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Record W3039130389

The Peripheral Immunophenotype in Neurodevelopmental Disorders

2018· dissertation· en· W3039130389 on OpenAlexaboutno aff
Grace Teskey

Bibliographic record

VenueMacSphere (McMaster University) · 2018
Typedissertation
Languageen
FieldNeuroscience
TopicAutism Spectrum Disorder Research
Canadian institutionsnot available
Fundersnot available
KeywordsImmunophenotypingPeripheralMedicinePathologyNeurosciencePsychologyImmunologyInternal medicineFlow cytometry
DOInot available

Abstract

fetched live from OpenAlex

The factors contributing to the severity of the neurodevelopmental disorders autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are largely unknown. Previous studies have indicated immune abnormalities in these disorders, such as increased inflammation and altered immune cell numbers. We, in collaboration with the Province of Ontario Neurodevelopmental Disorder (POND) Network, analyzed markers of intestinal permeability and inflammation in children diagnosed with ASD or ADHD, as well as typically developing controls. Plasma from these participants was used to investigate levels of soluble inflammation, denoted by circulating acute phase proteins, as well as circulating levels of markers of intestinal epithelial damage and bacterial translocation. Peripheral blood mononuclear cells were isolated from these participants and used to construct an immunophenotype of ASD and ADHD, focusing on monocytes and monocyte activation and maturation. These data were then compared with scores of behaviour severity to identify associations between inflammation and behaviour in these disorders. We identified increased soluble inflammation in ASD, indicated by increased circulating C-reactive protein. We associated this inflammation with intestinal permeability, indicated by increased circulating LPS. Classical monocyte frequency was significantly lower in ASD and these monocytes displayed an altered migratory phenotype, indicated by a reduction in CCR2 expression. Furthermore, we have identified potential maladaptive monocyte responses to soluble inflammation in both ASD and ADHD, with altered monocyte phenotypes in response to inflammatory mediators compared to typically developing controls. Finally, we identified that changes in monocyte phenotype are associated with more severe behaviours in both ASD and ADHD. These findings imply that inflammation and immune abnormalities contribute to the severity of neurodevelopmental disorders.

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 categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Other · Consensus signal: Other
Teacher disagreement score0.959
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0020.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0390.000

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 head0.013
GPT teacher head0.236
Teacher spread0.223 · 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.

Study designNot applicable
Domainnot available
GenreOther

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
Published2018
Admission routes1
Has abstractyes

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