{"id":"https://openalex.org/W4387489293","doi":"https://doi.org/10.21614/sgo-588","title":"Therapeutic Implications of PTEN Loss in Patients with Cowden Syndrome and Renal Cell Cancer","display_name":"Therapeutic Implications of PTEN Loss in Patients with Cowden Syndrome and Renal Cell Cancer","publication_year":2023,"publication_date":"2023-01-01","ids":{"openalex":"https://openalex.org/W4387489293","doi":"https://doi.org/10.21614/sgo-588"},"language":"en","primary_location":{"id":"doi:10.21614/sgo-588","doi":"https://doi.org/10.21614/sgo-588","is_oa":true,"landing_page_url":"http://dx.doi.org/10.21614/sgo-588","pdf_url":"https://www.sgo-iasgo.com/pdfs/2023-3-136.pdf","source":{"id":"https://openalex.org/S4210219519","display_name":"Surgery Gastroenterology and Oncology","issn_l":"2559-723X","issn":["2559-723X","2601-1700"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","poland-20","russia-white-list-4"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Surgery, Gastroenterology and Oncology","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"diamond","oa_url":"https://www.sgo-iasgo.com/pdfs/2023-3-136.pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5018011603","display_name":"Katia Lanzafame","orcid":"https://orcid.org/0000-0001-7358-3946","observed_orcids":["https://orcid.org/0000-0001-7358-3946"]},"institutions":[{"id":"https://openalex.org/I4210160210","display_name":"Azienda Ospedaliero Universitaria Policlinico \"G.Rodolico - San Marco\"","ror":"https://ror.org/051tt6c85","country_code":"IT","type":"healthcare","lineage":["https://openalex.org/I4210160210"]}],"countries":["IT"],"is_corresponding":true,"raw_author_name":"Katia Lanzafame","raw_affiliation_strings":["Division of Medical Oncology, A.O.U. Policlinico \"G. Rodolico -S. Marco\", Catania, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Medical Oncology, A.O.U. Policlinico \"G. Rodolico -S. Marco\", Catania, Italy","institution_ids":["https://openalex.org/I4210160210"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5043631669","display_name":"Nicola Inzerilli","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210160210","display_name":"Azienda Ospedaliero Universitaria Policlinico \"G.Rodolico - San Marco\"","ror":"https://ror.org/051tt6c85","country_code":"IT","type":"healthcare","lineage":["https://openalex.org/I4210160210"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Nicola Inzerilli","raw_affiliation_strings":["Division of Medical Oncology, A.O.U. Policlinico \"G. Rodolico -S. Marco\", Catania, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Medical Oncology, A.O.U. Policlinico \"G. Rodolico -S. Marco\", Catania, Italy","institution_ids":["https://openalex.org/I4210160210"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5023724430","display_name":"Rosaria Carciotto","orcid":"https://orcid.org/0000-0002-8531-808X","observed_orcids":["https://orcid.org/0000-0002-8531-808X"]},"institutions":[{"id":"https://openalex.org/I4210160210","display_name":"Azienda Ospedaliero Universitaria Policlinico \"G.Rodolico - San Marco\"","ror":"https://ror.org/051tt6c85","country_code":"IT","type":"healthcare","lineage":["https://openalex.org/I4210160210"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Rosaria Carciotto","raw_affiliation_strings":["Division of Medical Oncology, A.O.U. Policlinico \"G. Rodolico -S. Marco\", Catania, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Medical Oncology, A.O.U. Policlinico \"G. Rodolico -S. Marco\", Catania, Italy","institution_ids":["https://openalex.org/I4210160210"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034450716","display_name":"Claudio Longhitano","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210160210","display_name":"Azienda Ospedaliero Universitaria Policlinico \"G.Rodolico - San Marco\"","ror":"https://ror.org/051tt6c85","country_code":"IT","type":"healthcare","lineage":["https://openalex.org/I4210160210"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Claudio Longhitano","raw_affiliation_strings":["Division of Medical Oncology, A.O.U. Policlinico \"G. Rodolico -S. Marco\", Catania, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Medical Oncology, A.O.U. Policlinico \"G. Rodolico -S. Marco\", Catania, Italy","institution_ids":["https://openalex.org/I4210160210"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5052162438","display_name":"Stefania Stella","orcid":"https://orcid.org/0000-0002-7189-2312","observed_orcids":["https://orcid.org/0000-0002-7189-2312"]},"institutions":[{"id":"https://openalex.org/I39063666","display_name":"University of Catania","ror":"https://ror.org/03a64bh57","country_code":"IT","type":"education","lineage":["https://openalex.org/I39063666"]},{"id":"https://openalex.org/I4210160210","display_name":"Azienda Ospedaliero Universitaria Policlinico \"G.Rodolico - San Marco\"","ror":"https://ror.org/051tt6c85","country_code":"IT","type":"healthcare","lineage":["https://openalex.org/I4210160210"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Stefania Stella","raw_affiliation_strings":["Center of Experimental Oncology and Hematology, A.O.U. Policlinico \"G. Rodolico -S. Marco\", Catania, Italy","Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \"G. Rodolico -S. Marco\", Catania, Italy","institution_ids":["https://openalex.org/I4210160210"]},{"raw_affiliation_string":"Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy","institution_ids":["https://openalex.org/I39063666"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5104180820","display_name":"Lo Bianco Salvatore","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210105999","display_name":"Ospedale Garibaldi","ror":"https://ror.org/01q6hrg49","country_code":"IT","type":"healthcare","lineage":["https://openalex.org/I4210105999"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Lo Bianco Salvatore","raw_affiliation_strings":["Department of Oncology Surgery, ARNAS Garibaldi Catania, Catania, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Oncology Surgery, ARNAS Garibaldi Catania, Catania, Italy","institution_ids":["https://openalex.org/I4210105999"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101716809","display_name":"Lorenzo Rossi","orcid":"https://orcid.org/0000-0001-7039-8593","observed_orcids":["https://orcid.org/0000-0001-7039-8593"]},"institutions":[{"id":"https://openalex.org/I4404532900","display_name":"Istituto Oncologico della Svizzera Italiana","ror":"https://ror.org/04tty5b50","country_code":"CH","type":"healthcare","lineage":["https://openalex.org/I4210095212","https://openalex.org/I4404532900"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Lorenzo Rossi","raw_affiliation_strings":["Institute of Oncology of Southern Switzerland (IOSI), Bellinzona, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute of Oncology of Southern Switzerland (IOSI), Bellinzona, Switzerland","institution_ids":["https://openalex.org/I4404532900"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5043599930","display_name":"Paolo Giovanni Vigneri","orcid":"https://orcid.org/0000-0002-5943-6066","observed_orcids":["https://orcid.org/0000-0002-5943-6066"]},"institutions":[{"id":"https://openalex.org/I39063666","display_name":"University of Catania","ror":"https://ror.org/03a64bh57","country_code":"IT","type":"education","lineage":["https://openalex.org/I39063666"]},{"id":"https://openalex.org/I4210160210","display_name":"Azienda Ospedaliero Universitaria Policlinico \"G.Rodolico - San Marco\"","ror":"https://ror.org/051tt6c85","country_code":"IT","type":"healthcare","lineage":["https://openalex.org/I4210160210"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Paolo Vigneri","raw_affiliation_strings":["Center of Experimental Oncology and Hematology, A.O.U. Policlinico \"G. Rodolico -S. Marco\", Catania, Italy","Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy","Division of Medical Oncology, A.O.U. Policlinico \"G. Rodolico -S. Marco\", Catania, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \"G. Rodolico -S. Marco\", Catania, Italy","institution_ids":["https://openalex.org/I4210160210"]},{"raw_affiliation_string":"Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy","institution_ids":["https://openalex.org/I39063666"]},{"raw_affiliation_string":"Division of Medical Oncology, A.O.U. Policlinico \"G. Rodolico -S. Marco\", Catania, Italy","institution_ids":["https://openalex.org/I4210160210"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":4,"corresponding_author_ids":["https://openalex.org/A5018011603"],"corresponding_institution_ids":["https://openalex.org/I4210160210"],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"28","issue":"3","first_page":"136","last_page":"136"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10449","display_name":"Renal cell carcinoma treatment","score":0.9057999849319458,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10449","display_name":"Renal cell carcinoma treatment","score":0.9057999849319458,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":0.09000000357627869,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/cowden-syndrome","display_name":"Cowden syndrome","score":0.9800000190734863},{"id":"https://openalex.org/keywords/pten-loss","display_name":"PTEN loss","score":0.9769999980926514},{"id":"https://openalex.org/keywords/renal-cell-carcinoma","display_name":"renal cell carcinoma","score":0.8659999966621399},{"id":"https://openalex.org/keywords/mtor-inhibition","display_name":"mTOR inhibition","score":0.8059999942779541},{"id":"https://openalex.org/keywords/bevacizumab","display_name":"bevacizumab","score":0.8299999833106995},{"id":"https://openalex.org/keywords/anti-vegf-therapy","display_name":"anti-VEGF therapy","score":0.9279999732971191},{"id":"https://openalex.org/keywords/akt","display_name":"Akt","score":0.5889999866485596},{"id":"https://openalex.org/keywords/mtorc1","display_name":"mTORC1","score":0.9089999794960022},{"id":"https://openalex.org/keywords/tyrosine-kinase-inhibitors","display_name":"tyrosine kinase inhibitors","score":0.9729999899864197},{"id":"https://openalex.org/keywords/immunotherapy","display_name":"immunotherapy","score":0.9549999833106995},{"id":"https://openalex.org/keywords/treatment-response-biomarkers","display_name":"treatment response biomarkers","score":0.7839999794960022},{"id":"https://openalex.org/keywords/germline-pten-mutation","display_name":"PTEN germline mutation","score":0.9049999713897705}],"concepts":[{"id":"https://openalex.org/C2777609662","wikidata":"https://www.wikidata.org/wiki/Q416356","display_name":"PTEN","level":4,"score":0.9753506183624268},{"id":"https://openalex.org/C2780846426","wikidata":"https://www.wikidata.org/wiki/Q1138188","display_name":"Cowden syndrome","level":5,"score":0.9622663259506226},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.6854867935180664},{"id":"https://openalex.org/C555283112","wikidata":"https://www.wikidata.org/wiki/Q1637543","display_name":"Carcinogenesis","level":3,"score":0.6276227235794067},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.58371901512146},{"id":"https://openalex.org/C13514818","wikidata":"https://www.wikidata.org/wiki/Q5552256","display_name":"Germline mutation","level":4,"score":0.5285975933074951},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.4921380877494812},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.490204393863678},{"id":"https://openalex.org/C2777277851","wikidata":"https://www.wikidata.org/wiki/Q1348398","display_name":"Cancer syndrome","level":5,"score":0.467099130153656},{"id":"https://openalex.org/C526584372","wikidata":"https://www.wikidata.org/wiki/Q16399","display_name":"Thyroid","level":2,"score":0.44429445266723633},{"id":"https://openalex.org/C109825262","wikidata":"https://www.wikidata.org/wiki/Q1139164","display_name":"Germline","level":3,"score":0.4334127604961395},{"id":"https://openalex.org/C526805850","wikidata":"https://www.wikidata.org/wiki/Q188874","display_name":"Colorectal cancer","level":3,"score":0.42215657234191895},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.42208003997802734},{"id":"https://openalex.org/C142724271","wikidata":"https://www.wikidata.org/wiki/Q7208","display_name":"Pathology","level":1,"score":0.3536651134490967},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.3504902124404907},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.27556872367858887},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.2205856740474701},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2014434039592743},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.10202044248580933},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.088284432888031}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.21614/sgo-588","doi":"https://doi.org/10.21614/sgo-588","is_oa":true,"landing_page_url":"http://dx.doi.org/10.21614/sgo-588","pdf_url":"https://www.sgo-iasgo.com/pdfs/2023-3-136.pdf","source":{"id":"https://openalex.org/S4210219519","display_name":"Surgery Gastroenterology and Oncology","issn_l":"2559-723X","issn":["2559-723X","2601-1700"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","poland-20","russia-white-list-4"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Surgery, Gastroenterology and Oncology","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.21614/sgo-588","doi":"https://doi.org/10.21614/sgo-588","is_oa":true,"landing_page_url":"http://dx.doi.org/10.21614/sgo-588","pdf_url":"https://www.sgo-iasgo.com/pdfs/2023-3-136.pdf","source":{"id":"https://openalex.org/S4210219519","display_name":"Surgery Gastroenterology and Oncology","issn_l":"2559-723X","issn":["2559-723X","2601-1700"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","poland-20","russia-white-list-4"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Surgery, Gastroenterology and Oncology","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":1.0,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[{"display_name":"Systematic Review","id":"https://openalex.org/study-designs/systematic-review"}],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4387489293.pdf","grobid_xml":"https://content.openalex.org/works/W4387489293.grobid-xml"},"referenced_works_count":37,"referenced_works":["https://openalex.org/W41491586","https://openalex.org/W1565533127","https://openalex.org/W1898346180","https://openalex.org/W1965766554","https://openalex.org/W1976760382","https://openalex.org/W1979068335","https://openalex.org/W2033526699","https://openalex.org/W2037716205","https://openalex.org/W2082431132","https://openalex.org/W2092599637","https://openalex.org/W2106893670","https://openalex.org/W2108270671","https://openalex.org/W2111044431","https://openalex.org/W2114725617","https://openalex.org/W2118263932","https://openalex.org/W2125229905","https://openalex.org/W2142762160","https://openalex.org/W2143654068","https://openalex.org/W2170406539","https://openalex.org/W2201379305","https://openalex.org/W2222086386","https://openalex.org/W2316224796","https://openalex.org/W2320668004","https://openalex.org/W2471094912","https://openalex.org/W2593030814","https://openalex.org/W2754303337","https://openalex.org/W2790574591","https://openalex.org/W2796207353","https://openalex.org/W2884170377","https://openalex.org/W2949788532","https://openalex.org/W2951540166","https://openalex.org/W2965915703","https://openalex.org/W2971987441","https://openalex.org/W2978502334","https://openalex.org/W3015009229","https://openalex.org/W4294358748","https://openalex.org/W6748880539"],"related_works":["https://openalex.org/W2092599637","https://openalex.org/W2950903616","https://openalex.org/W1996222881","https://openalex.org/W2760009361","https://openalex.org/W2056730502","https://openalex.org/W2078965966","https://openalex.org/W1967344183","https://openalex.org/W2170406539","https://openalex.org/W2908672406","https://openalex.org/W2107244229"],"abstract_inverted_index":{"Purpose:":[0],"Patients":[1],"with":[2,25,56,67,116,148],"Cowden":[3,57,117,157],"syndrome":[4,158],"(CS)":[5],"have":[6,47],"an":[7,35],"increased":[8],"lifetime":[9],"risk":[10],"of":[11,29,44,52,75,99,110,114,126,182,197,202],"developing":[12],"cancers,":[13],"particularly":[14],"breast,":[15],"uterus,":[16],"thyroid,":[17],"colon":[18],"and":[19,69,77,101,152,168,172],"renal":[20,85,149,160],"cell":[21,86,150,161],"cancer.CS":[22],"is":[23,128],"associated":[24,159],"a":[26,31,96,200],"germline":[27],"mutation":[28],"PTEN,":[30],"gene":[32],"that":[33,42,92,123,141],"plays":[34],"important":[36],"role":[37,196],"in":[38,54,65,133,146,191],"carcinogenesis.This":[39],"review":[40,61],"hypothesized":[41],"inactivation":[43],"PTEN":[45,76,93,127,198],"could":[46,164],"dramatic":[48],"consequences":[49],"on":[50,108],"response":[51,79,203],"treatments":[53,83],"patients":[55,147,163],"Syndrome.Methods:":[58],"This":[59],"systematic":[60],"has":[62],"been":[63],"reported":[64],"line":[66],"PRISMA":[68],"AMSTAR,":[70],"we":[71],"investigated":[72],"to":[73,80,139,193,204],"deficit":[74],"the":[78,124,131,142,180,195],"current":[81],"available":[82],"for":[84,112,130],"cancer":[87],"(RCC).Results:":[88],"Preclinical":[89],"studies":[90,106,188],"showed":[91],"loss":[94,125],"determinate":[95],"growth":[97,136],"level":[98],"AKT":[100],"mTORC1.For":[102],"this":[103],"reason,":[104],"many":[105],"focused":[107],"inhibition":[109],"mTOR":[111,167],"treatment":[113],"patient":[115],"Syndrome's.In":[118],"addition,":[119],"preclinical":[120],"data":[121],"demonstrated":[122],"responsible":[129],"increase":[132],"vascular":[134],"endothelial":[135],"factor":[137],"(VEGF),":[138],"suggest":[140],"VEGF":[143,170],"antibody":[144],"bevacizumab":[145],"carcinoma":[151,162],"CS":[153],"should":[154],"be":[155,185],"indicated.Conclusion:":[156],"benefit":[165],"from":[166],"anti":[169],"therapy,":[171],"potentially":[173],"also":[174],"by":[175],"tyrosine":[176],"kinase":[177],"inhibitors.Otherwise,":[178],"immunotherapy":[179],"use":[181],"would":[183],"not":[184],"recommended.However,":[186],"confirmatory":[187],"are":[189],"needed":[190],"order":[192],"define":[194],"as":[199],"biomarker":[201],"treatment.":[205]},"counts_by_year":[],"updated_date":"2026-10-30T12:39:25.321706","created_date":"2023-10-11T00:00:00"}