{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:27075204", "kind": "science-record", "revision": 7, "content_hash": "sha256:6cf432b3feddbafd45d5d715bb5cfb1d1ca3d872671833df5fe986af2c393ea3", "created_at": "2026-11-01T15:40:17Z", "updated_at": "2026-11-01T21:59:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Mass spectrometry analysis of adipose-derived stem cells reveals a significant effect of hypoxia on pathways regulating extracellular matrix.", "doi": "10.1186/s13287-016-0310-7", "pmid": "27075204", "authors": ["Simone Riis", "Allan Stensballe", "Jeppe Emmersen", "Cristian Pablo Pennisi", "Svend Birkelund", "Vladimir Zachar", "Trine Fink"], "journal": "Stem cell research & therapy", "year": 2016, "abstract": "BACKGROUND: Adipose-derived stem cells (ASCs) are being increasingly recognized for their potential to promote tissue regeneration and wound healing. These effects appear to be partly mediated by paracrine signaling pathways, and are enhanced during hypoxia. Mass spectrometry (MS) is a valuable tool for proteomic profiling of cultured ASCs, which may help to reveal the identity of the factors secreted by the cells under different conditions. However, serum starvation which is essentially required to obtain samples compatible with secretome analysis by MS can have a significant influence on ASCs. Here, we present a novel and optimized culturing approach based on the use of a clinically relevant serum-free formulation, which was used to assess the effects of hypoxia on the ASC proteomic profile.\nMETHODS: Human ASCs from three human donors were expanded in StemPro® MSC SFM XenoFree medium. Cells were cultured for 24 h in serum- and albumin-free supplements in either normoxic (20 %) or hypoxic (1 %) atmospheres, after which the cells and conditioned medium were collected, subfractionated, and analyzed using MS. Prior to analysis, the secreted proteins were further subdivided into a secretome (>30 kDa) and a peptidome (3-30 kDa) fraction.\nRESULTS: MS analysis revealed the presence of 342, 98, and 3228 proteins in the normoxic ASC secretome, peptidome, and proteome, respectively. A relatively small fraction of the proteome (9.6 %) was significantly affected by hypoxia, and the most regulated proteins were those involved in extracellular matrix (ECM) synthesis and cell metabolism. No proteins were found to be significantly modulated by hypoxic treatment across all cultures for the secretome and peptidome samples.\nCONCLUSIONS: This study highlights ECM remodeling as a significant mechanism contributing to the ASC regenerative effect after hypoxic preconditioning, and further underscores considerable inter-individual differences in ASC response to hypoxia. The novel culture paradigm provides a basis for future proteomic studies under conditions that do not induce a stress response, so that the best responders can be accurately identified for prospective therapeutic use. Data are available via ProteomeXchange with identifier PXD003550.", "claims": [{"id": "claim-method", "statement": "MS measurements were grouped preservation-method wise, and two-sided t tests were performed to identify statistically significant changing proteins. The statistical tests were corrected for multiple hypothesis testing using permutation-based FDR, and the parameters were chosen to provide sufficient input in the subsequent analysis (FDR = 0.05, s0 = 0.1, and 250 randomizations). The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium [74] via the PRIDE partner repository with the dataset identifier PXD003550.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27075204", "locator": "sections[15] \"Data analysis\" paragraph 3", "quote": "MS measurements were grouped preservation-method wise, and two-sided t tests were performed to identify statistically significant changing proteins."}, {"asset": "source:pmid:27075204", "locator": "sections[15] \"Data analysis\" paragraph 3", "quote": "The statistical tests were corrected for multiple hypothesis testing using permutation-based FDR, and the parameters were chosen to provide sufficient input in the subsequent analysis (FDR = 0.05, s0 = 0.1, and 250 randomizations)."}, {"asset": "source:pmid:27075204", "locator": "sections[25] \"Availability of data\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium [74] via the PRIDE partner repository with the dataset identifier PXD003550."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium [74] via the PRIDE partner repository with the dataset identifier PXD003550.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27075204", "locator": "sections[25] \"Availability of data\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium [74] via the PRIDE partner repository with the dataset identifier PXD003550."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A small fraction (9.6%) of the ASC proteome was significantly affected by hypoxia, with no proteins significantly modulated across all cultures in the secretome and peptidome; protein-level comparisons used label-free quantitative MS analyzed with two-sided t tests, and the source proteomics data are available through ProteomeXchange under identifier PXD003550.", "kind": "quantitative", "target": {"value": 9.6, "unit": "per cent", "tolerance": null, "source": "A relatively small fraction of the proteome (9.6 %) was significantly affected by hypoxia, and the most regulated proteins were those involved in extracellular matrix (ECM) synthesis and cell metabolism."}, "evidence": [{"asset": "source:pmid:27075204", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A relatively small fraction of the proteome (9.6 %) was significantly affected by hypoxia, and the most regulated proteins were those involved in extracellular matrix (ECM) synthesis and cell metabolism."}, {"asset": "source:pmid:27075204", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "No proteins were found to be significantly modulated by hypoxic treatment across all cultures for the secretome and peptidome samples."}, {"asset": "source:pmid:27075204", "locator": "sections[0] \"Abstract\" paragraph 5", "quote": "Data are available via ProteomeXchange with identifier PXD003550."}, {"asset": "source:pmid:27075204", "locator": "sections[18] \"Identification of proteins\" paragraph 2", "quote": "Using reverse-phase UPLC, the peptides were separated according to their hydrophobicity."}, {"asset": "source:pmid:27075204", "locator": "sections[21] \"Effect of hypoxic treatment on the ASC proteome\" paragraph 2", "quote": "Statistical analysis of the difference between label-free samples of the proteome fraction from hypoxic preconditioned ASC 21 against the proteome fraction from normoxic preconditioned ASC21 with a two-sided t test."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A small fraction (9.6%) of the ASC proteome was significantly affected by hypoxia, with no proteins significantly modulated across all cultures in the secretome and peptidome; protein-level comparisons used label-free quantitative MS analyzed with two-sided t tests, and the source proteomics data are available through ProteomeXchange under identifier PXD003550.", "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:27075204"], "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. 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The statistical tests were corrected for multiple hypothesis testing using permutation-based FDR, and the parameters were chosen to provide sufficient input in the subsequent analysis (FDR = 0.05, s0 = 0.1, and 250 randomizations). The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium [74] via the PRIDE partner repository with the dataset identifier PXD003550."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "bootstrap_mean_difference", "expected_value": 9.6, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. 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Mass spectrometry (MS) is a valuable tool for proteomic profil", "to assess the effects of hypoxia on the ASC proteomic profile. METHODS: Human ASCs from three huma", "ass spectrometry (MS) is a valuable tool for proteomic profiling of cultured ASCs, which may help t"], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Methods Cell culture The cells were cultured in polystyrene tissue flasks (CELLSTAR®, Greine", "tachment. Unless stated otherwise, ASCs were cultured in StemPro+. 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At the evidence floor the work type comes from title framing and a fixed prior, not from anything in the paper, so the published work-type split should be read as a rough triage signal rather than a measured distribution. The impact is bounded but not removed: since 2026-10-23 the engine excludes floor-confidence records from the shortlist entirely and publishes them separately as held out, so the recommendation is unaffected even though the census is.","status":"unverified","severity":"high"},{"code":"runtime_is_modelled","basis":["Runtime is summed from published per-assay hour figures. Timing awaits the first executed replication.","4,407 of 5,529 records (79.7%) model to 0.00 hours because no assay was matched, which the ranking then reads as \"cheapest\".","0 of 10 shortlisted records carry a 0.00-hour estimate."],"claim":"Estimated replication runtime","gloss":"The hour figures are estimates built from assay mentions; timing awaits the first executed replication.","detail":"The hour figures are a cost model derived from the bench steps implied by each matched assay family. The first executed replication will supply measured timing. Records without an assay match currently receive a zero-hour model value.","status":"unverified","severity":"high"},{"code":"signal_score_without_citations","basis":["5,529 of 5,529 records (100.0%) have no citation count from the source metadata."],"claim":"Signal score","gloss":"The signal score uses publication-type weight because the mirror supplied zero citation counts.","detail":"The source supplied no citation counts for any record in this run, so the signal score is publication-type weight only. The citation term of the ranking is inert here, and the shortlist is ordered by publication type alone.","status":"unverified","severity":"high"},{"code":"abstract_absent","basis":["1,667 of 5,529 records (30.2%) carry no abstract at all."],"claim":"Evidence base for classification","gloss":"Some records contain a title and publication type only, defining the available classification evidence.","detail":"Where the mirror contains a title and publication types only, those fields define the classifier evidence. A methods section is required for fuller automated and human review.","status":"unverified","severity":"medium"},{"code":"classifier_agreement_measured","basis":["Published two-way decision agreement 77.7% (310 of 399 decidable records) from a stratified hand-check of 438 real records.","Three-way diagnostic agreement 73.9% (288 of 390 decidable records).","data_only agreement 75.2% (100 of 133 decidable).","48 record(s) could not be decided from title and abstract and were excluded from the denominator.","56 analysis-only records were published under another work type, so the data_only share is not an upper bound."],"claim":"Published automatable decision","gloss":"This figure has been checked against a human reading the same papers, so we know how often it is right.","detail":"The published automatable / not-automatable distribution comes from a rule-based classifier that was hand-checked against a fixed ground-truth definition. The agreement rates below are measured, not estimated. The three-way work type remains a diagnostic and is reported separately.","status":"measured","severity":"high"},{"code":"llm_comparison_not_measured","basis":["rule_based_v1+lex99e1195c7d6f produced 5,529 of 5,529 classifications.","Measured on 438 labelled records; these are RULE-BASED figures, not model results."],"claim":"Rule-based versus LLM agreement","gloss":"Every number here is the rule engine’s own. Model comparison begins when a working API credential is connected and measured.","detail":"The published two-way decision agreed with a human reading on 310 of 399 decidable records (77.7%). The diagnostic three-way label agreed on 288 of 390 decidable records (73.9%). Every percentage in this run belongs to the rule engine. Model comparison begins when a working API credential is connected and measured.","status":"not_measured","severity":"high"},{"code":"confidence_is_a_band","basis":["low band: 135 of 210 hand-judged records were correct, 64.3% [57.6, 70.5] (95% CI).","medium band: 80 of 104 hand-judged records were correct, 76.9% [68.0, 84.0] (95% CI).","high band: 73 of 76 hand-judged records were correct, 96.0% [89.0, 98.7] (95% CI).","A fitted calibrated probability was built, measured and withdrawn: it overstated held-out accuracy and reorders nothing."],"claim":"Confidence band and evidence score","gloss":"The confidence band carries a measured accuracy interval; 0.85 represents relative rank strength.","detail":"Confidence on this run is a BAND plus its measured accuracy interval. The number stored alongside each record is a monotone evidence score that orders records; 0.85 represents relative rank strength. A fitted probability was withdrawn after it overstated held-out accuracy. Threshold on the band.","status":"measured","severity":"medium"},{"code":"three_way_split_is_diagnostic","basis":["The corpus is published at the two-way decision: automatable or not-automatable. The three-way split (data_only / physical / mixed) is published as a diagnostic with its measured reliability attached, not as a claim, because the rule engine's `mixed` call cannot be defended.","The engine called 22 record(s) mixed; 10 matched the human judgement (45.5%, 95% CI 26.9-65.3).","The engine's `mixed` call is right on 10/22 hand-judged records (45.5%, 95% CI 26.9%-65.3%); a constant `physical` guess scores 36.4%.","The engine's `mixed` call does not reliably beat a constant `physical` guess on the hand-judged records it labels mixed.","The sign of that difference flips between two independent samples, so the three-way refinement is not demonstrably informative.","The mixed stratum contributes a disproportionate share of errors relative to its size.","At title-only depth the physical/mixed split collapses: a title says that work was done, not whether it was also analysed."],"claim":"The published decision is two-way","gloss":"The three-way split is shown for diagnosis only. The published split is two ways.","detail":"Count and filter the corpus on automatable versus not-automatable. The data_only / physical / mixed split remains an internal engine diagnostic because the mixed call has lower measured reliability.","status":"measured","severity":"medium"},{"code":"automatable_flag_unproven","basis":["6 of 29 assay families are marked automatable now: meta_analysis, machine_learning, survival_analysis, pca, molecular_docking, differential_expression.","The flag is a rule over assay family and work type; validation begins with the first executed replication.","It inherits the 75.2% data_only agreement rate, because the flag requires the record to be analysis-only."],"claim":"Automatable now","gloss":"This flag marks assay families the rules classify as data-only. The first executed replication will validate it.","detail":"This flag marks families the rules consider replicable from data alone. Its validity depends on the analysis-only classification and will be measured through an executed replication.","status":"unverified","severity":"medium"}],"confidence_policy":"band_with_measured_interval","confidence_contract":{"policy":"band_with_measured_interval","summary":"Confidence is reported as a BAND with a measured accuracy interval. The raw evidence score supplies monotone ordering. A fitted point estimate was withdrawn after it overstated held-out accuracy.","evidence_score":"A monotone evidence score in [0,1] built from cue mass, axis separation and text coverage. Use it to order records. Interpret 0.85 as relative rank strength.","confidence_band":"low | medium | high. Consumers threshold on this value.","band_accuracy":"Wilson 95% interval on the measured agreement of the hand-judged records in this band.","calibrated_confidence":"WITHDRAWN. Reintroduction requires held-out evidence demonstrating reliable estimates across every bin."},"band_accuracy":{"low":{"n":210,"low":0.576,"band":"low","high":0.7046,"agree":135,"accuracy":0.6429},"high":{"n":76,"low":0.8903,"band":"high","high":0.9865,"agree":73,"accuracy":0.9605},"medium":{"n":104,"low":0.6795,"band":"medium","high":0.8397,"agree":80,"accuracy":0.7692}},"provider":"rule_based_v1+lex99e1195c7d6f","lexicon_id":"99e1195c7d6f","contract_published_at":"2026-10-23T12:25:29.022232+00:00","confidence_is_band":true,"confidence_is_probability":false,"decision_taxonomy":"two_way","decidable_fraction_two_way":0.8854,"decidable_fraction_two_way_low":0.8565,"decidable_fraction_two_way_high":0.9143,"decidable_fraction_three_way":0.8586,"decidable_fraction_three_way_low":0.8287,"decidable_fraction_three_way_high":0.8884,"decidable_population":5529,"validation_sample_size":438,"three_way_cost_fraction":0.0268,"three_way_cost_records":148,"decision_counts":{"automatable":230,"not_automatable":5299},"decision_split":{"automatable":{"count":230,"share":0.04159884246699222},"not_automatable":{"count":5299,"share":0.9584011575330078}},"diagnostic_work_type_counts":{"mixed":24,"physical":5275,"data_only":230}}}