{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:11:42Z","timestamp":1788772302437,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hospital Research Project of Chi-na-Japan Friendship Hospital","award":["2025-HX-219"],"award-info":[{"award-number":["2025-HX-219"]}]},{"name":"Tong Xiaolin Academician Workstation Special Scientific Research Fund","award":["EF-YS-007"],"award-info":[{"award-number":["EF-YS-007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Background\/Objectives: Chronic pruritus of unknown origin (CPUO) is mechanistically poorly resolved, and its relationship to atopic dermatitis (AD) is unclear. We asked how much apparent separation survives removal of leakage. Methods: Public bulk skin data (GSE237920; four healthy, four AD, four CPUO) were analyzed by differential expression and an XOmiVAE-inspired latent model, with public single-cell and atlas resources for context. Every label-dependent step was then re-executed inside each cross-validation fold, with label permutation and 1000 bootstraps. A frozen composite niche score was applied unchanged to prurigo nodularis (GSE210854) and AD (GSE174582) cohorts. Results: Fully nested, the latent classifier separated CPUO from healthy skin (AUC 1.000; permutation p = 0.020) but not from AD (0.741; p = 0.140); randomized labels also reached 1.00. The composite score reached 0.919 against healthy skin but did not exceed its null (p = 0.086). Six genes recurred in \u226580% of bootstraps, five within the signature. Cell-type-restricted blood analysis recovered CPUO-associated monocyte CCL3 upregulation. In both validation cohorts, the frozen score was reduced, not elevated, in lesional skin. Conclusions: CPUO skin differs from healthy skin and occupies the low-inflammatory, epidermal-stress-dominated pole opposite lesional inflammatory skin, but cannot be robustly separated from AD at twelve samples.<\/jats:p>","DOI":"10.3390\/biomedicines14092000","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:07:06Z","timestamp":1788768426000},"page":"2000","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["XOmiVAE-Inspired Transcriptomic Analysis of Chronic Pruritus of Unknown Origin: A Cutaneous State Distinct from Healthy Skin but Not Robustly Separable from Atopic Dermatitis"],"prefix":"10.3390","volume":"14","author":[{"given":"Yue-Min","family":"Zou","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2154-1258","authenticated-orcid":false,"given":"Man-Ning","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Dong-Mei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Wen-Bo","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Yan-Ping","family":"Bai","sequence":"additional","affiliation":[{"name":"National Center for Integrative Medicine, China-Japan Friendship Hospital, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.2340\/00015555-0305","article-title":"Clinical Classification of Itch: A Position Paper of the International Forum for the Study of Itch","volume":"87","author":"Weisshaar","year":"2007","journal-title":"Acta Derm. 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