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Thus far, BP Track has collected electronic health record data from over 826 000 eligible patients with hypertension who completed ≈3.1 million ambulatory visits. Preliminary results demonstrate substantial room for improvement in BP control ( less then 140/90 mm Hg), which was 58% overall, and in the clinical processes relevant for BP control. For example, only 12% of patients with hypertension with a high BP measurement during an ambulatory visit received an order for a new antihypertensive medication. CONCLUSIONS The PCORnet Blood Pressure Control Laboratory is designed to be a reusable platform for efficient surveillance and comparative effectiveness research; results from demonstration projects are forthcoming.PURPOSE The purpose of OncoMX1 knowledgebase development was to integrate cancer biomarker and relevant data types into a meta-portal, enabling the research of cancer biomarkers side by side with other pertinent multidimensional data types. METHODS Cancer mutation, cancer differential expression, cancer expression specificity, healthy gene expression from human and mouse, literature mining for cancer mutation and cancer expression, and biomarker data were integrated, unified by relevant biomedical ontologies, and subjected to rule-based automated quality control before ingestion into the database. RESULTS OncoMX provides integrated data encompassing more than 1,000 unique biomarker entries (939 from the Early Detection Research Network [EDRN] and 96 from the US Food and Drug Administration) mapped to 20,576 genes that have either mutation or differential expression in cancer. Sentences reporting mutation or differential expression in cancer were extracted from more than 40,000 publications, and healthy gene expression data with samples mapped to organs are available for both human genes and their mouse orthologs. CONCLUSION OncoMX has prioritized user feedback as a means of guiding development priorities. By mapping to and integrating data from several cancer genomics resources, it is hoped that OncoMX will foster a dynamic engagement between bioinformaticians and cancer biomarker researchers. This engagement should culminate in a community resource that substantially improves the ability and efficiency of exploring cancer biomarker data and related multidimensional data.RATIONALE We previously demonstrated involvement of nicotinamide phosphoribosyl-transferase (NAMPT) in pulmonary arterial hypertension (PAH) and now examine NAMPT regulation and extracellular NAMPT's role in PAH vascular remodeling. METHODS NAMPT transcription and protein expression in human lung endothelial cell (EC) was assessed in response to PAH-relevant stimuli (PDGF, VEGF, TGFβ1 and hypoxia). Endothelial to mesenchymal transition (EndMT) was detected by SANI1 and PECAM1 immunofluorescence. An eNAMPT-neutralizing polyclonal antibody (pAb) was tested in a PAH model of monocrotaline (MCT) challenge in rats. RESULTS Plasma eNAMPT levels, significantly increased in IPAH patients, were highly correlated with indices of PAH severity. Extracelluar NAMPT increased EndMT and each PAH stimulus significantly increased EC NAMPT promoter activity involving transcription factors STAT5, SOX18, and SOX 17, a newly GWAS-defined PAH candidate gene. The hypoxia-induced transcription factor, HIF-2α, also potently regulated NAMPT promoter activity and HIF-2α binding sites were identified between -628bp and -328bp. The prolyl hydroxylase domain-containing protein 2 (PHD2) inhibitor (FG-4592) significantly increased NAMPT promoter activity and protein expression in a HIF-2α-dependent manner. Finally, the eNAMPT-neutralizing pAb significantly reduced MCT-induced vascular remodeling, PAH hemodynamic alterations and NFkB activation. CONCLUSIONS eNAMPT is a novel and attractive therapeutic target essential to PAH vascular remodeling.CONTEXT.— The use of neoadjuvant therapy in the management of early-stage invasive breast cancer is increasing. Residual Cancer Burden and other similar tools use pathologic characteristics of post-neoadjuvant therapy breast tumors to determine long-term outcome. However, there are no standardized guidelines for the pathologic evaluation of these specimens in the routine clinical setting. OBJECTIVE.— To assess current practices among Canadian pathologists and pathology assistants with regard to the processing and reporting of post-neoadjuvant therapy breast specimens. DESIGN.— An electronic survey was distributed to pathologists and pathology assistants across Canada. RESULTS.— Sixty-three responses were obtained. A total of 48% (15 of 31) of surveyed pathologists reported familiarity with the Residual Cancer Burden tool. A total of 40% (25 of 63) of respondents reported a lack of routine use of specimen photography, and 35% (22 of 63) reported a lack of routine use of grossing diagrams. There was significant variation with respect to tumor bed sampling; the most common method was to submit 1 block per centimeter of tumor (20 of 63; 32%). There was also significant variation in the method of measuring residual tumor; the most common method was to measure the largest cross-section of residual tumor (16 of 32; 50%). CONCLUSIONS.— There is a need for standardization of the evaluation of post-neoadjuvant therapy breast specimens in the routine clinical setting in Canada. We recommend the routine use of specimen mapping, submitting the largest cross section of tumor bed in toto, reporting tumor size as per American Joint Committee on Cancer and Residual Cancer Burden guidelines, and routinely including measurements of residual tumor cellularity and in situ disease in the final pathology report as per Residual Cancer Burden guidelines.CONTEXT.— The updated American Society of Clinical Oncology/College of American Pathologists guideline for human epidermal growth factor receptor 2 (HER2) testing in breast cancer requires pathologists to re-evaluate HER2 status. OBJECTIVE.— To define HER2 status of breast cancer using immunohistochemistry and fluorescence in situ hybridization. click here DESIGN.— Diagnostic reports of invasive breast cancers made between 2014 and 2018 with HER2 immunohistochemistry and fluorescence in situ hybridization results were retrieved. HER2 status was re-defined using the updated recommendations. RESULTS.— Of 2514 tumors, 89.7% (2254 of 2514) suggested for fluorescence in situ hybridization assay were HER2 immunohistochemistry 2+. Approximately 8.9% (225 of 2514) and 1.4% (35 of 2514) of tumors were of immunohistochemistry 0/1+ and 3+, respectively. Based on the average HER2 copy number and HER2CEP17 ratio, tumors were assigned into 5 groups, including 13.1% (330 of 2514) group 1 tumors, 2.1% (52 of 2514) group 2 tumors, 1.1% (27 of 2514) group 3 tumors, 7.
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