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Anna Piperno,1 Maria Teresa Sciortino,1 Elena Giusto,2 Monica Montesi,2 Silvia Panseri,2 Angela Scala1 1Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy; 2CNR-ISTEC, Institute of Science and Technology for Ceramics, National Research Council of Italy, Faenza, RA, ItalyCorrespondence: Angela ScalaDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, ItalyTel +39 090 6765515Fax +39 090 393897Email ascala@unime.itAbstract: Gene therapy is a promising approach for the treatment of several diseases, such as chronic or viral infections, inherited disorders, and cancer. The cellular internalization of exogenous nucleic acids (NA) requires efficient delivery vehicles to overcome their inherent pharmacokinetic drawbacks, e.g. electrostatic repulsions, enzymatic degradation, limited cellular uptake, fast clearance, etc. Nanotechnological advancements have enabled the use of polymer-based nanostructured biomaterials as safe and effective gene delivery systems, in addition to viral vector delivery methods. Among the plethora of polymeric nanoparticles (NPs), this review will provide a comprehensive and in-depth summary of the polyester-based nanovehicles, including poly(lactic-co-glycolic acid) (PLGA) and polylactic acid (PLA) NPs, used to deliver a variety of foreign NA, e.g. short interfering RNA (siRNA), messenger RNA (mRNA), and plasmid DNA (pDNA). The article will review the versatility of polyester-based nanocarriers including their recent application in the delivery of the clustered, regularly‐interspaced, short palindromic repeats/Cas (CRISPR/Cas) genome editing system for treating gene-related diseases. The remaining challenges and future trend of the targeted delivery of this revolutionary genome-editing system will be discussed. Special attention will be given to the pivotal role of nanotechnology in tackling emerging infections such as coronavirus disease 2019 (COVID-19): ground-breaking mRNA vaccines delivered by NPs are currently used worldwide to fight the pandemic, pushing the boundaries of gene therapy.Keywords: PLGA, PLA, siRNA, CRISPR, COVID-19, CLAN

Recently, Blanco-Chacón proved the equivalence between the Ring Learning With Errors and Polynomial Learning With Errors problems for some families of cyclotomic number fields by giving some upper bounds for the condition number Cond(Vn) of the Vandermonde matrix Vn associated to the nth cyclotomic polynomial. We prove some results on the singular values of Vn and, in particular, we determine Cond(Vn) for n = 2kpℓ, where k, ℓ ≥ 0 are integers and p is an odd prime number.

The population is continuously exposed to a background level of ionizing radiation due to the natural radioactivity and, in particular, with radon (222Rn). Radon gas has been classified as the second leading cause of lung cancer after tobacco smoke [1]. In the confined environment, radon concentration can reach harmful level and vary accordingly to many factors. Since the primary source of radon in dwellings is the subsurface, the risk assessment and reduction cannot disregard the identification of the local geology and the environmental predisposing factors. In this article, we propose a new methodology, based on the computation of the Gini coefficients at different spatial scales, to estimate the spatial correlation and the geographical variability of radon concentrations. This variability can be interpreted as a signature of the different subsurface geological conditions. The Gini coefficient computation is a statistical tool widely used to determine the degree of inhomogeneity of different kinds of distributions. We generated several simulated radon distributions, and the proposed tool has been validated by comparing the variograms based on the semi-variance computation with those ones based on the Gini coefficient. The Gini coefficient variogram is shown to be a good estimator of the inhomogeneity degree of radon concentration. Indeed, it allows to better constrain the critical distance below which the radon geological source can be considered as uniform at least for the investigated length scales of variability; it also better discriminates the fluctuations due to the environmental predisposing factors from those ones due to the random spatially uncorrelated noise.

ABOUT THE NON EUCLIDEAN NATURE OF INTERNET'S BIG DATA AND ITS CONSEQUENCES In this paper we discuss the non Euclidean nature of navigable Big Data, hinting as it could introduce – thanks to its combinatorial richness – the possibility of multiple interpretation spaces. We also propose that, in such structures, exploration algorithms have a paradoxical nature insofar they either enhance human biases or are useless. Finally, we propose that Internet could be used as an artificial universe for observing constructivism at work.

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.

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.

Introduction Tobacco-related diseases have a substantial economic impact in terms of medical expenses, loss of productivity, and premature death. Tobacco use is estimated to be responsible for more than 90000 deaths each year in Italy. We aimed to evaluate the annual direct economic impact on the National Health System of hospitalizations attributable to tobacco smoking in Italy. Methods We analyzed data from all the hospitalizations of patients aged ≥30 years that occurred in Italy for 12 selected tobacco-related diseases, during 2018. These diseases included oropharyngeal cancer, esophageal cancer, gastric cancer, lung cancer, pancreatic cancer, bladder cancer, laryngeal cancer, ischemic heart disease, stroke, diseases of arteries, arterioles, and capillaries, pneumonia and influenza, and chronic obstructive pulmonary disease. We obtained information on 984322 hospital discharge records, including each hospitalization's direct costs. Using relative risk estimates from the scientific literature, we computed the population attributable fraction for various tobacco-related diseases to estimate the economic impact attributable to tobacco smoking. Results One-third of all hospitalizations occurred in 2018 in Italy among people aged ≥30 years for 12 tobacco-related diseases were found to be attributable to smoking, accounting for a total cost of €1.64 billion. Among the diseases considered, those with the highest expenditures attributable to tobacco smoking were ischemic heart disease, cerebrovascular disease, and lung cancer, accounting for €556 million, €290 million, and €229 million, respectively. Conclusions Tobacco has a substantial economic impact in Italy, accounting for around 6% of the total cost of hospitalizations in 2018. This figure is expected to be largely underestimated due to several conservative assumptions adopted in the statistical analyses. It is imperative to prioritize comprehensive tobacco control measures to counteract the huge healthcare costs due to tobacco smoking.

Solar photovoltaic (SPV) arrays are crucial components of clean and sustainable energy infrastructure. However, SPV panels are susceptible to thermal degradation defects that can impact their performance, thereby necessitating timely and accurate fault detection to maintain optimal energy generation. The considered case study focuses on an intelligent fault detection and diagnosis (IFDD) system for the analysis of radiometric infrared thermography (IRT) of SPV arrays in a predictive maintenance setting, enabling remote inspection and diagnostic monitoring of the SPV power plant sites. The proposed IFDD system employs a custom-developed deep learning approach which relies on convolutional neural networks for effective multiclass classification of defect types. The diagnosis of SPV panels is a challenging task for issues such as IRT data scarcity, defect-patterns’ complexity, and low thermal image acquisition quality due to noise and calibration issues. Hence, this research carefully prepares a customized high-quality but severely imbalanced six-class thermographic radiometric dataset of SPV panels. With respect to previous approaches, numerical temperature values in floating-point are used to train and validate the predictive models. The trained models display high accuracy for efficient thermal anomaly diagnosis. Finally, to create a trust in the IFDD system, the process underlying the classification model is investigated with perceptive explainability, for portraying the most discriminant image features, and mathematical-structure-based interpretability, to achieve multiclass feature clustering.

Abstract Background We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney, caused by de novo variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative mode of action, wherein an increased level of AFF3 resulted in pathological effects. Methods Evolutionary constraints suggest that other modes-of-inheritance could be at play. We challenged this hypothesis by screening ID cohorts for individuals with predicted-to-be damaging variants in AFF3. We used both animal and cellular models to assess the deleteriousness of the identified variants. Results We identified an individual with a KINSSHIP-like phenotype carrying a de novo partial duplication of AFF3 further strengthening the hypothesis that an increased level of AFF3 is pathological. We also detected seventeen individuals displaying a milder syndrome with either heterozygous Loss-of-Function (LoF) or biallelic missense variants in AFF3. Consistent with semi-dominance, we discovered three patients with homozygous LoF and one compound heterozygote for a LoF and a missense variant, who presented more severe phenotypes than their heterozygous parents. Matching zebrafish knockdowns exhibit neurological defects that could be rescued by expressing human AFF3 mRNA, confirming their association with the ablation of aff3. Conversely, some of the human AFF3 mRNAs carrying missense variants identified in affected individuals did not rescue these phenotypes. Overexpression of mutated AFF3 mRNAs in zebrafish embryos produced a significant increase of abnormal larvae compared to wild-type overexpression further demonstrating deleteriousness. To further assess the effect of AFF3 variation, we profiled the transcriptome of fibroblasts from affected individuals and engineered isogenic cells harboring + / + , KINSSHIP/KINSSHIP, LoF/ + , LoF/LoF or KINSSHIP/LoF AFF3 genotypes. The expression of more than a third of the AFF3 bound loci is modified in either the KINSSHIP/KINSSHIP or the LoF/LoF lines. While the same pathways are affected, only about one third of the differentially expressed genes are common to the homozygote datasets, indicating that AFF3 LoF and KINSSHIP variants largely modulate transcriptomes differently, e.g. the DNA repair pathway displayed opposite modulation. Conclusions Our results and the high pleiotropy shown by variation at this locus suggest that minute changes in AFF3 function are deleterious.

Abstract Hematopoietic stem cell gene therapy (GT) using a γ-retroviral vector (γ-RV) is an effective treatment for Severe Combined Immunodeficiency due to Adenosine Deaminase deficiency. Here, we describe a case of GT-related T-cell acute lymphoblastic leukemia (T-ALL) that developed 4.7 years after treatment. The patient underwent chemotherapy and haploidentical transplantation and is currently in remission. Blast cells contain a single vector insertion activating the LIM-only protein 2 (LMO2) proto-oncogene, confirmed by physical interaction, and low Adenosine Deaminase (ADA) activity resulting from methylation of viral promoter. The insertion is detected years before T-ALL in multiple lineages, suggesting that further hits occurred in a thymic progenitor. Blast cells contain known and novel somatic mutations as well as germline mutations which may have contributed to transformation. Before T-ALL onset, the insertion profile is similar to those of other ADA-deficient patients. The limited incidence of vector-related adverse events in ADA-deficiency compared to other γ-RV GT trials could be explained by differences in transgenes, background disease and patient’s specific factors.

Abstract Background Medical school curricula strive to train community-engaged and culturally competent physicians, and many use service learning to instill these values in students. The current standards for medical service learning frameworks have opportunities for improvement, such as encouraging students to have more sustainable and reciprocal impact and to ingrain service learning as a value to carry throughout their careers rather than a one-time experience. PEDS 220: A COVID-19 Elective is a Stanford University course on the frontlines of this shift; it provides timely education on the COVID-19 pandemic, integrating community-oriented public health work to help mitigate its impact. Methods To analyze our medical service learning curriculum, we combined qualitative and quantitative methods to understand our students’ experiences. Participants completed the Course Experience Questionnaire via Qualtrics, and were invited to complete an additional interview via Zoom. Interview transcripts were analyzed using an interactive, inductive, and team-based codebook development process, where recurring themes were identified across participant interviews. Results We demonstrate through self-determination theory that our novel curriculum gives students valuable leadership and project management experience, awards strong academic and community-based connections, and motivates them to pursue future community-engaged work. Conclusions This educational framework, revolving around students, communities, and diversity, can be used beyond the COVID-19 pandemic at other educational institutions to teach students how to solve other emergent global health problems. Using proven strategies that empower future physicians to view interdisciplinary, community-engaged work as a core pillar of their responsibility to their patients and communities ensures long-term, sustainable positive impact. Trial registration N/A.

Abstract The single-photon quantum computing paradigm currently relies on the multi-port interference in linear optical devices, which is intrinsically based on probabilistic measurements outcome, and thus non-deterministic. Devising a fully deterministic, universal, and practically achievable quantum computing platform based on single-photon encoding and integrated photonic circuits is still an open challenge. Here we propose to exploit the interplay of distributed self-Kerr nonlinearity and localized hopping in quantum photonic interferometers to implement deterministic entangling quantum gates with dual rail photonic qubits. It is shown that a universal set of single- and two-qubit gates can be designed by a suitable concatenation of few optical interferometric elements, reaching optimal fidelities arbitrarily close to 100% that are theoretically demonstrated through a bound constrained optimization algorithm. The actual realization would require the concatenation of a few tens of elementary operations, as well as on-chip optical nonlinearities that are compatible with some of the existing quantum photonic platforms, as it is finally discussed.

Background:. ChatGPT, launched in 2022 and updated to Generative Pre-trained Transformer 4 (GPT-4) in 2023, is a large language model trained on extensive data, including medical information. This study compares ChatGPT’s performance on Plastic Surgery In-Service Examinations with medical residents nationally as well as its earlier version, ChatGPT-3.5. Methods:. This study reviewed 1500 questions from the Plastic Surgery In-service Examinations from 2018 to 2023. After excluding image-based, unscored, and inconclusive questions, 1292 were analyzed. The question stem and each multiple-choice answer was inputted verbatim into ChatGPT-4. Results:. ChatGPT-4 correctly answered 961 (74.4%) of the included questions. Best performance by section was in core surgical principles (79.1% correct) and lowest in craniomaxillofacial (69.1%). ChatGPT-4 ranked between the 61st and 97th percentiles compared with all residents. Comparatively, ChatGPT-4 significantly outperformed ChatGPT-3.5 in 2018–2022 examinations (P < 0.001). Although ChatGPT-3.5 averaged 55.5% correctness, ChatGPT-4 averaged 74%, a mean difference of 18.54%. In 2021, ChatGPT-3.5 ranked in the 23rd percentile of all residents, whereas ChatGPT-4 ranked in the 97th percentile. ChatGPT-4 outperformed 80.7% of residents on average and scored above the 97th percentile among first-year residents. Its performance was comparable with sixth-year integrated residents, ranking in the 55.7th percentile, on average. These results show significant improvements in ChatGPT-4’s application of medical knowledge within six months of ChatGPT-3.5’s release. Conclusion:. This study reveals ChatGPT-4’s rapid developments, advancing from a first-year medical resident’s level to surpassing independent residents and matching a sixth-year resident’s proficiency.

IntroductionAutosomal recessive osteopetrosis (ARO) is a rare genetic disease, characterized by increased bone density due to defective osteoclast function. Most of the cases are due to TCIRG1 gene mutation, leading to severe bone phenotype and death in the first years of life. The standard therapy is the hematopoietic stem cell transplantation (HSCT), but its success is limited by several constraints. Conversely, gene therapy (GT) could minimize the immune-mediated complications of allogeneic HSCT and offer a prompt treatment to these patients.MethodsThe Tcirg1-defective oc/oc mouse model displays a short lifespan and high bone density, closely mirroring the human condition. In this work, we exploited the oc/oc neonate mice to optimize the critical steps for a successful therapy.ResultsFirst, we showed that lentiviral vector GT can revert the osteopetrotic bone phenotype, allowing long-term survival and reducing extramedullary haematopoiesis. Then, we demonstrated that plerixafor-induced mobilization can further increase the high number of HSPCs circulating in peripheral blood, facilitating the collection of adequate numbers of cells for therapeutic purposes. Finally, pre-transplant non-genotoxic conditioning allowed the stable engraftment of HSPCs, albeit at lower level than conventional total body irradiation, and led to long-term survival and correction of bone phenotype, in the absence of acute toxicity.ConclusionThese results will pave the way to the implementation of an effective GT protocol, reducing the transplant-related complication risks in the very young and severely affected ARO patients.

Background: Circulating Tumor Cells (CTCs) represent a small, heterogeneous population that comprise the minority of cells able to develop metastasis. To trap and characterize CTCs with metastatic attitude, a CXCL12-loaded hyaluronic-gel (CLG) was developed. CXCR4+cells with invasive capability would infiltrate CLG. Methods: Human colon, renal, lung and ovarian cancer cells (HT29, A498, H460 and OVCAR8 respectively) were seeded on 150 μl Empty Gels (EG) or 300 ng/ml CXCL12 loaded gel (CLG) and allowed to infiltrate for 16 h. Gels were then digested and fixed with 2 % FA-HAse for human cancer cell enumeration or digested with HAse and cancer cells recovered. CLG-recovered cells migrated toward CXCL12 and were tested for colonies/spheres formation. Moreover, CXCR4, E-Cadherin and Vimentin expression was assessed through flow cytometry and RT-PCR. The clinical trial “TRAP4MET” recruited 48 metastatic/advanced cancer patients (8 OC, 8 LC, 8 GBM, 8 EC, 8 RCC and 8 EC). 10 cc whole blood were devoted to PBMCs extraction (7 cc) and ScreenCell™ filters (3 cc) CTCs evaluation. Ficoll-isolated patient's PBMCs were seeded over CLG and allowed to infiltrate for 16 h; gels were digested and fixed with 2 % FA-HAse, cells stained and DAPI+/CD45-/pan-CK + cells enumerated as CTCs. Results: Human cancer cells infiltrate CLG more efficiently than EG (CLG/EG ratio 1.25 for HT29/1.58 for A498/1.71 for H460 and 2.83 for OVCAR8). CLG-recovered HT29 cells display hybrid-mesenchymal features [low E-cadherin (40 %) and high vimentin (235 %) as compared to HT29], CXCR4 two-fold higher than HT29, efficiently migrate toward CXCL12 (two-fold higher than HT29) and developed higher number of colonies (171 ± 21 for HT29-CLG vs 131 ± 8 colonies for HT29)/larger spheres (spheroid area: 26561 ± 6142 μm2 for HT29-CLG vs 20297 ± 7238 for HT29). In TRAP4MET clinical trial, CLG-CTCs were isolated in 8/8 patients with OC, 6/8 with LC, 6/8 with CRC, 8/8 with EC, 8/8 with RCC cancer and 5/8 with GBM. Interestingly, in OC, LC and GBM, CLG isolated higher number of CTCs as compared to the conventional ScreenCell™ (CLG/SC ratio = 1.88 for OC, 2.47 for LC and 11.89 for GBM). Bland and Altman blot analysis and Passing and Bablok regression analysis showed concordance between the methodological approaches but indicate that SC and CLG are not superimposable suggesting that the two systems select cells with different features. Conclusion: CLG might represent a new and easy tool to isolate invasive CTCs in multiple cancers such as OC, LC and GBM at today orphan of reliable methods to consistently detect CTCs.

Abstract CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an embryonic role of CELSR3 in CNS and urinary tract formation.

In recent years, research in the smart city sector has experienced exponential growth, establishing itself as a fundamental and multifaceted field of study. Education is one of the sectors of interest in smart cities. Concurrently, the extensive academic literature on smart cities makes identifying the main areas of interest related to education, leading institutions and authors, potential interconnections between different disciplines, and existing gaps more complicated. This article maps the knowledge domain of education in smart cities through a bibliometric analysis to identify current trends, research networks, and topics of greatest interest. A total of 88 articles, published between 2000 and 2023, were examined using an interdisciplinary approach. The leading countries are mainly located in Europe and North America and include China. Bibliometrics provides an intellectual configuration of knowledge on education in smart cities; a co-word analysis identifies conceptual sub-domains in specific themes. In general, education within smart cities represents a universal challenge that requires a structured and interdisciplinary approach at all levels. Finally, this paper offers some suggestions for future research, adopting a more comprehensive view of the areas of investigation through a holistic analysis of stakeholders.

The rising demand for green energy to reduce carbon emissions is accelerating the integration of renewable energy sources (RESs) like wind and solar power. However, this shift presents significant challenges due to the inherent variability and intermittency of RESs, which impact power system stability and reliability. As a result, there is a growing need for enhanced flexibility to maintain stable and reliable operations. This study reviews recent advancements in power system flexibility enhancement, particularly concerning the integration of RESs, with a focus on the critical role of energy storage systems (ESSs) in mitigating these challenges. ESSs play a vital role in addressing the variability of RESs, supporting grid stability, and enabling energy consumption time shifting. While existing studies discuss power system flexibility, each typically addresses specific aspects. This comprehensive review evaluates flexibility measures for renewable-based electricity in terms of reliability and stability, highlighting the importance of ESSs in transmission, distribution networks, and end-user applications like residential buildings and vehicle-to-grid technologies to enhance overall system flexibility. Additionally, we identify recent challenges, such as the increased risk of grid congestion, frequency deviations, and the need for real-time supply and demand balancing, which necessitate innovative ESS applications. We propose future directions, including a transition pathway to promote the large-scale deployment of diverse ESS technologies to support grid modernization, enhance resilience, and foster sustainable power supply development. Our findings emphasize the growing research into optimizing power system stability and reliability, offering valuable guidance for future research and practical implementation.

Real-time simulation is a well-established approach employed across various domains, predominantly through Hardware-In-the-Loop (HIL) simulation. HIL technology enables more realistic simulations of complex systems, usually achieved by a closed-loop scheme between the hardware under test and the real-time simulator. In the field of power systems, it is also progressively deployed not only for academic aspects but also for industrial applications. A HIL model takes advantage of such merits as alleviating the risk of damage to the major real objects and reducing the cost as well as tedious efforts during the test. Besides, the evolution and increasing computing power of real-time simulators promise the capability to reach more accurate models that closely represent reality. Accordingly, this manuscript aims to investigate some applications of HIL grid-integrated technologies in transmission systems and discuss some future trends and scopes correlating to this context.

Introdução: O aumento da adiposidade abdominal provoca alterações do centro de gravidade, podendo levar a déficits de equilíbrio postural e da capacidade funcional durante a realização de tarefas cotidianas. A ativação dos músculos lombo-pélvicos, por meio do fortalecimento e conscientização postural, pode reduzir a sobrecarga mecânica aplicada sobre as estruturas passivas da coluna vertebral, melhorando a estabilidade do tronco e, consequentemente, o equilíbrio e a funcionalidade. Objetivo: Investigar os efeitos de três diferentes intervenções sobre a estabilidade lombo-pélvica, equilíbrio dinâmico, funcionalidade e mobilidade de tornozelos em mulheres adultas com obesidade. Materiais e métodos: A amostra foi composta por 60 mulheres obesas com idade de 30 a 50 anos e com IMC entre 30 e 39,9 kg/m2. As voluntárias foram randomizadas em três grupos: Grupo Exercício Físico, Grupo Interdisciplinar e Grupo Educação em Saúde. As voluntárias foram avaliadas nos momentos Basal, após 16 e 32 semanas, quanto à capacidade funcional, equilíbrio dinâmico e mobilidade dos tornozelos, IMC, perímetro de pescoço e cintura. Resultados: Houve redução da massa corporal e perímetro da cintura apenas no grupo interdisciplinar. Observou-se que a terapia interdisciplinar foi mais efetiva, quando comparada com o grupo Exercício ou com o grupo Educação em Saúde, para controle/prevenção de disfunções e alterações biomecânicas relacionadas ativação do músculo transverso do abdome, equilíbrio dinâmico, funcionalidade e mobilidade de tornozelos. Conclusão: Portanto, estratégias de intervenção interdisciplinares/interprofissionais devem ser estimuladas, visando a melhora de aspectos funcionais, em mulheres com obesidade.

Abstract Substrate-borne vibrational communication is common in pentatomids. Although several works exist on the vibrational communication of Halyomorpha halys, its vibrational behavior post diapause has not been investigated. In this study, we recorded H. halys overwintered adults using laser doppler vibrometers at three temperatures: 10 °C (inactivity), 18 °C (breaking of diapause), and 25 °C (peak of mating activity). The aim was to assess the effect of temperature on the signaling, motility, and survival of H. halys. The insects were sexed into different cages and recorded separately or joined with a cage of the opposite sex. We calculated the total time spent on signaling and walking per replica. The males predominantly emitted male signal 1 (MS1) throughout the four months of recordings. The females exclusively emitted female signal 2 (FS2) when joined with the opposite sex cage the first two months of recordings. Interestingly, they also started FS2 signaling when recorded separately, after two months. No signaling was recorded at 10 °C. At 25 °C, the signaling latency time before vibrational signaling was 24 h compared to 23 days at 18 °C. The short latency time at 25 °C correlated with a higher death rate in early stages of recording. Male walking activity was significantly higher in joined cages at 18 °C and 25 °C, suggesting the increased searching behavior near the opposite sex. Overwintered H. halys could adapt to different conditions whereas low temperatures maintain the diapause which is characterized by no signaling activity. Our results provide a foundation for bioclimatic modeling of climate change effects on H. halys and insights into the use of vibrational playbacks for mass trapping and monitoring as control techniques.

Abstract WDR44 prevents ciliogenesis initiation by regulating RAB11-dependent vesicle trafficking. Here, we describe male patients with missense and nonsense variants within the WD40 repeats (WDR) of WDR44, an X-linked gene product, who display ciliopathy-related developmental phenotypes that we can model in zebrafish. The patient phenotypic spectrum includes developmental delay/intellectual disability, hypotonia, distinct craniofacial features and variable presence of brain, renal, cardiac and musculoskeletal abnormalities. We demonstrate that WDR44 variants associated with more severe disease impair ciliogenesis initiation and ciliary signaling. Because WDR44 negatively regulates ciliogenesis, it was surprising that pathogenic missense variants showed reduced abundance, which we link to misfolding of WDR autonomous repeats and degradation by the proteasome. We discover that disease severity correlates with increased RAB11 binding, which we propose drives ciliogenesis initiation dysregulation. Finally, we discover interdomain interactions between the WDR and NH2-terminal region that contains the RAB11 binding domain (RBD) and show patient variants disrupt this association. This study provides new insights into WDR44 WDR structure and characterizes a new syndrome that could result from impaired ciliogenesis.

Lactococcus garvieae has been considered for a long time the only causal agent of lactococcosis. In recent years, different papers reported the involvement of other two bacterial species: Lactococcus petauri and Lactococcus formosensis. A different host tropism has been described for these species where L. garvieae and L. petauri are predominant species in fish and humans’ infections, while L. formosensis in bovine. L. garvieae has been reported as rare infectious agent in dog. This paper represents the first isolation of L. petauri in two domesticated dog cases from urine and skin samples, respectively. The recovered L. petauri has been identified using PCR and sequencing based on Internal Transcribe Spacer (ITS) and phylogenetic analysis showed that it belongs to the L. petauri cluster with a 100% of identity with sequences previously reported from fish isolates while there were differences with L. petauri isolated from urinary tract infection from humans. L. petauri in human infection has been considered not necessarily deriving from the ingestion of contaminated food but rather as an opportunistic pathogen colonization intestinal tract. Differences among virulotypes have been reported for humans and dogs, and a comparison was also made between the virulotyping of L. petauri and L. garvieae in dogs. The antimicrobial pattern showed susceptibility for the election treatment molecules. These data contribute to our understanding of the host trophism of this species which was misclassified for long time and provide new data on its virulence factors and antimicrobial resistance.

Remote sensing has proven to be a vital tool for monitoring and forecasting the quality and yield of crops. The utilization of innovative technologies such as Solar-Induced Fluorescence (SIF) and satellite measurements of column-averaged CO2 (xCO2) can enhance these estimations. SIF is a signal emitted by crops during photosynthesis, thus indicating photosynthetic activities. The concentration of atmospheric CO2 is a critical factor in determining the efficiency of photosynthesis. The aim of this study was to investigate the correlation between satellite-derived Solar-Induced Chlorophyll Fluorescence (SIF), column-averaged CO2 (xCO2), and Normalized Difference Vegetation Index (NDVI) and their association with sugarcane yield and sugar content in the field. This study was carried out in south-central Brazil. We used four localities to represent the region: Pradópolis, Araraquara, Iracemápolis, and Quirinópolis. Data were collected from orbital systems during the period spanning from 2015 to 2016. Concurrently, monthly data regarding tons of sugarcane per hectare (TCH) and total recoverable sugars (TRS) were gathered from 24 harvest locations within the studied plots. It was observed that TRS decreased when SIF values ranged between 0.4 W m−2 sr−1 μm−1 and 0.8 W m−2 sr−1 μm−1, particularly in conjunction with NDVI values below 0.5. TRS values peaked at 15 kg t−1 with low NDVI and xCO2 values, alongside SIF values lower than 0.4 W m−2 sr−1 μm−1 and greater than 1 W m−2 sr−1 μm−1. These findings underscore the potential of integrating SIF, xCO2, and NDVI measurements in the monitoring and forecasting of yield and sugar content in sugarcane crops.

Biomass gasification is a thermochemical process that produces a gaseous end product known as syngas, the main components of which are CO, CO2, and H2. Starting from syngas it is possible to upgrade this mixture into Synthetic Natural Gas (SNG) through a catalytic methanation process. In this work, a thermodynamic study was conducted to see how operative parameters such as the temperature of the methanation reactor, the quality of the syngas (related to different gasification technologies), and the presence of a conditioning stage based on water gas shift reaction, can influence the output variables as the conversion degree of the reactants, the mass yield and the low heating value of the final products.

Objective: Phenylketonuria (PKU) is a metabolic disorder necessitating lifelong management to prevent severe neurological impairments. This paper synthesises clinical practices from Italian specialist centres to delineate a unified approach for administering pegvaliase, a novel enzyme replacement therapy for PKU. Methods: Virtual meetings convened in September 2022, gathering a steering committee (SC) of experts from five Italian centres specialising in PKU. The SC reviewed, and discussed clinical practices, and formulated recommendations for pegvaliase treatment. Results: The SC outlined a comprehensive treatment roadmap for PKU management with pegvaliase, emphasising the importance of multidisciplinary care teams, patient selection, pre-treatment evaluation, and education. Recommendations include initial hospital-based pegvaliase administration, regular monitoring of phenylalanine and tyrosine levels, dietary adjustments, and management of adverse events. A consensus was reached on the need for a digital database to manage treatment plans and enhance communication between healthcare professionals and patients. Conclusion: The expert panel's consensus highlights the complexity of PKU management and the necessity for a coordinated, patient-centred approach. The recommendations aim to standardise care across Italian centres and provide a framework for integrating pegvaliase therapy into clinical practice, potentially informing international guidelines. Further research is warranted to evaluate the long-term impact of these practices on patient outcomes and quality of life.

Not available.

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (IPGSph1 and IPGSph2). By applying a logistic regression with both IPGS, (IPGSph2 (or indifferently IPGSph1) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%.

Despite the polluting potential olive mill wastewater (OMW) can be a useful source of nutrients and organic compounds to improve soil properties. The aim of this paper was to verify if biochar-based treatment of OMW could be an efficient method to contrast the richness in phenolic compounds and phytotoxicity of OMW making it more suitable. for soil amendment. In this study poplar biochar (BP) was more effective than conifer biochar (BC) in terms of adsorbing phenols and reducing phytotoxicity at different biochar rates (5 and 10 %). In soil amendment BP-treated OMW induced an increase of organic carbon by approximately 15 % and notably BP10 treated OMW enhanced available phosphorous by 25 % after 30 days of incubation. In soil amended with 10 % BP-treated OMW microbial biomass and enzymatic activities were significantly enhanced after 30 and 90 days, with no effect on cress seed germination. Therefore, biochar based-treatment could be cost-effective and able to facilitate the long-term management of OMW in terms of storage and disposal.

Introduction The Positive and Negative Syndrome Scale (PANSS) has been used as a universal instrument for clinical assessment of psychopathology in schizophrenia. Different studies have analyzed the factorial structure of this scale and have suggested a five-factor model: positive, negative, excited, depressive, and cognitive/disorganized factors. Two of the most used models are the Marder´s solution and the Wallwork´s one. Objectives The aim of this work was to study the correlations of the two cognitive factors (Marder and Wallwork) with a cognitive assessment performed with a standard cognitive battery, in a sample of patients with first psychotic episode of schizophrenia. Methods Seventy four patients with first psychotic episode of schizophrenia (26.9, SD:7.8 years old; 70.3% male) were included. The cognitive assessment was performed with the MATRICS Consensus Cognitive Battery (MCCB). The MCCB present seven cognitive domains: Speed of processing, Working memory, Attention/Vigilance, Verbal Learning, Visual Learning, Reasoning and Problem Solving, and Social cognition). Pearson correlations were performed between MCCB scores and Marder´s PANSS cognitive factor (P2, N5, G5, G10, G11, G13, G15) and Wallwork´s one (P2, N5, G11). Results Correlation between MCCB scores and cognitive factors of Marder and Wallwork can be seen in the table. Marder´s cognitive factor Wallwork´s cognitive factor Speed of processing r = -0.461; p

Abstract Catalysts are often employed to enable nonisothermal reaction kinetic studies when tracking cure progression of polyurethane reactions. However, when quickly reacting, catalyzed materials are prepared through mixing followed by the addition of fillers or additives, subsequent processing of the partially reacted material becomes difficult. Here, chemorheology is used to track changes in viscoelastic properties of uncatalyzed polybutadiene‐diisocyanate reactions for multiple days, which quantifies the degree of cure during polymerization. Viscosity profiles are accurately captured by the two‐stage Arrhenius model (r2>0.95), and conversion progress is adequately represented by the Kamal–Sourour model (r2>0.76). Transition state analysis via Wynne–Jones–Eyring–Evans theory (WJEE) reveals the presence of an associative mechanism according to entropic and enthalpic activation energies ΔS# = −96.9 J K−1 and ΔH# = 36.4 kJ, respectively. These rheokinetic modeling results align with Fourier transform infrared spectroscopy findings. To the knowledge, no rheokinetic studies have tracked cure progress of this uncatalyzed system for the extended timeframe presented here. The cure profile also presents unique viscosity growth, representative of molecular weight buildup, compared to catalyzed systems. This finding emphasizes the novelty of applying previously developed chemorheological models to multiday thermosetting reactions within a flow field in a manner that is generalizable to many long‐term curing systems.

Abstract Objective NPRL3‐related epilepsy (NRE) is an emerging condition set within the wide GATOR‐1 spectrum with a particularly heterogeneous and elusive phenotypic expression. Here, we delineated the genotype–phenotype spectrum of NRE, reporting an illustrative familial case and reviewing pertinent literature. Methods Through exome sequencing (ES), we investigated a 12‐year‐old girl with recurrent focal motor seizures during sleep, suggestive of sleep‐related hypermotor epilepsy (SHE), and a family history of epilepsy in siblings. Variant segregation analysis was performed by Sanger sequencing. All previously published NRE patients were thoroughly reviewed and their electroclinical features were analyzed and compared with the reported subjects. Results In the proband, ES detected the novel NPRL3 frameshift variant (NM_001077350.3): c.151_152del (p.Thr51Glyfs*5). This variant is predicted to cause a loss of function and segregated in one affected brother. The review of 76 patients from 18 publications revealed the predominance of focal‐onset seizures (67/74–90%), with mainly frontal and frontotemporal (32/67–47.7%), unspecified (19/67–28%), or temporal (9/67–13%) onset. Epileptic syndromes included familial focal epilepsy with variable foci (FFEVF) (29/74–39%) and SHE (11/74–14.9%). Fifteen patients out of 60 (25%) underwent epilepsy surgery, 11 of whom achieved complete seizure remission (11/15–73%). Focal cortical dysplasia (FCD) type 2A was the most frequent histopathological finding. Significance We reported an illustrative NPRL3‐related epilepsy (NRE) family with incomplete penetrance. This condition consists of a heterogeneous spectrum of clinical and neuroradiological features. Focal‐onset motor seizures are predominant, and almost half of the cases fulfill the criteria for SHE or FFEVF. MRI‐negative cases are prevalent, but the association with malformations of cortical developments (MCDs) is significant, especially FCD type 2a. The beneficial impact of epilepsy surgery in patients with MCD‐related epilepsy further supports the inclusion of brain MRI in the workup of NRE patients.