{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T18:24:50Z","timestamp":1748975090505,"version":"3.37.3"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672585","82071673","11804151"],"award-info":[{"award-number":["81672585","82071673","11804151"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Taishan Scholar Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,9]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Calcium ion (Ca2+) is essential for human physiology by regulating various signal transduction pathways inside all cells and in the blood circulation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>We compared circulating Ca2+ levels in the healthy control against 48 different types of human diseases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>A total of 144\u00a0201 independent test results of Ca2+ levels from 48 clinically defined diseases and 141\u00a0679 independent test results of Ca2+ from healthy individuals who came to the hospital for annual physical examination were retrieved during the past 5 years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Ca2+ was determined by the standard \u2018Arsenazo III method\u2019 in the clinical laboratory of Affiliated Hospital of Qingdao University. We analyzed all data using RStudio V.1.3.1073 and python libraries 3.8.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>All 48 types of diseases had decreased Ca2+ levels than the healthy control based on either mean or median values. Patients suffering from preeclampsia had the lowest Ca2+ levels among all 48 diseases. The perfect area under the curve, sensitivity, and specificity values of 1.0, 0.96 and 0.96 indicated that Ca2+ was an excellent biomarker for diagnosing preeclampsia. Extremely low Ca2+ was present in patients suffering kidney-related diseases. Since the correlation between each disease on the statistical features is proportional to their vector distance, the two-component analysis revealed that preeclampsia, sepsis and chronic obstructive pulmonary disease were closely related among 48 diseases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>All human diseases were associated with reduced circulating Ca2+ levels, where the decreased Ca2+ was a perfect biomarker for preeclampsia. Kidney-related conditions were related to over-down-regulation of Ca2+ levels. The resemblance of preeclampsia to sepsis and chronic obstructive pulmonary disease based on two-component analysis suggested that the three unrelated diseases might share a similar mechanism of the circulating Ca2+ regulation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/qjmed\/hcab222","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T20:15:59Z","timestamp":1629231359000},"page":"455-462","source":"Crossref","is-referenced-by-count":3,"title":["Reduced blood circulating calcium level is an outstanding biomarker for preeclampsia among 48 types of human diseases"],"prefix":"10.1093","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3013-1581","authenticated-orcid":false,"given":"S","family":"Xu","sequence":"first","affiliation":[{"name":"Systems Biology and Medicine Center for Complex Diseases, Center for Clinical Research, The Affiliated Hospital of Qingdao University From the , Qingdao 266003, China"},{"name":"Department 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