Jeffersonbentzen2748

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Error correction is a fundamental preprocessing step in many NGS pipelines, in particular for de novo genome assembly. However, existing error correction methods either suffer from high false positive rates since they break reads into independent k-mers or do not scale efficiently to large amounts of sequencing reads and complex genomes.

We present CARE - an alignment-based scalable error correction algorithm for Illumina data using the concept of minhashing. Minhashing allows for efficient similarity search within large sequencing read collections which enables fast computation of high-quality multiple alignments. Sequencing errors are corrected by detailed inspection of the corresponding alignments. Our performance evaluation shows that CARE generates significantly fewer false positive corrections than state-of-the-art tools (Musket, SGA, BFC, Lighter, Bcool, Karect) while maintaining a competitive number of true positives. When used prior to assembly it can achieve superior de novo assembly results for a number of real datasets. RGD(Arg-Gly-Asp)Peptides CARE is also the first multiple sequence alignment based error corrector that is able to process a human genome Illumina NGS dataset in only 4 hours on a single workstation using GPU acceleration.

CARE is open-source software written in C ++ (CPU version) and in CUDA/C ++ (GPU version). It is licensed under GPLv3 and can be downloaded at https//github.com/fkallen/CARE.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.

The recent emergence of the novel SARS-coronavirus 2 (SARS-CoV-2) and its international spread pose a global health emergency. The spike (S) glycoprotein binds ACE2 and promotes SARS-CoV-2 entry into host cells. The trimeric S protein binds the receptor using the receptor-binding domain (RBD) causing conformational changes in S protein that allow priming by host cell proteases. Unraveling the dynamic structural features used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal novel therapeutic targets. Using structures determined by X-ray crystallography and cryo-EM, we performed structural analysis and atomic comparisons of the different conformational states adopted by the SARS-CoV-2-RBD.

Here, we determined the key structural components induced by the receptor and characterized their intramolecular interactions. We show that κ-helix (polyproline-II) is a predominant structure in the binding interface and in facilitating the conversion to the active form of the S protein. We demonstrate a series of conversions between switch-like κ-helix and β-strand, and conformational variations in a set of short α-helices which affect the hinge region. These conformational changes lead to an alternating pattern in conserved disulfide bond configurations positioned at the hinge, indicating a possible disulfide exchange, an important allosteric switch implicated in viral entry of various viruses, including HIV and murine coronavirus. The structural information presented herein enables to inspect and understand the important dynamic features of SARS-CoV-2-RBD and propose a novel potential therapeutic strategy to block viral entry. Overall, this study provides guidance for the design and optimization of structure-based intervention strategies that target SARS-CoV-2.

We have implemented the proposed methods in an R package freely available at https//github.com/Grantlab/bio3d.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.

The human corticotropin-releasing hormone (CRH) test (hCRHtest) is used to differentiate Cushing disease (CD) from ectopic adrenocorticotropin (ACTH) secretion (EAS), to assess autonomous cortisol secretion by the adrenal glands, and to characterize pseudo-Cushing syndrome (CS) or adrenal insufficiency (AI).

The main outcome measure of this study was to assess the diagnostic accuracy of the hCRHtest.

We measured ACTH and cortisol levels; collected the peak values (peakACTH and peakcortisol), and calculated the percentage increases (∆%ACTH and ∆%cortisol) after an intravenous bolus of 100 μg hCRH.

This cross-sectional study of hCRH tests from 2010 to 2019 took place in a referral university hospital center.

We enrolled 200 patients 86 CD, 15 EAS, 18 adrenal CS, 25 mild adrenal autonomous cortisol secretion, 31 pseudo-CS, and 25 suspected AI.

The hCRHtest was performed mainly for the differential diagnosis of ACTH-dependent CS or adrenal lesions (P = .048). PeakACTH and peakcortisol were higher in CD, and ∆%ACTH and ∆%cortisol were able to differentiate CD from EAS with a sensitivity and specificity greater than 80%. In patients with low (< 10 pg/mL) or indeterminate (10-20 pg/mL) basalACTH levels, an absent or reduced peakACTH response was able to differentiate adrenal from ACTH-dependent forms. PeakACTH and peakcortisol after hCRHtest were lower in pseudo-CS than in CD, but ∆%ACTH and ∆%cortisol were similar. The role of hCRHtest in patients with AI was limited.

The hCRHtest test is the mainstay of the differential diagnosis of ACTH-dependent CS. It is also useful for pointing to a diagnosis of CD in the event of bilateral adrenal masses, and in patients with low basalACTH.

The hCRHtest test is the mainstay of the differential diagnosis of ACTH-dependent CS. It is also useful for pointing to a diagnosis of CD in the event of bilateral adrenal masses, and in patients with low basalACTH.

Prevention of surgical site infection (SSI) is a public health challenge. Our objective was to determine if pNPWT allows preventing SSI after laparotomy.

MEDLINE, Embase and Web of Science were searched on the 06.10.2019 for original studies reporting the incidences of SSI in patients undergoing open abdominal surgery with and without pNPWT. Risk difference (RD) between control and pNPWT patients and risk ratios (RR) for SSI were obtained using random effects models.

Twenty-one studies (2'930 patients, five RCT, 16 observational studies) were retained for the analysis. Pooled RD between patients with and without pNPWT was -12% (95%CI -17% to -8%, I2 54%, p&0.00001) in favor of pNPWT. That risk difference was -12% (95% CI -22 to -1%, I2 69%, p=0.03) when pooling only RCT (792 patients). pNPWT was protective against the incidence of SSI with a RR of 0.53 (95%CI 0.40-0.71, I 2 56%, p&0.0001). The effect on pNPWT was more prononced in studies with an incidence of SSI≥20% in the control arm. The preventive effect of pNPWT on SSI remained after correction for potential publication bias.