Daily Papers

Cold-start drug-drug interaction (DDI) prediction tests whether models can identify clinically significant interactions for drugs without training-time interaction history. Existing benchmarks mostly report aggregate edge-prediction scores, leaving a key evaluation question unanswered: when models receive molecular, textual, or knowledge-graph (KG) evidence, do they actually use the evidence that pharmacologically supports the interaction? We introduce ColdDDI, a reconstructible diagnostic benchmark built from DrugBank 5.1.13, with 1,900 approved small-molecule drugs and 565,731 positive DDI pairs. ColdDDI evaluates pairs with zero, one, or two unseen drugs. It also annotates each interaction by whether it changes drug exposure or drug effect, and by whether the biomedical knowledge graph contains shared enzymes, transporters, or targets that can plausibly mediate the interaction. These annotations separate evidence availability from predictive dependence. We evaluate eight conventional DDI methods and 13 LLMs; for open-weight LLMs, we test five prompt patterns and use masking, drug replacement, and channel-sensitivity metrics to probe knowledge utilization. ColdDDI exposes that, in the hardest split where both drugs are unseen, the main performance divide is mediator availability. A fine-tuned 1B LLM recovers 89-93% of interactions with a shared enzyme, transporter, or target, but only 40-62% without such a mediator. More importantly, KG-provided evidence is not always used; several KG-augmented baselines change little when the shared mediator is masked or disrupted, whereas fine-tuned LLMs respond strongly to this intervention. Thus, ColdDDI evaluates knowledge utilization rather than knowledge access alone, showing where cold-start DDI models rely on mechanistic evidence and where they fail despite receiving it. Code is available at https://github.com/0217ljh/ColdDDI-NeurIPS2026.

Modern recommendation is shifting from platform-centric personalization toward user-governed personalization, where a personal LLM agent can act on the user's behalf across services. We formalize this emerging paradigm as Personal-Agent Mediated Recommendation: a platform recommender ranks a candidate set using platform-local information, and a personal agent uses user-authorized cross-platform history to mediate the resulting ranking and produce the final top-K slate. Such mediation is nontrivial: the platform ranking can encode strong population evidence that the personal agent cannot observe, so effective mediation must therefore balance beneficial rescues against harmful overrides. To study this trade-off, we introduce MediateRec, a benchmark that includes scalable proxy cross-platform environments and a real cross-platform test under a controlled platform-agent information boundary. To train the agent to use cross-platform history effectively, we further propose Personal Attribution Mediation Optimization (PAMO), which counterfactually masks that history to estimate personal mediation support and reallocates rank-aware advantage mass under a platform-relative value floor. We theoretically prove that PAMO preserves cutoff-level advantage mass and is locally optimal among first-order reallocations that preserve this mass without lowering average platform-relative value. Experiments on MediateRec show that personal-agent mediation enables meaningful platform corrections, yet even strong proprietary LLMs introduce non-negligible harmful overrides. PAMO consistently improves over matched outcome-only RL across seen and unseen target platforms and on the real cross-platform test, while achieving a better rescue-harm balance.

Stackelberg games and their resulting equilibria have received increasing attention in the multi-agent reinforcement learning literature. Each stage of a traditional Stackelberg game involves a leader(s) acting first, followed by the followers. In situations where the roles of leader(s) and followers can be interchanged, the designated role can have considerable advantages, for example, in first-mover advantage settings. Then the question arises: Who should be the leader and when? A bias in the leader selection process can lead to unfair outcomes. This problem is aggravated if the agents are self-interested and care only about their goals and rewards. We formally define this leader selection problem and show its relation to fairness in agents' returns. Furthermore, we propose a multi-agent reinforcement learning framework that maximizes fairness by integrating mediators. Mediators have previously been used in the simultaneous action setting with varying levels of control, such as directly performing agents' actions or just recommending them. Our framework integrates mediators in the Stackelberg setting with minimal control (leader selection). We show that the presence of mediators leads to self-interested agents taking fair actions, resulting in higher overall fairness in agents' returns.

Interpretability provides a toolset for understanding how and why neural networks behave in certain ways. However, there is little unity in the field: most studies employ ad-hoc evaluations and do not share theoretical foundations, making it difficult to measure progress and compare the pros and cons of different techniques. Furthermore, while mechanistic understanding is frequently discussed, the basic causal units underlying these mechanisms are often not explicitly defined. In this paper, we propose a perspective on interpretability research grounded in causal mediation analysis. Specifically, we describe the history and current state of interpretability taxonomized according to the types of causal units (mediators) employed, as well as methods used to search over mediators. We discuss the pros and cons of each mediator, providing insights as to when particular kinds of mediators and search methods are most appropriate depending on the goals of a given study. We argue that this framing yields a more cohesive narrative of the field, as well as actionable insights for future work. Specifically, we recommend a focus on discovering new mediators with better trade-offs between human-interpretability and compute-efficiency, and which can uncover more sophisticated abstractions from neural networks than the primarily linear mediators employed in current work. We also argue for more standardized evaluations that enable principled comparisons across mediator types, such that we can better understand when particular causal units are better suited to particular use cases.