{"id":"https://openalex.org/W2973018133","doi":null,"title":"Defining and targeting combination immunotherapies in mouse models of cancer","display_name":"Defining and targeting combination immunotherapies in mouse models of cancer","publication_year":2019,"publication_date":"2019-06-28","ids":{"openalex":"https://openalex.org/W2973018133","mag":"2973018133"},"language":"en","primary_location":{"id":"pmh:oai:eprints.ucl.ac.uk.OAI2:10076051","doi":null,"is_oa":false,"landing_page_url":"https://discovery.ucl.ac.uk/id/eprint/10076051/","pdf_url":null,"source":{"id":"https://openalex.org/S4306400024","display_name":"UCL Discovery (University College London)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I45129253","host_organization_name":"University College London","host_organization_lineage":["https://openalex.org/I45129253"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Doctoral thesis, UCL (University College London).","raw_type":"Thesis"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5013096923","display_name":"Franz Demane","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Franz Demane","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5005610551","display_name":"Dafne Franz Demane","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Dafne Sofia","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.9980000257492065,"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/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.9980000257492065,"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/T10031","display_name":"T-cell and B-cell Immunology","score":0.0007999999797903001,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10580","display_name":"Immunotherapy and Immune Responses","score":0.0007999999797903001,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/inducible-t-cell-costimulator","display_name":"ICOS","score":0.7860000133514404},{"id":"https://openalex.org/keywords/icosl","display_name":"ICOSL","score":0.7260000109672546},{"id":"https://openalex.org/keywords/cancer-immunotherapy","display_name":"cancer immunotherapy","score":0.6690000295639038},{"id":"https://openalex.org/keywords/combination-immunotherapy","display_name":"combination immunotherapy","score":0.7540000081062317},{"id":"https://openalex.org/keywords/ctla-4-blockade","display_name":"CTLA-4 blockade","score":0.7770000100135803},{"id":"https://openalex.org/keywords/ipilimumab","display_name":"ipilimumab","score":0.9589999914169312},{"id":"https://openalex.org/keywords/antibody-isotypes","display_name":"antibody isotypes","score":0.5720000267028809},{"id":"https://openalex.org/keywords/fc-gamma-receptor","display_name":"Fc gamma receptor","score":0.6240000128746033},{"id":"https://openalex.org/keywords/tumor-microenvironment","display_name":"tumor microenvironment","score":0.628000020980835},{"id":"https://openalex.org/keywords/lung-cancer","display_name":"lung cancer","score":0.9049999713897705},{"id":"https://openalex.org/keywords/melanoma","display_name":"melanoma","score":0.8519999980926514},{"id":"https://openalex.org/keywords/anti-cd25","display_name":"anti-CD25","score":0.7570000290870667},{"id":"https://openalex.org/keywords/radiotherapy","display_name":"radiotherapy","score":0.4560000002384186},{"id":"https://openalex.org/keywords/chemotherapy","display_name":"chemotherapy","score":0.8050000071525574},{"id":"https://openalex.org/keywords/tumor-immunogenicity","display_name":"tumor immunogenicity","score":0.5950000286102295}],"concepts":[{"id":"https://openalex.org/C542903549","wikidata":"https://www.wikidata.org/wiki/Q422248","display_name":"Monoclonal antibody","level":3,"score":0.6067765355110168},{"id":"https://openalex.org/C154317977","wikidata":"https://www.wikidata.org/wiki/Q376266","display_name":"Cytotoxic T cell","level":3,"score":0.581307053565979},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5801441669464111},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.5763547420501709},{"id":"https://openalex.org/C2780868878","wikidata":"https://www.wikidata.org/wiki/Q1660197","display_name":"Immunogenicity","level":3,"score":0.5701473951339722},{"id":"https://openalex.org/C2781433595","wikidata":"https://www.wikidata.org/wiki/Q2459042","display_name":"Ipilimumab","level":4,"score":0.5664085149765015},{"id":"https://openalex.org/C2780674031","wikidata":"https://www.wikidata.org/wiki/Q2012719","display_name":"Cancer immunotherapy","level":4,"score":0.5392445921897888},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.5162013173103333},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.49831151962280273},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.4938078820705414},{"id":"https://openalex.org/C2778468042","wikidata":"https://www.wikidata.org/wiki/Q273976","display_name":"Blockade","level":3,"score":0.4931022822856903},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.4909122586250305},{"id":"https://openalex.org/C2776090121","wikidata":"https://www.wikidata.org/wiki/Q193529","display_name":"T cell","level":3,"score":0.4563283920288086},{"id":"https://openalex.org/C2776107976","wikidata":"https://www.wikidata.org/wiki/Q1786433","display_name":"Tumor microenvironment","level":3,"score":0.44654467701911926},{"id":"https://openalex.org/C159654299","wikidata":"https://www.wikidata.org/wiki/Q79460","display_name":"Antibody","level":2,"score":0.44602903723716736},{"id":"https://openalex.org/C2777658100","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Melanoma","level":2,"score":0.44184258580207825},{"id":"https://openalex.org/C147483822","wikidata":"https://www.wikidata.org/wiki/Q103537","display_name":"Antigen","level":2,"score":0.4191591143608093},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.27580809593200684},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.25178998708724976},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.13534298539161682},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.13227257132530212},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:eprints.ucl.ac.uk.OAI2:10076051","doi":null,"is_oa":false,"landing_page_url":"https://discovery.ucl.ac.uk/id/eprint/10076051/","pdf_url":null,"source":{"id":"https://openalex.org/S4306400024","display_name":"UCL Discovery (University College London)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I45129253","host_organization_name":"University College London","host_organization_lineage":["https://openalex.org/I45129253"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Doctoral thesis, UCL (University College London).","raw_type":"Thesis"},{"id":"mag:2973018133","doi":null,"is_oa":false,"landing_page_url":"https://discovery.ucl.ac.uk/id/eprint/10076051/","pdf_url":null,"source":{"id":"https://openalex.org/S4306508231","display_name":"Doctoral thesis, UCL (University College London).","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":"Doctoral thesis, UCL (University College London).","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":1.0,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":215,"referenced_works":["https://openalex.org/W100794221","https://openalex.org/W1480698358","https://openalex.org/W1520434148","https://openalex.org/W1538902372","https://openalex.org/W1545918761","https://openalex.org/W1602037964","https://openalex.org/W1617971067","https://openalex.org/W1635113215","https://openalex.org/W1661441964","https://openalex.org/W1667545291","https://openalex.org/W1752668680","https://openalex.org/W1767508090","https://openalex.org/W1838338895","https://openalex.org/W1863453661","https://openalex.org/W1863867804","https://openalex.org/W1868820697","https://openalex.org/W1913881492","https://openalex.org/W1939244106","https://openalex.org/W1941651450","https://openalex.org/W1962920088","https://openalex.org/W1964389846","https://openalex.org/W1965205681","https://openalex.org/W1970230889","https://openalex.org/W1971425687","https://openalex.org/W1972108403","https://openalex.org/W1972338421","https://openalex.org/W1978152737","https://openalex.org/W1979811833","https://openalex.org/W1980137951","https://openalex.org/W1981528932","https://openalex.org/W1981851073","https://openalex.org/W1982505108","https://openalex.org/W1983546578","https://openalex.org/W1983940041","https://openalex.org/W1985735048","https://openalex.org/W1985817960","https://openalex.org/W1986497348","https://openalex.org/W1987165863","https://openalex.org/W1988474688","https://openalex.org/W1988685761","https://openalex.org/W1992170557","https://openalex.org/W1992979622","https://openalex.org/W1994993231","https://openalex.org/W1997250936","https://openalex.org/W1998006783","https://openalex.org/W2001716606","https://openalex.org/W2004150448","https://openalex.org/W2004630197","https://openalex.org/W2006187748","https://openalex.org/W2012826189","https://openalex.org/W2013165543","https://openalex.org/W2013464021","https://openalex.org/W2016708646","https://openalex.org/W2016789384","https://openalex.org/W2026426963","https://openalex.org/W2026576427","https://openalex.org/W2027146979","https://openalex.org/W2029399624","https://openalex.org/W2032869058","https://openalex.org/W2034751554","https://openalex.org/W2035331552","https://openalex.org/W2040353461","https://openalex.org/W2041557663","https://openalex.org/W2042293669","https://openalex.org/W2042687451","https://openalex.org/W2044351980","https://openalex.org/W2046547447","https://openalex.org/W2046972425","https://openalex.org/W2048073154","https://openalex.org/W2048787440","https://openalex.org/W2049798004","https://openalex.org/W2050457398","https://openalex.org/W2054473251","https://openalex.org/W2054841768","https://openalex.org/W2056535502","https://openalex.org/W2057076190","https://openalex.org/W2057859692","https://openalex.org/W2059309195","https://openalex.org/W2061071534","https://openalex.org/W2063480372","https://openalex.org/W2064431192","https://openalex.org/W2065461308","https://openalex.org/W2068125497","https://openalex.org/W2068457469","https://openalex.org/W2070631889","https://openalex.org/W2071875829","https://openalex.org/W2073083233","https://openalex.org/W2076067786","https://openalex.org/W2076335749","https://openalex.org/W2076998084","https://openalex.org/W2082930742","https://openalex.org/W2083574998","https://openalex.org/W2083601592","https://openalex.org/W2084659308","https://openalex.org/W2086542713","https://openalex.org/W2088877484","https://openalex.org/W2093322080","https://openalex.org/W2093424661","https://openalex.org/W2093785165","https://openalex.org/W2094366129","https://openalex.org/W2097726328","https://openalex.org/W2097995306","https://openalex.org/W2098853737","https://openalex.org/W2099725888","https://openalex.org/W2100086637","https://openalex.org/W2100696012","https://openalex.org/W2101477183","https://openalex.org/W2101581360","https://openalex.org/W2101840064","https://openalex.org/W2104072610","https://openalex.org/W2104347254","https://openalex.org/W2104732141","https://openalex.org/W2106605927","https://openalex.org/W2107009614","https://openalex.org/W2107271904","https://openalex.org/W2107598346","https://openalex.org/W2108556253","https://openalex.org/W2108933323","https://openalex.org/W2110252240","https://openalex.org/W2111179508","https://openalex.org/W2112123471","https://openalex.org/W2112601576","https://openalex.org/W2112927491","https://openalex.org/W2114838127","https://openalex.org/W2117776343","https://openalex.org/W2118503880","https://openalex.org/W2118546263","https://openalex.org/W2119139416","https://openalex.org/W2121080857","https://openalex.org/W2123602110","https://openalex.org/W2128035403","https://openalex.org/W2128402413","https://openalex.org/W2128692203","https://openalex.org/W2128758225","https://openalex.org/W2131874142","https://openalex.org/W2133075384","https://openalex.org/W2134724142","https://openalex.org/W2136746908","https://openalex.org/W2136754957","https://openalex.org/W2138378181","https://openalex.org/W2139591061","https://openalex.org/W2141756397","https://openalex.org/W2142169541","https://openalex.org/W2143488332","https://openalex.org/W2143895308","https://openalex.org/W2144995154","https://openalex.org/W2145307016","https://openalex.org/W2145476394","https://openalex.org/W2148808612","https://openalex.org/W2149121521","https://openalex.org/W2149244682","https://openalex.org/W2152829491","https://openalex.org/W2155189639","https://openalex.org/W2155464214","https://openalex.org/W2157041114","https://openalex.org/W2164992400","https://openalex.org/W2166662937","https://openalex.org/W2168244200","https://openalex.org/W2172223853","https://openalex.org/W2187089797","https://openalex.org/W2218652881","https://openalex.org/W2221432805","https://openalex.org/W2228221433","https://openalex.org/W2252550602","https://openalex.org/W2264436110","https://openalex.org/W2282550179","https://openalex.org/W2319160167","https://openalex.org/W2334452812","https://openalex.org/W2338877604","https://openalex.org/W2395145382","https://openalex.org/W2397771749","https://openalex.org/W2398545566","https://openalex.org/W2419268404","https://openalex.org/W2466033276","https://openalex.org/W2468502134","https://openalex.org/W2508885742","https://openalex.org/W2509587195","https://openalex.org/W2510686645","https://openalex.org/W2514611659","https://openalex.org/W2529373149","https://openalex.org/W2535300095","https://openalex.org/W2535969070","https://openalex.org/W2537734913","https://openalex.org/W2565014445","https://openalex.org/W2567564314","https://openalex.org/W2567692508","https://openalex.org/W2568773821","https://openalex.org/W2587048937","https://openalex.org/W2587536205","https://openalex.org/W2592785733","https://openalex.org/W2605569733","https://openalex.org/W2607137647","https://openalex.org/W2616838116","https://openalex.org/W2618641368","https://openalex.org/W2691659998","https://openalex.org/W2749771768","https://openalex.org/W2750364489","https://openalex.org/W2753529762","https://openalex.org/W2753947930","https://openalex.org/W2758701828","https://openalex.org/W2761081415","https://openalex.org/W2767731416","https://openalex.org/W2784868445","https://openalex.org/W2790743957","https://openalex.org/W2793901188","https://openalex.org/W2797675588","https://openalex.org/W2801251503","https://openalex.org/W2807361763","https://openalex.org/W2808601843","https://openalex.org/W2886426705","https://openalex.org/W2886878155","https://openalex.org/W2887667630","https://openalex.org/W2889599863","https://openalex.org/W2891422389","https://openalex.org/W4313347784"],"related_works":["https://openalex.org/W4313383070","https://openalex.org/W2504565138","https://openalex.org/W2406367608","https://openalex.org/W3178377958","https://openalex.org/W2547551854","https://openalex.org/W2792738565","https://openalex.org/W3083158526","https://openalex.org/W2141756397","https://openalex.org/W2157041114","https://openalex.org/W2185355094"],"abstract_inverted_index":{"Checkpoint":[0],"blockade":[1],"has":[2,244],"achieved":[3],"long-lasting":[4],"anti-tumour":[5],"responses,":[6],"unfortunately":[7],"this":[8,326,380],"is":[9,394],"limited":[10,252],"to":[11,72,253,357,372,409],"a":[12,39,161],"fraction":[13],"of":[14,32,55,61,66,69,84,88,97,118,133,235,238,261,265,280,316,331,354,400,403,405],"patients,":[15,368],"highlighting":[16],"the":[17,27,59,62,86,95,116,131,137,180,233,245,259,278,281,303,329,332,340,351,385,398,401],"need":[18],"for":[19,42,396],"more":[20],"effective":[21],"therapies.":[22,169],"This":[23],"thesis":[24,381],"focuses":[25],"on":[26,319],"rational":[28],"proposal":[29],"and":[30,48,57,79,182,202,226,269,286,296,305,314,322,408],"design":[31,225],"new":[33,228],"cancer":[34,243,406],"immunotherapies":[35,407],"through:":[36],"(1)":[37],"proposing":[38],"novel":[40],"immunomodulatory-target":[41],"cancer-immunotherapy,":[43],"Inducible":[44],"T-cell":[45,186],"co-stimulator":[46],"(ICOS),":[47],"studying":[49],"its":[50],"efficacy":[51,96],"in":[52,91,115,136,164,179,221,277,301,339,367,379,384],"murine":[53],"models":[54,68,83,237,264,356],"cancer;":[56],"(2)":[58],"description":[60],"immune":[63],"tumour-microenvironment":[64],"(TME)":[65],"mouse":[67,236,263],"lung":[70,239,242,266],"cancer,":[71],"propose":[73],"strategies":[74,371],"that":[75,105,123,142,173,183,209,391],"promote":[76,130,157,289],"increased":[77],"immunogenicity":[78],"tumour":[80],"rejection.":[81],"In":[82],"melanoma,":[85],"absence":[87],"ICOS/ICOSL":[89],"pathway":[90],"ICOS-/-":[92],"mice,":[93],"impaired":[94],"anti-CTLA-4":[98],"(Cytotoxic":[99],"T-lymphocyte":[100],"antigen-4)":[101],"therapy.":[102],"Additionally,":[103],"patients":[104],"received":[106],"ipilimumab":[107],"(anti-CTLA-4)":[108],"monoclonal":[109],"antibody":[110,168],"(mAb)":[111],"had":[112],"an":[113,124,143],"increase":[114],"frequency":[117],"ICOS+":[119],"T-cells.":[120,324],"We":[121,170,271],"hypothesised":[122],"agonistic":[125,144],"non-depleting":[126],"anti-ICOS":[127,145,175,184,203,213],"mAb":[128,204,295,298],"will":[129],"function":[132],"activated":[134],"T-cells":[135,178],"TME.":[138],"Here":[139,256],"we":[140,231,257],"show":[141],"mAb,":[146],"with":[147,166,205,212,250,293,370],"either":[148,159],"mIgG1":[149,185],"(non-depleting)":[150],"or":[151,163],"mIgG2a":[152],"(depleting)":[153],"isotype,":[154],"does":[155],"not":[156,273],"survival,":[158],"as":[160],"monotherapy":[162],"combination":[165,229,291,327],"other":[167],"also":[171],"showed":[172],"both":[174,302,355],"isotypes":[176],"eliminated":[177],"TME":[181,260,279],"elimination":[187],"was":[188,299],"Fc-engagement":[189],"independent.":[190],"These":[191],"results":[192],"were":[193,337],"replicated":[194],"using":[195],"mice":[196],"expressing":[197],"human":[198,206],"Fc\u03b3":[199],"receptors":[200],"(Fc\u03b3Rs)":[201],"(h)IgGs,":[207],"demonstrating":[208],"anti-cancer":[210],"therapy":[211,292],"mAbs":[214],"should":[215],"be":[216],"carefully":[217],"evaluated":[218,300],"before":[219],"use":[220],"clinical":[222],"trials.":[223],"To":[224,288],"test":[227],"therapies,":[230,389],"described":[232,258],"immune-TME":[234,386],"cancer.":[240],"Currently,":[241],"highest":[246],"mortality":[247],"among":[248],"cancers,":[249],"immunotherapy-benefit":[251],"some":[254],"patients.":[255],"two":[262],"cancer:":[267],"KPB6.F1":[268,282,304,341],"CMT-167.":[270],"did":[272],"find":[274],"significant":[275],"differences":[276,336,345],"model":[283],"after":[284],"radiotherapy":[285],"chemotherapy.":[287],"immunogenicity,":[290],"anti-CD25":[294],"anti-4-1BB":[297],"CMT-167":[306,333],"models.":[307],"Anti-4-1BB":[308],"promoted":[309],"proliferation,":[310],"granzyme":[311],"B":[312],"production":[313],"expression":[315],"activation":[317],"markers":[318],"effector":[320],"CD4+":[321],"CD8+":[323],"Whilst":[325],"reduced":[328],"tumour-burden":[330],"model,":[334,342],"no":[335],"observed":[338],"suggesting":[343,390],"intrinsic":[344],"between":[346],"them.":[347],"Further":[348],"work":[349,377],"describing":[350],"differential":[352],"response":[353],"specific":[358],"therapies":[359],"could":[360],"provide":[361],"important":[362],"information":[363],"regarding":[364],"resistant":[365],"tumours":[366],"together":[369],"overcome":[373],"those":[374],"resistances.":[375],"The":[376],"presented":[378],"describes":[382],"variations":[383],"following":[387],"different":[388],"further":[392],"investigation":[393],"crucial":[395],"understanding":[397],"biology":[399],"mechanism":[402],"action":[404],"improve":[410],"their":[411],"efficacy.":[412]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2019-09-19T00:00:00"}
