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Physiologically Informed Deep Learning: A Multi-Scale Framework for Next-Generation PBPK Modeling

24 February 2026 at 13:00
arXiv:2602.18472v1 Announce Type: cross Abstract: Physiologically Based Pharmacokinetic (PBPK) modeling is a cornerstone of model-informed drug development (MIDD), providing a mechanistic framework to predict drug absorption, distribution, metabolism, and excretion (ADME). Despite its utility, adoption is hindered by high computational costs for large-scale simulations, difficulty in parameter identification for complex biological systems, and uncertainty in interspecies extrapolation. In this work, we propose a unified Scientific Machine Learning (SciML) framework that bridges mechanistic rigor and data-driven flexibility. We introduce three contributions: (1) Foundation PBPK Transformers, which treat pharmacokinetic forecasting as a sequence modeling task; (2) Physiologically Constrained Diffusion Models (PCDM), a generative approach that uses a physics-informed loss to synthesize biologically compliant virtual patient populations; and (3) Neural Allometry, a hybrid architecture combining Graph Neural Networks (GNNs) with Neural ODEs to learn continuous cross-species scaling laws. Experiments on synthetic datasets show that the framework reduces physiological violation rates from 2.00% to 0.50% under constraints while offering a path to faster simulation.

PoTable: Towards Systematic Thinking via Plan-then-Execute Stage Reasoning on Tables

24 February 2026 at 13:00
arXiv:2412.04272v4 Announce Type: replace-cross Abstract: In recent years, table reasoning has garnered substantial research interest, particularly regarding its integration with Large Language Models (LLMs), which have revolutionized natural language applications. Existing LLM-based studies typically achieve step-by-step thinking for table reasoning guided by task semantics. While these approaches emphasize autonomous exploration and enhance fine-grained table understanding, they often overlook systematic thinking in the reasoning process. This oversight can lead to omitted steps, disorganized logic and misleading results, especially in complex scenarios. In this paper, we propose PoTable, a novel stage-oriented plan-then-execute approach that incorporates systematic thinking into table reasoning. Specifically, PoTable involves several distinct analytical stages with clear objectives to provide adequate guidance. To accomplish stage-specific goals, PoTable employs a plan-then-execute mechanism: it first plans the operation chain based on the stage objective, and then executes operations sequentially through code generation, real-time running and feedback processing. Consequently, PoTable produces reliable table reasoning results with highly accurate, step-wise commented and completely executable programs. It mirrors the workflow of a professional data analyst, offering advantages in both accuracy and explainability. Finally, we conduct extensive experiments on four datasets from the WikiTQ and TabFact benchmarks, where the results demonstrate the effectiveness, efficiency and explainability of PoTable. Our code is available at: https://github.com/Double680/PoTable.

STAPO: Stabilizing Reinforcement Learning for LLMs by Silencing Rare Spurious Tokens

arXiv:2602.15620v3 Announce Type: replace-cross Abstract: Reinforcement Learning (RL) has significantly improved large language model reasoning, but existing RL fine-tuning methods rely heavily on heuristic techniques such as entropy regularization and reweighting to maintain stability. In practice, they often suffer from late-stage performance collapse, leading to degraded reasoning quality and unstable training. Our analysis shows that the magnitude of token-wise policy gradients in RL is negatively correlated with token probability and local policy entropy. We find that training instability can be caused by a tiny fraction of tokens, approximately 0.01%, which we term spurious tokens. When such tokens appear in correct responses, they contribute little to the reasoning outcome but inherit the full sequence-level reward, leading to abnormally amplified gradient updates. To mitigate this instability, we design an S2T (silencing spurious tokens) mechanism to efficiently identify spurious tokens through characteristic signals with low probability, low entropy, and positive advantage, and then suppress their gradient perturbations during optimization. Incorporating this mechanism into a group-based objective, we propose Spurious-Token-Aware Policy Optimization (STAPO), which promotes stable and effective large-scale model refinement. Across six mathematical reasoning benchmarks using Qwen 1.7B, 8B, and 14B base models, STAPO consistently demonstrates superior entropy stability and achieves an average performance improvement of 7.13% ($\rho_{\mathrm{T}}$=1.0, top-p=1.0) and 3.69% ($\rho_{\mathrm{T}}$=0.7, top-p=0.9) over GRPO, 20-Entropy, and JustRL.
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