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Objective: We tested the effect of 27-hydroxycholesterol (27OHC) on the expression and synthesis of two membrane transporters involved in sterols extrusion from the intestinal epithelium into the gut lumen: ATP-binding cassette A1 (ABCA1) and G8 (ABCG8). Special attention was given to ABCG8, a key player in the intestinal cell discharge of plant sterols. Methods: Differentiated CaCo-2 intestinal cells were supplemented with 27OHC, and added to the cell incubation medium at a final concentration of 1 or 5 μM. These 27OHC externally added amounts were proven to reach intracellular oxysterol levels within the range of those normally recovered in the human peripheral blood. Results: An up-regulation of the ABCA1 and ABCG8 mRNAs was observed in the CaCo-2 cells supplemented with 27OHC. Moreover, both 1 μM and 5 μM 27OHC induced a net, and steady, statistically significant, increase of both ABCA1 and ABCG8 protein levels. Of interest, the cellular pre-treatment with diphenylene iodonium, a selective inhibitor of NADPH oxidase, i.e. a major intracellular source of reactive oxygen species, fully inhibited the 27OHC enhancement of both ABCA1 and ABCG8 protein synthesis. Conclusion: This in vitro study shows for the first time that the addition of 27OHC to intestinal epithelial cells up-regulates ABCG8, the transporter discharging plant sterols into the gut lumen, besides confirming to induce ABCA1 as well. Importantly, the 27OHC-dependent up-regulation of the two transporters appears to involve a redox mechanism rather than the canonical liver-X-receptors-dependent pathway. Significance statement The 27OHC introduced with the diet might modulate the plant sterol extrusion in the gut, in parallel with that of cholesterol.

This paper proves the existence of solutions that solve the Nonlinear Partial differential equation on the exterior of the ball centered at the origin in R^{N} with radius R > 0, with boundary conditions u = 0 on the boundary, and u ( x ) approaches 0 as | x | approaches infinity. When the function is local Lipschitzian grows superlinear at infinity and singular at 0. Also N > 2, f ( u ) ~ (-1 ) / ( |u| ^{q-1} u ) for small u with 0 < q < 1, and f ( u ) ~ | u |^{ p-1} u for large | u | with p > 1. Also, K ( x ) ~ | x |^ { - ( Alpha) } with 2 < Alpha < 2 ( N - 1 ) for large | x |. We used the fixed point method and other techniques to prove the existence.

We studied the compositional written skills and spelling competence of individuals with a severe hearing impairment, examining qualitative and quantitative characteristics of their texts, the psycholinguistic variables modulating their productions, and writing errors following a fine-grained analysis. Sixteen deaf young adults, educated in bilingual settings, were examined and compared to a group of control hearing subjects matched for gender, age, and education. Writing skills were examined through both written composition and written picture-naming tasks. Concerning compositional skills, deaf participants produced shorter and less informative texts, with fewer adjectives and subordinates, and were qualitatively worse with respect to texts produced by hearing controls. Words produced by deaf participants were those acquired earlier and facilitated by a higher lexical neighbourhood. Errors were mainly semantic, morphological, and syntactic errors, reflecting general linguistic weakness. Spelling errors were few, with phonologically nonplausible misspellings relative to controls, and with phonologically plausible ones being quite rare. In the picture-naming task, deaf people had a greater number of all types of errors with respect to their text, including semantic and morphological errors. Their spelling performance featured mainly phonologically nonplausible misspellings, while phonologically plausible ones were relatively few and comparable to controls. Overall, the writing of deaf adults reveal limitations in grammar and lexical-sematic linguistic competence. This was associated with spelling deficits characterized mainly by the poorer use of phonological sublexical spelling procedures. However, in an ecologic context, their spelling deficits appear not so important as has been claimed in the literature.

In this study, we analyzed the emotional and motivational aspects characterizing the profile of university students with Specific Learning Disorders (SLD). We assessed 61 university students, 32 with SLD (age = 23.6) and 29 in the control group (age = 23.00). The results highlighted that individuals with SLD exhibit higher levels of anxiety and depression and lower resilience compared to the control group. The Multidimensional Perfectionism Scale – Short Form, which explores perfectionism, did not reveal differences between the groups. Conversely, lower scores emerged in SLD students for the intrinsic motivation sub-scales of the Academic Motivation Scale. This indicates less engagement in studying out of personal cognitive curiosity. The Self-Regulated Knowledge Scale – University, which measures various cognitive strategies, showed significantly lower scores in the SLD group for knowledge linking, knowledge training, and knowledge critique. This suggests a lower frequency with which SLD students attempt to connect new knowledge with what they already possess, apply their knowledge, ask questions, and critically analyze what they have learned. Therefore, psychological and motivational consequences are evident in this population and can impact well-being and quality of life.

IntroductionSeasonal influenza generally represents an underestimated public health problem with significant socioeconomic implications. Monitoring and detecting influenza epidemics are important tasks that require integrated strategies. Wastewater-based epidemiology (WBE) is an emerging field that uses wastewater data to monitor the spread of disease and assess the health of a community. It can represent an integrative surveillance tool for better understanding the epidemiology of influenza and prevention strategies in public health.MethodsWe conducted a study that detected the presence of Influenza virus RNA using a wastewater-based approach. Samples were collected from five wastewater treatment plants in five different municipalities, serving a cumulative population of 555,673 Sicilian inhabitants in Italy. We used the RT-qPCR test to compare the combined weekly average of Influenza A and B viral RNA in wastewater samples with the average weekly incidence of Influenza-like illness (ILI) obtained from the Italian national Influenza surveillance system. We also compared the number of positive Influenza swabs with the viral RNA loads detected from wastewater. Our study investigated 189 wastewater samples.ResultsCumulative ILI cases substantially overlapped with the Influenza RNA load from wastewater samples. Influenza viral RNA trends in wastewater samples were similar to the rise of ILI cases in the population. Therefore, wastewater surveillance confirmed the co-circulation of Influenza A and B viruses during the season 2022/2023, with a similar trend to that reported for the weekly clinically confirmed cases.ConclusionWastewater-based epidemiology does not replace traditional epidemiological surveillance methods, such as laboratory testing of samples from infected individuals. However, it can be a valuable complement to obtaining additional information on the incidence of influenza in the population and preventing its spread.

Women, children and adolescents (WCA), especially in low-income and middle-income countries (LMICs), will bear the worst consequences of climate change during their lifetimes, despite contributing the least to global greenhouse gas emissions. Investing in WCA can address these inequities in climate risk, as well as generating large health, economic, social and environmental gains. However, women’s, children’s and adolescents’ health (WCAH) is currently not mainstreamed in climate policies and financing. There is also a need to consider new and innovative financing arrangements that support WCAH alongside climate goals.We provide an overview of the threats climate change represents for WCA, including the most vulnerable communities, and where health and climate investments should focus. We draw on evidence to explore the opportunities and challenges for health financing, climate finance and co-financing schemes to enhance equity and protect WCAH while supporting climate goals.WCA face threats from the rising burden of ill-health and healthcare demand, coupled with constraints to healthcare provision, impacting access to essential WCAH services and rising out-of-pocket payments for healthcare. Climate change also impacts on the economic context and livelihoods of WCA, increasing the risk of displacement and migration. These impacts require additional resources to support WCAH service delivery, to ensure continuity of care and protect households from the costs of care and enhance resilience. We identify a range of financing solutions, including leveraging climate finance for WCAH, adaptive social protection for health and adaptations to purchasing to promote climate action and support WCAH care needs.

State-of-the-art topological devices require the use of topologically protected surface states to drive electronic transport. In this paper, we examine a tunable topological system, Ge(BixSb1-x)2Te4, for a range of x values from 0 to 1, using a combination of Fourier transform scanning tunneling spectroscopy and angle-resolved photoemission spectroscopy. Our results show that the Dirac point shifts linearly with x, crossing the Fermi energy near x=0.7. This observation of a smoothly tunable, isolated Dirac point crossing through the topological transport regime and having strong linear dependence with substitution can be critical for future topological spintronics applications.

Abstract Background Even acknowledging the game-changing results achieved in the treatment of metastatic melanoma with the use of immune checkpoint inhibitors (ICI), a large proportion of patients (40–60%) still fail to respond or relapse due to the development of resistance. Alterations in the expression of Human Leukocyte Antigen class I (HLA-I) molecules are considered to play a major role in clinical resistance to ICI. Cellular immunotherapy with HLA-independent CAR-redirected lymphocytes is a promising alternative in this challenging setting and dedicated translational models are needed. Methods In this study, we propose an HLA-independent therapeutic strategy with Cytokine Induced Killer lymphocytes (CIK) genetically engineered with a Chimeric Antigen Receptor (CAR) targeting the tumor antigen CSPG4 as effector mechanism. We investigated the preclinical antitumor activity of CSPG4-CAR.CIK in vitro and in a xenograft murine model focusing on patient-derived melanoma cell lines (Mel) with defective expression of HLA-I molecules. Results We successfully generated CSPG4-CAR.CIK from patients with metastatic melanoma and reported their intense activity in vitro against a panel of CSPG4-expressing patient-derived Mel. The melanoma killing activity was intense, even at very low effector to target ratios, and not influenced by the expression level (high, low, defective) of HLA-I molecules on target cells. Furthermore, CAR.CIK conditioned medium was capable of upregulating the expression of HLA-I molecules on melanoma cells. A comparable immunomodulatory effect was replicated by treatment of Mel cells with exogenous IFN-γ and IFN-α. The antimelanoma activity of CSPG4-CAR.CIK was successfully confirmed in vivo, obtaining a significant tumor growth inhibition of an HLA-defective Mel xenograft in immunodeficient mice. Conclusions In this study we reported the intense preclinical activity of CSPG4-CAR.CIK against melanoma, including those with low or defective HLA-I expression. Our findings support CSPG4 as a valuable CAR target in melanoma and provide translational rationale for clinical studies exploring CAR-CIK cellular immunotherapies within the challenging setting of patients not responsive or relapsing to immune checkpoint inhibitors.

The issue of literacy challenges among dyslexic adults remains a significant concern. This study investigates spelling deficits among highly educated adults with dyslexia learning a transparent orthography. Thirty-eight Italian dyslexic university students were examined and compared to a group of age- and education-matched typical readers. Firstly, we analyzed spelling performance using a Passage Dictation Test. Additionally, lists of words varying in length and word frequency were dictated under two experimental conditions: a normal condition (NC) and an articulatory suppression condition (ASC). The ASC assessed the participants’ ability to spell with interference to the phonological (sublexical) spelling procedure, i.e., the most likely compensated spelling strategy of Italian dyslexic spellers. The results clearly indicated that, in spelling the meaningful passage, dyslexic participants underperformed compared to the controls, with a prevalence of lexical errors, despite the comparison with the normative reference data showing only mild spelling difficulties. In spelling isolated words in normal conditions, dyslexic participants performed within the reference norms and as accurately as control participants across all stimuli (short words, high- and low-frequency words), except for long words, where their spelling difficulties were evident. Articulatory suppression significantly impaired dyslexics’ performance on short stimuli, reducing the usual sublexical advantage associated with them, and exacerbated misspellings on long words. Additionally, articulatory suppression disproportionately affected dyslexics’ performance on high-frequency words, diminishing the typical lexical advantage associated with these words. Results are discussed in terms of their theoretical, clinical, and educational implications.

This paper reports on a research project in Responsible Tourism (Prayag, Hosany, & Odeh, 2013) carried out at the University of Salento in collaboration with the local administrations of some seaside resorts in Southern Italy affected by migrants' massive arrivals. This project, which involves tourists, migrants, university students in intercultural mediation and local communities, applies a model of Experiential-Linguistics (Lakoff & Johnson, 1999) to a multimodal Ethnopoetic analysis (Hymes, 2003; Kress, 2009) of (a) non-Western migrants' traumatic accounts of journeys across the sea, reported in their own ELF variations (Guido, 2008, 2018), (b) Western epic narratives of Mediterranean dramatic voyages rendered from Ancient Greek and Latin into modern ELF variations, and (c) multimodal representations of the ethnopoetic rhythms of such ancient and modern sea-journey narratives through the production of a promotional video. The aim is to highlight the experiential common roots shared by classical-epic and contemporary migration narratives. Three main research phases will be explored, which are characterised by pedagogical activities meant to foster an active, multicultural community integration, as well as a view of tourism as an inclusive social experience.

This work reports the results of the analyses performed on a set of glass finds from the “Gaetano Chierici” collection in the Civic Museums of Reggio Emilia. Forty-eight typologically heterogeneous glass finds were included in the list of the analyzed objects, dating from the fifth century BCE to the first century CE. The objects primarily consisted of glass beads; however, bangles, pinheads, and one vessel fragment were also included in the set. The items were analyzed using non-invasive spectroscopic methods that were implemented with portable equipment on the museum’s premises. Fiber optic reflectance spectroscopy was used to identify the coloring species in the glass matrix, while X-ray fluorescence spectrometry provided compositional information. Both techniques allowed for a discussion of the mechanisms of coloring and opacification, as well as the raw materials used for this purpose. The results provided a complex picture of the various colorants used to manipulate the appearance of the glass, which was a crucial aspect in the creation of the personal adornments represented by these glass items. The data revealed evidence of different sources of raw glass and colorants. Most of the samples were colored with cobalt, but iron and copper also influenced the color of many of them. Both white and yellow were utilized for the glass decorations, and these colors were achieved with the addition of either antimony-containing crystals or tin-containing ones. This finding suggests that the transition from antimonate to stannate started as early as the second century BCE. The “Gaetano Chierici” collection contains representative objects distributed throughout the investigated period. The results obtained here are a starting point for future studies of glass technology and provenance in the area.

Prostate cancer (PC) is the most common type of tumor in men. In the early stage of the disease, it is sensitive to androgen deprivation therapy. In patients with metastatic castration-sensitive prostate cancer (mHSPC), chemotherapy and second-generation androgen receptor therapy have led to increased survival. However, despite advances in the management of mHSPC, castration resistance is unavoidable and many patients develop metastatic castration-resistant disease (mCRPC). In the past few decades, immunotherapy has dramatically changed the oncology landscape and has increased the survival rate of many types of cancer. However, immunotherapy in prostate cancer has not yet given the revolutionary results it has in other types of tumors. Research into new treatments is very important for patients with mCRPC because of its poor prognosis. In this review, we focus on the reasons for the apparent intrinsic resistance of prostate cancer to immunotherapy, the possibilities for overcoming this resistance, and the clinical evidence and new therapeutic perspectives regarding immunotherapy in prostate cancer with a look toward the future.

Abstract Several types of (mostly) blue-green glass beads from Iron-Age archaeological sites in Central Italy were studied using a range of spectroscopic techniques: portable X-Ray Fluorescence spectrometry, Fibre Optics Reflectance Spectroscopy, Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectrometry, micro-Raman spectroscopy and Laser Ablation Inductively Coupled Plasma Mass Spectrometry. Complementary information was gathered from each technique and discussed in the frame of the archaeological typology of the objects. The systematic evaluation of the results allowed us to draw some conclusions on the raw materials employed for primary production and to highlight some provenance indicators in the glass. Some of the beads found in the Iron Age (IA) contexts were preliminarily attributed to the Final Bronze Age (FBA) production based on their typology, and the compositional data obtained in this work confirmed that they were low magnesium high potassium (LMHK) glass, typical of FBA in the Italian peninsula. Other beads were assigned to low magnesium glass (LMG) or high magnesium glass (HMG), thus giving further information on the fluxing agents employed in the Early Iron Age (EIA) and beyond. Colour variations among the beads reflected their chemical composition, with different bead typologies coloured in a specific way. In some instances, it was possible to establish different origins for the colouring raw materials. The provenance of the samples was difficult to place, but the chemical evidence suggested a subdivision within the raw glass used to produce the beads: for one set of samples, a local origin of the glass could be hypothesised, whereas several production sites in the Near East were suggested for most of the beads considered in this study. Some preliminary clues for the local working of imported glass were also highlighted for one typological group.

Food distribution and abundance can affect intra- and inter-dietary variation in non-human primates, influencing feeding ecology and altering behaviour. Natural and/or human-induced actions can influence the dynamics between primates and the environment, with associated impacts on socio-ecology and demography. This relationship in anthropogenic landscapes, however, is poorly understood. Here, we use DNA metabarcoding to obtain high resolution dietary diversity data, and multivariate generalised linear models to investigate variation in the diet of this threatened primate. We characterise the diet of the western red colobus (Piliocolobus badius) in both the better preserved Gola Rainforest National Park (GRNP, Sierra Leone), and in the fragmented forests of Cantanhez National Park (CNP, Guinea-Bissau), and evaluate biological, ecological and temporal differences. Dietary plant species richness was high in both protected areas, and the type of plants consumed varied significantly across seasons, space, and time. Although we identify dependence on a few key plants, red colobus in CNP consumed a higher average number of plant taxa than in GRNP, and 11% of the diet consisted of cultivated foods (e.g. mango). This is the first time a molecular approach has been used to investigate red colobus diet, and reveal dietary flexibility in degraded forests. Predicting the consequences of dietary change on long-term population persistence, however, remains a significant knowledge gap. Nevertheless, our results provide critical information to inform targeted regional conservation planning and implementation.

IntroductionRecombination activating genes (RAG) 1 and 2 defects are the most frequent form of severe combined immunodeficiency (SCID). Patients with residual RAG activity have a spectrum of clinical manifestations ranging from Omenn syndrome to delayed-onset combined immunodeficiency, often associated with granulomas and/or autoimmunity (CID-G/AI). Lentiviral vector (LV) gene therapy (GT) has been proposed as an alternative treatment to the standard hematopoietic stem cell transplant and a clinical trial for RAG1 SCID patients recently started. However, GT in patients with hypomorphic RAG mutations poses additional risks, because of the residual endogenous RAG1 expression and the general state of immune dysregulation and associated inflammation.MethodsIn this study, we assessed the efficacy of GT in 2 hypomorphic Rag1 murine models (Rag1F971L/F971L and Rag1R972Q/R972Q), exploiting the same LV used in the clinical trial encoding RAG1 under control of the MND promoter.Results and discussionStarting 6 weeks after transplant, GT-treated mice showed a decrease in proportion of myeloid cells and a concomitant increase of B, T and total white blood cells. However, counts remained lower than in mice transplanted with WT Lin- cells. At euthanasia, we observed a general redistribution of immune subsets in tissues, with the appearance of mature recirculating B cells in the bone marrow. In the thymus, we demonstrated correction of the block at double negative stage, with a modest improvement in the cortical/medullary ratio. Analysis of antigenspecific IgM and IgG serum levels after in vivo challenge showed an amelioration of antibody responses, suggesting that the partial immune correction could confer a clinical benefit. Notably, no overt signs of autoimmunity were detected, with B-cell activating factor decreasing to normal levels and autoantibodies remaining stable after GT. On the other hand, thymic enlargement was frequently observed, although not due to vector integration and insertional mutagenesis. In conclusion, our work shows that GT could partially alleviate the combined immunodeficiency of hypomorphic RAG1 patients and that extensive efficacy and safety studies with alternative models are required before commencing RAG gene therapy in thesehighly complex patients.

High-energy particle impacts due to background or cosmic radiation have been identified as sources of correlated errors in superconducting qubit arrays. Iaia et al. achieve a suppression of correlated error rate by channeling the energy away from the qubits via a thick metal layer at the bottom of the chip.

Stocking of native and non-native fish species is a widespread practice commonly used to enhance inland recreational fisheries, appropriate when intense harvesting and the degradation or lack of suitable habitat decrease the abundance of the managed species below carrying capacity. In spite of its popularity, this practice is often poorly informed by scientific information. Salmonids are arguably the most popular and commercially valuable freshwater fishes being managed for recreational fisheries. Stocking of both native and non-native taxa has been practiced for almost two centuries in Europe, dramatically altering the structure and function of riverine and lacustrine ecosystems. In the Verbano-Cusio Ossola Province, northern Italy, within the Lake Maggiore catchment, we measured large numerical mismatches between stocking of cultured native (Salmo marmoratus) plus non-native trout taxa (S. trutta, S. ghigii, Oncorhynchus mykiss) and the number of fishes captured by local anglers. These observations highlight the need for future studies to estimate the stocking effectiveness of S. marmoratus, a critically endangered species of significant cultural and economic value.