 75% (n = 674) were characterized by a major criterion. In the remaining HF cohort, 52% (n = 227 of 437) of subjects were classified as MHF after application of the minor criteria. Conclusion: HF is a common finding in the general middle-aged population and the majority of cases are classified as MHF. The new classification provides useful criteria for defining MHF.

In Europe, more than two-thirds of the population live in urban areas. The management of urban green areas and trees is becoming increasingly relevant involving different players and stakeholders, as well for keeping a focus on the Sustainable Development Goals. Society and policy makers are often unaware of the disservices that neglecting these areas can cause. Appropriate monitoring interventions can protect both citizens and trees themselves. The aim of the study was to assess the risk potential in urban trees in Bologna suburbs (Italy). For each tree in the city of Bologna, three target variables identifying the number and categories of streets, buildings, and walking and cycle paths near the tree were considered and used as covariates. A multiple regression model assessing the relationship between a dependent synthetic spatial variable (digital number, DN), proxy of the likelihood of tree failure, and the three independent covariates was estimated. Both the number of streets and walking and cycle paths in the area surrounding a tree are shown to be significantly associated with the DN value. The use of open data can assist in monitoring and maintaining urban green areas. The tool supports a virtuous circle between stakeholders in urban systems through sustainability and efficiency.

This study investigated the mechanism of how lauric arginate ethyl ester (LAE) improves the photoinactivation of bacteria by curcumin after diluting the 100 µmol/L stock curcumin-LAE micelle solution to the concentration used during the treatment based on the curcumin concentration. The photoinactivation of bacteria was conducted by irradiating the 1 µmol/L curcumin-LAE solution containing cocktails of Escherichia coli and Listeria innocua strains (7 log CFU/mL) for 5 min with UV-A light (λ = 365 nm). The changes in solution turbidity, curcumin stability, and bacterial morphology, viability, and recovery were observed using SEM, TEM, and live/dead cell assays. The study found that LAE enhances the photoinactivation of bacteria by increasing the permeability of cell membranes which could promote the interaction of reactive oxygen species produced by photosensitized curcumin with the cell components. The combination of curcumin and LAE was demonstrated to be more effective in inhibiting bacterial recovery at pH 3.5 for E. coli, while LAE alone was more effective at pH 7.0 for L. innocua.

In cirrhotic patients listed for liver transplantation (LT) with a history of hepatic encephalopathy (HE), rifaximin reduces the number of hospitalizations, but whether it influences the time to first hospitalization is unknown. Aims: to evaluate the time-dependent impact of rifaximin on the risk of all-cause hospitalization and dropout in patients on the LT waiting list. Methods: Consecutive patients listed for LT were retrospectively enrolled. After balancing populations with and without rifaximin treatment using the inverse probability therapy weighting analysis, Fine–Gray multivariable competing risk analyses were run to explore risk factors for the first episode of hospitalization and dropout. Results: When comparing 92 patients taking rifaximin to the untreated group of 152, rifaximin treatment was not associated with any of the study outcomes. In the subset of patients with a history of HE at waitlist entry (N = 81 rifaximin-treated and N = 39 untreated), rifaximin intake was independently associated with a lower risk of hospitalization for all causes (SHR 0.638; 95.0% CI 0.418–0.973; p = 0.037) and for HE (SHR 0.379; 95.0% CI 0.207–0.693; p = 0.002). Conclusions: cirrhotic LT candidates with a prior history of HE rifaximin treatment are associated with a lower risk of time-dependent all-cause hospitalization, likely due to its unique effect on gut microbiome composition/function.

Increasing reports of neurological and psychiatric outcomes due to psychostimulant synthetic cathinones (SCs) have recently raised public concern. However, the understanding of neurotoxic mechanisms is still lacking, particularly for the under-investigated αPHP, one of the major MDPV derivatives. In particular, its effects on neural stem/progenitor cell cultures (NSPCs) are still unexplored. Therefore, in the current in vitro study, the effects of increasing αPHP concentrations (25–2000 μM), on cell viability/proliferation, morphology/ultrastructure, genotoxicity and cell death pathways, have been evaluated after exposure in murine NSPCs, using a battery of complementary techniques, i.e., MTT and clonogenic assay, flow cytometry, immunocytochemistry, TEM, and patch clamp. We revealed that αPHP was able to induce a dose-dependent significant decrease of the viability, proliferation and clonal capability of the NSPCs, paralleled by the resting membrane potential depolarization and apoptotic/autophagic/necroptotic pathway activation. Moreover, ultrastructural alterations were clearly observed. Overall, our current findings demonstrate that αPHP, damaging NSPCs and the morpho-functional fundamental units of adult neurogenic niches may affect neurogenesis, possibly triggering long-lasting, irreversible CNS damage. The present investigation could pave the way for a broadened understanding of SCs toxicology, needed to establish an appropriate treatment for NPS and the potential consequences for public health.

Cardiac troponins are key diagnostic and prognostic biomarkers in acute myocardial infarction and, more generally, for the detection of myocardial injury. Since the introduction of the first immunochemistry methods, there has been a remarkable evolution in analytical performance, especially concerning a progressive improvement in sensitivity. However, the measurement of circulating troponins remains rarely susceptible to analytical interferences. We report a case of persistently elevated troponin I concentrations in a patient with known ischemic heart disease, which almost led to unnecessary diagnostic–therapeutic interventions. A prompt laboratory consultation by the cardiologist ultimately led to the identification of an analytical interference due to troponin macrocomplexes (macrotroponin) causing elevated troponin values in the absence of a clinical presentation compatible with myocardial damage.

The development of process-driven systems and the advancements in digital twins have led to the birth of new ways of monitoring and analyzing systems, i.e., digital process twins. Specifically, a digital process twin can allow the monitoring of system behavior and the analysis of the execution status to improve the whole system. However, the concept of the digital process twin is still theoretical, and process-driven systems cannot really benefit from them. In this regard, this work discusses how to effectively exploit a digital process twin and proposes an implementation that combines the monitoring, refinement, and enactment of system behavior. We demonstrated the proposed solution in a multi-robot scenario.

Background: Multiple randomized trials have established adjuvant endocrine therapy (ET) and whole breast irradiation (WBI) as the standard approach after breast-conserving surgery (BCS) in early-stage breast cancer. The omission of WBI has been studied in multiple trials and resulted in reduced local control with maintained survival rates and has therefore been adapted as a treatment option in selected patients in several guidelines. Omitting ET instead of WBI might also be a valuable option as both treatments have distinctly different side effect profiles. However, the clinical outcomes of BCS + ET vs. BCS + WBI have not been formally analyzed. Methods: We performed a systematic literature review searching for randomized trials comparing BCS + ET vs. BCS + WBI in low-risk breast cancer patients with publication dates after 2000. We excluded trials using any form of chemotherapy, regional nodal radiation and mastectomy. The meta-analysis was performed using a two-step process. First, we extracted all available published event rates and the effect sizes for overall and breast-cancer-specific survival (OS, BCSS), local (LR) and regional recurrence, disease-free survival, distant metastases-free interval, contralateral breast cancer, second cancer other than breast cancer and mastectomy-free interval as investigated endpoints and compared them in a network meta-analysis. Second, the published individual patient data from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) publications were used to allow a comparison of OS and BCSS. Results: We identified three studies, including a direct comparison of BCS + ET vs. BCS + WBI (n = 1059) and nine studies randomizing overall 7207 patients additionally to BCS only and BCS + WBI + ET resulting in a four-arm comparison. In the network analysis, LR was significantly lower in the BCS + WBI group in comparison with the BCS + ET group (HR = 0.62; CI-95%: 0.42–0.92; p = 0.019). We did not find any differences in OS (HR = 0.93; CI-95%: 0.53–1.62; p = 0.785) and BCSS (OR = 1.04; CI-95%: 0.45–2.41; p = 0.928). Further, we found a lower distant metastasis-free interval, a higher rate of contralateral breast cancer and a reduced mastectomy-free interval in the BCS + WBI-arm. Using the EBCTCG data, OS and BCSS were not significantly different between BCS + ET and BCS + WBI after 10 years (OS: OR = 0.85; CI-95%: 0.59–1.22; p = 0.369) (BCSS: OR = 0.72; CI-95%: 0.38–1.36; p = 0.305). Conclusion: Evidence from direct and indirect comparison suggests that BCS + WBI might be an equivalent de-escalation strategy to BCS + ET in low-risk breast cancer. Adverse events and quality of life measures have to be further compared between these approaches.

Bigels have been mainly applied in the pharmaceutical sector for the controlled release of drugs or therapeutics. However, these systems, with their intricate structures, hold great promise for wider application in food products. Besides their classical role as carrier and target delivery vehicles for molecules of interest, bigels may also be valuable tools for building complex food structures. In the context of reducing or even eliminating undesirable (but often highly functional) food components, current strategies often critically affect food structure and palatability. The production of solid fat systems that are trans-fat-free and have high levels of unsaturated fatty acids is one of the challenges the food industry currently faces. According to recent studies, bigels can be successfully used as ingredients for total or partial solid fat replacement in complex food matrices. This review aims to critically assess current research on bigels in food and pharmaceutical applications, discuss the role of bigel composition and production parameters on the characteristics of bigels and further expand the use of bigels as solid fat replacers and functional food ingredients. The hydrogel:oleogel ratio, selected gelators, inclusion of surfactants and encapsulation of molecules of interest, and process parameters (e.g., temperature, shear rate) during bigel production play a crucial role in the bigel’s rheological and textural properties, microstructure, release characteristics, biocompatibility, and stability. Besides exploring the role of these parameters in bigel production, future research directions for bigels in a food context are explored.

Deep within online forums, we often stumble across body shaming. Words like “fat” and “ugly” are tossed around, hurting those they target. But can we peel back the layers of these online communities? In this study, social network analysis is used to shine a light on body shaming on Reddit, a well-known online platform. This paper presents a comprehensive social network analysis of body shaming on Reddit, one of the largest online platforms. The research delves into the intricacies of body shaming by identifying key actors, communities, and patterns of behavior and communication related to body shaming. The results show how behavior and communication differ across Reddit’s various subgroups, and how user activity and the length of comments can vary. Through the application of topic modeling, the main subjects discussed in each subgroup were identified. This enables an understanding of what drives discussions about body shaming. The findings provide valuable insights into the spread and normalization of harmful behaviors and attitudes related to body shaming, which can inform the development of targeted interventions aimed at reducing this harmful behavior and promoting more positive and inclusive attitudes towards body image and weight.

One of the most appealing approaches for regulating gene expression, named the “microRNA therapeutic” method, is based on the regulation of the activity of microRNAs (miRNAs), the intracellular levels of which are dysregulated in many diseases, including cancer. This can be achieved by miRNA inhibition with antimiRNA molecules in the case of overexpressed microRNAs, or by using miRNA-mimics to restore downregulated microRNAs that are associated with the target disease. The development of new efficient, low-toxic, and targeted vectors of such molecules represents a key topic in the field of the pharmacological modulation of microRNAs. We compared the delivery efficiency of a small library of cationic calix[4]arene vectors complexed with fluorescent antimiRNA molecules (Peptide Nucleic Acids, PNAs), pre-miRNA (microRNA precursors), and mature microRNAs, in glioma- and colon-cancer cellular models. The transfection was assayed by cytofluorimetry, cell imaging assays, and RT-qPCR. The calix[4]arene-based vectors were shown to be powerful tools to facilitate the uptake of both neutral (PNAs) and negatively charged (pre-miRNAs and mature microRNAs) molecules showing low toxicity in transfected cells and ability to compete with commercially available vectors in terms of delivery efficiency. These results could be of great interest to validate microRNA therapeutics approaches for future application in personalized treatment and precision medicine.

Liver cirrhosis development is a multifactorial process resulting from a combination of environmental and genetic factors. The aim of the study was to develop accurate non-invasive diagnostic and prognostic models for alcoholic cirrhosis. Consecutive subjects with at-risk alcohol intake were retrospectively enrolled (110 cirrhotic patients and 411 non-cirrhotics). At enrollment, the data about lifetime drinking history were collected and all patients were tested for Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409, Transmembrane 6 Superfamily 2 (TM6SF2) rs58542926, and hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) rs72613567 variants. In cross-sectional analyses, models for the diagnosis of cirrhosis were developed using multivariate logistic regression. A predictive score for cirrhosis development over 24 years was built by evaluating time-dependent AUC curves. The best diagnostic accuracy was demonstrated by the model, which also includes daily alcohol consumption, duration of hazardous alcohol use, and genetic variants, with AUCs of 0.951 (95% CI 0.925–0.977) and 0.887 (95% CI 0.925–0.977) for cirrhosis and compensated cirrhosis, respectively. The predictive model for future cirrhosis development (AUC of 0.836 95% CI: 0.769–0.904) accounted for age at onset of at-risk alcohol consumption and the number of PNPLA3 and HSD17B13 variant alleles. We have developed accurate genetic and alcohol consumption models for the diagnosis of alcoholic cirrhosis and the prediction of its future risk.

Understanding the landscape evolution and human-environmental interaction within it is one of the key tasks of early Holocene research. As mobile hunter–gatherers leave few traces of structural organization, understanding their habitats is relevant for comprehending these people. Rarely does the spatial distribution of artifacts correspond to the real pattern of past human activity, but rather shows the pattern of identified artifacts. Geophysical investigations try to fill this gap and have been applied increasingly in archaeological prospection delivering landscape reconstruction, which are verified and fine-tuned using corings and excavations. Despite promising 3D models, a tool to predict the location of undiscovered former human presence and the conditions which influenced people to move across the landscape is not well developed. The primary goal of this paper is to present a methodology for connecting spatial patterns of past human activity based on archaeological and geophysical data. We discuss different GPR (ground-penetrating radar) facies classified at the shoreline of the former Lake Duvensee and geomorphological variables, which leads to the possibility of understanding where and why people chose preferred areas to settle on former islands. We also demonstrate that Mesolithic hunter–gatherer groups preferred dry areas with access to open water for short-term campsites and flatter and more protected areas for specialized and repeatedly occupied campsites. The cardinal orientation of a campsite seems to be secondary to the local peat over-growing process and access to water.

We aimed to evaluate the magnesium content in human cirrhotic liver and its correlation with serum AST levels, expression of hepatocellular injury, and MELDNa prognostic score. In liver biopsies obtained at liver transplantation, we measured the magnesium content in liver tissue in 27 cirrhotic patients (CIRs) and 16 deceased donors with healthy liver (CTRLs) by atomic absorption spectrometry and within hepatocytes of 15 CIRs using synchrotron-based X-ray fluorescence microscopy. In 31 CIRs and 10 CTRLs, we evaluated the immunohistochemical expression in hepatocytes of the transient receptor potential melastatin 7 (TRPM7), a magnesium influx chanzyme also involved in inflammation. CIRs showed a lower hepatic magnesium content (117.2 (IQR 110.5–132.9) vs. 162.8 (IQR 155.9–169.8) μg/g; p < 0.001) and a higher percentage of TRPM7 positive hepatocytes (53.0 (IQR 36.8–62.0) vs. 20.7 (10.7–32.8)%; p < 0.001) than CTRLs. In CIRs, MELDNa and serum AST at transplant correlated: (a) inversely with the magnesium content both in liver tissue and hepatocytes; and (b) directly with the percentage of hepatocytes stained intensely for TRPM7. The latter also directly correlated with the worsening of MELDNa at transplant compared to waitlisting. Magnesium depletion and overexpression of its influx chanzyme TRPM7 in hepatocytes are associated with severity of hepatocyte injury and prognosis in cirrhosis. These data represent the pathophysiological basis for a possible beneficial effect of magnesium supplementation in cirrhotic patients.

The molecular characterization of endometrial carcinoma (EC) has recently been included in the ESGO/ESTRO/ESP guidelines. The study aims to evaluate the impact of integrated molecular and pathologic risk stratification in the clinical practice and the relevance of pathologic parameters in predicting prognosis in each EC molecular subgroup. ECs were classified using immunohistochemistry and next-generation sequencing into the four molecular classes: POLE mutant (POLE), mismatch repair deficient (MMRd), p53 mutant (p53abn), and no specific molecular profile (NSMP). According to the WHO algorithm, 219 ECs were subdivided into the following molecular subgroups: 7.8% POLE, 31% MMRd, 21% p53abn, 40.2% NSMP. Molecular classes as well as ESGO/ESTRO/ESP 2020 risk groups were statistically correlated with disease-free survival. Considering the impact of histopathologic features in each molecular class, stage was found to be the strongest prognostic factor in MMRd ECs, whereas in the p53abn subgroup, only lymph node status was associated with recurrent disease. Interestingly, in the NSMP tumor, several histopathologic features were correlated with recurrence: histotype, grade, stage, tumor necrosis, and substantial lymphovascular space invasion. Considering early-stage NSMP ECs, substantial lymphovascular space invasion was the only independent prognostic factor. Our study supports the prognostic importance of EC molecular classification and demonstrated the essential role of histopathologic assessment in patients’ management.

We aimed to evaluate the standard of care of adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) in elderly female patients (≥65 years) treated outside of clinical trials and to identify potential factors related to the omission of RT and the interaction with endocrine therapy (ET). All women treated with BCS at two major breast centers between 1998 and 2014 were evaluated. Data were provided by the Tumor Registry Munich. Survival analyses were conducted using the Kaplan–Meier method. Prognostic factors were identified using multivariate Cox regression analysis. The median follow-up was 88.4 months. Adjuvant RT was performed in 82% (2599/3171) of patients. Irradiated patients were younger (70.9 vs. 76.5 years, p < 0.001) and were more likely to receive additional chemotherapy (p < 0.001) and ET (p = 0.014). Non-irradiated patients more often had non-invasive DCIS tumors (pTis: 20.3% vs. 6.8%, p < 0.001) and did not undergo axillary surgery (no axillary surgery: 50.5% vs. 9.5%, p < 0.001). Adjuvant RT was associated with improved locoregional tumor control after BCS in invasive tumors (10-year local recurrence-free survival (LRFS): 94.0% vs. 75.1%, p < 0.001, 10-year lymph node recurrence-free survival (LNRFS): 98.1% vs. 93.1%, p < 0.001). Multivariate analysis confirmed significant benefits for local control with postoperative RT. Furthermore, RT led to increased locoregional control even in patients who received ET (10-year LRFS 94.8% with ET + RT vs. 78.1% with ET alone, p < 0.001 and 10-year LNRFS: 98.2% vs. 95.0%, p = 0.003). Similarly, RT alone had significantly better locoregional control rates compared to ET alone (10-year LRFS 92.6% with RT alone vs. 78.1% with ET alone, p < 0.001 and 10-year LNRFS: 98.0% vs. 95.0%, p = 0.014). The present work confirms the efficacy of postoperative RT for breast carcinoma in elderly patients (≥65 years) treated in a modern clinical setting outside of clinical trials, even in patients who receive ET.

Osteoarthritis negatively impacts the patient’s quality of life. Qualitative research is an effective tool in detecting the various emotions experienced by patients with osteoarthritis. Such studies play a crucial role in promoting comprehension of the patient’s experiences of health and illness among healthcare professionals, including nurses. The purpose of this study is to examine patients’ perceptions during the pre-admission process for total hip replacement (THR). The study utilized a qualitative descriptive methodology with a phenomenological approach. A sample of patients awaiting THR consented to participate in the study and were interviewed until data saturation was achieved. The results of the phenomenological analysis resulted in the identification of three themes: 1—Surgery generates mixed feelings; 2—Pain negatively impacts daily life activities; 3—Pain requires personal strategies to be alleviated. Patients awaiting THR demonstrate frustration and anxiety. They experience intense pain during daily activities, which persists even during night rest.

Background: “FODMAPs” (fermentable-oligo-, di-, monosaccharides, and polyols) are a group of fermentable carbohydrates and polyols largely diffused in food products. Despite their beneficial effects as prebiotics, people affected by irritable bowel syndrome manifest symptoms when eating these carbohydrates. A low-FODMAP diet seems to be the only possible therapy proposed for symptom management. Bakery products are a common source of FODMAPs, whose pattern and total amount can be affected by their processing. This work aims at studying some of the technological parameters that can influence the FODMAPs pattern in bakery products during the production process. Methods: high-performance anion exchange chromatography coupled to a pulsed amperometric detector (HPAEC-PAD) was used as a highly selective system for carbohydrates evaluation analyses on flours, doughs, and crackers. These analyses were performed using two different columns, the CarboPac PA200 and CarboPac PA1, which are selective for oligosaccharide and simple sugar separation, respectively. Results: emmer and hemp flours were selected to prepare doughs as they contained low oligosaccharide content. Two different mixes of ferments were used at different times of fermentation to evaluate the best conditions to achieve low-FODMAP crackers. Conclusion: the proposed approach allows carbohydrate evaluation during crackers processing and permits the selection of opportune conditions to obtain low-FODMAP products.

From December 2020 to February 2022, 66 lava fountains (LF) occurred at Etna volcano (Italy). Despite their short duration (an average of about two hours), they produced a strong impact on human life, environment, and air traffic. In this work, the measurements collected from the Spinning Enhanced Visible and InfraRed Imager (SEVIRI) instrument, on board Meteosat Second Generation (MSG) geostationary satellite, are processed every 15 min to characterize the volcanic clouds produced during the activities. In particular, a quantitative estimation of volcanic cloud top height (VCTH) and ash/ice/SO2 masses’ time series are obtained. VCTHs are computed by integrating three different retrieval approaches based on coldest pixel detection, plume tracking, and HYSPLIT models, while particles and gas retrievals are realized simultaneously by exploiting the Volcanic Plume Retrieval (VPR) real-time procedure. The discrimination between ashy and icy pixels is carried out by applying the Brightness Temperature Difference (BTD) method with thresholds obtained by making specific Radiative Transfer Model simulations. Results indicate a VCTH variation during the entire period between 4 and 13 km, while the SO2, ash, and ice total masses reach maximum values of about 50, 100, and 300 Gg, respectively. The cumulative ash, ice, and SO2 emitted from all the 2020–2022 LFs in the atmosphere are about 750, 2300, and 670 Gg, respectively. All the retrievals indicate that the overall activity can be grouped into 3 main periods in which it passes from high (December 2020 to March 2021), low (March to June 2021), and medium/high (June 2021 to February 2022). The different products have been validated by using TROPOspheric Monitoring Instrument (TROPOMI) polar satellite sensor, Volcano Observatory Notices for Aviation (VONA) bulletins, and by processing the SEVIRI data considering a different and more accurate retrieval approach. The products’ cross-comparison shows a generally good agreement, except for the SO2 total mass in case of high ash/ice content in the volcanic cloud.

The EFSA-approved claim that olive oil is beneficial for cardiovascular health suffers from ambiguities that lead to a vague and potentially subjective interpretation of the underlying analytical data. Misunderstandings among customers, but also market distortions are possible consequences. In this study, a rapid and simple analytical technique is presented that circumvents the ambiguity by measuring levels of putative health-promoting compounds as the equivalent of tyrosol and hydroxytyrosol, cleaving such moieties from more complex constituents such as oleuropein and oleocanthal. Since the direct hydrolysis of the olive oil is the central element of the process, the reaction temperature, time, reagent concentration and reagent type were optimized. In addition, the influence of co-solvents, which might support the intermittent miscibility of the two phases during hydrolysis, was investigated. The analytical and economic implications are discussed particularly in the context of a commonly used technique.

Liquid biopsy (LB) is an emerging diagnostic tool that analyzes biomarkers in the blood (and possibly in other body fluids) to provide information about tumor genetics and response to therapy. This review article provides an overview of LB applications in human cancer with a focus on breast cancer patients. LB methods include circulating tumor cells and cell-free tumor products, such as circulating tumor DNA. LB has shown potential in detecting cancer at an early stage, monitoring tumor progression and recurrence, and predicting patient response to therapy. Several studies have demonstrated its clinical utility in breast cancer patients. However, there are limitations to LB, including the lack of standardized assays and the need for further validation. Future potential applications of LB include identifying the minimal residual disease, early detection of recurrence, and monitoring treatment response in various cancer types. LB represents a promising non-invasive diagnostic tool with potential applications in breast cancer diagnosis, treatment, and management. Further research is necessary to fully understand its clinical utility and overcome its current limitations.

(1) Background: We investigated, for the first time, whether dietary simple sugar intake affects MELD score changes over time in a cohort of cirrhotic liver transplant candidates. (2) Methods: the MELD score, dietary habits using a 3-day food diary, and visceral adipose tissue index (VATI) measured with CT scan were assessed in 80 consecutive outpatient cirrhotic patients at baseline, after counseling to follow current nutritional guidelines. The MELD score was reassessed after six months and the DELTA-MELD was calculated as the MELD at the second assessment minus the MELD at baseline. (3) Results: Compared with the baseline, the MELD score of cirrhotic patients at the end of the study was decreased, stable, or increased in 36%, 8% and 56% of patients, respectively. In separate multiple linear regression models, DELTA-MELD was positively and independently correlated with the daily intake of simple sugars expressed in g/kg body weight (p = 0.01) or as a percentage of total caloric intake (p = 0.0004) and with the number of daily portions of fruit, added sugar, jam, and honey (p = 0.003). These associations were present almost exclusively in patients with VATI above the median value. (4) Conclusions: In cirrhotic patients with high amounts of visceral adipose tissue the consumption of simple sugars and fructose should be limited to improve their clinical outcome.

Electronic Word of Mouth (eWoM) has been largely studied for social platforms, such as Yelp and TripAdvisor, which are highly investigated in the context of digital marketing. However, it can also have interesting applications in other contexts. Therefore, it can be challenging to investigate this phenomenon on generic social platforms, such as Facebook, Twitter, and Reddit. In the past literature, many authors analyzed eWoM on Facebook and Twitter, whereas it was little considered in Reddit. In this paper, we focused exactly on this last platform. In particular, we first propose a model for representing and evaluating the eWoM Power of Reddit posts. Then, we illustrate two possible applications, namely the definition of lifespan templates and the construction of profiles for Reddit posts. Lifespan templates and profiles are ultimately orthogonal to each other and can be jointly employed in several applications.

Wash trading is considered a highly inopportune and illegal behavior in regulated markets. Instead, it is practiced in unregulated markets, such as cryptocurrency or NFT (Non-Fungible Tokens) markets. Regarding the latter, in the past many researchers have been interested in this phenomenon from an “ex-ante” perspective, aiming to identify and classify wash trading activities before or at the exact time they happen. In this paper, we want to investigate the phenomenon of wash trading in the NFT market from a completely different perspective, namely “ex-post”. Our ultimate goal is to analyze wash trading activities in the past to understand whether the game is worth the candle, i.e., whether these illicit activities actually lead to a significant profit for their perpetrators. To the best of our knowledge, this is the first paper in the literature that attempts to answer this question in a “structured” way. The efforts to answer this question have enabled us to make some additional contributions to the literature in this research area. They are: (i) a framework to support future “ex-post” analyses of the NFT wash trading phenomenon; (ii) a new dataset on wash trading transactions involving NFTs that can support further future investigations of this phenomenon; (iii) a set of insights of the NFT wash trading phenomenon extracted at the end of an experimental campaign.

The BRAF p.V600E mutation represents the most specific marker for papillary thyroid carcinoma and is potentially related to aggressive behavior and persistent disease. BRAF alterations other than the p.V600E are less common in thyroid carcinoma and represent an alternative mechanism of BRAF activation with unclear clinical significance. The study aims to describe the frequency and clinicopathologic characteristics of BRAF non-V600E mutations in a large cohort (1654 samples) of thyroid lesions characterized by next-generation sequencing. BRAF mutations have been found in 20.3% (337/1654) of thyroid nodules, including classic (p.V600E) mutation in 19.2% (317/1654) of samples and non-V600E variants in 1.1% of cases (19/1654). BRAF non-V600E alterations include 5 cases harboring p.K601E, 2 harboring p.V600K substitutions, 2 with a p.K601G variant, and 10 cases with other BRAF non-V600E alterations. BRAF non-V600E mutations have been reported in one case of follicular adenoma, three cases of conventional papillary thyroid carcinoma, eight cases of follicular variant of papillary carcinomas, one case of columnar cell variant papillary thyroid carcinoma, one case of oncocytic follicular carcinoma, and two bone metastasis of follicular thyroid carcinoma. We confirm that BRAF non-V600E mutations are uncommon and typically found in indolent follicular-patterned tumors. Indeed, we show that BRAF non-V600E mutations can be found in tumors with metastatic potential. However, in both aggressive cases, the BRAF mutations were concomitant with other molecular alterations, such as TERT promoter mutation.

Satellite microwave (MW) and millimetre-wave (MMW) passive sensors can be used to detect volcanic clouds because of their sensitivity to larger volcanic particles (i.e., size bigger than 20 µm). In this work, we combine the MW-MMW observations with thermal-infrared (TIR) radiometric data from the Low Earth Orbit (LEO) spectroradiometer to have a complete characterisation of volcanic plumes. We describe new physical-statistical methods, which combine machine learning techniques, aimed at detecting and retrieving volcanic clouds of two highly explosive eruptions: the 2014 Kelud and 2015 Calbuco test cases. For the detection procedure, we compare the well-known split-window methods with a machine learning algorithm named random forest (RF). Our work highlights how the machine learning method is suitable to detect volcanic clouds using different spectral signatures without fixing a threshold. Moreover, the RF model allows images to be automatically processed with promising results (90% of the area correctly identified). For the retrieval procedure of the mass of volcanic particles, we consider two methods, one based on the maximum likelihood estimation (MLE) and one using the neural network (NN) architecture. Results show a good comparison of the mass obtained using the MLE and NN methods for all the analysed bands. Summing the MW-MMW and TIR estimates, we obtain the following masses: 1.11 ± 0.40 × 1011 kg (MLE method) and 1.32 ± 0.47 × 1011 kg (NN method) for Kelud; 4.48 ± 1.61 × 1010 kg (MLE method) and 4.32 ± 1.56 × 1010 kg (NN method) for Calbuco. This work shows how machine learning techniques can be an effective tool for volcanic cloud detection and how the synergic use of the TIR and MW-MMW observations can give more accurate estimates of the near-source volcanic clouds.

Background: Treatment guidelines recommend the tocilizumab use in patients with a CRP of >7.5 mg/dL. We aimed to estimate the causal effect of glucocorticoids + tocilizumab on mortality overall and after stratification for PaO2/FiO2 ratio and CRP levels. Methods: This was an observational cohort study of patients with severe COVID-19 pneumonia. The primary endpoint was day 28 mortality. Survival analysis was conducted to estimate the conditional and average causal effect of glucocorticoids + tocilizumab vs. glucocorticoids alone using Kaplan–Meier curves and Cox regression models with a time-varying variable for the intervention. The hypothesis of the existence of effect measure modification by CRP and PaO2/FiO2 ratio was tested by including an interaction term in the model. Results: In total, 992 patients, median age 69 years, 72.9% males, 597 (60.2%) treated with monotherapy, and 395 (31.8%), adding tocilizumab upon respiratory deterioration, were included. At BL, the two groups differed for median values of CRP (6 vs. 7 mg/dL; p < 0.001) and PaO2/FiO2 ratio (276 vs. 235 mmHg; p < 0.001). In the unadjusted analysis, the mortality was similar in the two groups, but after adjustment for key confounders, a significant effect of glucocorticoids + tocilizumab was observed (adjusted hazard ratio (aHR) = 0.59, 95% CI: 0.38–0.90). Although the study was not powered to detect interactions (p = 0.41), there was a signal for glucocorticoids + tocilizumab to have a larger effect in subsets, especially participants with high levels of CRP at intensification. Conclusions: Our data confirm that glucocorticoids + tocilizumab vs. glucocorticoids alone confers a survival benefit only in patients with a CRP > 7.5 mg/dL prior to treatment initiation and the largest effect for a CRP > 15 mg/dL. Large randomized studies are needed to establish an exact cut-off for clinical use.

In this study, we focus on the eruption of Mount Etna on Christmas 2018, which emitted great amounts of SO2 from 24th to 30th December into the free troposphere. Simulations based on two different estimations of SO2 emission fluxes are conducted with the chemistry-transport model MOCAGE in order to study the impact of these estimations on the volcanic plume modeling. The two flux emissions used are retrieved (1) from the ground-based network FLAME, located on the flank of the volcano, and (2) from the spaceborne instrument SEVIRI onboard the geostationary satellite MSG. Multiple spaceborne observations, in the infrared and ultraviolet bands, are used to evaluate the model results. Overall, the model results match well with the plume location over the period of the eruption showing the good transport of the volcanic plume by the model, which is linked to the use of a realistic estimation of the altitude of injection of the emissions. However, there are some discrepancies in the plume concentrations of SO2 between the two simulations, which are due to the differences between the two emission flux estimations used that are large on some of the days. These differences are linked to uncertainties in the retrieval methods and observations used to derive SO2 volcanic fluxes. We find that the uncertainties in the satellite-retrieved column of SO2 used for the evaluation of the simulations, linked to the instrument sensitivity and/or the retrieval algorithm, are sometimes nearly as large as the differences between the two simulations. This shows a limitation of the use of satellite retrievals of SO2 concentrations to quantitatively validate modeled volcanic plumes. In the paper, we also discuss approaches to improve the simulation of SO2 concentrations in volcanic plumes through model improvements and also via more advanced methods to more effectively use satellite-derived products.

Normally, econometric models that forecast the Italian Industrial Production Index do not exploit information already available at time t + 1 for their own main industry groupings. The new strategy proposed here uses state–space models and aggregates the estimates to obtain improved results. The performance of disaggregated models is compared at the same time with a popular benchmark model, a univariate model tailored on the whole index, with persistent not formally registered holidays, a vector autoregressive moving average model exploiting all information published on the web for main industry groupings. Tests for superior predictive ability confirm the supremacy of the aggregated forecasts over three steps horizon using absolute forecast error and quadratic forecast error as a loss function. The datasets are available online.

Although the impact of floods on the agricultural sector is relevant, with potential consequences on food security, in the new EU Common Agricultural Policy (CAP) proposal, agricultural risk management tools have been reinforced and extended. As far as we know, guidelines for the estimation of insurance indemnities related to flooding damage in the European livestock sector have not been proposed yet, unlike what has occurred in extra-European contexts. The present research proposes a model to identify the components of flood damage on dairy farms aimed at categorizing the cost typologies related to flood events by implementing a what-if approach. Our results highlight that collecting data about the vulnerability of a farm is an essential condition to assess the severity of damage from an economic perspective. In fact, even if some of the variables considered cause large economic losses per se, others are mainly related to poor management of issues related to the health of the herd (i.e., mastitis, lameness, other diseases). Such issues can be exacerbated by floods. Herd management, which includes comprehensive data collection, is essential for the calculation of economic losses in a single farm case and is also indispensable for the calculation of indemnity for the recovery of farming activities.

Salmonella is a Gram-negative enteric bacterium responsible for the foodborne and waterborne disease salmonellosis, which is the second most reported bacterial zoonosis in humans. Many animals are potential sources of salmonellosis, including dogs, cats, and other pets. We report the case of an outbreak of salmonellosis in a family in central Italy, affecting two children and involving their three dogs as carriers. One of the children needed medical care and hospitalisation. Isolation and analysis of stool samples from the sibling and the animals present in the house were carried out. Serotyping allowed the identification of S. enterica subsp. enterica serovar Typhimurium in its monophasic variant for all the isolates. The results of whole-genome sequencing confirmed that the strains were tightly related. The minimum inhibitory concentration (MIC) test documented the resistance to ampicillin, sulfamethoxazole, and tetracycline. The origin of the zoonotic outbreak could not be assessed; however, the case study showed a clear passage of the pathogen between the human and non-human members of the family. The possibility of a transmission from a dog to a human suggests the need for further studies on the potential ways of transmission of salmonellosis through standard and alternative feed.

Liquid biopsy has dramatically changed cancer management in the last decade; however, despite the huge number of miRNA signatures available for diagnostic or prognostic purposes, it is still unclear if dysregulated miRNAs in the bloodstream could be used to develop miRNA-based therapeutic approaches. In one author’s previous work, nine miRNAs were found to be dysregulated in early-stage colon cancer (CRC) patients by NGS analysis followed by RT-dd-PCR validation. In the present study, the biological effects of the targeting of the most relevant dysregulated miRNAs with anti-miRNA peptide nucleic acids (PNAs) were verified, and their anticancer activity in terms of apoptosis induction was evaluated. Our data demonstrate that targeting bloodstream up-regulated miRNAs using anti-miRNA PNAs leads to the down-regulation of target miRNAs associated with inhibition of the activation of the pro-apoptotic pathway in CRC cellular models. Moreover, very high percentages of apoptotic cells were found when the anti-miRNA PNAs were associated with other pro-apoptotic agents, such as sulforaphane (SFN). The presented data sustain the idea that the targeting of miRNAs up-regulated in the bloodstream with a known role in tumor pathology might be a tool for the design of protocols for anti-tumor therapy based on miRNA-targeting molecules.

Assessing the behavioural responses of floating wolves to human presence is crucial for investigating the chance of wolf populations expanding into urbanised landscapes. We studied the movement ecology of three rehabilitated wolves in a highly human-dominated landscape (Po Plain, Italy) to explore wolf’s plasticity amid widespread human pressure. To reach this aim, we estimated individual 95% utilisation distributions (UD) after the release and inspected both 95% UDs and net squared displacements to identify individual movement patterns; tested for differences in movement patterns during day and night; and analysed the selection of resting sites during dispersal movement in a highly human-altered environment. Both the 95% UDs and step lengths were smaller for wolves settling in suitable areas than for those settling in more urbanised areas. All wolves exhibited strong temporal segregation with humans during all movement phases, particularly while dispersing across highly urbanised areas. Main roads and proximity to built-up areas were shown to limit wolves’ dispersal, whereas small-wooded patches that provide shelter during rest facilitated long-distance movements. This study provides important insights into wolf movement and settling in urban and peri-urban areas, providing critical knowledge to promote human–carnivore coexistence.

The concept of scope was introduced in Social Network Analysis to assess the authoritativeness and convincing ability of a user toward other users on one or more social platforms. It has been studied in the past in some specific contexts, for example to assess the ability of a user to spread information on Twitter. In this paper, we propose a new investigation on scope, as we want to assess the scope of the sentiment of a user on a topic. We also propose a multi-dimensional definition of scope. In fact, besides the traditional spatial scope, we introduce the temporal one, which has never been addressed in the literature, and propose a model that allows the concept of scope to be extended to further dimensions in the future. Furthermore, we propose an approach and a related set of parameters for measuring the scope of the sentiment of a user on a topic in a social network. Finally, we illustrate the results of an experimental campaign we conducted to evaluate the proposed framework on a dataset derived from Reddit. The main novelties of this paper are: (i) a multi-dimensional view of scope; (ii) the introduction of the concept of sentiment scope; (iii) the definition of a general framework capable of analyzing the sentiment scope related to any subject on any social network.