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To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia:THY1(CD90)+HLA-DRAhisublining fibroblasts,IL1B+pro-inflammatory monocytes,ITGAX+TBX21+autoimmune-associated B cells andPDCD1+peripheral helper T (TPH) cells and follicular helper T (TFH) cells. We defined distinct subsets of CD8+T cells characterized byGZMK+,GZMB+, andGNLY+phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributedIL6expression toTHY1+HLA-DRAhifibroblasts andIL1Bproduction to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.

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We have developed a sales-support system for door-to-door sales of cosmetics based on a system called Skin-Expert, a skin-image grading service that includes analysis and diagnosis. Skin-Expert analyzes a customer's current skin quality from a picture of the skin. Several parameters are extracted by image processing, and the skin grading is done by rules generated by data mining from a baseline of grades given by human skin-care experts. Communication with the Skin-Expert is through a cellular telephone with a camera, using e-mail software and a Web browser. Salespeople photograph the customer's skin using the camera in a standard cellular telephone and then send an e-mail message that includes the picture as an attachment to our analysis system. Other parameters associated with the customer (for example, age and gender) are included in the body of the message. The picture is analyzed by our skin-grading system, and the results are made available as a page in HTML format on a customer-accessible Web site. An e-mail is sent when the results are available, usually within minutes. Salespeople check the results by using a Web browser on their cellular telephones. The output not only provides a grading result but also gives recommendations for the care and cosmetics that are most suitable for the customer. Our system integrates cellular communication, Web technology, computer analysis, data mining, and an expert system. Though salespeople use only a cellular telephone with very little computing power as the front end, they can take advantage of intelligent services such as computer grading and data mining. The salespeople do not need to think about what is running in the background, and there is no requirement that end users have any special hardware.