Daily Papers

Central to our understanding of chemical reactivity is the principle of mass conservation, which is fundamental for ensuring physical consistency, balancing equations, and guiding reaction design. However, data-driven computational models for tasks such as reaction product prediction rarely abide by this most basic constraint. In this work, we recast the problem of reaction prediction as a problem of electron redistribution using the modern deep generative framework of flow matching. Our model, FlowER, overcomes limitations inherent in previous approaches by enforcing exact mass conservation, thereby resolving hallucinatory failure modes, recovering mechanistic reaction sequences for unseen substrate scaffolds, and generalizing effectively to out-of-domain reaction classes with extremely data-efficient fine-tuning. FlowER additionally enables estimation of thermodynamic or kinetic feasibility and manifests a degree of chemical intuition in reaction prediction tasks. This inherently interpretable framework represents a significant step in bridging the gap between predictive accuracy and mechanistic understanding in data-driven reaction outcome prediction.

The advancement of machine learning and the availability of large-scale reaction datasets have accelerated the development of data-driven models for computer-aided synthesis planning (CASP) in the past decade. Here, we detail the newest version of ASKCOS, an open source software suite for synthesis planning that makes available several research advances in a freely available, practical tool. Four one-step retrosynthesis models form the basis of both interactive planning and automatic planning modes. Retrosynthetic planning is complemented by other modules for feasibility assessment and pathway evaluation, including reaction condition recommendation, reaction outcome prediction, and auxiliary capabilities such as solubility prediction and quantum mechanical descriptor prediction. ASKCOS has assisted hundreds of medicinal, synthetic, and process chemists in their day-to-day tasks, complementing expert decision making. It is our belief that CASP tools like ASKCOS are an important part of modern chemistry research, and that they offer ever-increasing utility and accessibility.

It is fundamental for science and technology to be able to predict chemical reactions and their properties. To achieve such skills, it is important to develop good representations of chemical reactions, or good deep learning architectures that can learn such representations automatically from the data. There is currently no universal and widely adopted method for robustly representing chemical reactions. Most existing methods suffer from one or more drawbacks, such as: (1) lacking universality; (2) lacking robustness; (3) lacking interpretability; or (4) requiring excessive manual pre-processing. Here we exploit graph-based representations of molecular structures to develop and test a hypergraph attention neural network approach to solve at once the reaction representation and property-prediction problems, alleviating the aforementioned drawbacks. We evaluate this hypergraph representation in three experiments using three independent data sets of chemical reactions. In all experiments, the hypergraph-based approach matches or outperforms other representations and their corresponding models of chemical reactions while yielding interpretable multi-level representations.

The task of chemical reaction predictions (CRPs) plays a pivotal role in advancing drug discovery and material science. However, its effectiveness is constrained by the vast and uncertain chemical reaction space and challenges in capturing reaction selectivity, particularly due to existing methods' limitations in exploiting the data's inherent knowledge. To address these challenges, we introduce a data-curated self-feedback knowledge elicitation approach. This method starts from iterative optimization of molecular representations and facilitates the extraction of knowledge on chemical reaction types (RTs). Then, we employ adaptive prompt learning to infuse the prior knowledge into the large language model (LLM). As a result, we achieve significant enhancements: a 14.2% increase in retrosynthesis prediction accuracy, a 74.2% rise in reagent prediction accuracy, and an expansion in the model's capability for handling multi-task chemical reactions. This research offers a novel paradigm for knowledge elicitation in scientific research and showcases the untapped potential of LLMs in CRPs.

Transformer-based deep neural networks have revolutionized the field of molecular-related prediction tasks by treating molecules as symbolic sequences. These models have been successfully applied in various organic chemical applications by pretraining them with extensive compound libraries and subsequently fine-tuning them with smaller in-house datasets for specific tasks. However, many conventional methods primarily focus on single molecules, with limited exploration of pretraining for reactions involving multiple molecules. In this paper, we propose ReactionT5, a novel model that leverages pretraining on the Open Reaction Database (ORD), a publicly available large-scale resource. We further fine-tune this model for yield prediction and product prediction tasks, demonstrating its impressive performance even with limited fine-tuning data compared to traditional models. The pre-trained ReactionT5 model is publicly accessible on the Hugging Face platform.

Understanding and forecasting audience reactions to video content are crucial for improving content creation, recommendation systems, and media analysis. To enable audience reaction prediction and other content engagement applications, we introduce Video2Reaction, a multimodal dataset that maps short movie segments to a distribution of induced emotions of viewers in the wild, as expressed through social media. Video2Reaction spans more than 10,000 videos and serves as a reliable benchmark as well as a training resource for audience reaction prediction. To enable cost-effective continuous annotations as reactions may change over time, we develop a two-stage multi-agent pipeline using only open-source LLMs, achieving 86% correctness under blind human verification despite the inherently noisy and subjective nature of the task. We establish the first benchmark for video-to-reaction-distribution prediction in the wild and show that pretrained foundation video models fail in zero-shot settings, while finetuning transforms them into state-of-the-art predictors capable of modeling both full reaction distributions and dominant responses from video alone. However, the task remains challenging: even the strongest methods achieve only 77% Top-3 F1 in dominant reaction prediction (LLaVA-Next), highlighting a substantial gap in modeling collective audience reaction. \modification{Dataset and code are available at our project page: https://information-fusion-lab-umass.github.io/video2reaction-bench.github.io

Molecule-text modeling, which aims to facilitate molecule-relevant tasks with a textual interface and textual knowledge, is an emerging research direction. Beyond single molecules, studying reaction-text modeling holds promise for helping the synthesis of new materials and drugs. However, previous works mostly neglect reaction-text modeling: they primarily focus on modeling individual molecule-text pairs or learning chemical reactions without texts in context. Additionally, one key task of reaction-text modeling -- experimental procedure prediction -- is less explored due to the absence of an open-source dataset. The task is to predict step-by-step actions of conducting chemical experiments and is crucial to automating chemical synthesis. To resolve the challenges above, we propose a new pretraining method, ReactXT, for reaction-text modeling, and a new dataset, OpenExp, for experimental procedure prediction. Specifically, ReactXT features three types of input contexts to incrementally pretrain LMs. Each of the three input contexts corresponds to a pretraining task to improve the text-based understanding of either reactions or single molecules. ReactXT demonstrates consistent improvements in experimental procedure prediction and molecule captioning and offers competitive results in retrosynthesis. Our code is available at https://github.com/syr-cn/ReactXT.

Recent advances in large language models (LLMs) have enabled molecular reasoning for property prediction. However, toxicity arises from complex biological mechanisms beyond chemical structure, necessitating mechanistic reasoning for reliable prediction. Despite its importance, current benchmarks fail to systematically evaluate this capability. LLMs can generate fluent but biologically unfaithful explanations, making it difficult to assess whether predicted toxicities are grounded invalid mechanisms. To bridge this gap, we introduce ToxReason, a benchmark grounded in the Adverse Outcome Pathway (AOP) that evaluates organ-level toxicity reasoning across multiple organs. ToxReason integrates experimental drug-target interaction evidence with toxicity labels, requiring models to infer both toxic outcomes and their underlying mechanisms from Molecular Initiating Event (MIE) to Adverse Outcome (AO). Using ToxReason, we evaluate toxicity prediction performance and reasoning quality across diverse LLMs. We find that strong predictive performance does not necessarily imply reliable reasoning. Furthermore, we show that reasoning-aware training improves mechanistic reasoning and, consequently, toxicity prediction performance. Together, these results underscore the necessity of integrating reasoning into both evaluation and training for trustworthy toxicity modeling.

Many chemical concepts can be well defined in the context of quantum chemical theories. Examples are the electronegativity scale of Mulliken and Jaffe and the hard and soft acids and bases concept of Pearson. The sound theoretical basis allows for a systematic definition of such concepts. However, while they are often used to describe and compare chemical processes in terms of reactivity, their predictive power remains unclear. In this work, we elaborate on the predictive potential of chemical reactivity concepts, which can be crucial for autonomous reaction exploration protocols to guide them by first-principles heuristics that expoit these concepts.

According to the Stimulus Organism Response (SOR) theory, all human behavioral reactions are stimulated by context, where people will process the received stimulus and produce an appropriate reaction. This implies that in a specific context for a given input stimulus, a person can react differently according to their internal state and other contextual factors. Analogously, in dyadic interactions, humans communicate using verbal and nonverbal cues, where a broad spectrum of listeners' non-verbal reactions might be appropriate for responding to a specific speaker behaviour. There already exists a body of work that investigated the problem of automatically generating an appropriate reaction for a given input. However, none attempted to automatically generate multiple appropriate reactions in the context of dyadic interactions and evaluate the appropriateness of those reactions using objective measures. This paper starts by defining the facial Multiple Appropriate Reaction Generation (fMARG) task for the first time in the literature and proposes a new set of objective evaluation metrics to evaluate the appropriateness of the generated reactions. The paper subsequently introduces a framework to predict, generate, and evaluate multiple appropriate facial reactions.

Large Language Models (LLMs) with strong abilities in natural language processing tasks have emerged and have been rapidly applied in various kinds of areas such as science, finance and software engineering. However, the capability of LLMs to advance the field of chemistry remains unclear. In this paper,we establish a comprehensive benchmark containing 8 practical chemistry tasks, including 1) name prediction, 2) property prediction, 3) yield prediction, 4) reaction prediction, 5) retrosynthesis (prediction of reactants from products), 6)text-based molecule design, 7) molecule captioning, and 8) reagent selection. Our analysis draws on widely recognized datasets including BBBP, Tox21, PubChem, USPTO, and ChEBI, facilitating a broad exploration of the capacities of LLMs within the context of practical chemistry. Three GPT models (GPT-4, GPT-3.5,and Davinci-003) are evaluated for each chemistry task in zero-shot and few-shot in-context learning settings with carefully selected demonstration examples and specially crafted prompts. The key results of our investigation are 1) GPT-4 outperforms the other two models among the three evaluated; 2) GPT models exhibit less competitive performance in tasks demanding precise understanding of molecular SMILES representation, such as reaction prediction and retrosynthesis;3) GPT models demonstrate strong capabilities in text-related explanation tasks such as molecule captioning; and 4) GPT models exhibit comparable or better performance to classical machine learning models when applied to chemical problems that can be transformed into classification or ranking tasks, such as property prediction, and yield prediction.

Modeling and generating human reactions poses a significant challenge with broad applications for computer vision and human-computer interaction. Existing methods either treat multiple individuals as a single entity, directly generating interactions, or rely solely on one person's motion to generate the other's reaction, failing to integrate the rich semantic information that underpins human interactions. Yet, these methods often fall short in adaptive responsiveness, i.e., the ability to accurately respond to diverse and dynamic interaction scenarios. Recognizing this gap, our work introduces an approach tailored to address the limitations of existing models by focusing on text-driven human reaction generation. Our model specifically generates realistic motion sequences for individuals that responding to the other's actions based on a descriptive text of the interaction scenario. The goal is to produce motion sequences that not only complement the opponent's movements but also semantically fit the described interactions. To achieve this, we present MoReact, a diffusion-based method designed to disentangle the generation of global trajectories and local motions sequentially. This approach stems from the observation that generating global trajectories first is crucial for guiding local motion, ensuring better alignment with given action and text. Furthermore, we introduce a novel interaction loss to enhance the realism of generated close interactions. Our experiments, utilizing data adapted from a two-person motion dataset, demonstrate the efficacy of our approach for this novel task, which is capable of producing realistic, diverse, and controllable reactions that not only closely match the movements of the counterpart but also adhere to the textual guidance. Please find our webpage at https://xiyan-xu.github.io/MoReactWebPage.

Reaction diagram parsing (RxnDP) is critical for extracting chemical synthesis information from literature. Although recent Vision-Language Models (VLMs) have emerged as a promising paradigm to automate this complex visual reasoning task, their application is fundamentally bottlenecked by the inability to align visual chemical entities with pre-trained knowledge, alongside the inherent discrepancy between token-level training and reaction-level evaluation. To address these dual challenges, this work enhances VLM-based RxnDP from two complementary perspectives: prompting representation and learning paradigms. First, we propose Identifier as Visual Prompting (IdtVP), which leverages naturally occurring molecule identifiers (e.g., bold numerals like 1a) to activate the chemical knowledge acquired during VLM pre-training. IdtVP enables powerful zero-shot and out-of-distribution capabilities, outperforming existing prompting strategies. Second, to further optimize performance within fine-tuning paradigms, we introduce Re3-DAPO, a reinforcement learning algorithm that leverages verifiable rewards to directly optimize reaction-level metrics, thereby achieving consistent gains over standard supervised fine-tuning. Additionally, we release the ScannedRxn benchmark, comprising scanned historical reaction diagrams with real-world artifacts, to rigorously assess model robustness and out-of-distribution ability. Our contributions advance the accuracy and generalization of VLM-based reaction diagram parsing. We will release data, models, and code on GitHub.

Clinical trials are crucial for drug development but are time consuming, expensive, and often burdensome on patients. More importantly, clinical trials face uncertain outcomes due to issues with efficacy, safety, or problems with patient recruitment. If we were better at predicting the results of clinical trials, we could avoid having to run trials that will inevitably fail more resources could be devoted to trials that are likely to succeed. In this paper, we propose Hierarchical INteraction Network (HINT) for more general, clinical trial outcome predictions for all diseases based on a comprehensive and diverse set of web data including molecule information of the drugs, target disease information, trial protocol and biomedical knowledge. HINT first encode these multi-modal data into latent embeddings, where an imputation module is designed to handle missing data. Next, these embeddings will be fed into the knowledge embedding module to generate knowledge embeddings that are pretrained using external knowledge on pharmaco-kinetic properties and trial risk from the web. Then the interaction graph module will connect all the embedding via domain knowledge to fully capture various trial components and their complex relations as well as their influences on trial outcomes. Finally, HINT learns a dynamic attentive graph neural network to predict trial outcome. Comprehensive experimental results show that HINT achieves strong predictive performance, obtaining 0.772, 0.607, 0.623, 0.703 on PR-AUC for Phase I, II, III, and indication outcome prediction, respectively. It also consistently outperforms the best baseline method by up to 12.4\% on PR-AUC.

Outcome-Based Education (OBE) emphasizes the development of specific competencies through student-centered learning. In this study, we reviewed the importance of OBE and implemented transformer-based models, particularly DistilBERT, to analyze an NLP dataset that includes student feedback. Our objective is to assess and improve educational outcomes. Our approach is better than other machine learning models because it uses the transformer's deep understanding of language context to classify sentiment better, giving better results across a wider range of matrices. Our work directly contributes to OBE's goal of achieving measurable outcomes by facilitating the identification of patterns in student learning experiences. We have also applied LIME (local interpretable model-agnostic explanations) to make sure that model predictions are clear. This gives us understandable information about how key terms affect sentiment. Our findings indicate that the combination of transformer models and LIME explanations results in a strong and straightforward framework for analyzing student feedback. This aligns more closely with the principles of OBE and ensures the improvement of educational practices through data-driven insights.

The Facebook network allows its users to record their reactions to text via a typology of emotions. This network, taken at scale, is therefore a prime data set of annotated sentiment data. This paper uses millions of such reactions, derived from a decade worth of Facebook post data centred around a Sri Lankan context, to model an eye of the beholder approach to sentiment detection for online Sinhala textual content. Three different sentiment analysis models are built, taking into account a limited subset of reactions, all reactions, and another that derives a positive/negative star rating value. The efficacy of these models in capturing the reactions of the observers are then computed and discussed. The analysis reveals that binary classification of reactions, for Sinhala content, is significantly more accurate than the other approaches. Furthermore, the inclusion of the like reaction hinders the capability of accurately predicting other reactions.

Chemical reaction prediction, involving forward synthesis and retrosynthesis prediction, is a fundamental problem in organic synthesis. A popular computational paradigm formulates synthesis prediction as a sequence-to-sequence translation problem, where the typical SMILES is adopted for molecule representations. However, the general-purpose SMILES neglects the characteristics of chemical reactions, where the molecular graph topology is largely unaltered from reactants to products, resulting in the suboptimal performance of SMILES if straightforwardly applied. In this article, we propose the root-aligned SMILES (R-SMILES), which specifies a tightly aligned one-to-one mapping between the product and the reactant SMILES for more efficient synthesis prediction. Due to the strict one-to-one mapping and reduced edit distance, the computational model is largely relieved from learning the complex syntax and dedicated to learning the chemical knowledge for reactions. We compare the proposed R-SMILES with various state-of-the-art baselines and show that it significantly outperforms them all, demonstrating the superiority of the proposed method.

High-throughput reaction condition (RC) screening is fundamental to chemical synthesis. However, current RC screening suffers from laborious and costly trial-and-error workflows. Traditional computer-aided synthesis planning (CASP) tools fail to find suitable RCs due to data sparsity and inadequate reaction representations. Nowadays, large language models (LLMs) are capable of tackling chemistry-related problems, such as molecule design, and chemical logic Q\&A tasks. However, LLMs have not yet achieved accurate predictions of chemical reaction conditions. Here, we present MM-RCR, a text-augmented multimodal LLM that learns a unified reaction representation from SMILES, reaction graphs, and textual corpus for chemical reaction recommendation (RCR). To train MM-RCR, we construct 1.2 million pair-wised Q\&A instruction datasets. Our experimental results demonstrate that MM-RCR achieves state-of-the-art performance on two open benchmark datasets and exhibits strong generalization capabilities on out-of-domain (OOD) and High-Throughput Experimentation (HTE) datasets. MM-RCR has the potential to accelerate high-throughput condition screening in chemical synthesis.

We develop a method to generate predictive regions that cover a multivariate response variable with a user-specified probability. Our work is composed of two components. First, we use a deep generative model to learn a representation of the response that has a unimodal distribution. Existing multiple-output quantile regression approaches are effective in such cases, so we apply them on the learned representation, and then transform the solution to the original space of the response. This process results in a flexible and informative region that can have an arbitrary shape, a property that existing methods lack. Second, we propose an extension of conformal prediction to the multivariate response setting that modifies any method to return sets with a pre-specified coverage level. The desired coverage is theoretically guaranteed in the finite-sample case for any distribution. Experiments conducted on both real and synthetic data show that our method constructs regions that are significantly smaller compared to existing techniques.

The global cost of drug discovery and development exceeds $200 billion annually. The main results of drug discovery and development are the outcomes of clinical trials, which directly influence the regulatory approval of new drug candidates and ultimately affect patient outcomes. Despite their significance, large-scale, high-quality clinical trial outcome data are not readily available to the public. Suppose a large clinical trial outcome dataset is provided; machine learning researchers can potentially develop accurate prediction models using past trials and outcome labels, which could help prioritize and optimize therapeutic programs, ultimately benefiting patients. This paper introduces Clinical Trial Outcome (CTO) dataset, the largest trial outcome dataset with around 479K clinical trials, aggregating outcomes from multiple sources of weakly supervised labels, minimizing the noise from individual sources, and eliminating the need for human annotation. These sources include large language model (LLM) decisions on trial-related documents, news headline sentiments, stock prices of trial sponsors, trial linkages across phases, and other signals such as patient dropout rates and adverse events. CTO's labels show unprecedented agreement with supervised clinical trial outcome labels from test split of the supervised TOP dataset, with a 91 F1.

Organic reaction mechanisms are the stepwise elementary reactions by which reactants form intermediates and products, and are fundamental to understanding chemical reactivity and designing new molecules and reactions. Although large language models (LLMs) have shown promise in understanding chemical tasks such as synthesis design, it is unclear to what extent this reflects genuine chemical reasoning capabilities, i.e., the ability to generate valid intermediates, maintain chemical consistency, and follow logically coherent multi-step pathways. We address this by introducing oMeBench, the first large-scale, expert-curated benchmark for organic mechanism reasoning in organic chemistry. It comprises over 10,000 annotated mechanistic steps with intermediates, type labels, and difficulty ratings. Furthermore, to evaluate LLM capability more precisely and enable fine-grained scoring, we propose oMeS, a dynamic evaluation framework that combines step-level logic and chemical similarity. We analyze the performance of state-of-the-art LLMs, and our results show that although current models display promising chemical intuition, they struggle with correct and consistent multi-step reasoning. Notably, we find that using prompting strategy and fine-tuning a specialist model on our proposed dataset increases performance by 50% over the leading closed-source model. We hope that oMeBench will serve as a rigorous foundation for advancing AI systems toward genuine chemical reasoning.

Modeling human-like action-to-reaction generation has significant real-world applications, like human-robot interaction and games. Despite recent advancements in single-person motion generation, it is still challenging to well handle action-to-reaction generation, due to the difficulty of directly predicting reaction from action sequence without prompts, and the absence of a unified representation that effectively encodes multi-person motion. To address these challenges, we introduce Think-Then-React (TTR), a large language-model-based framework designed to generate human-like reactions. First, with our fine-grained multimodal training strategy, TTR is capable to unify two processes during inference: a thinking process that explicitly infers action intentions and reasons corresponding reaction description, which serve as semantic prompts, and a reacting process that predicts reactions based on input action and the inferred semantic prompts. Second, to effectively represent multi-person motion in language models, we propose a unified motion tokenizer by decoupling egocentric pose and absolute space features, which effectively represents action and reaction motion with same encoding. Extensive experiments demonstrate that TTR outperforms existing baselines, achieving significant improvements in evaluation metrics, such as reducing FID from 3.988 to 1.942.

Retrosynthesis is one of the fundamental problems in organic chemistry. The task is to identify reactants that can be used to synthesize a specified product molecule. Recently, computer-aided retrosynthesis is finding renewed interest from both chemistry and computer science communities. Most existing approaches rely on template-based models that define subgraph matching rules, but whether or not a chemical reaction can proceed is not defined by hard decision rules. In this work, we propose a new approach to this task using the Conditional Graph Logic Network, a conditional graphical model built upon graph neural networks that learns when rules from reaction templates should be applied, implicitly considering whether the resulting reaction would be both chemically feasible and strategic. We also propose an efficient hierarchical sampling to alleviate the computation cost. While achieving a significant improvement of 8.1% over current state-of-the-art methods on the benchmark dataset, our model also offers interpretations for the prediction.

Progress in large language models is constrained by an evaluation bottleneck: build a benchmark, evaluate models and settings, then iterate. We therefore ask a simple question: can we forecast outcomes before running any experiments? We study text-only performance forecasting: estimating a model's score from a redacted task description and intended configuration, with no access to dataset instances. To support systematic study, we curate PRECOG, a corpus of redacted description-performance pairs spanning diverse tasks, domains, and metrics. Experiments show the task is challenging but feasible: models equipped with a retrieval module that excludes source papers achieve moderate prediction performance with well-calibrated uncertainty, reaching mean absolute error as low as 8.7 on the Accuracy subset at high-confidence thresholds. Our analysis indicates that stronger reasoning models engage in diverse, iterative querying, whereas current open-source models lag and often skip retrieval or gather evidence with limited diversity. We further test a zero-leakage setting, forecasting on newly released datasets or experiments before their papers are indexed, where GPT-5 with built-in web search still attains nontrivial prediction accuracy. Overall, our corpus and analyses offer an initial step toward open-ended anticipatory evaluation, supporting difficulty estimation and smarter experiment prioritization.

Large language models (LLMs) excel at processing information reactively but lack the ability to systemically explore hypothetical futures. They cannot ask, "what if we take this action? how will it affect the final outcome" and forecast its potential consequences before acting. This critical gap limits their utility in dynamic, high-stakes scenarios like strategic planning, risk assessment, and real-time decision making. To bridge this gap, we propose WiA-LLM, a new paradigm that equips LLMs with proactive thinking capabilities. Our approach integrates What-If Analysis (WIA), a systematic approach for evaluating hypothetical scenarios by changing input variables. By leveraging environmental feedback via reinforcement learning, WiA-LLM moves beyond reactive thinking. It dynamically simulates the outcomes of each potential action, enabling the model to anticipate future states rather than merely react to the present conditions. We validate WiA-LLM in Honor of Kings (HoK), a complex multiplayer game environment characterized by rapid state changes and intricate interactions. The game's real-time state changes require precise multi-step consequence prediction, making it an ideal testbed for our approach. Experimental results demonstrate WiA-LLM achieves a remarkable 74.2% accuracy in forecasting game-state changes (up to two times gain over baselines). The model shows particularly significant gains in high-difficulty scenarios where accurate foresight is critical. To our knowledge, this is the first work to formally explore and integrate what-if analysis capabilities within LLMs. WiA-LLM represents a fundamental advance toward proactive reasoning in LLMs, providing a scalable framework for robust decision-making in dynamic environments with broad implications for strategic applications.

Despite significant progress of generative models in the natural sciences, their controllability remains challenging. One fundamentally missing aspect of molecular or protein generative models is an inductive bias that can reflect continuous properties of interest. To that end, we propose the Regression Transformer (RT), a novel method that abstracts regression as a conditional sequence modeling problem. This introduces a new paradigm of multitask language models which seamlessly bridge sequence regression and conditional sequence generation. We thoroughly demonstrate that, despite using a nominal-scale training objective, the RT matches or surpasses the performance of conventional regression models in property prediction tasks of small molecules, proteins and chemical reactions. Critically, priming the same model with continuous properties yields a highly competitive conditional generative model that outperforms specialized approaches in a substructure-constrained, property-driven molecule generation benchmark. Our dichotomous approach is facilitated by a novel, alternating training scheme that enables the model to decorate seed sequences by desired properties, e.g., to optimize reaction yield. In sum, the RT is the first report of a multitask model that concurrently excels at predictive and generative tasks in biochemistry. This finds particular application in property-driven, local exploration of the chemical or protein space and could pave the road toward foundation models in material design. The code to reproduce all experiments of the paper is available at: https://github.com/IBM/regression-transformer

Knowledge of mixtures' phase equilibria is crucial in nature and technical chemistry. Phase equilibria calculations of mixtures require activity coefficients. However, experimental data on activity coefficients is often limited due to high cost of experiments. For an accurate and efficient prediction of activity coefficients, machine learning approaches have been recently developed. However, current machine learning approaches still extrapolate poorly for activity coefficients of unknown molecules. In this work, we introduce the SMILES-to-Properties-Transformer (SPT), a natural language processing network to predict binary limiting activity coefficients from SMILES codes. To overcome the limitations of available experimental data, we initially train our network on a large dataset of synthetic data sampled from COSMO-RS (10 Million data points) and then fine-tune the model on experimental data (20 870 data points). This training strategy enables SPT to accurately predict limiting activity coefficients even for unknown molecules, cutting the mean prediction error in half compared to state-of-the-art models for activity coefficient predictions such as COSMO-RS, UNIFAC, and improving on recent machine learning approaches.

Accelerating scientific discovery requires the identification of which experiments would yield the best outcomes before committing resources to costly physical validation. While existing benchmarks evaluate LLMs on scientific knowledge and reasoning, their ability to predict experimental outcomes - a task where AI could significantly exceed human capabilities - remains largely underexplored. We introduce SciPredict, a benchmark comprising 405 tasks derived from recent empirical studies in 33 specialized sub-fields of physics, biology, and chemistry. SciPredict addresses two critical questions: (a) can LLMs predict the outcome of scientific experiments with sufficient accuracy? and (b) can such predictions be reliably used in the scientific research process? Evaluations reveal fundamental limitations on both fronts. Model accuracies are 14-26% and human expert performance is approx20%. Although some frontier models exceed human performance model accuracy is still far below what would enable reliable experimental guidance. Even within the limited performance, models fail to distinguish reliable predictions from unreliable ones, achieving only approx20% accuracy regardless of their confidence or whether they judge outcomes as predictable without physical experimentation. Human experts, in contrast, demonstrate strong calibration: their accuracy increases from approx5% to approx80% as they deem outcomes more predictable without conducting the experiment. SciPredict establishes a rigorous framework demonstrating that superhuman performance in experimental science requires not just better predictions, but better awareness of prediction reliability. For reproducibility all our data and code are provided at https://github.com/scaleapi/scipredict

Humans exhibit adaptive, context-sensitive responses to egocentric visual input. However, faithfully modeling such reactions from egocentric video remains challenging due to the dual requirements of strictly causal generation and precise 3D spatial alignment. To tackle this problem, we first construct the Human Reaction Dataset (HRD) to address data scarcity and misalignment by building a spatially aligned egocentric video-reaction dataset, as existing datasets (e.g., ViMo) suffer from significant spatial inconsistency between the egocentric video and reaction motion, e.g., dynamically moving motions are always paired with fixed-camera videos. Leveraging HRD, we present EgoReAct, the first autoregressive framework that generates 3D-aligned human reaction motions from egocentric video streams in real-time. We first compress the reaction motion into a compact yet expressive latent space via a Vector Quantised-Variational AutoEncoder and then train a Generative Pre-trained Transformer for reaction generation from the visual input. EgoReAct incorporates 3D dynamic features, i.e., metric depth, and head dynamics during the generation, which effectively enhance spatial grounding. Extensive experiments demonstrate that EgoReAct achieves remarkably higher realism, spatial consistency, and generation efficiency compared with prior methods, while maintaining strict causality during generation. We will release code, models, and data upon acceptance.

Long-horizon LLM agents depend on intermediate information-gathering turns, yet training feedback is usually observed only at the final answer, because process-level rewards require high-quality human annotation. Existing turn-level shaping methods reward turns that increase the likelihood of a gold answer, but they require answer supervision or stable task-specific verifiers. Conversely, label-free RL methods extract self-signals from output distributions, but mainly at the answer or trajectory level and therefore cannot assign credit to intermediate turns. We propose Self-Induced Outcome Potential (SIOP), which treats semantic clusters of final answers as latent future outcome states for potential-based turn-level credit assignment. For each query, SIOP samples multiple rollouts, clusters final answers into semantic outcome modes, and builds a reliability-aware target distribution over these states. It then rewards turns for increasing posterior support for reliable future states using a tractable cluster-level approximation. The objective generalizes information-potential shaping from gold-answer supervision to settings without task-specific gold verifiers while avoiding the broadcasted rollout-level advantages used by standard GRPO. We formalize the framework, characterize its supervised gold-answer limit, and show that SIOP improves average performance over verifier-free outcome-level baselines on seven search-augmented agentic reasoning benchmarks while approaching a gold-supervised outcome baseline. Code is available at https://github.com/dl-m9/SIOP.git.

Machine learning has promised to change the landscape of laboratory chemistry, with impressive results in molecular property prediction and reaction retro-synthesis. However, chemical datasets are often inaccessible to the machine learning community as they tend to require cleaning, thorough understanding of the chemistry, or are simply not available. In this paper, we introduce a novel dataset for yield prediction, providing the first-ever transient flow dataset for machine learning benchmarking, covering over 1200 process conditions. While previous datasets focus on discrete parameters, our experimental set-up allow us to sample a large number of continuous process conditions, generating new challenges for machine learning models. We focus on solvent selection, a task that is particularly difficult to model theoretically and therefore ripe for machine learning applications. We showcase benchmarking for regression algorithms, transfer-learning approaches, feature engineering, and active learning, with important applications towards solvent replacement and sustainable manufacturing.

Activity and property prediction models are the central workhorses in drug discovery and materials sciences, but currently they have to be trained or fine-tuned for new tasks. Without training or fine-tuning, scientific language models could be used for such low-data tasks through their announced zero- and few-shot capabilities. However, their predictive quality at activity prediction is lacking. In this work, we envision a novel type of activity prediction model that is able to adapt to new prediction tasks at inference time, via understanding textual information describing the task. To this end, we propose a new architecture with separate modules for chemical and natural language inputs, and a contrastive pre-training objective on data from large biochemical databases. In extensive experiments, we show that our method CLAMP yields improved predictive performance on few-shot learning benchmarks and zero-shot problems in drug discovery. We attribute the advances of our method to the modularized architecture and to our pre-training objective.

Drug toxicity remains a major challenge in pharmaceutical development. Recent machine learning models have improved in silico toxicity prediction, but their reliance on annotated data and lack of interpretability limit their applicability. This limits their ability to capture organ-specific toxicities driven by complex biological mechanisms. Large language models (LLMs) offer a promising alternative through step-by-step reasoning and integration of textual data, yet prior approaches lack biological context and transparent rationale. To address this issue, we propose CoTox, a novel framework that integrates LLM with chain-of-thought (CoT) reasoning for multi-toxicity prediction. CoTox combines chemical structure data, biological pathways, and gene ontology (GO) terms to generate interpretable toxicity predictions through step-by-step reasoning. Using GPT-4o, we show that CoTox outperforms both traditional machine learning and deep learning model. We further examine its performance across various LLMs to identify where CoTox is most effective. Additionally, we find that representing chemical structures with IUPAC names, which are easier for LLMs to understand than SMILES, enhances the model's reasoning ability and improves predictive performance. To demonstrate its practical utility in drug development, we simulate the treatment of relevant cell types with drug and incorporated the resulting biological context into the CoTox framework. This approach allow CoTox to generate toxicity predictions aligned with physiological responses, as shown in case study. This result highlights the potential of LLM-based frameworks to improve interpretability and support early-stage drug safety assessment. The code and prompt used in this work are available at https://github.com/dmis-lab/CoTox.

Adapting large language models (LLMs) trained on broad organic chemistry to smaller, domain-specific reaction datasets is a key challenge in chemical and pharmaceutical R&D. Effective specialisation requires learning new reaction knowledge while preserving general chemical understanding across related tasks. Here, we evaluate Low-Rank Adaptation (LoRA) as a parameter-efficient alternative to full fine-tuning for organic reaction prediction on limited, complex datasets. Using USPTO reaction classes and challenging C-H functionalisation reactions, we benchmark forward reaction prediction, retrosynthesis and reagent prediction. LoRA achieves accuracy comparable to full fine-tuning while effectively mitigating catastrophic forgetting and better preserving multi-task performance. Both fine-tuning approaches generalise beyond training distributions, producing plausible alternative solvent predictions. Notably, C-H functionalisation fine-tuning reveals that LoRA and full fine-tuning encode subtly different reactivity patterns, suggesting more effective reaction-specific adaptation with LoRA. As LLMs continue to scale, our results highlight the practicality of modular, parameter-efficient fine-tuning strategies for their flexible deployment for chemistry applications.

Large language models (LLMs) have gained widespread interest due to their ability to process human language and perform tasks on which they have not been explicitly trained. This is relevant for the chemical sciences, which face the problem of small and diverse datasets that are frequently in the form of text. LLMs have shown promise in addressing these issues and are increasingly being harnessed to predict chemical properties, optimize reactions, and even design and conduct experiments autonomously. However, we still have only a very limited systematic understanding of the chemical reasoning capabilities of LLMs, which would be required to improve models and mitigate potential harms. Here, we introduce "ChemBench," an automated framework designed to rigorously evaluate the chemical knowledge and reasoning abilities of state-of-the-art LLMs against the expertise of human chemists. We curated more than 7,000 question-answer pairs for a wide array of subfields of the chemical sciences, evaluated leading open and closed-source LLMs, and found that the best models outperformed the best human chemists in our study on average. The models, however, struggle with some chemical reasoning tasks that are easy for human experts and provide overconfident, misleading predictions, such as about chemicals' safety profiles. These findings underscore the dual reality that, although LLMs demonstrate remarkable proficiency in chemical tasks, further research is critical to enhancing their safety and utility in chemical sciences. Our findings also indicate a need for adaptations to chemistry curricula and highlight the importance of continuing to develop evaluation frameworks to improve safe and useful LLMs.

Large Language Models (LLMs) and multi-agent systems have shown impressive capabilities in natural language tasks but face challenges in clinical trial applications, primarily due to limited access to external knowledge. Recognizing the potential of advanced clinical trial tools that aggregate and predict based on the latest medical data, we propose an integrated solution to enhance their accessibility and utility. We introduce Clinical Agent System (ClinicalAgent), a clinical multi-agent system designed for clinical trial tasks, leveraging GPT-4, multi-agent architectures, LEAST-TO-MOST, and ReAct reasoning technology. This integration not only boosts LLM performance in clinical contexts but also introduces novel functionalities. The proposed method achieves competitive predictive performance in clinical trial outcome prediction (0.7908 PR-AUC), obtaining a 0.3326 improvement over the standard prompt Method. Publicly available code can be found at https://anonymous.4open.science/r/ClinicalAgent-6671.

The recent success of large foundation models in artificial intelligence has prompted the emergence of chemical pre-trained models. Despite the growing interest in large molecular pre-trained models that provide informative representations for downstream tasks, attempts for multimodal pre-training approaches on the molecule domain were limited. To address this, we present a novel multimodal molecular pre-trained model that incorporates the modalities of structure and biochemical properties, drawing inspiration from recent advances in multimodal learning techniques. Our proposed model pipeline of data handling and training objectives aligns the structure/property features in a common embedding space, which enables the model to regard bidirectional information between the molecules' structure and properties. These contributions emerge synergistic knowledge, allowing us to tackle both multimodal and unimodal downstream tasks through a single model. Through extensive experiments, we demonstrate that our model shows remarkable capabilities in solving various meaningful chemical challenges, including conditional molecule generation, property prediction, molecule classification, and reaction prediction.

The integration of Multimodal Large Language Models (MLLMs) into chemistry promises to revolutionize scientific discovery, yet their ability to comprehend the dense, graphical language of reactions within authentic literature remains underexplored. Here, we introduce RxnBench, a multi-tiered benchmark designed to rigorously evaluate MLLMs on chemical reaction understanding from scientific PDFs. RxnBench comprises two tasks: Single-Figure QA (SF-QA), which tests fine-grained visual perception and mechanistic reasoning using 1,525 questions derived from 305 curated reaction schemes, and Full-Document QA (FD-QA), which challenges models to synthesize information from 108 articles, requiring cross-modal integration of text, schemes, and tables. Our evaluation of MLLMs reveals a critical capability gap: while models excel at extracting explicit text, they struggle with deep chemical logic and precise structural recognition. Notably, models with inference-time reasoning significantly outperform standard architectures, yet none achieve 50\% accuracy on FD-QA. These findings underscore the urgent need for domain-specific visual encoders and stronger reasoning engines to advance autonomous AI chemists.

This paper presents a multi-label topic model for financial texts like ad-hoc announcements, 8-K filings, finance related news or annual reports. I train the model on a new financial multi-label database consisting of 3,044 German ad-hoc announcements that are labeled manually using 20 predefined, economically motivated topics. The best model achieves a macro F1 score of more than 85%. Translating the data results in an English version of the model with similar performance. As application of the model, I investigate differences in stock market reactions across topics. I find evidence for strong positive or negative market reactions for some topics, like announcements of new Large Scale Projects or Bankruptcy Filings, while I do not observe significant price effects for some other topics. Furthermore, in contrast to previous studies, the multi-label structure of the model allows to analyze the effects of co-occurring topics on stock market reactions. For many cases, the reaction to a specific topic depends heavily on the co-occurrence with other topics. For example, if allocated capital from a Seasoned Equity Offering (SEO) is used for restructuring a company in the course of a Bankruptcy Proceeding, the market reacts positively on average. However, if that capital is used for covering unexpected, additional costs from the development of new drugs, the SEO implies negative reactions on average.

Open-weights reasoning language models generate long chains-of-thought (CoTs) before producing a final response, which improves performance but introduces additional alignment risks, with harmful content often appearing in both the CoTs and the final outputs. In this work, we investigate if we can use CoTs to predict final response misalignment. We evaluate a range of monitoring approaches, including humans, highly-capable large language models, and text classifiers, using either CoT text or activations. First, we find that a simple linear probe trained on CoT activations can significantly outperform all text-based methods in predicting whether a final response will be safe or unsafe. CoT texts are often unfaithful and can mislead humans and classifiers, while model latents (i.e., CoT activations) offer a more reliable predictive signal. Second, the probe makes accurate predictions before reasoning completes, achieving strong performance even when applied to early CoT segments. These findings generalize across model sizes, families, and safety benchmarks, suggesting that lightweight probes could enable real-time safety monitoring and early intervention during generation.

Large Language Models (LLMs) are increasingly embedded in autonomous agents that engage, converse, and co-evolve in online social platforms. While prior work has documented the generation of toxic content by LLMs, far less is known about how exposure to harmful content shapes agent behavior over time, particularly in environments composed entirely of interacting AI agents. In this work, we study toxicity adoption of LLM-driven agents on Chirper.ai, a fully AI-driven social platform. Specifically, we model interactions in terms of stimuli (posts) and responses (comments). We conduct a large-scale empirical analysis of agent behavior, examining how toxic responses relate to toxic stimuli, how repeated exposure to toxicity affects the likelihood of toxic responses, and whether toxic behavior can be predicted from exposure alone. Our findings show that toxic responses are more likely following toxic stimuli, and, at the same time, cumulative toxic exposure (repeated over time) significantly increases the probability of toxic responding. We further introduce two influence metrics, revealing a strong negative correlation between induced and spontaneous toxicity. Finally, we show that the number of toxic stimuli alone enables accurate prediction of whether an agent will eventually produce toxic content. These results highlight exposure as a critical risk factor in the deployment of LLM agents, particularly as such agents operate in online environments where they may engage not only with other AI chatbots, but also with human counterparts. This could trigger unwanted and pernicious phenomena, such as hate-speech propagation and cyberbullying. In an effort to reduce such risks, monitoring exposure to toxic content may provide a lightweight yet effective mechanism for auditing and mitigating harmful behavior in the wild.

A persistent challenge in machine learning for scientific applications is jointly achieving prediction and understanding. Statistical models excel on structured data but operate as black boxes, while existing interpretability methods are largely inspective: they answer "which features matter?" but do not articulate how features interact or refine explanations iteratively alongside human understanding. Asking an LLM to predict the target directly forces it to search the entire output space; we instead anchor predictions with a base model and ask the LLM the narrower question of what that model is missing. We introduce Multi-Agent Residual In-Context Learning (MARICL), an agentic framework in which LLM agents analyze where a base-model fails, hypothesize missing structure from high-residual examples provided in context, and produce explicit correction terms refined through multi-turn textual gradient optimization. Across nine benchmarks spanning scientific, biomedical, socioeconomic, and synthetic settings, MARICL improves consistently over its base model on all datasets. To test whether these corrections reflect real structure or batch-specific noise, we freeze formulas learned on one experimental batch of the Cell-Free Protein dataset and apply them (with no retraining and no further LLM calls) to held-out batches. Within the same reagent protocol, the frozen formulas improve predictions in over 92% of cases; across a different protocol, they fail systematically. The success boundary aligns with the biochemistry, not the batch count; direct evidence of mechanistic generalization.

Online misinformation poses a global risk with harmful implications for society. Ordinary social media users are known to actively reply to misinformation posts with counter-misinformation messages, which is shown to be effective in containing the spread of misinformation. Such a practice is defined as "social correction". Nevertheless, it remains unknown how users respond to social correction in real-world scenarios, especially, will it have a corrective or backfire effect on users. Investigating this research question is pivotal for developing and refining strategies that maximize the efficacy of social correction initiatives. To fill this gap, we conduct an in-depth study to characterize and predict the user response to social correction in a data-driven manner through the lens of X (Formerly Twitter), where the user response is instantiated as the reply that is written toward a counter-misinformation message. Particularly, we first create a novel dataset with 55, 549 triples of misinformation tweets, counter-misinformation replies, and responses to counter-misinformation replies, and then curate a taxonomy to illustrate different kinds of user responses. Next, fine-grained statistical analysis of reply linguistic and engagement features as well as repliers' user attributes is conducted to illustrate the characteristics that are significant in determining whether a reply will have a corrective or backfire effect. Finally, we build a user response prediction model to identify whether a social correction will be corrective, neutral, or have a backfire effect, which achieves a promising F1 score of 0.816. Our work enables stakeholders to monitor and predict user responses effectively, thus guiding the use of social correction to maximize their corrective impact and minimize backfire effects. The code and data is accessible on https://github.com/claws-lab/response-to-social-correction.

Recent world-action models (WAMs) show that co-training policies with future prediction can provide physical priors for action generation. Building on the future-prediction ability of video models, many WAMs generate future videos and recover actions with inverse-dynamics models, or use these predicted videos as goal conditions for action generation. In both cases, the world model is trained mostly on successful demonstrations and has little reason to predict the consequences of bad actions. We introduce FACT, a causal World-Action Model that predicts future video and task progress conditioned on the executed action. This action-conditioned interface allows failure rollouts to supervise action consequences, turning bad actions into valid future targets rather than being discarded. Failure-aware training makes the progress predictor aware of both successful and failed action outcomes, which can optionally be used to score sampled action candidates at inference. Extensive experiments on simulation and real-world bimanual manipulation tasks show that FACT outperforms many existing baselines, improves as failure data are incorporated into training, and reduces success-biased future hallucination under bad actions. See more details at https://fact-wam.github.io/

Adverse drug events (ADEs) significantly impact clinical research, causing many clinical trial failures. ADE prediction is key for developing safer medications and enhancing patient outcomes. To support this effort, we introduce CT-ADE, a dataset for multilabel predictive modeling of ADEs in monopharmacy treatments. CT-ADE integrates data from 2,497 unique drugs, encompassing 168,984 drug-ADE pairs extracted from clinical trials, annotated with patient and contextual information, and comprehensive ADE concepts standardized across multiple levels of the MedDRA ontology. Preliminary analyses with large language models (LLMs) achieved F1-scores up to 55.90%. Models using patient and contextual information showed F1-score improvements of 21%-38% over models using only chemical structure data. Our results highlight the importance of target population and treatment regimens in the predictive modeling of ADEs, offering greater performance gains than LLM domain specialization and scaling. CT-ADE provides an essential tool for researchers aiming to leverage artificial intelligence and machine learning to enhance patient safety and minimize the impact of ADEs on pharmaceutical research and development. The dataset is publicly accessible at https://github.com/ds4dh/CT-ADE.

The chemical reaction recommendation is to select proper reaction condition parameters for chemical reactions, which is pivotal to accelerating chemical science. With the rapid development of large language models (LLMs), there is growing interest in leveraging their reasoning and planning capabilities for reaction condition recommendation. Despite their success, existing methods rarely explain the rationale behind the recommended reaction conditions, limiting their utility in high-stakes scientific workflows. In this work, we propose ChemMAS, a multi-agent system that reframes condition prediction as an evidence-based reasoning task. ChemMAS decomposes the task into mechanistic grounding, multi-channel recall, constraint-aware agentic debate, and rationale aggregation. Each decision is backed by interpretable justifications grounded in chemical knowledge and retrieved precedents. Experiments show that ChemMAS achieves 20-35% gains over domain-specific baselines and outperforms general-purpose LLMs by 10-15% in Top-1 accuracy, while offering falsifiable, human-trustable rationales, which establishes a new paradigm for explainable AI in scientific discovery.

This study presents a hybrid framework for predicting movie success. The framework integrates multi-task learning (MTL), GPT-based sentiment analysis, and Susceptible-Infected-Recovered (SIR) propagation modeling. The study examines limitations in existing approaches. It models static production attributes, information dissemination, and audience sentiment at the same time. The framework uses 5,840 films from 2004 to 2024 and approximate 300,000 user reviews. It shows predictive performance with classification accuracy of 0.964 and regression metrics of MAE 0.388. Ablation analysis indicates component interactions. Selective feature combinations perform better than the comprehensive model. This result questions assumptions about feature integration. The model shows virality patterns between successful and unsuccessful films. Innovations include epidemiological modeling for information diffusion, multidimensional sentiment features from GPT-based analysis, and a shared representation architecture that optimizes multiple success metrics. The framework provides applications in the film production lifecycle. It also contributes to understanding how audience engagement leads to commercial outcomes.

In natural human-to-human conversations, participants often receive feedback signals from one another based on their follow-up reactions. These reactions can include verbal responses, facial expressions, changes in emotional state, and other non-verbal cues. Similarly, in human-machine interactions, the machine can leverage the user's follow-up utterances as feedback signals to assess whether it has appropriately addressed the user's request. Therefore, we propose using the likelihood of follow-up utterances as rewards to differentiate preferred responses from less favored ones, without relying on human or commercial LLM-based preference annotations. Our proposed reward mechanism, ``Follow-up Likelihood as Reward" (FLR), matches the performance of strong reward models trained on large-scale human or GPT-4 annotated data on 8 pairwise-preference and 4 rating-based benchmarks. Building upon the FLR mechanism, we propose to automatically mine preference data from the online generations of a base policy model. The preference data are subsequently used to boost the helpfulness of the base model through direct alignment from preference (DAP) methods, such as direct preference optimization (DPO). Lastly, we demonstrate that fine-tuning the language model that provides follow-up likelihood with natural language feedback significantly enhances FLR's performance on reward modeling benchmarks and effectiveness in aligning the base policy model's helpfulness.

Large-scale chemical reaction datasets are crucial for AI research in chemistry. However, existing chemical reaction data often exist as images within papers, making them not machine-readable and unusable for training machine learning models. In response to this challenge, we propose the RxnCaption framework for the task of chemical Reaction Diagram Parsing (RxnDP). Our framework reformulates the traditional coordinate prediction driven parsing process into an image captioning problem, which Large Vision Language Models (LVLMs) handle naturally. We introduce a strategy termed BBox and Index as Visual Prompt (BIVP), which uses our state-of-the-art molecular detector, MolYOLO, to pre-draw molecular bounding boxes and indices directly onto the input image. This turns the downstream parsing into a natural-language description problem. Extensive experiments show that the BIVP strategy significantly improves structural extraction quality while simplifying model design. We further construct the RxnCaption-15k dataset, an order of magnitude larger than prior real-world literature benchmarks, with a balanced test subset across four layout archetypes. Experiments demonstrate that RxnCaption-VL achieves state-of-the-art performance on multiple metrics. We believe our method, dataset, and models will advance structured information extraction from chemical literature and catalyze broader AI applications in chemistry. We will release data, models, and code on GitHub.

Within the field of causal inference, we consider the problem of estimating heterogeneous treatment effects from data. We propose and validate a novel approach for learning feature representations to aid the estimation of the conditional average treatment effect or CATE. Our method focuses on an intermediate layer in a neural network trained to predict the outcome from the features. In contrast to previous approaches that encourage the distribution of representations to be treatment-invariant, we leverage a genetic algorithm that optimizes over representations useful for predicting the outcome to select those less useful for predicting the treatment. This allows us to retain information within the features useful for predicting outcome even if that information may be related to treatment assignment. We validate our method on synthetic examples and illustrate its use on a real life dataset.

The success of drug discovery and development relies on the precise prediction of molecular activities and properties. While in silico molecular property prediction has shown remarkable potential, its use has been limited so far to assays for which large amounts of data are available. In this study, we use a fine-tuned large language model to integrate biological assays based on their textual information, coupled with Barlow Twins, a Siamese neural network using a novel self-supervised learning approach. This architecture uses both assay information and molecular fingerprints to extract the true molecular information. TwinBooster enables the prediction of properties of unseen bioassays and molecules by providing state-of-the-art zero-shot learning tasks. Remarkably, our artificial intelligence pipeline shows excellent performance on the FS-Mol benchmark. This breakthrough demonstrates the application of deep learning to critical property prediction tasks where data is typically scarce. By accelerating the early identification of active molecules in drug discovery and development, this method has the potential to help streamline the identification of novel therapeutics.

Can we better anticipate an actor's future actions (e.g. mix eggs) by knowing what commonly happens after his/her current action (e.g. crack eggs)? What if we also know the longer-term goal of the actor (e.g. making egg fried rice)? The long-term action anticipation (LTA) task aims to predict an actor's future behavior from video observations in the form of verb and noun sequences, and it is crucial for human-machine interaction. We propose to formulate the LTA task from two perspectives: a bottom-up approach that predicts the next actions autoregressively by modeling temporal dynamics; and a top-down approach that infers the goal of the actor and plans the needed procedure to accomplish the goal. We hypothesize that large language models (LLMs), which have been pretrained on procedure text data (e.g. recipes, how-tos), have the potential to help LTA from both perspectives. It can help provide the prior knowledge on the possible next actions, and infer the goal given the observed part of a procedure, respectively. To leverage the LLMs, we propose a two-stage framework, AntGPT. It first recognizes the actions already performed in the observed videos and then asks an LLM to predict the future actions via conditioned generation, or to infer the goal and plan the whole procedure by chain-of-thought prompting. Empirical results on the Ego4D LTA v1 and v2 benchmarks, EPIC-Kitchens-55, as well as EGTEA GAZE+ demonstrate the effectiveness of our proposed approach. AntGPT achieves state-of-the-art performance on all above benchmarks, and can successfully infer the goal and thus perform goal-conditioned "counterfactual" prediction via qualitative analysis. Code and model will be released at https://brown-palm.github.io/AntGPT

Drug-side effect research is vital for understanding adverse reactions arising in complex multi-drug therapies. However, the scarcity of higher-order datasets that capture the combinatorial effects of multiple drugs severely limits progress in this field. Existing resources such as TWOSIDES primarily focus on pairwise interactions. To fill this critical gap, we introduce HODDI, the first Higher-Order Drug-Drug Interaction Dataset, constructed from U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) records spanning the past decade, to advance computational pharmacovigilance. HODDI contains 109,744 records involving 2,506 unique drugs and 4,569 unique side effects, specifically curated to capture multi-drug interactions and their collective impact on adverse effects. Comprehensive statistical analyses demonstrate HODDI's extensive coverage and robust analytical metrics, making it a valuable resource for studying higher-order drug relationships. Evaluating HODDI with multiple models, we found that simple Multi-Layer Perceptron (MLP) can outperform graph models, while hypergraph models demonstrate superior performance in capturing complex multi-drug interactions, further validating HODDI's effectiveness. Our findings highlight the inherent value of higher-order information in drug-side effect prediction and position HODDI as a benchmark dataset for advancing research in pharmacovigilance, drug safety, and personalized medicine. The dataset and codes are available at https://github.com/TIML-Group/HODDI.

Automated scoring engines are increasingly being used to score the free-form text responses that students give to questions. Such engines are not designed to appropriately deal with responses that a human reader would find alarming such as those that indicate an intention to self-harm or harm others, responses that allude to drug abuse or sexual abuse or any response that would elicit concern for the student writing the response. Our neural network models have been designed to help identify these anomalous responses from a large collection of typical responses that students give. The responses identified by the neural network can be assessed for urgency, severity, and validity more quickly by a team of reviewers than otherwise possible. Given the anomalous nature of these types of responses, our goal is to maximize the chance of flagging these responses for review given the constraint that only a fixed percentage of responses can viably be assessed by a team of reviewers.

Machine learning shows promise in predicting the outcome of legal cases, but most research has concentrated on civil law cases rather than case law systems. We identified two unique challenges in making legal case outcome predictions with case law. First, it is crucial to identify relevant precedent cases that serve as fundamental evidence for judges during decision-making. Second, it is necessary to consider the evolution of legal principles over time, as early cases may adhere to different legal contexts. In this paper, we proposed a new framework named PILOT (PredictIng Legal case OuTcome) for case outcome prediction. It comprises two modules for relevant case retrieval and temporal pattern handling, respectively. To benchmark the performance of existing legal case outcome prediction models, we curated a dataset from a large-scale case law database. We demonstrate the importance of accurately identifying precedent cases and mitigating the temporal shift when making predictions for case law, as our method shows a significant improvement over the prior methods that focus on civil law case outcome predictions.

As a fundamental task in computational chemistry, retrosynthesis prediction aims to identify a set of reactants to synthesize a target molecule. Existing template-free approaches only consider the graph structures of the target molecule, which often cannot generalize well to rare reaction types and large molecules. Here, we propose T-Rex, a text-assisted retrosynthesis prediction approach that exploits pre-trained text language models, such as ChatGPT, to assist the generation of reactants. T-Rex first exploits ChatGPT to generate a description for the target molecule and rank candidate reaction centers based both the description and the molecular graph. It then re-ranks these candidates by querying the descriptions for each reactants and examines which group of reactants can best synthesize the target molecule. We observed that T-Rex substantially outperformed graph-based state-of-the-art approaches on two datasets, indicating the effectiveness of considering text information. We further found that T-Rex outperformed the variant that only use ChatGPT-based description without the re-ranking step, demonstrate how our framework outperformed a straightforward integration of ChatGPT and graph information. Collectively, we show that text generated by pre-trained language models can substantially improve retrosynthesis prediction, opening up new avenues for exploiting ChatGPT to advance computational chemistry. And the codes can be found at https://github.com/lauyikfung/T-Rex.

In large language model (LLM) pretraining, data quality is believed to determine model quality. In this paper, we re-examine the notion of "quality" from the perspective of pre- and post-training co-design. Specifically, we explore the possibility that pre-training on more toxic data can lead to better control in post-training, ultimately decreasing a model's output toxicity. First, we use a toy experiment to study how data composition affects the geometry of features in the representation space. Next, through controlled experiments with Olmo-1B models trained on varying ratios of clean and toxic data, we find that the concept of toxicity enjoys a less entangled linear representation as the proportion of toxic data increases. Furthermore, we show that although toxic data increases the generational toxicity of the base model, it also makes the toxicity easier to remove. Evaluations on Toxigen and Real Toxicity Prompts demonstrate that models trained on toxic data achieve a better trade-off between reducing generational toxicity and preserving general capabilities when detoxifying techniques such as inference-time intervention (ITI) are applied. Our findings suggest that, with post-training taken into account, bad data may lead to good models.

Toxicity remains a leading cause of early-stage drug development failure. Despite advances in molecular design and property prediction, the task of molecular toxicity repair - generating structurally valid molecular alternatives with reduced toxicity - has not yet been systematically defined or benchmarked. To fill this gap, we introduce ToxiMol, the first benchmark task for general-purpose Multimodal Large Language Models (MLLMs) focused on molecular toxicity repair. We construct a standardized dataset covering 11 primary tasks and 560 representative toxic molecules spanning diverse mechanisms and granularities. We design a prompt annotation pipeline with mechanism-aware and task-adaptive capabilities, informed by expert toxicological knowledge. In parallel, we propose an automated evaluation framework, ToxiEval, which integrates toxicity endpoint prediction, synthetic accessibility, drug-likeness, and structural similarity into a high-throughput evaluation chain for repair success. We systematically assess nearly 30 mainstream general-purpose MLLMs and design multiple ablation studies to analyze key factors such as evaluation criteria, candidate diversity, and failure attribution. Experimental results show that although current MLLMs still face significant challenges on this task, they begin to demonstrate promising capabilities in toxicity understanding, semantic constraint adherence, and structure-aware molecule editing.

Large Reasoning Models (LRMs) improve answer quality through explicit chain-of-thought, yet this very capability introduces new safety risks: harmful content can be subtly injected, surface gradually, or be justified by misleading rationales within the reasoning trace. Existing safety evaluations, however, primarily focus on output-level judgments and rarely capture these dynamic risks along the reasoning process. In this paper, we present SafeRBench, the first benchmark that assesses LRM safety end-to-end -- from inputs and intermediate reasoning to final outputs. (1) Input Characterization: We pioneer the incorporation of risk categories and levels into input design, explicitly accounting for affected groups and severity, and thereby establish a balanced prompt suite reflecting diverse harm gradients. (2) Fine-Grained Output Analysis: We introduce a micro-thought chunking mechanism to segment long reasoning traces into semantically coherent units, enabling fine-grained evaluation across ten safety dimensions. (3) Human Safety Alignment: We validate LLM-based evaluations against human annotations specifically designed to capture safety judgments. Evaluations on 19 LRMs demonstrate that SafeRBench enables detailed, multidimensional safety assessment, offering insights into risks and protective mechanisms from multiple perspectives.

Models that can predict the occurrence of events ahead of time with low false-alarm rates are critical to the acceptance of decision support systems in the medical community. This challenging task is typically treated as a simple binary classification, ignoring temporal dependencies between samples, whereas we propose to exploit this structure. We first introduce a common theoretical framework unifying dynamic survival analysis and early event prediction. Following an analysis of objectives from both fields, we propose Temporal Label Smoothing (TLS), a simpler, yet best-performing method that preserves prediction monotonicity over time. By focusing the objective on areas with a stronger predictive signal, TLS improves performance over all baselines on two large-scale benchmark tasks. Gains are particularly notable along clinically relevant measures, such as event recall at low false-alarm rates. TLS reduces the number of missed events by up to a factor of two over previously used approaches in early event prediction.

We propose JFAA, a JEPA-based Future Action Anticipation method for the EPIC-KITCHENS-100 (EK-100) Action Anticipation task. Inspired by the representation learning and future prediction ability of V-JEPA 2.1, JFAA uses a frozen encoder and predictor to extract observed context features and near-future latent tokens. A lightweight attentive probe is then trained to predict verb, noun, and action logits with separate task queries. To improve robustness, we further build a field-aware ensemble over selected epoch-level predictions, allowing each output field to benefit from its most reliable candidates. Experimental results on the official challenge server show that JFAA achieves first place in the EgoVis 2026 EK-100 Action Anticipation Challenge. Our code will be released at https://github.com/CorrineQiu/JFAA.

Forecasting real-world events requires language-model agents to reason under uncertainty from incomplete, time-bounded information. Yet evaluating whether agents genuinely forecast requires more than final-answer accuracy: a model may be correct by recalling memorized training facts, citing fabricated evidence, or producing an unsupported causal story. We present WorldReasoner, an evaluation framework for temporally valid event forecasting. Each task gives an agent a resolved forecasting question, a simulated forecast date, and access only to evidence available before that date; after resolution, the framework scores the submitted probability, cited evidence, and optional causal event graph. WorldReasoner reports three complementary axes: outcome quality against resolved answers, evidence quality over cited sources, and reasoning quality against post-resolution hindsight graphs. The benchmark is built by an agentic construction pipeline that generates forecasting questions, collects time-stamped evidence, and builds hindsight reference graphs at scale, yielding 345 resolved tasks derived from 14,141 articles with graphs covering 8,087 extracted events. Across six controlled agent settings, temporally valid retrieval is the strongest driver of outcome accuracy; causal graph construction improves key-event recovery; and correct graph-enabled forecasts are more strongly grounded in key events and relevant sources, yet agents still struggle to convert grounded evidence into calibrated probabilities.

Researchers and developers increasingly rely on toxicity scoring to moderate generative language model outputs, in settings such as customer service, information retrieval, and content generation. However, toxicity scoring may render pertinent information inaccessible, rigidify or "value-lock" cultural norms, and prevent language reclamation processes, particularly for marginalized people. In this work, we extend the concept of algorithmic recourse to generative language models: we provide users a novel mechanism to achieve their desired prediction by dynamically setting thresholds for toxicity filtering. Users thereby exercise increased agency relative to interactions with the baseline system. A pilot study (n = 30) supports the potential of our proposed recourse mechanism, indicating improvements in usability compared to fixed-threshold toxicity-filtering of model outputs. Future work should explore the intersection of toxicity scoring, model controllability, user agency, and language reclamation processes -- particularly with regard to the bias that many communities encounter when interacting with generative language models.

Hypothesis ranking is a crucial component of automated scientific discovery, particularly in natural sciences where wet-lab experiments are costly and throughput-limited. Existing approaches focus on pre-experiment ranking, relying solely on large language model's internal reasoning without incorporating empirical outcomes from experiments. We introduce the task of experiment-guided ranking, which aims to prioritize candidate hypotheses based on the results of previously tested ones. However, developing such strategies is challenging due to the impracticality of repeatedly conducting real experiments in natural science domains. To address this, we propose a simulator grounded in three domain-informed assumptions, modeling hypothesis performance as a function of similarity to a known ground truth hypothesis, perturbed by noise. We curate a dataset of 124 chemistry hypotheses with experimentally reported outcomes to validate the simulator. Building on this simulator, we develop a pseudo experiment-guided ranking method that clusters hypotheses by shared functional characteristics and prioritizes candidates based on insights derived from simulated experimental feedback. Experiments show that our method outperforms pre-experiment baselines and strong ablations.

Different from its counterpart outcome reward models (ORMs), which evaluate the entire responses, a process reward model (PRM) scores a reasoning trajectory step by step, providing denser and more fine grained rewards. However, training a PRM requires labels annotated at every intermediate step, presenting significant challenges for both manual and automatic data collection. This paper aims to address this challenge. Both theoretically and empirically, we show that an implicit PRM can be obtained at no additional cost, by simply training an ORM on the cheaper response-level labels. The only assumption is to parameterize the outcome reward as the log-likelihood ratios of the policy and reference models, which can be optimized regardless of the specific choice of loss objectives. In experiments, we instantiate our implicit PRMs with various objectives and evaluate their performance on MATH. We show that our implicit PRM outperforms a strong MCTS-based baseline \'a la Math-Shepherd using less than 1/38 of the training data. Its performance can be further improved with majority voting. We further find that scaling up instructions and responses benefits our implicit PRM, and the latter brings a larger gain. Particularly, we find that our implicit PRM, when instantiated with the cross-entropy (CE) loss, is more data-efficient and can keep improving generation models even when trained with only one response per instruction, the setup that suffers from extreme data scarcity and imbalance. Further, instructions should be relevant to downstream tasks while the diversity of responses does not bring gains. Surprisingly, training on extra Math-Shepherd step labels brings no further improvements to our implicit PRM trained on only outcome data. We hope that our work will encourage a rethinking of PRM training approaches and contribute to making training PRMs more accessible.

The way people respond to messaging from public health organizations on social media can provide insight into public perceptions on critical health issues, especially during a global crisis such as COVID-19. It could be valuable for high-impact organizations such as the US Centers for Disease Control and Prevention (CDC) or the World Health Organization (WHO) to understand how these perceptions impact reception of messaging on health policy recommendations. We collect two datasets of public health messages and their responses from Twitter relating to COVID-19 and Vaccines, and introduce a predictive method which can be used to explore the potential reception of such messages. Specifically, we harness a generative model (GPT-2) to directly predict probable future responses and demonstrate how it can be used to optimize expected reception of important health guidance. Finally, we introduce a novel evaluation scheme with extensive statistical testing which allows us to conclude that our models capture the semantics and sentiment found in actual public health responses.

The 100 MW cryogenic liquid oxygen/hydrogen multi-injector combustor BKD operated by the DLR Institute of Space Propulsion is a research platform that allows the study of thermoacoustic instabilities under realistic conditions, representative of small upper stage rocket engines. We use data from BKD experimental campaigns in which the static chamber pressure and fuel-oxidizer ratio are varied such that the first tangential mode of the combustor is excited under some conditions. We train an autoregressive Bayesian neural network model to forecast the amplitude of the dynamic pressure time series, inputting multiple sensor measurements (injector pressure/ temperature measurements, static chamber pressure, high-frequency dynamic pressure measurements, high-frequency OH* chemiluminescence measurements) and future flow rate control signals. The Bayesian nature of our algorithms allows us to work with a dataset whose size is restricted by the expense of each experimental run, without making overconfident extrapolations. We find that the networks are able to accurately forecast the evolution of the pressure amplitude and anticipate instability events on unseen experimental runs 500 milliseconds in advance. We compare the predictive accuracy of multiple models using different combinations of sensor inputs. We find that the high-frequency dynamic pressure signal is particularly informative. We also use the technique of integrated gradients to interpret the influence of different sensor inputs on the model prediction. The negative log-likelihood of data points in the test dataset indicates that predictive uncertainties are well-characterized by our Bayesian model and simulating a sensor failure event results as expected in a dramatic increase in the epistemic component of the uncertainty.

Toxic interactions in Open Source Software (OSS) communities reduce contributor engagement and threaten project sustainability. Preventing such toxicity before it emerges requires a clear understanding of how harmful conversations unfold. However, most proactive moderation strategies are manual, requiring significant time and effort from community maintainers. To support more scalable approaches, we curate a dataset of 159 derailed toxic threads and 207 non-toxic threads from GitHub discussions. Our analysis reveals that toxicity can be forecast by tension triggers, sentiment shifts, and specific conversational patterns. We present a novel Large Language Model (LLM)-based framework for predicting conversational derailment on GitHub using a two-step prompting pipeline. First, we generate Summaries of Conversation Dynamics (SCDs) via Least-to-Most (LtM) prompting; then we use these summaries to estimate the likelihood of derailment. Evaluated on Qwen and Llama models, our LtM strategy achieves F1-scores of 0.901 and 0.852, respectively, at a decision threshold of 0.3, outperforming established NLP baselines on conversation derailment. External validation on a dataset of 308 GitHub issue threads (65 toxic, 243 non-toxic) yields an F1-score up to 0.797. Our findings demonstrate the effectiveness of structured LLM prompting for early detection of conversational derailment in OSS, enabling proactive and explainable moderation.

The real-world impact of polarization and toxicity in the online sphere marked the end of 2020 and the beginning of this year in a negative way. Semeval-2021, Task 5 - Toxic Spans Detection is based on a novel annotation of a subset of the Jigsaw Unintended Bias dataset and is the first language toxicity detection task dedicated to identifying the toxicity-level spans. For this task, participants had to automatically detect character spans in short comments that render the message as toxic. Our model considers applying Virtual Adversarial Training in a semi-supervised setting during the fine-tuning process of several Transformer-based models (i.e., BERT and RoBERTa), in combination with Conditional Random Fields. Our approach leads to performance improvements and more robust models, enabling us to achieve an F1-score of 65.73% in the official submission and an F1-score of 66.13% after further tuning during post-evaluation.

Large Reasoning Models (LRMs) introduce new opportunities for safety monitoring through their Chain of Thought (CoT) reasoning. However, CoT is not always faithful to the model's final output, undermining its reliability as a monitoring tool. To address this, we investigate the hidden representations of LRMs to determine whether future behavior can be predicted from prompt and CoT representations. By evaluating a probe at each generated token, we construct a probe trajectory, the continuous evolution of a concept's probability across the reasoning process. We find that future model behavior is more distinguishable when examined over the full trajectory than from a single static prediction. To characterize these temporal dynamics, we extract signal-processing features that capture volatility, trend, and steady-state behavior, significantly improving the separation of future model states. We also present two methodological insights. First, template-based training data achieves near-parity with dynamically generated model responses, eliminating the need for a costly initial inference and labeling. Second, the choice of pooling operation is critical: average-pooling and last-token methods collapse to near-random performance, while max-pooling achieves up to 95% AUROC and yields stable probe trajectories. Using four datasets and four reasoning models across the domains of safety and mathematics, we demonstrate that trajectory features encode task-specific dynamics that improve outcome separability. These findings establish probe trajectories as a complementary framework for monitoring LRM behavior. Warning: This article contains potentially harmful content.

With the development of computer-assisted techniques, research communities including biochemistry and deep learning have been devoted into the drug discovery field for over a decade. Various applications of deep learning have drawn great attention in drug discovery, such as molecule generation, molecular property prediction, retrosynthesis prediction, and reaction prediction. While most existing surveys only focus on one of the applications, limiting the view of researchers in the community. In this paper, we present a comprehensive review on the aforementioned four aspects, and discuss the relationships among different applications. The latest literature and classical benchmarks are presented for better understanding the development of variety of approaches. We commence by summarizing the molecule representation format in these works, followed by an introduction of recent proposed approaches for each of the four tasks. Furthermore, we review a variety of commonly used datasets and evaluation metrics and compare the performance of deep learning-based models. Finally, we conclude by identifying remaining challenges and discussing the future trend for deep learning methods in drug discovery.

The approval success rate of drug candidates is very low with the majority of failure due to safety and efficacy. Increasingly available high dimensional information on targets, drug molecules and indications provides an opportunity for ML methods to integrate multiple data modalities and better predict clinically promising drug targets. Notably, drug targets with human genetics evidence are shown to have better odds to succeed. However, a recent tensor factorization-based approach found that additional information on targets and indications might not necessarily improve the predictive accuracy. Here we revisit this approach by integrating different types of human genetics evidence collated from publicly available sources to support each target-indication pair. We use Bayesian tensor factorization to show that models incorporating all available human genetics evidence (rare disease, gene burden, common disease) modestly improves the clinical outcome prediction over models using single line of genetics evidence. We provide additional insight into the relative predictive power of different types of human genetics evidence for predicting the success of clinical outcomes.

We developed an explainable artificial intelligence (AI) early warning score (xAI-EWS) system for early detection of acute critical illness. While maintaining a high predictive performance, our system explains to the clinician on which relevant electronic health records (EHRs) data the prediction is grounded. Acute critical illness is often preceded by deterioration of routinely measured clinical parameters, e.g., blood pressure and heart rate. Early clinical prediction is typically based on manually calculated screening metrics that simply weigh these parameters, such as Early Warning Scores (EWS). The predictive performance of EWSs yields a tradeoff between sensitivity and specificity that can lead to negative outcomes for the patient. Previous work on EHR-trained AI systems offers promising results with high levels of predictive performance in relation to the early, real-time prediction of acute critical illness. However, without insight into the complex decisions by such system, clinical translation is hindered. In this letter, we present our xAI-EWS system, which potentiates clinical translation by accompanying a prediction with information on the EHR data explaining it.

While Vision-Language Models (VLMs) have demonstrated significant potential in chemical visual understanding, current models are predominantly optimized for direct visual question-answering tasks. This paradigm often results in "black-box" systems that fail to utilize the inherent capability of Large Language Models (LLMs) to infer underlying reaction mechanisms. In this work, we introduce ChemVLR, a chemical VLM designed to prioritize reasoning within the perception process. Unlike conventional chemical VLMs, ChemVLR analyzes visual inputs in a fine-grained manner by explicitly identifying granular chemical descriptors, such as functional groups, prior to generating answers. This approach ensures the production of explicit and interpretable reasoning paths for complex visual chemical problems. To facilitate this methodology, we implement a cross-modality reverse-engineering strategy, combined with a rigorous filtering pipeline, to curate a large-scale reasoning-and-captioning dataset comprising 760k high-quality samples across molecular and reaction tasks. Furthermore, we adopt a three-stage training framework that systemically builds model perception and reasoning capacity. Experiments demonstrate that ChemVLR achieves state-of-the-art (SOTA) performance, surpassing both leading proprietary models and domain-specific open-source baselines. We also provide comprehensive ablation studies to validate our training strategy and data generation designs. Code and model weights will be available at https://github.com/xxlllz/ChemVLR.

With the advent of LLMs, various tasks across the natural language processing domain have been transformed. However, their application in predictive tasks remains less researched. This study compares large language models, including GatorTron-Base (trained on clinical data), Llama 8B, and Mistral 7B, against models like BioBERT, DocBERT, BioClinicalBERT, Word2Vec, and Doc2Vec, setting benchmarks for predicting Shock in critically ill patients. Timely prediction of shock can enable early interventions, thus improving patient outcomes. Text data from 17,294 ICU stays of patients in the MIMIC III database were scored for length of stay > 24 hours and shock index (SI) > 0.7 to yield 355 and 87 patients with normal and abnormal SI-index, respectively. Both focal and cross-entropy losses were used during finetuning to address class imbalances. Our findings indicate that while GatorTron Base achieved the highest weighted recall of 80.5%, the overall performance metrics were comparable between SLMs and LLMs. This suggests that LLMs are not inherently superior to SLMs in predicting future clinical events despite their strong performance on text-based tasks. To achieve meaningful clinical outcomes, future efforts in training LLMs should prioritize developing models capable of predicting clinical trajectories rather than focusing on simpler tasks such as named entity recognition or phenotyping.

While safety alignment for Multimodal Large Language Models (MLLMs) has gained significant attention, current paradigms primarily target malicious intent or situational violations. We propose shifting the safety frontier toward consequence-driven safety, a paradigm essential for the robust deployment of autonomous and embodied agents. To formalize this shift, we introduce OOD-MMSafe, a benchmark comprising 455 curated query-image pairs designed to evaluate a model's ability to identify latent hazards within context-dependent causal chains. Our analysis reveals a pervasive causal blindness among frontier models, with the highest 67.5% failure rate in high-capacity closed-source models, and identifies a preference ceiling where static alignment yields format-centric failures rather than improved safety reasoning as model capacity grows. To address these bottlenecks, we develop the Consequence-Aware Safety Policy Optimization (CASPO) framework, which integrates the model's intrinsic reasoning as a dynamic reference for token-level self-distillation rewards. Experimental results demonstrate that CASPO significantly enhances consequence projection, reducing the failure ratio of risk identification to 7.3% for Qwen2.5-VL-7B and 5.7% for Qwen3-VL-4B while maintaining overall effectiveness.

ReAct-style agents for search-intensive, multi-step reasoning tasks rely largely on their own internal judgment to decide what evidence to seek, which reasoning or action step to take next, and when to stop, often producing shallow, redundant, or poorly targeted trajectories. Prior work has explored rubrics as external quality signals, but existing uses are mostly evaluative rather than action-guiding: rubrics typically serve as training-time rewards or post-hoc evaluators of completed outputs, and in deep-research settings they are often coarse-grained and report-level rather than step-level. We introduce Co-ReAct, a rubric-guided action-selection framework that uses rubrics as step-level guidance during inference. At each decision step, Co-ReAct injects a rubric into the agent's context to guide the next Reason-or-Act decision, specifying what the agent should target in evidence seeking, search, reasoning, or self-evaluation. To make this guidance reliable, we train a dedicated rubric generator with GRPO. Unlike prior pairwise or binary preference formulations, our objective optimizes a list-wise Spearman rank-correlation reward against multi-judge expert consensus rankings, encouraging rubrics that are discriminative rather than merely plausible. On DeepResearchBench and SQA-CS-V2, Co-ReAct consistently improves over ReAct and representative test-time compute baselines across search agents built on both 8B/14B open-source and frontier closed-source base models. The trained rubric generator can also serve as a drop-in component that improves these baselines without changing their underlying decision mechanisms. Our code is publicly available at https://github.com/ZBWpro/Co-ReAct.

Retrieval-augmented generation (RAG) has emerged as a popular solution to mitigate the hallucination issues of large language models. However, existing studies on RAG seldom address the issue of predictive uncertainty, i.e., how likely it is that a RAG model's prediction is incorrect, resulting in uncontrollable risks in real-world applications. In this work, we emphasize the importance of risk control, ensuring that RAG models proactively refuse to answer questions with low confidence. Our research identifies two critical latent factors affecting RAG's confidence in its predictions: the quality of the retrieved results and the manner in which these results are utilized. To guide RAG models in assessing their own confidence based on these two latent factors, we develop a counterfactual prompting framework that induces the models to alter these factors and analyzes the effect on their answers. We also introduce a benchmarking procedure to collect answers with the option to abstain, facilitating a series of experiments. For evaluation, we introduce several risk-related metrics and the experimental results demonstrate the effectiveness of our approach.

Addressing the discrepancies between predictions and actual outcomes often aids individuals in expanding their thought processes and engaging in reflection, thereby facilitating reasoning in the correct direction. In this paper, we introduce PreAct, an agent framework that integrates prediction with reasoning and action. Leveraging the information provided by predictions, a large language model (LLM) based agent can offer more diversified and strategically oriented reasoning, which in turn leads to more effective actions that help the agent complete complex tasks. Our experiments demonstrate that PreAct outperforms the ReAct approach in accomplishing complex tasks and that PreAct can be co-enhanced when combined with Reflexion methods. We prompt the model with different numbers of historical predictions and find that historical predictions have a sustained positive effect on LLM planning. The differences in single-step reasoning between PreAct and ReAct show that PreAct indeed offers advantages in terms of diversity and strategic directivity over ReAct.

We study whether language models can evaluate the validity of their own claims and predict which questions they will be able to answer correctly. We first show that larger models are well-calibrated on diverse multiple choice and true/false questions when they are provided in the right format. Thus we can approach self-evaluation on open-ended sampling tasks by asking models to first propose answers, and then to evaluate the probability "P(True)" that their answers are correct. We find encouraging performance, calibration, and scaling for P(True) on a diverse array of tasks. Performance at self-evaluation further improves when we allow models to consider many of their own samples before predicting the validity of one specific possibility. Next, we investigate whether models can be trained to predict "P(IK)", the probability that "I know" the answer to a question, without reference to any particular proposed answer. Models perform well at predicting P(IK) and partially generalize across tasks, though they struggle with calibration of P(IK) on new tasks. The predicted P(IK) probabilities also increase appropriately in the presence of relevant source materials in the context, and in the presence of hints towards the solution of mathematical word problems. We hope these observations lay the groundwork for training more honest models, and for investigating how honesty generalizes to cases where models are trained on objectives other than the imitation of human writing.

Large language models (LLMs) are frequently fine-tuned or unlearned to adapt to new tasks or eliminate undesirable behaviors. While existing evaluation methods assess performance after such interventions, there remains no general approach for detecting unintended side effects, such as unlearning biology content degrading performance on chemistry tasks, particularly when these effects are unpredictable or emergent. To address this issue, we introduce MNEME, Model diffiNg for Evaluating Mechanistic Effects, a lightweight framework for identifying these side effects using sparse model diffing. MNEME compares base and fine-tuned models on task-agnostic data (for example, The Pile, LMSYS-Chat-1M) without access to fine-tuning data to isolate behavioral shifts. Applied to five LLMs across three scenarios: WMDP knowledge unlearning, emergent misalignment, and benign fine-tuning, MNEME achieves up to 95 percent accuracy in predicting side effects, aligning with known benchmarks and requiring no custom heuristics. Furthermore, we show that retraining on high-activation samples can partially reverse these effects. Our results demonstrate that sparse probing and diffing offer a scalable and automated lens into fine-tuning-induced model changes, providing practical tools for understanding and managing LLM behavior.

Identifying procedural errors online from egocentric videos is a critical yet challenging task across various domains, including manufacturing, healthcare, and skill-based training. The nature of such mistakes is inherently open-set, as unforeseen or novel errors may occur, necessitating robust detection systems that do not rely on prior examples of failure. Currently, however, no technique effectively detects open-set procedural mistakes online. We propose a dual branch architecture to address this problem in an online fashion: one branch continuously performs step recognition from the input egocentric video, while the other anticipates future steps based on the recognition module's output. Mistakes are detected as mismatches between the currently recognized action and the action predicted by the anticipation module. The recognition branch takes input frames, predicts the current action, and aggregates frame-level results into action tokens. The anticipation branch, specifically, leverages the solid pattern-matching capabilities of Large Language Models (LLMs) to predict action tokens based on previously predicted ones. Given the online nature of the task, we also thoroughly benchmark the difficulties associated with per-frame evaluations, particularly the need for accurate and timely predictions in dynamic online scenarios. Extensive experiments on two procedural datasets demonstrate the challenges and opportunities of leveraging a dual-branch architecture for mistake detection, showcasing the effectiveness of our proposed approach. In a thorough evaluation including recognition and anticipation variants and state-of-the-art models, our method reveals its robustness and effectiveness in online applications.

Recent progress in reasoning models suggests that generating plausible attempts for research-level mathematics may be within reach, but verification remains a bottleneck, consuming scarce expert time. We hypothesize that a meaningful solution should contain enough method-level information that, when applied to a neighborhood of related questions, it should yield better downstream performance than incorrect solutions. Building on this idea, we propose Consequence-Based Utility, an oracle-free evaluator that scores each candidate by testing its value as an in-context exemplar in solving related yet verifiable questions. Our approach is evaluated on an original set of research-level math problems, each paired with one expert-written solution and nine LLM-generated solutions. Notably, Consequence-Based Utility consistently outperforms reward models, generative reward models, and LLM judges on ranking quality. Specifically, for GPT-OSS-120B, it improves Acc@1 from 67.2 to 76.3 and AUC from 71.4 to 79.6, with similarly large AUC gains on GPT-OSS-20B (69.0 to 79.2). Furthermore, compared to LLM-Judges, it also exhibits a larger solver-evaluator gap, maintaining a stronger correct-wrong separation even on instances where the underlying solver often fails to solve.

Recent work has shown that asking language models to generate reasoning steps improves performance on many reasoning tasks. When moving beyond prompting, this raises the question of how we should supervise such models: outcome-based approaches which supervise the final result, or process-based approaches which supervise the reasoning process itself? Differences between these approaches might naturally be expected not just in final-answer errors but also in reasoning errors, which can be difficult to detect and are problematic in many real-world domains such as education. We run the first comprehensive comparison between process- and outcome-based approaches trained on a natural language task, GSM8K. We find that pure outcome-based supervision produces similar final-answer error rates with less label supervision. However, for correct reasoning steps we find it necessary to use process-based supervision or supervision from learned reward models that emulate process-based feedback. In total, we improve the previous best results from 16.8% to 12.7% final-answer error and 14.0% to 3.4% reasoning error among final-answer-correct solutions.

Artificial intelligence (AI) is increasingly embedded in scientific discovery, yet whether it can anticipate scientific progress remains unclear. To study this question, we introduce a temporally grounded evaluation framework for forecasting scientific progress under controlled knowledge constraints. We present CUSP (Cutoff-conditioned Unseen Scientific Progress), a multi-disciplinary and event-level benchmark that evaluates scientific forecasting in AI systems through feasibility assessment, mechanistic reasoning, generative solution design, and temporal prediction. Across 4,760 scientific events, we observe systematic and domain-dependent limitations in current frontier models. While models can identify plausible research directions from competing candidates, they fail to reliably predict whether scientific advances will be realized and systematically misestimate when they will occur. Performance is highly heterogeneous across domains, with the timing of AI progress more predictable than advances in biology, chemistry, and physics. Performance is largely insensitive to whether events occur before or after the training cutoff, suggesting these limitations cannot be explained solely by knowledge exposure in training data. Under controlled information access, additional pre-cutoff knowledge improves performance but does not close the gap to full-information settings, which becomes more pronounced for high-citation advances. Models also exhibit systematic overconfidence and strong response biases, indicating unreliable uncertainty estimation. Taken together, current AI systems fall short as predictive tools for scientific progress. Access to prior knowledge does not translate into reliable forecasting, and performance benefits more from post-event information than from forward-looking prediction.

As large language models (LLMs) are increasingly deployed in diverse user facing applications, aligning them with real user preferences becomes essential. Existing methods like Reinforcement Learning from Human Feedback (RLHF) rely on expert annotators trained on manually defined guidelines, whose judgments may not reflect the priorities of everyday users. We introduce Reinforcement Learning from User Feedback (RLUF), a framework for aligning LLMs directly to implicit signals from users in production. RLUF addresses key challenges of user feedback: user feedback is often binary (e.g., emoji reactions), sparse, and occasionally adversarial. We train a reward model, P[Love], to predict the likelihood that an LLM response will receive a Love Reaction, a lightweight form of positive user feedback, and integrate P[Love] into a multi-objective policy optimization framework alongside helpfulness and safety objectives. In large-scale experiments, we show that P[Love] is predictive of increased positive feedback and serves as a reliable offline evaluator of future user behavior. Policy optimization using P[Love] significantly raises observed positive-feedback rates, including a 28% increase in Love Reactions during live A/B tests. However, optimizing for positive reactions introduces reward hacking challenges, requiring careful balancing of objectives. By directly leveraging implicit signals from users, RLUF offers a path to aligning LLMs with real-world user preferences at scale.

The study demonstrates the capabilities of a vector-based approach for calculating stoichiometric coefficients in chemical equations, using black powder as an illustrative example. A method is proposed for selecting and constraining intermediate interactions between reactants, as well as for identifying final products. It is shown that even a small number of components can lead to a large number of final and intermediate products. Through concrete calculations, a correlation is established between the number of possible chemical equations and the number of reactants. A methodology is proposed for computing all possible chemical equations within a reaction system for arbitrary component ratios, enabling the derivation of all feasible chemical reactions. Additionally, a method is developed for calculating the chemical composition for a fixed set of reactants, allowing for the evaluation of the set of products resulting from all possible chemical interactions given a specified initial composition.

Surgical future prediction, driven by real-time AI analysis of surgical video, is critical for operating room safety and efficiency. It provides actionable insights into upcoming events, their timing, and risks-enabling better resource allocation, timely instrument readiness, and early warnings for complications (e.g., bleeding, bile duct injury). Despite this need, current surgical AI research focuses on understanding what is happening rather than predicting future events. Existing methods target specific tasks in isolation, lacking unified approaches that span both short-term (action triplets, events) and long-term horizons (remaining surgery duration, phase transitions). These methods rely on coarse-grained supervision while fine-grained surgical action triplets and steps remain underexplored. Furthermore, methods based only on future feature prediction struggle to generalize across different surgical contexts and procedures. We address these limits by reframing surgical future prediction as state-change learning. Rather than forecasting raw observations, our approach classifies state transitions between current and future timesteps. We introduce SurgFUTR, implementing this through a teacher-student architecture. Video clips are compressed into state representations via Sinkhorn-Knopp clustering; the teacher network learns from both current and future clips, while the student network predicts future states from current videos alone, guided by our Action Dynamics (ActDyn) module. We establish SFPBench with five prediction tasks spanning short-term (triplets, events) and long-term (remaining surgery duration, phase and step transitions) horizons. Experiments across four datasets and three procedures show consistent improvements. Cross-procedure transfer validates generalizability.

The success of language models, especially transformer-based architectures, has trickled into other domains giving rise to "scientific language models" that operate on small molecules, proteins or polymers. In chemistry, language models contribute to accelerating the molecule discovery cycle as evidenced by promising recent findings in early-stage drug discovery. Here, we review the role of language models in molecular discovery, underlining their strength in de novo drug design, property prediction and reaction chemistry. We highlight valuable open-source software assets thus lowering the entry barrier to the field of scientific language modeling. Last, we sketch a vision for future molecular design that combines a chatbot interface with access to computational chemistry tools. Our contribution serves as a valuable resource for researchers, chemists, and AI enthusiasts interested in understanding how language models can and will be used to accelerate chemical discovery.

Interpretability research now offers a variety of techniques for identifying abstract internal mechanisms in neural networks. Can such techniques be used to predict how models will behave on out-of-distribution examples? In this work, we provide a positive answer to this question. Through a diverse set of language modeling tasks--including symbol manipulation, knowledge retrieval, and instruction following--we show that the most robust features for correctness prediction are those that play a distinctive causal role in the model's behavior. Specifically, we propose two methods that leverage causal mechanisms to predict the correctness of model outputs: counterfactual simulation (checking whether key causal variables are realized) and value probing (using the values of those variables to make predictions). Both achieve high AUC-ROC in distribution and outperform methods that rely on causal-agnostic features in out-of-distribution settings, where predicting model behaviors is more crucial. Our work thus highlights a novel and significant application for internal causal analysis of language models.

Accurate protein-ligand binding affinity prediction is central to computational drug discovery, yet modern docking engines frequently disagree without indicating which prediction to trust. Consensus scoring and ensemble methods improve mean accuracy but treat all predictions identically without interpretable confidence measures or uncertainty decomposition, ignoring the chemical context of each protein-ligand pair. To address this limitation, we introduce RELIABLE-BA (RELIABiLity-aware Evidential fusion for Binding Affinity), an evidential framework for multi-engine binding affinity prediction. Our model comprises three steps: (1) modeling each engine as an evidential expert via Normal-Inverse-Gamma distributions, (2) scaling epistemic uncertainty through learned reliability from molecular context while preserving each expert's predictive mean, and (3) fusing experts through closed-form aggregation that captures both individual uncertainty and inter-engine disagreement. Experiments on the PDBBind and BDB2020+ benchmarks demonstrate competitive point prediction with substantially improved uncertainty calibration, and additional validation on the SARS-CoV-2 Mpro dataset and 5HT2A receptor demonstrates applicability to clinically relevant drug targets. Crucially, these uncertainty estimates enable reliable filtering of protein-ligand pairs, reducing prediction error by up to 25% when retaining only high-confidence pairs. To our knowledge, RELIABLE-BA is the first multi-engine binding affinity prediction framework to combine evidential fusion with context-dependent reliability, offering a principled path toward trustworthy AI-guided drug discovery. Our code is publicly available at https://github.com/yongchand/RELIABLE-BA.

Estimating the impact of continuous treatment variables (e.g., dosage amount) on binary outcomes presents significant challenges in modeling and estimation because many existing approaches make strong assumptions that do not hold for certain continuous treatment variables. For instance, traditional logistic regression makes strong linearity assumptions that do not hold for continuous treatment variables like time of initiation. In this work, we propose a semiparametric regression framework that decomposes effects into two interpretable components: a prognostic score that captures baseline outcome risk based on a combination of clinical, genetic, and sociodemographic features, and a treatment-interaction score that flexibly models the optimal treatment level via a nonparametric link function. By connecting these two parametric scores with Nadaraya-Watson regression, our approach is both interpretable and flexible. The potential of our approach is demonstrated through numerical simulations that show empirical estimation convergence. We conclude by applying our approach to a real-world case study using the International Warfarin Pharmacogenomics Consortium (IWPC) dataset to show our approach's clinical utility by deriving personalized warfarin dosing recommendations that integrate both genetic and clinical data, providing insights towards enhancing patient safety and therapeutic efficacy in anticoagulation therapy.

Large Language Models (LLMs) are powerful text generators, yet they can produce toxic or harmful content even when given seemingly harmless prompts. This presents a serious safety challenge and can cause real-world harm. Toxicity is often subtle and context-dependent, making it difficult to detect at the token level or through coarse sentence-level signals. Moreover, efforts to mitigate toxicity often face a trade-off between safety and the coherence, or fluency of the generated text. In this work, we present a targeted subspace intervention strategy for identifying and suppressing hidden toxic patterns from underlying model representations, while preserving overall ability to generate safe fluent content. On the RealToxicityPrompts, our method achieves strong mitigation performance compared to existing baselines, with minimal impact on inference complexity. Across multiple LLMs, our approach reduces toxicity of state-of-the-art detoxification systems by 8-20%, while maintaining comparable fluency. Through extensive quantitative and qualitative analyses, we show that our approach achieves effective toxicity reduction without impairing generative performance, consistently outperforming existing baselines.

Forecasting future events based on evidence of current conditions is an innate skill of human beings, and key for predicting the outcome of any decision making. In artificial vision for example, we would like to predict the next human action before it happens, without observing the future video frames associated to it. Computer vision models for action anticipation are expected to collect the subtle evidence in the preamble of the target actions. In prior studies recurrence modeling often leads to better performance, the strong temporal inference is assumed to be a key element for reasonable prediction. To this end, we propose a unified recurrence modeling for video action anticipation via message passing framework. The information flow in space-time can be described by the interaction between vertices and edges, and the changes of vertices for each incoming frame reflects the underlying dynamics. Our model leverages self-attention as the building blocks for each of the message passing functions. In addition, we introduce different edge learning strategies that can be end-to-end optimized to gain better flexibility for the connectivity between vertices. Our experimental results demonstrate that our proposed method outperforms previous works on the large-scale EPIC-Kitchen dataset.

Online toxic language causes real harm, especially in regions with limited moderation tools. In this study, we evaluate how large language models handle toxic comments in Serbian, Croatian, and Bosnian, languages with limited labeled data. We built and manually labeled a dataset of 4,500 YouTube and TikTok comments drawn from videos across diverse categories, including music, politics, sports, modeling, influencer content, discussions of sexism, and general topics. Four models (GPT-3.5 Turbo, GPT-4.1, Gemini 1.5 Pro, and Claude 3 Opus) were tested in two modes: zero-shot and context-augmented. We measured precision, recall, F1 score, accuracy and false positive rates. Including a short context snippet raised recall by about 0.12 on average and improved F1 score by up to 0.10, though it sometimes increased false positives. The best balance came from Gemini in context-augmented mode, reaching an F1 score of 0.82 and accuracy of 0.82, while zero-shot GPT-4.1 led on precision and had the lowest false alarms. We show how adding minimal context can improve toxic language detection in low-resource settings and suggest practical strategies such as improved prompt design and threshold calibration. These results show that prompt design alone can yield meaningful gains in toxicity detection for underserved Balkan language communities.

Recent advances in Language Models have enabled the protein modeling community with a powerful tool since protein sequences can be represented as text. Specifically, by taking advantage of Transformers, sequence-to-property prediction will be amenable without the need for explicit structural data. In this work, inspired by recent progress in Large Language Models (LLMs), we introduce PeptideBERT, a protein language model for predicting three key properties of peptides (hemolysis, solubility, and non-fouling). The PeptideBert utilizes the ProtBERT pretrained transformer model with 12 attention heads and 12 hidden layers. We then finetuned the pretrained model for the three downstream tasks. Our model has achieved state of the art (SOTA) for predicting Hemolysis, which is a task for determining peptide's potential to induce red blood cell lysis. Our PeptideBert non-fouling model also achieved remarkable accuracy in predicting peptide's capacity to resist non-specific interactions. This model, trained predominantly on shorter sequences, benefits from the dataset where negative examples are largely associated with insoluble peptides. Codes, models, and data used in this study are freely available at: https://github.com/ChakradharG/PeptideBERT

Mobile graphical user interface (GUI) agents have demonstrated remarkable capabilities in automating complex tasks, yet they introduce critical safety risks where a single erroneous action can lead to irreversible consequences. Existing safety mechanisms are primarily reactive, lacking the ability to assess risks before execution. In this paper, we introduce SeerGuard, a consequence-aware safety framework designed to mitigate these risks through pre-execution instruction-level screening and action-level risk assessment. Specifically, the action-level assessment analyzes agent-proposed actions within current GUI states, anticipating likely outcomes to identify risks before they are executed. To enable these capabilities, we construct a unified safety-augmented world model (SAWM) via multi-task learning, integrating semantic next-state prediction with safety risk assessment. Extensive experiments demonstrate that SeerGuard generalizes effectively across diverse mobile GUI agents. On Qwen3-VL-8B-Instruct, it increases the safety-utility score from 0.191 to 0.596 at ω=0.8 and reduces the risk-cost score from 0.347 to 0.130 at α=0.8. Further analyses on our SAWM validate the effectiveness of the instruction-level screening, alongside the capability of action risk assessment and next-state prediction.

Acute poly-substance intoxication requires rapid, life-saving decisions under substantial uncertainty, as clinicians must rely on incomplete ingestion details and nonspecific symptoms. Effective diagnostic reasoning in this chaotic environment requires fusing unstructured, non-medical narratives (e.g. paramedic scene descriptions and unreliable patient self-reports or known histories), with structured medical data like vital signs. While Large Language Models (LLMs) show potential for processing such heterogeneous inputs, they struggle in this setting, often underperforming simple baselines that rely solely on patient histories. To address this, we present DeToxR (Decision-support for Toxicology with Reasoning), the first adaptation of Reinforcement Learning (RL) to emergency toxicology. We design a robust data-fusion engine for multi-label prediction across 14 substance classes based on an LLM finetuned with Group Relative Policy Optimization (GRPO). We optimize the model's reasoning directly using a clinical performance reward. By formulating a multi-label agreement metric as the reward signal, the model is explicitly penalized for missing co-ingested substances and hallucinating absent poisons. Our model significantly outperforms its unadapted base LLM counterpart and supervised baselines. Furthermore, in a clinical validation study, the model indicates a clinical advantage by outperforming an expert toxicologist in identifying the correct poisons (Micro-F1: 0.644 vs. 0.473). These results demonstrate the potential of RL-aligned LLMs to synthesize unstructured pre-clinical narratives and structured medical data for decision support in high-stakes environments.

This paper shows how LLMs (Large Language Models) may be used to estimate a summary of the emotional state associated with piece of text. The summary of emotional state is a dictionary of words used to describe emotion together with the probability of the word appearing after a prompt comprising the original text and an emotion eliciting tail. Through emotion analysis of Amazon product reviews we demonstrate emotion descriptors can be mapped into a PCA type space. It was hoped that text descriptions of actions to improve a current text described state could also be elicited through a tail prompt. Experiment seemed to indicate that this is not straightforward to make work. This failure put our hoped for selection of action via choosing the best predict ed outcome via comparing emotional responses out of reach for the moment.

Large language models (LLMs) have emerged as powerful tools for analyzing complex datasets. Recent studies demonstrate their potential to generate useful, personalized responses when provided with patient-specific health information that encompasses lifestyle, biomarkers, and context. As LLM-driven health applications are increasingly adopted, rigorous and efficient one-sided evaluation methodologies are crucial to ensure response quality across multiple dimensions, including accuracy, personalization and safety. Current evaluation practices for open-ended text responses heavily rely on human experts. This approach introduces human factors and is often cost-prohibitive, labor-intensive, and hinders scalability, especially in complex domains like healthcare where response assessment necessitates domain expertise and considers multifaceted patient data. In this work, we introduce Adaptive Precise Boolean rubrics: an evaluation framework that streamlines human and automated evaluation of open-ended questions by identifying gaps in model responses using a minimal set of targeted rubrics questions. Our approach is based on recent work in more general evaluation settings that contrasts a smaller set of complex evaluation targets with a larger set of more precise, granular targets answerable with simple boolean responses. We validate this approach in metabolic health, a domain encompassing diabetes, cardiovascular disease, and obesity. Our results demonstrate that Adaptive Precise Boolean rubrics yield higher inter-rater agreement among expert and non-expert human evaluators, and in automated assessments, compared to traditional Likert scales, while requiring approximately half the evaluation time of Likert-based methods. This enhanced efficiency, particularly in automated evaluation and non-expert contributions, paves the way for more extensive and cost-effective evaluation of LLMs in health.

Deployed large reasoning models (LRMs) often behave unexpectedly. Test-time steering controls LRM outputs by intervening on their hidden representations, but it can degrade output quality. We argue that prior steering work implicitly relies on internal features that detect behavior in already generated text. We show that these detection features are poor predictors of future behavioral outcomes, and thus not the natural intervention target. Instead, we train activation probes to predict future behavior likelihoods from intermediate reasoning steps. These probes predict the most likely behavior with 64%-91% accuracy, revealing a separate type of internal prediction features. Building on these prediction features, we introduce a text-level steering method, Future Probe Controlled Generation. FPCG samples multiple candidate sentences and chooses the best one according to a probe predicting the future behavior likelihood. This enables steering with almost no output quality degradation. FPCG also enables steering in several evaluations where activation steering fails. These results show that distinguishing detection and prediction features enables a more nuanced approach to controlling LRM behaviors.

Recent progress has expanded the use of large language models (LLMs) in drug discovery, including synthesis planning. However, objective evaluation of retrosynthesis performance remains limited. Existing benchmarks and metrics typically rely on published synthetic procedures and Top-K accuracy based on single ground-truth, which does not capture the open-ended nature of real-world synthesis planning. We propose a new benchmarking framework for single-step retrosynthesis that evaluates both general-purpose and chemistry-specialized LLMs using ChemCensor, a novel metric for chemical plausibility. By emphasizing plausibility over exact match, this approach better aligns with human synthesis planning practices. We also introduce CREED, a novel dataset comprising millions of ChemCensor-validated reaction records for LLM training, and use it to train a model that improves over the LLM baselines under this benchmark.

Event Causality Identification (ECI) aims at determining whether there is a causal relation between two event mentions. Conventional prompt learning designs a prompt template to first predict an answer word and then maps it to the final decision. Unlike conventional prompts, we argue that predicting an answer word may not be a necessary prerequisite for the ECI task. Instead, we can first make a deterministic assumption on the existence of causal relation between two events and then evaluate its rationality to either accept or reject the assumption. The design motivation is to try the most utilization of the encyclopedia-like knowledge embedded in a pre-trained language model. In light of such considerations, we propose a deterministic assumption prompt learning model, called DAPrompt, for the ECI task. In particular, we design a simple deterministic assumption template concatenating with the input event pair, which includes two masks as predicted events' tokens. We use the probabilities of predicted events to evaluate the assumption rationality for the final event causality decision. Experiments on the EventStoryLine corpus and Causal-TimeBank corpus validate our design objective in terms of significant performance improvements over the state-of-the-art algorithms.

Large Language Models (LLMs) are increasingly used for zero-shot annotation and LLM-as-a-judge tasks, yet their reliability hinges on how model-internalized priors interact with user-provided instructions. We investigate three dimensions of this interaction: (1) how an LLM's familiarity with data and task definitions affects performance, (2) the extent to which additional information in prompts can correct zero-shot errors ("decision stickiness"), and (3) model susceptibility to misaligned task definitions. Through experiments on toxicity detection across diverse datasets (spanning social media, gaming, news, and forums) using both dense and mixture-of-experts models, we find that nearly two-thirds of zero-shot errors are resistant to correction, with an overall rescue rate (fraction of initial errors corrected by prompting) of only 34.8%. High-confidence errors prove especially resistant to correction. When given misaligned definitions, LLMs follow them while maintaining confidence levels unchanged from the aligned condition. Crucially, we introduce Definition-Specific Familiarity (DSF), which measures alignment between a model's internal concept and the task definition. After controlling for dataset-level confounds, DSF shows a positive association with model performance (partial r = +0.41), while three distinct memorization metrics (ROUGE-L, BERTScore, and embedding cosine similarity) all fail to show a positive association. These findings show the limitations of prompt-based correction in annotation tasks, highlighting the importance of definition alignment over text-level memorization.

The discourse around toxicity and LLMs in NLP largely revolves around detection tasks. This work shifts the focus to evaluating LLMs' reasoning about toxicity -- from their explanations that justify a stance -- to enhance their trustworthiness in downstream tasks. Despite extensive research on explainability, it is not straightforward to adopt existing methods to evaluate free-form toxicity explanation due to their over-reliance on input text perturbations, among other challenges. To account for these, we propose a novel, theoretically-grounded multi-dimensional criterion, Human-Aligned Faithfulness (HAF), that measures the extent to which LLMs' free-form toxicity explanations align with those of a rational human under ideal conditions. We develop six metrics, based on uncertainty quantification, to comprehensively evaluate \haf of LLMs' toxicity explanations with no human involvement, and highlight how "non-ideal" the explanations are. We conduct several experiments on three Llama models (of size up to 70B) and an 8B Ministral model on five diverse toxicity datasets. Our results show that while LLMs generate plausible explanations to simple prompts, their reasoning about toxicity breaks down when prompted about the nuanced relations between the complete set of reasons, the individual reasons, and their toxicity stances, resulting in inconsistent and nonsensical responses. We open-source our code and LLM-generated explanations at https://github.com/uofthcdslab/HAF.

Considerable effort has been dedicated to mitigating toxicity, but existing methods often require drastic modifications to model parameters or the use of computationally intensive auxiliary models. Furthermore, previous approaches have often neglected the crucial factor of language's evolving nature over time. In this work, we present a comprehensive perspective on toxicity mitigation that takes into account its changing nature. We introduce Goodtriever, a flexible methodology that matches the current state-of-the-art toxicity mitigation while achieving 43% relative latency reduction during inference and being more computationally efficient. By incorporating a retrieval-based approach at decoding time, Goodtriever enables toxicity-controlled text generation. Our research advocates for an increased focus on adaptable mitigation techniques, which better reflect the data drift models face when deployed in the wild. Code and data are available at https://github.com/for-ai/goodtriever.

Constructing prediction sets with coverage guarantees for unobserved outcomes is a core problem in modern statistics. Methods for predictive inference have been developed for a wide range of settings, but usually only consider test data points one at a time. Here we study the problem of distribution-free predictive inference for a batch of multiple test points, aiming to construct prediction sets for functions -- such as the mean or median -- of any number of unobserved test datapoints. This setting includes constructing simultaneous prediction sets with a high probability of coverage, and selecting datapoints satisfying a specified condition while controlling the number of false claims. For the general task of predictive inference on a function of a batch of test points, we introduce a methodology called batch predictive inference (batch PI), and provide a distribution-free coverage guarantee under exchangeability of the calibration and test data. Batch PI requires the quantiles of a rank ordering function defined on certain subsets of ranks. While computing these quantiles is NP-hard in general, we show that it can be done efficiently in many cases of interest, most notably for batch score functions with a compositional structure -- which includes examples of interest such as the mean -- via a dynamic programming algorithm that we develop. Batch PI has advantages over naive approaches (such as partitioning the calibration data or directly extending conformal prediction) in many settings, as it can deliver informative prediction sets even using small calibration sample sizes. We illustrate that our procedures provide informative inference across the use cases mentioned above, through experiments on both simulated data and a drug-target interaction dataset.

Recent advances in large language models (LLMs) have led to their extensive global deployment, and ensuring their safety calls for comprehensive and multilingual toxicity evaluations. However, existing toxicity benchmarks are overwhelmingly focused on English, posing serious risks to deploying LLMs in other languages. We address this by introducing PolygloToxicityPrompts (PTP), the first large-scale multilingual toxicity evaluation benchmark of 425K naturally occurring prompts spanning 17 languages. We overcome the scarcity of naturally occurring toxicity in web-text and ensure coverage across languages with varying resources by automatically scraping over 100M web-text documents. Using PTP, we investigate research questions to study the impact of model size, prompt language, and instruction and preference-tuning methods on toxicity by benchmarking over 60 LLMs. Notably, we find that toxicity increases as language resources decrease or model size increases. Although instruction- and preference-tuning reduce toxicity, the choice of preference-tuning method does not have any significant impact. Our findings shed light on crucial shortcomings of LLM safeguarding and highlight areas for future research.

Traditional AI methods often rely on task-specific model designs and training, which constrain both the scalability of model size and generalization across different tasks. Here, we introduce ChemFM, a large foundation model specifically developed for chemicals. By conducting a series of scaling experiments, we identify UniChem as the informative molecular database for pre-training the foundation model. ChemFM comprises 3 billion parameters and is pre-trained on 178 million molecules using self-supervised causal language modeling to extract generalizable molecular representations. This model can be adapted to diverse downstream chemical applications using either full-parameter or parameter-efficient fine-tuning methods. ChemFM consistently outperforms state-of-the-art task-specific AI models across all tested tasks. Notably, it achieves up to 67.48% performance improvement across 34 property prediction benchmarks, up to 33.80% reduction in mean average deviation between conditioned and actual properties of generated molecules in conditional molecular generation tasks, and up to 3.7% top-1 accuracy improvement across 4 reaction prediction datasets. Moreover, ChemFM demonstrates its superior performance in predicting antibiotic activity and cytotoxicity, highlighting its potential to advance the discovery of novel antibiotics. Furthermore, we demonstrate that, as a foundation model, ChemFM exhibits strong data efficiency, requiring significantly fewer labeled training samples to achieve state-of-the-art performance. We anticipate that ChemFM will significantly advance chemistry research by providing a foundation model capable of effectively generalizing across a broad range of tasks with minimal additional training.

Enzymes are important proteins that catalyze chemical reactions. In recent years, machine learning methods have emerged to predict enzyme function from sequence; however, there are no standardized benchmarks to evaluate these methods. We introduce CARE, a benchmark and dataset suite for the Classification And Retrieval of Enzymes (CARE). CARE centers on two tasks: (1) classification of a protein sequence by its enzyme commission (EC) number and (2) retrieval of an EC number given a chemical reaction. For each task, we design train-test splits to evaluate different kinds of out-of-distribution generalization that are relevant to real use cases. For the classification task, we provide baselines for state-of-the-art methods. Because the retrieval task has not been previously formalized, we propose a method called Contrastive Reaction-EnzymE Pretraining (CREEP) as one of the first baselines for this task and compare it to the recent method, CLIPZyme. CARE is available at https://github.com/jsunn-y/CARE/.

In medical applications, deep learning methods are built to automate diagnostic tasks. However, a clinically relevant question that practitioners usually face, is how to predict the future trajectory of a disease (prognosis). Current methods for such a problem often require domain knowledge, and are complicated to apply. In this paper, we formulate the prognosis prediction problem as a one-to-many forecasting problem from multimodal data. Inspired by a clinical decision-making process with two agents -- a radiologist and a general practitioner, we model a prognosis prediction problem with two transformer-based components that share information between each other. The first block in this model aims to analyze the imaging data, and the second block leverages the internal representations of the first one as inputs, also fusing them with auxiliary patient data. We show the effectiveness of our method in predicting the development of structural knee osteoarthritis changes over time. Our results show that the proposed method outperforms the state-of-the-art baselines in terms of various performance metrics. In addition, we empirically show that the existence of the multi-agent transformers with depths of 2 is sufficient to achieve good performances. Our code is publicly available at https://github.com/MIPT-Oulu/CLIMAT.

Large language models can produce toxic or inappropriate text even for benign inputs, creating risks when deployed at scale. Detoxification is therefore important for safety and user trust, particularly when we want to reduce harmful content without sacrificing the model's generation quality. Many existing approaches rely on model retraining, gradients, or learned auxiliary components, which can be costly and may not transfer across model families or to truly black-box settings. We introduce a test-time procedure that approximates the gradient of completion toxicity with respect to the input embeddings and uses a small number of descent steps to steer generation toward less toxic continuations. This is achieved with zeroth-order optimization that requires only access to input embeddings, a toxicity scoring function, and forward evaluations of the model. Empirically, the approach delivers robust toxicity reductions across models and prompts and, in most settings, achieves the best overall toxicity-quality trade-off. More broadly, our work positions word embeddings as effective control variables and encourages wider use of black-box optimization to guide autoregressive language models toward scalable, safer text generation, without requiring any training or access to intermediate computations.

Pretrained neural networks have attracted significant interest in chemistry and small molecule drug design. Embeddings from these models are widely used for molecular property prediction, virtual screening, and small data learning in molecular chemistry. This study presents the most extensive comparison of such models to date, evaluating 25 models across 25 datasets. Under a fair comparison framework, we assess models spanning various modalities, architectures, and pretraining strategies. Using a dedicated hierarchical Bayesian statistical testing model, we arrive at a surprising result: nearly all neural models show negligible or no improvement over the baseline ECFP molecular fingerprint. Only the CLAMP model, which is also based on molecular fingerprints, performs statistically significantly better than the alternatives. These findings raise concerns about the evaluation rigor in existing studies. We discuss potential causes, propose solutions, and offer practical recommendations.

Generalization, the ability to perform well beyond the training context, is a hallmark of biological and artificial intelligence, yet anticipating unseen failures remains a central challenge. Conventional approaches often take a ``bottom-up'' mechanistic route by reverse-engineering interpretable features or circuits to build explanatory models. While insightful, these methods often struggle to provide the high-level, predictive signals for anticipating failure in real-world deployment. Here, we propose using a ``top-down'' approach to studying generalization failures inspired by medical biomarkers: identifying system-level measurements that serve as robust indicators of a model's future performance. Rather than mapping out detailed internal mechanisms, we systematically design and test network markers to probe structure, function links, identify prognostic indicators, and validate predictions in real-world settings. In image classification, we find that task-relevant geometric properties of in-distribution (ID) object manifolds consistently forecast poor out-of-distribution (OOD) generalization. In particular, reductions in two geometric measures, effective manifold dimensionality and utility, predict weaker OOD performance across diverse architectures, optimizers, and datasets. We apply this finding to transfer learning with ImageNet-pretrained models. We consistently find that the same geometric patterns predict OOD transfer performance more reliably than ID accuracy. This work demonstrates that representational geometry can expose hidden vulnerabilities, offering more robust guidance for model selection and AI interpretability.

Causal inference, estimating causal effects from observational data, is a fundamental tool in many disciplines. Of particular importance across a variety of domains is the continuous treatment setting, where the variable of intervention has a continuous range. This setting is far less explored and represents a substantial shift from the binary treatment setting, with models needing to represent effects across a continuum of treatment values. In this paper, we present the first causal foundation model for the continuous treatment setting. Our model meta-learns the ability to predict causal effects across a wide variety of unseen tasks without additional training or fine-tuning. First, we design a novel prior over data-generating processes with continuous treatment variables in order to generate a rich causal training corpus. We then train a transformer to reconstruct individual treatment-response curves given only observational data, leveraging in-context learning to amortize expensive Bayesian posterior inference. Our model achieves state-of-the-art performance on individual treatment-response curve reconstruction tasks compared to causal models which are trained specifically for those tasks.

We investigate the predictability of large language model (LLM) capabilities: given records of past experiments using different model families, numbers of parameters, tasks, and numbers of in-context examples, can we accurately predict LLM performance on new experiment configurations? Answering this question has practical implications for LLM users (e.g., deciding which models to try), developers (e.g., prioritizing evaluation on representative tasks), and the research community (e.g., identifying hard-to-predict capabilities that warrant further investigation). We study the performance prediction problem on experiment records from BIG-bench. On a random train-test split, an MLP-based predictor achieves an R^2 score greater than 95%, indicating the presence of learnable patterns within the experiment records. We then formulate the problem of searching for "small-bench," an informative subset of BIG-bench tasks from which the performance on the full set can be maximally recovered. We find a subset as informative as BIG-bench Hard for evaluating new model families, while being 3times smaller. Additionally, we find competitive subsets by clustering task representations learned by our MLP-based predictor and selecting tasks close to cluster centroids, highlighting the importance of task diversity in constructing "small-bench."

Biosecurity evaluations of language models typically ask whether models produce hazardous output. This paper asks a complementary question: when a model refuses, is that refusal structurally sound, or does it disappear under modest changes to prompt framing, formatting, or output length? Across five architectures, no model cleanly discriminated benign from hazard. Gemma 2 2B-IT never genuinely refused across 75 prompts, hedging on every hazard-adjacent query. Gemma 4 E2B-IT refused 65/75 prompts with chat-template formatting and 0/75 without it. Both Gemma models collapsed to 0% under an 80-token cap. Qwen 2.5 1.5B and Phi-3-mini over-refused, flagging 83-87% of benign biology as hazardous. Llama 3.2 1B showed the only meaningful tier gradient (61-point spread). To probe what drives such over-refusal, we tested a panel of Schedule I but biologically non-toxic compounds (notably psilocybin cultivation, with FDA Breakthrough Therapy status). Some models refused these at rates exceeding genuinely hazardous biology, suggesting refusal tracks legality and cultural salience over CBRN hazard. To measure the internal side, we introduce a divergence score D comparing a model's surface response label to its internal sparse autoencoder (SAE) feature activations. Full D was computed on Gemma 2 2B-IT (Gemma Scope 1) and Gemma 4 E2B-IT (author-trained bio SAE). Two fine-tuned Gemma 2 domain SAEs were released. On Gemma 4, comply and refuse responses separated by a 0.647-point gap with zero overlap (n=75), though this is preliminary, with a narrow catalog, within-sample calibration, and Gemma-family-only SAE coverage. Built over one hackathon weekend on consumer hardware (GTX 1650 Ti Max-Q, plus Colab T4 for SAE training), this preliminary evidence suggests activation-level auditing may surface failure modes invisible to behavioral evaluation, with substantial variation across architectures.

Large language model-powered chatbots have transformed how people seek information, especially in high-stakes contexts like mental health. Despite their support capabilities, safe detection and response to crises such as suicidal ideation and self-harm are still unclear, hindered by the lack of unified crisis taxonomies and clinical evaluation standards. We address this by creating: (1) a taxonomy of six crisis categories; (2) a dataset of over 2,000 inputs from 12 mental health datasets, classified into these categories; and (3) a clinical response assessment protocol. We also use LLMs to identify crisis inputs and audit five models for response safety and appropriateness. First, we built a clinical-informed crisis taxonomy and evaluation protocol. Next, we curated 2,252 relevant examples from over 239,000 user inputs, then tested three LLMs for automatic classification. In addition, we evaluated five models for the appropriateness of their responses to a user's crisis, graded on a 5-point Likert scale from harmful (1) to appropriate (5). While some models respond reliably to explicit crises, risks still exist. Many outputs, especially in self-harm and suicidal categories, are inappropriate or unsafe. Different models perform variably; some, like gpt-5-nano and deepseek-v3.2-exp, have low harm rates, but others, such as gpt-4o-mini and grok-4-fast, generate more unsafe responses. All models struggle with indirect signals, default replies, and context misalignment. These results highlight the urgent need for better safeguards, crisis detection, and context-aware responses in LLMs. They also show that alignment and safety practices, beyond scale, are crucial for reliable crisis support. Our taxonomy, datasets, and evaluation methods support ongoing AI mental health research, aiming to reduce harm and protect vulnerable users.

Predicting drug efficacy and safety in vivo requires information on biological responses (e.g., cell morphology and gene expression) to small molecule perturbations. However, current molecular representation learning methods do not provide a comprehensive view of cell states under these perturbations and struggle to remove noise, hindering model generalization. We introduce the Information Alignment (InfoAlign) approach to learn molecular representations through the information bottleneck method in cells. We integrate molecules and cellular response data as nodes into a context graph, connecting them with weighted edges based on chemical, biological, and computational criteria. For each molecule in a training batch, InfoAlign optimizes the encoder's latent representation with a minimality objective to discard redundant structural information. A sufficiency objective decodes the representation to align with different feature spaces from the molecule's neighborhood in the context graph. We demonstrate that the proposed sufficiency objective for alignment is tighter than existing encoder-based contrastive methods. Empirically, we validate representations from InfoAlign in two downstream tasks: molecular property prediction against up to 19 baseline methods across four datasets, plus zero-shot molecule-morphology matching.

Automated computational analysis of the vast chemical space is critical for numerous fields of research such as drug discovery and material science. Representation learning techniques have recently been employed with the primary objective of generating compact and informative numerical expressions of complex data. One approach to efficiently learn molecular representations is processing string-based notations of chemicals via natural language processing (NLP) algorithms. Majority of the methods proposed so far utilize SMILES notations for this purpose; however, SMILES is associated with numerous problems related to validity and robustness, which may prevent the model from effectively uncovering the knowledge hidden in the data. In this study, we propose SELFormer, a transformer architecture-based chemical language model that utilizes a 100% valid, compact and expressive notation, SELFIES, as input, in order to learn flexible and high-quality molecular representations. SELFormer is pre-trained on two million drug-like compounds and fine-tuned for diverse molecular property prediction tasks. Our performance evaluation has revealed that, SELFormer outperforms all competing methods, including graph learning-based approaches and SMILES-based chemical language models, on predicting aqueous solubility of molecules and adverse drug reactions. We also visualized molecular representations learned by SELFormer via dimensionality reduction, which indicated that even the pre-trained model can discriminate molecules with differing structural properties. We shared SELFormer as a programmatic tool, together with its datasets and pre-trained models. Overall, our research demonstrates the benefit of using the SELFIES notations in the context of chemical language modeling and opens up new possibilities for the design and discovery of novel drug candidates with desired features.