Bibliographic record
Abstract
Introduction: Neuron development and survival are regulated by neurotrophins, including nerve growth factor (NGF).In female elderly people with overactive bladder syndrome (OAB), the levels of NGF in urine are reduced, which has been linked to elevated activity of the enzyme matrix metalloproteinase-9 (MMP-9), the main protease responsible for NGF degradation.These characteristics were also observed in animal models of type 1 diabetic bladder dysfunction, and improved by chronic treatment with THX-B, an antagonist of the proinflammatory receptor p75 NTR .The aim of this study was to investigate the functional benefit of p75 NTR antagonism on bladder function in aging mice.Methods: Male and female C57BL/6J mice, aged six and 12 months, were subjected to a four-week treatment of THX-B or PBS (control).Urination behaviors and patterns were measured using a voiding spot test.Bladder contractility was evaluated using organ baths in the presence of KCl, electrical field stimulation, and carbachol.Conscious cystometry was performed after bladder catheterization surgery to assess bladder contractility.ELISA kits were used to measure NGF and proNGF levels in urine.Immunoblotting was used to semi-quantify MMP-9, VachT, and PGP 9.5.Results: THX-B improved voiding behavior and bladder contractility compared to the control group: total urine volume, volume per micturition, and voiding frequency were reduced in 12-month-old male and female mice.Ex-vivo, bladder contractility stimulated by KCl, electrical field stimulation, and stimulation by carbachol were reduced in strips from mice after THX-B treatment.In female mice, conscious cystometry revealed a decrease in maximal voiding pressure, basal pressure, spontaneous activity, and micturition volume by THX-B treatment compared to controls.In males, THX-B decreased the maximal voiding pressure and residual volume.Moreover, THX-B treatment increased NGF urine levels in six-and 12-month-old male and female mice, restoring the NGF/proNGF imbalance.MMP-9 activity was decreased, but only in female mice.Conclusions: Our results suggest that the improved bladder parameters by THX-B is age-dependent and leads to improved bladder function only in 12-month-old mice.Decreased MMP-9 activity occurs exclusively in female mice, suggesting gender-specific pathways.THX-B could potentially be used as a therapeutic intervention to improve OAB in the female aging population.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.471 | 0.377 |
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".