Ferrari (Italy)

Core myopathies are congenital diseases with clinical, pathological and genetic heterogeneity. Main histological features are fiber "cores" showing a focally reduced oxidative enzyme activity. Dusty Core Disease (DuCD) differs from Central Core Myopathy for the presence of irregular areas, without clear borders and round/ovoidal shape, and myofibrillar disorganization characterized by reddish purple granular material depositions. This disorder is defined clinically by severe phenotypes with early onset of disease and molecularly by low level of RyR1 in muscle. Until now DuCD was associated only to biallelic recessive RYR1 mutations. We analyzed the clinical aspects, pathological features and mutational spectrum of four DuCD patients, belonging to our cohort of Congenital Myopathy probands. Molecular analysis detected 5 different RYR1 pathogenic variants, two of them so far unreported. Patients presented a heterogeneous phenotype ranging from severe recessive infantile forms to moderate dominant adult-onset presentations. Histological, immunological and ultrastructural techniques were employed to validate these dominant cases, which expand our knowledge on the inheritance of this subgroup of diseases.

Monitoring systems are essential tools for landslide risk mitigation. Monitoring reduces vulnerability by providing the data required for slope instability characterization and hazard assessment. Moreover, alert and alarm systems rely on the ability of monitoring networks to timely deliver reliable and precise measurements. Remote monitoring systems are not mature enough to ensure reliable early-warning capabilities; therefore, information redundancy is achieved by deploying a set of sensors directly on the landslide body. Commonly used devices include total stations, GPS receivers, automatic inclinometers, and ground-based radar systems. However, the harsh environmental conditions typical of unstable slopes frequently affect the instruments performance and the data availability. The lack of a stable power supply is one of the main limitations of these systems, often preventing their operation precisely during the most critical situations, such as thunderstorms. In addition, adverse atmospheric conditions, including fog or low cloud cover, can compromise the visibility of topographic benchmarks, reducing data availability when it is most needed. To address these limitations a nonlinear parametric model for forecasting landslide displacements based on rainfall input has been developed. The model is trained and continuously updated using displacement data acquired by the monitoring system. In the event of system failure, the model is able to simulate landslide kinematics by means of “virtual sensors”, forecasting displacements and detecting sudden accelerations of the landslide, thereby preserving the early-warning functionality. The approach was successfully tested using data from the monitoring system installed at the Rotolon landslide, located in the municipality of Recoaro Terme (Vicenza, Italy).

ABSTRACT Background Whole-genome sequencing (WGS) has improved the diagnosis of rare genetic disorders, yet interpretation of non-coding variants that affect splicing remains challenging. In silico predictions alone are insufficient, and short-read RNA sequencing may fail to capture complex or low-abundance splicing events. Targeted amplicon-based long-read RNA sequencing (Amp-LRS) offers a cost-effective approach for functional validation of candidate splice-altering variants. Methods We applied Amp-LRS to five patients with neurological disorders (central nervous system, peripheral nervous system, or muscle) harbouring candidate non-coding variants predicted to alter splicing. RNA was extracted from fibroblasts or peripheral blood, and full-length transcript amplicons were sequenced using Oxford Nanopore Technologies. Nonsense-mediated decay (NMD) inhibition was performed on fibroblast cultures using cycloheximide. Results Amp-LRS validated all five candidate variants, including intronic and UTR variants in POLR3A, OPA1, PYROXD1, GDAP1 , and SPG11 . Aberrant splicing events included exon skipping, intron retention, cryptic splice site activation, and pseudoexon inclusion, often resulting in frameshifts and premature termination codons. For POLR3A and OPA1 , multiple abnormal isoforms arose from single variants, highlighting the complexity of splicing disruption. Some pathogenic effects were detectable only in a minority of reads and variably enriched by NMD inhibition, consistent with being hypomorphic. The approach was successfully applied using accessible tissues and enabled multiplexed sequencing at low per-sample cost. Conclusions Amp-LRS is a sensitive, versatile, and cost-effective method for functional assessment of non-coding splice-altering variants identified by WGS. By enabling full-length transcript analysis from accessible tissues, this approach improves interpretation of variants of uncertain significance and could enhance molecular diagnosis in rare neurological diseases.

Networked measurements are essential for the design and implementation of cooperative cyber-physical systems in the Industry 4.0/5.0 era. Indeed, the need for accurate models of real-time communication systems and, especially, of their latency is paramount for enabling technologies such as advanced manufacturing solutions, simulation and industrial internet. This paper presents a novel approach to measuring latency in wireless communication networks, focusing on the metrological characterization of individual subsystem contributions. By leveraging Time-Sensitive Networking (TSN) for synchronization, and employing cost-effective hardware solutions, we aim to provide a structured assessment of the measurement system’s capability to isolate and quantify latency contributions of individual communication modules, from the protocol stack to the Wireless Network Interface Controller (WNIC). The proposed approach is practical, flexible, and adaptable to various environments and deployment scenarios, representing a significant advancement in latency measurement techniques for modern network environments.

ABSTRACTBackgroundNitrous oxide/oxygen (N2O/O2 50%/50%) is an effective and safe technique for procedural sedation in paediatric settings; however, the knowledge, use and perspectives of healthcare professionals regarding N2O/O2 remain limited.AimTo investigate the knowledge, use and perspectives of healthcare professionals regarding N2O/O2 in maternal–infant and emergency units.Study DesignA cross‐sectional study was conducted (March to December 2024) using (i) a sociodemographic information tool and (ii) a 16‐item questionnaire assessing knowledge, clinical use, perceived barriers and willingness to adopt N2O/O2. Descriptive and multivariate analyses were performed.ResultsOf 113 respondents, 40.7% reported currently using N2O/O2 in their clinical units, while 91.0% of non‐users expressed willingness to adopt it. Barriers included lack of equipment (92.9%) and training (84.1%). 91.1% considered N2O/O2 ethically acceptable, consistent with principles of beneficence, non‐maleficence and child comfort. Employment in emergency units and holding a three‐year nursing degree were significant predictors of N2O/O2 use.ConclusionsLimited Use of N2O/O2 in Italian Paediatrics Contrasts With Strong Professional Interest. Improving Training and Resources Could Enhance Access to Safe Paediatric Sedation.Relevance to Clinical PracticeTraining, equipment and guidelines are needed to translate willingness into real clinical practice, improving the safety and consistency of paediatric sedation.

Slender, lightweight and modern footbridges are particularly susceptible to vibrations induced by pedestrian activity. While extensive research has focused on vertical and lateral forces produced by walking, torsional moments generated by eccentrically walking pedestrians remain largely overlooked. Traditional assessments typically neglect these torsional effects, which can be critical when eccentric pedestrian loading excites torsional modes, especially in footbridges with asymmetric geometries. To address this, the paper considers the coupling between bending and torsional effects in both the pedestrian action and structure reaction, including pedestrian forces and moments, as well as bending-induced deflections and torsion-induced rotations of the cross-sections. A simplified method is also presented, allowing standard bending-only analyses to be easily adapted to include torsional effects using analytically derived correction factors. For validation, several experimental tests are conducted on an asymmetric curved footbridge located in Modena, Italy, characterised by coupled bending-torsional vertical modes and hosting different pedestrian densities, pacing frequencies, and crowd distributions (both uniform and eccentric). Experimental and numerical analyses demonstrate that neglecting torsional effects oversimplifies the assessment, highlighting the importance of accounting for bending-torsion coupling for the serviceability of asymmetric footbridges under eccentric near-resonance loading.

End-to-end latency is a critical metric in interactive and real-time systems, where even short delays can undermine usability, situational awareness, and trust. While most studies focus on network transmission delays, this overlooks other significant sources of latency, including sensor acquisition, processing, and especially visualization. Rendering pipelines are heavily influenced by hardware, visualization strategies, and data complexity, and in visualization-rich domains such as smart cities, these factors can add considerable overhead. Ignoring them leads to overly optimistic performance assessments and missed opportunities for optimization.In this work, we study the last mile of end-to-end latency, explicitly incorporating the visualization stage and bridging the gap between network-level metrics and user-perceived responsiveness. We introduce the Unreal Smart Cities Visualizer (USCV), a framework we have built to support precise latency assessment in realistic, data-intensive urban scenarios. Our contributions include highlighting the limits of network-centric evaluation, presenting a visualization-aware methodology, and demonstrating USCV as a tool for accurate end-to-end latency measurement.Our results show that visualization delays, particularly in latency-critical environments, are not negligible and cannot be underestimated.

The data that support the findings of this study are available in the Supplementary Materials of this article. File 1. Family tree shows no other relatives affected. Genetic testing on II.1 turned negative for VPS16 mutations. File 2. Figure 1 references. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.