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From Model Choice to Model Belief: Establishing a New Measure for LLM-Based Research

arXiv:2512.23184v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly used to simulate human behavior, but common practices to use LLM-generated data are inefficient. Treating an LLM's output ("model choice") as a single data point underutilizes the information inherent to the probabilistic nature of LLMs. This paper introduces and formalizes "model belief," a measure derived from an LLM's token-level probabilities that captures the model's belief distribution over choice alternatives in a single generation run. The authors prove that model belief is asymptotically equivalent to the mean of model choices (a non-trivial property) but forms a more statistically efficient estimator, with lower variance and a faster convergence rate. Analogous properties are shown to hold for smooth functions of model belief and model choice often used in downstream applications. The authors demonstrate the performance of model belief through a demand estimation study, where an LLM simulates consumer responses to different prices. In practical settings with limited numbers of runs, model belief explains and predicts ground-truth model choice better than model choice itself, and reduces the computation needed to reach sufficiently accurate estimates by roughly a factor of 20. The findings support using model belief as the default measure to extract more information from LLM-generated data.

Integrated Multi-Omics Profiling Identifies PDZ-Binding Kinase (PBK) as a Novel Prognostic Biomarker in Hepatocellular Carcinoma

J Hepatocell Carcinoma. 2025 Jul 17;12:1453-1469. doi: 10.2147/JHC.S493907. eCollection 2025.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) necessitates novel immunotherapeutic targets. PBK, a cancer/testis antigen (CTA), was identified as a pivotal hub gene influencing prognosis, tumor mutation burden (TMB), and immune microenvironment remodeling.

METHODS: PBK was prioritized using weighted gene co-expression network analysis (WGCNA) and differential expression screening in the TCGA-LIHC cohort, intersected with curated CTAs. Analyses assessed correlations with clinicopathological features (TNM stage, survival), genomic characterization (mutation frequencies), and functional validation via siRNA-mediated PBK knockdown in Huh7 cells (migration assay). Single-cell RNA sequencing (scRNA-seq) profiled of the tumor immune microenvironment.

RESULTS: PBK overexpression was significantly correlated with advanced TNM stage (P < 0.05) and poor survival (log-rank P = 0.003). Genomic analysis revealed distinct mutation profiles: high-PBK tumors exhibited increased TP53 mutation frequency (39% vs 17%) but decreased CTNNB1 mutations (20% vs 31%). Patients exhibiting with combined PBK overexpression and high TMB demonstrated the poorest prognosis. Functional validation confirmed that PBK knockdown significantly inhibited Huh7 cell migration capacity (P < 0.05). scRNA-seq analysis showed PBK-enriched tumors contained elevated proportions of immunosuppressive SPP1(+) macrophages (22.33% vs 6.6%, FDR corrected P < 0.001) and CD8(+) SLC4A10(+) MAIT cells (9.82% vs 4.7%, FDR corrected P < 0.001).

CONCLUSION: PBK synergistically drives HCC progression through three synergistic mechanisms: (1) promoting oncogenic mutation accumulation (eg, TP53), (2) increasing metastatic potential, and (3) reprogramming an immune-suppressive microenvironment enriched for SPP1(+) macrophages and CD8(+)SLC4A10(+) MAIT cells. This establishes PBK as a dual-purpose biomarker for prognostic stratification and immunotherapy resistance prediction, providing a mechanistic rationale for developing PBK-targeted therapies in HCC.

PMID:40697330 | PMC:PMC12279550 | DOI:10.2147/JHC.S493907

Correction: Proof-of-principle studies on a strategy to enhance nucleotide imbalance specifically in cancer cells

Cell Death Discovery, Published online: 30 November 2022; doi:10.1038/s41420-022-01275-z

Correction: Proof-of-principle studies on a strategy to enhance nucleotide imbalance specifically in cancer cells
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