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Increases in concentric hypertrophy are driven by natural selection in the Spontaneously Hypertensive Rat Colony

2021· article· en· W3167097056 on OpenAlexafffund
Emma Holjak, Iryna Savinova, Victoria A. Nelson, Anabelle M Ng, Leslie M. Ogilvie, Hermann J. Eberl, Brittany A. Edgett, Keith R. Brunt, Jeremy A. Simpson

Bibliographic record

VenueThe FASEB Journal · 2021
Typearticle
Languageen
FieldMedicine
TopicRenin-Angiotensin System Studies
Canadian institutionsSaint John Regional HospitalHorizon Health NetworkUniversity of Guelph
FundersCanadian Institutes of Health Research
KeywordsBlood pressureMedicineConcentric hypertrophyMuscle hypertrophyHeart failureLeft ventricular hypertrophyInternal medicineCardiac hypertrophyCardiologyPhysiologyEndocrinology

Abstract

fetched live from OpenAlex

Background Heart failure (HF) is a global health concern that affects nearly 26 million people each year. The Spontaneously Hypertensive Rat (SHR) was established in 1963 and is the most commonly used rodent model for studying human HF. Unlike humans, the SHRs develop hypertension around their reproductive age (i.e., when animals are selected for breeding), providing the opportunity for natural selection towards adaptive traits for hypertension‐induced heart failure. Therefore, the primary objective of this review was to evaluate whether SHRs have evolved over time to the cardiac sequelae of hypertension. We hypothesized that, while the severity of hypertension will remain stable within the SHR colony, the HF phenotype will become less pronounced with time as a result of compensatory changes to manage high blood pressure. Methods We performed a retrospective review evaluating several indices of cardiovascular health in the SHR over the past 60 years. For statistical analyses, studies that met the inclusion criteria were separated into 2 cohorts: Initial (mid‐late 1900’s) and Current (early 2000’s ‐present) Colony SHRs. Wistar‐Kyoto rats (i.e., normotensive rats used to establish the SHR line via selective breeding) were used as controls to normalize changes in technique and methods that have occurred over these decades. Results Systolic blood pressure did not differ between Initial and Current Colony SHRs, indicating that the severity of hypertension had remained stable within the SHR Colony over time. Current Colony SHRs presented with increased cardiac concentric hypertrophy (i.e., elevated heart weight and posterior wall thickness). Since these changes were not observed in the Wistar‐Kyoto control rats, cardiac‐derived changes in Current Colony SHRs were unlikely due to differences in techniques, equipment, anesthesia or environmental conditions. Conclusion These findings establish that the SHR colony has evolved over time, with greater concentric hypertrophy. Using natural selection to find positive adaptive traits may be advantageous in identifying new therapeutic treatment strategies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.005
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.005
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0020.002
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.012
GPT teacher head0.237
Teacher spread0.225 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2021
Admission routes2
Has abstractyes

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