Evidence map›Paper›PMID 40561578›Full record

ArticleComputers in biology and medicine2025

When less is statistically Equivalent: Lobe-Specific optimization of histopathological assessment in SARS-CoV-2 pneumonia.

Rachel Reader, Lincoln Hopkins, Koen K A Van Rompay, Katherine J Olstad, Amir Ardeshir

Abstract read
In one paragraph

Article in Computers in biology and medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

5 authors.

Rachel ReaderCalifornia National Primate Research Center, University of California-Davis, Davis, CA, USA; Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Lincoln HopkinsCalifornia National Primate Research Center, University of California-Davis, Davis, CA, USA.
Koen K A Van RompayCalifornia National Primate Research Center, University of California-Davis, Davis, CA, USA; Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Katherine J OlstadCalifornia National Primate Research Center, University of California-Davis, Davis, CA, USA; Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Amir ArdeshirDivision of Microbiology, Tulane National Primate Research Center, Covington, LA, USA; Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA, USA. Electronic address: aardeshir@tulane.edu.

Funding

National Institute on Aging (NIA) ColonyP51OD011107 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Simon J. Atkinson · 2012 to 2026
$191.5M
Tulane NPRC SPF Sheltered Outdoor Enclosure ExpansionP51OD011104 · OD · TULANE UNIVERSITY OF LOUISIANA · PI L Lee HAMM · 2012 to 2026
$142.4M
NIH HHS P51 OD011104NIH HHS P51 OD011107
6 · The paper itself

Abstract

backgroundPrecise histopathological assessment of pulmonary lesions in animal models is fundamental to evaluating COVID-19 interventions. The multifocal, heterogeneous distribution of SARS-CoV-2-induced pathology in rhesus macaques presents a critical challenge: balancing comprehensive evaluation against resource efficiency. No statistically-validated sampling optimization exists for this widely-used model. We hypothesized that lobe-specific, statistically-validated sampling thresholds could maintain assessment accuracy while significantly reducing analytical burden.

methodsWe developed a semi-quantitative scoring system targeting interstitial pneumonia-the predominant histopathological feature in SARS-CoV-2-infected rhesus macaques (n = 12). Two ACVP board-certified pathologists independently evaluated 710-1634 high-power fields (40 × magnification) per animal across seven lung lobes, achieving substantial inter-rater reliability (Cohen's κ = 0.74). To determine minimum sampling requirements maintaining statistical equivalence with comprehensive assessment, we employed bootstrapping simulation (10,000 iterations) combined with Two One-Sided Tests (TOST) equivalence analysis (bounds: ±0.25 pathology points).

resultsOptimal sampling percentages exhibited significant lobe-specific variability: left caudal (25 %, p = 0.047), right caudal (30 %, p = 0.038), left/right proximal, (50 %, p = 0.044/p = 0.043), right accessory (50 %, p = 0.172), right middle (60 %, p = 0.049), and left middle (75 %, p = 0.084). Power analysis demonstrated robust detection capability (range: 0.45-0.72) at α = 0.05. These optimized parameters reduce required field assessments by 25-75 % while maintaining statistical equivalence.

conclusionThis first anatomically-stratified, statistically-validated methodology significantly enhances histopathological assessment efficiency in the rhesus macaque COVID-19 model. By establishing lobe-specific minimum sampling thresholds that preserve statistical equivalence, our approach optimizes resource utilization while maintaining sensitivity to detect intervention effects, potentially accelerates preclinical therapeutic evaluations.

Indexed as

COVID-19LungSARS-CoV-2AnimalsDisease Models, AnimalMacaca mulattaMaleCOVID-19 pathologyHistopathological optimizationInterstitial pneumoniaRhesus macaque modelStatistical equivalence testing

Identifiers

PMID40561578
PMCPMC12413750

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.