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Abstract Background Gaucher disease (GD) is a rare, inherited, autosomal recessive disorder caused by a deficiency of the lysosomal enzyme, acid β-glucosidase. Its diagnosis is achieved via measurements of acid β-glucosidase activity in either fresh peripheral blood leukocytes or dried blood spots, and confirmed by identifying characteristic mutations in the GBA1 gene. Currently, several biomarkers are available for disease monitoring. Chitotriosidase has been used over the last 20 years to assess the severity of GD, but lacks specificity in GD patients. Conversely, the deacylated form of glucosylceramide, glucosylsphingosine (also known as lyso-Gb1), represents a more reliable biomarker characterized by its high sensitivity and specificity in GD. Main text Herein, we review the current literature on lyso-Gb1 and describe evidence supporting its usefulness as a biomarker for diagnosing and evaluating disease severity in GD and monitoring treatment efficacy. Conclusion Lyso-Gb1 is the most promising biomarker of GD, as demonstrated by its reliability in reflecting disease burden and monitoring treatment response. Furthermore, lyso-Gb1 may play an important role in the onset of monoclonal gammopathy of uncertain significance, multiple myeloma, and Parkinson’s disease in GD patients.

Recent research has found that neural networks for computer vision are vulnerable to several types of external attacks that modify the input of the model, with the malicious intent of producing a misclassification. With the increase in the number of feasible attacks, many defence approaches have been proposed to mitigate the effect of these attacks and protect the models. Mainly, the research on both attack and defence has focused on RGB images, while other domains, such as the infrared domain, are currently underexplored. In this paper, we propose two attacks, and we evaluate them on multiple datasets and neural network models, showing that the results outperform others established attacks, on both RGB as well as infrared domains. In addition, we show that our proposal can be used in an adversarial training protocol to produce more robust models, with respect to both adversarial attacks and natural perturbations that can be applied to input images. Lastly, we study if a successful attack in a domain can be transferred to an aligned image in another domain, without any further tuning. The code, containing all the files and the configurations used to run the experiments, is available https://github.com/jaryP/IR-RGB-domain-attackonline.

During the Conference on Cancer Long-term Survivors, held in Siracusa (Italy) on September 16, 2022, Oncologists, General Practitioners, Epidemiologists, Hematologists, Pediatric Oncologists, Nurses, Industry Medical Affairs and Patients' Advocates came together to discuss the clinical implications of the condition beyond acute cancer. The debate was based both on the current literature on this topic, and on the opinion of all participants. Specifically, numerous issues were discussed in the round tables, but focused mainly on the following topics: - REASONS FOR SUCCESS IN IMPROVING SURVIVAL RATES - REHABILITATION - LONG-TERM SURVEILLANCE - PEDIATRIC AND YOUNG ADULT ISSUES - SOCIAL, FINANCIAL AND INSURANCE ISSUES This Opinion Paper aims to stimulate a suitable support to the growing population of people cancer disease free or with long-term or late effects. The development of new models can promote actions towards the elimination of obstacles and difficulties in cancer survivorship care.

MXenes are two-dimensional nanomaterials that can be used as supercapacitors to store electrical energy. Here, the authors isolated chemical response from a single MXene flake and provide a new understanding of the surface chemistry of MXenes.

Abstract To date, the highly adapted cave microbial communities are challenged by the expanding anthropization of these subterranean habitats. Although recent advances in characterizing show-caves microbiome composition and functionality, the anthropic effect on promoting the establishment, or reducing the presence of specific microbial guilds has never been studied in detail. This work aims to investigate the whole microbiome (Fungi, Algae, Bacteria and Archaea) of four Italian show-caves, displaying different environmental and geo-morphological conditions and one recently discovered natural cave to highlight potential human-induced microbial traits alterations. Results indicate how show-caves share common microbial traits in contrast to the natural one; the first are characterized by microorganisms related to outdoor environment and/or capable of exploiting extra inputs of organic matter eventually supplied by tourist flows (i.e. Chaetomium and Phoma for fungi and Pseudomonas for bacteria). Yet, variation in microalgae assemblage composition was reported in show-caves, probably related to the effect of the artificial lighting. This study provides insights into the potential microbiome cave contamination by human-related bacteria (e.g. Lactobacillus and Staphylococcus) and commensal/opportunistic human associated fungi (e.g. Candida) and dermatophytes. This work is critical to untangle caves microbiome towards management and conservation of these fragile ecosystems.

The touristic use of caves causes multiple environmental alterations to the subterranean ecosystem, having potential effects on all components, from the atmosphere to lithosphere, hydrosphere, and biosphere. Setting a baseline on the current knowledge of the ecological status of world show caves is pivotal to implement monitoring and management programs aiming at their conservation. However, information on this topic is scattered throughout several publications, making it difficult to access data and ultimately delaying advances towards a sustainable touristic use of show caves. We provide a literature-based dataset relative to the knowledge on the ecological status of 265 show caves worldwide. Data were collated from 289 papers selected through a systematic literature survey of an initial set of more than 1,000 scientific papers. We made the compiled information available through two complementary datasets, reporting: (i) references of the selected papers and (ii) 44 fields relative to the main characteristics of show caves investigated in literature. These fields encompass information about geographic locations, cave general characteristics, natural heritage, and the specific environmental components—and related environmental parameters—investigated in each of the considered study. Such a dataset improves our accessibility to the basic information provided by literature on the ecological status of show caves, also pointing out some literature gaps that should be addressed by future research. By making these data freely available and re-usable, we hope to stimulate research in the field of cave tourism, cave conservation, and cave-based ecology.

2D MXene hydrogels are promising for diverse applications. Here, the authors report a universal 4D printing technology to manufacture MXene hydrogels with customizable geometry, high conductivity, and efficient pseudocapacitive energy storage ability.

Este artículo analiza la importante figura del director escolar en el sistema educativo español, en el que los aspectos burocráticoadministrativos y de gestión definen cada vez más sus características. El proceso de acceso a la función directiva, la falta de un adecuado reconocimiento de la carrera profesional, la escasa aplicación de la autonomía en un sistema todavía muy centralizado, la falta de una formación y evaluación estructurada, y las enormes responsabilidades en ámbitos muy diversos (económico, jurídico, didáctico, psicológico, relacional, de seguridad), manifiestan la urgente necesidad de revisar el liderazgo escolar, proponiendo una profunda reflexión cultural y educativo-pedagógica y un cambio radical de paradigma.

In this article, we describe a rare case of the nutcracker syndrome caused by combined compression of the left anteroaortic and retroaortic renal veins. Case description: A 42-year-old woman presented with microhematuria and left flank pain. The patient underwent computed tomography and Doppler ultrasound which showed the left renal veins with anteroaortic and retroaortic courses, with signs of compression. Compression of the anteroaortic renal vein was caused by a narrowing of the aortomesenteric space, whereas compression of the retroaortic renal vein was caused by a narrowing of the aortovertebral space.

In this work, phytochemical analysis on different extracts of Roccella tinctoria DC. was reported using different techniques with respect to the past. Twenty volatile and three non-volatile compounds were identified, some of which were found in this species for the first time. The methanolic extracts and their non-volatile components were then evaluated for their antitumor effects in cancerous A549 and Mz-ChA-1 cells and for their tolerability in non-cancerous BEAS-2B and H69 cells, showing IC50 values from 94.6 µg/mL to 416.4 µg/mL, in general. The same extracts and compounds were also tested for their antifungal effects in Candida albicans, with only compound 2 being active, with an MIC50 value of 87 µg/mL. In addition, they were tested for their anti-Candida adhesion activity, anti-Candida biofilm formation, and anti-Candida mature biofilm inhibition, with efficacy percentages generally above 50% but not for all of them. Lastly, the DF3 extract and compounds 1–2 were tested in vivo according to the Galleria mellonella survival assay, showing positive mortality rates above 50% at different concentrations. All these biological assays were conducted on this species for the first time. Comparisons with other lichens and compounds were also presented and discussed.

Background. Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with rapidly progressive evolution and an unfavorable outcome. Nintedanib (NTD) is an antifibrotic drug that has been shown to be effective in slowing down the progression of the disease. The aim of our study was to examine the efficacy, especially in terms of the functional decline, and the safety profile of NTD in patients treated with the recommended dose and subjects who reduced or suspended the therapy due to the occurrence of adverse reactions. Methods. We conducted a real-life retrospective study based on the experience of NTD use in two centers between 2015 and 2022. Clinical data were evaluated at baseline, at 6 and 12 months after the NTD introduction in the whole population and in subgroups of patients who continued the full-dose treatment, at a reduced dosage, and at the discontinuation of treatment. The following data were recorded: the demographic features, IPF clinical features, NTD therapeutic dosage, tolerability and adverse events, pulmonary function tests (PFTs), the duration of treatment upon discontinuation, and the causes of interruption. Results. There were 54 IPF patients who were included (29.6% females, with a median (IQR) age at baseline of 75 (69.0–79.0) years). Twelve months after the introduction of the NTD therapy, 20 (37%) patients were still taking the full dose, 11 (20.4%) had reduced it to 200 mg daily, and 15 (27.8%) had stopped treatment. Gastrointestinal intolerance predominantly led to the dose reduction (13.0%) and treatment cessation (20.4%). There were two deaths within the initial 6 months (3.7%) and seven (13.0%) within 12 months. Compared to the baseline, the results of the PFTs remained stable at 6 and 12 months for the entire NTD-treated population, except for a significant decline in the DLCO (% predicted value) at both 6 (38.0 ± 17.8 vs. 43.0 ± 26.0; p = 0.041) and 12 months (41.5 ± 15.3 vs. 44.0 ± 26.8; p = 0.048). The patients who continued treatment at the full dose or a reduced dosage showed no significant differences in the FVC and the DLCO at 12 months. Conversely, those discontinuing the NTD exhibited a statistically significant decline in the FVC (% predicted value) at 12 months compared to the baseline (55.0 ± 13.5 vs. 70.0 ± 23.0; p = 0.035). Conclusions. This study highlights the functional decline of the FVC at 12 months after the NTD initiation among patients discontinuing therapy but not among those reducing their dosage.

Grapevine adaptation to drought involves morphological, anatomical, and physiological modifications that could be viewed as a measure of drought avoidance. The main vine responses to drought consist of the regulation of carbon assimilation as a consequence of limited stomatal conductance, which is reflected in changes in plant water status. In this factorial study (2020–2021 growing seasons), two red cultivars, the local ‘Aglianico’, widely grown in Central-South Italy, and the international ‘Cabernet Sauvignon’, were used to evaluate how their interaction in three different environments can modify physiological adaptations and how yields and their qualitative traits can be modified. The lowest leaf water potential (−0.68 Mpa) for the two cultivars was registered in Molise, while the most stressed vine was found in Sicily for Aglianico (−1.86 MPa). At least in two of three locations, Molise and Campania, the detected stomatal conductance and the leaf water potential have shown that Cabernet Sauvignon can be classified as a near-isohydric cultivar, whereas Aglianico can be categorized as a near-anisohydric cultivar. The interactions between genotype x environment highlight different levels of adaptability between the two cultivars in different sites during each season. The data presented here contribute to a better understanding of the effects of genotype and environment interactions in progressive dry cultivation and how these interactions can modify the qualitative traits of grapes.

A partir de dados empíricos levantados pelas áreas de educação e saúde, o texto apresenta uma reflexão teórica acerca do quadro radical de imersão digital da sociedade contemporânea, propondo uma reflexão acerca dos impactos desse fenômeno na propriocepção corporal, incidindo nos processos imaginativos, de memória, de consciência e de identidade, gerando um quadro comportamental que tem sido designado como cansaço (Han, 2015), sedação (Baitello, 2012), ou ainda desaparecimento de si (Breton, 2003).

Reliable non-invasive biomarkers for the surveillance of patients at risk of hepatocellular carcinoma (HCC) development represent an unmet medical need. Recently, the liver-cancer-specific isoform of serine protease inhibitor Kazal (LC-SPIK) has been proposed as a valuable biomarker for the detection of HCC in patients with chronic liver disease of viral etiology. In the present study, we assessed the diagnostic accuracy of LC-SPIK, alone or in combination with standard serologic biomarkers (i.e., alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II, PIVKA-II), for the detection of HCC among patients with dysmetabolic liver disease. A total of 120 patients with non-alcoholic fatty liver disease (NAFLD), including 62 patients with a diagnosis of HCC and 58 with cirrhosis but without tumor, were retrospectively analyzed. The serum levels of LC-SPIK were measured by enzyme-linked immunosorbent assay (ImCare Biotech, Doylestown, PA). The serum LC-SPIK values were significantly different between patients with HCC (24.3, 17.6–39.8 ng/mL) and those with cirrhosis but without tumor (11.7, 8.7–18.2 ng/mL) (p < 0.001). By receiver operating characteristic curve analysis, we observed an area under the curve (AUC) of 0.841 for the detection of HCC; the combination with PIVKA-II further increased the accuracy to AUC = 0.926 (cross-validation). The promising results observed in the present pilot study foster additional research to investigate the usefulness of LC-SPIK for the stratification of the risk of HCC development in patients with NAFLD and advanced liver disease.

In the last three decades, bridge stock seismic retrofitting prioritization has become one of the cult topics for scientific discussions in the bridge management strategies. More recent methods are focusing on the evaluation of the generalized failure cost, of a specific bridge derived from direct and indirect costs induced to the users/residents of the area exposed to the seismic hazard as a consequence of bridge collapse. However, when these approaches have to be applied to large transport networks, appear still very complex and computational demanding, and therefore simplified methods to evaluate the impact in terms of social cost related to the reduced efficiency of a transportation network due to potential bridge failure, are required.In this work, a simplified method for seismic retrofitting prioritization on a bridge stock is proposed, which is based on a “blended” approach considering specific fragility curves according to several bridge features and condition state, seismic inputs and generalized failure costs related to the transportation network. The effectiveness of the method has been showed on a case study of a local bridge stock placed in central Italy and the obtained results have been compared with those provided by more refined transport simulation models, on one hand, and by more traditional prioritization approaches, on the other. It is highlighted that this method can be very useful for transportation network managers with in a limited budget scenario, in case of lack of information about possible earthquake-induced impacts on a transportation network efficiency.

A pesar de los múltiples estudios internacionales adelantados sobre el liderazgo escolar, falta mucho por saber acerca de cómo los directores emplean a diario su tiempo, y de la gran variabilidad de las actividades que llevan a término. El objetivo de este estudio es examinar en qué medida las prácticas y estilos de liderazgo de seis directores escolares de España e Italia coinciden o difieren en aspectos relevantes de su práctica profesional. La investigación recurre al método mixto y, en el marco de seis estudios de casos, administra entrevistas, cuestionarios y grupos focales.

ObjectiveTo evaluate the viability of exoscopes in the context of neurosurgical education and compare the use of a 4k3D exoscope to a traditional operative microscope in the execution of a task of anatomic structure identification on a model of cranial approach.Material and methodsA cohort of volunteer residents performed a task of anatomical structure identification with both devices three times across an experimental period of 2 months. We timed the residents’ performances, and the times achieved were analyzed. The volunteers answered two questionnaires concerning their opinions of the two devices.ResultsAcross tries, execution speed improved for the whole cohort. When using the exoscopes, residents were quicker to identify a single anatomical structure starting from outside the surgical field when deep structures were included in the pool. In all other settings, the two devices did not differ in a statistically significant manner. The volunteers described the exoscope as superior to the microscope in all the aspects the questionnaires inquired about, besides the depth of field perception, which was felt to be better with the microscope. Volunteers furthermore showed overwhelming support for training on different devices and with models of surgical approaches.ConclusionThe exoscope appeared to be non-inferior to the microscope in the execution of a task of timed identification of anatomical structures on a model of cranial approach carried out by our cohort of residents. In the questionnaires, the residents reported the exoscope to be superior to the microscope in eight of nine investigated domains. Further studies are needed to investigate the use of the exoscope in learning of microsurgical skills.

In the setting of follicular lymphoma (FL), frontline therapy with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP) has represented for many years the standard of care for patients with symptomatic advanced disease. More recently, the combination of bendamustine plus rituximab (R-B) has emerged as an alternative therapeutic option. We present a retrospective, multicenter, observational study aimed at comparing outcomes and toxicities observed in 145 patients diagnosed with grade 3A FL treated with a first line therapy in 15 Italian Fondazione Italiana Linfomi centers between the 1st of January 2014 and the 30th of May 2018. Seventy patients were treated with R-B and 75 with R-CHOP. In the R-B group, the median age at the time of diagnosis was 67 years compared with 59 years in the R-CHOP group. Patients in R-B group achieved a similar overall response rate (96% vs. 99%) and a better complete remission rate (87% vs. 80%, p=0.035) compared with patients in R-CHOP group. Progression free survival (PFS) was similar between individual treated with R-CHOP and R-B (48- month PFS 77.7% vs. 76.6% respectively, p=0.745). The overall survival was significantly longer with R-CHOP treatment (HR=0.16; 95% IC, 0.04-0.74; p=0.007); however, no statistical significant difference was observed after adjustment for age. With the limitations of the study design, our results suggest that both R-B and R-CHOP seem to be valid first-line treatment options in FL3A.

Mice exposed to environmental enrichment for 5 weeks display distinct microbiota composition and behavioral and metabolic profiles compared to mice exposed to a standard environment. Mice treated with a mixture of short-chain fatty acids that are produced by gut bacteria recapitulate some of the effects of this environmental enrichment.

Laser-powder bed fusion was identified as a promising technique for manufacturing metal matrix composites. However, over a decade later, little progress has been made in addressing the persisting issues hindering the wider exploitation and industrial usage of metal matrix composites. Therefore, the present study proposes the implementation of a feasible solution to accomplish research advancements in metal matrix composites. Where, the issues concerning their performance and cost have driven this study towards the development of a novel scanning strategy. A hatching system based on a sine wave was successfully developed and employed in the printing of metal matrix composites. Composites printed using the sinusoidal hatching exhibited an enhanced yield strength and ductility owing to the resultant grain refinement and texture. The dabber mode formation of material tracks promoted the growth of highly oriented intragranular cellular structures. Apart for playing an important role at the obtained hardness, this control over the cellular growth could also be used towards improving composite toughness. Additionally, besides improving composite performance, the sinusoidal hatching was also effective in reducing manufacturing lead time and process energy consumption.

The overuse and misuse of antibiotics have led to the emergence and spread of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacteria strains, usually associated with poorer patient outcomes and higher costs. In order to preserve the usefulness of these life-saving drugs, it is crucial to use them appropriately, as also recommended by the WHO. Moreover, innovative, safe, and more effective approaches are being investigated, aiming to revise drug treatments to improve their pharmacokinetics and distribution and to reduce the onset of drug resistance. Globally, to reduce the burden of antimicrobial resistance (AMR), guidelines and indications have been developed over time, aimed at narrowing the use and diminishing the environmental spread of these life-saving molecules by optimizing prescriptions, dosage, and times of use, as well as investing resources into obtaining innovative formulations with better pharmacokinetics, pharmacodynamics, and therapeutic results. This has led to the development of new nano-formulations as drug delivery vehicles, characterized by unique structural properties, biocompatible natures, and targeted activities such as state-of-the-art phospholipid particles generally grouped as liposomes, virosomes, and functionalized exosomes, which represent an attractive and innovative delivery approach. Liposomes and virosomes are chemically synthesized carriers that utilize phospholipids whose nature is predetermined based on their use, with a long track record as drug delivery systems. Exosomes are vesicles naturally released by cells, which utilize the lipids present in their cellular membranes only, and therefore, are highly biocompatible, with investigations as a delivery system having a more recent origin. This review will summarize the state of the art on microvesicle research, liposomes, virosomes, and exosomes, as useful and effective tools to tackle the threat of antibiotic resistance.