Methylmalonic acid concentration in dried blood spots – validation of a novel method for vitamin B12 status assessment
Bibliographic record
Abstract
Marginal vitamin B 12 (B 12 ) deficiency has been associated with an increased risk of adverse pregnancy outcomes and cognitive decline. About 10 % of the US population and 25 % of the Canadian population show inadequate B 12 status. Methylmalonic acid (MMA) is a functional biomarker for B 12 status and a sensitive indicator for marginal B 12 deficiency. To date, MMA concentrations are measured in plasma samples obtained from venipuncture. Dried blood spots (DBS) allow non‐invasive, simple collection of biological samples with no need of immediate processing or special storage. The goal of this study was to establish an analytical method for quantification of MMA in DBS and to validate its application for B 12 status assessment. Using liquid chromatography ‐ tandem mass spectrometry, we developed a simple, low‐cost assay that shows high imprecision (CV < 1.2 %) and good recovery (95 %). In 73 healthy female subjects (19 – 30 y), mean (± SD) concentrations of plasma MMA and DBS MMA were 163 ± 65 nmol/L (74 – 458 nmol/L) and 36.4 ± 11 pmol/DBS, respectively. There was a strong correlation between plasma and DBS MMA concentrations (R = 0.90 P < 0.001). This novel method was shown to be sensitive, reliable, and convenient. MMA analysis in DBS has the potential to be a more practical alternative for B 12 screening and to facilitate B 12 status assessment in large‐scale population‐based surveys and in populations living in less accessible areas. Grant Funding Source : ‘FNH Vitamin Research Fund’ University of British Columbia
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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 | 0.003 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".