Combining mobile-health (mHealth) and artificial intelligence (AI) methods to avoid suicide attempts: the Smartcrises study protocol

The screening of digital footprint for clinical purposes relies on the capacity of wearable technologies to collect data and extract relevant information’s for patient management. Artificial intelligence (AI) techniques allow processing of real-time observational information and continuously learning from data to build understanding. We designed a system able to get clinical sense from digital footprints based on the smartphone’s native sensors and advanced machine learning and signal processing techniques in order to identify suicide risk. Method/design: The Smartcrisis study is a cross-national comparative study. The study goal is to determine the relationship between suicide risk and changes in sleep quality and disturbed appetite. Outpatients from the Hospital Fundación Jiménez Díaz Psychiatry Department (Madrid, Spain) and the University Hospital of Nimes (France) will be proposed to participate to the study. Two smartphone applications and a wearable armband will be used to capture the data. In the intervention group, a smartphone application (MEmind) will allow for the ecological momentary assessment (EMA) data capture related with sleep, appetite and suicide ideations. Discussion: Some concerns regarding data security might be raised. Our system complies with the highest level of security regarding patients’ data. Several important ethical considerations related to EMA method must also be considered. EMA methods entails a non-negligible time commitment on behalf of the participants. EMA rely on daily, or sometimes more frequent, Smartphone notifications. Furthermore, recording participants’ daily experiences in a continuous manner is an integral part of EMA. This approach may be significantly more than asking a participant to complete a retrospective questionnaire but also more accurate in terms of symptoms monitoring. Overall, we believe that Smartcrises could participate to a paradigm shift from the traditional identification of risks factors to personalized prevention strategies tailored to characteristics for each patientThis study was partly funded by Fundación Jiménez Díaz Hospital, Instituto de Salud Carlos III (PI16/01852), Delegación del Gobierno para el Plan Nacional de Drogas (20151073), American Foundation for Suicide Prevention (AFSP) (LSRG-1-005-16), the Madrid Regional Government (B2017/BMD-3740 AGES-CM 2CM; Y2018/TCS-4705 PRACTICO-CM) and Structural Funds of the European Union. MINECO/FEDER (‘ADVENTURE’, id. TEC2015–69868-C2–1-R) and MCIU Explora Grant ‘aMBITION’ (id. TEC2017–92552-EXP), the French Embassy in Madrid, Spain, The foundation de l’avenir, and the Fondation de France. The work of D. Ramírez and A. Artés-Rodríguez has been partly supported by Ministerio de Economía of Spain under projects: OTOSIS (TEC2013–41718-R), AID (TEC2014–62194-EXP) and the COMONSENS Network (TEC2015–69648-REDC), by the Ministerio de Economía of Spain jointly with the European Commission (ERDF) under projects ADVENTURE (TEC2015– 69868-C2–1-R) and CAIMAN (TEC2017–86921-C2–2-R), and by the Comunidad de Madrid under project CASI-CAM-CM (S2013/ICE-2845). The work of P. Moreno-Muñoz has been supported by FPI grant BES-2016-07762

Co-receptor Binding Site Antibodies Enable CD4-Mimetics to Expose Conserved Anti-cluster A ADCC Epitopes on HIV-1 Envelope Glycoproteins

Human immunodeficiency virus type 1 (HIV-1) has evolved a sophisticated strategy to conceal conserved epitopes of its envelope glycoproteins (Env) recognized by antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. These antibodies, which are present in the sera of most HIV-1-infected individuals, preferentially recognize Env in its CD4-bound conformation. Accordingly, recent studies showed that small CD4-mimetics (CD4mc) able to “push” Env into this conformation sensitize HIV-1-infected cells to ADCC mediated by HIV+ sera. Here we test whether CD4mc also expose epitopes recognized by anti-cluster A monoclonal antibodies such as A32, thought to be responsible for the majority of ADCC activity present in HIV+ sera and linked to decreased HIV-1 transmission in the RV144 trial. We made the surprising observation that CD4mc are unable to enhance recognition of HIV-1-infected cells by this family of antibodies in the absence of antibodies such as 17b, which binds a highly conserved CD4-induced epitope overlapping the co-receptor binding site (CoRBS). Our results indicate that CD4mc initially open the trimeric Env enough to allow the binding of CoRBS antibodies but not anti-cluster A antibodies. CoRBS antibody binding further opens the trimeric Env, allowing anti-cluster A antibody interaction and sensitization of infected cells to ADCC. Therefore, ADCC responses mediated by cluster A antibodies in HIV-positive sera involve a sequential opening of the Env trimer on the surface of HIV-1-infected cells. The understanding of the conformational changes required to expose these vulnerable Env epitopes might be important in the design of new strategies aimed at fighting HIV-1