New Advances in Capillary Electrophoresis for Biomonitoring in Population Health and Newborn Screening of Cystic Fibrosis
Bibliographic record
Abstract
Biological markers (i.e., biomarkers) are essential in clinical and epidemiological studies as they may provide mechanistic insights into the developmental origins of disease, as well as improve diagnostic testing and risk assessment for disease prevention. However, major challenges remain due to the lack of rapid yet selective analytical methods for high throughput screening that are also amenable to volume-restricted specimens. This thesis includes two major research themes that take advantage of capillary electrophoresis (CE) separations, including (1) the targeted analysis of urinary iodide and thiocyanate for assessment of nutritional adequacy and tobacco smoke exposures in the population, and (2) the discovery of new biomarkers in sweat specimens that may improve universal newborn screening programs for cystic fibrosis (CF) infants beyond impaired chloride transport. Chapter II examines the prevalence and risk factors associated with iodine deficiency in 24 h urine samples collected from 800 participants across four clinical sites in Canada as part of the Prospective Urban and Rural Epidemiological (PURE) study when using CE with UV detection in conjunction with sample self-stacking. Importantly, regional variations in iodine status were revealed with participants from Quebec City and Vancouver at greater risk for iodine deficiency than Hamilton and Ottawa. Overall, iodine supplement use, thyroxine prescription, urinary sodium excretion, and self-reported dairy intake were found to be protective factors against iodine deficiency. Chapter III applied a validated CE assay to measure urinary thiocyanate as a biomarker of tobacco smoke and dietary exposures in an international cohort of 1000 participants from the PURE study spanning 14 countries with varied income status, smoking habits, and diet quality. Current smokers residing in high-income countries had the highest extent of cyanide exposure indicative of greater harms from tobacco smoke compared to middle- and low-income countries after adjusting for smoking intensity and other covariates. Chapter IV introduces a rapid CE method with indirect UV detection to simultaneously measure sweat chloride and bicarbonate from presumptive CF infants’ residual sweat samples. Although bicarbonate did not provide clinical value in neonatal CF diagnosis, sweat chloride testing by CE may reduce test failure rates due to insufficient volumes from infants in a clinical setting. Lastly, Chapter V applied an untargeted strategy to characterize the sweat metabolome from presumptive CF infants when using multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). A panel of sweat metabolites were found to discriminate CF from non-CF (i.e., unaffected carriers) infants, including aspartic acid, glutamine, oxoproline, and pilocarpic acid, which also correlated with sweat chloride. The clinical utility of these sweat metabolites to prognosticate late-onset CF infants from indeterminate sweat chloride test results was also explored. In summary, this thesis contributes innovative separation methods for biomarker screening and discovery in clinical and epidemiological studies for the prevention and early treatment of human diseases that benefit from optimal nutrition.
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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 | 0.004 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".