phenomenon · claim-type · cross-domain-transfer · mechanism · claim-relation · replication-status · limitation — grounded in the full text| phenomenon | secreted membrane-enclosed vesicles that co-isolate with non-vesicular carriers of the same cargo - protein complexes and lipoproteins— “However, the extracellular milieu is more complex as several body fluids (especially serum/plasma) harbour extracellular RNA (exRNA) in other non-EV carriers, including protein complexes (AGO2) ( 4 ) and lipoproteins” | |
| claim-type | method— “Therefore, we suggest that investigators report the amount of several proteins (3 or more) in at least a semi-quantitative manner in any EV preparation, including EV isolates from body fluids or obtained from secreting cells in vitro” | |
| method — evidence | — “An advanced search was performed in PubMed at the end of December 2013 to find, for each year of publication, all articles using the given term (singular or plural) as text word: exosome(s), microvesicles, oncosome(s), ectosome(s), prostasome(s), matrix/calcifying vesicle(s).” | |
| object of study — evidence | — “Importantly, it is currently technically challenging to obtain a totally pure EV fraction free from non-vesicular components for functional studies, and therefore there is a need to establish guidelines for analyses of these vesicles and reporting of scientific studies on EV biology.” | |
| research question — evidence | — “Separation of these non-vesicular entities from EV is not fully achieved by common EV isolation protocols, including centrifugation protocols or commercial kits that claim EV or “exosome” isolation/purification.” | |
| contribution — evidence | — “Unfortunately, the field of EV research has not matured to the point that we can propose a list of EV-specific “markers” that distinguish subsets of EVs from each other, for example, EVs produced via budding from the cell membrane or produced via endosomal compartments.” | |
| mechanism | extracellular RNA travels in NON-VESICULAR carriers too - AGO2 protein complexes, HDL and LDL - so a functional result attributed to EVs may belong to something else in the same preparation— “However, the extracellular milieu is more complex as several body fluids (especially serum/plasma) harbour extracellular RNA (exRNA) in other non-EV carriers, including protein complexes (AGO2) ( 4 ) and lipoproteins” | mechanisms[0] |
| mechanism | polymer precipitation, used by commercial kits, does not isolate EVs exclusively and is LIKELY to co-isolate RNA-protein complexes - the named case of a method whose output does not match its label— “In particular, polymer-based methods to precipitate EVs (used by some commercial kits) do not exclusively isolate EVs, and are likely to co-isolate other molecules, including RNA–protein complexes.” | mechanisms[1] |
| mechanism | THE FIELD'S MOST-USED WORD HAS NO AGREED MEANING, SAID IN THE FOUNDING GUIDELINE: `The term “exosomes” is the most commonly used word to designate any type of EV, and this has become a “buzz term” for EV-related science. The ACTUAL MEANING of this word, however, is NOT UNIVERSALLY ACCEPTED`. The word is simultaneously the most frequent and the least agreed.— “The term “exosomes” is the most commonly used word to designate any type of EV ( Fig. 1 ), and this has become a “buzz term” for EV-related science. The actual meaning of this word, however, is not universally accepted” | mechanisms[2] |
| mechanism | AND THE REASON NO MARKER CAN SETTLE IT IS STATED AS IMMATURITY, NOT DIFFICULTY: `the field of EV research has not matured to the point that we can propose a list of EV-specific “markers” that distinguish subsets of EVs from each other`. The categories are in use before anything can tell them apart. | mechanisms[3] |
| mechanism | THE PROTOCOL CHANGES THE OBJECT, STATED IN 2014: `the composition of recovered EVs vary vastly according to the protocols used`. doyle2019 demonstrates the same thing five years later as `different isolation methods ... from the same cell type results in different proteomic profiles`. Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | mechanisms[4] |
| critiques | commercial EV/exosome isolation kits and polymer precipitation methods, on the ground that they do not isolate EVs exclusively and co-isolate RNA-protein complexes Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | claim_relations[0] |
| critiques | the use of 'exosome' as a category label, on the ground that its meaning is not universally accepted and the isolated material is a mixture Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | claim_relations[1] |
| critiques | attributing a cargo or function to EVs from a preparation that also contains AGO2 complexes and lipoproteins carrying the same extracellular RNA Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | claim_relations[2] |
| sense | extracellular vesicles, 2014 - AS DEFINED HERE BY ENUMERATION, not by property: `exosomes, ectosomes, microvesicles, microparticles, apoptotic bodies and other EV subsets`. The 2023 statement replaces this with three properties (released, bilayer-delimited, non-replicating); THE LIST CAME FIRST AND THE PROPERTY CAME AFTER Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | senses[0] |
| sense | exosome, 2014 - A BUZZ TERM BY ITS OWN SOCIETY'S ACCOUNT. Used for any EV in practice, defined by endosomal origin in principle, and the isolated material `generally contains a mixture of EVs`. The 2023 statement discourages the word; this one only records that its meaning is not agreed Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | senses[1] |
| sense | `exosome-enriched` versus `exosome-specific` - THE DISTINCTION THE WHOLE PROBLEM TURNS ON, drawn here in 2014. A marker that is merely enriched cannot separate subsets; the field's subtype names had been treating enrichment as though it were specificity Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | senses[2] |
| sense | the 2014 HOPE - `we hope to eventually be able to provide specific markers and characteristics of EV subtypes`. READ AGAINST MISEV2023, WHICH REPORTS NO UNIVERSAL MARKERS AND DISCOURAGES THE TERMS, this is a field holding a definition open for nine years and then closing it the other way Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | senses[3] |
| sense | `gold-standard` DENIED, WITH THE CONSEQUENCE DRAWN: `Since there is currently no consensus on a “gold-standard” method to isolate and/or purify EVs, it cannot be claimed that there is an “optimal” method that should be uniformly used.` The absence of agreement is treated as barring a claim, not merely as an open question. Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | senses[4] |
| sense | A SOCIETY NAMES A CATEGORY AND THE LITERATURE DOES NOT FOLLOW: `the term “extracellular vesicles,” chosen as generic term at creation of ISEV in September 2011, is steadily growing` - while `from 2004 onwards, the term “exosome” has become the most often used`. A dated act of naming, and a measured record of it not taking. Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | senses[5] |
| control | investigators are asked to report proteins NOT expected to be enriched in EVs - Table I group 3 - alongside the ones that are, in at least a semi-quantitative manner and for three or more proteins — absent-declared-unreported Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. — rules out a preparation characterised only by what it was hoped to contain, which cannot reveal co-isolation of other intracellular origins Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | controls[0] |
| control | the EV-containing fluid must be collected gently, limiting cell disruption — absent-declared-unreported Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. — rules out intracellular vesicles released by mechanical damage being counted as extracellular ones - the document says the term 'EVs' MAY NOT BE APPROPRIATE for material isolated that way Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | controls[1] |
| control | the field's own term usage is counted from PubMed by year, with non-EV senses of 'exosome' and 'microvesicle' manually removed — partial Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. — rules out an impression about which words the literature uses, replaced by a count - and the count is honest about what it could NOT measure Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | controls[2] |
| control | whether any isolation method yields a pure EV fraction, or whether one can be named as the standard — failed Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. — rules out nothing - the document reports that a totally pure fraction is technically challenging to obtain and that there is no consensus gold standard Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | controls[3] |
| weight | commercial EV/exosome isolation kits and polymer precipitation methods, on the ground that they do not isolate EVs exclusively and co-isolate RNA-protein complexes — 0.9 Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | claim_relations[0] |
| weight | the use of 'exosome' as a category label, on the ground that its meaning is not universally accepted and the isolated material is a mixture — 0.85 Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | claim_relations[1] |
| weight | attributing a cargo or function to EVs from a preparation that also contains AGO2 complexes and lipoproteins carrying the same extracellular RNA — 0.8 Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | claim_relations[2] |
| note | exosomes —is-a→ extracellular vesicles — REPLACES the withdrawn 'part-of' edge on the same pair and the same sentence. The relation is class membership: the evidence names a class and lists its members. Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | concept_edges[2] |
| note | microvesicles —is-a→ extracellular vesicles — REPLACES the withdrawn 'part-of' edge on the same pair and the same sentence. The relation is class membership: the evidence names a class and lists its members. Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | concept_edges[3] |
| outcome | control — absent-declared-unreported Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | controls[0] |
| outcome | control — absent-declared-unreported Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | controls[1] |
| outcome | control — partial Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | controls[2] |
| outcome | control — failed Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | controls[3] |
| limitation | THE FIELD'S MOST-USED WORD HAS NO AGREED MEANING, and its own society says so: `exosomes` is `the most commonly used word to designate any type of EV` and `has become a BUZZ TERM`, whose `actual meaning ... is not universally accepted` Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | limitations[0] |
| limitation | THE FIELD CANNOT NAME THE MARKERS ITS OWN CATEGORIES WOULD NEED: it `has not matured to the point that we can propose a list of EV-specific markers` distinguishing EVs budded from the membrane from those of endosomal origin Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | limitations[1] |
| limitation | the proteins that were taken for markers are `exosome-ENRICHED` and not `exosome-SPECIFIC` - an enrichment describes a tendency and cannot draw a boundary, which is precisely what the names had been doing with it Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | limitations[2] |
| limitation | there is no consensus gold-standard isolation method and therefore no optimal one to prescribe - the document declines to name a method rather than naming a weak one Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | limitations[3] |
| limitation | one of the field's terms could not even be COUNTED: `microparticle` was excluded from the term-usage figure because it is massively used for non-vesicles Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | limitations[4] |
| limitation | THE DOCUMENT CALLS ITSELF AN EDITORIAL: `the minimal requirements presented in this editorial`. It is cited ever after as the first of a numbered guideline series, a status conferred on it later by its successor rather than claimed here. Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | limitations[5] |
finding · quantity · variable · definition · key-term — grounded in the full text| finding | Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | content_tags.findings[0] |
| finding | Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | content_tags.findings[1] |
| finding | Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | content_tags.findings[2] |
| finding | Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | content_tags.findings[3] |
| finding | Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | content_tags.findings[4] |
| finding | Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | content_tags.findings[5] |
| finding | Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | content_tags.findings[6] |
| quantity | or more proteins, reported semi-quantitatively, as the minimum characterisation of any EV preparation Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | content_tags.quantities[0] |
| quantity | the year from which `exosome` became the most-used term in the EV literature, against `extracellular vesicles` chosen as the generic term in 2011 Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | content_tags.quantities[1] |
| variable | markers Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | content_tags.variables[0] |
| definition | extracellular vesicles Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | content_tags.definitions[0] |
| definition | exosomes Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | content_tags.definitions[1] |
| concept | extracellular vesicles — not defined in this paper's own words; the generic term ISEV chose at its founding in 2011, defined in this document by the list of subtypes it covers Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | concepts[0] |
| concept | exosomes — not defined in this paper's own words; the field's most-used word, for EVs of endosomal origin in principle and for any EV in practice - named a buzz term by its own society Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | concepts[1] |
| concept | microvesicles — not defined in this paper's own words; one of the enumerated EV subsets in the 2014 umbrella definition Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | concepts[2] |
| concept | markers — not defined in this paper's own words; the molecular signatures that would distinguish EV subtypes, and which this document states the field cannot yet list Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | concepts[3] |
| concept | lipoproteins — not defined in this paper's own words; HDL and LDL - non-vesicular carriers of extracellular RNA that co-isolate with EVs and can carry the effect attributed to them Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | concepts[4] |
| concept | gold-standard — not defined in this paper's own words; EXPLICITLY DENIED TO EXIST for EV isolation in 2014 - and the paper draws the consequence that no method may be called optimal or used uniformly Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | concepts[5] |
| concept | buzz term — not defined in this paper's own words; what this paper calls 'exosomes' - the most-used word in the field, whose actual meaning it says is not universally accepted Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | concepts[6] |
| concept | extracellular vesicles — not defined in this paper's own words; THE GENERIC TERM CHOSEN BY FIAT AT THE FOUNDING OF A SOCIETY - 'chosen as generic term at creation of ISEV in September 2011' - and still losing to 'exosome' in usage three years later Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | concepts[7] |
| semi-quantitative | Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher. | content_tags.statistics[0] |
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