Toxoplasma gondii seropositivity and risk factors in pregnant women followed up by the Family Health Strategy

INTRODUCTION : Toxoplasmosis is a zoonotic infection caused by Toxoplasma gondii. It is transmitted by the ingestion of contaminated water and foods, by soil contaminated with cat feces, especially while handling it, and congenitally via the placenta. The diagnosis of maternal infection is made by serological detection of either IgM or IgG antibodies. This study assessed the seropositivity in pregnant women followed up by the Family Health Strategy (FHS) in Lages, Santa Catarina, Brazil. METHODS: The study was performed in 19 FHS units and included 148 childbearing women. The outcomes evaluated were IgM and IgG seropositivity and behavioral variables. RESULTS: IgG yielded positive results in 16% of the pregnant women, whereas IgM was positive in only 1%. CONCLUSIONS: The 1% IgM positivity rate for T. gondii indicates congenital toxoplasmosis is not common in Lages

Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program

Whole-genome sequencing (WGS), a powerful tool for detecting novel coding and non-coding disease-causing variants, has largely been applied to clinical diagnosis of inherited disorders. Here we leveraged WGS data in up to 62,653 ethnically diverse participants from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and assessed statistical association of variants with seven red blood cell (RBC) quantitative traits. We discovered 14 single variant-RBC trait associations at 12 genomic loci, which have not been reported previously. Several of the RBC trait-variant associations (RPN1, ELL2, MIDN, HBB, HBA1, PIEZO1, and G6PD) were replicated in independent GWAS datasets imputed to the TOPMed reference panel. Most of these discovered variants are rare/low frequency, and several are observed disproportionately among non-European Ancestry (African, Hispanic/Latino, or East Asian) populations. We identified a 3 bp indel p.Lys2169del (g.88717175_88717177TCT[4]) (common only in the Ashkenazi Jewish population) of PIEZO1, a gene responsible for the Mendelian red cell disorder hereditary xerocytosis (MIM: 194380), associated with higher mean corpuscular hemoglobin concentration (MCHC). In stepwise conditional analysis and in gene-based rare variant aggregated association analysis, we identified several of the variants in HBB, HBA1, TMPRSS6, and G6PD that represent the carrier state for known coding, promoter, or splice site loss-of-function variants that cause inherited RBC disorders. Finally, we applied base and nuclease editing to demonstrate that the sentinel variant rs112097551 (nearest gene RPN1) acts through a cis-regulatory element that exerts long-range control of the gene RUVBL1 which is essential for hematopoiesis. Together, these results demonstrate the utility of WGS in ethnically diverse population-based samples and gene editing for expanding knowledge of the genetic architecture of quantitative hematologic traits and suggest a continuum between complex trait and Mendelian red cell disorders

Isabelle/DOF. User and Implementation Manual (2024)

This is the final version. Available from AFP via the link in this recordThis manual describes Isabelle/DOF as available in the Archive of Formal Proofs (AFP). The latest development version as well as releases that can be installed as Isabelle component are available at https://git.logicalhacking.com/Isabelle_DOF/Isabelle_DOF/. Isabelle/DOF provides an implementation of a document ontology framework on top of Isabelle/HOL. The framework allows both for defining ontologies and enforcing them during document development and document evolution. Isabelle/DOF targets use-cases such as mathematical texts referring to a theory development or technical reports requiring a particular structure. The documentation generation features are sufficiently powerful to typeset the most common cases without using LaTeX. Isabelle/DOF is integrated into Isabelle’s IDE, which allows for smooth ontology development as well as immediate ontological conformance-checks during the editing of a document. Its checking facilities leverage the collaborative development of documents required to be consistent with an underlying ontological structure. This entry provides a user-manual with in-depth presentation of the design concepts of Isabelle/DOF’s Ontology Definition Language (ODL) and describe comprehensively its major commands. Many examples show typical best-practice applications of the system.IRT SystemX, Paris-Saclay, Franc

Using Deep Ontologies in Formal Software Engineering

This is the author accepted manuscript. The final version is available from Springer via the DOI on this recordIsabelle/DOF is an ontology framework on top of Isabelle. It allows for the formal development of ontologies as well as continuous conformity-checking of integrated documents annotated by ontological data. An integrated document may contain text, code, definitions, proofs, and user-programmed constructs supporting a wide range of formal methods. Isabelle/DOF is designed to leverage traceability in inte- grated documents by supporting navigation in Isabelle’s IDE as well as the document generation process. In this paper, we extend Isabelle/DOF with annotations of λ-terms, a pervasive data-structure underlying Isabelle used to syntactically represent expressions and formulas. Rather than introducing an own pro- gramming language for meta-data, we use Higher-order Logic (HOL) for expressions, data-constraints, ontological invariants, and queries via code-generation and reflection. This allows both for powerful query languages and logical reasoning over ontologies in, for example, ontological mappings. Our application examples cover documents targeting formal certifications such as CENELEC 50128 or Common Criteria

Sweep gas membrane distillation using stainless-steel hollow-fibers: from material to process

International audienc