Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

Hans Erik Bøtker, Derek J. Hausenloy, Ioanna Andreadou, Salvatore Antonucci, Kerstin Boengler, Sean M. Davidson, Soni Deshwal, Yvan Devaux, Fabio Di Lisa, Moises Di Sante, Panagiotis Efentakis, Saveria Femminò, David García‐Dorado, Zoltán Giricz, Borja Ibáñez, Efstathios K. Iliodromitis, Nina Kaludercic, Petra Kleinbongard, Markus Neuhäuser, Michel Ovize, Pasquale Pagliaro, Michael Rahbek-Schmidt, Marisol Ruiz‐Meana, Klaus‐Dieter Schlüter, Rainer Schulz, Andreas Skyschally, Catherine D. E. Wilder, Derek M. Yellon, Péter Ferdinandy, Gerd Heusch · Basic Research in Cardiology · 2018 · medicine · 10.1007/s00395-018-0696-8 · record botker2018-practical-guidelines-for-rigor-and
tag layer · index · concepts · authors · עברית

Where this record's text came from. 2026-08-22 and 2026-08-26 schema-0.3 passes: every quote verified as an exact substring of the staged text and anchored at merge time; concept terms verified present; every edge endpoint an existing node.

16 quotations on this page contain a reference number where the paper printed a superscript. This journal style prints citations as raised numerals — parameters^12,13 — and the extraction flattened them into the line, so the sentence reads parameters 12 , 13 . The digits are citation markers and not part of what the author wrote. The quotes keep them for the same reason they keep every other extraction fault: a quote is reproduced exactly or it proves nothing.

How to read this page. The article itself is not reproduced here — this paper is not cleared for redistribution, so what follows is the tag layer alone. The evidence sentences are withheld with the article. The table at the foot lists every tag the record carries; each row names the facet it belongs to, and the whose words column says whether the tag records the paper's own wording or the tagger's sentence about the paper. Every tag links to each other paper in the corpus carrying it. The machine-readable edition of the same thing is the TEI file beside this one, where the tags live in standOff, and the article is at its publisher via the link below. When we have changed our mind. Some entries in the table begin with a word in capitals and the reason for it. EVIDENCE CORRECTED — the finding still stands, but we had quoted the wrong sentence from the paper, and the quotation has been replaced with the right one. RETRACTED — the entry itself was wrong; it stays on the page, marked, with the reason, rather than being deleted. WITHDRAWN AND REPLACED — the entry was wrong, and a corrected version of it appears in the entries below. Each mark carries its own reason, in brackets, because the reasons differ from one entry to the next. An entry we have WITHDRAWN is removed from this page and kept in the record, with its reason. A line reading Audit and a date is a later re-reading of the entry against its whole sentence: DOUBTFUL means it was kept, and the reason says what is loose about it. Quotation marks inside the tagger's sentence. Where a tag is the tagger's own sentence, a phrase in quotation marks inside it is borrowed from the paper — the tagger's wording around it is not. The paper's own sentence is the evidence quote for that row; on this page it is withheld with the article, and the article is at its publisher. Nothing inside quotation marks anywhere on this page is ours: if it is quoted, it is the paper's. Whose words a concept carries. A concept entry records a term the paper itself uses, so the term, the sense given for it, and its evidence are the paper's own words, quoted where the paper fixes them. This is the opposite of a sense entry in the tag table, which is the tagger's sentence about how the paper uses a term. Where a concept entry could not be grounded in the paper's words, the entry says so on its own row.

Other fields define these differently the same word, defined another way in another discipline
reproducibility 6 fields · exploratory 2 fields · outlier 2 fields

Tags on this paper

Every tag the record carries, each linking to every other paper in the corpus that carries it. A tag appears here whether or not its words occur in the article — the spans below are only the ones a sentence in this paper licenses. Of the 19 concept tags on this paper, all 19 are grounded in a quoted sentence. All carry the tagger's gloss of what the term means in this paper, which is not something the article can license.

rigor reproducibility exploratory prospective propofol isoflurane ischemic preconditioning nitrite salvage index area at risk hazard ratio multiplicity effect size transcriptomics epitranscriptomics pseudouridine fifth nucleoside HL-1 cells adult cardiomyocytes outlier primary variable Infarct size expert-consensus

Method, as described: expert consensus of the EU-CARDIOPROTECTION COST Action, approved by its management committee, building on the ARRIVE and ICH E9/E6 guidelines

Legend

relation to other work	`claim_relations`	how this paper stands to another: agrees, contradicts, extends, qualifies
claim type	`claim_type`	the shape of the claim: existence, mechanism, method, critique, prediction, null
concept edge	`concept_edges`	an asserted relation between two concepts, with the sentence asserting it
concept	`concepts`	an idea the paper works with, quoted where the paper uses it
content tag	`content_tags`	a finding, definition, quantity, statistic or variable named in the paper
contribution	`contribution`	what the paper claims to add
control	`controls`	an experiment run to eliminate a rival explanation
limitation	`limitations`	what the paper says its evidence cannot support
mechanism	`mechanisms`	how the reported effect is said to come about
method	`method`	how the paper produced its evidence
object of study	`object_of_study`	what the paper is about — the thing it investigates
phenomenon	`phenomenon`	the effect or regularity under study
research question	`research_question`	the question the paper sets itself
sense	`senses`	a distinct use of a term, quoted where the paper fixes it

The paper

The full text is not reproduced here. This article is not cleared for redistribution, so the page carries the tag layer only. Its evidence sentences are withheld; the grounding status remains with each tag, and the article itself is at https://doi.org/10.1007/s00395-018-0696-8. The reading view exists for the papers whose licence permits it.

Every tag on this page

claim_relations 2 · claim_type 1 · concept_edges 6 · concepts 19 · content_tags 28 · contribution 1 · controls 4 · limitations 11 · mechanisms 9 · method 1 · object_of_study 1 · phenomenon 1 · research_question 1 · senses 7

Relations on this page carry a quotation for the claim. Where a relation was separately evidenced — and so tested against the vocabulary for its type — the row says so; none of 6 relations here carry that mark. The rest are the tagger’s reading of the sentence quoted beside them.

facet	tag	field	conf.	whose words
object_of_study	A THIRTY-AUTHOR CONSENSUS DEFINING WHAT COUNTS AS RIGOROUS in a field where thousands of preclinical studies produced exactly one unequivocal clinical translation - guidelines whose subject is the reliability of an evidence base, written by the people who produced it Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`object_of_study`		the paper's words
research_question	what design, conduct, analysis and reporting practices would make cardioprotection studies reproducible enough to be worth translating Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`research_question`		the paper's words
contribution	practical guidelines covering study design, randomisation, blinding, power, statistics, each experimental model with its own limitations, the omics technologies, and the design of clinical proof-of-concept and outcome trials Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`contribution`		the paper's words
claim_type	method Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`claim_type`		the paper's words
phenomenon	a field that cannot replicate itself, writing down what it will count as rigour Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`phenomenon`		the paper's words
method	expert-consensus Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: expert-consensus	`method`		the paper's words
mechanisms	THE PAPER DEFINES ITS OWN TWO WORDS AND MAKES ONE DEPEND ON THE OTHER: `we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment.` Rigour is a property of the doing; reproducibility is a property of what happens next, somewhere else Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[0]`	0.95	the tagger's words
mechanisms	AND THE FAILURE THAT MOTIVATES IT IS COUNTED: `literally thousands of experimental studies in various species and models ... so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[1]`	0.95	the tagger's words
mechanisms	AND A STANDARDISED MULTI-CENTRE REPLICATION FOUND ONE EFFECT OF THREE: `the CAESAR consortium ... in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[2]`	0.95	the tagger's words
mechanisms	AND TWO IMPLEMENTATIONS OF ONE NAMED TEST GIVE DIFFERENT ANSWERS: `Caveat - different statistical software packages work with slightly different assumptions and can come to different outcomes, as demonstrated for the Wilcoxon-Mann-Whitney`. Third consecutive record in this corpus where one construct measured two ways gives two answers - zook2016's aligners, ainsworth2020's five assays, and now a statistical test that has a name and a citation Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[3]`	0.95	the tagger's words
mechanisms	AND THE SURROGATES DO NOT PREDICT THE THING THEY STAND IN FOR, with the real definition arriving in a parenthesis immediately afterwards: `None of the above-mentioned variable/surrogate endpoints is indeed predictive of clinical outcomes in patients with acute myocardial infarction, i.e. truly indicative of `cardioprotection` (which is primarily infarct size reduction)` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[4]`	0.95	the tagger's words
mechanisms	AND ONE DRUG IS THE COMMON DENOMINATOR OF THE FAILURES: `propofol specifically abrogates the protection by remote ischemic conditioning in patients undergoing elective coronary artery bypass graft surgery ... and seems to be a common denominator of all studies that failed to see protection`. A confounder that explains a literature's negative results, named Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[5]`	0.95	the tagger's words
mechanisms	the choice of statistical test follows the shape of the data, not the field: one endpoint at one time point takes a t test or one-way ANOVA, sequential measurements take a two-way repeated-measures ANOVA Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[6]`	0.95	the tagger's words
mechanisms	an improving standard of care raises the sample size a trial needs, because the event rate the intervention must beat keeps falling Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[7]`	0.95	the tagger's words
mechanisms	the assumed effect size is imported from proof-of-concept studies - a 25% reduction in events is rationalised by 30% reductions in infarct size reported earlier Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[8]`	0.95	the tagger's words
limitations	THE INSTRUMENT DECIDES WHAT IS FOUND, STATED THREE TIMES IN THREE TECHNOLOGIES. RNA: `it is not recommended to use different kits in the same study, since some will favor the isolation of short RNAs while others will enrich the RNA fraction with long molecules` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`limitations[0]`	0.95	the tagger's words
limitations	proteomics: `the large abundance proteins mask the changes of low-abundance proteins which also make a significant contribution to cellular signalling` - and the targeted alternative `loses the unbiased feature of proteomics`. Coverage and accuracy traded against each other, explicitly Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`limitations[1]`	0.95	the tagger's words
limitations	and multiomics software: `their diversity in mathematical models and source data do not yet allow accurate comparison of different results` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`limitations[2]`	0.95	the tagger's words
limitations	AND THERE IS NO ACCEPTED METHOD FOR MISSING VALUES, QUOTED FROM SOMEBODY ELSE RATHER THAN ASSERTED: `Unfortunately, there is `NO METHODOLOGICAL APPROACH FOR HANDLING MISSING VALUES THAT IS UNIVERSALLY ACCEPTED IN ALL SITUATIONS`` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`limitations[3]`	0.95	the tagger's words
limitations	AND A COMMON PRACTICE IS REFUSED FOR A REASON THAT IS A ZERO-CLAIM ABOUT AN INSTRUMENT: `pretests are performed to test data for normality ... Those pretests cannot be recommended, since the failure to reject the null hypothesis does not imply that the null hypothesis holds, in particular since the power of the pretests is often low` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`limitations[4]`	0.95	the tagger's words
limitations	AND THE CHOICE OF DESIGN IS ADMITTED TO BE A COMPROMISE RATHER THAN A STANDARD: `The selection of the design ... always represents a compromise of a most rigorous approach vs. limited resources and feasibility. Clearly, an exploratory study, while aiming for novelty, is associated with a greater risk of false-positive findings ... whereas a prospective study aims for an existing specific hypothesis but provides more robust data` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`limitations[5]`	0.95	the tagger's words
limitations	and two authors of a rigour guideline hold commercial interests in the field, declared: shareholders in a company and a founder-CEO of a group of R&D companies. Not a defect - a disclosure, and it belongs next to the paper's subject the way hoste2006's `SOME MEMBERS OF OUR RESEARCH GROUP HAVE CONTRIBUTED TO THE CONSENSUS PROCESS BY WHICH RIFLE WAS DEVELOPED` does Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`limitations[6]`	0.85	the tagger's words
limitations	cardiac mortality has fallen steadily for 25 years and is now very low, so the outcome a cardioprotection trial must improve on is already excellent Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`limitations[7]`	0.95	the tagger's words
limitations	a clinical outcome trial on the composite endpoint needs patients in the thousands per arm, which the paper spells out rather than leaving implicit Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`limitations[8]`	0.95	the tagger's words
limitations	reduction of the biochemical marker by the intervention has ranged from no effect at all to a large reduction across previous studies Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`limitations[9]`	0.95	the tagger's words
limitations	stratified analyses must carry their own power calculations, or the stratification is not valid Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`limitations[10]`	0.95	the tagger's words
controls	pre-specified inclusion and exclusion criteria, blinding, randomisation and a power calculation before the experiment starts Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. eliminates: post-hoc adjustment of the study to its own result - stated as a prohibition: 'it is not permitted to change the sample size post hoc, to add a new randomized group, or to supplement additional experiments' · outcome: held	`controls[0]`	0.95	the tagger's words
controls	pretests for normality or homogeneity of variance before choosing a test Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. eliminates: nothing, and the paper refuses the practice: 'Those pretests cannot be recommended, since the failure to reject the null hypothesis does not imply that the null hypothesis holds' · outcome: failed	`controls[1]`	0.95	the tagger's words
controls	a consensus re-read when two human readers disagree about infarct size by more than 3% Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. eliminates: reader-dependent infarct size on the primary endpoint - a disagreement threshold that triggers a procedure rather than an argument · outcome: held	`controls[2]`	0.95	the tagger's words
controls	a surrogate endpoint that predicts clinical outcome Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. eliminates: nothing - the paper says none exists: 'None of the above-mentioned variable/surrogate endpoints is indeed predictive of clinical outcomes' · outcome: absent-not-in-staged-text	`controls[3]`	0.95	the tagger's words
concepts	rigor Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: rigor	`concepts[0]`	0.95	the paper's words
concepts	reproducibility Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: reproducibility	`concepts[1]`	0.95	the paper's words
concepts	exploratory Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: exploratory	`concepts[2]`	0.95	the paper's words
concepts	prospective Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: prospective	`concepts[3]`	0.95	the paper's words
concepts	propofol Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: propofol	`concepts[4]`	0.95	the paper's words
concepts	isoflurane Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: isoflurane	`concepts[5]`	0.95	the paper's words
concepts	ischemic preconditioning Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: ischemic preconditioning	`concepts[6]`	0.95	the paper's words
concepts	nitrite Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: nitrite	`concepts[7]`	0.95	the paper's words
concepts	salvage index Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: salvage index	`concepts[8]`	0.95	the paper's words
concepts	area at risk Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: area at risk	`concepts[9]`	0.95	the paper's words
concepts	hazard ratio Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: hazard ratio	`concepts[10]`	0.95	the paper's words
concepts	multiplicity Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: multiplicity	`concepts[11]`	0.95	the paper's words
concepts	effect size Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: effect size	`concepts[12]`	0.95	the paper's words
concepts	transcriptomics Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: transcriptomics	`concepts[13]`	0.95	the paper's words
concepts	epitranscriptomics Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: epitranscriptomics	`concepts[14]`	0.95	the paper's words
concepts	pseudouridine Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: pseudouridine	`concepts[15]`	0.9	the paper's words
concepts	fifth nucleoside Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: fifth nucleoside	`concepts[16]`	0.9	the paper's words
concepts	HL-1 cells Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: HL-1 cells	`concepts[17]`	0.95	the paper's words
concepts	adult cardiomyocytes Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: adult cardiomyocytes	`concepts[18]`	0.95	the paper's words
senses	`rigor` - DEFINED HERE AS A PROPERTY OF THE DOING: `standardized state-of-the-art design, conduct and reporting of a study` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[0]`	0.95	the tagger's words
senses	`reproducibility` - DEFINED AS A PROPERTY OF WHAT HAPPENS ELSEWHERE: `replication of results by another laboratory when performing exactly the same experiment`, and rigour is named as its PREREQUISITE Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[1]`	0.95	the tagger's words
senses	`cardioprotection` - the operative sense arrives in a parenthesis at the moment the surrogates are disowned: `truly indicative of `cardioprotection` (which is primarily infarct size reduction)` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[2]`	0.95	the tagger's words
senses	`outlier` - operationalised by Tukey's fences rather than by judgement: data outside `first quartile - 1.5 inter-quartile range and third quartile + 1.5 inter-quartile range` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[3]`	0.95	the tagger's words
senses	`primary variable` - `the variable capable of providing the most relevant and convincing evidence directly related to the primary objective of the trial`, quoted from ICH E9, with `ideally there is only one primary endpoint` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[4]`	0.95	the tagger's words
senses	`epitranscriptomics` - DEFINED ENTIRELY BY ITS PREFIX AND ITS SIBLING, IN ONE SENTENCE THAT DEFINES BOTH: `While transcriptomics refers to the characterization of gene expression at the ribonucleic acid (RNA) level, epitranscriptomics refers to post-transcriptional RNA modifications`. Neither term is given independently; the pair is introduced as a division of one territory. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[5]`	0.95	the tagger's words
senses	`pseudouridine` / `the fifth nucleoside` - AN ALIAS THAT NAMES A POSITION IN A LIST, NOT A STRUCTURE. `pseudouridine (also called the “fifth nucleoside”)`. The paper reaches for the older name in passing; it is the kind of name that stops being true when the list it counts is extended. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[6]`	0.85	the tagger's words
claim_relations	extends → the ARRIVE guidelines for reporting animal research and the ICH E9 and E6 guidelines for clinical trials, which this document adapts to cardioprotection Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`claim_relations[0]`	0.95	the tagger's words
claim_relations	builds-on → the CAESAR consortium's standardised multi-centre preclinical replication, whose result is the evidence that the field's preclinical base does not replicate Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`claim_relations[1]`	0.95	the tagger's words
concept_edges	exploratory —contrasted-with→ prospective Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. strength of the relation: 0.95 · note: 'an EXPLORATORY…' - and the choice between them 'VS. LIMITED RESOURCES…' also in: exploratory · prospective	`concept_edges[1]`	0.95	the tagger's words
concept_edges	propofol —distinct-from→ isoflurane Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. strength of the relation: 0.95 · note: 'Propofol seems…'. Equal on one axis, opposite on the one that decides the result also in: propofol · isoflurane	`concept_edges[2]`	0.95	the tagger's words
concept_edges	ischemic preconditioning —distinct-from→ nitrite Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. strength of the relation: 0.95 · note: 'identified ONLY…'. A standardised multi-centre replication separating one claimed effect from two that did not survive it Audit 2026-09-28: DOUBTFUL - read against its span and kept, but the span reports nitrite failing where preconditioning worked; distinct-from is loose. also in: ischemic preconditioning · nitrite	`concept_edges[3]`	0.95	the tagger's words
concept_edges	transcriptomics —distinct-from→ epitranscriptomics Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. strength of the relation: 1 · note: 'While X refers to ..., Y refers to ...' - the paper asserts the division outright, so weight 1.0. also in: transcriptomics · epitranscriptomics	`concept_edges[4]`	0.95	the tagger's words
concept_edges	pseudouridine —same-as→ fifth nucleoside Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. strength of the relation: 1 · note: 'also called' - an explicit alias, both names inside the one span. also in: pseudouridine · fifth nucleoside	`concept_edges[5]`	0.9	the tagger's words
concept_edges	HL-1 cells —distinct-from→ adult cardiomyocytes Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. strength of the relation: 1 · note: 'they do not represent true adult cardiomyocytes' - a flat denial of the model relation, in a paper whose subject is whether preclinical models support their conclusions. Not hedged: weight 1.0. also in: HL-1 cells · adult cardiomyocytes	`concept_edges[6]`	0.95	the tagger's words
content_tags	THE PAPER DEFINES ITS OWN TWO WORDS AND MAKES ONE DEPEND ON THE OTHER: rigor is `standardized state-of-the-art design, conduct and reporting`, and it is `a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[0]`	0.95	the tagger's words
content_tags	AND THE FAILURE IS COUNTED: `thousands of experimental studies ... so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[1]`	0.95	the tagger's words
content_tags	A STANDARDISED MULTI-CENTRE REPLICATION CONFIRMED ONE EFFECT OF THREE: CAESAR `identified only ischemic preconditioning, but not nitrite or sildenafil ... to reduce infarct size` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[2]`	0.95	the tagger's words
content_tags	TWO IMPLEMENTATIONS OF ONE NAMED TEST GIVE DIFFERENT ANSWERS: `different statistical software packages work with slightly different assumptions and can come to different outcomes, as demonstrated for the Wilcoxon-Mann-Whitney` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[3]`	0.95	the tagger's words
content_tags	THE SURROGATES DO NOT PREDICT WHAT THEY STAND IN FOR, AND THE REAL DEFINITION ARRIVES IN THE NEXT PARENTHESIS: `NONE ... is indeed predictive of clinical outcomes ... i.e. truly indicative of cardioprotection (which is primarily infarct size reduction)` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[4]`	0.95	the tagger's words
content_tags	ONE DRUG IS THE COMMON DENOMINATOR OF THE FAILURES: `propofol specifically abrogates the protection by remote ischemic conditioning ... and seems to be a common denominator of all studies that failed to see protection` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[5]`	0.95	the tagger's words
content_tags	THE INSTRUMENT DECIDES WHAT IS FOUND: `some will favor the isolation of short RNAs while others will enrich the RNA fraction with long molecules` - hence `not recommended to use different kits in the same study` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[6]`	0.95	the tagger's words
content_tags	AND ABUNDANCE HIDES ABUNDANCE: `the large abundance proteins mask the changes of low-abundance proteins which also make a significant contribution to cellular signalling` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[7]`	0.95	the tagger's words
content_tags	AND THE ANALYSIS TOOLS CANNOT BE COMPARED WITH EACH OTHER: `their diversity in mathematical models and source data do not yet allow accurate comparison of different results` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[8]`	0.95	the tagger's words
content_tags	NO ACCEPTED METHOD FOR MISSING VALUES, QUOTED RATHER THAN ASSERTED: `there is no methodological approach for handling missing values that is universally accepted in all situations` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[9]`	0.95	the tagger's words
content_tags	AND A COMMON PRACTICE IS REFUSED BECAUSE A NON-SIGNIFICANT PRETEST PROVES NOTHING: `Those pretests cannot be recommended, since the failure to reject the null hypothesis does not imply that the null hypothesis holds ... the power of the pretests is often low` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[10]`	0.95	the tagger's words
content_tags	AND A HUMAN DISAGREEMENT THRESHOLD TRIGGERS A PROCEDURE: `If the difference in infarct size between the readers exceeds 3%, a consensus reading is recommended` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[11]`	0.95	the tagger's words
content_tags	with the outlier included, the test gives t = 4.82 (36 df) and P < 0.001 Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[12]`	0.95	the tagger's words
content_tags	without the outlier, t = 6.08 (35 df), P < 0.001, and the group-mean difference is 20.06 (SD 10.03) Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[13]`	0.9	the tagger's words
content_tags	detecting a 0.1 increase in salvage index needs 83 patients per group at 80% power and two-sided alpha 0.05 Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[14]`	0.95	the tagger's words
content_tags	a biomarker reduction that was not powered for outcome nonetheless tracked increased survival and fewer events in an earlier study Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[15]`	0.9	the tagger's words
content_tags	`standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: rigor	`content_tags.definitions[0]`	0.95	the tagger's words
content_tags	`replication of results by another laboratory when performing exactly the same experiment` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: reproducibility	`content_tags.definitions[1]`	0.95	the tagger's words
content_tags	data outside Tukey's inner fences - `first quartile - 1.5 inter-quartile range and third quartile + 1.5 inter-quartile range` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: outlier	`content_tags.definitions[2]`	0.95	the tagger's words
content_tags	quoted from ICH E9: `the variable capable of providing the most relevant and convincing evidence directly related to the primary objective of the trial` Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: primary variable	`content_tags.definitions[3]`	0.95	the tagger's words
content_tags	3 — the disagreement between two human readers that triggers a consensus re-read Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[0]`	0.95	the tagger's words
content_tags	1.5 — Tukey's inner fences - the operational boundary of 'outlier' Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[1]`	0.95	the tagger's words
content_tags	1 — the number of studies that had unequivocally translated cardioprotection to improved clinical outcome, against thousands of experimental ones Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[2]`	0.95	the tagger's words
content_tags	the infarct size target and the salvage index change it corresponds to Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[3]`	0.95	the tagger's words
content_tags	current cardiac mortality, heart-failure rehospitalisation and composite endpoint incidence in the most recent cohort Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[4]`	0.95	the tagger's words
content_tags	`the gold standard primary endpoint` for cardioprotection, and the thing the surrogate endpoints fail to predict Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: Infarct size	`content_tags.variables[0]`	0.95	the tagger's words
content_tags	the same comparison run with and without the outlier, both t statistics, both P values, both mean differences and both confidence intervals Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.statistics[0]`	0.95	the tagger's words
content_tags	the worked survival-analysis power calculation, from assumed survival percentages to a hazard ratio to a per-group sample size Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.statistics[1]`	0.95	the tagger's words

Interpretive choices

Tags that could not be placed in the text:

none — every tag was located in the text

What was deliberately not tagged, and why, is recorded per paper by the tagger. Where a paper has no such record, this page says so rather than implying that nothing was declined.