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pmid:37006305

Analysis of potential immune-related genes involved in the pathogenesis of ischemia-reperfusion injury following liver transplantation.

Jiayu Guo · Shangting Han · Qi Chen · Tianyu Wang · Bo Yu · Jiangqiao Zhou · Tao Qiu

Frontiers in immunology · 2023 doi:10.3389/fimmu.2023.1126497

Paper

complete

Experiment

complete

Data

partial

Analysis

complete

Execution

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title
Analysis of potential immune-related genes involved in the pathogenesis of ischemia-reperfusion injury following liver transplantation.
doi
10.3389/fimmu.2023.1126497
pmid
37006305
authors array · 7 items
[0]
Jiayu Guo
[1]
Shangting Han
[2]
Qi Chen
[3]
Tianyu Wang
[4]
Bo Yu
[5]
Jiangqiao Zhou
[6]
Tao Qiu
journal
Frontiers in immunology
year
2023
abstract
Background: Hepatic ischemia-reperfusion (I/R) injury is an unavoidable pathological process that occurs after liver transplantation. However, the immune-related molecular mechanism still remains unclear. This study aims to further explore the biological mechanisms of immune-related genes in hepatic I/R injury. Methods: Gene microarray data was downloaded from the Gene Expression Omnibus (GEO) expression profile database and the differentially expressed genes (DEGs) were taken for intersection. After identifying common DEGs, functional annotation, protein-protein interaction (PPI) network, and modular construction were performed. The immune-related hub genes were obtained, which their upstream transcription factors and non-RNAs were predicted. Validation of the hub genes expression and immune infiltration were performed in a mouse model of hepatic I/R injury. Results: A total of 71 common DEGs were obtained from three datasets (GSE12720, GSE14951, GSE15480). The GO and KEGG enrichment analysis results indicated that immune and inflammatory response played an important role in hepatic I/R injury. Finally, 9 immune-related hub genes were identified by intersecting cytoHubba with immune-related genes, including SOCS3, JUND, CCL4, NFKBIA, CXCL8, ICAM1, IRF1, TNFAIP3, and JUN. Conclusion: Our study revealed the importance of the immune and inflammatory response in I/R injury following liver transplantation and provided new insights into the therapeutic of hepatic I/R injury.
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The three raw datasets were downloaded using the R “GEOquery” package, and then performed gene annotation, gene filtering, normalization, etc. on the three datasets. The differentially expressed genes (DEGs) were analyzed and compared between the pre-ischemic and reperfused liver tissue controls using the R “limma” package. Only those genes with adjusted P-value < 0.05 and |log2FC (fold change)| ≥ 0.5 were considered DEGs.
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The three raw datasets were downloaded using the R “GEOquery” package, and then performed gene annotation, gene filtering, normalization, etc. on the three datasets. The differentially expressed genes (DEGs) were analyzed and compared between the pre-ischemic and reperfused liver tissue controls using the R “limma” package. Only those genes with adjusted P-value < 0.05 and |log2FC (fold change)| ≥ 0.5 were considered DEGs.
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Publicly available datasets were analyzed in this study. This data can be found here: immune-related gene (http://www.immport.org/) and the Gene expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) (Accession: GSE12720, GSE14951 and GSE15480).
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and immune infiltration were performed in a mouse model of hepatic I/R injury. Results: A total of 7
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and immune infiltration were performed in a mouse model of hepatic I/R injury. Results: A tota
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of the Renmin hospital of Wuhan University. Mice were kept in an air-filtered, temperature-control
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The three raw datasets were downloaded using the R “GEOquery” package, and then performed gene annotation, gene filtering, normalization, etc. on the three datasets. The differentially expressed genes (DEGs) were analyzed and compared between the pre-ischemic and reperfused liver tissue controls using the R “limma” package. Only those genes with adjusted P-value < 0.05 and |log2FC (fold change)| ≥ 0.5 were considered DEGs.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37006305", "kind": "science-record", "revision": 4, "content_hash": "sha256:a42772040621d7e8027df807e59388be273de848811bb18f694951cb1d90b26d", "created_at": "2026-11-01T19:01:39Z", "updated_at": "2026-11-01T22:51:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis of potential immune-related genes involved in the pathogenesis of ischemia-reperfusion injury following liver transplantation.", "doi": "10.3389/fimmu.2023.1126497", "pmid": "37006305", "authors": ["Jiayu Guo", "Shangting Han", "Qi Chen", "Tianyu Wang", "Bo Yu", "Jiangqiao Zhou", "Tao Qiu"], "journal": "Frontiers in immunology", "year": 2023, "abstract": "Background: Hepatic ischemia-reperfusion (I/R) injury is an unavoidable pathological process that occurs after liver transplantation. However, the immune-related molecular mechanism still remains unclear. This study aims to further explore the biological mechanisms of immune-related genes in hepatic I/R injury.\nMethods: Gene microarray data was downloaded from the Gene Expression Omnibus (GEO) expression profile database and the differentially expressed genes (DEGs) were taken for intersection. After identifying common DEGs, functional annotation, protein-protein interaction (PPI) network, and modular construction were performed. The immune-related hub genes were obtained, which their upstream transcription factors and non-RNAs were predicted. Validation of the hub genes expression and immune infiltration were performed in a mouse model of hepatic I/R injury.\nResults: A total of 71 common DEGs were obtained from three datasets (GSE12720, GSE14951, GSE15480). The GO and KEGG enrichment analysis results indicated that immune and inflammatory response played an important role in hepatic I/R injury. Finally, 9 immune-related hub genes were identified by intersecting cytoHubba with immune-related genes, including SOCS3, JUND, CCL4, NFKBIA, CXCL8, ICAM1, IRF1, TNFAIP3, and JUN.\nConclusion: Our study revealed the importance of the immune and inflammatory response in I/R injury following liver transplantation and provided new insights into the therapeutic of hepatic I/R injury.", "claims": [{"id": "claim-method", "statement": "The three raw datasets were downloaded using the R “GEOquery” package, and then performed gene annotation, gene filtering, normalization, etc. on the three datasets. The differentially expressed genes (DEGs) were analyzed and compared between the pre-ischemic and reperfused liver tissue controls using the R “limma” package. Only those genes with adjusted P-value < 0.05 and |log2FC (fold change)| ≥ 0.5 were considered DEGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37006305", "locator": "sections[4] \"Differential expression analysis\" paragraph 2", "quote": "The three raw datasets were downloaded using the R “GEOquery” package, and then performed gene annotation, gene filtering, normalization, etc. on the three datasets. The differentially expressed genes (DEGs) were analyzed and compared between the pre-ischemic and reperfused liver tissue controls using the R “limma” package. Only those genes with adjusted P-value < 0.05 and |log2FC (fold change)| ≥ 0.5 were considered DEGs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: immune-related gene (http://www.immport.org/) and the Gene expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) (Accession: GSE12720, GSE14951 and GSE15480).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37006305", "locator": "sections[27] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: immune-related gene (http://www.immport.org/) and the Gene expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) (Accession: GSE12720, GSE14951 and GSE15480)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 71 common DEGs were obtained from three datasets (GSE12720, GSE14951, GSE15480).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37006305", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 71 common DEGs were obtained from three datasets (GSE12720, GSE14951, GSE15480)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 71 common DEGs were obtained from three datasets (GSE12720, GSE14951, GSE15480).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37006305"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE12720"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE12720"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37006305", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2023.1126497", "sha256": "sha256:2822c1aa8764278829861d4592068583e45cc817f2e3e980a5ce8fd7cd609f71", "bytes": 46993, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2023.1126497", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10060527", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE12720", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12720", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE12720", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: immune-related gene (http://www.immport.org/) and the Gene expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) (Accession: GSE12720, GSE14951 and GSE15480).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: immune-related gene (http://www.immport.org/) and the Gene expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) (Accession: GSE12720, GSE14951 and GSE15480).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM319257", "GSM319258", "GSM319259", "GSM319260", "GSM319261", "GSM319262", "GSM319263", "GSM319264", "GSM319265", "GSM319266", "GSM319267", "GSM319268", "GSM319269", "GSM319270", "GSM319271", "GSM319272", "GSM319273", "GSM319274", "GSM319275", "GSM319276", "GSM319277", "GSM319278", "GSM319279", "GSM319280", "GSM319281", "GSM319282", "GSM319283", "GSM319284", "GSM319285", "GSM319286", "GSM319287", "GSM319288", "GSM319289", "GSM319290", "GSM319291", "GSM319292", "GSM319293", "GSM319294", "GSM319295", "GSM319296", "GSM319297", "GSM319298", "GSM319299", "GSM319300", "GSM319301", "GSM319302", "GSM319303", "GSM319304", "GSM319305", "GSM319306", "GSM319307", "GSM319308", "GSM319309", "GSM319310", "GSM319311", "GSM319312", "GSM319313", "GSM319314", "GSM319315", "GSM319316", "GSM319317", "GSM319318", "GSM319319"], "sample_count": 63, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Unique early gene expression patterns in adult to adult living donor liver grafts compared to deceased donor grafts", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE14951", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14951", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14951", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: immune-related gene (http://www.immport.org/) and the Gene expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) (Accession: GSE12720, GSE14951 and GSE15480).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: immune-related gene (http://www.immport.org/) and the Gene expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) (Accession: GSE12720, GSE14951 and GSE15480).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM372247", "GSM372248", "GSM372249", "GSM372250", "GSM372251", "GSM372252", "GSM372254", "GSM372256", "GSM372257", "GSM372567", "GSM372599", "GSM372600", "GSM373314", "GSM373315", "GSM373324"], "sample_count": 15, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": " Gene expression profile in human orthotopic liver transplantation", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE15480", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE15480", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE15480", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: immune-related gene (http://www.immport.org/) and the Gene expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) (Accession: GSE12720, GSE14951 and GSE15480).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: immune-related gene (http://www.immport.org/) and the Gene expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) (Accession: GSE12720, GSE14951 and GSE15480).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM388400", "GSM388401", "GSM388402", "GSM388403", "GSM388404", "GSM388405", "GSM388406", "GSM388407", "GSM388408", "GSM388409", "GSM388410", "GSM388411", "GSM388412", "GSM388413", "GSM388414", "GSM388415", "GSM388416", "GSM388417", "GSM388418", "GSM388419", "GSM388420", "GSM388421", "GSM388422", "GSM388423"], "sample_count": 24, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Global Gene Expression in Deceased Donor Liver Transplantation with Ischemic Preconditioning", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE12720 not downloaded", "asset:data:geo:GSE12720 licence not read", "asset:data:geo:GSE14951 not downloaded", "asset:data:geo:GSE14951 licence not read", "asset:data:geo:GSE15480 not downloaded", "asset:data:geo:GSE15480 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The three raw datasets were downloaded using the R “GEOquery” package, and then performed gene annotation, gene filtering, normalization, etc. on the three datasets. The differentially expressed genes (DEGs) were analyzed and compared between the pre-ischemic and reperfused liver tissue controls using the R “limma” package. Only those genes with adjusted P-value < 0.05 and |log2FC (fold change)| ≥ 0.5 were considered DEGs."}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "pathway enrichment"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:37006305", "data:geo:GSE12720"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE12720"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:35:25Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13901, "completion_tokens": 1690, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:37006305", "type": "paper", "label": "pmid:37006305"}, {"id": "source:pmid:37006305", "type": "manuscript", "label": "PMID 37006305 full text"}, {"id": "data:geo:GSE12720", "type": "dataset", "label": "GEO GSE12720"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37006305", "type": "paper", "label": "pmid:37006305"}, {"id": "source:pmid:37006305", "type": "manuscript", "label": "PMID 37006305 full text"}, {"id": "data:geo:GSE12720", "type": "dataset", "label": "GEO GSE12720"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37006305", "type": "extraction", "used": ["source:pmid:37006305"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE12720", "type": "accession_resolution", "used": ["data:geo:GSE12720"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:37006305", "parent_hash": "sha256:40cd9cde5171b5b18d43b828980f3be51b8531e495c0f0fcabcb0b64a4782b1c", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE12720 licence not read", "asset:data:geo:GSE12720 not downloaded", "asset:data:geo:GSE14951 licence not read", "asset:data:geo:GSE14951 not downloaded", "asset:data:geo:GSE15480 licence not read", "asset:data:geo:GSE15480 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["d genes in hepatic I/R injury. Methods: Gene microarray data was downloaded from the Gene Expression"], "order_basis": "paper_text_order:418", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["and immune infiltration were performed in a mouse model of hepatic I/R injury. Results: A total of 7", "and immune infiltration were performed in a mouse model of hepatic I/R injury. Results: A tota", "of the Renmin hospital of Wuhan University. Mice were kept in an air-filtered, temperature-control", "d free access to a standard diet. 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