Johnstonodom0659

Systematic review of literature following release of the 2013 guideline reaffirms the use of a validation set of at least 60 cases, establishing intraobserver diagnostic concordance between WSI and glass slides and the use of a 2-week washout period between modalities. Although all discordances between WSI and glass slide diagnoses discovered during validation need to be reconciled, laboratories should be particularly concerned if their overall WSI-glass slide concordance is less than 95%.

Systematic review of literature following release of the 2013 guideline reaffirms the use of a validation set of at least 60 cases, establishing intraobserver diagnostic concordance between WSI and glass slides and the use of a 2-week washout period between modalities. Although all discordances between WSI and glass slide diagnoses discovered during validation need to be reconciled, laboratories should be particularly concerned if their overall WSI-glass slide concordance is less than 95%.Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients with other subtypes of AML. However, ∼40% of patients relapse, and the literature suggests that patients with inv(16) fare differently from those with t(8;21). We retrospectively analyzed 537 patients with CBF-AML, focusing on additional cytogenetic aberrations to examine their impact on clinical outcomes. Trisomies of chromosomes 8, 21, or 22 were significantly more common in patients with inv(16)/t(16;16) 16% vs 7%, 6% vs 0%, and 17% vs 0%, respectively. In contrast, del(9q) and loss of a sex chromosome were more frequent in patients with t(8;21) 15% vs 0.4% for del(9q), 37% vs 0% for loss of X in females, and 44% vs 5% for loss of Y in males. Hyperdiploidy was more frequent in patients with inv(16) (25% vs 9%, whereas hypodiploidy was more frequent in patients with t(8;21) (37% vs 3%. In multivariable analyses (adjusted for age, white blood counts at diagnosis, and KIT mutation status), trisomy 8 was associated with improved overall survival (OS) in inv(16), whereas the presence of other chromosomal abnormalities (not trisomy 8) was associated with decreased OS. In patients with t(8;21), hypodiploidy was associated with improved disease-free survival; hyperdiploidy and del(9q) were associated with improved OS. KIT mutation (either positive or not tested, compared with negative) conferred poor prognoses in univariate analysis only in patients with t(8;21).

In the kidney glucose is freely filtered by the glomerulus and, mainly, reabsorbed by sodium glucose cotransporter 2 (SGLT2) expressed in the early proximal tubule. Human proximal tubule epithelial cells (PTECs) undergo pathological and fibrotic changes seen in diabetic kidney disease (DKD) in response to elevated glucose. We developed a specific in vitro model of DKD using primary human PTECs with exposure to high D-glucose and TGF-β1 and propose a role for SGLT2 inhibition in regulating fibrosis.

Western blotting was performed to detect cellular and secreted proteins as well as phosphorylated intracellular signalling proteins. qPCR was used to detect CCN2 RNA. Gamma glutamyl transferase (GT) activity staining was performed to confirm PTEC phenotype. SGLT2 and ERK inhibition on high D-glucose, 25 mM, and TGF-β1, 0.75 ng/ml, treated cells was explored using dapagliflozin and U0126, respectively.

Only the combination of high D-glucose and TGF-β1 treatment significantly up-regulated CCN2 RNA and protein elation. Both outcomes were inhibited by dapagliflozin. We have identified a novel SGLT2 -ERK mediated promotion of TGF-β1/Smad3 signalling inducing a pro-fibrotic growth factor secretion. Our data evince support for substantial renoprotective benefits of SGLT2 inhibition in the diabetic kidney.Sus scrofa or pig was domesticated thousands of years ago. Through various indigenous breeds, different phenotypes were produced such as Chinese inbred miniature minipig or Wuzhishan pig (WZSP), which is broadly used in the life and medical sciences. The whole genome of WZSP was sequenced in 2012. Through a bioinformatics study of pig carbonic anhydrase (CA) sequences, we detected some β- and γ-class CAs among the WZSP CAs annotated in databases, while β- or γ-CAs had not previously been described in vertebrates. This finding urged us to analyze the quality of whole genome sequence of WZSP for the possible bacterial contamination. In this study, we used bioinformatics methods and web tools such as UniProt, European Bioinformatics Institute, National Center for Biotechnology Information, Ensembl Genome Browser, Ensembl Bacteria, RSCB PDB and Pseudomonas Genome Database. Our analysis defined that pig has 12 classical α-CAs and 3 CA-related proteins. Meanwhile, it was approved that the detected CAs in WZSP are categorized in the β- and γ-CA families, which belong to Pseudomonas spp. and Acinetobacter spp. The protein structure study revealed that the identified β-CA sequence from WZSP belongs to Pseudomonas aeruginosa with PDB ID 5JJ8, and the identified γ-CA sequence from WZSP belongs to P. aeruginosa with PDB ID 3PMO. Bioinformatics and computational methods accompanied with bacterial-specific markers, such as 16S rRNA and β- and γ-class CA sequences, can be used to identify bacterial contamination in mammalian DNA samples.Over the past couple of decades, the explosion of densely interconnected data has stimulated the research, development and adoption of graph database technologies. From early graph models to more recent native graph databases, the landscape of implementations has evolved to cover enterprise-ready requirements. Because of the interconnected nature of its data, the biomedical domain has been one of the early adopters of graph databases, enabling more natural representation models and better data integration workflows, exploration and analysis facilities. In this work, we survey the literature to explore the evolution, performance and how the most recent graph database solutions are applied in the biomedical domain, compiling a great variety of use cases. With this evidence, we conclude that the available graph database management systems are fit to support data-intensive, integrative applications, targeted at both basic research and exploratory tasks closer to the clinic.Hypoxia is a feature of most solid tumours and predicts for poor prognosis. Vorapaxar nmr In radiobiological hypoxia ( less then 0.1% O2) cells become up to three times more resistant to radiation. The biological response to radiobiological hypoxia is one of few physiologically relevant stresses that activates both the unfolded protein and DNA damage responses (UPR and DDR). Links between these pathways have been identified in studies carried out in normoxia. Based in part on these previous studies and recent work from our laboratory, we hypothesised that the biological response to hypoxia likely includes overlap between the DDR and UPR. While inhibition of the DDR is a recognised strategy for improving radiation response, the possibility of achieving this through targeting the UPR has not been realised. We carried out a systematic review to identify links between the DDR and UPR, in human cell lines exposed to less then 2% O2. Following PRISMA guidance, literature from January 2010 to October 2020 were retrieved via Ovid MEDLINE and evaluated. A total of 202 studies were included. LAMP3, ULK1, TRIB3, CHOP, NOXA, NORAD, SIAH1/2, DYRK2, HIPK2, CREB, NUPR1, JMJD2B, NRF2, GSK-3B, GADD45a, GADD45b, STAU1, C-SRC, HK2, CAV1, CypB, CLU, IGFBP-3 and SP1 were highlighted as potential links between the hypoxic DDR and UPR. Overall, we identified very few studies which demonstrate a molecular link between the DDR and UPR in hypoxia, however, it is clear that many of the molecules highlighted warrant further investigation under radiobiological hypoxia as these may include novel therapeutic targets to improve radiotherapy response.Interferon (IFN)-induced guanosine triphosphate hydrolysing enzymes (GTPases) have been identified as cornerstones of IFN-mediated cell-autonomous defence. Upon IFN stimulation, these GTPases are highly expressed in various host cells, where they orchestrate anti-microbial activities against a diverse range of pathogens such as bacteria, protozoan and viruses. IFN-induced GTPases have been shown to interact with various host pathways and proteins mediating pathogen control via inflammasome activation, destabilising pathogen compartments and membranes, orchestrating destruction via autophagy and the production of reactive oxygen species as well as inhibiting pathogen mobility. In this mini-review, we provide an update on how the IFN-induced GTPases target pathogens and mediate host defence, emphasising findings on protection against bacterial pathogens.Adults use distributed cues in the bodies of others to predict and counter their actions. To investigate the development of this ability, we had adults and 6- to 8-year-old children play a competitive game with a confederate who reached toward one of two targets. Child and adult participants, who sat across from the confederate, attempted to beat the confederate to the target by touching it before the confederate did. Adults used cues distributed through the head, shoulders, torso, and arms to predict the reaching actions. Children, in contrast, used cues in the arms and torso, but we did not find any evidence that they could use cues in the head or shoulders to predict the actions. These results provide evidence for a change in the ability to respond rapidly to predictive cues to others' actions from childhood to adulthood. Despite humans' sensitivity to action goals even in infancy, the ability to read cues from the body for action prediction in rapid interactive settings is still developing in children as old as 6 to 8 years of age.Across saccades, perceptual detectability of brief visual stimuli is strongly diminished. We recently observed that this perceptual suppression phenomenon is jumpstarted in the retina, suggesting that the phenomenon might be significantly more visual in nature than normally acknowledged. Here, we explicitly compared saccadic suppression strength when saccades were made across a uniform image of constant luminance versus when saccades were made across image patches of different luminance, width, and trans-saccadic luminance polarity. We measured perceptual contrast thresholds of human subjects for brief peri-saccadic flashes of positive (luminance increments) or negative (luminance decrements) polarity. Thresholds were >6-7 times higher when saccades translated a luminance stripe or edge across the retina than when saccades were made over a completely uniform image patch. Critically, both background luminance and flash luminance polarity strongly modulated peri-saccadic contrast thresholds. In addition, all of these very same visual dependencies also occurred in the absence of any saccades, but with qualitatively similar rapid translations of image patches across the retina. This similarity of visual dependencies with and without saccades supports the notion that perceptual saccadic suppression may be fundamentally a visual phenomenon, which strongly motivates neurophysiological and theoretical investigations on the role of saccadic eye movement commands in modulating its properties.