Activation of peripheral leukocyte migration before spontaneous labor at term
Bibliographic record
Abstract
BACKGROUND: Leukocytes are induced to migrate into the uterus at parturition, releasing cytokines and chemokines that activate it for delivery. A specific chemotactic signal is required for these actions, and published evidence suggests that it comes from the human fetal membranes and has a time-dependent component (ie, cells obtained at term in labor migrate more than cells obtained at term not yet in labor). The hypothesis that the fetal membrane chemoattractants activate the leukocytes to become responsive for migration was tested. OBJECTIVE: This study aimed to: (1) examine the changes in leukocyte migration-responsiveness longitudinally from the late third trimester, to in labor, to 3 days postpartum; (2) explore the specific week-to-week changes in migration before delivery; (3) define the timing of chemokine receptor expression patterns in leukocytes relative to migration and the changes in cytokine and chemokine concentrations in maternal serum; (4) examine the ability of term fetal membrane-conditioned medium and term maternal serum to increase cell responsiveness; and (5) test the potential of the leukocyte migration assay to predict delivery within 1 week. STUDY DESIGN: Leukocyte migration in response to a chemoattractive extract of term human fetal membranes was studied using a modified Boyden chamber. Flow cytometry assessed migrated cell phenotypes. The relationship between the expression of chemokine receptors and migration was tested using quantitative polymerase chain reaction, the bioassay, and regression analyses. Cytokines and chemokines in maternal serum were quantified using multiplex analysis. Conditioned medium from fetal membrane explants and maternal serum were evaluated for their abilities to enhance leukocyte migration using the bioassay. The ability of the bioassay to predict term delivery was assessed using receiver-operating characteristic curve and cost-curve analysis. RESULTS: The number of leukocytes that migrated at term delivery was increased relative to the late third trimester, followed by a significant fall in numbers that migrated at 3 days postpartum (P=.002). The largest increase in migrated cells occurred 1 to 2 weeks before delivery. The messenger RNA abundance of several chemokine receptors increased in peripheral leukocytes at term in labor relative to the third trimester, and this correlated with an increase in migrated cells in 5 of 6 cases (R=0.589 to 0.897; P<.03). The concentrations of several chemokines and cytokines in maternal serum increased with labor onset. Fetal membrane explant-conditioned medium and maternal serum obtained at term labor increased the responsiveness of leukocytes to fetal membrane chemoattractive extract. The bioassay was demonstrated to predict delivery within 7 days with excellent performance characteristics using a cohort prevalence of 71.7% (positive predictive value=96.1%; negative predictive value=58.5%; sensitivity=74.2%; specificity=92.3%; positive likelihood ratio=9.25; and negative likelihood ratio=0.28). A single determination was validated to have a high degree of confidence. CONCLUSION: Term human fetal membranes release chemoattractants near the end of pregnancy that increase in ability to activate and attract an increasing number of leukocytes as gestation advances.
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 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".