Nievesgustafsson1127

It is critical to identify potential causal targets for SARS-CoV-2, which may guide drug repurposing options. We assessed the associations between genetically predicted protein levels and COVID-19 severity. Leveraging data from the COVID-19 Host Genetics Initiative comparing 6492 hospitalized COVID-19 patients and 1 012 809 controls, we identified 18 proteins with genetically predicted levels to be associated with COVID-19 severity at a false discovery rate of less then 0.05, including 12 that showed an association even after Bonferroni correction. Of the 18 proteins, 6 showed positive associations and 12 showed inverse associations. In conclusion, we identified 18 candidate proteins for COVID-19 severity.

In a biomedical literature search, the link between a query and a document is often not established, because they use different terms to refer to the same concept. Distributional word embeddings are frequently used for detecting related words by computing the cosine similarity between them. However, previous research has not established either the best embedding methods for detecting synonyms among related word pairs or how effective such methods may be.

In this study, we first create the BioSearchSyn set, a manually annotated set of synonyms, to assess and compare 3 widely used word-embedding methods (word2vec, fastText, and GloVe) in their ability to detect synonyms among related pairs of words. We demonstrate the shortcomings of the cosine similarity score between word embeddings for this task the same scores have very different meanings for the different methods. To address the problem, we propose utilizing pool adjacent violators (PAV), an isotonic regression algorithm, to transform a cosine similarie the spring of 2019.Understanding the basic elements of the airway mucosal surfaces and how they form a functional barrier is essential in understanding disease initiation, progression, pathogenesis and ultimately treating chronic lung diseases. Using primary airway epithelial cell cultures, atomic force microscopy (AFM), multiangle light scattering, and quartz crystal micro balance with dissipation monitoring (QCMD) techniques, here we report that the membrane bound mucins (MBMs) found in the periciliary layer (PCL) of the airway surface are densely decorated with keratan sulfate (KS). AFM and immunoblotting show that the KS sidechains can be removed enzymatically with keratanase II (KII) treatment and the antibody accessibility for B2729 (MUC1), MUCH4 (MUC4), OC125 (MUC16) was substantially enhanced. Light scattering analysis confirmed that KII treatment removed ~ 40% of the mass from the mucin fractions. Surface binding experiments indicated that MBMs were able to pack into a tighter conformation following KS removal, suggesting that negatively charged KS sidechains play a role in mucin-mucin repulsion and contribute to "space filling" in the PCL. We also observed that soluble filtrate from the common airway pathogen Pseudomonas aeruginosa is capable of stripping KS from MBMs. Together, our findings indicate that KS glycosylation of MBMs may play an important role in the integrity of the airway mucosal barrier and its compromise in disease.

How does a history of dramatic weight loss linked to bariatric surgery impact IVF outcomes?

Women with a history of bariatric surgery who had undergone IVF had a comparable cumulative live birth rate (CLBR) to non-operated patients of the same BMI after the first IVF cycle.

In the current context of increasing prevalence of obesity in women of reproductive age, weight loss induced by bariatric surgery has been shown to improve spontaneous fertility in obese women. However, little is known on the clinical benefit of bariatric surgery in obese infertile women undergoing IVF.

This exploratory retrospective multicenter cohort study was conducted in 10287 IVF/ICSI cycles performed between 2012 and 2016. We compared the outcome of the first IVF cycle in women with a history of bariatric surgery to two age-matched groups composed of non-operated women matched on the post-operative BMI of cases, and non-operated severely obese women.

The three exposure groups of age-matched women undergoing their first IVF advocate for further discussion on whether bariatric surgery should be proposed in severely obese infertile women before IVF. However, in light of the present results, infertile women with a history of bariatric surgery can be reassured that surgery-induced dramatic weight loss has no significant impact on IVF prognosis.

This work was supported by unrestricted grants from FINOX-Gédéon Richter and FERRING Pharmaceuticals awarded to the ART center of the Clinique Mathilde to fund the data collection and the statistical analysis. Retinoid Receptor agonist There are no conflicts of interest to declare.

NCT02884258.

NCT02884258.We describe methods for assessing heterogeneity of treatment e↵ects over pre-specified subgroups in observational studies, using outcome model-based (g-formula), inverse probability weighting, doubly robust, and matching estimators of subgroup-specific potential outcome means, conditional average treatment e↵ects, and measures of het- erogeneity of treatment e↵ects. We compare the finite-sample performance of di↵erent estimators in simulation studies where we vary the total sample size, the relative fre- quency of each subgroup, the magnitude of treatment e↵ect in each subgroup, and the distribution of baseline covariates, for both continuous and binary outcomes. We find that the estimators' bias and variance vary substantially in finite samples, even when there is no unobserved confounding and no model misspecification. As an illustration, we apply the methods to data from the Coronary Artery Surgery Study to compare the e↵ect of surgery plus medical therapy versus medical therapy alone for chronic coronary artery disease in subgroups defined by previous myocardial infarction or left ventricular ejection fraction.Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are two conditions that frequently impact reciprocally on each other. Patients with HFrEF have an increased risk of stroke, hospitalization and mortality after they develop AF and vice versa, AF causing deterioration of the ejection fraction is also associated to increased mortality. Catheter ablation has emerged as an effective alternative to antiarrhythmic drug treatment to maintain sinus rhythm and some randomized trials have shown a potential benefit in terms of mortality and hospitalization. This review discusses the available evidence regarding catheter ablation treatment in this specific patient group.