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Record W3155588713

The Development of Local-acting Biologics to Treat Rheumatoid Arthritis

2019· dissertation· en· W3155588713 on OpenAlexfundno aff
Eric Neely

Bibliographic record

VenueTSpace · 2019
Typedissertation
Languageen
FieldMedicine
TopicMonoclonal and Polyclonal Antibodies Research
Canadian institutionsnot available
FundersUniversity of TorontoStem Cell Network
KeywordsRheumatoid arthritisMedicineInternal medicine
DOInot available

Abstract

fetched live from OpenAlex

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and progressive joint destruction. Anti-TNF biologics have been developed to treat RA and although effective in the majority of patients, they require repeated administration and systemically inhibit TNF. This systemic inhibition leads to systemic immune suppression and can result in side-effects including opportunistic infections, serious infections and malignancy. To address these limitations, I developed a novel, local-acting biologic known as TNF sticky trap. This biologic was shown capable of inhibiting TNF while sticking or localizing to the extracellular matrix (ECM) where it is produced or administered. Next, cell lines inducibly expressing this local-acting biologic were generated, characterized and evaluated for their therapeutic efficacy in an animal model of RA. A single injection of cells expressing TNF sticky trap was sufficient to reduce arthritis and this local-acting biologic was undetectable in the serum of treated animals. Lastly, to help advance the translation of RA cell therapies into the clinic, a cell safety mechanism was developed and characterized. The development of a safe cell therapy inducibly expressing local-acting biologics could avoid the limitations associated with systemic therapies and improve the current treatment of RA.

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: Other design · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.960
Threshold uncertainty score0.482

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 head0.039
GPT teacher head0.381
Teacher spread0.342 · 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 designOther design
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

Citations0
Published2019
Admission routes1
Has abstractyes

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