{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T21:38:51Z","timestamp":1780695531190,"version":"3.54.1"},"reference-count":42,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Surg"],"published-print":{"date-parts":[[2021,10,1]]},"DOI":"10.1001\/jamasurg.2021.3303","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T15:39:19Z","timestamp":1627486759000},"page":"917","source":"Crossref","is-referenced-by-count":9,"title":["Association Between <i>NEDD4L<\/i> Variation and the Genetic Risk of Acute Appendicitis"],"prefix":"10.1001","volume":"156","author":[{"given":"Apostolos","family":"Gaitanidis","sequence":"first","affiliation":[{"name":"Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haytham M. A.","family":"Kaafarani","sequence":"additional","affiliation":[{"name":"Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias A.","family":"Christensen","sequence":"additional","affiliation":[{"name":"Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Breen","sequence":"additional","affiliation":[{"name":"Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Fagenholz","sequence":"additional","affiliation":[{"name":"Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George C.","family":"Velmahos","sequence":"additional","affiliation":[{"name":"Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha R.","family":"Farhat","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts"},{"name":"Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"5","key":"soi210051r1","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1093\/oxfordjournals.aje.a115734","article-title":"The epidemiology of appendicitis and appendectomy in the United States.","volume":"132","author":"Addiss","year":"1990","journal-title":"Am J Epidemiol"},{"issue":"1","key":"soi210051r3","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1308\/003588413X13511609954851","article-title":"Role of the faecolith in modern-day appendicitis.","volume":"95","author":"Singh","year":"2013","journal-title":"Ann R Coll Surg Engl"},{"issue":"11","key":"soi210051r4","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1111\/ans.2012.82.issue-11","article-title":"Pathologies of the appendix: a 10-year review of 4670 appendicectomy specimens.","volume":"82","author":"Chandrasegaram","year":"2012","journal-title":"ANZ J Surg"},{"issue":"1","key":"soi210051r5","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/S1092-9134(00)90011-X","article-title":"The pathology of acute appendicitis.","volume":"4","author":"Carr","year":"2000","journal-title":"Ann Diagn Pathol"},{"issue":"1","key":"soi210051r6","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1136\/gut.2009.191320","article-title":"Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum\/necrophorum.","volume":"60","author":"Swidsinski","year":"2011","journal-title":"Gut"},{"issue":"4","key":"soi210051r7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0095414","article-title":"Culture-independent evaluation of the appendix and rectum microbiomes in children with and without appendicitis.","volume":"9","author":"Jackson","year":"2014","journal-title":"PLoS One"},{"issue":"3","key":"soi210051r8","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.jpedsurg.2013.06.026","article-title":"Acute appendicitis in children is associated with an abundance of bacteria from the phylum Fusobacteria.","volume":"49","author":"Zhong","year":"2014","journal-title":"J Pediatr Surg"},{"issue":"4","key":"soi210051r9","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/mi.2008.13","article-title":"Acute appendicitis is characterized by a uniform and highly selective pattern of inflammatory gene expression.","volume":"1","author":"Murphy","year":"2008","journal-title":"Mucosal Immunol"},{"issue":"3","key":"soi210051r10","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1080\/09637480050029647","article-title":"Fiber intake and childhood appendicitis.","volume":"51","author":"Adamidis","year":"2000","journal-title":"Int J Food Sci Nutr"},{"issue":"7","key":"soi210051r11","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1001\/archsurg.1983.01390070076015","article-title":"Acute appendicitis and dietary fiber.","volume":"118","author":"Arnbj\u00f6rnsson","year":"1983","journal-title":"Arch Surg"},{"issue":"4","key":"soi210051r12","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1177\/145749690709600405","article-title":"Heredity and familial tendency of acute appendicitis.","volume":"96","author":"Ergul","year":"2007","journal-title":"Scand J Surg"},{"issue":"8","key":"soi210051r13","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1053\/jpsu.2001.25765","article-title":"Acute appendicitis in children: the importance of family history.","volume":"36","author":"Gauderer","year":"2001","journal-title":"J Pediatr Surg"},{"key":"soi210051r14","article-title":"Familial history aggregation on acute appendicitis.","volume":"2017","author":"Sim\u00f3 Alari","year":"2017","journal-title":"BMJ Case Rep"},{"issue":"1","key":"soi210051r15","doi-asserted-by":"publisher","first-page":"3119","DOI":"10.1038\/s41598-017-03353-0","article-title":"Sequence variant at 4q25 near PITX2 associates with appendicitis.","volume":"7","author":"Kristjansson","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"soi210051r16","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s00439-018-1956-2","article-title":"Genetic association and differential expression of PITX2 with acute appendicitis.","volume":"138","author":"Orlova","year":"2019","journal-title":"Hum Genet"},{"issue":"1","key":"soi210051r17","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3390\/jpm6010011","article-title":"The Biobank Portal for Partners Personalized Medicine: a query tool for working with consented Biobank samples, genotypes, and phenotypes using i2b2.","volume":"6","author":"Gainer","year":"2016","journal-title":"J Pers Med"},{"issue":"2","key":"soi210051r19","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/nmeth.1785","article-title":"A linear complexity phasing method for thousands of genomes.","volume":"9","author":"Delaneau","year":"2011","journal-title":"Nat Methods"},{"issue":"3","key":"soi210051r20","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses.","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"issue":"18","key":"soi210051r22","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.1093\/bioinformatics\/btq419","article-title":"LocusZoom: regional visualization of genome-wide association scan results.","volume":"26","author":"Pruim","year":"2010","journal-title":"Bioinformatics"},{"issue":"1","key":"soi210051r23","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","article-title":"GCTA: a tool for genome-wide complex trait analysis.","volume":"88","author":"Yang","year":"2011","journal-title":"Am J Hum Genet"},{"issue":"2","key":"soi210051r24","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/ng.2876","article-title":"Advantages and pitfalls in the application of mixed-model association methods.","volume":"46","author":"Yang","year":"2014","journal-title":"Nat Genet"},{"issue":"3","key":"soi210051r25","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1002\/(ISSN)1098-2272","article-title":"Estimation of significance thresholds for genomewide association scans.","volume":"32","author":"Dudbridge","year":"2008","journal-title":"Genet Epidemiol"},{"issue":"4","key":"soi210051r26","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1002\/gepi.v32:4","article-title":"Estimation of the multiple testing burden for genomewide association studies of nearly all common variants.","volume":"32","author":"Pe\u2019er","year":"2008","journal-title":"Genet Epidemiol"},{"key":"soi210051r27","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1186\/1471-2164-9-516","article-title":"Establishing an adjusted p-value threshold to control the family-wide type 1 error in genome wide association studies.","volume":"9","author":"Duggal","year":"2008","journal-title":"BMC Genomics"},{"issue":"7414","key":"soi210051r28","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses.","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ"},{"issue":"1","key":"soi210051r30","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s12920-016-0200-y","article-title":"Acute appendicitis: transcript profiling of blood identifies promising biomarkers and potential underlying processes.","volume":"9","author":"Chawla","year":"2016","journal-title":"BMC Med Genomics"},{"issue":"3","key":"soi210051r33","first-page":"590","article-title":"Appendectomy in Australian twins.","volume":"47","author":"Duffy","year":"1990","journal-title":"Am J Hum Genet"},{"issue":"2","key":"soi210051r34","first-page":"377","article-title":"Inheritance of acute appendicitis: familial aggregation and evidence of polygenic transmission.","volume":"46","author":"Basta","year":"1990","journal-title":"Am J Hum Genet"},{"issue":"2","key":"soi210051r35","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1375\/twin.12.2.150","article-title":"Heritability and linkage analysis of appendicitis utilizing age at onset.","volume":"12","author":"Oldmeadow","year":"2009","journal-title":"Twin Res Hum Genet"},{"issue":"2","key":"soi210051r36","doi-asserted-by":"publisher","first-page":"F334","DOI":"10.1152\/ajprenal.00394.2004","article-title":"Nedd4-2 isoforms differentially associate with ENaC and regulate its activity.","volume":"289","author":"Itani","year":"2005","journal-title":"Am J Physiol Renal Physiol"},{"issue":"8","key":"soi210051r37","doi-asserted-by":"publisher","first-page":"3137","DOI":"10.1074\/jbc.M116.770065","article-title":"The ubiquitin ligase Nedd4L Regulates the Na\/K\/2Cl co-transporter NKCC1\/SLC12A2 in the colon.","volume":"292","author":"Jiang","year":"2017","journal-title":"J Biol Chem"},{"issue":"9","key":"soi210051r38","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0183774","article-title":"NDFIP allows NEDD4\/NEDD4L-induced AQP2 ubiquitination and degradation.","volume":"12","author":"Trimpert","year":"2017","journal-title":"PLoS One"},{"issue":"12","key":"soi210051r39","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1038\/sj.ejhg.5200747","article-title":"NEDD4L on human chromosome 18q21 has multiple forms of transcripts and is a homologue of the mouse Nedd4-2 gene.","volume":"9","author":"Chen","year":"2001","journal-title":"Eur J Hum Genet"},{"issue":"30","key":"soi210051r40","doi-asserted-by":"publisher","first-page":"28321","DOI":"10.1074\/jbc.M011487200","article-title":"Multiple WW domains, but not the C2 domain, are required for inhibition of the epithelial Na+ channel by human Nedd4.","volume":"276","author":"Snyder","year":"2001","journal-title":"J Biol Chem"},{"issue":"5","key":"soi210051r41","doi-asserted-by":"publisher","first-page":"F916","DOI":"10.1152\/ajprenal.00203.2003","article-title":"Alternate promoters and variable splicing lead to hNedd4\u20132 isoforms with a C2 domain and varying number of WW domains.","volume":"285","author":"Itani","year":"2003","journal-title":"Am J Physiol Renal Physiol"},{"issue":"8","key":"soi210051r42","doi-asserted-by":"publisher","first-page":"3216","DOI":"10.1073\/pnas.1010334108","article-title":"Deletion of the ubiquitin ligase Nedd4L in lung epithelia causes cystic fibrosis-like disease.","volume":"108","author":"Kimura","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"soi210051r2","volume-title":"Ashcraft\u2019s Pediatric Surgery","author":"Holcomb","year":"2010"},{"key":"soi210051r18","unstructured":"Michigan Imputation Server. Free next-generation genotype imputation service. Accessed June 14, 2021. https:\/\/imputationserver.sph.umich.edu\/index.html"},{"key":"soi210051r21","doi-asserted-by":"crossref","unstructured":"Turner? SD. qqman: An R package for visualizing GWAS results using Q-Q and Manhattan plots.? bioRxiv. May 2014:005165. doi:10.1101\/005165?","DOI":"10.1101\/005165"},{"key":"soi210051r29","unstructured":"Gene Expression Omnibus. Gene expression in acute appendicitis. Accessed June 14, 2021. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE9579"},{"key":"soi210051r31","unstructured":"Gene Expression Omnibus. Acute appendicitis: transcript profiling of blood identifies promising biomarkers and potential underlying processes. Accessed June 14, 2021. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE83091"},{"key":"soi210051r32","unstructured":"Gene Expression Omnibus. GEO2R. Accessed June 14, 2021. https:\/\/www.ncbi.nlm.nih.gov\/geo\/geo2r\/"}],"container-title":["JAMA Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamasurgery\/articlepdf\/2782356\/jamasurgery_gaitanidis_2021_oi_210051_1633626625.16822.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T03:20:23Z","timestamp":1634527223000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamasurgery\/fullarticle\/2782356"}},"subtitle":["A Multi-institutional Genome-Wide Association Study"],"short-title":[],"issued":{"date-parts":[[2021,10,1]]},"references-count":42,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamasurg.2021.3303","relation":{},"ISSN":["2168-6254"],"issn-type":[{"value":"2168-6254","type":"print"}],"subject":[],"published":{"date-parts":[[2021,10,1]]}}}