47: Decreased Nasal Nitric Oxide in Children with Isolated Midline Neuroanatomical Defects: A Possible Indicator of Ciliary Dysfunction?
Bibliographic record
Abstract
Cilia are microtubule-based structures marking the surfaces of most eukaryotic cell types, with crucial roles in cell division, axis determination, migration and differentiation. Ciliary mutations give rise to a spectrum of human disorders, collectively termed ‘ciliopathies’, with which midline neuroanatomical defects are strongly associated. However, an association between isolated neuroanatomical defects and ciliary dysfunction has never been proven. One test for ciliary function is measurement of nasal nitric oxide, which correlates with mean ciliary beat frequency. It is a sensitive, noninvasive test, currently used in screening for Primary Ciliary Dyskinesia. To determine whether children with congenital isolated midline neuroanatomical defects suffer from ciliary dysfunction, using measurement of nasal nitric oxide. We measured the nasal nitric oxide levels of 26 children ages 6–17, with congenital midline central nervous system defects, who are otherwise healthy. We evaluated the effect of a number of variables including: age, gender, and anomaly (brain, spinal cord, or combined) on our measurements. We compared our results to the previously established normal range (153.6-509.9 nL/min), and to the cutoff for children with Primary Ciliary Dyskinesia (77 nL/min). The overall range for nasal nitric oxide in our cohort was 56.5 to 334.7 nL/min, with age, gender, and anomaly not having a significant effect on the result. The overall mean, 217.7 nL/min, was significantly lower than the pre-established mean in normal children of the same age, 314.51 nL/min (P<0.05). Four subjects (15.4%) had mean nitric oxide levels below the lower end of normal, with two (7.7%) having values below the cutoff for Primary Ciliary Dyskinesia. This is the first study reporting an association between ciliary dysfunction and isolated congenital midline neuroanatomical defects, not in the context of any known syndrome or ciliopathy. A possible candidate underlying both includes tubulin, a gene family encoding the microtubule alpha and beta subunits, necessary for proper ciliary formation. The tubulin gene products play a pivotal role in neuronal migration, cortical laminar organization, and guidance of radial glia, and their mutations were shown to result in a number of neuroanatomical malformations. Further studies are warranted to investigate this possible genetic link. From a clinical perspective, longitudinal studies will be required to determine whether nasal ciliary dysfunction in children with congenital midline brain anomalies has any clinical bearing on their respiratory function later in life.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".