{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:55:30Z","timestamp":1789761330236,"version":"4.0.1"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1R01 CA228399-02A1"],"award-info":[{"award-number":["1R01 CA228399-02A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1R21 AG070721-02A1"],"award-info":[{"award-number":["1R21 AG070721-02A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Primary hyperparathyroidism (PHPT) is a common endocrine neoplastic disorder characterized by disrupted calcium homeostasis secondary to inappropriately elevated parathyroid hormone (PTH) secretion. Low levels of serum 25-hydroxyvitamin D (25OHD) are significantly more prevalent in PHPT patients than in the general population (1\u20133), but the basis for this association remains unclear. We employed a spatially defined in situ whole-transcriptomics and selective proteomics profiling approach to compare gene expression patterns and cellular composition in parathyroid adenomas from vitamin D-deficient or vitamin D-replete PHPT patients. A cross-sectional panel of eucalcemic cadaveric donor parathyroid glands was examined in parallel as normal tissue controls. Here, we report that parathyroid tumors from vitamin D-deficient PHPT patients (Def-Ts) are intrinsically different from those of vitamin D-replete patients (Rep-Ts) of similar age and preoperative clinical presentation. The parathyroid oxyphil cell content is markedly higher in Def-Ts (47.8%) relative to Rep-Ts (17.8%) and normal donor glands (7.7%). Vitamin D deficiency is associated with increased expression of electron transport chain and oxidative phosphorylation pathway components. Parathyroid oxyphil cells, while morphologically distinct, are comparable to chief cells at the transcriptional level, and vitamin D deficiency affects the transcriptional profiles of both cell types in a similar manner. These data suggest that oxyphil cells are derived from chief cells and imply that their increased abundance may be induced by low vitamin D status. Gene set enrichment analysis reveals that pathways altered in Def-Ts are distinct from Rep-Ts, suggesting alternative tumor etiologies in these groups. Increased oxyphil content may thus be a morphological indicator of tumor-predisposing cellular stress.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgad073","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T10:08:55Z","timestamp":1678356535000},"source":"Crossref","is-referenced-by-count":9,"title":["Digital spatial profiling of human parathyroid tumors reveals cellular and molecular alterations linked to vitamin D deficiency"],"prefix":"10.1093","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7323-7733","authenticated-orcid":false,"given":"Chia-Ling","family":"Tu","sequence":"first","affiliation":[{"name":"Endocrine Research Unit, Department of Medicine, San Francisco Department of Veterans Affairs Medical Center, University of California San Francisco , San Francisco, CA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6583-7176","authenticated-orcid":false,"given":"Wenhan","family":"Chang","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, Department of Medicine, San Francisco Department of Veterans Affairs Medical Center, University of California San Francisco , San Francisco, CA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3356-7316","authenticated-orcid":false,"given":"Julie A","family":"Sosa","sequence":"additional","affiliation":[{"name":"Endocrine Neoplasia Laboratory, Department of Surgery, University of California San Francisco , San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6853-8606","authenticated-orcid":false,"given":"James","family":"Koh","sequence":"additional","affiliation":[{"name":"Endocrine Neoplasia Laboratory, Department of Surgery, University of California San Francisco , San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"2023111515131802300_pgad073-B1","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/BF03344140","article-title":"A very high incidence of low 25 hydroxy-vitamin D serum concentration in a French population of patients with primary hyperparathyroidism","volume":"29","author":"Boudou","year":"2006","journal-title":"J Endocrinol Invest"},{"key":"2023111515131802300_pgad073-B2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s12020-016-1169-1","article-title":"Vitamin D and primary hyperparathyroidism: more insights into a complex relationship","volume":"55","author":"Walker","year":"2017","journal-title":"Endocrine"},{"key":"2023111515131802300_pgad073-B3","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/j.1365-2265.2005.02371.x","article-title":"Vitamin D status, seasonal variations, parathyroid adenoma weight and bone mineral density in primary hyperparathyroidism","volume":"63","author":"Moosgaard","year":"2005","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2023111515131802300_pgad073-B4","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1111\/j.1365-2265.2007.03109.x","article-title":"Vitamin D metabolites and skeletal consequences in primary hyperparathyroidism","volume":"68","author":"Moosgaard","year":"2008","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2023111515131802300_pgad073-B5","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s00198-004-1656-8","article-title":"Low levels of 25-hydroxy vitamin D are associated with elevated parathyroid hormone in healthy adolescent females","volume":"16","author":"Harkness","year":"2005","journal-title":"Osteoporos Int"},{"key":"2023111515131802300_pgad073-B6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12902-017-0221-3","article-title":"Vitamin D, parathyroid hormone and metabolic syndrome - the PORMETS study","volume":"17","author":"Raposo","year":"2017","journal-title":"BMC Endocr Disord"},{"key":"2023111515131802300_pgad073-B7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1365-2265.1992.tb02278.x","article-title":"The role of 1,25-dihydroxyvitamin D in the mechanism of acquired vitamin D deficiency","volume":"37","author":"Clements","year":"1992","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2023111515131802300_pgad073-B8","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.1073\/pnas.82.12.4270","article-title":"Regulation by vitamin D metabolites of messenger ribonucleic acid for preproparathyroid hormone in isolated bovine parathyroid cells","volume":"82","author":"Silver","year":"1985","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023111515131802300_pgad073-B9","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1210\/endo-125-2-935","article-title":"Influence of calcium and 1,25-dihydroxycholecalciferol on proliferation and proto-oncogene expression in primary cultures of bovine parathyroid cells","volume":"125","author":"Kremer","year":"1989","journal-title":"Endocrinology"},{"key":"2023111515131802300_pgad073-B10","doi-asserted-by":"crossref","first-page":"F1192","DOI":"10.1152\/ajprenal.00360.2009","article-title":"Deletion of the vitamin D receptor specifically in the parathyroid demonstrates a limited role for the receptor in parathyroid physiology","volume":"297","author":"Meir","year":"2009","journal-title":"Am J Physiol Renal Physiol"},{"key":"2023111515131802300_pgad073-B11","doi-asserted-by":"crossref","first-page":"E1499","DOI":"10.1210\/jc.2011-3366","article-title":"Differential gene expression by oxyphil and chief cells of human parathyroid glands","volume":"97","author":"Ritter","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2023111515131802300_pgad073-B12","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jprot.2018.02.029","article-title":"Comparative proteomic analysis of chief and oxyphil cell nodules in refractory uremic hyperparathyroidism by iTRAQ coupled LC-MS\/MS","volume":"179","author":"Li","year":"2018","journal-title":"J Proteomics"},{"key":"2023111515131802300_pgad073-B13","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1136\/jcp.20.4.591","article-title":"The parathyroid oxyphil cells","volume":"20","author":"Christie","year":"1967","journal-title":"J Clin Pathol"},{"key":"2023111515131802300_pgad073-B14","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1073\/pnas.1319742111","article-title":"Functional and genetic studies of isolated cells from parathyroid tumors reveal the complex pathogenesis of parathyroid neoplasia","volume":"111","author":"Shi","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023111515131802300_pgad073-B15","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1530\/ERC-17-0470","article-title":"Transcriptional profiling reveals distinct classes of parathyroid tumors in PHPT","volume":"25","author":"Koh","year":"2018","journal-title":"Endocr Relat Cancer."},{"key":"2023111515131802300_pgad073-B16","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s00726-022-03126-8","article-title":"Integrated transcriptomic and proteomic analyses for the characterization of parathyroid oxyphil cells in uremic patients","volume":"54","author":"Mao","year":"2022","journal-title":"Amino Acids"},{"key":"2023111515131802300_pgad073-B17","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0046-8177(84)80306-8","article-title":"Functioning oxyphil cell adenoma of the parathyroid gland: a clinicopathologic study of ten patients with hyperparathyroidism","volume":"15","author":"Bedetti","year":"1984","journal-title":"Hum Pathol"},{"key":"2023111515131802300_pgad073-B18","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.amjsurg.2007.01.040","article-title":"The positive effect of adenoma weight and oxyphil cell content on preoperative localization with 99mTc-sestamibi scanning for primary hyperparathyroidism","volume":"195","author":"Erbil","year":"2008","journal-title":"Am J Surg"},{"key":"2023111515131802300_pgad073-B19","doi-asserted-by":"crossref","first-page":"5948","DOI":"10.1210\/jc.2004-1597","article-title":"Oxyphil parathyroid adenoma: a malignant presentation of a benign disease","volume":"89","author":"Fleischer","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2023111515131802300_pgad073-B20","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1007\/s12022-015-9378-3","article-title":"Oxyphil cell parathyroid adenomas causing primary hyperparathyroidism: a clinico-pathological correlation","volume":"26","author":"Howson","year":"2015","journal-title":"Endocr Pathol"},{"key":"2023111515131802300_pgad073-B21","first-page":"QD07-08","article-title":"Functioning oxyphil parathyroid adenoma: a case report","volume":"8","author":"Metgudmath","year":"2014","journal-title":"J Clin Diagn Res"},{"key":"2023111515131802300_pgad073-B22","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s42255-020-0175-z","article-title":"PTH hypersecretion triggered by a GABA(B1) and Ca(2+)-sensing receptor heterocomplex in hyperparathyroidism","volume":"2","author":"Chang","year":"2020","journal-title":"Nat Metab"},{"key":"2023111515131802300_pgad073-B23","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1210\/jc.2010-2704","article-title":"The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know","volume":"96","author":"Ross","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2023111515131802300_pgad073-B24","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1210\/jc.2015-2022","article-title":"Vitamin D in primary hyperparathyroidism: effects on clinical, biochemical, and densitometric presentation","volume":"100","author":"Walker","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"2023111515131802300_pgad073-B25","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1472-6823-7-8","article-title":"Mitochondrial DNA mutations in oxyphilic and chief cell parathyroid adenomas","volume":"7","author":"Costa-Guda","year":"2007","journal-title":"BMC Endocr Disord"},{"key":"2023111515131802300_pgad073-B26","doi-asserted-by":"crossref","first-page":"bbaa163","DOI":"10.1093\/bib\/bbaa163","article-title":"An approach for normalization and quality control for NanoString RNA expression data","volume":"22","author":"Bhattacharya","year":"2021","journal-title":"Brief Bioinform"},{"key":"2023111515131802300_pgad073-B27","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/ng1180","article-title":"PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes","volume":"34","author":"Mootha","year":"2003","journal-title":"Nat Genet"},{"issue":"175","key":"2023111515131802300_pgad073-B28","doi-asserted-by":"crossref","DOI":"10.3791\/62528-v","article-title":"Three differential expression analysis methods for RNA sequencing: limma, EdgeR, DESeq2","author":"Liu","year":"2021","journal-title":"J Vis Exp."},{"key":"2023111515131802300_pgad073-B29","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3389\/fgene.2016.00164","article-title":"In papyro comparison of TMM (edgeR), RLE (DESeq2), and MRN normalization methods for a simple two-conditions-without-replicates RNA-Seq experimental design","volume":"7","author":"Maza","year":"2016","journal-title":"Front Genet"},{"key":"2023111515131802300_pgad073-B30","doi-asserted-by":"crossref","first-page":"e0157022","DOI":"10.1371\/journal.pone.0157022","article-title":"SARTools: a DESeq2- and EdgeR-based R pipeline for comprehensive differential analysis of RNA-Seq data","volume":"11","author":"Varet","year":"2016","journal-title":"PLoS One"},{"key":"2023111515131802300_pgad073-B31","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1007\/s12253-019-00787-x","article-title":"Mutation and expression of a candidate tumor suppressor gene EPB41L3 in gastric and colorectal cancers","volume":"26","author":"Son","year":"2020","journal-title":"Pathol Oncol Res"},{"key":"2023111515131802300_pgad073-B32","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1002\/ijc.32570","article-title":"Methylation of HPV 16 and EPB41L3 in oral gargles: associations with oropharyngeal cancer detection and tumor characteristics","volume":"146","author":"Giuliano","year":"2020","journal-title":"Int J Cancer"},{"key":"2023111515131802300_pgad073-B33","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.brainresbull.2009.07.006","article-title":"Role of the JNK-interacting protein 1\/islet brain 1 in cell degeneration in Alzheimer disease and diabetes","volume":"80","author":"Beeler","year":"2009","journal-title":"Brain Res Bull"},{"key":"2023111515131802300_pgad073-B34","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s42255-020-0175-z","article-title":"PTH hypersecretion triggered by a GABAB1 and Ca2+ -sensing receptor heterocomplex in hyperparathyroidism","volume":"2","author":"Chang","year":"2020","journal-title":"Nat Metab"},{"key":"2023111515131802300_pgad073-B35","doi-asserted-by":"crossref","first-page":"e54133","DOI":"10.15252\/embr.202154133","article-title":"Engagement of TRAIL triggers degranulation and IFN","volume":"23","author":"Hofle","year":"2022","journal-title":"EMBO Rep"},{"key":"2023111515131802300_pgad073-B36","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3390\/cells11010057","article-title":"TRAIL triggers CRAC-dependent calcium influx and apoptosis through the recruitment of autophagy proteins to death-inducing signaling complex","volume":"11","author":"Airiau","year":"2021","journal-title":"Cells"},{"key":"2023111515131802300_pgad073-B37","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s11033-021-06836-6","article-title":"SGK1, autophagy and cancer: an overview","volume":"49","author":"Ghani","year":"2022","journal-title":"Mol Biol Rep"},{"key":"2023111515131802300_pgad073-B38","doi-asserted-by":"crossref","first-page":"315","DOI":"10.14348\/molcells.2017.0066","article-title":"The expanding significance of inositol polyphosphate multikinase as a signaling hub","volume":"40","author":"Kim","year":"2017","journal-title":"Mol Cells"},{"key":"2023111515131802300_pgad073-B39","doi-asserted-by":"crossref","first-page":"704","DOI":"10.21873\/invivo.12756","article-title":"Down-regulation of AMPD3 is associated with poor survival in head and neck squamous cell carcinoma","volume":"36","author":"Hsu","year":"2022","journal-title":"In Vivo"},{"key":"2023111515131802300_pgad073-B40","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.matbio.2011.03.002","article-title":"Collagen VI is a basement membrane component that regulates epithelial cell-fibronectin interactions","volume":"30","author":"Groulx","year":"2011","journal-title":"Matrix Biol"},{"key":"2023111515131802300_pgad073-B41","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1253\/circrep.CR-20-0015","article-title":"Role of tissue-type plasminogen activator in remodeling of the ductus arteriosus","volume":"2","author":"Saito","year":"2020","journal-title":"Circ Rep"},{"key":"2023111515131802300_pgad073-B42","doi-asserted-by":"crossref","first-page":"59377","DOI":"10.18632\/oncotarget.11074","article-title":"XB130 is overexpressed in prostate cancer and involved in cell growth and invasion","volume":"7","author":"Chen","year":"2016","journal-title":"Oncotarget"},{"key":"2023111515131802300_pgad073-B43","doi-asserted-by":"crossref","first-page":"5592","DOI":"10.3892\/mmr.2017.7279","article-title":"XB130 enhances invasion and migration of human colorectal cancer cells by promoting epithelialmesenchymal transition","volume":"16","author":"Shen","year":"2017","journal-title":"Mol Med Rep"},{"key":"2023111515131802300_pgad073-B44","doi-asserted-by":"crossref","first-page":"e0259075","DOI":"10.1371\/journal.pone.0259075","article-title":"Adaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma","volume":"16","author":"Poosekeaw","year":"2021","journal-title":"PLoS One"},{"key":"2023111515131802300_pgad073-B45","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12957-021-02469-y","article-title":"Significant co-expression of putative cancer stem cell markers, EpCAM and CD166, correlates with tumor stage and invasive behavior in colorectal cancer","volume":"20","author":"Kalantari","year":"2022","journal-title":"World J Surg Oncol"},{"key":"2023111515131802300_pgad073-B46","doi-asserted-by":"crossref","first-page":"100031","DOI":"10.1016\/j.gene.2020.100031","article-title":"ALCAM (CD166) as a gene expression marker for human mesenchymal stromal cell characterisation","volume":"763S","author":"Brinkhof","year":"2020","journal-title":"Gene"},{"key":"2023111515131802300_pgad073-B47","doi-asserted-by":"crossref","first-page":"5753","DOI":"10.3390\/ijms23105753","article-title":"ALCAM\/CD166 is involved in the binding and uptake of cancer-derived extracellular vesicles","volume":"23","author":"Cardenes","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2023111515131802300_pgad073-B48","doi-asserted-by":"crossref","first-page":"e34850","DOI":"10.1371\/journal.pone.0034850","article-title":"Differential epigenetic regulation of TOX subfamily high mobility group box genes in lung and breast cancers","volume":"7","author":"Tessema","year":"2012","journal-title":"PLoS One"},{"key":"2023111515131802300_pgad073-B49","first-page":"1","article-title":"MicroRNA-1286 inhibits osteogenic differentiation of mesenchymal stem cells to promote the progression of osteoporosis via regulating FZD4 expression","volume":"24","author":"Zhou","year":"2020","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2023111515131802300_pgad073-B50","doi-asserted-by":"crossref","first-page":"118","DOI":"10.14712\/fb2021067030118","article-title":"Insulin-like growth factor binding protein 5: an important regulator of early osteogenic differentiation of hMSCs","volume":"67","author":"Zhang","year":"2021","journal-title":"Folia Biol (Praha)"},{"key":"2023111515131802300_pgad073-B51","doi-asserted-by":"crossref","first-page":"3993","DOI":"10.1210\/jc.2018-01225","article-title":"Primary hyperparathyroidism","volume":"103","author":"Bilezikian","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"2023111515131802300_pgad073-B52","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1007\/s12020-016-0931-8","article-title":"Impact of vitamin D deficiency on the clinical and biochemical phenotype in women with sporadic primary hyperparathyroidism","volume":"55","author":"Viccica","year":"2017","journal-title":"Endocrine"},{"key":"2023111515131802300_pgad073-B53","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/s12020-016-0974-x","article-title":"Vitamin D status in primary hyperparathyroidism: effect of genetic background","volume":"55","author":"Battista","year":"2017","journal-title":"Endocrine"},{"key":"2023111515131802300_pgad073-B54","first-page":"70","article-title":"The parathyroid adenoma. A histopathologic definition with a study of 172 cases of primary hyperparathyroidism","volume":"115","author":"Ghandur-Mnaymneh","year":"1984","journal-title":"Am J Pathol"},{"key":"2023111515131802300_pgad073-B55","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s12105-008-0088-8","article-title":"Parathyroid adenoma","volume":"2","author":"Wieneke","year":"2008","journal-title":"Head Neck Pathol"},{"issue":"Suppl 2","key":"2023111515131802300_pgad073-B56","first-page":"N30","article-title":"Molecular pathogenesis of primary hyperparathyroidism","volume":"17","author":"Arnold","year":"2002","journal-title":"J Bone Miner Res"},{"key":"2023111515131802300_pgad073-B57","first-page":"1443","article-title":"EPB41L3 is a potential tumor suppressor gene and prognostic indicator in esophageal squamous cell carcinoma","volume":"52","author":"Zeng","year":"2018","journal-title":"Int J Oncol"},{"key":"2023111515131802300_pgad073-B58","doi-asserted-by":"crossref","first-page":"111229","DOI":"10.1016\/j.mad.2020.111229","article-title":"Oncogene-induced senescence: from biology to therapy","volume":"187","author":"Zhu","year":"2020","journal-title":"Mech Ageing Dev"},{"key":"2023111515131802300_pgad073-B59","doi-asserted-by":"crossref","first-page":"eaao4827","DOI":"10.1126\/science.aao4827","article-title":"Secreted amyloid-beta precursor protein functions as a GABABR1a ligand to modulate synaptic transmission","volume":"363","author":"Rice","year":"2019","journal-title":"Science"},{"key":"2023111515131802300_pgad073-B60","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1530\/EJE-15-1062","article-title":"Diffuse parathyroid hormone expression in parathyroid tumors argues against important functional tumor subclones","volume":"174","author":"Haglund","year":"2016","journal-title":"Eur J Endocrinol"},{"key":"2023111515131802300_pgad073-B61","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3390\/jcm8030297","article-title":"Comparative gene expression profiles in parathyroid adenoma and normal parathyroid tissue","volume":"8","author":"Chai","year":"2019","journal-title":"J Clin Med"},{"key":"2023111515131802300_pgad073-B62","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1212\/WNL.0b013e318245d295","article-title":"\u03b2-Amyloid burden in healthy aging: regional distribution and cognitive consequences","volume":"78","author":"Rodrigue","year":"2012","journal-title":"Neurology"},{"key":"2023111515131802300_pgad073-B63","doi-asserted-by":"crossref","first-page":"101388","DOI":"10.1016\/j.arr.2021.101388","article-title":"Age-related amyloidosis outside the brain: a state-of-the-art review","volume":"70","author":"Tasaki","year":"2021","journal-title":"Ageing Res Rev"},{"key":"2023111515131802300_pgad073-B64","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1002\/jbmr.4665","article-title":"Epidemiology, pathophysiology, and genetics of primary hyperparathyroidism","volume":"37","author":"Minisola","year":"2022","journal-title":"J Bone Miner Res"},{"key":"2023111515131802300_pgad073-B65","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.jss.2022.03.014","article-title":"Effects of multi-stage procurement on the viability and function of human donor parathyroid glands","volume":"276","author":"Kelly","year":"2022","journal-title":"J Surg Res"},{"key":"2023111515131802300_pgad073-B66","doi-asserted-by":"crossref","first-page":"lqz019","DOI":"10.1093\/nargab\/lqz019","article-title":"Omics playground: a comprehensive self-service platform for visualization, analytics and exploration of Big Omics Data","volume":"2","author":"Akhmedov","year":"2020","journal-title":"NAR Genom Bioinform"},{"key":"2023111515131802300_pgad073-B67","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene Ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat Genet"},{"key":"2023111515131802300_pgad073-B68","doi-asserted-by":"crossref","first-page":"D325","DOI":"10.1093\/nar\/gkaa1113","article-title":"The Gene Ontology resource: enriching a GOld mine","volume":"49","author":"Gene Ontology Consortium","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2023111515131802300_pgad073-B69","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto Encyclopedia of Genes and Genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"2023111515131802300_pgad073-B70","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst"},{"key":"2023111515131802300_pgad073-B71","doi-asserted-by":"crossref","first-page":"e004757","DOI":"10.1136\/jitc-2022-004757","article-title":"Spatially resolved proteomic profiling identifies tumor cell CD44 as a biomarker associated with sensitivity to PD-1 axis blockade in advanced non-small-cell lung cancer","volume":"10","author":"Moutafi","year":"2022","journal-title":"J Immunother Cancer"}],"container-title":["PNAS Nexus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/pnasnexus\/advance-article-pdf\/doi\/10.1093\/pnasnexus\/pgad073\/49468648\/pgad073.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article-pdf\/2\/3\/pgad073\/53409608\/pgad073.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article-pdf\/2\/3\/pgad073\/53409608\/pgad073.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T17:59:20Z","timestamp":1700071160000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article\/doi\/10.1093\/pnasnexus\/pgad073\/7073721"}},"subtitle":[],"editor":[{"given":"Martha","family":"Field","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,3,1]]},"references-count":71,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3,3]]}},"URL":"https:\/\/doi.org\/10.1093\/pnasnexus\/pgad073","relation":{},"ISSN":["2752-6542"],"issn-type":[{"value":"2752-6542","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,3,1]]},"published":{"date-parts":[[2023,3,1]]},"article-number":"pgad073"}}