Notes

Flourish intervention development: making use of participatory action research rules to compliment a new mHealth app-based input to improve oncology attention.
We applied the initial model and updated model to a testing set of 427 WSIs (374 benign, 53 with carcinoma) which showed AUC values of 0.900 and 0.927, respectively. Using the pixel classification threshold selected from the validation set, the model achieved a sensitivity of 92% and specificity of 78%. The four false-negative classifications resulted from two small foci of DCIS (1 mm, 0.5 mm) and two foci of well-differentiated invasive carcinoma (3 mm, 1.5 mm). This proof-of-principle study demonstrates that a DMMN machine learning model can segment invasive carcinoma and DCIS in surgical margin specimens with high accuracy and has the potential to be used as a screening tool for pathologic assessment of these specimens.Membrane-bound extracellular vesicles (EVs), secreted by cells from all three domains of life, transport various molecules and act as agents of intercellular communication in diverse environments. Here we demonstrate that EVs produced by a hyperthermophilic and acidophilic archaeon Sulfolobus islandicus carry not only a diverse proteome, enriched in membrane proteins, but also chromosomal and plasmid DNA, and can transfer this DNA to recipient cells. Furthermore, we show that EVs can support the heterotrophic growth of Sulfolobus in minimal medium, implicating EVs in carbon and nitrogen fluxes in extreme environments. Finally, our results indicate that, similar to eukaryotes, production of EVs in S. islandicus depends on the archaeal ESCRT machinery. We find that all components of the ESCRT apparatus are encapsidated into EVs. Using synchronized S. check details islandicus cultures, we show that EV production is linked to cell division and appears to be triggered by increased expression of ESCRT proteins during this cell cycle phase. Using a CRISPR-based knockdown system, we show that archaeal ESCRT-III and AAA+ ATPase Vps4 are required for EV production, whereas archaea-specific component CdvA appears to be dispensable. In particular, the active EV production appears to coincide with the expression patterns of ESCRT-III-1 and ESCRT-III-2, rather than ESCRT-III, suggesting a prime role of these proteins in EV budding. Collectively, our results suggest that ESCRT-mediated EV biogenesis has deep evolutionary roots, likely predating the divergence of eukaryotes and archaea, and that EVs play an important role in horizontal gene transfer and nutrient cycling in extreme environments.Whole slide images (WSIs) pose unique challenges when training deep learning models. They are very large which makes it necessary to break each image down into smaller patches for analysis, image features have to be extracted at multiple scales in order to capture both detail and context, and extreme class imbalances may exist. Significant progress has been made in the analysis of these images, thanks largely due to the availability of public annotated datasets. We postulate, however, that even if a method scores well on a challenge task, this success may not translate to good performance in a more clinically relevant workflow. Many datasets consist of image patches which may suffer from data curation bias; other datasets are only labelled at the whole slide level and the lack of annotations across an image may mask erroneous local predictions so long as the final decision is correct. In this paper, we outline the differences between patch or slide-level classification versus methods that need to localize or WSI classification tasks. Furthermore, we find applying extensive augmentations helps more in WSI-based tasks compared to patch-level image classification.Transmission routes impact pathogen virulence and genetics, therefore comprehensive knowledge of these routes and their contribution to pathogen circulation is essential for understanding host-pathogen interactions and designing control strategies. Deformed wing virus (DWV), a principal viral pathogen of honey bees associated with increased honey bee mortality and colony losses, became highly virulent with the spread of its vector, the ectoparasitic mite Varroa destructor. Reproduction of Varroa mites occurs in capped brood cells and mite-infested pupae from these cells usually have high levels of DWV. The removal of mite-infested pupae by worker bees, Varroa Sensitive Hygiene (VSH), leads to cannibalization of pupae with high DWV loads, thereby offering an alternative route for virus transmission. We used genetically tagged DWV to investigate virus transmission to and between worker bees following pupal cannibalisation under experimental conditions. We demonstrated that cannibalization of DWV-infected pupae resulted in high levels of this virus in worker bees and that the acquired virus was then transmitted between bees via trophallaxis, allowing circulation of Varroa-vectored DWV variants without the mites. Despite the known benefits of hygienic behaviour, it is possible that higher levels of VSH activity may result in increased transmission of DWV via cannibalism and trophallaxis.
Ghrelin is an orexigenic hormone that increases food intake, adiposity, and insulin resistance through its receptor Growth Hormone Secretagogue Receptor (GHS-R). We previously showed that ghrelin/GHS-R signaling has important roles in regulation of energy homeostasis, and global deletion of GHS-R reduces obesity and improves insulin sensitivity by increasing thermogenesis. However, it is unknown whether GHS-R regulates thermogenic activation in adipose tissues directly.

We generated a novel adipose tissue-specific GHS-R deletion mouse model and characterized the mice under regular diet (RD) and high-fat diet (HFD) feeding. Body composition was measured by Echo MRI. Metabolic profiling was determined by indirect calorimetry. Response to environmental stress was assessed using a TH-8 temperature monitoring system. Insulin sensitivity was evaluated by glucose and insulin tolerance tests. Tissue histology was analyzed by hematoxylin/eosin and immunofluorescent staining. Expression of genes involved in thermogic target for treatment of obesity and metabolic syndrome.
These results show that GHS-R has cell-autonomous effects in adipocytes, and suppression of GHS-R in adipose tissues protects against diet-induced obesity and insulin resistance by modulating adipose angiogenesis and fibrosis. These findings suggest adipose GHS-R may constitute a novel therapeutic target for treatment of obesity and metabolic syndrome.
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