The Sentiworld Project: Global Mapping of Sentinel Surveillance Networks in General Practice

International audienceAbstract Background Sentinel networks composed of general practitioners (GPs) represent a powerful tool for epidemiologic surveillance and ad-hoc studies. Globalization necesitates greater international cooperation among sentinel networks. The aim of this study was to inventory GP sentinel networks involved in epidemiological surveillance on a global scale. Methods GP sentinel surveillance networks were inventoried globally between July 2016 and December 2019. Each identified network was required to fill out an electronic descriptive survey for inclusion. Results A total of 148 networks were identified as potential surveillance networks in general practice and were contacted. Among them, 48 were included in the study. Geographically, 33 networks (68.8%) were located in Europe and 38 (79.2%) had national coverage. The number of GPs registered in these networks represented between 0.1 and 100% of the total number of GPs in the network's country or region, with a median of 2.5%. All networks were involved in continuous epidemiologic surveillance and 47 (97.9%) monitored influenza-like illness. Data collection methods were paper-based forms ( n ~=\,26, 55.3%), electronic forms on a dedicated website ( n ~=\,18, 38.3%), electronic forms on a dedicated software program ( n ~=\,14, 29.8%), and direct extraction from electronic medical records ( n \,=\,14, 29.8%). Along with this study, a website has been created to share all data collected. Conclusions This study represents the first global geographic mapping of GP sentinel surveillance networks. By sharing this information, collaboration between networks will be easier, which can strengthen the quality of international epidemiologic surveillance. In the face of crises like that of COVID-19, this is more imperative than ever before

Phosphorylation status of the Kep1 protein alters its affinity for its protein binding partner alternative splicing factor ASF/SF2

Mutations in the Drosophila kep1 gene, encoding a single maxi KH (K homology) domain-containing RNA-binding protein, result in a reduction of fertility in part due to the disruption of the apoptotic programme during oogenesis. This disruption is concomitant with the appearance of an alternatively spliced mRNA isoform encoding the inactive caspase dredd. We generated a Kep1 antibody and have found that the Kep1 protein is present in the nuclei of both the follicle and nurse cells during all stages of Drosophila oogenesis. We have shown that the Kep1 protein is phosphorylated in ovaries induced to undergo apoptosis following treatment with the topoisomerase I inhibitor camptothecin. We have also found that the Kep1 protein interacts specifically with the SR (serine/arginine-rich) protein family member ASF/SF2 (alternative splicing factor/splicing factor 2). This interaction is independent of the ability of Kep1 to bind RNA, but is dependent on the phosphorylation of the Kep1 protein, with the interaction between Kep1 and ASF/SF2 increasing in the presence of activated Src. Using a CD44v5 alternative splicing reporter construct, we observed 99% inclusion of the alternatively spliced exon 5 following kep1 transfection in a cell line that constitutively expresses activated Src. This modulation in splicing was not observed in the parental NIH 3T3 cell line in which we obtained 7.5% exon 5 inclusion following kep1 transfection. Our data suggest a mechanism of action in which the in vivo phosphorylation status of the Kep1 protein affects its affinity towards its protein binding partners and in turn may allow for the modulation of alternative splice site selection in Kep1–ASF/SF2-dependent target genes