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Abstract Background Milk is essential for mammalian nutrition because it provides vital nutrients for growth and development. Milk composition, which is influenced by genetic and environmental factors, supports lactation, a complex process crucial for milk production and quality. Recent research has focused on noncoding RNAs, particularly microRNAs (miRNAs), which are present in body fluids and regulate gene expression post-transcriptionally. This study comprehensively characterizes miRNAs in milk of four livestock species, namely Bubalus bubalis, Capra hircus, Equus asinus, and Ovis aries and identifies potential target genes. Results High-throughput sequencing of milk RNA resulted in distinct read counts across species: B. bubalis (8,790,441 reads), C. hircus (12,976,275 reads), E. asinus (9,385,067 reads), and O. aries (7,295,297 reads). E. asinus had the highest RNA mapping rate (94.6%) and O. aries the lowest (84.8%). A substantially greater proportion of miRNAs over other small RNAs was observed for the donkey milk sample (7.74%) compared to buffalo (0.87%), goat (1.57%), and sheep (1.12%). Shared miRNAs, which included miR-200a, miR-200b, miR-200c, and miR-23a among others, showed varying expression levels across species, confirmed by qPCR analysis. Functional annotation of predicted miRNA target genes highlighted diverse roles, with an enrichment in functions linked to metabolism and immunity. Pathway analysis identified immune response pathways as significant, with several miRNAs targeting specific genes across species, suggesting their regulatory function in milk. Conclusions Both conserved and species-specific miRNAs were detected in milk of the investigated species. The identified target genes of these miRNAs have important roles in neonatal development, adaptation, growth, and immune response. Furthermore, they influence milk and meat production traits in livestock.

BackgroundMR fingerprinting (MRF) is a novel method for quantitative assessment of in vivo MR relaxometry that has shown high precision and accuracy. However, the method requires data acquisition using customized, complex acquisition strategies and dedicated post processing methods thereby limiting its widespread application.ObjectiveTo develop a deep learning (DL) network for synthesizing MRF signals from conventional magnitude-only MR imaging data and to compare the results to the actual MRF signal acquired.MethodsA U-Net DL network was developed to synthesize MRF signals from magnitude-only 3D T1-weighted brain MRI data acquired from 37 volunteers aged between 21 and 62 years of age. Network performance was evaluated by comparison of the relaxometry data (T1, T2) generated from dictionary matching of the deep learning synthesized and actual MRF data from 47 segmented anatomic regions. Clustered bootstrapping involving 10,000 bootstraps followed by calculation of the concordance correlation coefficient were performed for both T1 and T2 MRF data pairs. 95% confidence limits and the mean difference between true and DL relaxometry values were also calculated.ResultsThe concordance correlation coefficient (and 95% confidence limits) for T1 and T2 MRF data pairs over the 47 anatomic segments were 0.8793 (0.8136–0.9383) and 0.9078 (0.8981–0.9145) respectively. The mean difference (and 95% confidence limits) were 48.23 (23.0–77.3) s and 2.02 (−1.4 to 4.8) s.ConclusionIt is possible to synthesize MRF signals from MRI data using a DL network, thereby creating the potential for performing quantitative relaxometry assessment without the need for a dedicated MRF pulse sequence.

Generative artificial intelligence algorithms and applications pose new challenges to the creativity of artists and educators. This study delves into the aesthetic and methodological contradictions of computational creativity, where issues arise from the clash between Romantic aesthetics and the lack of a proper connection between digital and traditional culture. We posit that achieving an inclusive, sustainable, and creative use of digital media requires the development of aesthetically updated proprietary technology rooted in the cultural identities of its origin. Our research is based on a literature review, software design, and artistic practice, and it highlights the importance of the humanities, ethno-computation, and analogical processes and materials. We argue that technology by itself is insufficient in developing the essential skills needed to value computational creativity in artistic production and education.

Abstract Febrile seizures (FS) are commonly perceived by healthcare professionals as a self-limited condition with a generally ‘benign’ nature. Nonetheless, they frequently lead to pediatric consultations, and their management can vary depending on the clinical context. For parents and caregivers, witnessing a seizure can be a distressing experience, significantly impacting their quality of life. In this review, we offer an in-depth exploration of FS management, therapeutic interventions, and prognostic factors, with the aim of providing support for physicians and enhancing communication with families. We conducted a comprehensive literature search using the PubMed and Web of Science databases, spanning the past 50 years. The search terms utilized included “febrile seizure,” “complex febrile seizure,” “simple febrile seizure,” in conjunction with “children” or “infant.” Only studies published in English or those presenting evidence-based data were included in our assessment. Additionally, we conducted a cross-reference search to identify any additional relevant data sources. Our thorough literature search resulted in a compilation of references, with carefully selected papers thoughtfully integrated into this review.

Abstract Background To date, the etiology and risk factors of torticollis are still poorly defined in the pediatric literature. Especially in the Emergency Department (ED) scenario, it is critical to reliably distinguish benign and transient conditions from (potentially) life-threatening disorders. This study describes the clinical characteristics of a large sample of children with torticollis. The aim of our study was to detect epidemiology, etiology and predictive variables associated with a higher risk of life-threatening conditions in acute torticollis. Methods We conducted a pediatric retrospective study of acute torticollis over a 13-year period referred to the ED of a tertiary pediatric Hospital. We reported the characteristics in the overall sample and in two subgroups divided according to urgency of the underlying condition. Furthermore, we developed a multivariate model aimed at identifying the main clinical predictors of the need for urgent care. Results 1409 patients were analyzed (median age 5.7 years, IQR 5.8). A history of trauma was present in 393 patients (27.9%). The symptom most frequently associated with torticollis were pain (83.5%). At least one pathological finding was found in 5.4 to 7.9% of patients undergoing further imaging. Hospitalization was required in 11.1% of cases (median duration 4 days). The most frequent etiologies of torticollis were postural cause (43.1%), traumatic (29.5%), and infective/inflammatory (19.1%). A longer time from onset of torticollis and the presence of headache or vomiting were strongly correlated with an underlying urgent condition, after adjusting for the other clinically and statistically significant variables in the bivariate analysis. Conclusion Our study shows that an urgent condition most commonly occur in patients presenting with history of trauma or headache, vomiting and torticollis for more than 24 h should undergo further diagnostic evaluation and short-term follow-up, restricting invasive or expensive investigations to patients with clinical suspicion of an underlying harmful condition.

Abstract Background The KEYNOTE-048 trial showed that pembrolizumab-based first-line treatment for R/M HNSCC led to improved OS in the PD-L1 CPS ≥ 1 population when compared to the EXTREME regimen. However, the R/M HNSCC real-world population is generally frailer, often presenting with multiple comorbidities, worse performance status and older age than the population included in phase III clinical trials. Methods This is a retrospective, single-centre analysis of patients with R/M HNSCC treated with pembrolizumab-based first-line treatment. Results From February 2021 to March 2023, 92 patients were treated with pembrolizumab-based first-line treatment. Patients treated with pembrolizumab-based chemoimmunotherapy had better ECOG PS and younger age than those treated with pembrolizumab monotherapy. Median PFS and OS were 4 months and 8 months, respectively. PFS was similar among patients treated with pembrolizumab-based chemoimmunotherapy and pembrolizumab monotherapy, while patients treated with pembrolizumab monotherapy had worse OS (log-rank p =.001, HR 2.7). PFS and OS were improved in patients with PD-L1 CPS > = 20 (PFS: log-rank p =.005, HR 0.50; OS: log-rank p =.04, HR 0.57). Patients with higher ECOG PS scores had worse PFS and OS (PFS, log-rank p =.004; OS, log-rank p = 6e-04). In multivariable analysis, ECOG PS2 was associated with worse PFS and OS. Conclusions PFS in our real-world cohort was similar to the KEYNOTE-048 reference while OS was numerically inferior. A deeper understanding of clinical variables that might affect survival outcomes of patients with R/M HNSCC beyond ECOG PS and PD-L1 CPS is urgently needed.

We used WRF-Chem to simulate ash transport from eruptions of Chile’s Calbuco volcano on 22–23 April 2015. Massive ash and SO2 ejections reached the upper troposphere, and particulates transported over South America were observed over Argentina, Uruguay, and Brazil via satellite and surface data. Numerical simulations with the coupled Weather Research and Forecasting–Chemistry (WRF-Chem) model from 22 to 27 April covered eruptions and particle propagation. Chemical and aerosol parameters utilized the GOCART (Goddard Chemistry Aerosol Radiation and Transport) model, while the meteorological conditions came from NCEP-FNL reanalysis. In WRF-Chem, we implemented a more efficient methodology to determine the Eruption Source Parameters (ESP). This permitted each simulation to consider a sequence of eruptions and a time varying ESP, such as the eruption height and mass and the SO2 eruption rate. We used two simulations (GCTS1 and GCTS2) differing in the ash mass fraction in the finest bins (0–15.6 µm) by 2.4% and 16.5%, respectively, to assess model efficiency in representing plume intensity and propagation. Analysis of the active synoptic components revealed their impact on particle transport and the Andes’ role as a natural barrier. We evaluated and compared the simulated Aerosol Optical Depth (AOD) with VIIRS Deep Blue Level 3 data and SO2 data from Ozone Mapper and Profiler Suite (OMPS) Limb Profiler (LP), both of which are sensors onboard the Suomi National Polar Partnership (NPP) spacecraft. The model successfully reproduced ash and SO2 transport, effectively representing influencing synoptic systems. Both simulations showed similar propagation patterns, with GCTS1 yielding better results when compared with AOD retrievals. These results indicate the necessity of specifying lower mass fraction in the finest bins. Comparison with VIIRS Brightness Temperature Difference data confirmed the model’s efficiency in representing particle transport. Overestimation of SO2 may stem from emission inputs. This study demonstrates the feasibility of our implementation of the WRF-Chem model to reproduce ash and SO2 patterns after a multi-eruption event. This enables further studies into aerosol–radiation and aerosol–cloud interactions and atmospheric behavior following volcanic eruptions.

Abstract Background Relapse and refractory (R/R) rates after first‐line R‐CHOP in diffuse large B cell lymphomas (DLBCL) are ~40% and ~15% respectively. Aims We conducted a retrospective real‐world analysis aimed at evaluating clinical outcomes of R/R DLBCL patients. Material and Methods Overall, 403 consecutive DLBCL patients treated in two large hematological centers in Torino, Italy were reviewed. Results At a median follow up of 50 months, 5‐year overall survival from diagnosis (OS‐1) was 66.5%, and 2‐year progression free survival (PFS‐1) was 68%. 134 (34.4%) patients relapsed (n = 46, 11.8%) or were refractory (n = 88, 22.6%) to R‐CHOP. Most employed salvage treatments included platinum salt‐based regimens in 38/134 (28.4%), lenalidomide in 14 (10.4%). Median OS and PFS after disease relapse or progression (OS‐2 and PFS‐2) were 6.7 and 5.1 months respectively. No significant difference in overall response rate, OS‐2 or PFS‐2 in patients treated with platinum‐based regimens versus other regimens was observed. By multivariate analysis, age between 60 and 80 years, germinal center B cell type cell of origin and extranodal involvement of

Purpose To prove the safety and performance of the hypothermic corneal storage medium Corneal Chamber and the rinsing solution PSS-L in support of the new Conformité Européenne (CE) certification process in accordance with the Medical Device Regulation.Methods Fifteen (n=15) human donor corneas and 11 (n=11) porcine corneas were evaluated for the following parameters: endothelial cell density (ECD) and mortality, percentage of hexagonal cells (HEX%), coefficient of cellular area variation (CV%) and corneal transparency at Day 0 and after 14±1 days of storage in Corneal Chamber medium at 2–8°C. Then, the same parameters were assessed after rinsing of corneas in PSS-L for 1 min at room temperature. Evaluation of gentamicin sulfate carryover after corneal storage and PSS-L rinsing was performed by ultra-high performance liquid chromatography analysis on human corneas homogenates.Results Human and porcine corneas stored in Corneal Chamber medium showed a good overall quality of the tissue according to the quality parameters evaluated. In particular, mean ECD, HEX% and CV% did not show statistically significant changes at the end of storage and endothelial mortality increased to 3.1±3.3 and 7.8±3.5% in human and porcine corneas, respectively. Tissue rinsing with PSS-L did not affect the quality parameters evaluated before and gentamicin sulfate residues were absent in human corneas.Conclusions Corneal preservation in Corneal Chamber medium at 2–8°C for 14 days and the corneal rinse with PSS-L are safe and effective procedures allowing the preservation of the corneal quality parameters as well as the complete elimination of gentamicin sulfate from the tissues before transplantation.Cite Now

This prospective study aimed to (1) compare the diagnostic performance of 68Ga-PSMA-11 PET/CT with respect to conventional imaging (computed tomography (CT) and bone scintigraphy (BS)) in the primary staging of high-risk prostate cancer (PCa) patients and (2) validate PSMA-PET/CT accuracy in pelvic nodal staging in comparison with postoperative histopathology and assess PSMA-PET/CT’s impact on patient management. Sixty castration-sensitive high-risk (ISUP 4–5 and/or PSA > 20 ng/mL and/or cT3) PCa patients eligible for radical prostatectomy were enrolled (median PSA 10.10 [IQR: 6.22–17.95] ng/mL). PSMA-PET/CT, compared with CT, identified nodal (N) and/or distant metastases (M1) in 56.7% (34/60) vs. 13.3% (8/60) (p < 0.001) of patients: N + 45% vs. 13.3% (p < 0.001), M1a 11.7% vs. 1.7% (p = 0.03), M1b 23.3% vs. 1.7% (p < 0.001). Compared with BS, PSMA-PET/CT localized unknown skeletal metastases in 15% (9/60) of cases, with no false negative findings. Overall, PSMA-PET/CT led to a TNM upstaging in 45.0% (27/60) of cases, with no evidence of downstaging, resulting in a change in management in up to 28.8% (17/59) of patients. Compared with histopathology data (n = 32 patients), the per-patient accuracy of PSMA-PET/TC for detecting pelvic nodal metastases was 90.6%. Overall, the above evidence supports the use of PSMA-PET/CT in the diagnostic workup of high-risk prostate cancer staging.

Terrestrial ecosystems play a crucial role in global carbon cycling by sequestering carbon from the atmosphere and storing it primarily in living biomass and soil. Monitoring terrestrial carbon stocks is essential for understanding the impacts of changes in land use on carbon sequestration. This study investigates the potential of remote sensing techniques and the Google Earth Engine to map and monitor changes in the forests of Calabria (Italy) over the past two decades. Using satellite-sourced Corine land cover datasets and the InVEST model, changes in Land Use Land Cover (LULC), and carbon concentrations are analyzed, providing insights into the carbon dynamics of the region. Furthermore, cellular automata and Markov chain techniques are used to simulate the future spatial and temporal dynamics of LULC. The results reveal notable fluctuations in LULC; specifically, settlement and bare land have expanded at the expense of forested and grassland areas. These land use and land cover changes significantly declined the overall carbon stocks in Calabria between 2000 and 2024, resulting in notable economic impacts. The region experienced periods of both decline and growth in carbon concentration, with overall losses resulting in economic impacts up to EUR 357.57 million and carbon losses equivalent to 6,558,069.68 Mg of CO 2 emissions during periods of decline. Conversely, during periods of carbon gain, the economic benefit reached EUR 41.26 million, with sequestered carbon equivalent to 756,919.47 Mg of CO 2 emissions. This research aims to highlight the critical role of satellite data in enhancing our understanding and development of comprehensive strategies for managing carbon stocks in terrestrial ecosystems.

After the period of military anarchy in the third century, the imperial institution was transformed, taking on new and more solid forms. Between 284 and 410, imperial power shifted from the tetrarchy of Diocletian to the “charismatic” monarchy of Constantine and his successors, i.e. legitimised by divine grace as a divine gift. The main features of these phases will be analysed below, with attention also being paid to the alternative solution represented by the brief principate of Julian the Apostate (361-363) and to the changes that took place after the death of Theodosius (379-395), which made the Late Antique prince even more distant from his subjects.

This study analyses the trends of total aerosol and the main aerosol species over nine capitals in the Baltic Sea basin from 1989 to 2019 based on the Modern-Era Retrospective Analysis for Research and Applications, Version 2 Reanalysis. Aerosol speciation includes mineral dust, sea salt, sulphate (SO4), organic carbon (OC), and black carbon (BC). The mean total aerosol optical depth (AOD) values were the highest (up to 0.216) over the continental capitals (i.e., Warsaw, Berlin, and Vilnius). For each capital, the mean SO4 AOD was the main aerosol species, with a trend specular to total AOD. Apart from Warsaw, the mean BC AOD was the aerosol species with the lowest level. The composition of aerosols changed with respect to the species of anthropogenic origins (i.e., SO4, OC, and BC), with the percentage contribution to the total AOD decreasing for the SO4 AOD and increasing for the BC AOD. Also, the OC AOD showed an increase in the percentage contribution to total AOD for Copenhagen, Oslo, Stockholm, and the continental capitals. Anthropogenic aerosols contributed up to 90.3% of the total AOD, with the highest values over the continental capitals. For each capital, the minimum in the percentage contribution of anthropogenic AOD was between 2007 and 2008, likely due to the global financial crisis. Anthropogenic AOD as a percentage of the total AOD decreased from 1989 to 2008. Both the total and the SO4 AODs decreased over each capital. By contrast, the BC AOD increased over Stockholm, and both the OC and BC AODs increased over Berlin, Copenhagen, and Oslo. The decoupling of carbonaceous aerosols and the SO4 AOD trends was likely due to concurrent factors such as biomass burning and low-sulphur fuel policies. From 2000 to 2019, the inverse relationships between gross domestic products and SO4 AODs suggest a relative decoupling of economic growth from fossil fuels for Oslo, Stockholm, Tallinn, and Vilnius.

The genomes of positive-sense (+) single-stranded RNA (ssRNA) viruses are believed to be subjected to a wide range of RNA modifications. In this study, we focused on the chikungunya virus (CHIKV) as a model (+) ssRNA virus to study the landscape of viral RNA modification in infected human cells. Among the 32 distinct RNA modifications analysed by mass spectrometry, inosine was found enriched in the genomic CHIKV RNA. However, orthogonal validation by Illumina RNA-seq analyses did not identify any inosine modification along the CHIKV RNA genome. Moreover, CHIKV infection did not alter the expression of ADAR1 isoforms, the enzymes that catalyse the adenosine to inosine conversion. Together, this study highlights the importance of a multidisciplinary approach to assess the presence of RNA modifications in viral RNA genomes.

Many quiescent galaxies discovered in the early Universe by JWST raise fundamental questions on when and how these galaxies became and stayed quenched. Making use of the latest version of the semianalytic model GAEA that provides good agreement with the observed quenched fractions up to z ∼ 3, we make predictions for the expected fractions of quiescent galaxies up to z ∼ 7 and analyze the main quenching mechanism. We find that in a simulated box of 685 Mpc on a side, the first quenched massive ( M _⋆ ∼ 10 ^11 M _⊙ ), Milky Way–mass, and low-mass ( M _⋆ ∼ 10 ^9.5 M _⊙ ) galaxies appear at z ∼ 4.5, z ∼ 6.2, and before z = 7, respectively. Most quenched galaxies identified at early redshifts remain quenched for more than 1 Gyr. Independently of galaxy stellar mass, the dominant quenching mechanism at high redshift is accretion disk feedback (quasar winds) from a central massive black hole, which is triggered by mergers in massive and Milky Way–mass galaxies and by disk instabilities in low-mass galaxies. Environmental stripping becomes increasingly more important at lower redshift.

Background There is increasing evidence of autophagy activation in COPD, but its role is complex and probably regulated through cell type-specific mechanisms. This study aims to investigate the autophagic process at multiple levels within the respiratory system, using different methods to clarify conflicting results reported so far. Methods This cross-sectional study was performed on bronchial biopsies and peripheral lung samples obtained from COPD patients (30 and 12 per sample type, respectively) and healthy controls (25 and 22 per sample type, respectively), divided by smoking history. Subjects were matched for age and smoking history. We analysed some of the most important proteins involved in autophagosome formation, such as LC3 and p62, as well as some molecules essential for lysosome function, such as lysosome-associated membrane protein 1 (LAMP1). Immunohistochemistry was used to assess the autophagic process in both sample types. ELISA and transcriptomic analysis were performed on lung samples. Results We found increased autophagic stimulus in smoking subjects, regardless of respiratory function. This was revealed by immunohistochemistry through a significant increase in LC3 (p

Abstract Introduction The purpose of the study is to investigate, by T2 relaxation, non‐lesional white matter (WM) in relapsing–remitting (RR) multiple sclerosis (MS). Methods Twenty stable RR MS patients underwent 1.5T Magnetic Resonance Imaging (MRI) with 3D Fluid‐Attenuated Inversion‐Recovery (FLAIR), 3D‐T1‐weighted, and T2‐relaxation multi‐echo sequences. The Lesion Segmentation Tool processed FLAIR images to identify focal lesions (FLs), whereas T1 images were segmented to identify WM and FL sub‐volumes with T1 hypo‐intensity. Non‐lesional WM was obtained as the segmented WM, excluding FL volumes. The multi‐echo sequence allowed decomposition into myelin water, intra‐extracellular water, and free water (Fw), which were evaluated on the segmented non‐lesional WM. Correlation analysis was performed between the non‐lesional WM relaxation parameters and Expanded Disability Status Scale (EDSS), disease duration, patient age, and T1 hypo‐intense FL volumes. Results The T1 hypo‐intense FL volumes correlated with EDSS. On the non‐lesional WM, the median Fw correlated with EDSS, disease duration, age, and T1 hypo‐intense FL volumes. Bivariate EDSS correlation of FL volumes and WM T2‐relaxation parameters did not improve significance. Conclusion T2 relaxation allowed identifying subtle WM alterations, which significantly correlated with EDSS, disease duration, and age but do not seem to be EDSS‐predictors independent from FL sub‐volumes in stable RR patients. Particularly, the increase in the Fw component is suggestive of an uninvestigated prodromal phenomenon in brain degeneration.

AbstractThe great potential of the Global Navigation Satellite System (GNSS) in monitoring ground deformation is widely recognized. As with other geophysical data, GNSS time series can be significantly noisy, hiding elusive ground deformation signals. Several denoising techniques have been proposed to improve the signal-to-noise ratio over the years. One of the most effective denoising techniques has been proved to be multi-resolution decomposition through the discrete wavelet transform. However, wavelet analysis requires long data sets to be effective, as well as long computation times, that hinder its use as a real or near real-time monitoring tool. We propose training by a Convolutional Neural Network (CNN) to perform the equivalent of wavelet analysis to overcome these limitations. Once trained, the CNN model provides answers within seconds, making it feasible as a real-time data analysis tool. Our Machine Learning algorithm is tested on daily GNSS time series collected in the Campi Flegrei caldera (Southern Italy), which is a highly volcanic risk area. Without significant gaps, the retrieved RMSE and R2 values vary in the ranges 0.65–0.98 and 0.06–0.52 cm, respectively. These results are encouraging, as they hint at the possibility of applying this methodology in more effective real-time monitoring solutions for active volcanoes.

Dunbar syndrome is caused by the compression of the celiac artery by the median arcuate ligament (MAL) and the diaphragmatic crura, presenting with abdominal pain. The treatment is surgical, with the aim of dissecting and separating the diaphragmatic crura from the celiac axis, restoring blood flow in the celiac trunk. We propose the use of transesophageal echocardiography to measure the peak systolic velocity in the celiac trunk and to evaluate, in real time, the efficacy of the surgery during MAL resection. Two clinical cases with practical implications are reported. In one of these, the ultrasound exam was useful in providing an intraoperative confirmation of the outcome of the resection.

Abstract FIRES is defined as a disorder that requires a prior febrile infection starting between 2 weeks and 24 h before the onset of the refractory status epilepticus with or without fever at the onset of status epilepticus. The patients, previously normal, present in the acute phase recurrent seizures and status epilepticus followed by a severe course with usually persistent seizures and residual cognitive impairment. Boundary with “new onset refractory status epilepticus (NORSE) has not clearly established. Pathogenetic hypothesis includes inflammatory or autoimmune mechanism with a possible genetic predisposition for an immune response dysfunction. Various types of treatment have been proposed for the treatment of the acute phase of the disorder to block the rapid seizures evolution to status epilepticus and to treat status epilepticus itself. Prognosis is usually severe both for control of the seizures and for cognitive involvement. FIRES is an uncommon but severe disorder which must be carefully considered in the differential diagnosis with other epileptic encephalopathy.

IntroductionProstate cancer (PCa) is the most frequent tumor among men in Europe and has both indolent and aggressive forms. There are several treatment options, the choice of which depends on multiple factors. To further improve current prognostication models, we established the Turin Prostate Cancer Prognostication (TPCP) cohort, an Italian retrospective biopsy cohort of patients with PCa and long-term follow-up. This work presents this new cohort with its main characteristics and the distributions of some of its core variables, along with its potential contributions to PCa research.MethodsThe TPCP cohort includes consecutive non-metastatic patients with first positive biopsy for PCa performed between 2008 and 2013 at the main hospital in Turin, Italy. The follow-up ended on December 31st 2021. The primary outcome is the occurrence of metastasis; death from PCa and overall mortality are the secondary outcomes. In addition to numerous clinical variables, the study’s prognostic variables include histopathologic information assigned by a centralized uropathology review using a digital pathology software system specialized for the study of PCa, tumor DNA methylation in candidate genes, and features extracted from digitized slide images via Deep Neural Networks.ResultsThe cohort includes 891 patients followed-up for a median time of 10 years. During this period, 97 patients had progression to metastatic disease and 301 died; of these, 56 died from PCa. In total, 65.3% of the cohort has a Gleason score less than or equal to 3 + 4, and 44.5% has a clinical stage cT1. Consistent with previous studies, age and clinical stage at diagnosis are important prognostic factors: the crude cumulative incidence of metastatic disease during the 14-years of follow-up increases from 9.1% among patients younger than 64 to 16.2% for patients in the age group of 75-84, and from 6.1% for cT1 stage to 27.9% in cT3 stage.DiscussionThis study stands to be an important resource for updating existing prognostic models for PCa on an Italian cohort. In addition, the integrated collection of multi-modal data will allow development and/or validation of new models including new histopathological, digital, and molecular markers, with the goal of better directing clinical decisions to manage patients with PCa.

The trial of Basilius and Praetextatus in 510-511, according to Cassiodorus’s Variae and Gregory the Great’s Dialogi, is an event in the period between the end of the fifth century and the first half of the sixth that confirms the survival of pagan practices and beliefs in Rome. Some members of the senatorial aristocracy of Rome are involved in these practices. Indeed, despite the Christianization of the city, the ability to satisfy the desire to understand events, even if through an interpretation linked to ancient pagan knowledge, increases the influence and power of the senatorial families in their competition with other political and religious institutions for control of the Roman population. Basilius’s and Praetextatus’s necromantic practices were probably justified by the aim of gaining prestige in urban society through the knowledge of occult wisdom.

IntroductionHypnic headache (HH) is a primary headache, and it is considered a rare condition in children. The underlying mechanisms of HH are not yet fully understood. This systematic review aims to provide a comprehensive description of the clinical features of all published cases of pediatric HH. It will also discuss the differences in headache features between children and adults, the increased diagnostic sensitivity of the new diagnostic criteria (ICHD-3), potential pathophysiological hypotheses explaining the higher incidence in adults, differential diagnoses, and therapeutic options for children.MethodsA systematic search was conducted to identify and analyze articles reporting cases of HH in patients under the age of 18. The search was performed in major medical databases including Cochrane Library, EBSCO, Embase, Medline, PubMed, Science Direct, Scopus, and Web of Science. The search covered the period from 1988 to April 2023. Relevant studies were screened for eligibility, and data extraction was performed using a standardized approach.ResultsSeven children with HH were included in the analysis. The mean age of onset for headache attacks was 10 ± 4.3 years (range 3–15 years). The average time from the start of headaches to diagnosis was 15.8 ± 25.0 months (range 1–60 months). Headache features in children differed from those observed in adult HH patients. Children experienced throbbing/pulsating pain, while adults reported dull/pressure-like pain. Children also had lower frequency and shorter duration of attacks compared to adults. The use of ICHD-3 criteria appeared to be more sensitive and inclusive for diagnosing HH in children compared to the previous ICHD-2 criteria. The association of headache attacks with sleep suggests that HH may be a primary disorder with a chronobiological origin. Hypothalamic dysfunction and melatonin dysregulation, which are more prevalent in older individuals, could potentially explain the higher incidence of HH in adults. Other primary headaches and secondary causes should be ruled out. Melatonin prophylactic therapy may be considered for pediatric patients.DiscussionFurther evaluation of the clinical features of HH in children is needed. The development of specific diagnostic criteria for pediatric cases could improve diagnostic rates and enhance the management of children with HH.

This study aims to evaluate the impact of a single session of intraoral and extraoral photobiomodulation (PBM) on controlling pain and improving a patient’s daily activities following surgical extraction of the impacted mandibular third molar, using combined three wavelengths: “445 nm, 660 nm, and 970 nm”. A pilot study was conducted on 22 patients undergoing extraction of an impacted mandibular third molar. The patients were randomly divided into two groups: (1) The Test Group consisted of patients subjected to immediate postoperative PBM. The extraoral PBM parameters were power = 550 mW and spot area = 5 cm2, while the intraoral parameters were power = 200 mW and spot area = 2 cm2. (2) The Control Group consisted of the patients not subjected to PBM. For all the patients, the pain was evaluated via a Numeric Rating Scale (NRS) on day 0, day 1, day 3, and day 7 after surgical intervention. The patient’s daily activities were evaluated on day 7 via a custom-made questionnaire. A statistically significant difference was observed between groups in the pain NRS scores on day 0 (p = 0.022), day 1 (p = 0.047), and day 7 (p = 0.028). No significant difference was found on day 3 (p = 0.153). A marginal statistical significance was observed with the number of painkillers taken (p = 0.054). No significant difference was observed with the questionnaire score (p = 0.206). This pilot study showed a significant reduction in postoperative pain on days 0, 1, and 7 with a single session of intraoral and extraoral PBM. However, the number of painkillers taken and the scores of the daily activities questionnaire did not show statistical significance despite the observed better results in patients subjected to PBM.

Despite recent advances in prevention, detection and treatment, oral squamous cell carcinoma (OSCC) remains a global health concern, strongly associated with environmental and lifestyle risk factors and infection with oncogenic viruses. Merkel Cell Polyomavirus (MCPyV), well known to be the causative agent of Merkel Cell Carcinoma (MCC) has been found in OSCC, suggesting its potential role as a co-factor in the development of oral cavity cancers. To improve our understanding about MCPyV in oral cavities, the detection and analysis of MCPyV DNA, transcripts and miRNA were performed on OSCCs and oral potentially malignant disorders (OPMDs). In addition, the cellular miR-375, known to be deregulated in tumors, was examined. MCPyV DNA was found in 3 out of 11 OSCC and 4 out of 12 OPMD samples, with a viral mean value of 1.49 × 102 copies/mL. Viral integration was not observed and LTAg and VP1 transcripts were detected. Viral miRNAs were not detected whereas the cellular miR-375 was found over expressed in all MCPyV positive oral specimens. Our results reported evidence of MCPyV replication in both OSCC and OPMD suggesting the oral cavity as a site of replicative MCPyV infection, therefore underscoring an active role of this virus in the occurrence of oral lesions.

Background: Atraumatic limping is a frequent cause of consultation in Pediatric Emergency Departments (PED) and often represents a challenge for pediatricians for its variability in etiology ranging from benign causes to potential crippling conditions. The aims of this research are to illustrate the clinical features of acute limping children (LC) and to identify the possible red flags that could help to make a diagnosis of severe pathologies. Methods: We carried out a retrospective study about non-traumatic limping children referred to the PED of Bambino Gesù Children’s Hospital over a 2-year period. We divided the cohort into three groups based on the patient’s age: toddlers, children and adolescents. We considered crippling conditions: oncologic etiologies, bone or neurological infections, epiphysiolysis, Perthes disease, Guillain Barrè syndrome and non-accidental injuries. Results: We analyzed 485 patients. At clinical evaluation, 19.5% of the patients presented at least one sign and/or symptom of red flags. Crippling conditions (6.2% of the total population) showed red flags in 36.7%. Transient synovitis of the hip was the most frequent diagnosis. We found crippling conditions in 30 patients, mostly represented by toddlers. Conclusions: Our data suggest that toddlers and patients presenting red flags should be evaluated with particular suspicion because they have an increased risk of underlying severe conditions.

Abstract Discontinuation of antimicrobial stewardship programs (ASPs) and increased antibiotic use were described during SARS-CoV-2 pandemic. In order to measure COVID-19 impact on ASPs in a setting of high multidrug resistance organisms (MDRO) prevalence, a qualitative survey was designed. In July 2021, eighteen ID Units were asked to answer a questionnaire about their hospital characteristics, ASPs implementation status before the pandemic and impact of SARS-CoV-2 pandemic on ASPs after the 1st and 2nd pandemic waves in Italy. Nine ID centres (50%) reported a reduction of ASPs and in 7 cases (38.9%) these were suspended. After the early pandemic waves, the proportion of centres that restarted their ASPs was higher among the ID centres where antimicrobial stewardship was formally identified as a priority objective (9/11, 82%, vs 2/7, 28%). SARS-CoV-2 pandemic had a severe impact in ASPs in a region highly affected by COVID-19 and antimicrobial resistance but weaknesses related to the pre-existent ASPs might have played a role.

Abstract Background Cyclic Vomiting Syndrome (CVS) is a rare functional gastrointestinal disorder, which has a considerable burden on quality of life of both children and their family. Aim of the study was to evaluate the diagnostic modalities and therapeutic approach to CVS among Italian tertiary care centers and the differences according to subspecialties, as well as to explore whether potential predictive factors associated with either a poor outcome or a response to a specific treatment. Methods Cross-sectional multicenter web-based survey involving members of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP). Results A total of 67 responses were received and analyzed. Most of the respondent units cared for less than 20 patients. More than half of the patients were referred after 3 to 5 episodes, and a quarter after 5 attacks. We report different diagnostic approaches among Italian clinicians, which was particularly evident when comparing gastroenterologists and neurologists. Moreover, our survey demonstrated a predilection of certain drugs during emetic phase according to specific clinic, which reflects the cultural background of physicians. Conclusion In conclusion, our survey highlights poor consensus amongst clinicians in our country in the diagnosis and the management of children with CVS, raising the need for a national consensus guideline in order to standardize the practice.

The family of Malacoherpesviridae is currently represented by only two viruses infecting molluscs, Ostreid herpesvirus 1 (OsHV-1) and Haliotid herpesvirus 1 (HaHV-1), both causing detrimental infections in aquaculture species. Malacoherpesvirus-like sequences were also detected through genome sequencing projects in amphioxus (Branchiostoma species) and annelid worm (Capitella teleta), suggesting the existence of a hidden diversity of malacoherpesviruses in aquatic animals. Here, to extend the knowledge on malacoherpesvirus diversity, we searched for the presence of malacoherpesvirus relatives in genomic, transcriptomic and metagenomic datasets, including from the Tara Oceans expedition, and report 4 novel malacoherpesvirus-like genomes (MalacoHV1-4). Genomic analysis suggested gastropods and bivalves as the most probable hosts for these new malacoherpesviruses. Phylogenetic analysis based on the family B DNA polymerase placed the novel MalacoHV1 and MalacoHV3 as sister lineages of OsHV-1 and HaHV-1, respectively, whereas MalacoHV2 and MalacoHV4 showed higher divergence. The viral genome found associated with amphioxus together with MalacoHV4 formed a sister clade to the mollusc and annelid malacoherpesviruses, suggesting an early divergence of the two virus assemblages. In conclusion, although relatively rare in the available sequence databases, the previously undescribed malacoherpesviruses, MalacoHV1-4, circulate in aquatic ecosystems and should be considered as possible emerging viruses under changing environmental conditions.

IntroductionSuicidal attempts (SAs) in youth have been increasing during the last decades.MethodsWe studied consultations, SA, and suicidal ideation (SI) in a pediatric emergency department (ED).ResultsFrom 1 January 2011 to 31 May 2022, 606,159 patients accessed the ED, 8,397 of who had a child psychiatry consultation (CPC). CPCs increased significantly by 11 times in the last decade (155 in 2011 vs. 1,824 in 2021, p < 0.001); CPCs for SA increased significantly by 33 times, from 6 in 2011 to 200 in 2021 (3.9% of total CPC vs. 11%, p < 0.001). While total CPCs increased constantly during the entire period (annual percent change (APC) of 21.7 from 2011 to 2021 in a 0 joinpoint model), CPCs for SA increased significantly from 2011 to 2016, were approximately stable from 2016 to 2020, and then had a peak in 2021 after the COVID-19 pandemic (APC from 2011 to 2016 of 64.1, APC of 1.2 from 2016 to 2020, and APC of 230 after 2020 in a 2-joinpoint model).DiscussionTotal CPCs in ED as well as evaluation for SA and SI increased significantly during the last decade. CPCs for SA had an additional increase after the COVID-19 pandemic. This picture warrants timely and efficient improvements in emergency settings and mental health resources.

Abstract Neurological vertigo is a common symptom in children and adults presenting to the emergency department (ED) and its evaluation may be challenging, requiring often the intervention of different medical specialties. When vertigo is associated with other specific symptoms or signs, a differential diagnosis may be easier. Conversely, if the patient exhibits isolated vertigo, the diagnostic approach becomes complex and only through a detailed history, a complete physical examination and specific tests the clinician can reach the correct diagnosis. Approach to vertigo in ED is considerably different in children and adults due to the differences in incidence and prevalence of the various causes. The aim of this systematic review is to describe the etiopathologies of neurological vertigo in childhood and adulthood, highlighting the characteristics and the investigations that may lead clinicians to a proper diagnosis. Finally, this review aims to develop an algorithm that could represent a valid diagnostic support for emergency physicians in approaching patients with isolated vertigo, both in pediatric and adult age.

Abstract Background We proposed to analyze thoroughly the impact of the COVID-19 lockdown (CL) in changes of profiles and in trend of the domestic accidents (DAs) in children. Methods This was a single experience, cross-sectional study conducted at the emergency department (ED) of III trauma center. We enrolled children under 18 years admitted to ED with a diagnosis of DAs comparing the CL period from 10th March 2020 to 4th May 2020 with the same period of the previous year,10th March 2019 to 4th May 2019. Results In CL period, the cumulative incidence of ED visits for DAs increased from 86.88 to 272.13 per 1,000 children and the cumulative incidence of hospitalizations for DAs increased from 409.72 to 534.48 per 1,000 children. We reported in CL a decrease in the severity of ED presentation assessed by proxy measures: the level of priority ED visits reduced by 67% in CL period (OR: 0.33; 95%CI 0.22–0.48; p

Several guidelines including radiotherapy recommendations exist worldwide for the treatment of small cell lung cancer (SCLC). To evaluate the differences in radiotherapy recommendations we conducted a systematic review. PubMed and the sites of medical societies were searched for SCLC guidelines published in either English, Chinese, or Dutch. This was limited to January 2018 till February 2021 to only include up-to-date recommendations. Data was extracted and compared regarding the guideline's development method and radiotherapy recommendations. Eleven guidelines were identified (PubMed n=4, societies n=7) from Spain (n=1), Canada (n=1), America (n=3), United Kingdom (n=1), the Netherlands (n=1), and China (n=3), respectively. Nine guidelines assessed the strength of evidence (SOE) and specified the strength of recommendation (SOR), although methods were different. The major radiotherapy recommendations are similar although differences exist in thoracic radiotherapy (TRT) dose, time, and volume. Controversial areas are TRT in resected stage I-IIA (pN1), prophylactic cranial irradiation (PCI) in resected as well as unresected stage I-IIA, stereotactic body radiation therapy (SBRT) in unresected stage I-IIA, PCI time, and PCI versus magnetic resonance imaging (MRI) surveillance in stage IV. The existence of several overlapping guidelines for SCLC treatment indicates that guideline development is (unnecessarily) repeated by different organizations or societies. Improvement could be made by better international collaboration to avoid duplicating unnecessary work, which would spare a lot of time and resources. Efforts should be made to work together on controversial or unknown fields.

Abstract Background Intercepting earlier suspected TB (Tuberculosis) cases clinically is necessary to reduce TB incidence, so we described signs and symptoms of retrospective cases of pulmonary TB and tried to evaluate which could be early warning signs. Methods We conducted a retrospective descriptive study of pulmonary TB cases in children in years 2005–2017; in years 2018–2020 we conducted a cohort prospective study enrolling patients

Abstract Background Oral lichen planus (OLP) is an immune-mediated inflammatory chronic disease of the oral mucosa, with different patterns of clinical manifestations which range from keratotic manifestations (K-OLP) to predominantly non-keratotic lesions (nK-OLP). The aim of the study was to analyze the differences in the clinical, psychological profile and symptoms between Italian patients of the North and Central-South with K-OLP and nK-OLP. Methods 270 K-OLP and 270 nK-OLP patients were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) were administered. Results The Central-South K-OLP (CS-K-OLP) patients reported a higher frequency of pain/burning compared with the K-OLP patients of the North (N-K-OLP) with higher scores in the NRS and T-PRI (p value

Nowadays, the availability of affordable multi-constellation multi-frequency receivers has broadened access to accurate positioning. The abundance of satellite signals coupled with the implementation of ground- and satellite-based correction services has unlocked the potential for achieving real-time centimetre-level positioning with low-cost instrumentation. Most of the current and future applications cannot exploit well-consolidated satellite positioning techniques such as Network Real Time Kinematic (RTK) and Precise Point Positioning (PPP); the former is inapplicable for large user bases due to the necessity of a two-way communication link between the user and the NRTK service provider, while the latter necessitates long convergence times that are not in keeping with kinematic application. In this context, the hybrid PPP-RTK technique has emerged as a potential solution to meet the demand for real-time, low-cost, accurate, and precise positioning. This paper presents an Internet of Things (IoT) GNSS device developed with low-cost hardware; it leverages a commercial PPP-RTK correction service which delivers corrections via IP. The main target is to obtain both horizontal and vertical decimetre-level accuracies in urban kinematic tests, along with other requisites such as solution availability and the provision of connection ports for interfacing an IoT network. A vehicle-borne kinematic test has been conducted to evaluate the device performance. The results show that (i) the IoT device can deliver horizontal and vertical positioning solutions at decimetre-level accuracy with the targeted solution availability, and (ii) the provided IoT ports are feasible for gathering the position solutions over an internet connection.