No evidence for WU polyomavirus infection in chronic obstructive pulmonary disease

Human polyomaviruses are known to cause persistent or latent infections, which are reactivated under immunosuppression. Polyomaviruses have been found to immortalize cell lines and to possess oncogenic properties. Moreover, the recently discovered Merkel cell polyomavirus shows a strong association with human Merkel cell carcinomas. Another novel human polyomavirus, WU polyomavirus (WUPyV), has been identified in respiratory specimens from patients with acute respiratory tract infections (ARTI). WUPyV has been proposed to be a pathogen in ARTI in early life and immunocompromised individuals, but so far its role as a causative agent of respiratory disease remains controversial

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe

DIE SCHOPFUNG - (LA CREATION) Oratorio en 2 parties / J. HAYDN ; Irmgard SEEFRIED (soprano) - Richard HOLM (tenor) ; Kim BORG (basse) ; Igor MARKEVITCH, clavecin ; Choeur de la Cathedrale STE-EDWIGE ; ORCHESTRE PHILHARMONIQUE DE BERLIN ; Dir. Igoe MARKEVITCH

Titre uniforme : [Die Schöpfung. Hob XXI 2]. IntégraleBnF-Partenariats, Collection sonore - BelieveContient une table des matière

Increased IgE-antibodies to Staphylococcus aureus enterotoxins in patients with COPD

AbstractRecent evidence suggests that Staphylococcus aureus enterotoxins (SAEs) could modify airway disease by acting as superantigens, an immune response that can be monitored by detection of IgE antibodies to SAEs. We studied the expression of total IgE and specific IgE to SAEs using the Uni-CAP system in healthy controls, smokers without COPD and COPD patients. Only 1/10 controls (10%) and 1/16 smokers (6.3%) had IgE to SAEs compared to 7/18 patients with stable COPD (38.9%) and 21/54 patients with exacerbated COPD (38.9%). The IgE levels to SAEs of the patients with stable COPD (0.18 [0.05–26.2]kUA/l) and the patients with exacerbated COPD (0.09 [0.05–18.6]kUA/l) were significantly higher than those of smokers (n=16; 0.05 [0.05–0.82]kUA/l) and controls (n=11; 0.05 [0.05–0.9]kUA/l, P<0.05). IgE to SAEs decreased significantly in the exacerbated patients during hospitalization (0.13 [0.05–18.3] vs. 0.05 [0.05–11]kUA/l, P<0.001) going along with a significant increase in FEV1 (38.1 [16.9–79.5] vs. 51.6 [15–80]%predicted, P<0.001).Similarly to severe asthma, we found significantly elevated IgE to SAE in COPD patients. Our data for the first time suggest differences between healthy subjects, smokers and patients with established COPD regarding the role of bacterial products and point to a possible disease modifying role of SAEs