Bibliographic record
Abstract
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Clinical presentation of RMS is diverse with the common characteristic of skeletal muscle differentiation. Two major histologic subtypes of RMS exist, alveolar (RMS-A) and embryonal (RMS-E), each with varying clinical presentation. Despite continued improvement in multi-modal therapy, long-term survival of RMS remains 60–70% using current regimens. Molecular genetic studies in cancers have revealed a new level of understanding in tumorigenesis and have proven useful in designing novel therapeutics. Previous studies have shown that molecular genetic alterations in RMS were heterogeneous with some being subtype-associated. Since alterations of gene expression can directly lead to the onset and progression of cancer, expression analysis of RMS-A and RMS-E were studied by two different techniques: low-density cDNA expression array and Representational Difference Analysis (RDA). Using cDNA array, heterogeneous expression of paxillin was identified between RMS tumors, with an overall increased expression in RMS when compared to normal tissues. The role of paxillin, a focal adhesion protein, in RMS tumor invasion and metastasis is thus implicated. With RDA, a novel non-coding RNA, given the name NCRMS ( Non-Coding in RMS), was isolated with increased expression in RMS-A. Partial sequence identity to expressed sequence tags from various species strongly suggested functional importance, but the absence of protein-coding properties implied a mode of action at the RNA level. Alternatively spliced transcripts were also identified. NCRMS is located on chromosomal region 12g21, in-between a pair of myogenic regulators Myf5 and Myf6 and the growth factor Igf1. Striking similarity in the relative position and context of NCRMS was noted with a well-recognized non-coding gene H19 on chromosomal region 11p15. H19 is located in-between another myogenic regulator MyoD1 and the growth factor Igf2, a homolog of Igf1. Function of NCRMS may thus be postulated in relation to H19. Overall, the work in this thesis revealed additional molecular genetic alterations in RMS. These changes point to various aspects of RMS tumor development. The identification of these changes will contribute to further understanding of potential mechanisms in RMS tumorigenesis.
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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 | 0.000 |
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".