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Abstract Campi Flegrei is a densely populated volcanic area in Italy. Its inner caldera periodically experiences uplift and subsidence, known as bradyseism, also accompanied by seismic activity. In the last decade, with uplift rates up to 2 cm/month, about nine-thousand earthquakes were recorded. Upon request of the local administration, the most updated data were collected and analyzed to evaluate the risk management strategy consisting of structural retrofitting according to the building code. Here it is shown that the reference moment magnitude is in the range $$\left({{\mathrm{4.4,5.1}}}\right)$$ 4.4, 5.1 , based on fault mapping, geomorphological inference, earthquake relocation, stress-drop analysis, and ground motion modelling. Earthquake forecasting enabled computing the exceedance probabilities of these magnitudes. Earthquake engineering showed that the minimum magnitudes expected to cause exceedance of design ground motion, are larger than the reference magnitudes. Finally, the risk reduction implied by the safety levels of new constructions was assessed for reinforced concrete buildings.

Abstract Background Early prediction of non-invasive respiratory therapy (NIRT) failure is crucial to avoid needless prolongation of respiratory support and delayed endotracheal intubation. Data comparing the predictive value of oxygenation indices (OI) in COVID-19 receiving NIRT are scant. The aim of this monocentric retrospective study of prospectively collected data was to assess the effectiveness of different OI in predicting NIRT outcome at baseline (t0), 12 h (t12) and 24 h (t24) of treatment in hypoxemic patients with COVID-19-related pneumonia, managed in a Pulmonary Intermediate Care Unit (October 2020-June 2021). Methods We assessed the predictive value of SpO2/FiO2, PaO2/FiO2, standardised PaO2/FiO2 ratio (s-PaO2/FiO2), respiratory index (RI), arterial–alveolar oxygen gradient (a-ADO2), age adjusted arterial–alveolar oxygen ratio (adj-a-ADO2D). Receiver operating characteristics (ROC), AUC and best sensitivity–specificity cut-off values were calculated at t0, t12, t24. NIRT failure risk was adjusted for non-oxygenation predictors. Results Among 590 patients with COVID-19 infection, 368 met the eligibility criteria for inclusion in the study [mean (CI95%): PaO2/FiO2 214(206,8–221,9); PaCO2 mean 32,9 mmHg,(32,4–33,4)]. NIRT failure and hospital mortality rate were 23,4% and 19,6%, respectively. Older age, male gender, agitation/confusion, need for sedation, inability to tolerate prone positioning were independent predictors of NIRT failure. SpO2/FiO2, a-ADO2 and adj-aADO2 at t12 and t24, PaO2/FiO2 and RI at t24 were associated with NIRT failure. Prognostic predictivity of OI increased from t0 to t24. Greater ROC-AUC values were obtained with SpO2/FiO2 0,662 (0,60–0,72) (t0), PaO2/FiO2 0,697 (0,63–0,76) (t12) and s-PaO2/FiO2 0,769 (0,71–0,83) (t24). NIRT failure was independently predicted by PaO2/FiO2, s-PaO2/FiO2 and RI at any observation time and by SpO2/FiO2 and O2 gradients respectively at t0 and t24. SaO2/FiO2 ≤ 300 (t0), PaO2/FiO2 ≤ 151,7 (t12) and s-PaO2/FiO2 ≤ 160,4 (t24) turned out to be the best predictors of NIRT outcome. Conclusions OI showed different effectiveness in predicting NIRT failure within 24 h of treatment in COVID-19 related pneumonia. This may be due to the multi-factorial pathophysiology of hypoxemia. Our study empathises furthermore the role of non-oxygenation-related parameters in contributing to the outcome. These findings may be useful to build a predictive model also in no COVID-19 related hypoxemic pneumonia.

Abstract Background The phenomenon of suicide risk (SR) represents a psychiatric, social and environmental emergency. The acute psychiatric ward as the Italian Service for Psychiatric Diagnosis and Care (SPDC) represents the place where SR is high due to the acute and serious conditions of people hospitalized. The objective of this study was to evaluate the characteristics of subjects admitted to a SPDC over a 6-year period for SR represented by: suicidal ideation, attempted and failed suicide. Methods With a retrospective single-center observational design, we collected hospitalizations from 01/01/2017 to 31/12/2022 in the SPDC of AUSL-Modena for SR, analyzed the modality of SR and compared the demographic and clinical variables of subjects with SR with those hospitalized for other clinical reasons in the same period. Data were statistically analyzed. Results In the 6-year of study period, we collected 2,930 hospitalizations in the SPDC of AUSL- Modena and among them, 68% (n = 528) were carried out due to SR, which represented the second leading cause of hospitalization (18%), in particular among females (Pearson Chi2 = 17.41, p

ABSTRACT Introduction: The ureteral access sheath (UAS) is a medical device that enables repeated entrance into the ureter and collecting system during retrograde intrarenal surgery (RIRS). Its impact on stone-free rates, ureteral injuries, operative time, and postoperative complications remains controversial. Therefore, we performed a systematic review and meta-analysis comparing RIRS with versus without UAS for urolithiasis management. Purpose: To compare outcomes from retrograde intrarenal surgery (RIRS) for stone extraction with or without ureteral access sheath (UAS); evaluating stone-free rate (SFR), ureteral injuries, operative time, and postoperative complications. Materials and Methods: We systematically searched PubMed, Embase, and Cochrane Library in June 2024 for randomized controlled trials (RCTs) evaluating the efficacy and safety outcomes of UAS use in RIRS for urolithiasis treatment. Articles published between 2014 and 2024 were included. Pooled risk ratios (RRs) and mean differences (MDs) were calculated for binary and continuous outcomes, respectively. Results: Five RCTs comprising 466 procedures were included. Of these, 246 (52.7%) utilized UAS. The follow-up ranged from 1 week to 1 month. UAS reduced the incidence of postoperative fever (RR 0.49; 95% confidence interval [CI] 0.29–0.84; p=0.009), and postoperative infection (RR 0.50; 95% CI 0.30–0.83; p=0.008). There were no significant differences between groups in terms of SFR (RR 1.05; 95% CI 0.99–1.11; p=0.10), ureteral injuries (RR 1.29; 95% CI 0.95–1.75; p=0.11), operative time (MD 3.56 minutes; 95% CI −4.15 to 11.27 minutes; p=0.36), or length of stay (MD 0.32 days; 95% CI −0.42 to 1.07 days; p=0.40). Conclusion: UAS leads to a lower rate of post-operative fever and infection. However, UAS did not significantly reduce or increase the SFR or the rate of ureteral injuries during RIRS for patients with urolithiasis. The use of UAS should be considered to decrease the risk of infectious complications, particularly in those who may be at higher risk for such complications.

This study aimed to investigate the prevalence of paramphistomosis and confirm the species identity of rumen flukes from sheep and cattle of Sardinia (Italy), by molecular methods. From 2011 to 2014, 381 sheep and 59 cattle farms were selected and individual faecal samples were run on 15 sheep and 5 cattle for each farm, respectively. The prevalence at the slaughterhouse was calculated by examination of 356 sheep and 505 cattle. 13adult flukes collected from sheep and cattle and 5 belonging to the historical collection of Laboratory of Parasitology at the Department of Veterinary Medicine of Sassari, previously classified as Paramphistomum spp., were used for PCR amplification and sequencing of the ITS2+ rDNA. Previously classified Paramphistomum leydeni from South America were used as controls.

Abstract Coastal zones are dynamic interfaces shaped by the interplay of Land Cover (LC) and Land Use (LU), influenced by both natural processes and anthropogenic activities. Grasping the historical shifts in land is essential for safeguarding coastal benefits such as defense mechanisms, biodiversity conservation, and recreational spaces, alongside enhancing their management. LC and LU products offer a valuable option for monitoring urban development, vegetation coverage, and dry-beach areas. Herein, we present the first study of the spatiotemporal evolution of LC specifically tailored for coastal zones, using the coast of Sicily as an illustration. We used classified satellite imagery from Landsat and Sentinel missions as input for a semantic segmentation model based on deep neural networks. We trained the model with an extensive dataset of coastal images. Our classification and analysis of coastal LC dynamics from 1988 to 2022 provide insights at a high spatiotemporal resolution. We identified key factors driving urban transformation, underscoring the impact of urban expansion on vegetated areas, and explored its correlation with economic and demographic growth. This study includes a multiscale analysis of coastal changes, encompassing long-term trends and seasonal fluctuations across Sicilian beaches. Our findings can contribute to preserve coastal areas by informing policymaking aimed at sustainable management.

ABSTRACT Purpose: to identify risk factors for urinary septic shock in patients who underwent percutaneous nephrolithotomy (PCNL). Materials and Methods: Data from PCNL procedures performed between January 2009 and February 2020 were retrospectively analyzed. The study included all patients over 18 years old with kidney stones larger than 15 mm who underwent PCNL. Patients who underwent mini-PCNL or combined surgeries, such as ureteroscopy or bilateral procedures, were not included in the study. Logistic regression was conducted to determine the risk factors for urinary septic shock within 30 days post-operation in patients who underwent PCNL. Results: Urinary septic shock was observed in 8 out of the 1,424 patients analyzed (0.56%). The presence of comorbidities, evaluated using the Charlson Comorbidity Index (CCI) (OR 1.46 [CI 95% 1.15-1.86], p=0.01), larger stones (41.0 mm [IQR 30.0-47.5 mm] vs. 24.0 mm [IQR 17.0-35.0 mm], OR 1.03 [CI 95% 1.01-1.06], p=0.04), and a positive preoperative urine culture (OR 8.53 [CI 95% 1.71-42.45], p 2, larger stones (≥ 35 mm), and a positive preoperative urine culture were at even higher risk of urinary septic shock (OR 15.40 [CI 95% 1.77-134.21], p=0.01). Conclusion: Patients with larger stones, positive preoperative urine culture, and a higher CCI are at risk for urinary septic shock after PCNL. These findings are of utmost importance for optimizing the perioperative care of these patients to prevent life-threatening complications.

Abstract Eucalyptus species play an important role in the global carbon cycle, especially in reducing the greenhouse effect as well as storing atmospheric CO₂. Thus, assessing the amount of CO₂ released by the soil in forest areas can generate important information for environmental monitoring. This study aims to verify the relation between soil carbon dioxide (CO₂) flux (FCO₂), spectral bands, and vegetation indices (VIs) derived from a UAV-based multispectral camera over an area of eucalyptus species. Multispectral imageries (green, red-edge, and near-infrared) from the Parrot Sequoia sensor, derived vegetation indices, and the FCO₂ data from a LI-COR 8100 analyzer, combined with soil moisture and temperature data, were collected and related. The vegetation indices ATSAVI (Adjusted Transformed Soil-Adjusted VI), GSAVI (Green Soil Adjusted Vegetation Index), and SAVI (Soil-Adjusted Vegetation Index), which use soil correction factors, exhibited a strong negative correlation with FCO₂ for the species E. camaldulensis, E. saligna, and E. urophylla species. A Multivariate Analysis of Variance showed significance (p

Abstract Background Circulating cytokines can represent non-invasive biomarkers to improve prediction of clinical outcomes of cancer patients. Here, plasma levels of IL-8, CCL4, osteopontin, LIF and BDNF were determined at baseline (T0), after 2 months of therapy (T2) and, when feasible, at progression (TP), in 70 melanoma patients treated with BRAF and MEK inhibitors. The association of baseline cytokine levels with clinical response, progression-free survival (PFS) and overall survival (OS) was evaluated. Methods Cytokine concentrations were measured using the xMAP technology. Their ability to discriminate between responding (Rs) and non-responding (NRs) patients was assessed by Receiver Operating Characteristics analysis. PFS and OS were estimated with the Kaplan–Meier method. The Cox proportional hazard model was used in the univariate and multivariate analyses to estimate crude and adjusted hazard ratios with 95% confidence intervals. Results CCL4 and LIF were undetectable in the majority of samples. The median osteopontin concentration at T0 and T2 was significantly higher in NRs than in Rs. The median T0 and T2 values of IL-8 were also higher in NRs than in Rs, although the statistical significance was not reached. No differences were detected for BDNF. In 39 Rs with matched T0, T2, and TP samples, osteopontin and IL-8 significantly decreased from T0 to T2 and rose again at TP, while BDNF levels remained unchanged. In NRs, none of the cytokines showed a significant decrease at T2. Only osteopontin demonstrated a good ability to discriminate between Rs and NRs. A high IL-8 T0 level was associated with significantly shorter PFS and OS and higher risk of progression and mortality, and remained an independent negative prognostic factor for OS in multivariate analysis. An elevated osteopontin T0 concentration was also significantly associated with worse OS and increased risk of death. Patients with high IL-8 and high osteopontin showed the lowest PFS and OS, and in multivariate analysis this cytokine combination remained independently associated with a three- to six-fold increased risk of mortality. Conclusion Circulating IL-8 and osteopontin appear useful biomarkers to refine prognosis evaluation of patients undergoing targeted therapy, and deserve attention as potential targets to improve its clinical efficacy.

Abstract We define generalized dualities for heterotic and type I strings based on consistent truncations to half-maximal gauged supergravities in more than three dimensions. The latter are constructed from a generalized Scherk-Schwarz ansatz in heterotic double field theory that satisfies the strong constraint. Necessary and sufficient conditions on the resulting embedding tensor are discussed, showing that only certain gaugings, called geometric, can arise from this procedure. For all of them, we explicitly construct the internal geometry and gauge potentials. In general, this construction is not unique and permits different uplifts which are used to define generalized T-duality. Two examples are worked out underlying the utility of our approach to explore new dualities and uplifts of half-maximal gauged supergravities.

Abstract Background Taenia multiceps coenurosis is endemic in sheep from various regions worldwide. Dogs, the key hosts, shed T. multiceps eggs in their feces contaminating the pasture, and lambs are mostly infected during their first turnout into pastures. The disease is manifested in two forms: acute (due to the migrating oncospheres in the CNS) or chronic (due to the developing coenuri in the brain or spinal cord). Both forms are frequently accompanied by neurological symptoms. Methods Field trials conducted in an endemic region (Sardinia, Italy) to treat replacement lambs in six sheep flocks infected with acute coenurosis are summarized in this article. The article also reviews earlier reports on various approaches developed to treat and immunize sheep against coenurosis. Results Accurate detection of the time in which lambs become infected is crucial in deciding which treatment approach should be used. Acute disease can be successfully treated via chemotherapy. Results of field trials conducted in Sardinia revealed the efficacy of three (1-week apart) oxfendazole doses (14.15 mg/kg) in protecting apparently healthy lambs in the infected flocks from developing neurological symptoms. A single praziquantel dose (18.75 mg/kg) worked well for the same purpose and was also found significant in treating 5 of 16 clinically ill lambs in one flock. Earlier reports documented high rates of recovery (up to 100%) in clinically diseased lambs that received much higher doses (50–100 mg/kg) of praziquantel. However, chemotherapy is not preferred in chronic coenurosis since it can lead to rupture of the coenuri, giving rise to serious inflammation in the CNS. Surgical intervention is highly recommended in this case, and the pooled success rates for surgery in chronic-infected cases was estimated at 82.1% (95% CI 73.1–91.0%). However, various trials have been conducted to immunize sheep against T. multiceps coenurosis, and the 18k (Tm18) family of oncosphere antigens was found promising as a vaccine candidate. Conclusions In acute coenurosis, selection of the proper anthelmintic should be done after consulting the owner for several reasons: (1) costs of the used anthelmintic: treating a small flock of 100 sheep costs around 1170 and 660 € for praziquantel and oxfendazole, respectively; (2) withdrawal time of the used anthelmintic: No time is required before consuming meat and milk from praziquantel-treated sheep, whereas meat and milk from oxfendazole-treated sheep should not be consumed for 44 and 9 days, respectively, causing additional costs for the farmers. Since no commercial vaccines have yet been developed against T. multiceps coenurosis in sheep, preventive measures remain the cornerstone of controlling this serious disease. Graphical Abstract

Abstract Effectiveness in health care is a specific characteristic of each intervention and outcome evaluated. Especially with regard to surgical interventions, organization, structure and processes play a key role in determining this parameter. In addition, health care services by definition operate in a context of limited resources, so rationalization of service organization becomes the primary goal for health care management. This aspect becomes even more relevant for those surgical services for which there are high volumes. Therefore, in order to support and optimize the management of patients undergoing surgical procedures, the data analysis could play a significant role. To this end, in this study used different classification algorithms for characterizing the process of patients undergoing surgery for a femoral neck fracture. The models showed significant accuracy with values of 81%, and parameters such as Anaemia and Gender proved to be determined risk factors for the patient’s length of stay. The predictive power of the implemented model is assessed and discussed in view of its capability to support the management and optimisation of the hospitalisation process for femoral neck fracture, and is compared with different model in order to identify the most promising algorithms. In the end, the support of artificial intelligence algorithms laying the basis for building more accurate decision-support tools for healthcare practitioners.

By converting physical forces into electrical signals or triggering intracellular cascades, stretch-activated ion channels allow the cell to respond to osmotic and mechanical stress. Knowledge of the pathophysiological mechanisms underlying associations of stretch-activated ion channels with human disease is limited. Here, we describe 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment associated with progressive neurodegenerative brain changes carrying ten distinct heterozygous variants of TMEM63B, encoding for a highly conserved stretch-activated ion channel. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense, including the recurrent p.Val44Met in 7/17 individuals, or in-frame, all affecting conserved residues located in transmembrane regions of the protein. In 12 individuals, hematological abnormalities co-occurred, such as macrocytosis and hemolysis, requiring blood transfusions in some. We modeled six variants (p.Val44Met, p.Arg433His, p.Thr481Asn, p.Gly580Ser, p.Arg660Thr, and p.Phe697Leu), each affecting a distinct transmembrane domain of the channel, in transfected Neuro2a cells and demonstrated inward leak cation currents across the mutated channel even in isotonic conditions, while the response to hypo-osmotic challenge was impaired, as were the Ca2+ transients generated under hypo-osmotic stimulation. Ectopic expression of the p.Val44Met and p.Gly580Cys variants in Drosophila resulted in early death. TMEM63B-associated DEE represents a recognizable clinicopathological entity in which altered cation conductivity results in a severe neurological phenotype with progressive brain damage and early-onset epilepsy associated with hematological abnormalities in most individuals.

Background: Severe neonatal inflammatory conditions in very preterm infants (VPT:

Coastal erosion is a critical issue affecting shorelines worldwide, imposing effective monitoring and management strategies. We present the Coastal Dynamics Analyzer (CDA), a newly developed QGIS plugin designed for transect-based analysis of shoreline changes, enhancing both the accuracy and efficiency of coastal erosion studies. CDA seamlessly integrates into QGIS, providing an open-source, user-friendly tool that automates the calculation of key shoreline change metrics, including End Point Rate (EPR), Net Shoreline Movement (NSM), Shoreline Change Envelope (SCE), and Linear Regression Rate (LRR). This paper presents the motivation behind the CDA's development, its importance in addressing the limitations of existing tools such as the Digital Shoreline Analysis System (DSAS) and Analyzing Moving Boundaries Using R (AMBUR) and details its implementation. The plugin's functionalities are demonstrated through a case study in the Mediterranean Sea, showing its ability to generate accurate and reliable data for coastal management. By providing high quality results with considerable speed, CDA is promising to become a resource for researchers, coastal engineers, and policy makers involved in coastal erosion management and climate change adaptation planning.

Solid Phase Peptide Synthesis (SPPS) is the preferred technique for synthesizing bioactive peptides. However, traditional SPPS generates significant waste and employs hazardous solvents like DMF and DCM. The aim of this research is to investigate solvents and agents of coupling that align with the green chemistry and are suitable for all stages of SPPS. Some solvents, such as p-cymene and anisole, taken into consideration in this work, can be derived from renewable sources like plants and biomass, rendering them environmentally sustainable choices. However, many of these alternative solvents possess different physicochemical properties compared to DMF. To overcome this challenge, solvent mixtures are employed. In this study, we identified a novel green solvent mixture by combining anisole with NOP; its ability to swell different resins and its capability to solubilize all Fmoc protected amino acids was investigated. The same mixture was also assessed with a green coupling agent, TBEC, in combination with ETT as additive. Model peptides Aib-enkephalin and Aib-ACP were synthesized resulting in favorable outcomes in terms of peptide synthesis efficiency, 97.81% and 98.86%, respectively.

Background: Serum thromboxane B2 (sTXB2) is a validated biomarker of low-dose aspirin pharmacodynamics. In the original method, nonanticoagulated blood samples must be incubated at 37 °C immediately after withdrawal, centrifuged and serum supernatant should be frozen until assayed. Timely completion of all preanalytical steps may affect the feasibility and quality of sTXB2 measurements. The storage duration of frozen serum can also affect sTXB2 stability. Objectives: We assessed the stability of sTXB2 in clotted blood samples stored at 4 °C before further processing and in sera stored at −40 °C for over a decade. Methods: Venous whole blood withdrawn from individuals on chronic low-dose aspirin was dispensed in different tubes and immediately incubated at 37 °C for 1 hour. The reference tube was promptly processed following the original protocol; the remaining tubes were stored at 4 °C for 12 to 72 hours before further processing. Sera stored at a controlled −40 °C temperature for

IntroductionHigher stress levels are linked to increased body fat and decreased bone density, effects that can be exacerbated by lifestyle choices. This is particularly relevant for transgender and gender diverse (TGD) individuals, who often face additional stress from transphobia and social stigma. However, there is limited research on how stress affects body composition and bone health in TGD individuals, particularly in relation to gender-affirming hormone therapy (GAHT). This study examines the impact of perceived stress on these factors in TGD individuals before and after one year of GAHT, compared to a cisgender control group.MethodsThe study assessed 181 individuals, including 74 TGD participants (44 assigned female at birth [AFAB] and 30 assigned male at birth [AMAB]) and 107 controls (56 AFAB and 51 AMAB). Fifty-seven TGD participants completed follow-up one year after starting GAHT. Data collected included clinical history, blood tests, body composition, bone density, and quality of life assessments (Patient Health Questionnaire-9 [PHQ-9] and Perceived Stress Scale [PSS]).ResultsAfter one year of GAHT, TGD AFAB individuals showed a bone mineral density (BMD) similar to cisgender AMAB individuals, while TGD AMAB individuals’ BMD remained significantly lower than cisgender controls. TGD AFAB individuals experienced increases in muscle strength (+8% from baseline), while TGD AMAB individuals showed a 24% increase in fat mass from baseline and an approximate 8% reduction in lean mass. PSS and PHQ scores, initially higher in TGD individuals, did not change significantly after one year of GAHT. A significant correlation was found between body fat percentage and PHQ and PSS scores at baseline and one year after GAHT, respectively.DiscussionThese findings reveal a complex relationship between GAHT, body composition, and perceived stress in TGD individuals, highlighting the need for further research on stress and health outcomes in this population.

IntroductionThe lips fulfill various critical physiological roles besides being viewed as a fundamental aesthetic feature contributing to the perception of health and beauty. Therefore, any lip injury, abnormality, or congenital malformation, such as cleft lip, needs special attention in order to restore proper lip function and aesthetics. To achieve this goal, a better understanding of the complex lip anatomy, function, and biology is required, which can only be provided by basic research endeavors. However, the current lack of clinically relevant human lip cells and three-dimensional in vitro lip models, capable of replacing ethically questionable animal experimentations, represents a significant limitation in this area of research.MethodsTo address these limitations, we aimed to pioneer the introduction of immortalized healthy lip- and cleft lip-derived keratinocytes. Primary keratinocytes were isolated from patients’ samples and immortalized by introducing the catalytic domain of telomerase, combined with the targeted knockdown of the cell cycle inhibitor gene, p16INK4A. We then focused on validating the newly established cell lines by comparing their genetic stability and key phenotypic features with their primary keratinocyte counterparts.ResultsThe newly established immortalized keratinocyte cell lines demonstrated genetic stability and preserved the main phenotypic characteristics of primary keratinocytes, such as cellular morphology and differentiation capacity. Three-dimensional lip models, generated using these cell lines, proved to be effective and convenient platforms for screening applications, including wound healing and microbial infection of the lip epithelium.DiscussionThe establishment of immortalized keratinocytes derived from healthy and cleft lips represents a significant achievement in lip research. These cell lines and the associated three-dimensional lip models are valuable tools that can be used as convenient screening platforms for various assays in a multitude of lip-related research areas, including dermatology, skin care, wound healing, tissue engineering, and craniofacial anomalies. This work opens new avenues in studying lip abnormalities and provides unique tools for personalized medicine approaches beneficial to patients.