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Record W3206800672 · doi:10.11575/prism/39123

Studies on Hematogenous Dissemination of Lyme Disease Spirochetes

2021· dissertation· en· W3206800672 on OpenAlexfundaboutno aff
Xi Tan

Bibliographic record

VenueOpen MIND · 2021
Typedissertation
Languageen
FieldImmunology and Microbiology
TopicVector-borne infectious diseases
Canadian institutionsnot available
FundersFaculty of Dentistry, University of TorontoUniversity of Toronto
KeywordsLyme diseaseBorrelia burgdorferiDiseaseMedicineBiologyVirologyMicrobiologyImmunologyPathologyAntibody

Abstract

fetched live from OpenAlex

Lyme disease (LD), caused by various members of the genus Borrelia, is the most prevalent tick-transmitted illness in North America and Europe (Groshong & Blevins, 2014, Stanek et al., 2011). There is an increasing risk of LD in Canada. In 2014, the Government of Canada launched a national communication campaign to raise social awareness and promote individual preventive behaviors toward LD. Hematogenous dissemination is important for infection by Borrelia burgdorferi (B. burgdorferi). B. burgdorferi can attach to the vascular endothelium and disseminate into a variety of tissue types. B. burgdorferi hematogenous dissemination is a multistep process and consists of several successive stages: transient (tethering plus dragging) interactions, followed by stationary adhesion and/or extravasation (Norman et al., 2008, Coburn et al., 2013). However, the mechanism of borrelial vascular adhesion and extravasation remained unclear. We are using intravital microscopy (IVM) (Kumar et al., 2015, Secklehner et al., 2017, Stolp & Melican, 2016) to identify and characterize B. burgdorferi adhesins, which are believed to be involved in vascular adhesion, transmigration as well as tissue tropism (Coburn et al., 2013, Caine & Coburn, 2016). From the B. burgdorferi side, we have shown that OspC is a dermatan sulfate- (DS-) and fibronectin- (FN-) binding adhesin that is required for vascular transmigration and joint colonization in mice (Lin et al., 2020). We also identified that VlsE, a well-known antigenically variable outer surface lipoprotein, is a DS-binding adhesin that efficiently promotes transient adhesion to the microvasculature via its DS binding activity in vivo. Moreover, on the host side, we have shown that instead of phagocytizing B. burgdorferi, host neutrophils are involved in producing specific cytokines (TNF-α, MCP-1, IL-10) that activate the endothelium and potentiate B. burgdorferi escape into the surrounding tissue. Spirochete escape is not induced by paracellular permeability and appears to occur via a transcellular pathway. Neutrophil repurposing to promote bacterial extravasation represents a new and innovative pathogenic strategy (Tan et al., 2021). Our findings provide insight into the mechanism of Borrelia hematogenous dissemination and how LD spirochetes employ host immune cells for vascular extravasation.

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)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
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 head0.027
GPT teacher head0.340
Teacher spread0.313 · 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 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

Citations0
Published2021
Admission routes2
Has abstractyes

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Same venueOpen MINDSame topicVector-borne infectious diseasesFrench-language works237,207