Harmonization and standardization of data for a pan-European cohort on SARS- CoV-2 pandemic

The European project ORCHESTRA intends to create a new pan-European cohort to rapidly advance the knowledge of the effects and treatment of COVID-19. Establishing processes that facilitate the merging of heterogeneous clusters of retrospective data was an essential challenge. In addition, data from new ORCHESTRA prospective studies have to be compatible with earlier collected information to be efficiently combined. In this article, we describe how we utilized and contributed to existing standard terminologies to create consistent semantic representation of over 2500 COVID-19-related variables taken from three ORCHESTRA studies. The goal is to enable the semantic interoperability of data within the existing project studies and to create a common basis of standardized elements available for the design of new COVID-19 studies. We also identified 743 variables that were commonly used in two of the three prospective ORCHESTRA studies and can therefore be directly combined for analysis purposes. Additionally, we actively contributed to global interoperability by submitting new concept requests to the terminology Standards Development Organizations

How European Research Projects Can Support Vaccination Strategies: The Case of the ORCHESTRA Project for SARS-CoV-2

ORCHESTRA (“Connecting European Cohorts to Increase Common and Effective Response To SARS-CoV-2 Pandemic”) is an EU-funded project which aims to help rapidly advance the knowledge related to the prevention of the SARS-CoV-2 infection and the management of COVID-19 and its long-term sequelae. Here, we describe the early results of this project, focusing on the strengths of multiple, international, historical and prospective cohort studies and highlighting those results which are of potential relevance for vaccination strategies, such as the necessity of a vaccine booster dose after a primary vaccination course in hematologic cancer patients and in solid organ transplant recipients to elicit a higher antibody titer, and the protective effect of vaccination on severe COVID-19 clinical manifestation and on the emergence of post-COVID-19 conditions. Valuable data regarding epidemiological variations, risk factors of SARS-CoV-2 infection and its sequelae, and vaccination efficacy in different subpopulations can support further defining public health vaccination policies

Thermohaline Mixing and its Role in the Evolution of Carbon and Nitrogen Abundances in Globular Cluster Red Giants: The Test Case of Messier 3

We review the observational evidence for extra mixing in stars on the red giant branch (RGB) and discuss why thermohaline mixing is a strong candidate mechanism. We recall the simple phenomenological description of thermohaline mixing, and aspects of mixing in stars in general. We use observations of M3 to constrain the form of the thermohaline diffusion coefficient and any associated free parameters. This is done by matching [C/Fe] and [N/Fe] along the RGB of M3. After taking into account a presumed initial primordial bimodality of [C/Fe] in the CN-weak and CN-strong stars our thermohaline mixing models can explain the full spread of [C/Fe]. Thermohaline mixing can produce a significant change in [N/Fe] as a function of absolute magnitude on the RGB for initially CN-weak stars, but not for initially CN-strong stars, which have so much nitrogen to begin with that any extra mixing does not significantly affect the surface nitrogen composition.Comment: 33 Pages, 10 Figures. Accepted for publication in The Astrophysical Journa

Creation of a structured molecular genomics report for Germany as a local adaption of HL7's Genomic Reporting Implementation Guide

OBJECTIVE:The objective w:as to develop a dataset definition, information model, and FHIR® specification for key data elements contained in a German molecular genomics (MolGen) report to facilitate genomic and phenotype integration in electronic health records. MATERIALS AND METHODS: A dedicated expert group participating in the German Medical Informatics Initiative reviewed information contained in MolGen reports, determined the key elements, and formulated a dataset definition. HL7’s Genomics Reporting Implementation Guide (IG) was adopted as a basis for the FHIR® specification which was subjected to a public ballot. In addition, elements in the MolGen dataset were mapped to the fields defined in ISO/TS 20428:2017 standard to evaluate compliance. RESULTS: A core dataset of 76 data elements, clustered into 6 categories was created to represent all key information of German MolGen reports. Based on this, a FHIR specification with 16 profiles, 14 derived from HL7®’s Genomics Reporting IG and 2 additional profiles (of the FamilyMemberHistory and RiskAssessment resources), was developed. Five example resource bundles show how our adaptation of an international standard can be used to model MolGen report data that was requested following oncological or rare disease indications. Furthermore, the map of the MolGen report data elements to the fields defined by the ISO/TC 20428:2017 standard, confirmed the presence of the majority of required fields. CONCLUSIONS: Our report serves as a template for other research initiatives attempting to create a standard format for unstructured genomic report data. Use of standard formats facilitates integration of genomic data into electronic health records for clinical decision support

Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer

Two subtypes of thrombospondin (TSP-1 and TSP-2) have inhibitory roles in angiogenesis in vitro, although the biological significance of these TSP isoforms has not been determined in vivo. We examined TSP-1 and TSP-2 gene expression by reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. Thirty-eight of these 61 colon cancers were positive for TSP-2 expression and showed hepatic metastasis at a significantly lower incidence than those without TSP-2 expression (P = 0.02). TSP-2 expression was significantly associated with M0 stage in these colon cancers (P = 0.03), whereas TSP-1 expression showed no apparent correlation with these factors. The colon cancer patients with TSP-2 expression showed a significantly low frequency of liver metastasis correlated with the cell-associated isoform of vascular endothelial growth factor (VEGF-189) (P = 0.0006). Vascularity was estimated by CD34 staining, and TSP-2(–)/VEGF-189(+) colon cancers showed significantly increased vessel counts and density in the stroma (P < 0.0001). TSP-2(–)/VEGF-189(+) colon cancer patients also showed significantly poorer prognosis compared with those with TSP-2(+) / VEGF-189(–) (P = 0.0014). These results suggest that colon cancer metastasis is critically determined by angiogenesis resulting from the balance between the angioinhibitory factor TSP-2 and angiogenic factor VEGF-189. © 1999 Cancer Research Campaig

Human plague: An old scourge that needs new answers

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague’s resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a “One Health” approach

A comparison of no-slip, stress-free and inviscid models of rapidly rotating fluid in a spherical shell

We investigate how the choice of either no-slip or stress-free boundary conditions affects numerical models of rapidly rotating flow in Earth's core by computing solutions of the weakly-viscous magnetostrophic equations within a spherical shell, driven by a prescribed body force. For non-axisymmetric solutions, we show that models with either choice of boundary condition have thin boundary layers of depth E^(1/2), where E is the Ekman number, and a free-stream flow that converges to the formally inviscid solution. At Earth-like values of viscosity, the boundary layer thickness is approximately 1m, for either choice of condition. In contrast, the axisymmetric flows depend crucially on the choice of boundary condition, in both their structure and magnitude (either E^(-1/2) or E^(-1)). These very large zonal flows arise from requiring viscosity to balance residual axisymmetric torques. We demonstrate that switching the mechanical boundary conditions can cause a distinct change of structure of the flow, including a sign-change close to the equator, even at asymptotically low viscosity. Thus implementation of stress-free boundary conditions, compared with no-slip conditions, may yield qualitatively different dynamics in weakly-viscous magnetostrophic models of Earth's core. We further show that convergence of the free-stream flow to its asymptotic structure requires E ≤10^(-5)