Whitemonroe3055
Recent innovations in genetics and imaging are providing the means to reconstruct cell lineages, either by tracking cell divisions using live microscopy, or by deducing the history of cells using molecular recorders. A cell lineage on its own, however, is simply a description of cell divisions as branching events. A major goal of current research is to integrate this description of cell relationships with information about the spatial distribution and identities of the cells those divisions produce. Visualizing, interpreting and exploring these complex data in an intuitive manner requires the development of new tools. Here we present CeLaVi, a web-based visualization tool that allows users to navigate and interact with a representation of cell lineages, whilst simultaneously visualizing the spatial distribution, identities and properties of cells. CeLaVi's principal functions include the ability to explore and manipulate the cell lineage tree; to visualise the spatial distribution of cell clones at different depths of the tree; to colour cells in the 3D viewer based on lineage relationships; to visualise various cell qualities on the 3D viewer (e.g. gene expression, cell type) and to annotate selected cells/clones. All these capabilities are demonstrated with four different example data sets. find more CeLaVi is available at http//www.celavi.pro.Population genetic theory predicts that small effective population sizes (Ne) and restricted gene flow limit the potential for local adaptation. In particular, the probability of evolving similar phenotypes based on shared genetic mechanisms (i.e. parallel evolution), is expected to be reduced. We tested these predictions in a comparative genomic study of two ecologically similar and geographically co-distributed stickleback species (viz. Gasterosteus aculeatus and Pungitius pungitius). We found that P. pungitius harbours less genetic diversity and exhibits higher levels of genetic differentiation and isolation-by-distance than G. aculeatus. Conversely, G. aculeatus exhibits a stronger degree of genetic parallelism across freshwater populations than P. pungitius 2996 vs. 379 SNPs located within 26 vs. nine genomic regions show evidence of selection in multiple freshwater populations of G. aculeatus and P. pungitius, respectively. Most regions involved in parallel evolution in G. aculeatus showed increased levels of divergence, suggestive of selection on ancient haplotypes. In contrast, haplotypes involved in freshwater adaptation in P. pungitius were younger, and often associated with reduced diversity. In accordance with theory, the results suggest that connectivity and genetic drift play crucial roles in determining the levels and geographic distribution of standing genetic variation, providing evidence that population subdivision limits local adaptation and therefore also the likelihood of parallel evolution.Novel tools for in silico design of RNA constructs such as riboregulators are required in order to reduce time and cost to production for the development of diagnostic and therapeutic advances. Here, we present MoiRNAiFold, a versatile and user-friendly tool for de novo synthetic RNA design. MoiRNAiFold is based on Constraint Programming and it includes novel variable types, heuristics and restart strategies for Large Neighborhood Search. Moreover, this software can handle dozens of design constraints and quality measures and improves features for RNA regulation control of gene expression, such as Translation Efficiency calculation. We demonstrate that MoiRNAiFold outperforms any previous software in benchmarking structural RNA puzzles from EteRNA. Importantly, with regard to biologically relevant RNA designs, we focus on RNA riboregulators, demonstrating that the designed RNA sequences are functional both in vitro and in vivo. Overall, we have generated a powerful tool for de novo complex RNA design that we make freely available as a web server (https//moiraibiodesign.com/design/).Momilactone B is a natural product with dual biological activities, including antimicrobial and allelopathic properties, and play a major role in plant chemical defense against competitive plants and pathogens. The pharmacological effects of momilactone B on mammalian cells have also been reported. However, little is known about the molecular and cellular mechanisms underlying its broad bioactivity. In this study, the genetic determinants of momilactone B sensitivity in yeast were explored to gain insight into its mode of action. We screened fission yeast mutants resistant to momilactone B from a pooled culture containing genome-wide gene-overexpressing strains in a drug-hypersensitive genetic background. Overexpression of pmd1, bfr1, pap1, arp9, or SPAC9E9.06c conferred resistance to momilactone B. In addition, a drug-hypersensitive, barcoded deletion library was newly constructed and the genes that imparted altered sensitivity to momilactone B upon deletion were identified. Gene Ontology and fission yeast phenotype ontology enrichment analyses predicted the biological pathways related to the mode of action of momilactone B. The validation of predictions revealed that momilactone B induced abnormal phenotypes such as multiseptated cells and disrupted organization of the microtubule structure. This is the first investigation of the mechanism underlying the antifungal activity of momilactone B against yeast. The results and datasets obtained in this study narrow the possible targets of momilactone B and facilitate further studies regarding its mode of action.A suspected outbreak of influenza A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at a long-term care facility in Los Angeles County was, months later, determined to not involve influenza. To prevent inadvertent transmission of infections, facilities should use highly specific influenza diagnostics and follow Centers for Disease Control and Prevention (CDC) guidelines that specifically address infection control challenges.
Chiral switching, a strategy in which drug manufacturers develop a single-enantiomer formulation of a drug to be substituted for a racemic formulation, allows manufacturers to maintain market exclusivity for drugs losing patent protection, even without demonstrating superior efficacy or safety.
To identify and characterize all randomized clinical trials (RCTs) directly comparing a Food and Drug Administration (FDA)-approved single-enantiomer drug against a previously approved racemic drug for 1 or more efficacy or safety end points.
Drugs were identified using the Drugs@FDA database. Randomized clinical trials were identified using Ovid MEDLINE (1949 to October 22, 2019), Ovid Embase (1974 to October 22, 2019), Web of Science Core Collection (all years), ClinicalTrials.gov, and Cochrane Central Registry of Controlled Trials (CENTRAL, Wiley, Issue 8 of 12, October 22, 2019). Trials were characterized as favoring the single-enantiomer or racemic drugs based on whether the primary efficacy, secondary effic (60.0%), no RCTs were identified providing evidence of improved efficacy, based on primary end point results, or safety as compared with their racemic precursors.
The results of this systematic review suggest that most newly marketed FDA-approved single-enantiomer drugs are infrequently directly compared with their racemic precursors, and when compared, they are uncommonly found to provide improved efficacy or safety, despite their greater costs.
The results of this systematic review suggest that most newly marketed FDA-approved single-enantiomer drugs are infrequently directly compared with their racemic precursors, and when compared, they are uncommonly found to provide improved efficacy or safety, despite their greater costs.
Scaphoid fractures are the most common carpal fracture, but as many as 20% are not visible (ie, occult) in the initial injury radiograph; untreated scaphoid fractures can lead to degenerative wrist arthritis and debilitating pain, detrimentally affecting productivity and quality of life. Occult scaphoid fractures are among the primary causes of scaphoid nonunions, secondary to delayed diagnosis.
To develop and validate a deep convolutional neural network (DCNN) that can reliably detect both apparent and occult scaphoid fractures from radiographic images.
This diagnostic study used a radiographic data set compiled for all patients presenting to Chang Gung Memorial Hospital (Taipei, Taiwan) and Michigan Medicine (Ann Arbor) with possible scaphoid fractures between January 2001 and December 2019. This group was randomly split into training, validation, and test data sets. The images were passed through a detection model to crop around the scaphoid and were then used to train a DCNN model based on the Effic-71.6%) and specificity of 71.6% (95% CI, 69.0%-74.1%) with an AUROC of 0.810 when examining negative cases from the first model. Two-stage examination identified 20 of 22 cases (90.9%) of occult fracture.
In this study, DCNN models were trained to identify scaphoid fractures. This suggests that such models may be able to assist with radiographic detection of occult scaphoid fractures that are not visible to human observers and to reliably detect fractures of other small bones.
In this study, DCNN models were trained to identify scaphoid fractures. This suggests that such models may be able to assist with radiographic detection of occult scaphoid fractures that are not visible to human observers and to reliably detect fractures of other small bones.
The US Food and Drug Administration (FDA) uses 510(k) clearance and premarket approval (PMA) pathways to ensure device safety before marketing. Premarket approval evaluates high-risk medical devices and requires clinical trials, whereas 510(k) clearance evaluates moderate-risk devices and relies on benchtop (nonclinical and biomechanical) and descriptive data. Existing literature suggests that the clinical trials required by PMA are associated with reduced risk of recall compared with devices granted 510(k) clearance. Several investigators have found weaknesses in pivotal PMA trials, raising safety concerns. Furthermore, methodological factors may have led to a previous underestimation of recall risk for devices with PMA.
To compare risk of recall and high-risk recall between devices that received 510(k) clearance and those that received PMA and to compare the risk of recall between devices for medical specialties.
This cohort study compared devices with 510(k) clearance vs those with PMA that reached tg surveillance strategies and pivotal trials may improve device safety.
This study suggests that high-risk medical devices approved via PMA are associated with a greater risk of recall than previously reported. Most recalls are for devices with 510(k) clearance, also raising safety concerns. Strengthening postmarketing surveillance strategies and pivotal trials may improve device safety.
The Choosing Wisely guidelines indicate that preoperative testing is often unnecessary and wasteful for patients undergoing cataract operations. However, little is known about the impact of these widely disseminated guidelines within the US Veterans Health Administration (VHA) system.
To examine the extent, variability, associated factors, and costs of low-value tests (LVTs) prior to cataract operations in the VHA.
This cohort study examined records of all patients receiving cataract operations within the VHA in fiscal year 2017 (October 1, 2016, to September 31, 2017). Records from 135 facilities nationwide supporting both ambulatory and inpatient surgery were included.
A laboratory test occurring within 30 days prior to cataract surgery and within 30 days after clinic evaluation.
Overall national and facility-level rates and associated costs of receiving any of 8 common LVTs in the 30 days prior to cataract surgery. The patient characteristics, procedure type, and facility-level factors associated with receiving at least 1 test, the number of tests received, and receipt of a bundle of 4 tests (complete blood count, basic metabolic profile, chest radiograph, and electrocardiogram).
