Parental fitness questioned on the grounds of narcolepsy: Presentation of two cases

We report two cases of fathers whose parental fitness was questioned during divorce and custody litigation because of narcolepsy type 2 and type 1, respectively. These cases highlighted both the existence of a narcolepsy-related stigma and the need to involve sleep experts in custody assessments when concerns about the parental fitness are related to a sleep disorder, expanding the field of interest of the growing âsleep forensics"

AUTOMATED SEMANTIC AND SYNTACTIC BIM DATA VALIDATION USING VISUAL PROGRAMMING LANGUAGE

Building Information Modeling (BIM) is part of a digitalization process that, in recent years, has been revolutionizing the way buildings and infrastructures are designed, built, and maintained. Compared to traditional processes, BIM enhances the production and the management of data related to buildings and infrastructures throughout their life cycle. It is founded on a three-dimensional graphical model based on the specificity of project goals following the “level of information need” defined in BIM procurement documents. In this framework, an automated process for checking information within a BIM model plays a role of fundamental importance. Although this increases the model’s reliability, on the other hand, it decreases the time of working. Therefore, this research aims to develop a working methodology based on Visual Programming Language (VPL) for an automated BIM Data Validation process. This workflow aims to meet the growing need of owners to centralize data relating to their real estate assets to always have the appropriate one at the operational level. This methodology has been tested in different case studies to evaluate the strengths and weaknesses of using a standardization protocol in a large portfolio and complex buildings. This allows the huge amount of data from BIM models to be checked and summary reports to be produced, sharing with the various stakeholders involved in the knowledge process

Multi-Modal Embeddings for Isolating Cross-Platform Coordinated Information Campaigns on Social Media

Coordinated multi-platform information operations are implemented in a variety of contexts on social media, including state-run disinformation campaigns, marketing strategies, and social activism. Characterized by the promotion of messages via multi-platform coordination, in which multiple user accounts, within a short time, post content advancing a shared informational agenda on multiple platforms, they contribute to an already confusing and manipulated information ecosystem. To make things worse, reliable datasets that contain ground truth information about such operations are virtually nonexistent. This paper presents a multi-modal approach that identifies the social media messages potentially engaged in a coordinated information campaign across multiple platforms. Our approach incorporates textual content, temporal information and the underlying network of user and messages posted to identify groups of messages with unusual coordination patterns across multiple social media platforms. We apply our approach to content posted on four platforms related to the Syrian Civil Defence organization known as the White Helmets: Twitter, Facebook, Reddit, and YouTube. Results show that our approach identifies social media posts that link to news YouTube channels with similar factuality score, which is often an indication of coordinated operations.Comment: To appear in the 5th Multidisciplinary International Symposium on Disinformation in Open Online Media (MISDOOM 2023

Targeting the Spike: Repurposing Mithramycin and Dihydroergotamine to Block SARS-CoV-2 Infection

: The urgency to find complementary therapies to current SARS-CoV-2 vaccines, whose effectiveness is preserved over time and not compromised by the emergence of new and emerging variants, has become a critical health challenge. We investigate the possibility of jamming the opening of the Receptor Binding Domain (RBD) of the spike protein of SARS-CoV-2 with small compounds. Through in silico screening, we identified two potential candidates that would lock the Receptor Binding Domain (RBD) in a closed configuration, preventing the virus from infecting the host cells. We show that two drugs already approved by the FDA, mithramycin and dihydroergotamine, can block infection using concentrations in the μM range in cell-based assays. Further STD-NMR experiments support dihydroergotamine's direct interaction with the spike protein. Overall, our results indicate that repurposing of these compounds might lead to potential clinical drug candidates for the treatment of SARS-CoV-2 infection

Novel carboxylate-based glycolipids: TLR4 antagonism, MD-2 binding and self-assembly properties

New monosaccharide-based lipid A analogues were rationally designed through MD-2 docking studies. A panel of compounds with two carboxylate groups as phosphates bioisosteres, was synthesized with the same glucosamine-bis-succinyl core linked to different unsaturated and saturated fatty acid chains. The binding of the synthetic compounds to purified, functional recombinant human MD-2 was studied by four independent methods. All compounds bound to MD-2 with similar affinities and inhibited in a concentration-dependent manner the LPS-stimulated TLR4 signaling in human and murine cells, while being inactive as TLR4 agonists when provided alone. A compound of the panel was tested in vivo and was not able to inhibit the production of proinflammatory cytokines in animals. This lack of activity is probably due to strong binding to serum albumin, as suggested by cell experiments in the presence of the serum. The interesting self-assembly property in solution of this type of compounds was investigated by computational methods and microscopy, and formation of large vesicles was observed by cryo-TEM microscopy.TOLLerant project (H2020-MSC-ETN-642157), the Italian Ministry for Foreign Affairs and International Cooperation (MAECI) and Spanish MINECO (CTQ2014-57141-R and CTQ2017-88353-R grants) are acknowledged. Vesna Hodnik of University of Ljubljana for the help with SPR, Sandra Delgado of CIC BioGUNE for the Cryo-TEM images. RJ was partially funded by the research program P4-0176 by the Slovenian Research Agency

Control of Brain State Transitions with a Photoswitchable Muscarinic Agonist

Reproducció del document publicat a:https://doi.org/10.1002/advs.202005027The ability to control neural activity is essential for research not only in basic neuroscience, as spatiotemporal control of activity is a fundamental experimental tool, but also in clinical neurology for therapeutic brain interventions. Transcranial-magnetic, ultrasound, and alternating/direct current (AC/DC) stimulation are some available means of spatiotemporal controlled neuromodulation. There is also light-mediated control, such as optogenetics, which has revolutionized neuroscience research, yet its clinical translation is hampered by the need for gene manipulation. As a drug-based light-mediated control, the effect of a photoswitchable muscarinic agonist (Phthalimide-Azo-Iper (PAI)) on a brain network is evaluated in this study. First, the conditions to manipulate M2 muscarinic receptors with light in the experimental setup are determined. Next, physiological synchronous emergent cortical activity consisting of slow oscillations—as in slow wave sleep—is transformed into a higher frequency pattern in the cerebral cortex, both in vitro and in vivo, as a consequence of PAI activation with light. These results open the way to study cholinergic neuromodulation and to control spatiotemporal patterns of activity in different brain states, their transitions, and their links to cognition and behavior. The approach can be applied to different organisms and does not require genetic manipulation, which would make it translational to humans