P2‐032: Three‐dimensional telomere analysis in Alzheimer's disease (AD)
Bibliographic record
Abstract
Telomeres are linear TTAGGG repeats capping human chromosomes maintaining chromosomal integrity. Telomeres shorten progressively with each cell division and with age. The aims of our study was to analyze the three-dimensional (3D) architecture of telomeres in AD patients compared to age-matched normal controls in cells obtained from buccal swaps. 3D analysis allows for quantification of telomere numbers, length and aggregates. Buccal swaps were chosen because cells derive from the neuroectoderm from which brain tissue also originates, and they can be collected non-invasively. Twenty six patients with AD diagnosed and staged by standard procedures (mild = 14, moderate = 7, and severe = 6) and 26 cognitively normal age-matched controls were included in the study. Cells were obtained from buccal swaps using sterile Epicentre Biotechnologies swabs, smeared on VWR micro slides and frozen at -20° C. Quantitative fluorescence in situ hybridization (Q-FISH) technique was used for telomere numbers and length analysis in 30 interphase cells/person. Digital images were taken using Zeiss AxioImager Z1 with a cooled AxioCam HR B&W, DAPI, Cy3 filters in combination with a Planapo 63x/1.4 oil objective lens. Images were acquired by using AXIOVISION 4.8 (Zeiss) in multichannel mode followed by constrained iterative deconvolution. For every fluorochrome, 120 images stacks were acquired with a sampling distance of 200 nm along the z, and 102 nm in the XY axis. Quantitation of 3D nuclear telomeric signals was performed using TeloView. Differences in telomere intensity between AD patients and normal controls, were analyzed by Fisher exact test (number of telomeres) and Chi-Square (telomere length). Patients with mild to severe AD had significantly less number of telomeres and shorter telomeres than the control subjects (range from P<.001 to P<.0001). There was no difference in telomere aggregates between AD patients and controls. Smeared buccal swap cells are suitable for telomere 3D analysis in AD and normal controls. Subjects with AD, at any stage of the disease had less and shorter telomeres in their buccal cells when compared to their age-matched controls. No differences in aggregates distinguish the findings from the ones in cancer patients. Validation in a larger sample is warranted.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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".