P09 Long-term obeticholic acid (OCA) for Primary Biliary Cholangitis (PBC) in a clinical trial improved event free survival (death, liver transplant and hepatic decompensation) compared to external controls from the GLOBAL PBC real-world database
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Mice lacking expression of the phosphatases Sts-1 and Sts-2 (<i>Sts−/−</i>) are significantly resistant to disseminated candidiasis caused by the fungal pathogen <i>Candida albicans</i>. Resistance is associated with diminished levels of many inflammatory molecules, a reduction in kidney leukocyte infiltrates by 48 hours post infection, and an absence of inflammatory lesions. Unlike wild type mice, <i>Sts−/−</i> mice clear the infection from the kidney following inoculation with supra-lethal doses. To better understand parameters underlying the <i>Sts−/−</i> phenotype of enhanced resistance, we examined the kinetics of fungal clearance at early time points. We observed enhanced fungal clearance within <i>Sts−/−</i> kidneys beginning at 12–18 hrs. post infection. This corresponds to the timeframe when innate leukocytes such as Ccr2+ inflammatory monocytes (IMs) begin entering the tissue to counter the infection. To examine the role of IMs in promoting enhanced fungal clearance evident in <i>Sts−/−</i> animals, we infected mice lacking Ccr2 expression. Loss of Ccr2 abrogated both the fungal clearance and the survival advantage of <i>Sts−/−</i> mice. Analysis of innate anti-fungal effector responses revealed enhanced production of reactive oxygen species by phagocytes lacking Sts expression, with no apparent differences in the responses of other effector pathways. Downstream of fungal receptor Dectin-1, the Syk kinase was hyper-activated in <i>Sts−/−</i> cells. Our results identify Syk as a target of Sts activity in phagocytes and highlight a novel mechanism regulating the anti-fungal immune response. Further understanding of this regulatory pathway could aid in the development of therapeutics to protect against invasive candidiasis.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.000 | 0.000 |
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 it