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Abstract Recently, much interest has been raised for the characterization of signaling molecules carried by extracellular vesicles (EVs), which are particularly enriched in milk (mEVs). Such interest is linked to the capability of EVs to cross biological barriers, resist acidification in the gastric environment, and exert modulation of the immune system, mainly through their microRNA (miRNA) content. We characterized the small-RNA cargo of colostrum EVs (colosEVs) and mEVs from Italian Mediterranean buffalo through next generation sequencing. Colostrum (first milking after birth) and milk (day 50 of lactation) were sampled from seven subjects from five farms. ColosEVs and mEVs were subjected to morphological characterization, followed by high-depth sequencing of small RNA libraries produced from total RNA. The main difference was the amount of EV in the two samples, with colostrum showing 10 to 100-fold higher content than milk. For both matrices, miRNA was the most abundant RNA species (95% for colosEVs and 96% for mEVs) and three lists were identified: colosEV-specific, mEV-specific and shared most expressed. Gene ontology (GO) enrichment analysis on miRNA targets highlighted many terms related to the epigenetic, transcriptional and translational regulations across the three lists, with a higher number of enriched terms for colosEV-specific miRNAs. Terms specific to colosEVs were related to “cell differentiation” and “microvillus assembly”, while for mEV “cardiac and blood vessel development” and “mitochondria” emergerd. Immune modulation terms were found for both sample-specific miRNAs. Overall, both matrices carry a similar molecular message in terms of biological processes potentially modulated into receiving cells, but there is significant difference in the abundance, with colostrum containing much more EVs than milk. Moreover, colosEVs carry molecules involved in signal transduction, cell cycle and immune response, as for mEVs and EVs of other previously characterized species, but with a special enrichment for miRNAs with epigenetic regulation capacities. These beneficial characteristics of colosEVs and mEVs are essential for the calf and could also be exploited for the therapeutic purposes in humans, although further studies are necessary to measure the sanitization treatment impact on EV conservation, especially in buffalo where milk is consumed almost exclusively after processing.

The previous two decades have been marked by profound societal transformations, including ongoing developments in the illegal drug market and the emergence of numerous novel psychoactive substances. Nevertheless, a comprehensive understanding of the diverse clinical presentations of psychopathological conditions, particularly within the domain of psychotic symptoms, remains deficient. In this clinical overview, our aim is to provide a detailed analysis of the psychotic manifestations induced by various substances. Exogenous psychoses may present with visual hallucinations, delusional perceptions, and paranoid ideation, frequently accompanied by an ego-dystonic experience that deviate from an individual's customary self-identity. Variations in the presentation of symptoms are also influenced by the specific pharmacological pathways with which the substance interacts. Visual hallucinations characterized by vivid colours and associated with positive or negative emotional experiences are most frequently linked to the serotonergic pathway. Paranoid ideation and auditory hallucinations are primarily associated with the dopaminergic pathways. Dissociative responses, often characterized by feelings of derealization and somatopsychic depersonalization, are typically elicited through glutamatergic pathways. Lastly, the endocannabinoid pathways are associated with anxiety-related psychosis-like states, ideas of reference, grandiose delusions, and paranoid delusions.

Dengue virus (DENV) has been expanding its range to temperate areas that are not usually affected, where the spread of vectors has been facilitated by global trade and climate change. In Europe, there have been many cases of DENV imported from other regions in the past few years, leading to local outbreaks of DENV among people without travel history. Here we describe the epidemiological and molecular investigations of three transmission events locally acquired DENV infections caused by serotypes 1, 2 and 3, respectively, in the Latium Region from August to November 2023. Next-generation or Sanger sequencing was used to obtain the whole genomes, or the complete E-gene of the viruses, respectively. The structure of the DENV-1 and DENV-3 sequences was analysed to identify amino acid changes that were not found in the closest related sequences. The major cluster was supported by DENV-1 (originated in South America), with 42 autochthonous infections almost occurring in the eastern area of Rome, probably due to a single introduction followed by local sustained transmission. Seven DENV-1 subclusters have been identified by mutational and phylogenetic analysis. Structural analysis indicated changes whose meaning can be explained by the adaptation of the virus to human hosts and vectors and their interactions with antibodies and cell receptors.

We analyze the structures of the low-spin (LS) ground state and the high-spin (HS) lowest excited state of the iron-(II)-tris bipyridine complex ([Fe(bpy)3]2+) using density functional theory PBE methods, modeling the solvent interactions with conductor-like polarizable continuum model. These calculations are globally benchmarked against a wide range of experimental observables that include ultraviolet-visible linear absorption and circular dichroism (CD) spectra and Fe K-edge x-ray absorption near edge spectra (XANES). The calculations confirm the already established D3 geometry of the LS state, as well as a departure from this geometry for the HS state, with the appearance of inequivalent Fe–N bond elongations. The simulated structures nicely reproduce the above-mentioned experimental observables. We also calculate the vibrational modes of the LS and HS states. For the former, they reproduce well the vibrational frequencies from published infrared and Raman data, while for the latter, they predict very well the low-frequency vibrational coherences, attributed to Fe-N stretch modes, which were reported in ultrafast spectroscopic experiments. We further present calculations of the high-frequency region, which agree with recent ultrafast transient infrared spectroscopy studies. This work offers a common basis to the structural information encoded in the excited state CD and the Fe K XANES of the HS state tying together different structural IR, UV-visible, and x-ray observables.

Abstract Background In Italy, since the 2020–2021 flu season, the flu vaccine recommendation was extended to all children aged 6 months to 6 years and quadrivalent Live-Attenuated Influenza Vaccine (qLAIV) was introduced. Since school-aged children are important carriers of annual influenza epidemics, a school-based influenza vaccination program may potentially increase vaccine uptake. Recent studies, conducted in the UK and the US, show that school-based vaccination can reach higher percentage of paediatric vaccination coverage compared to children vaccinated in other settings. Methods During 2022–2023 flu season in 9 preschools located in Milan healthcare personnel vaccinated children with qLAIV at the end of a school day. A Google Form questionnaire was administered to preschoolers’ parents of all preschools within the Municipality of Milan. Results In the preschools engaged in the vaccination program, 233 out of 1939 children were vaccinated (12%). Among these, 61 (26.2%) had never been vaccinated for influenza before. Vaccination coverage was 11.5% for Italian children and 14.3% for children coming from an immigrant background. We collected 3659 questionnaire responses, divided according to study participation status (371 from preschools that participated in the vaccination program and 3288 from other preschools in Milan). 57% of the families who answered to the questionnaire vaccinated their children for flu. qLAIV accounted for 85.6% of vaccinations. We observed a statistically significant difference in the percentage of vaccinated children between those attending a school participating in the project (67.9%) and children attending other schools (56%) (p

We present an artificial intelligence (AI)-enhanced monitoring framework designed to assist personnel in evaluating and maintaining animal welfare using a modular architecture. This framework integrates multiple deep learning models to automatically compute metrics relevant to assessing animal well-being. Using deep learning for AI-based vision adapted from industrial applications and human behavioral analysis, the framework includes modules for markerless animal identification and health status assessment (e.g., locomotion score and body condition score). Methods for behavioral analysis are also included to evaluate how nutritional and rearing conditions impact behaviors. These models are initially trained on public datasets and then fine-tuned on original data. We demonstrate the approach through two use cases: a health monitoring system for dairy cattle and a piglet behavior analysis system. The results indicate that scalable deep learning and edge computing solutions can support precision livestock farming by automating welfare assessments and enabling timely, data-driven interventions.

Methane (CH4) from livestock, particularly enteric CH4 emission (EME), is one contributor to greenhouse gas emissions and climate change. This review analyzed 1294 scientific abstracts on EME in ruminants from 1986 to May 2024, using Scopus® data. Descriptive statistics, text mining, and topic analysis were performed. Publications on EME have risen significantly since 2005, with the Journal of Dairy Science being the most frequent publisher. Most studies (82.1%) were original research, with Northern Hemisphere countries leading in publication numbers. The most frequent terms were “milk”, “cow”, and “diet”, while key research topics included greenhouse gas emissions from livestock, diet composition, and prediction models. Despite progress, some areas like CH4 emission from animals need further investigation.

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.

Carmelo Bene (1937–2002) was an Italian theatre artist who radically transformed the practice and conception of Western theatre from a series of points of view. He dramaturgically re-conceived famous plays, innovatively worked on voice, and reached to film and music, as well as engaged his theatre vision with philosophy. This introductory essay on Bene’s philosophical thought and theatrical praxis seeks to arouse interest in his work among English readers, so as to spark interdisciplinary conversations across a variety of fields including Italian studies, critical theory, European theatre, film studies, performance philosophy, and aesthetics. To elucidate some of the distinctive and exemplificatory traits of Benean anti-representational theatre, special attention is paid to one of his readings, Lectura Dantis (1981), and to one of his plays, Pinocchio, ovvero lo spettacolo della Provvidenza (1998) – both of which are among the most significant performances in Bene’s career.

Abstract The Italian territory is located at the heart of one of the global hot spots of climate change, where the implementation of climate‐smart land management practices is imperative to guarantee the present and future maintenance of ecosystem functions as well as the sustainability of human socioeconomic activities. The project HIGHLANDER (HIGH performance computing to support smart LAND sERvices) led by Cineca aims at building a comprehensive and multi‐sector framework for land‐management decision‐making in Italy. The project relies on high quality information on different components of the landscape, with a focus on climate‐driven processes, and state‐of‐the‐art computing infrastructures. The HIGHLANDER Data Portal maximizes the impact of HIGHLANDER results by providing access to data products and services. In this article, we describe the architectural features of the platform, as well as the available HIGHLANDER datasets and downstream applications.

Mycobacterium avium subsp. paratuberculosis (MAP) is the aetiological agent of paratuberculosis (Johne’s disease) in both domestic and wild ruminants. In the present study, using a whole-genome sequence (WGS) approach, we investigated the genetic diversity of 15 Mycobacterium avium field strains isolated in the last 10 years from red deer inhabiting the Stelvio National Park and affected by paratuberculosis. Combining de novo assembly and a reference-based method, followed by a pangenome analysis, we highlight a very close relationship among 13 MAP field isolates, suggesting that a single infecting event occurred in this population. Moreover, two isolates have been classified as Mycobacterium avium subsp. hominissuis, distinct from the other MAPs under comparison but close to each other. This is the first time that this subspecies has been found in Italy in samples without evident epidemiological correlations, having been isolated in two different locations of the Stelvio National Park and in different years. Our study highlights the importance of a multidisciplinary approach incorporating molecular epidemiology and ecology into traditional infectious disease knowledge in order to investigate the nature of infectious disease in wildlife populations.

Abstract Background About 80% of the roughly 7,000 known rare diseases are single gene disorders, about 85% of which are ultra-rare, affecting less than one in one million individuals. NGS technologies, in particular whole genome sequencing (WGS) in paediatric patients suffering from severe disorders of likely genetic origin improve the diagnostic yield allowing targeted, effective care and management. The aim of this study is to perform a systematic review and meta-analysis to assess the effectiveness of WGS, with respect to whole exome sequencing (WES) and/or usual care, for the diagnosis of suspected genetic disorders among the paediatric population. Methods A systematic review of the literature was conducted querying relevant electronic databases, including MEDLINE, EMBASE, ISI Web of Science, and Scopus from January 2010 to June 2022. A random-effect meta-analysis was run to inspect the diagnostic yield of different techniques. A network meta-analysis was also performed to directly assess the comparison between WGS and WES. Results Of the 4,927 initially retrieved articles, thirty-nine met the inclusion criteria. Overall results highlighted a significantly higher pooled diagnostic yield for WGS, 38.6% (95% CI: [32.6 – 45.0]), in respect to WES, 37.8% (95% CI: [32.9 – 42.9]) and usual care, 7.8% (95% CI: [4.4 – 13.2]). The meta-regression output suggested a higher diagnostic yield of the WGS compared to WES after controlling for the type of disease (monogenic vs non-monogenic), with a tendency to better diagnostic performances for Mendelian diseases. The network meta-analysis showed a higher diagnostic yield for WGS compared to WES (OR = 1.54, 95%CI: [1.11 – 2.12]). Conclusions Although whole genome sequencing for the paediatric population with suspected genetic disorders provided an accurate and early genetic diagnosis in a high proportion of cases, further research is needed for evaluating costs, effectiveness, and cost-effectiveness of WGS and achieving an informed decision-making process. Trial Registration This systematic review has not been registered.

This review explores a variety of techniques that utilize air injections beneath a vessel’s hull to reduce drag and consequently improve energy efficiency. It focuses on the methodologies of microbubble drag reduction (MBDR), air layer drag reduction (ALDR), and air cavity drag reduction (ACDR), offering insights into their design, operational mechanisms, and potential applications. This review provides a detailed examination of the underlying principles of these technologies, incorporating a blend of experimental research, numerical simulations, and mathematical modelling to offer a comprehensive understanding. It references recent experimental data, highlighting how these findings corroborate with numerical simulations and are further explained through mathematical models. Conclusively, this review accentuates the transformative influence of air injection methods in drag reduction within the maritime industry, emphasizing their pivotal role in boosting operational efficiency, reducing environmental impact, and driving the evolution of naval design and transportation. Through a balanced and detailed analysis, this review provides a holistic view of the current state and future prospects of these innovative resistance reduction strategies.

Oscillating Water Column (OWC) systems harness wave energy using a partially submerged chamber with an underwater opening. The Savonius turbine, a vertical-axis wind turbine, is well-suited for this purpose due to its efficiency at low speeds and self-starting capability, making it an ideal power take-off (PTO) mechanism in OWC systems. This study tested an OWC device with a Savonius turbine in an air duct to evaluate its performance under varying flow directions and loads. An innovative aspect was assessing the influence of power augmenters (PAs) positioned upstream and downstream of the turbine. The experimental setup included load cells, Pitot tubes, differential pressure sensors and rotational speed sensors. Data obtained were used to calculate pressure differentials across the turbine and torque. The primary goal of using PA is to increase the CP–λ curve area without modifying the turbine geometry, potentially enabling interventions on existing turbines without rotor dismantling. Additionally, another novelty is the implementation of a regression Machine-Learning algorithm based on decision trees to analyze the influence of various features on predicting pressure differences, thereby broadening the scope for further testing beyond physical experimentation.

Disruptions to the ER-Golgi network can lead to neurodevelopmental disorders, though our understanding of these Golgipathies remains incomplete. Here Lauri, Tartaglia and colleagues show that ARF3 mutations cause a rare pediatric neurological disorder and perform detailed molecular characterization in fish.

Many activities of daily living require quick shifts between symmetric and asymmetric bimanual actions. Bimanual motor control has been mostly studied during continuous repetitive tasks, while little research has been carried out in experimental settings requiring dynamic changes in motor output generated by both hands. Here, we performed functional magnetic resonance imaging (MRI) while healthy volunteers performed a visually guided, bimanual pinch force task. This enabled us to map functional activity and connectivity of premotor and motor areas during bimanual pinch force control in different task contexts, requiring mirror-symmetric or inverse-asymmetric changes in discrete pinch force exerted with the right and left hand. The bilateral dorsal premotor cortex showed increased activity and effective coupling to the ipsilateral supplementary motor area (SMA) in the inverse-asymmetric context compared to the mirror-symmetric context of bimanual pinch force control while the SMA showed increased negative coupling to visual areas. Task-related activity of a cluster in the left caudal SMA also scaled positively with the degree of synchronous initiation of bilateral pinch force adjustments, irrespectively of the task context. The results suggest that the dorsal premotor cortex mediates increasing complexity of bimanual coordination by increasing coupling to the SMA while SMA provides feedback about motor actions to the sensory system.

Background: There is evidence that temporal duration is spatially represented on a horizontal mental timeline (MTL) with relatively short durations represented on the left and long duration on the right side. Most of this evidence comes from the visual domain. Objective: With the present study, we investigated whether temporal duration judgements of visual and auditory stimuli might be affected by spatial biases in time representation. Methods: Participants were asked to estimate the temporal duration of a target with respect to a reference stimulus. Two different exposure times were used for the reference (fast and slow), and three exposure times for the target with respect to the reference (shorter, equal, longer). Two versions of the task were implemented to probe visual and auditory temporal processing. Results: Participants showed enhanced performance when the target had longer duration than the reference independently of the type of task, but they were affected in opposite ways by the reference exposure time, in the two tasks. Best performance was observed for the fast reference in the visual domain and for the slow reference in the auditory one. Discussion: We argue that these findings provide evidence that temporal judgments of visual and auditory stimuli are affected by the duration of the reference stimulus, besides the duration of the target stimulus. Interestingly, they suggest putative leftward and rightward spatial biases in time representation for the visual and auditory domains, respectively, although future studies are necessary to further investigate these initial findings.

We present an artificial intelligence (AI)-enhanced monitoring framework designed to assist personnel in evaluating and maintaining animal welfare using a modular architecture. This framework integrates multiple deep learning models to automatically compute metrics relevant to assessing animal well-being. Using deep learning for AI-based vision adapted from industrial applications and human behavioral analysis, the framework includes modules for markerless animal identification and health status assessment (e.g., locomotion score and body condition score). Methods for behavioral analysis are also included to evaluate how nutritional and rearing conditions impact behaviors. These models are initially trained on public datasets and then fine-tuned on original data. We demonstrate the approach through two use cases: a health monitoring system for dairy cattle and a piglet behavior analysis system. The results indicate that scalable deep learning and edge computing solutions can support precision livestock farming by automating welfare assessments and enabling timely, data-driven interventions. [ABSTRACT FROM AUTHOR]

We analyze the structures of the low-spin (LS) ground state and the high-spin (HS) lowest excited state of the iron-(II)-tris bipyridine complex ([Fe(bpy)3]2+) using density functional theory PBE methods, modeling the solvent interactions with conductor-like polarizable continuum model. These calculations are globally benchmarked against a wide range of experimental observables that include ultraviolet-visible linear absorption and circular dichroism (CD) spectra and Fe K-edge x-ray absorption near edge spectra (XANES). The calculations confirm the already established D3 geometry of the LS state, as well as a departure from this geometry for the HS state, with the appearance of inequivalent Fe–N bond elongations. The simulated structures nicely reproduce the above-mentioned experimental observables. We also calculate the vibrational modes of the LS and HS states. For the former, they reproduce well the vibrational frequencies from published infrared and Raman data, while for the latter, they predict very well the low-frequency vibrational coherences, attributed to Fe-N stretch modes, which were reported in ultrafast spectroscopic experiments. We further present calculations of the high-frequency region, which agree with recent ultrafast transient infrared spectroscopy studies. This work offers a common basis to the structural information encoded in the excited state CD and the Fe K XANES of the HS state tying together different structural IR, UV-visible, and x-ray observables. [ABSTRACT FROM AUTHOR]