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Research data keyboard_double_arrow_right Dataset 2020figshare CIHR, NSERCCIHR ,NSERCKerr, Craig H.; Skinnider, Michael A.; Andrews, Daniel D. T.; Madero, Angel M.; Chan, Queenie W. T.; R. Greg Stacey; Stoynov, Nikolay; Jan, Eric; Foster, Leonard J.;Additional file 6. Autocorrelation z scores between pairs of stimulated and unstimulated chromatograms.
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You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.12486869&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.12486869&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2017Figshare ANR | RESET-AID Consortium, WT, UKRI | Study of the interplay of... +1 projectsANR| RESET-AID Consortium ,WT ,UKRI| Study of the interplay of genetic, biochemical, and lifestyle factors on coronary heart disease incidence ,CIHRCheung, Warren; Xiaojian Shao; Morin, Andréanne; Siroux, Valérie; Kwan, Tony; Ge, Bing; Aïssi, Dylan; Chen, Lu; Vasquez, Louella; Allum, Fiona; Guénard, Frédéric; Bouzigon, Emmanuelle; Marie-Michelle Simon; Boulier, Elodie; Redensek, Adriana; Watt, Stephen; Avik Datta; Clarke, Laura; Flicek, Paul; Mead, Daniel; Paul, Dirk; Beck, Stephan; Bourque, Guillaume; Lathrop, Mark; Tchernof, André; Marie-Claude Vohl; Demenais, Florence; Pin, Isabelle; Downes, Kate; Stunnenberg, Hendrick; Soranzo, Nicole; Pastinen, Tomi; Grundberg, Elin;Summary of AS and NAS methylation tests on the 2.2 million CpGs tested across any of the datasets. This file contains a file of tab-separated values (.txt text file) with the following columns: (1) CpG chromosome, (2) CpG location, (3) corrected GIT p value, (4) corrected mQTL p value, (5) corrected ASM p value, (6) ChromHMM state. (ZIP 19804 kb)
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You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.c.3714919_d3&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2021SciELO journals CIHRCIHRAuthors: Lima, Maria Alice Dias Da Silva; Giselda Quintana Marques; Adalvane Nobres Damaceno; Santos, Mariana Timmers Dos; +2 AuthorsLima, Maria Alice Dias Da Silva; Giselda Quintana Marques; Adalvane Nobres Damaceno; Santos, Mariana Timmers Dos; Witt, Regina Rigatto; Acosta, Aline Marques;ABSTRACT The study aimed to identify available instruments in the literature to evaluate the structure of primary health network in health systems. An integrated review of literature was carried out in health sciences, education, and management Databases, as follows: Medical Literature Analysis and Retrieval System Online (Medline), including the Cochrane Library, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ABI Inform, Latin American and Caribbean on Health Sciences Literature (Lilacs), and the Business Source Complete (Ebsco). Manuscripts published in English and Portuguese from 1995 to 2019 were included. The final sample contained nine articles, in which eight instruments were identified. They had as a common feature the approach on longitudinality, interprofessional communication, care coordination, access to health services, and quality of care. An emphasis was noted on an instrument developed in the Brazilian health system context as a useful tool to support health care workers and managers in the situational diagnosis of potentialities and fragilities of Primary Health Care and Health Care Networks.
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For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.14282643&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2022Taylor & Francis CIHRCIHRAuthors: Pluthero, Fred G.; Kahr, Walter H. A.;Pluthero, Fred G.; Kahr, Walter H. A.;Many roles of human platelets in health and disease are linked to their ability to transport and secrete a variety of small molecules and proteins carried in dense (δ-) and α-granules. Determination of granule number and content is important for diagnosis of platelet disorders and for studies of platelet structure, function, and development. We have optimized methods for detection and localization of platelet proteins via antibody and lectin staining, imaging via structured illumination laser fluorescence microscopy (SIM), and three-dimension (3D) image analysis. The methods were validated via comparison with published studies based on electron microscopy and high-resolution fluorescence microscopy. The α-granule cargo proteins thrombospondin-1 (TSP1), osteonectin (SPARC), fibrinogen (FGN), and Von Willebrand factor (VWF) were localized within the granule lumen, as was the proteoglycan serglycin (SRGN). Colocalization analysis indicates that staining with fluorescently labeled wheat germ agglutinin (WGA) allows detection of α-granules as effectively as immunostaining for cargo proteins, with the advantage of not requiring antibodies. RAB27B was observed to be concentrated at dense granules, allowing them to be counted via visual scoring and object analysis. We present a workflow for counting dense and α-granules via object analysis of 3D SIM images of platelets stained for RAB27B and with WGA. Abbreviation: SIM: structured illumination microscopy; WGA: wheat germ agglutinin; FGN: fibrinogen; TSP1: thrombospondin 1; ER: endoplasmic reticulum Platelets support blood clotting, wound healing, and other essential processes. These functions rely on the ability of platelets to transport and release small molecules like serotonin carried in dense granules and a wide range of proteins carried in alpha granules. Several conditions have been linked to abnormalities in one or more of platelet granule number, content, structure, and function. These conditions can be difficult to diagnose because platelet granules are so small they cannot be consistently resolved by conventional light microscopy, while higher power electron microscopy is not widely accessible. The goal of this study was to develop a method for counting and examining platelet dense and alpha granules without the need of electron microscopy. Key to this was the discovery that alpha granules can be reliably stained with the plant lectin wheat germ agglutinin, which has the advantages of being a smaller and less expensive molecule than the antibodies commonly used to detect alpha granule cargo proteins. We also establish that dense granules can be detected with high specificity via antibody staining of the membrane-associated protein RAB27B. We used structured illumination laser fluorescence microscopy to obtain high-resolution images of stained platelets. These were assembled into 3D renders using image analysis software, which was used to validate a protocol for rapidly counting granules within individual platelets. Our method supports the relatively rapid, accurate, and cost-effective assessment of platelet granules. We have already shown that it can confirm dense granule deficiency, and we anticipate that this approach will also prove useful in diagnosing and studying alpha granule abnormalities.
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You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.21781461&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2019figshare CIHRCIHRTianyuan Lu; Klein, Kathleen; InĂŠs Colmegna; Lora, Maximilien; Greenwood, Celia; Hudson, Marie;Additional file 2: Table S2. Summary of CHG-based DMGs.
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You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.10049450&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.10049450&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2017Taylor & Francis CIHR, NSERCCIHR ,NSERCAuthors: Gagarinova, Alla; Phanse, Sadhna; Miroslaw Cygler; Babu, Mohan;Gagarinova, Alla; Phanse, Sadhna; Miroslaw Cygler; Babu, Mohan;Introduction: The threat bacterial pathogens pose to human health is increasing with the number and distribution of antibiotic-resistant bacteria, while the rate of discovery of new antimicrobials dwindles. Proteomics is playing key roles in understanding the molecular mechanisms of bacterial pathogenesis, and in identifying disease outcome determinants. The physical associations identified by proteomics can provide the means to develop pathogen-specific treatment methods that reduce the spread of antibiotic resistance and alleviate the negative effects of broad-spectrum antibiotics on beneficial bacteria. Areas covered: This review discusses recent trends in proteomics and introduces new and developing approaches that can be applied to the study of protein-protein interactions (PPIs) underlying bacterial pathogenesis. The approaches examined encompass options for mapping proteomes as well as stable and transient interactions in vivo and in vitro. We also explored the coverage of bacterial and human-bacterial PPIs, knowledge gaps in this area, and how they can be filled. Expert commentary: Identifying potential antimicrobial candidates is confounded by the complex molecular biology of bacterial pathogenesis and the lack of knowledge about PPIs underlying this process. Proteomics approaches can offer new perspectives for mechanistic insights and identify essential targets for guiding the discovery of next generation antimicrobials.
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You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.5387743.v1&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2016Taylor & Francis CIHRCIHRLiu, Feng; Cai, Ping; Imir Metushi; Jinze Li; Nakayawa, Tetsuya; Libia Vega; Uetrecht, Jack;Amodiaquine (AQ) is associated with a relatively high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. A previous study reported that a combination of high dose AQ and glutathione (GSH) depletion led to liver injury. However, the characteristics of this toxicity were very different from AQ-induced liver injury in humans. We developed a model of AQ-induced liver injury with characteristics similar to the injury in humans by treating mice with lower doses of AQ for several weeks. In this study we found that not only did GSH depletion not increase AQ covalent binding to hepatic proteins at this lower dose, but also it paradoxically prevented the liver injury. We extended the model to rats and found AQ treatment led to a mild delayed onset liver injury that resolved despite continued treatment with AQ. Immunohistochemistry indicated the presence of Kupffer cell activation, apoptosis and hepatocyte proliferation in the liver. There was also an increase in serum IL-2, IL-5, IL-9, IL-12, MCP-1 and TGFβ, but a decrease in leptin. Coincident with the elevated serum ALT, the number of liver CD4+ T-cells, IL-17 secreting cells and TH17/Treg cells increased at Week 3 and decreased during continued treatment. Increases in NK1.1+ cells and activated M2 macrophages were also observed during liver injury. These results suggest that the outcome of the liver injury was determined by the balance between effector and regulatory cells. Co-treatment with cyclosporin prevented AQ-induced liver injury, which supports an immune mechanism. Retinoic acid (RA), which has been reported to enhance natural killer (NK) cell activity, exacerbated AQ-induced liver injury. These results suggest that AQ-induced IDILI is immune mediated and the subsequent adaptation appears to represent immune tolerance.
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For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2012Springer Science and Business Media LLC CIHRCIHRAuthors: Gunther Eysenbach;Gunther Eysenbach;add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1186/isrctn70542690&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1186/isrctn70542690&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2016Figshare CIHRCIHRAuthors: Huang, Barbara; Boutros, Paul;Huang, Barbara; Boutros, Paul;AUC results for low p/n data. Low p/n results for prediction accuracy using AUC as the performance metric for non-cross-validation results, 10-fold cross-validation and stratified 10-fold cross-validation. Ranks indicate the relative performance of different models with lower ranks representing higher performing models i.e., a rank of 1 is the best model. The default settings (n tree = 500, m try = 3, sampsize = 720) are found on row 1502 of the table. (CSV 116 kb)
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You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.c.3626282_d2&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2021figshare CIHR, NSERCCIHR ,NSERCNovakovsky, Gherman; Saraswat, Manu; Fornes, Oriol; Mostafavi, Sara; Wasserman, Wyeth W.;Additional file 12: Table S1. Total number of ones, zeros and nulls in the sparse matrix for the 163 TFs used in this study.
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For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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Research data keyboard_double_arrow_right Dataset 2020figshare CIHR, NSERCCIHR ,NSERCKerr, Craig H.; Skinnider, Michael A.; Andrews, Daniel D. T.; Madero, Angel M.; Chan, Queenie W. T.; R. Greg Stacey; Stoynov, Nikolay; Jan, Eric; Foster, Leonard J.;Additional file 6. Autocorrelation z scores between pairs of stimulated and unstimulated chromatograms.
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You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.12486869&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.12486869&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2017Figshare ANR | RESET-AID Consortium, WT, UKRI | Study of the interplay of... +1 projectsANR| RESET-AID Consortium ,WT ,UKRI| Study of the interplay of genetic, biochemical, and lifestyle factors on coronary heart disease incidence ,CIHRCheung, Warren; Xiaojian Shao; Morin, Andréanne; Siroux, Valérie; Kwan, Tony; Ge, Bing; Aïssi, Dylan; Chen, Lu; Vasquez, Louella; Allum, Fiona; Guénard, Frédéric; Bouzigon, Emmanuelle; Marie-Michelle Simon; Boulier, Elodie; Redensek, Adriana; Watt, Stephen; Avik Datta; Clarke, Laura; Flicek, Paul; Mead, Daniel; Paul, Dirk; Beck, Stephan; Bourque, Guillaume; Lathrop, Mark; Tchernof, André; Marie-Claude Vohl; Demenais, Florence; Pin, Isabelle; Downes, Kate; Stunnenberg, Hendrick; Soranzo, Nicole; Pastinen, Tomi; Grundberg, Elin;Summary of AS and NAS methylation tests on the 2.2 million CpGs tested across any of the datasets. This file contains a file of tab-separated values (.txt text file) with the following columns: (1) CpG chromosome, (2) CpG location, (3) corrected GIT p value, (4) corrected mQTL p value, (5) corrected ASM p value, (6) ChromHMM state. (ZIP 19804 kb)
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You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.c.3714919_d3&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2021SciELO journals CIHRCIHRAuthors: Lima, Maria Alice Dias Da Silva; Giselda Quintana Marques; Adalvane Nobres Damaceno; Santos, Mariana Timmers Dos; +2 AuthorsLima, Maria Alice Dias Da Silva; Giselda Quintana Marques; Adalvane Nobres Damaceno; Santos, Mariana Timmers Dos; Witt, Regina Rigatto; Acosta, Aline Marques;ABSTRACT The study aimed to identify available instruments in the literature to evaluate the structure of primary health network in health systems. An integrated review of literature was carried out in health sciences, education, and management Databases, as follows: Medical Literature Analysis and Retrieval System Online (Medline), including the Cochrane Library, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ABI Inform, Latin American and Caribbean on Health Sciences Literature (Lilacs), and the Business Source Complete (Ebsco). Manuscripts published in English and Portuguese from 1995 to 2019 were included. The final sample contained nine articles, in which eight instruments were identified. They had as a common feature the approach on longitudinality, interprofessional communication, care coordination, access to health services, and quality of care. An emphasis was noted on an instrument developed in the Brazilian health system context as a useful tool to support health care workers and managers in the situational diagnosis of potentialities and fragilities of Primary Health Care and Health Care Networks.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2022Taylor & Francis CIHRCIHRAuthors: Pluthero, Fred G.; Kahr, Walter H. A.;Pluthero, Fred G.; Kahr, Walter H. A.;Many roles of human platelets in health and disease are linked to their ability to transport and secrete a variety of small molecules and proteins carried in dense (δ-) and α-granules. Determination of granule number and content is important for diagnosis of platelet disorders and for studies of platelet structure, function, and development. We have optimized methods for detection and localization of platelet proteins via antibody and lectin staining, imaging via structured illumination laser fluorescence microscopy (SIM), and three-dimension (3D) image analysis. The methods were validated via comparison with published studies based on electron microscopy and high-resolution fluorescence microscopy. The α-granule cargo proteins thrombospondin-1 (TSP1), osteonectin (SPARC), fibrinogen (FGN), and Von Willebrand factor (VWF) were localized within the granule lumen, as was the proteoglycan serglycin (SRGN). Colocalization analysis indicates that staining with fluorescently labeled wheat germ agglutinin (WGA) allows detection of α-granules as effectively as immunostaining for cargo proteins, with the advantage of not requiring antibodies. RAB27B was observed to be concentrated at dense granules, allowing them to be counted via visual scoring and object analysis. We present a workflow for counting dense and α-granules via object analysis of 3D SIM images of platelets stained for RAB27B and with WGA. Abbreviation: SIM: structured illumination microscopy; WGA: wheat germ agglutinin; FGN: fibrinogen; TSP1: thrombospondin 1; ER: endoplasmic reticulum Platelets support blood clotting, wound healing, and other essential processes. These functions rely on the ability of platelets to transport and release small molecules like serotonin carried in dense granules and a wide range of proteins carried in alpha granules. Several conditions have been linked to abnormalities in one or more of platelet granule number, content, structure, and function. These conditions can be difficult to diagnose because platelet granules are so small they cannot be consistently resolved by conventional light microscopy, while higher power electron microscopy is not widely accessible. The goal of this study was to develop a method for counting and examining platelet dense and alpha granules without the need of electron microscopy. Key to this was the discovery that alpha granules can be reliably stained with the plant lectin wheat germ agglutinin, which has the advantages of being a smaller and less expensive molecule than the antibodies commonly used to detect alpha granule cargo proteins. We also establish that dense granules can be detected with high specificity via antibody staining of the membrane-associated protein RAB27B. We used structured illumination laser fluorescence microscopy to obtain high-resolution images of stained platelets. These were assembled into 3D renders using image analysis software, which was used to validate a protocol for rapidly counting granules within individual platelets. Our method supports the relatively rapid, accurate, and cost-effective assessment of platelet granules. We have already shown that it can confirm dense granule deficiency, and we anticipate that this approach will also prove useful in diagnosing and studying alpha granule abnormalities.
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For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2019figshare CIHRCIHRTianyuan Lu; Klein, Kathleen; InĂŠs Colmegna; Lora, Maximilien; Greenwood, Celia; Hudson, Marie;Additional file 2: Table S2. Summary of CHG-based DMGs.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.10049450&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2017Taylor & Francis CIHR, NSERCCIHR ,NSERCAuthors: Gagarinova, Alla; Phanse, Sadhna; Miroslaw Cygler; Babu, Mohan;Gagarinova, Alla; Phanse, Sadhna; Miroslaw Cygler; Babu, Mohan;Introduction: The threat bacterial pathogens pose to human health is increasing with the number and distribution of antibiotic-resistant bacteria, while the rate of discovery of new antimicrobials dwindles. Proteomics is playing key roles in understanding the molecular mechanisms of bacterial pathogenesis, and in identifying disease outcome determinants. The physical associations identified by proteomics can provide the means to develop pathogen-specific treatment methods that reduce the spread of antibiotic resistance and alleviate the negative effects of broad-spectrum antibiotics on beneficial bacteria. Areas covered: This review discusses recent trends in proteomics and introduces new and developing approaches that can be applied to the study of protein-protein interactions (PPIs) underlying bacterial pathogenesis. The approaches examined encompass options for mapping proteomes as well as stable and transient interactions in vivo and in vitro. We also explored the coverage of bacterial and human-bacterial PPIs, knowledge gaps in this area, and how they can be filled. Expert commentary: Identifying potential antimicrobial candidates is confounded by the complex molecular biology of bacterial pathogenesis and the lack of knowledge about PPIs underlying this process. Proteomics approaches can offer new perspectives for mechanistic insights and identify essential targets for guiding the discovery of next generation antimicrobials.
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You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.5387743.v1&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2016Taylor & Francis CIHRCIHRLiu, Feng; Cai, Ping; Imir Metushi; Jinze Li; Nakayawa, Tetsuya; Libia Vega; Uetrecht, Jack;Amodiaquine (AQ) is associated with a relatively high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. A previous study reported that a combination of high dose AQ and glutathione (GSH) depletion led to liver injury. However, the characteristics of this toxicity were very different from AQ-induced liver injury in humans. We developed a model of AQ-induced liver injury with characteristics similar to the injury in humans by treating mice with lower doses of AQ for several weeks. In this study we found that not only did GSH depletion not increase AQ covalent binding to hepatic proteins at this lower dose, but also it paradoxically prevented the liver injury. We extended the model to rats and found AQ treatment led to a mild delayed onset liver injury that resolved despite continued treatment with AQ. Immunohistochemistry indicated the presence of Kupffer cell activation, apoptosis and hepatocyte proliferation in the liver. There was also an increase in serum IL-2, IL-5, IL-9, IL-12, MCP-1 and TGFβ, but a decrease in leptin. Coincident with the elevated serum ALT, the number of liver CD4+ T-cells, IL-17 secreting cells and TH17/Treg cells increased at Week 3 and decreased during continued treatment. Increases in NK1.1+ cells and activated M2 macrophages were also observed during liver injury. These results suggest that the outcome of the liver injury was determined by the balance between effector and regulatory cells. Co-treatment with cyclosporin prevented AQ-induced liver injury, which supports an immune mechanism. Retinoic acid (RA), which has been reported to enhance natural killer (NK) cell activity, exacerbated AQ-induced liver injury. These results suggest that AQ-induced IDILI is immune mediated and the subsequent adaptation appears to represent immune tolerance.
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For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.3486581.v1&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2012Springer Science and Business Media LLC CIHRCIHRAuthors: Gunther Eysenbach;Gunther Eysenbach;add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1186/isrctn70542690&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1186/isrctn70542690&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2016Figshare CIHRCIHRAuthors: Huang, Barbara; Boutros, Paul;Huang, Barbara; Boutros, Paul;AUC results for low p/n data. Low p/n results for prediction accuracy using AUC as the performance metric for non-cross-validation results, 10-fold cross-validation and stratified 10-fold cross-validation. Ranks indicate the relative performance of different models with lower ranks representing higher performing models i.e., a rank of 1 is the best model. The default settings (n tree = 500, m try = 3, sampsize = 720) are found on row 1502 of the table. (CSV 116 kb)
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You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.c.3626282_d2&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euResearch data keyboard_double_arrow_right Dataset 2021figshare CIHR, NSERCCIHR ,NSERCNovakovsky, Gherman; Saraswat, Manu; Fornes, Oriol; Mostafavi, Sara; Wasserman, Wyeth W.;Additional file 12: Table S1. Total number of ones, zeros and nulls in the sparse matrix for the 163 TFs used in this study.
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You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.16689798&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.6084/m9.figshare.16689798&type=result"></script>'); --> </script>
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