ZeroFold: Protein-RNA Binding Affinity Predictions from Pre-Structural Embeddings

The accurate prediction of protein-RNA binding affinity remains an unsolved problem in structural biology, limiting opportunities in understanding gene regulation and designing RNA-targeting therapeutics. A central obstacle is the structural flexibility of RNA, as, unlike proteins, RNA molecules exist as dynamic conformational ensembles. Thus, committing to a single predicted structure discards information relevant to binding. Here, we show that this obstacle can be addressed by extracting pre-structural embeddings, which are intermediate representations from a biomolecular foundation model captured before the structure decoding step. Pre-structural embeddings implicitly encode conformational ensemble information without requiring predicted structures. We build ZeroFold, a transformer-based model that combines pre-structural embeddings from Boltz-2 for both protein and RNA molecules through a cross-modal attention mechanism to predict binding affinity directly from sequence. To support training and evaluation, we construct PRADB, a curated dataset of 2,621 unique protein-RNA pairs with experimentally measured affinities drawn from four complementary databases. On a held-out test set constructed with 40% sequence identity thresholds, ZeroFold achieves a Spearman correlation of 0.65, a value approaching the ceiling imposed by experimental measurement noise. Under progressively fairer evaluation conditions that control for training-set overlap, ZeroFold compares favourably with respect to leading structure-based and leading sequence-based predictors, with the performance gap widening as sequence similarity to competitor training data is reduced. These results illustrate how pre-structural embeddings offer a representation strategy for flexible biomolecules, opening a route to affinity prediction for protein-RNA pairs for which no structural data exist.

Limits of Imagery Reasoning in Frontier LLM Models

Large Language Models (LLMs) have demonstrated impressive reasoning capabilities, yet they struggle with spatial tasks that require mental simulation, such as mental rotation. This paper investigates whether equipping an LLM with an external ``Imagery Module'' -- a tool capable of rendering and rotating 3D models -- can bridge this gap, functioning as a ``cognitive prosthetic.'' We conducted experiments using a dual-module architecture in which a reasoning module (an MLLM) interacts with an imagery module on 3D model rotation tasks. Performance was lower than expected, with accuracy reaching at most 62.5%. Further investigation suggests that even when the burden of maintaining and manipulating a holistic 3D state is outsourced, the system still fails. This reveals that current frontier models lack the foundational visual-spatial primitives required to interface with imagery. Specifically, they lack: (1) the low-level sensitivity to extract spatial signals such as (a) depth, (b) motion, and (c) short-horizon dynamic prediction; and (2) the capacity to reason contemplatively over images, dynamically shifting visual focus and balancing imagery with symbolic and associative information.

PARHAF, a human-authored corpus of clinical reports for fictitious patients in French

The development of clinical natural language processing (NLP) systems is severely hampered by the sensitive nature of medical records, which restricts data sharing under stringent privacy regulations, particularly in France and the broader European Union. To address this gap, we introduce PARHAF, a large open-source corpus of clinical documents in French. PARHAF comprises expert-authored clinical reports describing realistic yet entirely fictitious patient cases, making it anonymous and freely shareable by design. The corpus was developed using a structured protocol that combined clinician expertise with epidemiological guidance from the French National Health Data System (SNDS), ensuring broad clinical coverage. A total of 104 medical residents across 18 specialties authored and peer-reviewed the reports following predefined clinical scenarios and document templates. The corpus contains 7394 clinical reports covering 5009 patient cases across a wide range of medical and surgical specialties. It includes a general-purpose component designed to approximate real-world hospitalization distributions, and four specialized subsets that support information-extraction use cases in oncology, infectious diseases, and diagnostic coding. Documents are released under a CC-BY open license, with a portion temporarily embargoed to enable future benchmarking under controlled conditions. PARHAF provides a valuable resource for training and evaluating French clinical language models in a fully privacy-preserving setting, and establishes a replicable methodology for building shareable synthetic clinical corpora in other languages and health systems.

ALMAB-DC: Active Learning, Multi-Armed Bandits, and Distributed Computing for Sequential Experimental Design and Black-Box Optimization

Sequential experimental design under expensive, gradient-free objectives is a central challenge in computational statistics: evaluation budgets are tightly constrained and information must be extracted efficiently from each observation. We propose \textbf{ALMAB-DC}, a GP-based sequential design framework combining active learning, multi-armed bandits (MAB), and distributed asynchronous computing for expensive black-box experimentation. A Gaussian process surrogate with uncertainty-aware acquisition identifies informative query points; a UCB or Thompson-sampling bandit controller allocates evaluations across parallel workers; and an asynchronous scheduler handles heterogeneous runtimes. We present cumulative regret bounds for the bandit components and characterize parallel scalability via Amdahl's Law. We validate ALMAB-DC on five benchmarks. On the two statistical experimental-design tasks, ALMAB-DC achieves lower simple regret than Equal Spacing, Random, and D-optimal designs in dose--response optimization, and in adaptive spatial field estimation matches the Greedy Max-Variance benchmark while outperforming Latin Hypercube Sampling; at $K=4$ the distributed setting reaches target performance in one-quarter of sequential wall-clock rounds. On three ML/engineering tasks (CIFAR-10 HPO, CFD drag minimization, MuJoCo RL), ALMAB-DC achieves 93.4\% CIFAR-10 accuracy (outperforming BOHB by 1.7\,pp and Optuna by 1.1\,pp), reduces airfoil drag to $C_D = 0.059$ (36.9\% below Grid Search), and improves RL return by 50\% over Grid Search. All advantages over non-ALMAB baselines are statistically significant under Bonferroni-corrected Mann--Whitney $U$ tests. Distributed execution achieves $7.5\times$ speedup at $K = 16$ agents, consistent with Amdahl's Law.

Development of a European Union Time-Indexed Reference Dataset for Assessing the Performance of Signal Detection Methods in Pharmacovigilance using a Large Language Model

Background: The identification of optimal signal detection methods is hindered by the lack of reliable reference datasets. Existing datasets do not capture when adverse events (AEs) are officially recognized by regulatory authorities, preventing restriction of analyses to pre-confirmation periods and limiting evaluation of early detection performance. This study addresses this gap by developing a time-indexed reference dataset for the European Union (EU), incorporating the timing of AE inclusion in product labels along with regulatory metadata. Methods: Current and historical Summaries of Product Characteristics (SmPCs) for all centrally authorized products (n=1,513) were retrieved from the EU Union Register of Medicinal Products (data lock: 15 December 2025). Section 4.8 was extracted and processed using DeepSeek V3 to identify AEs. Regulatory metadata, including labelling changes, were programmatically extracted. Time indexing was based on the date of AE inclusion in the SmPC. Results: The database includes 17,763 SmPC versions spanning 1995-2025, comprising 125,026 drug-AE associations. The time-indexed reference dataset, restricted to active products, included 1,479 medicinal products and 110,823 drug-AE associations. Most AEs were identified pre-marketing (74.5%) versus post-marketing (25.5%). Safety updates peaked around 2012. Gastrointestinal, skin, and nervous system disorders were the most represented System Organ Classes. Drugs had a median of 48 AEs across 14 SOCs. Conclusions: The proposed dataset addresses a critical gap in pharmacovigilance by incorporating temporal information on AE recognition for the EU, supporting more accurate assessment of signal detection performance and facilitating methodological comparisons across analytical approaches.

Generalized multi-object classification and tracking with sparse feature resonator networks

In visual scene understanding tasks, it is essential to capture both invariant and equivariant structure. While neural networks are frequently trained to achieve invariance to transformations such as translation, this often comes at the cost of losing access to equivariant information - e.g., the precise location of an object. Moreover, invariance is not naturally guaranteed through supervised learning alone, and many architectures generalize poorly to input transformations not encountered during training. Here, we take an approach based on analysis-by-synthesis and factoring using resonator networks. A generative model describes the construction of simple scenes containing MNIST digits and their transformations, like color and position. The resonator network inverts the generative model, and provides both invariant and equivariant information about particular objects. Sparse features learned from training data act as a basis set to provide flexibility in representing variable shapes of objects, allowing the resonator network to handle previously unseen digit shapes from the test set. The modular structure provides a shape module which contains information about the object shape with translation factored out, allowing a simple classifier to operate on centered digits. The classification layer is trained solely on centered data, requiring much less training data, and the network as a whole can identify objects with arbitrary translations without data augmentation. The natural attention-like mechanism of the resonator network also allows for analysis of scenes with multiple objects, where the network dynamics selects and centers only one object at a time. Further, the specific position information of a particular object can be extracted from the translation module, and we show that the resonator can be designed to track multiple moving objects with precision of a few pixels.

Evaluating Image Editing with LLMs: A Comprehensive Benchmark and Intermediate-Layer Probing Approach

Evaluating text-guided image editing (TIE) methods remains a challenging problem, as reliable assessment should simultaneously consider perceptual quality, alignment with textual instructions, and preservation of original image content. Despite rapid progress in TIE models, existing evaluation benchmarks remain limited in scale and often show weak correlation with human perceptual judgments. In this work, we introduce TIEdit, a benchmark for systematic evaluation of text-guided image editing methods. TIEdit consists of 512 source images paired with editing prompts across eight representative editing tasks, producing 5,120 edited images generated by ten state-of-the-art TIE models. To obtain reliable subjective ratings, 20 experts are recruited to produce 307,200 raw subjective ratings, which accumulates into 15,360 mean opinion scores (MOSs) across three evaluation dimensions: perceptual quality, editing alignment, and content preservation. Beyond the benchmark itself, we further propose EditProbe, an LLM-based evaluator that estimates editing quality via intermediate-layer probing of hidden representations. Instead of relying solely on final model outputs, EditProbe extracts informative representations from intermediate layers of multimodal large language models to better capture semantic and perceptual relationships between source images, editing instructions, and edited results. Experimental results demonstrate that widely used automatic evaluation metrics show limited correlation with human judgments on editing tasks, while EditProbe achieves substantially stronger alignment with human perception. Together, TIEdit and EditProbe provide a foundation for more reliable and perceptually aligned evaluation of text-guided image editing methods.

Semi-Automated Knowledge Engineering and Process Mapping for Total Airport Management

Documentation of airport operations is inherently complex due to extensive technical terminology, rigorous regulations, proprietary regional information, and fragmented communication across multiple stakeholders. The resulting data silos and semantic inconsistencies present a significant impediment to the Total Airport Management (TAM) initiative. This paper presents a methodological framework for constructing a domain-grounded, machine-readable Knowledge Graph (KG) through a dual-stage fusion of symbolic Knowledge Engineering (KE) and generative Large Language Models (LLMs). The framework employs a scaffolded fusion strategy in which expert-curated KE structures guide LLM prompts to facilitate the discovery of semantically aligned knowledge triples. We evaluate this methodology on the Google LangExtract library and investigate the impact of context window utilization by comparing localized segment-based inference with document-level processing. Contrary to prior empirical observations of long-context degradation in LLMs, document-level processing improves the recovery of non-linear procedural dependencies. To ensure the high-fidelity provenance required in airport operations, the proposed framework fuses a probabilistic model for discovery and a deterministic algorithm for anchoring every extraction to its ground source. This ensures absolute traceability and verifiability, bridging the gap between "black-box" generative outputs and the transparency required for operational tooling. Finally, we introduce an automated framework that operationalizes this pipeline to synthesize complex operational workflows from unstructured textual corpora.

Avoiding Over-smoothing in Social Media Rumor Detection with Pre-trained Propagation Tree Transformer

Deep learning techniques for rumor detection typically utilize Graph Neural Networks (GNNs) to analyze post relations. These methods, however, falter due to over-smoothing issues when processing rumor propagation structures, leading to declining performance. Our investigation into this issue reveals that over-smoothing is intrinsically tied to the structural characteristics of rumor propagation trees, in which the majority of nodes are 1-level nodes. Furthermore, GNNs struggle to capture long-range dependencies within these trees. To circumvent these challenges, we propose a Pre-Trained Propagation Tree Transformer (P2T3) method based on pure Transformer architecture. It extracts all conversation chains from a tree structure following the propagation direction of replies, utilizes token-wise embedding to infuse connection information and introduces necessary inductive bias, and pre-trains on large-scale unlabeled datasets. Experiments indicate that P2T3 surpasses previous state-of-the-art methods in multiple benchmark datasets and performs well under few-shot conditions. P2T3 not only avoids the over-smoothing issue inherent in GNNs but also potentially offers a large model or unified multi-modal scheme for future social media research.

CFCML: A Coarse-to-Fine Crossmodal Learning Framework For Disease Diagnosis Using Multimodal Images and Tabular Data

In clinical practice, crossmodal information including medical images and tabular data is essential for disease diagnosis. There exists a significant modality gap between these data types, which obstructs advancements in crossmodal diagnostic accuracy. Most existing crossmodal learning (CML) methods primarily focus on exploring relationships among high-level encoder outputs, leading to the neglect of local information in images. Additionally, these methods often overlook the extraction of task-relevant information. In this paper, we propose a novel coarse-to-fine crossmodal learning (CFCML) framework to progressively reduce the modality gap between multimodal images and tabular data, by thoroughly exploring inter-modal relationships. At the coarse stage, we explore the relationships between multi-granularity features from various image encoder stages and tabular information, facilitating a preliminary reduction of the modality gap. At the fine stage, we generate unimodal and crossmodal prototypes that incorporate class-aware information, and establish hierarchical anchor-based relationship mining (HRM) strategy to further diminish the modality gap and extract discriminative crossmodal information. This strategy utilize modality samples, unimodal prototypes, and crossmodal prototypes as anchors to develop contrastive learning approaches, effectively enhancing inter-class disparity while reducing intra-class disparity from multiple perspectives. Experimental results indicate that our method outperforms the state-of-the-art (SOTA) methods, achieving improvements of 1.53% and 0.91% in AUC metrics on the MEN and Derm7pt datasets, respectively. The code is available at https://github.com/IsDling/CFCML.