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Abstract PI3K/AKT/mTOR pathway is implicated in breast cancer progression and recurrence. The identification of PIK3CA and AKT1 mutations and loss of PTEN serve as selection criterion for targeted therapies involving selective inhibitors. However, they do not consistently align with pathway activation, and high-cost determinations limit their routine application. PI3K-downstream epigenetic regulatory mechanisms broaden the alterations that amplify pathway activity and, consequently, sensitivity to selective inhibitors. In this retrospective observational study, conducted within a cohort of early-stage breast cancer patients, we determined phosphorylated ribosomal protein S6 (pS6) at Ser240/244 by immunohistochemistry as an indicator of PI3K pathway activation. Log-Rank test and Cox proportional hazards regression were used to analyze the clinical relevance of pS6, alone and together with clinicopathological variables, regarding recurrence-free survival. ROC curves and the area under the curves were used to evaluate the calibration and discrimination properties of uni- and multivariate models. Our results show that a high percentage of pS6 positive tumor cells was associated with an unfavorable prognosis in a cohort of 129 hormone receptor positive/HER2 negative breast cancer patients (Hazard Ratio = 5.92; Log-Rank p = 9.5e-08; median follow-up = 53 months). When assessed in combination with lymph node status, the predictive capacity was higher compared to both univariate models individually. In conclusion, pS6 could represent a novel independent marker for predicting recurrence risk in luminal breast cancer.

The study of rock chemistry is a milestone in understanding fluid–rock interactions and fluid migration in subduction zones. When combined with thermodynamic models, it can provide direct insight into fluid composition, metasomatic reactions, and pressure–temperature (P–T) conditions, as well as their role in rock deformation. Here, a shear zone – located in the Mont Avic area of the Zermatt-Saas zone (Western Alps) – is analyzed. This shear zone consists of several blocks of different lithotypes, including a Ca-rich metasomatite block embedded in a serpentinite mylonitic matrix, and structurally underlies a coherent eclogitic mafic unit. This work aims to estimate the pressure–temperature conditions of the Ca-rich metasomatism and the amount of fluid involved. The brecciation exhibits mosaic breccia textures with clasts comprising ∼80 vol % of garnet, together with omphacite, epidote, titanite, rutile, and apatite hosted in an omphacite matrix. Quantitative chemical mapping of the garnet reveals primary garnet cores with embayment and lobate edges with a chemical composition similar to unaltered reference eclogite garnet. These primary garnet cores are overlain by Ca-rich metasomatic garnet rims with oscillatory chemical zoning. The oscillatory chemical zoning, together with the morphology of the primary garnet cores, suggests repeated influxes of external Ca-rich fluid that destabilized the primary garnet cores and promoted the growth of Ca-rich rims. Mass balance calculations between precursor metabasite and Ca-metasomatite indicate multiple fluid sources involving dehydrated serpentinite, calcic metasediments, and metabasites with time-integrated fluid fluxes calculated between 11.5×103 and 5.5×104 mfluid3 mrock-2, consistent with channelized fluid flow in an open system. Thermodynamic modeling of garnet from unbrecciated and non-metasomatized metabasites – from the Savoney eclogitic mafic unit – indicates peak metamorphic conditions of 2.5±0.1 GPa and 535±40 °C, consistent with regional estimates. Pressure–temperature conditions of metasomatism were constrained using P–X and T–X phase modeling (where X represents changes in bulk CaO and Na2O composition) between 2.6–2.2 GPa and 570–500 °C, showing that Ca-rich fluid percolation occurred close to the metamorphic peak (i.e., prograde to the peak or early exhumation path).

In mountain ranges, crustal-scale faults localize multiple episodes of deformation. It is therefore common to observe current or past geothermal systems along these structures. Understanding the fluid circulation channelized in fault zones is essential to characterize the thermochemical evolution of associated hydrothermal systems. We present a study of a palaeo-system of the Pic de Port Vieux thrust fault. This fault is a second-order thrust associated with the Gavarnie thrust in the Axial Zone of the Pyrenees. The study focused on phyllosilicates which permit the constraint of the evolution of temperature and redox of fluids at the scale of the fault system. Combined X-ray absorption near-edge structure (XANES) spectroscopy and electron probe microanalysis (EPMA) on synkinematic chlorite, closely linked to microstructural observations, were performed in both the core and damage zones of the fault zone. Regardless of the microstructural position, chlorite from the damage zone contains iron and magnesium (Fetotal / (Fetotal + Mg) about 0.4), with Fe3+ accounting for about 30 % of the total iron. Chlorite in the core zone is enriched in total iron, but individual Fe3+/Fetotal ratios range from 15 % to 40 %, depending on the microstructural position of the grain. Homogeneous temperature conditions about 280–290 °C have been obtained by chlorite thermometry. A scenario is proposed for the evolution of fluid–rock interaction conditions at the scale of the fault zone. It involves the circulation of a single hydrothermal fluid with homogeneous temperature but several redox properties. A highly reducing fluid evolves due to redox reactions involving progressive dissolution of hematite, accompanied by crystallization of Fe2+-rich and Fe3+-rich chlorite in the core zone. This study shows the importance of determining the redox state of iron in chlorite to calculate their temperature of formations and to consider the fluid evolution at the scale of a fault.

Modelling magma transport requires robust numerical schemes for chemical advection. Current numerical schemes vary in their ability to be mass conservative, computationally efficient, and accurate. This study compares four of the most commonly used numerical schemes for advection: an upwind scheme, a weighted essentially non-oscillatory (WENO-5) scheme, a semi-Lagrangian (SL) scheme, and a marker-in-cell (MIC) method. The behaviour of these schemes is assessed using the passive advection of two different magmatic compositions. This is coupled in 2D with the temporal evolution of a melt anomaly that generates porosity waves. All algorithms, except the upwind scheme, are able to predict the melt composition with reasonable accuracy, but none of them is fully mass conservative. However, the WENO-5 scheme shows the best mass conservation. In terms of total running time and when multithreaded, the upwind, SL, and WENO-5 schemes show similar performance, while the MIC scheme is the slowest due to reseeding and removal of markers. The WENO-5 scheme has a reasonable total run time, has the best mass conservation, is easily parallelisable, and is therefore best suited for this problem.

Abstract BackgroundVirtual reality (VR) is a type of extended reality (XR) technology that is seeing increasing adoption in health care. There is robust evidence articulating how consumer-grade VR presents significant cybersecurity and privacy risks due to the often ubiquitous and wide range of data collection and user monitoring, as well as the unique user impact of attacks due to the immersive nature of the technology. However, little is known about how these risks translate in the use of VR systems in health care settings. ObjectiveThe objective of this scoping review is to identify potential cybersecurity risks associated with clinical XR systems, with a focus on VR, and potential mitigations for them. MethodsThe scoping review followed the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews), and publications were reviewed using Covidence software. The Google Scholar database was searched using the predefined search terms. The inclusion criteria of the articles were restricted to relevant primary studies published from 2017 to 2024. Furthermore, reviews, abstracts, viewpoints, opinion pieces, and low-quality studies were excluded. Additionally, data on publication statistics, topic, technology, cyber threats, and risk mitigation were extracted. These data were synthesized and analyzed using the STRIDE (spoofing, tampering, repudiation, information disclosure, denial of service, and elevation of privilege) framework, enterprise risk management framework, and National Institute of Standards and Technology Cybersecurity Framework, as well as developing threat taxonomies. ResultsGoogle Scholar returned 482 articles that matched the search criteria. After title and abstract screening, 53 studies were extracted for a full-text review, of which 29 were included for analysis. Of these, the majority were published in the last 4 years and had a focus on VR. The greatest cyber threat identified to XR components was information disclosure followed by tampering when mapped against the STRIDE framework. The majority of risk mitigation strategies provide confidentiality and integrity and can potentially address these threats. Only 3 of 29 papers mention XR in the context of health care and none of the identified threats or mitigations have been studied in a clinical setting. ConclusionsThis scoping review identified privacy threats where personal and health-related data may be inferred from VR usage data, potentially breaching confidentiality, as the most significant threat posited for health care VR systems. Additionally, immersive manipulation threats were highlighted, which could potentially risk user safety when launched from a compromised VR system. Many potential mitigations were identified for these threats, but these mitigations must first be assessed for their effectiveness and suitability for health care services. Furthermore, health care services should consider the usage and governance of XR for each individual application based on risk threshold and perceived benefits. Finally, it is also important to note that this scoping review was limited by the quality and scope of the studies returned by Google Scholar.

Campi Flegrei caldera is an Italian high-risk volcano experiencing a progressively more intense long-term uplift, accompanied by increasing seismicity and geochemical emissions over the last two decades. Ground deformation shows an axisymmetric bell-shaped pattern, with a maximum uplift of about 120 cm, from 2005, in the caldera central area. We analyzed Sentinel-1 and COSMO-SkyMed Multi-Temporal DInSAR measurements and GNSS data to reveal and investigate a geodetic anomaly that has clearly manifested since 2021, locally deviating from the typical bell-shaped deformation pattern. This anomaly is located east of Pozzuoli town, in the Mt. Olibano–Accademia area, covers an area of about 1.3 km2 and shows, in comparison to surrounding areas, a maximum uplift deficit of about 9 cm between 2021 and 2023. To investigate the anomaly causes, we analyzed the caldera seismicity and inverted the DInSAR data to determine the primary source of the ground deformation pattern, which is consistent with a penny-shaped source located approximately 3800 m beneath the Pozzuoli town, with a radius of about 1200 m. We also found that the time evolution of the uplift deficit in the geodetic anomaly area correlates well with the earthquake occurrence, with the greater magnitude events clustering in this area. These considerations suggest the geodetic anomaly is a local response to the tensile stress regime produced by the inflating primary deformation source. This phenomenon can be influenced by the Mt. Olibano–Accademia lava domes lithological heterogeneities that may induce a localized reaction to ground deformation during the inflationary phase. Our interpretation aligns with the concentration of earthquakes and hydrothermal fluid emissions in this area, indicating the presence of faults, fractures, and fluid circulation. Accordingly, the geodetic anomaly area represents a zone of crustal weakness that requires careful monitoring and study.

BackgroundThe use of Non-Pharmaceutical Interventions (NPIs) during the COVID-19 pandemic is debated. Understanding the consequences these measures may have on vulnerable populations including children and adolescents is important.MethodsThis is a multicenter, quasi-experimental before-after study involving 12 hospitals of the North Italian Emilia-Romagna Region, with NPI implementation as the intervention event. The 3 years preceding NPI implementation (in March 2020) constituted the pre-pandemic phase. The subsequent 2 years were further subdivided into a school closure phase (SC) and a subsequent mitigation measures phase (MM) with milder restrictions. Interrupted Time Series (ITS) regression analysis was used to calculate PED Standardized Incidence Rate Ratios (SIRR) on the diagnostic categories exhibiting the greatest frequency and/or variation.ResultsIn the 60 months of the study there were 765,215 PED visits. Compared to the pre-pandemic rate, overall PED presentations dropped by 58 and 39% during SC and MM, respectively. “Symptoms, signs and Ill-defined conditions,” “Injury and poisoning” and “Diseases of the Respiratory System” accounted for 74% of the reduction. A different pattern was instead seen for “Mental Disorders,” which exhibited the smallest decrease during SC, and is the only category which rose already at the end of SC. ITS analysis confirmed the strong decrease during SC (level change, IRR 0.17, 95%CI 0.12–0.27) and a significant increase in MM (slope change, IRR 1.23, 95%CI 1.13–1.33), with the sharpest decline (−94%) and rise (+36%) observed in the “Diseases of the Respiratory System” category. Mental Disorders showed a significant increasing trend of 1% monthly over the whole study period exceeding pre-pandemic levels at the end of MM. Females and adolescents showed higher increasing rates both in SC and MM.ConclusionNPIs appear to have influenced PED attendance in different ways according to diagnostic categories, mirroring different mechanisms of action. These effects are beneficial in some cases and harmful in others, and establishing a clear balance between pros and cons is a difficult task for public health decision makers. The role of NPIs on PED use appropriateness deserves investigation. The rise in pediatric mental disorders independent of the pandemic makes interventions addressing these issues urgent.

Introducción: La cirugía mínimamente invasiva de columna se ha vuelto cada vez más popular en los últimos años. Se han desarrollado técnicas nuevas y menos invasivas que se han convertido en procedimientos de elección para determinadas enfermedades. El tamaño del corredor aorto-psoas es un factor determinante al elegir la técnica oblicua de fusión intersomática. Objetivos: Describir las modificaciones en el tamaño del corredor aorto-psoas en decúbito lateral derecho y decúbito supino mediante resonancia magnética y su asociación con el índice de masa corporal. Materiales y Métodos: Se realizó una resonancia magnética de los espacios discales de L1-L2 a L4-L5 a 13 voluntarios en decúbito supino y decúbito lateral derecho. Se midió el corredor y se comparó el tamaño en cada nivel. Resultados: El tamaño del corredor aorto-psoas y de la distancia arteria-disco tuvo un aumento estadísticamente significativo al posicionar al paciente en decúbito lateral derecho. Conclusiones: La resonancia magnética es de suma importancia en la planificación prequirúrgica, pues deja en evidencia la movilidad de las estructuras abdominales. Se producen cambios significativos en el corredor aorto-psoas y la distancia arteria-disco al ubicar al paciente en decúbito lateral derecho. Sin embargo, estos cambios no tienen una relación significativa con el índice de masa corporal.

In this work, the airborne Synthetic Aperture Radar (SAR) infrastructure developed at the Institute for Electromagnetic Sensing of the Environment (IREA) of the National Research Council of Italy (CNR) is described. This infrastructure allows IREA-CNR to plan and execute airborne SAR campaigns and to process the acquired data with a twofold aim. On one hand, the aim is to develop research activities; on the other hand, the aim is to support the emergency prevention and management activities of the Department of Civil Protection of the Italian Presidency of the Council of Ministers, for which IREA-CNR serves as National Centre of Competence. Such infrastructure consists of a flight segment and a ground segment that include a multi-frequency airborne SAR sensor based on the Frequency-Modulated Continuous Wave (FMCW) technology and operating in the X- and L-bands, an Information Technology (IT) platform for data storage and processing and an airborne SAR data processing chain. In this work, the technical aspects related to the flight and ground segments of the infrastructure are presented. Moreover, a discussion on the response times and characteristics of the final products that can be achieved with the infrastructure is provided with the aim of showing its capabilities to support the monitoring activities required in a possible emergency scenario. In particular, as a case study, the acquisition and subsequent interferometric processing of airborne SAR data relevant to the Stromboli volcanic area in the Sicily region, southern Italy, are presented

Human leishmaniasis is facing important epidemiological changes in Southern Europe, driven by increased urbanization, climate changes, emerging of new animal reservoirs, shifts in human behavior and a growing population of immunocompromised and elderly individuals. In this evolving epidemiological landscape, we analyzed the clinical and epidemiological characteristics of human leishmaniasis in the Tuscany region of Central Italy. Through a multicentric retrospective analysis, we collected clinical and demographic data about all cases of leishmaniasis recorded between 2018 and 2023. We observed 176 cases of human leishmaniasis, with 128 (72.7%) visceral leishmaniasis (VL) and 47 (26.7%) cutaneous leishmaniasis (CL). Among these, 92.2% of VL and 85.1% of CL cases were autochthonous. The cumulative incidence of autochthonous human leishmaniasis was 0.22 cases per 100,000 inhabitants in 2018, but reached 1.81/100,000 in 2023. We identified three main areas of transmission: around the city of Florence (North-East Tuscany), around Grosseto city (South-West Tuscany) and Elba Island. Our findings confirm that the epidemiology of leishmaniasis is undergoing significant changes in Central Italy. Awareness towards this emerging health threat and surveillance strategies need to be improved in order to reliably assess the disease’s burden. Further research is needed in a “One-Health” perspective, to clarify the epidemiological dynamics at the environmental, reservoir, vector and human levels. The role of climate change and specific climatic factors affecting the epidemiological patterns of human leishmaniasis should be assessed. Further knowledge in these fields would promote targeted control and prevention strategies at regional and national levels.

Background: Kawasaki disease (KD) is a systemic vasculitis of medium arteries, particularly involving coronary arteries. Coronary artery lesions (CALs) is the most serious complication in the acute stage, potentially leading to ischemic cardiomyopathy, myocardial infarction and sudden death. Environmental factors and genetic background contribute to individual susceptibility to develop CALs. The aim of this study was to define the risk factors for CALs in an Italian cohort. Methods: Data of KD patients from 10 Italian sites were registered into a REDCap database where demographic and clinical data, laboratory findings and coronary status were recorded. KD was diagnosed according to AHA definition. We used multiple logistic regression analysis to identify independent risk factors for CALs. Results: A total of 517 patients were enrolled, mainly Caucasians (83.6%). Presentation was complete in 321 patients (62.8%) and IVIG responsiveness in 360 (70%). CALs developed in 136/517 (26.31%). Gender, age, ethnicity, clinical presentation, fever duration, non-coronary cardiac events, Hb, albumin and CRP were significantly different between patients with and without CALs, while seasonality was not. Male gender, age < 18 months, Asian ethnicity, incomplete presentation and fever > 10 days were independent risk factors for CALs. Conclusions: Age younger than 18 months, incomplete KD and longer fever duration are risk factors for CALs. Asian ethnicity also represents a risk factor in our Italian Cohort.

Background/Objectives: Levothyroxine (L-T4) is available for use in congenital hypothyroidism (CH) in three formulations: tablets, drops, and oral solution. This study aims to compare the efficacy and safety of all three L-T4 formulations. Methods: We enrolled 63 children born between January 2019 and April 2023 in the Emilia-Romagna Region (Italy) and diagnosed with CH by newborn screening. They were divided according to the L-T4 formulation used: drops (Group D), oral solution (Group S), and tablets (Group T). Clinical and laboratory data were collected up to 3 years after the start of replacement therapy. Results: Serum-free thyroxine (sFT4) and thyroid stimulating hormone (sTSH) normalization occurred within the first month of treatment in most patients of all groups. No negative effects on growth and cognitive development were observed. At 7–15 days we found higher median sTSH levels (p = 0.031) and a greater percentage of patients with sTSH > 5 µU/mL (p = 0.011) in Group S than in Group T, but comparable sFT4 levels. At 12 months, a greater percentage of patients of Group D showed sFT4 values below the normal range than Group S (p = 0.011) and Group T (p = 0.038); Conclusions: Overall, our study reported an equal efficacy of the L-T4 oral solution compared to drops and tablets in CH treatment. A larger series of patients and a long-term follow-up are needed.