Transcriptome-informed multi-modal AI for predicting neoadjuvant therapy response from breast cancer biopsies

Scarcity of labeled data limits development of deep learning biomarkers in oncology. We develop a two-stage AI model predicting pathological complete response (pCR) to neoadjuvant therapy in breast cancer. The first stage learns the transcriptome from histopathology using 8,742 patients across 32 cancer types, corroborated by pathologist review and spatial agreement with measured expression. This simplifies the second stage to predicting pCR from inferred expression and clinical variables. Developed using 1,080 patients (five cohorts) and evaluated in 1,412 patients (nine cohorts), the model achieves a pooled AUROC of 0.79 (95% CI, 0.73-0.85), discriminating responders within molecular subtypes. It outperforms histopathological biomarkers, remaining stable across intratumoral sampling and with minimal biopsy tissue. Ablations show transcriptome-wide inference improves discrimination over clinical variables alone or one-stage pathology models, and robustness by avoiding genomic assays' gene selection constraints. These results indicate that biologically informed compression may generalize to data-sparse applications in precision oncology.

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arXiv AI Papers·há 3 dias☆

Language Models Learn to Improve Language Models↗

Large language models (LLMs) are increasingly used to automate AI research, including language-model (LM) development, offering a potential path toward recursive self-improvement. However, turning experimental feedback into a learned ability to propose effective improvements across models faces two challenges. First, training such an ability with real feedback is expensive: reinforcement learning (RL) requires evaluating tens of thousands of proposals, each potentially requiring a full model-training run. Even at ten GPU-hours per run, reward collection alone would consume hundreds of thousands of GPU-hours, motivating a cheaper surrogate. Second, surrogate feedback can become unreliable as policy optimization favors overestimated proposals when the proposal distribution shifts. To address these challenges, we propose LM2LM, which trains LLMs with RL to generate effective LM improvement proposals. To provide scalable feedback, we use a research world model (RWM), a frozen LLM that predicts proposal gains from real experimental records provided in context, as the reward model for RL. To maintain feedback reliability, we periodically execute current-policy proposals ranked highly by the RWM and add their measured outcomes to its context. Across eight autoregressive and diffusion LM development environments, real-execution evaluations on held-out tasks show that LM2LM enables Qwen3.8-27B to outperform GPT-6-sol, even when GPT-6-sol is given 300 real experimental records in context, while requiring 33% lower data-generation cost. LM2LM also generalizes to a model family unseen during training.

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arXiv AI Papers·há 3 dias☆

How Finite-Rank Bottlenecks Shape the Low-Rank Adaptation Landscape↗

Low-rank adaptation (LoRA) has become the standard method for parameter-efficient fine-tuning of large pretrained models, yet theoretical explanations for why low-rank updates suffice remain incomplete. Most existing analyses rely on the Neural Tangent Kernel (NTK) regime, which linearizes the network around the pretrained weights. In this work, we take a different approach that requires no linearization: our key observation is that, once the backbone is frozen, the loss sees each adapted weight matrix only through a finite-rank linear map induced by the frozen activations. Trace-norm regularization then forces the optimizer to pick a low-rank matrix among all matrices that produce the same observed output. This yields global minimizers whose ranks are controlled by the rank of this map, which we call the bottleneck rank, rather than the sample size. For multi-head attention, we obtain tighter rank upper bounds by exploiting two additional invariances: row-wise softmax is insensitive to additive row constants in the score matrix, and value updates are observable only after attention weighting and frozen output projection. For the factorized LoRA objective with weight decay, we prove a complementary result on the nonconvex side: after an arbitrarily small generic positive semidefinite perturbation, every first-order stationary point is rank-deficient once the LoRA rank exceeds a threshold determined by the bottleneck rank. Finally, we show that global minimizers of the perturbed objective are near-optimal for the original trace-norm problem, and we provide uniform generalization bounds governed by the spectral structure of the frozen features.

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arXiv AI Papers·há 3 dias☆

Robust Function Calling for LLM Agents Under Interface Drift↗

Tool-augmented language-model agents rely on interface text: tool descriptions, argument schemas, and the candidate tool list shown at inference time. These interfaces often change after deployment even when the underlying tool semantics remain fixed, creating a practical reliability problem for function-calling systems. We study this failure mode as interface drift and evaluate whether a lightweight, training-free repair layer can recover robustness without retraining the base model. Our method, SchemaShield-Lite, combines schema validation, candidate-set retry for missing tool names, and one-shot constrained repair. On Qwen3.5-9B, it raises DICE-300 accuracy from 0.717 to 0.813 and BFCL-200 accuracy from 0.580 to 0.805, recovering 19/22 and 33/45 drift-induced failures with no observed repair harms. Naive retry does not explain the gains. Ablations show that candidate-set drift, especially distractor tools, accounts for most observed damage, while description and schema edits alone are less harmful. The results position validation-and-repair as a practical robustness layer for deployed LLM-agent tool use.

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arXiv AI Papers·há 3 dias☆

SETAREH Transform: A Sorting-Assisted Haar-Wavelet Sparsification Method for Approximate Inner-Product Computation↗

Modern deep learning systems increasingly rely on high-dimensional vector operations, in which large input and parameter vectors are repeatedly stored, transferred, and processed. Although substantial research has focused on reducing neural-network model size through pruning, quantization, knowledge distillation, and efficient architectures, the storage, memory-traffic, and communication costs associated with repeatedly presented high-dimensional input vectors remain important practical considerations, particularly in distributed and edge-computing environments. This paper proposes the SETAREH (Sorting-assisted Energy-concentrating Transform for Approximate Representation using Haar wavelets) transform, a Haar-wavelet-based sparsification approach for approximating the inner product between a fixed high-dimensional coefficient vector and successive input vectors. By applying the same sequence of permutations and Haar transforms to both vectors, SETAREH preserves the exact inner product before truncation. It then retains only a subset of the transformed coefficient-input pairs, reducing their representation cost while introducing a controllable approximation error. To evaluate SETAREH, we consider two complementary experimental settings: a synthetic Gaussian-vector baseline and a real apparent-age estimation task using a convolutional neural network on the APPA-REAL dataset. The results show that SETAREH can approximate the evaluated inner products using substantially fewer transformed coefficient-input pairs than the original vector dimension. The findings support its use as a potential structured data-representation method for repeated inner products with fixed weights, while the practical benefit depends on approximation accuracy and the cost of storing or transmitting permutation metadata.

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