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Record W4408592015 · doi:10.1101/2025.03.18.644000

Integrated histopathology of the human pancreas throughout stages of type 1 diabetes progression

2025· preprint· en· W4408592015 on OpenAlexaff
Verena van der Heide, Sara McArdle, Michael S. Nelson, Karen Cerosaletti, Sacha Gnjatic, Zbigniew Mikulski, Amanda L. Posgai, Irina Kusmartseva, Mark A. Atkinson, Dirk Homann

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDiabetes and associated disorders
Canadian institutionsInstitute of Nutrition, Metabolism and Diabetes
Fundersnot available
KeywordsHistopathologyPancreasType 2 diabetesType (biology)Diabetes mellitusMedicinePathologyBiologyInternal medicineEndocrinologyEcology

Abstract

fetched live from OpenAlex

SUMMARY Type 1 diabetes (T1D) is a progressive autoimmune condition that culminates in the loss of insulin-producing beta cells. Pancreatic histopathology provides essential insights into disease initiation and progression yet an integrated perspective of in situ pathogenic processes is lacking due to limited sample availability, the dispersed nature of anatomical lesions, and often restricted analytical dimensionality. Here, we combined multiplexed immunostaining, high-magnification whole-slide imaging, digital pathology, and semi-automated image analysis strategies to interrogate pancreatic tail and head regions obtained from organ donors across T1D stages including at-risk and at-onset cases. Deconvolution of architectural features, endocrine cell composition, immune cell burden, and spatial relations of ∼25,000 islets revealed a series of novel histopathological correlates especially in the prodromal disease stage preceding clinical T1D. Altogether, our comprehensive “single-islet” analyses permit the reconstruction of a revised natural T1D history with implications for further histopathological investigations, considerations of pathogenetic modalities, and therapeutic interventions.

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)0.000
metaresearch head score (Gemma)0.000
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
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 head0.008
GPT teacher head0.244
Teacher spread0.236 · 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".

Quick stats

Citations8
Published2025
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicDiabetes and associated disordersFrench-language works237,207