{"doi":"10.3390/v16111715","title":"Spectrum of Non-Nucleoside Reverse Transcriptase Inhibitor-Associated Drug Resistance Mutations in Persons Living with HIV-1 Receiving Rilpivirine","abstract":"INTRODUCTION: Few data are currently available on the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) resistance mutations selected in persons living with HIV-1 (PLWH) who develop virological failure while receiving rilpivirine (RPV). METHODS: We analyzed pooled HIV-1 RT genotypic data from 280 PLWH in the multicenter EuResist database and 115 PLWH in the Stanford HIV Drug Resistance Database (HIVDB) who received RPV as their only NNRTI. RESULTS: Among the 395 PLWH receiving RPV, 180 (45.6%) had one or more NNRTI-associated DRMs. Overall, 44 NNRTI-associated DRMs were identified, including 26 that occurred in two or more PLWHs. Seven mutations had a prevalence ≥10% among the 180 PLWH with one or more NNRTI-associated DRM: E138K (32.2%), V90I (25.0%), K101E (17.8%), Y181C (17.2%), E138A (13.9%), H221Y (12.2%), and K103N (10.6%). Y181C was significantly more likely to co-occur with K101E, V179F, H221Y, and M230L. Ten novel non-polymorphic mutations at known NNRTI-associated mutation positions were also identified, usually in just one PLWH: L100F, V108A, T139I, P225S, M230V, Y232C, and T240A/I/M/S. CONCLUSIONS: Our analysis extends the spectrum of mutations emerging in PLWH receiving RPV. Additional phenotypic characterization of RPV-selected mutations is necessary to better understand their biological and possible clinical significance.","journal":"Viruses","year":2024,"id":466659,"datarank":0.36316202221403754,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.12174633534892244,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.12174633534892244,"corpus_percentile":50.916686006033885,"corpus_rank":6346,"citation_count":4,"citer_count":3,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.5265,"is_data_producer":true,"deposit_databanks":{"GENBANK":["PQ368914-PQ369225"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":45.8333,"fair_percentile":59.49250993579945,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1261742,"name":"Jinru Zhou","orcid":null,"position":1,"is_corresponding":false},{"id":1298812,"name":"Giulia Di Teodoro","orcid":"0000-0002-0418-0067","position":2,"is_corresponding":false},{"id":1258504,"name":"Francesca Incardona","orcid":"0000-0002-7386-8551","position":3,"is_corresponding":false},{"id":776385,"name":"Carole Seguin‐Devaux","orcid":"0000-0003-0636-5222","position":4,"is_corresponding":false},{"id":792885,"name":"Rolf Kaiser","orcid":"0000-0002-2640-2548","position":5,"is_corresponding":false},{"id":295651,"name":"Ana Abecasis","orcid":"0000-0002-3903-5265","position":6,"is_corresponding":false},{"id":1298813,"name":"Perpétua Gómes","orcid":"0000-0003-3271-8255","position":7,"is_corresponding":false},{"id":555836,"name":"Kaiming Tao","orcid":"0000-0001-8731-1271","position":8,"is_corresponding":false},{"id":370715,"name":"Maurizio Zazzi","orcid":"0000-0002-0344-6281","position":9,"is_corresponding":false},{"id":14780,"name":"Robert W. Shafer","orcid":"0000-0003-2513-2643","position":10,"is_corresponding":false},{"id":1152750,"name":"Pavithra Nagarajan","orcid":"0000-0002-0036-9970","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T02:05:06.743102Z","pmid":"39599830","pmcid":"PMC11599002","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":77.7778,"fair_a":37.5,"fair_i":0.0,"fair_r":8.3333,"fair_zscore":0.4506,"fair_rationale":{"fair_score":45.83,"has_llm":true,"taxonomy_version":"fair_taxonomy_v5","dimensions":{"F":{"name":"Findable","score":77.78,"criteria":[{"key":"f_dataset_pid","label":"Persistent identifier for the data","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"GenBank PQ368914-PQ369225","grounded":true,"rationale":"The paper provides GenBank accession numbers, which are persistent identifiers. [majority verdict 'yes' (3/5 passes agreed)]","anchors":["RDA-F1-01D — FAIR Data Maturity Model: 'Data is identified by a persistent identifier' (priorit","RDA-F1-02D — FAIR Data Maturity Model: 'Data is identified by a globally unique identifier'","FsF-F1-02D — F-UJI/FAIRsFAIR: 'Data is assigned a persistent identifier'"],"scored":true,"signal":null},{"key":"f_repository_named","label":"Named repository","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"GenBank","grounded":true,"rationale":"The paper names GenBank, a community-standard repository, as the holder of the nucleotide sequences. [majority verdict 'yes' (3/5 passes agreed)]","anchors":["RDA-F4-01M — FAIR Data Maturity Model: metadata is offered so it can be harvested and indexed (","NIH DMS Policy Element 4 (NOT-OD-21-014) — name the repository where data will be archived","NSTC Desirable Characteristics of Data Repositories (2022) — 'Long-Term Sustainability', 'Reten"],"scored":true,"signal":null},{"key":"f_data_availability_statement","label":"Data-availability statement","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"Previously unpublished nucleotide sequences are available at GenBank PQ368914-PQ369225 . Access to data from the EuResist Network is subject to certain restrictions. 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[majority verdict 'yes' (3/5 passes agreed)]","anchors":["Colavizza, Hrynaszkiewicz, Staden, Whitaker & McGillivray (2020), 'The citation advantage of li","Springer Nature research data policy — Data Availability Statements: standard statement templat","RDA-F3-01M — metadata clearly and explicitly includes the identifier of the data it describes"],"scored":false,"signal":null},{"key":"f_discovery_metadata","label":"Description of the dataset as an object","kind":"llm","weight":2.0,"fraction":0.5,"verdict":"partial","evidence":"The EIDB contained 320 RT sequences from 280 previously NNRTI-naïve PLWH who received an RPV-containing regimen.","grounded":true,"rationale":"The dataset's content is described in a sentence in the results, not in an itemised inventory. [majority verdict 'partial' (4/5 passes agreed)]","anchors":["RDA-F2-01M — 'Rich metadata is provided to allow discovery' (priority Essential)","FsF-F2-01M — F-UJI: 'Metadata includes descriptive core elements to support data findability'","FsF-R1-01MD — F-UJI: 'Metadata specifies the content of the data'"],"scored":false,"signal":null},{"key":"f_dataset_cited","label":"Dataset formally cited","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":"Previously unpublished nucleotide sequences are available at GenBank PQ368914-PQ369225.","grounded":false,"rationale":"The dataset identifier appears only in the body text, not as a reference list entry. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","anchors":["FORCE11 Joint Declaration of Data Citation Principles (2014) — data should be cited as a first-","RDA-F3-01M — metadata clearly and explicitly includes the identifier of the data it describes","FsF-F3-01M — F-UJI: 'Metadata includes the identifier of the data it describes'"],"scored":true,"signal":null}]},"A":{"name":"Accessible","score":37.5,"criteria":[{"key":"a_data_openly_accessible","label":"Access route free of preconditions","kind":"llm","weight":2.0,"fraction":0.5,"verdict":"partial","evidence":"Previously unpublished nucleotide sequences are available at GenBank PQ368914-PQ369225.","grounded":false,"rationale":"The text gives a route to the data with no stated precondition. [downgraded to 'partial' — no verifiable quote from the paper] [majority verdict 'partial' (4/5 passes agreed)]","anchors":["RDA-A1.1-01D — 'Data is accessible through a free access protocol'","FsF-A1-01M — F-UJI: 'Metadata contains access level and access conditions of the data'","NSTC Desirable Characteristics of Data Repositories (2022) — 'Free and Easy Access'"],"scored":true,"signal":null},{"key":"a_access_conditions_stated","label":"Access level labelled","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":"Previously unpublished nucleotide sequences are available at GenBank PQ368914-PQ369225.","grounded":false,"rationale":"The paper states the data are available at GenBank but does not use an explicit access-level label. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (3/5 passes agreed)]","anchors":["FsF-A1-01M — F-UJI: 'Metadata contains access level and access conditions of the data'","RDA-A1-01M — metadata contains information to enable the user to get access to the data","COAR Controlled Vocabularies — Access Rights v1.0 (open / embargoed / restricted / metadata-onl"],"scored":false,"signal":null},{"key":"a_controlled_access_for_sensitive","label":"Gatekeeper for sensitive data","kind":"llm","weight":0.5,"fraction":1.0,"verdict":"yes","evidence":"Access to data from the EuResist Network is subject to certain restrictions. They can be requested by submitting a study application form available at https://www.euresist.org/become-a-partner (last accessed 28 October 2024), pending approval from the EuResist Network.","grounded":true,"rationale":"The paper's restricted data component (EuResist Network) names an institutional gatekeeper (the EuResist Network) with a formal application process. [majority verdict 'yes' (3/5 passes agreed)]","anchors":["NIH Genomic Data Sharing Policy (NOT-OD-14-124) — controlled-access via a Data Access Committee","RDA-A1.2-01D — 'Data is accessible through an access protocol that supports authentication and ","NIH DMS Policy Element 5 (NOT-OD-21-014) — Access, Distribution, or Reuse Considerations (conse"],"scored":false,"signal":null},{"key":"a_timeline_retention","label":"Availability timing & retention","kind":"llm","weight":0.5,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No temporal commitment is stated for the data. [majority verdict 'no' (4/5 passes agreed)]","anchors":["NIH DMS Plan Element 4 (NOT-OD-21-014) — Data Preservation, Access, and Associated Timelines","NSTC Desirable Characteristics (2022), Organizational Infrastructure: 'Retention Policy'","RDA-A2-01M — 'Metadata is guaranteed to remain available after data is no longer available'"],"scored":false,"signal":null}]},"I":{"name":"Interoperable","score":0.0,"criteria":[{"key":"i_open_nonproprietary_format","label":"Open file format","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No file format token is named for the released data.","anchors":["FsF-R1.3-02D — F-UJI: 'Data is available in a file format recommended by the target research co","RDA-R1.3-02D — data is expressed in a machine-understandable community standard","RDA-I1-01D — data uses a knowledge representation expressed in a standardised format"],"scored":true,"signal":null},{"key":"i_community_standard_vocabulary","label":"Community standard / vocabulary","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No community standard is named as being applied to the data. [majority verdict 'no' (2/5 passes agreed)]","anchors":["RDA-R1.3-01M — 'Metadata complies with a community standard' (priority Essential)","RDA-R1.3-01D — 'Data complies with a community standard'","RDA-I2-01M — '(Meta)data use vocabularies that follow FAIR principles'"],"scored":false,"signal":null},{"key":"i_qualified_references","label":"Identifiers for the resources the data depend on","kind":"llm","weight":0.5,"fraction":0.0,"verdict":"no","evidence":"2zd1","grounded":false,"rationale":"The paper gives the PDB identifier 2zd1 for the crystal structure used in the analysis. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","anchors":["RDA-I3-01M — '(meta)data include references to other (meta)data'","RDA-I3-03M — 'metadata includes qualified references to other metadata'","FsF-I3-01M — F-UJI: 'Metadata includes links between the data and its related entities'"],"scored":false,"signal":null}]},"R":{"name":"Reusable","score":8.33,"criteria":[{"key":"r_reuse_license","label":"Reuse licence","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No licence is named for the data.","anchors":["RDA-R1.1-01M — 'Metadata includes information about the licence under which the data can be reu","RDA-R1.1-02M — 'Metadata refers to a standard reuse licence'","RDA-R1.1-03M — 'Metadata refers to a machine-understandable reuse licence'"],"scored":true,"signal":null},{"key":"r_provenance_methods","label":"Provenance of the data","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":"All sequences were submitted to the HIVDB genotypic resistance interpretation program to extract the following information: (1) the positions in RT that were sequenced; (2) HIV-1 subtype; (3) the number of stop codons, deletion mutations, and signature APOBEC mutations; (4) the mutations assigned a mutation penalty score for any NNRTI; and (5) non-polymorphic mutations that did not receive a mutation penalty score but have been previously reported to be significantly more common in NNRTI-experienced compared with NNRTI-naïve persons, which we refer to as unscored non-polymorphic NNRTI-selected mutations.","grounded":false,"rationale":"The paper describes the analysis steps generically without naming specific instruments or kits. 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'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No licence is named for the data.","gain":16.67,"priority":"essential","scored":true},{"key":"a_data_openly_accessible","dimension":"A","label":"Access route free of preconditions","action":"Remove the precondition or justify it. Release the data at publication with no embargo, no registration wall, and no approval step — NIH's zero-embargo public- access rule (NOT-OD-25-101) has already made 'available at publication' the federal baseline for the article; the data should not lag behind it. For genomics / sequencing data, deposit in GEO (GSE accession), SRA (SRP/SRR) or ENA/BioProject (PRJEB/PRJNA).","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Previously unpublished nucleotide sequences are available at GenBank PQ368914-PQ369225.","why":"The text gives a route to the data with no stated precondition. [downgraded to 'partial' — no verifiable quote from the paper] [majority verdict 'partial' (4/5 passes agreed)]","gain":8.33,"priority":"essential","scored":true},{"key":"f_dataset_cited","dimension":"F","label":"Dataset formally cited","action":"Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. Cite the genomics / sequencing repository accession (e.g. from GEO (GSE accession), SRA (SRP/SRR) or ENA/BioProject (PRJEB/PRJNA)) in the reference list.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"Previously unpublished nucleotide sequences are available at GenBank PQ368914-PQ369225.","why":"The dataset identifier appears only in the body text, not as a reference list entry. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","gain":8.33,"priority":"important","scored":true},{"key":"i_open_nonproprietary_format","dimension":"I","label":"Open file format","action":"Release the data in an open, community-standard format (CSV/TSV, JSON, HDF5, NetCDF, FASTQ, VCF, NIfTI…) instead of — or alongside — any proprietary or instrument-native format, and name the format in the paper. A dataset that needs a €2,000 licence to open is not reusable. Prefer open genomics / sequencing formats such as FASTQ, BAM or VCF.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No file format token is named for the released data.","gain":8.33,"priority":"important","scored":true},{"key":"x_code_availability","dimension":"R","label":"Analysis code available","action":"Publish the analysis code in a public forge, archive a tagged release with a DOI (Zenodo/Software Heritage), and cite that DOI in the paper. NIH DMS Element 2 asks for the tools and code, not only the data — and 'available on request' is not a locator. Archive the analysis code in a versioned repository (GitHub + a Zenodo release DOI).","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No code availability is mentioned.","gain":8.33,"priority":"important","scored":true},{"key":"r_versioning","dimension":"R","label":"Snapshot identified","action":"Version the deposit and cite the exact version analysed (a version-specific DOI, or an accession with its version suffix). A reader reproducing your work against 'the current release' is reproducing it against a different dataset.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No version token or date is given for the data.","gain":4.17,"priority":"useful","scored":true},{"key":"f_discovery_metadata","dimension":"F","label":"Description of the dataset as an object","action":"Add a 'Data Records' section: itemise every file in the deposit and every variable or sample it holds, with counts and units. Describe the dataset as an object in its own right, not as a by-product of the findings — this is what makes it discoverable to someone who is not looking for your paper.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"The EIDB contained 320 RT sequences from 280 previously NNRTI-naïve PLWH who received an RPV-containing regimen.","why":"The dataset's content is described in a sentence in the results, not in an itemised inventory. [majority verdict 'partial' (4/5 passes agreed)]","gain":0.0,"priority":"essential","scored":false},{"key":"a_access_conditions_stated","dimension":"A","label":"Access level labelled","action":"State the access level in words, using the standard vocabulary: 'These data are open access' / 'These data are controlled access'. A reader — and a harvester — should not have to infer the access level from the presence of a download link.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"Previously unpublished nucleotide sequences are available at GenBank PQ368914-PQ369225.","why":"The paper states the data are available at GenBank but does not use an explicit access-level label. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (3/5 passes agreed)]","gain":0.0,"priority":"important","scored":false},{"key":"i_community_standard_vocabulary","dimension":"I","label":"Community standard / vocabulary","action":"Adopt and NAME your domain's data standard — the minimum-information checklist, metadata schema, or ontology your community uses (MIAME/MINSEQE, ISA-Tab, BIDS, an OBO ontology, HL7 FHIR/OMOP) — and say which one you followed. A reporting checklist standardises your paper; it does nothing for your data. In genomics / sequencing, describe the data with MIAME, MINSEQE or MIxS.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No community standard is named as being applied to the data. [majority verdict 'no' (2/5 passes agreed)]","gain":0.0,"priority":"important","scored":false},{"key":"r_provenance_methods","dimension":"R","label":"Provenance of the data","action":"Name the instruments, kits, and software — with versions — that produced the data, not just the verbs. 'Reads were aligned' is not provenance; 'aligned with STAR v2.7.9a to GRCh38' is, because someone else can rerun it.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"All sequences were submitted to the HIVDB genotypic resistance interpretation program to extract the following information: (1) the positions in RT that were sequenced; (2) HIV-1 subtype; (3) the number of stop codons, deletion mutations, and signature APOBEC mutations; (4) the mutations assigned a mutation penalty score for any NNRTI; and (5) non-polymorphic mutations that did not receive a mutation penalty score but have been previously reported to be significantly more common in NNRTI-experienced compared with NNRTI-naïve persons, which we refer to as unscored non-polymorphic NNRTI-selected mutations.","why":"The paper describes the analysis steps generically without naming specific instruments or kits. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","gain":0.0,"priority":"important","scored":false},{"key":"r_documentation_codebook","dimension":"R","label":"Documentation / codebook","action":"Ship a README and a data dictionary IN the deposit — every file, every variable, its units, its allowed values, its missing-value codes. It is the cheapest single thing that makes a dataset usable by someone who was not in the lab, and a table buried in the article does not travel with the data.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No documentation object is named as accompanying the data.","gain":0.0,"priority":"important","scored":false},{"key":"i_qualified_references","dimension":"I","label":"Identifiers for the resources the data depend on","action":"Cite by identifier every resource the data depend on — the source datasets' accessions, the reference build (GRCh38 / GCA_000001405.28), the cohort application number, the code DOI — and register those relations on the dataset record (IsDerivedFrom, IsSupplementTo). A name is not a link: it cannot be resolved, versioned, or followed by a machine.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"2zd1","why":"The paper gives the PDB identifier 2zd1 for the crystal structure used in the analysis. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","gain":0.0,"priority":"useful","scored":false},{"key":"a_timeline_retention","dimension":"A","label":"Availability timing & retention","action":"State when the data become available AND how long they will be retained — cite the repository's preservation policy. NIH DMS Element 4 asks for both; most papers give neither.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No temporal commitment is stated for the data. [majority verdict 'no' (4/5 passes agreed)]","gain":0.0,"priority":"useful","scored":false}],"suggestions":["Attach a standard, machine-readable open licence to the deposit — CC0 or CC BY, which is what Horizon Europe and most funders expect — and print the licence identifier in the paper. 'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","Remove the precondition or justify it. Release the data at publication with no embargo, no registration wall, and no approval step — NIH's zero-embargo public- access rule (NOT-OD-25-101) has already made 'available at publication' the federal baseline for the article; the data should not lag behind it. For genomics / sequencing data, deposit in GEO (GSE accession), SRA (SRP/SRR) or ENA/BioProject (PRJEB/PRJNA).","Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. Cite the genomics / sequencing repository accession (e.g. from GEO (GSE accession), SRA (SRP/SRR) or ENA/BioProject (PRJEB/PRJNA)) in the reference list.","Release the data in an open, community-standard format (CSV/TSV, JSON, HDF5, NetCDF, FASTQ, VCF, NIfTI…) instead of — or alongside — any proprietary or instrument-native format, and name the format in the paper. A dataset that needs a €2,000 licence to open is not reusable. Prefer open genomics / sequencing formats such as FASTQ, BAM or VCF.","Publish the analysis code in a public forge, archive a tagged release with a DOI (Zenodo/Software Heritage), and cite that DOI in the paper. NIH DMS Element 2 asks for the tools and code, not only the data — and 'available on request' is not a locator. Archive the analysis code in a versioned repository (GitHub + a Zenodo release DOI)."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v8","fulltext_source":"epmc_xml"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v8","fair_fulltext_source":"epmc_xml","fair_has_llm":true,"fair_computed_at":"2026-07-20T13:04:58.736379Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}