A deep dive into the open literature shows that there are t hree fundamental limitations to current ML approaches, namely blackbox brittleness (which renders models uninterpretable and unreliable under distribution shift [2]), causal blindness (which conflates correlation with causation [3]), and alignment failures (which produce systems optimizing objectives misaligned with human values [4]) . These deficiencies stem from a profound philosophical poverty in how ML conceptualizes knowledge, reasoning, and values. The first fundamental limitation, b lackbox brittleness, manifests when trained models fail on seemingly trivial variations of their training distribution. For example, a vision model that accurately identifies stop signs under normal conditions might misclassify them entirely when small adversarial perturbations are applied [5] . Not surprisingly, t h e same brittleness extends beyond adversarial examples to everyday distribution shifts (e.g., natural language processing models exhibit performance degradation when processing text from different cultural contexts, etc.) [6] .

The rapid proliferation of high-quality synthetic data -- generated by advanced AI models or collected as auxiliary data from related tasks -- presents both opportunities and challenges for statistical inference. This paper introduces a GEneral Synthetic-Powered Inference (GESPI) framework that wraps around any statistical inference procedure to safely enhance sample efficiency by combining synthetic and real data. Our framework leverages high-quality synthetic data to boost statistical power, yet adaptively defaults to the standard inference method using only real data when synthetic data is of low quality. The error of our method remains below a user-specified bound without any distributional assumptions on the synthetic data, and decreases as the quality of the synthetic data improves. This flexibility enables seamless integration with conformal prediction, risk control, hypothesis testing, and multiple testing procedures, all without modifying the base inference method. We demonstrate the benefits of our method on challenging tasks with limited labeled data, including AlphaFold protein structure prediction, and comparing large reasoning models on complex math problems.

Time series analysis has emerged as an important tool for improving patient diagnosis and management in healthcare applications. However, these applications commonly face two critical challenges: time misalignment and data sparsity. Traditional approaches address these issues through a two-step process of imputation followed by prediction. We propose MAGIC (Multi-tAsk Gaussian Process for Imputation and Classification), a novel unified framework that simultaneously performs class-informed missing value imputation and label prediction within a hierarchical multi-task Gaussian process coupled with functional logistic regression. To handle intractable likelihood components, MAGIC employs Taylor expansion approximations with bounded error analysis, and parameter estimation is performed using EM algorithm with block coordinate optimization supported by convergence analysis. We validate MAGIC through two healthcare applications: prediction of post-traumatic headache improvement following mild traumatic brain injury and prediction of in-hospital mortality within 48 hours after ICU admission. In both applications, MAGIC achieves superior predictive accuracy compared to existing methods. The ability to generate real-time and accurate predictions with limited samples facilitates early clinical assessment and treatment planning, enabling healthcare providers to make more informed treatment decisions.

Spike-and-wave discharges (SWDs) are the electroencephalographic hallmark of absence epilepsy, yet their manual identification in multi-day recordings remains labour-intensive and error-prone. We present a lightweight hybrid pipeline that couples analytical features with a shallow artificial neural network (ANN) for accurate, patient-specific SWD detection in long-term, monopolar EEG. A two-sided moving-average (MA) filter first suppresses the high-frequency components of normal background activity. The residual signal is then summarised by the mean and the standard deviation of its normally distributed samples, yielding a compact, two-dimensional feature vector for every 20s window. These features are fed to a single-hidden-layer ANN trained via back-propagation to classify each window as SWD or non-SWD. The method was evaluated on 780 channels sampled at 256 Hz from 12 patients, comprising 392 annotated SWD events. It correctly detected 384 events (sensitivity: 98%) while achieving a specificity of 96.2 % and an overall accuracy of 97.2%. Because feature extraction is analytic, and the classifier is small, the pipeline runs in real-time and requires no manual threshold tuning. These results indicate that normal-distribution descriptors combined with a modest ANN provide an effective and computationally inexpensive solution for automated SWD screening in extended EEG recordings.

Infectious diseases continue to pose a serious threat to public health, underscoring the urgent need for effective computational approaches to screen novel anti-infective agents. Oligopeptides have emerged as promising candidates in antimicrobial research due to their structural simplicity, high bioavailability, and low susceptibility to resistance. Despite their potential, computational models specifically designed to predict associations between oligopeptides and infectious diseases remain scarce. This study introduces a prompt-guided graph-based contrastive learning framework (PGCLODA) to uncover potential associations. A tripartite graph is constructed with oligopeptides, microbes, and diseases as nodes, incorporating both structural and semantic information. To preserve critical regions during contrastive learning, a prompt-guided graph augmentation strategy is employed to generate meaningful paired views. A dual encoder architecture, integrating Graph Convolutional Network (GCN) and Transformer, is used to jointly capture local and global features. The fused embeddings are subsequently input into a multilayer perceptron (MLP) classifier for final prediction. Experimental results on a benchmark dataset indicate that PGCLODA consistently outperforms state-of-the-art models in AUROC, AUPRC, and accuracy. Ablation and hyperparameter studies confirm the contribution of each module. Case studies further validate the generalization ability of PGCLODA and its potential to uncover novel, biologically relevant associations. These findings offer valuable insights for mechanism-driven discovery and oligopeptide-based drug development. The source code of PGCLODA is available online at https://github.com/jjnlcode/PGCLODA.

Background and Aims: Large language models (LLMs) have shown remarkable generalization and transfer capabilities by learning from vast corpora of text and web data. Their semantic representations allow cross-task knowledge transfer and reasoning, offering promising opportunities for data-scarce and heterogeneous domains such as clinical medicine. Yet, in diagnostic tasks like sarcopenia, major challenges remain: interpretability, transparency, and deployment efficiency. Traditional machine learning (TML) models provide stable performance and feature-level attribution, ensuring traceable and auditable decision logic, but lack semantic breadth. Conversely, LLMs enable flexible inference but often function as opaque predictors. Existing integration strategies remain shallow, rarely embedding the structured reasoning of TML into LLM inference. Methods: Using sarcopenia diagnosis as a case study, SHapley Additive exPlanations (SHAP) were extracted from a baseline XGBoost model and transformed into structured, LLM-compatible representations. An actor-critic reinforcement learning (RL) strategy guided the LLM to reason over these SHAP-based inputs, producing calibrated rationales and refined decision rules. The distilled reasoning was consolidated into a structured knowledge repository and deployed via retrieval-augmented generation (RAG) for case-based inference. Results: (Omitted here.) Conclusion: By coupling SHAP-derived statistical evidence with reinforcement-trained LLM reasoning, CANDLE mitigates the interpretability-performance trade-off, enhances predictive accuracy, and preserves high decision consistency. The framework offers a scalable approach to knowledge assetization of TML models, enabling interpretable, reproducible, and clinically aligned decision support in sarcopenia and potentially broader medical domains.

The large language models (LLMs) are able to generate high-quality texts in multiple languages. Such texts are often not recognizable by humans as generated, and therefore present a potential of LLMs for misuse (e.g., plagiarism, spams, disinformation spreading). An automated detection is able to assist humans to indicate the machine-generated texts; however, its robustness to out-of-distribution data is still challenging. This notebook describes our mdok approach in robust detection, based on fine-tuning smaller LLMs for text classification. It is applied to both subtasks of Voight-Kampff Generative AI Detection 2025, providing remarkable performance (1st rank) in both, the binary detection as well as the multiclass classification of various cases of human-AI collaboration.

Vision-Language Models (VLMs) have demonstrated strong capabilities in aligning visual and textual modalities, enabling a wide range of applications in multimodal understanding and generation. While they excel in zero-shot and transfer learning scenarios, VLMs remain susceptible to misclassification, often yielding confident yet incorrect predictions. This limitation poses a significant risk in safety-critical domains, where erroneous predictions can lead to severe consequences. In this work, we introduce TrustVLM, a training-free framework designed to address the critical challenge of estimating when VLM's predictions can be trusted. Motivated by the observed modality gap in VLMs and the insight that certain concepts are more distinctly represented in the image embedding space, we propose a novel confidence-scoring function that leverages this space to improve misclassification detection. We rigorously evaluate our approach across 17 diverse datasets, employing 4 architectures and 2 VLMs, and demonstrate state-of-the-art performance, with improvements of up to 51.87% in AURC, 9.14% in AUROC, and 32.42% in FPR95 compared to existing baselines. By improving the reliability of the model without requiring retraining, TrustVLM paves the way for safer deployment of VLMs in real-world applications. The code is available at https://github.com/EPFL-IMOS/TrustVLM.