Towards a European Health Research and Innovation Cloud (HRIC)

The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Radio SLAM for 6G Systems at THz Frequencies: Design and Experimental Validation

International audienceNext-generation wireless networks will see the convergence of communication and sensing, also exploiting the availability of large bandwidths in the THz spectrum and electrically large antenna arrays on handheld devices. In particular, it is envisaged that user devices will be able to automatically scan their surroundings by steering a very narrow antenna beam and collecting echoes reflected by objects and walls. These data will be utilized to derive a map of the surrounding indoor environment and infer users trajectories using simultaneous localization and mapping (SLAM) techniques. In this paper, we address this scenario by proposing original radio-SLAM (R-SLAM) algorithms, derived from image processing techniques, to map the environment and pinpoint the device position in the map starting from measurements sensed by a mobile THz radar. Initially, to fully understand the THz backscattering phenomenon, we provide an experimental characterization of the THz backscattering channel in indoor environments. Then, the performance of the proposed algorithms is assessed using realworld THz radar measurements and is compared with state-ofthe-art SLAM techniques, demonstrating the superiority of the proposed approache

Application of nanotechnology in pediatric dentistry

BACKGROUND: The aim of this work was to study and pro- duce a dental adhesive with antibacterial properties through the use of micro and nanometric fillers based on graphene. METHODS: Graphene is the name given to a flat monolayer of carbon atoms tightly packed into a two-dimensional (2D) honeycomb lattice, and is a basic building block for graphitic materials of all other dimensionalities. It is extremely durable and hard (100 times more than steel), transparent and flexible. In addition, it present, at room temperature, an electrical conductivity superior to any other sub- stance and in recent years he has shown raised interest also in the biomedical field. In the present study it was developed and produced an den- tin/enamel adhesive with antibacterial properties thanks to the introduction of the graphene nanoplatelets (GNP) used as filler, starting from a common commercial adhesive used in dentistry and its widely-known properties. The GNP have been made from expanded graphite (EG), which in turn was produced from graphite intercalation compounds via rapid evaporation of the intercalant at elevated temperatures. The GNP thus obtained, have been incorporated into the commercial adhesive with the technique of solution processing. Antibacterial tests were carried out treating our experimental adhesive with bacterial strains of Streptococcus mutans. The antimicrobic effects of the adhesive were analyzed at both zero time 0 and after aging (1 week). Furthermore, tests of resistance to microtensile were carried out. RESULTS: Tests have shown that GNP present toxicity on microorganisms, thanks to mechanic interaction by wrapping and trapping bacteria. Furthermore, they show also an antibiofilm effect causing fractures in the structure of the same biofilm. The produced material shows a high efficacy the first days of application in which the bacteria mortality was detected by 100% and then the stoppage of biofilm growth. After the aging of the material concordant results were obtained, with a slight decrease of bacteria mortality as the hours passed. The mechanical tests analysis, in order to study the binding strength in the adhesive by GNP introduction, has shown a value by 29,1 MPa, slightly inferior to the value shown by the corresponding commercial adhesive. The given testing value is anyway included within the average of values referred to dental adhesives currently on the market. CONCLUSIONS: The undertook study permitted to develop an enamel dentinal adhesive with innovative antimicrobic properties. The main component of such properties is GNP, which has shown also a high biocompatibility on both human and animal cells. By analyzing bacterial cells in suspension by the method of Colony Forming Units (CFU), it was observed that GNP not only have toxicity on single cells, but also an antibiofilm effect interfering with the vital cycle of the same, thus inhibiting its development. Mechanical tests have shown excellent characteristics of the experimental adhesive so much that it can be considered virtually competitive

Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3

Objective: To retrospectively investigate safety and efficacy of nusinersen in a large cohort of adult Italian patients with spinal muscular atrophy (SMA). Methods: Inclusion criteria were: (1) clinical and molecular diagnosis of SMA2 or SMA3; (2) nusinersen treatment started in adult age (>18 years); (3) clinical data available at least at baseline (T0-beginning of treatment) and 6 months (T6). Results: We included 116 patients (13 SMA2 and 103 SMA3) with median age at first administration of 34 years (range 18-72). The Hammersmith Functional Rating Scale Expanded (HFMSE) in patients with SMA3 increased significantly from baseline to T6 (median change +1 point, p<0.0001), T10 (+2, p<0.0001) and T14 (+3, p<0.0001). HFMSE changes were independently significant in SMA3 sitter and walker subgroups. The Revised Upper Limb Module (RULM) in SMA3 significantly improved between T0 and T14 (median +0.5, p=0.012), with most of the benefit observed in sitters (+2, p=0.018). Conversely, patients with SMA2 had no significant changes of median HFMSE and RULM between T0 and the following time points, although a trend for improvement of RULM was observed in those with some residual baseline function. The rate of patients showing clinically meaningful improvements (as defined during clinical trials) increased from 53% to 69% from T6 to T14. Conclusions: Our data provide further evidence of nusinersen safety and efficacy in adult SMA2 and SMA3, with the latter appearing to be cumulative over time. In patients with extremely advanced disease, effects on residual motor function are less clear

Adults with spinal muscular atrophy: a large-scale natural history study shows gender effect on disease

Natural history of spinal muscular atrophy (SMA) in adult age has not been fully elucidated yet, including factors predicting disease progression and response to treatments. Aim of this retrospective, cross-sectional study, is to investigate motor function across different ages, disease patterns and gender in adult SMA untreated patients