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Record W4405896422 · doi:10.1073/pnas.2412561121

Comparing integrative ventilatory and renal acid–base acclimatization in lowlanders and Tibetan highlanders during ascent to 4,300 m

2024· article· en· W4405896422 on OpenAlexafffund
Nicole Johnson, Jessica A. Dickenson, Benjamin W.L. MacKenzie, Rodion Isakovich, Anne Kalker, Janne Bouten, Nicholas D. J. Strzalkowski, Taylor S. Harman, Pontus Holmström, Ajaya Jang Kunwar, Nilam Thakur, Sunil Dhungel, Nima Sherpa, Abigail W. Bigham, Tom D. Brutsaert, Trevor A. Day

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHigh Altitude and Hypoxia
Canadian institutionsMount Royal University
FundersNatural Sciences and Engineering Research Council of CanadaNational Academy of SciencesNational Academies of Sciences, Engineering, and MedicineNational Science Foundation
KeywordsAcclimatizationRespiratory compensationHypocapniaEffects of high altitude on humansRespiratory alkalosisAlkalosisAcid–base homeostasisMetabolic alkalosisRespiratory systemAcidosisOxygenationHypoxic ventilatory responseHyperoxiaInternal medicineMedicineMetabolic acidosisBiologyPhysiologyHypercapniaAnaerobic exerciseAnatomyLungEcology

Abstract

fetched live from OpenAlex

With over 14 million people living above 3,500 m, the study of acclimatization and adaptation to high altitude in human populations is of increasing importance, where exposure to high altitude (HA) imposes a blood oxygenation and acid–base challenge. A sustained and augmented hypoxic ventilatory response protects oxygenation through ventilatory acclimatization, but elicits hypocapnia and respiratory alkalosis. A subsequent renally mediated compensatory metabolic acidosis corrects pH toward baseline values, with a high degree of interindividual variability. Differential renal compensation between acclimatizing lowlanders (LL) and Tibetan highlanders (TH; Sherpa) with ascent was previously unknown. We assessed ventilatory and renal acclimatization between unacclimatized LL and TH during incremental ascent from 1,400 m to 4,300 m in age- and sex-matched groups of 15-LL (8F) and 14-TH (7F) of confirmed Tibetan ancestry. We compared respiratory and renally mediated blood acid–base acclimatization (PCO 2 , [HCO 3 − ], pH) in both groups before (1,400 m) and following day 8 to 9 of incremental ascent to 4,300 m. We found that following ascent to 4,300 m, LL had significantly lower PCO 2 ( P <0.0001) and [HCO 3 − ] ( P <0.0001), and higher pH ( P = 0.0037) than 1,400 m, suggesting respiratory alkalosis and only partial renal compensation. Conversely, TH had significantly lower PCO 2 ( P < 0.0001) and [HCO 3 − ] ( P < 0.0001), but unchanged pH ( P = 0.1), suggesting full renal compensation, with significantly lower PCO 2 ( P = 0.01), [HCO 3 − ] ( P < 0.0001) and pH ( P = 0.005) than LL at 4,300 m. This demonstration of differential integrative respiratory–renal responses between acclimatizing LL and TH may indicate selective pressure on TH, and highlights the important role of the kidneys in acclimatization.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.165
Threshold uncertainty score0.160

Codex and Gemma teacher scores by category

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

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 head0.026
GPT teacher head0.293
Teacher spread0.267 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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".

Quick stats

Citations13
Published2024
Admission routes2
Has abstractyes

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