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Macrophages play prominent roles in bacteria recognition and clearance, including Borrelia burgdorferi (Bb), the Lyme disease spirochete. To elucidate mechanisms by which MyD88/TLR signaling enhances clearance of Bb by macrophages, we studied wildtype (WT) and MyD88
Bb-stimulated bone marrow-derived macrophages (BMDMs).
MyD88
BMDMs exhibit impaired uptake of spirochetes but comparable maturation of phagosomes following internalization of spirochetes. RNA-sequencing of infected WT and MyD88
BMDMs identified a large cohort of differentially expressed MyD88-dependent genes associated with re-organization of actin and cytoskeleton during phagocytosis along with several MyD88-independent chemokines involved in inflammatory cell recruitment. We computationally generated networks which identified several MyD88-dependent intermediate proteins (Rhoq and Cyfip1) that are known to mediate inflammation and phagocytosis respectively.
Our findings show that MyD88 signaling enhances, but is not required, for bacterial uptake or phagosomal maturation and provide mechanistic insights into how MyD88-mediated phagosomal signaling enhances Bb uptake and clearance.
Our findings show that MyD88 signaling enhances, but is not required, for bacterial uptake or phagosomal maturation and provide mechanistic insights into how MyD88-mediated phagosomal signaling enhances Bb uptake and clearance.
Colocalization is a statistical method used in genetics to determine whether the same variant is causal for multiple phenotypes, for example, complex traits and gene expression. It provides stronger mechanistic evidence than shared significance, which can be produced through separate causal variants in linkage disequilibrium. Current colocalization methods require full summary statistics for both traits, limiting their use with the majority of reported GWAS associations (e.g. GWAS Catalog). We propose a new approximation to the popular coloc method that can be applied when limited summary statistics are available. Our method (POint EstiMation of Colocalization, POEMColoc) imputes missing summary statistics for one or both traits using LD structure in a reference panel, and performs colocalization using the imputed summary statistics.
We evaluate the performance of POEMColoc using real (UK Biobank phenotypes and GTEx eQTL) and simulated datasets. We show good correlation between posterior probabilities of nt to disease etiology and for matches to approved drug mechanisms. POEMColoc R package is available at https//github.com/AbbVie-ComputationalGenomics/POEMColoc .
We find that colocalization analysis performed with full summary statistics can be closely approximated when only the summary statistics of the top SNP are available for one or both traits. When applied to the full GWAS Catalog and GTEx eQTL, we find that colocalized trait-gene pairs are enriched in tissues relevant to disease etiology and for matches to approved drug mechanisms. click here POEMColoc R package is available at https//github.com/AbbVie-ComputationalGenomics/POEMColoc .
Detection of copy number variations (CNVs) from high-throughput next-generation whole-genome sequencing (WGS) data has become a widely used research method during the recent years. However, only a little is known about the applicability of the developed algorithms to ultra-low-coverage (0.0005-0.8×) data that is used in various research and clinical applications, such as digital karyotyping and single-cell CNV detection.
Here, the performance of six popular read-depth based CNV detection algorithms (BIC-seq2, Canvas, CNVnator, FREEC, HMMcopy, and QDNAseq) was studied using ultra-low-coverage WGS data. Real-world array- and karyotyping kit-based validation were used as a benchmark in the evaluation. Additionally, ultra-low-coverage WGS data was simulated to investigate the ability of the algorithms to identify CNVs in the sex chromosomes and the theoretical minimum coverage at which these tools can accurately function. Our results suggest that while all the methods were able to detect large CNVs, many methze ultra-low-coverage CNV detection.
For successful lighted stylet intubation, bending the lighted stylet with an appropriate angle is a prerequisite. The purpose of this study was to compare three different bend angles of 70, 80, and 90 degrees for lighted stylet intubation.
The patient trachea was intubated with a lighted stylet bent at 70, 80, or 90 degrees according to the randomly allocated groups (group I, II, and III, respectively). A lighted stylet combined with a tracheal tube was prepared with a bend angle of 70, 80, or 90 degrees according to the assigned group. We checked the success rate at the first attempt and overall success rate for the two attempts. Additionally, we measured search time, which was time from insertion of the bent union into the patient mouth to the start of advancing the tracheal tube while separating it from the lighted stylet, and evaluated postoperative sore throat (POST) at 2, 4, and 24h after the recovery from anesthesia.
There was no statistically significant difference between group I, II, and III fnd 90 degrees.
ClinicalTrials.gov Identifier NCT03693235 , registered on 30 September 2018.
ClinicalTrials.gov Identifier NCT03693235 , registered on 30 September 2018.
Preoperative anxiety is prevalent and has harmful effects on postoperative outcomes. However, to date, it is still unclear (i) to what extent patients perceive preoperative anxiety as emotionally distressful, (ii) whether patients would welcome support from anesthesiologists in coping with their anxiety, and (iii) whether anxiety scores are useful for everyday clinical practice to determine patients' need for support.
1082 patients scheduled to undergo elective procedures under general anesthesia were eligible for this cross-sectional study carried out at a university hospital. Preoperative anxiety, resulting in emotional distress, and patients' desire for anesthesiologists' support in coping with their anxiety were assessed dichotomously (no vs. yes) and analyzed descriptively. The intensity of anxiety was evaluated using the Amsterdam Preoperative Anxiety and Information Scale (range 4-20). Associations between the intensity of anxiety and the resulting desire for support were analyzed using logistic regression.