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Apr 21

Breaking Bad Tokens: Detoxification of LLMs Using Sparse Autoencoders

Large language models (LLMs) are now ubiquitous in user-facing applications, yet they still generate undesirable toxic outputs, including profanity, vulgarity, and derogatory remarks. Although numerous detoxification methods exist, most apply broad, surface-level fixes and can therefore easily be circumvented by jailbreak attacks. In this paper we leverage sparse autoencoders (SAEs) to identify toxicity-related directions in the residual stream of models and perform targeted activation steering using the corresponding decoder vectors. We introduce three tiers of steering aggressiveness and evaluate them on GPT-2 Small and Gemma-2-2B, revealing trade-offs between toxicity reduction and language fluency. At stronger steering strengths, these causal interventions surpass competitive baselines in reducing toxicity by up to 20%, though fluency can degrade noticeably on GPT-2 Small depending on the aggressiveness. Crucially, standard NLP benchmark scores upon steering remain stable, indicating that the model's knowledge and general abilities are preserved. We further show that feature-splitting in wider SAEs hampers safety interventions, underscoring the importance of disentangled feature learning. Our findings highlight both the promise and the current limitations of SAE-based causal interventions for LLM detoxification, further suggesting practical guidelines for safer language-model deployment.

  • 6 authors
·
May 20, 2025

Redefining Experts: Interpretable Decomposition of Language Models for Toxicity Mitigation

Large Language Models have demonstrated impressive fluency across diverse tasks, yet their tendency to produce toxic content remains a critical challenge for AI safety and public trust. Existing toxicity mitigation approaches primarily manipulate individual neuron activations, but these methods suffer from instability, context dependence, and often compromise the model's core language abilities. To address these shortcomings, we investigate three key questions: the stability of neuron-level toxicity indicators, the advantages of structural (layer-wise) representations, and the interpretability of mechanisms driving toxic generation. Through extensive experiments on Jigsaw and ToxiCN datasets, we show that aggregated layer-wise features provide more robust signals than single neurons. Moreover, we observe conceptual limitations in prior works that conflate toxicity detection experts and generation experts within neuron-based interventions. To mitigate this, we propose a novel principled intervention technique, EigenShift, based on eigen-decomposition of the language model's final output layer. This method selectively targets generation-aligned components, enabling precise toxicity suppression without impairing linguistic competence. Our method requires no additional training or fine-tuning, incurs minimal computational cost, and is grounded in rigorous theoretical analysis.

  • 4 authors
·
Sep 20, 2025

Breaking Bad Molecules: Are MLLMs Ready for Structure-Level Molecular Detoxification?

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.

  • 8 authors
·
Jun 12, 2025

CoTox: Chain-of-Thought-Based Molecular Toxicity Reasoning and Prediction

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.

  • 7 authors
·
Aug 5, 2025 2

IndicLLMSuite: A Blueprint for Creating Pre-training and Fine-Tuning Datasets for Indian Languages

Despite the considerable advancements in English LLMs, the progress in building comparable models for other languages has been hindered due to the scarcity of tailored resources. Our work aims to bridge this divide by introducing an expansive suite of resources specifically designed for the development of Indic LLMs, covering 22 languages, containing a total of 251B tokens and 74.8M instruction-response pairs. Recognizing the importance of both data quality and quantity, our approach combines highly curated manually verified data, unverified yet valuable data, and synthetic data. We build a clean, open-source pipeline for curating pre-training data from diverse sources, including websites, PDFs, and videos, incorporating best practices for crawling, cleaning, flagging, and deduplication. For instruction-fine tuning, we amalgamate existing Indic datasets, translate/transliterate English datasets into Indian languages, and utilize LLaMa2 and Mixtral models to create conversations grounded in articles from Indian Wikipedia and Wikihow. Additionally, we address toxicity alignment by generating toxic prompts for multiple scenarios and then generate non-toxic responses by feeding these toxic prompts to an aligned LLaMa2 model. We hope that the datasets, tools, and resources released as a part of this work will not only propel the research and development of Indic LLMs but also establish an open-source blueprint for extending such efforts to other languages. The data and other artifacts created as part of this work are released with permissive licenses.

  • 12 authors
·
Mar 10, 2024

Human-Aligned Faithfulness in Toxicity Explanations of LLMs

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.

  • 4 authors
·
Jun 23, 2025

A Chemical Modelling Roadmap Linking Protoplanetary Disks and Exoplanet Atmospheres

[Abridged] This review paper discussed which chemical effects may be at play in a planet-forming disk midplane, which effects are relevant under different conditions, and which tools are available for modelling chemical kinetics in a disk midplane. The review goes on to discuss some important efforts in the planet formation modelling community to treat chemical evolution, and, vice versa, efforts in the chemical modelling community to implement more physical effects related to planet formation into the chemical modelling. The aim of this review is both to outline some concepts related to planet formation chemistry, but also to encourage, not just collaboration between the planet formation modelling community and the astrochemical community, but also assistance and guidance from one community to the other. Guidance, regarding which effects, out of many, might be more relevant than others under certain planet formation conditions, and regarding why certain included effects lead to certain important modelling outcomes. As the research fields of exoplanet atmospheres and protoplanetary disks near new frontiers in observational insights with upcoming facilities, developing appropriate modelling frameworks (including physical and chemical effects) is paramount to ultimately enable the linking of a chemically characterised exoplanet atmospheres to its formation history in its natal protoplanetary disk.

  • 1 authors
·
Oct 30, 2022

Chinese Toxic Language Mitigation via Sentiment Polarity Consistent Rewrites

Detoxifying offensive language while preserving the speaker's original intent is a challenging yet critical goal for improving the quality of online interactions. Although large language models (LLMs) show promise in rewriting toxic content, they often default to overly polite rewrites, distorting the emotional tone and communicative intent. This problem is especially acute in Chinese, where toxicity often arises implicitly through emojis, homophones, or discourse context. We present ToxiRewriteCN, the first Chinese detoxification dataset explicitly designed to preserve sentiment polarity. The dataset comprises 1,556 carefully annotated triplets, each containing a toxic sentence, a sentiment-aligned non-toxic rewrite, and labeled toxic spans. It covers five real-world scenarios: standard expressions, emoji-induced and homophonic toxicity, as well as single-turn and multi-turn dialogues. We evaluate 17 LLMs, including commercial and open-source models with variant architectures, across four dimensions: detoxification accuracy, fluency, content preservation, and sentiment polarity. Results show that while commercial and MoE models perform best overall, all models struggle to balance safety with emotional fidelity in more subtle or context-heavy settings such as emoji, homophone, and dialogue-based inputs. We release ToxiRewriteCN to support future research on controllable, sentiment-aware detoxification for Chinese.

  • 6 authors
·
May 21, 2025

Systematic Rectification of Language Models via Dead-end Analysis

With adversarial or otherwise normal prompts, existing large language models (LLM) can be pushed to generate toxic discourses. One way to reduce the risk of LLMs generating undesired discourses is to alter the training of the LLM. This can be very restrictive due to demanding computation requirements. Other methods rely on rule-based or prompt-based token elimination, which are limited as they dismiss future tokens and the overall meaning of the complete discourse. Here, we center detoxification on the probability that the finished discourse is ultimately considered toxic. That is, at each point, we advise against token selections proportional to how likely a finished text from this point will be toxic. To this end, we formally extend the dead-end theory from the recent reinforcement learning (RL) literature to also cover uncertain outcomes. Our approach, called rectification, utilizes a separate but significantly smaller model for detoxification, which can be applied to diverse LLMs as long as they share the same vocabulary. Importantly, our method does not require access to the internal representations of the LLM, but only the token probability distribution at each decoding step. This is crucial as many LLMs today are hosted in servers and only accessible through APIs. When applied to various LLMs, including GPT-3, our approach significantly improves the generated discourse compared to the base LLMs and other techniques in terms of both the overall language and detoxification performance.

  • 4 authors
·
Feb 27, 2023

RealToxicityPrompts: Evaluating Neural Toxic Degeneration in Language Models

Pretrained neural language models (LMs) are prone to generating racist, sexist, or otherwise toxic language which hinders their safe deployment. We investigate the extent to which pretrained LMs can be prompted to generate toxic language, and the effectiveness of controllable text generation algorithms at preventing such toxic degeneration. We create and release RealToxicityPrompts, a dataset of 100K naturally occurring, sentence-level prompts derived from a large corpus of English web text, paired with toxicity scores from a widely-used toxicity classifier. Using RealToxicityPrompts, we find that pretrained LMs can degenerate into toxic text even from seemingly innocuous prompts. We empirically assess several controllable generation methods, and find that while data- or compute-intensive methods (e.g., adaptive pretraining on non-toxic data) are more effective at steering away from toxicity than simpler solutions (e.g., banning "bad" words), no current method is failsafe against neural toxic degeneration. To pinpoint the potential cause of such persistent toxic degeneration, we analyze two web text corpora used to pretrain several LMs (including GPT-2; Radford et. al, 2019), and find a significant amount of offensive, factually unreliable, and otherwise toxic content. Our work provides a test bed for evaluating toxic generations by LMs and stresses the need for better data selection processes for pretraining.

  • 5 authors
·
Sep 23, 2020

Automated Identification of Toxic Code Reviews Using ToxiCR

Toxic conversations during software development interactions may have serious repercussions on a Free and Open Source Software (FOSS) development project. For example, victims of toxic conversations may become afraid to express themselves, therefore get demotivated, and may eventually leave the project. Automated filtering of toxic conversations may help a FOSS community to maintain healthy interactions among its members. However, off-the-shelf toxicity detectors perform poorly on Software Engineering (SE) datasets, such as one curated from code review comments. To encounter this challenge, we present ToxiCR, a supervised learning-based toxicity identification tool for code review interactions. ToxiCR includes a choice to select one of the ten supervised learning algorithms, an option to select text vectorization techniques, eight preprocessing steps, and a large-scale labeled dataset of 19,571 code review comments. Two out of those eight preprocessing steps are SE domain specific. With our rigorous evaluation of the models with various combinations of preprocessing steps and vectorization techniques, we have identified the best combination for our dataset that boosts 95.8% accuracy and 88.9% F1 score. ToxiCR significantly outperforms existing toxicity detectors on our dataset. We have released our dataset, pre-trained models, evaluation results, and source code publicly available at: https://github.com/WSU-SEAL/ToxiCR

  • 4 authors
·
Feb 25, 2022

LinEAS: End-to-end Learning of Activation Steering with a Distributional Loss

The growing use of generative models in daily life calls for efficient mechanisms to control their generation, to e.g., produce safe content or provide users with tools to explore style changes. Ideally, such mechanisms should require low volume of unpaired data (i.e., without explicit preference), and should be cheap, both at train and inference time, while preserving output quality. Recent research has shown that such mechanisms can be obtained by intervening exclusively on model activations, with the goal of correcting distributional differences between activations seen when using prompts from a source vs. a target set (e.g., toxic and non-toxic sentences). While cheap, these fast methods are inherently crude: their maps are tuned locally, not accounting for their impact on downstream layers, resulting in interventions that cause unintended shifts when used out-of-sample. We propose in this work linear end-to-end activation steering (LinEAS), an approach trained with a global loss that accounts simultaneously for all layer-wise distributional shifts. In addition to being more robust, the loss used to train LinEAS can be regularized with sparsifying norms, which can automatically carry out neuron selection. LinEAS only requires a handful of unpaired samples to be effective, and beats similar baselines on toxicity mitigation in language models, becoming competitive with oracle-dependent methods that have access to strong supervision. LinEAS is modality-agnostic and we empirically find that it outperforms existing activation steering methods at mitigating and including new concepts at the output of single-step text-to-image generation models.

apple Apple
·
Mar 11, 2025 1

Beyond Hate: Differentiating Uncivil and Intolerant Speech in Multimodal Content Moderation

Current multimodal toxicity benchmarks typically use a single binary hatefulness label. This coarse approach conflates two fundamentally different characteristics of expression: tone and content. Drawing on communication science theory, we introduce a fine-grained annotation scheme that distinguishes two separable dimensions: incivility (rude or dismissive tone) and intolerance (content that attacks pluralism and targets groups or identities) and apply it to 2,030 memes from the Hateful Memes dataset. We evaluate different vision-language models under coarse-label training, transfer learning across label schemes and a joint learning approach that combines the coarse hatefulness label with our fine-grained annotations. Our results show that fine-grained annotations complement existing coarse labels and, when used jointly, improve overall model performance. Moreover, models trained with the fine-grained scheme exhibit more balanced moderation-relevant error profiles and are less prone to under-detection of harmful content than models trained on hatefulness labels alone (FNR-FPR, the difference between false negative and false positive rates: 0.74 to 0.42 for LLaVA-1.6-Mistral-7B; 0.54 to 0.28 for Qwen2.5-VL-7B). This work contributes to data-centric approaches in content moderation by improving the reliability and accuracy of moderation systems through enhanced data quality. Overall, combining both coarse and fine-grained labels provides a practical route to more reliable multimodal moderation.

  • 4 authors
·
Mar 23

Dynamics of Toxicity in Political Podcasts

Toxicity in digital media poses significant challenges, yet little attention has been given to its dynamics within the rapidly growing medium of podcasts. This paper addresses this gap by analyzing political podcast data to study the emergence and propagation of toxicity, focusing on conversation chains-structured reply patterns within podcast transcripts. Leveraging state-of-the-art transcription models and advanced conversational analysis techniques, we systematically examine toxic discourse in over 30 popular political podcasts in the United States. Our key contributions include: (1) creating a comprehensive dataset of transcribed and diarized political podcasts, identifying thousands of toxic instances using Google's Perspective API, (2) uncovering concerning trends where a majority of episodes contain at least one toxic instance, (3) introducing toxic conversation chains and analyzing their structural and linguistic properties, revealing characteristics such as longer durations, repetitive patterns, figurative language, and emotional cues tied to anger and annoyance, (4) identifying demand-related words like 'want', 'like', and 'know' as precursors to toxicity, and (5) developing predictive models to anticipate toxicity shifts based on annotated change points. Our findings provide critical insights into podcast toxicity and establish a foundation for future research on real-time monitoring and intervention mechanisms to foster healthier discourse in this influential medium.

  • 6 authors
·
Jan 21, 2025

Toxicity Ahead: Forecasting Conversational Derailment on GitHub

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.

  • 5 authors
·
Dec 16, 2025 2

Frontier AI Risk Management Framework in Practice: A Risk Analysis Technical Report

To understand and identify the unprecedented risks posed by rapidly advancing artificial intelligence (AI) models, this report presents a comprehensive assessment of their frontier risks. Drawing on the E-T-C analysis (deployment environment, threat source, enabling capability) from the Frontier AI Risk Management Framework (v1.0) (SafeWork-F1-Framework), we identify critical risks in seven areas: cyber offense, biological and chemical risks, persuasion and manipulation, uncontrolled autonomous AI R\&D, strategic deception and scheming, self-replication, and collusion. Guided by the "AI-45^circ Law," we evaluate these risks using "red lines" (intolerable thresholds) and "yellow lines" (early warning indicators) to define risk zones: green (manageable risk for routine deployment and continuous monitoring), yellow (requiring strengthened mitigations and controlled deployment), and red (necessitating suspension of development and/or deployment). Experimental results show that all recent frontier AI models reside in green and yellow zones, without crossing red lines. Specifically, no evaluated models cross the yellow line for cyber offense or uncontrolled AI R\&D risks. For self-replication, and strategic deception and scheming, most models remain in the green zone, except for certain reasoning models in the yellow zone. In persuasion and manipulation, most models are in the yellow zone due to their effective influence on humans. For biological and chemical risks, we are unable to rule out the possibility of most models residing in the yellow zone, although detailed threat modeling and in-depth assessment are required to make further claims. This work reflects our current understanding of AI frontier risks and urges collective action to mitigate these challenges.

  • 37 authors
·
Jul 22, 2025 2

Leveraging Side Information for Ligand Conformation Generation using Diffusion-Based Approaches

Ligand molecule conformation generation is a critical challenge in drug discovery. Deep learning models have been developed to tackle this problem, particularly through the use of generative models in recent years. However, these models often generate conformations that lack meaningful structure and randomness due to the absence of essential side information. Examples of such side information include the chemical and geometric features of the target protein, ligand-target compound interactions, and ligand chemical properties. Without these constraints, the generated conformations may not be suitable for further selection and design of new drugs. To address this limitation, we propose a novel method for generating ligand conformations that leverage side information and incorporate flexible constraints into standard diffusion models. Drawing inspiration from the concept of message passing, we introduce ligand-target massage passing block, a mechanism that facilitates the exchange of information between target nodes and ligand nodes, thereby incorporating target node features. To capture non-covalent interactions, we introduce ligand-target compound inter and intra edges. To further improve the biological relevance of the generated conformations, we train energy models using scalar chemical features. These models guide the progress of the standard Denoising Diffusion Probabilistic Models, resulting in more biologically meaningful conformations. We evaluate the performance of SIDEGEN using the PDBBind-2020 dataset, comparing it against other methods. The results demonstrate improvements in both Aligned RMSD and Ligand RMSD evaluations. Specifically, our model outperforms GeoDiff (trained on PDBBind-2020) by 20% in terms of the median aligned RMSD metric.

  • 3 authors
·
Aug 2, 2023

Model Surgery: Modulating LLM's Behavior Via Simple Parameter Editing

Large Language Models (LLMs) have demonstrated great potential as generalist assistants, showcasing powerful task understanding and problem-solving capabilities. To deploy LLMs as AI assistants, it is crucial that these models exhibit desirable behavioral traits, such as non-toxicity and resilience against jailbreak attempts. Current methods for detoxification or preventing jailbreaking usually involve Supervised Fine-Tuning (SFT) or Reinforcement Learning from Human Feedback (RLHF), which requires finetuning billions of parameters through gradient descent with substantial computation cost. Furthermore, models modified through SFT and RLHF may deviate from the pretrained models, potentially leading to a degradation in foundational LLM capabilities. In this paper, we observe that surprisingly, directly editing a small subset of parameters can effectively modulate specific behaviors of LLMs, such as detoxification and resistance to jailbreaking. Specifically, for a behavior that we aim to avoid, we employ a linear classifier, which we term the behavior probe, to classify binary behavior labels within the hidden state space of the LLM. Using this probe, we introduce an algorithm to identify a critical subset of LLM parameters that significantly influence this targeted behavior. Then we directly edit these selected parameters by shifting them towards the behavior probe. Such a direct parameter editing method necessitates only inference-level computational resources. Experiments demonstrate that in the representative detoxification task, our approach achieves reductions of up to 90.0\% in toxicity on the RealToxicityPrompts dataset and 49.2\% on ToxiGen, while maintaining the LLM's general capabilities in areas such as common sense, question answering, and mathematics. Our code is available at https://github.com/lucywang720/model-surgery.

  • 8 authors
·
Jul 11, 2024 4

A Vector-Based Algorithm for Generating Complete Balanced Reaction Sets with Arbitrary Numbers of Reagents

We present a vector-based method to balance chemical reactions. The algorithm builds candidates in a deterministic way, removes duplicates, and always prints coefficients in the lowest whole-number form. For redox cases, electrons and protons/hydroxide are treated explicitly, so both mass and charge are balanced. We also outline the basic principles of the vector formulation of stoichiometry, interpreting reactions as integer vectors in composition space, this geometric view supports compact visualizations of reagent-product interactions and helps surface distinct reaction families. The method enumerates valid balances for arbitrary user-specified species lists without special-case balancing rules or symbolic tricks, and it provides a clean foundation for developing new algorithmic variants (e.g., alternative objectives or constraints). On representative examples (neutralization, double displacement, decomposition, classical redox, small multicomponent sets) and a negative control, the method produced correct integer balances. When multiple balances exist, we report a canonical one - minimizing the total coefficient sum with a simple tie-breaker - without claiming global optimality beyond the solutions the search enumerates. The procedure applies per reaction and extends to reaction networks via consistent per-reaction application. We do not report runtimes, broader benchmarking and code/data release are planned.

  • 3 authors
·
Oct 29, 2025

HODDI: A Dataset of High-Order Drug-Drug Interactions for Computational Pharmacovigilance

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.

  • 6 authors
·
Feb 10, 2025

Evaluation data contamination in LLMs: how do we measure it and (when) does it matter?

Hampering the interpretation of benchmark scores, evaluation data contamination has become a growing concern in the evaluation of LLMs, and an active area of research studies its effects. While evaluation data contamination is easily understood intuitively, it is surprisingly difficult to define precisely which samples should be considered contaminated and, consequently, how it impacts benchmark scores. We propose that these questions should be addressed together and that contamination metrics can be assessed based on whether models benefit from the examples they mark contaminated. We propose a novel analysis method called ConTAM, and show with a large scale survey of existing and novel n-gram based contamination metrics across 13 benchmarks and 7 models from 2 different families that ConTAM can be used to better understand evaluation data contamination and its effects. We find that contamination may have a much larger effect than reported in recent LLM releases and benefits models differently at different scales. We also find that considering only the longest contaminated substring provides a better signal than considering a union of all contaminated substrings, and that doing model and benchmark specific threshold analysis greatly increases the specificity of the results. Lastly, we investigate the impact of hyperparameter choices, finding that, among other things, both using larger values of n and disregarding matches that are infrequent in the pre-training data lead to many false negatives. With ConTAM, we provide a method to empirically ground evaluation data contamination metrics in downstream effects. With our exploration, we shed light on how evaluation data contamination can impact LLMs and provide insight into the considerations important when doing contamination analysis. We end our paper by discussing these in more detail and providing concrete suggestions for future work.

  • 7 authors
·
Nov 6, 2024

Causal Attribution of Coastal Water Clarity Degradation to Nickel Processing Expansion at the Indonesia Morowali Industrial Park, Sulawesi

Indonesia's nickel ore export ban has driven rapid expansion of smelting and hydrometallurgical processing capacity at the Indonesia Morowali Industrial Park (IMIP), now the world's largest integrated nickel processing complex, on the coast of Central Sulawesi. Whether this industrialization has degraded the adjacent marine environment remains unquantified. We apply Bayesian structural time-series (BSTS) causal inference to a multi-decadal, multi-sensor satellite ocean color record of the diffuse attenuation coefficient at 490 nm, K_d(490), to test for a causal link between IMIP expansion and nearshore turbidity change. A consensus structural breakpoint, a significant posterior causal effect estimated against a Banda Sea counterfactual, and a distribution-free placebo rank test collectively establish that coastal water clarity deteriorated after the transition from initial nickel pig iron production to hyper-expansion of high-pressure acid leaching facilities for battery-grade nickel. Satellite-derived land cover analysis independently corroborates this timing, showing substantial built-area growth and concurrent tree cover loss within the IMIP footprint. The resulting euphotic zone shoaling occurs in oligotrophic waters supporting high marine biodiversity, where even moderate optical degradation may impair coral photosynthesis and compress depth-dependent reef habitat. These findings quantify a marine environmental cost absent from Indonesia's mineral downstreaming policy discourse and demonstrate a transferable, satellite-based quasi-experimental framework for causal impact assessment at coastal industrial sites in data-limited tropical settings.

On the Proactive Generation of Unsafe Images From Text-To-Image Models Using Benign Prompts

Text-to-image models like Stable Diffusion have had a profound impact on daily life by enabling the generation of photorealistic images from textual prompts, fostering creativity, and enhancing visual experiences across various applications. However, these models also pose risks. Previous studies have successfully demonstrated that manipulated prompts can elicit text-to-image models to generate unsafe images, e.g., hateful meme variants. Yet, these studies only unleash the harmful power of text-to-image models in a passive manner. In this work, we focus on the proactive generation of unsafe images using targeted benign prompts via poisoning attacks. We propose two poisoning attacks: a basic attack and a utility-preserving attack. We qualitatively and quantitatively evaluate the proposed attacks using four representative hateful memes and multiple query prompts. Experimental results indicate that text-to-image models are vulnerable to the basic attack even with five poisoning samples. However, the poisoning effect can inadvertently spread to non-targeted prompts, leading to undesirable side effects. Root cause analysis identifies conceptual similarity as an important contributing factor to the side effects. To address this, we introduce the utility-preserving attack as a viable mitigation strategy to maintain the attack stealthiness, while ensuring decent attack performance. Our findings underscore the potential risks of adopting text-to-image models in real-world scenarios, calling for future research and safety measures in this space.

  • 5 authors
·
Oct 25, 2023

Deep literature reviews: an application of fine-tuned language models to migration research

This paper presents a hybrid framework for literature reviews that augments traditional bibliometric methods with large language models (LLMs). By fine-tuning open-source LLMs, our approach enables scalable extraction of qualitative insights from large volumes of research content, enhancing both the breadth and depth of knowledge synthesis. To improve annotation efficiency and consistency, we introduce an error-focused validation process in which LLMs generate initial labels and human reviewers correct misclassifications. Applying this framework to over 20000 scientific articles about human migration, we demonstrate that a domain-adapted LLM can serve as a "specialist" model - capable of accurately selecting relevant studies, detecting emerging trends, and identifying critical research gaps. Notably, the LLM-assisted review reveals a growing scholarly interest in climate-induced migration. However, existing literature disproportionately centers on a narrow set of environmental hazards (e.g., floods, droughts, sea-level rise, and land degradation), while overlooking others that more directly affect human health and well-being, such as air and water pollution or infectious diseases. This imbalance highlights the need for more comprehensive research that goes beyond physical environmental changes to examine their ecological and societal consequences, particularly in shaping migration as an adaptive response. Overall, our proposed framework demonstrates the potential of fine-tuned LLMs to conduct more efficient, consistent, and insightful literature reviews across disciplines, ultimately accelerating knowledge synthesis and scientific discovery.

  • 3 authors
·
Apr 17, 2025